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Background: In the multicentre randomized trial BRIOS (Breast Reconstruction In One Stage), direct‐to‐implant (DTI) breast reconstruction with an acellular dermal matrix (ADM) was associated with a markedly higher postoperative complication rate compared with two‐stage tissue expander/implant breast reconstruction. This study aimed to identify factors that contribute to the occurrence of complications after DTI ADM‐assisted breast reconstruction. Methods: Data were obtained from the BRIOS study, including all patients treated with DTI ADM‐assisted breast reconstruction. Logistic regression analyses were performed to identify factors predictive of postoperative complications. Results: Fifty‐nine patients (91 breasts) were included, of whom 27 (35 breasts) developed a surgical complication. Reoperations were performed in 29 breasts (32 per cent), with prosthesis removal in 22 (24 per cent). In multivariable analyses, mastectomy weight was associated with complications (odds ratio (OR) 1·94, 95 per cent c.i. 1·33 to 2·83), reoperations (OR 1·70, 1·12 to 2·59) and removal of the implant (OR 1·55, 1·11 to 2·17). Younger patients (OR 1·07, 1·01 to 1·13) and those who received adjuvant chemotherapy (OR 4·83, 1·15 to 20·24) more frequently required reoperation. In univariable analyses, adjuvant radiotherapy showed a trend towards more complications (OR 7·23, 0·75 to 69·95) and removal of the implant (OR 5·12, 0·76 to 34·44), without reaching statistical significance. Conclusion: Breast size appeared to be the most significant predictor of complications in DTI ADM‐assisted breast reconstruction. The technique should preferably be performed in patients with small to moderate sized breasts. Registration number: NTR5446 ( http://www.trialregister.nl). [ABSTRACT FROM AUTHOR]

Background: Task-shifting from primary care physicians (PCPs) to nurses is a means of overcoming PCP shortages and meeting the needs of patients receiving primary care. The aim of this overview of systematic reviews is to assess the effects of delegation or substitution of PCPs' activities by nurses on patient relevant, clinical, professional and health services-related outcomes., Methods: We conducted a systematic literature search for secondary literature in Medline, Embase, Pubmed, the Cochrane Library, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL). We included systematic reviews and meta-analyses that analysed randomised controlled trials (RCTs) and controlled, prospective trials in English and German. Abstracts and full-text articles were screened independently by two reviewers. Full-text articles were assessed using the Overview Quality Assessment Questionnaire. After data extraction a narrative synthesis was performed. We defined patient-relevant outcomes as our primary outcomes., Results: We included six systematic reviews. The interventions included first contact, history taking and assessment, patient education, review of drug treatment, referrals to GPs and other health professionals, ordering further investigations and ongoing care. Two meta-analyses showed a relative risk reduction of mortality in favour of nurse-led care, whereby the reduction in one analysis was significant. The effect was highest in the group of more highly qualified nurse practitioners (RR 0.19), as opposed to nurse practitioners (RR 0.76) and registered nurses (RR 0.92). Two meta-analyses showed a relative risk reduction in hospital admissions and patient satisfaction. Whereas care conducted by physicians and registered nurses led to the same outcomes, care conducted by nurse practitioners led to better outcomes (RR 0.74). An analysis according to nursing group showed that patients were more satisfied with treatment by registered nurses (SMD 1.37) than with treatment conducted by nurse practitioners and more qualified nurse practitioners (SMD 0.17). In terms of patient-relevant outcomes, no differences were observed between physician-led care and nurse-led care in terms of physical function, quality of life and pain., Conclusion: Nurse-led care is probably as safe or safer than physician-led care in terms of mortality and hospital admissions. However, the impact of nursing staff training has not been sufficiently examined., Competing Interests: Declarations Ethics approval and consent to participate The overview of systematic reviews did not involve human participants. Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Task-shifting from primary care physicians (PCPs) to nurses is one option to better and more efficiently meet the needs of the population in primary care and to overcome PCP shortages. This protocol outlines an overview of systematic reviews to assess the effects of delegation or substitution by nurses of PCPs' activities regarding clinical, patient-relevant, professional and health services-related outcomes., Methods and Analysis: We will conduct a systematic literature search for secondary literature in PubMed/MEDLINE, EMBASE, CINAHL and Cochrane databases. Systematic reviews, meta-analyses and Health Technology Assessments in German and English comprising randomised controlled trials and prospective controlled trials will be considered for inclusion. Search terms will include Medical Subject Headings combined with free text words. At least one-third of abstracts and full-text articles are reviewed by two independent reviewers. Methodological quality will be assessed using the Overview Quality Assessment Questionnaire. We will only consider reviews