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Drug–drug interactions (DDIs) cause significant morbidity and mortality, especially in patients with HIV with opportunistic infections such as tuberculosis. However, the literature on quantitative signal detection analyses for DDIs within the national spontaneous reporting systems (SRSs) of countries with high HIV/tuberculosis burdens is lacking. Our objective was to explore the utility of using post-marketing SRSs in quantitative signal detection analyses of DDIs. A case/non-case analysis using the Zimbabwean adverse drug reaction (ADR) database obtained from VigiBase® was utilized for quantitative signal detection using 2 × 2 contingency table calculations. Cases were defined as individual case safety reports (ICSRs) with the ADR of interest, and non-cases included the rest of the ICSRs. The exposure of interest was the use of a drug of interest. Signals of disproportionate reporting (SDRs) were observed for hepatotoxicity for the combined use of highly active antiretroviral therapy (HAART) and antitubercular treatments (ATT) [ADR reporting odds ratio (ROR) 43.78; 95% CI 5.24–366.08], HAART and isoniazid (ROR 44.84; 95% CI 5.36–374.99), and isoniazid and nevirapine-based HAART (ROR 35.60; 95% CI 9.39–134.89). SDRs were also observed for the combined use of nevirapine-based HAART and co-trimoxazole for Stevens–Johnson syndrome (ROR 28.91; 95% CI 14.00–59.70), severe cutaneous ADRs (ROR 16.10; 95% CI 9.40–27.57), and rash (OR 2.18; 95% CI 1.69–2.81). It is feasible to conduct signal detection analyses for DDIs within relatively small SRS databases. However, the observed potential SDR for the respective DDI should be investigated further as the method is only a hypothesis-generation analysis.

We aimed to determine the reporting trends and characteristics of Individual Case Safety Reports (ICSRs) from the Zimbabwean national pharmacovigilance system. ICSRs submitted to VigiBaseTM, the World Health Organisation's ICSR database between January 1993 and December 2017 were retrospectively reviewed with respect to the suspected medicine, System Organ Class (SOC), adverse drug reaction (ADR) type and seriousness, Anatomic Therapeutic Chemical (ATC) group, age, and gender. In total, 4071 ICSRs were submitted to VigiBaseTM from targeted spontaneous reporting (n = 2909; 71.5%), vaccine surveillance (n = 679; 16.7%), and passive spontaneous reporting (n = 483; 11.9%), respectively. The median age, ICSR completeness score and timeliness of reporting were 34.0 years (IQR: 14.0; 43.0), 0.90 (IQR: 0.70; 1.00), and 548.0 days (IQR: 266:1131), respectively. More than half of the ICRS were from female patients (n = 2233; 54.9%). Antiretrovirals, antibiotics, vaccines, and anti‐tubercular medicines were reported in 62.9%, 27.9%, 16.7%, and 13.3% of submitted ICSRs, respectively. The most frequent ADRs involved the skin and subcutaneous systems (n = 1111; 20.5%), nervous system (n = 733; 13.5%), and gastrointestinal disorders system (n = 654; 12.1%). The number of ADRs reported for each patient was significantly related to the reported medicine's ATC category (P = .001. The number of ADRs was significantly related to the use of antiretroviral agents. In conclusion, Zimbabwe has made significant progress in establishing a functional pharmacovigilance system. However, the present system reports on a limited therapeutic spectrum of medicines and potentially underestimates the national ADR burden. Further work is required to strengthen the more sustainable spontaneous reporting system which potentially captures a variety of therapeutic classes.

The development of appropriate dosage forms for paediatric antiretroviral therapy is key for improved therapeutic outcomes in children. The focus of this study was to improve solubility, dissolution rate, drug release and maintain high drug permeability. A nanoemulsion was prepared using emulsion inversion point and evaluated. The nanoemulsion had nevirapine (3% w/w). In vitro drug release studies were performed using dialysis membrane. Permeability studies using the Caco-2 cell model were performed for the formulation. The optimized nevirapine nanoemulsion had a mean droplet size of 36.09±12.27nm, low pdI of 0.598 and zeta potential of -7.87±4.35mV. At pH 2, the nanoemulsion released 76 ± 2 % of nevirapine within 2 h, while at pH 6.4 value representing the small intestine, amount of nevirapine released was 41.6± 4 %. The permeability rate of the nevirapine nanoemulsion was 30.02 x 10-6cm/s and higher than that of propranolol. Efflux ratio was 0.02 indicating low chance of drug efflux occurring. The results showed that a modified liquid drug release formulations of nevirapine could improve rate of dissolution and maintain high permeability and low drug efflux improving bioavailability of nevirapine in vivo.

Few studies describe the adverse drug event profiles in patients simultaneously receiving antiretroviral and anti-tubercular medicines in resource-limited countries. To describe and compare the adverse drug reaction profiles in patients on highly active antiretroviral therapy only (HAART), HAART and isoniazid preventive therapy (HHART), and HAART and antitubercular treatment (ATTHAART). We analysed individual case safety reports (ICSRs) for patients on antiretroviral therapy and antitubercular treatment submitted to the national pharmacovigilance centre during the targeted spontaneous reporting (TSR) programme from 1 September 2012 through 31 August 2016. All reports considered certain, probable or possible were included in the analysis. A total of 1076 ICSRs were included in the analysis. Most of the reports were from the HAART only group (n = 882; 82.0%), followed by patients on HHART (n = 132; 12.3%), and ATTHAART (n = 62; 5.7%). The ATTHAART (35.5%) and HHAART (34.1%) had a higher frequency of hepatic disorders than the HAART group (5.0%) (p

