Drivers of disease severity and burden of hidradenitis suppurativa: a cross-sectional analysis on 553 German patients.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory disease of the inverse skin regions with an age peak at around 40 years and an estimated prevalence of 1%. Nodules and abscesses can develop into fistules and scarring, which cause severe pain. HS is a progressive, life-defining disease that leads to physical limitations, inability to work, and social isolation. There is still little data on the drivers of disease severity and burden. METHOD: The cross-sectional study is based on the baseline data of 553 participants of the health care research project "EsmAiL," which was carried out as a multicenter randomized controlled trial. It included adult HS-patients presenting with at least three inflammatory lesions and at least a moderate impact on quality of life. RESULTS: Disease activity increases with age. Men are more severely affected than women but feel less burdened. Obesity negatively influences disease activity and disease burden. Affected individuals have a higher level of education than the age adjusted population, but the unemployment rate is significantly higher. Disease activity significantly reduces quality of life and promotes depression and anxiety. CONCLUSIONS: HS is a severe and debilitating dermatosis. As a result of the well-established factors involved, HS requires a multi-causal approach to management, in addition to medical and surgical treatment. This must take into account all available therapeutic options, as well as patient education to reduce risk factors and pain, and psychological support. HS requires interdisciplinary and multi-professional care. To prevent disease progression, a structured treatment plan is needed.

A center-based, ambulatory care concept for hidradenitis suppurativa improves patient outcomes and is also cost-effectiveness.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting approximately 1% of the population. The patient journey through the German health care system leads to high disease burden and substantial treatment costs. The EsmAiL study showed that an innovative, interprofessional, multimodal care-concept reduces disease activity and burden of HS compared to standard care. This paper examines the costs of treating HS in Germany and compares them with those of the innovative care concept implemented in EsmAiL. METHODS: EsmAiL was a two-arm, multicenter, prospective randomized controlled trial including 553 adults with HS. The study was registered in the German Clinical Trials Registry (DRKS00022135). The control group (CG) remained in standard care, whereas the intervention group (IG) was referred to specialized so-called 'acne-inversa-centres (AiZ)' where patients were treated with a structured, interdisciplinary approach. The present paper analyses the treatment costs for a subpopulation based on health insurance cost data from the two largest German health insurers. Quality-Adjusted Life Years (QALY) was assessed based on Dermatology Life Quality Index (DLQI). RESULTS: Total annual treatment costs per patient were €3,966.07 in standard care (n = 89) and €3,974.37 in the innovative care (n = 93). The costs per additional QALY amounted to €12,698.72 in the IG. Given the conventional and established threshold of €22,600 to €33,900 per QALY, the innovative treatment in AiZ proved to be cost-effective. CONCLUSION: Treatment costs of HS are substantial and increase with disease severity. The new form of care is cost-effective and is expected to decrease costs in the long run.

A structured, multimodal form of care reduces costs in the treatment of Hidradenitis suppurativa compared to standard care.

Experiences of relatives of patients with delirium due to an acute health event - A systematic review of qualitative studies.

OBJECTIVE: Evaluate relatives' experience of delirium due to an acute health event in a loved person and to compile practical suggestions for health care professionals from these synthesized results. BACKGROUND: Delirium resulting from an acute health event places patients at increased risk for prolonged hospitalization and mortality. A delirium episode also affects family members who may assist in the diagnosis and recovery from this condition. INCLUSION CRITERIA: Qualitative studies of family members or other caregivers who witnessed patient delirium in a clinical setting were included if they had appropriate verbatim evidence. Studies dealing exclusively with delirium in the context of dementia, cancer, palliative care, or drug dependence were excluded, and if quotes could not be clearly allocated to relatives. METHODS: A systematic review of qualitative studies adapted from the Joanna Briggs Institute meta-aggregation approach. A systematic literature search was conducted in CINAHL complete®, MEDLINE®, and several dissertation databases in September 2022. RESULTS: Eight qualitative studies based on semi-structured interviews were included. In total 75 findings from 105 relatives were aggregated into 13 categories. Finally, three synthesized findings reveal suggestions for health care professionals: providing information adequately, communication and integration during health care and understanding relatives' perspective on delirium experience. CONCLUSION: The identified burdens and needs of relatives should be considered by health care professionals to enhance the delirium experience for them, thus improving patient care by involving relatives with a better understanding.

