Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial.

BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) events in patients with type 2 diabetes at high cardiovascular risk, chronic kidney disease, or prevalent HF irrespective of ejection fraction. Whereas the EMPACT-MI trial (Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients With Acute Myocardial Infarction) showed that empagliflozin does not reduce the risk of the composite of hospitalization for HF and all-cause death, the effect of empagliflozin on first and recurrent HF events after myocardial infarction is unknown. METHODS: EMPACT-MI was a double-blind, randomized, placebo-controlled, event-driven trial that randomized 6522 patients hospitalized for acute myocardial infarction at risk for HF on the basis of newly developed left ventricular ejection fraction of <45% or signs or symptoms of congestion to receive empagliflozin 10 mg daily or placebo within 14 days of admission. In prespecified secondary analyses, treatment groups were analyzed for HF outcomes. RESULTS: Over a median follow-up of 17.9 months, the risk for first HF hospitalization and total HF hospitalizations was significantly lower in the empagliflozin compared with the placebo group (118 [3.6%] versus 153 [4.7%] patients with events; hazard ratio, 0.77 [95% CI, 0.60, 0.98]; P=0.031, for first HF hospitalization; 148 versus 207 events; rate ratio, 0.67 [95% CI, 0.51, 0.89]; P=0.006, for total HF hospitalizations). Subgroup analysis showed consistency of empagliflozin benefit across clinically relevant patient subgroups for first and total HF hospitalizations. The need for new use of diuretics, renin-angiotensin modulators, or mineralocorticoid receptor antagonists after discharge was less in patients randomized to empagliflozin versus placebo (all P<0.05). CONCLUSIONS: Empagliflozin reduced the risk of HF in patients with left ventricular dysfunction or congestion after acute myocardial infarction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04509674.

Low awareness of the transitivity assumption in complex networks of interventions: a systematic survey from 721 network meta-analyses.

BACKGROUND: The transitivity assumption is the cornerstone of network meta-analysis (NMA). Violating transitivity compromises the credibility of the indirect estimates and, by extent, the estimated treatment effects of the comparisons in the network. The present study offers comprehensive empirical evidence on the completeness of reporting and evaluating transitivity in systematic reviews with multiple interventions. METHODS: We screened the datasets of two previous empirical studies, resulting in 361 systematic reviews with NMA published between January 2011 and April 2015. We updated our evidence base with an additional 360 systematic reviews with NMA published between 2016 and 2021, employing a pragmatic approach. We devised assessment criteria for reporting and evaluating transitivity using relevant methodological literature and compared their reporting frequency before and after the PRISMA-NMA statement. RESULTS: Systematic reviews published after PRISMA-NMA were more likely to provide a protocol (odds ratio (OR): 3.94, 95% CI: 2.79-5.64), pre-plan the transitivity evaluation (OR: 3.01, 95% CI: 1.54-6.23), and report the evaluation and results (OR: 2.10, 95% CI: 1.55-2.86) than those before PRISMA-NMA. However, systematic reviews after PRISMA-NMA were less likely to define transitivity (OR: 0.57, 95% CI: 0.42-0.79) and discuss the implications of transitivity (OR: 0.48, 95% CI: 0.27-0.85) than those published before PRISMA-NMA. Most systematic reviews evaluated transitivity statistically than conceptually (40% versus 12% before PRISMA-NMA, and 54% versus 11% after PRISMA-NMA), with consistency evaluation being the most preferred (34% before versus 47% after PRISMA-NMA). One in five reviews inferred the plausibility of the transitivity (22% before versus 18% after PRISMA-NMA), followed by 11% of reviews that found it difficult to judge transitivity due to insufficient data. In justifying their conclusions, reviews considered mostly the comparability of the trials (24% before versus 30% after PRISMA-NMA), followed by the consistency evaluation (23% before versus 16% after PRISMA-NMA). CONCLUSIONS: Overall, there has been a slight improvement in reporting and evaluating transitivity since releasing PRISMA-NMA, particularly in items related to the systematic review report. Nevertheless, there has been limited attention to pre-planning the transitivity evaluation and low awareness of the conceptual evaluation methods that align with the nature of the assumption.

