Polypharmacy Management in a Gender Perspective: At the Heart of the Problem: Analysis of Major Cardiac Diseases, SARS-CoV-2 Affection and Gender Distribution in a Cohort of Patients in Internal Medicine Ward.

BACKGROUND: COVID-19 patients with any pre-existing major cardio-vascular disease (CVD) are at the highest risk of viral infection and of developing severe disease. The pathophysiological mechanism is characterized by the viral link to angiotensin-converting enzyme 2 (ACE2) and the involvement of the endothelial system with the release of cytokines and the inflicting of direct damage to the myocardium, the induction of microthrombosis, and the initiation of alterations in oxygen diffusion. The aim of the study is to analyze the clinical course and outcomes in patients (gender-stratified) with pre-existing major CVD. METHODS: Out of the 1833 (973 M/860 F) patients admitted to the Internal Medicine COVID-19 Unit of "Castelli Hospital", Lazio, Italy, from 1 January 2021 to 31 December 2021, 600 patients (320 M/280 F) with a mean age of 77 (78.6 M/75.1 F) previously had CVD. Demographic characteristics, length of the stay (LOS) and oxygen therapy were evaluated. RESULTS: All of the CVD COVID-19 patients underwent non-invasive ventilation (NIV). CVD was linked with increased LOS (21 days F/22 M) compared to no CVD (19 days). In total, 32.7% of total patients had major CVD. CONCLUSIONS: Timely identification and evaluation of patients with pre-existing major CVD are fundamental for adequate treatment based on gender, severity, state of illness and for risk reduction.

Unnecessary hospitalisations and polypharmacy practices in Romania: A health system evaluation for strengthening primary health care.

Background: Children and pregnant women usually have multiple contacts with the health care system. While most conditions can be managed by primary health care (PHC) providers, hospitalisations are nevertheless common and often unjustified. The number of hospitalizations decreased in Romania at the start of the COVID-19 pandemic. While this is likely due to the disruption of health services and public health measures established to limit the spread of COVID-19, it also suggests that a proportion of hospitalisations prior to the pandemic were unnecessary. This healthcare system evaluation in Romania quantified unnecessary and unnecessarily prolonged hospitalisations in children, pregnant women and women hospitalised for delivery, and assessed antibiotic and polypharmacy practices in these groups. Methods: We conducted the healthcare system evaluation in 10 hospitals across the country. We extracted data from medical records of patients hospitalized between 2019 and 2020. In each hospital, we randomly selected 40 medical records for each of the following groups: children 2-59 months of age, pregnant women, and women hospitalised for delivery. Clinical data were compared against WHO standards indicating a need for inpatient treatment or antibiotic therapy. Results: Among 209 children and 349 pregnant women, unnecessary hospitalisations accounted for 57.9% and 56.2% of hospitalisations, respectively. Among necessary hospitalisations, a large proportion was unnecessarily prolonged, including 44.4% (n = 32/72) in children, 23.3% (n = 34/146) in pregnant women, and 45.8% (n = 110/240) in women after delivery. The proportion of unnecessary and unnecessarily prolonged hospitalisations did not differ between the pre-pandemic, the lockdown, and the post-lockdown periods. Antibiotics were prescribed to 53.1% (n = 43/81) of children with diarrhoea, while 50.8% (n = 61/120) of women with caesarean section received an unjustified prolonged course of antibiotics. Children and women were commonly prescribed unnecessary medications. Conclusions: Findings of this evaluation should inform evidence-based decisions and actions for strengthening PHC and the healthcare system structure and improving the management of common diseases in mothers, newborns, and children. The evaluation should be repeated periodically to monitor progress.

Alcohol, the overlooked drug: clinical pharmacist perspectives on addressing alcohol in primary care.

