Interest in neurology during medical clerkship in three Nigerian medical schools

Background  

This study sought to ascertain perception of Nigerian medical students of neurology in comparison with 7 other major medical specialties. To also determine whether neurology was the specialty students consider most difficult and the reasons for this and to appraise their opinion on how neurosciences and neurology were taught in their different universities.     

Efficacy of deep venous thrombosis prophylaxis in the medical intensive care unit

The purpose of this study was to determine the incidence of deep venous thrombosis in medical intensive care unit patients receiving deep venous thrombosis prophylaxis. This was a prospective cohort study of 141 consecutive adult patients anticipated to remain in the medical intensive care unit for >48 hours. Deep venous thrombosis prophylaxis was provided using subcutaneous unfractionated heparin or a sequential compression device according to risk-stratified protocol. Compression ultrasound was performed. Fourteen patients (9.9%) developed deep venous thrombosis on follow-up studies. Incidence of deep venous thrombosis was 7.9% per person year (95% confidence interval, 4.8-12.8). Two of 14 developed pulmonary embolism. Eight patients required full anticoagulation with intravenous heparin or coumadin. In-hospital mortality was similar in both groups. Patients with deep venous thrombosis had a statistically higher risk of pulmonary embolism: 14.2% (95% confidence interval, 2.0-43.0) versus 0.0% (95% confidence interval, 0-3; P = .009). Incidence of deep venous thrombosis is high in medical intensive care unit patients receiving standard prophylaxis. Adherence to strict deep venous thrombosis prophylaxis protocol and exploration of other prophylaxis regimens should be pursued.     

The epidemiology of stroke in Africa: A systematic review of existing methods and new approaches

Accurate epidemiological surveillance of the burden of stroke is direly needed to facilitate the development and evaluation of effective interventions in Africa. The authors therefore conducted a systematic review of the methodology of stroke epidemiological studies conducted in Africa from 1970 to 2017 using gold standard criteria obtained from landmark epidemiological publications. Of 1330 articles extracted, only 50 articles were eligible for review grouped under incidence, prevalence, case‐fatality, health‐related quality of life, and disability‐adjusted life‐years studies. Because of various challenges, no study fulfilled the criteria for an excellent stroke incidence study. The relatively few stroke epidemiology studies in Africa have significant methodological flaws. Innovative approaches leveraging available information and communication technology infrastructure are recommended to facilitate rigorous epidemiological studies for accurate stroke surveillance in Africa.     

Spirometric standards for healthy Nigerian children and adolescents.

Forced vital capacity (FVC), forced expiratory volume in one second (FEV1.0) and peak expiratory flow rates (PEFR) were determined in 131 school children and adolescents aged between 5 and 20 years to determine normal values among Nigerian school children. The results were analyzed with respect to the ages, heights, weights, chest circumference and body surface areas of the subjects. A good correlation was observed between these anthropometric measurements and the indices of pulmonary function. The mean values of FVC, FEV1.0, and PEFR were lower than those reported in caucasian children but similar to the available data in the literature for African children. Mean FEV1.0, FVC and PEFR values were higher in males than in females at most ages.     

Outcome after renal transplantation in children: results of follow-up by nephrologists in a primary referral center

Pediatric patients who receive a kidney transplant require extended follow-up to monitor graft function and for management of complications. Because of convenience, most patients are sent back to the nephrologists who referred them for transplantation (the primary nephrologist) for long-term care. As a consequence, many pediatric nephrologists who provide this extended care are not associated with a transplant center. It is not known if this arrangement yields satisfactory outcomes for children and adolescents who receive a kidney transplant. The objective was to determine if clinical outcomes are satisfactory in pediatric renal transplant recipients who were followed up by their primary nephrologists after the procedure. A chart review was carried out on all renal transplant recipients seen in the renal clinic at Schneider Children's Hospital (SCH) from 1982 to 2001. Patients were eligible if they were followed up by the primary referring nephrologists at SCH for a minimum of 6 months after transplantation. Relevant demographic and clinical outcome data were compiled. Twenty-eight patients who received a total of 33 renal allografts [living related donors (LRD) 15 and cadaveric donors (CD) 18] were seen during the study period. The transplantations in 19 children (68%) were carried out at Montefiore Hospital (Bronx, NY, USA), while the rest were performed at other centers. There were three (11%) deaths, two LRD patients and one CD patient. The group of 25 surviving patients consisted of 17 males and eight females, age range 4-28 yr (mean 17.2 yr). The mean duration of renal allograft survival was 6.3 +/- 5.3 yr and the mean duration of follow-up was 6.1 +/- 5.3 yr. The most recent serum creatinine ranged from 0.5 to 3.8 mg/dL with a mean of 1.3 +/- 0.8 mg/dL. There were several complications including acute rejection, renal artery stenosis, and hydronephrosis in the allograft. The team of primary referring nephrologists successfully treated all of these except the child with hydronephrosis. The primary nephrologist who refers pediatric patients to a tertiary care transplant center can accomplish long-term follow-up of renal transplant recipients after discharge from the transplant center. The clinical outcomes are acceptable and compare favorably with the results described in the literature that have been achieved in patients followed up at transplant centers. Problems rarely developed that required referral back to the transplant center for management. This approach to care is recommended because it is more likely to foster compliance by both patients and parents.     

