Effects of Different Cryotherapy Techniques on Skin Surface Temperature, Agility and Balance – Comparison Between Cold Water Immersion, Game Ready®, And Ice Pack: A Randomised Clinical Trial

Introduction

Cryotherapy is widely used for the treatment of acute soft tissue [1] to reduced pain, slow edema formation, decreased tissue temperature and cell permeability, induced superficial vasoconstriction, and prevention of secondary hypoxic injury [2,3]. However, its results are directly associated with the technique used, application time, decrease in skin temperature, and depth of cold penetration [4]. Among the cryotherapy techniques the ice pack is a low-cost device which is easily accessible, causing a reduction in tissue temperature and physiological changes to at least one centimeter [5,6], the cold water immersion (CWI) allows a greater body area to be exposed to cold [7], maintaining tissue cooling for longer and providing increased analgesia [8] and cryotherapy with intermittent compression can deliver similar results [9,10]. The literature shows that cryotherapy with intermittent compression is widely used for recovery of ligament injuries [11], total knee arthroplasty [12] and reduction in post-operative pain [10].

This form of application is effective in reducing pain [10,13,14], improving tissue oxygenation and microcirculation, and providing faster recovery from ligament disorders [15]. In addition, Murgier at. al. Murgier, et al. [11] reported that pneumatic compression and cryotherapy may reduce pain and postoperative blood loss, and lead to higher functional scores [12]. On the other hand, cryotherapy and intermittent compression equipment are more expensive and less accessible for health professionals. Several studies have aimed to evaluate the differences between the application of cryotherapy techniques, with divergent methods and contradictory results [10,16,17]. In addition, Hawkins and Hawkins [18] reported that sports physical therapists applied cryotherapy with great variability for acute or sub-acute ankle sprain and that efforts need to be made to substantiate the evidence of cryotherapy application [19].

Thus, little is known about the differences between the applications of an ice pack, cold water immersion, and cryotherapy associated with intermittent compression for the purpose of reducing skin surface temperature (related to treatment efficacy) and changing agility and balance. Therefore, new research should include controlled and reproducible different techniques. To contribute to discussions on the effects and indications of different techniques of cryotherapy on the ankle joint, the present study aimed to establish differences between applications of cryotherapy techniques on the ankle superficial skin temperature (SST) in different regions of this joint; the effects on agility and dynamic balance were also evaluated. We hypothesized that the three cryotherapy techniques studied would have the same effects on decreasing skin temperature, agility and balance. In addition, we hypothesized that the anterior, posterior, and lateral regions of the ankle would present different values of cooling. Thus, the results may support clinical decision making and aid choices made according to preference among the techniques.

Methods

This was a randomized clinical study, approved by the Research Ethics Committee of the institution (case N. 2.117.378) and registered at http://www.clinicaltrials.gov (ID NCT03659474). All procedures were performed at the physiotherapy outpatient clinic of the University. Twenty young and physically active subjects (ten men and ten women), without injuries or complaints in the ankle participated in the study. The women’s evaluations were carried out outside the menstrual period, since when they are menstruating, worsening in agility and dynamic balance can occur [20]. The sample size was calculated based on the results of the manuscript “The Magnitude of Tissue Cooling during Cryotherapy with Varied Types of Compression” [21], considering the SST over the mid-portion of the right gastrocnemius belly in twenty minutes after application of ice only and the elastic wrap. The values used were the means of each group (15.51 and 11.01) with a standard deviation of 4.39 (p <0.05). The program used was the Power and Sample Size, with a 95% confidence interval, 5% alpha level, and test power of 90%. Thus, 20 participants were recruited.

All participants underwent cryotherapy for the ankle with three different applications: cold water immersion (CWI), cryotherapy+Game Ready® compression (CGRC), or icepack (IP). Entries were randomly performed by a researcher not involved in the study through the platform http://www.ramdom.org and recorded in three different periods, with a 48-hour interval between measurements (Figure 1). All participants performed the three interventions, and there was no sample loss. Initially, a pre-intervention evaluation was performed where the SSTs of the anterior, lateral, and posterior regions of the ankle were collected with a professional Flir C2® thermal camera (FLIR® systems, Inc. Washington, USA). The thermographic camera had automatic ZOOM, it was positioned perpendicularly to the ankle, with a distance of 30 centimeters from the anterior joint line of the ankle, lateral malleolus and midpoint of the calcaneus tendon. In sequence, the Y test and Side Hop Test (SHT) were developed, already used in previous studies for the analysis of dynamic balance (22,23) and agility (24), respectively. Participants were familiarized with the tests prior to conducting the data collection.

After the baseline assessment, the participants performed a warm-up with a 15-minute walk on the treadmill (Movement®) at a constant and comfortable pace. Immediately after walking, subjects were referred to one of three cryotherapy techniques for testing. For the CWI group, the ankle joint was immersed in cold water up to the mid portion of the tibia, at approximately 4°C [22], controlled by the thermal camera. For the CGRC group, the ankle joint was wrapped (cold wrap) using maximum dynamic intermittent compression (established by the equipment) and programmed to maintain a temperature of 1°C, according to the manufacturer’s instructions. For the IP group, the ankle joint was wrapped with three ice packs, each containing 500g of crushed ice. All treatments were performed for 20 minutes. The ambient temperature was always between 25 and 27 degrees Celsius. During cryotherapy applications, the participants sat on a comfortable chair, with their knee and ankle at 90º (Figure 2).

Figure 1: Flow chart depicting methodology for the assessments and interventions using cryotherapy.

Figure 2: Cryotherapy techniques.
A. cryotherapy using cold water immersion
B. cryotherapy + Game Ready® compression; and
C. cryotherapy using an ice pack.

The same position was adopted for the three interventions to reduce the effects of the peripheral blood flow on the cooling and rewarming of the skin. The SST assessment was performed immediately after, 10 minutes, 20 minutes, and 30 minutes after the cryotherapy techniques. The same procedure was carried out for the functional tests. The participants attended data collection on three distinct days and were randomized into one of the three interventional groups each day. Statistical analysis was performed using SPSS software version 2.2 (SPSS Inc. Chicago, Ill, USA). The level of significance was set at 5%. The Shapiro Wilk test was used to establish the normality of the data. The values obtained were compared using a two-way repeated measure ANOVA, one-way ANOVA, and the Bonferroni post-test. To verify the effect size (d), the following formula was used: d= (x1−x2)/averages of the standard deviations (SDs), where x1 is the average of the analyzed variable in the initial assessment, and x2 is the average of the analyzed variable in the final assessment [23]. The average of the SDs was calculated through the arithmetic mean of the standard deviations related to the initial and final assessments: (SD1+ SD2)/2. The effect size was defined as ≤ 0.5 representing a small effect, between >0.5 and ≤ 0.8, a medium effect, and > 0.8, a large effect [23].

Results

Twenty physically active subjects (10 men and 10 women) with a mean age of 21.4±1.9 years, weight of 70.7±12.4kg, and height of 1.7±0.07 meters participated in this study. The subjects engaged in physical activities (gym, soccer, running and other exercises) three to five times a week and were present at the three different data collection moments; there were no sample losses. The three cryotherapy application techniques significantly decreased the SST in the anterior, lateral, and posterior regions of the ankle when the time periods (baseline, immediately post, post10, 20, and 30 minutes) were compared. However, the IP group showed no significant difference for cooling of the anterior region of the ankle 30 minutes after application. In addition, only the CWI group (anterior, lateral, and posterior region of the ankle) and the CGRC group(posterior region of the ankle) exhibited SST sunder 15ºC (Table 1), related to analgesic effects [24]. The comparisons between the three application techniques showed that the CWI induced lower SST values for the anterior and lateral regions of the ankle at up to 10 minutes after application.

Table 1: Assessment of the SST for the anterior, lateral, and posterior regions of the ankle after the application of different cryotherapy techniques.

Note: SSP: superficial skin temperature. CWI: cold water immersion. CGRC: cryotherapy + Game Ready® compression. IP: Icepack. *Significant difference between baseline and rewarming time using the same cryotherapy technique established by repeated measures ANOVA. #Results established by one-way ANOVA for comparison between groups using CWI at different moments.

Both the CWI and CGRC applied to the posterior region of the ankle were equally effective in reducing SST at 10 minutes after the intervention. However, application of CWI produced the lowest temperature in the evaluated regions, except in the posterior region immediately after the ankle was removed from immersion (Table 1). Analysis of the effect size for SST of the anterior ankle demonstrated larger effect sizes for CWI (d = 0.90) and CGRC (d = 0.80), and a smaller effect (d = 0.20) for IP 30-minutes after application. For the lateral and posterior regions of the ankle all the application techniques demonstrated large effects (d > 0.8) for the reduction in SST at up to 30-minutes post-application. Functional performance based on the SHT indicated that the subjects in the CWI group performed worse immediately after application, with a significantly increased time. The subjects in the CGRC group showed improvement 30-minutesafter application, which was not expected. However, no performance differences were identified in the IP group (Table 2).

In addition, subjects in the IP group, even with no performance differences in the SHT at different moments, obtained better results when compared to the CWI group. For the Y test, no significant differences were identified at any moments or between the techniques used (Table 2). For the effect size produced by the different cryotherapy techniques, the CGRC group presented a large effect (d = 0.8) between the initial assessment and after 30 minutes, with improvement in agility performance (SHT). The CWI group demonstrated a large and negative effect (d = 1) between the baseline and immediately after assessments, with worse functional performance in the same test. The results obtained in the present study demonstrated significant differences between the techniques for the reduction in SST as well as changes in agility performance of the participants.

Table 2: Functional performance in the SHT and Y tests after applying different cryotherapy techniques.

Note: SHT: Side Hop Test. CWI: cold water immersion. CGRC: cryotherapy + Game Ready® compression. IP: Ice pack. *Significant difference between application times using the same cryotherapy technique established by repeated measures ANOVA. #Results established by one-way ANOVA for comparison between groups using CWI.

Discussion

The present study showed the cooling of the anterior, lateral and posterior ankle regions, and the posterior region of the ankle showed the lowest skin surface temperature (SST). All the cryotherapy techniques analyzed significantly decreased the SST; however, local cold water immersion (CWI) was better at decreasing SST when compared to cryotherapy + Game Ready® compression (CGRC) and ice pack (IP), up to 10 minutes after the end of the applications, in all regions. The importance of analyzing SST in different regions is justified by the different sites of injury in this joint (direct trauma, ligament injuries, Achilles tendon ruptures, inflammation of burses, etc.), which may respond unequally to the application of cold. The results revealed that the three techniques of cryotherapy applications significantly decreased the SST for up to 30-minutes of rewarming. The CWI group exhibited lower SST values in the anterior and lateral regions of the ankle (approximately 15 degrees immediately after application and better values at up to 10-minutes of rewarming), which is related to a local analgesic effect through inhibiting nerve conduction velocity [25].

However, 20-minutes after application in the anterior and lateral regions of the ankle, the subjects in the CWI and CGRC groups performed better than those in the IP group, which always exhibited higher SST values. These results contradict those by Kennet, Hardaker, Hobbs, & Selfe [26] and Hawkins, Shurtz, & Spears [9] who found lower temperatures after applying a ice pack compared to compression therapy. It is believed that greater rewarming after ice pack application may have occurred due to the lack of compression and worse contact between the skin and ice [21]. The cooling of the posterior region of the ankle demonstrated lower temperatures in all the techniques used, which may be justified by the decreased blood circulation of the Achilles tendon and bursa located in the posterior region of the ankle, since the connective tissue under the skin has less blood flow than the muscles, which does not favor the reheating of this place. It is worth noting that even after 10 minutes the CWI and CGRC groups presented better cooling results.

The best results associated with CWI application can be explained by the greater cooling area of contact [7], the hydrostatic pressure that redirected the skin blood flow to the central circulation [27], and the local vasoconstriction that reduces the fluid flux into the interstitial space. The intervention with CGRC provided satisfactory results that may be related to cooling associated with compression [12]. The results achieved for the effects of cryotherapy on agility performance, evaluated by SHT, confirmed the findings of previous studies, such as those reported by Macedo, et al. [22] and Furmanek, Słomka, & Juras [28] who showed worse functional performance immediately after CWI application. It has commonly been assumed that reduction in nerve conduction velocity may reduce the sensitivity of the afferent mechanoreceptors and the sensitivity of the muscle spindles with less afferent sensory information, causing damage to both the neuromuscular control and functional performance [4,25,29].

Moreover, Kilby, Molenaar, & Newell [30] and Oba, et al. [31] highlighted that the ankle joint capsule is more superficial than the majority of joints, and therefore, the receptors may be more influenced by cryotherapy application. However, after 10-minutes rewarming following CWI and at all intervention moments after CGRC and IP application, the agility performance returned to baseline values, which should be considered for the planning of physical and functional activities, training,and even for the return to sport after cryotherapy. These findings agree with those of Williams, Miller, Sebastianelli, & Vairo Williams, et al. [32] who reported that a 15-minute application of crushed ice on the ankle was not able to change the function of joint receptors. Finally, the Y test did not demonstrate any change after the application of the cryotherapy techniques, which may have occurred because this is a simple and easy test for young and healthy individuals, such as the participants of this study. Thus, we can infer that CWI was the best technique to reduce SST, followed by CGRC, and the IP provided the worst cooling.

This finding is important for clinical practice, since CWI application is widely used, low cost, and produced better results for the variables analyzed. For the posterior region of the ankle, CWI and CGRC were similar in cooling, and even at high cost the CGRC is an appropriate choice and can be used according to the preference of the physiotherapist or the patient. In addition, 10 minutes after the application of CWI, agility is worse and greater care must be taken. As limitations of this study it should be pointed out that healthy individuals were evaluated, intramuscular temperature analysis would be more reliable regarding the application of these techniques, and a force platform would be more appropriate to evaluate balance. Further research should complement the results obtained in this study.

Conclusion

The present study concluded that there is a difference in the application of the three cryotherapy techniques. The applications of CWI and CGRC were more effective in cooling and maintaining lower SST of the ankle. These two modalities should be the preferred treatment options for the anterior, lateral, and posterior regions of the ankle. CWI reduced agility performance at up to 10 minutes after cooling. Dynamic balance was not altered by any of the cryotherapy techniques tested. Ethics Committee of the State University of Londrina (UEL), Londrina, Paraná (Opinion No. 2.117.378). Clinical Trials (NCT03659474).

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Joint Aches, Rash, and Fever in A Patient on Mepolizumab

Introduction

Sarcoidosis is a systemic disease characterized by noncaseating granuloma formations in one or more organ systems. Löfgren syndrome is an acute form of sarcoidosis that presents with a classic triad of arthritis or periarthritis, erythema nodosum (EN), and bilateral hilar lymphadenopathy (BHL). The heterogeneous presentations of Löfgren syndrome, especially in the setting of additional rheumatologic diseases, requires high clinical suspicion and acumen for early diagnosis and treatment. We present a case of a 29-year-old male with Löfgren syndrome.

Case Report

29-year-old male with possible eosinophilic granulomatosis with polyangiitis (eGPA)) with severe persistent asthma controlled on mepolizumab presented with arthralgias, rash, and fevers a week after a camping trip. He denied any consumption of unfiltered water, tick bites, trauma, sick contacts, cough, diarrhea, dysuria, or vomiting. His polyarthralgias were asymmetric, present in large joints of all four extremities, and unresponsive to ibuprofen. The patient’s history was notable for a presumptive diagnosis of eGPA dating back to a systemic inflammatory illness at age 16, which manifested with eosinophilia, pericarditis, palpable purpura, pulmonary infiltrates, nephritis and asthma, although the diagnosis was never biopsy confirmed. He had been managed with daily prednisone (20 mg/day) for over a decade due to a lack of health insurance and had been unable to taper due to recurrent asthma, sinusitis, and rashes. Three months prior to presentation, the patient was started on mepolizumab 100mg sq monthly and was able to taper completely off of prednisone.

He was admitted to an outside hospital for severe right ankle swelling and underwent incision and drainage of his right posterior tendon tibial sheath for suspected septic arthritis. The aspirarate was clear, non-purulent and without growth on culture. Laboratory investigations were significant for WBC of 5.08 (ref 4.31-6.4 uL), normal absolute eosinophils, angiotensin converting enzyme (ACE) of 44 U/L (ref 9-67 U/L), negative chlamydia and gonorrhea PCR, and negative ANA and ANCA titers. He also had a negative quantiferon gold test four months prior to presentation. A chest CT demonstrated extensive, bilateral hilar and mediastinal adenopathy (Figure 1). He was started on vancomycin and discharged with cephalexin for right ankle cellulitis. His symptoms transiently improved on antibiotics but he was rehospitalized for progressive arthralgia, fevers, and new onset tender nodules on the left forearm four days later. On readmission, he was febrile to 38.1 C with otherwise normal vital signs.

Figure 1: Chest CT demonstrating bilateral hilar lymphadenopathy.

Physical exam was significant for pain with active and passive range of motion of large joints most pronounced in the right elbow, right wrist, right ankle and left knee. He had ill defined, pink erythematous patches on bilateral anterior lower extremities and 4 subcutaneous, slightly tender nodules on his upper and lower extremities. His laboratory analysis was significant for a WBC 9.52 K/cu mm (ref 3.5 – 10.8 K/cu mm) with 2% of eosinophil (ref 1-3%), creatinine of 1.32 (baseline of 1), ESR 58 mm/hr (ref 0-15 mmg/ hr), CRP 103 mg/L (ref <10 mg/L), and urine analysis without protein, blood, or WBC. Skin biopsy of the subcutaneous nodule on the left shin nodule demonstrated both sarcoidal and tuberculoid (intermittent central necrosis) granulomatous septal panniculitis without evidence of vasculitis (Figure 2). Although the presence of caseation and few eosinophils in his biopsy favored eGPA, his clinical presentation argued more for acute sarcoidosis.

Figure 2: Skin tissue biopsy of subcutaneous nodules demonstrate sarcoidal and tuberculoid granulomatous septal panniculitis.

The differential diagnosis included infection, eGPA nodules, and Löfgren syndrome. Cultures and quantiferon were negative making infectious panniculitis less likely. EGPA nodules were considered, however this patient’s ankle arthritis, erythema nodosum, and hilar lymphadenopathy were most consistent with Löfgren syndrome. He was started on a dexamethasone 16-day taper starting at 6 mg daily and mepolizumab was continued. Post-discharge follow-up with rheumatology demonstrated resolution of arthritis, erythema nodosum, along with normalization of inflammatory markers. Three months post-treatment, his chest x-ray demonstrated decreased appearance of mediastinal and hilar lymphadenopathy when compared to prior CT (Figure 3). One year later, the patient continues to take mepolizumab without corticosteroids, and has had no recurrence of his symptoms.

Figure 3: Chear x-ray three months post steroid taper demonstrating decrease in BHL.

