Marc Blockman

Rescue therapy with high-dose oral phenobarbitone loading for refractory status epilepticus

Aim:  Parenteral phenobarbitone was unavailable in South Africa from 2005 to 2006. This study aimed to establish the effectiveness of enteral phenobarbitone in the management of childhood status epilepticus.

Dosage adjustment in medical patients with renal impairment at Groote Schuur Hospital

BACKGROUND Many drugs are eliminated by the kidneys and therefore may require dose adjustment in patients with renal impairment. The need for dose adjustment is frequently neglected by prescribers. METHODS We reviewed folders of patients admitted to the Groote Schuur Hospital general medical wards between January and March 2008. Patients with renal impairment, defined as an estimated glomerular filtration rate (eGFR) < or = 50 ml per minute per 1.73 m2, were identified. In-patient prescriptions were captured if they were written after clinical notes indicated impaired renal function, or > or = 1 day after renal function tests were performed. We determined what proportion of these prescriptions required dose adjustment and whether drug doses were appropriately adjusted. RESULTS We found renal impairment in 32% (97/301) of medical admissions. There were 615 prescription entries for the 97 patients with renal impairment. Dose adjustment was required in 19% (117/615) of prescription entries, and only 32% (37/117) of these prescription entries were correctly dose adjusted. Of 97 patients, 69 received one or more drugs that required dose adjustment (median 1, range 1 - 5). All drug doses were correctly adjusted in 12% (8/69) of patients. Importantly, in the majority of patients (59% (41/69)) no doses had been correctly adjusted. CONCLUSION Consistent with international studies, drug dose adjustment in patients with renal impairment in a South African hospital was frequently neglected. Strategies to alert clinicians of the need for dose adjustment in renal impairment should be considered, including automated eGFR reporting and computerised aids to guide drug dosing, that account for renal impairment.

Adverse Drug Reactions Causing Admission to Medical Wards: A Cross-Sectional Survey at 4 Hospitals in South Africa.

AbstractLimited data exist on the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa, which has high HIV and tuberculosis prevalence. We determined the proportion of adult admissions attributable to ADRs at 4 hospitals in South Africa. We characterized drugs implicated in, risk factors for, and the preventability of ADR-related admissions.We prospectively followed patients admitted to 4 hospitals’ medical wards over sequential 30-day periods in 2013 and identified suspected ADRs with the aid of a trigger tool. A multidisciplinary team performed causality, preventability, and severity assessment using published criteria. We categorized an admission as ADR-related if the ADR was the primary reason for admission.There were 1951 admissions involving 1904 patients: median age was 50 years (interquartile range 34–65), 1057 of 1904 (56%) were female, 559 of 1904 (29%) were HIV-infected, and 183 of 1904 (10%) were on antituberculosis therapy (ATT). There were 164 of 1951 (8.4%) ADR-related admissions. After adjustment for age and ATT, ADR-related admission was independently associated (P ⩽ 0.02) with female sex (adjusted odds ratio [aOR] 1.51, 95% confidence interval [95% CI] 1.06–2.14), increasing drug count (aOR 1.14 per additional drug, 95% CI 1.09–1.20), increasing comorbidity score (aOR 1.23 per additional point, 95% CI 1.07–1.41), and use of antiretroviral therapy (ART) if HIV-infected (aOR 1.92 compared with HIV-negative/unknown, 95% CI 1.17–3.14). The most common ADRs were renal impairment, hypoglycemia, liver injury, and hemorrhage. Tenofovir disoproxil fumarate, insulin, rifampicin, and warfarin were most commonly implicated, respectively, in these 4 ADRs. ART, ATT, and/or co-trimoxazole were implicated in 56 of 164 (34%) ADR-related admissions. Seventy-three of 164 (45%) ADRs were assessed as preventable.In our survey, approximately 1 in 12 admissions was because of an ADR. The range of ADRs and implicated drugs reflect South Africas high HIV and tuberculosis burden. Identification and management of these ADRs should be considered in HIV and tuberculosis care and treatment programs and should be emphasized in health care worker training programmes.

Nevirapine Concentrations in Preterm and Low Birth Weight HIV-Exposed Infants: Implications for Dosing Recommendations

World Health Organisation guidelines recommend nevirapine 2 mg/kg/d for HIV-exposed infants <2 kg, but 4–6 mg/kg/d for infants >2 kg. In 116 low birth weight infants, nevirapine 2 mg/kg/d until 14 days, and 4 mg/kg/d thereafter, was safe (1 mild possibly related rash) and achieved target plasma concentrations. Concentrations decreased with treatment duration. Routine dose increase at 14 days should be considered.

Strengthening pharmacovigilance in South Africa

This report outlines findings and recommendations of a national pharmacovigilance workshop held in August 2012 in South Africa (SA). A survey of current pharmacovigilance activities, conducted in preparation for the meeting, identified multiple programmes collecting drug safety data in SA, with limited co-ordination at national level. The meeting resolved that existing pharmacovigilance programmes need to be strengthened and consolidated to ensure that important local safety issues are addressed, data can be pooled and compared and outputs shared more widely. Pharmacovigilance activities should inform treatment guidelines with the goal of improving patient care. A variety of pharmaco-epidemiological approaches should be employed, including nesting drug safety studies within existing sentinel cohorts and the creation of a pregnancy exposure registry. The attendees agreed on key principles that will inform a national pharmacovigilance plan and compiled a list of priority pharmacovigilance issues facing public health programmes in SA.