if they include controlled trials, if the profession that substituted or delegated tasks was a nurse, if the profession of the control was a PCP, if the assessed intervention was the same in the intervention and control group and if the Overview Quality Assessment Questionnaire score is ≥5. The corrected covered area will be calculated to describe the degree of overlap of studies in the reviews included in the study. We will report the overview according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses., Ethics and Dissemination: The overview of secondary literature does not require the approval of an Ethics Committee and will be published in a peer-reviewed journal., Prospero Registration Number: CRD42020183327., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Health information is a prerequisite for informed choices-decisions, made by individuals about their own health based on knowledge and in congruence with own preferences. Criteria for development, content and design have been defined in a corresponding guideline. However, no instruments exist that provide reasonably operationalised measurement items. Therefore, we drafted the checklist, MAPPinfo, addressing the existing criteria with 19 items., Objectives: The current study aimed to validate MAPPinfo., Methods: Five substudies were conducted subsequently at the Martin Luther University Halle-Wittenberg, Germany and the Medical University of Graz, Austria: (1) to determine content validity through expert reviews of the first draft, (2) to determine feasibility using 'think aloud' in piloting with untrained users, (3) to determine inter-rater reliability and criterion validity through a pretest on 50 health information materials, (4) to determine construct validity using 50 developers' self-declarations about development methods as a reference standard, (5) to determine divergent validity in comparison with the Ensuring Quality Information for Patients (EQIP) (expanded) Scale. The analyses used were qualitative methods and correlation-based methods for determining both inter-rater reliability and validity., Results: The instrument was considered by experts to operationalise the existing guidelines convincingly. Health and nursing science students found it easy to understand and use. It also had good interrater reliability (mean of T coefficients = .79) and provided a very good estimate of the reference standard (Spearman's rho = .89), implying sound construct validity. Finally, comparison with the EQIP instrument revealed important and distinct areas of similarities and differences., Conclusions: The new instrument is ready for use as a screening instrument without the need for training. According to its underpinning concept the instrument exclusively comprises items which are justified by either ethics or research evidence, implying negligence of not yet evidence based, however, potentially important criteria. Further research is needed to complete the body of evidence-based criteria, aiming at an extension of the guideline and MAPPinfo., Trial Registration Number: AsPredicted22546; date of registration: 24 July 2019., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kasper et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: No population-based data on awareness and knowledge of palliative care currently exist in Austria. We therefore conducted a survey to determine the general awareness and knowledge of palliative care in Styria, a federal state in Austria. We also asked participants to imagine what services they would need as a patient or family member, where they themselves would like to receive such services, and what fears they imagined patients with a terminal illness would have., Methods: A descriptive cross-sectional survey consisting of 18 questions that address several aspects of palliative care was carried out in the adult population of Styria, Austria, from October 2019 to March 2020., Results: A total of 419 questionnaires were analyzed, whereby 70.3% of respondents had at least heard of palliative care. Of these, significantly more were female, had a university degree and were aged 50 to 64. The main goal of palliative care was chosen correctly by 67.1% of participants, with the proportion of correct answers increasing in line with education and reaching 82.0% among university graduates. Overall, 73.2% believed that the greatest need of terminally ill persons was a reduction in physical suffering, whereas the greatest perceived need of relatives was the availability of specialist care around the clock. About one-third believed that the greatest fear of palliative patients was that of death, which was chosen significantly more often by men than women. If terminally ill, some 39% of respondents would wish to be looked after at home by professional carers, and women and people that had completed high school chose this answer significantly more often. The most desired service that should be provided to patients and relatives was home pain management at 69.9%, followed by time off for family caregivers at 58.0%. This item was chosen significantly more often by women., Conclusions: To facilitate the care of severely ill patients at home, it would make sense to develop targeted information campaigns. These should also attempt to deliver targeted information to less informed groups of people, such as young, poorly educated men, in order to raise their awareness of the difficulties and challenges of providing care to terminally ill patients and thus increase the acceptance of support options.

