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Background: Weight loss interventions have not been advocated for overweight/obese older adults due to potential loss of skeletal muscle and strength impacting on physical function with potential loss of independence. Carotenoids and polyphenols are inversely associated with sarcopenic symptomology. This paper reports the protocol of a study evaluating the efficacy of a high-protein, energy restricted diet rich in carotenoids and polyphenols on body composition, muscle strength, physical performance and quality of life in overweight and obese older adults.Methods: This randomised controlled clinical trial will recruit community-dwelling, healthy overweight and obese older adults (≥60 years) for a 12-week weight loss intervention. Seventy-three participants will be recruited and randomized to an energy restricted (~30% restriction), isocaloric diet (30% protein; 30% carbohydrate; 40% fat) enriched with either: a) 375 g/d of high carotenoid vegetables, 300 g/d high carotenoid fruit, and 40-60 ml extra-virgin olive oil (EVOO); or b) 375 g/d of lower carotenoid vegetables, 300 g/d lower carotenoid fruit, and 40-60 ml Polyunsaturated fatty acid (PUFA) based oil. All participants will receive individual dietary counselling each fortnight for the duration of the study and will be asked to maintain their habitual level of physical activity throughout the study. The primary outcome will be appendicular skeletal muscle (ASM) assessed by dual energy X-ray absorptiometry (DXA). Secondary outcomes will include body weight, fat-free mass (FFM), fat mass (FM), muscle strength (Isometric hand-grip strength), physical performance (Short Physical Performance Battery), physical activity (International Physical Activity Questionnaire) and health related quality of life (SF-36). Outcomes will be measured at baseline and at week 12.Discussion: The results of this study will provide a novel insight relating to the potential influence of high carotenoid and polyphenol intakes on attenuation of ASM during dietary energy-restricted weight loss in overweight and obese older adults.Trial Registration: The trial was registered on the Australia New Zealand Clinical Trials Register ( ACTRN12616001400459 ); Trial registration date: 10th October, 2016. [ABSTRACT FROM AUTHOR]

Background: While hearing aids for a contralateral routing of signals (CROS-HA) and bone conduction devices have been the traditional treatment for single-sided deafness (SSD) and asymmetric hearing loss (AHL), in recent years, cochlear implants (CIs) have increasingly become a viable treatment choice, particularly in countries where regulatory approval and reimbursement schemes are in place. Part of the reason for this shift is that the CI is the only device capable of restoring bilateral input to the auditory system and hence of possibly reinstating binaural hearing. Although several studies have independently shown that the CI is a safe and effective treatment for SSD and AHL, clinical outcome measures in those studies and across CI centers vary greatly. Only with a consistent use of defined and agreed-upon outcome measures across centers can high-level evidence be generated to assess the safety and efficacy of CIs and alternative treatments in recipients with SSD and AHL.Methods: This paper presents a comparative study design and minimum outcome measures for the assessment of current treatment options in patients with SSD/AHL. The protocol was developed, discussed, and eventually agreed upon by expert panels that convened at the 2015 APSCI conference in Beijing, China, and at the CI 2016 conference in Toronto, Canada.Results: A longitudinal study design comparing CROS-HA, BCD, and CI treatments is proposed. The recommended outcome measures include (1) speech in noise testing, using the same set of 3 spatial configurations to compare binaural benefits such as summation, squelch, and head shadow across devices; (2) localization testing, using stimuli that rove in both level and spectral content; (3) questionnaires to collect quality of life measures and the frequency of device use; and (4) questionnaires for assessing the impact of tinnitus before and after treatment, if applicable.Conclusion: A protocol for the assessment of treatment options and outcomes in recipients with SSD and AHL is presented. The proposed set of minimum outcome measures aims at harmonizing assessment methods across centers and thus at generating a growing body of high-level evidence for those treatment options. [ABSTRACT FROM AUTHOR]