A centre-based ambulatory care concept for hidradenitis suppurativa improves disease activity, disease burden and patient satisfaction: results from the randomized controlled EsmAiL trial.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory disease of the inverse skin regions that occurs in young women, in particular, and affects approximately 1% of the population. Outpatient care is often inadequate and usually cannot prevent progression. OBJECTIVES: To evaluate in the EsmAiL ('Evaluation eines strukturierten und leitlinienbasierten multmodalen Versorgungskonzepts für Menschen mit Akne inversa') trial whether an innovative care concept can decrease disease activity and burden, and improve patient satisfaction. METHODS: EsmAiL was conducted as a two-arm, multicentre, prospective, randomized controlled trial that included 553 adults with HS. Inclusion criteria were a minimum of three inflammatory lesions and at least a moderate impact of the disease on quality of life. The control group (CG) remained under standard care, while patients in the intervention group (IG) were treated according to a trial-specific, multimodal concept. The primary endpoint was the absolute change in International Hidradenitis Suppurativa Severity Score System (IHS4). RESULTS: In total, 274 patients were randomized to the IG and 279 to the CG. Altogether, 377 attended the final assessment after 12 months of intervention. Participants in the IG (n = 203) achieved a mean improvement in IHS4 of 9.3 points, while the average decrease in IHS4 in patients in the CG (n = 174) was 5.7 points (P = 0.003). Patients treated under the new care concept also reported a statistically significantly higher decrease in pain, Dermatology Life Quality Index and Hospital Anxiety and Depression Scale scores compared with those in the CG (P < 0.001). Patient satisfaction was also statistically significantly higher in the IG compared with the CG (P < 0.001). CONCLUSIONS: The establishment of standardized treatment algorithms in so-called 'acne inversa centres' in the ambulatory setting has a substantial, positive impact on the course of HS and significantly improves patient satisfaction.

Measurement instruments to evaluate diaper dermatitis in children: Systematic review of measurement properties.

AIM: The aim of this study was to summarize and evaluate the empirical evidence on the measurement properties of diaper dermatitis (DD) measurement instruments in children. DESIGN: Systematic review. METHODS: MEDLINE, CINAHL and EMBASE were systematically searched until 14 June 2021. Citation searching was conducted in Scopus. The risk of bias, the reported measurement properties and the quality of evidence were evaluated using the COSMIN framework. The reporting follows the PRISMA 2020 statement. RESULTS: We identified 1200 records in the databases and 108 records during citation searching and included four studies describing three measurement instruments for DD in children and their measurement properties. We considered the content validity inconsistent for all three instruments. The study authors reported internal consistency, reliability and construct validity for one instrument. We rated the quality of evidence from very low to moderate.

[Recommendations of the S3 Guideline "Use of Extracorporeal Circulation (ECLS/ ECMO) for Cardiac and Circulatory Failure" of the Association of Scientific Medical Societies in Germany]. / Empfehlungen der S3-Leitlinie (AWMF) "Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen".

In recent years, the use of mechanical support for patients with cardiac or circulatory failure has continuously increased, leading to 3,000 ECLS/ECMO (extracorporeal life support/extracorporeal membrane oxygenation) implantations annually in Germany. Due to the lack of guidelines, there is an urgent need for evidence-based recommendations addressing the central aspects of ECLS/ECMO therapy. In July 2015, the generation of a guideline level S3 according to the standards of the Association of the Scientific Medical Societies in Germany (AWMF) was announced by the German Society for Thoracic and Cardiovascular Surgery (GSTCVS). In a well-structured consensus process, involving experts from Germany, Austria and Switzerland, delegated by 16 scientific societies and the patients' representation, the guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" was created under guidance of the GSTCVS, and published in February 2021. The guideline focuses on clinical aspects of initiation, continuation, weaning and aftercare, herein also addressing structural and economic issues. This article presents an overview on the methodology as well as the final recommendations.

Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure -A clinical practice Guideline Level 3.