Herbal medicines are considered an intricate and integral part of humankind's knowledge systems. Time has proven their efficacy and safety for both human and animal applications. Modern science, guided by indigenous knowledge systems can further optimize the use of various herbal products. To widen the current focus on herbal medicines, a study was carried-out to determine antioxidant properties, phytochemical and mineral contents of some medicinal plants used in ethnoveterinary practices in the management of animal wounds in Zimbabwe. The studied plants were Cissus quadrangularis L, Erythrina abyssinica Lam. ExDC. and Adenium multiflorum Klotzsch. Radical scavenging activities, antioxidant properties were determined using the DPPH and the β-carotene-linoleic acid model while the total phenolic content was determined using the Folin C method, flavonoid content using the aluminium assay and mineral content was investigated using the ICP-OES method. All extracts investigated exhibited radical scavenging activities and antioxidant properties, with C. quadrangularis leaf extracts exhibiting superior activities such as radical scavenging (EC50 of 21.04 ± 3.00 μg/ml) and antioxidant properties (ORR of 0.03 ± 0.01). Variations were observed in the total phenolic, flavonoid and metal contents. C. quadrangularis leaf extracts exhibited highest amounts of total phenolic and flavonoid contents. The E. abyssinica (bark) and A. multiflorum extracts exhibited moderate (40–70%) affinity for protein binding while the rest of the extracts exhibited high affinity. Their antioxidant properties, phytochemical profile and mineral content justify applications in animal wound management and many other human and/or animal uses.

BACKGROUNDThe aim of this study was to assess the cost effectiveness of introducing individual-donation nucleic acid testing (ID-NAT), in addition to serologic tests, compared with the exclusive use of serologic tests for the identification of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) I and II among blood donors in Zimbabwe. STUDY DESIGN AND METHODSThe costs, health consequences, and cost effectiveness of adding ID-NAT to serologic tests, compared with serologic testing alone, were estimated from a health care perspective using a decision-analytic model. RESULTSThe introduction of ID-NAT in addition to serologic tests would lower the risk of HBV, HCV, and HIV transmission to 46.9, 0.3, and 2.7 per 100,000 donations, respectively. ID-NAT would prevent an estimated 25, 6, and 9 HBV, HCV, and HIV transfusion-transmitted infections per 100,000 donations, respectively. The introduction of this intervention would result in an estimated 212 quality-adjusted life-years (QALYs) gained. The incremental cost-effectiveness ratio is estimated at US$17,774/QALY, a value far more than three times the gross national income per capita for Zimbabwe. CONCLUSIONAlthough the introduction of NAT could further improve the safety of the blood supply, current evidence suggests that it cannot be considered cost effective. Reducing the test costs for NAT through efficient donor recruitment, negotiating the price of reagents, and the efficient use of technology will improve cost effectiveness.

A 29-year-old Black female patient was admitted to a psychiatric ward with symptoms of major depressive disorder with psychosis. The patient was started on amitriptyline 50 mg/day and haloperidol 10 mg/day. On day 4 post-admission, the preferred first-line antidepressant, fluoxetine, became available and the patient was switched from amitriptyline to fluoxetine 20 mg/day. On the same day, the dose of haloperidol was reduced to 5 mg/day. Thirteen days post-initiation of these medications the patient became talkative, associated with emotional lability, an expansive mood, irritability and restlessness. The working diagnosis was changed to bipolar affective disorder in the manic phase. Fluoxetine was discontinued and carbamazepine 600 mg/day was added to the patient’s treatment regimen. Her manic symptoms started to resolve; however, 14 days post-initiation of carbamazepine, the patient had a fever; itchy, discharging eyes; respiratory distress; generalised symmetrical erythematosus rash; buccal ulceration; and conjunctival injection with difficulty opening her eyes. Carbamazepine was immediately discontinued and the patient received intravenous fluid resuscitation. The patient recovered considerably after 12 days of symptomatic and supportive management, and was transferred back to the psychiatric ward for the continuation of bipolar disorder management. Lithium therapy was instituted and the patient was subsequently discharged. Using the Algorithm of Drug causality for Epidermal Necrolysis (ALDEN) Stevens–Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) drug causality scoring system, carbamazepine and fluoxetine were evaluated as ‘very probable’ and ‘possible’ causes of SJS, respectively, in this patient. Fluoxetine-induced SJS was considered on account of previous case reports, however no evidence of causality was found in this patient. Consecutive administration with a potential increase in carbamazepine due to inhibition of cytochrome P450 (CYP) 3A4 metabolism by fluoxetine was also not ruled out. A diagnosis of carbamazepine-induced SJS was made and was considered an idiosyncratic adverse drug reaction.

BACKGROUND: There is lack of published data on the costs of blood and blood transfusion in sub-Saharan Africa. This study aimed to assess the unit costs of producing blood in Zimbabwe using an activity-based costing (ABC) method. STUDY DESIGN AND METHODS: A management accounting approach, based on the ABC method, was used to develop a cost model for blood. The production of blood was broken down into recruitment, collection, testing, processing, and storage plus distribution. Data for the year 2013 were collected retrospectively from budgets, financial and expenditure reports, databases, and interviews with transfusion personnel and managers. All direct and indirect costs, in 2013 US$, were allocated, accordingly, to the activities of blood acquisition. RESULTS: The total cost of producing safe blood in Zimbabwe for the year 2013 was US$8.6 million. Variable costs accounted for 51.2% of the total cost of production. The unit production costs for red blood cells (RBCs) were US$15.94 for recruitment, US$34.62 for collection, US$17.88 for testing, US$11.49 for processing, and US$3.06 for storage plus distribution. The overall cost of production of one unit of whole blood was US$118.42 and RBCs was US$130.94 constituting 12.4 and 13.7% of the country's annual GDP per capita. CONCLUSIONS: The high unit cost of producing blood relative to the annual GDP per capita demonstrates that acquiring safe blood is a burden on the health care sector in Zimbabwe. Introducing additional safety measures, such as nucleic acid amplification testing and pathogen reduction technology, although desirable, will further increase this burden.