Discussion

Sarcoidosis, first described by dermatologist Jonathan Hutchinson in 1877, is a systemic disease of unknown etiology resulting in noncaseating granuloma formation in any organ [1]. The diagnosis is likely in the presence of clinical symptoms of organ involvement with radiographic correlation, tissue biopsy with histological evidence of granulomas, and exclusion of other diseases with granuloma formation. Exclusion of other granulomatous diseases include granulomatosis with polyangiitis, exposures to particulates (beryllium, dust), and infections such as mycobacterium, coccidiomycosis, and syphilis are important considerations. Löfgren syndrome, first described by pulmonologist Sven Löfgren in 1946, is a subset of sarcoidosis with a distinct phenotype [2,3]. Unlike the chronic often insidious development of sarcoidosis, Löfgren syndrome presents acutely with the classic clinical triad of polyarthritis or periarthritis, BHL, and EN. Fever and uveitis may also be present.

The arthritis or periarthritis is most commonly observed at the ankles but can affect elbows, knees, and metacarpophalangeal joints. Articular symptoms usually precede or present concomitantly with development of tender, erythematous, subcutaneous nodules called EN. Of note, biopsy is not necessary to diagnose Löfgren syndrome. Our case of a 29-year-old male with a history for possible eGPA and severe asthma on mepolizumab who presented with migratory polyarthritis, EN, BHL, and fever is consistent with Löfgren syndrome. Infectious etiologies were considered but less likely given absent history of tick bites, negative sexually transmitted disease and quantiferon gold test, non-purulent right ankle aspirate, and absence of growth on cultures. His history of possible eGPA presented a unique clinical challenge to differentiate from Löfgren syndrome. EGPA, a rare medium size vasculitis, can present with fever, arthralgia, and rash [4]. EGPA can cause subcutaneous nodules on extensor surfaces, which show granuloma on biopsy and may also show eosinophilia and/or vasculitis. Although presence of fibrinoid changes and few eosinophils on skin biopsy made eGPA possible, lack of palpable purpura, necrotic plaques, or retiform purpura on skin exam and overall clinical presentation made a vasculitis etiology less likely.

Given the patient’s recent initiation of mepolizumab, an IL-5 humanized monoclonal antibody, drug-induced sarcoidosis-linked reaction (DISR) was also considered [5]. DISR is a multisystem, granulomatous reaction with an indistinguishable phenotype to sarcoidosis. The four most common classes of drugs to cause DISR include tumor necrosis factor-inhibitors, interferons, antiretroviral therapy, and immune checkpoint inhibitors (Chopra). DISR has a temporal association with initiation of the offending drug and often will self-resolve after the withholding of the suspected drug. Mepolizumab is an anti IL-5 therapy, which is relatively new, but thus far has not been reported to cause DISR. Because this patient remained on mepolizumab even after Löfgren syndrome was diagnosed and had clinical improvement, DISR secondary to mepolizumab is less likely. The diagnosis of Löfgren syndrome in our patient required a multidisciplinary team that recognized the clinical constellation of acute migratory polyarthritis, BHL, and EN. In a young patient with acute arthritis and skin lesions, acute sarcoid should be considered. Work-up should include a chest x-ray to identify BLH and skin biopsy may be helpful in recognizing erythema nodosum. Although Löfgren syndrome is a self-limiting condition, a course of systemic steroids may relieve symptoms and provide quicker recovery

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National TB Elimination Program in Uttar Pradesh, India: A Case Study of a Country Within the Country

Background

Prevailing Situation of Tuberculosis in India

Tuberculosis (TB) is the world’s most deadly infectious disease; it claims more than a million lives each year and affects a million more. It is the leading cause of death from a single infectious agent ranking above HIV/AIDS [1]. The global TB situation is dire with TB causing a significant mortality and morbidity [1]. India is the second-most populous country in the world with one fourth of the global incident TB cases occurring in India annually [2]. In 2019, out of the estimated global annual incidence of 10.0 million TB cases, 2.6 million were estimated to have occurred in India [1]. TB is a major public health problem in India, and it has a huge impact on the health and economy of the country [3]. Despite of the fact that TB is a curable disease if there is timely diagnosis and initiation of treatment, around two million people develop TB and 1.5 million die of TB in India every year.1 Poor primary health care and infrastructure in rural areas, irrational use of first- and second-line anti-TB drugs, unregulated private health care, rising prevalence of HIV TB comorbidity, widespread malnutrition fueled by poverty are some of the major challenges to control TB in India [4]. In addition, COVID-19 pandemic threatens to impact the progress made so far in reducing the burden of TB disease posing a considerable challenge for TB control efforts in India [1].

Journey of TB

The journey of TB control in India started with the establishment of sanatoria [5]. This was a maiden attempt in controlling the transmission of infection disease provided a timely diagnosis and initiation of treatment. Around two million people develop TB and 1.5 million die of TB in India every year [1]. The saga of TB control in India spans many decades. It is the most ancient disease with its description available in the ancient Vedas [6]. The evolution of the disease has been need-based, relating to problems of a technical, operational and managerial nature that arose over a period of time in the country [7]. As with most other countries, the initial anti- TB measures implemented in India were unplanned and ad hoc in nature, confined mainly to the establishment of hospitals and sanatoria [8]. This was due partly to lack of resources and partly to a preoccupation by way of isolation. Simultaneously, around the time India gained independence, effective drugs against TB began to be available (Streptomycin 1944, PAS 1946, Thiacetazone 1950, Isoniazid 1952 and Rifampicin1966) [8].

An estimated 4000 clinics and 5,00,000 beds were required for TB control according to western standards of the time in India [9]. Owing to money restrains, attention was directed to prevention of TB by way of BCG vaccination. Along with BCG vaccination, chest radiography, sputum microscopy for case finding, and ambulatory domiciliary chemotherapy for treatment were the other available tools for the control of TB. In order to apply these tools on a large scale, genesis of National TB control Programme (NTP) happened [9]. Now despite of the existence of NTP since 1962, no appreciable change was observed in the epidemiological situation of TB in the country. The situation was further threatened with the emergence of the HIV-AIDS epidemic and the spread of multi-drug resistance TB.7 In view of this, in 1992, came the Revised National TB Control Programme (RNTCP) which was renamed as National TB Elimination Program (NTEP) in 2020 [8,10].

National TB Elimination Program (NTEP)

To revitalize the TB control programme in India, NTEP adopted the internationally recommended Directly Observed Treatment Short-course (DOTS) strategy, as the most systematic and costeffective approach [8]. It started with as a pilot in 1993 and was launched countrywide as a national programme in 1997. Rapid expansion of NTEP began in late 1998. Thirty percent of the country’s population was covered by the end of 2000, and by the end of 2002, 50%of the country’s population was covered under the NTEP. By December 2005, around 97% (about 1080 million) of the population had been covered, and the entire country was covered under DOTS by 24th March 2006 [11]. NTEP was set in motion in Uttar Pradesh (UP) way back in 2006 when in other state it was already attaining maturity [12]. UP being the most populous and vast state in the country contributes to the highest number of TB cases. It is the vastest state in India in terms of demography as well as geography making it challenging to manage the program with 75 districts [13]. UP contributes to 20% of the total notified TB cases in India [2]. Hence, it was decided to review the existing situation of TB in UP and new innovations undertaken to combat TB in UP.

Methodology

Uttar Pradesh is bounded by Nepal on the North, Himachal Pradesh on the north-west, Haryana on the west, Rajasthan on the southwest, Madhya Pradesh on the south and south- west and Bihar on the east. Situated between 23o 52’N and 31o 28 N latitudes and 77o 3’ and 84o 39’E longitudes, this is the fourth largest state in the country [14]. Uttar Pradesh is the densely populous state in the country accounting for 16.4 per cent of the country’s population. It is also the fourth largest state in geographical area covering 9.0 per cent of the country’s geographical area, encompassing 2, 94,411 square kilometers and comprising of 75 districts, 18 divisions, 901 development blocks and 200 million inhabited villages. The density of population in the state is 829 person per square kilometers as against 382 for the country [15]. This case study analyzes the current situation of the NTEP in UP. New initiatives were studied to understand their potential. The case study is based on the analysis of secondary data from the management information systems of the national, state and district levels. Information regarding health infrastructure and human resources was collected from Annual TB report, 2021. Data and information were also obtained from official website of the TBC-India.

Current Scenario

Infrastructure

In NTEP infrastructure, UP is headed by State TB cell (STC) located at Lucknow. The State TB Training and Demonstration Centre (STDC) is situated at Agra. STDC was built to effectively monitor and supervise the program. It is a premier institute in the state to impart quality training and workshops to all the key managers and supervisors in the state. The state has established five Regional TB programmatic Monitoring Units (RTPMUs) for better programmatic monitoring [12]. The state has 75 District Tuberculosis Centers (DTC), 993 Tuberculosis units (TU) and 2063 Designated Microscopy Centers (DMC) [2]. In laboratory infrastructure, there are 11 Culture & Drug Susceptibility Testing (C & DST) laboratories out of which 5 are having LPA facility, including 2 Intermediate Reference Laboratory (IRL) and 148 CBNAAT/ TrueNAT sites are operational in the state [2]. A total of 23 DR-TB centers have been established for the management of DR-TB [2].

Case Finding

Since the programme Implementation in 2006, the state has seen noticeable achievement in improving the prevailing situation of TB and thus contributing to the achievement of Millennium Development Goal [12]. UP being the most populous and vast state in the country, it contributes to the highest number of TB cases, and it has made significant efforts in achieving these targets. The New Smear Positive case detection rate in the year 2007 which was the initial phase of implementation of NTEP in UP was 99606 per lakh population [12]. The Annual Case Notification Rate achieved in the year 2020 against target was 61% [2]. Although the state is struggling to achieve the expected rate of more than 70%, the improvement in terms of number is worth noticing. The treatment success rate of UP of 2019 cohort was 83% as compared to the national average of 82%. In the present study, Presumptive TB examination rate (erstwhile Suspect examination rate) and case notification rate (CNR) were examined for the past 10 years.

Presumptive TB examination refers to a person with any of the symptoms and signs suggestive of TB including cough for more than two weeks, significant weight loss, hemoptysis, any abnormality in chest radiograph [16]. As seen from Table 1, Presumptive TB examination per lakh population has increased which relates to a more robust and strengthened case finding activities. Presumptive TB examination rate is the number of presumptive TB cases who have undergone sputum examination per lakh population per year while case notification rate is the number of tuberculosis cases registered in a specified time period (per year) in unit population (per lakh) in a defined area (e.g., TU/district/state) [16]. This depends on the extent to which patients utilize the health services. CNR is remaining steady/decreasing which denotes that even though case finding efforts are accelerated (which is reflected from Presumptive TB examination over the years), case load remains unaffected which is also one of the achievements of NTEP-UP (Tables 1 & 2).

Table 1: Key indicators of case finding activities of NTEP – UP.

Table 2: Physical infrastructure of NTEP in UP.

NTEP was implemented in Gujarat state in 1998 and it is one of the better performing states as far as control of TB is concerned [17]. There are other states in India who have better indicators, but they are small states. Gujarat is demographically comparable to UP state [18], and its key indicators of case finding are much higher compared to UP [2]. In the year 2015, which is considered as benchmark for TB free certification [2] the presumptive TB examination rate in Gujarat was 884 per lakh population which increased to 1164 in 2020 along with increase in CNR from 128 to 173 per lakh population in 2020 while Presumptive TB examination of UP was 624 per lakh population in 2015 which decrease to 482 in 2020 along with increase in CNR from 115 to 158 per lakh population which suggests that despite a decrease efforts for case detection, case notification has increase as compared to 2015 [2,19]. Hence, more of vigorous active case finding strategies are required.

UP is one of the five states besides Maharashtra, Madhya Pradesh, Gujarat and Rajasthan that contributes half of the total notified TB cases in India [2]. The annual TB case notification is increase during the last 10 years. It is evident from, there is a doubling observed in case notification rate from 2011 to 2019 with a fall in 2020 probably due to COVID-19 pandemic situation in the country. Apart from Ladakh, Lakshadweep, Mizoram and Sikkim, all the states and UTs in India presented a decrease in TB notification rates in the March-April 2020 [2]. The same was observed in UP with the first half of 2020 witnessing a 50% fall in TB notification due to vast hampering of the nationwide health system and restriction of movement due to lockdown situation [2]. But the state took vigorous steps like Active case finding and TB-COVID bi- directional screening which helped in increasing the TB notification by 26% in the last half of 2020 [2]. A well-planned screening for active TB among the high-risk groups is an established effective strategy to improve early case detection [2]. Active case finding activities were being implemented in NTEP since 2017 [20,21]. UP conducted ACF activities with 10121 patients diagnosed of TB among 43 million population mapped in 20202 and 14000 TB patients diagnosed among 56 million population mapped in 2019 [22] with the help of mobile TB diagnostic van enabling early TB diagnosis especially in hard-to-reach areas.

One of the major hindrances in TB detection is poorly established specimen collection and transportation systems in India [23]. Even though UP piloted the use of public postal service for sample transportation in 2019 when nationwide efforts were being made to link the sputum transport with India postal services28, it still needs to strengthen and monitor the engagement of public postal service for sample transportation. Figure 1 reveals that private TB case notification have increased over the past 10 years. Much of this increase in notification is credited to the directly transferred benefit (DBT) scheme of NTEP2 and the fact that the TB was declared as a notifiable disease in May 2012 [24]. UP has shown a considerable achievement in private case notification rate over a period of last 7 years since private sector started notifying TB cases.

Figure 1: Comparison of Private Sector notification of NTEP-UP and India.

Multi-Drug Resistant TB

Drug resistant TB is one of the major impediments to achieving the National strategic plan (NSP) goal of ending TB in India [10]. India bears 27% of the global burden of multi-drug resistant TB (MDR-TB) cases [2] An estimated 1,24,000 people developed MDRTB in India in 2019, i.e., 9.1 cases per one lakh population [2]. The first national anti-TB drug resistance survey reported 28% of TB patients resistant to any drugs and 6.2% having MDR TB. India is one of the countries with highest burden of MDR-TB in the world and UP is the one state which contributes to the maximum load of MDR-TB in India [2]. UP has introduced Programmatic management of drug resistant TB services in all 75 districts in 2013 [12]. It has 23 nodal DR-TB centers operationalized by airborne infection control measures [2]. UP contributes to 25% of total DRTB case notification of India [2] (Figure 2) In 2020, Universal drug susceptibility testing. was offered to 60% of notified TB patients in. DR-TB Case notification rate in UP is 5.3 per lakh population in 2020 Thus, more intensive efforts are required to offered UDST to all the eligible DR-TB patients [2]. (Figure 2) reveals an increasing trend of DR-TB cases in the last 10 years with a fall observed in the year 2020 due to COVID-19 pandemic when the overall case notification was reduced.

Figure 2: Trend of Drug resistant TB in NTEP-UP.

TB-HIV

Human Immunodeficiency Virus (HIV) is a risk factor for TB which not only increases the risk of reactivating latent TB infection but also increases the risk of rapid TB progression soon after the TB infection or reinfection. TB in people living with HIV is very difficult to diagnose and treat owing to challenges related to comorbidity, pill burden, co-toxicity and drug interactions [25]. India accounts for the highest burden of TB-HIV co-infected cases [2] India initiated provider-initiated testing and counselling among presumptive TB cases for early detection of HIV [2]. UP is a low HIV prevalence state. Out of the total TB-HIV burden, UP contributes about 6.95% of the total TB-HIV burden in India.2 In 2020, there were 2356 TB HIV co-infected patients diagnosed with HIV among those tested. Guidelines on prevention and management of TB in people living with HIV at ART centers recommended all TB-HIV coinfected patients should receive cotrimoxazole prophylactic therapy to prevent development of other common opportunistic infections [26].

In 2020, 94% of the total diagnosed HIV patients with TB were initiated on CPT whereas 92% were initiated on ART.2 UP reported high coverage of HIV testing among TB patients notified in 2019 especially in the public sector (85%) [27]. In UP, State TBHIV coordination committee (STCC) and State Technical Working Group (STWG) monitors key policy related to TB-HIV collaborative activities. District TB officers were given the charge of District HIV Nodal officers in 2008 making them the focal point for both TB and HIV related activities and better implementation of policy decisions [12,27-30].

Regional TB Programme Management Units: An Innovative Idea

Over the years India has been trying to initiate and implement new ideas of controlling and eliminating Tuberculosis from the country. Thus, in line with the Country’s view the State of Uttar Pradesh is working on the same path and has taken new initiatives to achieve the goals. Though the complete implementation of NTEP in the state was in the year 2006, in year 2014 an innovation through National Health Mission was conceived which lead to the establishment of four Regional TB Program Management Unit (RTPMU) at Agra, Bareilly, Lucknow and Varanasi. Recently, fifth RTPMU was inaugurated at Gorakhpur, UP [12]. Because of the fact that UP being a large state with 75 districts thus NTEP-UP has always faced a challenge of intensive monitoring, supervision and evaluation of all the districts in the programme from one State unit which is the State TB Cell at Lucknow [12]. Thus, a felt need for decentralization of the State Program Management, Supervision & Monitoring from State Head Quarter to the Regional levels units was seen.

The vision of RTPMU is handholding of districts with supportive supervision Each RTPMU is working as a satellite unit of both STC (State TB Cell) at Lucknow & STDC (States NTEP training and quality assurance establishment located) at Agra and are performing their key roles while supporting the districts linked to them which has led to a more effective Administration, Supervision, Monitoring, Training, External Quality Assurance, Reviews, Logistic management etc. [12]. Functions of RTPMU are to share the responsibilities of STC and STDC to effectively supervise, monitor and provide training as well as feedback to their linked districts for TB control. RTPMU is managed by a regional TB program management officer (RTPMO), 2 Deputy RTPMO, Consultant, Data entry operator and office assistant [12]. Thus, since the establishment of the five RTPMU’s state has achieved a noteworthy improvement in the key indicators and had shown the National Program Managers at Government of India & WHO that the preconceived notion of UP being a nonperforming state is gradually negated [31].

Conclusion

UP contributes to the maximum case load of drug sensitive TB (20%) and DR-TB (25%) in India. Being a vast and populous state with 75 districts, it has a mammoth task lying ahead to eliminate TB by 2025. The usual notion of UP being a nonperforming state is gradually changing. This is reflected in the efforts put by the NTEPUP and the achievements attained so far be it in terms of active case finding of TB cases, increase in private sector notification, using Indian postal service to improved sputum specimen transportation, mobile medical van facilities in hard-to-reach area and better monitoring of the program in the state. The RTPMUs established shows the decentralization efforts of the state linking each district to a particular RTPMU and increasing the accountability for TB. And these efforts are on-going, be it the recent establishment of RTPMU Gorakhpur or the Chief Minister of UP urging ministers and lawmakers to adopt one TB patient each to achieve the target of making UP free of TB which shows the hardcore commitment of the state to eliminate TB. Private sector notification and the proportion of UDST offered to TB patients needs to be further increased in UP. A more focused approach is required for each and every component of the TB program in UP. as a slight change in TB situation in UP will have a huge impact on the nation’s TB status and thus will pave way for eliminating TB from India by 2025.

