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Thyroid eye disease (TED) remains challenging for clinicians to evaluate and manage. Novel therapies have recently emerged, and their specific roles are still being determined. Most patients with TED develop eye manifestations while being treated for hyperthyroidism and under the care of endocrinologists. Endocrinologists, therefore, have a key role in diagnosis, initial management, and selection of patients who require referral to specialist care. Given that the need for guidance to endocrinologists charged with meeting the needs of patients with TED transcends national borders, and to maximize an international exchange of knowledge and practices, the American Thyroid Association and European Thyroid Association joined forces to produce this consensus statement. ispartof: THYROID vol:32 issue:12 pages:1439-1470 ispartof: location:United States status: published

Background In the photodynamic therapy (PDT) of non‐aggressive basal cell carcinomas (BCCs), 5‐aminolevulinic acid nanoemulsion (BF‐200ALA) has shown non‐inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL‐PDT in the treatment of BCCs. Objectives To compare the histological clearance, tolerability (pain and post‐treatment reaction), and cosmetic outcome of MAL, BF‐200 ALA, and low‐concentration HAL in the PDT of non‐aggressive BCCs. Methods Ninety‐eight histologically verified non‐aggressive BCCs met the inclusion criteria, and 54 patients with 95 lesions completed the study. The lesions were randomized to receive LED‐PDT in two repeated treatments with MAL, BF‐200 ALA, or HAL. Efficacy was assessed both clinically and confirmed histologically at three months by blinded observers. Furthermore, cosmetic outcome, pain, post‐treatment reactions fluorescence, and photobleaching were evaluated. Results According to intention‐to‐treat analyses, the histologically confirmed lesion clearance was 93.8% (95% confidence interval [CI] = 79.9–98.3) for MAL, 90.9% (95% CI = 76.4–96.9) for BF‐200 ALA, and 87.9% (95% CI = 72.7–95.2) for HAL, with no differences between the arms (p=0.84). There were no differences between the arms as regards pain, post‐treatment reactions, or cosmetic outcome. Conclusions PDT with low‐concentration HAL and BF‐200 ALA have a similar efficacy, tolerability, and cosmetic outcome compared to MAL. HAL is an interesting new option in dermatological PDT, since good efficacy is achieved with a low concentration. peerReviewed

Background and aims: Approximately 25% of patients with diabetes mellitus type 2 (DMII) develop painful diabetic neuropathy (PDN). PDN is known to affect both mental and physical wellbeing, resulting in anxiety, depression, low quality of life and physical disability. Pharmacological treatment of PDN aims at pain relief and is often ineffective and/or has many side effects. Rehabilitation treatment modalities that are designed to help the patient deal with PDN related complaints, are mostly focussed on either physical (e.g. exercise therapy) or psychological aspects (e.g. cognitive behavioural therapy, CBT). There is emerging evidence that PDN can be approached from a biopsychosocial perspective, in which physical and psychosocial aspects are integrated. From this biopsychosocial approach it is plausible that integrated treatment modalities such as acceptance commitment therapy (ACT) or exposure in vivo (EXP) could be effective in patients with PDN. The objective of this review was to provide an overview of the current evidence on the effects of rehabilitation treatments that combine exercise therapies with psychological therapies in order to improve physical activity (PA) and quality of life (QoL) in patients with PDN.Methods: Systematic review of the current literature. EMBASE, MEDLINE, Medline In-Process citations and e-Pubs ahead-of-print, Pedro, Web of Science, PsycINFO, CENTRAL, PubMed and Google Scholar were searched. All studies on interventions combining exercise therapy with psychological interventions in patients with PDN, aged >18 years, were included. Outcome measures were PA, QoL.Results: The search resulted in 1603 records after removing duplicates. After screening on titles and abstracts, 100 records remained. From these, not one study reported on interventions that combined exercise therapy with psychological interventions. Through a secondary hand search, a total of three reviews were identified that described a total of five studies regarding either physical or psychological interventions in patients with PDN. These studies reported moderate effects of (1) mindfulness meditation on QoL, (2) CBT on pain severity, (3) mindfulness-based stress reduction intervention on function, health-related QoL, pain catastrophizing and depression, (4) aerobic exercise on QoL and (5) Tai Chi on glucose control, balance, neuropathic symptoms, and some dimensions of QoL in patients with PDN. All studies were of a moderate quality, and results should be interpreted with caution.Conclusions: Based on increasing knowledge in the domain of chronic pain, it could be assumed that integrated rehabilitation treatments for patients with PUN are beneficial. There is no literature to support this and more research should be done on integrated biopsychosocial interventions in patients with PDN.

Background and aims Approximately 25% of patients with diabetes mellitus type 2 (DMII) develop painful diabetic neuropathy (PDN). PDN is known to affect both mental and physical wellbeing, resulting in anxiety, depression, low quality of life and physical disability. Pharmacological treatment of PDN aims at pain relief and is often ineffective and/or has many side effects. Rehabilitation treatment modalities that are designed to help the patient deal with PDN related complaints, are mostly focussed on either physical (e.g. exercise therapy) or psychological aspects (e.g. cognitive behavioural therapy, CBT). There is emerging evidence that PDN can be approached from a biopsychosocial perspective, in which physical and psychosocial aspects are integrated. From this biopsychosocial approach it is plausible that integrated treatment modalities such as acceptance commitment therapy (ACT) or exposure in vivo (EXP) could be effective in patients with PDN. The objective of this review was to provide an overview of the current evidence on the effects of rehabilitation treatments that combine exercise therapies with psychological therapies in order to improve physical activity (PA) and quality of life (QoL) in patients with PDN. Methods Systematic review of the current literature. EMBASE, MEDLINE, Medline In-Process citations and e-Pubs ahead-of-print, Pedro, Web of Science, PsycINFO, CENTRAL, PubMed and Google Scholar were searched. All studies on interventions combining exercise therapy with psychological interventions in patients with PDN, aged >18 years, were included. Outcome measures were PA, QoL. Results The search resulted in 1603 records after removing duplicates. After screening on titles and abstracts, 100 records remained. From these, not one study reported on interventions that combined exercise therapy with psychological interventions. Through a secondary hand search, a total of three reviews were identified that described a total of five studies regarding either physical or psychological interventions in patients with PDN. These studies reported moderate effects of (1) mindfulness meditation on QoL, (2) CBT on pain severity, (3) mindfulness-based stress reduction intervention on function, health-related QoL, pain catastrophizing and depression, (4) aerobic exercise on QoL and (5) Tai Chi on glucose control, balance, neuropathic symptoms, and some dimensions of QoL in patients with PDN. All studies were of a moderate quality, and results should be interpreted with caution. Conclusions Based on increasing knowledge in the domain of chronic pain, it could be assumed that integrated rehabilitation treatments for patients with PDN are beneficial. There is no literature to support this and more research should be done on integrated biopsychosocial interventions in patients with PDN. Implications This empty review highlights the importance that more research should be done on integrated biopsychosocial interventions in patients with PDN. Currently, our research group is performing a study on the effects of EXP treatment in patients with PDN.

