Assessment of pharmacovigilance guidelines in the Southern African Development Community: A document review.

BACKGROUND: Lack of harmonization in pharmacovigilance (PV) practice in resource-limited states in Africa has led to differentiation and marginalization, thus creating an environment where weak or absent PV systems may benefit from regional guidelines. PURPOSE: To compare the PV guidelines of Southern African Development Community (SADC) member states to international guidelines and identify areas for improvement for aligning PV practice within the SADC region. METHODS: We utilized a 73-item checklist to assess the PV guidelines of the SADC member states. Checklist parameters were rated using binary scoring. RESULTS: Only seven (Botswana, Mauritius, Namibia, South Africa, Tanzania, Zambia, and Zimbabwe) of the 16 SADC member states had guidelines to assess. Of these, only four had supporting legislation. All seven national medicines regulatory authorities (NMRA)'s guidelines required reporting of local serious adverse drug reactions (ADRs). Four NMRAs implemented device vigilance; none specified submission timelines for ADRs associated with substandard or falsified medicines. Only three NMRAs required electronic transmission of individual case safety reports in the E2B format. Five NMRAs mandated safety monitoring during interventional clinical trials. Five NMRAs required aggregate reporting through periodic safety update reports. Only two NMRAs required submission of the development safety update report. Regarding risk management, four NMRAs required notification of actions taken by foreign NMRAs and four NMRAs expected to review Dear Healthcare Professional Letters before distribution by the marketing authorization holder. CONCLUSIONS: Areas for improvement of guidelines to establish common process standards and allow for synchronized submissions of comparable data to SADC NMRAs are provided.

Challenges facing drug utilization research in the Latin American region.

PURPOSE: The International Society of Pharmacoepidemiology (ISPE) in collaboration with the Latin America Drug Utilization Research Group (LatAm DURG), the Medicines Utilization Research in Africa (MURIA) group, and the Uppsala Monitoring Center, is leading an initiative to understand challenges to drug utilization research (DUR) in the Latin American (LatAm) and African regions with the goal of communicating results and proposing solutions to these challenges in four scientific publications. The purpose of this first manuscript is to identify the main challenges associated with DUR in the LatAm region. METHODS: Drug utilization (DU) researchers in the LatAm region voluntarily participated in multiple discussions, contributed with local data and reviewed successive drafts and the final manuscript. Additionally, we carried out a literature review to identify the most relevant publications related to DU studies from the LatAm region. RESULTS: Multiple challenges were identified in the LatAm region for DUR including socioeconomic inequality, access to medical care, complexity of the healthcare system, limited investment in research and development, limited institutional and organization resources, language barriers, limited health education and literacy. Further, there is limited use of local DUR data by decision makers particularly in the identification of emerging health needs coming from social and demographic transitions. CONCLUSIONS: The LatAm region faces challenges to DUR which are inherent in the healthcare and political systems, and potential solutions should target changes to the system.

Treatment Cost and Psychological Impact of Burkitt Lymphoma on Ghanaian Families and Caregivers.

OBJECTIVE: Before June 2022, the treatment cost of Burkitt lymphoma (BL) in Ghana was mainly borne by the child's family or caregiver. We determined the treatment cost of BL in children and its psychological impact on parents and caregivers. METHOD: This prospective observational study assessed the direct medical and nonmedical costs (US dollars [USD]) incurred during the treatment of a child with BL for 6 consecutive months using a cost diary. Productivity losses and the psychological impact on parents and caregivers were assessed using a self-administered questionnaire and the Caregiver Quality of Life Index-Cancer (CQOLC). RESULTS: Of the 25 participants, 7 abandoned the treatment of their children, and 4 withdrew because the children passed away. The median (Q1, Q3) cost for treating BL per child for caregivers/parents (N = 12) was USD 947.42 (USD 763.03, USD 1953.05). Direct medical costs formed 71% (USD 11 458.97) of total treatment costs. Working hours of parents before the child's cancer diagnosis decreased from a median (Q1, Q3) of 44.00 (20.00, 66.00) hours to 1.50 (0, 20.00) hours after the diagnosis. The mean (SD) CQOLC score was 107.92 (15.89), with higher scores in men (111.00 [17.26]), married participants (111.26 [17.29]), Higher National Diploma certificate holders (113.00 [1.41]), and participants earning a monthly income more than USD 84.60. CONCLUSION: Treatment costs reduced the overall household income of 5 families. Parents and caregivers experienced reduced work hours and loss of employment. CQOLC scores were higher in married participants, those with a higher educational background, and those with higher income.

