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Despite the availability of extensive literature on the effect of angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs) on COVID-19 outcomes, the evidence is still controversial. We aimed to provide a comprehensive assessment of the effect of ACEIs/ARBs on COVID-19-related outcomes by summarising the currently available evidence.An umbrella review was conducted using Medline (OVID), Embase, Scopus, Cochrane library and medRxiv from inception to 1 February 2021. Systematic reviews with meta-analysis that evaluated the effect of ACEIs/ARBs on COVID-19-related clinical outcomes were eligible. Studies' quality was appraised using the AMSTAR 2 Critical Appraisal Tool. Data were analysed using the random-effects modelling including several subgroup analyses. Heterogenicity was assessed using IOverall, 47 reviews were eligible for inclusion. Out of the nine COVID-19 outcomes evaluated, there was significant associations between ACEIs/ARBs use and each of death (OR = 0.80, 95%CI = 0.75-0.86; ICollective evidence from observational studies indicate a good quality evidence on the significant association between ACEIs/ARBs use and reduction in death and death/ICU admission, but poor-quality evidence on both reducing severe COVID-19 and increasing hospitalisation. Our findings further support the current recommendations of not discontinuing ACEIs/ARBs therapy in patients with COVID-19.

Introduction: The coronavirus (COVID-19) pandemic has impacted healthcare worldwide. It has altered service delivery and posed challenges to practitioners in relation to workload, well-being and support. Within primary care, changes in physicians’ activities have been identified and innovative work solutions implemented. However, evidence is lacking regarding the impact of the pandemic on pharmacy personnel who work in primary care. Aim: To explore the impact of the pandemic on the working practice (including the type of services provided) and job satisfaction of pharmacists and pharmacy technicians within Scottish general practice. Due to the stressful nature of the pandemic, we hypothesise that job satisfaction will have been negatively affected. Methods: An online questionnaire was distributed in May–July 2021, approximately 15 months since initial lockdown measures in the UK. The questionnaire was informed by previous literature and underwent expert review and piloting. Analysis involved descriptive statistics, non-parametric statistical tests and thematic analysis. Results: 180 participants responded (approximated 16.1% response rate): 134 pharmacists (74.4%) and 46 technicians (25.6%). Responses indicated greater involvement with administrative tasks and a reduction in the provision of clinical services, which was negatively perceived by pharmacists. There was an increase in remote working, although most participants continued to have a physical presence within general practices. Face-to-face interactions with patients reduced, which was negatively perceived by participants, and telephone consults were considered efficient yet less effective. Professional development activities were challenged by increased workloads and reduced support available. Although workplace stress was apparent, there was no indication of widespread job dissatisfaction. Conclusion: The pandemic has impacted pharmacists and technicians, but it is unknown if changes will be permanent, and there is a need to understand which changes should continue. Future research should explore the impact of altered service delivery, including remote working, on patient care.

The introduction of clinical pharmacy services is part of a multi-disciplinary approach to reduce pressure on primary care. Ascertaining the impact of clinical pharmacists in general practice is vital to ensure intended benefits are achieved. However, this is complicated by poor quality evidence, multiple interventions, and a lack of agreement regarding outcome measures.To develop an outcomes framework for clinical pharmacy services delivered in Scottish general practice using a consensus methodology.A modified nominal group technique (NGT) was conducted using Microsoft Teams and Qualtrics. This involved a pre-NGT questionnaire, silent generation of ideas, round robin, discussions, ranking, and a final consensus exercise. A selective sampling strategy recruited experienced pharmacists from Scottish health regions. NGT ranking results were used to signify relative importance of the outcome areas. NGT discussions underwent inductive thematic analysis to explore key areas considered.Overall, 13 (median: 24 years of experience) pharmacists participated, representing 11 of 14 Scottish regions. In total, 21 outcome areas, derived from the literature and a pre-NGT questionnaire, were considered during the NGT ranking exercise. Consensus identified five important outcome areas: Patient Experience, Medication Related Adverse Events, Cost-Effectiveness, Medication Optimisation, and Health Related Quality of Life. Thematic analysis highlighted the importance of the outcome framework's target audience, factors influencing the interpretation of outcomes, and the feasibility of the associated outcome measures.The five key outcome areas will facilitate evidence-based decisions regarding service delivery. Future work should develop a measurement plan, involving routinely collected sources of outcomes data. The feasibility of collecting outcomes in the real-world context should be considered, identifying measures which are easy to collect within existing data infrastructures. This paper describes a replicable method to gain consensus for a national approach to data collection from a strong theoretical basis using an online methodology.