For the treatment of superficial basal cell carcinoma, a prospective, noninferiority, randomized controlled multicenter trial with 601 patients showed that 5% imiquimod cream was superior and 5-fluorouracil cream not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) at 1 and 3 years after treatment. No definite conclusion could be drawn regarding the superiority of imiquimod over 5-fluorouracil. We now present the 5-year follow-up results according to the intention-to-treat analysis. Five years after treatment, the probability of tumor-free survival was 62.7% for methyl aminolevulinate photodynamic therapy (95% confidence interval [CI] = 55.3-69.2), 80.5% for imiquimod (95% CI = 74.0-85.6), and 70.0% for 5-fluorouracil (95% CI = 62.9-76.0). The hazard ratio for treatment failure of imiquimod and 5-fluorouracil were 0.48 (95% CI = 0.32-0.71, P < 0.001) and 0.74 (95% CI = 0.53-1.05, P = 0.09), respectively, when compared with methyl aminolevulinate photodynamic therapy. Compared with 5-fluorouracil, imiquimod showed a hazard ratio of 0.65 (95% CI 0.43-0.98, P = 0.04). In conclusion, 5 years after treatment, the results of this trial show that 5% imiquimod cream is superior to both methyl aminolevulinate photodynamic therapy and 5-fluorouracil cream in terms of efficacy for superficial basal cell carcinoma. We therefore consider 5% imiquimod cream as the first choice for noninvasive treatment in most primary superficial basal cell carcinomas.

We illustrate the approach of randomising treatments and compare it with the traditional approach of randomising patients, using a case study drawn from the authors’ experience in clinical trials. The setting is a double-blind parallel two-arm randomised controlled trial (RCT), but the method in this paper can be extended to single-blind, cross-over, or multi-arm RCTs.We propose the concept of two different levels of blinding: full blinding and partial blinding. We subsequently show how to maintain the maximal level of blinding. Using an example, we show that a pharmacist can be fully blinded if the investigational medical products (IMPs) that they prescribe (instead of patients) are randomised, and they can be partially blinded if they need to dispense replacement (i.e., surplus) IMPs. A small number of surplus IMPs is commonly required in a clinical trial to replace lost or damaged IMPs. We note that the concept of full blinding and partial blinding is different from double-blind trial, and the level of blinding is relevant in both single-blind and double-blind trials.A trial statistician needs to work closely with all parties in the design of the randomisation, including the pharmacist, the trial manager, and the manufacturer. We detail what should and should not be shown in the various documents that the trial statistician need to provide to the pharmacist and to the manufacturer. We provide template tables for these documents. Keywords: Randomisation, Blinding, Single-blind, Double-blind, Placebo, Randomised controlled trial (RCT), Investigational medical product (IMP), Pharmacist

The assessment of the quality of life (QoL) in minilaparotomy cholecystectomy (MC) versus laparoscopic cholecystectomy (LC) with the ultrasonic dissection in both groups has not been addressed earlier. Initially, 109 patients with non-complicated symptomatic gallstone disease were randomized to undergo either MC (n = 59) or LC (n = 50). RAND-36 survey was conducted preoperatively and at 4 weeks and 6 months postoperatively. The end point of our study was to determine differences in health status in MC versus LC groups. QoL improved significantly in both groups, and the recovery was similar in the two groups, except from the higher score in 'health change' subscale at 4 weeks in MC group [MC score 75.0 (25.0) vs. LC score 56.5 (23.2), p = 0.008]. The MC and LC groups combined, RAND-36 scores increased significantly in 'physical functioning' [combined mean (SD) preoperative score 80.5 (23.9) vs. 6-month postoperative score 86.5 (21.7), p = 0.015], 'vitality' [64.5 (19.2) vs. 73.5 (18.3), p = 0.001], 'health change' [43.0 (21.6) vs. 74.6 (25.4), p = 0.0001] and 'bodily pain' scores [57.7 (26.3) vs. 75.5 (25.5), p = 0.001], respectively. Four RAND-36 domains indicated statistically significant health status differences in comparing the preoperative and postoperative RAND-36 scores in LC and MC groups combined. Four RAND-36 domains indicated a significant positive change in QoL after cholecystectomy.

