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 Butcher 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 mono therapies 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

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

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

Local Treatment of Chronic Wounds in Patients With Peripheral Vascular Disease, Chronic Venous Insufficiency, and Diabetes

<p>Background: A chronic wound is defined as an area where the skin is not intact that fails to heal within eight weeks. Such wounds usually develop on the lower limbs as a complication of diabetes, venous insufficiency, or inadequate arterial perfusion. Most of the roughly 45 000 limb amputations performed in Germany each year are necessitated by non-healing chronic wounds.</p><p>Methods: In the development of this S3 guideline, a systematic search was performed that yielded 4998 references including 38 randomized, controlled trials and 26 systematic reviews, which were used as the basis for the recommendations and statements made in the guideline. Twelve member societies of the umbrella Association of Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften, AWMF), as well as the German Association of Nursing Science (Deutsche Gesellschaft fur Pflegewissenschaft, and patient representatives participated in the consensus rounds in which the guideline's recommendations and statements were agreed upon.</p><p>Results: This guideline contains seven evidence-based recommendations and 30 good clinical practice (GCP) recommendations. Evidence-based recommendations are given in favor of hydrogel, hyperbaric oxygenation, and integrated care, and against the use of medicinal honey and growth factors. Terms are defined precisely in order to ease communication and to specify what is meant by "wound debridement" (a procedure performed by a physician) as opposed to cleansing a wound. Under the premise of preventing pain, exudation, and maceration, local therapeutic agents can be chosen on the basis of the scientific evidence, the patient's preference, the physician's experience, and the wound situation. Costs should also be considered.</p><p>Conclusion: Scant evidence is available to answer many of the relevant questions about chronic wounds. There are valid data in support of hyperbaric oxygen and integrated care. More research is needed.</p>

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

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

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

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. 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). 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. 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.</p