Introduction Cohort event monitoring (CEM) is an intensive method of post-marketing surveillance for medicines safety. The method is based on prescription event monitoring, which began in the 1970s, and has since been adapted by WHO for monitoring the safety of medicines used in Public Health Programmes. CEM aims to capture all adverse events that occur in a defined group of patients after starting treatment with a specific medicine during the course of routine clinical practice. Objective The aims of this study were to describe the experiences of National Pharmacovigilance Centres (NCs) that have used CEM to monitor artemisinin-based combination therapy (ACT) for uncomplicated malaria in the African setting, to raise awareness of some of the challenges encountered during implementation and to highlight aspects of the method that require further consideration. Method A questionnaire-based survey was conducted to capture the experiences of NCs that have implemented CEM for active post-marketing surveillance of antimalarial medicines in sub-Saharan Africa. Six NCs were identified as having implemented CEM programmes and were invited to participate in the survey; five NCs indicated willingness to participate and were sent the questionnaire to complete. Results Four NCs responded to the survey—Ghana, Kenya, Nigeria and Zimbabwe—providing information on the implementation of a total of six CEM programmes. Their experiences indicate that CEM has helped to build pharmacovigilance capacity within the participating NCs and at the monitoring sites, and that healthcare providers (HCPs) are generally willing to participate in implementing the CEM method. All of the programmes took longer than expected to complete: contributing factors included a prolonged enrolment period and unexpectedly slow data entry. All of the programmes exceeded their budget by 11.1–63.2 %. Data management was identified as a challenge for all participating NCs. Conclusions The reported experiences of four NCs that have undertaken CEM studies on ACTs indicate that CEM has helped to build pharmacovigilance capacity within NCs and monitoring sites and that HCPs are willing to participate in CEM programmes; however, the method was found to be labour intensive and data management was identified as a challenge. Reducing the workload associated with CEM, particularly in relation to data management, and integrating the method into the routine work of HCPs and NCs should be considered for future implementation. Electronic supplementary material The online version of this article (doi:10.1007/s40264-015-0331-7) contains supplementary material, which is available to authorized users.

Plants have arrays of phytoconstituents that have wide ranging biological effects like antioxidant, anti-inflammatory and antimicrobial properties key in wound management. In vivo wound healing properties of ointments made of crude methanolic extracts (10% extract w/w in white soft paraffin) of three plant species, Cissus quadrangularis L. (whole aerial plant parts), Adenium multiflorum Klotzsch (whole aerial plant parts) and Erythrina abyssinica Lam. Ex DC. (leaves and bark) used in ethnoveterinary medicine were evaluated on BALB/c female mice based on wound area changes, regular observations, healing skin's percentage crude protein content and histological examinations. White soft paraffin and 3% oxytetracycline ointment were used as negative and positive controls, respectively. Wound area changes over a 15 day period for mice treated with C. quadrangularis and A. multiflorum extract ointments were comparable to those of the positive control (oxytetracycline ointment). Wounds managed with the same extract ointments exhibited high crude protein contents, similar to what was observed on animals treated with the positive control. Histological evaluations revealed that C. quadrangularis had superior wound healing properties with the wound area completely returning to normal skin structure by day 15 of the experiment. E. abyssinica leaf and bark extract ointments exhibited lower wound healing properties though the leaf extract exhibited some modest healing properties.

Background/Case Studies: Blood utilization and blood transfusion costs are generally perceived to be increasing at a time when healthcare budgets continue being constricted. There is a paucity of published data on the production costs of blood and the costs of blood transfusion in sub-Saharan Africa. Blood transfusion costs from developed countries are likely not transferable to the sub-Sahara African region, due to differences in models for collecting blood, the level of processing into components, and implementation of sophisticated blood safety measures. This study aimed to assess the unit costs of production of blood at the national blood service by using standardized methodology. Study Design/Methods: A management accounting approach, based on the Activity- Based Costing (ABC) methodology, was chosen to develop the cost model from the provider's perspective. The production of blood was broken down into recruitment, collection, processing and storage, and distribution. Data covering the calendar year of 2013 were collected retrospectively from the budgets, financial and expenditure reports, databases, and interviews with transfusion personnel and managers. All direct and indirect costs (capital and recurrent), in 2013 US$, were allocated accordingly to the components of blood acquisition. Results/Findings: Of the 70,834 donation visits (including repeat visits) that were screened in 2013, 67,440 visits (95.2%) were accepted for donation and, of these, the number of useful units of whole blood collected was 67,422 (99.9%). The total number of units of safe blood prepared was 70,636, and the total number of units distributed was 62,624 (88.7%). The total cost of producing blood for the year 2013 stood at US$8.3 million. Recurrent costs accounted for 94.2% of the total cost of production. The major cost drivers for the recurrent costs were personnel (38.5%) and laboratory supplies (31.9%). The unit production costs for recruitment, collection, processing, storage, and distribution were US$22.44, US$30.90, USD$73.00, and USD$5.75, respectively. The overall unit production cost for 2013 was US$132.10, 18.5% of the country's GDP per capita. Conclusion: These findings show that acquiring safe blood in an underdeveloped country is an expensive undertaking compared to that in the United States (0.4% of GDP). To account for all of the blood transfusion costs, this study has to be expanded to include all of the vein-to-vein incurred costs of transfusion.

