Determinants of health-related quality of life in healthy children and adolescents during the COVID-19 pandemic: Results from a prospective longitudinal cohort study.

Understanding health-related quality of life (HRQOL) in children and adolescents, during a pandemic and afterwards, aids in understanding how circumstances in their lives impact their well-being. We aimed to identify determinants of HRQOL from a broad range of biological, psychological, and social factors in a large longitudinal population-based sample. Data was taken from a longitudinal sample (n = 1843) of children and adolescents enrolled in the prospective school-based cohort study Ciao Corona in Switzerland. The primary outcome was HRQOL, assessed using the KINDL total score and its subscales (each from 0, worst, to 100, best). Potential determinants, including biological (physical activity, screen time, sleep, etc.), psychological (sadness, anxiousness, stress), and social (nationality, parents' education, etc.) factors, were assessed in 2020 and 2021 and HRQOL in 2022. Determinants were identified in a data-driven manner using recursive partitioning to define homogeneous subgroups, stratified by school level. Median KINDL total score in the empirically identified subgroups ranged from 68 to 83 in primary school children and from 69 to 82 in adolescents in secondary school. The psychological factors sadness, anxiousness, and stress in 2021 were identified as the most important determinants of HRQOL in both primary and secondary school children. Other factors, such as physical activity, screen time, chronic health conditions, or nationality, were determinants only in individual subscales. CONCLUSION: Recent mental health, more than biological, physical, or social factors, played a key role in determining HRQOL in children and adolescents during pandemic times. Public health strategies to improve mental health may therefore be effective in improving HRQOL in this age group. WHAT IS KNOWN: • Assessing health-related quality of life (HRQOL) in children and adolescents aids in understanding how life circumstances impact their well-being. • HRQOL is a complex construct, involving biological, psychological, and social factors. Factors driving HRQOL in children and adolescents are not often studied in longitudinal population-based samples. WHAT IS NEW: • Mental health (stress, anxiousness, sadness) played a key role in determining HRQOL during the coronavirus pandemic, more than biological or social factors. • Public health strategies to improve mental health may be effective in improving HRQOL in children.

Perioperative outcome assessment from the perspectives of different stakeholders: need for reconsideration?

Standardised and universal perioperative endpoint reporting are the cornerstone for outcomes assessment, reliable clinical trials, and health services research. The Outcome4medicine initiative recently reported consensus recommendations on how to assess the quality of surgical interventions, proposing a framework for surgical outcome assessment and quality improvement after medical interventions. In the same field, the Standardised Endpoints in Perioperative Medicine - Core Outcome Measures for Perioperative and Anaesthetic Care (StEP-COMPAC) group recently proposed standardised and valid measures of mortality and morbidity, derived from a three-stage Delphi process. Here a core group of the Outcome4medicine conference discusses how these two initiatives are aligned and emphasises the importance of standardised outcome assessment by integrating the perspectives of different stakeholders.

Needs assessment in community-dwelling older adults toward digital interventions to promote physical activity: Cross-sectional survey study.

Background: Tackling physical inactivity represents a key global public health challenge. Strategies to increase physical activity (PA) are therefore warranted. Despite the rising availability of digital interventions (DIs), which offer tremendous potential for PA promotion, there has been inadequate attention to the special needs of older adults. Objective: The aim was to investigate community-dwelling older adults' needs, requirements, and preferences toward DIs to promote PA. Methods: The target population of this cross-sectional study was community-dwelling older adults (≥60 years old) within German-speaking Switzerland. Potential respondents were informed about the study and sent a link to a self-developed and self-administered online survey by our cooperating institutions. Results: Overall, 922 respondents who completed the online survey were included in the final analysis. The mean age of the sample was 72 years (SD 6.4, range 60-98). The preferred delivery mode of DIs to promote PA was a website (428/922, 46.4%) and 80.3% (740/922) preferred video-based structures. Most respondents expressed the need for personal access, personal goals, personal messages, and a personal contact in case of problems or questions (585/817, 71.6%; 546/811, 67.3%; 536/822, 65.2%; 536/822, 65.2%). Memory training, psychological wellbeing, and nutrition were mainly rated as relevant additional content of DIs to promote PA (690/849, 81.2%; 661/845, 78.2%, 619/849, 72.9%). Conclusion: Community-dwelling older adults may be willing to use DIs to promote PA in the long term, but this study identified particular needs and requirements in terms of design, technological realization, delivery mode, support, and individualization/personalization among the sample. Our results can inform future developments of DIs to promote PA specifically tailored to older adults. However, caution is warranted in interpreting the findings due to the sample's high PA and education levels.