BACKGROUND: Attempts to routinely embed brief interventions in health systems have long been challenging, with healthcare professionals concerned about role adequacy, legitimacy, and support. This is the first study to explore clinical pharmacists' experiences of discussing alcohol with patients in their new role in UK primary care, in developing a novel approach to brief intervention. It investigates their confidence with the subject of alcohol in routine practice and explores views on a new approach, integrating alcohol into the medication review as another drug directly linked to the patient's health conditions and medicines, rather than a separated 'healthy living' issue. The study forms part of wider efforts to repurpose and reimagine the potential application of brief interventions and to rework their contents. METHODS: Longitudinal qualitative study of 10 recruits to the new clinical pharmacist role in English primary care, involving three semi-structured interviews over approximately 16 months, supplemented by 10 one-off interviews with pharmacists already established in general practice. RESULTS: When raised at all, enquiring about alcohol in medication reviews was described in terms of calculating dose and level of consumption, leading to crude advice to reduce drinking. The idea was that those who appeared dependent should be referred to specialist services, though few such referrals were recalled. Pharmacists acknowledged that they were not currently considering alcohol as a drug in their practice and were interested in learning more about this concept and the approach it entailed, particularly in relation to polypharmacy. Some recognised a linked need to enhance consultation skills. CONCLUSIONS: Alcohol complicates routine clinical care and adversely impacts patient outcomes, even for those drinking at seemingly unremarkable levels. Changing clinical practice on alcohol requires engaging with, and supportively challenging, routine practices and entrenched ideas of different kinds. Framing alcohol as a drug may help shift the focus from patients with alcohol problems to problems caused for patients by alcohol. This is less stigmatising and provides role legitimacy for pharmacists to address alcohol clinically in medication reviews, thus providing one element in the formation of a new prevention paradigm. This approach invites further innovations tailored to other healthcare professional roles.

Polypharmacy in Hypertension: Should Hypertensive Therapy Be Re-evaluated Periodically?

Although hypertension is highly prevalent in older adults, treatment goals require both an understanding of the various guidelines available, as well as appreciation of the unique medical, cognitive, psychosocial, and functional heterogeneity of our individual geriatric patients that may place them outside those guidelines. As a patient's clinical status changes over time, clinicians may consider deprescribing their blood pressure medications when their risks begin to outweigh their benefits. Unique clinical circumstances and incorporating the time to benefit of hypertension control help guide clinical decision-making.

Evaluation of potential drug-drug interactions and polypharmacy in hospitalized COVID-19 patients.

Background: Drugs that are used in COVID-19 infection, may interact with each other, as well as with the drugs for comorbidities, used concomitantly with COVID-19 treatment. Objectives: It is quite important to calculate and present the patients' exposure to clinically important potential drug-drug interactions (pDDIs). We aimed to investigate the pDDIs and the burden of polypharmacy in COVID-19. Methods: The medical records of 126 consecutive inpatients with COVID-19 treatment were retrospectively analyzed. The Lexi-interact database was used to investigate pDDIs. Results: According to the Lexi-interact database, 605 pDDIs were detected. Of these pDDIs, 23 (3.8%) were A risk category interaction, 186 (30.7%) were B risk category interaction, 339 (56%) were C risk category interaction, 54 (8.9%) were D risk category interaction, and 3 (0.5%) were X risk category interaction. Sixty-five-point five percent of pDDIs (n=396) were clinically important pDDIs (C, D, and X categories), and 69 patients (54.8%) had at least one clinically important pDDIs. The most interacting drug was hydroxychloroquine (n=171, 28.3%). Hydroxychloroquine was also the most interacting drug in the C risk category (n=101, 29.8%) and had 19 pDDIs with metformin, 16 pDDIs with beta-blockers, 13 pDDIs with acetylsalicylic acid, and 10 pDDIs with insulin in the C risk category. Enoxaparin was the most interacting drug (n=25, 46.3%) in the D risk category and most of them were with acetylsalicylic acid (n=12). The most common possible clinical manifestations of pDDIs were QT prolongation, hypoglycemia, and hemorrhage. One hundred and eighteen patients (93.6%) used five or more drugs daily. There was a significant positive correlation between the number of drugs prescribed to patients and the number of clinically important pDDIs (r=0.80, p<0.001). Conclusions: Clinically important pDDIs are common among COVID-19 patients and the majority of pDDIs require monitoring of therapy. COVID-19 patients should be closely observed for QT prolongation, hypoglycemia, and hemorrhage due to pDDIs during treatment.

The impact of polypharmacy on 30-day COVID-related mortality in nursing home residents: a multicenter retrospective cohort study.

