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Nina L Wittwer,1,2 Christoph R Meier,1– 3 Carola A Huber,4 Henriette E Meyer zu Schwabedissen,1 Samuel Allemann,1,* Cornelia Schneider1,2,* 1Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; 2Hospital Pharmacy, University Hospital Basel, Basel, Switzerland; 3Boston Collaborative Drug Surveillance Program, Lexington, MA, USA; 4Department of Health Sciences, Helsana Insurance Group, Zürich, Switzerland*These authors contributed equally to this workCorrespondence: Samuel Allemann, Pharmaceutical Care Research Group University of Basel, Department of Pharmaceutical Sciences, Klingelbergstrasse 50, Basel, 4056, Switzerland, Tel +41 61 207 61 76, Email s.allemann@unibas.chPurpose: In Switzerland 167 drugs on the market contain information about pharmacogenetics in their drug label (PGx drug). Preemptive pharmacogenetic testing is reimbursed by health care insurance for only seven drugs (abacavir, carbamazepine, 6-mercaptopurine, azathioprine, 5-fluorouracil, capecitabine, and irinotecan) although, it is proposed to be a cost-effective approach to personalized medicine. The aim of this study was to describe the use of PGx drugs and their corresponding genes in Switzerland.Methods: We identified 90 drugs with dosing recommendations from the Pharmacogenetic Knowledgebase involving 24 genes. We assessed the utilization of those drugs between 2016 and 2020, using claims data from a large Swiss insurance company (Helsana).Results: Of 841 491 persons with drug claims during the whole study period, 78.7% were exposed to PGx drugs. Ibuprofen, pantoprazole, and tramadol had the highest number of users. Seven genes (CYP2C19, CYP2C9, CYP2D6, SLCO1B1, HLA-B, MT-RNR1, and VKORC1) were responsible for over 95% of all potential drug-gene interactions.Conclusion: The prevalence of PGx drug prescriptions is high in the Swiss population. Therefore, intensified preemptive testing may be a useful option as a substantial amount of the Swiss population might benefit.Keywords: PGx, drug use, claims data, pharmacoepidemiology

Salome Landolt,1 Thomas Rosemann,1 Eva Blozik,1,2 Beat Brüngger,2 Carola A Huber1,2 1Institute of Primary Care, University of Zürich, University Hospital Zürich, Zürich, Switzerland; 2Department of Health Sciences, Helsana Insurance Group, Zürich, SwitzerlandCorrespondence: Carola A HuberHelsana Insurance Group, P.O. 8081, Zürich, SwitzerlandTel + 41 43 340 6341Fax +41 43 340 0434Email carola.huber@helsana.chPurpose: This study aimed to give a nationwide comprehensive picture of the prevalence and prescription patterns of benzodiazepines (BZ) and Z-drugs (ZD) in Switzerland and to analyze the association with adverse health care outcomes.Patients and Methods: A population-based, cross-sectional study was conducted, using a large health insurance database in Switzerland. Records from all adult patients with ≥ 1 prescription for a benzodiazepine and/or a Z-drug in 2018 were included. We calculated the prevalence of BZ and ZD user (extrapolated to the Swiss general population), the number of prescriptions and the type of provider (among each BZ and ZD only user). Multivariate logistic regression models were performed to estimate the association between drug prescription and the risk of hospitalization in different healthcare settings.Results: Of a total of 844ʹ692 patients, 95ʹ179 had ≥ 1 BZ and/or ZD prescription in 2018. The extrapolated one-year prevalence for the general Swiss population was 8.1% for a BZ prescription, 3.5% for a ZD prescription, and 10.5% for a BZ and/or ZD prescription, and continuously increased with age. The majority of the elderly (over 65 years) had ≥ 1 prescription (BZ: 51.9%; ZD: 56.9%; BZ and/or ZD: 53.5). The proportion of patients with ≥ 6 prescriptions per year was 23.1% for BZ only user and 35.2% for ZD only user. Most patients had ≥ 1 prescription from a general practitioner. Regression models showed a higher likelihood to be admitted to acute care, psychiatry, rehabilitation, or nursing home with ≥ 1 prescription for a benzodiazepine and/or a Z-drug.Conclusion: This study is the first to give a nationwide overview of the current use of benzodiazepines and Z-drugs in Switzerland based on health insurance claims data. The results revealed a remarkably high prevalence among the general Swiss population, especially in older generations. The negative consequences of heavy BZ and ZD use are a crucial public health problem, that should be addressed.Keywords: anxiolytics, sedatives, pharmacoepidemiology, health insurance claims data

Carola A Huber,1,2 Michael Nagler,3 Thomas Rosemann,2 Eva Blozik,1,2 Markus Näpflin,1 Stefan Markun2 1Department of Health Sciences, Helsana Insurance Group, Zürich, Switzerland; 2Institute of Primary Care, University of Zürich, University Hospital Zürich, Zürich, Switzerland; 3University Institute of Clinical Chemistry, Inselspital Bern University Hospital, University of Bern, Bern, SwitzerlandCorrespondence: Carola A HuberDepartment of Health Sciences, Helsana Insurance Group, P.O. Box, 8081, Zürich, SwitzerlandTel +41 43 340 6341Fax +41 43 340 0434Email carola.huber@helsana.chBackground: Micronutrient laboratory tests (MLT) are increasing in many healthcare systems. This study assessed time trends of annual MLT incidence in the Swiss population and examined the frequency of specific MLT, defined as the number of yearly tests performed in individual persons.Methods: For annual time trends, we used a longitudinal design with a seven-year observation period (2012– 2018) and for yearly testing frequency we used a cross-sectional design (2018 only). The database consisted of nationwide insurance claims from adult persons.Results: Persons with MLT compared to persons without were older (mean age 57.1 years vs 48.6 years) and to a higher proportion female (65.1% vs 45.5%). Between 2012 and 2018, we included 6.7 million person years and found an increase in the proportion of persons receiving any MLT from 24.5% to 35.0%. Tests with strongest absolute increase during the observation period were vitamin D (from 7.4% of persons to 20.4%), vitamin B12 (from 9.0% to 17.6%) and ferritin (from 17.4% to 26.6%). In 2018, vitamin D and vitamin B12 tests were performed more than once in 4.5% and 3.3% of the population, respectively.Conclusion: We found that the Swiss population undergoes MLT with high and increasing frequency. Testing for vitamin D, vitamin B12 and ferritin is very common and of questionable appropriateness.Keywords: laboratory testing, micronutrient, claims data, trend

Carola A Huber,1 Reto Agosti,2 Markus Näpflin,1 Eva Blozik1,31Department of Health Sciences, Helsana Insurance Group, Zürich, Switzerland; 2Headache Center Hirslanden, Hirslanden Hospital Group, Zürich, Switzerland; 3Department of Medicine, University of Medical Centre Freiburg, Freiburg, GermanyPurpose: The newly developed calcitonin gene-related peptide (CGRP) antagonists were recently launched on the US and European market, with Switzerland as the second country worldwide. To enable forthcoming comparisons with established migraine therapy, the aim of this study was to provide a comprehensive picture of migraine (prophylactic) treatment patterns. Recent data in daily clinical practice are lacking.Patients and methods: This population-based cohort study included enrollees from a Swiss Healthcare Insurance Database with at least one triptan prescription in 2015. Treatment patterns were defined by assessing subsequent triptan and prophylactic medication use (after index prescription for triptan) within the following year, divided into four quarters.Results: Triptans were used by 10,090 patients (1.3%) in 2015. Most of them used triptan only (82.6%), 12.9% changed the treatment between triptan and prophylactics, and 4.5% received both in combination within 1year. Among triptan users with ≥1 prophylactic prescription in the first quarter, 48.6% used beta-blockers (BB), 40.7% “other prophylactics than BB (eg, topiramate)”, and 10.7% “a combination of both”. Most patients who received both BB and other prophylactics in the first quarter used this drug combination continuously over all four quarters.Conclusion: This study provides comprehensive data on treatment patterns prior to the introduction of a new drug class in migraine therapy. The majority of triptan users had no prophylactic medication therapy; however, a small, but relevant group used BB and other prophylactics concurrently in all quarters. Findings quantify the population in potential need for optimized migraine therapy, ie, the potential target population of the novel CGRP-targeted drugs.Keywords: innovation, headache, migraine, preventive medication, drugs, real-world data