Certainty of the Global Burden of Disease 2019 Modelled Prevalence Estimates for Musculoskeletal Conditions: A Meta-Epidemiological Study.

Objectives: To describe and assess the risk of bias of the primary input studies that underpinned the Global Burden of Disease Study (GBD) 2019 modelled prevalence estimates of low back pain (LBP), neck pain (NP), and knee osteoarthritis (OA), from Australia, Brazil, Canada, Spain, and Switzerland. To evaluate the certainty of the GBD modelled prevalence evidence. Methods: Primary studies were identified using the GBD Data Input Sources Tool and their risk of bias was assessed using a validated tool. We rated the certainty of modelled prevalence estimates based on the GRADE Guidelines 30-the GRADE approach for modelled evidence. Results: Seventy-two primary studies (LBP: 67, NP: 2, knee OA: 3) underpinned the GBD estimates. Most studies had limited representativeness of their study populations, used suboptimal case definitions and applied assessment instruments with unknown psychometric properties. The certainty of modelled prevalence estimates was low, mainly due to risk of bias and indirectness. Conclusion: Beyond the risk of bias of primary input studies for LBP, NP, and knee OA in GBD 2019, the certainty of country-specific modelled prevalence estimates still have room for improvement.

A discrete choice experiment on price and flavour effects on the appeal of nicotine products: a pilot study among young adults in Switzerland.

AIMS: To explore the effects of prices and flavour availability on the appeal of different tobacco and nicotine products, including conventional cigarettes, Electronic Nicotine Delivery Systems (ENDS) and Heated Tobacco Systems (HTS) among an adult population in Switzerland. METHODS: We performed a Discrete Choice Experiment among a group of Swiss aged ≥18 years via the online recruiting platform Prolific in a convenience sample. Our sample included both non-smokers and smokers. We used a within-subject, alternative-specific block design in a series of choice sets including different smoking products. We fixed the attributes of nicotine content (high or medium) and harmfulness (in years of life lost) for each product. Attributes of interest included price (ranging from CHF 5 to 25 in increments of 5) and flavour (fruity/menthol vs none/tobacco flavour). We performed a conditional logistic regression on the attributes' influence on the appeal of cigarettes, ENDS and HTS. RESULTS: A total of 108 out of 153 participants (n = 25 smokers and n = 83 non-smokers, completion rate = 71%) successfully completed our pilot survey experiment. We found that, in general, increasing the price of combustible cigarettes, ENDS and HTS by one standard deviation (around CHF 7) reduced their appeal by approximately 66% (relative risk [RR]: 0.34; 95% CI: 0.28-0.42). Unflavoured alternative nicotine products were found to be less appealing than flavoured products, especially for non-smokers, with a 86% decrease in appeal (RR: 0.14; 95% CI: 0.13-0.16). For non-smokers, an increase in price by one standard deviation was associated with a decrease in the appeal of any product by approximately 19% (RR: 0.81; 95% CI: 0.72-0.92). For smokers, the effect sizes were smaller, but overall, the appeal of all products decreased with increasing prices and reduced flavours. CONCLUSIONS: Our Discrete Choice Experiment suggests that, for the Swiss context, limiting the availability of flavours for alternative smoking products has the potential to reduce their appeal to non-smokers by 86% and that a small but significant increase in prices to CHF 15 for cigarettes, ENDS and HTS could lead to a major (around 66%) decrease in their appeal.

Survival modelling and cost-effectiveness analysis of treatments for newly diagnosed metastatic hormone-sensitive prostate cancer.