Aims Worldwide applications of extracorporeal circulation for mechanical support in cardiac and circulatory failure, which are referred to as extracorporeal life support (ECLS) or veno-arterial extracorporeal membrane oxygenation (va-ECMO), have dramatically increased over the past decade. In spite of the expanding use and the immense medical as well as socio-economic impact of this therapeutic approach, there has been a lack of interdisciplinary recommendations considering the best available evidence for ECLS treatment. Methods and Results In a multiprofessional, interdisciplinary scientific effort of all scientific societies involved in the treatment of patients with acute cardiac and circulatory failure, the first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy was developed in a structured approach under regulations of the AWMF (Association of the Scientific Medical Societies in Germany) and under use of GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria. This article presents all recommendations created by the expert panel, addressing a multitude of aspects for ECLS initiation, continuation, weaning and aftercare as well as structural and personnel requirements. Conclusions This first evidence- and expert consensus-based guideline (level S3) on ECLS/ECMO therapy should be used to apply the best available care nationwide. Beyond clinical practice advice, remaining important research aspects for future scientific efforts are formulated.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

[Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure : Short version of the S3 guideline]. / Einsatz der extrakorporalen Zirkulation (ECLS/ECMO) bei Herz- und Kreislaufversagen : Kurzversion der AWMF-S3-Leitlinie.

In Germany, a remarkable increase regarding the usage of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS) systems has been observed in recent years with approximately 3000 ECLS/ECMO implantations annually since 2015. Despite the widespread use of ECLS/ECMO, evidence-based recommendations or guidelines are still lacking regarding indications, contraindications, limitations and management of ECMO/ECLS patients. Therefore in 2015, the German Society of Thoracic and Cardiovascular Surgery (GSTCVS) registered the multidisciplinary S3 guideline "Use of extracorporeal circulation (ECLS/ECMO) for cardiac and circulatory failure" to develop evidence-based recommendations for ECMO/ECLS systems according to the requirements of the Association of the Scientific Medical Societies in Germany (AWMF). Although the clinical application of ECMO/ECLS represents the main focus, the presented guideline also addresses structural and economic issues. Experts from 17 German, Austrian and Swiss scientific societies and a patients' organization, guided by the GSTCVS, completed the project in February 2021. In this report, we present a summary of the methodological concept and tables displaying the recommendations for each chapter of the guideline.

Towards User-Oriented Recommendations for Local Therapy of Leg and Foot Ulcers-An Update of a S3-German Guideline.

BACKGROUND: The German S3- guideline on local therapy of leg ulcers and diabetic foot ulcers is in the process of being updated. Major goals are to improve the guidelines' applicability and to take steps towards a living guideline according to current methodological standards. The aim of this article is to describe the main measures to achieve these goals. METHODS: The context of the guideline in the field of local wound care and the stakeholder requirements are briefly described. Based on a derived framework, the project team adjusted the methods for the guideline. RESULTS: Main adjustments are more specific inclusion criteria, online consensus meetings and the use of an authoring and publication platform to provide information in a multi-layered format. A new set of practice-oriented key questions were defined by the guideline panel to foster the formulation of action-oriented recommendations. CONCLUSIONS: The set of new key questions addressing practical problems and patients' preferences as well as the adjustments made to improve not only the guidelines' applicability, but also the feasibility of the further dynamic updating processes in the sense of a living guideline, should be steps in the right direction.

Souvenaid for Alzheimer's disease.