Development of a checklist for the assessment of pharmacovigilance guidelines in Southern Africa: a document review.

Introduction: National regulatory systems in Southern Africa reflect various stages of maturity, and pharmacovigilance (PV) practices are not aligned. In the absence of guidance for formulating PV guidelines in Southern African Development Community (SADC) countries, this study aimed to create a checklist that may be used to assess the rigour of PV guidelines in this region and provide guidance for the National Medicines Regulatory Agency (NMRA) authors. Methods: A document analysis was performed based on harmonised international guidelines (n = 22) that prescribed methods of PV regulation to identify themes and items to incorporate into a checklist. The contextualisation of the checklist to the African pharmaceutical environment was accomplished by referencing peer-reviewed journal articles (n = 7). The checklist was subjected to face and content validation by non-experts and PV experts. Results: The document review yielded 5 themes, 18 sub-themes, and 73 items structured into the checklist. Themes encompassed PV systems, definitions, individual case safety reporting, aggregate reporting, and risk management. Under PV systems, aspects of the quality management system were outlined, that is, the legal basis for PV, a description of the marketing authorisation holder's (MAH's) PV system, archiving of data, contracting of PV tasks, and the duties of the person responsible for the MAH's PV obligations. Definitions of the key terms and major stakeholders were identified. Reporting of individual case safety reports (ICSRs) was explicated by considering the criteria for reporting, categories of reportable information, expedited reporting requirements, reporting timelines, and ICSR reporting format. Aggregate report submission during the development and post-marketing phases was addressed. Risk management encompassed signal detection, re-evaluation of the benefit-risk ratio, the safety decision-making process, risk management planning, risk minimisation and safety communication. Conclusion: The developed checklist can contribute towards assisting SADC NMRAs to formulate national PV guidelines that reflect current international practice, with local context incorporated. Plain Language Summary: Developing a checklist for the evaluation of medicine safety guidelines in Southern Africa Introduction: In Southern African Development Community (SADC) countries, the guidelines for medicine safety [pharmacovigilance (PV)] that marketing authorisation holders (MAHs) and healthcare professionals need to adhere to, are not aligned. We saw the need to develop a checklist that can be used to evaluate these guidelines.Methods: We studied international documents issued by the World Health Organization (WHO), the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), the Council for International Organizations of Medical Sciences (CIOMS) and the European Medicines Agency (EMA). On the organisational websites, we obtained 22 documents and identified 73 checklist items. All the items were arranged under 5 themes and 18 sub-themes to create the checklist. We adapted the checklist to the local context by using seven journal articles addressing PV concerns in Africa. Experts checked the content and usability of the checklist.Results: The themes were PV systems, definitions, individual case safety reporting (ICSR), combined reporting and risk management. PV systems had six sub-themes: legal structure, description of the MAH's PV system, contractual agreements, information storage, the qualified person responsible for PV (QPPV) and where the QPPV is located. We included the definitions of keywords and role-players. The ICSR theme had five sub-themes, i.e. criteria for reporting, categories of reportable information, expedited reporting, reporting timelines, and reporting format. Submission of summary reports comprised an overview of the safety profile of a medicine once it is approved by regulators, as well as during clinical trials. Risk management included signal detection, re-evaluation of the benefit-risk ratio, safety decision-making process, risk management planning, risk minimisation, and safety communication. The checklist is applied by allocating yes/no scoring per item.Conclusion: The checklist may be used by regulators within SADC to assess their PV guidelines for alignment with international standards and suitability to the local environment.

