A mixed methods analysis of the medication review intervention centered around the use of the 'Systematic Tool to Reduce Inappropriate Prescribing' Assistant (STRIPA) in Swiss primary care practices.

BACKGROUND: Electronic clinical decision support systems (eCDSS), such as the 'Systematic Tool to Reduce Inappropriate Prescribing' Assistant (STRIPA), have become promising tools for assisting general practitioners (GPs) with conducting medication reviews in older adults. Little is known about how GPs perceive eCDSS-assisted recommendations for pharmacotherapy optimization. The aim of this study was to explore the implementation of a medication review intervention centered around STRIPA in the 'Optimising PharmacoTherapy In the multimorbid elderly in primary CAre' (OPTICA) trial. METHODS: We used an explanatory mixed methods design combining quantitative and qualitative data. First, quantitative data about the acceptance and implementation of eCDSS-generated recommendations from GPs (n = 21) and their patients (n = 160) in the OPTICA intervention group were collected. Then, semi-structured qualitative interviews were conducted with GPs from the OPTICA intervention group (n = 8), and interview data were analyzed through thematic analysis. RESULTS: In quantitative findings, GPs reported averages of 13 min spent per patient preparing the eCDSS, 10 min performing medication reviews, and 5 min discussing prescribing recommendations with patients. On average, out of the mean generated 3.7 recommendations (SD=1.8). One recommendation to stop or start a medication was reported to be implemented per patient in the intervention group (SD=1.2). Overall, GPs found the STRIPA useful and acceptable. They particularly appreciated its ability to generate recommendations based on large amounts of patient information. During qualitative interviews, GPs reported the main reasons for limited implementation of STRIPA were related to problems with data sourcing (e.g., incomplete data imports), preparation of the eCDSS (e.g., time expenditure for updating and adapting information), its functionality (e.g., technical problems downloading PDF recommendation reports), and appropriateness of recommendations. CONCLUSIONS: Qualitative findings help explain the relatively low implementation of recommendations demonstrated by quantitative findings, but also show GPs' overall acceptance of STRIPA. Our results provide crucial insights for adapting STRIPA to make it more suitable for regular use in future primary care settings (e.g., necessity to improve data imports). TRIAL REGISTRATION: Clinicaltrials.gov NCT03724539, date of first registration: 29/10/2018.

Time requirements for perioperative glucose management using fully closed-loop versus standard insulin therapy: A proof-of-concept time-motion study.

AIMS: To compare the time required for perioperative glucose management using fully automated closed-loop versus standard insulin therapy. METHODS: We performed a time-motion study to quantify the time requirements for perioperative glucose management with fully closed-loop (FCL) and standard insulin therapy applied to theoretical scenarios. Following an analysis of workflows in different periods of perioperative care in elective surgery patients receiving FCL or standard insulin therapy upon hospital admission (pre- and intra-operatively, at the intermediate care unit and general wards), the time of process-specific tasks was measured by shadowing hospital staff. Each task was measured 20 times and its average duration in combination with its frequency according to guidelines was used to calculate the cumulative staff time required for blood glucose management. Cumulative time was calculated for theoretical scenarios consisting of elective minor and major abdominal surgeries (pancreatic surgery and sleeve gastrectomy, respectively) to account for the different care settings and lengths of stay. RESULTS: The FCL insulin therapy reduced the time required for perioperative glucose management compared to standard insulin therapy, across all assessed care periods and for both perioperative pathways (range 2.1-4.5). For a major abdominal surgery, total time required was 248.5 min using FCL versus 753.9 min using standard insulin therapy. For a minor abdominal surgery, total time required was 68.6 min and 133.2 min for FCL and standard insulin therapy, respectively. CONCLUSIONS: The use of fully automated closed-loop insulin delivery for inpatient glucose management has the potential to alleviate the workload of diabetes management in an environment with adequately trained staff.

Real-World Cost-Effectiveness of Pulmonary Vein Isolation for Atrial Fibrillation: A Target Trial Approach.

OBJECTIVES: Randomized controlled trials of pulmonary vein isolation (PVI) for treating atrial fibrillation (AF) have proven the procedure's efficacy. Studies assessing its empirical cost-effectiveness outside randomized trial settings are lacking. We aimed to evaluate the effectiveness and cost-effectiveness of PVI versus medical therapy for AF. METHODS: We followed a target trial approach using the Swiss-AF cohort, a prospective observational cohort study that enrolled patients with AF between 2014 and 2017. Resource utilization and cost information were collected through claims data. Quality of life was measured with EQ-5D-3L utilities. We estimated incremental cost-effectiveness ratios (ICERs) from the perspective of the Swiss statutory health insurance system. RESULTS: Patients undergoing PVI compared with medical therapy had a 5-year overall survival advantage with a hazard ratio of 0.75 (95% CI 0.46-1.21; P = .69) and a 19.8% SD improvement in quality of life (95% CI 15.5-22.9; P < .001), at an incremental cost of 29 604 Swiss francs (CHF) (95% CI 16 354-42 855; P < .001). The estimated ICER was CHF 158 612 per quality-adjusted life-year (QALY) gained within a 5-year time horizon. Assuming similar health effects and costs over 5 additional years changed the ICER to CHF 82 195 per QALY gained. Results were robust to the sensitivity analyses performed. CONCLUSIONS: Our results show that PVI might be a cost-effective intervention within the Swiss healthcare context in a 10-year time horizon, but unlikely to be so at 5 years, if a willingness-to-pay threshold of CHF 100 000 per QALY gained is assumed. Given data availability, we find target trial designs are a valuable tool for assessing the cost-effectiveness of healthcare interventions outside of randomized controlled trial settings.