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Intradural Pressure Profile after Administration of Totilac® Compared to Mannitol® for Patients Undergoing Hematomal Evacuation Craniotomy

Background

Hemmorhage cerebral injury requires management to control the increase in intracranial pressure (ICP), including the surgical strategy and administration of hyperosmolar solution [1]. The hyperosmolar solution that has been widely used is mannitol 20% (Mannitol®). Mannitol® increase diuresis directly in the loop of Henle. Hypertonic sodium lactate (Totilac®), a relatively new hyperosmolar solution, can be used as an alternative in the management of increased ICP [2]. Besides having an higher osmotic reflection coefficient (σ), [3] the lactate content can theoretically be an energy source for ischemic brain cells [4]. Totilac® has the potential to increase diuresis indirectly by increasing intravascular volume [5]. From these properties, totilac® with the basic component of hypertonic saline, is considered superior in maintaining intravascular volume compared to mannitol®. Therefore, we want to compare the intradural pressure profile after administration of Totilac® and Mannitol® in patients undergoing hematomal evacuation craniotomy.

Methods

The study was conducted at a tertiary care hospital during April-July 2018. The study was approved by the Medical and Health Research Ethics Committee of FKKMK UGM and Dr. Sardjito Hospital. Informed consents were acquired from all subjects before participating in this study. The patients included for the study aged 18-65 years and who underwent emergency hematomal evacuation craniotomy for indications of intracerebral hematoma (ICH) or subdural hematoma (SDH). The exclusion criteria were unresolved shock, ongoing massive bleeding, allergic to lactate, impaired renal function, hyponatremia [Na+] <130 meq / L, hypernatremia [Na+]> 150 meq / L, history of uncontrolled diabetes mellitus, history of uncontrolled hypertension. The study subjects were allocated into two groups using permuted block techniques randomization. Group M received mannitol®, whereas group T had Totilac®. The allocated group information was given in a sealed envelope when the patient arrived at the surgery room. In operating room, Anaesthesia was induced with 2.5 mg of midazolam, fentanyl 2 mcg/kg, propofol 2 mg/kg, lidocaine 1.5 mg/kg, and rocuronium 0.6-1 mg/kg for tracheal intubation.

Anaesthesia was maintained with sevoflurane 2% with delivery gas of FiO2 50%. The depth of anesthesia was monitored by maintaining bispectral index value between 40-60. Controlled ventilation was set with a tidal volume of 6-8 ml/kg, PEEP 3-5, a minute volume of 80-120 ml/kgBW/ minute and a maximum peak inspiratory pressure of 30 mmHg. Maintenance fluid was given according to the needs of patients with a composition of 0.9% NaCl:RL = 3: 1. Blood lost was replaced with colloids with the same volume. Blood component was given if the bleeding exceeded maximum allowable blood lost. Another crystalloid was given to replace the urine output with 2/3 of the volume of it. Baseplate of invasive monitor were placed at the level of the tragus, following changes in the position of the patient. Invasive monitors were prepared with CVP mode on a scale of 0-30 and being zeroed every time a subject changes position. Intradural pressure measurement was performed by the surgeon through puncture using needle no.23 when the duramater was still intact.

The needle was placed in the subdural space parallel to the duramater then was connected to an invasive monitor device. The intradural pressure, hemodynamic and other parameters are measured when opening the cranium as a baseline, 5th, 10th and 15th minutes after hypertonic solution administered by rezeroing before recording the value. Analyses were done on all subjects who had received treatment according to the protocol. Data were expressed in terms of numbers and percentages, mean and standard deviations. The data between the two groups were analyzed for differences using independent t‑tests or paired t-test for numerical data and Chi square tests for categorical data. Data were analysed using SPSS 24 software computer program.

Results

A total of 27 patients were assessed for eligibility for this study. Randomization was performed on 27 patients. As shown in Figure 1, 3 subjects were excluded from analysis because of unable to follow the study procedure due to laceration of duramater during craniotomy. One-third of subjects are women as shown in Table 1. The average age of the subjects in group M was 50.75 + 13.4 years and in the T group it was 47.75 + 12.07, which was not difference significantly. There was no difference in the ratio of BMI and physical status based on ASA physical status (p= 0.667 and 0.155, consecutively). The distribution of trauma and non-trauma cases was also balanced in both groups. The level of brain relaxation was assessed in this study by measuring intradural pressure. Table 2 shows significant decreases of intradural pressure in the 5th, 10th and 15th minute after hypertonic solution administered in each group compared to baseline when the cranium was opened. Table 3 shows the change from baseline in intradural pressure between groups at 5th, 10th, 15th minute after hypertonic solution administered were similar. The difference in MAP between groups was found to be significant at all periods of measurement, as shown in Table 4. Group M has higher change from baseline of urine production at the end of observation compared to group T, as shown in Table 4.

Table 1: Demographic Data.

Table 2: Mean of intradural pressure compared to baseline.

Figure 1: Study sample.

Table 3: Mean of intradural pressure change from baseline.

Table 4: MAP and urine output.

Discussion

In this study, there was a significant decrease in intradural pressure in each group. It is well known that Mannitol® and hypertonic sodium lactate solutions with its hyperosmolar properties are part of ICP control management. The most significant decrease in group M occurred in the 10th minute after the cranium was opened, whereas the T group experienced the highest difference in the 5th minute after the cranium opened. This shows a different peak onset difference in each solution, although it is stated that Mannitol® peak onset and hypertonic sodium lactate solution are almost correspondent (15-20 minutes) [5]. Properties of hypertonic sodium lactate solutions that draw fluids from interstitial to intravascular be superior in controlling cerebral edem because its reflection coefficient is greater than Mannitol [5]. A study by Hisam, et al. showed hypertonic sodium lactate had a significantly better brain relaxation effect than Mannitol® assessed from a comparison of brain relaxation assessed subjective when an open cranium with BRS in COT [6].

Sokhal, et al. found that there was a significant difference in the decrease of intradural pressure in both groups with tumor removal craniotomy, but brain relaxation assessed by operators with the BRS method in the study did not differ significantly between the two groups. In this study, the difference in intradural pressure was not linearly related to brain relaxation that occurred, because the determinant component of ICT was not only from brain relaxation, where large tumor mass and intravascular volume also played a role in determining intradural pressure [7]. Previous studies conducted by Sharma, et al. the number of samples of 31 subjects who underwent aneurysm repair surgery also showed a meaningless difference in the decrease in intracranial pressure between groups M and T [8] this result is due to the aneurysm surgery itself the incidence of extravasation of fluid is not promising. Wirawijaya, et al. revealed no significant differences in brain relaxation in patients with craniotomy surgery to remove tumors that received 3% NaCl, Mannitol, and hypertonic sodium lactate [9].

In addition, nutritional support in the form of exogenous lactate that can be a source of energy in injured cells also decreases the progression of intersective edema resulting from cell death [2,10]. The study conducted by A Daniel (2014) states that lactate supplementation is an important component in brain metabolism that is experiencing injury, especially in the penumbra region that has the potential to experience cellular death [11]. Hamzah, et al. showed that ATP biomarkers in experimental animal models that experienced ICH experienced a significant increase in the administration of hypertonic sodium lactate solution compared to Mannitol® and NaCl 3%. The study also suggested that the comparison of the area of necrosis in the animal brain was significantly different, whereas in the hypertonic sodium lactate group it was much smaller than in the Mannitol® group, with p = 0,000.10 but they did not mention the correlation between the two findings.

The effect of diuretic Totilac® solution on the results of the study was significantly lower than Mannitol®. Previous research also showed similar results [6-9]. This was due to the Mannitol® properties acting in the loop Henle which resulted in increased urine production. In contrast to hypertonic sodium lactate, the diuretic effect is a result of increased intravascular volume, so that increased urine production is not a direct influence on the organ of urine formation. Based on this, hypertonic sodium lactate is a better choice in patients with intravascular volume disorders, because the diuretic effect of hypertonic sodium lactate will not appear in conditions of hypovolemia or dehydration [5]. The results of the insignificant decrease of intradural pressure in this study can be caused by the duration of the onset of the incident until the intervention was performed. In addition, the possibility of still active bleeding also affects intradural pressure. Even though brain relaxation has been achieved, the addition of volume in the third space can also increase intradural pressure. We could not manage this parameter and analyze it because we could not evaluate hematoma enhancement during surgery.

For the next research, it is necessary to do a comparative test of quantitative assessment methods using invasive monitors with BRS. A comparative study of the size of the needles used also needs to be done, so that it can avoid the possibility of blockages and clinging during the measurement period while not causing premature trauma to the dura mater. The use of invasive monitor equipment in this study is still relatively new even though it has been proven to determine the magnitude of pressure on other body locations. The use of needle number 23 can still allow for blockages and slacking during the measurement period.

Conclusion

Totilac® administration had similar intradural pressure profile effect compared to Mannitol® in hematomal evacuation craniotomy case.

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Extensive Proof-of-Concept Studies in TNF-Alpha Antagonists might be Responsible for A Delay of Patient Access in Pediatric Rheumatology

Introduction

In order to improve the route to market for approved pediatric therapeutics, the current Pediatric Regulation in the EU and the Food and Drug Administration (FDA) Amendments Act (FDAAA) were both adopted in 2007. These include incentives for the pharmaceutical industry to perform pediatric clinical studies, for example granting an extended patent protection time or marketing exclusivity for orphan medicinal products for a limited period. Between 2007 and 2013, the European Medicines Agency (EMA) and its Pediatric Committee assessed more than 600 pediatric investigation plans (PIPs) with an aim to provide data on the efficacy and safety of medicines for diseases of children. After almost a decade of experience of PIPs, it seemed important to evaluate the usability of data derived from clinical trials for new medicinal products in children for marketing authorization. This is particularly important in order to understand the need for, and extent of, clinical studies for new drugs in children in the future. The aim of this study is to evaluate whether proof-of-concept clinical trials need to be carried out at the existing rate and frequency, and whether data to support the use of new drugs in children can be extrapolated from adult trials of equivalent indications with focus on rheumatology. This evaluation should help to outline new guidance for clinical trials for new drugs in children to prevent unnecessary extensive trials of ‘me-too’ drugs.

Strategy

The review compared the effects of immune-modulatory drugs in adults and children, selected using the following criteria:
a) Biologics in the same class to treat arthritis
b) Clinically tested for the same or a similar indication in children and adults
c) Subject to a PIP in children and approved for use in adults. Drugs selected for this review are biologics targeting TNF-α including adalimumab, etanercept, golimumab, and infliximab.

TNF-α Inhibitors Tested in Adults and Children

Etanercept (Enbrel, Pfizer) is a soluble decoy receptor for TNF. It was the first TNF-α inhibitor launched for treatment of RA. The drug was FDA-approved in November 1998, and by the EMA in February 2000. It is approved for the treatment of RA, JIA, psoriatic arthritis, plaque psoriasis and ankylosing spondylitis [1] as the first biologic to treat JIA. Adalimumab (Humira, Abbot [now: AbbVie]) is a monoclonal anti-TNF-α inhibitor. It was the first fully human IgG1 protein to be approved by the FDA in December 2002. It was approved by the EMA in September 2003. Adalimumab is indicated for the treatment of RA, JIA, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, psoriasis and ulcerative colitis [2]. It was approved for JIA in 2008. Golimumab (Simponi, Janssen Biotech) is a human anti-TNFα IgG1κ monoclonal antibody. Golimumab was approved in US and Canada as a treatment for RA, psoriatic arthritis, and spondylitis, and is undergoing regulatory review in the EU [3] for these indications. Golimumab missed the primary endpoint in JIA. Infliximab (Remicade, Janssen Biotech) is a chimeric monoclonal antibody directed against TNF-α which induces apoptosis in TNF-α-receptor + cells. Infliximab is only approved for RA. It failed to meet primary endpoint in JIA and therefore has not been approved by the FDA in children for JIA. A waiver for the PIP was agreed in the EU. Infliximab is used off label in JIA as it has not been approved for this indication.

Search Strategy

The search was focused on RA in adults and on JIA, prescribing information, clinical trials websites and the FDA and EMA websites in order to identify relevant study information [4-16]. Keywords employed for the searches: Adalimumab, etanercept, golimumab, infliximab; juvenile idiopathic arthritis, JIA, juvenile rheumatoid arthritis, JRA, systemic juvenile idiopathic arthritis, SJIA, polyarticular juvenile idiopathic arthritis, PJIA; pediatrics, children, adults; tumor necrosis factor inhibitors, TNF-α, phase III.

Statistical Meta-Analysis

Statistical analysis was performed using a logistic regression with random effects. The primary outcomes are the ACR50 and ACR70. The dependent variable is the number of patients who reach ACR50 or ACR70 based on the total number of patients treated. Independent variables are treatment, age group (children vs. adults) and time. Treatment is a categorical variable, which compares several treatment regimens with placebo. As not every study has a placebo control arm, we therefore performed an implicit comparison with placebo. The variance of the random effects takes the variability between studies into account. Moreover, as several time points within a study are considered, this model takes also within study correlation into account. The comparison aimed to reveal different treatment responses in children compared to adults. This comparison is quantified using the odds ratio with a 95% confidence interval. Additionally, the response probability adjusted for treatment and time is given with a 95% confidence interval for each group. Calculations were performed with prpc glimmix, SAS 9.4.

Results

A comparative analysis using clinical and pharmacokinetic data was performed, based on data obtained from pivotal studies of biologics for the treatment of inflammation in children vs. adults and evaluated in terms of efficacy, safety and dose used. In total, one or two pivotal pediatric trials, and four to seven pivotal studies in adults for all biologics were identified. All drugs were given as either monotherapy or in combination with methotrexate, and either placebo-controlled or without control. The following section summarizes results (Tables 1-6) obtained from meta-analyses.

Table 1a: Comparison of clinical trials with etanercept in children and adults.

Table 1b: Pharmacology data of clinical trials with etanercept in children and adults.

Abbreviations:
PD: Pharmacodynamics
PK: Pharmacokinetics
ka: First-order absorption rate constant
C_{ss, trough}: steady-state trough concentration
C_max: Maximum serum concentration
C_min: Minimum serum concentration
T_max: Time to reach the maximum concentration
V_ss: Distribution volume
V_c: Volume of distribution in the central compartment
V_p: Volume of distribution in the peripheral compartment
C_l: Clearance
Q: Intercompartment clearance

Table 2a: Comparison of clinical trials with adalimumab in children and adults.

Table 2b: Pharmacology data of clinical trials with adalimumab in children and adults.

Table 3a: Comparison of clinical trials with infliximab in children and adults.

Table 3b: Pharmacology data of clinical trials with infliximab in children and adults.

Table 4: Meta-Analysis: Results on ACR50 and ACR70 for etanercept showed a treatment effect for etanercept.

Table 5: Meta-analysis: Results on ACR50 and ACR70 for Adalimumab. Comparative data for adalimumab studies in children and adults confirmed a treatment effect in both groups.

However, there is no statistically significant treatment difference effect in the between-age or study-duration group for the endpoints ACR 50 and ACR 70.

Table 6: Meta-Analysis: Results on ACR50 and ACR70 for infliximab. Meta analysis of study data on infliximab shows no statistically significant treatment effect between adults and children.

We do not present forest plots for infliximab due to numerically instable results.

Etanercept

A single pediatric clinical trial (JIA-I [17]) in 2000 was identified from the drug prescribing information (Table 1a). This trial involved a total of 120 patients; 51 were part of a double-blind, placebo-controlled study with a nearly 1:1 ratio (26:25), and 69 participated in an open-label trial with etanercept only. A total of four studies in RA in adults, two in 1999 (Study I [18] and II [19]), one in 2000 (Study III [20, 21]) and one in 2004 (Study IV [22, 23]) were identified. Two compared etanercept with placebo, and two compared etanercept with methotrexate.

Dosage and Study Duration

Children were dosed for three to four months with 0.4 mg/ kg bw etanercept, and a maximum of 25 mg per dose. Across all studies, adults received 10 or 25 mg etanercept over a period of six or twelve months. Only two trials [17, 24] included a placebo in the control arm and etanercept only in the study drug arm. All other trials in adults were performed in combination with methotrexate in experimental and placebo groups (Table 1a).

ACR Response

Assessment of the ACR study data differed between children and adults. The pediatric studies used the ACR30, ACR50 and ACR70 criteria and the adult studies the ACR20, ACR50 and ACR70 criteria. Thus, only the data for ACR50 and ACR70 could be considered for direct comparison (Table 1a and Figure 1). In addition, the selected time schedule for ACR assessment differed greatly between studies. While ACR50 and ACR70 were evaluated in week 12 or 16 in children, these were evaluated in week 4, 24 or week 48 in adults. Only Study II and Study IV showed an assessment in week 12. The respective numbers had to be estimated from figures in the publication. In the JIA study of Lovell et al., 64% of the 69 patients met the definition of 50% improvement, and 36% the definition of 70% improvement at the end of the study [17]. There was a similar rate in the Moreland et al., study (59% of the 25 mg group achieved an ACR20 response and 40% achieved an ACR50 response) at 24 weeks [24].

The response rate achieved with etanercept treatment in combination with methotrexate varied between 39-59% for ACR50 at 25 mg and 15-36% for ACR70 at 24 weeks in all other three studies in adults. Meta-analysis showed a treatment effect for etanercept in both, adults and children. However, no effect of age or study duration on the treatment effect could be measured (Table 4 and Figure 1). Thus, the results obtained on drug efficacy and dose showed no difference in adults and children.

Figure 1: Forest plot results on ACR50 (A) and ACR70 (B) ETANERCEPT as graphical representation of the meta-analysis here includes five studies [17-20].
The first column shows names of the covariates in the model. Odds ratios for dose levels are reported with placebo as the reference. Results are shown together with 95% confidence interval. The black dot on each line shows you the odds ratio for each variable.

Meta-Analysis Results of ACR50 AND ACR70

Results of mixed-effects logistic regression for adults and children concerning treatment effects, age group (adults vs children) and study duration (time in weeks) can be viewed in the following tables. numDF, degrees of freedom of term; denDF, degrees of freedom of error term; F, variance ratio; P, error probability; critical value of significance: p<0.05.

Adverse Events

Most frequent adverse events (AEs) in both children and adults were injection site reaction, upper respiratory tract infection, headache, rhinitis, nausea and rash. The drug demonstrated a favorable risk-benefit profile in children and adults. No lifethreatening events were observed (Table 1a).

Pharmacokinetics

The population pharmacokinetic analysis by Yim et al. confirmed that 0.8 mg/kg once weekly and 0.4 mg/kg twice-weekly subcutaneous regimens of etanercept had equivalent clinical outcomes. This served as a basis for the recent FDA approval of the 0.8 mg/kg once-weekly regimen in pediatric patients with JRA [25] (Table 1b).

