Prescribing indicators at primary health care centers within the WHO African region: a systematic analysis (1995-2015)

Abstract Background Rational medicine use is essential to optimize quality of healthcare delivery and resource utilization. We aim to conduct a systematic review of changes in prescribing patterns in the WHO African region and comparison with WHO indicators in two time periods 1995–2005 and 2006–2015. Methods Systematic searches were conducted in PubMed, Scopus, Web of science, Africa-Wide Nipad, Africa Journals Online (AJOL), Google scholar and International Network for Rational Use of Drugs (INRUD) Bibliography databases to identify primary studies reporting prescribing indicators at primary healthcare centres (PHCs) in Africa. This was supplemented by a manual search of retrieved references. We assessed the quality of studies using a 14-point scoring system modified from the Downs and Black checklist with inclusions of recommendations in the WHO guidelines. Results Forty-three studies conducted in 11 African countries were included in the overall analysis. These studies presented prescribing indicators based on a total 141,323 patient encounters across 572 primary care facilities. The results of prescribing indicators were determined as follows; average number of medicines prescribed per patient encounter = 3.1 (IQR 2.3–4.8), percentage of medicines prescribed by generic name =68.0 % (IQR 55.4–80.3), Percentage of encounters with antibiotic prescribed =46.8 % (IQR 33.7–62.8), percentage of encounters with injection prescribed =25.0 % (IQR 18.7–39.5) and the percentage of medicines prescribed from essential medicines list =88.0 % (IQR 76.3–94.1). Prescribing indicators were generally worse in private compared with public facilities. Analysis of prescribing across two time points 1995–2005 and 2006–2015 showed no consistent trends. Conclusions Prescribing indicators for the African region deviate significantly from the WHO reference targets. Increased collaborative efforts are urgently needed to improve medicine prescribing practices in Africa with the aim of enhancing the optimal utilization of scarce resources and averting negative health consequences

Adverse-Drug-Reaction-Related Hospitalisations in Developed and Developing Countries: A Review of Prevalence and Contributing Factors

© 2016, Springer International Publishing Switzerland.Adverse drug reactions (ADRs) are one of the leading causes of hospital admissions and morbidity in developed countries and represent a substantial burden on healthcare delivery systems. However, there is little data available from low- and middle-income countries. This review compares the prevalence and characteristics of ADR-related hospitalisations in adults in developed and developing countries, including the mortality, severity and preventability associated with these events, commonly implicated drugs and contributing factors. A literature search was conducted via PubMed, Scopus, Web of Science, Embase, ProQuest and Google Scholar to find articles published in English from 2000 to 2015. Relevant observational studies were included. The median (with interquartile range [IQR]) prevalence of ADR-related hospitalisation in developed and developing countries was 6.3 % (3.3–11.0) and 5.5 % (1.1–16.9), respectively. The median proportions of preventable ADRs in developed and developing countries were 71.7 % (62.3–80.0) and 59.6 % (51.5–79.6), respectively. Similarly, the median proportions of ADRs resulting in mortality in developed and developing countries were 1.7 % (0.7–4.8) and 1.8 % (0.8–8.0), respectively. Commonly implicated drugs in both settings were antithrombotic, non-steroidal anti-inflammatory and cardiovascular drugs. Older age, female gender, number of medications, renal impairment and heart failure were reported to be associated with an increased risk for ADR-related hospitalisation in both settings while HIV/AIDS was implicated in developing countries only. The majority of ADRs were preventable in both settings, highlighting the importance of improving medication use, particularly in vulnerable patient groups such as the elderly, patients with multiple comorbidities and, in developing countries, patients with HIV/AIDS

Predictors of adverse drug reaction-related hospitalisation in Southwest Ethiopia: A prospective cross-sectional study