Bleeding and ischaemic events after first bleed in anticoagulated atrial fibrillation patients: risk and timing.

AIMS: To determine the risk of subsequent adverse clinical outcomes in anticoagulated patients with atrial fibrillation (AF) who experienced a new bleeding event. METHODS AND RESULTS: Anticoagulated AF patients were followed in two prospective cohort studies. Information on incident bleeding was systematically collected during yearly follow-up visits and events were adjudicated as major bleeding or clinically relevant non-major bleeding (CRNMB) according to the International Society on Thrombosis and Haemostasis guidelines. The primary outcome was a composite of stroke, myocardial infarction (MI), or all-cause death. Time-updated multivariable Cox proportional-hazards models were used to compare outcomes in patients with and without incident bleeding. Median follow-up was 4.08 years [interquartile range (IQR): 2.93-5.98]. Of the 3277 patients included (mean age 72 years, 28.5% women), 646 (19.7%) developed a new bleeding, 297 (9.1%) a major bleeding and 418 (12.8%) a CRNMB. The incidence of the primary outcome was 7.08 and 4.04 per 100 patient-years in patients with and without any bleeding [adjusted hazard ratio (aHR): 1.36, 95% confidence interval (CI): 1.16-1.61; P < 0.001; median time between a new bleeding and a primary outcome 306 days (IQR: 23-832)]. Recurrent bleeding occurred in 126 patients [incidence, 8.65 per 100 patient-years (95% CI: 7.26-10.30)]. In patients with and without a major bleeding, the incidence of the primary outcome was 11.00 and 4.06 per 100 patient-years [aHR: 2.04, 95% CI: 1.69-2.46; P < 0.001; median time to a primary outcome 142 days (IQR: 9-518)], and 59 had recurrent bleeding [11.61 per 100 patient-years (95% CI: 8.99-14.98)]. The incidence of the primary outcome was 5.29 and 4.55 in patients with and without CRNMB [aHR: 0.94, 95% CI: 0.76-1.15; P = 0.53; median time to a composite outcome 505 days (IQR: 153-1079)], and 87 had recurrent bleeding [8.43 per 100 patient-years (95% CI: 6.83-10.40)]. Patients who had their oral anticoagulation (OAC) discontinued after their first bleeding episode had a higher incidence of the primary composite than those who continued OAC (63/89 vs. 159/557 patients; aHR: 4.46, 95% CI: 3.16-6.31; P < 0.001). CONCLUSION: In anticoagulated AF patients, major bleeding but not CRNMB was associated with a high risk of adverse outcomes, part of which may be explained by OAC discontinuation. Most events occurred late after the bleeding episode, emphasizing the importance of long-term follow-up in these patients.

Silent brain infarcts impact on cognitive function in atrial fibrillation.

AIMS: We aimed to investigate the association of clinically overt and silent brain lesions with cognitive function in atrial fibrillation (AF) patients. METHODS AND RESULTS: We enrolled 1227 AF patients in a prospective, multicentre cohort study (Swiss-AF). Patients underwent standardized brain magnetic resonance imaging (MRI) at baseline and after 2 years. We quantified new small non-cortical infarcts (SNCIs) and large non-cortical or cortical infarcts (LNCCIs), white matter lesions (WML), and microbleeds (Mb). Clinically, silent infarcts were defined as new SNCI/LNCCI on follow-up MRI in patients without a clinical stroke or transient ischaemic attack (TIA) during follow-up. Cognition was assessed using validated tests. The mean age was 71 years, 26.1% were females, and 89.9% were anticoagulated. Twenty-eight patients (2.3%) experienced a stroke/TIA during 2 years of follow-up. Of the 68 (5.5%) patients with ≥1 SNCI/LNCCI, 60 (88.2%) were anticoagulated at baseline and 58 (85.3%) had a silent infarct. Patients with brain infarcts had a larger decline in cognition [median (interquartile range)] changes in Cognitive Construct score [-0.12 (-0.22; -0.07)] than patients without new brain infarcts [0.07 (-0.09; 0.25)]. New WML or Mb were not associated with cognitive decline. CONCLUSION: In a contemporary cohort of AF patients, 5.5% had a new brain infarct on MRI after 2 years. The majority of these infarcts was clinically silent and occurred in anticoagulated patients. Clinically, overt and silent brain infarcts had a similar impact on cognitive decline. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02105844, https://clinicaltrials.gov/ct2/show/NCT02105844.

Nonregistration, discontinuation, and nonpublication of randomized trials: A repeated metaresearch analysis.

