Nature-based social interventions to address loneliness among vulnerable populations: a common study protocol for three related randomized controlled trials in Barcelona, Helsinki, and Prague within the RECETAS European project.

BACKGROUND: The negative effects of loneliness on population health and wellbeing requires interventions that transcend the medical system and leverage social, cultural, and public health system resources. Group-based social interventions are a potential method to alleviate loneliness. Moreover, nature, as part of our social and health infrastructure, may be an important part of the solutions that are needed to address loneliness. The RECETAS European project H2020 (Re-imagining Environments for Connection and Engagement: Testing Actions for Social Prescribing in Natural Spaces) is an international research project aiming to develop and test the effectiveness of nature-based social interventions to reduce loneliness and increase health-related quality of life. METHODS: This article describes the three related randomized controlled trials (RCTs) that will be implemented: the RECETAS-BCN Trial in Barcelona (Spain) is targeting people 18+ from low socio-economic urban areas; the RECETAS-PRG Trial in Prague (Czech Republic) is addressing community-dwelling older adults over 60 years of age, and the RECETAS-HLSNK trial is reaching older people in assisted living facilities. Each trial will recruit 316 adults suffering from loneliness at least sometimes and randomize them to nature-based social interventions called "Friends in Nature" or to the control group. "Friends in Nature" uses modifications of the "Circle of Friends" methodology based on group processes of peer support and empowerment but including activities in nature. Participants will be assessed at baseline, at post-intervention (3 months), and at 6- and 12-month follow-up after baseline. Primary outcomes are the health-related quality-of-life according to 15D measure and The De Jong Gierveld 11-item loneliness scale. Secondary outcomes are health and psychosocial variables tailored to the specific target population. Nature exposure will be collected throughout the intervention period. Process evaluation will explore context, implementation, and mechanism of impact. Additionally, health economic evaluations will be performed. DISCUSSION: The three RECETAS trials will explore the effectiveness of nature-based social interventions among lonely people from various ages, social, economic, and cultural backgrounds. RECETAS meets the growing need of solid evidence for programs addressing loneliness by harnessing the beneficial impact of nature on enhancing wellbeing and social connections. TRIAL REGISTRATION: Barcelona (Spain) trial: ClinicalTrials.gov, ID: NCT05488496. Registered 29 July 2022. Prague (Czech Republic) trial: ClinicalTrials.gov, ID: NCT05522140. Registered August 25, 2022. Helsinki (Finland) trial: ClinicalTrials.gov, ID: NCT05507684. Registered August 12, 2022.

Determinants of low health-related quality of life in patients with myelodysplastic syndromes: EUMDS Registry study.

Patients with myelodysplastic syndromes (MDS) frequently experience a significant symptom burden, which reduces health-related quality of life (HRQoL). We aimed to identify determinants of low HRQoL in patients recently diagnosed with MDS, for guiding early intervention strategies. We evaluated longitudinal data in 2205 patients with MDS during their first year after diagnosis. Median values of EQ-5D 3-level (EQ-5D-3L) index (0.78) and visual analog scale (VAS) score (0.70) were used as thresholds for low HRQoL. In addition, the 5 dimensions of EQ-5D-3L were analyzed for impairments (any level vs "no problem" category). After multiple imputation of missing values, we used generalized estimating equations (GEE) to estimate odds ratios (OR) for univariable determinant screening (P < .15), and to subsequently derive multivariable models for low HRQoL with 95% confidence intervals (CI). Multivariable GEE analysis showed the following independent determinants (OR, 95% CI) for low EQ-5D index: increased age (60-75 years: 1.33, 1.01-1.75; >75: 1.84, 1.39-2.45), female sex (1.70, 1.43-2.03), high serum ferritin level (≥1000 vs ≤300 µg/L: 1.41, 1.06-1.87), comorbidity burden (per unit: 1.11, 1.02-1.20), and reduced Karnofsky performance status (KPS, per 10 units: 0.62, 0.58-0.67). For low VAS score, additional determinants were transfusion dependence (1.53, 1.03-2.29), low hemoglobin <10 g/dL (1.34, 1.12-1.61), and high body mass index (≥30 vs 23-29.9 kg/m2: 1.26, 1.02-1.57). Sex, KPS, comorbidity burden, hemoglobin count, and transfusion burden were determinants for all EQ-5D dimensions. Low HRQoL is determined by multiple factors, which should be considered in the management and shared decision making of patients with MDS. This trial was registered at www.clinicaltrials.gov as #NCT00600860.

Core set of patient-reported outcomes for myelodysplastic syndromes: an EUMDS Delphi study involving patients and hematologists.