© 2017 Angamo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Adverse drug reactions (ADRs) are important causes of morbidity and mortality in the healthcare system; however, there are no studies reporting on the magnitude and risk factors associated with ADR-related hospitalisation in Ethiopia. Objectives: To characterise the reaction types and the drugs implicated in admission to Jimma University Specialized Hospital, Southwest Ethiopia, and to identify risk factors associated with ADR-rel ated hospitalisation. Methods: A prospective cross-sectional study was conducted from May 2015 to August 2016 among consenting patients aged =18 years consecutively admitted to medical wards taking at least one medication prior to admission. ADR-related hospitalisations were determined through expert review of medical records, laboratory tests, patient interviews and physical observation. ADR causality was assessed by the Naranjo algorithm followed by consensus review with internal medicine specialist. ADR preventability was assessed using Schumock and Thornton’s criteria. Only definite and probable ADRs that provoked hospitalisation were considered. Binary logistic regression was used to identify independent predictors of ADR-related hospitalisation. Results: Of 1,001 patients, 103 (10.3%) had ADR-related admissions. Common ADRs responsible for hospitalisation were hepatotoxicity (35, 29.4%) and acute kidney injury (27, 22.7%). The drug classes most frequently implicated were antitubercular agents (45, 25.0%) followed by antivirals (22, 12.2%) and diuretics (19, 10.6%). Independent predictors of ADR-related hospitalisation were body mass index (BMI) < 18.5 kg/m 2 (adjusted odd ratio [AOR] = 1.69; 95% confidence interval [CI] = 1.10–2.62; p = 0.047), pre-existing renal disease (AOR = 2.84; 95%CI = 1.38–5.85, p = 0.004), pre-existing liver disease (AOR = 2.61; 95%CI = 1.38–4.96; p = 0.003), number of comorbidities =4 (AOR = 2.09; 95%CI = 1.27–3.44; p = 0.004), number of drugs =6 (AOR = 2.02; 95%CI = 1.26–3.25; p = 0.004) and history of previous ADRs (AOR = 24.27; 95%CI = 11.29–52.17; p < 0.001). Most ADRs (106, 89.1%) were preventable. Conclusions: ADRs were a common cause of hospitalisation. The majority of ADRs were preventable, highlighting the need for monitoring and review of patients with lower BMI, ADR history, renal and liver diseases, multiple comorbidities and medications. ADR predictors should be integrated into clinical pathways and pharmacovigilance systems

Adherence to medication for the treatment of psychosis: rates and risk factors in an Ethiopian population

Background: Medication-taking behavior, specifically non-adherence, is significantly associated with treatment outcome and is a major cause of relapse in the treatment of psychotic disorders. Non-adherence can be multifactorial; however, the rates and associated risk factors in an Ethiopian population have not yet been elucidated. The principal aim of this study was to evaluate adherence rates to antipsychotic medications, and secondarily to identify potential factors associated with non-adherence, among psychotic patients at tertiary care teaching hospital in Southwest Ethiopia.Methods: A cross-sectional study was conducted over a 2-month period in 2009 (January 15th to March 20th) at the Jimma University Specialized Hospital. Adherence was computed using both a compliant fill rate method and self-reporting via a structured patient interview (focusing on how often regular medication doses were missed altogether, and whether they missed taking their doses on time). Data were analyzed using SPSS for windows version 16.0, and chi-square and Pearsons r tests were used to determine the statistical significance of the association of variables with adherence.Result: Three hundred thirty six patients were included in the study. A total of 75.6% were diagnosed with schizophrenia, while the others were diagnosed with other psychotic disorders. Most (88.1%) patients were taking only antipsychotics, while the remainder took more than one medication. Based upon the compliant fill rate, 57.5% of prescription fills were considered compliant, but only 19.6% of participants had compliant fills for all of their prescriptions. In contrast, on the basis of patients self-report, 52.1% of patients reported that they had never missed a medication dose, 32.0% sometimes missed their daily doses, 22.0% only missed taking their dose at the specific scheduled time, and 5.9% missed both taking their dose at the specific scheduled time and sometimes missed their daily doses. The most common reasons provided for missing medication doses were: forgetfulness (36.2%); being busy (21.0%); and a lack of sufficient information about the medication (10.0%). Pill burden, medication side-effects, social drug use, and duration of maintenance therapy each had a statistically significant association with medication adherence (P ≤ 0.05).Conclusion: The observed rate of antipsychotic medication adherence in this study was low, and depending upon the definition used to determine adherence, it is either consistent or low compared to previous reports, which highlights its pervasive and problematic nature. Adherence must therefore be considered when planning treatment strategies with antipsychotic medications, particularly in countries such as Ethiopia. © 2012 Alene et al.; licensee BioMed Central Ltd

Moderate hypoxia followed by reoxygenation results in blood-brain barrier breakdown via oxidative stress-dependent tight-junction protein disruption.