BACKGROUND: Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been designed to support the formation and function of synapses in the brain, which are thought to be strongly correlated with cognitive function. If effective, it might improve symptoms of Alzheimer's disease and also prevent the progression from prodromal Alzheimer's disease to dementia. We sought in this review to examine the evidence for this proposition. OBJECTIVES: To assess the effects of Souvenaid on incidence of dementia, cognition, functional performance, and safety in people with Alzheimer's disease. SEARCH METHODS: We searched ALOIS, i.e. the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science (ISI Web of Science), Cinahl (EBSCOhost), Lilacs (BIREME), and clinical trials registries up to 24 June 2020. We also reviewed citations of reference lists of landmark papers, reviews, and included studies for additional studies and assessed their suitability for inclusion in the review. SELECTION CRITERIA: We included randomised, placebo-controlled trials which evaluated Souvenaid in people diagnosed with mild cognitive impairment (MCI) due to AD (also termed prodromal AD) or with dementia due to AD, and with a treatment duration of at least 16 weeks. DATA COLLECTION AND ANALYSIS: Our primary outcome measures were incidence of dementia, global and specific cognitive function, functional performance, combined cognitive-functional outcomes and adverse events. We selected studies, extracted data, assessed the quality of trials and intended to conduct meta-analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We present all outcomes grouped by stage of AD. MAIN RESULTS: We included three randomised, placebo-controlled trials investigating Souvenaid in 1097 community-dwelling participants with Alzheimer's disease. One study each included participants with prodromal AD, mild AD dementia and mild-to-moderate AD dementia. We rated the risks of bias of all trials as low. One study (in prodromal AD) was funded by European grants. The other two studies were funded by the manufacturer of Souvenaid. One trial investigated the incidence of dementia in people with prodromal AD at baseline, and found little to no difference between the Souvenaid group and the placebo group after 24 months (RR 1.09, 95% CI 0.82 to 1.43; 1 trial, 311 participants; moderate quality of evidence). In prodromal AD, and in mild and mild-to-moderate Alzheimer's disease dementia, Souvenaid probably results in little or no difference in global or specific cognitive functions (moderate quality of evidence). Everyday function, or the ability to perform activities of daily living, were measured in mild and mild-to-moderate AD dementia. Neither study found evidence of a difference between the groups after 24 weeks of treatment (moderate quality of evidence). Two studies investigated combined cognitive-functional outcomes with the Clinical Dementia Rating Sum of Boxes and observed conflicting results. Souvenaid probably results in slight improvement, which is below estimates of meaningful change, in participants with prodromal Alzheimer's disease after 24 months (moderate quality of evidence), but probably has little to no effect in mild-to-moderate Alzheimer's disease dementia after 24 weeks (moderate quality of evidence). Adverse effects observed were low in all trials, and the available data were insufficient to determine any connection with Souvenaid. AUTHORS' CONCLUSIONS: Two years of treatment with Souvenaid probably does not reduce the risk of progression to dementia in people with prodromal AD. There is no convincing evidence that Souvenaid affects other outcomes important to people with AD in the prodromal stage or mild-to-moderate stages of dementia. Conflicting evidence on combined cognitive-functional outcomes in prodromal AD and mild AD dementia warrants further investigation. Adverse effects of Souvenaid seem to be uncommon, but the evidence synthesised in this review does not permit us to make a definitive statement on the long-term tolerability of Souvenaid. The effects of Souvenaid in more severe AD dementia or in people with AD at risk of nutritional deficiencies remain unclear.

Agreement between the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) interview and a paper-administered adaption.

BACKGROUND: The Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW) is a prevalent face-to-face interview method for measuring quality of life by integrating respondent-generated dimensions. To apply this method in clinical trials, a paper-administered alternative would be of interest. Therefore, our study aimed to analyze the agreement between the SEIQoL-DW and a paper questionnaire version (SEIQoL-PF/G). METHODS: In a crossover design, both measures were completed in a random sequence. 104 patients at a heart surgery hospital in Germany were randomly assigned to receive either the SEIQoL-DW or the SEIQoL-PF/G as the first measurement in the sequence. Patients were approached on their earliest stable day after surgery. The average time between both measurements was 1 day (mean 1.3; SD 0.8). Agreement regarding the indices, ratings, and weightings of nominated life areas (cues) was explored using Bland-Altman plots with 95% limits of agreement (LoA). Agreement of the SEIQoL indices was defined as acceptable if the LoA did not exceed a threshold of 10 scale points. Data from n = 99 patients were included in the agreement analysis. RESULTS: Both measures led to similarly nominated cues. The most frequently nominated cues were "physical health" and "family". In the Bland-Altman plot, the indices showed a mean of differences of 2 points (95% CI, - 1 to 6). The upper LoA showed a difference of 36 points (95% CI, 30 to 42), and the lower LoA showed a difference of - 31 points (95% CI, - 37 to - 26). Thus, the LoAs and confidence intervals exceeded the predefined threshold. The Bland-Altman plots for the cue levels and cue weights showed similar results. The SEIQoL-PF/G version showed a tendency for equal weighting of cues, while the weighting procedure of the SEIQoL-DW led to greater variability. CONCLUSIONS: For cardiac surgery patients, use of the current version of the SEIQoL-PF/G as a substitute for the SEIQoL-DW is not recommended. The current questionnaire weighting method seems to be unable to distinguish weighting for different cues. Therefore, the further design of a weighting method without interviewer support as a paper-administered measure of individual quality of life is desirable.

Environmental and behavioural modifications for improving food and fluid intake in people with dementia.

