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Vitamin B12 is an essential micronutrient required for optimal hemopoetic, neuro-cognitive and cardiovascular function. Biochemical and clinical vitamin B12 deficiency has been demonstrated to be highly prevalent among patients with type 1 and type 2 diabetes mellitus. It presents with diverse clinical manifestations ranging from impaired memory, dementia, delirium, peripheral neuropathy, sub acute combined degeneration of the spinal cord, megaloblastic anemia and pancytopenia. This review article offers a current perspective on the physiological roles of vitamin B12, proposed pathophysiological mechanisms of vitamin B12 deficiency, screening for vitamin B12 deficiency and vitamin B12 supplementation among patients with diabetes mellitus.

BackgroundCurrently, Sub Saharan Africa is faced with a substantial burden from diabetes mellitus. In most of the African countries, screening for diabetes related complications and control of blood pressure and glycaemic levels is often suboptimal.The study aimed at assessing the extent of optimal glycaemic and blood pressure control and the frequency of screening for diabetic complications in adult ambulatory Ugandan diabetic patients.MethodsThis was a retrospective study of 250 medical records of adult diabetic patients attending the outpatient diabetic clinic at St. Raphael of St. Francis hospital Nsambya in Kampala, Uganda.ResultsThe mean age of the patients was 51.6 ± 9.2 years with the majority being females (155, 62%). Using fasting blood glucose levels assessed in all the patients, optimal glycemic control of <7.2 mmol/l was noted in 42.8% of the patients. Glycated haemoglobin was performed at least once in the last year in 24 (9.6%) patients , of which 5 (20.8%) of these attained optimal control of <7%. Optimal blood pressure (BP) control defined as BP ≤140/80 mmHg was noted in 56% of the patients. Hypertension and diabetic neuropathy were the most screened for diabetic complications in 100% and 47.2% of the patients respectively and were also the most prevalent diabetic complications (76.4% and 31.2% respectively).ConclusionsThis study demonstrates that glycemic and blood pressure control and screening for diabetic complications among the adult ambulatory diabetic patients in this urban diabetic clinic is suboptimal. This substantiates development and implementation local guidelines to improve diabetes care.

BackgroundEquitable access to affordable medicines and diagnostic tests is an integral component of optimal clinical care of patients with asthma and chronic obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about the availability, cost and affordability of medicines and diagnostic tests essential in asthma and COPD management.MethodsData on the availability, cost and affordability of 17 medicines and 2 diagnostic tests essential in asthma and COPD management were collected from 22 public hospitals, 23 private and 85 private pharmacies. The percentage of the available medicines and diagnostic tests, the median retail price of the lowest priced generic brand and affordability in terms of the number of days’ wages it would cost the least paid public servant were analysed.ResultsThe availability of inhaled short acting beta agonists (SABA), oral leukotriene receptor antagonists (LTRA), inhaled LABA-ICS combinations and inhaled corticosteroids (ICS) in all the study sites was 75%, 60.8%, 46.9% and 45.4% respectively. None of the study sites had inhaled long acting anti muscarinic agents (LAMA) and inhaled long acting beta agonist (LABA)-LAMA combinations. Spirometry and peak flow-metry as diagnostic tests were available in 24.4% and 6.7% of the study sites respectively. Affordability ranged from 2.2 days’ wages for inhaled salbutamol to 17.1 days’ wages for formoterol/budesonide inhalers and 27.8 days’ wages for spirometry.ConclusionMedicines and diagnostic tests essential in asthma and COPD care are not widely available in Uganda and remain largely unaffordable. Strategies to improve access to affordable asthma and COPD medicines and diagnostic tests should be implemented in Uganda.

SummaryBackgroundCross-resistance after first-line antiretroviral therapy (ART) failure is expected to impair activity of nucleoside reverse-transcriptase inhibitors (NRTIs) in second-line therapy for patients with HIV, but evidence for the effect of cross-resistance on virological outcomes is limited. We aimed to assess the association between the activity, predicted by resistance testing, of the NRTIs used in second-line therapy and treatment outcomes for patients infected with HIV.MethodsWe did an observational analysis of additional data from a published open-label, randomised trial of second-line ART (EARNEST) in sub-Saharan Africa. 1277 adults or adolescents infected with HIV in whom first-line ART had failed (assessed by WHO criteria with virological confirmation) were randomly assigned to a boosted protease inhibitor (standardised to ritonavir-boosted lopinavir) with two to three NRTIs (clinician-selected, without resistance testing); or with raltegravir; or alone as protease inhibitor monotherapy (discontinued after week 96). We tested genotypic resistance on stored baseline samples in patients in the protease inhibitor and NRTI group and calculated the predicted activity of prescribed second-line NRTIs. We measured viral load in stored samples for all patients obtained every 12–16 weeks. This trial is registered with Controlled-Trials.com (number ISRCTN 37737787) and ClinicalTrials.gov (number NCT00988039).FindingsBaseline genotypes were available in 391 (92%) of 426 patients in the protease inhibitor and NRTI group. 176 (89%) of 198 patients prescribed a protease inhibitor with no predicted-active NRTIs had viral suppression (viral load <400 copies per mL) at week 144, compared with 312 (81%) of 383 patients in the protease inhibitor and raltegravir group at week 144 (p=0·02) and 233 (61%) of 280 patients in the protease inhibitor monotherapy group at week 96 (p<0·0001). Compared with results with no active NRTIs, 95 (85%) of 112 patients with one predicted-active NRTI had viral suppression (p=0·3) and 20 (77%) of 26 patients with two or three active NRTIs had viral suppression (p=0·08). Over all follow-up, greater predicted NRTI activity was associated with worse viral load suppression (global p=0·0004).InterpretationGenotypic resistance testing might not accurately predict NRTI activity in protease inhibitor-based second-line ART. Our results do not support the introduction of routine resistance testing in ART programmes in low-income settings for the purpose of selecting second-line NRTIs.FundingEuropean and Developing Countries Clinical Trials Partnership, UK Medical Research Council, Institito de Salud Carlos III, Irish Aid, Swedish International Development Cooperation Agency, Instituto Superiore di Sanita, WHO, Merck.

