Potentially Inappropriate Medication Use in Primary Care in Switzerland.

Importance: Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM and recommend alternative prescribing, but the complexity of available lists limits their applicability and the amount of data available on PIM prescribing. Objective: To determine PIM prevalence and the most frequently prescribed PIMs according to 6 well-known PIM lists and to develop a best practice synthesis for clinicians. Design, Setting, and Participants: This cross-sectional study used anonymized electronic health record data of Swiss primary care patients aged 65 years or older with drug prescriptions from January 1, 2020, to December 31, 2021, extracted from a large primary care database in Switzerland, the FIRE project. Data analyses took place from October 2022 to September 2023. Exposure: PIM prescription according to PIM criteria operationalized for use with FIRE data. Main Outcomes and Measures: The primary outcomes were PIM prevalence (percentage of patients with 1 or more PIMs) and PIM frequency (percentage of prescriptions identified as PIMs) according to the individual PIM lists and a combination of all 6 lists. The PIM lists used were the American 2019 Updated Beers criteria, the French list by Laroche et al, the Norwegian General Practice Norwegian (NORGEP) criteria, the German PRISCUS list, the Austrian list by Mann et al, and the EU(7) consensus list of 7 European countries. Results: This study included 115 867 patients 65 years or older (mean [SD] age, 76.0 [7.9] years; 55.8% female) with 1 211 227 prescriptions. Among all patients, 86 715 (74.8%) were aged 70 years or older, and 60 670 (52.4%) were aged 75 years or older. PIM prevalence among patients 65 years or older was 31.5% (according to Beers 2019), 15.4% (Laroche), 16.1% (NORGEP), 12.7% (PRISCUS), 31.2% (Mann), 37.1% (EU[7]), and 52.3% (combined list). PIM prevalence increased with age according to every PIM list (eg, according to Beers 2019, from 31.5% at age 65 years or older to 37.4% for those 75 years or older, and when the lists were combined, PIM prevalence increased from 52.3% to 56.7% in those 2 age groups, respectively). PIM frequency was 10.3% (Beers 2019), 3.9% (Laroche), 4.3% (NORGEP), 2.4% (PRISCUS), 6.7% (Mann), 9.7% (EU[7]), and 19.3% (combined list). According to the combined list, the 5 most frequently prescribed PIMs were pantoprazole (9.3% of all PIMs prescribed), ibuprofen (6.9%), diclofenac (6.3%), zolpidem (4.5%), and lorazepam (3.7%). Almost two-thirds (63.5%) of all PIM prescriptions belonged to 5 drug classes: analgesics (26.9% of all PIMs prescribed), proton pump inhibitors (12.1%), benzodiazepines and benzodiazepine-like drugs (11.2%), antidepressants (7.0%), and neuroleptics (6.3%). Conclusions and Relevance: In this cross-sectional study of adults aged 65 or older, PIM prevalence was high, varied considerably depending on the criteria applied, and increased consistently with age. However, only few drug classes accounted for the majority of all prescriptions that were PIM according to any of the 6 PIM lists, and by considering this manageable number of drug classes, clinicians could essentially comply with all 6 PIM lists. These results raise awareness of the most common PIMs and emphasize the need for careful consideration of their risks and benefits and targeted deprescribing.

Importance of different electronic medical record components for chronic disease identification in a Swiss primary care database: a cross-sectional study.