BACKGROUND: Weight loss, malnutrition and dehydration are common problems for people with dementia. Environmental modifications such as, change of routine, context or ambience at mealtimes, or behavioural modifications, such as education or training of people with dementia or caregivers, may be considered to try to improve food and fluid intake and nutritional status of people with dementia. OBJECTIVES: Primary: To assess the effects of environmental or behavioural modifications on food and fluid intake and nutritional status in people with dementia. Secondary: To assess the effects of environmental or behavioural modifications in connection with nutrition on mealtime behaviour, cognitive and functional outcomes and quality of life, in specific settings (i.e. home care, residential care and nursing home care) for different stages of dementia. To assess the adverse consequences or effects of the included interventions. SEARCH METHODS: We searched the Specialized Register of Cochrane Dementia and Cognitive Improvement (ALOIS), MEDLINE, Eembase, PsycINFO, CINAHL, ClinicalTrials.gov and the World Health Organization (WHO) portal/ICTRP on 17 January 2018. We scanned reference lists of other reviews and of included articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) investigating interventions designed to modify the mealtime environment of people with dementia, to modify the mealtime behaviour of people with dementia or their caregivers, or both, with the intention of improving food and fluid intake. We included people with any common dementia subtype. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed the risk of bias of included trials. We assessed the quality of evidence for each outcome using the GRADE approach. MAIN RESULTS: We included nine studies, investigating 1502 people. Three studies explicitly investigated participants with Alzheimer's disease; six did not specify the type of dementia. Five studies provided clear measures to identify the severity of dementia at baseline, and overall very mild to severe stages were covered. The interventions and outcome measures were diverse. The overall quality of evidence was mainly low to very low.One study implemented environmental as well as behavioural modifications by providing additional food items between meals and personal encouragement to consume them. The control group received no intervention. Differences between groups were very small and the quality of the evidence from this study was very low, so we are very uncertain of any effect of this intervention.The remaining eight studies implemented behavioural modifications.Three studies provided nutritional education and nutrition promotion programmes. Control groups did not receive these programmes. After 12 months, the intervention group showed slightly higher protein intake per day (mean difference (MD) 0.11 g/kg, 95% confidence interval (CI) -0.01 to 0.23; n = 78, 1 study; low-quality evidence), but there was no clear evidence of a difference in nutritional status assessed with body mass index (BMI) (MD -0.26 kg/m² favouring control, 95% CI -0.70 to 0.19; n = 734, 2 studies; moderate-quality evidence), body weight (MD -1.60 kg favouring control, 95% CI -3.47 to 0.27; n = 656, 1 study; moderate-quality evidence), or score on Mini Nutritional Assessment (MNA) (MD -0.10 favouring control, 95% CI -0.67 to 0.47; n = 656, 1 study; low-quality evidence). After six months, the intervention group in one study had slightly lower BMI (MD -1.79 kg/m² favouring control, 95% CI -1.28 to -2.30; n = 52, 1 study; moderate-quality evidence) and body weight (MD -8.11 kg favouring control, 95% CI -2.06 to -12.56; n = 52, 1 study; moderate-quality evidence). This type of intervention may have a small positive effect on food intake, but little or no effect, or a negative effect, on nutritional status.Two studies compared self-feeding skills training programmes. In one study, the control group received no training and in the other study the control group received a different self-feeding skills training programme. For both comparisons the quality of the evidence was very low and we are very uncertain whether these interventions have any effect.One study investigated general training of nurses to impart knowledge on how to feed people with dementia and improve attitudes towards people with dementia. Again, the quality of the evidence was very low so that we cannot be certain of any effect.Two studies investigated vocal or tactile positive feedback provided by caregivers while feeding participants. After three weeks, the intervention group showed an increase in calories consumed per meal (MD 200 kcal, 95% CI 119.81 to 280.19; n = 42, 1 study; low-quality evidence) and protein consumed per meal (MD 15g, 95% CI 7.74 to 22.26; n = 42, 1 study; low-quality evidence). This intervention may increase the intake of food and liquids slightly; nutritional status was not assessed. AUTHORS' CONCLUSIONS: Due to the quantity and quality of the evidence currently available, we cannot identify any specific environmental or behavioural modifications for improving food and fluid intake in people with dementia.

[Needs assessment to improve the applicability and methodological quality of a German S3 guideline]. / Bedarfsanalyse zur Verbesserung der Anwendbarkeit und methodischen Qualität einer S3-Leitlinie.