Quality of recovery could be influenced positively if there is less postoperative sore throat (POST). Eating a popsicle might attenuate this sore throat. Especially for bariatric surgery, early recovery is important. Adding popsicles to the postoperative protocol could be beneficial. Our hypothesis is that offering a popsicle in the recovery room to patients after bariatric surgery will decrease POST and will increase quality of postoperative recovery. Patients undergoing elective bariatric surgery, between the 23 February 2015 and 3 April, were randomised to either the popsicle group or control group. Primary endpoint was the incidence of POST and secondly if a reduction in POST influences quality of recovery at the first day postoperative measured with the Bariatric Quality Of Recovery (BQoR) questionnaire. One hundred and thirty-three patients were assessed for eligibility. For the final analysis, 44 patients in the intervention and 65 in the control group were available. Eating a popsicle after bariatric surgery had no significant effect on the incidence of POST. Significant effects (in favour of the popsicle group) were seen in muscle pain score (p = 0.047) and sore mouth score (p = 0.012). Popsicle intragroup analysis revealed that eating the whole popsicle (compared to partially eating the popsicle) has positive effects on nausea (p = 0.059), feeling cold (p = 0.008), and mean total comfort score (p = 0.011). Of the patients who became nauseous and/or had to vomit because of the popsicle, n = 4 had more severe pain (p = 0.04) and the mean pain score was higher (p = 0.09). The present study demonstrates that offering a popsicle early during recovery after bariatric surgery is feasible without adverse effects, although eating popsicle did not reduce postoperative sore throat. There are possible beneficial effects, such as reduced muscle pains and less sore mouth, that may enhance the quality of recovery. More research is necessary to further substantiate the effect of eating popsicles on the quality of recovery in this patient population.Trial Registration: Registration number: NTR4943 (http://www.trialregister.nl). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12262-016-1560-4) contains supplementary material, which is available to authorized users.

Objective: Meta-analyses of antidepressant drug treatment trials have found that increasing age is associated with a less favourable outcome. Because the prevalence of geriatric characteristics, like disability, medical co-morbidity, malnutrition, cognitive (dys) function and frailty increase with age and are associated with depression, these characteristics are likely to modify the treatment outcome of antidepressant drugs in late-life depression. This review examines how these five characteristics are taken into account in randomised controlled trials (RCTs) with antidepressant drugs for major depressive disorder in patients aged 60 years or above. Design: A systematic search in PubMED, PsychInfo and EMBASE, from the year 2000 onwards, yielded 27 RCTs, with a total of 6356 subjects with a median age of 71 years. Two reviewers independently assessed whether each characteristic was considered as inclusion or exclusion criterion, descriptive variable, stratification variable, co-variable, outcome measure, or in adverse effect monitoring. Results: Malnutrition and frailty were not taken into account in any study. Disability was used as an outcome measure in five studies. Two studies explicitly included a population with possibly serious medical co-morbidity. Cognitive status was the only condition taken into account as co-variable (n = 3) or stratifying variable (n = 1) and was used as outcome measure in seven studies. Conclusions: We conclude that geriatric characteristics are rarely taken into account in RCTs on anti-depressant drugs in late-life depression, and studies including the oldest adults are underrepresented. This warrants recruitment of the oldest adults and adjustment of treatment strategies in future studies. Copyright (C) 2016 John Wiley & Sons, Ltd.

BACKGROUND: Increasing age is associated with a natural decline in cognitive function and is the greatest risk factor for dementia. Cognitive decline and dementia are significant threats to independence and quality of life in older adults. Therefore, identifying interventions that help to maintain cognitive function in older adults or that reduce the risk of dementia is a research priority. Cognitive training uses repeated practice on standardised exercises targeting one or more cognitive domains and may be intended to improve or maintain optimal cognitive function. This review examines the effects of computerised cognitive training interventions lasting at least 12 weeks on the cognitive function of healthy adults aged 65 or older and has formed part of a wider project about modifying lifestyle to maintain cognitive function. We chose a minimum 12 weeks duration as a trade‐off between adequate exposure to a sustainable intervention and feasibility in a trial setting. OBJECTIVES: To evaluate the effects of computerised cognitive training interventions lasting at least 12 weeks on cognitive function in cognitively healthy people in late life. SEARCH METHODS: We searched to 31 March 2018 in ALOIS (www.medicine.ox.ac.uk/alois), and we performed additional searches of MEDLINE, Embase, PsycINFO, CINAHL, ClinicalTrials.gov, and the WHO Portal/ICTRP (www.apps.who.int/trialsearch), to ensure that the search was as comprehensive and as up‐to‐date as possible to identify published, unpublished, and ongoing trials. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi‐RCTs, published or unpublished, reported in any language. Participants were cognitively healthy people, and at least 80% of the study population had to be aged 65 or older. Experimental interventions adhered to the following criteria: intervention was any form of interactive computerised cognitive intervention ‐ including computer exercises, computer games, mobile devices, gaming console, and virtual reality ‐ that involved repeated practice on standardised exercises of specified cognitive domain(s) for the purpose of enhancing cognitive function; the duration of the intervention was at least 12 weeks; cognitive outcomes were measured; and cognitive training interventions were compared with active or inactive control interventions. DATA COLLECTION AND ANALYSIS: We performed preliminary screening of search results using a 'crowdsourcing' method to identify RCTs. At least two review authors working independently screened the remaining citations against inclusion criteria. At least two review authors also independently extracted data and assessed the risk of bias of included RCTs. Where appropriate, we synthesised data in random‐effects meta‐analyses, comparing computerised cognitive training (CCT) separately with active and inactive controls. We expressed treatment effects as standardised mean differences (SMDs) with 95% confidence intervals (CIs). We used GRADE methods to describe the overall quality of the evidence for each outcome. MAIN RESULTS: We identified eight RCTs with a total of 1183 participants. The duration of the interventions ranged from 12 to 26 weeks; in five trials, the duration of intervention was 12 or 13 weeks. The included studies had moderate risk of bias, and the overall quality of evidence was low or very low for all outcomes. We compared CCT first against active control interventions, such as watching educational videos. Negative SMDs favour CCT over control. Trial results suggest slight improvement in global cognitive function at the end of the intervention period (12 weeks) (standardised mean difference (SMD) ‐0.31, 95% confidence interval (CI) ‐0.57 to ‐0.05; 232 participants; 2 studies; low‐quality evidence). One of these trials also assessed global cognitive function 12 months after the end of the intervention; this trial provided no clear evidence of a persistent effect (SMD ‐0.21, 95% CI ‐0.66 to 0.24; 77 participants; 1 study; low‐quality evidence). CCT may result in little or no difference at the end of the intervention period in episodic memory (12 to 17 weeks) (SMD 0.06, 95% CI ‐0.14 to 0.26; 439 participants; 4 studies; low‐quality evidence) or working memory (12 to 16 weeks) (SMD ‐0.17, 95% CI ‐0.36 to 0.02; 392 participants; 3 studies; low‐quality evidence). Because of the very low quality of the evidence, we are very uncertain about the effects of CCT on speed of processing and executive function. We also compared CCT to inactive control (no interventions). We found no data on our primary outcome of global cognitive function. At the end of the intervention, CCT may lead to slight improvement in episodic memory (6 months) (mean difference (MD) in Rivermead Behavioural Memory Test (RBMT) ‐0.90 points, 95% confidence interval (CI) ‐1.73 to ‐0.07; 150 participants; 1 study; low‐quality evidence) but can have little or no effect on executive function (12 weeks to 6 months) (SMD ‐0.08, 95% CI ‐0.31 to 0.15; 292 participants; 2 studies; low‐quality evidence), working memory (16 weeks) (MD ‐0.08, 95% CI ‐0.43 to 0.27; 60 participants; 1 study; low‐quality evidence), or verbal fluency (6 months) (MD ‐0.11, 95% CI ‐1.58 to 1.36; 150 participants; 1 study; low‐quality evidence). We could not determine any effects on speed of processing because the evidence was of very low quality. We found no evidence on quality of life, activities of daily living, or adverse effects in either comparison. AUTHORS' CONCLUSIONS: We found low‐quality evidence suggesting that immediately after completion of the intervention, small benefits of CCT may be seen for global cognitive function when compared with active controls, and for episodic memory when compared with an inactive control. These benefits are of uncertain clinical importance. We found no evidence that the effect on global cognitive function persisted 12 months later. Our confidence in the results was low, reflecting the overall quality of the evidence. In five of the eight trials, the duration of the intervention was just three months. The possibility that more extensive training could yield larger benefit remains to be more fully explored. We found substantial literature on cognitive training, and collating all available scientific information posed problems. Duration of treatment may not be the best way to categorise interventions for inclusion. As the primary interest of older people and of guideline writers and policymakers involves sustained cognitive benefit, an alternative would be to categorise by length of follow‐up after selecting studies that assess longer‐term effects.