Adalimumab

Two pediatric clinical trials, PJIA-I [26] and PJIA-II [27], were identified in the prescribing information. These were carried out in 2008 and 2014 and involved a total of 336 patients; 133 as part of a double-blind, placebo-controlled study (75 received methotrexate as supplemental therapy, 58 did not) and 203 in an open-label trial with adalimumab with or without methotrexate (112 and 91, respectively) (Table 2a). In comparison, five pivotal studies in adults, two in 2003 (RA-I [28] and RA-IV [29]), two in 2004 (RA-II [30] and RA-III [31]) and one in 2006 (RA-V [32]) were identified. Two compared adalimumab to placebo, and two were placebocontrolled plus methotrexate. One study compared adalimumab to methotrexate only, as well as to adalimumab plus methotrexate.

Dosage and Study Duration

The studies in children were carried out over 12 to 30 months with 24 mg/m² adalimumab, and a maximum of 20 or 40 mg per dose. Adults received 20, 40 or 80 mg over a period of six, six and a half or 13-24 months. The drug was given subcutaneously in all cases. The PI allows 10, 20 or 40 mg for children, depending on the body weight, and 40 mg is the approved dosage for adults as described in PI (Table 2a).

ACR response

Assessment of ACRs included were ACR30, ACR50, ACR70 and ACR90 for children, and ACR20, ACR50 and ACR70 for adults. Children were evaluated in week 12, 16, 24, 48, 60 and/or 96, and adults in week 24, 26, 52 and/or week 104. Thus, only ACR50 and ACR70 at 24 weeks are comparable (Table 2a and Figure 2). PJIA-II and RA-I, RA-III and RA-IV assessed ACR50 and ACR70 in week 24. However, these studies are not well comparable as their design differs considerably. PJIA-II was a placebo-controlled study, while RA-II and RA-III tested placebo plus methotrexate. RA-IV was also placebo-controlled, but allowed DMARDs during the study, whereas PJIA-II did not. Only studies with adalimumab in combination with methotrexate at week 24 were eligible for ACR50 and ACR70 comparative analyses. In the pediatric study PJIA-II, 83% of patients achieved ACR50, and in the adult RA-I study, 22% reached ACR50 at week 24 with 20 mg maximum dose treatment. In the PJIA-I study, ACR50 was achieved in 64% of the children at the 40 mg maximum dose compared with 37% in the RA-I study, 86% in the RA-III study and 59% in the RA-V study, respectively. 73% of children achieved ACR70 in the PJIA-II study, whereas only 7% and 9% of adult patients using 20 mg at 24 weeks were comparable as demonstrated in the RA-I and RA-II studies, respectively. At a 40 mg dose of adalimumab the response varied between 46% and 71% at weeks 16-48 in the PJIA-I study compared with 37%, 23%, 86% and 59% with the combination of adalimumab and methotrexate in adults in RA-I, RA-II, RA-III and RA-V studies, respectively.

Figure 1: Forest plot results on ACR50 (A) and ACR70 (B) ADALIMUMAB, includes seven studies in the meta-analysis [25-31]. The first column shows names of the covariates in the model.
Odds ratios for dose levels are reported with placebo as the reference. Results are shown together with 95% confidence interval. Odds ratios for dose levels are reported with placebo as the reference. Results are shown together with 95% confidence interval.

Meta analysis of ACR50/70 revealed that comparative data for adalimumab studies in children and adults confirmed a treatment effect in both groups. However, there is no statistically significant treatment difference effect in the study duration for the endpoints ACR 50 and ACR 70 (Table 5 and Figure 2). Similar to etanercept, results obtained on adalimulab on efficacy and dose showed no difference in adult and children.

Adverse Events

The most common event was injection site reactions. The most common AEs leading to discontinuation of adalimumab treatment were clinical flare reaction, rash and pneumonia. The rate of serious infections was 4.6 per 100 patients (Table 2a).

Pharmacokinetics

A higher apparent clearance of adalimumab in the presence of Neutralizing anti-adalimumab antibody (AAA) and lower clearance with increasing age in patients aged 40 to >75 years was observed in population pharmacokinetic analyses in patients with RA. No gender-related pharmacokinetic differences were observed after correction for a patient’s body weight. Healthy volunteers and patients with rheumatoid arthritis displayed similar adalimumab pharmacokinetics. C_max, T_max, bioavailability and elimination values are only available for adults as described in the PI (Table 2b).

Golimumab

Golimumab has been confirmed to be an effective treatment for patients with RA in phase III clinical trials as evaluated by traditional measures of disease activity. The efficacy and safety profile of golimumab appears to be similar to other anti-TNF agents. However, golimumab has the potential advantage of once monthly subcutaneous administration and the possibility of both subcutaneous and intravenous administration. A study of CNTO 148 (golimumab) in children with juvenile idiopathic arthritis (GO-KIDS trial) to evaluate the efficacy and safety of golimumab is ongoing. This study enrolls patients who have active JIA and at least five joints with active arthritis that have poor response to methotrexate. The GO-KIDS trial consists of three parts and aims to assess the efficacy and safety of golimumab in pediatric patients aged 2 to <18 years with active JIA with a polyarticular course (at least five joints) despite therapy with methotrexate (10 to 30 mg/m²/week) for at least 6 months [33]. The trial involved 173 patients (87.9% white, 75.7% female; median age 12 years, age 2 to 17 years) with moderately active disease. Nineteen (11%) patients discontinued in part 1 of the trial due to lack of efficacy (n=14), adverse effects (n=4), and withdrawal of consent (n=1).

Dosage and Study Duration

The drug (the usual adult dose for RA of an initial dose of 50 mg subcutaneously once a month or 2 mg per kg iv infusion over 30 minutes at weeks 0 and 4, then every 8 weeks thereafter. It should be given in combination with methotrexate. Corticosteroids, nonbiologic DMARDs, analgesics and/or NSAIDs may be continued during treatment with this drug [33].

ACR Response

During the first phase of the trial, 151 of the remaining 173 (87.3%) patients achieved a 30% improvement from baseline in 3 of the 6 assessed criteria (active joint count, limitation of motion joint count, physician global assessment, patient/parent global assessment, Childhood Health Assessment Questionnaire, and acute-phase reactant level) without worsening of the remaining criteria, and 36.1% of patients displayed inactive disease status. The investigators randomized 154 patients to part 2 of the trial. The primary endpoint was not met; at week 48 the flare rates were comparable in those receiving placebo and golimumab (52.6% vs. 59.0%; P=0.41). The major secondary endpoints were also comparable between the placebo and treatment groups. The rates of inactive disease/clinical remission in patients receiving placebo + methotrexate or golimumab + methotrexate, for example, were 27.6%/11.8% and 39.7%/12.8%, respectively. Children with JIA in at least five joints displayed a rapid response to golimumab during the open-label, part 1 portion of the trial. During this portion of the trial, 36% of patients displayed inactive disease following the golimumab injection schedule. The sustained improvement in JIR was maintained in the placebo and treatment groups compared with baseline.

Adverse Events

Through week 48, adverse events, serious adverse events, and serious infections were reported in 87.9%, 13.3%, and 2.9% of all randomized patients, respectively. The most frequent serious adverse event was exacerbation of JIR. Death, active tuberculosis, or malignancy did not occur. Golimumab missed the primary endpoint in JIA. The reasons for the similarity in flare rates between the arms is unclear, and further study is needed if the regimen ultimately proves worthy of clinical use [33]. No Meta analysis for Golimumab on adult and pediatric data could be performed, as the data from the study in JIA is not publically available.

Infliximab

Study Description: A multicenter randomized doubleblind placebo-controlled trial of infliximab in 117 children with polyarticular JIA did not find a statistically significant effect of infliximab 3 mg/kg intravenous infusion therapy plus methotrexate on ACR-Pedi responses as compared with placebo at 14 weeks [34]. The open-label extension (OLE, 52–204 weeks) of the study involved 78 patients. However, 34% discontinued infliximab prematurely, mostly by withdrawing consent due to lack of efficacy [35]. Overall, 30% of the children continued the study up to week 204 (Table 3a). The two pivotal studies in RA in adults were performed in 1999 (Study RA I, ATTRACT, [36]) and 2004 (Study RA II, ASPIRE, [37]). Both trials were placebo-controlled and allowed methotrexate. They worked with 3, 6 or 10 mg/kg i.v. application of infliximab.

ACR Response: After 14 weeks, following crossover from placebo to infliximab 6 mg/kg, ACR50 and ACR70 responses at week 52 were achieved in 70% and 52% of the children. However, there was no statistically significant difference between the placebo group and the treatment group. Meta analysis supports that study data on infliximab shows no statistically significant treatment effect in children compared to adults. Also, the impact of age and study duration did not play a significant role (Table 6).

Adverse Events: The pediatric trial demonstrated that infliximab was safe, though the 3 mg/kg group had a less favorable safety profile, with a higher incidence of injection-site reactions and more serious infections. As the efficacy of infliximab in a pivotal study has not revealed a superior effect compared with placebo [34], the FDA did not approve infliximab for JIA, although it is still used in children. It is recommended as backup drug to treat JIA in the guidelines for JIA treatment [38] at the usual pediatric dose for JIA: 10 years or older: 3 mg/kg via iv infusion at weeks 0, 2, and 6, followed by infusions every 8 weeks [39]. Moreover, infliximab is approved for the therapy of refractory Crohn’s disease in children over 6 years (Table 3a).

Pharmacokinetics: The childrens’ trial observed formation of antibodies to infliximab, antinuclear antibody or anti-dsDNA antibodies in greater proportion in the 3 mg/kg group [34,35]. This confirmed results from one adult study [37], although other studies could not detect anti-chimeric antibodies, or only below detection limit [36,40,41] (Table 3b).

Discussion

The introduction of PIPs aimed to initiate a formal approval process for new medicinal products to avoid unauthorized use in children. In this review, the JIA indication in children, with RA as a counterpart in adults, and TNF-α blocking agents were selected as model diseases and drugs for comparison and evaluation of the data obtained from clinical studies in the new immunomodulatory drug space. TNF blocking agents are currently the only drug group with a number of compounds authorized in children and adults to treat JIA and in adults in RA, thus providing most experience in this drug class. Studies with etanercept in children showed the utility of TNF-α blocking agents in JIA for the first time. The PI for etanercept allows a dose of 0.8 mg/kg for children <63 kg and up to 50 mg for children ≥63 kg. 50 mg is also the approved dose for adults. The detailed PK parameters to support the dose selection in either population could not be identified and were addressed in only a few studies. A direct comparison of ACR response between children and adults was only partially possible as the time points for assessments differed considerably between both groups. Thus, it is unclear how the dose for children was selected. However, as the dose is set at a similar level for adults and children, these studies supported the idea that the dose for children could potentially have been extrapolated from the adult studies. Furthermore, no new safety issues or efficacy data were identified in proof-of-concept trials with children. Thus, the pediatric study results did not lead to any significant differences in dosage or safety profile compared with those in adults but confirmed the efficacy in JIA. Meta-analysis showed no difference on the treatment effect for etanercept in adults and children.

Similar findings were true for the comparison of dosage between adult and children for adalimumab. The PI shows a dose of 10, 20 or 40 mg for children, depending on the body weight; 40 mg is the approved dosage for adults. Thus, the pediatric study results did not lead to any significant differences in dosage that could not have been predicted from the adult studies. ACR response data was also only partially directly comparable due to difference in assessment values and schedules. In addition, no new safety and efficacy data was obtained by these studies. However, no statistically significant treatment difference effect in the beween-age or study-duration group for the endpoints ACR 50 and ACR 70 (Table 5) could be observed. Golimumab was used in trials described above in JIA or RA. So far, no new safety and efficacy aspects have been identified in the JIA study, but the primary endpoint was not met in children. Adverse effects with anti-TNF-α blockers are generally mild e.g. local skin reactions/infusion reactions, and are mostly transient. Minor infections e.g. upper respiratory tract infections are common. The risk of developing tuberculosis seems higher with the monoclonal antibody’s infliximab and adalimumab, compared with etanercept [42,43]. Autoimmune phenomena such as drug-induced lupus, demyelinating disease, uveitis, psoriasis and inflammatory bowel disease were rather rare.

The risk of malignancies was reported to be increased in children. The post-marketing surveillance data on anti- TNF-α agents collected by the FDA reported 48 malignancies developing in children, of which 20 occurred in children with rheumatic conditions [44]. However, 88% of these children were also receiving other immunosuppressive drugs, including corticosteroids, azathioprine and methotrexate. Approximately 50% of the malignancies reported were lymphomas, leukemia and melanoma. The FDA and EMA added a boxed warning with regard to the possible increased risk of malignancy, especially lymphomas, in children treated with anti-TNF-α agents. Despite this, a recent summary of worldwide pediatric malignancies in children treated with etanercept did not find an overall increased risk. However, the authors acknowledged that it is difficult to assess the actual risk due to the rarity of malignant events, the underlying higher risk of lymphomas and leukemias in children with JIA and the confounding use of other immunosuppressants [45].

The time before the marketing approval of drugs is particularly important, as the overall aim of drug development in clinical trials should focus on patient benefit to make sure that access of drugs to patients is as simple and fast as possible. However, the studies performed to support marketing approvals in children does not seem to support this overall aim, as shown in the model based on TNF-α blocking agents. Therefore, prolonging the drug approvals process does not benefit children, and promotes off-label pediatric used as these drugs are already marketed for use in adults. All four TNF-α blocking agents discussed here are approved in adults for RA, and all have been tested in children for JIA. The results broadly confirm the findings in adult studies other than infliximab, which has not been approved at a dose of 3 mg/kg for JIA (although it is continued to be used in children). Based on the similarity of dose administered in adults and children, the assumption is that the key parameters are likely to be similar across age groups for a range of biologics. Therefore, the question arises – is it important to carry out confirmatory studies in children? Are these studies really necessary or can the data for biologics be extrapolated if the expression of the respective target is the same in adults and children? The data reviewed suggests that the results obtained in adult RA studies are likely to be useful in predicting the dose, efficacy and safety for children with JIA. It therefore does not support further performance of extensive proof-of-concept studies in children.

Conclusions

The overall aim of drug development in clinical trials should focus on patient benefit, making sure that patient access to drugs is as simple and fast as possible. However, the studies performed to support marketing approvals in children do not seem to support this overall aim, and actually prolong the approvals process. They also promote off-label paediatric use as the drugs are already marketed for use in adults. All four of the TNF-α blocking agents discussed here are approved in adults for RA, and all have been tested in children in JIA. Based on the similarity of dose administered in adults and children for the two biologics approved in children, the assumption is that the key parameters are likely to be similar across age groups for a range of biologics. Therefore, the question arises – is it important to carry out confirmatory studies in children? Are large pivotal studies really necessary or can the data for biologics be extrapolated if the expression of the respective target is the same in adults and children? Our review of the data suggests that the results obtained in adult RA studies are likely to be useful in predicting the dose, efficacy and safety for children with JIA. It therefore does not support further performance of extensive proof-of-concept studies in children in specific targeted indications and based on mode of actions of a medicinal product.

However, infliximab and golimumab missed the primary endpoint for efficacy in JIA. The failure of these two drugs suggests that the differences in PK/PD parameters might play an important role in children’s immune responses to biologic drugs, especially those expressed as chimeric or pegylated proteins. This differing immune response may have a bigger role in children than in adults, with higher levels of immunogenicity and neutralizing antibodies reducing the efficacy of the drugs. It is interesting to note that there were no studies identified in the public domain that looked at these drugs in terms of target expression in lymphocytes, or PK/ PD studies in children. The data reviewed suggests that the results obtained in adult RA studies are likely to be useful in predicting the dose, efficacy and safety for children with JIA for certain products, however, the results from the two unapproved drugs might indicate that expression studies of the target and PK/PD studies are important to translate adult studies successfully in children. The need for further extensive efficacy and safety studies in children is therefore challenged. PK/PD studies plus modelling and simulation based on adult dose may be needed in children to help in finding optimal dose for children and to confirm a PD effect. In certain situations, for example in drugs of the same class, an extrapolation approach could avoid unnecessary further studies in the pediatric population.

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Prevalence and Socio-Demographic Correlates of Substance Use Among Patients Attending the drug Unit of the University of Port Harcourt Teaching Hospital

Introduction

According to the World Health Organization [1], substance use refers to the use of any psychoactive substances or drugs, which include licit and illicit drugs, other than which are medically indicated. The United Nations Organizations on Drug Council [2] stated that substance use is a major public health problem all over the world. In 2011, it was estimated that 167 to 315 million people aged 15 to 64 years globally had used an illicit substance in the preceding year [3]. The estimated global burden of alcohol and illicit drugs use is 5.4% while tobacco is 3.7% [4]. Psychoactive substance use poses a threat to the health, social and economic fabric of families, communities and nations [5]. Drug dependence is a growing public health problem and consequences of drug dependence cost the community heavily [6]. This habit not only affects health, education and occupational career, but it also incurs a huge financial and social burden on the society.
A national survey of substance use conducted among 10,609 Nigerians aged 15-64 years in the six geopolitical zones of the country recorded a lifetime prevalence of 39% for alcohol, 6.6% for cannabis and 12.2% for cigarettes [7]. In Nigeria, the most common types of used substances include stimulants and amphetamines such as caffeine, tobacco, nicotine, ephedrine; hallucinogens such as marijuana and narcotics such as heroine and codeine. Others include alcohol and sedatives [8]. These substances are largely used due to the belief that they relieve stress and anxiety, and some of them induce sleep, ease tension, cause relaxation or help users to forget their problems. The consequences of their abuse could result in physical dependence [8].
The United Nations Organizations on Drug Council [2] submitted that prevalence of any drug use in Nigeria is estimated at 14.4 per cent or 14.3 million people aged between 15 and 64 years; a situation which implies that the extent of drug use in Nigeria is comparatively high when compared with the 2016 global annual prevalence of any drug use of 5.6 per cent among the adult population. Accordingly, one in seven persons aged 15-64 years in Nigeria had used a drug (other than tobacco and alcohol) in the past year [2]. The social consequences of drug use are also evident in Nigeria. Some of which include disruption in family lives, loss in productivity and legal problems as a consequence of drug use in their communities. Also, some individuals in the general population had experienced negative consequences due to other peoples’ drug use in their families, workplace and communities [5].
Despite the highly reported consequences of substance use, in different parts of the world including Nigeria, a good number of individuals’ reports being addicted to specific drugs and presents at healthcare facilities for medical assistance [4]. In fact, in University of Port Harcourt Teaching Hospital, Rivers State Nigeria, some people who have willingly presented themselves for clinical counseling are currently on drug rehabilitation. Nonetheless, there is dearth of evidence on the prevalence of substance use disorders in Nigerian communities, a situation which justifies the need for this study on the prevalence and socio-demographic correlates of substance use disorders among individuals on drug rehabilitation in University of Port Harcourt Teaching Hospital.

Methodology (Materials and Method)

Study Design

Descriptive retrospective design was used in this study.