Tacrolimus and lopinavir/ritonavir interaction in liver transplantation

OBJECTIVE: To report an interaction between tacrolimus and the protease inhibitor combination lopinavir/ritonavir in a liver transplant patient.CASE SUMMARY: A 48-year-old white male liver transplant recipient receiving tacrolimus 5 mg twice daily for immunosuppression started highly active antiretroviral therapy for his HIV-positive status. Three days after initiation of lopinavir/ritonavir, the tacrolimus concentration rose sharply to toxic levels. Subsequent tacrolimus doses were withheld until tacrolimus concentrations normalized over 15 days. The tacrolimus dose was reestablished at a much lower dose, 0.5 mg once weekly. An objective causality assessment revealed that the adverse event was highly probable.DISCUSSION: Tacrolimus is metabolized in the liver via CYP3A4. Protease inhibitors are known to inhibit CYP3A4 and have been documented to increase tacrolimus concentrations, putting the patient at risk of developing nephrotoxic and/or neurotoxic symptoms. In this case, concomitant use of lopinavir/ritonavir caused tacrolimus concentrations to rise more dramatically than had been previously reported in the literature for other protease inhibitors.CONCLUSIONS: Extreme caution must be used when administering tacrolimus concomitantly with lopinavir/ritonavir. Therapeutic concentrations of tacrolimus can be maintained with tacrolimus doses that are far below standard dosages.     

Compartmental pharmacokinetic analysis of oral amprenavir with secondary peaks

Amprenavir is a protease inhibitor that has been shown to have secondary peaks postulated to be due to enterohepatic recycling. We propose a model to describe the pharmacokinetics of amprenavir which accommodates the secondary peak(s). A total of 82 healthy human immunodeficiency virus (HIV)-seronegative subjects were administered a single 600-mg dose of amprenavir as part of adult AIDS Clinical Trials Group protocol A5043. Serial blood samples were obtained over 24 h. Samples were analyzed for amprenavir and fit to a compartmental model using ADAPT II software, with all relevant parameters conditional with respect to bioavailability. The model accommodated secondary peaks by incorporating clearance out of the central compartment with delayed instantaneous release back into the gut compartment. The data were weighted by the inverse of the estimated measurement error variance; model discrimination was determined using Akaike's Information Criteria. A total of 76 subjects were evaluable in the study analysis. The data were best fit by a two-compartment model, with 98.7% of the subjects demonstrating a secondary peak. Amprenavir had a mean total clearance of 1.163 liters/h/kg of body weight (0.7), a central volume of distribution of 1.208 liters/kg (0.8), a peripheral volume of distribution of 8.2 liters/kg (0.81), and distributional clearance of 0.04 liters/h/kg (0.81). The time to the secondary peak was 7.86 h (0.17), and clearance into a recycling compartment was 0.111 liters/kg/h (0.74). Amprenavir pharmacokinetics has been well described using a two-compartment model with clearance to a recycling compartment and release back into the gut. The nature of the secondary peaks may be an important consideration for the interpretation of amprenavir plasma concentrations during therapeutic drug monitoring.     

Performance of a rapid antigen test for the diagnosis of congenital malaria

OBJECTIVE: To assess the performance of OptiMAL, a rapid malaria antigen capture dipstick, in diagnosing congenital malaria. METHODS: Live newborns aged 0-3 days, delivered at Olabisi Onabanjo University Teaching Hospital, Sagamu, Nigeria between August 2004 and January 2005, were screened for malaria parasitaemia with an immunochromatographic test (OptiMAL) and blood film microscopy. OptiMAL detects plasmodium lactate dehydrogenase (pLDH). RESULTS: Twenty-one of 192 newborns (10.9%) were diagnosed with congenital malaria by blood film microscopy. The OptiMAL test was negative in all infants. CONCLUSION: OptiMAL rapid malaria antigen capture dipstick might not be useful for diagnosing malaria parasitaemia in newborns. Blood film microscopy remains the gold standard for the diagnosis of congenital malaria.     

