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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

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.

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.

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.

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.

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.

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.

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.