IntroductionSpecialised early intervention services have demonstrated improved outcomes in first-episode psychosis (FEP); however, clinical gains may not be sustained after patients are transferred to regular care. Moreover, many patients with FEP remain socially isolated with poor functional outcomes. To address this, our multidisciplinary team has developed a moderated online social media therapy (HORYZONS) designed to enhance social functioning and maintain clinical gains from specialist FEP services. HORYZONS merges: (1) peer-to-peer social networking; (2) tailored therapeutic interventions; (3) expert and peer-moderation; and (4) new models of psychological therapy (strengths and mindfulness-based interventions) targeting social functioning. The aim of this trial is to determine whether following 2 years of specialised support and 18-month online social media-based intervention (HORYZONS) is superior to 18 months of regular care.Methods and analysisThis study is a single-blind randomised controlled trial. The treatment conditions include HORYZONS plus treatment as usual (TAU) or TAU alone. We recruited 170 young people with FEP, aged 16–27 years, in clinical remission and nearing discharge from Early Psychosis Prevention and Intervention Centre, Melbourne. The study includes four assessment time points, namely, baseline, 6-month, 12-month and 18-month follow-up. The study is due for completion in July 2018 and included a 40-month recruitment period and an 18-month treatment phase. The primary outcome is social functioning at 18 months. Secondary outcome measures include rate of hospital admissions, cost-effectiveness, vocational status, depression, social support, loneliness, self-esteem, self-efficacy, anxiety, psychological well-being, satisfaction with life, quality of life, positive and negative psychotic symptoms and substance use. Social functioning will be also assessed in real time through our Smartphone Ecological Momentary Assessment tool.Ethics and disseminationMelbourne Health Human Research Ethics Committee (2013.146) provided ethics approval for this study. Findings will be made available through scientific journals and forums and to the public via social media and the Orygen website.Trial registration numberACTRN12614000009617; Pre-results.

BACKGROUND: Pre-clinical evidence suggests a period early after stroke during which the brain is most receptive to rehabilitation, if it is provided as high-dose motor training. OBJECTIVE: To evaluate the feasibility of repetitive gait training within the first 3 months post-stroke and the effects on gait-specific outcomes. METHODS: PubMed, Web of Science, Cochrane Library, Rehab Data and PEDro databases were searched systematically. Randomized controlled trials were included to descriptively analyse the feasibility and quantitatively investigate the effectiveness of repetitive gait training compared with conventional therapy. RESULTS: Fifteen randomized controlled trials were included. Repetitive training can safely be provided through body weight support and locomotor assistance from therapists or a robotic device. No difference in drop-out rates was reported despite the demanding nature of the intervention. The meta-analysis yielded significant, but small, effects on walking independence and endurance. Training with end-effector robots appears most effective. CONCLUSION: Robots enable a substantial, yet feasible, increase in the quantity of walking practice early post-stroke, which might enhance functional recovery. However, the mechanisms underlying these effects remain poorly understood. ispartof: Journal of Rehabilitation Medicine vol:51 issue:2 pages:78-88 ispartof: location:Sweden status: published