Patient-reported outcomes (PROs) are relevant and valuable end points in the care of patients with myelodysplastic syndromes (MDS). However, a consensus-based selection of PROs for MDS, derived by both patients and hematologists, is lacking. We aimed to develop a core set of PROs for patients with MDS as part of the prospective European LeukemiaNet MDS (EUMDS) Registry. According to international guidelines, candidate PROs were identified from a comprehensive literature search of MDS studies. Overall, 40 PROs were selected and evaluated in a two-round Delphi survey by 40 patients with MDS and 38 hematologists in the first round and 38 patients and 32 hematologists in the second round. Based on an agreement scale and predefined inclusion criteria, both patients and hematologists selected "general quality of life" as a core PRO. Hematologists also selected "transfusion-dependency burden" and "ability to work/activities of daily living" as core PROs. The second Delphi round increased PRO rating agreements. Statistically significant rating differences between patients and hematologists were observed for 28 PROs (Mann-Whitney U test; P < .05) in the first round and for 19 PROs in the second round, with "disease knowledge" and "confidence in health care services" rated notably higher by patients. The overall mean PRO ratings correlation between the 2 groups was moderate (Spearman's rank correlation coefficient = 0.5; P < .05). This first consensus on a core set of PROs jointly developed by patients and hematologists forms the basis for patient-centered care in daily practice and clinical research.

Causal evidence in health decision making: methodological approaches of causal inference and health decision science.

Objectives: Public health decision making is a complex process based on thorough and comprehensive health technology assessments involving the comparison of different strategies, values and tradeoffs under uncertainty. This process must be based on best available evidence and plausible assumptions. Causal inference and health decision science are two methodological approaches providing information to help guide decision making in health care. Both approaches are quantitative methods that use statistical and modeling techniques and simplifying assumptions to mimic the complexity of the real world. We intend to review and lay out both disciplines with their aims, strengths and limitations based on a combination of textbook knowledge and expert experience. Methods: To help understanding and differentiating the methodological approaches of causal inference and health decision science, we reviewed both methods with the focus on aims, research questions, methods, assumptions, limitations and challenges, and software. For each methodological approach, we established a group of four experts from our own working group to carefully review and summarize each method, followed by structured discussion rounds and written reviews, in which the experts from all disciplines including HTA and medicine were involved. The entire expert group discussed objectives, strengths and limitations of both methodological areas, and potential synergies. Finally, we derived recommendations for further research and provide a brief outlook on future trends. Results: Causal inference methods aim for drawing causal conclusions from empirical data on the relationship of pre-specified interventions on a specific target outcome and apply a counterfactual framework and statistical techniques to derive causal effects of exposures or interventions from these data. Causal inference is based on a causal diagram, more specifically, a directed acyclic graph (DAG), which encodes the assumptions regarding the causal relations between variables. Depending on the type of confounding and selection bias, traditional statistical methods or more complex g-methods are needed to derive valid causal effects. Besides the correct specification of the DAG and the statistical model, assumptions such as consistency, positivity, and exchangeability must be checked when aiming at causal inference. Health decision science aims for guiding policy decision making regarding health interventions considering and balancing multiple competing objectives of a decision based on data from multiple sources and studies, for example prevalence studies, clinical trials and long-term observational routine effectiveness studies, and studies on preferences and costs. It involves decision analysis, a systematic, explicit and quantitative framework to guide decisions under uncertainty. Decision analyses are based on decision-analytic models to mimic the course of disease as well as aspects and consequences of the intervention in order to quantitatively optimize the decision. Depending on the type of decision problem, decision trees, state-transition models, discrete event simulation models, dynamic transmission models, or other model types are applied. Models must be validated against observed data, and comprehensive sensitivity analyses must be performed to assess uncertainty. Besides the appropriate choice of the model type and the valid specification of the model structure, it must be checked if input parameters of effects can be interpreted as causal parameters in the model. Otherwise results will be biased. Conclusions: Both causal inference and health decision science aim for providing best causal evidence for informed health decision making. The strengths and limitations of both methods differ and a good understanding of both methods is essential for correct application but also for correct interpretation of findings from the described methods. Importantly, decision-analytic modeling should be combined with causal inference when developing guidance and recommendations regarding decisions on health care interventions.

New Perspective for Soft Tissue Closure in Medication-Related Osteonecrosis of the Jaw (MRONJ) Using Barbed Sutures.