Introduction Coronavirus disease 2019 (COVID-19) is caused by the “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2), and commonly presents with fever, loss of smell/taste, and a persistent cough; in severe cases, patients require hospitalisation and external ventilation. Advanced age and pre-existing conditions such as cardiovascular diseases and diabetes have been associated with an increased risk of COVID-19 related mortality. Based on their mechanisms of action and widespread use among patients at high risk of poor disease outcomes, the impact of renin-angiotensin-aldosterone system (RAAS) inhibitors – including angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) – on COVID-19 related outcomes has become a topic of interest, resulting in rapid dissemination of a large number of predominantly retrospective, observational studies since early 2020. Since many of these studies were limited in scope and results were inconclusive, systematic reviews and meta-analyses of published and unpublished findings swiftly followed. Aim To assess the effect of ACEIs and ARBs on COVID-19 related outcomes by summarising the currently available evidence. Methods Umbrella review of systematic reviews and subsequent meta-analysis. Eligible for inclusion were systematic reviews with meta-analysis focusing on patients with or without COVID-19 exposed to ACEIs and/or ARBs compared to patients not exposed to the medication. Outcomes of interest included risk of infection; hospitalisation; severity; and death. Reviews were identified through a literature search in Medline, EMBASE, Scopus, the Cochrane database of systematic reviews, and medRxiv, from 2019 until 1st of February 2021. Data was extracted using a standardised extraction sheet; the AMSTAR 2 Critical Appraisal Tool for systematic reviews was used for quality assessment. Heterogeneity between studies was evaluated using I2 statistics, and findings of included meta-analyses were summarised using random-effects models. The protocol was registered with PROSPERO (CRD42021233398). Results Out of an initial 157 publications, 66 systematic reviews underwent full text screening; after further exclusions based on pre-specified criteria, 47 studies were identified to be relevant. The number of included studies as well as the outcomes of interest varied widely between reviews, with death being the most common. Odds ratio for risk of COVID-19 infection among patients treated with ACEIs/ARBs versus patients not on treatment was 0.99 (95% Confidence Interval (CI) 0.97 – 1.02; 19 studies, I2 = 24.7%); and for hospitalisation among COVID-19 patients treated with ACEIs/ARBs versus not on treatment, 1.23 (95% CI 1.04 – 1.46; 11 studies, I2 = 76.4%); severe disease 0.86 (95% CI 0.78 – 0.95; 28 studies, I2 = 68%); and death, 0.80 (95% CI 0.75 – 0.86; 47 studies, I2 = 51.9%). Conclusion While treatment with ACEIs or ARBs does not appear to impact the risk of COVID-19 infection, it appears that patients on treatment have lower risks of severe disease and mortality compared to patients not on ACEIs/ARBS treatment. Findings should be interpreted cautiously as the systematic reviews/meta-analyses included in this study were of variable quality, and there was high heterogeneity among studies for most outcomes. Findings will inform evidenced-based guidelines on the appropriate measures for patients at risk of COVID-19 infection and prescribed RAAS inhibitors.