BACKGROUND: In metastatic hormone-sensitive prostate cancer (mHSPC) treatment, survival benefits have been shown by adding docetaxel or recent androgen receptor axis-targeted therapies (ARATs) abiraterone, apalutamide, or enzalutamide to androgen deprivation therapy (ADT). However, the optimal treatment strategy in terms of costs and effects is unclear, not least due to high ARAT costs. METHODS: To assess treatment cost-effectiveness, we developed a Markov cohort model with health states of progression-free disease, progressive disease and death for men with newly diagnosed mHSPC, with a 30-year time horizon. Survival data, adverse events and utilities were informed by randomized controlled trial results, our meta-analysis of re-created individual patient survival data, and publicly available sources of unit costs. We applied a Swiss healthcare payer perspective and discounted costs and effects by 3%. RESULTS: We found a significant overall survival benefit for ADT+abiraterone versus ADT+docetaxel. The corresponding incremental cost-effectiveness ratio (ICER) was predicted to be EUR 39,814 per quality-adjusted life-year (QALY) gained. ADT+apalutamide and ADT+enzalutamide incurred higher costs and lower QALYs compared to ADT+abiraterone. For all ARATs, drug costs constituted the most substantial cost component. Results were stable except for a large univariable reduction in the pre-progression utility under ADT+abiraterone and very large variations in drug prices. CONCLUSIONS: Our model projected ADT+abiraterone to be cost-effective compared to ADT+docetaxel at a willingness-to-pay threshold of EUR 70,400/QALY (CHF 100,000 applying purchasing power parities). Given lower estimated QALYs for ADT+apalutamide and ADT+enzalutamide compared to ADT+abiraterone, the former only became cost-effective (the preferred) treatment option(s) at substantial 75-80% (80-90%) price reductions.

Performance Score (T2D)-A New Perspective in the Assessment of Six-Minute Walking Tests in Pulmonary Rehabilitation.

Because absolute changes in outcomes are difficult to interpret and the minimal clinically important difference (MCID) is not suitable to address this challenge, a novel method of classifying outcomes by relating changes to baseline values is warranted. We used the "performance score" (T2D), which reflects individual performance, enabling us to consider the functional status at the beginning of rehabilitation without dealing with the problems of mathematical coupling or regression effects, as encountered in ANCOVA. To illustrate the T2D, we retrospectively analyzed changes in the six-minute walking test (6MWT) in COPD patients undergoing outpatient pulmonary rehabilitation and compared the results with absolute differences related to a predetermined MCID. We evaluated a total of 575 COPD patients with a mean age of 61.4 ± 9.2 years. 6MWT improved significantly, with a mean change of 32.3 ± 71.2. A total of 105/311 participants who had reached the MCID were still classified as "below average" by the T2D. Conversely, 76/264 patients who had not reached the MCID were classified as "above average". This new performance measure accounts for the patient's current status and for changes over time, potentially representing a simple and user-friendly tool that can be used to quantify a patient's performance and response to rehabilitation.

Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement-the Mobilise-D study protocol.

BACKGROUND: The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. METHODS/DESIGN: The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson's Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. DISCUSSION: The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility. TRIAL REGISTRATION: ISRCTN12051706.

Fingolimod versus interferon beta 1-a: Benefit-harm assessment approach based on TRANSFORMS individual patient data.

Background: Fingolimod is a disease-modifying drug approved for multiple sclerosis but its benefit-harm balance has never been assessed compared to other active treatments. Objectives: Our aim was to compare the benefits and harms of fingolimod with interferon beta-1a using individual patient data from TRial Assessing injectable interferon versus FTY720 Oral in RRMS trial. Methods: We modelled the health status of patients over time including Expanded Disability Status Scale measurements, relapses and any adverse events. We assessed the mean health status between arms and the proportion of patients whose health deteriorated or improved relatively to baseline, using a prespecified minimal important difference of 4.6. We performed sensitivity analyses to test our assumptions. Results: Main and sensitivity analyses favoured fingolimod 0.5 mg over interferon beta-1a. The average health status difference was 1.01 (95% CI 0.93-1.08). Patients on fingolimod 0.5 mg were 0.47 (95% CI: 0.35-0.63, p < 0.001) times less likely to experience a relevant decline in health status compared to interferon beta-1a patients, with a number needed to treat of 7.10 [5.18, 11.23]. Conclusions: Fingolimod's net benefit over interferon beta-1a did not reach the clinical relevance over 1 year, but the decreased risk for health status deterioration may be more pronounced more long term and patients may prefer less treatment burden associated with fingolimod.

