Prevalence of Mycoplasma genitalium infection among HIV PrEP users: a systematic review and meta-analysis.

OBJECTIVES: To summarise the prevalence of Mycoplasma genitalium (MG) and antibiotic-resistant MG infection among HIV pre-exposure prophylaxis (PrEP) users. METHODS: We searched MEDLINE, Embase, Web of Science and Global Index Medicus up to 30 September 2022. We included studies reporting the prevalence of MG and/or antibiotic-resistant MG infection among PrEP users. Two reviewers independently searched for studies and extracted data. A systematic review with random-effects meta-analysis was performed to quantitatively summarise the results of included studies. The critical appraisal of included studies was conducted with the Joanna Briggs Institute checklist for prevalence studies and the quality of evidence was assessed with Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: A total of 15 studies were included in the systematic review, with 2341 individuals taking PrEP. Studies were conducted in high-income level countries between 2014 and 2019. Median age of participants varied from 23.5 to 40 years. The majority were men (85%) and among them, 93% were men who have sex with men. To identify MG, urine samples were analysed in 14 studies, rectal or anal swabs in 12 studies, oral or pharyngeal swabs in 9 studies, and urethral or vaginal in 3 studies. The pooled point prevalence of MG among PrEP users was 16.7% (95% CI 13.6% to 20.3%; 95% prediction interval (95% PI) 8.2% to 31.1%). The pooled point prevalence of macrolide-resistant infections was 82.6% (95% CI 70.1% to 90.6%; 95% PI 4.7% to 99.8%) and the prevalence of fluoroquinolone-resistant infections was 14.3% (95% CI 1.8% to 42.8%). Individuals taking PrEP have a higher chance of being infected with MG compared with those not taking PrEP (OR 2.30; 95% CI 1.6 to 3.4). The quality of evidence was very low to moderate. CONCLUSION: We observed a high prevalence of MG and its macrolide resistance among PrEP users, highlighting the need to reinforce prevention strategies against sexually transmitted infections in this population. PROSPERO REGISTRATION NUMBER: CRD42022310597.

Development of a core outcome set for myelodysplastic syndromes - a Delphi study from the EUMDS Registry Group.

Treatment options for myelodysplastic syndromes (MDS) vary widely, depending on the natural disease course and patient-related factors. Comparison of treatment effectiveness is challenging as different endpoints have been included in clinical trials and outcome reporting. Our goal was to develop the first MDS core outcome set (MDS-COS) defining a minimum set of outcomes that should be reported in future clinical studies. We performed a comprehensive systematic literature review among MDS studies to extract patient- and/or clinically relevant outcomes. Clinical experts from the European LeukemiaNet MDS (EUMDS) identified 26 potential MDS core outcomes and participated in a three-round Delphi survey. After the first survey (56 experts), 15 outcomes met the inclusion criteria and one additional outcome was included. The second round (38 experts) resulted in six included outcomes. In the third round, a final check on plausibility and practicality of the six included outcomes and their definitions was performed. The final MDS-COS includes: health-related quality of life, treatment-related mortality, overall survival, performance status, safety, and haematological improvement. This newly developed MDS-COS represents the first minimum set of outcomes aiming to enhance comparability across future MDS studies and facilitate a better understanding of treatment effectiveness.

[Linkage of Clinical and Claims Data in the Evaluation of Post-Stroke Care - SeDaStro: Experiences from the Tyrolian StrokeCard Program]. / Linkage von klinischen Primärdaten und Krankenkassenabrechnungsdaten in der Evaluation der Schlaganfallversorgung ­ SeDaStro: Erfahrungen aus dem Tiroler StrokeCard-Programm.