Carola A Huber, Oliver Reich Department of Health Sciences, Helsana Group, Zürich, Switzerland Background: The drug-dispensing channel is a scarcely explored determinant of medication adherence, which is considered as a key indicator for the quality of care among patients with diabetes mellitus. In this study, we investigated the difference in adherence between diabetes patients who obtained their medication directly from a prescribing physician (physician dispensing [PD]) or via a pharmacy.Methods: A retrospective cohort study was conducted using a large health care claims database from 2011 to 2014. Patients with diabetes of all ages and receiving at least one oral antidiabetic drug (OAD) prescription were included. We calculated patients’ individual adherence to OADs defined as the proportion of days covered (PDC), which was measured over 1 year after patient identification. Good adherence was defined as PDC ≥80%. Multivariate logistic regression analysis was performed to assess the relationship between the PDC and the dispensing channel (PD, pharmacy).Results: We identified a total of 10,430 patients prescribed drugs by a dispensing physician and 16,292 patients receiving drugs from a pharmacy. Medication adherence was poor in both patient groups: ~40% of the study population attained good adherence to OADs. We found no significant impact of PD on the adherence level in diabetes patients. Covariates associated significantly with good adherence were older age groups, male sex, occurrence of comorbidity and combined diabetes drug therapy.Conclusion: In conclusion, adherence to antihyperglycemic medication is suboptimal among patients with diabetes. The results of this study provide evidence that the dispensing channel does not have an impact on adherence in Switzerland. Certainly, medication adherence needs to be improved in both supply settings. Physicians as well as pharmacists are encouraged to develop and implement useful tools to increase patients’ adherence behavior. Keywords: diabetes, medication adherence, dispensing channel, physician dispensing, pharmacy

Carola A Huber,1 Michael Brändle,2 Roland Rapold,1 Oliver Reich,1 Thomas Rosemann3 1Department of Health Sciences, Helsana Group, Zürich, 2Division of Endocrinology and Diabetes, Department of Internal Medicine, Kantonsspital St Gallen, St Gallen, 3Institute of Primary Care, University of Zürich, University Hospital Zürich, Zürich, Switzerland Background: The link between guideline adherence and outcomes is a highly demanded issue in diabetes care. We aimed to assess the adherence to guidelines and its impact on hospitalization using a simple set of performance measures among patients with diabetes. Methods: We performed a retrospective cohort study, using health care claims data for adult patients with treated diabetes (2011–2013). Patients were categorized into three drug treatment groups (with oral antidiabetic agents [OAs] only, in combination with insulin, and insulin only). Performance measures were based on international established guidelines for diabetes care. Multivariate logistic regression models predicted the probability of hospitalization (2013) by adherence level (2011) among all treatment groups. Results: A total of 40,285 patients with diabetes were enrolled in 2011. Guideline adherence was quite low: about 70% of all patients received a biannual hemoglobin A1c measurement and 19.8% had undergone an annual low-density lipoprotein cholesterol test. Only 4.8% were exposed to full adherence including all performance measures (OAs: 3.7%; insulin: 7.7%; and in combination: 7.2%). Increased guideline adherence was associated with decreased probability of hospitalization. This effect was strongest in patients using OAs and insulin in combination. Conclusion: Our study showed that measures to reflect physicians’ guideline adherence in diabetes care can easily be calculated based on already available datasets. Furthermore, these measures are clearly linked with the probability of hospitalization suggesting that a better guideline adherence by physicians could help to prevent a large number of hospitalizations. Keywords: diabetes, adherence, guidelines, hospitalization, antidiabetic agents, insulin

Carola A Huber,1 Peter Diem,2 Matthias Schwenkglenks,3 Roland Rapold,1 Oliver Reich1 1Department of Health Sciences, Helsana Group, Zürich, Switzerland; 2Department of Endocrinology, Diabetes and Clinical Nutrition, Inselspital, Bern University Hospital, and University of Bern, Bern, Switzerland; 3Institute of Social and Preventive Medicine, University of Zürich, Zürich, Switzerland Background: Estimating the prevalence of comorbidities and their associated costs in patients with diabetes is fundamental to optimizing health care management. This study assesses the prevalence and health care costs of comorbid conditions among patients with diabetes compared with patients without diabetes. Distinguishing potentially diabetes- and nondiabetes-related comorbidities in patients with diabetes, we also determined the most frequent chronic conditions and estimated their effect on costs across different health care settings in Switzerland. Methods: Using health care claims data from 2011, we calculated the prevalence and average health care costs of comorbidities among patients with and without diabetes in inpatient and outpatient settings. Patients with diabetes and comorbid conditions were identified using pharmacy-based cost groups. Generalized linear models with negative binomial distribution were used to analyze the effect of comorbidities on health care costs. Results: A total of 932,612 persons, including 50,751 patients with diabetes, were enrolled. The most frequent potentially diabetes- and nondiabetes-related comorbidities in patients older than 64 years were cardiovascular diseases (91%), rheumatologic conditions (55%), and hyperlipidemia (53%). The mean total health care costs for diabetes patients varied substantially by comorbidity status (US$3,203–$14,223). Patients with diabetes and more than two comorbidities incurred US$10,584 higher total costs than patients without comorbidity. Costs were significantly higher in patients with diabetes and comorbid cardiovascular disease (US$4,788), hyperlipidemia (US$2,163), hyperacidity disorders (US$8,753), and pain (US$8,324) compared with in those without the given disease. Conclusion: Comorbidities in patients with diabetes are highly prevalent and have substantial consequences for medical expenditures. Interestingly, hyperacidity disorders and pain were the most costly conditions. Our findings highlight the importance of developing strategies that meet the needs of patients with diabetes and comorbidities. Integrated diabetes care such as used in the Chronic Care Model may represent a useful strategy. Keywords: diabetes, comorbidity, chronic diseases, costs

David Eisner, Marco Zoller, Thomas Rosemann, Carola A Huber, Nina Badertscher, Ryan TandjungInstitute for General Practice and Health Services Research, University of Zurich, Zurich, SwitzerlandBackground and objectives: Prevention is a challenging area of primary care. In Switzerland, little is known about attitudes to and performance of screening and prevention services in general practice. To implement prevention services in primary care it is important to know about not only potential facilitators but also barriers. Primary care encompasses the activities of general practitioners, including those with particular interest and/or specializations (eg, pediatrics, gynecology). The aim of this study was to review all studies with a focus on prevention services which have been conducted in Switzerland and to reveal barriers and facilitators for physicians to participate in any preventive measures.Methods: The Cochrane Library, PubMed, EMBASE and BIOSIS were searched from January 1990 through December 2010. Studies focussing on preventive activities in primary care settings were selected and reviewed. The methodological quality of the identified studies was classified according to the guidelines in the Consolidated Standards of Reporting Trials (CONSORT) statement.Results: We identified 49 studies including 45 descriptive studies and four randomised controlled trials (RCTs). Twelve studies addressed the prevention of epidemics, eleven out of them vaccinations. Further studies focused on lifestyle changes, physical activity counselling, smoking cessation, cardiovascular prevention and cancer screening. Perceived lack of knowledge/training and lack of time were the most commonly stated barriers. Motivation, feasibility and efficiency were the most frequently reported supporting factors for preventive activities. The methodological quality was weak, only one out of four RCTs met the applied quality criteria.Conclusion: Most studies focussing on screening and prevention activities in primary care addressed vaccination, lifestyle modification or cardiovascular disease prevention. Identified barriers and facilitators indicate a need for primary-care-adapted education and training which are easy to handle, time-saving and reflect the specific needs of general practitioners. If new prevention programs are to be implemented in general practices, RCTs of high methodological quality are needed to assess their impact.Keywords: disease prevention, primary care, Switzerland, epidemic, screening, education, descriptive study

Coffee is one of the most relevant agricultural products globally, due to its significant economic, social and environmental impact, especially in producing countries such as Peru. In particular, the San Martín region stands out for its production of 83425 tons of parchment coffee in an area of ​​81000 hectares. Root-knot nematodes, especially of the genus Meloidogyne, are a significant threat to coffee cultivation, affecting plant water and nutrient uptake. Accurate and rapid detection of these nematodes is crucial for their effective control. The objective was based on the rapid molecular detection of the root-knot nematode Meloidogyne incognita in coffee roots by PCR with the specific primers MI-F and MI-R to amplify a band of 999 bp. The isolation of DNA allowed concentrations between 59.1 to 39.4 ng/µL and absorbance ranges from 1.92 to 2.00, being determined as good quality DNA. This study focuses on the molecular detection of M. incognita in coffee roots. These results allow accurate and rapid detection of nematodes in coffee, and thus be able to control this pathogen in time.