Completeness of pharmaceutical industry insulin adverse event reports from Africa and the Middle East.

BACKGROUND: Growing numbers of patients with diabetes mellitus in Africa and the Middle East on antidiabetic therapies necessitate understanding adverse event reporting in these regions. We assessed pharmaceutical industry insulin individual case safety report (ICSR) completeness and completeness-associated variables. RESEARCH DESIGN AND METHODS: The observational cross-sectional study, set in an insulin-manufacturing company's safety database, assessed vigiGrade® completeness scores of African and Middle Eastern post-marketing ICSRs from January to December 2018, and case variables effects on completeness. Low vigiGrade® scores indicated poorly documented ICSRs. RESULTS: We analyzed 4854 ICSRs; 59.8% from the Middle East. The mean vigiGrade® score was 0.58. Middle Eastern ICSRs had higher mean scores than African ICSRs (0.65 vs. 0.46, p<0.001). Scores peaked at 0.32, 0.70, and 1.00 for Middle Eastern ICSRs compared to 0.35 and 0.50 for African ICSRs. Middle Eastern serious (0.77 vs. 0.47; p<0.001) and solicited (0.70 vs. 0.48; p<0.001) ICSRs had higher mean scores than African ICSRs. Mean scores were highest for Middle Eastern physicians (0.89) and other healthcare professionals (0.82), whereas, in Africa, scores were highest for consumer- (0.47) and pharmacist-reported ICSRs (0.47) (p<0.001). CONCLUSIONS: Middle Eastern pharmaceutical industry insulin ICSRs were documented with greater detail than African ICSRs. Seriousness, report source, and reporter type significantly impacted ICSR completeness.

Incidence patterns of childhood cancer in two tertiary hospitals in Ghana from 2015 to 2019: A retrospective observational study.

BACKGROUND: Accurate epidemiological data are vital in estimating the burden of disease in a country. Little is known about the incidence of childhood cancer in Ghana. This study describes the incidence patterns of cancer in children below 14 years and 11 months from 2015 to 2019 at the only two main pediatric cancer referral centers in Ghana: Korle Bu Teaching Hospital (KBTH) and Komfo Anokye Teaching Hospital (KATH). METHOD: Data on the incidence of cancer in children below 14 years and 11 months were collected retrospectively between 1st January 2015 and 31st December 2019 from patients' medical folders at KBTH and the cancer registry at the pediatric units of KATH. Descriptive statistics were used to describe the data. Incident rates expressed as age-specific rates (ASRs) per 100,000 person-years using population estimates for age groups and sex in each year, were determined by age groups (0-4, 5-9, 10-14 years and 11 months), sex, region of residence and cancer types based on the International Childhood Cancer Classification, third edition. RESULTS: The total ASR per 100,000 person-years from 2015 to 2019 was 9.36 based on 1073 cases observed. The ASR increased from 1.6 per 100,000 person-years in 2015-2.41 in 2017, thereafter decreasing to 1.45 in 2019. The ASR was higher in male children (2.10 per 100,000 person-years), children between 0 and 4 years (0.27 per 100,000 person-years), and children living in the Greater Accra region (4.17 per 100,000 person-years). The most prevalent cancers were lymphomas (2.17 per 100,000 person-years) and leukemia (1.88 per 100,000 person-years). CONCLUSION: The study provides baseline information on the incidence patterns of childhood cancer from 2015 to 2019, addressing a critical gap in childhood cancer epidemiology in Ghana.

Antibiotic consumption by Access, Watch and Reserve index in public sector of Limpopo province, South Africa: 2014-2018.

