Discrepancy between antibiotic pack sizes and guideline recommendations: a real-world analysis based on claims data.

PURPOSE: Antibiotics are often only available in predefined pack sizes, which may not align with guideline recommendations. This can result in leftover pills, leading to inappropriate self-medication or waste disposal, which can both foster the development of antibiotic resistance. The magnitude of inappropriate pack sizes is largely unknown. The objective of this study was to evaluate the potential non-conformity of prescribed antibiotic pack sizes. METHODS: This retrospective observational study was based on claims data from a large Swiss health insurance company. The study analysed the prescriptions of eleven different antibiotic substances recommended for the five most common indications for antibiotics in Switzerland. All prescriptions for adult outpatients issued by general practitioners in 2022 were included and extrapolated to the entire Swiss population. Potential non-conformity was defined as a mismatch between the total dosage in a pack and the total dosage recommended. RESULTS: A total of n = 947,439 extrapolated prescriptions were analysed. In 10 of 23 of all analysed substance/indication combinations none of the prescribed packs aligned with the respective guideline recommendation. Considering pack sizes in which the total prescribed dosage of a substance did not correspond to any of the total dosages recommended in at least one of the guidelines, 31.6% of prescriptions were potentially non-conform and an estimated number of 2.7 million tablets were overprescribed. CONCLUSIONS: We found a large discrepancy between prescribed pack sizes and guideline recommendations. Since inadequately prepacked antibiotics may lead to antibiotic resistance and unnecessary waste, efforts are needed to implement alternatives like exact pill dispensing.

Prescriber-level surveillance of outpatient antimicrobial consumption to enable targeted antimicrobial stewardship: a nationwide observational study, Switzerland, 2015 to 2022.

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.

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

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

Comparison of Motivational Short Interventions to Improve Smokers' Health Behavior (The COSMOS Study): A Pragmatic Cluster-Randomized Two-Arm Trial in General Practice.

INTRODUCTION: Helping smokers to quit is an important task of general practitioners (GPs). However, achieving tobacco abstinence is difficult, and smokers who fail may still want to improve their health in other ways. Therefore, Swiss GPs developed a multithematic coaching concept that encourages health behavior changes beyond smoking cessation alone. AIMS AND METHODS: To compare the effectiveness of such coaching with state-of-the-art smoking cessation counseling, we conducted a pragmatic cluster-randomized two-arm trial with 56 GPs in German-speaking Switzerland and 149 of their cigarette smoking patients. GPs were instructed in either multithematic health coaching or smoking cessation counseling. After 12 months, we compared their patients' improvements in cigarette consumption, body weight, physical inactivity, alcohol consumption, stress, unhealthy diet, and a health behavior of their own choice, using hierarchical logistic regression models and Fisher's exact and t tests. RESULTS: Over 95% of all participants achieved clinically relevant improvements in at least one health behavior, with no difference between study arms (health coaching vs. smoking cessation counseling: aOR = 1.21, 95% CI = [0.03-50.76]; and aOR = 1.78, 95% CI = [0.51-6.25] after non-responder imputation). Rates of clinically relevant improvements in the individual health behaviors did not differ between study arms either (they were most frequent in physical activity, achieved by 3 out of 4 patients), nor did the extent of the improvements. CONCLUSIONS: Multithematic health coaching and state-of-the art smoking cessation counseling were found to be comparable interventions, both in terms of smoking cessation success and, quite unexpectedly, their effects on other health behaviors. IMPLICATIONS: The findings of our study suggest that in general practice, multithematic health coaching is an effective smoking cessation intervention, and conversely, monothematic smoking cessation counseling also achieves the beneficial effects of a multithematic health behavior intervention. This opens up the possibility for GPs to support their smoking patients in improving their health behavior in additional and more flexible ways.

[Shared Decision-Making in Preventive Activities]. / Shared Decision-Making in der Prävention.