BACKGROUND: We previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs. METHODS AND FINDINGS: We included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations. CONCLUSIONS: We have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.

Factors associated with health-related quality of life among home-dwelling older adults aged 75 or older in Switzerland: a cross-sectional study.

BACKGROUND: HRQoL is an indicator of individuals' perception of their overall health, including social and environmental aspects. As a multidimensional concept, HRQoL can be influenced by a multitude of factors. Studies of HRQoL and factors associated with it among home-dwelling older adults have often been limited to inpatient settings or to a sub-population with a chronic disease. Studying HRQoL and its correlating factors among this population, by providing an ecological lens on factors beyond the individual level, can provide a better understanding of the construct and the role of the environment on how they perceive their HRQoL. Thus, we aimed to assess the HRQoL and investigate the correlates of HRQOL among home-dwelling older adults, guided by the levels of the ecological model. METHODS: This is a cross-sectional population survey conducted in 2019 in Canton Basel-Landschaft, in northwestern Switzerland, and includes a sample of 8786 home-dwelling older adults aged 75 and above. We assessed HRQoL by using the EQ-index and the EQ-VAS. The influence of independent variables at the macro, meso and micro level on HRQoL was tested using Tobit multiple linear regression modelling. RESULTS: We found that having a better socio-economic status as denoted by higher income, having supplementary insurance and a higher level of education were all associated with a better HRQoL among home-dwelling older adults. Furthermore, being engaged in social activities was also related to an improved HRQoL. On the other hand, older age, female gender, presence of multimorbidity and polypharmacy as well as social isolation and loneliness were found to all have a negative impact on HRQoL. CONCLUSIONS: Understanding factors related to HRQoL by using an ecological lens can help identify factors beyond the individual level that impact the HRQoL of home-dwelling older adults. Our study emphasises the importance of social determinants of health and potential disparities that exists, encouraging policymakers to focus on policies to reduce socio-economic disparities using a life-course approach, which consequently could also impact HRQoL in later stages of life.

Cost-effectiveness of voretigene neparvovec in the treatment of patients with inherited retinal disease with RPE65 mutation in Switzerland.

OBJECTIVE: We aimed to evaluate the cost-effectiveness of voretigene neparvovec (VN) compared with standard of care (SoC) for patients with inherited retinal disease (IRD) caused by a biallelic RPE65-mutation. VN is a live, non-replicating adeno-associated virus serotype 2 (AAV2). SoC is best supportive care provided to patients with visual impairment. Patients under SoC may experience progressive vision loss leading to complete blindness. METHODS: We adapted a previously published Markov cohort model for IRD. An annual cycle length, life-long time horizon, discount rate of 3% for cost and health outcomes, and Swiss health system perspective were used. Data from a randomised controlled phase III trial of VN versus SoC (ClinicalTrials.gov: NCT00999609) were used to estimate transitions between health states in the first year, after which VN patients were assumed to remain for 39 subsequent years in the health state they were in at the end of the first year. After the 40th year for VN patients and 1st year for SoC patients, visual decline was modelled based on observational data on the natural progression of the disease. Quality-adjusted life years (QALYs) were calculated based on an external study which elicited clinicians' EQ-5D-5L-based utility estimates for IRD patients with a RPE65-mutation. Costs (Swiss Francs (CHF), year 2018-2019) included drug acquisition/ administration, adverse events, testing for sufficient viable retinal cells, and healthcare-related costs of blindness. Societal costs of blindness were added in a complementary analysis. Robustness of the model results were tested in sensitivity and scenario analyses. RESULTS: For the base-case, VN resulted in incremental costs per patient of CHF 764'402 (VN: CHF 901'654, SoC: CHF 137'252), incremental blindness-free years of 7.67 (VN: 28.32, SoC: 20.65) and incremental QALYs of 6.73 (VN: 18.35, SoC: 11.62), leading to an incremental cost-effectiveness ratio of CHF 113'526 per QALY gained. In probabilistic sensitivity analysis, the cost-effectiveness of VN was better than CHF 100,000 per QALY gained in 41% of iterations. For the scenario analysis in which a societal perspective was adopted and for which a 50% work-related productivity loss from blindness was assumed, incremental costs of CHF 423,837 and an ICER of CHF 62'947 per QALY gained were produced. The scenario assuming VN treatment effect lasts for 20 years produced an ICER of CHF 156'171 per QALY gained, whereas assuming a life-long VN treatment effect resulted in an ICER of CHF 96'384 per QALY gained. CONCLUSION: The incremental cost-effectiveness ratio of VN compared to the SoC was estimated to be CHF 113'526 and CHF 62'947 per QALY gained, respectively, from a Swiss healthcare system, and societal perspective assuming a 50% productivity loss.

[Polypharmacy and inappropriate medications in multimorbid elderly patients - What OPERAM taught us and will teach us]. / Polypharmacie et medicaments inappropriés chez les patients âgés multimorbides - Ce que l'étude OPERAM nous apprend et va nous apprendre.