BackgroundDespite the burgeoning burden of diabetes mellitus (DM) and cardiovascular diseases (CVD) in low and middle income countries (LMIC), access to affordable essential medicines and diagnostic tests for DM and CVD still remain a challenge in clinical practice. The Access to Cardiovascular diseases, Chronic Obstructive pulmonary disease, Diabetes mellitus and Asthma Drugs and diagnostics (ACCODAD) study aimed at providing contemporary information about the availability, cost and affordability of medicines and diagnostic tests integral in the management of DM and CVD in Uganda.MethodsThe study assessed the availability, cost and affordability of 37 medicines and 19 diagnostic tests in 22 public hospitals, 23 private hospitals and 100 private pharmacies in Uganda. Availability expressed as a percentage, median cost of the available lowest priced generic medicine and the diagnostic tests and affordability in terms of the number of days’ wages it would cost the least paid public servant to pay for one month of treatment and the diagnostic tests were calculated.ResultsThe availability of the medicines and diagnostic tests in all the study sites ranged from 20.1% for unfractionated heparin (UFH) to 100% for oral hypoglycaemic agents (OHA) and from 6.8% for microalbuminuria to 100% for urinalysis respectively. The only affordable tests were blood glucose, urinalysis and serum ketone, urea, creatinine and uric acid. Parenteral benzathine penicillin, oral furosemide, glibenclamide, bendrofluazide, atenolol, cardiac aspirin, digoxin, metformin, captopril and nifedipine were the only affordable drugs.ConclusionThis study demonstrates that the majority of medicines and diagnostic tests essential in the management of DM and CVD are generally unavailable and unaffordable in Uganda. National strategies promoting improved access to affordable medicines and diagnostic tests and primary prevention measures of DM and CVD should be prioritised in Uganda.

SummaryBackgroundMillions of HIV-infected people worldwide receive antiretroviral therapy (ART) in programmes using WHO-recommended standardised regimens. Recent WHO guidelines recommend a boosted protease inhibitor plus raltegravir as an alternative second-line combination. We assessed whether this treatment option offers any advantage over the standard protease inhibitor plus two nucleoside reverse-transcriptase inhibitors (NRTIs) second-line combination after 144 weeks of follow-up in typical programme settings.MethodsWe analysed the 144-week outcomes at the completion of the EARNEST trial, a randomised controlled trial done in HIV-infected adults or adolescents in 14 sites in five sub-Saharan African countries (Uganda, Zimbabwe, Malawi, Kenya, Zambia). Participants were those who were no longer responding to non-NRTI-based first-line ART, as assessed with WHO criteria, confirmed by viral-load testing. Participants were randomly assigned to receive a ritonavir-boosted protease inhibitor (lopinavir 400 mg with ritonavir 100 mg, twice per day) plus two or three clinician-selected NRTIs (protease inhibitor plus NRTI group), protease inhibitor plus raltegravir (400 mg twice per day; protease inhibitor plus raltegravir group), or protease inhibitor monotherapy (plus raltegravir induction for first 12 weeks, re-intensified to combination therapy after week 96; protease inhibitor monotherapy group). Randomisation was by computer-generated randomisation sequence, with variable block size. The primary outcome was viral load of less than 400 copies per mL at week 144, for which we assessed non-inferiority with a one-sided α of 0·025, and superiority with a two-sided α of 0·025. The EARNEST trial is registered with ISRCTN, number 37737787.FindingsBetween April 12, 2010, and April 29, 2011, 1837 patients were screened for eligibility, of whom 1277 patients were randomly assigned to an intervention group. In the primary (complete-case) analysis at 144 weeks, 317 (86%) of 367 in the protease inhibitor plus NRTI group had viral loads of less than 400 copies per mL compared with 312 (81%) of 383 in the protease inhibitor plus raltegravir group (p=0·07; lower 95% confidence limit for difference 10·2% vs specified non-inferiority margin 10%). In the protease inhibitor monotherapy group, 292 (78%) of 375 had viral loads of less than 400 copies per mL; p=0·003 versus the protease inhibitor plus NRTI group at 144 weeks. There was no difference between groups in serious adverse events, grade 3 or 4 adverse events (total or ART-related), or events that resulted in treatment modification.InterpretationProtease inhibitor plus raltegravir offered no advantage over protease inhibitor plus NRTI in virological efficacy or safety. In the primary analysis, protease inhibitor plus raltegravir did not meet non-inferiority criteria. A regimen of protease inhibitor with NRTIs remains the best standardised second-line regimen for use in programmes in resource-limited settings.FundingEuropean and Developing Countries Clinical Trials Partnership (...