Shared Decision-Making in Preventive Activities Abstract. Shared Decision-Making (SDM) is particularly useful in conditions where decisions are preference-sensitive, i.e., where preferences and values of patients are crucial for the further proceeding. This typically applies to conditions where the potential benefit and the potential harm are similar. Preventive activities are characterized by the fact that there is no current burden of disease and the benefit to expect is far in the future. Therefore, it is preference-sensitive if the current effort really pays off. The procedure of SDM in (preventive) counselling can be classified into three steps: Team Talk, Option Talk and Decision Talk. For every step, we present examples of how to talk. After an overview of the current evidence, we present four examples of how to apply SDM in preventive conditions: quit-smoking counselling, lifestyle coaching, vaccination counselling and screening for cancer. Finally, we focus on the role of activated patients and point out the opportunity for SDM during check-up examinations. For all these implementation issues useful tools and links are presented. In summary, important elements of SDM, such as patient centeredness, clarifying needs/goals and shared responsibility, are crucial for the entire spectre of caring for patients, not only for prevention.

Swiss GPs' preferences for antidepressant treatment in mild depression: vignette-based quantitative analysis.

BACKGROUND: GPs frequently prescribe antidepressants in mild depression. The aim of this study was to examine, how often Swiss GPs recommend antidepressants in various clinical presentations of mild depression and which factors contribute to antidepressant treatment recommendations. METHODS: We conducted an online survey among Swiss GPs with within-subject effect analysis. Alternating case vignettes described a typical female case of mild depression according to International Classification of Diseases, 10th edition criteria, with and without anxiety symptoms and sleep problems. GPs indicated for each vignette their preferred treatments (several recommendations were possible). Additionally, we assessed GP characteristics, attitudes towards depression treatments, and elements of clinical decision-making. RESULTS: Altogether 178 GPs completed the survey. In the initial description of a case with mild depression, 11% (95%-CI: 7%-17%) of GPs recommended antidepressants. If anxiety symptoms were added to the same case, 29% (23%-36%) recommended antidepressants. If sleep problems were mentioned, 47% (40%-55%) recommended antidepressants, and if both sleep problems and anxiety symptoms were mentioned, 63% (56%-70%) recommended antidepressants. Several factors were independently associated with increased odds of recommending antidepressants, specifically more years of practical experience, an advanced training in psychosomatic and psychosocial medicine, self-dispensation, and a higher perceived effectiveness of antidepressants. By contrast, a higher perceived influence of patient characteristics and the use of clinical practice guidelines were associated with reduced odds of recommending antidepressants. CONCLUSIONS: Consistent with depression practice guidelines, Swiss GPs rarely recommended antidepressants in mild depression if no co-indications (i.e., sleep problems and anxiety symptoms) were depicted. However, presence of sleep problems and anxiety symptoms, many years of practical experience, overestimation of antidepressants' effectiveness, self-dispensation, an advanced training in psychosomatic and psychosocial medicine, and non-use of clinical practice guidelines may independently lead to antidepressant over-prescribing.

["Smarter Medicine" in ambulatory general internal medicine, at present and in future]. / Smarter Medicine in der ambulanten Allgemeinen Inneren Medizin.

"Smarter Medicine" in ambulatory general internal medicine, at present and in future Abstract. Overuse and inappropriate care resulting in potential harm and unwarranted waste of healthcare resources were leading to the international "Choosing Wisely" campaign (CWC) almost a decade ago. In Switzerland, the movement started 2014 / 15 under the label "Smarter Medicine", with a top-5 list of interventions better to avoid in ambulatory general internal medicine (GIM). Yet from the beginning of the international CWC campaign, its effectiveness has been questioned, and we don't know if the "Smarter Medicine" top-5 list for ambulatory GIM efficiently is reducing overuse and inappropriate care, as there is almost no evaluation data available. The prerequisites for an efficient reduction of overuse and inappropriate care are a. the scientific evidence for the recommendations, b. the recommendations coming from a trusted source, c. reliable data for the evaluation, d. the active role of patients, the public, professional healthcare societies and politicians. Another key factor for a successful implementation is the involvement of the final users at an early stage of recommendation development. Keeping this in mind, we recently developed new suggestions for interventions better to avoid, in collaboration with 538 general practitioners. These suggestions lead to a next top-5 list for the ambulatory GIM.