Polypharmacy and inappropriate medication use are very common in multimorbid older patients. This population has unfortunately been excluded from most large, randomized studies. In a recent multicenter randomized study (OPERAM), we included over 2000 multimorbid patients. We found that 86% of the patients aged 70 years and more had inappropriate medications and that these medications could be discontinued without negative impact on the health of these patients. This cohort of multimorbid patients will be followed for 10 years to evaluate their prognosis, life expectancy, treatments and quality of life, with numerous projects to better understand the inappropriate prescribing of individual drugs and their consequences on the health of this population.

La polypharmacie et les médicaments inappropriés sont très fréquents chez les patients âgés multimorbides. Cette population a malheureusement été exclue de la plupart des grandes études randomisées. Dans une récente étude randomisée multicentrique (OPERAM), nous avons inclus plus de 2000 patients multimorbides. Celle-ci a montré que 86 % des patients âgés de 70 ans et plus avaient des médicaments inappropriés et qu'il était possible de stopper leur administration, sans répercussion négative sur leur santé. Ces patients multimorbides constituent une cohorte qui va être suivie sur 10 ans pour évaluer leurs pronostic, espérance de vie, traitements et qualité de vie. Cela permettra la réalisation de nombreux projets, notamment pour mieux comprendre les conséquences de la prescription inappropriée de médicaments.

The INSPIRE Population Survey: development, dissemination and respondent characteristics.

BACKGROUND: Most older adults prefer to continue living at home despite increasing care needs and demand for services. To aid in maintaining independence, integrated care models for community-dwelling older people are promoted as the most cost-effective approach. The implementation of such care models is challenging and often the end-users are not involved or their needs are not considered. We conducted a population survey in order to understand the needs and preferences of home-dwelling older adults living in Canton Basel-Landschaft, Switzerland. The aims of this paper are to chronicle the development of the INSPIRE Population Survey, outline its variables and measurements, describe the marketing strategy utilized for survey dissemination and report on the response rate and respondent characteristics. METHODS: The INSPIRE Population Survey, conducted between March and August 2019, is a cross-sectional survey of older adults aged 75 and older living at home in Canton Basel-Landschaft. The questionnaire was developed by expert input and stakeholder involvement. Its readability and acceptability were pilot-tested with older people. To ensure the likelihood of a high and representative response rate, a meticulous step-by-step marketing strategy was developed prior to the dissemination of the questionnaire. RESULTS: The overall response rate was 30.7% (n = 8,846), with variations between 20.6 and 34.5% across the different care regions in the canton. A generally higher response rate was found in the care regions with a higher density and which bordered the urban city of Basel. We received support from local stakeholders, policy makers and media through using a broad combination of marketing channels and targeting our community partners who have a strong relationship with our target audience. CONCLUSIONS: Although recruiting older adults in research is challenging, our study shows that a high response rate can be achieved by developing the survey through expert input and by involving all important stakeholders, including older adults, throughout the entire process.

Systematic early versus late mobilization or standard early mobilization in mechanically ventilated adult ICU patients: systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis aimed to determine the effectiveness of systematic early mobilization in improving muscle strength and physical function in mechanically ventilated intensive care unit (ICU) patients. METHODS: We conducted a two-stage systematic literature search in MEDLINE, EMBASE and the Cochrane Library until January 2019 for randomized controlled trials (RCTs) examining the effects of early mobilization initiated within 7 days after ICU admission compared with late mobilization, standard early mobilization or no mobilization. Priority outcomes were Medical Research Council Sum Score (MRC-SS), incidence of ICU-acquired weakness (ICUAW), 6-min walk test (6MWT), proportion of patients reaching independence, time needed until walking, SF-36 Physical Function Domain Score (PFS) and SF-36 Physical Health Component Score (PCS). Meta-analysis was conducted where sufficient comparable evidence was available. We evaluated the certainty of evidence according to the GRADE approach. RESULTS: We identified 12 eligible RCTs contributing data from 1304 participants. Two RCTs were categorized as comparing systematic early with late mobilization, nine with standard early mobilization and one with no mobilization. We found evidence for a benefit of systematic early mobilization compared to late mobilization for SF-36 PFS (MD 12.3; 95% CI 3.9-20.8) and PCS (MD 3.4; 95% CI 0.01-6.8), as well as on the proportion of patients reaching independence and the time needed to walking, but not for incidence of ICUAW (RR 0.62; 95% CI 0.38-1.03) or MRC-SS. For systematic early compared to standard early mobilization, we found no statistically significant benefit on MRC-SS (MD 5.8; 95% CI - 1.4 to 13.0), incidence of ICUAW (RR 0.90; 95% CI 0.63-1.27), SF-36 PFS (MD 8.1; 95% CI - 15.3 to 31.4) or PCS (MD - 2.4; 95% CI - 6.1 to 1.3) or other priority outcomes except for change in 6MWT from baseline. Generally, effects appeared stronger for systematic early compared to late mobilization than to standard early mobilization. We judged the certainty of evidence for all outcomes as very low to low. CONCLUSION: The evidence regarding a benefit of systematic early mobilization remained inconclusive. However, our findings indicate that the larger the difference in the timing between the intervention and the comparator, the more likely an RCT is to find a benefit for early mobilization. STUDY REGISTRATION: PROSPERO (CRD42019122555).

