Clinical pharmacists' knowledge, attitude, perception, and beliefs about the role of pharmacogenetic testing for genes polymorphisms when prescribing mercaptopurine.

Background: Single nucleotide polymorphisms in the gene encoding proteins involved in mercaptopurine metabolism can influence drug efficacy and safety. This study aims to assess clinical pharmacists' knowledge about mercaptopurine-related genes and their polymorphisms and investigate their attitudes, perceptions, and beliefs about the need for and importance of pharmacogenetic testing for mercaptopurine. Methods: A cross-sectional descriptive study was conducted among oncology/hematology clinical pharmacists in Saudi Arabia using an online-questionnaire developed by experts in the field. The questionnaire consists of four-sections exploring clinical pharmacists' knowledge, attitudes, perceptions, and beliefs about the importance of gene testing and genes polymorphism when prescribing mercaptopurine. Descriptive statistics were used to analyze the data in the study. Results: A total of 41 oncology/hematology clinical pharmacists responded to the survey invitation. Almost half of them had more than 10 years of work experience, but only 17 % of them received formal training in pharmacogenetics. The overall level of knowledge about pharmacogenetics among participants was low, with a mean score of 2.8 points (1.7) out of 8 items. However, around 76 % agreed that it is important to perform pharmacogenetic screening prior to prescribing mercaptopurine, and almost 93 % state that it will influence their dosage recommendation. Most of the participants had a good perception (95.1 %) of their role in genetic testing for medication selection, dosing, and monitoring; however, about 10 % of surveyed pharmacists reported not being completely responsible about recommending pharmacogenetic testing. The surveyed pharmacists had a good belief in the importance of pharmacogenetic testing and their overall attitude was positive toward the use of pharmacogenetic testing, with emphasis on the importance of training on the proper assessment and interpretation of pharmacogenetic tests. Conclusions: Pharmacists demonstrated good perception and positive attitude toward pharmacogenetic testing, despite the low level of knowledge and limited formal training. Thus, more attention to developing national guidelines on pharmacogenetic testing is warranted to ensure successful pharmacogenetic testing implementation.

Obesity Prevalence and Association with Spirometry Profiles, ICU Admission, and Comorbidities Among Patients with COPD: Retrospective Study in Two Tertiary Centres in Saudi Arabia.

Background: Obesity is common among chronic obstructive pulmonary disease (COPD) patients and is associated with an increase in acute exacerbation episodes. However, data on obesity's impact on and association with clinical outcomes among patients with COPD are limited. This study aimed to determine overweight and obesity prevalence and associations with spirometry profiles, intensive care unit (ICU) admission, and comorbidities in patients with COPD. Methods: In this retrospective cohort study, we reviewed the electronic health records of adult individuals diagnosed with COPD who visited the studied pulmonary clinics between 1 January 2018 and 31 December 2022 and then collected key demographic variables and relevant clinical outcomes and comorbidities. Results: A total of 474 patients with COPD were included in the final analysis, of whom 60% were male. The occurrences of overweight and obesity were 32.7% and 38.2%, respectively. The presence of comorbidities was high in obese patients (78.4%), followed by overweight patients (63.8%) with COPD. Obese and overweight patients had the highest ward admission rates (38.3% and 34.2%, respectively). ICU admissions were higher in obese and overweight patients (16% and 12%, respectively) compared with normal-weight patients (9%). Although no significant correlation was found between body mass index and spirometry parameters, comorbidities and ICU admission were linked to overweight and obesity in COPD patients (AOR: 1.82 95% CI: 1.15 to 2.86 and AOR: 3.34 95% CI 1.35 to 8.22, respectively). Conclusion: Our findings imply that obesity in COPD is prevalent and is associated with adverse clinical outcomes including a greater number of comorbidities and higher rates of hospitalization and admission to ICUs although no associations were found between body weight and spirometry parameters. Further studies are needed to assess whether implementing and optimising obesity screening and management at an early stage in COPD can prevent further deterioration.

Role of prostanoids, nitric oxide and endothelin pathways in pulmonary hypertension due to COPD.