Outcomes of steroid-resistant nephrotic syndrome in children not treated with intensified immunosuppression.

BACKGROUND: The aim of the current PodoNet registry analysis was to evaluate the outcome of steroid-resistant nephrotic syndrome (SRNS) in children who were not treated with intensified immunosuppression (IIS), focusing on the potential for spontaneous remission and the role of angiotensin blockade on proteinuria reduction. METHODS: Ninety-five pediatric patients who did not receive any IIS were identified in the PodoNet Registry. Competing risk analyses were performed on 67 patients with nephrotic-range proteinuria at disease onset to explore the cumulative rates of complete or partial remission or progression to kidney failure, stratified by underlying etiology (genetic vs. non-genetic SRNS). In addition, Cox proportional hazard analysis was performed to identify factors predicting proteinuria remission. RESULTS: Eighteen of 31 (58.1%) patients with non-genetic SRNS achieved complete remission without IIS, with a cumulative likelihood of 46.2% at 1 year and 57.7% at 2 years. Remission was sustained in 11 children, and only two progressed to kidney failure. In the genetic subgroup (n = 27), complete resolution of proteinuria occurred very rarely and was never sustained; 6 (21.7%) children progressed to kidney failure at 3 years. Almost all children (96.8%) received proteinuria-lowering renin-angiotensin-aldosterone system (RAAS) antagonist treatment. On antiproteinuric treatment, partial remission was achieved in 7 of 31 (22.6%) children with non-genetic SRNS and 9 of 27 children (33.3%) with genetic SRNS. CONCLUSION: Our results demonstrate that spontaneous complete remission can occur in a substantial fraction of children with non-genetic SRNS and milder clinical phenotype. RAAS blockade increases the likelihood of partial remission of proteinuria in all forms of SRNS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Does a closed reduction improve aesthetical and functional outcome after nasal fracture?

BACKGROUND AND PURPOSES: How closed reduction (CR) to repair a nasal fracture affects the patient's quality of life (QoL) has not been investigated. Here, we assessed QoL before and after CR using disease-specific questionnaires and compared the QoL scores of patients with nasal fractures with normative scores from a reference cohort. METHODS: This was a prospective study of 96 patients with nasal fractures undergoing CR. Patients were interviewed about aesthetic, functional, and QoL issues before and after surgery using the Functional Rhinoplasty Outcome Inventory (FROI-17) and the Rhinoplasty Outcome Evaluation (ROE). Photographs of the nasal area were taken before and after surgery and reviewed. Data were compared with those from a reference cohort (n = 1000). RESULTS: Most fractures were type I (80.6%) and most were caused by sport-related accidents (36.5%). The ROE scores increased from 67.3 preoperatively to 73.4 postoperatively (p = 0.001). The FROI-17 also improved, indicating the overall effect of the nose on QoL (p = 0.002). Compared with the reference cohort, patients felt more affected by nasal symptoms before surgery (- 9.37, p = 0.02) than by more general aspects. ROE scores returned to normative values after surgery (p < 0.001). The postoperative cohort had lower scores for the FROI-17 item overall effects of the nose on QoL than the reference cohort did, although the nasal symptom score remained higher in patients than in reference controls. CONCLUSIONS: This study showed that CR can improve the aesthetical but not the functional outcome of the nose.

Diagnostic Performance of Pancreatic Cytology with the Papanicolaou Society of Cytopathology System: A Systematic Review, before Shifting into the Upcoming WHO International System.