[Prevention of low-value care: What's the role of the general practitioner?] / Prävention von Fehl- und Überversorgung.

Prevention of low-value care: What's the role of the general practitioner? Abstract. Low-value care, defined as inappropriate care (potential harm exceeding the benefit) or overuse (unnecessary care), is a challenge for patients, healthcare providers, politicians and healthcare systems. We give some examples of low-value interventions in Switzerland. There are many triggers of low-value care. For example, new technology may lead to an earlier detection of disease but this is not necessarily translating into a benefit for the patient (overdiagnosis). Other reasons are organizational shortcomings, supply-driven demand, commercially motivated extension of disease definitions (disease mongering), and the impact of social or cultural beliefs. Correspondingly, it's not a simple task to tackle low-value care. As an answer, several concepts and campaigns have been developed during the last few years, such as Quaternary Prevention, Choosing Wisely or Preventing Overdiagnosis. Their aim is to protect individuals from medical interventions that are likely to cause more harm than benefit. What's the role of the general practitioner (GP) in the prevention of low-value care? First, to be aware of such inappropriate interventions and to be open-minded to question the own professional attitude. Second, as a trusted person by the patient, the GP has the unique opportunity to balance benefit and harm of an intervention together with the patient and to discuss these issues in a participative way (shared decision making), using techniques like team talk, option talk and decision talk. In summary, the protection of patients from inappropriate care, overuse and harm is an important part of our professional performance.

Interaction Energetics and Druggability of the Protein-Protein Interaction between Kelch-like ECH-Associated Protein 1 (KEAP1) and Nuclear Factor Erythroid 2 Like 2 (Nrf2).

Development of small molecule inhibitors of protein-protein interactions (PPIs) is hampered by our poor understanding of the druggability of PPI target sites. Here, we describe the combined application of alanine-scanning mutagenesis, fragment screening, and FTMap computational hot spot mapping to evaluate the energetics and druggability of the highly charged PPI interface between Kelch-like ECH-associated protein 1 (KEAP1) and nuclear factor erythroid 2 like 2 (Nrf2), an important drug target. FTMap identifies four binding energy hot spots at the active site. Only two of these are exploited by Nrf2, which alanine scanning of both proteins shows to bind primarily through E79 and E82 interacting with KEAP1 residues S363, R380, R415, R483, and S508. We identify fragment hits and obtain X-ray complex structures for three fragments via crystal soaking using a new crystal form of KEAP1. Combining these results provides a comprehensive and quantitative picture of the origins of binding energy at the interface. Our findings additionally reveal non-native interactions that might be exploited in the design of uncharged synthetic ligands to occupy the same site on KEAP1 that has evolved to bind the highly charged DEETGE binding loop of Nrf2. These include π-stacking with KEAP1 Y525 and interactions at an FTMap-identified hot spot deep in the binding site. Finally, we discuss how the complementary information provided by alanine-scanning mutagenesis, fragment screening, and computational hot spot mapping can be integrated to more comprehensively evaluate PPI druggability.

Effect of a patient-centred deprescribing procedure in older multimorbid patients in Swiss primary care - A cluster-randomised clinical trial.