PURPOSE: Both the coronavirus (COVID-19) disease and polypharmacy pose a serious threat to nursing home (NH) residents. This study aimed to assess the impact of polypharmacy on 30-day COVID-related mortality in NH residents with COVID-19. METHODS: Multicenter retrospective cohort study including NH residents from 15 NHs in the Netherlands. The impact of polypharmacy on 30-day COVID-related mortality was evaluated and assessed using multivariable logistic regression analyses with correction for age, sex, CCI, BMI and vaccination status. RESULTS: In total, 348 NH residents were included, with a mean age of 84 years (SD = 8); 65% were female, 70% lived in a psychogeriatric ward, with a main diagnosis of dementia. 30-day COVID-related mortality was 27.3%. We found a significant, positive association between the total number of medications and 30-day COVID-related mortality (OR 1.09; 95% CI 1.001-1.20, p = 0.046), after adjustment for age, sex, Charlson Comorbidity Index (CCI), Body Mass Index (BMI) and vaccination status. After additional correction for dementia (model 2) and use of PPI, vitamin D, antipsychotics and antithrombotics (model 3), this effect remained positive, but was no longer significant. CONCLUSION: Nursing home residents with a higher number of medications and who were not vaccinated, had a higher 30-day COVID-related mortality. These findings have important implications for the management of COVID-19 in the frail NH population. As such they underline the importance of deprescribing on the one hand, but also of improving vaccination rates on the other.

Individualising Life Expectancy Is Necessary for Optimal Prescribing.

One possible cause of overprescribing (or insufficient deprescribing) is the failure to explicitly address the individual's life expectancy (LE). For example, if a LE estimate shows the person has six months to live, this should influence the prescribing of a medication that offers benefits only over a much longer LE. Predicting exactly the number of years a person will live is impossible, but probabilistic forecasting is possible and arguably essential, both for the selection of the optimal intervention and for meeting the 'reasonable patient' standard of information about the harms and benefits of alternative options. One side-effect of the COVID-19 pandemic has been to bring mortality into greater prominence, hopefully facilitating its discussion in the clinic as part of the 'new normal'. This paper outlines the case for introducing LE into prescribing decisions as a way of making more individualised decisions and potentially reducing overprescribing. It concentrates on how the clinical task of arriving at individualised estimates of LE might be tackled, especially in the case of the growing number of older patients with heterogeneous sociodemographic characteristics who are experiencing multiple long term conditions of varying severity and are frequently subject to 'polypharmacy'.

Sedative polypharmacy mediates the effect of mechanical ventilation on delirium in critically ill COVID-19 patients: A retrospective cohort study.

BACKGROUND: Polypharmacy of sedatives (PP) is a potentially modifiable, iatrogenic risk factor for ICU delirium. The extent to which sedative PP influenced development of high rates of delirium among critically ill COVID-19 patients is unknown. We tested the hypothesis that PP, defined as the use of four or more classes of intravenous agents, is a mediator in the causal pathway of mechanical ventilation and delirium. METHODS: Retrospective cohort study of adults admitted with a primary diagnosis of RT-PCR+ for SARS-CoV2 to ICUs of a tertiary-level academic medical center between February 2020 and April 2021. Mediation analysis was conducted with bootstrap estimation to assess whether an association between mechanical ventilation and delirium was mediated by PP. Analyses were adjusted for potential confounders related to mechanical ventilation, mediator, and outcome, including age, gender, vasopressor use, median RASS scores, SOFA score within 24 h of admission, and maximum CRP levels. RESULTS: A total of 212 patients were included in the analysis. Of total patients, 72.6%(154/212) of patients had delirium (CAM-ICU+) during ICU stay. 54.7%(116/212) patients received PP. Mechanical ventilation (OR 3.81 [1.16-12.52]) and PP (OR 7.38 [2.4-22.68]) were identified as risk factors for development of ICU delirium after adjusting for prespecified confounders. PP acts as a mediator in the causal pathway between mechanical ventilation and delirium. 39% (95% CI: 17%-94%) of the effect of mechanical ventilation on delirium was mediated through PP. CONCLUSION: PP mediates approximately 39% of the effect of mechanical ventilation on delirium, which is clinically and statistically significant. Studies should assess whether mitigating PP could lead to reduction in ICU delirium. IMPLICATION STATEMENT: PP of sedatives (defined as use of four or more intravenous agents) mediates approximately 39% of the effect of mechanical ventilation on development of ICU delirium. Avoidance of sedative PP may represent a viable strategy for reduction of ICU delirium.