AIMS AND OBJECTIVES: Data linkage is of paramount importance in the evaluation of treatment regimens for chronic diseases where different health care sectors are involved. A comprehensive picture of long-term treatment effects and, in particular, the cost-effectiveness ratio of treatment approaches can only be drawn when data from various sources are merged and analyzed together. METHODOLOGICAL PROBLEMS AND CHALLENGES: Regarding post-acute stroke care, the present study gives an example of an exact deterministic data linkage procedure including clinical patient records and claims data of TGKK, the main Tyrolean statutory health insurance fund. Typical problems known from other data linkage projects also emerged in the so-called StrokeCard program conducted at the Medical University of Innsbruck. Distinctive Austrian features (the majority of the Austrian population benefits from a mandatory social insurance system without freedom of choice) facilitated the feasibility of the data linkage procedures. RESULTS: Over the recruitment period 01/2014-12/2015, 540 patients could be assigned to the operative dataset. Of these, 367 patients were part of the StrokeCard group (i. e. the treatment group), and 173 belonged to the usual care group (i. e. the control group); 11 patients did not complete the one-year follow-up period (7 treatment group patients vs. 4 control group patients); 7 of them died during the study (5 treatment group patients vs. 2 control group patients). For all 540 patients, TGKK claims data were available for the time-frames of one year before recruitment and one year after discharge from the University hospital. All data could be used in the health-economic evaluation of the StrokeCard program. CONCLUSIONS: The linking of clinical patient records with data collected by SHI funds opens a window of opportunities for analyses of medical care. Counter-intuitively, Austrian health services research activities have limited experience in data linkage approaches, alhough studies based on the linkage of clinical patient records and claims data are indispensable for the evaluation of complex multi-sectoral treatment schemes. The current project proves the feasibility of data linkage mechanisms in the Austrian context. This should be regarded as an impetus for extending data linkage principles to evaluation studies in the future.

Sex-Related Differences After a Single Bout of Maximal Eccentric Exercise in Response to Acute Effects: A Systematic Review and Meta-analysis.

Morawetz, D, Blank, C, Koller, A, Arvandi, M, Siebert, U, and Schobersberger, W. Sex-related differences after a single bout of maximal eccentric exercise in response to acute effects: a systematic review and meta-analysis. J Strength Cond Res 34(9): 2697-2707, 2020-The most prominent effects after unaccustomed eccentric exercise are muscle damage, muscle soreness, strength loss, and higher concentrations of muscle proteins in the plasma. The aim of this systematic review is to evaluate sex-related differences in these acute effects. A systematic literature search in MEDLINE following the PRISMA guidelines was performed. Inclusion criteria were the difference in absolute outcomes between sexes in eccentric muscle strength, strength loss after eccentric exercise, blood concentrations of creatine kinase (CK), and delayed onset muscle soreness (DOMS). Results for maximal eccentric torque and CK data were pooled using a random-effect meta-analysis. A meta-regression was conducted to explain heterogeneity. Based on the 23 included trials, men showed significantly higher absolute eccentric strength. No sex-related differences were detected when normalizing strength for body mass, cross-sectional area of the muscle, or fat-free mass. Women displayed a tendency toward greater relative strength loss immediately after exercise. The absolute CK concentrations of men were significantly higher after exercise-induced muscle damage. No significant difference was found between sexes in DOMS. Untrained men and women display similar responses in all measures of relative muscle strength and DOMS. Apart from the enzymatic activity after exercise and the levels of absolute eccentric torque, there is no evidence for sex-related differences immediately after eccentric exercise. Therefore, eccentric training might have the same impact on men and women. One potential sex difference with practical relevance would be the possible difference in fatigue pattern immediately after eccentric exercise.

Mortality of Critically Ill Children Requiring Continuous Renal Replacement Therapy: Effect of Fluid Overload, Underlying Disease, and Timing of Initiation.