Background: Donor selection is one of the first steps in blood donation aimed at improving the safety of blood and blood products. It is the only line of protection for donors and against certain infections for which testing is not performed. There is paucity of published data on reasons for donor deferral characteristics in Sub-Saharan Africa. Aims: To quantify the rate and reasons for blood donor deferral among voluntary non-remunerated blood donors in Zimbabwe. Methods: A retrospective audit of all blood donors who reported for donation at the National Blood Service Zimbabwe (NBSZ) or any of its collection sites, for the period, 1 January 2011-31 December 2011, was conducted. Eleven deferral categories were created that included malaria, medication, high risk behaviour, feeling unwell, positive TTI results, medical diagnoses, blood pressure, other infections, failed copper sulphate test, donor reactions and other reasons. Deferral rates per 10,000 donor visits were determined for each deferral category and for subgroups based on blood donation status (first time or repeat), sex, age and donation site (fixed or mobile). Results: 51,893 prospective blood donors presented for donation in 2011 and the majority were first time blood donors (62.2%). Most of the prospective donors (74.1%) presented for donation at mobile sites. There were 48,241 (93.0%) donors eligible to donate and 3652 (7.0%) deferred donor visits. The overall deferral rates ranged from 2 per 10,000 visits for donor reactions to 371 per 10,000 visits for positive TTI results. Deferral rates varied by the different demographic subcategories; donor status, sex, age and donation site. Positive TTI results and failed copper sulphate test had overly high rates of deferral across all the demographic subcategories (range 1 per 10,000 to 299 per 10,000 visits). Summary/conclusions: Donor deferrals are fairly common in Zimbabwe. The overall rate of deferral is comparable to values reported in middle - high income countries, however the causes and demographics differ. This may indicate differences in donor selection criteria and practice. Understanding reasons for donor deferral is important for the development of appropriate and cost-effective education, donor selection, recruitment and marketing strategies. Table 1: Number of presenting donors at the National Blood Service Zimbabwe centers and donation outcome for year 2011. (Table presented).

Oral ketoconazole was recently the subject of regulatory safety warnings because of its association with increased risk of inducing hepatic injury. However, the relative hepatotoxicity of antifungal agents has not been clearly established. The aim of this study was to compare the hepatotoxicity induced by five commonly prescribed oral antifungal agents. Rats were treated with therapeutic oral doses of griseofulvin, fluconazole, itraconazole, ketoconazole, and terbinafine. After 14 days, only ketoconazole had significantly higher ALT levels (p=0.0017) and AST levels (p=0.0008) than the control group. After 28 days, ALT levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, griseofulvin, and terbinafine, respectively. The AST levels were highest in the rats treated with ketoconazole followed by itraconazole, fluconazole, terbinafine, and griseofulvin, respectively. All drugs significantly elevated ALP levels after 14 days and 28 days of treatment (p<0.0001). The liver enzyme levels suggested that ketoconazole had the highest risk in causing liver injury followed by itraconazole, fluconazole, terbinafine, and griseofulvin. However, histopathological changes revealed that fluconazole was the most hepatotoxic, followed by ketoconazole, itraconazole, terbinafine, and griseofulvin, respectively. Given the poor correlation between liver enzymes and the extent of liver injury, it is important to confirm liver injury through histological examination.

Health-related quality of life (HRQoL) is a broad concept reflecting a patient's general subjective perception of the effect of an illness or intervention on physical, psychological and social aspects of their daily life. HRQoL among patients infected with HIV has become an important indicator of impact of disease and treatment outcomes. A cross-sectional survey was carried out at Chitungwiza Central Hospital, Zimbabwe, to assess HRQoL in patients with HIV/AIDS receiving antiretroviral therapy (ART), using two validated instruments. The HIV/AIDS-targeted quality of life (HAT-QoL) and EuroQoL Five-dimensions-Three-level (EQ-5D-3L) instruments were used to assess HRQoL. Internal consistency reliability and convergent validity of the two instruments were also evaluated. For construct validity, the relationships between HRQoL scores and socio-economic and HIV/AIDS-related characteristics were explored. The median scores for the HAT-QoL dimensions ranged from 33.3 (financial worries) to 100 (HIV mastery). A considerably low HAT-QoL dimension score of 50.0 was observed for sexual function. There were ceiling effects for all HAT-QoL dimension scores except for financial worries and disclosure worries. Floor effects were observed for financial worries and sexual function. The median of the EQ-5D-3L index and visual analogue scale (VAS) was 0.81 and 79.0, respectively. There were no floor or ceiling effects for both the EQ-5D-3L index and VAS. The overall scale Cronbach's alpha was 0.83 for HAT-Qol and 0.67 for EQ-5D-3L. HAT-QoL demonstrated good convergent validity with EQ-5D index (0.58) and VAS (0.40). A higher level of HRQoL was positively and significantly related to income, education and employment. The patients' self-reported HRQoL was generally satisfactory in all the HAT-QoL dimensions as well as the two components on the EQ-5D-3L instrument. The two instruments demonstrated good measurement properties in HIV/AIDS patients receiving ART and have potential for use, alongside biomarkers, in monitoring outcomes of interventions.