BACKGROUND: Primary care databases collect electronic medical records with routine data from primary care patients. The identification of chronic diseases in primary care databases often integrates information from various electronic medical record components (EMR-Cs) used by primary care providers. This study aimed to estimate the prevalence of selected chronic conditions using a large Swiss primary care database and to examine the importance of different EMR-Cs for case identification. METHODS: Cross-sectional study with 120,608 patients of 128 general practitioners in the Swiss FIRE ("Family Medicine Research using Electronic Medical Records") primary care database in 2019. Sufficient criteria on three individual EMR-Cs, namely medication, clinical or laboratory parameters and reasons for encounters, were combined by logical disjunction into definitions of 49 chronic conditions; then prevalence estimates and measures of importance of the individual EMR-Cs for case identification were calculated. RESULTS: A total of 185,535 cases (i.e. patients with a specific chronic condition) were identified. Prevalence estimates were 27.5% (95% CI: 27.3-27.8%) for hypertension, 13.5% (13.3-13.7%) for dyslipidaemia and 6.6% (6.4-6.7%) for diabetes mellitus. Of all cases, 87.1% (87.0-87.3%) were identified via medication, 22.1% (21.9-22.3%) via clinical or laboratory parameters and 19.3% (19.1-19.5%) via reasons for encounters. The majority (65.4%) of cases were identifiable solely through medication. Of the two other EMR-Cs, clinical or laboratory parameters was most important for identifying cases of chronic kidney disease, anorexia/bulimia nervosa and obesity whereas reasons for encounters was crucial for identifying many low-prevalence diseases as well as cancer, heart disease and osteoarthritis. CONCLUSIONS: The EMR-C medication was most important for chronic disease identification overall, but identification varied strongly by disease. The analysis of the importance of different EMR-Cs for estimating prevalence revealed strengths and weaknesses of the disease definitions used within the FIRE primary care database. Although prioritising specificity over sensitivity in the EMR-C criteria may have led to underestimation of most prevalences, their sex- and age-specific patterns were consistent with published figures for Swiss general practice.

The Impact of COVID-19 on Mental Healthcare Utilization in Switzerland Was Strongest Among Young Females-Retrospective Study in 2018-2020.

Objectives: To provide a thorough assessment of the impact of the COVID-19 pandemic on the utilization of inpatient and outpatient mental healthcare in Switzerland. Methods: Retrospective cohort study using nationwide hospital data (n > 8 million) and claims data from a large Swiss health insurer (n > 1 million) in 2018-2020. Incidence proportions of different types of psychiatric inpatient admissions, psychiatric consultations, and psychotropic medication claims were analyzed using interrupted time series models for the general population and for the vulnerable subgroup of young people. Results: Inpatient psychiatric admissions in the general population decreased by 16.2% (95% confidence interval: -19.2% to -13.2%) during the first and by 3.9% (-6.7% to -0.2%) during the second pandemic shutdown, whereas outpatient mental healthcare utilization was not substantially affected. We observed distinct patterns for young people, most strikingly, an increase in mental healthcare utilization among females aged <20 years. Conclusion: Mental healthcare provision for the majority of the population was largely maintained, but special attention should be paid to young people. Our findings highlight the importance of monitoring mental healthcare utilization among different populations.

Adolescents' self-reported health status, behaviours and health issues addressed during routine school doctor consultations in Switzerland: an observational study.

BACKGROUND: We aimed to investigate the self-reported health status and behaviours of 7th-grade adolescents, associations with gender and educational track, as well as health issues addressed during routine school doctor consultations in Switzerland. METHODS: Data on health status and behaviours, specifically general well-being, stimulant and addictive substance use, bullying/violence, exercise, nutrition and health protection, and puberty/sexuality, were drawn from routinely collected self-assessment questionnaires from 1076 (of a total of 1126) students from 14 schools in the Swiss canton of Zug in 2020. Data on health issues addressed in school doctor consultations were collected by nine school doctors (for 595 individual consultations). Multilevel logistic regression analyses were used to investigate the association of gender and educational track with unfavourable health status or behaviours. RESULTS: Although 92% (n = 989) of the students reported being happy or satisfied overall, 21% (n = 215) often or almost always felt sad, and 5-10% had repeatedly been seriously physically hurt (n = 67), sexually harassed with words (n = 88) or experienced uncomfortable physical contact (n = 60). Female gender and a lower educational track were associated with unfavourable health status. In 90% (n = 533) of the school doctor consultations, at least one topic of disease prevention or health promotion was addressed, whereby the topics addressed depended strongly on the individual school doctors. CONCLUSIONS: Our findings revealed that unfavourable health status and behaviours were prevalent among adolescents but the health topics addressed in school doctor consultations were not tailored to students' self-reported health issues. A school-based approach that strengthens adolescents' health literacy and provides opportunities for patient-centred counselling has the potential to improve the current and future health of adolescents and, ultimately, adults. To realise this potential, it is essential for school doctors to be sensitised and trained to address students' health concerns. Emphasis should be placed on the importance of patient-centred counselling, the high prevalence of bullying, and gender and educational differences.