Background: The World Health Organization (WHO) classified antibiotics into three categories in 2017 - Access, Watch and Reserve (AWaRe) - intending to reduce the consumption of Watch and Reserve antibiotics while increasing the use of Access antibiotics. Antibiotic consumption by AWaRe in South Africa is undetermined because of data and research scarcity. Objectives: The aim of this study was to quantify, describe and track antibiotic consumption between 2014 and 2018 in the public sector of the Limpopo province, South Africa, using the WHO's AWaRe classification for 2021. Method: Antibiotic consumption was quantified from pharmaceutical sales data for 2014-2018 by defined daily dose (DDD) per 1000 inhabitants per day (DID) and described according to the AWaRe classification. The change in antibiotic consumption was measured by compound annual growth rate (CAGR), Access-to-Watch index (AW-I), 75% drug utilisation index (DU75%) and amoxicillin index (AI). Results: The absolute consumption of Access antibiotics decreased by a 4.0% CAGR from 3.7 DID in 2014 to 3.0 DID in 2018, with relative consumption remaining above 80.0%. Relative consumption of Watch antibiotics increased by 15.8% CAGR from 7.8% in 2014 to 19.7% by 2018. The AW-I decreased from 10.4 in 2015 to 4.1 in 2018. The AI increased from 17.8% in 2015 to 42.0% in 2018. Parenteral formulations' DU75% comprised one Watch (ceftriaxone) and two Access (metronidazole and benzylpenicillin) antibiotics. Conclusion: In Limpopo province's public sector, the consumption of Watch antibiotics increased, while Access antibiotics consumption decreased, as reflected by both relative consumption and the decrease in the AW-I. The determinants of the Watch antibiotics increase require research attention. Contribution: Our study addressed the paucity of surveillance and research data on antibiotic consumption in the Limpopo province, South Africa, according to the WHO AWaRe classification.

Antibiotic consumption in the public sector of the Limpopo province, South Africa, 2014-2018.

Background: Antibiotic consumption (ABC) surveillance is a critical component of the strategic priority response to the increasing antibiotic resistance threat. Levels of ABC at the national and provincial levels in South Africa are unknown because of inadequate ABC surveillance systems and literature. Antibiotic consumption in the public sector of Limpopo province, South Africa, 2014-2018. Methods: This retrospective study used sales data retrieved from a pharmaceutical warehouse distribution database to quantify ABC. Antibiotic consumption was measured by the defined daily dose (DDD) per 1000 inhabitants per day (DID) and 75% drug utilisation index (DU75%). Change in consumption was measured by the compound annual growth rate (CAGR). Results: Between 2014 and 2018, the mean ABC was 4.6 ± 1.0 DID, with an overall decrease of 1.6% in the CAGR. Penicillins (2.3 ± 0.8; 50.0%), sulphonamide and trimethoprim combinations (1.4 ± 0.3 DID; 30.4%) were the most consumed antibiotics. Macrolides had the highest relative increase in consumption during the study period, with a CAGR of 18.5%. In contrast, tetracyclines had the highest relative decrease in consumption, with a CAGR of 100.0%. The CAGR ratio for broad- to narrow-spectrum increased by 39.3%, from 0.4 in 2014 to 2.1 in 2018. The DU75% comprised amoxicillin (28.4%), sulphamethoxazole and trimethoprim (SMX-TMP) (27.2%), doxycycline (12.3%) and azithromycin (9.2%). Conclusion: While ABC remained relatively stable throughout the study, there was an increase in broad-spectrum ABC that requires further investigation. Contribution: This study contributes ABC surveillance data in Southern Africa, described by ATC classification, which is essential for monitoring and evaluating antibiotic stewardship programmes.

Individual Case Safety Reports Analysis for Patients with Diabetes Mellitus on Insulin in Africa and the Middle East.