The establishment and strengthening of poisons centres was identified as a regional priority at the first African regional meeting on the Strategic Approach to International Chemicals Management (SAICM) in June 2006. At this meeting, the possibility of a subregional poisons centre, that is, a centre in one country serving multiple countries, was suggested. The WHO Headquarters following consultation with counterparts at the WHO Regional Office for Africa (AFRO) and the SAICM Africa Regional Focal Point successfully submitted a proposal to the SAICM Quick Start Programme (QSP) Trust Fund Committee for a feasibility study into a subregional poisons centre in the Eastern Africa subregion. However, before such a study could be conducted it was deemed necessary to carry out a literature review on the patterns and epidemiology of poisoning in this region so as to inform the feasibility study. The current paper presents the results of this literature review. The literature search was done in the months of June and July 2012 by two independent reviewers with no language or publication date restrictions using defined search terms on PUBMED. After screening, the eventual selection of articles for review and inclusion in this study was done by a third reviewer.

Background Recent evidence from case reports, observational studies, and randomized trials suggests that long-term use of antidepressants increases the risk of developing diabetes. However, the nature of the relationship between antidepressants and diabetes remains unclear. Objective To determine whether there is an association between antidepressant use and the risk of developing type 2 diabetes mellitus. Methods A nested case–control study using the Texas Medicaid prescription claims database was conducted. Data were extracted for new users of either antidepressant agents (exposed) or benzodiazepines (unexposed) from January 1, 2002 through December 31, 2009. Patients aged 18–64 years without a history of diabetes were included in the cohort. The adjusted odds ratio (OR) and 95% confidence interval (CI) for the risk of diabetes associated with antidepressant exposure was computed using conditional logistic regression, controlling for demographic and clinical covariates. Main outcome measure Development of type 2 diabetes mellitus Results Among the total sample (N = 44,715), the majority were in the exposed (N = 35,552) vs. the unexposed (N = 9,163) group. A total of 2,943 cases of type 2 diabetes mellitus and 11,748 matched controls (1:4) were identified using risk-set sampling. Cases and controls were matched using age and gender. Antidepressant use was associated with an increase in the risk of (type-2) diabetes when compared to benzodiazepine use [Adjusted Odds Ratio (OR) = 1.512; 95% CI 1.345–1.700]. The association was observed with serotonin-norepinephrine reuptake inhibitors (OR = 1.742; 95% CI 1.472–2.060), tricyclic antidepressants (OR = 1.533; 95% CI 1.295–1.814), selective serotonin reuptake inhibitors (OR = 1.457; 95% CI 1.279–1.659), “Other” antidepressants (OR = 1.318; 95% CI 1.129–1.540). Conclusions Antidepressant use was associated with an increased risk of (type-2) diabetes. This association was observed for tricyclic antidepressants, serotonin-reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and other antidepressants.

Purpose To compare the multivariable-adjusted logistic regression model with the propensity score-matched, propensity score-stratified and propensity score-adjusted logistic regression models in estimating the effect of exposure to antidepressant agents in increasing the risk for type 2 diabetes mellitus. Methods A retrospective cohort study in the USA, using the Texas Medicaid prescription claims database was conducted from 1 January 1 2002 to 31 December 2009. Patients aged 18–64 years with new prescriptions for antidepressants (exposed group) or benzodiazepines (unexposed group) during the study period constituted the base population. Patients without diabetes at cohort entry were included in the study. Propensity scores, which predicted exposure to antidepressant agents, were used to create propensity score-matched, propensity score-stratified and propensity score-adjusted logistic regression models. Results A total of 44 715 patients formed the study sample. The risk estimates varied across different analytic methods. The propensity score-matched logistic regression model yielded the highest risk estimate (relative risk (RR) = 1.931; 95% confidence interval (CI): 1.705 to 2.187). The propensity score-stratified model (RR = 1.457; 95% CI: 1.127 to 1.884), the propensity score-adjusted regression model (RR = 1.491; 95% CI: 1.334 to 1.665) and the multivariable-adjusted logistic regression model (RR = 1.478; 95% CI: 1.323 to 1.653) yielded similar risk estimates. Conclusions Propensity score techniques using pharmacy claims data with a limited number of covariates yielded varied estimates of the treatment effect. The propensity score-matched model yielded a less biased treatment effect estimate than the multivariable-adjusted, the propensity score-stratified, and the propensity score-adjusted regression models.

Objectives Attention deficit/hyperactivity disorder (ADHD) medication users frequently take ‘drug holidays’ during the summer months. The study objective was to compare ADHD medication adherence for the school year (SY, 270 days) and for the entire year (EY, 365 days) by medication type, medication class and duration of action. Methods Continuously enrolled Texas Medicaid children (≤18 years) who had two or more prescription claims for an ADHD medication served as the study population. SY (1 September–31 May) and EY (1 January–31 December) prescription claims were extracted from July 2002 to December 2008. Key findings Overall mean (±SD) adherence for SY (n = 50 842) and EY (n = 62 789) time frames was 62.2% (±26.2%) and 49.8% (±30.3%), respectively. The overall frequency of patients who were adherent (medication possession ratio, ≥80%) was higher during SY (28.3%) than during EY (22.1%). Regarding medication type, mean adherence for immediate-release stimulants (52.8 versus 37.2%), extended-release stimulants (63.7 versus 52.1%), pro-drug stimulants (63.5 versus 47.6%) and non-stimulants (62.9 versus 52.5%) was higher during SY than EY, respectively. Regarding medication class, mean adherence for stimulants (62.1 versus 49.4%) and non-stimulants (62.9 versus 52.5%) was higher during SY than EY. Similarly, regarding duration of action, mean adherence for short-acting agents (52.2 versus 37.2%) and long-acting agents (63.4 versus 52.2%) was higher during SY than EY, respectively. Conclusions Patients were more adherent during the SY compared to the EY. Due to unique patient medication-taking behaviors, ADHD medication adherence differs depending on the time frame used.