Patient Preference Studies for Advanced Prostate Cancer Treatment Along the Medical Product Life Cycle: Systematic Literature Review.

Background: Patient preference studies can inform decision-making across all stages of the medical product life cycle (MPLC). The treatment landscape for advanced prostate cancer (APC) treatment has substantially changed in recent years. However, the most patient-relevant aspects of APC treatment remain unclear. This systematic review of patient preference studies in APC aimed to summarize the evidence on patient preferences and patient-relevant aspects of APC treatments, and to evaluate the potential contribution of existing studies to decision-making within the respective stages of the MPLC. Methods: We searched MEDLINE and EMBASE for studies evaluating patient preferences related to APC treatment up to October 2020. Two reviewers independently performed screening, data extraction and quality assessment in duplicate. We descriptively summarized the findings and analyzed the studies regarding their contribution within the MPLC using an analytical framework. Results: Seven quantitative preference studies were included. One study each was conducted in the marketing approval and the health technology assessment (HTA) and reimbursement stage, and five were conducted in the post-marketing stage of the MPLC. While almost all stated to inform clinical practice, the specific contributions to clinical decision-making remained unclear for almost all studies. Evaluated attributes related to benefits, harms, and other treatment-related aspects and their relative importance varied relevantly between studies. All studies were judged of high quality overall, but some methodological issues regarding sample selection and the definition of patient-relevant treatment attributes were identified. Conclusion: The most patient-relevant aspects regarding the benefits and harms of APC treatment are not yet established, and it remains unclear which APC treatments are preferred by patients. Findings from this study highlight the importance of transparent reporting and discussion of study findings according to their aims and with respect to their stage within the MPLC. Future research may benefit from using the MPLC framework for analyzing or determining the aims and design of patient preference studies.

Treatments for Metastatic Hormone-sensitive Prostate Cancer: Systematic Review, Network Meta-analysis, and Benefit-harm assessment.

CONTEXT: Multiple treatments for metastatic, hormone-sensitive prostate cancer (mHSPC) are available, but their effects on health-related quality of life (HRQoL) and benefit-harm balance remain unclear. OBJECTIVE: To assess clinical effectiveness regarding survival and HRQoL, safety, and benefit-harm balance of mHSPC treatments. EVIDENCE ACQUISITION: We searched MEDLINE, EMBASE, CENTRAL, and ClinicalTrials.gov until March 1, 2022. Randomized controlled trials (RCTs) comparing docetaxel, abiraterone, enzalutamide, apalutamide, darolutamide, and radiotherapy combined with androgen deprivation therapy (ADT) mutually or with ADT alone were eligible. Three reviewers independently performed screening, data extraction, and risk of bias assessment in duplicate. EVIDENCE SYNTHESIS: Across ten RCTs, we found relevant survival benefits for ADT + docetaxel (high certainty according to the Grading of Recommendations, Assessment, Development and Evaluation [GRADE]), ADT + abiraterone (moderate certainty), ADT + enzalutamide (low certainty), ADT + apalutamide (high certainty), and ADT + docetaxel + darolutamide (high certainty) compared with ADT alone. ADT + radiotherapy appeared effective only in low-volume de novo mHSPC. We found a short-term HRQoL decrease lasting 3-6 mo for ADT + docetaxel (moderate certainty) and a potential HRQoL benefit for ADT + abiraterone up to 24 mo of follow-up (moderate certainty) compared with ADT alone. There was no difference in HRQoL for ADT + enzalutamide, ADT + apalutamide, or ADT + radiotherapy over ADT alone (low-high certainty). Grade 3-5 adverse effect rates were increased with all systemic combination treatments. A benefit-harm assessment showed high probabilities (>60%) for a net clinical benefit with ADT + abiraterone, ADT + enzalutamide, and ADT + apalutamide, while ADT + docetaxel and ADT + docetaxel + darolutamide appeared unlikely (<40%) to be beneficial. CONCLUSIONS: Despite substantial survival benefits, no systemic combination treatment showed a clear HRQoL improvement compared with ADT alone. We found evidence for a short-term HRQoL decline with ADT + docetaxel and a higher net clinical benefit with ADT + abiraterone, ADT + apalutamide and ADT + enzalutamide. While individualized decision-making remains important and economic factors need to be considered, the evidence may support a general preference for the combination of ADT with androgen receptor axis-targeted therapies over docetaxel-containing strategies. PATIENT SUMMARY: We assessed different combination treatments for metastatic hormone-sensitive prostate cancer. While survival was better with all systemic combination treatments, there was no clear improvement in health-related quality of life compared with androgen deprivation therapy alone. Novel hormonal combination treatments had a more favorable benefit-harm balance than combination treatments that include chemotherapy.