Objectives: A prospective parallel cohort trial was conducted to compare outcomes of patients treated with maxillary protraction vs LeFort 1 maxillary advancement surgery.Setting and Sample Population: The primary site for the clinical trial is Children's Hospital Los Angeles; the satellite test site is Seattle Children's Hospital. All patients have isolated cleft lip and palate and a skeletal Class III malocclusion.Material and Methods: A total of 50 patients, ages 11-14, will be recruited for the maxillary protraction cohort. The maxillary surgery cohort consists of 50 patients, ages 16-21, who will undergo LeFort 1 maxillary advancement surgery. Patients with additional medical or cognitive handicaps were excluded from the study.Results: Current recruitment of patients is on track to complete the study within the proposed recruitment period.Conclusion: This observational trial is collecting information that will examine dental, skeletal, financial and quality-of-life issues from both research cohorts. [ABSTRACT FROM AUTHOR]

Background: Misophonia is a condition marked by dysregulated emotions and behaviors in response to trigger sounds, often chewing, breathing, or coughing. Evidence suggests that misophonia develops in adolescence and the emotions and behaviors are a conditioned response to distress, resulting in social avoidance, stress, and family conflict. In addition, co-occurrence with other psychiatric illnesses such as anxiety, OCD, and Tourette syndrome is common. A transdiagnostic cognitive behavioral therapeutic (CBT) approach appears appropriate. There are currently no controlled studies of youth with misophonia. The current paper describes the approach to a pilot randomized, blinded family-based treatment study for youth ages 8-16 years. Preliminary results from a pilot open trial also are described.Methods: A 2-phase dual site telehealth treatment study using a transdiagnostic CBT approach, the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders in Children and Adolescents (UP-C/A; Ehrenreich-May et al., 2018), is proposed. Phase 1 consisted of a 4-case pilot of UP-C/A. Phase 2 includes a randomized trial comparing the UP-C/A to a standard relaxation and education protocol.Results: Preliminary results from the pilot show modest improvements in evaluator-rated misophonia symptoms on the Clinical Global Impression Severity and Improvement scales.Limitations: There is little research to inform evidence-based practice for youth with misophonia. Study limitations include lack of standardized misophonia assessment instruments and an absence of formal diagnostic criteria.Conclusions: The current paper describes proposed methods for the first randomized controlled trial for youth with misophonia and their families along with results from a 4-case pilot. [ABSTRACT FROM AUTHOR]

Propensity score methods are commonly used in statistical analyses of observational data to reduce the impact of confounding bias in estimations of average treatment effect. While the propensity score is defined as the conditional probability of a subject being in the treatment group given that subject's covariates, the most precise estimation of average treatment effect results from specifying the propensity score as a function of true confounders and predictors only. This property has been demonstrated via simulation in multiple prior research articles. However, we have seen no theoretical explanation as to why this should be so. This paper provides that theoretical proof. Furthermore, this paper presents a method for performing the necessary variable selection by means of elastic net regression, and then estimating the propensity scores so as to obtain optimal estimates of average treatment effect. The proposed method is compared against two other recently introduced methods, outcome-adaptive lasso and covariate balancing propensity score. Extensive simulation analyses are employed to determine the circumstances under which each method appears most effective. We applied the proposed methods to examine the effect of pre-cardiac surgery coagulation indicator on mortality based on a linked dataset from a retrospective review of 1390 patient medical records at Jewish Hospital (Louisville, KY) with the Society of Thoracic Surgeons database. [ABSTRACT FROM AUTHOR]