OBJECTIVE: To identify risk factors associated with mortality in critically ill children requiring continuous renal replacement therapy. DESIGN: Retrospective observational study based on a prospective registry. SETTING: Tertiary and quaternary referral 30-bed PICU. PATIENTS: Critically ill children undergoing continuous renal replacement therapy were included in the study. INTERVENTIONS: Continuous renal replacement therapy. MEASUREMENTS AND MAIN RESULTS: Overall mortality was 36% (n = 58) among the 161 patients treated with continuous renal replacement therapy during the study period and was significantly higher in patients on extracorporeal membrane oxygenation (47.5%, 28 of 59) than in patients not requiring extracorporeal membrane oxygenation (28.4%, 29 of 102; p = 0.022). According to the admission diagnosis, we found the highest mortality in patients with onco-hematologic disease (77.8%) and the lowest in patients with renal disease (5.6%). Based on multivariate logistic regression analysis, the presence of higher severity of illness score at admission (adjusted odds ratio, 1.49; 95% CI, 1.18-1.89; p < 0.001), onco-hematologic disease (odds ratio, 17.10; 95% CI, 4.10-72.17; p < 0.001), fluid overload 10%-20% (odds ratio, 3.83; 95% CI, 1.33-11.07; p = 0.013), greater than 20% (odds ratio, 15.03; 95% CI, 4.03-56.05; p < 0.001), and timing of initiation of continuous renal replacement therapy (odds ratio, 1.01; 95% CI, 1.00-1.01; p = 0.040) were independently associated with mortality. In our population, the odds of dying increases by 1% for every hour of delay in continuous renal replacement therapy initiation from ICU admission. CONCLUSIONS: Mortality in children requiring continuous renal replacement therapy remains high and seems to be related to the underlying disease, the severity of illness, and the degree of fluid overload. In critically ill children at high risk for developing acute kidney injury and fluid overload, earlier initiation of continuous renal replacement therapy might result in decreased mortality.

Cost utility of fractional flow reserve-guided percutaneous coronary intervention in multivessel coronary artery disease in Brazil.

OBJECTIVE: The fractional flow reserve (FFR) versus angiography for multivessel evaluation (FAME) study has demonstrated that FFR substantially reduces major adverse cardiac events and resource utilization in coronary artery disease (CAD) patients. We aimed to assess the cost utility of FFR in percutaneous coronary interventions (PCI) from the perspective of the Brazilian Public Health System (SUS). DESIGN: Patient-level cost-utility analysis along the FAME study. PARTICIPANTS: Multivessel coronary artery disease patients. INTERVENTION: PCI, either guided by FFR or by angiography alone. SETTING: The procedure costs were based on the mean amount of unitary resource utilization multiplied by the costs from SUS reimbursement list. The utilities were derived using Brazilian weights for time trade-off European Quality of Life-5 Dimensions. The World Health Organization recommendation based on gross domestic product per capita (international dollars [I$] 35 876/quality-adjusted life year [QALY]) was used as willingness-to-pay threshold. MAIN OUTCOME MEASURE: We determined the incremental cost-utility ratio (ICUR) in I$ per QALY gained during the 1-year time horizon. RESULTS: One-year costs were I$ 8931 for the angiography-guided PCI and I$ 8968 for the FFR-guided PCI, resulting in an incremental cost of I$ 37. Effectiveness during 1 year was 0.798 QALYs for angiography-guided PCI and 0.811 for FFR-guided PCI, resulting in an incremental effectiveness of 0.013 QALYs. The base-case ICUR of FFR versus angiography-guided PCI was 2780 I$/QALY. Cost-saving results are achieved with a FFR price reduction of at least 2.2%. CONCLUSIONS: Developing countries should give attention to strategies proven to be cost-effective in other health systems. In our analysis, FFR-guided PCI is very cost-effective in the Brazilian SUS and with a minimal price reduction of the device, FFR could be cost saving.

Chokeberry juice supplementation in type 2 diabetic patients - impact on health status.

Recent literature evidence indicates the potential use of chokeberry preparations in the prevention and treatment of some chronic noncommunicable diseases. The aim of the present study was to evaluate the effects of the three months oral chokeberry juice supplementation in type 2 diabetic patients, as well as its influence on hematological parameters and certain parameters of the renal dysfunction. The study was designed as an open-label trial, which included 35 patients who have received the herbal supplement, polyphenol-rich chokeberry juice (150 ml/day, three times a day for 50 ml), in addition to their standard therapy. Chokeberry juice as a rich source of polyphenol compounds could be an effective preventive and therapeutic agent in diabetes mellitus type 2. Hematological and biochemical parameters were measured at baseline, after 3 months with the chokeberry juice supplementation and after the next 3 months without the chokeberry juice supplementation (follow-up period). Significant difference was noticed in the levels of LDL-cholesterol, glycated hemoglobin and serum creatinine (p < 0.05), as well as in the levels of some hematological parameters, such as white blood cell and lymphocyte count (p < 0.01), hematocrit, blood hemoglobin, mean corpuscular volume, hemoglobin and hemoglobin concentration and red blood cell count (p < 0.05). The daily consumption of the chokeberry juice could improve the health status in patients with type 2 diabetes mellitus, in combination with their standard therapy.