BACKGROUND: Management of patients with polypharmacy is challenging, and evidence for beneficial effects of deprescribing interventions is mixed. This study aimed to investigate whether a patient-centred deprescribing intervention of PCPs results in a reduction of polypharmacy, without increasing the number of adverse disease events and reducing the quality of life, among their older multimorbid patients. METHODS: This is a cluster-randomised clinical study among 46 primary care physicians (PCPs) with a 12 months follow-up. We randomised PCPs into an intervention and a control group. They recruited 128 and 206 patients if ≥60 years and taking ≥five drugs for ≥6 months. The intervention consisted of a 2-h training of PCPs, encouraging the use of a validated deprescribing-algorithm including shared-decision-making, in comparison to usual care. The primary outcome was the mean difference in the number of drugs per patient (dpp) between baseline and after 12 months. Additional outcomes focused on patient safety and quality of life (QoL) measures. RESULTS: Three hundred thirty-four patients, mean [SD] age of 76.2 [8.5] years participated. The mean difference in the number of dpp between baseline and after 12 months was 0.379 in the intervention group (8.02 and 7.64; p = 0.059) and 0.374 in the control group (8.05 and 7.68; p = 0.065). The between-group comparison showed no significant difference at all time points, except for immediately after the intervention (p = 0.002). There were no significant differences concerning patient safety nor QoL measures. CONCLUSION: Our straight-forward and patient-centred deprescribing procedure is effective immediately after the intervention, but not after 6 and 12 months. Further research needs to determine the optimal interval of repeated deprescribing interventions for a sustainable effect on polypharmacy at mid- and long-term. Integrating SDM in the deprescribing process is a key factor for success. TRIAL REGISTRATION: Current Controlled Trials, prospectively registered ISRCTN16560559 Date assigned 31/10/2014. The Prevention of Polypharmacy in Primary Care Patients Trial (4P-RCT).

A cross-sectional study of Swiss ambulatory care services use by multimorbid patients in primary care in the light of the Andersen model.

BACKGROUND: Multimorbidity is frequently encountered in primary care and is associated with increasing use of healthcare services. The Andersen Behavioral Model of Health Services Use is a multilevel framework classifying societal, contextual, and individual characteristics about the use of healthcare services into three categories: 1. predisposing factors, 2. enabling factors, and 3. need factors. The present study aimed to explore multimorbid patients' use of ambulatory healthcare in terms of homecare and other allied health services, visits to GPs, and number of specialists involved. A secondary aim was to apply Andersen's model to explore factors associated with this use. METHOD: In a cross-sectional study, 100 Swiss GPs enrolled up to 10 multimorbid patients each. After descriptive analyses, we tested the associations of each determinant and outcome variable of healthcare use, according to the Andersen model: predisposing factors (patient's demographics), enabling factors (health literacy (HLS-EU-Q6), deprivation (DipCare)), and need factors (patient's quality of life (EQ-5D-3L), treatment burden (TBQ), severity index (CIRS), number of chronic conditions, and of medications). Logistic regressions (dichotomous variables) and negative binomial regressions (count variables) were calculated to identify predictors of multimorbid patients' healthcare use. RESULTS: Analyses included 843 multimorbid patients; mean age 73.0 (SD 12.0), 28-98 years old; 48.3% men; 15.1% (127/843) used homecare. Social deprivation (OR 0.75, 95%CI 0.62-0.89) and absence of an informal caregiver (OR 0.50, 95%CI 0.28-0.88) were related to less homecare services use. The use of other allied health services (34.9% (294/843)) was associated with experiencing pain (OR 2.49, 95%CI 1.59-3.90). The number of contacts with a GP (median 11 (IQR 7-16)) was, among other factors, related to the absence of an informal caregiver (IRR 0.90, 95%CI 0.83-0.98). The number of specialists involved (mean 1.9 (SD 1.4)) was linked to the treatment burden (IRR 1.06, 95%CI 1.02-1.10). CONCLUSION: Multimorbid patients in primary care reported high use of ambulatory healthcare services variably associated with the Andersen model's factors: healthcare use was associated with objective medical needs but also with contextual or individual predisposing or enabling factors. These findings emphasize the importance of adapting care coordination to individual patient profiles.

A Central Region of NF-κB Essential Modulator Is Required for IKKß-Induced Conformational Change and for Signal Propagation.

NF-κB essential modulator (NEMO) regulates NF-κB signaling by acting as a scaffold for the kinase IKKß to direct its activity toward the NF-κB inhibitor, IκBα. Here, we show that a highly conserved central region of NEMO termed the intervening domain (IVD, amino acids 112-195) plays a key role in NEMO function. We determined a structural model of full-length NEMO by small-angle X-ray scattering and show that full-length, wild-type NEMO becomes more compact upon binding of a peptide comprising the NEMO binding domain of IKKß (amino acids 701-745). Mutation of conserved IVD residues (9SG-NEMO) disrupts this conformational change in NEMO and abolishes the ability of NEMO to propagate NF-κB signaling in cells, although the affinity of 9SG-NEMO for IKKß compared to that of the wild type is unchanged. On the basis of these results, we propose a model in which the IVD is required for a conformational change in NEMO that is necessary for its ability to direct phosphorylation of IκBα by IKKß. Our findings suggest a molecular explanation for certain disease-associated mutations within the IVD and provide insight into the role of conformational change in signaling scaffold proteins.