Background/objective: Evidence-based clinical pathways can be a useful tool for guideline implementation. However, there seem to be barriers to the use of clinical pathways. The aim of the present questionnaire survey was to assess the perceived usability of the clinical pathway "Overweight/obesity in children and adolescents at primary care level" and to identify factors promoting and hindering the use of the clinical pathway., Methods: In January 2020, an online questionnaire survey was sent out to 3,916 general practitioners and 470 pediatricians in Austria. The data collected were analysed descriptively., Results: A total of 148 people took part in the questionnaire survey (response rate 3.7 %). The majority of respondents indicated that they, in general, perceive evidence-based clinical pathways as helpful (90 %) and also make use of them (57 %). Few respondents (9 %) felt well-informed about new clinical pathways developed in Austria. Most of the respondents considered the clinical pathway "Overweight/obesity in children and adolescents at primary care level" as a useful support (60 %), as a reference work (72 %) or as a facilitator for justifying their approach to their patients (68 %). However, a large proportion of the respondents stated that the clinical pathway is not easily applicable in everyday practice. The three most frequently cited barriers to using the clinical pathway were lack of time resources, lack of structures and lack of financial incentives. Other display and access options (e. g., individualisation, integration into practice software) were most frequently cited as factors that might promote the use of the pathway., Conclusion: Although the majority of the respondents had positive expectations regarding the use of the clinical pathway "Overweight/obesity in children and adolescents at primary care level", many of them still perceived its usability in everyday clinical practice as difficult. The necessary next steps to improve the use of evidence-based clinical pathways seem to be: an economic and practicable design, easy accessibility of clinical pathways and the creation of framework conditions that facilitate their use in everyday practice., (Copyright © 2021. Published by Elsevier GmbH.)

Introduction: Health information is a prerequisite of informed decision-making. Criteria for development, content and presentation have recently been published in a corresponding guideline. Within a systematic search, 27 relevant checklists were identified, none of them, however, complying with the guideline or providing reasonably operationalised measurement items. Therefore, a draft of a checklist with 19 criteria was drafted. The current study aims at developing and validating this measure of quality., Methods and Analysis: The validation design consists of five single studies to be conducted at the University of Halle-Wittenberg/Germany and Graz/Austria. (1) Achieving content validity through expert reviews of the first draft, (2) achieving feasibility using 'think aloud' in piloting with untrained users, (3) pretesting the instrument applied to health information materials without use of secondary sources: determining inter-rater reliability and criterion validity, (4) determining construct validity using information on proceedings and methods in the development process provided by the developers and (5) determining divergent validity in comparison with the Ensuring Quality Information for Patients (EQUIP) (expanded) Scale. The substudies will use varying samples of experts, students and developers and will apply the instrument to materials of various domains. Sample sizes will be adjusted to the particular research designs and questions. Analyses will employ qualitative methods, such as content analyses and discourse within the expert panel, and correlation-based methods both for determining inter-rater reliability and validity., Ethics and Dissemination: The project is approved by the ethics committee of the Martin Luther University Halle-Wittenberg (approval number: 2019 115). Results will be published, and the instrument made accessible on public health platforms. It is meant to become a certification standard. MAPPinfo can be used as a screening instrument without training or secondary sources. Although developed in the German language, the instrument will be applicable also in other languages., Trial Registration Number: AsPredected22546; date of registration: 24 July 2019., Protocol Version: July 2020., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patient information materials and decision aids are essential tools for helping patients make informed decisions and share in decision-making. The aim of this study was to investigate the quality of the written patient information materials available at general practices in Styria, Austria., Methods: We asked general practitioners to send in all patient information materials available in their practices and to answer a short questionnaire. We evaluated the materials using the Ensuring Quality Information for Patients (EQIP-36) instrument., Results: A total of 387 different patient information materials were available for quality assessment. These materials achieved an average score of 39 out of 100. The score was below 50 for 78% of all materials. There was a significant lack of information on the evidence base of recommendations. Only 9 % of the materials provided full disclosure of their evidence sources. We also found that, despite the poor quality of the materials, 89% of general practitioners regularly make active use of them during consultations with patients., Conclusion: Based on international standards, the quality of patient information materials available at general practices in Styria is poor. The vast majority of the materials are not suitable as a basis for informed decisions by patients. However, most Styrian general practitioners use written patient information materials on a regular basis in their daily clinical practice. Thus, these materials not only fail to help raise the health literacy of the general population, but may actually undermine efforts to enable patients to make shared informed decisions. To increase health literacy, it is necessary to make high quality, evidence-based and easy-to-understand information material available to patients and the public. For this, it may be necessary to set up a centralized and independent clearinghouse.