Introduction:  The use of interventional radiology (IR) in the treatment of pediatric solid tumors has markedly increased over the last three decades. However, data on effectiveness of IR-techniques, such as embolization/ablation, are scarce. In this systematic review and meta-analysis, we examined the outcomes of IR-procedures in the treatment of solid tumors in children.Materials and Methods:  Using a defined search strategy, we searched for studies reporting the use of IR-techniques for pediatric solid tumors from 1980 to 2017. Reports with less than three patients, review, and opinion articles were excluded. The study was conducted under preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. We analyzed dichotomous and continuous variables by appropriate statistical methods.Results:  Of 567 articles screened, 21 papers met the inclusion criteria (12 retrospective, 7 prospective, and 2 randomized-control trials). Many of the analyzed papers described relatively small cohorts of patients. IR-guided procedures were mainly rescue procedures to treat primarily unresectable tumors, local recurrences, or metastases. Inclusion/exclusion criteria and success definition were not specified in most reports. Major side effects were documented in 17/286 (6%) infants, while minor side effects were self-limiting in most patients. Six studies had a comparison between tumor embolization (127 infants) to surgery or chemotherapy without IR-procedures (113 controls). The meta-analysis showed lower mortality (16 vs. 47%) and surgical time for resection (206 vs. 250 m), higher 2-year tumor-free survival (82 vs. 36%), and favorable histology in IR group (p < 0.001 for all).Conclusion:  IR-guided techniques are promising in the treatment of pediatric solid tumors. Further prospective (randomized) trials are needed to clarify efficacy. [ABSTRACT FROM AUTHOR]

Background: Physiologic data that is automatically collected during anesthesia is widely used for medical record keeping and clinical research. These data contain artifacts, which are not relevant in clinical care, but may influence research results. The aim of this study was to explore the effect of different methods of filtering and processing artifacts in anesthesiology data on study findings in order to demonstrate the importance of proper artifact filtering.Methods: The authors performed a systematic literature search to identify artifact filtering methods. Subsequently, these methods were applied to the data of anesthesia procedures with invasive blood pressure monitoring. Different hypotension measures were calculated (i.e., presence, duration, maximum deviation below threshold, and area under threshold) across different definitions (i.e., thresholds for mean arterial pressure of 50, 60, 65, 70 mmHg). These were then used to estimate the association with postoperative myocardial injury.Results: After screening 3,585 papers, the authors included 38 papers that reported artifact filtering methods. The authors applied eight of these methods to the data of 2,988 anesthesia procedures. The occurrence of hypotension (defined with a threshold of 50 mmHg) varied from 24% with a median filter of seven measurements to 55% without an artifact filtering method, and between 76 and 90% with a threshold of 65 mmHg. Standardized odds ratios for presence of hypotension ranged from 1.16 (95% CI, 1.07 to 1.26) to 1.24 (1.14 to 1.34) when hypotension was defined with a threshold of 50 mmHg. Similar variations in standardized odds ratios were found when applying methods to other hypotension measures and definitions.Conclusions: The method of artifact filtering can have substantial effects on estimates of hypotension prevalence. The effect on the association between intraoperative hypotension and postoperative myocardial injury was relatively small. Nevertheless, the authors recommend that researchers carefully consider artifacts handling and report the methodology used. [ABSTRACT FROM AUTHOR]

Background: We sought to determine whether subjective outcomes one or more years after antireflux surgery are affected by the operating surgeon.Methods: We reviewed records of patients who had antireflux surgery from June 2000 to June 2002 and mailed the patients a 19-item survey that focused on current medication use, postoperative symptom improvement, and satisfaction with surgery. We tested the significance of predictor variables using chi-squared and Fisher exact tests for categorical variables and analysis of variance for continuous variables.Results: We mailed the survey to 74 patients. Ninety-one percent of the operations were initially laparoscopic, with 5 (7%) subsequently converting to open. Ninety-five percent of patients were taking protein pump inhibitors (PPIs) preoperatively. Surgeons (n = 7) were divided into four groups, with the four surgeons who did two or fewer procedures in one group. Fifty-two of 74 patients (70%) responded to the survey (mean age, [SD] 44 [21] years, 37% male). The mean duration of followup was 2.1 [0.46] years. Thirty-eight percent of patients were taking medications for gastroesophageal reflux disease at the time of survey completion. It was found that the surgeon had an influence on patients' perceptions of the success of the surgery and whether having surgery was a good idea. We did not identify a statistically significant effect of the surgeon on preoperative symptom severity, postoperative ability to belch, dysphagia, medication use, and lifestyle.Conclusion: A patient's surgeon has an effect on satisfaction with antireflux surgery. Further research should clarify specific practices of the surgeon (patient selection, operative technique, followup) associated with best outcome. [ABSTRACT FROM AUTHOR]

