Tenofovir disoproxil fumarate associated nephrotoxicity: a retrospective cohort study at two referral hospitals in Namibia.

INTRODUCTION: The incidence and risk factors of tenofovir disoproxil fumarate (TDF)-related renal impairment (RI) in Namibia are unknown where TDF-containing ART regimens are used as the first line for HIV. METHODOLOGY: A retrospective cohort study among HIV-infected patients at two intermediate hospitals. A decline in estimated glomerular filtration rate (eGFR) was significant if it was ≥25% and included a change to a lower eGFR stage. New-onset RI was defined as an eGFR <50 mL/min/1.73m2 . RESULTS: 10 387 patients were included: 11.4% (n = 1182) experienced the decline in eGFR. Of these, 0.6% (n = 62) migrated to eGFR stages IV and V. The incidence was 4.5 (95% CI: 4.3-4.8) per 100 patient years. RI developed in 400 patients for an incidence rate of 2.4 (95% CI: 2.2-2.6) cases per 100 patient years. Risk factors with effect sizes >2.0, for decline-in-eGFR were baseline eGFR >60 (aHR = 15.6); hyperfiltration (aHR = 5.0); and pregnancy (aHR = 2.4); while for RI, they were hyperfiltration (aHR = 4.1) and pregnancy (aHR = 29). CONCLUSION: The incidence of decline-in-eGFR was higher than in other sub-SSA countries, but not RI. A high baseline eGFR had the greatest risk for the decline, and hyperfiltration for the RI.

An analysis of policies for cotrimoxazole, amoxicillin and azithromycin use in Namibia's public sector: Findings and therapeutic implications.

BACKGROUND: Despite Namibia's robust medicine use systems and policies, antibiotic use indicators remain suboptimal. Recent medicine use surveys rank cotrimoxazole, amoxicillin and azithromycin (CAA) among the most used medicines. However, there is rising resistance to CAA (55.9%-96.7%). Unfortunately, to date, there have been limited studies evaluating policies to improve antibiotic use in Namibia. AIM: To evaluate public sector pharmaceutical policies and guidelines influencing the therapeutic use of CAA antibiotics in Namibia. METHODS: Evaluate Namibia's pharmaceutical policies and guidelines for CAA use through quantitative text analysis. The main outcome variables were the existence of antibiotic policies, therapeutic indications per antibiotic and the type/level of healthcare facility allowed to use the antibiotic. RESULTS: Policies for antibiotic use were limited, with only the draft Namibia Medicines Policy having a statement on antibiotic use. Several essential antibiotics had no therapeutic indications mentioned in the guidelines. Twenty-nine antibiotics were listed for 69 therapeutic indications; CAA (49.3%) antibiotics and ATC J01C/J01D (48%) having the highest indications per antibiotic. For CAA antibiotics, this suggested use was mainly for acute respiratory infections (n=22, 37.2%). Published policies (58.6%-17/29) recommended antibiotics for use at the primary healthcare (PHC) level, with CAA antibiotics recommended mostly for respiratory tract infections and genitourinary infections. CONCLUSIONS: Policy and guidelines for antibiotic use in Namibia are not comprehensive and are skewed towards PHCs. Existing policies promote the wide use of CAA antibiotics, which may inadvertently result in their inappropriate use enhancing resistance rates. This calls for the development of more comprehensive antibiotic guidelines and essential medicine lists in tandem with local antimicrobial resistance patterns. In addition, educational initiatives among all key stakeholder groups.

Effect of tenofovir containing ART on renal function in patients with moderate/severe reduced creatinine clearance at baseline: A retrospective study at two referral hospitals in Namibia.

