Introduction The Dutch Pharmacogenetics Working Group (DPWG) indicated a list of actionable genotypes that affect patients’ response to more 50 drugs; these drugs which show variable effects based on patients’ genetic traits were named as pharmacogenetics (PGX) drugs. Preemptive genetic testing before using these drugs may protect certain patients from serious adverse reactions and could help in avoiding treatment failures. The objectives of this study include identifying the rate of PGX drug usage among Dutch population, estimating the level of users who carry the actionable genotypes and determining the main genes involved in drug’s effect variability. Methods Usage of PGX drugs over 2011–2017 by the insured population (an average of 11.4 million) in outpatient clinics in Netherlands was obtained from the publically available GIP databank. The data of 45 drugs were analyzed and their interactions with selected pharmacogenes were estimated. Frequency of actionable genotypes of 249 Dutch parents was obtained from the public database: Genome of Netherlands (GoNL), to identify the pattern of genetic characteristics of Dutch population. Results Over a 7 year period, 51.3 million exposures of patients to PGX drugs were reported with an average of 5.3 exposures per each drug user. One quarterof the exposures (12.4 million) are predicted to be experienced by individuals with actionable genotypes (risky exposures). Up to 60% of the risky exposures (around 7.5 million) were related to drugs metabolized by CYP2D6. SLCO1B1, and CYP2C19 were also identified among the top genes affecting response of drugs users (involved in about 22 and 12.4% of the risky exposures, respectively). Cardiovascular medications were the top prescribed PGX drug class (43%), followed by gastroenterology (29%) and psychiatry/neurology medications (15%). Women use more PGX drugs than men (55.8 vs. 44.2%, respectively) with the majority (84%) of users in both sexes are above 45 years. Conclusion PGX drugs are commonly used in Netherlands. Preemptive panel testing for CYP2D6, SLCO1B1, and CYP2C19 only could be useful to predict 95% of vulnerable patients’ exposures to PGX drugs. Future studies to assess the economic impact of preemptive panel testing on patients of older age are suggested.
Antibiotic resistance (ABR) is an emerging global threat to public health. Substantial evidence has indicated that community pharmacists (CPs) can play a critical role in managing the ever-increasing threat of antibiotic resistance. This study aimed to determine the knowledge, attitude, and practices of CPs (n = 180) towards antibiotics and antibiotic resistance as well as to improve the rational use of antibiotics. A two-phase mixed-methods (quantitative and qualitative) online study was conducted in Pakistan from August 2019 to March 2020 by using validated questionnaires and semi-structured interview data. Different statistical methods were used to tabulate the quantitative data, whereas inductive thematic analysis was conducted to categorize themes from the qualitative data and to draw conclusions. Approximately 64.4% of the CPs were male (mean: 29–33 years old). Overall, CPs had good knowledge of and were familiar with multidrug-resistant organisms and their roles in ABR (65.6%, median = 1, and IQR = 1), although their knowledge was poor in differentiating some antibiotic groups with their respective ABR patterns (31.1%, median = 1, and IQR = 1). Most CPs have a positive attitude towards antibiotics, with most (90.0%) identifying ABR as a critical issue in public health (median = 1 and IQR = 0). Overall, CPs’ practices towards antibiotics were somewhat acceptable, where they leaned towards educating patients about the rational use of antibiotics (52.8%, median = 1, and IQR = 1). The two main themes discovered (antibiotics and counseling of patients) were related to self-medication, while educational intervention is the main subtheme. ABR is multifactorial, with subthemes related to budget, time constraints, incompetent staff, the absence of CPs, the lack of training, and the enforcement of laws and regulations being the needs of the hour in Pakistan. Effective antibiotic stewardship programs, patient education, and awareness campaigns about antibiotics and ABR along with training of the CPs are important factors that have to be addressed in a timely manner.
Background Pakistan is facing a growing population of people living with human immunodeficiency (HIV). In this randomized controlled trial, we investigate if a pharmacist-led intervention can increase adherence to antiretroviral therapy (ART) for people living with HIV (PLWH). Methods Adults with HIV, who have been taking ART for more than 3 months were randomly assigned to receive either a pharmacist-led intervention or their usual care. Measures of adherence were collected at 1) baseline 2) just prior to delivery of intervention and 3) 8 weeks later. The primary outcomes were CD4 cell count and self-reported adherence measured with the AIDS Clinical Trial Group (ACTG) questionnaire. Results Post-intervention, the intervention group showed a statistically significant increase in CD4 cell counts as compared to the usual care group (p = 0.0054). In addition, adherence improved in the intervention group, with participants being 5.96 times more likely to report having not missed their medication for longer periods of time (p = 0.0086) while participants in the intervention group were 7.74 times more likely to report missing their ART less frequently (p < 0.0001). Conclusions The findings support the improvement in ART adherence and HIV management. Trial registration The trial is registered with Australian New Zealand Clinical Trials Registry (ACTRN12618001882213). Registered 20 November 2018.
Antibiotic resistance is a global public health threat and is associated with high mortality due to antibiotics’ inability to treat bacterial infections. Enterobacter xiangfangensis is an emerging antibiotic-resistant bacterial pathogen from the Enterobacter genus and has the ability to acquire resistance to multiple antibiotic classes. Currently, there is no effective vaccine against Enterobacter species. In this study, a chimeric vaccine is designed comprising different epitopes screened from E. xiangfangensis proteomes using immunoinformatic and bioinformatic approaches. In the first phase, six fully sequenced proteomes were investigated by bacterial pan-genome analysis, which revealed that the pathogen consists of 21,996 core proteins, 3785 non-redundant proteins and 18,211 redundant proteins. The non-redundant proteins were considered for the vaccine target prioritization phase where different vaccine filters were applied. By doing so, two proteins; ferrichrome porin (FhuA) and peptidoglycan-associated lipoprotein (Pal) were shortlisted for epitope prediction. Based on properties of antigenicity, allergenicity, water solubility and DRB*0101 binding ability, three epitopes (GPAPTIAAKR, ATKTDTPIEK and RNNGTTAEI) were used in multi-epitope vaccine designing. The designed vaccine construct was analyzed in a docking study with immune cell receptors, which predicted the vaccine’s proper binding with said receptors. Molecular dynamics analysis revealed that the vaccine demonstrated stable binding dynamics, and binding free energy calculations further validated the docking results. In conclusion, these in silico results may help experimentalists in developing a vaccine against E. xiangfangensis in specific and Enterobacter in general.
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