Medication Review and Enhanced Information Transfer at Discharge of Older Patients with Polypharmacy: a Cluster-Randomized Controlled Trial in Swiss Hospitals.

BACKGROUND: Medication safety in patients with polypharmacy at transitions of care is a focus of the current Third WHO Global Patient Safety Challenge. Medication review and communication between health care professionals are key targets to reduce medication-related harm. OBJECTIVE: To study whether a hospital discharge intervention combining medication review with enhanced information transfer between hospital and primary care physicians can delay hospital readmission and impact health care utilization or other health-related outcomes of older inpatients with polypharmacy. DESIGN: Cluster-randomized controlled trial in 21 Swiss hospitals between January 2019 and September 2020, with 6 months follow-up. PARTICIPANTS: Sixty-eight senior physicians and their blinded junior physicians included 609 patients ≥ 60 years taking ≥ 5 drugs. INTERVENTIONS: Participating hospitals were randomized to either integrate a checklist-guided medication review and communication stimulus into their discharge processes, or follow usual discharge routines. MAIN MEASURES: Primary outcome was time-to-first-readmission to any hospital within 6 months, analyzed using a shared frailty model. Secondary outcomes covered readmission rates, emergency department visits, other medical consultations, mortality, drug numbers, proportions of patients with potentially inappropriate medication, and the patients' quality of life. KEY RESULTS: At admission, 609 patients (mean age 77.5 (SD 8.6) years, 49.4% female) took a mean of 9.6 (4.2) drugs per patient. Time-to-first-readmission did not differ significantly between study arms (adjusted hazard ratio 1.14 (intervention vs. control arm), 95% CI [0.75-1.71], p = 0.54), nor did the 30-day hospital readmission rates (6.7% [3.3-10.1%] vs. 7.0% [3.6-10.3%]). Overall, there were no clinically relevant differences between study arms at 1, 3, and 6 months after discharge. CONCLUSIONS: The combination of a structured medication review with enhanced information transfer neither delayed hospital readmission nor improved other health-related outcomes of older inpatients with polypharmacy. Our results may help researchers in balancing practicality versus stringency of similar hospital discharge interventions. STUDY REGISTRATION: ISRCTN18427377, https://doi.org/10.1186/ISRCTN18427377.

Impact of the COVID-19 Pandemic on Elective and Emergency Inpatient Procedure Volumes in Switzerland - A Retrospective Study Based on Insurance Claims Data.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) pandemic forced hospitals to redistribute resources for the treatment of patients with coronavirus disease 2019 (COVID-19), yet the impact on elective and emergency inpatient procedure volumes is unclear. METHODS: We analyzed anonymized data on 234 921 hospitalizations in 2017-2020 (55.9% elective) from a big Swiss health insurer. We used linear regression models to predict, based on pre-pandemic data, the expected weekly numbers of procedures in 2020 in the absence of a pandemic and compared these to the observed numbers in 2020. Compensation effects were investigated by discretely integrating the difference between the two numbers over time. RESULTS: During the first COVID-19 wave in spring 2020, elective procedure numbers decreased by 52.9% (95% confidence interval -64.5% to -42.5%), with cardiovascular and orthopedic elective procedure numbers specifically decreasing by 45.5% and 72.4%. Elective procedure numbers normalized during summer with some compensation of postponed procedures, leaving a deficit of -9.9% (-15.8% to -4.5%) for the whole year 2020. Emergency procedure numbers also decreased by 17.1% (-23.7% to -9.8%) during the first wave, but over the whole year 2020, net emergency procedure volumes were similar to control years. CONCLUSION: Inpatient procedure volumes in Switzerland decreased considerably in the beginning of the pandemic but recovered quickly after the first wave. Still, there was a net deficit in procedures at the end of the year. Health system leaders must work to ensure that adequate access to non-COVID-19 related care is maintained during future pandemic phases in order to prevent negative health consequences.