BACKGROUND: Clinical practice guidelines can change the practice in healthcare only if their recommendations are implemented in a comprehensive way. The German S3 guideline "Local Therapy of Chronic Wounds in Patients with Peripheral Vascular Disease, Chronic Venous Insufficiency, and Diabetes" will be updated in 2017. The emphasis here is on the guideline's validity, user-friendliness and implementation into practice. Therefore, the aim was to identify the improvements required in regard to the guideline's methods and content presentation. METHODS: The methodological approach used was the critical appraisal of the guideline according to established quality criteria and an additional stakeholder survey. Both were conducted between August and November 2016. The guideline and its related documents were reviewed independently by two researchers according to the criteria of the "Appraisal of Guidelines for Research and Evaluation" (AGREE-II). Published reviews and peer reviews by external experts and organisations were also taken into account. For the stakeholder survey, a questionnaire with open questions was distributed by e-mail and via the Internet to health professionals and organisations involved in the care of patients with leg ulcers in Germany. The questions were aimed at amendments and new topics based on the stakeholders' experience in inpatient and outpatient care. In addition, the survey focused on gathering suggestions to improve the applicability of the guideline. Suggested new topics and amendments were summarised thematically. The stakeholders' suggestions to improve the applicability, the results of the critical appraisal and the relevant aspects of the external reviews were then summarised according to the AGREE-II domains and presented in a cause and effect diagram. RESULTS: 17 questionnaires (out of 864 sent out by e-mail) were returned. Due to high practice relevance, the stakeholders suggested an expansion of the inclusion criteria to patients with infected wounds and pressure ulcers. They also proposed that plastic surgical procedures, several specific wound products and complementary measures should be included. The guideline is of high methodical quality with respect to the systematic synthesis and the formal expert recommendations. From both the stakeholders' and reviewers' perspectives, the guideline should be more in line with what guideline users regarded as key issues. The recommendations should be more action-oriented. Implementation concepts should be provided to teach, implement and evaluate the guideline in healthcare facilities. The updating process should also follow current standards for guideline development, for systematic reviews and for managing conflict of interests. CONCLUSION: The guideline is of high methodological quality but currently difficult to implement in clinical practice. The structured evaluation clearly reflects not only the potential for improvement but also provides a transparent theoretical framework for experts and scientific medical societies involved in the guideline updating process. Although some valuable insights were gained from the stakeholders' perspective, the representativeness is limited by the low response rate.

Omega-3 fatty acids for the treatment of dementia.