A bias-adjusted evidence synthesis of RCT and observational data: the case of total hip replacement.

Evaluation of clinical effectiveness of medical devices differs in some aspects from the evaluation of pharmaceuticals. One of the main challenges identified is lack of robust evidence and a will to make use of experimental and observational studies (OSs) in quantitative evidence synthesis accounting for internal and external biases. Using a case study of total hip replacement to compare the risk of revision of cemented and uncemented implant fixation modalities, we pooled treatment effect estimates from OS and RCTs, and simplified existing methods for bias-adjusted evidence synthesis to enhance practical application. We performed an elicitation exercise using methodological and clinical experts to determine the strength of beliefs about the magnitude of internal and external bias affecting estimates of treatment effect. We incorporated the bias-adjusted treatment effects into a generalized evidence synthesis, calculating both frequentist and Bayesian statistical models. We estimated relative risks as summary effect estimates with 95% confidence/credibility intervals to capture uncertainty. When we compared alternative approaches to synthesizing evidence, we found that the pooled effect size strongly depended on the inclusion of observational data as well as on the use bias-adjusted estimates. We demonstrated the feasibility of using observational studies in meta-analyses to complement RCTs and incorporate evidence from a wider spectrum of clinically relevant studies and healthcare settings. To ensure internal validity, OS data require sufficient correction for confounding and selection bias, either through study design and primary analysis, or by applying post-hoc bias adjustments to the results. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.

Gender differences in the association between grip strength and mortality in older adults: results from the KORA-age study.

BACKGROUND: Reduced muscular strength in the old age is strongly related to activity impairment and mortality. However, studies evaluating the gender-specific association between muscularity and mortality among older adults are lacking. Thus, the objective of the present study was to examine gender differences in the association between muscular strength and mortality in a prospective population-based cohort study. METHODS: Data used in this study derived from the Cooperative Health Research in the Region of Augsburg (KORA)-Age Study. The present analysis includes 1,066 individuals (mean age 76 ± 11 SD years) followed up over 3 years. Handgrip strength was measured using the Jamar Dynamometer. A Cox proportional hazard model was used to determine adjusted hazard ratios of mortality with 95% confidence intervals (95% CI) for handgrip strength. Potential confounders (i.e. age, nutritional status, number of prescribed drugs, diseases and level of physical activity) were pre-selected according to evidence-based information. RESULTS: During the follow-up period, 56 men (11%) and 39 women (7%) died. Age-adjusted mortality rates per 1,000 person years (95% CI) were 77 (59-106), 24 (13-41) and 14 (7-30) for men and 57 (39-81), 14 (7-27) and 1 (0-19) for women for the first, second and third sex-specific tertile of muscular strength, respectively. Low handgrip strength was significantly associated with all-cause mortality among older men and women from the general population after controlling for significant confounders. Hazard ratios (95% CI) comparing the first and second tertile to the third tertle were 3.33 (1.53-7.22) and 1.42 (0.61-3.28), respectively. Respective hazard ratios (95% CI) for mortality were higher in women than in men ((5.23 (0.67-40.91) and 2.17 (0.27-17.68) versus 2.36 (0.97-5.75) and 0.97 (0.36-2.57)). CONCLUSIONS: Grip strength is inversely associated with mortality risk in older adults, and this association is independent of age, nutritional status, number of prescribed drugs, number of chronic diseases and level of physical activity. The association between muscular strength and all-cause mortality tended to be stronger in women. It seems to be particularly important for the weakest to enhance their levels of muscular strength in order to reduce the risk of dying early.

Improving the quality of percutaneous revascularisation in patients with multivessel disease in Australia: cost-effectiveness, public health implications, and budget impact of FFR-guided PCI.