Prescription of tenofovir disoproxil fumarate (TDF) for patients with baseline creatinine clearances (CrCl) <60 mL/min is said to increase risk of further decline in CrCl. Study objectives were to assess incidence of improvement and predictors thereof; to assess incidence of decline and transition to lower stages of CrCl; and comparison of declines between patients with a baseline CrCl < 60mL/min (group-I) and ≥ 60 mL/min (group-II). The study was retrospective, included patients 16 yrs or older who received TDF-containing ART. Improvement and decline were defined as ≥ 25% increase or decrease in CrCl, respectively. Binary logistic regression was performed to identify predictors of improvement. Groups I and II had 2862 and 7526 patients, respectively. In group-I, improvement in CrCl was observed in 40.1% (n = 1146), and was associated with stage IV of CrCl (adjusted Odds Ratio [aOR]=13.4 [95% CI: 6.7 - 26.9, P < .001]); male gender (aHR = 1.8 [95% CI: 1.5 - 2.2, P < .001]); and a poor HIV-status (aHR = 1.2 [95% CI: 1.0 - 1.4], P = .033). In group-I and group-II, respectively, decline occurred in 2.3% and 13.0%, (P < .001); transition to lower stages occurred in 1.0% and 25.2% (P < .001); and migration to stage IV CrCl occurred in 1.0% and 0.5% (P < .001). Improvement was more likely than decline in group-I patients. Although, group-I patients were more likely to experience new onset severe reduced CrCl than group-II patients, the proportions were extremely low. TDF should not be withheld from HIV-positive patients with a baseline CrCl < 60 mL/min.

Corrigendum to "Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications".

[This corrects the article DOI: 10.1155/2021/9996193.].

Records linkage of electronic databases for the assessment of adverse effects of antiretroviral therapy in sub-Saharan Africa.

PURPOSE: In 2009, the Ministry of Health and Social Services in Namibia decided to conduct a confirmatory assessment of the risk of anemia associated with zidovudine (AZT)-based highly active antiretroviral therapy (HAART) using records contained in three electronic databases. These records did not share a unique identifying number. The first step was to apply probabilistic record linkage methods to link records in the three databases. METHODS: Records of persons, aged 19-65 years, newly initiated on HAART between January 2007 and June 2008, were selected from a pharmacy electronic dispensing tool (EDT) and linked to an electronic medical records database (ePMS) and a laboratory database (MEDITECH). Using the paper-based clinical record as the gold standard, we measured the sensitivity of the starting HAART regimen, that is, proportion of AZT users in the clinical record correctly identified in electronic record, and specificity of severe anemia, that is, proportion of non-cases of severe anemia in the clinical records correctly identified in the electronic record. Kappa and intraclass correlation coefficients were used to determine reliability. RESULTS: A total of 12 358 records were selected from EDT. Seventy-six percent and 58% of EDT records were linked to ePMS and MEDITECH, respectively. The sensitivity of the starting HAART regimen was 98%, whereas specificity of severe anemia was 100%. The reliability scores for variables including weight, hemoglobin, and CD4 counts were moderate to perfect and ranged from 0.59 to 0.99. CONCLUSION: Probabilistic record linkage methods were effective for records linkage in this sub-Saharan African setting.

Assessing smoking cessation services and pharmacotherapy in Namibia: findings and implications for future policy initiatives.

BACKGROUND: Tobacco smoking is a considerable barrier to reducing morbidity and mortality associated with non-communicable diseases (NCDs). However, few studies in sub-Saharan Africa have explored access to smoking cessation programs including smoking cessation pharmacotherapy (SCP). This needs to be addressed given the growing burden of NCDs across sub-Saharan Africa including Namibia. METHODS: Multi-facility cross-sectional survey among physicians in both public and private sectors in Namibia. RESULTS: Of the 106 physicians recruited, 69% practiced in public health facilities and 92% were nonsmokers. Sixty-seven percent offer smoking cessation services, with 64% of these offering SCP. This was mainly nicotine replacement therapy (53%) and bupropion SR (41%). Overall, all physicians had a low knowledge score of SCP (<50%). The mean knowledge score though was 77% lower among physicians in public versus private sectors (OR = 0.23, 95%CI: 0.14-0.35, p < 0.001). Principal barriers to prescribing SCP were inadequate knowledge and/or lack of smoking cessation guidelines. This is not surprising with SCP medicines not currently listed within the public medicine list in Namibia. CONCLUSION: Despite good attitudes toward SCP, there are concerns with physicians' knowledge and practices especially in the public sector. There is an urgent need to address this and integrate services to reduce NCDs in Namibia.

Antimicrobial resistance among bacteria isolated from urinary tract infections in females in Namibia, 2016-2017.