BACKGROUND: The growing numbers of patients with diabetes mellitus in Africa and the Middle East on antidiabetic therapies necessitate an understanding of adverse event (AE) reporting in these regions. OBJECTIVE: The aim of the study was to provide an AE reporting overview in patients using insulin in Africa and the Middle East by characterizing and comparing individual case safety reports (ICSRs) features. METHODS: The cross-sectional study analyzed ICSR data from a global pharmaceutical company's pharmacovigilance database for January to December 2018 to describe and compare patient demographics, report sources, reporter types, ICSR seriousness, suspect products, indication for insulin use and AE preferred terms, by country. RESULTS: Overall 7076 ICSRs were analyzed, 63.6% from the Middle East. Most ICSRs were nonserious (91.5%), from solicited sources (83.5%), and reported by consumers (70.7%). Patients from the Middle East were, on average, 34.2 years of age, had gestational diabetes mellitus as indication (64.3%), insulin detemir as suspect product (76.5%), and exposure during pregnancy as AE preferred term (89.1%). Patients from Africa were 48.1 years old on average, a higher proportion of type 2 diabetes mellitus was observed (52.2%), human insulin was the suspect product (51.6%), and blood glucose increased the AE preferred term (23.1%). Few macrovascular and microvascular complications were reported (< 1% in both regions). Associations between the region and patient age, gender, report sources, reporter types, indications for insulin use, suspect products, and AE preferred term were significant (p < 0.001). CONCLUSION: ICSRs features were region-specific and dependent on patient age, gender, report sources, reporter types, suspect products, and AE preferred terms.

Coexisting Conditions among Children and Adolescents with Cancer in a Section of the South African Private Health Sector: Perspectives from Drug Utilization Data.

Coexisting conditions are relatively common in children with cancer, however, there is a paucity of information on the prevalence of coexisting conditions in children with cancer in South Africa. This cross-sectional study aimed at investigating the common coexisting conditions occurring in children and adolescents younger than 19 years undergoing cancer chemotherapy in a section of the South African private health sector. Medicine claims data from 1 January 2008 to 31 December 2017 were queried to identify coexisting conditions using the International Classification of Diseases, Tenth Revision (ICD-10) codes indicated on reimbursed claims. Where ICD-10 codes per claim were non-specific, the pharmacological drug classes of non-cytotoxic medications claimed alongside these codes were categorized using the Monthly Index of Medical Specialties (MIMS) classification system and analyzed using the drug utilization 90% (DU90%) principle. Analysis of sub-pharmacologic drug classes was stratified according to gender and age groups. The reimbursement category of these medicines was noted. Data were analyzed descriptively. A total of 173 participants were included in the study. ICD-10 codes were available for 13.65% (N = 2631) of medicine claims. Diseases of the respiratory system (J00-J99, 7.15%), gastrointestinal tract (K00-K95, 1.60%), and skin disorders (L00-L99, 0.95%) were the most prevalent specific diagnoses identified. Non-specific ICD-10 codes were recorded on 86.35% (n = 2272) of non-cytotoxic medicine claims. The most frequently utilized pharmacological classes of medications included antimicrobial agents (17.40%), respiratory system agents (13.91%), and analgesics (10.64%). As determined from ICD-10 codes and medication claimed on reimbursed claims, children and adolescents being treated for cancers mostly suffered from acute conditions, in particular, microbial infections and diseases of the respiratory system. This indicates the need for the integration of antimicrobial surveillance programs into childhood and adolescent cancer care to curb antimicrobial infections.

Childhood cancers in a section of the South African private health sector: Analysis of medicines claims data.