Broken bones and apple brandy: resilience and sensemaking of general practitioners and their at-risk patients during the COVID-19 pandemic in Switzerland.

In early 2020, when the first COVID-19 cases were confirmed in Switzerland, the federal government started implementing measures such as national stay-at-home recommendations and a strict limitation of health care services use. General practitioners (GPs) and their at-risk patients faced similar uncertainties and grappled with subsequent sensemaking of the unprecedented situation. Qualitative interviews with 24 GPs and 37 at-risk patients were conducted which were analyzed using thematic analysis. Weick's (1993) four sources of -resilience - improvisation, virtual role systems, attitudes of wisdom and respectful interaction - heuristically guide the exploration of on-the-ground experiences and informal ways GPs and their at-risk patients sought to ensure continuity of primary care. GPs used their metaphorical Swiss army knives of learned tools as well as existing knowledge and relationships to adapt to the extenuating circumstances. Through improvisation, GPs and patients found pragmatic solutions, such as using local farmer apple brandy as disinfectant or at-home treatments of clavicle fractures. Through virtual role systems, GPs and patients came to terms with new and shifting roles, such as "good soldier" and "at-risk patient" categorizations. Both parties adopted attitudes of wisdom by accepting that they could not know everything. They also diversified their sources of information through personal relationships, formal networks, and the internet. The GP-patient relationship grew in importance through respectful interaction, and intersubjective reflection helped make sense of shifting roles and ambiguous guidelines. The empirical analysis of this paper contributes to theoretical considerations of sensemaking, resilience, crisis settings and health systems.

Cost-Effectiveness, Burden of Disease and Budget Impact of Inclisiran: Dynamic Cohort Modelling of a Real-World Population with Cardiovascular Disease.

OBJECTIVE: We aimed to estimate the cost-effectiveness, burden of disease and budget impact of inclisiran added to standard-of-care lipid-lowering therapy in the real-world secondary cardiovascular prevention population in Switzerland. METHODS: An open-cohort Markov model captured event risks by sex, age and low-density lipoprotein cholesterol based on epidemiological and real-world data. Low-density lipoprotein cholesterol reduction with add-on inclisiran was based on trial results and translated to meta-analysis-based relative risks of cardiovascular events. Unit costs for 2018 were based on publicly available sources, adopting a Swiss healthcare system perspective. Price assumptions of Swiss francs (CHF) 500 and CHF 3,000 per dose of inclisiran were evaluated, combined with uptake assumptions for burden of disease and budget impact. The assessment of cost-effectiveness used a discount rate of 3% per year. We performed deterministic and probabilistic sensitivity analyses, and extensive scenario analyses. RESULTS: Patients treated with inclisiran gained a 0.291 qualityadjusted life-year at an incremental cost per QALY gained of CHF 21,107/228,040 (life-long time horizon, discount rate 3%) under the lower/higher price. Inclisiran prevented 1025 cardiovascular deaths, 3425 acute coronary syndrome episodes, and 1961 strokes in 48,823 patients ever treated during 10 years; the 5-year budget impact was CHF 49.3/573.4 million under the lower/higher price. Estimates were sensitive to calibration targets and treatment eligibility; burden of disease/budget impact results also to uptake. Limitations included uncertainties about model assumptions and the size and characteristics of the population modelled. CONCLUSIONS: Inclisiran may be cost-effective at a willingness to pay of CHF 30,000 if priced at CHF 500; a threshold upwards of CHF 250,000 will be required if priced at CHF 3000. Inclisiran could enable important reductions in cardiovascular burden particularly under broader eligibility with a budget impact range from moderate to high depending on price.