PURPOSE: The international multicentre FAME Study (n=1,005) demonstrated significant health benefits for patients undergoing multivessel percutaneous coronary intervention (PCI) guided by fractional flow reserve (FFR) measurement compared with angiography guidance alone (ANGIO). We determined the cost-effectiveness and the public health/budget impact for Australia. METHODS: We performed a prospective economic evaluation comparing FFR vs. ANGIO in patients with multivessel disease based on original patient-level FAME data. We used Australian utilities (EQ-5D) and costs to calculate quality-adjusted life years (QALYs) and incremental cost-effectiveness adopting the societal perspective. The public health and budget impact from the payer's perspective was based on Australian PCI registries. Uncertainty was explored using deterministic sensitivity analyses and the bootstrap method (n=5,000 samples). RESULTS: The cost-effectiveness analysis showed that FFR was cost-saving and reduces costs by 1,776 AUD per patient during one year. Over a two-year time horizon, the public health impact ranged from 7.8 to 73.9 QALYs gained and the budget impact from 1.8 to 14.5 million AUD total cost savings. Sensitivity analyses demonstrated that FFR was cost-saving over a wide range of assumptions. CONCLUSIONS: FFR-guided PCI in patients with multivessel coronary disease substantially reduces cardiac events, improves QALYs and is cost-saving in the Australian health care system.

Incidence of Medication-Related Osteonecrosis of the Jaw in Patients With Breast Cancer During a 20-Year Follow-Up: A Population-Based Multicenter Retrospective Study.

PURPOSE: Medication-related osteonecrosis of the jaw (MRONJ) is one of the most important toxicities of antiresorptive therapy, which is standard practice for patients with breast cancer and bone metastases. However, the population-based incidence of MRONJ is not well established. We therefore performed a retrospective multicenter study to assess the incidence for a whole Austrian federal state (Tyrol). MATERIALS AND METHODS: This retrospective multicenter study was conducted between 2000 and 2020 at all nine breast centers across Tyrol, Austria. Using the cancer registry, the total Tyrolean population was screened for all patients with breast cancer. All patients with breast cancer and bone metastases receiving antiresorptive therapy were finally included in the study. RESULTS: From 8,860 patients initially screened, 639 individuals were eligible and included in our study. Patients received antiresorptive therapy once per month without de-escalation of therapy. MRONJ was diagnosed in 56 (8.8%, 95% CI, 6.6 to 11.0) patients. The incidence of MRONJ was 11.6% (95% CI, 8.0 to 15.3) in individuals treated with denosumab only, 2.8% (95% CI, 0.7 to 4.8) in those treated with bisphosphonates only, and 16.3% (95% CI, 8.8 to 23.9) in the group receiving bisphosphonates followed by denosumab. Individuals developed MRONJ significantly earlier when treated with denosumab. Time to MRONJ after treatment initiation was 4.6 years for individuals treated with denosumab only, 5.1 years for individuals treated with bisphosphonates only, and 8.4 years for individuals treated with both consecutively. CONCLUSION: MRONJ incidence in breast cancer patients with bone metastases was found to be considerably higher, especially for patients receiving denosumab, when compared with available data in the literature. Additionally, patients treated with denosumab developed MRONJ significantly earlier.

A monocentric, randomized, double-blind, controlled crossover trial of nasturtium (Tropaeolum majus) on the lipid regulator prostaglandin E2.

Scope: As prostaglandin E2 (PGE2) has important roles in physiological and inflammatory functions, a double-blind randomized controlled crossover study to investigate the potential of nasturtium (Tropaeolum majus) for modulating PGE2 was conducted, aiming at clarifying the role of benzyl isothiocyanate (BITC). As secondary parameters leukotriene 4 (LTB4), and cytokine release (tumor necrosis factor alpha, TNF-α; interleukins IL-1ß, IL-10, and IL-12) were quantified. Methods and results: Thirty-four healthy female participants consumed 1.5 g nasturtium containing BITC, (verum) or no BITC (control) twice a day for 2 weeks each. Nasturtium intervention resulted in an increase in mean PGE2 levels in serum samples (verum: 1.76-fold, p ≤ 0.05; control: 1.78-fold, p ≤ 0.01), and ex vivo stimulated peripheral blood mononuclear cells (PBMC) (verum: 1.71-fold, p ≤ 0.01; control: 1.43-fold). Using a pre-to-post responder analysis approach, 18 of 34 subjects showed a > 25% PGE2 increase in serum, while it was >25% decreased for 9 subjects (stimulated PBMC: 14 and 8 of 28, respectively). Under the selected conditions, the BITC content of nasturtium did not affect the observed changes in PGE2. Verum intervention also increased mean LTB4 serum level (1.24-fold, p ≤ 0.01), but not in LPS stimulated PBMC, and significantly increased TNF-α release in stimulated PBMC after 3 h (verum: 1.65-fold, p = 0.0032; control: 1.22-fold, p = 0.7818). No change was seen in the anti-inflammatory cytokine IL-10, or the pro-inflammatory cytokines IL-1ß, and IL-12. Conclusion: In contrast to the previously reported in vitro results, on average, LPS activated PBMC and serum from both groups showed increased PGE2 levels. Further analyses suggest that PGE2 release after intervention could possibly depend on the baseline PGE2 level. Identification of phenotypes that respond differently to the nasturtium intervention could be useful to establish personalized approaches for dosing phytopharmaceuticals medicines.