BACKGROUND: The emergence of antimicrobial resistance (AMR) among bacterial pathogens demands a local understanding of the epidemiological situation. This information is needed both for clinical treatment decision-making purposes as well as for the revision of current care guidelines. Clinical AMR data from Namibia is sparse, whilst urinary tract infections remain not only widespread but they disproportionally affect females. This paper aims to describe the national antimicrobial resistance situation of major bacterial uropathogens in females within the 14 Namibian regions. METHOD: Retrospective countrywide information on clinical urine cultures performed in females in Namibia in 2016-2017 was obtained from the national public health laboratory, Namibia Institute of Pathology (NIP). The data set included both microbiological findings as well as antimicrobial susceptibility test (AST) results. The AST was done as per the Clinical and Laboratory Standards Institute (CLSI) guidelines. Resistance to 3rd generation cephalosporins was indicative of Extended Spectrum-ß-lactamase (ESBL) production. Data analysis was done with WHONET using expert interpretation rules. RESULTS: In total, 22,259 urinary cultures were performed, of which 13,673 (61.4%) were culture positive. Gram-negative bacterial species accounted for 72.6% of the findings. The most common pathogens identified were Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis. Most of these were from young females, with a median age ranging from 28 to 32 years for the various pathogens. Resistance to ampicillin was 77.7% in E. coli and 84.9% in K. pneumoniae. In E. coli, resistance to 1st line empiric therapy antibiotic, nitrofurantoin, was below 13%, except for one region that showed 59.2% resistance. Resistance to third generation cephalosporin (3GC) was used as a proxy for ESBL production. By year 2017, 3GC resistance was 22%, 31.4% and 8.3% for E. coli, K. pneumoniae and P. mirabilis, respectively. CONCLUSION: We report high resistance to ampicillin, quinolones and sulfamethoxazole-trimethoprim amongst E. coli. Resistance rates to third-generation cephalosporins was also concerningly high at 22%. Resistance to carbapenems was low. However, superiority of nitrofurantoin was found, which provides rational support for the usefulness of nitrofurantoin as an empiric therapy regimen for the treatment of urinary tract infections in this setting.

Tackling antimicrobial resistance across sub-Saharan Africa: current challenges and implications for the future.

INTRODUCTION: Antimicrobial resistance (AMR) is a concern as this increases morbidity, mortality, and costs, with sub-Saharan Africa having the highest rates globally. Concerns with rising AMR have resulted in international, Pan-African, and country activities including the development of national action plans (NAPs). However, there is variable implementation across Africa with key challenges persisting. AREAS COVERED: Consequently, there is an urgent need to document current NAP activities and challenges across sub-Saharan Africa to provide future guidance. This builds on a narrative review of the literature. EXPERT OPINION: All surveyed sub-Saharan African countries have developed their NAPs; however, there is variable implementation. Countries including Botswana and Namibia are yet to officially launch their NAPs with Eswatini only recently launching its NAP. Cameroon is further ahead with its NAP than these countries; though there are concerns with implementation. South Africa appears to have made the greatest strides with implementing its NAP including regular monitoring of activities and instigation of antimicrobial stewardship programs. Key challenges remain across Africa. These include available personnel, expertise, capacity, and resources to undertake agreed NAP activities including active surveillance, lack of focal points to drive NAPs, and competing demands and priorities including among donors. These challenges are being addressed, with further co-ordinated efforts needed to reduce AMR.

Nevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin.