BACKGROUND: Yoga is an ancient body-mind practice which originated in India and is popular in the Western world as a form of relaxation and exercise. It has been of interest for people with schizophrenia to determine the efficacy of yoga delivered as a package of care versus non-standard care. OBJECTIVES: To examine the effects of yoga as part of a package of care versus non-standard care for schizophrenia. SEARCH METHODS: We searched the Cochrane Schizophrenia Group Trials Register (latest 15 May 2018) which is based on regular searches of MEDLINE, PubMed, Embase, CINAHL, BIOSS, AMED, PsychINFO, and registries of clinical trials. We searched the references of all included studies. There are no language, date, document type, or publication status limitations for inclusion of records in the register. SELECTION CRITERIA: All randomised controlled trials (RCTs) including people with schizophrenia comparing yoga as part of a package of care with non-standard care. DATA COLLECTION AND ANALYSIS: There were no data to analyse as no studies met the inclusion criteria. MAIN RESULTS: The searches identified 30 studies that could be relevant to this review. After careful inspection, 29 were excluded and one is awaiting classification. No data were available for analyses. AUTHORS' CONCLUSIONS: In view of the lack of evidence from RCTs, it is currently not possible for us to comment on the use of yoga as part of a package of care versus non-standard care. ispartof: COCHRANE DATABASE OF SYSTEMATIC REVIEWS vol:4 issue:4 ispartof: location:England status: published

BACKGROUND: Research mainly focuses on motor recovery of the upper limb after stroke. Less attention has been paid to somatosensory recovery. OBJECTIVE: To review and summarize the effect of upper limb somatosensory interventions on somatosensory impairment, motor impairment, functional activity and participation after stroke. METHODS: Biomedical databases Ovid Medline, EMBASE, Web of Science, PEDro, and OTseeker were searched with an update in May 2018. Randomized controlled trials investigating the effect of somatosensory-specific interventions focusing on exteroceptive, proprioceptive or higher cortical somatosensory dysfunction, or any combination were eligible for inclusion. Quality of included studies were assessed using Physiotherapy Evidence Database (PEDro) scale. Standardized Mean Differences and Mean Differences and 95% confidence intervals were calculated and combined in meta-analyses. RESULTS: Active somatosensory interventions did not show a significant effect on somatosensation and activity, but demonstrated a significant improvement in motor impairment (SMD = 0.73, 95% CI = 0.14 to 1.32). No study evaluating active somatosensory intervention included participation. Passive somatosensory interventions significantly improved light touch sensation (SMD = 1.13, 95% CI = 0.20 to 2.05). Passive somatosensory interventions did not show significant effects on proprioception and higher cortical somatosensation, motor impairment, activity and participation. CONCLUSIONS: To date, there is low quality evidence suggesting active somatosensory interventions having a beneficial effect on upper limb impairment and very low quality evidence suggesting passive somatosensory interventions improving upper limb light touch sensation. There is a need for further well-designed trials of somatosensory rehabilitation post stroke. ispartof: NEUROREHABILITATION vol:44 issue:4 pages:459-477 ispartof: location:Netherlands status: published

Background Bone marrow concentrate (BMC) has shown promise in the treatment of several orthopedic conditions. This registry study investigated the use of autologous BMC and platelet products for percutaneous anterior cruciate ligament (ACL) treatment. Methods Twenty-nine patients presenting to a single outpatient interventional musculoskeletal and pain practice with symptomatic grade 1, 2, or 3 ACL tears with less than 1 cm retraction were enrolled. Patients were treated with a percutaneous ACL injection of autologous BMC and platelet products using fluoroscopic guidance. Pre- and post-treatment magnetic resonance imaging analysis was completed for 23 patients using ImageJ software for an objective quantitative analysis of pixel density as a proxy for ACL integrity. Subjective clinical outcome measures collected pre-treatment and at 1, 3, 6, 12, 18, 24, and 36 months post-treatment include the Numerical Pain Scale (NPS), the Lower Extremity Functional Scale (LEFS), the International Knee Documentation Committee (IKDC) form, and a modified version of the Single Assessment Numeric Evaluation. Results Seventy-seven percent of patients treated with BMC injections into the ACL showed significant improvement (p Conclusion In symptomatic patients with grade 1, 2, or even grade 3 tears with minimal retraction, ACL treatment with percutaneous injection of BMC and platelet products shows promise as a non-surgical alternative. However, a larger randomized controlled trial is warranted to confirm these findings. Trial registration NCT03011398. A Clinical Registry of Orthobiologics Procedures. https://clinicaltrials.gov/ct2/show/NCT03011398?term=orthobiologics&rank=1. Registered 29 December 2016. Enrollment 1 December 2011-retrospectively registered

Background: There have been concerns that recurrences after noninvasive therapy for basal cell carcinoma (BCC) transform into a "more aggressive'' histologic subtype.Objective: We sought to evaluate the proportion of patients with a nonsuperficial treatment failure after noninvasive therapy for superficial BCC.Methods: An observational study was performed using data from a single blind, noninferiority, randomized controlled trial (March 2008-August 2010) with 5-year follow-up in patients with primary superficial BCC treated with methylaminolevulinate-photodynamic therapy, 5-fluorouracil, or imiquimod. Data were used from 166 adults with a histologically confirmed treatment failure.Results: A nonsuperficial subtype was found in 64 of 166 treatment failures (38.6%). Proportions with a more aggressive subtype than the primary tumor were 51.3% (38/74) for early and 28.3% (26/92) for later treatment failures (P = .003). The proportion of more aggressive early failures was significantly lower after imiquimod (26.3%) compared with methylaminolevulinate-photodynamic therapy (54.8%, P = .086) and 5-fluorouracil (66.7%, P = .011).Limitations: There was limited information on the exact time of occurrence of treatment failures.Conclusion: More aggressive treatment failure recurrences after noninvasive therapy for superficial BCC occur most often within the first 3 months posttreatment, probably indicating underdiagnosis of more aggressive components in the primary tumor rather than transformation.