A qualitative study to investigate Swiss hospital personnel's perceived importance of and experiences with patient's mental-somatic multimorbidities.

BACKGROUND: Mental-somatic multimorbidity in general hospital settings is associated with long hospital stays, frequent rehospitalization, and a deterioration of disease course, thus, highlighting the need for treating hospital patients more holistically. However, there are several challenges to overcome to address mental health conditions in these settings. This study investigated hospital personnel's perceived importance of and experiences with mental-somatic multimorbidities of patients in hospital settings in Basel, Switzerland, with special consideration of the differences between physicians and nurses. METHODS: Eighteen semi-structured interviews were conducted with nurses (n = 10) and physicians (n = 8) in different hospitals located in Basel, Switzerland. An inductive approach of the framework analysis was used to develop the themes. RESULTS: Four themes emerged from the data analysis: 1) the relevance of mental-somatic multimorbidity within general hospitals, 2) health professionals managing their emotions towards mental health, 3) knowledge and competencies in treating patients with mental-somatic multimorbidity, and 4) interprofessional collaboration for handling mental-somatic multimorbidity in hospital settings.The mental-somatic multimorbidities in general hospital patients was found to be relevant among all hospital professionals, although the priority of mental health was higher for nurses than for physicians. This might have resulted from different working environments or in efficient interprofessional collaboration in general hospitals. Physicians and nurses both highlighted the difficulties of dealing with stigma, a lack of knowledge of mental disorders, the emphasis place on treating somatic disorders, and competing priorities and work availability, which all hindered the adequate handling of mental-somatic multimorbidity in general hospitals. CONCLUSION: To support health professionals to integrate mental health into their work, proper environments within general hospitals are needed, such as private rooms in which to communicate with patients. In addition, changes in curriculums and continuing training are needed to improve the understanding of mental-somatic multimorbidities and reduce negative stereotypes. Similarly, interprofessional collaboration between health professionals needs to be strengthened to adequately identify and treat mentally multimorbid patients. A stronger focus should be placed on physicians to improve their competencies in considering patient mental health in their daily somatic treatment care.

Humidification of indoor air for preventing or reducing dryness symptoms or upper respiratory infections in educational settings and at the workplace.

BACKGROUND: Indoor exposure to dry air during heating periods has been associated with dryness and irritation symptoms of the upper respiratory airways and the skin. The irritated or damaged mucous membrane poses an important entry port for pathogens causing respiratory infections. OBJECTIVES: To determine the effectiveness of interventions that increase indoor air humidity in order to reduce or prevent dryness symptoms of the eyes, the skin and the upper respiratory tract (URT) or URT infections, at work and in educational settings. SEARCH METHODS: The last search for all databases was done in December 2020. We searched Ovid MEDLINE, Embase, CENTRAL (Cochrane Library), PsycINFO, Web of Science, Scopus and in the field of occupational safety and health: NIOSHTIC-2, HSELINE, CISDOC and the In-house database of the Division of Occupational and Environmental Medicine, University of Zurich. We also contacted experts, screened reference lists of included trials, relevant reviews and consulted the WHO International Clinical Trials Registry Platform (ICTRP). SELECTION CRITERIA: We included controlled studies with a parallel group or cross-over design, quasi-randomised studies, controlled before-and-after and interrupted time-series studies on the effects of indoor air humidification in reducing or preventing dryness symptoms and upper respiratory tract infections as primary outcomes at workplace and in the educational setting. As secondary outcomes we considered perceived air quality, other adverse events, sick leave, task performance, productivity and attendance and costs of the intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full texts for eligibility, extracted data and assessed the risks of bias of included studies. We synthesised the evidence for the primary outcomes 'dry eye', 'dry nose', 'dry skin', for the secondary outcome 'absenteeism', as well as for 'perception of stuffiness' as the harm-related measure. We assessed the certainty of evidence using the GRADE system. MAIN RESULTS: We included 13 studies with at least 4551 participants, and extracted the data of 12 studies with at least 4447 participants. Seven studies targeted the occupational setting, with three studies comprising office workers and four hospital staff. Three of them were clustered cross-over studies with 846 participants (one cRCT), one parallel-group controlled trial (2395 participants) and three controlled before-and-after studies with 181 participants. Five studies, all CTs, with at least 1025 participants, addressing the educational setting, were reported between 1963 and 1975, and in 2018. In total, at least 3933 (88%) participants were included in the data analyses. Due to the lack of information, the results of the risk of bias assessment remained mainly unclear and the assessable risks of bias of included studies were considered as predominantly high. Primary outcomes in occupational setting:  We found that indoor air humidification at the workplace may have little to no effect on dryness symptoms of the eye and nose (URT). The only cRCT showed a significant decrease in dry eye symptoms among working adults (odds ratio (OR) 0.54, 95% confidence interval (CI) 0.37 to 0.79) with a low certainty of the evidence. The only cluster non-randomised cross-over study showed a non-significant positive effect of humidification on dryness nose symptoms (OR 0.87, 95% CI 0.53 to 1.42) with a low certainty of evidence. We found that indoor air humidification at the workplace may have little and non-significant effect on dryness skin symptoms. The pooled results of two cluster non-RCTs showed a non-significant alleviation of skin dryness following indoor air humidification (OR 0.66, 95% CI 0.33 to 1.32) with a low certainty of evidence. Similarly, the pooled results of two before-after studies yielded no statistically significant result (OR 0.69, 95% CI 0.33 to 1.47) with very low certainty of evidence No studies reported on the outcome of upper respiratory tract infections. No studies conducted in educational settings investigated our primary outcomes. Secondary outcomes in occupational setting: Perceived stuffiness of the air was increased during the humidification in the two cross-over studies (OR 2.18, 95% CI 1.47 to 3.23); (OR 1.70, 95% CI 1.10 to 2.61) with low certainty of evidence. Secondary outcomes in educational setting: Based on different measures and settings of absenteeism, four of the six controlled studies found a reduction in absenteeism following indoor air humidification (OR 0.54, 95% CI 0.45 to 0.65; OR 0.38, 95% CI 0.15 to 0.96; proportion 4.63% versus 5.08%). AUTHORS' CONCLUSIONS: Indoor air humidification at the workplace may have little to no effect on dryness symptoms of the eyes, the skin and the URT. Studies investigating illness-related absenteeism from work or school could only be summarised narratively, due to different outcome measures assessed. The evidence suggests that increasing humidification may reduce the absenteeism, but the evidence is very uncertain. Future RCTs involving larger sample sizes, assessing dryness symptoms more technically or rigorously defining absenteeism and controlling for potential confounders are therefore needed to determine whether increasing indoor air humidity can reduce or prevent dryness symptoms of the eyes, the skin, the URT or URT infections at work and in educational settings over time.