Taxation options for nicotine and tobacco products in Switzerland - a review of tax policies.

Alternative nicotine products such as electronic nicotine delivery systems (ENDS) and tobacco heating systems have gained worldwide popularity. Findings suggest ENDS to be probably less harmful than combustible cigarettes, but evidence on long-term health effects is still lacking. The potential risk reduction by using tobacco heating systems instead of combustible cigarettes has largely been studied by tobacco industry-sponsored research. Evidence on the extent of risk reduction is key for risk-adapted taxation policies, which will be discussed soon in the Swiss parliament. Evidence on the effects of tax policies in the USA shows that the level of taxation of ENDS, tobacco heating systems and combustible cigarettes has an effect on switches between these products. Therefore, excise taxes influencing one another need to be considered. In Switzerland, tobacco heating systems are currently taxed at a level of 12%, whereas ENDS are not subject to tobacco excise taxation as yet, because they do not meet the legal definition of a tobacco product. This article analyses approaches for imposing taxes on tobacco and nicotine products and possible outcomes, depending on the intended public health goals. At least three tax models can be considered. Tax model A would apply a very small tax on ENDS and a higher tax for tobacco products, which could increase incentives for smokers to switch to vaping but comes with risks of increased vaping initiation among the youth and subsequent switch to or dual use of tobacco products. In contrast, model B would levy a moderate tax on ENDS and an increased tax on tobacco products, which could limit initiation among youth, incentivise to switch from smoking to vaping and discourage dual use. In model C, a comparable tax level for ENDS, tobacco heating systems and combustible cigarettes is levied. This could have overall positive effects in reducing tobacco- and nicotine-associated burden of disease by discouraging initiation in youth, overall consumption and dual use, but could discourage switching to less harmful products. When applying these tax models to current sales prices of these products we found that no public health goal, such as protecting youth and reducing tobacco-associated morbidity and mortality can be achieved. The price of tobacco products is too low to achieve any price differentiation that reflects the different risks associated with ENDS and tobacco products. In order to achieve any public health goal with one of these tax models, prices for tobacco products need to be increased substantially.

Burden of post-COVID-19 syndrome and implications for healthcare service planning: A population-based cohort study.

BACKGROUND: Longer-term consequences after SARS-CoV-2 infection are becoming an important burden to societies and healthcare systems. Data on post-COVID-19 syndrome in the general population are required for the timely planning of healthcare services and resources. The objective of this study was to assess the prevalence of impaired health status and physical and mental health symptoms among individuals at least six months after SARS-CoV-2 infection, and to characterize their healthcare utilization. METHODS: This population-based prospective cohort study (Zurich SARS-CoV-2 Cohort) enrolled 431 adults from the general population with polymerase chain reaction-confirmed SARS-CoV-2 infection reported to health authorities between 27 February 2020 and 05 August 2020 in the Canton of Zurich, Switzerland. We evaluated the proportion of individuals reporting not to have fully recovered since SARS-CoV-2 infection, and the proportion reporting fatigue (Fatigue Assessment Scale), dyspnea (mMRC dyspnea scale) or depression (DASS-21) at six to eight months after diagnosis. Furthermore, the proportion of individuals with at least one healthcare contact after their acute illness was evaluated. Multivariable logistic regression models were used to assess factors associated with these main outcomes. RESULTS: Symptoms were present in 385 (89%) participants at diagnosis and 81 (19%) were initially hospitalized. At six to eight months, 111 (26%) reported not having fully recovered. 233 (55%) participants reported symptoms of fatigue, 96 (25%) had at least grade 1 dyspnea, and 111 (26%) had DASS-21 scores indicating symptoms of depression. 170 (40%) participants reported at least one general practitioner visit related to COVID-19 after acute illness, and 10% (8/81) of initially hospitalized individuals were rehospitalized. Individuals that have not fully recovered or suffer from fatigue, dyspnea or depression were more likely to have further healthcare contacts. However, a third of individuals (37/111) that have not fully recovered did not seek further care. CONCLUSIONS: In this population-based study, a relevant proportion of participants suffered from longer-term consequences after SARS-CoV-2 infection. With millions infected across the world, our findings emphasize the need for the timely planning of resources and patient-centered services for post-COVID-19 care.