Background: The strengthening of primary health care is one major goal of the current national health reform in Austria. In this context, a new interdisciplinary concept was developed in 2014 that defines structures and requirements for future primary health care facilities., Objective: The aim of this project was the development of quality indicators for the evaluation of the scheduled primary health care facilities in Austria, which are in accordance with the new Austrian concept., Methods: We used the RAND/NPCRDC method for the development and selection of the quality indicators. We conducted systematic literature searches for existing measures in international databases for quality indicators as well as in bibliographic databases. All retrieved measures were evaluated and rated by an expert panel in a 2-step process regarding relevance and feasibility., Results: Overall, the literature searches yielded 281 potentially relevant quality indicators, which were summarized to 65 different quality measures for primary health care. Out of these, the panel rated and accepted 30 measures as relevant and feasible for use in Austria. Five of these indicators were structure measures, 14 were process measures and the remaining 11 were outcome measures. Based on the Austrian primary health care concept, the final set of quality indicators was grouped in the 5 following domains: Access to primary health care (5), quality of care (15), continuity of care (5), coordination of care (4), and safety (1)., Conclusion: This set of quality measures largely covers the four defined functions of primary health care. It enables standardized evaluation of primary health care facilities in Austria regarding the implementation of the Austrian primary health care concept as well as improvement in healthcare of the population., Competing Interests: Dieses Projekt wurde vom Hauptverband der österreichischen Sozialversicherungsträger gefördert. Die Autoren geben an, dass keine Interessenskonflikte bestehen., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: The protein kinase C theta (PKCθ) has an important and non-redundant function downstream of the antigen receptor and co-receptor complex in T lymphocytes. PKCθ is not only essential for activation of NF-κB, AP-1 and NFAT and subsequent interleukin-2 expression, but also critical for positive selection and development of regulatory T lymphocytes in the thymus. Several domains regulate its activity, such as a pseudosubstrate sequence mediating an auto-inhibitory intramolecular interaction, the tandem C1 domains binding diacylglycerol, and phosphorylation at conserved tyrosine, threonine as well as serine residues throughout the whole length of the protein. To address the importance of the variable domain V1 at the very N-terminus, which is encoded by exon 2, a mutated version of PKCθ was analyzed for its ability to stimulate T lymphocyte activation., Methods: T cell responses were analyzed with promoter luciferase reporter assays in Jurkat T cells transfected with PKCθ expression constructs. A mouse line expressing mutated instead of wild type PKCθ was analyzed in comparison to PKCθ-deficient and wild type mice for thymic development and T cell subsets by flow cytometry and T cell activation by quantitative RT-PCR, luminex analysis and flow cytometry., Results: In cell lines, the exon 2-replacing mutation impaired the transactivation of interleukin-2 expression by constitutively active mutant form of PKCθ. Moreover, analysis of a newly generated exon 2-mutant mouse line (PKCθ-E2 mut ) revealed that the N-terminal replacement mutation results in an hypomorph mutant of PKCθ combined with reduced PKCθ protein levels in CD4 + T lymphocytes. Thus, PKCθ-dependent functions in T lymphocytes were affected resulting in impaired thymic development of single positive T lymphocytes in vivo. In particular, there was diminished generation of regulatory T lymphocytes. Furthermore, early activation responses such as interleukin-2 expression of CD4 + T lymphocytes were significantly reduced even though cell viability was not affected. Thus, PKCθ-E2 mut mice show a phenotype similar to conventional PKCθ-deficient mice., Conclusion: Taken together, PKCθ-E2 mut mice show a phenotype similar to conventional PKCθ-deficient mice. Both our in vitro T cell culture experiments and ex vivo analyses of a PKCθ-E2-mutant mouse line independently validate the importance of PKCθ downstream of the antigen-receptor complex for activation of CD4 + T lymphocytes.