Aim of the review Although there are several case reports in literature linking use of antidepressants and disturbances in glucose control, it is difficult to identify risk factors for serious adverse drug events from individual case reports. The aim of this review is to provide a descriptive analysis of the demographic and clinical characteristics of published glucose dysregulation case reports following initiation of antidepressant agents. Methods Published case reports of glucose dysregulation associated with antidepressants were accessed through PubMed (Medline), PsycINFO, and Web of Science (WOS) between January 1, 1970 and April 30, 2010. The following key words were used: antidepressant agents, glucose dysregulation, hypoglycemia, hyperglycemia, diabetes mellitus, and diabetic ketoacidosis. Case reports were excluded if glucose dysregulation occurred after a drug overdose/improper dosing or after the patient was prescribed drugs known to cause glucose disturbances in addition to antidepressant agents. Results Out of the 17 cases reports reviewed, nine (53%) were of hyperglycemia while eight (47%) were of hypoglycemia. Hyperglycemia was reported following treatment with clomipramine, fluvoxamine, imipramine, mianserin, mirtazapine, paroxetine, and sertraline. Hypoglycemia was reported following treatment with doxepine, fluoxetine, imipramine, nefazodone, nortriptyline, maprotiline, and sertraline. Fourteen out of the seventeen patients were female (82%) while ten had a history of diabetes mellitus (59%). The average age of the patients was 53.9 (SD = 17.5) years (range: 24–84 years). The time to onset of glucose dysregulation ranged from 4 days to 5 months after initiation of antidepressant therapy. More than two-thirds (68%) of the cases (n = 11) reported glucose control disturbances within 1 month of therapy. Conclusions It is not clear from published case reports whether changes in glucose regulation, following antidepressant therapy initiation are due to antidepressants or changes in mood and lifestyle. Nonetheless, healthcare providers should be aware of the potential changes in glucose regulation especially in the first month of antidepressant therapy, and use appropriate clinical and laboratory monitoring to prevent serious adverse events in patients at risk.

Objectives To investigate the state of health economic research in Russia available in the English language by describing the number and characteristics of the articles, and assessing the quality of these articles. Methods The study assessed the state of health economics and pharmacoeconomics research in Russia. We conducted a literature search to identify health economics articles pertaining to Russia. Each article in the final sample was scored by two reviewers independently using the data-collection form designed for the study. Key findings In total, 16 studies investigating a wide variety of diseases were included in the study. These articles were published in 15 different journals all based outside of Russia between 1994 and 2009. On average, each article was written by seven authors. Most first authors had medical/clinical training and resided in the USA (n = 8) at the time of publication of the study. Based on a scale of 1–10, with 10 indicating the highest quality, the mean quality score for all studies was 8.09 (SD = 1.29) and 25% of the articles were of fair quality (score 5–7). The quality of articles was statistically significantly related (P non-pharmaceuticals) and primary training of the first author (medical > non-medical). Conclusions The conduct of health economics and pharmacoeconomics research in Russia in the English language is limited and, on average, the published articles were of good quality. However, about one-quarter of published articles were of fair quality. More health economics research in English is warranted in Russia.

Objective Pharmacists in the United States (U.S.) are encouraged to report serious adverse drug events (ADEs) to the Food and Drug Administration (FDA) through MedWatch. The aim of this study is to investigate the beliefs and opinions of Texas pharmacists toward reporting ADEs to the FDA. Methods The comments made by pharmacists in state-wide mail survey about reporting serious ADEs to the FDA were independently content analyzed and categorized into themes by two raters. Some comments contained more than one idea and these were categorized into different themes. Main outcome Beliefs and opinions of Texas pharmacists toward ADE reporting. Results A total of 86 pharmacists provided comments on ADE reporting. Texas pharmacists had positive opinions about reporting ADEs to the FDA (e.g., important, valuable and positive). Respondents cited many constraints that impeded the reporting of ADEs: lack of time, failure to know which ADEs to report, difficulty in linking ADEs to a specific drug, lack of patient history, lack of compensation, fear of malpractice suits, limited support from employers and mistrust of the FDA. Pharmacists recommended continuing education and training to raise awareness on ADE reporting and streamlining the reporting process to enhance pharmacists’ reporting behavior. Conclusions Despite pharmacists having positive opinions about reporting ADEs to the FDA, actual reporting may be impeded by a myriad of challenges involved in reporting ADEs. ADE reporting can be improved through addressing these challenges. Continuing education and on-the-job training on ADE reporting are imperative.