BACKGROUND: rifampicin lowers nevirapine plasma concentrations by inducing cytochrome P450. However, few data are available on this interaction during the lead-in period of nevirapine treatment. METHODS: eighteen HIV-1/tuberculosis co-infected adults receiving rifampicin daily as part of anti-tuberculosis therapy were evenly randomized to nevirapine initiation by dose escalation (NVP200) or nevirapine initiation at 200 mg twice daily (NVP400). Subjects underwent 12 h intensive pharmacokinetic sampling on Days 7, 14 and 21 of nevirapine treatment. A minimum effective concentration (MEC) of 3000 ng/mL was used to interpret nevirapine concentrations 12 h after dosing (C(12)). TRIAL REGISTRATION NUMBER: NCT00617643 (www.clinicaltrials.gov). RESULTS: day 7 geometric mean nevirapine C(12) [90% confidence interval (CI)] was 1504 (1127-2115) ng/mL and 3148 (2451-4687) ng/mL in the NVP200 and NVP400 arms, respectively (P < 0.01). Nevirapine C(12) on Days 14 and 21 was similar. On Day 21, nevirapine concentration in 64% of patients was below the MEC. On Day 7, geometric mean area under the curve (AUC(0-12)) was lower in the NVP200 arm, 25 223 (90% CI, 21 978-29 695) ng·h/mL versus 43 195 (35 607-57 035) ng·h/mL in the NVP400 arm (P  <  0.01). Similarly, on Day 14, nevirapine AUC(0-12) was lower in the NVP200 arm 23 668 (18 253-32 218) ng·h/mL versus the NVP400 arm 44 918 (36 264-62 769) ng·h/mL (P = 0.03). CONCLUSIONS: in co-treated patients, nevirapine concentrations were below the MEC during initiation with dose escalation. Nevirapine initiation at the maintenance dose of 200 mg twice daily is preferred. Sub-therapeutic nevirapine concentrations were common at Day 21 with either regimen. Evaluation of higher nevirapine maintenance doses may be considered.

Antibiotics' susceptibility patterns of bacterial isolates causing lower respiratory tract infections in ICU patients at referral hospitals in Namibia.

BACKGROUND: Lower respiratory tract infections (LRTIs) are a particular public health concern especially among sub-Saharan African countries. This is especially the case in Namibia, where LRTIs are currently the third leading cause of death, 300 deaths in children under 5 years of age. To reduce the burden of LRTIs on health systems and ensure appropriate patient management, it is critical to know the most prevalent pathogens leading to LRTIs and their susceptibility patterns in the local setting. Consequently, the objective of this study was to formulate cumulative antibiograms for Intensive Care Units (ICUs) of referral hospitals in Namibia to guide future antibiotic use. METHODS: A retrospective analytical cross-sectional study was conducted over 2 years. The cumulative antibiograms were constructed in accordance with current guidelines. RESULTS: A total of 976 first isolate cultures were obtained from ICUs of the different referral hospitals. K. pneumoniae (8.8%, 8.1%) was a predominant pathogen in Windhoek Central hospital ICU in 2017 and 2018. In Oshakati intermediate hospital ICU, Enterobacter sp. (22.2%) and P. aeruginosa (37.5%) were the common pathogens in 2017 and 2018, respectively. A. baumannii isolates were >90% susceptibility to colistin, carbapenems, and tigecycline in 2017. In 2017, K. pneumoniae isolates were more susceptible to carbapenems (94% and 93.8% among isolates), amikacin (89.3%), and tigecycline (88.7%). In 2018, K. pneumoniae isolates were 100% susceptible amikacin, colistin, and carbapenems. S. maltophilia isolates were more than 80% susceptible to all the tested antibiotics. S. aureus isolates were 100% susceptible to linezolid, rifampicin, teicoplanin, and vancomycin in 2017 and in 2018. Its susceptibility to these antibiotics did not change. CONCLUSION: The susceptibility patterns of the common isolated gram-negative pathogens were highly variable. Meropenem in combination with gentamicin is now the recommended antibiotic combination for empiric therapy for patients with LRTIs in Windhoek Central Hospital ICU.

Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications.

BACKGROUND: Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. RESULTS: Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. CONCLUSIONS: There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

Challenges and Innovations Brought about by the COVID-19 Pandemic Regarding Medical and Pharmacy Education Especially in Africa and Implications for the Future.

BACKGROUND: Multiple measures introduced early to restrict COVID-19 have dramatically impacted the teaching of medical and pharmacy students, exacerbated by the lack of infrastructure and experience with e-learning at the start of the pandemic. In addition, the costs and reliability of the Internet across Africa pose challenges alongside undertaking clinical teaching and practical programmes. Consequently, there is a need to understand the many challenges and how these were addressed, given increasingly complex patients, to provide future direction. METHOD: An exploratory study was conducted among senior-level medical and pharmacy educators across Africa, addressing four key questions, including the challenges resulting from the pandemic and how these were dealt with. RESULTS: Staff and student members faced multiple challenges initially, including adapting to online learning. In addition, concerns with the lack of equipment (especially among disadvantaged students), the costs of Internet bundles, and how to conduct practicals and clinical teaching. Multiple activities were undertaken to address these challenges. These included training sessions, developing innovative approaches to teaching, and seeking ways to reduce Internet costs. Robust approaches to practicals, clinical teaching, and assessments have been developed. CONCLUSIONS: Appreciable difficulties to teaching arising from the pandemic are being addressed across Africa. Research is ongoing to improve education and assessments.