Objectives: Identification of sufficiently trustworthy top 5 list recommendations from the US Choosing Wisely campaign., Setting: Not applicable., Participants: All top 5 list recommendations available from the American Board of Internal Medicine Foundation website., Main Outcome Measures/interventions: Compilation of US top 5 lists and search for current German highly trustworthy (S3) guidelines. Extraction of guideline recommendations, including grade of recommendation (GoR), for suggestions comparable to top 5 list recommendations. For recommendations without guideline equivalents, the methodological quality of the top 5 list development process was assessed using criteria similar to that used to judge guidelines, and relevant meta-literature was identified in cited references. Judgement of sufficient trustworthiness of top 5 list recommendations was based either on an 'A' GoR of guideline equivalents or on high methodological quality and citation of relevant meta-literature., Results: 412 top 5 list recommendations were identified. For 75 (18%), equivalents were found in current German S3 guidelines. 44 of these recommendations were associated with an 'A' GoR, or a strong recommendation based on strong evidence, and 26 had a 'B' or a 'C' GoR. No GoR was provided for 5 recommendations. 337 recommendations had no equivalent in the German S3 guidelines. The methodological quality of the development process was high and relevant meta-literature was cited for 87 top 5 list recommendations. For a further 36, either the methodological quality was high without any meta-literature citations or meta-literature citations existed but the methodological quality was lacking. For the remaining 214 recommendations, either the methodological quality was lacking and no literature was cited or the methodological quality was generally unsatisfactory., Conclusions: 131 of current US top 5 list recommendations were found to be sufficiently trustworthy. For a substantial number of current US top 5 list recommendations, their trustworthiness remains unclear. Methodological requirements for developing top 5 lists are recommended., Competing Interests: Competing interests: KH, TS, MEA, NP, AD, KJ and AS have support from the Techniker Krankenkasse, a German health insurance provider, for the submitted work., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: All major guidelines on antihypertensive therapy recommend weight loss; anti-obesity drugs may be able to help in this respect., Primary Objectives: To assess the long-term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events)., Secondary Objectives: To assess the long-term effects of pharmacologically induced reduction in body weight in adults with essential hypertension on change from baseline in systolic blood pressure, change from baseline in diastolic blood pressure, and body weight reduction., Search Methods: We obtained studies using computerised searches of the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Ovid EMBASE, the clinical trials registry ClinicalTrials.gov, and from handsearches in reference lists and systematic reviews (status as of 13 April 2015)., Selection Criteria: Randomised controlled trials in hypertensive adults of at least 24 weeks' duration that compared long-term pharmacologic interventions for weight loss with placebo. , Data Collection and Analysis: Two review authors independently selected studies, assessed risk of bias, and extracted data. Where appropriate and in the absence of significant heterogeneity between studies (P > 0.1), we pooled studies using fixed-effect meta-analysis. When heterogeneity was present, we used the random-effects method and investigated the cause of heterogeneity., Main Results: After updating the literature search, which was extended to include four new weight-reducing drugs, we identified one additional study of phentermine/topiramate, bringing the total number of studies to nine that compare orlistat, sibutramine, or phentermine/topiramate to placebo and thus fulfil our inclusion criteria. We identified no relevant studies investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion. No study included mortality and cardiovascular morbidity as predefined outcomes. Incidence of gastrointestinal side effects was consistently higher in those participants treated with orlistat versus those treated with placebo. The most frequent side effects were dry mouth, constipation, and headache with sibutramine, and dry mouth and paresthaesia with phentermine/topiramate. In participants assigned to orlistat, sibutramine, or phentermine/topiramate body weight was reduced more effectively than in participants in the usual-care/placebo groups. Orlistat reduced systolic blood pressure as compared to placebo by -2.5 mm Hg (mean difference (MD); 95% confidence interval (CI): -4.0 to -0.9 mm Hg) and diastolic blood pressure by -1.9 mm Hg (MD; 95% CI: -3.0 to -0.9 mm Hg). Sibutramine increased diastolic blood pressure compared to