This study assessed the state of health economic evaluation (including pharmacoeconomic) research in Nigeria. A literature search was conducted to identify health economic articles pertaining to Nigeria. Two reviewers independently scored each article in the final sample using a data collection form designed for the study. A total of 44 studies investigating a wide variety of diseases were included in the review. These articles were published in 34 different journals, mostly based outside of Nigeria, between 1988 and 2009. On average, each article was written by four authors. Most first authors had medical/clinical affiliations and resided in Nigeria at the time of publication of the study. Based on a 1 to 10 scale, with 10 indicating the highest quality, the mean quality score for all studies was 7.29 (SD 1.21) and 59% of the articles were of fair quality (score 5-7); 5% were of even lower quality. The quality of articles was statistically significantly (por = 0.05) related to the country of residence of the primary author (non-Nigeria = higher), country of the journal (non-Nigeria = higher), primary objective of the study (economic analysis = higher) and type of economic analysis conducted (economic evaluations higher than cost studies). The conduct of health economic (including pharmacoeconomic) research in Nigeria was limited and about two-thirds of published articles were of sub-optimal quality. More and better quality health economic research in Nigeria is warranted.

Background:Background: Economic factors are a limiting factor toward the implementation of many health programmes and interventions. Economic evaluation has a great potential to contribute toward cost-effective healthcare delivery in South Africa. Little is known about the characteristics and quality of health economic (including pharmacoeconomic) research in South Africa. Abstract: Objective and Methods:Objective and Methods: This study assessed the state of health economic (including pharmacoeconomic) research in South Africa. PUBMED, MEDLINE, HealthSTAR, EconLit and PsycINFO databases were searched to identify health economic articles pertaining to South Africa published between 1 January 1977 and 30 April 2010. The searches used the following Medical Subject Headings (MeSH) terms and text words alone and in combination: 'costs', 'health' and 'South Africa'. Our study included only original economic studies/analyses that pertained to South Africa, addressed a health-related topic, and had a statement or word in the title, abstract or keywords that indicated that an economic (including cost) analysis had been conducted. The study only included complete peer-reviewed publications (e.g. abstracts were excluded) that were reported in the English language. Two reviewers independently scored each article in the final sample using the data collection form designed for the study. Abstract: Results:Results: In total, 108 studies investigating a wide variety of diseases were included in the study. These articles were published in 39 different journals mostly based outside of South Africa between 1977 and 2010. On average, each article was written by three authors. Most first authors had medical/clinical training and resided in South Africa at the time of publication of their study. Based on a 1-10 scale, with 10 indicating the highest quality, the mean quality score for all studies was 7.59 (SD 1.42) and half of the articles were of good quality (score 8-10) The quality of studies was related to the country in which the journal publishing the article was based (outside South Africa - higher); current residence of the primary author (outside South Africa - higher); method of economic analysis (economic evaluations higher than cost studies); type of data used (secondary higher than primary); primary training of the first author (health economics/pharmacoeconomics - higher); type of medical function (diagnosis - higher); study perspective (societal - higher); primary health intervention (pharmaceuticals - higher); study design (modelling - higher); number of authors (more - higher); and year of publication (more recent - higher) &lsqb;p ≤ 0.05&rsqb;. Abstract: Conclusion:Conclusion: Half of the articles were of poor or fair quality. Measures are needed to promote the commissioning of more and better quality health economic and pharmacoeconomic studies in South Africa.

Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART).Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record.Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used wereAllium Sativum(72.7%),Bidens pilosa(66.0%),Eucalyptus globulus(52.3%),Moringa oleifera(44.1%),Lippia javanica(36.3%), andPeltoforum africanum(34.3%). Two indigenous herbs,Musakavakadzi(OR=0.25; 95% CI 0.076–0.828) andPeltoforum africanum(OR=0.495; 95% CI 0.292–0.839) reduced the occurrence of adverse drug events.Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles.

(1) Describe ADHD medication use, adherence and persistence. (2) Determine factors (e.g., medication type, demographics, concomitant medication use) associated with ADHD medication adherence and persistence. (3) Compare ADHD medication costs.Continuously enrolled Texas Medicaid children (3-18 years) with ≥ 2 ADHD prescription claims (July 2002-December 2008) were included. Prescription claims were grouped by medication type (i.e., immediate-release, extended-release, prodrug, non-stimulant); medication class (i.e., stimulant, non-stimulant); and duration of action (i.e., long-acting, short-acting). Adherence, using medication possession ratio, was measured continuously and dichotomously (80% cut-off). Persistence was days of continuous therapy without a 30-day gap and medication costs were reimbursement amount paid to dispensing pharmacies.The study sample (n = 62,789) was primarily 6-12 years (61.7%) and male (69.2%). The majority of the subjects were prescribed extended-release agents (70.3%), stimulant agents (86.4%), and long-acting agents (84.5%). Adherence and persistence (adherence mean ± SD; adherence dichotomous; persistence mean ± SD) varied among medication type and was highest for non-stimulants (52.5 ± 30.9; 25.8%; 153.3 ± 124.3), followed by extended-release stimulants (52.1 ± 30.2; 24.1%; 143.7 ± 120.8), prodrug stimulants (47.6 ± 30.9; 21.1%; 113.3 ± 100.5) and immediate-release stimulants (37.2 ± 27.1; 9.8%; 95.4 ± 92.6). Logistic regression showed immediate-release stimulant users were 67% less adherent than non-stimulant users (p0.0001) and linear regression showed immediate-release, extended-release and long-acting users (p0.0001) were significantly less persistent than non-stimulant users. Females, increase in total number of medications, and comorbid medications were associated with better adherence and persistence. Non-stimulant agents ($4.04 ± $2.15) had the highest mean medication cost per patient per day and immediate-release stimulants had the lowest ($1.24 ± $0.97).ADHD medication adherence and persistence was suboptimal. Although there was no difference in adherence between long-acting stimulant and non-stimulant users, non-stimulant users were more persistent compared to stimulant users. This study was limited due to the use of retrospective prescription claims data, which cannot capture actual patient use patterns, ICD-9 diagnoses, family history and support, or side effect profiles. Because ADHD can be effectively treated with pharmacotherapy, providers should be proactive in identifying patients with poor adherence and intervene to address barriers to medication adherence and persistence.