The COVID-19 Social Monitor longitudinal online panel: Real-time monitoring of social and public health consequences of the COVID-19 emergency in Switzerland.

BACKGROUND: The COVID-19 pandemic challenges societies in unknown ways, and individuals experience a substantial change in their daily lives and activities. Our study aims to describe these changes using population-based self-reported data about social and health behavior in a random sample of the Swiss population during the COVID-19 pandemic. The aim of the present article is two-fold: First, we want to describe the study methodology. Second, we want to report participant characteristics and study findings of the first survey wave to provide some baseline results for our study. METHODS: Our study design is a longitudinal online panel of a random sample of the Swiss population. We measure outcome indicators covering general well-being, physical and mental health, social support, healthcare use and working state over multiple survey waves. RESULTS: From 8,174 contacted individuals, 2,026 individuals participated in the first survey wave which corresponds to a response rate of 24.8%. Most survey participants reported a good to very good general life satisfaction (93.3%). 41.4% of the participants reported a worsened quality of life compared to before the COVID-19 emergency and 9.8% feelings of loneliness. DISCUSSION: The COVID-19 Social Monitor is a population-based online survey which informs the public, health authorities, and the scientific community about relevant aspects and potential changes in social and health behavior during the COVID-19 emergency and beyond. Future research will follow up on the described study population focusing on COVID-19 relevant topics such as subgroup differences in the impact of the pandemic on well-being and quality of life or different dynamics of perceived psychological distress.

Global variation of risk thresholds for initiating statins for primary prevention of cardiovascular disease: a benefit-harm balance modelling study.

BACKGROUND: We previously showed that the 10-year cardiovascular disease (CVD) risk threshold to initiate statins for primary prevention depends on the baseline CVD risk, age, sex, and the incidence of statin-related harm outcome and competing risk for non-CVD death. As these factors appear to vary across countries, we aimed in this study to determine country-specific thresholds and provide guidelines a quantitative benefit-harm assessment method for local adaptation. METHODS: For each of the 186 countries included, we replicated the benefit-harm balance analysis using an exponential model to determine the thresholds to initiate statin use for populations aged 40 to 75 years, with no history of CVD. The analyses took data inputs from a priori studies, including statin effect estimates (network meta-analysis), patient preferences (survey), and baseline incidence of harm outcomes and competing risk for non-CVD (global burden of disease study). We estimated the risk thresholds above which the benefits of statins were more likely to outweigh the harms using a stochastic approach to account for statistical uncertainty of the input parameters. RESULTS: The 5th and 95th percentiles of the 10-year risk thresholds above which the benefits of statins outweigh the harms across 186 countries ranged between 14 and 20% in men and 19-24% in women, depending on age (i.e., 90% of the country-specific thresholds were in the ranges stated). The median risk thresholds varied from 14 to 18.5% in men and 19 to 22% in women. The between-country variability of the thresholds was slightly attenuated when further adjusted for age resulting, for example, in a 5th and 95th percentiles of 14-16% for ages 40-44 years and 17-21% for ages 70-74 years in men. Some countries, especially the islands of the Western Pacific Region, had higher thresholds to achieve net benefit of statins at 25-36% 10-year CVD risks. CONCLUSIONS: This extensive benefit-harm analysis modeling shows that a single CVD risk threshold, irrespective of age, sex and country, is not appropriate to initiate statin use globally. Instead, countries need to carefully determine thresholds, considering the national or subnational contexts, to optimize benefits of statins while minimizing related harms and economic burden.

Outcome preferences of older people with multiple chronic conditions and hypertension: a cross-sectional survey using best-worst scaling.