Temporal trends and regional disparities in cancer screening utilization: an observational Swiss claims-based study.

BACKGROUND: We examined colorectal, breast, and prostate cancer screening utilization in eligible populations within three data cross-sections, and identified factors potentially modifying cancer screening utilization in Swiss adults. METHODS: The study is based on health insurance claims data of the Helsana Group. The Helsana Group is one of the largest health insurers in Switzerland, insuring approximately 15% of the entire Swiss population across all regions and age groups. We assessed proportions of the eligible populations receiving colonoscopy/fecal occult blood testing (FOBT), mammography, or prostate-specific antigen (PSA) testing in the years 2014, 2016, and 2018, and calculated average marginal effects of individual, temporal, regional, insurance-, supply-, and system-related variables on testing utilization using logistic regression. RESULTS: Overall, 8.3% of the eligible population received colonoscopy/FOBT in 2014, 8.9% in 2016, and 9.2% in 2018. In these years, 20.9, 21.2, and 20.4% of the eligible female population received mammography, and 30.5, 31.1, and 31.8% of the eligible male population had PSA testing. Adjusted testing utilization varied little between 2014 and 2018; there was an increasing trend of 0.8% (0.6-1.0%) for colonoscopy/FOBT and of 0.5% (0.2-0.8%) for PSA testing, while mammography use decreased by 1.5% (1.2-1.7%). Generally, testing utilization was higher in French-speaking and Italian-speaking compared to German-speaking region for all screening types. Cantonal programs for breast cancer screening were associated with an increase of 7.1% in mammography utilization. In contrast, a high density of relevant specialist physicians showed null or even negative associations with screening utilization. CONCLUSIONS: Variation in cancer screening utilization was modest over time, but considerable between regions. Regional variation was highest for mammography use where recommendations are debated most controversially, and the implementation of programs differed the most.

Baseline characteristics and comparability of older multimorbid patients with polypharmacy and general practitioners participating in a randomized controlled primary care trial.

OBJECTIVES: Recruiting general practitioners (GPs) and their multimorbid older patients for trials is challenging for multiple reasons (e.g., high workload, limited mobility). The comparability of study participants is important for interpreting study findings. This manuscript describes the baseline characteristics of GPs and patients participating in the 'Optimizing PharmacoTherapy in older multimorbid adults In primary CAre' (OPTICA) trial, a study of optimization of pharmacotherapy for multimorbid older adults. The overall aim of this study was to determine if the GPs and patients participating in the OPTICA trial are comparable to the real-world population in Swiss primary care. DESIGN: Analysis of baseline data from GPs and patients in the OPTICA trial and a reference cohort from the FIRE ('Family medicine ICPC Research using Electronic medical records') project. SETTING: Primary care, Switzerland. PARTICIPANTS: Three hundred twenty-three multimorbid (≥ 3 chronic conditions) patients with polypharmacy (≥ 5 regular medications) aged ≥ 65 years and 43 GPs recruited for the OPTICA trial were compared to 22,907 older multimorbid patients with polypharmacy and 227 GPs from the FIRE database. METHODS: We compared the characteristics of GPs and patients participating in the OPTICA trial with other GPs and other older multimorbid adults with polypharmacy in the FIRE database. We described the baseline willingness to have medications deprescribed of the patients participating in the OPTICA trial using the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. RESULTS: The GPs in the FIRE project and OPTICA were similar in terms of sociodemographic characteristics and their work as a GP (e.g. aged in their fifties, ≥ 10 years of experience, ≥ 60% are self-employed, ≥ 80% work in a group practice). The median age of patients in the OPTICA trial was 77 years and 45% of trial participants were women. Patients participating in the OPTICA trial and patients in the FIRE database were comparable in terms of age, certain clinical characteristics (e.g. systolic blood pressure, body mass index) and health services use (e.g. selected lab and vital data measurements). More than 80% of older multimorbid patients reported to be willing to stop ≥ 1 of their medications if their doctor said that this would be possible. CONCLUSION: The characteristics of patients and GPs recruited into the OPTICA trial are relatively comparable to characteristics of a real-world Swiss population, which indicates that recruiting a generalizable patient sample is possible in the primary care setting. Multimorbid patients in the OPTICA trial reported a high willingness to have medications deprescribed. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT03724539 ), KOFAM (Swiss national portal) ( SNCTP000003060 ), Universal Trial Number (U1111-1226-8013).