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.

Causal analyses with target trial emulation for real-world evidence removed large self-inflicted biases: systematic bias assessment of ovarian cancer treatment effectiveness.

BACKGROUND AND OBJECTIVES: Drawing causal conclusions from real-world data (RWD) poses methodological challenges and risk of bias. We aimed to systematically assess the type and impact of potential biases that may occur when analyzing RWD using the case of progressive ovarian cancer. METHODS: We retrospectively compared overall survival with and without second-line chemotherapy (LOT2) using electronic medical records. Potential biases were determined using directed acyclic graphs. We followed a stepwise analytic approach ranging from crude analysis and multivariable-adjusted Cox model up to a full causal analysis using a marginal structural Cox model with replicates emulating a reference randomized controlled trial (RCT). To assess biases, we compared effect estimates (hazard ratios [HRs]) of each approach to the HR of the reference trial. RESULTS: The reference trial showed an HR for second line vs. delayed therapy of 1.01 (95% confidence interval [95% CI]: 0.82-1.25). The corresponding HRs from the RWD analysis ranged from 0.51 for simple baseline adjustments to 1.41 (95% CI: 1.22-1.64) accounting for immortal time bias with time-varying covariates. Causal trial emulation yielded an HR of 1.12 (95% CI: 0.96-1.28). CONCLUSION: Our study, using ovarian cancer as an example, shows the importance of a thorough causal design and analysis if one is expecting RWD to emulate clinical trial results.

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.

Effect of Tai Chi on muscle strength, physical endurance, postural balance and flexibility: a systematic review and meta-analysis.

OBJECTIVE: To investigate the impact of Tai Chi training on muscle strength, physical endurance, postural balance and flexibility, as measured by tests commonly used in health-related fitness or competitive sports contexts. DESIGN: Systematic review and meta-analysis. DATA SOURCES: The following databases were searched up to 31 July 2020: CINAHL, Cochrane Library, MEDLINE via PubMed and SPORTDiscus. ELIGIBILITY CRITERIA FOR STUDIES: Inclusion: (1) Randomised controlled trials published in German or English; (2) Tai Chi used as an intervention to improve physical performance; (3) Test methods commonly used in health-related fitness or competitive sports and (4) Participants aged ≥16 years (irrespective of health status). Exclusion: (1) Studies not focusing on Tai Chi or including Tai Chi mixed with other interventions and (2) Modified or less than eight Tai Chi movements. RESULTS: Out of 3817 records, 31 studies were included in the review, 21 of them in the meta-analysis. Significant improvements in handgrip strength (2.34 kg, 95% CI 1.53 to 3.14), walking distance during 6 min (43.37 m, 95% CI 29.12 to 57.63), standing time in single-leg-stance with open eyes (6.41 s, 95% CI 4.58 to 8.24) and thoracolumbar spine flexibility (2.33 cm, 95% CI 0.11 to 4.55) were observed. CONCLUSION: Tai Chi training seems to moderately improve physical fitness when evaluated by tests used in health-related fitness or competitive sports. Moreover, thoracolumbar spine flexibility seems to be a factor in the improvement of postural balance. Further research is needed, including younger healthy participants performing a widely used, standardised form (eg, Peking-style routine) with high-intensity movements (eg, use of lower stances).