Barriers and enablers for deprescribing among older, multimorbid patients with polypharmacy: an explorative study from Switzerland.

BACKGROUND: Polypharmacy is an increasing problem, leading to increased morbidity and mortality, especially in older, multimorbid patients. Consequently, there is a need for reduction of polypharmacy. The aim of this study was to explore attitudes, beliefs, and concerns towards deprescribing among older, multimorbid patients with polypharmacy who chose not to pursue at least one of their GP's offers to deprescribe. METHODS: Exploratory study using telephone interviews among patients of a cluster-randomized study in Northern Switzerland. The interview included a qualitative part consisting of questions in five pre-defined key areas of attitudes, beliefs, and concerns about deprescribing and an open explorative question. The quantitative part consisted of a rating of pre-defined statements in these areas. RESULTS: Twenty-two of 87 older, multimorbid patients with polypharmacy, to whom their GP offered a drug change, did not pursue all offers. Nineteen of these 22 were interviewed by telephone. The 19 patients were on average 76.9 (SD 10.0) years old, 74% female, and took 8.9 (SD 2.6) drugs per day. Drugs for acid-related disorders, analgesics and anti-inflammatory drugs were the three most common drug groups where patient involvement and the shared-decision-making (SDM) process led to the joint decision to not pursue the GPs offer. Eighteen of 19 patients fully trusted their GP, 17 of 19 participated in SDM even before this study and 8 of 19 perceived polypharmacy as a substantial burden. Conservatism/inertia and fragmented medical care were the main barriers towards deprescribing. No patient felt devalued as a consequence of the deprescribing offer. Our exploratory findings were supported by patients' ratings of predefined statements. CONCLUSION: We identified patient involvement in deprescribing and coordination of care as key issues for deprescribing among older multimorbid patients with polypharmacy. GPs concerns regarding patients' devaluation should not prevent them from actively discussing the reduction of drugs. TRIAL REGISTRATION: ISRCTN16560559 .

Factors associated with patients' and GPs' assessment of the burden of treatment in multimorbid patients: a cross-sectional study in primary care.

BACKGROUND: Multimorbid patients may experience a high burden of treatment. This has a negative impact on treatment adherence, health outcomes and health care costs. The objective of our study was to identify factors associated with the self-perceived burden of treatment of multimorbid patients in primary care and to compare them with factors associated with GPs assessment of this burden. METHOD: A cross sectional study in general practices, 100 GPs in Switzerland and up to 10 multimorbid patients per GP. Patients reported their self-perceived burden of treatment using the Treatment Burden Questionnaire (TBQ, possible score 0-150), whereas GPs evaluated the burden of treatment on a Visual Analog Scale (VAS) from 1 to 9. The study explored medical, social and psychological factors associated with burden of treatment, such as number and type of chronic conditions and drugs, severity of chronic conditions (CIRS score), age, quality of life, deprivation, health literacy. RESULTS: The GPs included 888 multimorbid patients. The overall median TBQ was 20 and the median VAS was 4. Both patients' and GPs' assessment of the burden of treatment were inversely associated with patients' age and quality of life. In addition, patients' assessment of their burden of treatment was associated with a higher deprivation score and lower health literacy, and with having diabetes or atrial fibrillation, whereas GPs' assessment of this burden was associated with the patient having a greater number of chronic conditions and drugs, and a higher CIRS score. CONCLUSION: Both from patients' and GPs' perspectives TB appears to be higher in younger patients. Whereas for patients the burden of treatment is associated with socio-economic and psychological factors, GPs' assessments of this burden are associated with medical factors. Including socio-economic and psychological factors on patients' self-perception is likely to improve GPs' assessments of their patients' burden of treatment thus favoring patient-centered care.