BACKGROUND: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish and plant sources are commonly considered as a promising non-medical alternative to improve brain functions and slow down the progression of dementia. This assumption is mostly based on findings of preclinical studies and epidemiological research. Resulting explanatory models aim at the role omega-3 PUFAs play in the development and integrity of the brain's neurons, their protective antioxidative effect on cell membranes and potential neurochemical mechanisms directly related to Alzheimer-specific pathology. Epidemiological research also found evidence of malnutrition in people with dementia. Considering this and the fact that omega-3 PUFA cannot be synthesised by humans, omega-3 PUFAs might be a promising treatment option for dementia. OBJECTIVES: To assess the efficacy and safety of omega-3 polyunsaturated fatty acid (PUFA) supplementation for the treatment of people with dementia. SEARCH METHODS: We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group (ALOIS), MEDLINE, EMBASE, PsycINFO, CINAHL, ClinicalTrials.gov and the World Health Organization (WHO) portal/ICTRP on 10 December 2015. We contacted manufacturers of omega-3 supplements and scanned reference lists of landmark papers and included articles. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which omega-3 PUFA in the form of supplements or enriched diets were administered to people with Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD) or frontotemporal dementia (FTD). DATA COLLECTION AND ANALYSIS: The primary outcome measures of interest were changes in global and specific cognitive functions, functional performance, dementia severity and adverse effects. Two review authors independently selected studies, extracted data and assessed the quality of trials according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We received unpublished data from the trial authors and collected adverse effects information from the published articles. We conducted meta-analyses for available outcome measures at six months. MAIN RESULTS: We included three comparable randomised, placebo-controlled trials investigating omega-3 PUFA supplements in 632 participants with mild to moderate AD over six, 12 and 18 months. We found no studies investigating other types of dementia. All trials were of high methodological quality. The overall quality of evidence for most of the outcomes was high.There was no evidence of a benefit from omega-3 PUFAs on cognitive function when measured at six months with the Alzheimer's Disease Assessment Scale - Cognitive subscale (standardised mean difference (SMD) -0.02, 95% confidence interval (CI) -0.19 to 0.15; 566 participants; 3 studies; high quality evidence) or Mini-Mental State Examination (mean difference (MD) 0.18, 95% CI -1.05 to 1.41; 202 participants; 2 studies; high quality evidence) or on activities of daily living (SMD -0.02, 95% CI -0.19 to 0.16; 544 participants; 2 studies; high quality evidence). There was also no effect at six months of treatment on severity of dementia measured with the Clinical Dementia Rating - Sum of Boxes (MD -0.00, 95% CI -0.58 to 0.57; 542 participants; 2 studies; high quality evidence) or on quality of life measured with the Quality of Life Alzheimer's Disease scale (MD -0.10, 95% CI -1.28 to 1.08; 322 participants; 1 study; high quality evidence). There was no difference at six months on mental health measured with the Montgomery-Åsberg Depression Rating Scale (MD -0.10, 95% CI -0.74 to 0.54; 178 participants: 1 study; high quality of evidence) or the Neuropsychiatric Inventory (SMD 0.10, 95% CI -0.07 to 0.27; 543 participants; 2 studies; high quality of evidence). One very small study showed a benefit for omega-3 PUFAs in instrumental activities of daily living after 12 months of treatment (MD -3.50, 95% CI -4.30 to -2.70; 22 participants; moderate quality evidence). The included studies did not measure specific cognitive function. The studies did not report adverse events well. Two studies stated that all adverse events were mild and that they did not differ in overall frequency between omega-3 PUFA and placebo groups. Data from one study showed no difference between groups in frequency of any adverse event (risk ratio (RR) 1.02, 95% CI 0.95 to 1.10; 402 participants; 1 study; moderate quality evidence) or any serious adverse event (RR 1.05, 95% CI 0.78 to 1.41; 402 participants; 1 study; high quality evidence) at 18 months of treatment. AUTHORS' CONCLUSIONS: We found no convincing evidence for the efficacy of omega-3 PUFA supplements in the treatment of mild to moderate AD. This result was consistent for all outcomes relevant for people with dementia. Adverse effects of omega-3 PUFAs seemed to be low, but based on the evidence synthesised in this review, we cannot make a final statement on tolerability. The effects on other populations remain unclear.

A systematic review of randomised controlled trials of radiotherapy for localised prostate cancer.

BACKGROUND: Prostate cancer is the second most frequently diagnosed cancer and the sixth leading cause of cancer death in males. A systematic review of randomised controlled trials (RCTs) of radiotherapy and other non-pharmacological management options for localised prostate cancer was undertaken. METHODS: A search of thirteen databases was carried out until March 2014. RCTs comparing radiotherapy (brachytherapy (BT) or external beam radiotherapy (EBRT)) to other management options i.e. radical prostatectomy (RP), active surveillance, watchful waiting, high intensity focused ultrasound (HIFU), or cryotherapy; each alone or in combination, e.g. with adjuvant hormone therapy (HT), were included. Methods followed guidance by the Centre for Reviews and Dissemination and the Cochrane Collaboration. Indirect comparisons were calculated using the Bucher method. RESULTS: Thirty-six randomised controlled trials (RCTs, 134 references) were included. EBRT, BT and RP were found to be effective in the management of localised prostate cancer. While higher doses of EBRT seem to be related to favourable survival-related outcomes they might, depending on technique, involve more adverse events, e.g. gastrointestinal and genitourinary toxicity. Combining EBRT with hormone therapy shows a statistically significant advantage regarding overall survival when compared to EBRT alone (Relative risk 1.21, 95% confidence interval 1.12-1.30). Aside from mixed findings regarding urinary function, BT and radical prostatectomy were comparable in terms of quality of life and biochemical progression-free survival while favouring BT regarding patient satisfaction and sexual function. There might be advantages of EBRT (with/without HT) compared to cryoablation (with/without HT). No studies on HIFU were identified. CONCLUSIONS: Based on this systematic review, there is no strong evidence to support one therapy over another as EBRT, BT and RP can all be considered as effective monotherapies for localised disease with EBRT also effective for post-operative management. All treatments have unique adverse events profiles. Further large, robust RCTs which report treatment-specific and treatment combination-specific outcomes in defined prostate cancer risk groups following established reporting standards are needed. These will strengthen the evidence base for newer technologies, help reinforce current consensus guidelines and establish greater standardisation across practices.