Study Subjects

The target population consisted of all adult males and females on drug rehabilitation in University of Port Harcourt Teaching. Only subjects who been on drug rehabilitation for a minimum period of six months and were willing to participate were included in the study. The study was conducted from January 2018 to February 2020. A sample size of 104 subjects was selected using the purposive sampling technique. Sample size determination was done using sample size determination formula by Cochran as shown below:
N= Z2P (1-P)/d2
Where N= Sample size
P= Prevalence of drug use = (6.6%) = [0.066] [7].
d= Sampling error that can be tolerated (0.05)
Z= Level of Significance
N= 1.962 0.066(1-0.066)/0.0025
= 0.2368115904 (0.856)/0.0025
=94.725
=94.7
10% non-respondent= 94.7 of 10% =9.47
N=94.7+9.47=104.17

Data Collection

The Nigerian Epidemiological Network on Drug use for drug patients who attended UPTH treatment facility from January 2018 to February 2020 were retrieved and used in the study following ethical clearance.

Data Analysis

Analysis of data was done using the Statistical Package for Social Sciences (SPSS) software version 20.

Results

Table 1 shows that majority of the respondents were males, 94.2%, had tertiary education, 75.0% and were single, 89.4%. Table 2 shows that sex of individuals influences their substance use behaviour, as majority of the respondents that uses substances/ drugs were males (P<0.05).
Table 3 shows that marital status of individuals influences their substance use behaviour, as majority of the respondents that uses substances/drugs were singles (P<0.05).
Table 4 shows that educational status of individuals influence their substance use behaviour, as majority of the respondents that uses substances/drugs had tertiary education (P<0.05).
Table 5 shows the prevalence of substance use disorders among individuals on drug rehabilitation in University of Port Harcourt Teaching Hospital. Out of the 104 respondents, 42.3% use cannabis, 13.5% consume alcohol, 11.5% use tobacco, 9.62% use opioids, 7.69% use Tramadol, 4.81% use cocaine, 3.85% use codeine, 2.88% use Pentazocine,1.98% use cracked cocaine, while 0.96% use sedative hypnotics and hallucinogens.

Table 1: Socio-Demographic Characteristics of the Subjects (n=104).

Table 2: Sex of Subjects and Use of Substances among Individuals on Drug Rehabilitation in University of Port Harcourt Teaching Hospital (n=104).

Table 3: Marital Status of Subjects and Use of Substances among Individuals on Drug Rehabilitation in University of Port Harcourt Teaching Hospital (n=104).

Table 4: Educational Status of Subjects and Use of Substances among Individuals on Drug Rehabilitation in University of Port Harcourt Teaching Hospital (n=104).

Table 5: Prevalence of Substance Use Disorders among Individuals on drug Rehabilitation in University of Port Harcourt Teaching Hospital (N=104).

Discussion

The study findings revealed an increasing prevalence of substance use. Out of the 104 respondents, 42.3% used cannabis, 13.5% consumed alcohol, 11.5% used tobacco, 9.62% used opioids, 7.69% used Tramadol, 4.81% used cocaine, 3.85% used codeine, 2.88% used Pentazocine, 1.98% used cracked cocaine, while 0.96% used sedative hypnotics and hallucinogens. These results agree with the findings of Oshodin [8], Adamson et al. [7], Morello et al. [9] and Jegede et al. [10]. Generally, cannabis, alcohol and tobacco appear cheaper and more readily available to the average Nigerian drug user than the other substances, a situation that explains why they are more prevalent. This may not be the case in other sub- Saharan African countries and the rest of the world.
It was also discovered that sex, marital and educational status of individuals influence their substance use behaviour, as majority of the subjects were males 98 (94.2%), singles 93 (89.4%), and had tertiary education 73 (75.0%). These results are in consonance with the assertion of Okpataku [11]. The married ones were less likely to use drugs etc. A possible reason for this socio-demographic correlate could be that males are usually more adventurous than the female folks! Although this assertion may be considered true to a large extent, it is actually not absolute as Adolfo et al. [12] in their study reported otherwise. They found out that drug use was more prevalent among women. The possible reason for this difference could be that of setting and culture. Whereas this present study was conducted in Port Harcourt, South-South Nigeria, Adolfo et al. [12] conducted theirs in Spain, Europe. On the other hand, drug use being more prevalent among singles could be due to the fact that they generally have more freedom and less restriction in the adventures of life more than the married, divorced and widowed etc. Also, the fact that most of the drug users had tertiary education explains the fact that growth, peer pressure or exposure to a higher degree of thinking/learning could actually predispose one to certain habits such as drug abuse etc. This may actually not be absolute globally as some other studies have identified substantial drug use among high school students, dropouts and street hustlers [2].

Conclusion

In conclusion, there is a high prevalence of drug use in the society; cannabis and alcohol are the most substances of use/ misuse. There is a significant relationship between socialdemographic characteristics of individuals and their potential to use substances as sex, marital and educational status of individuals influences the extent to which they use drugs and related items. A substantial proportion of the subjects that use substances/drugs were males’ singles and had tertiary education.

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Pulsatile Vs Non-Pulsatile Intracranial Blood Flow: Animal Model of Blood Flow Restoration in Brain Tamponade

Introduction

In neurosurgical practice brain tamponade represents the ultimate limit for treatment. It is defined as a progressive intracranial pressure (ICP) increase up to values close to arterial blood pressure producing a reverberating flow pattern in the cerebral arteries with no net flow [1-3]. Nowadays, patients reaching such a condition are labeled as untreatable due to the lack of effective treatment. Decompressive craniectomy might in peculiar conditions, such as in very little children, overcome the aforementioned limit thanks to the incredible capability of a still growing brain to recover from extensive injuries but that is not the case in adult or elder patient. Throughout the literature there are several papers addressing the matter but still no clear advance was proposed. In fact, many of the papers are still at the animal levels also due to the actual difficulties in creating an ethically approvable human model. This aspect is linked to the fact the patients near brain tamponade conditions have to be rapidly treated whenever possible being hard to create a double group-controlled study. Furthermore, it is not so easy to define the actual limit in which brain tamponade become irreversible. The authors themselves, in previous papers, highlighted how even in prolonged brain tamponade conditions, metabolism inside the neuronal cells still continue even after prolonged ischemia time [4,5].
The idea of overcoming the blockage in cerebral blood flow modifying its modality derived from a previous report of residual arterial and venous pulsation even in tamponade brains [1]. In order to do so, we hereby present an animal model in which changing the modalities of brain blood supply from pulsatile to continuous it might be possible to maintain cerebral perfusion even in conditions of highly elevated intracranial pressure.

Material and Methods

Five male sheeps (30-35 Kg) were sedated using intramuscular Atropine (0,5-1 mg) and Ketamine (10 mg/Kg). Each animal was placed supine on the operating table, intubated and anesthetized with Halothane (0,8-1%) and Pancuronium Bromide (0,5 mg/h intravenously administrated). These sheeps were evaluated for the whole duration of the procedure using:
a) Electrocardiogram
b) Systemic arterial bold pressure (measured through a line in the obturator artery) (SAP)
c) Carotid arterial blood pressure (CAP)
d) Middle cerebral artery blood flow measured using doppler ultrasound (placed to an ad-hoc craniotomic window)
e) ICP measured using an intra-parenchymal sensor (ICP Express Codman) placed using a parietal burr hole.
Once sedated each animal was prepared in the following way. Two inguinal incisions were made to isolate the femoral arteries that were exposed trough blunt dissection and cannulated. Similarly, through a neck midline incision the carotid arteries were found and prepared. In the meanwhile, a hydraulic circuit was created to ensure extracorporeal circulation. Such a circuit was composed by sylastic tubes, a peristaltic pump, a three-liter reservoir placed at 3-meter height from the ground and lastly from a mechanism granting pulsatility in order to mimic cardiac output. This mechanism is composed by an electric engine connected to a piston compressing the elastic portion of the tube exiting the reservoir. By doing so modifying the compression speed and the distance of the piston from the tube is possible to modify pulsation frequency and amplitude. The described circuit has three terminals, one for each femoral artery and the remaining one for the left carotid artery (the terminal ends with a Y connector). The whole circuit is replenished before starting with saline solution added with 25000 unit of heparin in order to avoid clotting inside it. To avoid animal hypovolemic state, the reservoir is filled with a liter of saline solution before starting.
To create a condition of intracranial hypertension saline solution will be sent into the subdural space using a 20 Gauge needle inserted through a small, angulated burr hole which is also sealed with acrylic resin in order not to let the fluid escape around the needle. Infusion flow speed was regulated according to the parameter measure by the intra-parenchymal sensor. After clamping of the brachiocephalic trunk, the circuit can be activated. Whenever doing so, the blood taken from the femoral arteries is aspirated and carried into the reservoir from where, thanks to gravity, it flows into the left carotid artery. Thanks to the Y connector the blood in the left carotid artery can flow both toward the brain and towards the base of the brachiocephalic trunk granting blood supply to the whole brachiocephalic territory. The pulsation machine intervenes in this setting in order to transform a pulsatile flow into a continuous one without creating relevant changes in medium arterial pressure. Once completed animal preparation, three different experimental conditions were evaluated in order to measure the cerebral perfusion pressure (CPP=CAP-ICP) value at which cerebral blood flow (CBF) blockage appear in each of them.
The aforementioned conditions are:
a) Normal condition
b) Continuous laminar flow created using EC
c) Combined model. In this model the brain is submitted to pulsatile circulation created with the aforementioned pulsatile machine in EC switching in a second moment to continuous flow in order to evaluate differential response to flow modifications.
At the end of the experiment the animals were sacrificed being still under general anesthesia using an intravenous administration of 10 mEq potassium chloride. The whole experiment was carried on in accordance with the EU Directive 2010/63/EU for animal experiments.

Results

A. Model 1: mean CAP value is 110 mmHg (ranging from 100 to 130 mmHg) while mean ICP value is 15 mmHg (ranging from 12 to 18 mmHg) and mean MCA speed is about 10 cm/sec. Starting saline subdural infusion, ICP value start increasing while CBF progressively decrease. This process continues until ICP reaches 70 mmHg with consequential CBF blockage. Even though no blood flow can be measured at this moment, CPP is still present and greater than 40 mmHg. At the same moment, a different behavior of CBF velocity can be observed. In fact, even if CPP is still present flow velocity reaches zero concomitantly wit tamponade. Both observations tend to recover baseline condition once stopped infusion.
B. Model 2: the initial increase in ICP and decrease in CBF speed is the same of model 1 but, unlike with pulsatile flow, CBF arrest is reached with higher ICP value. In fact, ICP values similar to CAP are needed in this case with a residual CPP of 15-16 mmHg to observe cerebral tamponade. The observation concerning CBF speed overlaps what seen in model 1. As in model 1 this condition is reversible after infusion arrest.
C. Model 3: the combined model shows firstly how normal cardiac circulation can be achieved using pulsatile EC with similar results on CPP and CBF speed. On the other hand, it shows how, switching from pulsatile to continuous flow in absence of relevant changes in CPP, a gradual and stable intracranial circulation can be obtained as documented by doppler ultrasound. The aforementioned results are summarized in Figure 1.

Figure 1: Blood flow velocity in different circulations.

Discussion

Throughout the literature, there are very few reports regarding flow typology in intracranial circulation. Such papers are mostly related to intracranial changes after ischemic heart failure. Reviewing the literature trying to select the most fitting papers, only two authors slightly address the problem. the first one only mentions non pulsatile blood flow as something unclear as well as a potential sign for proximal arterial occlusion [6], while the other one, suggests the importance of pulsatile flow during reperfusion without addressing at all flow modifications during tamponade [7]. To overcome such a lack of evidence on the matter, the authors devised the presented experiment. The aim was to analyze whether changing cerebral blood flow from pulsatile to non-pulsatile was possible to overcome brain tamponade. Such an experiment was founded on the idea that the very “normal” blood pulsation coupled with Starling resistor functioning is at the base of cerebral tamponade. Physical laws states that flow is driven by the presence of a pressure gradient between two compartments connected by a channel. Thus, as long there is a gradient there will be flow, no matter how small the caliber of the channel will become. Flow stops then after the closure of the channel or after disappearance of the gradient. The application of such physical law to the intracranial system were evaluated for the first time by Chopp et al. who created a model simulating the intracranial space and its modifications during infusion tests [8].
In order to describe what happen in normal conditions, it is important to remember that intracranial circulation is pulsatile and that pressure wave propagation speed inside the vascular system is slower than the liquoral one due to the resistance in capillaries and veins. Thus, whenever there is an increase in intracranial pressure, the aforementioned difference in transient propagation speed lead to an early closure of the veins and of the Starling resistor before intravasal pressure could match outer one maintaining positive flow. When the vein walls contact each other the possibility to re-open is lost leading to tamponade. On the other hand, if the circulation were non-pulsatile a net flow would be always present thanks to the persistence of pressure gradient. Such persistence is granted by the absence of a pulsation wave preventing the previously described vein closure mechanism. The channels will become smaller in an asymptotic way never actually closing and preventing the reach of zero net flow. Obviously, this situation is theoretical and in reality, the channels will eventually close, but a greater intracranial pressure would be needed. In order to demonstrate such an assumption, we have created a model of selective extracorporeal brachiocephalic circulation in order to send laminar flow to the brain without affecting body circulation.
The selection of the sheep as animal model was made in order to simplify the experiment having this animal a peculiar anatomy of the brachiocephalic trunk. In fact, in this setting all of the vessels, emerging in the human from the aortic arch, start from this trunk. From left to right it emerges first the left subclavian artery the two carotid arteries and last the right subclavian artery. Such conformation simplifies the experiment granting the selectivity control of the cerebral blood flow through the manipulation of a single vessel. Nonetheless, it is important to remember that collateral circulation might be present in selected cases reducing the power of the experimental model. In the sheep model though, such collaterals disperse most of their contribution to the spinal roots and to the neck muscle making the amount of cerebral distribution negligible. Dividing the experiment into three moments granted us the possibility not to miss biases in the model. In model 1 the authors confirmed a similar trend between sheeps and humans regarding brain tamponade. Blood flow ceases concomitantly with an increase of ICP over CPP reaching brain tamponade even in condition of persistent low CPP. Model 2 differs from model 1 in the need for a higher ICP value to reach tamponade and flow absence. Such a finding suggests a higher threshold to be reached in order to cause it. Finally, model 3 unites the previous ones and improves them showing how a change in flow type might overcome a preexisting tamponade situation offering a possible novel treatment strategy. The most striking data reside in the reappearance of blood flow during tamponade after the change from pulsatile flow to continuous one.

Conclusion

Brain tamponade in neurosurgery represents nowadays the terminal line for treatment. Every effort has to be made in order to find a way to overcome such a limit. Our data might represent the first step in that direction showing how changing cerebral flow even tamponade can temporarily overcome. Even though this is only an animal experiment it might open the way to further animal experiment and thus to human ones.

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Fungal Skin Diseases and Related Factors in Outpatients of Three Tertiary Care Hospitals of Dhaka, an Urban City of Bangladesh: Cross-Sectional Study

Introduction

Globally, fungal skin diseases are very common in human. As a densely populated developing country and having poor hygiene, sanitation practice, Bangladesh is no different to fungal skin infections. The skin protects us from microbes and the elements of skin help in regulating body temperature and permit the sensations of touch, heat, and cold. As it interfaces with the environment, skin plays an important immunity role in protecting the body against pathogens. It is subject to a wide range of medical conditions and infections ranging from simple manifestations to complicated ones like skin cancer. Symptoms and severity of skin disorders vary greatly. They can be temporary or permanent and may be painless or painful. Some have situational causes, while others may be genetic. Some skin conditions are minor, and others can be life-threatening. However, fungal, bacterial, parasitic and viral infections are very common in the healthy people. Several types of parasitic, bacterial and fungal infections are found which causes negligible mortality but most of the diseases have chronic course and sufferings [1].
The skin is the body’s initial defense against parasites, fungi, bacteria, viruses and other microbes. But skin and venereal diseases cause a large part of illness. About 50% of people in Bangladesh suffer from skin disorders in their lifetime. Incidence of infection on skin is very frequent due to some environmental, natural, occupational and individual habitat variations. It increases when people are herded together and facilities for washing the body and clothing are reduced. Recurrence, excessive use of chemicals and cosmetics, environmental pollution, delayed marriage etc is the major leading factors for the initiation and transmission of the diseases.
About 80% of population in Bangladesh live in the rural areas, where poverty, literacy, ignorance, high family members, disease and disasters are the constant companion of them. Increasing population, socio economic conditions have become poor and due to this population explosion, all the reversible socio-demographic conditions go in favor of disease occurrence, recurrence, and complications. In addition, overcrowding, urbanization, industrialization, migration, excessive use of chemicals and cosmetics, environmental pollution, greenhouse effect, education, delayed marriage and use of multiple partners are also the major leading factors for inflation and transmission of diseases.
Skin and venereal diseases are one of the major public health problems in developing countries. Though it occurs in all class of society but people living in insanitary and poor housings conditions suffer more from the disease, poverty-stricken people with poor hygienic habits and unclean clothing are the usual victims of these diseases. Symptoms of infection depends on the type of organisms that has caused the infection and both symptom and appearance also depend on the part of the body infected. In many studies it has been shown that 30-40% of our population is suffering from skin diseases. Of which about 80% are scabies and pyogenic infections.
Children are the worst sufferers from these diseases (Khanum and Alam 2010). The relation between the skin and venereal diseases of the diabetic patients of different age group and sociodemographic characteristics is very complicated. The sociodemographic aspects are very important to know because in different societies and social groups explain the causes of illness, the type of treatment they believe and to whom they turn if they go get ill (Khanum et al. 2007).
In human anatomy, the largest outer organ, covering throughout the whole body is skin. Skin performs a very significant role in immunization by defending against outer microbes and pathogens. Moreover, the elements of skin help the body to regulate the temperature throughout the body and create the feelings of heat, cold and touch. However, this important organ of the body has been exposed to a variety of infections and medical sufferings varying from simple acne to very intricating skin cancer types. Worldwide, among human diseases, the most common is skin disease. It can affect individuals anytime during their lifetime [1], can strike at any age, can spread over all societies and cultures. In time skin disease can lead to systematic disorders. Its damaging effects lead to physical disability even death [2].
In 2010, the global burden of disease [GBD] published that skin diseases ranked fourth as the prominent reason for non-fatal disease burden affecting both high- and low-income countries [3]. In 2013, GBD published that skin diseases are responsible for 39 million years lived with disability [YLDs] and in case of disabilityadjusted life years [DALYs] sit has attributed 1.79% to the global burden of diseases [4].