The Papanicolaou Society of Cytopathology (PSC) reporting system classifies pancreatobiliary samples into six categories (I-VI), providing guidance for personalized management. As the World Health Organization (WHO) has been preparing an updated reporting system for pancreatobiliary cytopathology, this systematic review aimed to evaluate the risk of malignancy (ROM) of each PSC category, also the sensitivity and specificity of pancreatic FNA cytology using the current PSC system. Five databases were investigated with a predefined search algorithm. Inclusion and exclusion criteria were applied to select the eligible studies for subsequent data extraction. A study quality assessment was also performed. Eight studies were included in the qualitative analysis. The ROM of the PSC categories I, II, III, IV, V, VI were in the ranges of 8-50%, 0-40%, 28-100%, 0-31%, 82-100%, and 97-100%, respectively. Notably, the ROM IVB ("neoplastic-benign") subcategory showed a 0% ROM. Four of the included studies reported separately the ROMs for the IVO subcategory ("neoplastic-other"; its overall ROM ranged from 0 to 34%) with low (LGA) and high-grade atypia (HGA). ROM for LGA ranged from 4.3 to 19%, whereas ROM for HGA from 64 to 95.2%. When the subcategory IVO with HGA was considered as cytologically positive, together with the categories V and VI, there was a higher sensitivity of pancreatic cytology, at minimal expense of the specificity. Evidence suggests the proposed WHO international system changes-shifting the IVB entities into the "benign/negative for malignancy" category and establishing two new categories, the "pancreatic neoplasm, low-risk/grade" and "pancreatic neoplasm, high-risk/grade"-could stratify pancreatic neoplasms more effectively than the current PSC system.

Comparing the diagnostic performance of radiotracers in recurrent prostate cancer: a systematic review and network meta-analysis.

PURPOSE: Many radiotracers are currently available for the detection of recurrent prostate cancer (rPC), yet many have not been compared head-to-head in comparative imaging studies. There is therefore an unmet need for evidence synthesis to guide evidence-based decisions in the selection of radiotracers. The objective of this study was therefore to assess the detection rate of various radiotracers for the rPC. METHODS: The PUBMED, EMBASE, and the EU and NIH trials databases were searched without date or language restriction for comparative imaging tracers for 13 radiotracers of principal interest. Key search terms included 18F-PSMA-1007, 18F-DCPFyl, 68Ga-PSMA-11, 18F-PSMA-11, 68Ga-PSMA-I&T, 68Ga-THP-PSMA, 64Cu-PSMA-617, 18F-JK-PSMA-7, 18F-Fluciclovine, 18F-FABC, 18F-Choline, 11C-Choline, and 68Ga-RM2. Studies reporting comparative imaging data in humans in rPC were selected. Single armed studies and matched pair analyses were excluded. Twelve studies with eight radiotracers were eligible for inclusion. Two independent reviewers screened all studies (using the PRISMA-NMA statement) for inclusion criteria, extracted data, and assessed risk of bias (using the QUADAS-2 tool). A network meta-analysis was performed using Markov-Chain Monte Carlo Bayesian analysis to obtain estimated detection rate odds ratios for each tracer combination. RESULTS: A majority of studies were judged to be at risk of publication bias. With the exception of 18F-PSMA-1007, little difference in terms of detection rate was revealed between the three most commonly used PSMA-radiotracers (68Ga-PSMA-11, 18F-PSMA-1007, 18F-DCFPyl), which in turn showed clear superiority to choline and fluciclovine using the derived network. CONCLUSION: Differences in patient-level detection rates were observed between PSMA- and choline-radiotracers. However, there is currently insufficient evidence to favour one of the four routinely used PSMA-radioligands (PSMA-11, PSMA-1007, PSMA-I&T, and DCFPyl) over another owing to the limited evidence base and risk of publication bias revealed by our systematic review. A further limitation was lack of reporting on diagnostic accuracy, which might favour radiotracers with low specificity in an analysis restricted only to detection rate. The NMA derived can be used to inform the design of future clinical trials and highlight areas where current evidence is weak.

