Understanding and managing polypharmacy in patients with asthma: a mixed methods study

INTRODUCTION: Problematic polypharmacy, where patients are prescribed multiple medications that are not therapeutically beneficial and can cause unnecessary and potentially harmful adverse drug reactions, can be mitigated using medication reviews. Polypharmacy can occur in patients with asthma taking multiple types of inhalers and medications for their asthma. They often have other medicated comorbidities, particularly those with difficult-to-treat or severe asthma. We have limited knowledge of the trajectory of polypharmacy management in patients with asthma. Therefore, it is imperative that we gain a better understanding of asthma polypharmacy management to control inappropriate polypharmacy given asthma’s association with polypharmacy and multimorbidities (where patients develop two or more co-morbidities concurrently). This study explored how existing polypharmacy management techniques may have impacted inappropriate polypharmacy generally and, specifically, in patients with asthma to provide a lens into how we might revise future medication management procedures, guidelines and resources in polypharmacy and asthma healthcare practice. METHODS: This mixed methods study included qualitative interviews focused on medication management processes and issues to provide a broader understanding of asthma polypharmacy that informed quantitative data analysis. The interviews were conducted to identify differences between general polypharmacy and asthma polypharmacy. Recruitment involved purposive and snowballing techniques to ensure a diverse population and reach saturation in responses. Two cohorts were questioned regarding polypharmacy treatment management and barriers involved in its implementation. The first focused upon healthcare professionals (HCP) (n=21) with a polypharmacy specialisation. Five GPs, four consultants and twelve general practice and hospital pharmacists were interviewed. The second study focused on asthma HCPs (n=32). Eight GPs, eight asthma specialist consultants, nine pharmacists and seven nurses were interviewed. To determine the extent to which the interviews captured wider clinical practice, quantitative analysis explored pattern changes in a retrospective longitudinal data set containing Scottish asthma patient records (n = 671,238; 51.12% women) from 2009 to 2017 using R studio. The data was stratified by multimorbidity, age, socioeconomic background and gender. Differences in deprescribing and hospital admissions due to adverse drug reactions were also analysed. RESULTS: The GPs interviewed noted that, in general polypharmacy, structured medication reviews occurred less frequently than informal medication reviews, due to time constraints. However, amongst patients with asthma, asthma annual reviews were strongly adhered to and contained a medication review though polypharmacy was not a specific focus. HCPs noted that roles and the allocation of responsibilities when conducting medication reviews, repeat prescription monitoring and deprescribing in primary and secondary care were not well-defined, reflecting confusion about which HCPs were charged with these ‘responsibilities’. Specialist nurses in asthma and pharmacists felt less confident than physicians in removing medications lest their patients’ symptoms or illness returned and preferred lowering dosages instead by stepwise deprescribing as noted in asthma guidelines for inhaled and oral steroids. Interprofessional communication between primary and secondary care was very limited, particularly regarding patient medication changes. The dataset analysis revealed that the onset of asthma polypharmacy typically occurred at 50-59 years of age but arose at a younger age (40-49) amongst those from lower socioeconomic backgrounds, especially men. Polypharmacy also coincided with increased levels of multimorbidity. These patterns were also identified by HCPs in the interviews. Since 2012, polypharmacy has steadily decreased and deprescribing gradually increased – coinciding with the introduction of the Scottish Polypharmacy Guidance, which offers detailed advice on conducting medication reviews and deprescribing. Stepping down medication was found to be more prevalent than outright removal, (also confirmed in the interviews). Patients taking 15+ medications had the highest levels of hospital admissions across all patients over the age of 50, particularly between ages 70 and 90, possibly due to increased frailty. Though overall prescribing/deprescribing patterns broadly followed Tudor Hart’s inverse care law, whereby, access to care by different social demographics is inversely promotional to need, deprescribing of medications over time observed in the 5-9 medication category was irrespective of social class, age and/or gender. The widely observed differential access to care flagged by Tudor Hart appeared to be eroded by the increased engagement of older frail patients across the board (regardless of demographic) with healthcare services. CONCLUSION: Current polypharmacy policies target frail over-75s with polypharmacy. Polypharmacy seemingly decreased amongst this demographic suggesting that their increased engagement with health services due to their frailty increases their opportunities to have a medication review. However, polypharmacy is often experienced by those significantly younger than 75, particularly, we have shown, amongst younger multimorbid patients from lower socioeconomic backgrounds (especially men). This, the study suggests, may be because of their lower engagement with healthcare services. Targeting demographics with less interaction with healthcare services could advance polypharmacy mitigation/management. The potentially low levels of deprescribing observed confirms HCP acknowledgement that structured medication reviews are occurring less frequently and systematically than suggested by policy (though they occur under certain contingencies such as the asthma annual review). The continuing high level of hospital admissions amongst patients prescribed 10+ medications calls into question the adequacy of medication reviews performed for atrisk patients requiring polypharmacy management. Clarifying the function and roles associated with medication reviews across care systems could enhance the discovery of inappropriate polypharmacy in patients and prevent unnecessary drug related hospital admissions. Undertaking mixed methods analysis, involving both detailed qualitative interviews and large-scale quantitative modelling, presents challenges to the researcher in terms of both the scale of research work and the range of tools and skills that need to be deployed. It does, however, offer important additional insights – particularly in this case the opportunity to link HCP perceptions about care processes with more general modelling of patient morbidity patterns and engagement with health services that are not necessarily apparent to respondents involved

