PHARMACY

The relationship between depression and vitamin D deficiency is complex, with evidence mostly from studies affected by confounding and reverse causality. We examined the causality and direction of the relationship between 25-hydroxyvitamin D (25(OH)D) and depression in bi-directional Mendelian randomization (MR) analyses using information from up to 307,618 white British participants from the UK Biobank and summary results from the SUNLIGHT (n = 79,366) and Psychiatric Genomics consortia (PGC 113,154 cases and 218,523 controls). In observational analysis, the odds of depression decreased with higher 25(OH)D concentrations (adjusted odds ratio (OR) per 50% increase 0.95, 95%CI 0.94–0.96). In MR inverse variance weighted (IVW) using the UK Biobank, there was no association between genetically determined serum 25(OH)D and depression (OR per 50% higher 0.97, 95%CI 0.90–1.05) with consistent null association across all MR approaches and in data from PGC consortium. In contrast, genetic l...

Background: Beside the fact of poor adherence to antiretroviral drugs in resource limited country, serious adverse effects of the drugs and treatment failure complicate the whole management of antiretroviral therapy. Consequently, treatment ...

Inappropriate use of antibiotics can potentially lead to antimicrobial resistance and increase the necessity to use more expensive antibiotics to treat common and life threatening infections. The major goal of this research was to determine antibiotics utilization and their cost among in-patients treated in Ayder Referral Hospital. An institution based cross-sectional study was conducted in medical, gynecology and obstetrics, and surgical wards from September to December, 2012. The prevalence of antibiotics use was 35.5%. Antibiotic therapy was found to be inappropriate in 137 patients (80.6%). Keywords: irrational drug use, antibiotics, ayder referral hospital, cost, inpatients.

Background: The non-nucleoside reverse transcriptase inhibitor efavirenz is recommended as part of first-line therapy in HIV-infected patients and prescribed at a standard dose of 600 mg once daily. EFV is extensively metabolized primarily by hepatic CYP2B6 with partial involvement of CYP3A4 and CYP2A6. The aim of the study was to assess CYP 2B6 G516T polymorphism and their impact in efavirenz based therapy Methods: A computerized literature search was conducted using the Medline, PubMed, and High wire. Statistical analysis was conducted using comprehensive Meta analysis version 2 software. Result: From fifty four articles only twenty two articles were included in the study based on the inclusion criteria. The average frequency of CYP 2B6 G516T polymorphism, from forest plot of 7 studies, was around 30% which strengthened the idea of substantial number of this polymorphism. Most of the studies had high proportion of mutant allele and the average of the all is around 49%. The mean pl...

About one-third of the world's population lack access to essential medicines and this is further compounded by inappropriate prescription, dispensing, sale and use of the available medicines. The objective of the study was to assess the patterns of medicine use among health facilities in eastern Ethiopia using World Health Organization's Prescribing, Patient Care and Health facility indicators. A cross sectional study was carried out in eight randomly selected health centers and data were collected retrospectively as well as prospectively. Prescribing indicators were assessed retrospectively using 636 prescriptions selected by systematic random sampling technique among prescriptions filled between September 2013 and September 2014. Patient care indicators were assessed prospectively by interviewing 708 patients from the health facilities. Health facilities were assessed through observation. Data were entered and analyzed using Statistical Packages for Social Sciences version...

Background Depression is more common in obese than non-obese individuals, especially in women, but the causal relationship between obesity and depression is complex and uncertain. Previous studies have used genetic variants associated with BMI to provide evidence that higher body mass index (BMI) causes depression, but have not tested whether this relationship is driven by the metabolic consequences of BMI nor for differences between men and women. Methods We performed a Mendelian randomization study using 48 791 individuals with depression and 291 995 controls in the UK Biobank, to test for causal effects of higher BMI on depression (defined using self-report and Hospital Episode data). We used two genetic instruments, both representing higher BMI, but one with and one without its adverse metabolic consequences, in an attempt to ‘uncouple’ the psychological component of obesity from the metabolic consequences. We further tested causal relationships in men and women separately, and ...

Obesity and depression are both highly prevalent public health disorders and evidence on their relationship is inconsistent. This study examined whether depressive symptoms are associated with current obesity, and further, whether obesity in turn is associated with an increased odds of depressive symptoms five years later after accounting for potential lifestyle confounders and depressive symptoms at baseline. Data were obtained from the 1958 British birth cohort (N = 9217 for cross-sectional and 7340 for prospective analysis). Clinical Interview Schedule-Revised and Mental Health Inventory-5 were used for screening depressive symptoms at ages 45 and 50 years, respectively. General and central obesity were defined using measurements of body mass index (BMI) and waist circumference (WC) at 45 years, respectively. There was a cross-sectional association between depressive symptoms and obesity: participants with ≥2 depressive symptoms had 31% (95%CI 11% to 55%) higher odds of general a...