Safety and donor site morbidity of the transverse musculocutaneous gracilis (TMG) flap in autologous breast reconstruction-A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVES: The transverse musculocutaneous gracilis (TMG) flap has gained popularity for breast reconstruction. However, the literature regarding its donor site morbidity is heterogeneous. This systematic review sought to clarify the evidence on donor site morbidity. METHODS: A systematic literature search was conducted. We included all articles reporting on donor-site morbidity of the TMG flap for breast reconstruction. The results were analyzed in R and its extension meta. A generalized linear mixed model was used to combine proportions and their 95% confidence intervals (CIs) in a random-effects meta-analysis. RESULTS: Nineteen articles provided an overall sample of 843 TMG flaps. The total flap loss was low at 2% (95% CI, 1%-3%). All patients were normal weight (pooled body mass index 22.75, 95% CI, 21.88-23.63). The incidence of wound dehiscence (8%, 95% CI, 4%-16%), seroma (4%, 95% CI, 2%-7%), hematoma (2%, 95% CI, 1%-4%) and infection (0%-5%) on the TMG donor site was low. Functional impairments included sensory disturbance (0%-74%), motoric deficits (0%-50%), and changes in the genital region (0%-24%), all of which were modest. CONCLUSIONS: This review confirms the safety and low donor site morbidity of the TMG flap in normal-weight patients, which is comparable to that of other popular free flaps in breast reconstruction.

Prognostic role of the Donor Risk Index, the Eurotransplant Donor Risk Index, and the Balance of Risk score on graft loss after liver transplantation.

This study aimed to identify cutoff values for donor risk index (DRI), Eurotransplant (ET)-DRI, and balance of risk (BAR) scores that predict the risk of liver graft loss. MEDLINE and Web of Science databases were searched systematically and unrestrictedly. Graft loss odds ratios and 95% confidence intervals were assessed by meta-analyses using Mantel-Haenszel tests with a random-effects model. Cutoff values for predicting graft loss at 3 months, 1 year, and 3 years were analyzed for each of the scores. Measures of calibration and discrimination used in studies validating the DRI and the ET-DRI were summarized. DRI ≥ 1.4 (six studies, n = 35 580 patients) and ET-DRI ≥ 1.4 (four studies, n = 11 666 patients) were associated with the highest risk of graft loss at all time points. BAR > 18 was associated with the highest risk of 3-month and 1-year graft loss (n = 6499 patients). A DRI cutoff of 1.8 and an ET-DRI cutoff of 1.7 were estimated using a summary receiver operator characteristic curve, but the sensitivity and specificity of these cutoff values were low. A DRI and ET-DRI score ≥ 1.4 and a BAR score > 18 have a negative influence on graft survival, but these cutoff values are not well suited for predicting graft loss.

Systematic reviews in surgery-recommendations from the Study Center of the German Society of Surgery.

BACKGROUND: Systematic reviews are an important tool of evidence-based surgery. Surgical systematic reviews and trials, however, require a special methodological approach. PURPOSE: This article provides recommendations for conducting state-of-the-art systematic reviews in surgery with or without meta-analysis. CONCLUSIONS: For systematic reviews in surgery, MEDLINE (via PubMed), Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) should be searched. Critical appraisal is at the core of every surgical systematic review, with information on blinding, industry involvement, surgical experience, and standardisation of surgical technique holding special importance. Due to clinical heterogeneity among surgical trials, the random-effects model should be used as a default. In the experience of the Study Center of the German Society of Surgery, adherence to these recommendations yields high-quality surgical systematic reviews.

Atherosclerosis is aggravated by iron overload and ameliorated by dietary and pharmacological iron restriction.