In this paper a study on the process of densification of oil palm empty fruit bunches (OPEFB) is presented. An empirical-statistical model that allows the evaluation of densification process is obtained through an experimental factorial design. The main purpose of the experimental arrangement is to find the appropriate reference values for the experimental factors - moisture content, fiber length and compaction time-with which optimal performance responses of briquettes are achieved. Statistical models are obtained that explain in an acceptable way the influence of independent experimental factors on the mechanical properties of briquettes, such as briquettes density, durability index and compressive strength. It is possible to conclude that briquettes manufactured with the appropriate reference values, moisture content of 8% w.b., fiber length of 73.6 mm and a compaction time of 26.6 s respectively, meet mechanical and thermal requirements that are required in the most representative standards for biomass briquettes for energy purposes. Results obtained in the current investigation can be used as reference for the design of an industrial pilot plant destined to the densification of EFB of African oil palm.

La presente investigación tiene como objetivo, analizar las percepciones que tienen los docentes de grado preescolar en relación a la lúdica y los cambios que ha adquirido como competencia, en su implementación para el fortalecimiento y formación pedagógica de los docentes de Preescolar de las instituciones educativas públicas de los Municipios de Planeta Rica y Pueblo Nuevo en el Departamento Córdoba- Colombia; por lo cual se buscó la identificación de elementos fundamentales en la articulación de las practicas lúdicas en el contexto laboral del docente y directivo docente en el nivel de educación inicial en Preescolar.

Esta investigación descriptiva analiza las percepciones de periodistas del caribe colombiano sobre los posibles cambios percibidos en el periodismo local a partir de la inserción de las nuevas tecnologías en las labores que desarrollan en Montería y Cartagena de Indias (Colombia). Dentro de los hallazgos se resaltan que los periodistas de estas ciudades perciben grandes beneficios que les ha brindado las TIC en términos de acceso a fuentes de información, facilitación de labores de redacción y edición de contenidos; sin embargo resaltan algunos usos tecnológicos inapropiados que están afectando la calidad periodística en algunas empresas informativas: la pérdida del contacto con la realidad y las fuentes, la reducción de la profesión a retransmisión de información o noticia, y el ejercicio de la práctica periodística desde competencias tecnológicas que dejan de lado las competencias profesionales y éticas.

Abstract Background The worldwide increase in obesity is becoming a major health concern. General practitioners (GPs) play a central role in managing obesity. We aimed to examine Swiss GPs self-reported practice in diagnosis and treatment of obesity with a special focus on the performance of waist measurement. Methods A structured self-reported questionnaire was mailed to 323 GPs recruited from four urban physician networks in Switzerland. Measures included professional experience, type of practice, obesity-related continuing medical education (CME) and practice in dealing with obesity such as waist measurement. We assessed the association between the performance of waist measurement and obesity-related CME by multivariate ordered logistic regression controlling for GP characteristics as potential confounders. Results A total of 187 GPs responded to the questionnaire. More than half of the GPs felt confident in managing obesity. The majority of the GPs (73%) spent less than 4 days in the last 5 years on obesity-related CME. More than half of GPs gave advice to reduce energy intakes (64%), intakes of high caloric and alcoholic drinks (56%) and to increase the physical activity (78%). Half of the GPs seldom performed waist measurement and documentation. The frequency of obesity-related CME was independently associated with the performance of waist measurement when controlled for GPs' characteristics by multivariate ordered logistic regression. Conclusions The majority of GPs followed guideline recommendations promoting physical activity and dietary counselling. We observed a gap between the increasing evidence for waist circumference assessment as an important measure in obesity management and actual clinical practice. Our data indicated that specific obesity-related CME might help to reduce this gap.

Abstract Background In previous years, out- of-hours primary care has been organised in large-scale organisations in many countries. This may have lowered the threshold for many patients to present health problems at nights and during the weekend. Comparisons of out-of-hours care between countries require internationally comparable figures on symptoms and diagnoses, which were not available. This study aimed to describe the symptoms and diagnoses in out-of-hours primary care services in regions in eight European countries. Methods We conducted a retrospective observational study based on medical records from out-of-hours primary care services in Belgium, Denmark, Germany, the Netherlands, Norway, Slovenia, Spain, and Switzerland. We aimed to include data on 1000 initial contacts from up to three organisations per country. Excluded were contacts with an administrative reason. The International Classification for Primary Care (ICPC) was used to categorise symptoms and diagnoses. In two countries (Slovenia and Spain) ICD10 codes were translated into ICPC codes. Results The age distribution of patients showed a high consistency across countries, while the percentage of males varied from 33.7% to 48.3%. The ICPC categories that were used most frequently concerned: chapter A 'general and unspecified symptoms' (mean 13.2%), chapter R 'respiratory' (mean 20.4%), chapter L 'musculoskeletal' (mean 15.0%), chapter S 'skin' (mean 12.5%), and chapter D 'digestive' (mean 11.6%). So, relatively high numbers of patients presenting with infectious diseases or acute pain related syndromes. This was largely consistent across age groups, but in some age groups chapter H ('ear problems'), chapter L ('musculoskeletal') and chapter K ('cardiovascular') were frequently used. Acute life-threatening problems had a low incidence. Conclusions This international study suggested a highly similar diagnostic scope in out-of-hours primary care services. The incidence rates of acute life-threatening health problems were low in all countries.

Abstract Background Emergency Departments (ED) in Switzerland are faced with increasing numbers of patients seeking non-urgent treatment. The high rate of walks-ins with conditions that may be treated in primary care has led to suggestions that those patients would best cared for in a community setting rather than in a hospital. Efficient reorganisation of emergency care tailored to patients needs requires information on the patient populations using the various emergency services currently available. The aim of this study is to evaluate the differences between the characteristics of walk-in patients seeking treatment at an ED and those of patients who use traditional out-of-hours GP (General Practitioner) services provided by a GP-Cooperative (GP-C). Methods In 2007 and 2009 data was collected covering all consecutive patient-doctor encounters at the ED of a hospital and all those occurring as a result of contacting a GP-C over two evaluation periods of one month each. Comparison was made between a GP-C and the ED of the Waid City Hospital in Zurich. Patient characteristics, time and source of referral, diagnostic interventions and mode of discharge were evaluated. Medical problems were classified according to the International Classification of Primary Care (ICPC-2). Patient characteristics were compared using non-parametric tests and multiple logistic regression analysis was applied to investigate independent determinants for contacting a GP-C or an ED. Results Overall a total of 2974 patient encounters were recorded. 1901 encounters were walk-ins and underwent further analysis (ED 1133, GP-C 768). Patients consulting the GP-C were significantly older (58.9 vs. 43.8 years), more often female (63.5 vs. 46.9%) and presented with non-injury related medical problems (93 vs. 55.6%) in comparison with patients at the ED. Independent determining factors for ED consultation were injury, male gender and younger age. Walk-in distribution in both settings was equal over a period of 24 hours and most common during daytime hours (65%). Outpatient care was predominant in both settings but significantly more so at the GP-C (79.9 vs. 85.7%). Conclusions We observed substantial differences between the two emergency settings in a non gate-keeping health care system. Knowledge of the distribution of diagnoses, their therapy, of diagnostic measures and of the factors which determine the patients' choice of the ED or the GP-C is essential for the efficient allocation of resources and the reduction of costs.

Abstract Background Placebos play an important role in clinical trials and several surveys have shown that they are also common in daily practice. Previous research focused primarily on the frequency of placebo use in outpatient care. Our aim was to explore physicians' views on the use of placebos in daily practice, whereby distinction was made between pure placebos (substances with no pharmacological effect, e.g. sugar pills) and impure placebos (substances with pharmacological effect but not on the condition being treated, e.g. antibiotics in viral infections or vitamins). Methods We performed semi-structured interviews with a sample of twelve primary care physicians (PCPs). The interview addressed individual definitions of a placebo, attitudes towards placebos and the participants' reasons for prescribing them. The interviews were transcribed and analysed using qualitative content analysis. Results The definition of a placebo given by the majority of the PCPs in our study was one which actually only describes pure placebos. This definition, combined with the fact that most impure placebos were not regarded as placebos at all, means that most of the participating PCPs were not aware of the extent to which placebos are used in daily practice. The PCPs stated that they use placebos (both pure and impure) mainly in the case of non-severe diseases for which there was often no satisfactory somatic explanation. According to the PCPs, cases like this are often treated by complementary and alternative therapies and these, too, are associated with placebo effects. However, all PCPs felt that the ethical aspects of such treatment were unclear and they were unsure as to how to communicate the use of placebos to their patients. Most of them would appreciate ethical guidelines on how to deal with this issue. Conclusions Many PCPs seem to be unaware that some of the drugs they prescribe are classified as impure placebos. Perceptions of effectiveness and doubts about the legal and ethical aspects of the use of placebos by PCPs may discourage their application. Dissemination of guidelines and consensus papers may be one approach, but it has to be acknowledged that the topic itself is in conflict with the PCPs' perception of themselves as professional and reliable physicians.

