Association of CYP2C19*2 and *17 genetic variants with hypertension in Pakistani population

Purpose: To investigate the association of *2 and *17 single nucleotide polymorphisms (SNPs) of CYP2C19 gene with hypertension in Pakistani population. Methods: The study was conducted on 527 hypertensive patients and 530 unrelated healthy controls from selected regions of Pakistan. DNA was extracted from leukocytes and all patients and controls were genotyped for two SNPs (rs4244285 and rs12248560) of CYP2C19 gene by allele specific polymerase chain reaction (AS-PCR). Results: Multi-allelic polymorphism in CYP2C19 identified four distinct phenotypes known as ultra-rapid metabolizer (UM), extensive metabolizer (EM), intermediate metabolizer (IM) and poor metabolizer (PM) in hypertensive patients and controls. For CYP2C19*2 polymorphisms, overall wild type and mutant allele frequency were 75 and 25 % in hypertensive patients, and 64.2 and 35.8 % in controls. For CYP2C19*17 polymorphisms, the overall wild type and mutant allele frequency were 66.6 and 33.4 % in hypertensive patients and 75.6 % and 24.4 % in controls. Significant difference in allele frequencies for CYP2C19*2 and *17 was demonstrated between hypertensive and non-hypertensive subjects. Conclusion: To the best of our knowledge, this is the first report on CYP2C19 frequencies in hypertensive Pakistani patients. The finds should help clinicians to determine a suitable optimal dosage of some drugs in order to reduce side effects

Adherence challenges with drugs for pre-exposure prophylaxis to prevent HIV infection.

Background: There are 34 million people living with human immunodeficiency virus (HIV) worldwide and each year this number increases. Until a vaccine is discovered, the prevention of new HIV infections remains an urgent priority. Several trials studying the use of oral and topical agents for the prevention of HIV infection have already been completed. Adherence has proved to be a major challenge in achieving product efficacy. Aim of the review: To provide the clinical pharmacist with an understanding of the oral pre-exposure prophylaxis (PrEP) and topical microbicide product pipeline whilst emphasizing the critical importance of adherence to these drugs to avert HIV infection. Methods: PubMed/Medline and the web-based clinical trials registry (ClinTrials.gov) were searched using appropriate key words. For the time period 1992–2013—all phase II and phase III safety and effectiveness studies—testing agents for prevention of HIV infection were included in the review. Efficacy estimates, adherence estimates and reported challenges with adherence were extracted. Results: Twenty-four phase II and III clinical trials were found during review. Of these, 20 trials have been completed, and six trials show effectiveness in preventing HIV infection. The majority of the successful trials were to oral PrEP and to date only one microbicide trial of a vaginal antiretroviral microbicide gel has showed effectiveness. Adherence to study product played a major role in trial outcomes and there are several reasons for non-adherence. These include high on-trial pregnancy rates, low trial retention rates, low participant perception of risk, participant characteristics such as age <25 years, single status, migratory partners and trial fatigue. Study product characteristics such as dosage form, dosing interval, as well as associated adverse events may also influence adherence. Conclusion: Moderate to high adherence is critical to demonstrate efficacy of drugs for HIV prevention. For topical agents, intermittent use associated with coitus is more effective than daily use, particularly if sex is infrequent or partners migrant. For oral agents, daily use is effective but the motivation to use the drug and high risk perception is important. In serodiscordant couples, early initiation of highly active antiretroviral therapy in the infected partner affords almost complete protection to the negative partner. Drugs need to be tailored to the population at risk and availability of multiple drug options are important

Real-World Experience of Monitoring Practice of Endocrinopathies Associated with the Use of Novel Targeted Therapies among Patients with Solid Tumors

Background: Cancer treatments have gradually evolved into targeted molecular therapies characterized by a unique mechanism of action instead of non-specific cytotoxic chemotherapies. However, they have unique safety concerns. For instance, endocrinopathies, which are defined as unfavorable metabolic alterations including thyroid disorders, hyperglycemia, dyslipidemia, and adrenal insufficiency necessitate additional monitoring. The aim of this study was to assess the prevalence of monitoring errors and develop strategies for monitoring cancer patients who receive targeted therapies. Method: A retrospective chart review was used to assess the prevalence of monitoring errors of endocrinopathies among cancer patients who received targeted therapies over one year. All of the adult cancer patients diagnosed with a solid tumor who received targeted therapies were included. The primary outcome was to determine the prevalence of monitoring errors of endocrinopathies. The secondary outcomes were to assess the incidences of endocrinopathies and referral practice to endocrinology services. Results: A total of 128 adult patients with solid tumors were involved. The primary outcome revealed a total of 148 monitoring errors of endocrinopathies. Monitoring errors of the lipid profile and thyroid functions were the most common error types in 94% and 92.6% of the patients treated with novel targeted therapies, respectively. Subsequently, 57% of the monitoring errors in the blood glucose measures were identified. Targeted therapies caused 63 events of endocrinopathies, hyperglycemia in 32% of the patients, thyroid disorders in 15.6% of them and dyslipidemia in 1.5% of the patients. Conclusion: Our study showed a high prevalence of monitoring errors among the cancer patients who received targeted therapies which led to endocrinopathies. It emphasizes the importance of adhering to monitoring strategies and following up on the appropriate referral process

Expression of IFN-Gamma is significantly reduced during severity of covid-19 infection in hospitalized patients.

Cytokines play an important role in SARS-CoV-2 infection progression and severity. A number of inflammatory cytokines have been directly associated with disease severity including IL-6 (interleukin-6), IL-10, TNF-α (tumor necrosis factor alpha), IFN-γ (interferon-gamma). Here, in this study, the aim was to better understand the interplay between host immune response mediated by cytokines and severity of SARS-CoV-2 infection by assessing cytokine expression. Therefore, we measured expression levels of a total of 12 genes (IFNA-1, IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-7, IL-10, IL-11, IL-13, IL-15, and IL-27) encoding inflammatory, anti-inflammatory and regulatory cytokines using QRT-PCR in hospitalized patients with severe infection compared to mildly infected. IFN-γ was identified as a potent marker of disease severity as indicated previously. Moreover, levels of IL-7 were also found to be partially reduced in patients compared to the healthy controls and linked negatively to disease severity. Identification of these cytokines may be helpful in not only understanding disease pathogenesis but also in better management of the patients after covid infection

Socio-demographic characteristics of study participants (n = 230).

Socio-demographic characteristics of study participants (n = 230).</p