AIMS: Whether and how iron affects the progression of atherosclerosis remains highly debated. Here, we investigate susceptibility to atherosclerosis in a mouse model (ApoE-/- FPNwt/C326S), which develops the disease in the context of elevated non-transferrin bound serum iron (NTBI). METHODS AND RESULTS: Compared with normo-ferremic ApoE-/- mice, atherosclerosis is profoundly aggravated in iron-loaded ApoE-/- FPNwt/C326S mice, suggesting a pro-atherogenic role for iron. Iron heavily deposits in the arterial media layer, which correlates with plaque formation, vascular oxidative stress and dysfunction. Atherosclerosis is exacerbated by iron-triggered lipid profile alterations, vascular permeabilization, sustained endothelial activation, elevated pro-atherogenic inflammatory mediators, and reduced nitric oxide availability. NTBI causes iron overload, induces reactive oxygen species production and apoptosis in cultured vascular cells, and stimulates massive MCP-1-mediated monocyte recruitment, well-established mechanisms contributing to atherosclerosis. NTBI-mediated toxicity is prevented by transferrin- or chelator-mediated iron scavenging. Consistently, a low-iron diet and iron chelation therapy strongly improved the course of the disease in ApoE-/- FPNwt/C326S mice. Our results are corroborated by analyses of serum samples of haemochromatosis patients, which show an inverse correlation between the degree of iron depletion and hallmarks of endothelial dysfunction and inflammation. CONCLUSION: Our data demonstrate that NTBI-triggered iron overload aggravates atherosclerosis and unravel a causal link between NTBI and the progression of atherosclerotic lesions. Our findings support clinical applications of iron restriction in iron-loaded individuals to counteract iron-aggravated vascular dysfunction and atherosclerosis.

Relative Efficacy of Spironolactone, Eplerenone, and cAnRenone in patients with Chronic Heart failure (RESEARCH): a systematic review and network meta-analysis of randomized controlled trials.

This study aims to assess the comparative benefit and risk profile of treatment with mineralocorticoid receptor antagonists (MRAs) with regard to all-cause mortality (primary endpoint), cardiovascular mortality, or heart failure (HF)-related hospitalization (secondary endpoints) and the safety endpoints hyperkalemia, acute renal failure, and gynecomastia in patients with chronic HF. We conducted a systematic review and network meta-analysis following PRISMA-P and PRISMA-NMA guidelines. From 16 different sources, 14 randomized controlled trials totaling 12,213 patients testing an active treatment of either spironolactone, eplerenone, or canrenone/potassium-canreonate in adults with symptomatic HF due to systolic dysfunction reporting any of the above endpoints were retained. Efficacy in comparison to placebo/standard medical care with respect to all-cause mortality was confirmed for spironolactone and eplerenone while no conclusion could be drawn for canrenone (HR 0.69 (0.62; 0.77), 0.82 (0.75; 0.91), and 0.50 (0.17; 1.45), respectively). Indirect comparisons hint a potential (non-significant) preference of spironolactone over eplerenone (HR 0.84 (0.68; 1.03)). The overall risk of bias was low to intermediate. Results for secondary endpoints as well as sensitivity analyses essentially mirrored these findings. The beta-blocker adjusted meta-analysis for the primary endpoint showed the same tendency as the unadjusted one (HR 0.39 (0.07; 2.03)). Results need to be interpreted with caution, though, as the resultant mix of patient- and study-level covariates produced unstable statistical modeling. We found no significant and systematic superiority of either MRA regarding efficacy toward all endpoints considered in both direct and indirect comparisons.

Changes of clinical parameters at implants: A retrospective comparison of implants versus natural teeth over 5 years of supportive periodontal therapy.

OBJECTIVES: To compare clinical parameters of implants versus natural teeth over a period of 5 years during supportive periodontal therapy (SPT). MATERIAL AND METHODS: A total of 421 SPT patients were screened for implants (I) and corresponding control teeth (C). Data (patient level [P ]: sex, age, smoking status, systemic diseases, adherence, oral hygiene indices, mean probing depth [PD]P , bleeding on probing [BOP]P , periodontal risk profile; implant/control tooth level [I/C ]: PDI/C , BOPI/C ; site level at implants [SITE ]: position, dental arch, aspect, BOPSITE ) were assessed at the first SPT session where the implant was probed (T1) and 5 years later (T2). The influence of patient and implant/control-related factors on PDI/C /BOPI/C was tested (linear mixed model) as well as the influence of site-specific factors on the PDSITE change (multilevel regression). RESULTS: A total of 70 patients (151 implants) were included. Mean PDI was 2.75 ± 0.85 mm (T1) and 2.87 ± 0.79 mm (T2). Mean PDC was 2.42 ± 0.66 mm (T1) and 2.49 ± 0.71 mm (T2). BOPI increased from 8.62 ± 15.01% (T1) to 24.06 ± 26.79% (T2) and BOPC from 9.97 ± 17.78% (T1) to 15.52 ± 22.69% (T2). The differences between implants and controls were significant for BOP (p = .0032). At T2, BOPI/C was associated with periodontal risk (p = .0351). The site-specific analysis revealed an association of BOPSITE at T1 with the progression of PDSITE (p = .0058). CONCLUSIONS: Probing depths of implants and controls seem to change similarly during SPT but retention of inflammation-free conditions at implants appears to be more difficult compared to natural teeth. Patients with a high-risk profile appear to have an increased susceptibility for BOP around implants, and BOP at implants seems to be a predictor for further PD increase.