Fungal Disease: Ringworm (Dermatophytosis)

Ringworm, also known as dermatophytosis or Tinea, is a fungal infection of the skin. The name “ringworm” is a misnomer, since the infection is caused by a fungus, not a worm. Ringworm infection can affect both humans and animals. The infection initially presents with red patches on affected areas of the skin and later spreads to other parts of the body. The infection may affect the skin of the scalp, feet, groin, beard, or other areas. Ringworm can go by different names depending on the part of the body affected.
1. Tinea capitis [Ringworm of the scalp] is a fungal infection affecting on scalp.
2. Tinea corporis [Ringworm of the body] is a fungal infection that affects the skin of body.
3. Tinea cruris [Jock itch] is a fungal infection that affects the warm and moist area such as buttocks, groin, inner thighs etc.
4. Tinea pedis [Athlete’s foot] is a fungal infection that affects the skin of feet.
5. Tineaunguium [Onychomycosis] is a fungal infection that affects either the fingernails or toenails.
6. Tinea facie is a fungal infection that affects the face.
7. Tinea barbae is a fungal infection that affects the beard area of men.
8. Tinea mannum is a fungal infection that affects the area of hands.
9. Tinea versicoloris a fungal infection that affects the whole body as the form of discolored patches of skin.
Dermatophytosis tends to get worse during summer, with symptoms alleviating during the winter. The disease can be transmitted between animals and humans [zoonotic disease]. Three different types of fungi can cause this infection. They are called Trichophyton, Microsporum and Epidermophyton. It’s possible that these fungi may live for an extended period as spores in soil. Humans and animals can contract ringworm after direct contact with this soil. The infection can also spread through contact with infected animals or humans. The infection is commonly spread among children and by sharing items that may not be clean. Fungi thrive in moist, warm areas, such as locker rooms, tanning beds, swimming pools and in skin folds. It can be spread by sharing sport goods, towels, and clothing.
Symptoms and severity of skin disorders vary greatly. The consequence of this problem is serious for the patient as well as for the society. Among skin diseases, fungal, bacterial, parasitic and viral infections are very common. The distributional pattern of skin diseases varies widely from country to country, even within the country itself [1]. Although they are attributable to a very insignificant mortality rate but most of the skin diseases comes with a possibility of prolonged sufferings thus raising public health concerns in developing countries.
Bangladesh is a densely populated country with 164.69 million population and 24% of people live under the poverty line [5] and the majority of the population suffer from different infections and contagious diseases. Study conducted by Khanum and Alam, it has been shown that 30-40% of our population is suffering from skin diseases [6]. Approximately, 40% of people live in urban cities and the highest 10.3 million people live in Dhaka city [7]. Several papers have studied common skin and venereal diseases in Bangladesh [8-14] but our paper is specifically concerned about fungal skin diseases and their associated factors in three tertiary care hospitals of an urban city, Dhaka, Bangladesh.
According to the 2010 GBD, fungal skin infections were among the top 10 most dominant diseases globally [3]. According to the 2013 GBD, 0.15% of DALYs of the global burden of skin diseases are contributed by fungal skin diseases [4]. In rural areas of Bangladesh fungal skin infections are very common [15]. A study on the common skin diseases revealed that out of 440 patients 13% had fungal infections [11]. Other studies of Bangladesh showed prevalence ranging from 15.5%- 26.7% [12-14]. India, neighboring country to Bangladesh also reported that Fungal diseases were the highest group of all skin diseases with 18.74% prevalence [16] and second highest with 17.19% prevalence [17]. In Pakistan, a study conducted in 2017 showed 34.80% prevalence of fungal skin infections out of 95983 patients in a tertiary care hospital of Karachi [18]. A community-based survey studying the skin diseases of South Asian Americans found that fungal had 11% prevalence after Acne and Eczema [19].
Numerous factors can influence the prevalence of skin infections mentioning geographical and cultural factors [20-21], educational status, nutritional status, socio-economic status, as well as seasons, overcrowding, unhygienic habits, and environments are significant factors of defining the distribution of skin diseases in developing countries [1,22-24]. The socio-demographic aspects are very significant to know because in different societies and social clusters rationalize the reasons of illness, what types of treatments and whom they believe in case of their treatments [5].

Materials and Methods

This research study was performed at the Dermatology Department of the Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders [BIRDEM], Dhaka Medical College and Hospital [DMCH] and Uttara Adhunik Medical College and Hospital [UAMCH]. The study was undertaken from 25th March 2018 to 10th February 2019. A total of 800 outdoor patients were randomly selected of all genders, ages, sexes, with different occupations irrespective of their skin problems during the data collection period of BIRDEM, DMCH, and UAMCH. The present study was conducted in two steps, firstly collecting samples and data through personal interviews and secondly laboratory confirmation of the diseases and their pathogens. A literature review was carried out about the factors relating to skin diseases before a structured questionnaire was prepared for interviewing the patients about their demographics and socio-economical aspects.

Statistical Analysis

Analysis of the data has been achieved by using the statistical software SPSS [version-20.0] and the results were presented in percentages. We have matched our results with comparable studies of other cities of the country and nearby countries through similar hospital attendance-based studies.

Ethical Approval

We informed each and every patient about our study aims, methods as well as we assured them about their privacy and confidentiality at any stage of the study [at the time of data, sample collection and laboratory diagnosis] before including them into our study. We also made it flexible to the patients to enter the study and also to withdraw their consent.

Results

In the present observation cross-sectional study has been outlined to determine the prevalence of the fungal skin diseases of tertiary care hospitals in an urban city. The present study also provides a descriptive profile of factors related to the fungal skin diseases including demographical, personal hygiene aspect and socio-economic status of the outpatients attending the Dermatology Department of major three tertiary care hospitals in Dhaka city, Bangladesh.
There were a combination of skin infections including fungal, viral, bacterial, parasitic, sexually transmitted diseases [STD] but maximum patients had fungal skin infections. Among the 800 patients, 310 patients were infected with fungal infections [38.75%]. It was observed, of those 310 patients 183 [59%] were male patients and 127 [41%] were female patients. Out of 310 fungal infected patients, most of the patients, were infected by ringworm [81.61%] and the lowest prevalence was found in case of Oral thrush [2.9%] (Table 1). Besides, ringworm patients were infected by Pityriasis versicolor, Seborrhoeic dermatitis. Among 253 patients of ringworm patients the highest prevalence was found in case of Onchomycosis [21.94%] and the lowest prevalence was found in case of Tinea capitis [0.97%] (Figure 1).

Table 1: Prevalence of fungal skin infections of skin among the patients.

Figure 1: Prevalence of ringworm causing agents among the patients.

Among the 183 male patients highest 66.67% were infected by Oral thrush/ Candidiasis and lowest 42.86% were infected by Seborrhoeic dermatitis whereas, among the 127 female patients highest 57.14% were infected by Seborrhoeic dermatitis and 33.33% were infected by Oral thrush/ Candidiasis] (Table 2). Moreover, in ringworm causing agents highest 67.65% male were infected by Tinea pedis and lowest 20% males were infected by Tinea facie while in female group highest 80% were infected by Tinea facie and lowest 32.35% were infected by Tinea pedis (Table 3).

Table 2: Prevalence of fungal skin diseases according to the gender of patients.

Table 3: Prevalence of ringworm causing agents according to gender of patients.

It was also observed that out of total 310 fungal infected patients, the highest burden of fungal infections was present among the patients of age group of 31-45 [32.26%] and the lowest burden of infections was belonged to the patients of age group of 0-15 [6.13%] (Table 4). This was also similar for the prevalence of the specific ringworm causing agents. Age group of 31-45 years had highest prevalence [32.81%] and 0-15 years group had lowest prevalence [4.74%] (Table 5). Finally, we observed the factors from the personal interviews of the 310 patients mentioning marital status, socio-economic status, educational status, monthly income, occupation, seasons, religions, sources of water, residence location, regular bath, regular types of clothes, personal items sharing, history of recurrent infections, times of recurrent infections, overcrowding of family (Table 6).

Table 4: Prevalence of fungal infections in different age groups.

Table 5: Prevalence of ringworm causing agents in different age groups.

Table 6: Prevalence of fungal infections according to considered factors.

Discussion

In the present investigation, out of total 800 patients, 310 patients had fungal infections with the highest prevalence [38.75%] followed by other fungal skin problems. Out of fungal infections ringworm had highest prevalence [81.61%] followed by Pityriasis versicolor, Seborrhoeic dermatitis and Oral thrush/ Candidiasis. Among the ringworm, onchomycosis [27.42%], Tinea corporis [21.94%], Tinea cruris [16.45%] had the highest prevalence. It was also observed were male patients had high prevalence [59%] than female patients [41%]. In case of age group patients contained among the age group of 31-45 had the highest [32.26%] and the lowest prevalence of patients belonged to the age group of 0-15 [6.13%]. Outcomes of this study are similar to results of some studies while contradicts to some.
In 1993, a study performed by Hossain [25] found that fungal infection [20.19%], and seborrhoeic dermatitis [8.80%] were most common among the skin diseases [25]. In 1995, Bahmadan et al. [22] reported that in Abha city from Saudi Arabia among the fungal disease developing pathogens, Tinea capitis [9.6%] and Tinea pedis [1.9%] were most common [22] but we found Tinea corporis [21.94%], Tinea cruris [16.45%] had the highest prevalence. In 2011, a study conducted by Rahman et al. found Tinea corporis [22.63%] was the most frequent infection as well as males were mostly infected with fungal infections which is similar to the results of this present study [15].
In 2007, study by Khanam et al. informed that among the fungal infected patient’s majority [42.7%] were infected by ringworm, 45.36% by Pityrious versicolor and lowest [12%] were infected by Candidiasis. Khanum also reported that the prevalence of fungal infection was in highest in 40-49 age group [25.33%] and less in 20-29 age group [14.66%] and prevalence in male was highest [61.33%] than female [38.66%] [8]. In 2012, one study from a Dhamrai area near Dhaka performed by Nafiza et al. had reported that among the patients with cutaneous skin diseases, fungal infections were the commonest and highest [22.9%] and males had high prevalence [63.4%] than females [36.6%] [12]. In 2017, Haque et al. revealed among the 504 patients who were surveyed from Rajshahi, an unbar city of Bangladesh with different types of skin disease, male had highest prevalence of fungal infections [26].
In this present study we had explored not only the demographical and socio-economic aspects but also seasonal aspect and the hygiene habits of the patients to better understand the factors related to the fungal skin diseases. It has been witnessed in. this study, that among the fungal infected patients who were married [71.93%], had secondary education [36.45%], earned 12000-20000tk monthly [38.06%] and had upper-middle class status [38.06%] had higher prevalence. Moreover, patients who were Muslims [86.13%], had businesses [39.73%], lived in urban areas [69.35%], used tap water as the source of water [69.35%] also had higher prevalence of fungal infections of skin. In case of personal hygiene of the patients, who wears cotton clothes regularly [27.74%], baths regularly [60%], shares personal items [63.87%], had recurrent infections [62.9%] and had overcrowding of family [66.13%] had higher prevalence. Additionally, in summer season fungal infections had higher prevalence [59.68%]. This study had found high prevalence in Muslims as the study was conducted in an Islamic country.
There are several studies conducted in Bangladesh had found different results than ours. According to them, the prevalence was higher is rural areas [15], among students [10], patients from low socio-economic status [9], among illiterate patients [9,10], in rainy season [8]. According to Khanum et al. 52.16% of the patients with low socio-economic status showed a high reoccurrence of skin disease which contradicts our study result [8]. From these observations it can be said that skin infections in patients is very frequent in urban regions even if the urban cities of the country have improved standard of living, hygiene and sanitation, better quality healthcare facilities, education, and nutritious food to lessen the fungal skin diseases rather than the rural part of country. So, the present study has tried to give an approximate fungal skin disease prevalence scenario with related factors of the whole country.

Conclusion

Present cross-sectional study has provided some unique results and findings which would add to the scientific literature and health policies as it is first of its kind. No other research work has evaluated the prevalence of fungal skin diseases of an urban city with associated factors in Bangladesh. Moreover, this work can also be scaled up to other pathogens of skin diseases. However, there is no vaccine against skin diseases it is very difficult to control its transmission so to control this disease is to improve socioeconomic condition, change the personal hygiene behaviour and taking appropriate preventive measures.

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Hyper Prevalence of Malnutrition in Nigerian Context

Introduction

Diet is the number one risk factor for disease in the world; carrying a superior risk of ill health than smoking or drinking alcohol Mills, et al. [1]. According to the World Health Organization (WHO), 462 million adults are underweight, while 1.9 billion adults are overweight and obese. In children under 5 years of age, 155 million are stunted, 52 million are wasted, 17 million are severely wasted and 41 million are overweight or obese [2]. The importance of nutrition cannot be over emphasized in any country of the world, be it developed, developing or under developed. This is because nutrition determines the social, economic, intellectual and technological advancement of any nation. While the significance of nutrition for growth, development and advancement is globally recognized, universal efforts in battling hunger and malnutrition have not really been achieved on a global scale [3,4]. Globally, there is hunger and malnutrition ravaging the world with a current estimated value of 1 in 9 people out of the 820 million people who are hungry or undernourished. A study conducted by [4] states that there has been a perpetual increase in these figures since 2015, especially in Africa, West Asia and Latin America. Similarly, approximately 113 million people across 53 countries experience acute hunger, as a result of conflict and food insecurity, climate shocks and economic instability [5]. However, more than onethird of the world’s adult population is overweight or obese, with growing trends over the past twenty years Ng, et al. [6].
The 2020 Global Nutrition Report presents the latest data and evidence on the state of global nutrition. Among children under 5 years of age, 149.0 million are stunted, 49.5 million are wasted and 40.1 million are overweight, and there are 677.6 million obese adults. It further states that there is now an increased global recognition that poor diet and resultant malnutrition are among the greatest health and societal challenges of our time. In addition, malnutrition continues at unacceptably high levels on a universal scale despite the little improvements that has been made to combat it. [7] emphasises that countries affected by conflict or other forms of fragility are at a higher risk for malnutrition. Moreover, it further illustrates that in 2016, 1.8 billion people (24% of the world’s population) were living in fragile or extremely delicate countries. This digit is projected to grow to 2.3 billion people by 2030 and 3.3 billion by 2050. International Food Policy Research Institute, [8] notes that the prevalence of stunting or restricted growth among children under five years reduced to 23.8% from 36.9% between 1990 and 2015. Nonetheless, the Food and Agricultural Organization of the United Nations [9] indicated that in 2017, the number of undernourished people increased from 777 million to 815 million between 2015 and in 2016, about 155 million children below the age of 5 were too short for their age. Furthermore, approximately 52 million did not weigh enough for their height while about 41 million was overweight. Previous researches like Black, et al. [8,10], and [11] indicated that malnutrition is connected to nearly half of all deaths among children under the age of five.
On the contrary, more than 28 million adults and children in the United Kingdom (UK) are overweight or obese, which is catalysing a diet related health problem with escalating rates of noncommunicable diseases, including type 2 diabetes, cardiovascular disease and certain forms of cancer [12]. The treatment of obesity and its consequences in England alone currently costs the NHS £16 billion every year, the majority of which is spent on type 2 diabetes, [13]. This is more than the £13.6 billion per year spent on the fire and police services combined. The wider economic toll of obesity and related conditions is estimated to be the equivalent of 3% of the GDP Dobbs, et al. [14]. The most common form of malnutrition in the developing countries is under nutrition whilepresently Nigeria is one of the African countries listed among the 20 countries responsible for 80% of global malnutrition. Out of the sum of 233 million undernourished people in Africa, 220 million are from the Sub Saharan. Whereas South Sudan is lacking of globally comparable data, estimates show that the food and nutritional shortfalls are dreadful. For example, by January-March 2019, 5.2 million South Sudanese (49% of the total population) continued to face acute food insecurity Black, et al. [15]. Within this context, this paper seeks to evaluate hyper prevalence of malnutrition in Nigerian context.
The Basic Tools of Scientific Enquiry
1. What are the factors or causes of hyper prevalence of malnutrition in Nigeria?
2. What are the mental and intellectual effects of hyper prevalence of malnutrition in Nigeria of under five children?
3. What are the impacts of hyper prevalence of malnutrition on the future of the Nigeria economy?

Literature Review

A report by the Food and Agriculture Organization of the United Nations [16] indicates that more than 14% of the population in developing countries were undernourished in the period between 2011 and 2013. Malnutrition includes both nutrient deficiencies and excesses and is defined by the World Food Programme (WFP) as “a state in which the physical function of an individual is diminished or weakened to the point where the person can no longer maintain normal or adequate bodily performance processes such as growth, pregnancy, lactation, physical work, and resistance to and recovering from disease” [17]. Additionally, [18] states that malnutrition frequently begins at conception, and child malnutrition is connected to poverty, low levels of education, and poor access to health services, including reproductive health and family planning. Furthermore, the World Health Organization, [2] states that malnutrition occurs due to an imbalance in the body, whereby the nutrients required by the body and the amount used by the body do not balance. Additionally, it stipulated that there are several forms of malnutrition and these include two broad categories namely under nutrition and over nutrition. Under nutrition manifests as wasting or low weight for height (acute malnutrition), stunting or low height for age (chronic malnutrition), underweight or low weight for age, and mineral and vitamin deficiencies or excessiveness. While over nutrition includes overweight, obesity and dietrelated non-communicable diseases (NCDs) such as diabetes mellitus, heart disease, some forms of cancer and stroke.
In the 21st century, malnutrition in children has three main strands. The first is the continuing plague of undernutrition. Despite its reduction in many parts of the world, undernutrition is still depriving many children of the energy and nutrients they need to grow well and is connected to the deaths of children from 6 months to under 5 of age each year [19]. The second strand is hidden hunger. This is as a result of the deficiencies in essential vitamins and minerals such as vitamins A and B, iron and zinc. It is often unseen, and often ignored; hidden hunger robs children of their health and vitality and even their lives. The third strand is overweight, which is also called obesity in its more severe form. It was formally regarded as a condition of the rich, overweight now afflicts more and more children, even in underdeveloped and developing countries. It is has also been considered as a threat to stimulating a rise in diet-related noncommunicable diseases (NCDs) later in life; such as heart disease, which is the leading cause of death worldwide [20]. World Health Organization (WHO) reported that 462 million adults are underweight, while 1.9 billion adults are overweight or obese. In children under 5 years of age, 155 million are stunted, 52 million are wasted, 17 million are severely wasted and 41 million are overweight or obese [2]. There is a diversemanifestation of malnutrition, but the pathways to addressing prevention are important and include exclusive breastfeeding for the first two years of life, diverse and nutritious foods during childhood, healthy environments, access to basic services such as water, hygiene, health and sanitation, as well as pregnant and lactating women having proper maternal nutrition before, during and after the respective phases (before pregnancy and after delivery) [21].
The smallest or least advantaged are the most likely to suffer from malnutrition and its longstanding consequences. A research report by Hancock, et al. [22] states that the most deprived white children measured across England in 2012-2013 were on average more than a centimetre shorter in height by the age of 10 years than the least deprived children. These children are not likely to catch up growth losses from their early years. Obese children in England are more than twice as likely to live in the most deprived areas compared with comfortable areas and this gap is increasing over time [23]. Poor children are also more likely than wealthy children to suffer from poor health as a result of food insecurity. In addition, over 60% of paediatricians surveyed throughout the UK in late 2016 said that food insecurity contributed to the unpleasant health among children they treat [24]. Currently, nearly one in three people in the world suffers from at least one form of malnutrition, including obesity, under nutrition or vitamin and mineral deficiencies. Due to the rise in obesity, high income countries are presently contributing to the greatest number of malnourished people, but low income and middle income countries are meeting up fast. Hence, in Africa, the number of children who are overweight or obese has nearly doubled from 5.4 million in 1990 to 10.6 million in 2014 (Global Panel on Agriculture and Food Systems for Nutrition, 2016). Despite this rise in figure, other forms of malnutrition have not gone away, as deficiencies in vitamins and minerals continue to affect billions of people worldwide.