Measurement properties of EQ-5D-3L and EQ-5D-5L in recording self-reported health status in older patients with substantial multimorbidity and polypharmacy.

BACKGROUND: The EQ-5D-3L and EQ-5D-5L are two generic health-related quality of life measures, which may be used in clinical and health economic research. They measure impairment in 5 aspects of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The aim of this study was to assess the performance of the EQ-5D-3L and EQ-5D-5L in measuring the self-reported health status of older patients with substantial multimorbidity and associated polypharmacy. METHODS: Between 2017 and 2019, we administered EQ-5D-3L and EQ-5D-5L to a subset of patients participating in the OPERAM trial at 6 months and 12 months after enrolment. The OPERAM trial is a two-arm multinational cluster randomised controlled trial of structured medication review assisted by a software-based decision support system versus usual pharmaceutical care, for older people (aged ≥ 70 years) with multimorbidity and polypharmacy. In the psychometric analyses, we only included participants who completed the measures in full at 6 and 12 months. We assessed whether responses to the measures were consistent by assessing the proportion of EQ-5D-5L responses, which were 2 or more levels away from that person's EQ-5D-3L response. We also compared the measures in terms of informativity, and discriminant validity and responsiveness relative to the Barthel Index, which measures independence in activities of daily living. RESULTS: 224 patients (mean age of 77 years; 56% male) were included in the psychometric analyses. Ceiling effects reported with the EQ-5D-5L (22%) were lower than with the EQ-5D-3L (29%). For the mobility item, the EQ-5D-5L demonstrated better informativity (Shannon's evenness index score of 0.86) than the EQ-5D-3L (Shannon's evenness index score of 0.69). Both the 3L and 5L versions of EQ-5D demonstrated good performance in terms of discriminant validity, i.e. (out of all items of the EQ-5D-3L and EQ-5D-5L, the pain/discomfort and anxiety/depression items had the weakest correlation with the Barthel Index. Both the 3L and 5L versions of EQ-5D demonstrated good responsiveness to changes in the Barthel Index. CONCLUSION: Both EQ-5D-3L and EQ-5D-5L demonstrated validity and responsiveness when administered to older adults with substantial multimorbidity and polypharmacy who were able to complete the measures.

Use of selective serotonin reuptake inhibitors, other antidepressant medication, and risk of cataract: a case-control study based on Swiss claims data.

PURPOSE: Three previous studies reported controversial results regarding selective serotonin reuptake inhibitor (SSRI) exposure and cataract development. We therefore aimed to assess risk of cataract associated with previous exposure to SSRI using data from a large health insurance in Switzerland. METHODS: In a case-control study, we analyzed individuals insured by the Helsana Group, a large Swiss health insurance provider. We matched patients aged 40 years or older with cataract extraction (i.e., a proxy for a cataract diagnosis) in 2014 or 2015 to four control patients, on age, sex, date of cataract extraction, and area of residence. Exposure of interest was the number of SSRI claims prior to cataract extraction. We conducted conditional logistic regression analyses to calculate odds ratios (OR) with 95% confidence intervals (CI). We adjusted our analyses for the presence of hypertension, diabetes, glaucoma, systemic steroid use, and use of other antidepressant drugs. RESULTS: We identified 13,773 cataract cases and 51,625 matched controls. Compared with non-use, long-term use of SSRI (≥ 20 claims) was not associated with an altered risk of cataract (adjusted OR 0.93, 95% CI 0.84-1.04). The analysis of the individual drug substances also yielded no statistically significant association between drug exposure and the risk of cataract. CONCLUSIONS: According to our study, use of SSRI does not change the risk of cataract in the overall population.

Going beyond the mean: economic benefits of myocardial infarction secondary prevention.