Pulmonary hypertension (PH) due to chronic obstructive pulmonary disease (COPD) is classified as Group 3 PH, with no current proven targeted therapies. Studies suggest that cigarette smoke, the most risk factor for COPD can cause vascular remodelling and eventually PH as a result of dysfunction and proliferation of pulmonary artery smooth muscle cells (PASMCs) and pulmonary artery endothelial cells (PAECs). In addition, hypoxia is a known driver of pulmonary vascular remodelling in COPD, and it is also thought that the presence of hypoxia in patients with COPD may further exaggerate cigarette smoke-induced vascular remodelling; however, the underlying cause is not fully understood. Three main pathways (prostanoids, nitric oxide and endothelin) are currently used as a therapeutic target for the treatment of patients with different groups of PH. However, drugs targeting these three pathways are not approved for patients with COPD-associated PH due to lack of evidence. Thus, this review aims to shed light on the role of impaired prostanoids, nitric oxide and endothelin pathways in cigarette smoke- and hypoxia-induced pulmonary vascular remodelling and also discusses the potential of using these pathways as therapeutic target for patients with PH secondary to COPD.

Inhaled therapies targeting prostacyclin pathway in pulmonary hypertension due to COPD: systematic review.

Background: Pulmonary hypertension due to chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) is classified as group 3 pulmonary hypertension. Inhaled treprostinil, a prostaglandin I2 analogue also known as prostacyclin, has recently been approved as a first drug for patients with pulmonary hypertension secondary to ILD. However, due to a lack of evidence, no therapies are currently approved for those with COPD-associated pulmonary hypertension. Thus, this systematic review aims to summarise the current evidence to assess the impact of inhaled prostaglandin I2 analogue use on the pulmonary hemodynamics, exercise function, lung function, and gas exchange in patients with pulmonary hypertension due to COPD. Methods: We systematically searched the electronic databases of Medline, Embase, Scopus and Cochrane from inception to 1 February 2023. Studies of adult patients with a confirmed diagnosis of COPD-associated pulmonary hypertension who received inhaled drugs targeting the prostacyclin pathway were included in the systematic review. Case reports, systematic reviews, conference abstracts with no full text, non-full-text articles, non-English manuscripts and book chapters were excluded from this systematic review. A risk-of-bias assessment was carried out for the studies included in this review, using two different Cochrane risk-of-bias tools for randomised and non-randomised clinical trials. Results: A total of four studies met our inclusion criteria and were included in this systematic review. The results of one prospective clinical trial showed an improvement in the pulmonary hemodynamics (e.g., cardiac index, cardiac output and mean pulmonary artery pressure) in response to inhaled prostacyclin use in patients with pulmonary hypertension secondary to COPD. However, the severity of dyspnoea, lung function, exercise capacity and gas exchange were not affected when inhaled prostacyclin was used for patients with COPD-related pulmonary hypertension. Conclusion: This systematic review demonstrated that although inhaled prostacyclin does not seem to improve COPD-related outcomes (e.g., lung function and exercise capacity), short-term use of inhaled prostacyclin has the potential to reduce mean pulmonary artery pressure and pulmonary vascular resistance without impairing ventilation-perfusion mismatch. Further studies with larger sample sizes are warranted. Systematic review registration: CRD42022372803, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=372803.

Statins and Risk of Thrombosis in Critically ill Patients with COVID-19: A Multicenter Cohort Study.

PURPOSE: Coagulation abnormalities are one of the most important complications of severe COVID-19, which might lead to venous thromboembolism (VTE). Hypercoagulability with hyperfibrinogenemia causes large vessel thrombosis and major thromboembolic sequelae. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic effect. This study aims to evaluate the effectiveness of statins in reducing the risk of thrombosis among hospitalized critically ill patients with COVID-19. METHODS: A multicenter, retrospective cohort study of all critically ill adult patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were categorized based on their usage of statins throughout their ICU stay and were matched with a propensity score. The primary endpoint was the odds of all cases of thrombosis; other outcomes were considered secondary. RESULTS: A total of 1039 patients were eligible; following propensity score matching, 396 patients were included (1:1 ratio). The odds of all thrombosis cases and VTE events did not differ significantly between the two groups (OR 0.84 (95% CI 0.43, 1.66), P = 0.62 and OR 1.13 (95% CI 0.43, 2.98), P = 0.81, respectively. On multivariable Cox proportional hazards regression analysis, patients who received statin therapy had lower 30-day (HR 0.72 (95 % CI 0.54, 0.97), P = 0.03) and in-hospital mortality (HR 0.67 (95 % CI 0.51, 0.89), P = 0.007). Other secondary outcomes were not statistically significant between the two groups except for D-dimer levels (peak) during ICU stay. CONCLUSION: The use of statin therapy during ICU stay was not associated with thrombosis reduction in critically ill patients with COVID-19; however, it has been associated with survival benefits.