METHODS: A systematic search of English articles and gray literature, published from January 2010, was performed on databases including MEDLINE, Embase, Scopus, NHSEED, health technology assessment, Cochrane Library, etc. The included studies were EEs with DAMs that compared the costs and outcomes of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, angiotensin-receptor neprilysin inhibitors, beta-blockers, mineralocorticoid-receptor agonists, and sodium-glucose cotransporter-2 inhibitors. The study quality was evaluated using the Bias in Economic Evaluation (ECOBIAS) 2015 checklist and Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklists.
RESULTS: A total of 59 EEs were included. Markov model, with a lifetime horizon and a monthly cycle length, was most commonly used in evaluating GDMTs for HFrEF. Most EEs conducted in the high-income countries demonstrated that novel GDMTs for HFrEF were cost-effective compared with the standard of care, with the standardized median incremental cost-effectiveness ratio (ICER) of $21 361/quality-adjusted life-year. The key factors influencing ICERs and study conclusions included model structures, input parameters, clinical heterogeneity, and country-specific willingness-to-pay threshold.
CONCLUSIONS: Novel GDMTs were cost-effective compared with the standard of care. Given the heterogeneity of the DAMs and ICERs, alongside variations in willingness-to-pay thresholds across countries, there is a need to conduct country-specific EEs, particularly in low- and middle-income countries, using model structures that are coherent with the local decision context.
Materials and Methods: We have developed and validated 2D and 3D QSAR models by using multiple linear regression, partial least square regression, and k-nearest neighbor-molecular field analysis methods.
Results: 2D QSAR models had q2: 0.950 and pred_r2: 0.877 and 3D QSAR models had q2: 0.899 and pred_r2: 0.957. These results showed that the models werere predictive.
Conclusion: Parameters such as hydrogen count and hydrophilicity were involved in 2D QSAR models. The 3D QSAR study revealed that steric and hydrophobic descriptors were negatively contributed to neuraminidase inhibitory activity. The results of this study could be used as platform for design of better anti-influenza drugs.
Methods: Sources for this publication were identified through searches of PubMed for articles published between 31st December 2019 and 4th June 2020, using combinations of search terms. Guidelines and updates from reputable agencies were also consulted. Only articles published in the English language were included.
Results: The volume of literature on COVID-19 continues to expand, with 17,845 articles indexed on PubMed by 4th June 2020, 130 of which were deemed particularly relevant to the subject matter of this review. Older patients are more likely to progress to severe COVID-19 disease requiring intensive care unit (ICU) admission. Patients with pre-existing cardiovascular disease, especially hypertension and coronary heart disease, are at greatly increased risk of developing severe and fatal COVID-19 disease. A controversial aspect of the management of COVID-19 disease has been the use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Obese COVID-19 patients are more likely to require complex ICU management. Putative mechanisms of increased COVID-19 disease severity in diabetes include hyperglycaemia, altered immune function, sub-optimal glycaemic control during hospitalisation, a pro-thrombotic and pro-inflammatory state. Patients with mental health disorders are particularly vulnerable to social isolation, and this has been compounded by the suspension of non-emergency care in hospitals around the world, making it difficult for patients with chronic mental illness to attend outpatient appointments.
Conclusions: The global pandemic of COVID-19 disease has had a disproportionately negative impact on patients living with chronic medical illness. Future research should be directed at efforts to protect vulnerable patients from possible further waves of COVID-19 and minimising the negative impact of pandemic mitigation strategies on these individuals.
METHODS: Orchidectomized, adult male Sprague-Dawley rats were treated subcutaneously with 125 μg/kg/day and 250 μg/kg/day testosterone with or without flutamide (androgen receptor blocker) and finasteride (5α-reductase inhibitor) for seven (7) days. Following treatment completion, in vivo perfusion of vas deferens lumen was performed and changes in fluid secretion rate, pH and HCO3- content were measured with and without bafilomycin, a V-ATPase inhibitor. Rats were then sacrificed and vas deferens were harvested and subjected for V-ATPase A1 and B1/2 protein expression and distribution analysis by western blotting and immunohistochemistry, respectively.
RESULTS: In sham-operated and testosterone-treated orchidectomized rats, higher fluid secretion rate, which was not antagonized by bafilomycin but lower HCO3- content and pH which were antagonized by bafilomycin were observed when compared to orchidectomized-only and orchidectomized, testosterone-treated rats receiving flutamide or finasteride, respectively. Bafilomycin had no effect on fluid secretion rate, HCO3- content and pH in orchidectomized and testosterone-treated orchidectomized rats receiving flutamide and finasteride. V-ATPase A1 and B1/2 proteins were expressed at high levels in vas deferens and were highly distributed at the apical membrane of luminal epithelium and in muscle layer of this organ, mainly in sham and testosterone-treated orchidectomized rats.
CONCLUSIONS: V-ATPase is involved in acidification of vas deferens fluid under testosterone influence.