Utility of medicines information leaflets in hypertensive care in a setting with low health literacy: A cross-sectional study.

Introduction: Higher levels of health literacy improve utilization of health information, medication adherence and outcomes. Few studies evaluate the utility of medicines information in hypertensive care in settings with low health literacy. Aim: To determine the level of health literacy and utility of medicines information leaflets (MILs) among hypertensive patients in public health care in Namibia. Methods: A hospital-based survey among hypertensive patients receiving care at a referral hospital in Namibia from the 8 June 2018 to 29 June 2018. Patient's health literacy and utility of MIL were assessed using three literacy tools and a survey questionnaire. Quantitative data were analysed using descriptive statistics and qualitative thematic content analysis for factors associate with the utility of the MIL. Results: Of the 139 patients, 63% were female and the mean age was 45.7 (range: 19.0-84.0) years. Over 85.6% had of low literacy skills (Rapid Estimate of Literacy in Medicine (REALM) score <44, that is, unable to read simple health materials), 38.8% had positive Single Item Literacy Screener (SILS) scores (⩾2, require help to read medicines information) and 66.9% had inadequate skills for comprehension, appraisal and decision-making with regard to health information (Health Literacy Skills Instrument-Short Form (HLSI-SF) score <70%). The level of access to and utility of MIL were low, 32.4% and 34.6%, respectively. The main factors associated with poor utility of the MIL were low patient health literacy, lack of guidelines on the use of MIL and MIL written in non-native languages. Conclusion: Low rates of health literacy and utility of MIL were observed among hypertensive patients in Namibia. The integration of health literacy programmes, and MIL guidelines are needed to promote utility of medicine information and improve medication adherence.

Ongoing and planned activities to improve the management of patients with Type 1 diabetes across Africa; implications for the future.

BACKGROUND: Currently about 19 million people in Africa are known to be living with diabetes, mainly Type 2 diabetes (T2DM) (95%), estimated to grow to 47 million people by 2045. However, there are concerns with early diagnosis of patients with Type 1 diabetes (T1DM) as often patients present late with complications. There are also challenges with access and affordability of insulin, monitoring equipment and test strips with typically high patient co-payments, which can be catastrophic for families. These challenges negatively impact on the quality of care of patients with T1DM increasing morbidity and mortality. There are also issues of patient education and psychosocial support adversely affecting patients' quality of life. These challenges need to be debated and potential future activities discussed to improve the future care of patients with T1DM across Africa. METHODOLOGY: Documentation of the current situation across Africa for patients with T1DM including the epidemiology, economics, and available treatments within public healthcare systems as well as ongoing activities to improve their future care. Subsequently, provide guidance to all key stakeholder groups going forward utilizing input from senior-level government, academic and other professionals from across Africa. RESULTS: Whilst prevalence rates for T1DM are considerably lower than T2DM, there are concerns with late diagnosis as well as the routine provision of insulin and monitoring equipment across Africa. High patient co-payments exacerbate the situation. However, there are ongoing developments to address the multiple challenges including the instigation of universal health care and partnerships with non-governmental organizations, patient organizations, and pharmaceutical companies. Their impact though remains to be seen. In the meantime, a range of activities has been documented for all key stakeholder groups to improve future care. CONCLUSION: There are concerns with the management of patients with T1DM across Africa. A number of activities has been suggested to address this and will be monitored.

Review of Ongoing Activities and Challenges to Improve the Care of Patients With Type 2 Diabetes Across Africa and the Implications for the Future.