Body Composition and Body Weight Changes at Different Altitude Levels: A Systematic Review and Meta-Analysis.

Changes in body composition and weight loss frequently occur when humans are exposed to hypoxic environments. The mechanisms thought to be responsible for these changes are increased energy expenditure resulting from increased basal metabolic rate and/or high levels of physical activity, inadequate energy intake, fluid loss as well as gastrointestinal malabsorption. The severity of hypoxia, the duration of exposure as well as the level of physical activity also seem to play crucial roles in the final outcome. On one hand, excessive weight loss in mountaineers exercising at high altitudes may affect performance and climbing success. On the other, hypoxic conditioning is presumed to have an important therapeutic potential in weight management programs in overweight/obese people, especially in combination with exercise. In this regard, it is important to define the hypoxia effect on both body composition and weight change. The purpose of this study is to define, through the use of meta-analysis, the extent of bodyweight -and body composition changes within the three internationally classified altitude levels (moderate altitude: 1500-3500 m; high altitude: 3500-5300 m; extreme altitude: >5300 m), with emphasis on physical activity, nutrition, duration of stay and type of exposure.

Guidance for a causal comparative effectiveness analysis emulating a target trial based on big real world evidence: when to start statin treatment.

Aim: The aim of this project is to describe a causal (counterfactual) approach for analyzing when to start statin treatment to prevent cardiovascular disease using real-world evidence. Methods: We use directed acyclic graphs to operationalize and visualize the causal research question considering selection bias, potential time-independent and time-dependent confounding. We provide a study protocol following the 'target trial' approach and describe the data structure needed for the causal assessment. Conclusion: The study protocol can be applied to real-world data, in general. However, the structure and quality of the database play an essential role for the validity of the results, and database-specific potential for bias needs to be explicitly considered.

Recommendations for primary studies evaluating therapeutic medical devices were identified and systematically reported through reviewing existing guidance.

OBJECTIVES: The aim of the study was to review existing recommendations on study design, conduct, analysis, and reporting for primary studies of therapeutic medical devices (TMDs) and the closely related field of interventional procedures. STUDY DESIGN AND SETTING: We performed a targeted literature review of publications with recommendations for study design, conduct, analysis, and reporting for primary studies of TMDs and related technologies. We combined an electronic database search with a systematic screening of tables of content of selected journals and scanning the reference lists of relevant articles. RESULTS: We identified 40 publications authored or commissioned primarily by regulators, health technology assessment agencies, and expert groups. We identified study designs of randomized clinical trials that specifically address the quick, incremental development of TMDs and provider and patient preferences. The importance of contextual factors for TMD interventions should be considered during the selection of patients, providers, and centers, as well as in data collection and analysis. We also identified guidance for the analysis and quantification of learning curves as well as for the design and analysis of large registries of high quality. CONCLUSION: The methodology to conduct primary research for TMDs should be disseminated to support improvement of the evidence base for health technology assessments.

Ten recommendations for assessing the comparative effectiveness of therapeutic medical devices: a targeted review and adaptation.

OBJECTIVES: The aim of this study was to review existing guidance on the methods for evaluation of the comparative effectiveness (CE) of therapeutic medical devices (TMDs) and develop recommendations for systematic reviews (SRs) of CE of TMDs as part of health technology assessments. STUDY DESIGN AND SETTING: We performed a targeted literature review of evaluation frameworks and recommendations for evaluation methods for TMDs and related technologies. An electronic database search was combined with systematic screening of tables of content of selected journals and scanning the reference lists of relevant papers. RESULTS: We identified a framework for SRs of complex interventions (FSRCIs) and three documents providing detailed methodology for TMD evaluation. We applied the FSRCIs to TMD evaluation taking into account the more complex composition of the intervention, its rapid, incremental development, as well as the dependency of treatment effects on contextual factors and user proficiency. In 10 recommendations, including a template for a logic model for TMD, we summarized relevant factors that should be systematically considered. CONCLUSION: The quality of SRs of CE assessments of TMDs can be improved by applying these recommendations. This also may require an increase of the quality of primary studies.