BACKGROUND: Although childhood cancers are rare, increases in incidence have been observed in recent times. There is a paucity of data on the current incidence of childhood cancers in South Africa. AIM: This study described the epidemiology of childhood cancers in a section of the private health sector of South Africa, using medicines claims data. SETTING: This study was designed on a nationally representative medicine claims database. METHOD: A longitudinal open-cohort study employing children younger than 19 years and diagnosed with cancers between 2008 and 2017 was conducted using medicine claims data from a South African Pharmaceutical Benefit Management company. Cases were identified using International Classification of Diseases, Tenth Revision (ICD-10) diagnostic codes C00 to C97, together with a medicine claim reimbursed from oncology benefits. Crude incidence rates were calculated per million persons younger than 19 years on the database and standardised using the Segi 1960 world population. Temporal trends in incidence rates, analysed using the joinpoint regression, were reported as annual percentage changes (APCs). RESULTS: Overall, 173 new cases of childhood cancers were identified in the database, translating into an age-standardised incidence rate (ASR) of 82.3 per million. Annual incidence of cancer decreased from 76.7 per million in 2008 to 58.2 per million in 2017. More incident cases were identified in males (68.8%). The highest proportion of incident cases was recorded for leukaemias (39.9%), the 5-9 year age group (34.1%) and the Gauteng Province (49.7%). CONCLUSION: The incidence of childhood cancers decreased over time in the section of the private health sector studied. Leukaemias were the major drivers of childhood cancer incidence.

Assessment of post-operative pain medication adherence after day case orthopaedic surgery: A prospective, cross-sectional study.

BACKGROUND AND AIM: Patients struggle to adhere to prescribed pain medication after surgery because of, inter alia, side effects, sleep disturbances and pain severity. This study aimed to determine the influence of various factors on, the extent of adherence to prescribed post-operative pain medication (POPM) measured by participant-reported pill count (PRPC) following day case orthopaedic surgery at a private South African hospital. METHODS: This prospective, quantitative cross-sectional study involving 120 participants (51 males, 69 females), used a structured questionnaire completed through a telephonic survey, 4 days after orthopaedic surgery. Measurements included PRPC adherence (adherent vs. non-adherent), in relation to post-operative adherence behaviour (POAB), normal medicine adherence behaviour (NMAB), pain severity affecting sleep and mobility, treatment side effects and patient demographic characteristics. RESULTS: Based on PRPC measurement 56.7% (n = 68) of participants were adherent. PRPC was significantly associated with severe pain affecting falling sleep (p = .001), pain causing awakening from sleep (p = .035) and POAB (p < .001, Cramér's V = 0.5). PRPC adherence was independent from gender (p = .140), age (p = .822), smoking status (p = 1.000), type and event of side effects (p > .300), NMAB (p = .601) and the treatment regimen (i.e. unimodal vs. bimodal or multimodal) (p = .511). CONCLUSION: Non-adherence (overuse or misuse) of prescribed POPM can be a result of severe pain, influencing sleep and movement after orthopaedic surgery, indicating a need for the review of these regimens in order to optimise care.

Standards of aminoglycoside therapeutic drug monitoring in a South African private hospital: perspectives and implications.

BACKGROUND: Therapeutic drug monitoring (TDM) is essential to ensure that aminoglycoside peak concentrations are high enough for effective antimicrobial treatment and trough levels are low enough to minimise toxicity. Inappropriate utilisation of TDM may lead to suboptimal therapy, toxicity and waste of resources. This study aimed to investigate the standard of aminoglycoside TDM performed in adult hospitalised patients. DESIGN: An observational, descriptive, cross-sectional study. SETTING: A 221-bed private hospital. PARTICIPANTS: All patients, older than 18 years, on intravenous aminoglycosides for more than 48 hours were included. INTERVENTIONS: None, was observational. A computerised database and patient files were used to obtain the information required for this study. Descriptive statistical analysis was used. MAIN OUTCOMES MEASURES: Aminoglycoside blood levels and estimated glomerular filtration rate (eGFR) in the patients. RESULTS: One hundred and three (103) patients were included: 65 on gentamicin and 38 on amikacin. Blood levels were performed in only 19 gentamicin (29.23%) and 22 amikacin (57.89%) patients. Trough levels were taken more than 2 hours before the next dose in 12 gentamicin (63.16%) and 12 amikacin (54.54%) patients. The majority of patients (96.92% on gentamicin and 84.21% on amikacin) received once daily doses. TDM was performed in all patients with an estimated glomerular filtration rate (eGFR) lower than 60 mL/min/1.73m2 and in 23.31% of gentamicin patients and 56.76% of amikacin patients with an eGFR higher than 60 mg/min/1.73m2. CONCLUSIONS: Incorrect sampling times and unnecessary levels taken in patients with normal renal function indicate a need for aminoglycoside treatment guidelines in the private hospital. FUNDING: None.

