Reliability of anthropometric measurements of a digi-board in comparison to an analog height board in Namibian children under 5 years.

Poor measurement quality has set back the utility of anthropometry in defining childhood malnutrition, prompting calls for alternative measurement techniques. This study aimed to assess the reliability of anthropometric measurements using a digital height board in comparison to an analog height board in Namibian children under 5 years of age. A cross-sectional, descriptive study was conducted (n = 425) between the age of 6 and 59 months, using anthropometric measurements of weight, height and mid-upper arm circumference. Two trained enumerators each collected four height measurements of each child: two using an analog height board and two using a digi-board. The repeated height measurements between and within the enumerators were used to determine intra- and interobserver reliability. Reliability of the digi-board was assessed using the technical error of measurement (TEM), relative TEM (%TEM), intraclass correlation and a Bland-Altman analysis to assess the agreement between the two methods. In all these assessments, the analog height board was considered as the gold standard and used for comparison. The digi-board showed superiority to the analog height board in terms of reliability (analog TEM = 0.22, digi-board TEM = 0.16). Although the digi-board has potential to improve child anthropometry, further clinical and large survey studies are needed to validate the used of this tool in routine population-based surveys.

Corn? When did I eat corn? Gastrointestinal transit time in health science students.

The objective of this study was to determine gastrointestinal transit time in first-year health science students with a laboratory practical exercise conducted in two cohorts (classes of 2018 and 2019) of first-year health sciences students at the Health Science Campus in Windhoek, Namibia. All first-year health science students undertaking the Physiology course were invited to take part in the laboratory exercise. The primary outcome was the measurement of gastrointestinal transit time from the amount of time taken for ingested whole-kernel sweetcorn to be eliminated, which was calculated as the time period between ingestion of corn and the time of corn first seen in the stool and the time corn was last seen in the stool. The secondary outcome was an association between emotional irritability and/or anxiety and gastrointestinal transit time. The study analyzed responses of 175 students, who reported a median transit time of 29 (1-99) h. There was no difference in gastrointestinal transit time between male and female students. Likewise, there was no difference in the duration of the corn in the bowel between male and female students. Students who reported being worried and irritable during the exercise had more bowel movements before they saw corn in their stool and had slower transit times, respectively. A wider range of transit time was reported in a group of young, healthy students compared with previous studies in the literature. There were no differences between male and female student bowel activity. Anxiety did impact the bowel activity of the participants.

Optimizing treatment outcome of first-line anti-tuberculosis drugs: the role of therapeutic drug monitoring.

INTRODUCTION: Tuberculosis (TB) remains one of the world's deadliest communicable diseases. Although cure rates of the standard four-drug (rifampicin, isoniazid, pyrazinamide, ethambutol) treatment schedule can be as high as 95-98 % under clinical trial conditions, success rates may be much lower in less well resourced countries. Unsuccessful treatment with these first-line anti-TB drugs may lead to the development of multidrug resistant and extensively drug resistant TB. The intrinsic interindividual variability in the pharmacokinetics (PK) of the first-line anti-TB drugs is further exacerbated by co-morbidities such as HIV infection and diabetes. METHODS: Therapeutic drug monitoring has been proposed in an attempt to optimize treatment outcome and reduce the development of drug resistance. Several studies have shown that maximum plasma concentrations (C max), especially of rifampicin and isoniazid, are well below the proposed target C max concentrations in a substantial fraction of patients being treated with the standard four-drug treatment schedule, even though treatment's success rate in these studies was typically at least 85 %. DISCUSSION: The proposed target C max concentrations are based on the concentrations of these agents achieved in healthy volunteers and patients receiving the standard doses. Estimation of C max based on one or two sampling times may not have the necessary accuracy since absorption rate, especially for rifampicin, may be highly variable. In addition, minimum inhibitory concentration (MIC) variability should be taken into account to set clinically meaningful susceptibility breakpoints. Clearly, there is a need to better define the key target PK and pharmacodynamic (PD) parameters for therapeutic drug monitoring (TDM) of the first-line anti-TB drugs to be efficacious, C max (or area under the curve (AUC)) and C max/MIC (or AUC/MIC). CONCLUSION: Although TDM of first-line anti-TB drugs has been successfully used in a limited number of specialized centers to improve treatment outcome in slow responders, a better characterization of the target PK and/or PK/PD parameters is in our opinion necessary to make it cost-effective.

Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator.

The blood anion nitrite contributes to hypoxic vasodilation through a heme-based, nitric oxide (NO)-generating reaction with deoxyhemoglobin and potentially other heme proteins. We hypothesized that this biochemical reaction could be harnessed for the treatment of neonatal pulmonary hypertension, an NO-deficient state characterized by pulmonary vasoconstriction, right-to-left shunt pathophysiology and systemic hypoxemia. To test this, we delivered inhaled sodium nitrite by aerosol to newborn lambs with hypoxic and normoxic pulmonary hypertension. Inhaled nitrite elicited a rapid and sustained reduction ( approximately 65%) in hypoxia-induced pulmonary hypertension, with a magnitude approaching that of the effects of 20 p.p.m. NO gas inhalation. This reduction was associated with the immediate appearance of NO in expiratory gas. Pulmonary vasodilation elicited by aerosolized nitrite was deoxyhemoglobin- and pH-dependent and was associated with increased blood levels of iron-nitrosyl-hemoglobin. Notably, from a therapeutic standpoint, short-term delivery of nitrite dissolved in saline through nebulization produced selective, sustained pulmonary vasodilation with no clinically significant increase in blood methemoglobin levels. These data support the concept that nitrite is a vasodilator acting through conversion to NO, a process coupled to hemoglobin deoxygenation and protonation, and evince a new, simple and inexpensive potential therapy for neonatal pulmonary hypertension.

Developing a grass-roots method for monitoring medicines shortages in southern Africa: Report of a pilot in Namibia.

Shortages of medicines is a global problem that can have significant impact on health outcomes of patients and reduce the effectiveness of public health programmes. There are a multitude of reasons for medicines shortages occurring, however, and it is important for specific country settings to better understand the issues affecting medicines supply in order to effectively intervene. Namibia relies heavily on imports of medicines as it does not have an adequate pharmaceutical industry sector developed enough to produce sufficient medicines for the burden of disease arising. In addition, because there is no unifying system of medicines monitoring it is difficult to plan interventions to resolve common medicines shortages. This study reports the findings from a pilot survey that was undertaken to improve the information monitoring of medicines shortages in Namibia. The survey sought information from medicines suppliers from various pharmacy sectors who may provide a vital insight into how medicines shortages should be monitored and the causes of shortages observed in Namibia. A more robust survey as part of a broader system can be informed by this survey to address the shortage of medicines in Namibia and surrounding region.

A pragmatic approach to introducing mixed methods research training for pharmacy students in Namibia.

BACKGROUND AND PURPOSE: Pharmacy and medical training were introduced for the first time in Namibia in 2011 and 2010 respectively. All students must complete a research project as part of their training, which is supported by various courses in the respective curricula including research methods. Following a revision of the medical curriculum, there was an opportunity to review the way research methods was taught for both degrees, piloting in pharmacy then expanding to other disciplines. An educational activity that was part of the research methods course for training pharmacy students in Namibia is described. EDUCATIONAL ACTIVITY AND SETTING: The activity described related to a new approach in the running of the research methods course for pharmacy students and included, in a portfolio-based approach, a group project. Students were tasked to collect qualitative data from medical student colleagues that they then needed to codify and ultimately articulate into a survey questionnaire. The questionnaire was subsequently sent out to collect responses on medicines-related items that could be analyzed quantitatively in subsequent teaching sessions. Supportive lectures, tutorials and portfolio assignments were provided during the project. Data were collected the following year to create a more substantive dataset and a screencast video made to benefit future students in the course. FINDINGS AND DISCUSSION: Through the course of this activity students developed a questionnaire survey tool based on qualitative responses to brief interviews with medical students and emergent themes based on qualitative analyses. A dataset was created that allowed demonstration of quantitative analyses and extraction of sub-scales from the questionnaire. Further educational resources were developed to ensure sustainability of this educational resource and retention in the taught curriculum. SUMMARY: The current article discusses the development, implementation and evaluation of this research methods course component. The application of data collected as part of the activity and its relevance to the educational activity is examined as well as lessons learned for the future running of the project and further evaluation.