Simulation and data-generation for random-effects network meta-analysis of binary outcome.

The performance of statistical methods is frequently evaluated by means of simulation studies. In case of network meta-analysis of binary data, however, available data-generating models (DGMs) are restricted to either inclusion of two-armed trials or the fixed-effect model. Based on data-generation in the pairwise case, we propose a framework for the simulation of random-effect network meta-analyses including multiarm trials with binary outcome. The only one of the common DGMs used in the pairwise case, which is directly applicable to a random-effects network setting uses strongly restrictive assumptions. To overcome these limitations, we modify this approach and derive a related simulation procedure using odds ratios as effect measure. The performance of this procedure is evaluated with synthetic data and in an empirical example.

Likelihood-based random-effects meta-analysis with few studies: empirical and simulation studies.

BACKGROUND: Standard random-effects meta-analysis methods perform poorly when applied to few studies only. Such settings however are commonly encountered in practice. It is unclear, whether or to what extent small-sample-size behaviour can be improved by more sophisticated modeling. METHODS: We consider likelihood-based methods, the DerSimonian-Laird approach, Empirical Bayes, several adjustment methods and a fully Bayesian approach. Confidence intervals are based on a normal approximation, or on adjustments based on the Student-t-distribution. In addition, a linear mixed model and two generalized linear mixed models (GLMMs) assuming binomial or Poisson distributed numbers of events per study arm are considered for pairwise binary meta-analyses. We extract an empirical data set of 40 meta-analyses from recent reviews published by the German Institute for Quality and Efficiency in Health Care (IQWiG). Methods are then compared empirically as well as in a simulation study, based on few studies, imbalanced study sizes, and considering odds-ratio (OR) and risk ratio (RR) effect sizes. Coverage probabilities and interval widths for the combined effect estimate are evaluated to compare the different approaches. RESULTS: Empirically, a majority of the identified meta-analyses include only 2 studies. Variation of methods or effect measures affects the estimation results. In the simulation study, coverage probability is, in the presence of heterogeneity and few studies, mostly below the nominal level for all frequentist methods based on normal approximation, in particular when sizes in meta-analyses are not balanced, but improve when confidence intervals are adjusted. Bayesian methods result in better coverage than the frequentist methods with normal approximation in all scenarios, except for some cases of very large heterogeneity where the coverage is slightly lower. Credible intervals are empirically and in the simulation study wider than unadjusted confidence intervals, but considerably narrower than adjusted ones, with some exceptions when considering RRs and small numbers of patients per trial-arm. Confidence intervals based on the GLMMs are, in general, slightly narrower than those from other frequentist methods. Some methods turned out impractical due to frequent numerical problems. CONCLUSIONS: In the presence of between-study heterogeneity, especially with unbalanced study sizes, caution is needed in applying meta-analytical methods to few studies, as either coverage probabilities might be compromised, or intervals are inconclusively wide. Bayesian estimation with a sensibly chosen prior for between-trial heterogeneity may offer a promising compromise.

Interprofessional collaboration in nursing homes (interprof): development and piloting of measures to improve interprofessional collaboration and communication: a qualitative multicentre study.