Abstract Background In Switzerland, General Practitioners (GPs) play an important role for out-of-hours emergency care as one service option beside freely accessible and costly emergency departments of hospitals. The aim of this study was to evaluate the services provided and the economic consequences of a Swiss GP out-of-hours service. Methods GPs participating in the out-of-hours service in the city of Zurich collected data on medical problems (ICPC coding), mode of contact, mode of resource use and services provided (time units; diagnostics; treatments). From a health care insurance perspective, we assessed the association between total costs and its two components (basic costs: charges for time units and emergency surcharge; individual costs: charges for clinical examination, diagnostics and treatment in the discretion of the GP). Results 125 GPs collected data on 685 patient contacts. The most prevalent health problems were of respiratory (24%), musculoskeletal (13%) and digestive origin (12%). Home visits (61%) were the most common contact mode, followed by practice (25%) and telephone contacts (14%). 82% of patients could be treated by ambulatory care. In 20% of patients additional technical diagnostics, most often laboratory tests, were used. The mean total costs for one emergency patient contact were €144 (95%-CI: 137-151). The mode of contact was an important determinant of total costs (mean total costs for home visits: €176 [95%-CI: 168-184]; practice contact: €90 [95%-CI: 84-98]; telephone contact: €48 [95%-CI: 40-55]). Basic costs contributed 83% of total costs for home visits and 70% of total costs for practice contacts. Individual mean costs were similarly low for home visits (€30) and practice contacts (€27). Medical problems had no relevant influence on this cost pattern. Conclusions GPs managed most emergency demand in their out-of-hours service by ambulatory care. They applied little diagnostic testing and basic care. Our findings are of relevance for policy makers even from other countries with different pricing policies. Policy makers should be interested in a reimbursement system promoting out-of-hours care run by GPs as one valuable service option.

Background: Integrated care models (ICMs) might be an effective strategy to improve patients' quality of care. The aim of this study was to compare different ICMs such as family-doctor models, and a standard care model (SCM) regarding patients' drug safety in Swiss primary care., Methods: We performed an observational study using health insurance claims data from patients who were continuously enrolled in an ICM or in a SCM between 2020 and 2021. ICMs included family-doctor model (FDM), family-doctor model light (FDM-light) and the telemedicine model (TM). Drug safety was assessed by the prescription of potentially inappropriate proton pump-inhibitors (PIPPI), opioids (PIO), medications (PIM), and polypharmacy. Propensity-score-weighted multiple logistic regression models were used to examine the association between different types of ICMs and drug safety., Results: Patients in FDM had significantly lower odds of receiving PIPPI (OR, 0.86; CI 95%, 0.83-0.89), PIO (OR, 0.81; CI 95%, 0.76-0.85), PIM (OR, 0.94; CI 95%, 0.91-0.97), and polypharmacy (OR, 0.94; CI 95%, 0.91-0.97) compared to patients in SCM. Potentially inappropriate prescribing was also lower in patients in TM and partly in FDM-light than in SCM. Persons enrolled in FDM were less likely to receive PIM (OR, 0.93; CI 95%, 0.89-0.97) and polypharmacy (OR, 0.94; CI 95%, 0.90-0.99) than those in FDM-light, whereas the odds of receiving PIPPI and polypharmacy were higher in FDM than in TM., Conclusion: ICMs were significantly associated with higher drug safety compared to SCM for most outcomes. Findings suggest that patients may benefit most from ICMs with a high degree of coordination or gatekeeping. ICM may represent an effective approach to improve patients' drug safety and, thus, to reduce the risk of adverse events., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Farcher et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

BackgroundIn Europe and other high-income countries, antibiotics are mainly prescribed in the outpatient setting, which consists of primary, specialist and hospital-affiliated outpatient care. Established surveillance platforms report antimicrobial consumption (AMC) on aggregated levels and the contribution of the different prescriber groups is unknown.AimTo determine the contribution of different prescribers to the overall outpatient AMC in Switzerland.MethodsWe conducted a retrospective observational study using claims data from one large Swiss health insurance company, covering the period from 2015 to 2022. We analysed antibiotic prescriptions (ATC code J01) prescribed in the Swiss outpatient setting. Results were reported as defined daily doses per 1,000 inhabitants per day (DID) and weighted according to the total population of Switzerland based on census data.ResultsWe analysed 3,663,590 antibiotic prescriptions from 49 prescriber groups. Overall, AMC ranged from 9.12 DID (2015) to 7.99 DID (2022). General internal medicine (40.1% of all prescribed DID in 2022), hospital-affiliated outpatient care (20.6%), group practices (17.3%), paediatrics (5.4%) and gynaecology (3.7%) were the largest prescriber groups. Primary care accounted for two-thirds of the prescribed DID. Quantity and type of antibiotics prescribed varied between the prescriber groups. Broad-spectrum penicillins, tetracyclines and macrolides were the most prescribed antibiotic classes.ConclusionPrimary care contributed considerably less to AMC than anticipated, and hospital-affiliated outpatient care emerged as an important prescriber. Surveillance at the prescriber level enables the identification of prescribing patterns within all prescriber groups, offering unprecedented visibility and allowing a more targeted antibiotic stewardship according to prescriber groups.

Purpose: Long-term use of hydrochlorothiazide increases the risk of non-melanoma skin cancer. We aimed to evaluate potential changes in the use of hydrochlorothiazide in Switzerland after a direct healthcare professional communication (DHPC) in November 2018 by Swissmedic., Methods: We performed interrupted time-series analyses using a large Swiss healthcare claims database (2015-2021). Within monthly intervals, we quantified the total number of claims and the total dispensed 'defined daily doses' (DDD) for preparations containing (1) hydrochlorothiazide, (2) angiotensin-converting enzyme (ACE) inhibitors and angiotensin-II-receptor blockers (ARB), (3) calcium-channel blockers (CCB) and (4) thiazide-like diuretics per 10 000 persons. Using segmented linear regression, we quantified the pre-DHPC trend, the immediate change and the post-DHPC change in trend for total claims and DDD for the four drug classes weighted for the demographic distribution of the Swiss population., Results: ACE inhibitors and ARB were the most frequently claimed antihypertensive drugs with 300-400 claims per 10 000 persons, which increased by 5.4% during the study period. The average number of hydrochlorothiazide claims (157/10 000 persons in 2015) declined by 35% between 2015 and 2021. The decrease started prior to the DHPC, but the DHPC was associated with an immediate 6.1% decline and an accelerated decline in claims over time after the DHPC (similar results for DDD). This coincided with a 23% increase in claims of CCB (dihydropyridine type) over 7 years, whereas use of other antihypertensives increased less., Conclusion: Our results suggest that the DHPC by Swissmedic in 2018 accelerated a pre-existing decline in the use of hydrochlorothiazide in Switzerland., (© 2024 The Author(s). Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Background: Prostate cancer (PC) is the most prevalent cancer in men in Switzerland. However, evidence on the real-world health care use of PC patients is scarce. The aim of this study is to describe health care utilization, treatment patterns, and medical costs in PC patients over a period of five years (2014-2018)., Method: We used routinely collected longitudinal individual-level claims data from a major provider of mandatory health insurance in Switzerland. Due to the lack of diagnostic coding in the claims data, we identified treated PC patients based on the treatments received. We described health care utilization and treatment pathways for patients with localized and metastatic PC. Costs were calculated from a health care system perspective., Results: A total of 5591 PC patients met the inclusion criteria. Between 2014 and 2018, 1741 patients had outpatient radiotherapy for localized or metastatic PC and 1579 patients underwent radical prostatectomy. 3502 patients had an androgen deprivation therapy (ADT). 9.5% of these patients had a combination therapy with docetaxel, and 11.0% had a combination with abiraterone acetate. Docetaxel was the most commonly used chemotherapy (first-line; n = 413, 78.4% of all patients in chemotherapy). Total medical costs of PC in Switzerland were estimated at CHF 347 m (95% CI 323-372) in 2018., Conclusion: Most PC patients in this study were identified based on the use of ADT. Medical costs of PC in Switzerland amounted to 0.45% of total health care spending in 2018. Treatment of metastatic PC accounted for about two thirds of spending., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Prescription sequence symmetry analysis (PSSA) is used to detect adverse event signals using administrative claims databases. In this study, we investigated whether PSSA can be applied to gauge the effects of PCV13 vaccination on antibiotic prescription rates in elderly patients., Methods: We studied prescription records of patients aged 65 or older between 1 January 2014 and 31 December 2020, from the Helsana Swiss claims database. PSSA was performed to explore the relationship between 13-valent pneumococcal conjugate vaccine (PCV13) and six antibiotics recommended by the Swiss Society of Infectious Diseases for community-acquired pneumonia treatment (amoxicillin-clavulanate, azithromycin, clarithromycin, doxycycline, levofloxacin, and moxifloxacin), three additional antibiotics (amoxicillin, ciprofloxacin, and fosfomycin), and ten control drugs., Results: Amoxicillin-clavulanate, clarithromycin, and levofloxacin were more likely to be prescribed before than after vaccination, for all time windows between 25 and 104 weeks. Adjusted sequence ratio (ASR) values ranged from 0.599 to 0.614, 0.508 to 0.568, and 0.514 to 0.752, respectively. Lower prescription rates after vaccination were also observed for azithromycin (all time windows between 38 and 104 weeks, ASR 0.705-0.739) and moxifloxacin (all time windows between 52 and 104 weeks, ASR 0.658-0.772). PCV13 did not have statistically significant associations with doxycycline, amoxicillin, ciprofloxacin, fosfomycin, or any of the ten controls., Discussion: The lower prescription rate of antibiotics for community-acquired pneumonia after vaccination could be attributed to a protective effect of PCV13. This novel application of PSSA can be used to compare the real-world impact of other vaccines on drug consumption., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate claims patterns for metamizole and other non-opioid analgesics in Switzerland. To characterise users of these non-opioid analgesics regarding sex, age, comedications and canton of residence., Methods: We conducted a retrospective descriptive study using administrative claims data of outpatient prescribed non-opioid analgesics of the Swiss health insurance company Helsana between January 2014 and December 2019. First, we evaluated the number of claims and defined daily doses  per year of metamizole, ibuprofen, diclofenac and paracetamol in adults aged 18 years or over. Second, we characterised new users of these non-opioid analgesics in terms of sex, age, claimed comedications and canton of residence., Results: From 2014 to 2019, among the investigated non-opioid analgesics, metamizole showed the highest increase in claims (+9545 claims, +50%) and defined daily doses (+86,869 defined daily doses, +84%) per 100,000 adults. Metamizole users had the highest median age (62 years [IQR: 44-77]) compared to ibuprofen (47 years [IQR: 33-62]), diclofenac (57 years [IQR: 43-71]) and paracetamol (58 years [IQR: 39-75]) users. Metamizole users also more frequently claimed proton pump inhibitors, anticoagulants, platelet aggregation inhibitors and antihypertensive drugs than users of other non-opioid analgesics. While metamizole was most frequently claimed in German-speaking regions of Switzerland, ibuprofen and paracetamol were most frequently claimed in the French-speaking regions and diclofenac in German- and Italian-speaking regions., Conclusion: In Switzerland, metamizole was increasingly claimed between 2014 and 2019. Metamizole was most frequently claimed by older adults and patients with comedications suggestive of underlying conditions, which can be worsened or caused by use of nonsteroidal anti-inflammatory drugs. The lack of studies regarding the effectiveness and safety of metamizole in this population warrants further investigation.