Protein Identification of Venoms of the African Spitting Cobras, Naja mossambica and Naja nigricincta nigricincta.

Cobra snakes, including Naja mossambica and Naja nigricincta nigricincta, are one of the major groups of snakes responsible for snakebites in southern Africa, producing significant cytotoxicity and tissue damage. The venom of N. mossambica has been briefly characterised, but that of N. n. nigricincta is not reported. The current study identifies the venom proteins of N. mossambica and N. n. nigricincta. This is achieved using sodium dodecyl sulphate (SDS)-polyacrylamide gel eletrophroresis (PAGE), followed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Most of the proteins were less than 17 kDa in both snakes. N. mossambica was found to have 75 proteins in total (from 16 protein families), whereas N.n. nigricincta had 73 (from 16 protein families). Of these identified proteins, 57 were common in both snakes. The proteins identified belonged to various families, including the three-finger toxins (3FTx), Cysteine-rich secretory proteins (CRiSP), Phospholipase A2 (PLA2) and Venom metalloproteinase M12B (SVMP). The current study contributes to the profile knowledge of snake venom compositions, which is of fundamental value in understanding the proteins that play a major role in envenomation.

Creating clinical pharmacy capacity in Namibia: a collaboration to establish a post-graduate pharmacy degree programme.

Namibia has previously relied on external training of pharmacists but began in-country training in 2011. In response to an identified need for postgraduate clinical pharmacy development and training in the country, a Master's degree was set up at the University of Namibia in 2016. The country has a considerable health burden of HIV and TB as well as a shortage of healthcare professionals. A UK clinical diploma model was adapted to meet the specific needs of the country and wider region, ensuring students could access the course over a sparsely populated, but large geographical spread, in addition to providing work-based learning, embedding research skills for future development, and focusing on the health needs of Namibia. The course uses online learning platforms and contact sessions to cover both knowledge and skill acquisition throughout the 3 years of the course. UK and US clinical pharmacists are utilised to provide specialist input, both remotely and within student workplaces, and further support has come from collaborations, including cross-site visits, with the UK-based pharmacy school whose diploma model was adapted. Challenges have included a shortage of clinical mentors, also compounding the students' difficulty in visualising their future roles, as well as lone practitioners finding it hard to attend all contact sessions. The initial dropout rates of earlier cohorts have since reduced with greater understanding of the programme, and enthusiasm for the course remains high. The aim for the Master's is to train students to become competent clinical pharmacists, thus having the knowledge and skills to mentor future cohorts of the course, as well as expanding the specialty within the country.

High levels of HIV drug resistance among adults failing second-line antiretroviral therapy in Namibia.

To support optimal third-line antiretroviral therapy (ART) selection in Namibia, we investigated the prevalence of HIV drug resistance (HIVDR) at time of failure of second-line ART. A cross-sectional study was conducted between August 2016 and February 2017. HIV-infected people ≥15 years of age with confirmed virological failure while receiving ritonavir-boosted protease inhibitor (PI/r)-based second-line ART were identified at 15 high-volume ART clinics representing over >70% of the total population receiving second-line ART. HIVDR genotyping of dried blood spots obtained from these individuals was performed using standard population sequencing methods. The Stanford HIVDR algorithm was used to identify sequences with predicted resistance; genotypic susceptibility scores for potential third-line regimens were calculated. Two hundred thirty-eight individuals were enrolled; 57.6% were female. The median age and duration on PI/r-based ART at time of enrolment were 37 years and 3.46 years, respectively. 97.5% received lopinavir/ritonavir-based regimens. The prevalence of nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and PI/r resistance was 50.6%, 63.1%, and 13.1%, respectively. No significant association was observed between HIVDR prevalence and age or sex. This study demonstrates high levels of NRTI and NNRTI resistance and moderate levels of PI resistance in people receiving PI/r-based second-line ART in Namibia. Findings underscore the need for objective and inexpensive measures of adherence to identify those in need of intensive adherence counselling, routine viral load monitoring to promptly detect virological failure, and HIVDR genotyping to optimize selection of third-line drugs in Namibia.