BACKGROUND: There has been an appreciable increase in the number of people in Africa with metabolic syndrome and Type 2 diabetes (T2DM) in recent years as a result of a number of factors. Factors include lifestyle changes, urbanisation, and the growing consumption of processed foods coupled with increasing levels of obesity. Currently there are 19 million adults in Africa with diabetes, mainly T2DM (95%), estimated to grow to 47 million people by 2045 unless controlled. This has a considerable impact on morbidity, mortality and costs in the region. There are a number of issues to address to reduce the impact of T2DM including improving detection rates and current access to services alongside addressing issues of adherence to prescribed medicines. There are also high rates of co-morbidities with infectious diseases such as HIV and tuberculosis in patients in Africa with T2DM that require attention. OBJECTIVE: Document ongoing activities across Africa to improve the care of patients with T2DM especially around issues of identification, access, and adherence to changing lifestyles and prescribed medicines. In addition, discussing potential ways forward to improve the care of patients with T2DM based on ongoing activities and experiences including addressing key issues associated with co-morbidities with infectious diseases. OUR APPROACH: Contextualise the findings from a wide range of publications including internet based publications of national approaches coupled with input from senior level government, academic and other professionals from across Africa to provide future guidance. ONGOING ACTIVITIES: A number of African countries are actively instigating programmes to improve the care of patients with T2DM starting with improved diagnosis. This recognises the growing burden of non-communicable diseases across Africa, which has been neglected in the past. Planned activities include programmes to improve detection rates and address key issues with diet and lifestyle changes, alongside improving monitoring of care and activities to enhance adherence to prescribed medicines. In addition, addressing potential complexities involving diabetes patients with infectious disease co-morbidities. It is too early to fully assess the impact of such activities. CONCLUSION: There are a number of ongoing activities across Africa to improve the management of patients with diabetes including co-morbidities. However, more needs to be done considering the high and growing burden of T2DM in Africa. Ongoing research will help further benefit resource allocation and subsequent care.

Response to the Novel Corona Virus (COVID-19) Pandemic Across Africa: Successes, Challenges, and Implications for the Future.

BACKGROUND: The COVID-19 pandemic has already claimed considerable lives. There are major concerns in Africa due to existing high prevalence rates for both infectious and non-infectious diseases and limited resources in terms of personnel, beds and equipment. Alongside this, concerns that lockdown and other measures will have on prevention and management of other infectious diseases and non-communicable diseases (NCDs). NCDs are an increasing issue with rising morbidity and mortality rates. The World Health Organization (WHO) warns that a lack of nets and treatment could result in up to 18 million additional cases of malaria and up to 30,000 additional deaths in sub-Saharan Africa. OBJECTIVE: Document current prevalence and mortality rates from COVID-19 alongside economic and other measures to reduce its spread and impact across Africa. In addition, suggested ways forward among all key stakeholder groups. OUR APPROACH: Contextualise the findings from a wide range of publications including internet-based publications coupled with input from senior-level personnel. ONGOING ACTIVITIES: Prevalence and mortality rates are currently lower in Africa than among several Western countries and the USA. This could be due to a number of factors including early instigation of lockdown and border closures, the younger age of the population, lack of robust reporting systems and as yet unidentified genetic and other factors. Innovation is accelerating to address concerns with available equipment. There are ongoing steps to address the level of misinformation and its consequences including fines. There are also ongoing initiatives across Africa to start addressing the unintended consequences of COVID-19 activities including lockdown measures and their impact on NCDs including the likely rise in mental health disorders, exacerbated by increasing stigma associated with COVID-19. Strategies include extending prescription lengths, telemedicine and encouraging vaccination. However, these need to be accelerated to prevent increased morbidity and mortality. CONCLUSION: There are multiple activities across Africa to reduce the spread of COVID-19 and address misinformation, which can have catastrophic consequences, assisted by the WHO and others, which appear to be working in a number of countries. Research is ongoing to clarify the unintended consequences given ongoing concerns to guide future activities. Countries are learning from each other.

Pharmacotherapeutic interventions for bipolar disorder type II: addressing multiple symptoms and approaches with a particular emphasis on strategies in lower and middle-income countries.