BackgroundSeveral treatment options are available for stress urinary incontinence (SUI), including pelvic floor muscle training (PFMT), drug therapy and surgery. Problems exist such as adherence to PFMT regimens, side effects linked to drug therapy and the risks associated with surgery. We have evaluated an alternative treatment, electrical stimulation (ES) with non-implanted devices, which aims to improve pelvic floor muscle function to reduce involuntary urine loss.ObjectivesTo assess the effects of electrical stimulation with non-implanted devices, alone or in combination with other treatment, for managing stress urinary incontinence or stress-predominant mixed urinary incontinence in women. Among the outcomes examined were costs and cost-effectiveness.Search methodsWe searched the Cochrane Incontinence Specialised Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearches of journals and conference proceedings (searched 27 February 2017). We also searched the reference lists of relevant articles and undertook separate searches to identify studies examining economic data.Selection criteriaWe included randomised or quasi-randomised controlled trials of ES with non-implanted devices compared with any other treatment for SUI in women. Eligible trials included adult women with SUI or stress-predominant mixed urinary incontinence (MUI). We excluded studies of women with urgency-predominant MUI, urgency urinary incontinence only, or incontinence associated with a neurologic condition. We would have included economic evaluations had they been conducted alongside eligible trials.Data collection and analysisTwo review authors independently screened search results, extracted data from eligible trials and assessed risk of bias, using the Cochrane 'Risk of bias' tool. We would have performed economic evaluations using the approach recommended by Cochrane Economic Methods.Main resultsWe identified 56 eligible trials (3781 randomised participants). Eighteen trials did not report the primary outcomes of subjective cure, improvement of SUI or incontinence-specific quality of life (QoL). The risk of bias was generally unclear, as most trials provided little detail when reporting their methods. We assessed 25% of the included trials as being at high risk of bias for a variety of reasons, including industry funding and baseline differences between groups. We did not identify any economic evaluations.For subjective cure of SUI, we found moderate-quality evidence that ES is probably better than no active treatment (risk ratio (RR) 2.31, 95% CI 1.06 to 5.02). We found a similar result for cure or improvement of SUI (RR 1.73, 95% CI 1.41 to 2.11), but the quality of evidence was lower. We are very uncertain if there is a difference between ES and sham treatment in terms of subjective cure because of the very low quality of evidence (RR 2.21, 95% CI 0.38 to 12.73). For subjective cure or improvement, ES may be better than sham treatment (RR 2.03, 95% CI 1.02 to 4.07). The effect estimate was 660/1000 women cured/improved with ES compared to 382/1000 with no active treatment (95% CI 538 to 805 women); and for sham treatment, 402/1000 women cured/improved with ES compared to 198/1000 with sham treatment (95% CI 202 to 805 women).Low-quality evidence suggests that there may be no difference in cure or improvement for ES versus PFMT (RR 0.85, 95% CI 0.70 to 1.03), PFMT plus ES versus PFMT alone (RR 1.10, 95% CI 0.95 to 1.28) or ES versus vaginal cones (RR 1.09, 95% CI 0.97 to 1.21).Electrical stimulation probably improves incontinence-specific QoL compared to no treatment (moderate quality evidence) but there may be little or no difference between electrical stimulation and PFMT (low quality evidence). It is uncertain whether adding electrical stimulation to PFMT makes any difference in terms of quality of life, compared with PFMT alone (very low quality evidence). There may be little or no difference between electrical stimulation and vaginal cones in improving incontinence-specific QoL (low quality evidence). The impact of electrical stimulation on subjective cure/improvement and incontinence-specific QoL, compared with vaginal cones, PFMT plus vaginal cones, or drugs therapy, is uncertain (very low quality evidence).In terms of subjective cure/improvement and incontinence-specific QoL, the available evidence comparing ES versus drug therapy or PFMT plus vaginal cones was very low quality and inconclusive. Similarly, comparisons of different types of ES to each other and of ES plus surgery to surgery are also inconclusive in terms of subjective cure/improvement and incontinence-specific QoL (very low-quality evidence).Adverse effects were rare: in total nine of the women treated with ES in the trials reported an adverse effect. We identified insufficient evidence to compare the risk of adverse effects in women treated with ES compared to any other treatment. We were unable to identify any economic data.Authors' conclusionsThe current evidence base indicated that electrical stimulation is probably more effective than no active or sham treatment, but it is not possible to say whether ES is similar to PFMT or other active treatments in effectiveness or not. Overall, the quality of the evidence was too low to provide reliable results. Without sufficiently powered trials measuring clinically important outcomes, such as subjective assessment of urinary incontinence, we cannot draw robust conclusions about the overall effectiveness or cost-effectiveness of electrical stimulation for stress urinary incontinence in women.

Background: Cognitive training (CT) refers to guided cognitive exercises designed to improve specific cognitive functions, as well as enhance performance in untrained cognitive tasks. Positive effects of CT on cognitive functions in healthy elderly people and persons with mild cognitive impairment have been reported, but data regarding the effects of CT in patients with dementia is unclear. Objective: We systematically reviewed the current evidence from randomized controlled trials (RCTs) to find out if CT improves or stabilizes cognition and/or everyday functioning in patients with mild and moderate Alzheimer's disease. Results: Altogether, 31 RCTs with CT as either the primary intervention or part of a broader cognitive or multi-component intervention were found. A positive effect was reported in 24 trials, mainly on global cognition and training-specific tasks, particularly when more intensive or more specific CT programs were used. Little evidence of improved everyday functioning was found. Conclusions: Despite some positive findings, the inaccurate definitions of CT, inadequate sample sizes, unclear randomization methods, incomplete datasets at follow-up and multiple testing may have inflated the results in many trials. Future high quality RCTs with appropriate classification and specification of cognitive interventions are necessary to confirm CT as an effective treatment option in Alzheimer's disease.

To examine which attributes of a non-invasive treatment for superficial BCC (sBCC) are valued by patients, a discrete choice experiment (DCE) was performed alongside a clinical trial in which methylaminolevulinate photodynamic therapy (MAL-PDT), 5-fluorouracil and imiquimod were compared.1 Treatment options were described by the following attributes: effectiveness, cosmetic result, treatment process and side-effects. Effectiveness was defined as the probability that complete tumour clearance is achieved 12 months after treatment with levels of 75%,80%,85% and 90%.2-4 This article is protected by copyright. All rights reserved.