Risk scores for predicting HIV incidence among adult heterosexual populations in sub‐Saharan Africa: a systematic review and meta‐analysis

IntroductionSeveral HIV risk scores have been developed to identify individuals for prioritized HIV prevention in sub‐Saharan Africa. We systematically reviewed HIV risk scores to: (1) identify factors that consistently predicted incident HIV infection, (2) review inclusion of community‐level HIV risk in predictive models and (3) examine predictive performance.MethodsWe searched nine databases from inception until 15 February 2021 for studies developing and/or validating HIV risk scores among the heterosexual adult population in sub‐Saharan Africa. Studies not prospectively observing seroconversion or recruiting only key populations were excluded. Record screening, data extraction and critical appraisal were conducted in duplicate. We used random‐effects meta‐analysis to summarize hazard ratios and the area under the receiver‐operating characteristic curve (AUC‐ROC).ResultsFrom 1563 initial search records, we identified 14 risk scores in 13 studies. Seven studies were among sexually active women using contraceptives enrolled in randomized‐controlled trials, three among adolescent girls and young women (AGYW) and three among cohorts enrolling both men and women. Consistently identified HIV prognostic factors among women were younger age (pooled adjusted hazard ratio: 1.62 [95% confidence interval: 1.17, 2.23], compared to above 25), single/not cohabiting with primary partners (2.33 [1.73, 3.13]) and having sexually transmitted infections (STIs) at baseline (HSV‐2: 1.67 [1.34, 2.09]; curable STIs: 1.45 [1.17; 1.79]). Among AGYW, only STIs were consistently associated with higher incidence, but studies were limited (n = 3). Community‐level HIV prevalence or unsuppressed viral load strongly predicted incidence but was only considered in 3 of 11 multi‐site studies. The AUC‐ROC ranged from 0.56 to 0.79 on the model development sets. Only the VOICE score was externally validated by multiple studies, with pooled AUC‐ROC 0.626 [0.588, 0.663] (I ²: 64.02%).ConclusionsYounger age, non‐cohabiting and recent STIs were consistently identified as predicting future HIV infection. Both community HIV burden and individual factors should be considered to quantify HIV risk. However, HIV risk scores had only low‐to‐moderate discriminatory ability and uncertain generalizability, limiting their programmatic utility. Further evidence on the relative value of specific risk factors, studies populations not restricted to “at‐risk” individuals and data outside South Africa will improve the evidence base for risk differentiation in HIV prevention programmes.PROSPERO NumberCRD42021236367     

FDA Approval Summary: Revised Indication and Dosing Regimen for Ponatinib Based on the Results of the OPTIC Trial

On December 18, 2020, US Food and Drug Administration (FDA) approved a supplemental application for ponatinib extending the indication in patients with chronic-phase chronic myeloid leukemia (CP-CML) to patients with resistance or intolerance of at least 2 prior kinase inhibitors. Ponatinib was initially approved in December 2012 but was briefly voluntarily withdrawn due to serious safety concerns including the risk of arterial occlusive events (AOE). It returned to the market in December 2013 with an indication limited to patients with T315I mutation or for whom no other tyrosine kinase inhibitor (TKI) therapy was indicated with revised warnings and precautions. A post-marketing requirement was issued to identify the optimal safe and effective dose for CP-CML. Thus, the OPTIC trial was performed, which randomized patients to 1 of 3 doses, 45 mg, 30 mg, or 15 mg, with a dose reduction to 15 mg on achievement of MR2 (BCR-ABL^IS ≤1%). Patients enrolled were treated with at least 2 prior TKIs or had a T315I mutation. Patients with a history of clinically significant, uncontrolled, or active cardiovascular disease were excluded. Efficacy was established on an interim analysis based on the rate of MR2 at 12 months in the modified intent-to-treat population of 261 patients, with 88, 86, and 87 patients in the 45, 30, and 15 mg cohorts, respectively. With a median follow-up of 28 months, the rate of achievement of MR2 at 12 months was 42%, 28%, and 24% in the respective cohorts. The safety profile was consistent with that observed in prior evaluations of ponatinib with notable adverse reactions including pancreatitis, hypertension, hyperlipidemia, liver dysfunction, and AOE. Of patients treated at the 45/15 mg dose, AOEs were seen in 13%, with a higher rate being observed in patients age 65 or older compared to younger patients. A readjudication of AOEs seen on the prior pivotal phase 2 study resulted in a rate of 26%. Overall, the results supported a modification of the recommended dose for patients with CP-CML to 45 mg until the achievement of MR2 followed by a reduction to 15 mg. The expansion of the indication to patients with exposure to 2 prior TKIs was approved given data showing that ponatinib could be successfully used for the treatment of this population with appropriate monitoring and screening for risk factors.