The impact of the COVID-19 pandemic on the continuity of care for at-risk patients in Swiss primary care settings: A mixed-methods study.

Continuity of care is important for the health of aging individuals with comorbidities. When initial coronavirus mitigation campaigns involved messaging such as "Stay at home-stay safe," and banned provision of non-urgent care, at-risk patients depending upon regular consultations with general practitioners (GPs) faced confusion about the possibility of seeking non-COVID-19 related healthcare. We employed a sequential explanatory mixed-methods design, consisting of a quantitative component followed by a qualitative component, to understand at-risk patients' health services use during the COVID-19 pandemic in Switzerland. Quantitatively, we used electronic medical records data from 272 GPs and 266,796 patients. Based on pre-pandemic data, we predicted weekly consultation counts as well as weekly measurement counts (blood pressure, glycated hemoglobin, and low-density lipoprotein cholesterol) per 100 patients that would be expected in 2020 in absence of a pandemic and compared those to actual observed values. Qualitatively, we conducted 23 semi-structured interviews with 24 GPs (∼45 min) and 37 interviews with at-risk patients (∼35 min). Quantitative results demonstrate a significant decrease in consultation and measurement counts during the first shutdown period, with consultation counts quickly returning to normal and moving within expected values for the rest of 2020. Qualitative data contextualize these findings with GPs describing constantly implementing material, administrative, and communication changes. GPs reported communication gaps with the authorities and noted a lack of clear guidelines delineating how to define "at-risk patients" and what cases were "urgent" to treat during shutdowns. Patient interviews show that patient-level factors, such as fear of contracting coronavirus, perceptions that GPs were overburdened, and a sense of solidarity, influenced patients' decisions to consult less at the beginning of the pandemic. Findings demonstrate communication gaps during pandemic periods and provide valuable lessons for future pandemic preparedness, particularly the need for contingency plans for the overall healthcare system instead of plans focusing only on the infectious agent itself.

Prescription Rates, Polypharmacy and Prescriber Variability in Swiss General Practice-A Cross-Sectional Database Study.

Purpose: The frequency of medication prescribing and polypharmacy has increased in recent years in different settings, including Swiss general practice. We aimed to describe patient age- and sex-specific rates of polypharmacy and of prescriptions of the most frequent medication classes, and to explore practitioner variability in prescribing. Methods: Retrospective cross-sectional study based on anonymized electronic medical records data of 111 811 adult patients presenting to 116 Swiss general practitioners in 2019. We used mixed-effects regression analyses to assess the association of patient age and sex with polypharmacy (≥5 medications) and with the prescription of specific medication classes (second level of the Anatomical Therapeutic Chemical Classification System). Practitioner variability was quantified in terms of the random effects distributions. Results: The prevalence of polypharmacy increased with age from 6.4% among patients aged 18-40 years to 19.7% (41-64 years), 45.3% (65-80 years), and 64.6% (81-92 years), and was higher in women than in men, particularly at younger ages. The most frequently prescribed medication classes were antiinflammatory and antirheumatic products (21.6% of patients), agents acting on the renin-angiotensin system (19.9%), analgesics (18.7%), and drugs for acid related disorders (18.3%). Men were more often prescribed agents targeting the cardiovascular system, whereas most other medications were more often prescribed to women. The highest practitioner variabilities were observed for vitamins, for antiinflammatory and antirheumatic products, and for mineral supplements. Conclusion: Based on practitioner variability, prevalence, and risk potential, antiinflammatory drugs and polypharmacy in older patients appear to be the most pressing issues in current drug prescribing routines.