Aims: Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment., Methods: The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment., Results: 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained., Conclusions: Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial., Competing Interests: Competing interests: JHB reports grant support from the Swiss National Foundation of Science, The Swiss Heart Foundation and the Stiftung Kardio; grant support, speakers and consultation fees to the institution from Bayer, Sanofi and Daichii Sankyo. EB reports grants from Swiss Cancer Research Foundation, Amgen, MSD, Novartis, Vifor, all outside the submitted work. MB is supported by grants from the Swiss National Science Foundation and the Swiss Heart Foundation. LB reports personal fees and non-financial support from Amgen, grants from AstraZeneca, personal fees and non-financial support from Bayer, personal fees from Bristol-Myers Squibb, personal fees from Claret Medical, grants from Swiss National Science Foundation, grants from University of Basel, grants from Swiss Heart Foundation, outside the submitted work. DC received consulting fees from Roche Diagnostics, and speaker fees from Servier and BMS/Pfizer, all outside of the current work. MK reports grants from Bayer, grants from Pfizer, grants from Boston Scientific, grants from BMS, grants from Biotronik, grants and personal fees from Daiichi Sankyo. GM has received advisory board and/or speaker’s fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Gebro Pharma, Novartis and Vifor, all outside of the submitted study. AM reports fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St. Jude Medical and Biosense Webster; speaker honoraria from Biosense Webster, Medtronic, Abbott/St Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort, Novartis, and consultant honoraria for Biosense Webster, Medtronic, Abbott/St. Jude Medcal and Biotronik. SO received research grants from the Swiss National Science Foundation and from the Swiss Heart Foundation, research grants from Foundation for CardioVascular Research Basel, research grants from Roche, educational and speaker office grants from Roche, Bayer, Novartis, Sanofi AstraZeneca, Daiichi-Sankyo and Pfizer. TR has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the sitem insel support fund, all for work outside the submitted study. Speaker/consulting honoraria or travel support from Abbott/SJM, Astra Zeneca, Brahms, Bayer, Biosense-Webster, Biotronik, Boston-Scientific, Daiichi Sankyo, Medtronic, Pfizer-BMS and Roche, all for work outside the submitted study. Support for his institution’s fellowship programme from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific and Medtronic for work outside the submitted study. MS reports grants from Swiss National Science Foundation, for the conduct of the study; grants from Amgen, grants from MSD, grants from Novartis, grants from Pfizer, grants from Roche, grants and personal fees from BMS and personal fees from Sandoz, all outside the submitted work. MS-B reports grants from the European Commission outside of the present work. CS has received speaker honoraria from Biosense Webster and Medtronic and research grants from Biosense Webster, Daiichi-Sankyo and Medtronic. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Many western countries are challenged by delayed and insufficient vaccination coverage rates in children, and thus missing WHO coverage targets. This study aimed to estimate vaccination coverage and timeliness in Swiss children over a decade. Furthermore, we evaluated the impact of COVID-19, regional variations, and the adherence to the amended vaccination schedule in 2019., Methods: Retrospective observational study with Swiss health insurance claims data including birth cohorts 2012-2021 of children continuously observed until ages 13, 25, and 48 months respectively. We used population-weighted proportions and time-to-event analyses to describe coverage and timeliness of diphtheria/tetanus/pertussis/poliomyelitis/haemophilus influenzae type b (DTaP-IPV-Hib), measles/mumps/rubella (MMR), hepatitis B (HBV), pneumococcal (PCV), and meningococcal (MCV) vaccinations according to the national schedule. The potential impact of COVID-19 and vaccination schedule adherence were evaluated descriptively. Logistic regression was used to investigate regional factors potentially associated with non-vaccination., Results: 120,073 children, representing between 12 and 17 % of all Swiss children born in corresponding years, were included. Coverage remained stable or improved over the years. The 2019 amendment of the national immunization schedule was associated with an increase of ~10 % points in full coverage in Swiss children for DTaP-IPV-Hib, MMR and HBV despite the concurrent COVID-19 pandemic. Nonetheless, full vaccination coverage remained below 90 % with many vaccination series being delayed or not completed. The comparison across the different vaccines revealed large differences in coverage. Moreover, we observed large regional differences in non-vaccination with children living in rural and German-speaking areas more likely to be entirely unvaccinated., Conclusion: Full vaccination coverage in Swiss children is still below 90 % with many vaccinations administered delayed. Given regional differences, missed or delayed booster vaccinations, and differences in vaccine-specific acceptability, more effort may be needed to achieve national vaccination targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Tumor markers (TM) are crucial in the monitoring of cancer treatment. However, inappropriate requests for screening reasons have a high risk of false positive and negative findings, which can lead to patient anxiety and unnecessary follow-up examinations. We aimed to assess the appropriateness of TM testing in outpatient practice in Switzerland. We conducted a retrospective cohort study based on healthcare claims data. Patients who had received at least one out of seven TM tests (CEA, CA19-9, CA125, CA15-3, CA72-4, Calcitonin, or NSE) between 2018 and 2021 were analyzed. Appropriate determinations were defined as a request with a corresponding cancer-related diagnosis or intervention. Appropriateness of TM determination by patient characteristics and prescriber specialty was estimated by using multivariate analyses. A total of 51,395 TM determinations in 36,537 patients were included. An amount of 41.6% of all TM were determined appropriately. General practitioners most often determined TM (44.3%) and had the lowest number of appropriate requests (27.8%). A strong predictor for appropriate determinations were requests by medical oncologists. A remarkable proportion of TM testing was performed inappropriately, particularly in the primary care setting. Our results suggest that a considerable proportion of the population is at risk for various harms associated with misinterpretations of TM test results.