placebo by +3.2 mm Hg (MD; 95% CI: +1.4 to +4.9 mm Hg). The one trial that investigated phentermine/topiramate suggested it lowered blood pressure., Authors' Conclusions: In people with elevated blood pressure, orlistat and sibutramine reduced body weight to a similar degree, while phentermine/topiramate reduced body weight to a greater extent. In the same trials, orlistat and phentermine/topiramate reduced blood pressure, while sibutramine increased it. We could include no trials investigating rimonabant, liraglutide, lorcaserin, or naltrexone/bupropion in people with elevated blood pressure. Long-term trials assessing the effect of orlistat, liraglutide, lorcaserin, phentermine/topiramate, or naltrexone/bupropion on mortality and morbidity are unavailable and needed. Rimonabant and sibutramine have been withdrawn from the market, after long-term trials on mortality and morbidity have confirmed concerns about the potential severe side effects of these two drugs. The European Medicines Agency refused marketing authorisation for phentermine/topiramate due to safety concerns, while the application for European marketing authorisation for lorcaserin was withdrawn by the manufacturer after the Committee for Medicinal Products for Human Use judged the overall benefit/risk balance to be negative.

Background: All major guidelines for antihypertensive therapy recommend weight loss. Thus dietary interventions that aim to reduce body weight might be a useful intervention to reduce blood pressure and adverse cardiovascular events associated with hypertension., Objectives: Primary objectivesTo assess the long-term effects of weight-reducing diets in people with hypertension on all-cause mortality, cardiovascular morbidity, and adverse events (including total serious adverse events, withdrawal due to adverse events, and total non-serious adverse events). Secondary objectivesTo assess the long-term effects of weight-reducing diets in people with hypertension on change from baseline in systolic blood pressure, change from baseline in diastolic blood pressure, and body weight reduction., Search Methods: We obtained studies from computerised searches of the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Hypertension Specialised Register, Ovid MEDLINE, and Ovid EMBASE, and from searches in reference lists, systematic reviews, and the clinical trials registry ClinicalTrials.gov (status as of 2 February 2015)., Selection Criteria: We included randomised controlled trials (RCTs) of at least 24 weeks' duration that compared weight-reducing dietary interventions to no dietary intervention in adults with primary hypertension., Data Collection and Analysis: Two review authors independently assessed risk of bias and extracted data. We pooled studies using fixed-effect meta-analysis. In case of moderate or larger heterogeneity as measured by Higgins I(2), we used a random-effects model., Main Results: This review update did not reveal any new studies, so the number of included studies remained the same: 8 studies involving a total of 2100 participants with high blood pressure and a mean age of 45 to 66 years. Mean treatment duration was 6 to 36 months. We judged the risk of bias as unclear or high for all but two trials. No study included mortality as a predefined outcome. One RCT evaluated the effects of dietary weight loss on a combined endpoint consisting of the necessity of reinstating antihypertensive therapy and severe cardiovascular complications. In this RCT, weight-reducing diet lowered the endpoint compared to no diet: hazard ratio 0.70 (95% confidence interval (CI), 0.57 to 0.87). None of the studies evaluated adverse events as designated in our protocol. There was low-quality evidence for a blood pressure reduction in participants assigned to weight loss diets as compared to controls: systolic blood pressure: mean difference (MD) -4.5 mm Hg (95% CI -7.2 to -1.8 mm Hg) (3 of 8 studies included in analysis), and diastolic blood pressure: MD -3.2 mm Hg (95% CI -4.8 to -1.5 mm Hg) (3 of  8  studies included in analysis). There was moderate-quality evidence for weight reduction in dietary weight loss groups as compared to controls: MD -4.0 kg (95% CI -4.8 to -3.2) (5 of 8 studies included in analysis). Two studies used withdrawal of antihypertensive medication as their primary outcome. Even though we did not consider this a relevant outcome for our review, the results of these studies strengthen the finding of reduction of blood pressure by dietary weight loss interventions., Authors' Conclusions: In this update, the conclusions remain the same, as we found no new trials. In people with primary hypertension, weight loss diets reduced body weight and blood pressure, however the magnitude of the effects are uncertain due to the small number of participants and studies included in the analyses. Whether weight loss reduces mortality and morbidity is unknown. No useful information on adverse effects was reported in the relevant trials.