Depression affects all aspects of an individual’s life but evidence relating to the causal effects on health is limited. We used information from 337,536 UK Biobank participants and performed hypothesis-free phenome-wide association analyses between major depressive disorder (MDD) genetic risk score (GRS) and 925 disease outcomes. GRS–disease outcome associations passing the multiple-testing corrected significance threshold ( P  < 1.9 × 10 −3 ) were followed by Mendelian randomisation (MR) analyses to test for causality. MDD GRS was associated with 22 distinct diseases in the phenome-wide discovery stage, with the strongest signal observed for MDD diagnosis and related co-morbidities including anxiety and sleep disorders. In inverse-variance weighted MR analyses, MDD was associated with several inflammatory and haemorrhagic gastrointestinal diseases, including oesophagitis (OR 1.32, 95% CI 1.18–1.48), non-infectious gastroenteritis (OR 1.25, 95% CI 1.06–1.48), gastrointestinal haemorrhage (OR 1.26, 95% CI 1.11–1.43) and intestinal E.coli infections (OR 3.24, 95% CI 1.74–6.02). Signals were also observed for symptoms/disorders of the urinary system (OR 1.36, 95% CI 1.19–1.56), asthma (OR 1.23, 95% CI 1.06–1.44), and painful respiration (OR 1.28, 95% CI 1.14–1.44). MDD was associated with disorders of lipid metabolism (OR 1.22, 95% CI 1.12–1.34) and ischaemic heart disease (OR 1.30, 95% CI 1.15–1.47). Sensitivity analyses excluding pleiotropic variants provided consistent associations. Our study indicates a causal link between MDD and a broad range of diseases, suggesting a notable burden of co-morbidity. Early detection and management of MDD is important, and treatment strategies should be selected to also minimise the risk of related co-morbidities.

Observational and Mendelian randomization (MR) studies link obesity and cancer, but it remains unclear whether these depend upon related metabolic abnormalities. We used information from 321,472 participants in the UK biobank, including 30,561 cases of obesity-related cancer. We constructed three genetic instruments reflecting higher adiposity together with either “unfavourable” (82 SNPs), “favourable” (24 SNPs) or “neutral” metabolic profile (25 SNPs). We looked at associations with 14 types of cancer, previously suggested to be associated with obesity. All genetic instruments had a strong association with BMI (p < 1 × 10−300 for all). The instrument reflecting unfavourable adiposity was also associated with higher CRP, HbA1c and adverse lipid profile, while instrument reflecting metabolically favourable adiposity was associated with lower HbA1c and a favourable lipid profile. In MR-inverse-variance weighted analysis unfavourable adiposity was associated with an increased risk of non-hormonal cancers (OR = 1.22, 95% confidence interval [CI]:1.08, 1.38), but a lower risk of hormonal cancers (OR = 0.80, 95%CI: 0.72, 0.89). From individual cancers, MR analyses suggested causal increases in the risk of multiple myeloma (OR = 1.36, 95%CI: 1.09, 1.70) and endometrial cancer (OR = 1.77, 95%CI: 1.16, 2.68) by greater genetically instrumented unfavourable adiposity but lower risks of breast and prostate cancer (OR = 0.72, 95%CI: 0.61, 0.83 and OR = 0.81, 95%CI: 0.68, 0.97, respectively). Favourable or neutral adiposity were not associated with the odds of any individual cancer. Higher adiposity associated with a higher risk of non-hormonal cancer but a lower risk of some hormone related cancers. Presence of metabolic abnormalities might aggravate the adverse effects of higher adiposity on cancer. Further studies are warranted to investigate whether interventions on adverse metabolic health may help to alleviate obesity-related cancer risk.

Background The APOE gene has three main alleles; APOE-E2, E3 and E4 (global frequencies: 8%, 78%, 14%) carrying differential risk for conditions such as dementia and cardiovascular disease. Due to the clinical significance of variation at this locus, we explored disease associations of APOE genotypes using a hypothesis-free, phenome-wide association study (PheWAS) approach. Methods Utilising medical and genetic data available from the UK Biobank for 337,484 white British participants aged 37–73 years, we screened for associations between APOE genotypes (E4E4, E3E4, E2E4, E2E3 and E2E2) and ≥825 disease outcomes, using E3E3 as a reference. Results Case-control PheWAS analyses revealed associations with 37 disease outcomes from 17 distinct conditions after multiple test correction. As expected, E4E4 and E3E4 associated with risk of Alzheimer’s disease (p < 10-46 for both), hypercholesterolemia (p < 10-17), and cardiovascular diseases (p < 10-4). Novel findings included E4-ass...