Application of hydrophilic polymers for the preparation of tadalafil solid dispersions: micromeritics properties, release and erectile dysfunction studies in male rats

The objective of the present study was to improve the dissolution rate and aphrodisiac activity of tadalafil by using hydrophilic polymers. Solid dispersions were prepared by solvent evaporation-Rota evaporator using Koliphore 188, Kollidon® VA64, and Kollidon® 30 polymers in a 1:1 ratio. Prepared tadalafil-solid dispersions (SDs) evaluated for yield, drug content, micromeritics properties, physicochemical characterizations, and aphrodisiac activity assessment. The optimized SDs TK188 showed size (2.175 ± 0.24 µm), percentage of content (98.89 ± 1.23%), yield (87.27 ± 3.13%), bulk density (0.496 ± 0.005 g/cm3), true density (0.646 ± 0.003 g/cm3), Carr’s index (23.25 ± 0.81), Hausner ratio (1.303 ± 0.003) and angle of repose (<25°). FTIR spectrums revealed tadalafil doesn’t chemically interact with used polymers. XRD and DSC analysis represents TK188 SDs were in the amorphous state. Drug release was 97.17 ± 2.43% for TK188, whereas it was 32.76 ± 2.65% for pure drug at the end of 2 h with 2.96-fold increase in dissolution and followed release kinetics of Korsmeyer Peppa’s model. MDT and DE were noted to be 17.48 minutes and 84.53%, respectively. Furthermore, TK188 SDs showed relative improvement in the sexual behavior of the male rats. Thus the developed SDs TK188 could be potential tadalafil carriers for the treatment of erectile dysfunction

Pattern of Antibiotic Dispensing at Pharmacies According to the WHO Access, Watch, Reserve (AWaRe) Classification in Bangladesh

The WHO Essential Medicines List Access, Watch, and Reserve (AWaRe) classification could facilitate antibiotic stewardship and optimal use. In Bangladesh, data on antibiotic dispensing in pharmacies according to the AWaRe classification are scarce. We aimed to explore antibiotic dispensing pattern in pharmacies according to the WHO AWaRe classification to aid pharmacy-targeted national antibiotic stewardship program (ASP). From January to July 2021, we interviewed drug-sellers from randomly selected pharmacies and randomly selected customers attending the pharmacies. We collected data on demographics and medicines purchased. We classified the purchased antibiotics into the Access, Watch, and Reserve groups among 128 pharmacies surveyed, 98 (76.6%) were licensed; 61 (47.7%) drug-sellers had pharmacy training. Of 2686 customers interviewed; 580 (21.6%) purchased antibiotics. Among the 580 customers, 523 purchased one, 52 purchased two, and 5 purchased three courses of antibiotics (total 642 courses). Of the antibiotic courses, the Watch group accounted for the majority (344, 53.6%), followed by the Access (234, 36.4%) and Reserve (64, 10.0%) groups. Approximately half of the antibiotics (327/642, 50.9%) were purchased without a registered physician’s prescription. Dispensing of non-prescribed antibiotics was higher in the Access group (139/234, 59.4%), followed by Watch (160/344, 46.5%) and Reserve (28/64, 43.8%) groups. These findings highlight the need to implement strict policies and enforce existing laws, and pharmacy-targeted ASP focusing on proper dispensing practices to mitigate antimicrobial resistance in Bangladesh

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field