Correction to: The effects of shared decision-making compared to usual care for prostate cancer screening decisions: a systematic review and meta-analysis.

Following publication of the original article [1], the authors notified us of a misleading data presentation in Table 4.

The effects of shared decision-making compared to usual care for prostate cancer screening decisions: a systematic review and meta-analysis.

BACKGROUND: Shared decision-making (SDM) is recommended for men facing prostate cancer (PC) screening decisions. We synthesize the evidence on the comparative effectiveness of SDM with usual care. METHODS: We searched academic and grey literature databases, and other sources for primary randomised controlled trials (RCTs) published in English comparing SDM to usual care and conducted in primary and specialised care. We assessed the individual study risk of bias, and calculated the study-specific and pooled relative risks (RR) or standardised mean differences (SMD) [with 95% confidence intervals (CI)] to perform random-effects meta-analyses for SDM-related and patient outcomes. RESULTS: Four RCTs comparing SDM to usual care, involving 1760 men, were included. SDM improved knowledge (SMD 0.23, 95%CI 0.02 to 0.43; 2 RCTs), but was not different to usual care in reducing either patient participation in prostate-specific antigen (PSA) testing (RR 1.03, 95%CI 0.90 to 1.19; 2 RCTs) or decisional conflict (SMD -0.04, 95%CI -0.23 to 0.15; SMD -0.05, 95%CI -0.24 to 0.14; 2 RCTs). Individual trial estimates (46.7%) also suggest that SDM may reduce or neutralise physicians' tendency for PSA screening, and may improve the accuracy of patients' perception of lifetime-risks and men's views towards screening. There was no evidence on the effects of SDM on health outcomes. The studies represent various interventions and outcomes and are prone to risk of bias. CONCLUSIONS: There is currently insufficient evidence to support a clear association of SDM on patient- and SDM-related outcomes for decisions about PSA testing. Further research needs to assess the clinical effectiveness of SDM using well-defined SDM interventions and outcomes. It should address the absence of evidence, particularly on health outcomes.

Appropriateness of bone density measurement in Switzerland: a cross-sectional study.

BACKGROUND: According to the WHO, osteoporosis is one of the most important non- communicable diseases worldwide. Different screening procedures are controversially discussed, especially concerning the concomitant issues of overdiagnosis and harm caused by inappropriate Dual X-ray Absorptiometry (DXA). The aim of this study was to evaluate the frequency and appropriateness of DXA as screening measure in Switzerland considering individual risk factors and to evaluate covariates independently associated with potentially inappropriate DXA screening. METHODS: Retrospective cross-sectional study using insurance claim data of 2013. Among all patients with DXA screening, women < 65 and men < 70 years without osteoporosis or risk factors for osteoporosis were defined as receiving potentially inappropriate DXA. Statistics included descriptive measures and multivariable regressions to estimate associations of relevant covariates with potentially inappropriate DXA screening. RESULTS: Of 1,131,092 patients, 552,973 were eligible. Among those 2637 of 10,000 (26.4%) underwent potentially inappropriate DXA screening. Female sex (Odds ratio 6.47, CI 6.41-6.54) and higher age showed the strongest association with any DXA screening. Female gender (Odds ratio 1.84, CI 1.49-2.26) and an income among the highest 5% (Odds ratio 1.40, CI 1.01-1.98) were significantly positively associated with potentially inappropriate DXA screening, number of chronic conditions (Odds ratio 0.67, CI 0.65-0.70) and living in the central region of Switzerland (Odds ratio 0.67, CI 0.48-0.95) negatively. CONCLUSION: One out of four DXAs for screening purpose is potentially inappropriate. Stakeholders of osteoporosis screening campaigns should focus on providing more detailed information on appropriateness of DXA screening indications (e.g. age thresholds) in order to avoid DXA overuse.

Multimorbidity: can general practitioners identify the health conditions most important to their patients? Results from a national cross-sectional study in Switzerland.