Objectives To compare the efficacy of nasal antiseptic ointment and silver nitrate cautery in the treatment of children with recurrent epistaxis. Methods In this prospective and randomized study, a hundred children with recurrent epistaxis were assigned into two groups. In group 1, patients underwent silver nitrate cauterization, in group 2 patients were treated with nasal antiseptic ointment (oxytetracycline hydrochloride-polymyxin B sulfate); and both groups were followed for 3 months. All of the patients were investigated for allergy with skin prick test. Results The ages of patients were similar in both groups (group 1: 9.2 ± 2.7; group 2: 8.2 ± 2.2; p = 0.069). Thirty-eight percent of the patients in group 1 and 52% of the patients in group 2 had epistaxis in the three months follow-up. The difference between groups was not significant ( p = 0.159). Thirteen (26%) of the patients in group 1 and 12 (24%) of the patients in group 2 were found to have allergic symptoms and positive prick test. The rate of allergy was similar in both groups ( p = 0.817). Conclusion Nasal antiseptic ointment and silver nitrate cauterization were found to have similar outcomes in the treatment of recurrent epistaxis.

Objective: To evaluate the primary and clinical outcomes in laparoscopic and small-incision cholecystectomy.Design: Blinded randomized single-center trial emphasizing methodologic quality and generalizability.Setting: General teaching hospital in the NetherlandsPatients: A total of 257 patients undergoing cholecystectomy for symptomatic cholecystolithiasis.Interventions: Laparoscopic cholecystectomy and small-incision cholecystectomy, performed mainly by surgical residents.Main Outcome Measures: Complications and symptom relief were primary outcome measures; conversion rate, operative time, and hospital stay were secondary out-come measures. Feasibility of performing both procedures by residents was evaluated as well.Results: In the 257 patients, surgical residents performed 105 laparoscopic and 118 small-incision cholecystectomies. There were no significant differences in complications, conversion rates, and hospital stay. Operative time was significantly shorter with the small-incision technique.Conclusions: No differences in primary clinical outcome measures were found between laparoscopic and small-incision cholecystectomy in this randomized trial with emphasis on methodologic quality and generalizability. The gold standard status of laparoscopic cholecystectomy is questionable.Trial Registration: isrctn.org Identifier: ISRCTN67485658.

Background: Upper abdominal surgery, including laparoscopic cholecystectomy (LC), is associated with post-operative pulmonary dysfunction. LC has, by consensus, become the treatment of choice for symptomatic cholecystolithiasis. The small-incision cholecystectomy (SIC), a procedure which does not require a pneumoperitoneum threatens to be lost to clinical practice even though there is evidence of equality. We hypothesized that the SIC technique should be equal and might even be superior to the LC when considering post-operative pulmonary function due to the short incision length.Methods: A single-centre, randomized clinical trial was performed including patients scheduled for elective cholecystectomy. Pulmonary flow-volume curves were measured pre-operatively, post-operatively, and at follow up. Blood gas analyses were measured pre-operative, in the recovery phase and on post-operative day 1. Anaesthesia, analgesics, and peri-operative care were standardized by protocol. Post-operatively, patients and caregivers were blinded to the procedure.Results: A total of 257 patients were analysed. There was one pulmonary complication (pneumonia) in the LC group. In both groups, similar reductions of approximately 20% in pulmonary function parameters occurred, with complete recovery to pre-operative values. Patients in the SIC group consumed more analgesia when compared with the LC group without impact on blood gas analysis. Patients converted to a conventional open technique showed significant differences in six of the eight parameters in pulmonary function tests.Conclusion: When evaluated with strict methodology and standardization of care, no clinically relevant differences were found between SIC and LC regarding pulmonary function. Our results suggest that the popularity of the laparoscopic technique cannot be attributed to pulmonary preservation.

Background: Dysfunction of the cervicothoracic spine and the adjacent ribs (also called the shoulder girdle) is considered to predict occurrence and poor outcome of shoulder symptoms. it can be treated with manipulative therapy, but scientific evidence for the effectiveness of such therapy is lacking. Objective: To study the effectiveness of manipulative therapy for the shoulder girdle in addition to usual medical care for relief of shoulder pain and dysfunction. Design: Randomized, controlled trial. Setting: General practices in Groningen, the Netherlands. Patients: 150 patients with shoulder symptoms and dysfunction of the shoulder girdle. Interventions: All patients received usual medical care from their general practitioners. Only the intervention group received additional manipulative therapy, up to 6 treatment sessions in a 12-week period. Measurements: Patient-perceived recovery, severity of the main complaint, shoulder pain, shoulder disability, and general health. Data were collected during and at the end of the treatment period (at 6 and 12 weeks) and during the follow-up period (at 26 and 52 weeks). Results: During treatment (6 weeks), no significant differences were found between study groups. After completion of treatment (12 weeks), 43% of the intervention group and 21% of the control group reported full recovery. After 52 weeks, approximately the same difference in recovery rate (17 percentage points) was seen between groups. During the intervention and follow-up periods, a consistent between-group difference in severity of the main complaint, shoulder pain and disability, and general health favored additional manipulative therapy. Limitations: The sample size was small, and assessment of end points was subjective. Conclusion: manipulative therapy for the shoulder girdle in addition to usual medical care accelerates recovery of shoulder symptoms.