Evidence-Responsive Health Training to HIV/TB Risks in Namibia.

Training health-care students in settings with high-prevalence HIV and tuberculosis (TB) presents a challenge to reduce the risk of infection during their clinical training while maintaining quality education. We sought to gauge the risk of exposure to HIV and TB and identify associated variables through two cross-sectional surveys of health students at the University of Namibia. In the HIV exposure survey, overall almost one-quarter of students (N = 367) reported exposure to HIV-most often needle-stick injury-with a much higher rate reported in senior years (73% in year 6). One in 10 students responding to the TB survey were found to have been exposed to TB (N = 290). Regression analyses suggested that time-related factors were a common predictor of risk of both HIV and TB in this setting. We consider that the overall exposure rate to HIV and TB was high, suggesting that training could be improved to reduce the risks of exposure.

Health workforce planning in Namibia: assessing a pilot workforce survey of pharmacists.

BACKGROUND: Southern Africa lacks resources necessary to combat presenting health challenges. This crisis will likely be remedied through the in-country training of healthcare professionals, for example, in Namibia. Monitoring the workforce will be essential to inform planning in health services and training. A national pilot workforce survey in Namibia using a multi-modal sampling approach aimed to test methodology for describing the pharmacy workforce and quantifying preferences towards further training. METHODS: The survey tool included questions relating to socio-demographics, professional and practice aspects. A conjoint analysis approach was utilised to quantify preferences around study programme, modality of study and cost. KEY FINDINGS: Respondents (N = 135; ~20% response) represented a diverse range of individuals in various pharmacy sectors in Namibia. The majority of respondents reported female gender, private sector working, studying outside Namibia and societal group membership. Societal membership and pharmacy ownership - indicators of professional engagement - were associated with higher age; ownership was also associated with study outside Namibia and practice in community pharmacy. Regarding further study preferences, respondents placed more importance on study programme and modality over cost with the most preferred scenario being a 2-year full-time Masters programme in pharmaceutical industry/regulation by distance learning at the highest cost bracket. CONCLUSIONS: This national survey sampled the population of pharmacists in Namibia exploring the composition of the profession and preferences towards training. Further work will validate the findings and provide ongoing monitoring of the pharmacy workforce that can be expanded to other professional groups over a larger geographical area.

Health students' knowledge and infectious disease exposure: findings from a cross-sectional study in Namibia.

BACKGROUND: Namibia has recently introduced a number of health training programmes that expose students to infectious disease risks such as human immunodeficiency virus (HIV) and tuberculosis (TB). We explored the knowledge of students in relation to HIV and TB and whether or not there was evidence of exposure. METHODS: We conducted two cross-sectional surveys of Namibian health students (medicine and pharmacy) in 2018. RESULTS: There was a strong association between knowledge and exposure to HIV, but not TB (i.e. explicit exposure versus latent). Regression analysis suggested the time-related risk (age/year of study) to be predictive of knowledge in both studies. The training rotation in the respiratory unit predicted TB knowledge and post-exposure prophylaxis predicted HIV knowledge. CONCLUSIONS: Knowledge of TB and HIV appears mostly related to the duration of study in health students. Exposure or specific experience may enhance knowledge. Future training in infection control may be better focussed on improving knowledge in earlier years.

Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation.

BACKGROUND: The recent discovery that nitrite is an intrinsic vasodilator and signaling molecule at near-physiological concentrations has raised the possibility that nitrite contributes to hypoxic vasodilation and to the bioactivity of nitroglycerin and mediates the cardiovascular protective effects of nitrate in the Mediterranean diet. However, important questions of potency, kinetics, mechanism of action, and possible induction of tolerance remain unanswered. METHODS AND RESULTS: In the present study, we performed biochemical, physiological, and pharmacological studies using nitrite infusion protocols in 20 normal human volunteers and in nonhuman primates to answer these questions, and we specifically tested 3 proposed mechanisms of bioactivation: reduction to nitric oxide by xanthine oxidoreductase, nonenzymatic disproportionation, and reduction by deoxyhemoglobin. We found that (1) nitrite is a relatively potent and fast vasodilator at near-physiological concentrations; (2) nitrite functions as an endocrine reservoir of nitric oxide, producing remote vasodilation during first-pass perfusion of the opposite limb; (3) nitrite is reduced to nitric oxide by intravascular reactions with hemoglobin and with intravascular reductants (ie, ascorbate); (4) inhibition of xanthine oxidoreductase with oxypurinol does not inhibit nitrite-dependent vasodilation but potentiates it; and (5) nitrite does not induce tolerance as observed with the organic nitrates. CONCLUSIONS: We propose that nitrite functions as a physiological regulator of vascular function and endocrine nitric oxide homeostasis and suggest that it is an active metabolite of the organic nitrates that can be used therapeutically to bypass enzymatic tolerance.