Price trends of reimbursed oncological drugs in Switzerland in 2005-2019: A descriptive analysis.

Increasing oncological treatment costs are a major global concern with the risk of entailing two-tiered health care. Among cost determining factors is the price of individual drugs. In recognition of the central role of this factor, we present a comprehensive overview of the development of monthly prices of oncological drugs introduced over the last 15 years in Switzerland. We identified all oncological drugs newly reimbursed by mandatory health insurance in 2005-2019, and searched public repositories for their package prices, indications with approval dates, and treatment regimens for the calculation of (indication-specific) monthly prices. We found 81 products covering 77 different substances (39.5% protein kinase inhibitors, 21.0% monoclonal antibodies). Most indications related to the topography "blood", followed by "lung and thorax" and "digestive tract". From 2005­2009 to 2015­2019, the median monthly product price over all distinct indications of all products decreased by 7.56% (CHF 5,699 [interquartile range 4,483­7,321] to CHF 5,268 [4,019­6,967]), whereas it increased by 73.7% for monoclonal antibodies. In December 2019, six products had monthly prices over CHF 10,000, all approved for hematological or dermatological cancers. Our analysis suggests that individual price developments of oncological drugs are presently not the major driver of rising cancer treatment costs. However, rising launch prices of some new, mostly hematological drugs are of concern and require continued monitoring.

Impact of the COVID-19 Pandemic on the Intensity of Health Services Use in General Practice: A Retrospective Cohort Study.

Objectives: We aimed to explore the impact of the Swiss shutdown in spring 2020 on the intensity of health services use in general practice. Methods: Based on an electronic medical records database, we built one patient cohort each for January-June 2019 (control, 173,523 patients) and 2020 (179,086 patients). We used linear regression to model weekly consultation counts and blood pressure (BP) and glycated hemoglobin (HbA1c) measurement counts per 100 patients and predicted non-shutdown values. Analyses were repeated for selected at-risk groups and different age groups. Results: During the shutdown, weekly consultation counts were lower than predicted by -17.2% (total population), -16.5% (patients with hypertension), -17.5% (diabetes), -17.6% (cardiovascular disease), -15.7% (patients aged <60 years), -20.4% (60-80 years), and -14.5% (>80 years). Weekly BP counts were reduced by -35.3% (total population) and -35.0% (hypertension), and HbA1c counts by -33.2% (total population) and -29.8% (diabetes). p-values <0.001 for all reported estimates. Conclusion: Our results document consequential decreases in consultation counts and chronic disease monitoring during the shutdown. It is crucial that health systems remain able to meet non-COVID-19-related health care needs.

Quantification of adipocyte numbers in transgenic mice via the Cre-LoxP recombination sites.

This protocol describes a method to assess adipocyte numbers within a specific depot based on their inducible genomic label. By extracting DNA from a complete adipose tissue depot stemming from two transgenic mouse lines (Adipoq-CreERT2 x ROSA26-tdRFP and Ucp1-CreERT2 x ROSA26-tdRFP), the number of adipocytes can be determined based on the quantification of the recombined LoxPRed sites. This highly sensitive system allows for the quantification of white, brown, and brite/beige adipocytes in a spatially unbiased and size-independent manner. For complete details on the use and execution of this protocol, please refer to Moser et al. (2021).

Physician-dispensing as a determinant of clinical and process measurements in patients at increased cardiovascular risk: A cross-sectional study in Swiss general practice.