Methylphenidate and atomoxetine prescribing trends in children in the Western Cape Province of South Africa, 2005-2013.

BACKGROUND: There is paucity of data on methylphenidate and atomoxetine prescribing patterns in South African children. AIM: To describe the prescribing trends of these agents in children residing in the Western Cape Province. SETTING: South African private health sector. METHODS: Longitudinal drug utilisation study on medicine claims data from 2005-2013, focussing on the number of patients and prescriptions per patient. RESULTS: The total number of patients increased by 29.5% from 2005 to 2013. The majority were boys (male:female ratio, 3.5:1), and between the ages of > 6 and ≤12 years in 2005 and >12 and ≤18 years in 2013. More than 75% of patients received methylphenidate or atomoxetine in the City of Cape Town Metropolitan municipality. Prescriptions for methylphenidate and atomoxetine increased by 45.5% overall from 2005 to 2013 (p < 0.001), with that for methylphenidate and atomoxetine increasing by 36.0% and 314.5%, respectively. The average number of annual methylphenidate prescriptions per patient increased from 3.96 ± 2.92 (95% CI, 3.69-4.23) in 2005 to 4.38 ± 2.85 (95% CI, 4.14-4.61) in 2013 (Cohen's d = 0.14) and for atomoxetine from 2.58 ± 1.86 (95% CI, 1.80-3.37) in 2005 to 4.85 ± 3.66 (95% CI, 3.84-5.86) in 2013 (Cohen's d = 0.62). CONCLUSION: Although the total number of patients and prescribing of methylphenidate and atomoxetine increased significantly from 2005 to 2013, a slight downward trend was observed in the mean number of prescriptions per patient per year from 2008 onwards. These prescribing patterns warrant further research.

Prevalence of potentially serious drug-drug interactions among South African elderly private health sector patients using the Mimica Matanovic/Vlahovic-Palcevski protocol.

OBJECTIVES: To determine the prevalence of potentially serious drug-drug interactions (DDIs) and their relationship with gender and age, among elderly in South Africa. METHODS: A cross-sectional study was conducted using pharmaceutical claims data for 2013, for a total of 103 420 medical scheme beneficiaries' ≥65 years. All medications dispensed within one calendar month where the days' supply of medication dispensed overlapped, were grouped as one prescription. DDIs per prescription were then identified using the Mimica Matanovic/Vlahovic-Palcevski DDI protocol. Results were interpreted using effect sizes, that is Cramér's V, Cohen's d and Cohen's ƒ2 . KEY FINDINGS: A total of 331 659 DDIs were identified on 235 870 (25.8%, N = 912 713) prescriptions (mean 0.36 (SD 0.7) (95% CI, 0.36 to 0.37)). Women encountered 63.5% of all DDIs. Effect sizes for the association between DDIs and age group (Cramér's V = 0.06), and gender (Cramér's V = 0.05) was negligible. There was no difference between men and women regarding the mean number of DDIs identified per prescription (Cohen's d = 0.10). The number of medicine per prescription (ƒ2 = 0.51) was the biggest predictor of the DDIs. The most frequent interacting drug combinations were between central nervous system medicines (30.6%). CONCLUSION: Our study is the first to report the prevalence of potentially serious DDIs among an elderly population in the South African private health sector utilising the Mimica Matanovic/Vlahovic-Palcevski DDI protocol. Overall, we identified DDIs in approximately 26% of the prescriptions in our study. Age and gender were not found to be predictors of potentially serious DDIs.