Unlabelled: A strong link exists between gastroesophageal reflux disease (GERD) and airway diseases. Surgical therapy has been recommended as it is more effective than medical therapy in the short-term, but there is little data on the effectiveness of surgery long-term. We analyzed the long-term response of GERD-related airway disease after laparoscopic anti-reflux surgery (LARS).Methods: In 2004, we contacted 128 patients with airway symptoms and GERD who underwent laparoscopic antireflux surgery (LARS) between 12/1993 and 12/ 2002. At median follow-up of 53 months (19-110 mo) we studied the effects on symptoms, esophageal acid exposure, and medication use and we analyzed the data to determine predictors of successful resolution of airway symptoms.Results: Cough, hoarseness, wheezing, sore throat, and dyspnea improved in 65-75% of patients. Heartburn improved in 91% (105/116) of patients and regurgitation in 92% (90/98). The response rate for airway symptoms was the same in patients with and without heartburn. Almost every patient took proton pump inhibitors (PPIs) preoperatively (99%, 127/128) and 61% (n = 78) were taking double or triple dose. Postoperatively, 33% (n = 45) of patients were using daily antiacid therapy but no one was on double dose. The only factor that predicted a successful surgical outcome was the presence of abnormal reflux in the pharynx as determined by 24-hour pharyngeal pH monitoring. One hundred eleven (87%) patients rated their results as excellent (n = 78, 57%) or good (n = 33, 24%).Conclusion: LARS provides an effective and durable barrier to reflux, and in so doing improves GERD-related airway symptoms in approximately 70% of patients and improves typical GERD symptoms in approximately 90% of patients. Pharyngeal pH monitoring identifies those patients more likely to benefit from LARS, but better diagnostic tools are needed to improve the response of airway symptoms to that of typical esophageal symptoms. [ABSTRACT FROM AUTHOR]

Background: Concerns about the cost and convenience of postsurgical physical therapy (PT) have sparked interest in unsupervised, home-based rehabilitation. However, the effectiveness of unsupervised home exercise after primary TKA has not been previously evaluated.Questions/purposes: (1) Can unsupervised home exercise after surgery provide noninferior recovery of passive knee flexion compared with formal outpatient PT? (2) Does a web-based platform for home-based exercise provide an advantage compared with a printed PT manual?Methods: We conducted a randomized, noninferiority trial involving 290 patients (20% of the 1464 eligible patients who could be contacted) who underwent primary TKA from March 2016 to April 2018. We included patients > 18 years old who were undergoing primary, unilateral TKA and provided written consent. We excluded patients with preoperative knee flexion < 90°, patients considering surgical intervention in a hip or the contralateral knee, patients discharged to an extended care facility, and revision or conversion TKA. We randomized patients to one of three groups: outpatient PT, unsupervised home exercise using a web-based platform (web PT), or unsupervised home exercise using a printed paper manual (paper PT). We also implemented a "delayed recovery intervention" within the home exercise program, in which patients were obliged to begin outpatient PT if knee flexion was < 70° at 2 weeks or < 90° at 4 weeks. The primary outcome was change in knee flexion from preoperative baseline after 4 to 6 weeks and 6 months. Secondary outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), time back to activities of daily living, and time off narcotics. All analyses were intention to treat, and the noninferiority margin was 5% with maximum flexion as the outcome of interest for this parameter.Results: Adjusted differences in change in passive flexion for web PT +3° (95% confidence interval [CI], -1.2° to 6.4°) and paper PT +5° (95% CI, 0.99°-8.6°) were not inferior to outpatient PT based on a predefined 5° margin. Change in knee flexion from baseline was 0° for outpatient PT, -2° for web PT, and -1° for paper PT after 4 to 6 weeks and 8°, 8°, and 12° for the three groups, respectively, after 6 months. Additionally, there was no difference in the change in KOOS from baseline at 4 to 6 weeks or 6 months postoperatively as well as time back to work, driving, and walking without an assistive device.Conclusions: Unsupervised home exercise is an effective rehabilitation strategy after primary TKA and was noninferior to formal outpatient PT in selected patients. It is worthwhile to reconsider the current practice of automatically designating patients for outpatient PT after primary TKA, because appropriately selected patients with adequate clinical support can achieve similar results at home.Level Of Evidence: Level I, therapeutic study. [ABSTRACT FROM AUTHOR]