Background: Plasma fatty acids in the de novo lipogenesis including plamitoleic acid have been associated with a higher risk of blood pressure and type 2 diabetes (two major risk factors for heart failure -HF). However, limited data are available on the association between plasma levels of palmitoleic acid and HF risk. Objective: To test the hypothesis that plasma palmitoleic acid concentration is associated with an increased risk of HF. In a secondary aim, we examined whether stearoyl-CoA desaturase indices, cis -vaccenic acid, and oleic acid were associated with HF risk. Methods: We used a prospective nested case-control design for this project among participants of the Physicians' Health Study. For each of the 788 HF cases, we used the risk set method to randomly select a control among all eligible controls at the time of the index case occurrence. Each control was matched on age, year of birth, race, and time of blood collection of the index case. We used gas chromatography to measure plasma phospolipid fatty acids on frozen blood samples collected between 1997 and 2001 on study subjects free of HF. HF events were ascertained via annual follow-up questionnaires and validated in a subsample through review of medical records (positive predictive value 91% -- 50 confirmed out of 55 self-reported cases). Results: Mean age was 58.7 ± 8.0 years. In a conditional logistic regression controlling for matching factors, odds ratios (95% CI) for HF were 1.0 (reference), 1.00 (0.75–1.33), 1.22 (0.91–1.64), and 1.48 (1.10–1.99) across consecutive quartiles of palmitoleic acid (p trend 0.005). Additional adjustment for body mass index, smoking, alcohol intake, exercise, prevalent diabetes and coronary disease, marine omega-3 fatty acids, hypertension treatment, and plasma stearic acid did not alter the results [OR: 1.0, 1.00 (0.72–1.37), 1.23 (0.89–1.72), and 1.51 (1.06–2.15) from the lowest to the highest quartile, p trend 0.014]. When analyzed as a continuous variable, each standard deviation increase of plasma palmitoleic acid was associated with a 15% higher odds of HF [OR: 1.15 (1.01–1.31)] in a multivariable adjusted model. In a secondary analysis, plasma phospholipid oleic acid (18:1n−9) and cis-vaccenic acid (18:1n−7) were not associated with the odds of HF. Indices of stearoyl-CoA desaturase-1 (16:1n−7 to 16:0 ratio) and desaturase-2 (18:1n−9 to 18:0 ratio) were not significantly associated with the odds of HF. Conclusion: Our data showed that plasma concentration of palmitoleic acid is positively associated with the risk of HF in male physicians. This suggests that fatty acids in the de novo lipogenesis may play a role in the development of HF.

This study investigates the auto-oxidation reaction of human normal adult hemoglobin (Hb A) and the effects of distal heme pocket substitutions, P50, and tetramer-dimer dissociation on the rate and mechanism of auto-oxidation. Recombinant hemoglobins (rHbs) with single amino acid substitutions at helical positions E11 and B10 have been expressed in Escherichia coli and purified, as well as di-α linked and octameric rHbs. These rHbs include: rHb (αV62L), rHb (αV62I), rHb (βV67L), rHb (βV67I), rHb(αL29W), rHb(αL29F), rHb(α-Gly-α/β gene di-α/β), rHb(diαL29F), rHb(diαL29W), and rHb(βG83C). Auto-oxidation measurements were conducted with 32μM heme in MES buffer (pH 6.5) for 60 hours at 35 °C. A monophasic nature of auto-oxidation has been observed for Hb A and a biphasic nature for all other rHbs. In comparison to the other mutants, including di-α linked and octameric rHbs, rHb (αL29F) is most resistant to oxidation and rHb (αL29W) is the least resistant to oxidation. Characterization of three novel rHbs; (βL28F, βV67I), (αL29F, βV67I), (αL29F,αV62I) will test whether the fast and slow phases of the observed biphasic nature of auto-oxidation can be attributed to the mutated and wild-type subunits, respectively. Our studies will also provide new insights into the roles of amino acid residues in the distal heme pockets on the structure-function relationship in hemoglobin(Supported by NIH grants HL-024525 and GM-084614, HHMI, and The Arnold and Mabelle Beckman Undergraduate Research Scholars Program).