A novel method of measuring reduction of nitrite-induced methemoglobin applied to fetal and adult blood of humans and sheep.

The reaction of nitrite with deoxyhemoglobin results in the production of nitric oxide and methemoglobin, a reaction recently proposed as an important oxygen-sensitive source of vasoactive nitric oxide during hypoxic and anoxic stress, with several animal studies suggesting that nitrite may have therapeutic potential. Accumulation of toxic levels of methemoglobin is suppressed by reductase enzymes present within the erythrocyte. Using a novel method of measuring methemoglobin reductase activity in intact erythrocytes, we compared fetal and adult sheep and human blood. After nitrite-induced production of 20% methemoglobin, the blood was equilibrated with carbon monoxide, which effectively stopped further production. Methemoglobin disappearance was first order in nature with specific rate constants (k x 1,000) of 12.9 +/- 1.3 min(-1) for fetal sheep, 5.88 +/- 0.26 min(-1) for adult sheep, 4.27 +/- 0.34 for adult humans, and 3.30 +/- 0.15 for newborn cord blood, all statistically different from one another. The effects of oxygen tensions, pH, hemolysis, and methylene blue are reported. Studies of temperature dependence indicated an activation energy of 8,620 +/- 1,060 calories/mol (2.06 kJ/mol), appreciably higher than would be characteristic of processes limited by passive membrane diffusion. In conclusion, the novel methodology permits absolute quantification of the reduction of nitrite-induced methemoglobin in whole blood.

The measurement of blood and plasma nitrite by chemiluminescence: pitfalls and solutions.

There are a number of difficulties involved in the quantification of nitrite in biological systems. These difficulties result from oxidation of nitrite (within minutes) by heme proteins, such as hemoglobin, myoglobin, cytoglobin, and neuroglobin; its low levels in vivo; and its ubiquitous presence in laboratory buffers and glassware. The goal of this review is to present an assay suitable for the sensitive and specific measurement of intravascular nitrite in mammals using the chemiluminescence-based nitric oxide analyzer and to inform the reader on how to evade the pitfalls pertinent to nitrite determination in biological matrices.

Cerebral oxygenation during postasphyxial seizures in near-term fetal sheep.

After exposure to asphyxia, infants may develop both prolonged, clinically evident seizures and shorter, clinically silent seizures; however, their effect on cerebral tissue oxygenation is unclear. We therefore examined the hypothesis that the increase in oxygen delivery during postasphyxial seizures might be insufficient to meet the needs of increased metabolism, thus causing a fall in tissue oxygenation, in unanesthetized near-term fetal sheep in utero (gestational age 125+/-1 days). Fetuses were administered an infusion of the specific adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine, followed by 10 mins of asphyxia induced by complete umbilical cord occlusion. The fetuses then recovered for 3 days. Sixty-one episodes of electrophysiologically defined seizures were identified in five fetuses. Tissue PO(2) (tPO(2)) did not change significantly during short seizures (<3.5 mins), 5.2+/-0.2 versus baseline 5.6+/-0.1 mm Hg (NS), but fell to 2.2+/-0.2 mm Hg during seizures lasting more than 3.5 mins (P<0.001). During prolonged seizures, cortical blood flow did not begin to increase until tPO(2) had begun to fall, and then rose more slowly than the increase in metabolism, with a widening of the brain to blood temperature gradient. In conclusion, in the immature brain, during prolonged, but not short seizures, there is a transient mismatch between cerebral blood flow and metabolism leading to significant cerebral deoxygenation.