BACKGROUND: Given both the increase of nursing home residents forecast and challenges of current interprofessional interactions, we developed and tested measures to improve collaboration and communication between nurses and general practitioners (GPs) in this setting. Our multicentre study has been funded by the German Federal Ministry of Education and Research (FK 01GY1124). METHODS: The measures were developed iteratively in a continuous process, which is the focus of this article. In part 1 "exploration of the situation", interviews were conducted with GPs, nurses, nursing home residents and their relatives focusing on interprofessional interactions and medical care. They were analysed qualitatively. Based on these results, in part 2 "development of measures to improve collaboration", ideas for improvement were developed in nine focus groups with GPs and nurses. These ideas were revisited in a final expert workshop. We analysed the focus groups and expert workshop using mind mapping methods, and finally drew up the compilation of measures. In an exploratory pilot study "study part 3" four nursing homes chose the measures they wanted to adopt. These were tested for three months. Feasibility and acceptance of the measures were evaluated via guideline interviews with the stakeholders which were analysed by content analyses. RESULTS: Six measures were generated: meetings to establish common goals, main contact person, standardised pro re nata medication, introduction of name badges, improved availability of nurse/GP and standardised scheduling/ procedure for nursing home visits. In the pilot study, the measures were implemented in four nursing homes. GPs and nurses reviewed five measures as feasible and acceptable, only the designation of a "main contact person" was not considered as an improvement. CONCLUSIONS: Six measures to improve collaboration and communication could be compiled in a multistep qualitative process respecting the perspectives of involved stakeholders. Five of the six measures were positively assessed in an exploratory pilot study. They could easily be transferred into the daily routine of other nursing homes, as no special models have to exist in advance. Impact of the measures on patient oriented outcomes should be examined in further research. TRIAL REGISTRATION: Not applicable.

Left Ventricular Function, Congestion, and Effect of Empagliflozin on Heart Failure Risk After Myocardial Infarction.

BACKGROUND: Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). OBJECTIVES: This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. METHODS: In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months. RESULTS: Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. CONCLUSIONS: In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674).

Effects of Physical Activity Interventions on Strength, Balance and Falls in Middle-Aged Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Weak lower body strength and balance impairments are fundamental risk factors for mobility impairments and falls that can be improved by physical activity (PA). Previous meta-analyses have focused on these risk factors in adults aged ≥ 65 years. Yet, the potential of PA for improving these risk factors in middle-aged populations has not been systematically investigated. This systematic review and meta-analysis aim to examine the effect of general and structured PA on lower limb strength, postural balance and falls in middle-aged adults. METHODS: A computerized systematic literature search was conducted in the electronic databases MEDLINE, CINAHL, Web of Science and Cochrane Library. PA intervention types were classified according to the ProFaNE taxonomy. Randomized controlled trials exploring the effects of PA on strength (e.g., leg press one-repetition-maximum), balance (e.g., single limb stance) and falls (e.g., fall rates) in adults aged 40-60 years were systematically searched and included in a network analysis. Moderator analyses were performed for specific subgroups (age, sex, low PA). The methodological quality of the included studies was assessed using the Physiotherapy Evidence Database (PEDro) Scale. RESULTS: Out of 7170 articles screened, 66 studies (median PEDro score 5) with 3387 participants were included. Strong, significant effects on muscle strength were found for strength (SMD = 1.02), strength-aerobic (SMD = 1.41), strength-endurance (SMD = 0.92) and water-based (SMD = 1.08) training (52 studies, I2 = 79.3%). Strength training (SMD = 1.16), strength-aerobic (SMD = 0.98) and 3D training (SMD = 1.31) improved postural balance (30 studies, I2 = 88.1%). Moderator analyses revealed significant effects of specific intervention types on certain subgroups and subdomains of strength and balance. No studies were found measuring falls. CONCLUSIONS: Structured PA interventions in middle-aged adults improve strength and balance outcomes related to functional impairments and falls. Strength training increases both strength and balance and can be recommended to prevent age-related functional decline. However, the interpretability of the results is limited due to considerable heterogeneity and the overall low methodological quality of the included studies. Long-term trials are needed to determine the preventive potential of PA on strength, balance and falls. This meta-analysis may inform guidelines for tailored training during middle age to promote healthy aging. Prospero registration: CRD42020218643.