BACKGROUND: Older people with hypertension and multiple chronic conditions (MCC) receive complex treatments and face challenging trade-offs. Patients' preferences for different health outcomes can impact multiple treatment decisions. Since evidence about outcome preferences is especially scarce among people with MCC our aim was to elicit preferences of people with MCC for outcomes related to hypertension, and to determine how these outcomes should be weighed when benefits and harms are assessed for patient-centered clinical practice guidelines and health economic assessments. METHODS: We sent a best-worst scaling preference survey to a random sample identified from a primary care network of Kaiser Permanente (Colorado, USA). The sample included individuals age 60 or greater with hypertension and at least two other chronic conditions. We assessed average ranking of patient-important outcomes using conditional logit regression (stroke, heart attack, heart failure, dialysis, cognitive impairment, chronic kidney disease, acute kidney injury, fainting, injurious falls, low blood pressure with dizziness, treatment burden) and studied variation across individuals. RESULTS: Of 450 invited participants, 217 (48%) completed the survey, and we excluded 10 respondents who had more than two missing choices, resulting in a final sample of 207 respondents. Participants ranked stroke as the most worrisome outcome and treatment burden as the least worrisome outcome (conditional logit parameters: 3.19 (standard error 0.09) for stroke, 0 for treatment burden). None of the outcomes were always chosen as the most or least worrisome by more than 25% of respondents, indicating that all outcomes were somewhat worrisome to respondents. Predefined subgroup analyses according to age, self-reported life-expectancy, degree of comorbidity, number of medications and antihypertensive treatment did not reveal meaningful differences. CONCLUSIONS: Although some outcomes were more worrisome to patients than others, our results indicate that none of the outcomes should be disregarded for clinical practice guidelines and health economic assessments.

Balance of benefits and harms of different blood pressure targets in people with multiple chronic conditions: a quantitative benefit-harm assessment.

OBJECTIVE: Recent studies suggest that a systolic blood pressure (SBP) target of 120 mm Hg is appropriate for people with hypertension, but this is debated particularly in people with multiple chronic conditions (MCC). We aimed to quantitatively determine whether benefits of a lower SBP target justify increased risks of harm in people with MCC, considering patient-valued outcomes and their relative importance. DESIGN: Highly stratified quantitative benefit-harm assessment based on various input data identified as the most valid and applicable from a systematic review of evidence and based on weights from a patient preference survey. SETTING: Outpatient care. PARTICIPANTS: Hypertensive patients, grouped by age, gender, prior history of stroke, chronic heart failure, chronic kidney disease and type 2 diabetes mellitus. INTERVENTIONS: SBP target of 120 versus 140 mm Hg for patients without history of stroke. PRIMARY AND SECONDARY OUTCOME MEASURES: Probability that the benefits of a SBP target of 120 mm Hg outweigh the harms compared with 140 mm Hg over 5 years (primary) with thresholds >0.6 (120 mm Hg better), <0.4 (140 mm Hg better) and 0.4 to 0.6 (unclear), number of prevented clinical events (secondary), calculated with the Gail/National Cancer Institute approach. RESULTS: Considering individual patient preferences had a substantial impact on the benefit-harm balance. With average preferences, 120 mm Hg was the better target compared with 140 mm Hg for many subgroups of patients without prior stroke, especially in patients over 75. For women below 65 with chronic kidney disease and without diabetes and prior stroke, 140 mm Hg was better. The analyses did not include mild adverse effects, and apply only to patients who tolerate antihypertensive treatment. CONCLUSIONS: For most patients, a lower SBP target was beneficial, but this depended also on individual preferences, implying individual decision-making is important. Our modelling allows for individualised treatment targets based on patient preferences, age, gender and co-morbidities.

A novel approach to increase physical activity in older adults in the community using citizen science: a mixed-methods study.

OBJECTIVES: The aims of this study were to implement a novel, community-based physical activity (PA) intervention in a Swiss town with active participation of elderly participants and to evaluate its effectiveness, feasibility, acceptability and sustainability. METHODS: The CAPACITY intervention combined important determinants of PA, used smartphone apps to provide feedback/facilitate interaction, and followed a citizen science approach to enable participants to organize walking groups. We targeted persons > 60 years from Wetzikon. Assessments took place at baseline and after 6 months, during this intervention period, and 11 months after step-wise withdrawal of the study team. RESULTS: Twenty-nine persons were included in the study; 25 conducted 6-month follow-up. They had a significant increase in moderate-to-vigorous PA (p = 0.046) but not in daily steps (p = 0.331). After the intervention period, key participants took over organization, independently organized monthly get-togethers, added new walking routes and continuously recruit new participants. Eleven months after withdrawal of the study team, 61 people regularly walk in groups together. CONCLUSIONS: The novel CAPACITY intervention was successfully implemented, transferred to participants and is now self-sustainable for almost 1 year in the community.