Purpose: Antidepressant use has increased in many European countries, mostly driven by longer treatment duration. The aim of this study was to provide prevalence rates of long-term users of antidepressants for the Swiss population over the last decade and to investigate associated factors for longer use., Methods: We examined the prevalence rates of individuals with at least one prescription for antidepressants using longitudinal health claims data for 2013 to 2021. We defined short- (< one year), medium- (one-two years), and long-term users (> two years) for 2015 to 2019. We applied a binary logistic regression model to investigate the effects of population (gender, age, area of living, language, health insurance plan, and nursing home) and treatment characteristics (psychiatric or psychotherapeutic care) on long-term compared to short- and medium-term users in 2019., Results: In 2021, 9% of the Swiss population (n = 770,698) received at least one antidepressant prescription, which remained stable since 2013. In 2019, the proportion of long-term users was 57.4%, with steady increase since 2015. The proportion of medium- and short-term users has decreased. Older age, being a woman, living in an urban area, living in a nursing home, being enrolled in a standard care plan, and receiving psychiatric or psychotherapeutic care were factors positively associated with being a long-term user., Conclusion: The proportion of long-term users in Switzerland is high and steadily increasing. Given the ongoing debate about the confounding effects of relapse and withdrawal, more research is needed to investigate longer use of antidepressants that could indicate overprescribing., (© 2023. The Author(s).)

Background: A novel incentive scheme based on a joint agreement of a large Swiss health insurance with 56 physician networks was implemented in 2018. This study evaluated the effect of its implementation on adherence to evidence-based guidelines among patients with diabetes in managed care models., Methods: We performed a retrospective cohort study, using health care claims data from patients with diabetes enrolled in a managed care plan (2016-2019). Guideline adherence was assessed by four evidence-based performance measures and four hierarchically constructed adherence levels. Generalized multilevel models were used to examine the effect of the incentive scheme on guideline adherence., Results: A total of 6'273 patients with diabetes were included in this study. The raw descriptive statistics showed minor improvements in guideline adherence after the implementation. After adjusting for underlying patient characteristics and potential differences between physician networks, the likelihood of receiving a test was moderately but consistently higher after the implementation of the incentive scheme for most performance measures, ranging from 18% (albuminuria: OR, 1.18; 95%-CI, 1.05-1.33) to 58% (HDL cholesterol: OR, 1.58; 95%-CI, 1.40-1.78). Full adherence was more likely after implementation of the incentive scheme (OR, 1.37; 95%-CI, 1.20-1.55), whereas level 1 significantly decreased (OR, 0.74; 95%-CI, 0.65 - 0.85). The proportions of the other adherence levels were stable., Conclusion: Incentive schemes including transparency of the achieved performance may be able to improve guideline adherence in patients with diabetes and are promising to increase quality of care in this patient population., (© 2023. The Author(s).)

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., Competing Interests: AS, CB, and CAH were employed at Helsana Group. Author EB was employed by SWICA Health Services Research. The remaining authors declare that they do not have any conflicts of interest., (Copyright © 2023 Rachamin, Jäger, Schweighoffer, Signorell, Bähler, Huber, Blozik, Seifritz, Grischott and Senn.)

Objective: Evidence on long-term costs of atrial fibrillation (AF) and associated factors is scarce. As part of the Swiss-AF prospective cohort study, we aimed to characterise AF costs and their development over time, and to assess specific patient clusters and their cost trajectories., Methods: Swiss-AF enrolled 2415 patients with variable duration of AF between 2014 and 2017. Patient clusters were identified using hierarchical cluster analysis of baseline characteristics. Ongoing yearly follow-ups include health insurance clinical and claims data. An algorithm was developed to adjudicate costs to AF and related complications., Results: A subpopulation of 1024 Swiss-AF patients with available claims data was followed up for a median (IQR) of 3.24 (1.09) years. Average yearly AF-adjudicated costs amounted to SFr5679 (€5163), remaining stable across the observation period. AF-adjudicated costs consisted mainly of inpatient and outpatient AF treatment costs (SFr4078; €3707), followed by costs of bleeding (SFr696; €633) and heart failure (SFr494; €449). Hierarchical analysis identified three patient clusters: cardiovascular (CV; N=253 with claims), isolated-symptomatic (IS; N=586) and severely morbid without cardiovascular disease (SM; N=185). The CV cluster and SM cluster depicted similarly high costs across all cost outcomes; IS patients accrued the lowest costs., Conclusion: Our results highlight three well-defined patient clusters with specific costs that could be used for stratification in both clinical and economic studies. Patient characteristics associated with adjudicated costs as well as cost trajectories may enable an early understanding of the magnitude of upcoming AF-related healthcare costs., Competing Interests: Competing interests: AA is a consultant with Abbott, Boston Scientific, Backbeat, Cairdac, Corvia, EP Solutions, Medtronic, Microport CRM, Philips and XSpline; participates in clinical trials sponsored by Boston Scientific, Medtronic, Microport CRM, Philips and XSpline; and has intellectual properties assigned to Boston Scientific, Biosense Webster and Microport CRM. JHB reports grant support from the Swiss National Foundation of Science, the Swiss Heart Foundation and the Stiftung Kardio; grant support, speakers and consultation fees to the institution from Bayer, Sanofi and Daiichi Sankyo. DC received consulting fees from Roche Diagnostics, and speaker fees from Servier and BMS/Pfizer, all outside of the current work. MK reports personal fees from Bayer, personal fees from Böhringer Ingelheim, personal fees from Pfizer/BMS, personal fees from Daiichi Sankyo, personal fees from Medtronic, personal fees from Biotronik, personal fees from Boston Scientific, personal fees from Johnson&Johnson, personal fees from Roche, grants from Bayer, grants from Pfizer, grants from Boston Scientific, grants from BMS, grants from Biotronik and grants from Daiichi Sankyo. GM has received consultant fees for taking part in advisory boards from Novartis, Boehringer Ingelheim, Bayer, AstraZeneca and Daiichi Sankyo, all outside of the presented work. AM reports fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St Jude Medical and Biosense Webster; speaker honoraria from Biosense Webster, Medtronic, Abbott/St Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort and Novartis; and consultant honoraria for Biosense Webster, Medtronic, Abbott/St Jude Medical and Biotronik. TR has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation and the sitem insel support fund, all for work outside the submitted study; speaker/consulting honoraria or travel support from Abbott/SJM, AstraZeneca, Brahms, Bayer, Biosense Webster, Biotronik, Boston Scientific, Daiichi Sankyo, Medtronic, Pfizer/BMS and Roche, all for work outside the submitted study; support for his institution’s fellowship programme from Abbott/SJM, Biosense Webster, Biotronik, Boston Scientific and Medtronic for work outside the submitted study. MS reports grants from the Swiss National Science Foundation, for the conduct of the study; grants from Amgen, grants from MSD, grants from Novartis, grants from Pfizer, grants from Roche, grants and personal fees from BMS and personal fees from Sandoz, all outside the submitted work. MS-B reports grants from the European Commission outside of the present work. CS has received speaker honoraria from Biosense Webster and Medtronic and research grants from Biosense Webster, Daiichi Sankyo and Medtronic. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The optimal use of opioids after knee replacement (KR) remains to be determined, given the growing evidence that opioids are no more effective than other analgesics and that their adverse effects can impair quality of life. Therefore, the objective is to examine opioid prescriptions after KR., Design: In this retrospective study, we used descriptive statistics and estimated the association of prognostic factors using generalised negative binomial models., Setting: The study is based on anonymised claims data of patients with mandatory health insurance at Helsana, a leading Swiss health insurance., Participants: Overall, 9122 patients undergoing KR between 2015 and 2018 were identified., Primary and Secondary Outcome Measures: Based on reimbursed bills, we calculated the dosage (morphine equivalent dose, MED) and the episode length (acute: <90 days; subacute: ≥90 to <120 days or <10 claims; chronic: ≥90 days and ≥10 claims or ≥120 days). The incidence rate ratios (IRRs) for postoperative opioids were calculated., Results: Of all patients, 3445 (37.8%) received opioids in the postoperative year. A large majority had acute episodes (3067, 89.0%), 2211 (65.0%) had peak MED levels above 100 mg/day and most patients received opioids in the first 10 postoperative weeks (2881, 31.6%). Increasing age (66-75 and >75 vs 18-65) was associated with decreased IRR (0.776 (95% CI 0.7 to 0.859); 0.723 (95% CI 0.649 to 0.805)), whereas preoperative non-opioid analgesics and opioids were associated with higher IRR (1.271 (95% CI 1.155 to 1.399); 3.977 (95% CI 4.409 to 3.591))., Conclusion: The high opioid demand is unexpected given that current recommendations advise using opioids only when other pain therapies are ineffective. To ensure medication safety, it is important to consider alternative treatment options and ensure that benefits outweigh potential risks., Competing Interests: Competing interests: The authors declare that they have no conflicts of interest. Helsana Group provided support in the form of salaries for authors (KW, MN, SB and EB), without having any additional role in the study design, data collection and analysis, decision to publish or preparation of the manuscript., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prevention of recurrent venous thromboembolism (VTE) is considered a main goal of VTE management. However, the extent to which physicians adhere to the recommendations from evidence-based guidelines is unknown., Aim: From a large, prospective clinical cohort, we aimed to (1) quantify the adherence of treatment recommendations to evidence-based guidelines and establish its predictors, and (2) estimate its impact on clinical outcomes and costs in patients with VTE., Methods: We included 6'243 consecutive patients with VTE treated at the university outpatient unit. Detailed clinical characteristics and treatment recommendations were recorded. Adherence of treatment recommendations to evidence-based guidelines at risk assessment was assessed in terms of duration of anticoagulant treatment. Data on death were obtained from the Swiss Central Compensation Office. Health care claims data recorded between 2014 and 2019 were retrieved from Helsana, one of the largest Swiss health insurance companies., Results: The adherence to evidence-based guidelines was 36.1%. Among patients with non-adherence, overtreatment was present in 70.1%. Significant patient-related predictors of guideline adherence were (a) age above 50 years, (b) male sex, (c) pulmonary embolism, (d) unprovoked VTE, (e) multiple VTE, (f) laboratory tests not ordered, and (g) various cardiovascular comorbidities. Non-adherence was not significantly associated with mortality, hospitalization, admission to nursing home, and costs., Conclusions: The adherence to evidence-based guidelines was low, and several unrelated predictors appeared. Although these results need to be confirmed in other settings, they highlight the need for implementation of evidence-based guidelines in clinical practice., Competing Interests: This study received funding from an unrestricted research grant of Bayer Healthcare. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. EB reports grants from Novartis, grants from MSD, grants from Vifor, grants from Bayer, grants from Swiss Cancer Research Foundation, outside the submitted work. JK reports grants from Baxalta US Inc., member of the Takeda group of companies, personal fees from Shire, member of the Takeda group of companies, personal fees from Ablynx, now part of Sanofi, personal fees from Roche, from SOBI, from Federal Office of Public Health, Switzerland, outside the submitted work; and The Hemophilia Comprehensive Care Center (HCCC) is part of the Department of Hematology and Central Hematology Laboratory, Inselspital, Bern University Hospital, which receives third party funds for the project “Interprofessional Hemophilia Care” by Bayer, CSL-Behring, Octapharma, Novo Nordisk, Roche, and Sobi. All fees or honoraria go to JK's institution Insel Gruppe AG, Inselspital, Bern University Hospital. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mertins, Nilius, Boss, Knuchel, Signorell, Huber, Blozik, Kremer Hovinga, Bachmann and Nagler.)