Introduction: Appropriately managing mental disorders is a growing priority across countries in view of the impact on morbidity and mortality. This includes patients with bipolar disorders (BD). Management of BD is a concern as this is a complex disease with often misdiagnosis, which is a major issue in lower and middle-income countries (LMICs) with typically a limited number of trained personnel and resources. This needs to be addressed.Areas covered: Medicines are the cornerstone of managing patients with Bipolar II across countries including LMICs. The choice of medicines, especially antipsychotics, is important in LMICs with high rates of diabetes and HIV. However, care is currently compromised in LMICs by issues such as the stigma, cultural beliefs, a limited number of trained professionals and high patient co-payments.Expert opinion: Encouragingly, some LMICs have introduced guidelines for patients with BD; however, this is very variable. Strategies for the future include addressing the lack of national guidelines for patients with BD, improving resources for mental disorders including personnel, improving medicine availability and patients' rights, and monitoring prescribing against agreed guidelines. A number of strategies have been identified to improve the treatment of patients with Bipolar II in LMICs, and will be followed up.

Steady-state pharmacokinetic comparison of generic and branded formulations of stavudine, lamivudine and nevirapine in HIV-infected Ugandan adults.

BACKGROUND: We aimed to compare the steady-state pharmacokinetic parameters and tolerability of Triomune 40 (stavudine 40 mg, lamivudine 150 mg and nevirapine 200 mg) and branded formulations of these drugs in HIV-infected Ugandans. METHODS: This includes a randomized, open-label, cross-over study of HIV-infected patients stable on therapy for 1 month. Patients were randomized to generic or branded formulation. Plasma pharmacokinetics were assessed after 1 month. The following day, alternate formulation was administered, and 1 month later, drug pharmacokinetics were re-assessed. Plasma pharmacokinetics were determined using HPLC-UV detection. Similarity between steady-state pharmacokinetic parameters was assessed using the US Food and Drug Administration standards for bioequivalency testing. Tolerability was assessed using questionnaires. RESULTS: Sixteen (10 females) patients completed the study. Median (IQR) age, weight and CD4 count were 37 (33.7-40) years, 65 (63.4-66) kg and 292 (220.7-344.5) cells/mm(3), respectively. All patients received co-trimoxazole. The geometric mean ratio (90% CI) for stavudine, lamivudine and nevirapine was 0.92 (0.78-1.08), 1.11 (0.95-1.30) and 0.84 (0.64-1.11), respectively, for C(max), and 0.83 (0.70-0.97), 1.06 (0.94-1.20) and 0.88 (0.71-1.10), respectively, for AUC. Stavudine plasma concentrations were significantly lower for the generic formulation. Pharmacokinetic parameter inter-individual variability ranged from 29% to 99%. There were no differences in tolerability for the two formulations. CONCLUSIONS: Pharmacokinetic profiles of generic and branded drugs were similar. Differences particularly with regard to stavudine were demonstrated. Surveillance of the quality of generic antiretroviral drugs in the target populations is needed. Capacity building for pharmacokinetic research in resource-limited settings is a priority.

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets.

Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases, and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growth in both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated to finance new medicines as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimize the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need.

Evidence on the cost-effectiveness of lifelong antiretroviral therapy for prevention of mother-to-child transmission of HIV: implications for resource-limited countries in sub-Saharan Africa.

INTRODUCTION: The 2016 World Health Organization (WHO) consolidated guideline recommends lifelong antiretroviral therapy (ART) for all HIV-infected pregnant and breastfeeding women for preventing mother-to-child HIV transmission (PMTCT). Ambiguity remains about the cost-effectiveness of this strategy in resource-limited developing countries. Areas covered: We reviewed model-based studies on the cost-effectiveness of lifelong ART (formerly Option B+) relative to previous WHO guidelines for PMTCT. Our search using PubMed, Medline and Google Scholar for articles on Option B+ resulted in the final inclusion of seven studies published between 2012 and 2016. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to assess the quality of reporting. Outcomes of interest, which included infant infections averted, maternal quality and length of life, and the Incremental Cost Effectiveness Ratio (ICER), were used in comparing cost-effectiveness. Expert commentary: Despite most model-based studies favouring lifelong ART (Option B+) in terms of its cost-effectiveness in comparison to Options A and B, inclusiveness of the evidence remains weak for generalization. This is largely because setting specificity for providing lifelong ART to all pregnant and breastfeeding women may differ significantly in each setting. Consequently, future cost-effectiveness studies should be robust, setting-specific, and endeavor to assess the willingness and ability to pay of each setting.