Perspectives on Malnutrition in Nigeria

Over the years, two main types of malnutrition have been identified in Nigerian children: (1) protein-energy malnutrition and (2) micronutrient malnutrition. The protein-energy malnutrition is common among the preschool children and constitutes a major public health problem in the country. “Stunting” is usually defined as low height for age, however, it is a deficit of linear growth and failure to reach genetic potential that reflects long term and cumulative effects of inadequate dietary intake and poor health conditions [25]. Succinctly, underweight is low weight for age, stunting (low height for age) and wasting (low weight for height) are all manifestations of under nutrition. All these expose the child to health risks and in their severe forms; they constitute a threat to the child’s survival [26]. In 1983–1984, the National Health and Nutrition Survey (HANS) conducted by the Federal Ministry of Health estimated the prevalence of wasting to be around 20% (FGN 1983–1984). A research by the Demographic and Health Survey (DHS) in 1986 shows that children between the ages of 6–36 months in Ondo State (Southwestern Nigeria) suffered 6.8% prevalence of wasting, underweight of 28.1%, and stunting of 32.4%.
In February 1990, an anthropometric survey of preschool children (2–5 years old) in seven states was conducted and found underweight prevalence ranging from 15% in Akure (Ondo State) to 52% in Kaduna (Kaduna State) while stunting prevalence ranged from 14% in Iyero-Ekiti (Ondo State) to 46% in Kaduna. Similarly, the 1990 DHS conducted by the Federal Office of Statistics estimated the prevalence of wasting at 9%, underweight at 36%, and stunting at 43% among the preschool children in Nigeria. These figures show a decline compared to the figures published in 1994 by UNICEF-Nigeria from a 1992 survey conducted among women and children in 10 states; the UNICEF reported the prevalence of wasting among women and children at 10.1%, underweight 28.3%, and stunting 52.3%. Furthermore, there was a decrease in prevalence of stunting in the 2003 NDHS with 11% of children wasting, 24% underweight, and 42% of children stunted [27]. As at 2008, prevalence of underweight had declined to 23% and stunting had reduced to 41% but wasting increased to 14% (NDHS, 2008).
Similar trends were reported by the 2001–2003 Nigerian Food Consumption and Nutrition Survey (NFCNS). The study reported 9% wasting, 25% underweight, and 42% stunting, with significant variations across rural and urban areas, geopolitical zones, and agro-ecological zones Maziya-Dixon, et al. [28]. The study also shows that the prevalence of stunting was lowest in the southeast at 16%; it reached 18% in the south and 55% in the northwest of Nigeria. The result further shows that among the states, stunting was highest among children in Kebbi (61%). The 2003 report of NDHS also indicates that among the rural children (43% stunted) were disadvantaged compared to urban children (29% stunted). Children living in the Northwest geopolitical zone stood out as being particularly underprivileged at 55% compared to 43 % in the Northeast zone, 31% in North Central, 25% in the Southwest, 21% in the South-South, and 20 % in the Southeast. The Multiple Indicator Cluster Survey (MICS), reported that there was a decrease in the prevalence of malnutrition in Nigeria with 34 % of children under five stunted, 31 % underweight, and 16% wasted, while about 15% of children had low birth (at less than 2,500 grams at birth) [29]. It is obvious from the 2013 NDHS that the proportion of children who are stunted has been decreasing over the years. However, the degree of wasting has worsened, indicating a more recent nutritional deficiency among children in the country. Prevalence of stunting decreased to 37%, with a higher concentration among rural children (43%) than urban (26%). Nevertheless, there has been an increase in the proportion of children underweight (29 %) and the proportion wasting (18%) [30]. It is graphically clear based on the data from these different studies that, malnutrition of children under five has been a consistent problem in Nigeria over time, with just little improvement reported despite its escalation in the country. Malnutrition contributed to 53% of deaths among children under five in Nigeria, and levels of wasting and stunting are still very high [31].

Empirical Review

Malnutrition is a global public health problem in both children and adults universally [2]. Annually, malnutrition claims the lives of 3 million children under age five and costs the global economy billions of dollars in lost productivity and health care costs. However those losses are almost entirely preventable. A large body of scientific evidence like [32-34] show that improving nutrition during the critical 1,000 day period from a woman’s pregnancy to her child’s second birthday has the potential to save lives, help millions of children to fully develop and deliver greater economic prosperity. Furthermore, Shrimpton, et al. [35] stated that malnutrition is currently an important global problem; as it affects all people despite the geography, socioeconomic status, sex and gender, overlapping households, communities and countries. In addition, anyone can experience malnutrition but the most susceptible groups affected are children, adolescents, women, as well as people who are immunecompromised, or facing the challenges of poverty.
Young malnourished children are affected by compromised immune systems by yielding to infectious diseases and are prone to cognitive development delays; damaging long term psychological and intellectual development effects, as well as mental and physical development that are compromised due to stunting [10,36]. A malnutrition cycle exists in populations experiencing chronic under nutrition and in this cycle, the nutritional requirements are not met in pregnant women. Thus, infants born to these mothers are of low birth weight, are unable to reach their full growth potential and may therefore be stunted, susceptible to infections, illness, and mortality early in life. The cycle is worsened when low birth weight females grow into malnourished children and adults, and are therefore more likely to give birth to infants of low birth weight as well [37]. Malnutrition is not just a health issue but also affects the global burden of malnutrition socially, economically, developmentally and medically, affecting individuals, their families and communities with serious and long lasting consequences [2].
It is very significant that malnutrition is addressed in children as it manifestations and symptoms begin to appear in the first 2 years of life [35]. Overlapping with the mental development and growth periods in children, protein energy malnutrition (PEM) is said to be a problem at the ages of 6 months to 2 years. Therefore, this age and period is considered a window period during which it is essential to prevent or manage acute and chronic malnutrition [38]. Furthermore, children less than 5 years of age have a disease burden of 35% Black, et al. [10]. In 2008, 8.8 million global deaths in children less than 5 years old were due to underweight, of which 93% occurred in Africa and Asia. Walton, et al. [39] stated that approximately one in every seven children faces mortality before their fifth birthday in Sub Saharan Africa (SSA) due to malnutrition. Nigeria is the most populous nation in Africa and has a population of almost 186 million people in 2016 UNICEF [40]. With a high fertility rate of 5.38 children per woman, the population is growing at an annual rate of 2.6 percent, escalating and worsening overcrowded conditions. Hence, by 2050, Nigeria’s population is expected to grow to an astounding 440 million, which will make it the third most populous country in the world, after India and China (Population Reference Bureau, 2013). A report by the Nigeria Federal Ministry of Health [41] states that scarcity of resources and land in rural areas has resulted in Nigeria having one of the highest urban growth rates in the world at 4.1 percent. Furthermore, out of the 157 countries in progress toward meeting the Sustainable Development Goals (SDGs), Nigeria ranks 145th Sachs, et al. [42].
Malnutrition in childhood and pregnancy has many adverse consequences for child survival and longstanding wellbeing. It also has extensive consequences for human capital, economic productivity, and national development generally. These consequences of malnutrition should be a significant concern for policy makers in Nigeria, which has the highest number of children under 5 years with chronic malnutrition (stunting or low height for age) in SubSaharan Africa at more than 11.7 million, according to the Demographic and Health Survey National Population Commission and ICF International [43]. According to the World Bank [44], Nigeria’s economy is the largest in Africa and is well positioned to play a leading role in the global economy. However, despite the strong economic growth over the last decade, poverty has remained significantly high, with increasing inequality and provincial disparities. In addition, it is estimated that 69 percent of Nigerians live below the relative poverty line (US$1.25 per day), compared to the 27 percent in 1980.

Theoretical Framework

This study is anchored on two theories, which include the Theory of Reasoned Action (TRA) and the Theory of Planned Behaviour (TBP). Theory of Reasoned Action was formulated by Martin Fishbein and IcekAjzen towards the end of the 1960s. On the other hand, IcerkAjzen proposed the Theory of Planned Behaviour in 1985; which was an extension from the TRA. The Theory of Reasoned Action and Theory of Behaviour Planned combine two sets of belief variables, which are ‘behavioural attitudes’ and ‘the subjective norms’. The behavioural attitudes are defined as the multiplicative sum of the individual’s relevant likelihood and evaluation related to behavioural beliefs. On the other hand, subjective norms are referent beliefs about what behaviours others expect and the degree to which the individual wants to comply with others’ expectations. The summary of the two theories suggest that a person’s health behavior is determined by their intention to perform a behavior (behavioural intention) it also is predicated by a person’s attitude toward the behavior, and the subjective norms regarding the behavior.
The Theory of Reasoned Action has been criticised because it is said to ignore the social nature of human action Kippax, et al. [45]. These behavioral and normative beliefs are derived from individuals’ perceptions of the social world they inhabit, and are hence likely to reflect the ways in which economic or other external factors shape behavioral choices or decisions. In addition, there is a compelling logical case to the effect that the model is inherently biased towards individualistic, rationalistic, interpretations of human behavior. Its focus on subjective perception does not essentially permit it to take meaningful account of social realities. However individuals’ beliefs about such issues are unlikely going to reflect the accurate potential and observable social facts. As such, the Theory of Planned Behavior updated the Theory of Reasoned Action to include a component of perceived behavioral control, which brings about one’s perceived ability to enact the target behavior. Actually, perceived behavioral control was added to the model to extend its applicability beyond purely volitional behaviors. Previous to this addition, the model was relatively unsuccessful at predicting behaviors that were not mainly under volitional control. Therefore, the Theory of Planned Behavior proposed that the primary determinants of behavior are an individual’s behavioral intention and perceived behavioral control.
A constructive use of the TRA and TBP in research and public health intervention programmes might well contribute valuably to understanding issues related to health inequalities and the roles that other environmental factors have in determining health behaviors and outcomes. In spite of the criticism, the general theoretical framework of the TRA and TPB has been widely used in the retrospective analysis of health behaviors and to a lesser extent in predictive investigations and the design of health interventions Hardeman, et al. [46]. This is why there is a connection between the study and the theory; since it is health related within theoretical postulations.

Methodology

The study uses secondary data such as significant texts, journals, newspapers, official publications, historical documents and the Internet. However, the research was strictly limited to available or recorded information about malnutrition, its prevalence, effects and impacts on the Nigeria economy that can be found in scholarly journals, books and the internet. The study adopts content analysis as its method of analysis, whereby the existing literature will be considered for the analysis.

Findings and Discussion

Based on the stated research questions, the findings and discussions are purely based on the research questions. The questions are discussed as follows:

RQ1: What are the Factors or Causes of Hyper Prevalence of Malnutrition in Nigeria?

The causes of malnutrition and food insecurity in Nigeria are multidimensional and include very poor infant and young child breastfeeding or feeding practices, which contribute to high rates of illness and poor nutrition among children under 2 years; lack of access to healthcare, water, and sanitation; armed conflict, mainly in the north; irregular rainfall and climate change; hyper unemployment level; and poverty Nigeria Federal Ministry of Health, Family Health Department [41]. While chronic and seasonal food insecurity occurs throughout the country, and is worsened by volatile and rising food prices, the impact of conflict and other shocks has resulted in acute levels of food insecurity in the North East zone FEWSNET [47]. Furthermore, an approximated 3.1 million people in the states of Borno, Yobe, and Adamawa received emergency food assistance and cash transfers in the first half of 2017 but, the numbers who need assistance is likely far bigger because much of the North East zone has been inaccessible to humanitarian or aid agencies FEWSNET [47].
World Bank [44] stated that the current administration, led by President Muhammadu Buhari, identifies fighting corruption, increasing security, tackling unemployment, diversifying the economy, enhancing climate resilience, and boosting the living standards of Nigerians as its core policy priorities. On the contrary, the country is seriously facing a major challenge of threat in the northeast because of the militant Islamic group, Boko Haram, which is destroying infrastructure and conducting assassinations and abductions. As of August 2017, conflict in northeastern Nigeria had displaced more than 1.7 million people within the country and forced nearly 205,000 people to flee into neighboring Cameroon, Chad, and Niger Republic, making it difficult to access food resources in the regions. In addition, violence has interrupted agricultural and income generating activities, reducing household purchasing power and access to food. Furthermore, populations in the regions of northeastern Nigeria are inaccessible to humanitarian assistance and markets are in terrible conditions USAID [48]. Hence, diet related non communicable diseases are also on the increase in Nigeria due to globalization, urbanization, lifestyle transition, socio cultural factors, and poor maternal, fetal, and infant nutrition Nigeria Federal Ministry of Health, Family Health Department [41].
Other factors include, those related to women’s empowerment, such as mothers’ working status, control over resources and educational attainment. In rural areas, children of working mothers are significantly less possible to be undernourished than children living in households where mothers do not work (Ajieroh, 2009). Hence, in Nigeria, children from the poorest households are almost 3 times more likely to be stunted and almost 4.3 times more likely to be severely stunted compared to children from the richest households. Similarly, according to NPC and ICF International (2014) the findings of a study of factors affecting Nigerian children’s nutritional status suggest that households’ economic status is significantly associated with their nutritional status. This is because the very poor and the poor constitute 74% of the population and cannot afford a nutritious diet.
Furthermore, the analyses of regional differences in child malnutrition reveal important spatial inequalities. The prevalence of underweight, stunting and wasting is generally higher in the northern than the southern states. The highest proportions of malnourished children were found mainly in Bauchi, Jigawa, Kaduna, Katsina, Kebbi, Sokoto and Zamfara states. In all these states the occurrence of stunting exceeds 50%. In other states, such as Gombe, Taraba, Yobe and Kano, the prevalence of stunting exceeds 40%. All the states in the North West (except Jigawa and Zamfara) show higher figure than the national average prevalence of acute malnutrition (wasting). In addition, the North-Eastern states of Bauchi, Borno and Yobe have excessively high burden of wasting, with Kano State showing more than twice the national average (39.7%). Severe acute malnutritionis highest in Kaduna (27.6%) and Kano (25.1%) and lowest in Bayelsa (1.3%).
Consequently, the UN Office for the Coordination of Humanitarian Affairs (2014) stated that Nigeria has the second highest acute malnutrition burden in the world, with an estimated 3.78 million children suffering from wasting.

RQ2: What are the Mental and Intellectual Effects of Hyper Prevalence of Malnutrition in Nigeria of Under Five Children?

The growth of the brain, including neurodevelopment begins in the womb within one week of conception. During this period of rapid growth, protein and energy (from carbohydrates and fat sources) are extremely important. A lack of these nutrients can have very damaging effects. Fuglestad, et al. [49] showed a higher occurrence of brain abnormalities at two years of age among children affected by foetal under nutrition. Furthermore, studies of young children with protein energy malnutrition alsoindicated brain atrophy; a shrinking of brain cells due to a lack of nutrients Blaack, et al. [10]. In addition, inadequate calories have continue to affect children’s brain growth and enlargement immediately in the first months after birth, which was supposed to be a time of fast neurodevelopment, including the establishment of the parts of the brain fundamental for memory (the hippocampal-prefrontal connections Fuglestad, et al. [49].
The deficiency of iron also complicates the growth period of a child. Iron deficiency before two to three years of age may results in intense and possibly permanent myelin (fatty lipids and lipoproteins, which surround the axon of a nerve) changes Fuglestad, et al. [48]. Iron also facilitates the production of neurotransmitters – the chemicals that pass messages between neurons, and it is involved in the function of neuroreceptors, which receive the neurotransmitters’ messages Jukes, et al. [50]. According to Allen [51], emergent evidence suggests that maternal iron deficiency in pregnancy reduces foetal iron stores, perhaps into the first year of life. This leads to greater risk of damages in future mental and physical development.
Furthermore, the deficiency of iron is a strong risk factor for both short and long terms cognitive, motor and socio emotional deterioration Prado & Dewey [52]. Besides, longitudinal study like Grantham-McGregor, et al. [53] have indicated that children who are anaemic during infancy have poorer cognition, lower school achievement and are more likely to have behaviour problems in later childhood; an effect that could occur as a result of direct biological processes or as a consequence of the impact of anaemia on children’s education experiences. Iron deficiency is pervasive. Virtually half of children in low and middleincome countries, that is 47% of under 5 are affected by anaemia, and half of these cases are due to iron deficiency World Health Organization [54]. According to the World Health Organization (WHO), 42% of pregnant women (56 million) suffer from anaemia Goonewardene, et al. [55].
Iodine deficiency is known to be the world’s single greatest cause of preventable mental retardation. In 2007, WHO estimated that nearly 2 billion people had deficient iodine intake, and one third of them are children of school age The Lancet [56]. Iodine is indispensable to the production of thyroid hormones, which are essential for the development of the central nervous system. Serious iodine deficiency before and during pregnancy can lead to underproduction of thyroid hormones in the mother and cretinism (a condition of severely stunted and mental growth due to birth deficiency of thyroid hormones) in the child Prado, et al. [51]. Cretinism is characterized by mental retardation, deaf mutism (a psychological disorder in which it is difficult for the individual to speak in certain situations), partial deafness, facial deformities and cruelly stunted growth. It can lead on average to a loss of 10–15 intelligent quotient (IQ) points Morgane, et al. [57]. In addition, Fuglestad, et al. [48] stated that mild iodine deficiency can decrease motor skills.
Zinc plays an important role in brain development and is known to be vital for efficiency of communication between neurons in the hippocampus, where learning and memory processes occur Duke University Medical Center [58]. It is also fundamental to other biological processes that affect brain development, including DNA and RNA synthesis and the metabolism of protein, carbohydrates and fat Prado, et al. [51]. Additionally, Hamadani, et al. [59] stated that although the results of studies on the impact of zinc supplementation on cognitive outcomes are inconsistent, there appears to be a relationship between zinc deficiency and children’s cognitive and motor development, including among low birth weight children Folate is prerequisite during initial foetal development to prevent neural tube defects and make sure that the neural tube forms accurately to create the brain and spinal cord. Iron folate supplementation is also significant for pregnant and breastfeeding mothers to prevent iron deficiency anaemia Black, [10]. Vitamin B12 and folate works together to produce red blood cells. Black [10] further stated that the deficiencies in both could affect brain development in infants. Like iron, vitamin B12 is also essential to the myelination process. Neurological symptoms of vitamin B12 deficiency appear to affect the central nervous system and in severe cases cause brain atrophy.

RQ3: What are the Impacts of Hyper Prevalence of Malnutrition on the Future of the Nigeria Economy?