To determine whether there is an association between antidepressant use and the risk of developing type 2 diabetes.This study was a retrospective cohort analysis using the Texas Medicaid prescription claims database. Data were extracted for new users of either antidepressant agents (exposed) or benzodiazepines (unexposed) from January 1, 2002 through December 31, 2009. Patients aged 18-64 years without a prior history of diabetes were included. Cox proportional hazards regression was used to examine the association between diabetes incidence among exposed and unexposed groups, while controlling for demographic and clinical covariates.Among the total study population (N = 44,715), the majority were in the exposed (N = 35,552) versus the unexposed (N = 9,163) group. A total of 2,943 patients (6.6%) developed type 2 diabetes during the follow-up period. Antidepressant use was associated with an increase in the risk of diabetes when compared to benzodiazepine use (adjusted hazard ratio [HR] 1.558, 95% confidence interval [CI] 1.401-1.734). The association was observed with tricyclic antidepressants (TCAs; HR 1.759, 95% CI 1.517-2.040), serotonin-norepinephrine reuptake inhibitors (SNRIs; HR 1.566. 95% CI 1.351-1.816), selective serotonin reuptake inhibitors (SSRIs; HR 1.481, 95% CI 1.318-1.665), and "other" antidepressants (HR 1.376; 95% CI 1.198-1.581).The results of this study suggest that antidepressant use is associated with an increased risk of diabetes. This association was observed with use of TCAs, SNRIs, SSRIs, and "other" antidepressants.

OBJECTIVES: This study sought to estimate the average outpatient cost of providing adult antiretroviral therapy (ART) at an urban care centre for the first year following ART initiation. METHODS: A retrospective, ingredients-based costing approach was implemented, as previously described in literature. Medical records for a convenient sample of 120 patients were reviewed 1 year after ART initiation. Subjects were assigned to any one of the following outcome categories based on their status at the end of the study period: in care and responding (IC); in care but not responding (NR); or no longer in care at study site (NIC). Average cost per outcome category was estimated based on resource utilisation, in 2013 US$. RESULTS: The overall annual retention in care was 93.3%. At the end of the first 12 months of ART care, 109 (90.8%) of the patients were IC, 7 (6.7%) patients were NIC and 3 (2.5%) patients were NR. The average outpatient cost per patient initiated was USD $461. The costs were structured as follows; outpatient visits (49.2%), medications (26.4%), laboratory tests (21.8%) and fixed costs (2.6%). The average cost to produce an IC patient was US$ 472, NR US$ 438 and NIC US$ 322. The average cost of producing a patient in care and responding to ART represented 49.2% of the country's GDP per capita for 2013. This estimate excludes building and utility costs because they were unavailable, hence the actual average cost may be higher. CONCLUSIONS: These findings show that maintaining an HIV/AIDS patient in care and responding to ART is an expensive undertaking relative to the country's GDP per capita. This underscores the need for periodic costing studies as a way of continually monitoring the costs and cost structures associated with caring for people living with HIV and AIDS, as this would aid in planning and decision-making.

would not include at least one of these terms in the title, abstract or keywords. Re-analysis of the search terms including 'economic' and 'economics' did not elicit any additional articles that met our inclusion criteria. Our choices for inclusion criteria were also questioned. As mentioned in our article, ''The study only included complete peer-reviewed publications (e.g. abstracts were excluded) that were reported in the English language.'' Books are not routinely included when conducting sys- tematic reviews of literature as they are not always peer reviewed in the same sense as scientific articles. Given that books were excluded, no further discussion about pub- lished books was provided in the article. In addition, our study included only original economic studies/analyses (e.g. no reviews) that pertained to South Africa. Studies covering more than one country were included if they had data pertaining to South Africa. Eighteen articles were excluded because they did not have any specific data per- taining to South Africa as per the a priori inclusion criteria. Gow and colleagues (2) point out that we did not include discussion about important institutions and important researchers who are working in health economics in South Africa. These institutions/organizations/researchers are, indeed, furthering the science while positively impacting the health of the South African population. However, in order to maintain our objectivity, it was not the purpose of our study to review the activities of institutions, research organizations or individual researchers outside of what they have published in indexed journals. It was suggested that we arbitrarily excluded some research articles. We followed standard procedures to select as many articles as possible that met the inclusion criteria. In addition, we searched the references in the original articles in order to uncover any articles that may have been missed. A limitation that we listed in our paper

The International Journal of Clinical Pharmacy has been alerted to a case of duplicate publication in the following papers. Int J Clin Pharm. 2012 Jun;34(3):432-8. Epub 2012 Jan 18. Use of antidepressants and the risk of type 2 diabetes mellitus: a nested case–control study. Khoza S, Barner JC, Bohman TM, Rascati K, Lawson K, Wilson JP. Eur J Clin Pharmacol. 2011 Nov 26. [Epub ahead of print]. Use of antidepressant agents and the risk of type 2 diabetes. Khoza S, Barner JC, Bohman TM, Rascati K, Lawson K, Wilson JP. The International Journal of Clinical Pharmacy is retracting the paper. We sincerely apologize to the scientific community for any inconvenience that this might have caused.