Clinical excellence and the NICEties of value-based priority setting.

1They suggested that scrutiny of expensive new medications and technologies by a NICE-like body would lead to appropriate rationing. NICE refers to the UK’s National Institute of Health and Clinical Excellence, a government-funded but politically independent body tasked with evaluating the clinical efficacy and cost-effectiveness of medicines and health devices. Its efficacy in improving quality of care and resource allocation is still unclear, and similar attempts in the United States have failed because of the political sensitivity of perceived rationing in that country. 2 The proposal to establish a similar unit in South Africa appeared unduly optimistic to Taylor, 3 who observed correctly that setting cost-effectiveness thresholds is not a rationing strategy in the absence of a concurrent mechanism and commitment to forego established expenditure on other less cost-effective items. (This is an issue which has not yet been resolved by the United Kingdom’s NICE.) She also observed that costeffectiveness analysis is time-consuming, extremely resourceintensive, and arguably not easy to perform on a large scale in South Africa at present.

The impact of the National HIV Health Care Worker Hotline on patient care in South Africa

BackgroundSouth Africa has a huge burden of illness due to HIV infection. Many health care workers managing HIV infected patients, particularly those in rural areas and primary care health facilities, have minimal access to information resources and to advice and support from experienced clinicians. The Medicines Information Centre, based in the Division of Clinical Pharmacology at the University of Cape Town, has been running the National HIV Health Care Worker (HCW) Hotline since 2008, providing free information for HIV treatment-related queries via telephone, fax and e-mail.ResultsA questionnaire-based study showed that 224 (44%) of the 511 calls that were received by the hotline during the 2-month study period were patient-specific. Ninety-four completed questionnaires were included in the analysis. Of these, 72 (77%) were from doctors, 13 (14%) from pharmacists and 9 (10%) from nurses. 96% of the callers surveyed took an action based on the advice received from the National HIV HCW Hotline. The majority of actions concerned the start, dose adaption, change, or discontinuation of medicines. Less frequent actions taken were adherence and lifestyle counselling, further investigations, referring or admission of patients.ConclusionsThe information provided by the National HIV HCW Hotline on patient-specific requests has a direct impact on the management of patients.

Leaving the party -- withdrawal of South African essential medicines.

Extracted from text ... In August 2004 pharmacies and drug depots were advised that the sole supplier of parenteral phenobarbitone in South Africa, essential for the management of status epilepticus in children, was stopping production at the end of the same year. Alternative protocols for the management of status epilepticus resulted in more children requiring intensive care intervention (N = 9) at the Red Cross Childrens Hospital, over a 2-month period, than had occurred in any 12-month period since 2000 (2000 N = 3, 2001 N = 1, 2002 N = 1, 2003 N = 2, 2004 N = 7). Other agents that have suffered or are at risk of the same fate are ..

Poor anticoagulation control in patients taking warfarin at a tertiary and district-level prothrombin clinic in Cape Town, South Africa

BACKGROUND Warfarin is the most commonly used anticoagulant for both primary and secondary prevention of thromboembolism. For anticoagulation efficacy, the international normalised ratio (INR) needs to be within the therapeutic range for at least 65% of time on warfarin. OBJECTIVES To describe INR control in patients on long-term warfarin and identified predictors of good INR control at two dedicated warfarin follow-up clinics in Cape Town, South Africa (SA). METHODS We reviewed clinical records of patients in care at the INR clinics at Mitchells Plain Community Health Centre and Groote Schuur Hospital. We included patients who had been on warfarin therapy for at least 27 months and excluded patients with <6 months of INR monitoring data or a >70-day gap between INR tests in the calculation period, and if >25% of follow-up time was at an alternative site. The time in therapeutic range (TTR) over 180 days using the Rosendaal method was calculated, and we categorised INR control as good if the TTR was ≥65%. We constructed a multivariate logistic regression model to identify associations with good INR control. RESULTS We included 363 patients, with a median age of 55 years (interquartile range (IQR) 44 - 64), of whom 65.6% were women. The most common indications for warfarin were valvular heart disease (45.7%) and atrial fibrillation (25.1%). The mean TTR was 47%, with only 91/363 patients having good INR control. In a multivariate model adjusted for age, sex, clinic and target INR, patients aged ≥55 years were more likely to have good INR control than younger patients (adjusted odds ratio 1.69, 95% confidence interval 1.03 - 2.79). Poorly controlled patients had more frequent INR monitoring than those with good INR control, with a median of 8 INRs (IQR 6 - 10) v. 6 INRs (IQR 5 - 8) in the 180-day period (p<0.0001). CONCLUSIONS Only 25.1% of patients in our study achieved good INR control, despite regular INR monitoring. There is an urgent need to improve anticoagulation control of patients receiving warfarin in SA. Validated dosing algorithms are required, and access to lower warfarin dosage formulations may optimise individual dose titration. Advocacy for these formulations is advised.

Metabolic acidosis in a patient with metformin overdose

We report a rare fatal case of acute metformin overdose in a 19-year-old woman.