Background: The level of quality of care of ambulatory services in Switzerland is almost completely unknown. Since health insurance claims are the only nationwide applicable and available data source for this purpose, a set of 24 quality indicators (QI) for the measurement of quality of primary care has been previously developed and implemented. The present paper reports on an evidence-based update and extension of the initial QI set., Methods: Established pragmatic 6-step process based on informal consensus and potential QI extracted from international medical practice guidelines and pre-existing QI for primary care. Experts rated potential QI based on strength of evidence, relevance for Swiss public health, and controllability in the Swiss primary care context. Feasibility of a preliminary set of potential new QI was tested using claims data of persons with basic mandatory health insurance at one of the largest Swiss health insurers. This test built the basis for expert consensus on the final set of new QI. Additionally, two diabetes indicators included in the previous QI set were re-evaluated., Results: Of 23 potential new indicators, 19 of them were selected for feasibility testing. The expert group consented a final set of 9 additional QI covering the domains general aspects/efficiency (2 QI), diagnostic measures (1 QI), geriatric care (2 QI), osteoarthritis (1 QI), and drug safety (3 QI). Two pre-existing diabetes indicators were updated., Conclusions: Additional QI relating to overuse and intersectoral care aspects extend the options of measuring quality of primary care in Switzerland based on claims data and complement the initial QI set., (© 2022. The Author(s).)

Background: Thrombophilia screening is widely done in clinical practice, and it is claimed that the extent of venous thromboembolism (VTE) recurrence risk in patients with common defects is still not fully understood., Aim: We aimed to summarize data of all observational studies prospectively assessing the association of heterozygous factor V Leiden (FVL) mutation and recurrent VTE in patients with VTE, and to calculate pooled relative risks (RR), overall and in various subgroups., Methods: We searched MEDLINE and EMBASE databases for cohort studies prospectively assessing VTE recurrence in patients with and without FVL mutation (PROSPERO: CRD42021182800). Data were extracted on cohort and study-level. The methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). RR were calculated overall and in subgroups using a random-effects model., Results: From 31 cohorts, 24 studies were finally included summarizing 13,571 patients. Heterozygous FVL mutation was identified in 2,840 individuals (21%). The methodological quality was estimated to be high in 20 studies (83%). The overall RR was 1.46 (95% CI: 1.31, 1.64), consistent across subgroups., Conclusions: Pooling all high-quality epidemiological data, the risk of recurrent VTE was increased by 46% in patients with heterozygous FVL mutation. Against the background of established risk factors, the FVL mutation plays only a marginal role in the risk assessment for recurrent VTE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Eppenberger, Nilius, Anagnostelis, Huber and Nagler.)

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is routinely used for bacterial identification. It would be highly beneficial to also be able to use the technology as a fast way to detect clinically relevant clones of bacterial species. However, studies to this aim have often had limited success. The methods used for data acquisition, processing and data interpretation are highly diverse amongst studies on MALDI-TOF MS sub-species typing. In addition to this, feasibility may depend on the bacterial species and strains investigated, making it difficult to determine what methods may or may not work. In our paper, we have reviewed recent research on MALDI-TOF MS typing of bacterial strains. Although we found a lot of variation amongst the methods used, there were approaches shared by multiple research groups. Multiple spectra of the same isolate were often combined before further analysis for strain distinction. Many groups used a protein extraction step to increase resolution in their MALDI-TOF MS results. Peaks at a high mass range were often excluded for data interpretation. Three groups have found ways to determine feasibility of MALDI-TOF MS typing for their set of strains at an early stage of their project.

Objectives: The quality of ambulatory care in Switzerland is widely unknown. Therefore, this study aimed to evaluate the recently proposed quality indicators (QIs) based on a nationwide healthcare claims database and determine their association with the risk of subsequent hospitalisation at patient-level., Design: Retrospective cohort study., Setting: Inpatient and outpatient claims data of a large health insurance in Switzerland covering all regions and population strata., Participants: 520 693 patients continuously insured during 2015 and 2016., Measures: A total of 24 QIs were obtained by adapting the existing instruments to the Swiss national context and measuring at patient-level. The association between each QI and hospitalisation in the subsequent year was assessed using multiple logistic regression models., Results: The proportion of patients with good adherence to QIs was high for the secondary prevention of diabetes and myocardial infarction (glycated haemoglobin (HbA1c) control, 89%; aspirin use, 94%) but relatively low for polypharmacy (53%) or using potentially inappropriate medications (PIMs) in the elderly (PIM, 33%). Diabetes-related indicators such as the HbA1c control were significantly associated with a lower risk of hospitalisation (OR, 0.87; 95% CI, 0.80 to 0.95), whereas the occurrence of polypharmacy and PIM increased the risk of hospitalisation in the following year (OR, 1.57/1.08; 95% CI, 1.51 to 1.64/1.05 to 1.12)., Conclusions: This is the first study to evaluate the recently presented QIs in Switzerland using nationwide real-life data. Our study suggests that the quality of healthcare, as measured by these QIs, varied. The majority of QIs, in particular QIs reflecting chronic care and medication use, are considered beneficial markers of healthcare quality as they were associated with reduced risk of hospitalisation in the subsequent year. Results from this large practical test on real-life data show the feasibility of these QIs and are beneficial in selecting the appropriate QIs for healthcare implementation in general practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A parturient with unknown thrombotic thrombocytopenic purpura (TTP) received spinal anesthesia for cesarean delivery with subsequent discovery of a platelet count of 7000 × 10/L. Neurologic recovery was normal. Limited data exist to determine the risk of spinal epidural hematoma (SEH) in severely thrombocytopenic patients because they often receive alternate labor analgesia or general anesthesia during cesarean delivery. There is reporting bias in the literature toward cases in which severely thrombocytopenic patients sustain complications after regional anesthesia. It is important to report all cases of neuraxial anesthesia in severely thrombocytopenic patients, including those such as ours, wherein patients recover normally.