AIMS: In some healthcare systems, physicians are allowed to dispense drugs; in others, drug-dispensing is restricted to pharmacists. Whether physician-dispensing affects patient health is unknown. Thus, we aimed to investigate associations between physician-dispensing and clinical and process measurements in patients with selected long-term conditions indicating increased cardiovascular risk. METHODS: Retrospective cross-sectional study in 2018 based on data from electronic medical records of 22405 patients (73.6% physician-dispensing) in Switzerland with medications for diabetes mellitus, arterial hypertension, or lipid-related disorders. We used multilevel regression models to determine the associations between physician-dispensing and clinical measurements (glycated hemoglobin [HbA1c], systolic blood pressure [sBP], low-density lipoprotein cholesterol [LDL-C]) or process measurements (number of annual clinical measurements, consultations, and drug prescriptions). RESULTS: Median (interquartile range) HbA1c value was 6.8% (6.3-7.5) both for the physician-dispensing and pharmacist-dispensing group, sBP was 137 (126-150) and 136 mmHg (126-149), and LDL-C was 2.3 (1.8-3.0) and 2.5 mmol/L (1.9-3.2). After adjustments, the physician-dispensing group had 4% lower LDL-C levels (p = 0.041), 12% more frequent HbA1c measurements (p = 0001), 16% higher annual consultation rates (p < 0.05 for all conditions), and equal number of different drugs, compared to the pharmacist-dispensing group. CONCLUSIONS: We found no relevant differences in selected clinical measurements between physician- and pharmacist-dispensing, and mixed results in process measurements. Our results do not indicate that one drug-dispensing channel is superior to the other.

Implementation of a complex intervention to improve hospital discharge: process evaluation of a cluster randomised controlled trial.

OBJECTIVES: To study the implementation of a cluster randomised controlled effectiveness-implementation hybrid trial testing the effectiveness of a medication review at hospital discharge combined with a communication stimulus between hospital physicians (HPs) and general practitioners (GPs) on rehospitalisation of multimorbid older patients. DESIGN: Extension of Grant's mixed method process evaluation framework to trials with multilevel clustering. SETTING: General internal medicine wards in Swiss hospitals. PARTICIPANTS: Convenience samples of 15 chief physicians (of 21 hospitals participating in the effectiveness trial), 60 (74) senior HPs, 65 (164) junior HPs and 187 (411) GPs. IMPLEMENTATION STRATEGY: Two-hour teaching sessions for senior HPs on a patient-centred, checklist-guided discharge routine. PROCESS EVALUATION COMPONENTS: Data collection on recruitment, delivery and response from chief physicians (semistructured interviews), senior HPs, junior HPs, GPs (surveys) and patients (via HPs). Quantitative data were summarised using descriptive statistics, and interviews analysed using thematic analysis. OUTCOME MEASURES: Intervention dose (quantitative), implementation fidelity (qualitative), feasibility and acceptability, facilitators and barriers, implementation support strategies. RESULTS: Recruitment of hospitals was laborious but successful, with 21 hospitals recruited. Minimal workload and a perceived benefit for the clinic were crucial factors for participation. Intervention dose was high (95% of checklist activities carried out), but intervention fidelity was limited (discharge letters) or unknown (medication review). Recruitment and retention of patients was challenging, partly due to patient characteristics (old, frail) and the COVID-19 pandemic: Only 612 of the anticipated 2100 patients were recruited, and 31% were lost to follow-up within the first month after discharge. The intervention was deemed feasible and helpful by HPs, and the relevance of the topic appreciated by both HPs and GPs. CONCLUSIONS: The results from this evaluation will support interpretation of the findings of the effectiveness study and may inform researchers and policy makers who aim at improving hospital discharge. TRIAL REGISTRATION NUMBER: ISRCTN18427377.

Quantification of adipocyte numbers following adipose tissue remodeling.

To analyze the capacity of white and brown adipose tissue remodeling, we developed two mouse lines to label, quantitatively trace, and ablate white, brown, and brite/beige adipocytes at different ambient temperatures. We show here that the brown adipocytes are recruited first and reach a peak after 1 week of cold stimulation followed by a decline during prolonged cold exposure. On the contrary, brite/beige cell numbers plateau after 3 weeks of cold exposure. At thermoneutrality, brown adipose tissue, in spite of being masked by a white-like morphology, retains its brown-like physiology, as Ucp1+ cells can be recovered immediately upon beta3-adrenergic stimulation. We further demonstrate that the recruitment of Ucp1+ cells in response to cold is driven by existing adipocytes. In contrast, the regeneration of the interscapular brown adipose tissue following ablation of Ucp1+ cells is driven by de novo differentiation.