The aim of this study was to compare the effectiveness of barbed versus smooth sutures for soft tissue closure of exposed jawbone sites in medication-related osteonecrosis of the jaw (MRONJ) patients. Exposed necrotic jawbone sites surgically managed by intraoral soft tissue closure were evaluated. Either barbed sutures (Stratafix™ or V-Loc™) together with Prolene® or Vicryl® sutures were used. We estimated the effect of barbed sutures (BS) with Prolene® compared to smooth sutures (Vicryl®) on the hazard rate of intraoral soft tissue dehiscence using a multivariate Cox regression model within a target trial framework, adjusting for relevant confounders. In total, 306 operations were performed in 188 sites. In the primary analysis 182 sites without prior surgery were included. Of these, 113 sites developed a dehiscence during follow-up. 84 sites were operated using BS and Prolene®. A total of 222 sites were operated with Vicryl® (control group). In the BS group, the median time to event (i.e., dehiscence) was 148 days (interquartile range (IQR), 42-449 days) compared to 15 days (IQR, 12-52 days) in the control group. The hazard rate of developing intraoral dehiscence was 0.03 times (95%-confidence interval (CI): 0.01; 0.14, p < 0.001) lower for BS patients compared to the control group. Within the limits of a retrospective study, BS showed a high success rate and are therefore recommended for soft tissue closure of exposed jawbone sites in MRONJ patients. Additional studies are warranted to further evaluate this novel application of BS.

Are There Associations Between Submaximal and Maximal Aerobic Power and International Ski Federation World Cup Ranking in Elite Alpine Skiers?

PURPOSE: To analyze the predictive value of parameters of submaximal and maximal cardiopulmonary exercise performance on International Ski Federation (Fédération Internationale de Ski) World Cup ranking (FIS ranking) in elite Austrian Alpine skiers. METHODS: Over 7 World Cup seasons (2012-2018), exercise data (maximal oxygen uptake and maximum power output, lactate threshold 2, and ventilatory threshold 2, based on stepwise cycle spiroergometry) were analyzed to determine whether there was a correlation between world FIS ranking and exercise capacity of male and female elite Alpine skiers. RESULTS: The data of 39 male skiers (age: 27.67 [4.20] y, body mass index: 26.03 [1.25] kg/m2) and 36 female skiers (age: 25.49 [3.18] y, body mass index: 22.97 [1.71] kg/m2) were included in this study. The maximum oxygen uptake and maximum power output ranged from 4.37 to 4.42 W/kg and 53.41 to 54.85 mL/kg/min in men and from 4.17 to 4.30 W/kg and 45.96 to 49.16 mL/kg/min in women, respectively, over the 7 seasons; the yearly mean FIS ranking ranged from 17 to 24 in men and 9 to 18 in women. In a fixed-effects model used for the subsequent panel regression analysis, no statistically significant effect on FIS ranking was found for the exercise parameters of interest. CONCLUSIONS: Neither maximal aerobic tests nor maximum power output significantly predicted competitive performance, as indexed by the FIS ranking. This reinforces the assumption that no single parameter determines competition performance in this complex sport. Therefore, identifying the optimum amount of endurance training remains a major challenge for athletes and coaches, as does identifying and improving the factors that determine performance.

Effectiveness, benefit harm and cost effectiveness of colorectal cancer screening in Austria.

BACKGROUND: Clear evidence on the benefit-harm balance and cost effectiveness of population-based screening for colorectal cancer (CRC) is missing. We aim to systematically evaluate the long-term effectiveness, harms and cost effectiveness of different organized CRC screening strategies in Austria. METHODS: A decision-analytic cohort simulation model for colorectal adenoma and cancer with a lifelong time horizon was developed, calibrated to the Austrian epidemiological setting and validated against observed data. We compared four strategies: 1) No Screening, 2) FIT: annual immunochemical fecal occult blood test age 40-75 years, 3) gFOBT: annual guaiac-based fecal occult blood test age 40-75 years, and 4) COL: 10-yearly colonoscopy age 50-70 years. Predicted outcomes included: benefits expressed as life-years gained [LYG], CRC-related deaths avoided and CRC cases avoided; harms as additional complications due to colonoscopy (physical harm) and positive test results (psychological harm); and lifetime costs. Tradeoffs were expressed as incremental harm-benefit ratios (IHBR, incremental positive test results per LYG) and incremental cost-effectiveness ratios [ICER]. The perspective of the Austrian public health care system was adopted. Comprehensive sensitivity analyses were performed to assess uncertainty. RESULTS: The most effective strategies were FIT and COL. gFOBT was less effective and more costly than FIT. Moving from COL to FIT results in an incremental unintended psychological harm of 16 additional positive test results to gain one life-year. COL was cost saving compared to No Screening. Moving from COL to FIT has an ICER of 15,000 EUR per LYG. CONCLUSIONS: Organized CRC-screening with annual FIT or 10-yearly colonoscopy is most effective. The choice between these two options depends on the individual preferences and benefit-harm tradeoffs of screening candidates.