Effects of a long-term home-based exercise training programme using minimal equipment vs. usual care in COPD patients: a study protocol for two multicentre randomised controlled trials (HOMEX-1 and HOMEX-2 trials).

BACKGROUND: Exercise training is an important component of pulmonary rehabilitation (PR) programmes in chronic obstructive pulmonary disease (COPD), but the great majority of COPD patients who would benefit from PR never follow such programmes or fail to maintain exercise training after PR completion. Against this background, we developed an exercise training programme that requires minimal equipment and can be implemented long-term in the patient's home-setting. The aims of the HOMEX-1 and HOMEX-2 trials are to assess the effectiveness of this home-based exercise training programme in two groups of COPD patients over the course of one year: patients who have completed PR (HOMEX-1 trial) and patients who did not enrol in existing PR programmes within the last two years (HOMEX-2 trial). METHODS: HOMEX-1 and HOMEX-2 are multicentre, parallel group, randomised controlled trials. For both trials each, it is planned to include 120 study participants with a diagnosis of COPD. Participants will be randomised with a 1:1 ratio into the intervention group or the control group (usual care/no intervention). The intervention consists of minimal-equipment exercise training elements with progressive level of intensity, conducted by the participant during six days per week and instructed and coached by a trained health care professional during three home visits and regular telephone calls during one year. Primary outcome is change in dyspnoea (domain of Chronic Respiratory Questionnaire) from baseline to 12-months follow-up. Secondary outcomes are change in dyspnoea over the course of the year (assessed at 3, 6 and 12 month) and change in functional exercise capacity, physical activity, health-related quality of life, health status, exacerbations and symptoms from baseline to 12 months follow-up. In addition, explanatory, safety and cost-effectiveness outcomes will be assessed. We will conduct intention-to-treat analyses separately per trial and per protocol analyses as sensitivity analyses. DISCUSSION: The HOMEX-1 and HOMEX-2 trials assess a novel intervention that provides an innovative way of making exercise training as accessible as possible for COPD patients. If the intervention proves to be effective long-term, it will fill the gap of providing an easily accessible and feasible intervention so that more COPD patients can follow an exercise programme. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: HOMEX-1 NCT03461887 (registration date: March 12, 2018; retrospectively registered); HOMEX-2 NCT03654092 (registration date: August 31, 2018).

Patterns of care for Multiple Sclerosis in a setting of universal care access: A cross-sectional study.

BACKGROUND: Current guidelines recommend regular neurological MS care in persons diagnosed with MS, but little is known about implementation of this recommendation or potential access barriers. This study examined disease-specific and sociodemographic differences between MS patients in Neurological Care (NeC), General Practitioner Care (GPC), or no Physician Care (NoPC) to identify group differences and characteristics that may suggest care access barriers. METHODS: Patient-reported data were analyzed from 1038 Swiss Multiple Sclerosis Registry participants by means of multivariable regression to identify systematic differences across the three care groups. Assessments included comprehensive data on clinical, sociodemographic, and geographic factors. RESULTS: 89% reported being in regular care by a neurologist (56% in private practices, 44% in hospitals), 5% were in GPC, and 6% reported No Physician Care (NoPC). Compared with the NeC group, patients not seeing a neurologist included two subgroups, one consisting of persons with a primary progressive MS (PPMS) and/or an extended MS history. The second subgroup included persons with a recent MS diagnosis within the last 2 years. Within the NeC group, the patients seen in private practices were of older age and more frequently female compared to those at clinics, but no differences were detected with regard to disability status, MS type, or treatment patterns. CONCLUSIONS: Access to neurological care is high in Switzerland. Given the emerging paradigm for early treatment and new drugs for progressive MS, regular neurology visits should be promoted among patient groups currently less in neurological care such as persons with PPMS or recently diagnosed.