BACKGROUND: We present the design of the Groningen Manipulation Study. This randomized controlled trial is part of the Dutch Shoulder Disability Study, a comprehensive prognostic cohort study on shoulder disorders, with randomized controlled interventions in subcohorts. OBJECTIVE: To evaluate the effectiveness of manipulative treatment of the structures of the shoulder girdle, in addition to standard treatment by the general practitioner for relief of shoulder symptoms and prevention of persistent or recurrent shoulder symptoms. METHODS: A total of 250 patients with shoulder symptoms and a functional limitation of the shoulder girdle will be included from 30 general practices in Groningen, The Netherlands. All participating patients receive standard treatment by the general practitioner and will be randomly allocated to additional manipulative treatment. Evaluation measurements take place 6, 12, 26, and 52 weeks after randomization. CONCLUSION: The short-term primary outcome measure is the proportion of patients with relief of shoulder complaints and the long-term primary outcome is the proportion of patients without persistent or recurrent shoulder symptoms. Dependent and independent variables include a structured medical history, a physical examination of the shoulder and shoulder girdle, and a measure of the mobility of the cervico-thoracic spine with a 6-degree-of-freedom electromagnetic tracking device. Record 2 of 8 - PreMedline on SilverPlatter January Week 4

The aim of the current study was to investigate recovery of visuospatial neglect during the first year after stroke. Visuospatial neglect was measured using two frequently and widely used tests: the letter cancellation test (LCT) and the line bisection test (LBT). This was a prospective cohort study of 101 stroke patients. Of these 101 patients, 51 patients showed visuospatial neglect. All time-dependent measures were taken weekly, starting from within 14 days after stroke onset. From week 10-20 biweekly measurements were obtained. Follow-up measurements were performed at weeks 26, 38, and finally 52. For the present study, number of misses in the LCT, split on contralesional versus ipsilesional side, as well as the deviation from the actual midpoint in mm in the LBT were used. The longitudinal relationship of (bi)weekly time on improvement in LBT and LCT were investigated using random coefficient analysis and joinpoint analyses. Results indicated that progress of time is an independent covariate that reflects neurological recovery of visuospatial neglect. Additionally, trend changes were obtained in between 12 and 14 weeks post-stroke with respect to the neglected side. This is the first prospective cohort study in which the time course of neglect is investigated by using intensive serial measurements in the early months post-stroke. (c) 2012 Elsevier Ltd. All rights reserved.

Purpose: To examine whether motor performance and motor learning in healthy subjects can be segregated into a number of distinct motor abilities which are linked to intact processing in different motor-related brain regions (M1, S1, SMA, PMC) early during learning. Methods: Seven young healthy subjects trained in eight motor arm tasks (Arm Ability Training, AAT) once a day for 5 days using their left non-dominant arm. Except for day 1 (baseline), training was performed before and after applying an inhibitory form of repetitive transcranial magnetic stimulation (cTBS, continuous theta burst) to either M1, S1, SMA, or PMC. Results: A principal component analysis of the motor behaviour data suggested four independent motor abilities: aiming, speed, steadiness, and visuomotor tracking. AAT induced substantial motor learning across abilities. Within session effects of cTBS revealed that activity in primary somatosensory cortex (S1) was relevant for motor performance and learning across all tasks whereas M1 was specifically involved in rapid tapping movements, PMC in ballistic arm navigation in extra-personal space; performance on a non-trained motor tasks was not affected by cTBS. Conclusions: Cortical sensory and motor areas including S1, M1, and PMC functionally contribute to early motor learning in a differential manner across motor abilities.

Background “Patient-Reported Outcome” (PRO) is used as an umbrella term for different concepts for measuring subjectively perceived health status e. g. as treatment effects. Their common characteristic is, that the appraisal of the health status is reported by the patient himself. In order to describe the informative value of PRO in Health Technology Assessment (HTA) first an overview of concepts, classifications and methods of measurement is given. The overview is complemented by an empirical analysis of clinical trials and HTA-reports on rheumatoid arthritis and breast cancer in order to report on type, frequency and consequences of PRO used in these documents. Methods For both issues systematic reviews of the literature have been performed. The search for methodological literature covers the publication period from 1990 to 2009, the search for clinical trials of rheumatoid arthritis and breast cancer covers the period 2005 to 2009. Both searches were performed in the medical databases of the German Institute of Medical Documentation and Information (DIMDI). The search for HTA-reports and methodological papers of HTA-agencies was performed in the CRD-Databases (CRD = Centre for Reviews and Dissemination) and by handsearching the websites of INAHTA member agencies (INAHTA = International Network of Agencies for Health Technology Assessment). For all issues specific inclusion and exclusion criteria were defined. The methodological quality of randomized controlled trials (RCT) was assessed by a modified version of the Cochrane Risk of Bias Tool. For the methodological part information extraction from the literature is structured by the report’s chapters, for the empirical part data extraction sheets were constructed. All information is summarized in a qualitative manner. Results Concerning the methodological issues the literature search retrieved 158 documents (87 documents related to definition or classification, 125 documents related to operationalisation of PRO). For the empirical analyses 225 RCT (rheumatoid arthritis: 77; breast cancer: 148) and 40 HTA-reports and method papers were found. The analysis of the methodological literature confirms the role of PRO as an umbrella term for a variety of different concepts. The newest classification system facilitates the description of PRO measures by construct, target population and the method of measurement. Steps of operationalisation involve defining a conceptual framework, instrument development, exploration of measurement properties or, possibly, the modification of existing instruments. Seven out of 59 RCT analysing the effects of antibody therapy for rheumatoid arthritis define PRO as the primary endpoint, 38 trials utilize composite measures (ACR, DAS) and ten trials report clinical or radiological parameters as the primary endpoint. Six out of 123 chemotherapy trials for breast cancer define PRO as the primary endpoint, while 98 trials report clinical endpoints (survival, tumour response, progression) in their primary analyses. Discrepancies in the number of trials result from inaccurate specifications of endpoints in the publications. This distribution is reflected in the HTA-reports: while almost all reports on rheumatoid arthritis refer to PRO, this is only the case in about half of the reports on breast cancer. Conclusions As definition and classification of PRO are concerned, coherent concepts are found in the literature. Their operationalisation and implementation must be guided by scientific principles. The type and frequency of PRO used in clinical trials largely depend on the disease analysed. The HTA-community seems to pursue the utilization of PRO proactively – in case of missing data the need for further research is stated., GMS Health Technology Assessment; 7:Doc01; ISSN 1861-8863