TRPM7 deficiency exacerbates cardiovascular and renal damage induced by aldosterone-salt

Hyperaldosteronism causes cardiovascular disease as well as hypomagnesemia. Mechanisms are ill-defined but dysregulation of TRPM7, a Mg2+-permeable channel/α-kinase, may be important. We examined the role of TRPM7 in aldosterone-dependent cardiovascular and renal injury by studying aldosterone-salt treated TRPM7-deficient (TRPM7+/Δkinase) mice. Plasma/tissue [Mg2+] and TRPM7 phosphorylation were reduced in vehicle-treated TRPM7+/Δkinase mice, effects recapitulated in aldosterone-salt-treated wild-type mice. Aldosterone-salt treatment exaggerated vascular dysfunction and amplified cardiovascular and renal fibrosis, with associated increased blood pressure in TRPM7+/Δkinase mice. Tissue expression of Mg2+-regulated phosphatases (PPM1A, PTEN) was downregulated and phosphorylation of Smad3, ERK1/2, and Stat1 was upregulated in aldosterone-salt TRPM7-deficient mice. Aldosterone-induced phosphorylation of pro-fibrotic signaling was increased in TRPM7+/Δkinase fibroblasts, effects ameliorated by Mg2+ supplementation. TRPM7 deficiency amplifies aldosterone-salt-induced cardiovascular remodeling and damage. We identify TRPM7 downregulation and associated hypomagnesemia as putative molecular mechanisms underlying deleterious cardiovascular and renal effects of hyperaldosteronism

PREVALENCE OF COMPLICATIONS AFTER ODONTOPLASTY

Background:Cosmetic dentistry, also known as enameloplasty, is what odontoplasty refers to. This cosmetic dentistry treatment that strives to enhance the function of human teeth also includes contouring and reshaping of the teeth. Enhancing the look of a persons teeth by modifying their size, length, or even shape is a popular cosmetic procedure nowadays. This research aimed to assess and understand the issues and complications that are reported to have been faced by many people who have gone through the procedure of odontoplasty. Methods:A cross-sectional study was used to understand the prevalence of complications after odontoplasty. The philosophy of positivism is appropriate for this research as it helped in the descriptive assessment of the quantitative data gathered. An inductive research approach would be implemented because this approach relies on building up new theories and developing perceptions from existing theories. This is the need of this research work, and therefore an approach of inductive nature would be the best fit.The sampling method that was implemented is stratified random sampling, which would help consider those individuals in the UK going through the odontoplasty procedure. The sample age group is within the range of 25-40 years. Results:Study included 562 participants in which all of them responded to study survey questions. The most frequent complication was weak tooth (n= 268, 47.7%). More than third of study participants didnt support the changing of natural appearance of the tooth (n= 216, 38.4%). However, 63% would like to further changing the existing shape and size of their teeth (n= 354). On the other hand, 241 participants believed that odontoplasty is a necessity (42.9%). The same percentage almost recommended others to undergo odontoplasty (n= 239, 42.5%). 312 participants felt moderate pain (55.5%) is more than half of study participants. The most frequent reason why participants underwent odontolplasty was bad shape of teeth (n= 259, 46.1%). Conclusion:The most prevalent consequence was weak teeth. More over a third of survey participants opposed altering the tooths natural look, according to the study findings. However, more than half of individuals would desire to modify their present tooth form and size. Some participants, however, thought that odontoplasty is necessary. Over fifty percent of subjects reported moderate discomfort. About half of them claimed that it would endure for extended period of tim

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research