Medicine possession ratio as proxy for adherence to antiepileptic drugs: prevalence, associations, and cost implications.

OBJECTIVE: To determine the adherence status to antiepileptic drugs (AEDs) among epilepsy patients; to observe the association between adherence status and age, sex, active ingredient prescribed, treatment period, and number of comorbidities; and to determine the effect of nonadherence on direct medicine treatment cost of AEDs. METHODS: A retrospective study analyzing medicine claims data obtained from a South African pharmaceutical benefit management company was performed. Patients of all ages (N=19,168), who received more than one prescription for an AED, were observed from 2008 to 2013. The modified medicine possession ratio (MPRm) was used as proxy to determine the adherence status to AED treatment. The MPRm was considered acceptable (adherent) if the calculated value was ≥80%, but ≤110%, whereas an MPRm of <80% (unacceptably low) or >110% (unacceptably high) was considered nonadherent. Direct medicine treatment cost was calculated by summing the medical scheme contribution and patient co-payment associated with each AED prescription. RESULTS: Only 55% of AEDs prescribed to 19,168 patients during the study period had an acceptable MPRm. MPRm categories depended on the treatment period (P>0.0001; Cramer's V=0.208) but were independent of sex (P<0.182; Cramer's V=0.009). Age group (P<0.0001; Cramer's V=0.067), active ingredient (P<0.0001; Cramer's V=0.071), and number of comor-bidities (P<0.0001; Cramer's V=0.050) were statistically but not practically significantly associated with MPRm categories. AEDs with an unacceptably high MPRm contributed to 3.74% (US$736,376.23) of the total direct cost of all AEDs included in the study, whereas those with an unacceptably low MPRm amounted to US$3,227,894.85 (16.38%). CONCLUSION: Nonadherence to antiepileptic treatment is a major problem, encompassing ~20% of cost in our study. Adherence, however, is likely to improve with the treatment period. Further research is needed to determine the factors influencing epileptic patients' prescription refill adherence.

Prescribing patterns of non-steroidal anti-inflammatory drugs in chronic kidney disease patients in the South African private sector.

Background Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used pharmaceutical agents worldwide. NSAIDs are considered nephrotoxic and should therefore be used with caution or be avoided completely in high risk patients, such as chronic kidney disease (CKD) patients. Objective This study aimed to investigate the prescribing of NSAIDs in CKD patients in order to generate awareness and improve the outcome of these patients. Setting The study was conducted using medicine claims data in the private health sector of South Africa. Method A descriptive, quantitative study was performed, using retrospective data obtained from a Pharmaceutical Benefit Management company. Data from 1 January 2009 to 31 December 2013 were analysed. The study population consisted of all patients with an ICD-10 code for a CKD (N18), in association with a paid claim for an NSAID. Main outcome measure The stratification of NSAID prescribing volume among the CKD population in terms of gender, age, NSAID type, dosage and prescriber type. Results The prescribing of NSAIDs in CKD patients varied between 26 and 40 % over the 5 year study period. No association between gender and CKD patients who received NSAIDs versus those who did not was found, with p > 0.05 and Cramer's V < 0.1 for each year of the study. The association between age groups and CKD patients who received NSAIDs versus those who did not was statistically significant, but practically weak (p < 0.05; Cramer's V ≥ 0.1). Most NSAID prescriptions (52-63 %) were for patients aged 35-64 years. Diclofenac (34.25 %) was the single most frequently prescribed NSAID, but the COX-2-inhibitors (celecoxib, meloxicam and etoricoxib) were the preferred NSAID class to be prescribed. The majority (61.6 %) of the NSAIDs were prescribed by general medical practitioners in dosages meeting and even exceeding the recommended daily dosage of patients with normal kidney function. Conclusions Even though NSAIDs are regarded as nephrotoxic drugs, they are still being prescribed to at-risk CKD patients, in particular, the elderly.