Re-canalization of cerebral vessels in ischemic stroke is pivotal to rescue dysfunctional brain areas that are exposed to moderate hypoxia within the penumbra from irreversible cell death. Goal of the present study was to evaluate the effect of moderate hypoxia followed by reoxygenation (MHR) on the evolution of reactive oxygen species (ROS) and blood-brain barrier (BBB) integrity in brain endothelial cells (BEC). BBB integrity was assessed in BEC in vitro and in microvessels of the guinea pig whole brain in situ preparation. Probes were exposed to MHR (2 hours 67-70 mmHg O2, 3 hours reoxygenation, BEC) or towards occlusion of the arteria cerebri media (MCAO) with or without subsequent reperfusion in the whole brain preparation. In vitro BBB integrity was evaluated using trans-endothelial electrical resistance (TEER) and transwell permeability assays. ROS in BEC were evaluated using 2',7'-dichlorodihydrofluorescein diacetate (DCF), MitoSox and immunostaining for nitrotyrosine. Tight-junction protein (TJ) integrity in BEC, stainings for nitrotyrosine and FITC-albumin extravasation in the guinea pig brain preparation were assessed by confocal microscopy. Diphenyleneiodonium (DPI) was used to investigate NADPH oxidase dependent ROS evolution and its effect on BBB parameters in BEC. MHR impaired TJ proteins zonula occludens 1 (ZO-1) and claudin 5 (Cl5), decreased TEER, and significantly increased cytosolic ROS in BEC. These events were blocked by the NADPH oxidase inhibitor DPI. MCAO with or without subsequent reoxygenation resulted in extravasation of FITC-albumin and ROS generation in the penumbra region of the guinea pig brain preparation and confirmed BBB damage. BEC integrity may be impaired through ROS in MHR on the level of TJ and the BBB is also functionally impaired in moderate hypoxic conditions followed by reperfusion in a complex guinea pig brain preparation. These findings suggest that the BBB is susceptible towards MHR and that ROS play a key role in this process

MCAO followed by reperfusion leads to the generation of ROS in cerebral microvessels.

<p>Images from a representative control (<b>A</b>) hemisphere and its contralateral tMCAO hemisphere (<b>B</b>) of the neocortex are shown. MAP 2 (red), Fluorescein isothiocyanate –albumin (FITC-albumin; green) and anti-nitrotyrosine (blue) are displayed (n = 3 brains). Perfused control hemispheres (contralateral to tMCAO) displayed an intact MAP2 immunoreactivity, no FITC-albumin extravasation and absence of nitrotyrosine formation (<b>A</b>). In the penumbra of corresponding tMCAO hemispheres MAP2 damage was present as well as large and diffuse FITC-albumin extravasation. Here we found that cerebral microvessels (indicated by arrows and inset) were immunoreactive for nitrotyrosine indicating the formation of ROS (<b>B</b>). Note the cytosolic staining pattern of nitrotyrosine indicating the cytosolic localization of ROS.</p

MHR impairs TEER in Brain endothelial cells and increases transcellular permeability towards high molecular mass molecules.

<p>Trans-endothelial resistance values detected with ECIS (<b>A</b>) were significantly lower in BEC after MHR than in normoxic conditions (normoxia 1 <u>+</u> 0.004 vs. MHR no inhibitor 0.77 <u>+</u> 0.02, P < 0.0001; n = 169 - 288 TEER measurements from 3 experiments). DPI prevented the decrease of TEER significantly (MHR+DPI 0.98 <u>+</u> 0.01 vs. MHR no inhibitor 0.77 <u>+</u> 0.02, P < 0.0001; n = 168 - 192 TEER measurements from 3 experiments). MHR resulted in an increase of FITC-Dextran (150,000 Dalton) permeability in bEnd.3 monolayers (normoxia 1 <u>+</u> 0.09 vs. MHR 2.27 <u>+</u> 0.75, P < 0.05; n = 7-15 permeability assays, <b>B</b>). </p

MHR disrupts BEC integrity on the level of tight junction proteins.

<p>BEC displayed a physiological arrangement of TJ proteins Claudin 5 (<b>A</b>) and zonula occludens 1 (<b>B</b>) in a co-localizing manner (<b>C</b>) with only few TJ gaps (arrowheads). MHR disrupted the continuous arrangement of both junctional proteins in BEC (arrowheads <b>D-F</b>). Here, DPI blocked TJ injury in MHR, only few TJ disruptions were detected in BEC pre-treated with the NADPH oxidase inhibitor DPI (arrowheads <b>G-I</b>). Representative images from 3 experiments per group are shown. Quantitative analyses of Cl5 (Cl5 normoxia: 5.85 <u>+</u> 0.33 vs. Cl5 MHR: 2.72 <u>+</u> 0.54, P < 0.0001; n = 12 cells per group from 3 experiments, <b>J</b>) and ZO-1 (ZO-1 normoxia: 12.53 <u>+</u> 1.27 vs. ZO-1 MHR: 3.98 <u>+</u> 0.67, P < 0.0001; n = 12 cells per group from 3 experiments, <b>K</b>) integrity on cell membranes revealed that both junctional proteins are significantly perturbed in MHR. DPI pre-treatment significantly restored TJ integrity at cellular membranes under MHR (Cl5 MHR: 2.72 <u>+</u> 0.54 vs. Cl5 MHR+DPI: 6.57 <u>+</u> 0.69, P = 0.0002; ZO-1 MHR: 3.98 <u>+</u> 0.67 vs. ZO-1 MHR+DPI 10.55 <u>+</u> 1.21, P < 0.0001; n = 12 cells per group from 3 experiments). </p