BACKGROUND: Faced with patients suffering from more than one chronic condition, or multimorbidity, general practitioners (GPs) must establish diagnostic and treatment priorities. Patients also set their own priorities to handle the everyday burdens associated with their multimorbidity and these may be different from the priorities established by their GP. A shared patient-GP agenda, driven by knowledge of each other's priorities, would seem central to managing patients with multimorbidity. We evaluated GPs' ability to identify the health condition most important to their patients. METHODS: Data on 888 patients were collected as part of a cross-sectional Swiss study on multimorbidity in family medicine. For the main analyses on patients-GP agreement, data from 572 of these patients could be included. GPs were asked to identify the two conditions which their patient considered most important, and we tested whether either of them agreed with the condition mentioned as most important by the patient. In the main analysis, we studied the agreement rate between GPs and patients by grouping items medically-related into 46 groups of conditions. Socio-demographic and clinical variables were fitted into univariate and multivariate models. RESULTS: In 54.9% of cases, GPs were able to identify the health condition most important to the patient. In the multivariate model, the only variable significantly associated with patient-GP agreement was the number of chronic conditions: the higher the number of conditions, the less likely the agreement. CONCLUSION: GPs were able to correctly identify the health condition most important to their patients in half of the cases. It therefore seems important that GPs learn how to better adapt treatment targets and priorities by taking patients' perspectives into account.

Ligand deconstruction: Why some fragment binding positions are conserved and others are not.

Fragment-based drug discovery (FBDD) relies on the premise that the fragment binding mode will be conserved on subsequent expansion to a larger ligand. However, no general condition has been established to explain when fragment binding modes will be conserved. We show that a remarkably simple condition can be developed in terms of how fragments coincide with binding energy hot spots--regions of the protein where interactions with a ligand contribute substantial binding free energy--the locations of which can easily be determined computationally. Because a substantial fraction of the free energy of ligand binding comes from interacting with the residues in the energetically most important hot spot, a ligand moiety that sufficiently overlaps with this region will retain its location even when other parts of the ligand are removed. This hypothesis is supported by eight case studies. The condition helps identify whether a protein is suitable for FBDD, predicts the size of fragments required for screening, and determines whether a fragment hit can be extended into a higher affinity ligand. Our results show that ligand binding sites can usefully be thought of in terms of an anchor site, which is the top-ranked hot spot and dominates the free energy of binding, surrounded by a number of weaker satellite sites that confer improved affinity and selectivity for a particular ligand and that it is the intrinsic binding potential of the protein surface that determines whether it can serve as a robust binding site for a suitably optimized ligand.

Inappropriate use of arthroscopic meniscal surgery in degenerative knee disease.

Background and purpose - Current evidence suggests that arthroscopic knee surgery has no added benefit compared with non-surgical management in degenerative meniscal disease. Yet in many countries, arthroscopic partial meniscectomy (APM) remains among the most frequently performed surgeries. This study quantifies and characterizes the dynamics of the current use of knee arthroscopies in Switzerland in a distinctively non-traumatic patient group. Methods - We assessed a non-accident insurance plan of a major Swiss health insurance company for surgery rates of APM, arthroscopic debridement and lavage in patients over the age of 40, comparing the years 2012 and 2015. Claims were analyzed for prevalence of osteoarthritis, related interventions and the association of surgery with insurance status. Results - 648,708 and 647,808 people were examined in 2012 and 2015, respectively. The incidence of APM, debridement, and lavage was 388 per 105 person-years in 2012 and 352 per 105 person-years in 2015 in non-traumatic patients over the age of 40, consisting mostly of APM (96%). Between years, APM surgery rates changed in patients over the age of 65 (p < 0.001) but was similar in patients aged 40-64. Overall prevalence of osteoarthritis was 25%. Insurance status was independently associated with arthroscopic knee surgery. Interpretation - APM is widely used in non-traumatic patients in Switzerland, which contrasts with current evidence. Many procedures take place in patients with degenerative knee disease. Surgery rates were similar in non-traumatic middle-aged patients between 2012 and 2015. Accordingly, the potential of inappropriate use of APM in non-traumatic patients in Switzerland is high.