Inferior control of low-density lipoprotein cholesterol in women is the primary sex difference in modifiable cardiovascular risk: A large-scale, cross-sectional study in primary care.

BACKGROUND AND AIMS: Sex differences in cardiovascular prevention have been reported, yet the role of sex with regard to different modifiable risk factors such as low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (BP), and glycated hemoglobin (HbA1c) in primary care settings is unclear. Therefore, we studied sex differences in assessment and measured values of LDL-C, BP, and HbA1c in primary and secondary cardiovascular prevention delivered by general practitioners. METHODS: This cross-sectional study was based on electronic medical records of 59,092 primary care patients (51.9% women) aged 40-79 years in Switzerland. Multilevel regression was used to model associations of sex with assessment and measured values of LDL-C, BP, and HbA1c in 2018. RESULTS: In both primary and secondary prevention, women had lower LDL-C assessment rates (age-adjusted odds ratio (aOR) 0.71 [95% confidence interval (CI) 0.67 to 0.75] and 0.70 [CI 0.51 to 0.95]), and higher measured LDL-C values than men (age-adjusted difference 0.30 mmol/L [CI 0.25 to 0.35] and 0.28 mmol/L [CI 0.07 to 0.48]). Compared with men, women in primary prevention displayed lower BP and HbA1c assessment frequencies (aOR 0.77 [CI 0.73 to 0.81] and 0.76 [CI 0.71 to 0.80]) and measured values (age-adjusted difference -2.49 mmHg [CI -2.99 to -1.79] and -0.19% [CI -0.24 to -0.14]), while there was no sex difference in secondary prevention. Age-dependent increases in measured values of LDL-C, BP, and HbA1c were greater in women than men. CONCLUSIONS: Control of LDL-C in women in primary care should be improved to reduce sex-based inequalities in prevention of cardiovascular disease.

Heart failure epidemiology and treatment in primary care: a retrospective cross-sectional study.

AIMS: Heart failure is one of the leading causes of morbidity and mortality worldwide, but little is known on heart failure epidemiology and treatment in primary care. This study described patients with heart failure treated by general practitioners, with focus on drug prescriptions and especially on the only specific treatment for heart failure with reduced ejection fraction, namely sacubitril/valsartan. METHODS AND RESULTS: This was a retrospective cross-sectional study using data from an electronic medical record database of Swiss general practitioners from 2016 to 2019. Multilevel logistic regression was used to find determinants of sacubitril/valsartan prescription; odds ratios (ORs) and 95% confidence intervals (CIs) were reported. We identified 1288 heart failure patients (48.5% women; age: median 85 years, interquartile range 77-90 years) by means of diagnosis code, representing 0.5% of patients consulting a general practitioner during the observation period. About 73.6% received a renin-angiotensin-aldosterone system inhibitor, 67.8% a beta-blocker, 34.6% a calcium channel blocker, 86.1% a diuretic, and 40.1% another cardiac drug. Sacubitril/valsartan was prescribed in 6% predominantly male patients (OR 2.10, CI 1.25-3.84), of younger age (OR 0.59 per increase in 10 years, CI 0.49-0.71), with diabetes mellitus (OR 1.76, CI 1.07-2.90). The recommended starting dose for sacubitril/valsartan was achieved in 67.1% and the target dose in 28.6% of patients. CONCLUSIONS: Prevalence of heart failure among patients treated by general practitioners was low. Considering the disease burden and association with multimorbidity, awareness of heart failure in primary care should be increased, with the aim to optimize heart failure therapy.