Purpose: In course of the new migraine drug development on the global market it is important to quantify the current burden of migraine medication. This study aimed to estimate the comorbidity burden and its relation to healthcare costs in patients using triptans in Switzerland by analyzing a large population-based database., Methods: This retrospective cohort study was based on Swiss health insurance claims data (2015/2016). The study sample comprised adult patients with ≥1 triptan prescription in 2015. We evaluated pharmaceutically treated comorbid conditions (CCs) and costs (12 months after index prescription) of patients using triptan. Multivariable linear regression models with log-transformed outcomes were performed to identify the factors related to healthcare costs., Results: From a total of 749 092, we identified 10,090 patients using triptans (1-year prevalence of 1.35%), whereas 58.9% had ≥2 CCs. The most frequent CCs were pain- and rheumatologic-related diseases and psychological disorders. Among triptan users, the mean total healthcare costs were highest in older patients with ≥2 CCs (>64 years: migraine with ≥2 CC "12 331 SFr"). Multivariate regression analyses showed that psychological disorders had the strongest impact on healthcare costs (Coefficient: 1.29; 95%-CI: 1.27-1.31)., Conclusions: The present study provides an overview of comorbidities and its related costs in migraine patients, which helps to quantify the current burden of migraine. This is relevant as the recently licensed CGRP antagonists are likely to change current treatment schemes for migraine, which strongly depends also on the comorbidities. The present study might therefore be helpful for the future development of treatment guidelines., (© 2019 John Wiley & Sons, Ltd.)

In our current study we were identifying 26 bacterial isolates using a SCIEX 5800 TOF/TOF MALDI instrument and an external database. The results were compared with the results of a Vitek® MS system and in case of discrepancies at the species level 16s rRNA sequencing was performed for further verification., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The aim of the study was to examine the prevalence of and factors associated with antidepressant (AD) prescriptions in order to draw a comprehensive picture of prescribing practices in Switzerland., Method: We conducted a population-based, cross-sectional descriptive study using a large Swiss healthcare claims database, covering approximately 13% of the Swiss population. AD prescription was determined by identifying patients (N = 105,663) with health claims data of at least 1 AD prescription in the year 2016. AD medication was identified using ATC-codes classified by the World Health Organisation. Univariate, bivariate and multivariate analyses using logistic regression were performed., Results: The extrapolated 1-year prevalence of AD prescription was 8.7% (95% CI, 8.7-8.8) with two thirds of AD recipients being female and the average age being 59 years (SD = 19.1). The regional distribution of prescription rates varied between cantons and ranged from 6.5 to 11.7%. Logistic regression revealed higher prescription rates among females compared to males (OR: 1.52) and an increased probability of AD prescription by age up until 54 years (OR: 2.25) and ≥ 85 years (OR: 2.32). Comorbidity is associated with higher odds (OR: 3.26 with 1-2 comorbidities) and enrollment in a managed care plan (compared to standard care) with lower odds for an AD prescription (OR: 0.85)., Conclusion: This study is the first in Switzerland to describe the prevalence of and factors associated with AD prescription based on a large health claims database reflecting routine care. The results provide important information about regional variation, prescription source, and potential over-prescription in the treatment of depressive disorders.

Bimanual coordination is impaired in Parkinson's disease (PD), affecting patients' quality of life. Besides dysfunction of the basal ganglia network, alterations of cortical oscillatory coupling, particularly between prefrontal and (pre-)motoric areas, are thought to underlie this impairment. Here, we studied 16 PD patients OFF and ON medication and age-matched healthy controls recording high-resolution electroencephalography (EEG) during performance of spatially coupled and uncoupled bimanual finger movements. Dynamic causal modeling (DCM) for induced responses was used to infer task-induced effective connectivity within a network comprising bilateral prefrontal cortex (PFC), lateral premotor cortex (lPM), supplementary motor area (SMA), and primary motor cortex (M1). Performing spatially coupled movements, excitatory left-hemispheric PFC to lPM coupling was significantly stronger in controls compared to unmedicated PD patients. Levodopa-induced enhancement of this connection correlated with increased movement accuracy. During performance of spatially uncoupled movements, PD patients OFF medication exhibited inhibitory connectivity from left PFC to SMA. Levodopa intake diminished these inhibitory influences and restored excitatory PFC to lPM coupling. This restoration, however, did not improve motor function. Concluding, our results indicate that lateralization of prefrontal to premotor connectivity in PD can be augmented by levodopa substitution and is of compensatory nature up to a certain extent of complexity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: Secondary medication prevention after acute myocardial infarction (MI) is strongly recommended in international guidelines, but actual use, adherence, and outcomes in current clinical practice are largely unknown. Therefore, the aims of this study were to determine the current adherence to medications for secondary prevention after MI and to estimate the association between medication adherence and mortality and major adverse cardiovascular events (MACE) in a large real-world population., Methods: Using a large health care claims database, patients were selected who had been hospitalized with MI between 2012 and 2015 (N = 4349). Adherence to drug therapy after discharge was measured as the medication possession rate (MPR) per year (0%-100%, indicating the number of days with medication supplied relative to the total number of days) for the individual drug classes. The relationship between MPR and the risk of MACE and death was assessed by using Cox proportional hazards regression models., Findings: A high proportion of patients with low MPR (0%-79%) was observed for all drug classes (47.6% for dual antiplatelet therapy (DAPT), 23.5% for lipid-lowering drugs (LLDs), 47.3% for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and 88.1% for beta-blockers (BB). Women and elderly patients were less likely to receive LLDs. Patients with high adherence to DAPT, LLDs, and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (MPR ≥80%) had a significantly reduced risk for all-cause mortality and MACE (LLD-group)., Implications: In a real-life setting, adherence to drug therapy for secondary cardiovascular prevention after MI was only moderate. Increased use of evidence-based treatment such as DAPT and LLDs in current clinical practice may improve long-term outcomes of patients with MI. Moreover, providing clear information, improved care transition, and a close collaboration between clinicians and physicians involved in an early outpatient follow-up is required., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In most countries, surprisingly little is known on how national healthcare spending is distributed across diseases. Single-disease cost-of-illness studies cover only a few of the diseases affecting a population and in some cases lead to untenably large estimates. The objective of this study was to decompose healthcare spending in 2011, according to Swiss National Health Accounts, into 21 collectively exhaustive and mutually exclusive major disease categories. Diseases were classified following the Global Burden of Disease Study. We first assigned the expenditures directly mapping from National Health Accounts to the 21 diseases. The remaining expenditures were assigned based on diagnostic codes and clues contained in a variety of microdata sources. Expenditures were dominated by non-communicable diseases with a share of 79.4%. Cardiovascular diseases stood out with 15.6% of total spending, followed by musculoskeletal disorders (13.4%), and mental and substance use disorders (10.6%). Neoplasms (6.0% of the total) ranked only sixth, although they are the leading cause of premature death in Switzerland. These results may be useful for the design of health policies, as they illustrate how healthcare spending is influenced by the epidemiological transition and increasing life expectancy. They also provide a plausibility check for single cost-of-illness studies. Our study may serve as a starting point for further research on the drivers of the constant growth of healthcare spending.

Goals: The aim of this study was to compare upper gastrointestinal (UGI) versus lower gastrointestinal (LGI) delivery routes of fecal microbiota transplantation (FMT) for refractory or recurrent/relapsing Clostridium difficile infection (CDI)., Background: FMT has been proven to be a safe and highly effective therapeutic option for CDI. Delivery, however, could be via the UGI or LGI routes, and it is unclear as to which route provides better clinical outcome., Study: A systematic search for studies that reported the use of FMT for CDI treatment was conducted. Individual patient data that included demographic (age and sex) and clinical (route of FMT delivery, CDI outcome after FMT, and follow-up time) information were obtained. Kaplan-Meier cumulative hazard curves and Cox proportional hazard models were used to assess clinical failure after FMT by the route of delivery., Results: Data from 305 patients treated with FMT (208 via LGI route and 97 via UGI route) for CDI were analyzed. At 30 and 90 days, the risk of clinical failure was 5.6% and 17.9% in the UGI group compared with 4.9% and 8.5% in the LGI delivery route group, respectively. A time-varying analysis suggested a 3-fold increase in hazard of clinical failure for UGI delivery (hazard ratio, 3.43; 95% confidence interval, 1.32-8.93) in the period after 30 days., Conclusions: FMT delivered via the LGI seems to be the most effective route for the prevention of recurrence/relapse of CDI. A randomized controlled trial is necessary to confirm whether FMT delivered via the LGI is indeed superior to that delivered via the UGI route.