According to Save the Child [60] the benefits of good nutrition do not stop with better educational results. By improving cognitive abilities, health, physical strength and stature, good nutrition in the early years can lead to greater wages in adulthood and hence promote the economic development of an entire country. In addition, Save the Child [60] presented evidence that stunted children earn as much as 20% less than their counterparts, and uses this to estimate that today’s malnutrition could potentially cost the global economy $125 billion when children born now reach working age. Hence, the interrelation between improved nutrition and economic growth is of great importance for human and economic development. It is a two way relationship. On the one hand, inclusive economic growth can contribute towards reductions in the prevalence of malnutrition. On the other hand, declines in malnutrition can have a transformative effect on the economic ability of individuals and the whole societies. Thus, by means of its impact both on children’s cognitive development and on their physical health and development, malnutrition can have momentous effects on an individual’s economic wellbeing in future. The World Bank (2006) suggests that malnutrition results in10% lower lifetime earnings, whilestudy like Save the Child [60], that modeled the impact of malnutrition in the first 2-5 years of life placed this figure at 20%.
Lancet Series (2008) reviewed cohort studies from Brazil, Guatemala, India, the Philippines and South Africa that all monitored children into adulthood, and established that stunting is associated with reduced earnings in later life. Similarly, Victoria, et al. [61] stated that the same review discovered that less severe stunting in Brazil and Guatemala was associated with higher adult incomes among both men and women. Furthermore, models using proof from across these longitudinal studies, combined with evidence on the relationship between education and earnings taken from 51 countries, have estimated that children who are stunted at age five earn 22% less than their non stunted counterparts. In addition, data from the same study has been used to evaluate that individuals who were not stunted in early childhood were more likely, by 28 percentage points to work in higher paying skilled labour or white collar work and earned as much as 66% more as adults Hoddinott, et al. [62].
Part of the impact of malnutrition on earnings may be because of the influence on children’s physical development. Study like Morganeet, et al. [56] has confirmed the correlation between adult height and wages.For example, a large cross sectional study in Brazil found that a 1% increase in adults’ height was associated with a 2.4% increase in earnings. Francis and Iyare (2006) and Islam et al., (2006) stated that there is a flawless association between education levels, and individuals’ subsequent earnings. Very importantly, the latest evidence suggests that it is actual learning and the acquisition of skills that matter most, not just the number of years spent in school Hanushek, et al. [63]. This is another reason why early childhood development, boosted by good nutrition, is very vital. Hence, children need to start school ready to learn, rather than struggling to understand what the teacher is trying to teach and impart. Therefore, according to Currie, et al. [64] given the significance of cognitive and educational outcomes on wages, this is likely to be a key pathway that links nutrition to later economic wellbeing.
In actual fact, nutrition’s relationships with cognitive and educational development may be the most important pathway in terms of its impacts on wages. Save the Child [59] reported that the economic impacts of malnutrition are larger for those working in more skilled jobs than for those in manual jobs. Baird, et al. [65] showed that among those working for wages or operating small businesses as adults, those who had received an intervention to improve nutrition as children worked on average five extra hours per week, and earned 20% more than those who didn’t. These impacts were much larger than increases seen for farm workers. Hence, nutrition is not only significant for increasing economic outcomes of individuals; it is important for nations’ economic development. Malnutrition also affects national economies by increasing healthcare costs, as people who were malnourished as children are more likely to fall ill to diseases Currie, et al. [64-78].

Conclusion

Diet is the number one risk factor for disease in the world; carrying a superior risk of ill health than smoking or drinking alcohol. According to the World Health Organization, 462 million adults are underweight, while 1.9 billion adults are overweight and obese. In children under 5 years of age, 155 million are stunted, 52 million are wasted, 17 million are severely wasted and 41 million are obese. Globally, there is hunger and malnutrition ravaging the world with a current estimated value of 1 in 9 people out of the 820 million people who are hungry or undernourished. Thus, the study found that presently Nigeria is one of the African countries listed among the 20 countries responsible for 80% of global malnutrition. The finding of the study also revealed that over the years, two main types of malnutrition have been identified in Nigerian children: protein-energy malnutrition and micronutrient malnutrition. The study discovered that the causes of malnutrition and food insecurity in Nigeria are multidimensional and include very poor infant and young child breastfeeding or feeding practices, which contribute to high rates of illness and poor nutrition among children under 2 years. The study discovered that young children with protein energy malnutrition suffer from brain atrophy; a shrinking of brain cells due to a lack of nutrients. The findings of the study revealed that stunted children earn as much as 20% less than their counterparts, and that today’s malnutrition could potentially cost the global economy $125 billion. The study concludes that nutrition is not only significant for increasing economic outcomes of individuals; it is important for nations’ economic development, especially for a developing country like Nigeria.

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Effect of Operating Parameters and Particle Size of Calcium Carbonate on the Physical Properties of Latex Paint

Introduction

Paint is a liquid which spreads over a substrate in the form of thin layer and it is transformed into a solid adherent film [1]. There are two major functions of paint. One protection and other is decoration. The earliest known use of paints dates back more than 30,000 years to cave paintings in Spain [2]. These paints were simply mixtures of colored earth, soot, grease, and other natural substances. The ancient Greeks, Romans, and Egyptians used natural resins and raw materials to decorate and identify statues, tools, vessels, and buildings [2,3]. These natural ingredients include vegetable gums, starches, and amber. In China and India, shellac resins and beeswax were used over 2000 years ago as a decorative coating which also doubled as a protective function [4]. The earliest paint formulation dates back roughly 900 years to a German goldsmith and monk, Rodgerus von Helmershausen [2,3]. His formulation described the manufacturing of paint by mixing linseed oil and amber, referred to as paint boiling, which was further refined and developed into the Industrial Revolution [2,3]. Synthetic polymer chemistry also developed at this time with Carothers and others in the 1920s [5]. Paint is used to protect and color the substrate. Components of paint are solvent, pigment, filler, additives and binder. A coating is a product based on organic binders, which provides a cohesive, non-absorbent, protective film [2]. Differences in the composition of the various coatings systems are presented in (Tables 1 & 2).

Table 1: Typical composition of various coating systems.

Table 2: Differences between step-growth and chain-growth polymerization.

Common to all three coating systems are the resin and additive. Clear coats are optically inactive; therefore pigments and fillers are not present. Powder coatings are not in a liquid medium; therefore a solvent is not present. Paints are liquid materials that are optically opaque coatings that form when applied by brushing, rolling or spraying [2,3]. The technical definition of a binder is the non-volatile part of a paint excluding the pigments and filler, which includes the non-volatile additives [2]. Binder forms the film of the paint. Binder is a polymer which has impact on important properties of the paint like adhesion to the substrate, sheen, application properties, color acceptance, durability and flexibility. There are different types of binders like synthetic binders and natural binders. Water based paints binders include poly vinyl acetates, poly vinyl acrylic, styrene acrylic, pure acrylics, etc. Oil-based paints include alkyd resins, polyurethane resins, melamine resins, etc. Natural oils or fatty oils were important film forming agents which were able to convert a low viscosity liquid into a solid [3]. Synthetic resins came about in the 1920s with the advancements in polymer chemistry. The primary benefits of synthetic resins are that products can be tailored with specific properties with nearly unlimited availability. The different resin systems are mentioned above, all of which are either step-growth or chain-growth polymerization [6].

Chain-growth reactions typically have three reactions – initiation, propagation, and termination. Step-growth polymerizations are reactions between functional or multifunctional monomers without an initiation or termination step. Characteristics common in pigments include extreme optical characteristics, particles smaller than 10 μm, being insoluble in water and most organic solvents, and being chemically inert or chemically stable [7]. A comparison between the organic and inorganic pigments is presented in (Table 3) [2]. Colored inorganic pigments are typically variants of iron oxides [3]. Pigments are used for giving color contribution in paints. There are different types of pigments like natural or synthetic. Pigments give opacity to the paint film. There are many kinds of pigments like titanium dioxide, phthalocynine blue, pthalocyninered, iron oxide, etc. Common filler materials include carbonates, silicon dioxide, silicic acids, silicates, and sulfates [2,3,6]. Fillers are used to give toughness and lower the cost of the paint by increasing the density of the paint. The examples of natural fillers are grounded calcium carbonate, magnesium silicate, etc. The examples of synthetic fillers are precipitated calcium carbonate, aluminum silicate, etc. These pigments and extenders are commercially available in solid or slurry form. Slurry is an aqueous solution that contains dispersed pigments or extenders. In a paint application, the pigment and extenders are eventually dispersed in some sort of medium.
The dispersion process involves 3 steps – wetting, separation, and stabilization [6]. The refractive index can be described as the degree of bending of light as it passes through a material. This value is a dimensionless value and is typically referenced to light traveling in a vacuum. Larger refractive indexes reflect a greater degree of bending of light. The refractive index of pigments and film formers are presented in (Table 4). TiO2 is not used as a biocide, but has some antimicrobial properties due to the photo catalytic reaction mentioned earlier [8,9]. Filler or extender particles such as calcium carbonate (CaCO3) primary serve as replacement for the binder material. Reasons include the lower cost of filler materials or formulation above critical pigment volume concentration. Pigment volume concentration (PVC) is the most widely accepted quantitative description of paint film composition [1]. PVC is expressed as volume percentage of the pigments and fillers to that of the volume of the dry film expressed as a whole number. Volume is used rather than weight because pigments scatter based on volume. PVC values are quantifiable between 0 – 100. Solvent is used to form a homogenized mixture by dissolving the polymer and pigments. Solvent also adjusts the viscosity of the paint. Solvent is a volatile part of the paint. Functions of solvent also include flow control flow, stability of paint liquid and improving application properties.

Table 3: Comparison between inorganic and organic pigments.

Table 4: Refractive Index (R.I.) of Common Materials in Paint.

The main solvent for water based paints is water. The solvent for oil-based paints can be white spirit, mineral turpentine oil, alcohols, ketones, etc. Additives are liquids which gives dramatic effect on paint quality. There are different functions of different additives. Some additives change the surface tension of the paint film; some additives enhance the flow pattern of the paint or improve the appearance of the paint. Different additives have different impact on the liquid paint or paint film like changing wet edge, increasing stability of the pigments used, ant freezing effect, low foaming, less skinning, etc. There are different types of paint additives like gelling agents, hydroxyethyl cellulose, emulsifiers, different biocides, UV stabilizers, etc. Emulsion paints are waterbased paints containing water, binder, additives and pigments. Curing of Emulsion latex paints is done by coalescence. Coalescence is a process in which the coalescing solvent draws together and the binder particles are soften to bind them together into irreversibly bound networked structures. Alkyd enamel are paints that cure by oxidative crosslinking. These paints need drier additives like cobalt naphthenate, calcium naphthenate and lead naphthenate to start oxidation process for drying. Some paints are one or two package coatings. These paints dry through a chemical reaction.

Materials and Methods

The following Instruments and Analyzers Were used to Analyze Various Properties of Paint Samples

1. Conventional Agitator, (laboratory mixer manufactured by BEVS Industrial Co. Ltd., China. Model: BEVS 2501/1)
2. Brookfield DV2T viscometer
3. Nano grinding machine (nano mill manufactured by Dongguan Longley Machinery Co. Ltd. China. Model no. NT-1L)
4. Spectrophotometer, model data color 110
5. Grind Gauge, sheen UK, range 0-100 μm
6. Hiding Power Charts, sheen UK, Coated, 255 x 140 mm
7. Automatic film applicator (manufactured by BEVS Industrial Co. Ltd., China. Model Number :BEVS1811/2)
8. Tri-Glossmaster , sheen UK, angles 20-60-85°
9. Wet abrasion scrub tester
10. Stop watch
11. Cryptometer , sheen UK, with K007 plates
12. Pyknometer, sheen UK
13. Malvern Mastersizer, Malvern Instruments Ltd. UK.
14. Brookfield KU-1+ viscometer
15. High speed agitator, rpm 1400

The Following Chemicals were used in the Preparation of Paint Samples

1. Water
2. Dispersant, solution of an ammonium salt of an acrylic polymer in water
3. Calcium carbonate, 400 mesh particle size
4. Hydroxyethyl cellulose thickener powder
5. Ammonium hydroxide solution (25% actives)
6. Latex binder, which is ter polymer of vinyl acrylic emulsion
7. Biocide A, a water based combination of chloromethyl-/ methylisothiazolone (CMI/ MI) and O-formal
8. Biocide B, a combination of two isothiazalone derivatives that can provide broad-spectrum micro-organism control in waterbased coatings

Sample Preparation

Determination of Dispersant Demand

The first step in sample preparation was to determine dispersant demand for current 400 mesh calcium carbonate sample. The complete covering of the surface is an indispensable prerequisite to achieve an ideal stabilization of the dispersed pigments. The fact that the viscosity of pigment slurry reaches a minimum when the pigment surface is completely covered with a dispersant is used to determine the dispersant demand. The dispersant is added in portions to the stirred pigment slurry. After the addition and mixing the viscosity is measured at low shear rates (e.g. with a Brookfield viscometer). The dispersant is added until a minimum of viscosity or constant viscosity is obtained in the viscosity measurements [10].

Procedure for Dispersant Determination

440 gm water was taken in 2500 mL agitated tank of laboratory mixer (Figure 1). Mixing at 500 rpm was started and 1500 gm calcium carbonate of particle size 400 mesh was added in mixing tank. Dispersion of calcium carbonate slurry was done for 05 minutes under 1000 rpm. Viscosity was measured at 25C using Brookfield KU-1+ viscometer following the standard ASTM D562. i.e. “Standard Test Method for Consistency of Paints Measuring Krebs Unit (KU) Viscosity Using a Stormer-Type Viscometer”. The effect of successive addition of 2 gm dispersant on the viscosity of the sample was observed under the same operating conditions as shown in the (Table 5). The procedure was continued till no significant change in viscosity was observed. (Figure 2) shows that optimum dispersant demand was 22 gm for 1500 gm CaCO3 of particle size 400 mesh after which no significant change in viscosity was observed.

Table 5: Dispersant requirement.

Figure 1: BEVS laboratory mixer.

Figure 2: Viscosity versus Dispersant quantity.

Calcium Carbonate Slurries Preparation

The composition of calcium carbonate slurry was prepared as shown in (Table 6) using nano mill (Figure 3) adjusting pneumatic pump pressure between 0.2 to 0.4 MPa. The speed of the nano shaft was adjusted at 2500rpm.Flow rate of calcium carbonate slurry coming out of the nano mill was adjusted around 3 gm/ sec. Dispersion was checked through ASTM-D 1210. i.e. “Standard Test Method for Fineness of Dispersion of Pigment-Vehicle Systems by Hegman-Type Gage”. The term ‘fineness of grind’ is defined as the reading obtained on a gauge under specified conditions of test and the reading indicates the depth of the gauge at which discrete solid particles are readily discernible. Dispersion of calcium carbonate slurry found on hegman guage was below 10 micron. The similar composition (Table 6) was prepared using laboratory mixer. Dispersion of calcium carbonate slurry found on hegman guage was 50 micron.

Table 6: Calcium carbonate slurry composition.

Figure 3: Nano mill.

Determination of Various Properties of Paint Samples

Panels Applications

Panels are applied on hiding power charts through Automatic Film Applicator following the standard ASTM D 823-95.i.e. “Producing Films of Uniform Thickness of Paint, Varnish, and Related Products on Test Panels” as shown in (Figure 4). This standard is under the jurisdiction of ASTM Committee D01 on Paint and Related Coatings, Materials, and Applications and are the direct responsibility of Subcommittee D01.23 on Physical Properties of Applied Paint Films. From the panels drawn, difference in physical properties of latex paints were observed in terms of viscosity, density, pH values, wet hiding, gloss, smoothness, drying time, whiteness, scrubs and opacity. The results so obtained are summarized in (Tables 7 & 8).

Table 7: Latex Paint composition.

Table 8: Specifications of paint samples manufactured through Nano Mill and Conventional Agitator.

Figure 4: Comparison of Wet panel (left) and Dried panel (right) for
(a) nano mill
(b) and conventional agitator.

Wet and Dry Opacity

Wet hiding was checked through Crypto meter. The Crypto meters offer a quick method to determine the wet opacity, hiding power and coverage in square meters per liter of liquid coating materials. A small sample of liquid coating (approximately 4ml) was applied on the joint line of the black and white base plate, the top plate (pins facing downwards) was placed across base plate joint line the sample forms a wedge of paint, (maximum thickness nearest the pins) by sliding the plate back and forth till the sample perfectly hides both the black and the white section of the base plate. At the position of hiding a reading was observed on the engraved scale of the Base Plate, this was then converted into covering power (Square meters/liter).Top Plates (number K007) were offered with each of the Crypto meter products to cover a range of film thickness.

Gloss Measurements

Gloss was tested through Tri-Gloss master following the standard ASTM D2457. i.e. “Standard Test Method for Specular Gloss of Plastic Films and Solid Plastics”.

Dry Hiding and Whiteness

Dry Opacity was checked through Spectrophotometer data color 110.

Drying Time

Drying time was measured through stop watch at ambient temperature.

Adhesion / Scrubs

Scrubs were checked through Wet abrasion scrub tester following the standard ASTM D 3450. i.e. “Standard Test Method for Wash ability Properties of Interior Architectural Coatings”.

Viscosity

Viscosity was tested through Brookfield DV2T latest viscometer following the standard ASTM D1084. i.e. “Standard Test Methods for Viscosity of Adhesives”.

Density

Densities of the samples were measured through Pyknometer following the standard ASTM D1475. i.e. “Standard Test Method for Density of Liquid Coatings, Inks, and Related Products”.

Specific Surface Area and Particle Size

Specific surface area and Particle size of calcium carbonate slurries manufactured through nano mill as well as through conventional agitator was tested with Malvern Mastersizer

PH Value

PH values of the samples were tested through pH meter following the standard ASTM ASTM E70 – 07(2015). i.e. “Standard Test Method for pH of Aqueous Solutions with the Glass Electrode”.

Discussion and Results

Paint in which calcium carbonate slurry processed from Nano mill showed brilliant results in terms of wet opacity, dry opacity, gloss, smoothness and drying time compared to the paint in which calcium carbonate slurry processed through laboratory mixer as shown in (Figure 4). All quality parameters were significantly increased in the paint in which calcium carbonate slurry processed from Nano mill.

Conclusion

It is observed that with the reduction of particle size of calcium carbonate, latex paint showed better results in terms of better hiding, better whiteness, higher gloss, more adhesion. Calcium carbonate slurry processed through Nano mill showed exceptionally good compared to conventional agitator. The slurry processed through Nano Mill reduced the particle size of calcium carbonate from 37.5 microns to 2.63 microns while the slurry processed through conventional agitator reduced the particle size of calcium carbonate from 37.5 microns to 18.05 microns. Furthermore, the paint manufactured with Nano mill slurry showed better Whiteness, wet hiding, dry hiding, adhesion and gloss than the paint manufactured with conventional agitator.

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