Background: Protein kinase C-θ (PKCθ) plays an important role in signal transduction down-stream of the T cell receptor and T cells deficient of PKCθ show impaired NF-κB as well as NFAT/AP-1 activation resulting in strongly decreased IL-2 expression and proliferation. However, it is not yet entirely clear, how the function of PKCθ - upon T cell activation - is regulated on a molecular level., Findings: Employing a yeast two-hybrid screen and co-immunoprecipitation analyses, we here identify coronin 1A (Coro1A) as a novel PKCθ-interacting protein. We show that the NH2-terminal WD40 domains of Coro1A and the C2-like domain of PKCθ are sufficient for the interaction. Furthermore, we confirm a physical interaction by GST-Coro1A mediated pull-down of endogenous PKCθ protein. Functionally, wild-type but not Coro1A lacking its actin-binding domain negatively interferes with PKCθ-dependent NF-κB, Cyclin D1 and IL-2 transactivation when analysed with luciferase promoter activation assays in Jurkat T cells. This could be phenocopied by pharmacological inhibitors of actin polymerization and PKC, respectively. Mechanistically, Coro1A overexpression attenuates both lipid raft and plasma membrane recruitment of PKCθ in CD3/CD28-activated T cells. Using primary CD3(+) T cells, we observed that (opposite to PKCθ) Coro1A does not localize preferentially to the immunological synapse. In addition, we show that CD3(+) T cells isolated from Coro1A-deficient mice show impaired IKK/NF-κB transactivation., Conclusions: Together, these findings both in Jurkat T cells as well as in primary T cells indicate a regulatory role of Coro1A on PKCθ recruitment and function downstream of the TCR leading to NF-κB transactivation.

In January 2014, the first nationwide quality-assured breast cancer screening program addressing women aged ≥ 40 years was introduced in Austria. As part of the process of developing a patient information leaflet, the Evidence Based Medicine (EBM) Review Center of the Medical University of Graz was charged with the task of assessing the potential benefits and harms of breast cancer screening from the available evidence. Based on these results, key figures were derived for mortality, false-positive and false-negative mammography results, and overdiagnosis, considering Austria-specific incidence rates for breast cancer and breast cancer mortality. Furthermore, the current evidence regarding age limits and screening interval, which were the subjects of controversial public discussions, was analyzed. A systematic search for primary and secondary literature was performed and additional evidence was screened, e. g., evaluation reports of European breast cancer screening programs. On the basis of the available evidence and of the Austrian breast cancer mortality and incidence rates, it can be assumed that - depending on the age group - 1 to 4 breast cancer deaths can be avoided per 1,000 women screened in a structured breast cancer screening program, while the overall mortality remains unchanged. On the other hand, 150 to 200 of these 1,000 women will be affected by false-positive results and 1 to 9 women by overdiagnosis due to the structured breast cancer screening. Therefore, the overall benefit-harm balance is uncertain. If women from 40 to 44 or above 70 years of age are considered, who can also participate in the Austrian screening program, even a negative benefit-harm balance seems possible. However, with the implementation of quality standards in breast cancer screening and the dissemination of a patient information leaflet, an improvement in the medical treatment situation, specifically in terms of informed decision-making, can be expected., (Copyright © 2015. Published by Elsevier GmbH.)