Implementation of targeted deprescribing of potentially inappropriate medications in patients on hemodialysis.

PURPOSE: Patients on hemodialysis have a high risk of medication-related problems. Studies using deprescribing algorithms to reduce the number of inappropriate medications in this population have been published, but none have used a patient-partnership approach. Our study evaluated the impact of a similar intervention with a patient-partnership approach. METHODS: The objective was to describe the implementation of a pharmacist-led intervention with a patient-partnership approach using deprescribing algorithms and its impact on the reduction of inappropriate medications in patients on hemodialysis. Eight algorithms were developed by pharmacists and nephrologists to assess the appropriateness of medications. Pharmacists identified patients taking targeted medications. Following patient enrollment, pharmacists assessed medications with patients and applied the algorithms. With patient consent, deprescription was suggested to nephrologists if applicable. Specific data on each targeted medication were collected at 4 and 16 weeks. Descriptive statistics were used to examine the effects of the deprescribing intervention. RESULTS: Of 270 patients, 256 were taking at least one targeted medication. Of the 122 patients taking at least one targeted medication who were approached to participate, 66 were included in the study. At enrollment, these patients were taking 252 targeted medications, of which 59 (23.4%) were determined to be inappropriate. Deprescription was initiated for 35 of these 59 medications (59.3%). At 4 weeks, 33 of the 59 medications (55.9%) were still deprescribed, while, at 16 weeks, 27 of the 59 medications (45.8%) were still deprescribed. Proton pump inhibitors and benzodiazepines or Z-drugs were the most common inappropriate medications, and allopurinol was the most deprescribed medication. CONCLUSION: A pharmacist-led intervention with a patient-partnership approach and using deprescribing algorithms reduced the number of inappropriate medications in patients on hemodialysis.

Detecting Drug-Drug Interactions in COVID-19 Patients.

COVID-19 patients with multiple comorbid illnesses are more likely to be using polypharmacy to treat their COVID-19 disease and comorbid conditions. Previous literature identified several DDIs in COVID-19 patients; however, various DDIs are unrecognized. This study aims to discover novel DDIs by conducting comprehensive research on the FDA Adverse Event Reporting System (FAERS) data from January 2020 to March 2021. We applied seven algorithms to discover DDIs. In addition, the Liverpool database containing DDI confirmed by clinical trials was used as a gold standard to determine novel DDIs in COVID-19 patients. The seven models detected 2,516 drug-drug pairs having adverse events (AEs), 49 out of which were confirmed by the Liverpool database. The remaining 2,467 drug pairs tested to be significant by the seven models can be candidate DDIs for clinical trial hypotheses. Thus, the FAERS database, along with informatics approaches, provides a novel way to select candidate drug-drug pairs to be examined in COVID-19 patients.

Development of an intervention to improve informational continuity of care in older patients with polypharmacy at the interface between general practice and hospital care: protocol for a participatory qualitative study in Germany.

INTRODUCTION: Older patients with multimorbidity, polypharmacy and related complex care needs represent a growing proportion of the population and a challenge for healthcare systems. Particularly in transitional care (hospital admission and hospital discharge), medical errors, inappropriate treatment, patient concerns and lack of confidence in healthcare are major problems that may arise from a lack of information continuity. The aim of this study is to develop an intervention to improve informational continuity of care at the interface between general practice and hospital care. METHODS AND ANALYSIS: A qualitative approach will be used to develop our participatory intervention. Overall, 32 semistructured interviews with relevant stakeholders will be conducted and analysed. The stakeholders will include healthcare professionals from the outpatient setting (general practitioners, healthcare assistants, ambulatory care nurses) and the inpatient setting (clinical doctors, nurses, pharmacists, clinical information scientists) as well as patients and informal caregivers. At a series of workshops based on the results of the stakeholder analyses, we aim to develop a participatory intervention that will then be implemented in a subsequent pilot study. The same stakeholder groups will be invited for participation in the workshops. ETHICS AND DISSEMINATION: Ethical approval for this study was waived by the Ethics Committee of Goethe University Frankfurt because of the nature of the proposed study. Written informed consent will be obtained from all study participants prior to participation. Results will be tested in a pilot study and disseminated at (inter)national conferences and via publication in peer-reviewed journals. TRIAL REGISTATION NUMBER: Clinical Trials Register: registration number DRKS00027649.