BACKGROUND: Using the example of secondary prophylaxis of myocardial infarction (MI), our aim was to establish a framework for assessing cost consequences of compliance with clinical guidelines; thereby taking cost trajectories and cost distributions into account. METHODS: Swiss mandatory health insurance claims from 1840 persons with hospitalization for MI in 2014 were analysed. Included persons were predominantly male (74%), had a median age of 73 years, and 71% were pre-exposed to drugs for secondary prophylaxis, prior to index hospitalization. Guideline compliance was defined as being prescribed recommended 4-class drug prophylaxis including drugs from the following four classes: beta-blockers, statins, aspirin or P2Y12 inhibitors, and angiotension-converting enzyme inhibitors or angiotensin receptor blockers. Health care expenditures (HCE) accrued over 1 year after index hospitalization were compared by compliance status using two-part regression, trajectory analysis, and counterfactual decomposition analysis. RESULTS: Only 32% of persons received recommended 4-class prophylaxis. Compliant persons had lower HCE (- 4865 Swiss Francs [95% confidence interval - 8027; - 1703]) and were more likely to belong to the most favorable HCE trajectory (with 6245 Swiss Francs average annual HCE and comprising 78% of all studied persons). Distributional analyses showed that compliance-associated HCE reductions were more pronounced among persons with HCE above the median. CONCLUSIONS: Compliance with recommended prophylaxis was robustly associated with lower HCE and more favorable cost trajectories, but mainly among persons with high health care expenditures. The analysis framework is easily transferrable to other diseases and provides more comprehensive information on HCE consequences of non-compliance than mean-based regressions alone.

Degree of regional variation and effects of health insurance-related factors on the utilization of 24 diverse healthcare services - a cross-sectional study.

BACKGROUND: Regional variation in healthcare utilization could reflect unequal access to care, which may lead to detrimental consequences to quality of care and costs. The aims of this study were to a) describe the degree of regional variation in utilization of 24 diverse healthcare services in eligible populations in Switzerland, and b) identify potential drivers, especially health insurance-related factors, and explore the consistency of their effects across the services. METHODS: We conducted a cross-sectional study using health insurance claims data for the year of 2014. The studied 24 healthcare services were predominantly outpatient services, ranging from screening to secondary prevention. For each service, a target population was identified based on applicable clinical recommendations, and outcome variable was the use of the service. Possible influencing factors included patients' socio-demographics, health insurance-related and clinical characteristics. For each service, we performed a comprehensive methodological approach including small area variation analysis, spatial autocorrelation analysis, and multilevel multivariable modelling using 106 mobilité spaciale regions as the higher level. We further calculated the median odds ratio in model residuals to assess the unexplained regional variation. RESULTS: Unadjusted utilization rates varied considerably across the 24 healthcare services, ranging from 3.5% (osteoporosis screening) to 76.1% (recommended thyroid disease screening sequence). The effects of health insurance-related characteristics were mostly consistent. A higher annual deductible level was mostly associated with lower utilization. Supplementary insurance, supplementary hospital insurance and having chosen a managed care model were associated with higher utilization of most services. Managed care models showed a tendency towards more recommended care. After adjusting for multiple influencing factors, the unexplained regional variation was generally small across the 24 services, with all MORs below 1.5. CONCLUSIONS: The observed utilization rates seemed suboptimal for many of the selected services. For all of them, the unexplained regional variation was relatively small. Our findings confirmed the importance and consistency of effects of health insurance-related factors, indicating that healthcare utilization might be further optimized through adjustment of insurance scheme designs. Our comprehensive approach aids in the identification of regional variation and influencing factors of healthcare services use in Switzerland as well as comparable settings worldwide.

Cost Estimates for Human Immunodeficiency Virus (HIV) Care and Patient Characteristics for Health Resource Use From Linkage of Claims Data With the Swiss HIV Cohort Study.

BACKGROUND: Comprehensive and representative data on resource use are critical for health policy decision making but often lacking for human immunodeficiency virus (HIV) infection. Privacy-preserving probabilistic record linkage of claim and cohort study data may overcome these limitations. METHODS: Encrypted dates of birth, sex, study center, and antiretroviral therapy (ART) from the Swiss HIV Cohort Study (SHCS) records for 2012 and 2013 were linked by privacy-preserving probabilistic record linkage with claim data from the largest health insurer covering 15% of the Swiss residential population. We modeled predictors for mean annual costs adjusting for censoring and grouped patients by cluster analysis into 3 risk groups for resource use. RESULTS: The matched subsample of 1196 patients from 9326 SHCS and 2355 claim records was representative for all SHCS patients receiving ART. The corrected mean (standard error) total costs in 2012 and 2013 were $30462 ($582) and $30965 ($629) and mainly accrued in ambulatory care for ART (70% of mean costs). The low-risk group for resource use had mean (standard error) annual costs of $26772 ($536) and $26132 ($589) in 2012 and 2013. In the moderate- and high-risk groups, annual costs for 2012 and 2013 were higher by $3526 (95% confidence interval, $1907-$5144) (13%) and $4327 ($2662-$5992) (17%) and $14026 ($8763-$19289) (52%) and $13567 ($8844-$18288) (52%), respectively. CONCLUSIONS: In a representative subsample of patients from linkage of SHCS and claim data, ART was the major cost factor, but patient profiling enabled identification of factors related to higher resource use.