Objective: A systematic review and meta-analysis focusing on patient-relevant outcomes and blood pressure was conducted to assess the clinical effectiveness of stress-reduction techniques in adults with essential hypertension., Methods: Systematic reviews and randomized controlled trials (RCTs) were identified as part of a systematic search in six electronic databases ending September 2012. RCTs comparing stress-reduction techniques versus no such techniques with a follow-up of at least 24 weeks and published in English or German were included. Outcomes of interest were death, cardiovascular morbidity/mortality, end-stage renal disease, health-related quality of life, adverse events, changes in blood pressure, and changes in antihypertensive medication. When appropriate, meta-analyses were used to combine data., Results: Seventeen RCTs analyzing different stress-reduction techniques such as biofeedback, relaxation or combined interventions were identified. Data were not reported for most of the patient-relevant outcomes, and meta-analyses could only be used to evaluate effects on blood pressure. The data indicated a blood pressure-lowering effect, but the studies had methodological shortcomings and heterogeneity between them was high. Mean group differences for DBP ranged from -10 to 1 mmHg and for SBP from -12 to 10 mmHg. In terms of antihypertensive medication, no favorable effects of stress-reduction techniques could be identified., Conclusions: The available RCTs on stress-reduction techniques used for at least 24 weeks appeared to indicate a blood pressure-lowering effect in patients with essential hypertension, but this should be interpreted with caution because of major methodological limitations. A benefit of specific stress-reduction techniques in hypertensive patients remains unproven.

Myocutaneous (MC) free flaps are useful for many reconstructive indications. Perforator flaps have become standard of care. The anterolateral thigh flap (ALT) donor site is popular. With the ALT flap varying sizes of vastus lateralis (VL) muscle can be harvested as a MC flap. The skin islands of these flaps have a great range of freedom when dissected on their perforator. It was hypothesised that the VL-ALT perforator flap would offer adequate tissue volume combining maximal freedom in planning with minimal donor site morbidity. From November 2001 to February 2003 a free partial VL with ALT perforator flap was used in 11 patients to reconstruct large defects. Indications for adding a muscular component were exposed bone, skull base, (artificial) dura, or osteosynthesis material, open sinuses, and lack of muscular bulk. Flaps were planned as standard ALT flaps, after which three types of dissection were performed: I. true MC flap; II. muscle flap with a skin island on one perforator, which could be rotated up to 180 degrees ; III. chimera skin perforator flap with muscle being harvested on a separate branch from the source vessel or on a side branch of the skin perforator. Mean skin size of the MC-ALT flaps was 131 cm2. Mean muscle part size of the MC-ALT flaps was 268 cm3. Muscular parts were custom designed for all defects. No total or partial flap failures were seen. Colour mismatch was seen in 6 of 8 patients, when skin was used in the facial area in this all white population. Excessive flap bulk was found in 8 of 11 patients at 6 weeks, however, only in 2 of 11 patients after 6 months. Patients were satisfied with the functional result (8 of 11 patients) as well as the cosmetic result of their reconstruction (7 of 11 patients). All less satisfied patients had received their flap for external facial skin reconstruction. Donor site morbidity was minimal. The combined free partial VL with ALT perforator flap proved valuable as a (chimera type) MC flap with maximal freedom of planning to meet specific reconstructive demands and minimal donor site morbidity.

Hereditary isolated brachydactyly type C (OMIM 113100) mostly follows an autosomal dominant pattern of inheritance with a marked variability in expression. This phenotype has been mapped to two different loci on chromosomes 12q24 and 20q11.2. The latter locus contains the cartilage-derived morphogenetic protein (CDMP)1 gene, in which a null mutation has been found in patients with malformations restricted to the upper limbs. A more complex brachydactyly type C phenotype has been mapped to chromosome 12q24. Differences in complexity of these phenotypes have been attributed to locus heterogeneity. Clinical subclassification based on the degree of complexity of the phenotype has therefore been suggested. We present patients with a complex brachydactyly type C phenotype in whom there is considerable intra- and interfamilial variability in expression. We show that clinical subclassification based on the complexity of the brachydactyly type C phenotype related to the genetic defect is not feasible. We present evidence that differences in complexity are not only due to locus heterogeneity, but that genetic modifiers and/or environmental factors must also play a role.