Exploring the associations between polypharmacy and COVID-19-related hospitalisations and deaths: a population-based cohort study among older adults in Quebec, Canada.

OBJECTIVES: To study the association between polypharmacy and the risk of hospitalisation and death in cases of COVID-19 in the population over the age of 65. DESIGN: Population-based cohort study. SETTING: Quebec Integrated Chronic Disease Surveillance System, composed of five medico-administrative databases, in the province of Quebec, Canada. PARTICIPANTS: 32 476 COVID-19 cases aged over 65 whose diagnosis was made between 23 February 2020 and 15 March 2021, and who were covered by the public drug insurance plan (thus excluding those living in long-term care). We counted the number of different medications they claimed between 1 April 2019 and 31 March 2020. OUTCOME MEASURES: Robust Poisson regression was used to calculate relative risk of hospitalisation and death associated with the use of multiple medications, adjusting for age, sex, chronic conditions, material and social deprivation and living environment. RESULTS: Of the 32 476 COVID-19 cases included, 10 350 (32%) were hospitalised and 4146 (13%) died. Compared with 0-4 medications, polypharmacy exposure was associated with increased hospitalisations, with relative risks ranging from 1.11 (95% CI 1.04 to 1.19) for those using 5-9 medications to 1.62 (95% CI 1.51 to 1.75) for those using 20+. Similarly, the risk of death increased with the number of medications, from 1.13 (95% CI 0.99 to 1.30) for those using (5-9 medications to 1.97 (95% CI 1.70 to 2.27) (20+). Increased risk was mainly observed in younger groups. CONCLUSIONS: Polypharmacy was significantly associated with the risk of hospitalisations and deaths related to COVID-19 in this cohort of older adults. Polypharmacy may represent a marker of vulnerability, especially for younger groups of older adults.

Person-centred care provided by a multidisciplinary primary care team to improve therapeutic adequacy in polymedicated elderly patients (PCMR): randomised controlled trial protocol.

INTRODUCTION: The increase in elderly population has led to an associated increase in multiple pathologies, frailty, polypharmacy, healthcare costs, decreased quality of life and mortality. We designed an intervention based on person-centred care model. This article outlines a study protocol, which aims to explore the effects of the intervention to improve therapeutic adequacy in polymedicated elderly patients. METHODS AND ANALYSIS: An open, randomised, multicentre, controlled clinical trial. The study population includes polymedicated (≥8 prescription medications) patients ≥75 years old. In the intervention group, the multidisciplinary team (primary care pharmacist, family doctor and nurse) will meet to carry out multidimensional reviews (frailty, clinical complexity, morbidity and therapeutic adequacy) of the study subjects. If changes are proposed to the treatment plan, a clinical interview will be conducted with the patient to agree on changes in accordance with their preferences. Follow-up visits will be scheduled at 6 and 12 months. In the control group, where the usual clinical practice will be followed, the necessary data will be collected to compare the results.The key variables are the variation in the mean number of incidents (potentially inappropriate prescription) per patient, the number of medications, the number of changes implemented to the treatment plan and the variation in the number of hospital admissions. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of the IDIAPJGol and by the University of Barcelona's Bioethics Commission. The results are expected to be published in peer reviewed open-access journals, and as part of a doctoral thesis. TRIAL REGISTRATION NUMBER: NCT04188470. Pre-results.

Minimization of the Drug and Gene Interactions in Polypharmacy Therapies Augmented with COVID-19 Medications.

Medications Dexamethasone, Remdesivir or Colchicine, used to treat COVID-19 patients, have significant interactions with other medications and the human genome. The study presented in this paper investigates how to use the Personalized Medicine Therapy Optimization Method (PM-TOM) to minimize these interactions in polypharmacy therapies of COVID-19 patients. We applied PM-TOM on the EMR database of Harvard Personal Genome Project (PGP), drug database DrugBank and Comprehensive Toxicogenomics Database (CTD) to analyze polypharmacy therapies augmented with these medications. The main finding is that these COVID-19 medications significantly increase the drug and gene interactions in partially optimized (or unoptimized) therapies, which is not the case in the fully optimized ones. For example, the test results show that in polypharmacy treatments for patients having between 3 and 8 conditions, the average number of drug and gene interactions in partially optimized therapies ranges from 3 to 18 after adding Remdesivir, 4.3 to 20 Colchicine, and 4.7 to 23 Dexamethasone. On the other hand, these interactions in fully optimized therapies range only 0.6 to 5.2, 1.2 to 7, and 2.7 to 11, respectively. These results suggest that polypharmacy therapies should be carefully examined before adding these medications. This recommendation applies to all other situations when polypharmacy patients may conduct new serious conditions, such as COVID-19, requiring additional medications with a high number of drug and gene interactions.

Telemedication Reviews to Optimize Medication Prescription for Older People in Nursing Homes.

Introduction: Older people living in nursing homes (NH) are at a higher risk of preventable drug-related adverse events because of age-related physiological changes, polypathology, and polypharmacy. NH residents are particularly exposed to potentially inappropriate medications (PIMs). Many strategies have been developed to improve the quality and the safety of drug prescription in NH, including medication reviews (MRs). Methods: In the context of the application of telemedicine, we developed and are currently implementing a novel hospital expert-based MRs through tele-expertise (or "telemedication review," telemedication reviews hereafter [TMR]) in French NH residents. The impact of these TMR on unplanned hospitalizations 3 months after implementation is assessed. TMR consider all available sociodemographic, clinical, biological, and pharmaceutical data pertaining to the patient and are performed in accordance with their health care objectives. Results: The preliminary results for the 39 TMRs performed to date (September 2021) showed that a total of 402 PIMs were detected, and all residents had at least one PIM. We also present the feasibility and the usefulness of this novel TMR for NH, illustrating these preliminary results with two concrete TMR experiences. Among the 39 TMR performed, the average acceptance rate of expert recommendations made to general practitioners (GP) working in NH was ∼33%. Discussion and Conclusions: The success of this novel TMR depends on how the proposed prescription adjustments made by the hospital expert team are subsequently integrated into health care practices. The low acceptance rate by GP highlights the need to actively involve these professionals in the process of developing TMR, with a view to encouraging them to act on proposed adjustments.

Polypharmacy Exposure, Aging Populations, and COVID-19: Considerations for Healthcare Providers and Public Health Practitioners in Africa.

Given the continent's growing aging population and expanding prevalence of multimorbidity, polypharmacy is an increasingly dire threat to the health of persons living in Africa. The COVID-19 pandemic has only exacerbated these issues. Widespread misinformation, lack of vaccine access, and attempts to avoid being infected have resulted in increases in Africans' willingness to take multiple prescription and nonprescription medications and supplements. Issues with counterfeit pharmaceuticals and the relatively new recognition of emergency medicine as a specialty across the continent also create unique challenges for addressing this urgent public health need. Experts have called for more robust pharmaceutical regulation and healthcare/public health infrastructure investments across the continent. However, these changes take time, and more near-term strategies are needed to mitigate current health needs. In this commentary, we present a nonexhaustive set of immediately implementable recommendations that can serve as local strategies to address current polypharmacy-related health needs of Africans. Importantly, our recommendations take into consideration that not all healthcare providers are emergency medicine trained and that local trends related to polypharmacy will change over time and require ever-evolving public health initiatives. Still, by bolstering training to safeguard against provider availability biases, practicing evidence-based prescribing and shared decision making, and tracking and sharing local trends related to polypharmacy, African healthcare providers and public health practitioners can better position themselves to meet population needs. Furthermore, although these recommendations are tailored to Africans, they may also prove useful to providers and practitioners in other regions facing similar challenges.