Background: Impaired physical function due to chemotherapy-induced peripheral neuropathy (CIPN) symptoms may lead to diminished quality of life. However, even with the knowledge of the effects of CIPN on physical function, clinicians infrequently assess and manage CIPN. Interventions that prioritize the early identification of CIPN to provide prompt treatment may reduce the impact of CIPN on physical function. The purpose of this paper is to compare self-reported physical function in individuals receiving neurotoxic chemotherapy between Electronic Symptom Assessment-Cancer (ESRA-C) intervention group (e.g., opportunity for symptom screening, self-care recommendations, communication coaching, and symptom tracking) and control group participants (i.e., electronic assessment alone). Secondary outcomes include pain intensity, sensory/motor CIPN, depression, fatigue, and insomnia.Methods: The data used in this paper are a subset of a randomized controlled trial that examined the impact of the ESRA-C intervention on symptom distress in individuals receiving cancer treatment. Since the interest in this analysis is on the effects of neurotoxic chemotherapy on physical function, subjects were included if they received platinum and/or taxane-based chemotherapy and completed the baseline and end-of-treatment measures. Participants completed standardized questionnaires of physical function, CIPN, fatigue, depression, pain intensity, and insomnia prior to treatment, 3-6 weeks after treatment initiation, and after the completion of treatment. Changes in mean scores are compared between groups using linear mixed models adjusting for age.Results: Intervention group participants reported significantly less reduction in physical functioning (baseline: 87.4/100; end-of-treatment: 84.5/100) relative to the control (baseline: 90.2/100; end-of-treatment: 81.8/100) (p = 0.011). For secondary measures, significantly less depression (p = 0.005) was observed in the intervention group as compared to the control, but otherwise, there were no between-group differences. Among participants who received high cumulative doses of neurotoxic chemotherapy, the intervention group reported significantly less severe sensory (p = 0.007) and motor CIPN (p = 0.039) relative to the control.Conclusion: Use of the ESRA-C intervention led to less reduction in physical function in comparison to the control in individuals receiving neurotoxic chemotherapy. Further research is needed to confirm our findings and to identify how electronic symptom assessment technology may mediate physical function preservation.Trial Registration: ClinicalTrials.Gov NCT00852852 . Registered 27 February 2009. [ABSTRACT FROM AUTHOR]

Background: Melanoma incidence has quadrupled since 1970 and melanoma is now the second most common cancer in individuals under 50. Targeted immunotherapies for melanoma now potentially enable long-term remission even in advanced melanoma, but these melanoma survivors require ongoing surveillance, with implications for NHS resources and significant social and psychological consequences for patients. Total skin self-examination (TSSE) can detect recurrence earlier and improve clinical outcomes but is underperformed in the UK. To support survivors, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) intervention was developed to prompt and improve TSSE performance, with subsequent reporting of concerns and submission of skin photos to a Dermatology Nurse Practitioner (DNP). ASICA was delivered as a randomized pilot trial.Methods: This paper reports on process evaluation. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using Microsoft Excel and SPSS. We explored which participants used ASICA, and how frequently, to report any skin concerns. We also determined how the interactions had worked in terms of quality of skin photographs submitted, clinical assessments made by the DNP, and the assessments and decisions made for each concern. Finally, we explored significant events occurring during the trial. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using SPSS. A semi-structured interview was undertaken with the DNP to gain perspective on the range of concerns presented and how they were resolved.Results: Of 121 recruited melanoma patients receiving ASICA for 12 months, 69 participants submitted a total of 123 reports detailing 189 separate skin-related concerns and including 188 skin photographs. Where participants fully complied with follow-up by the DNP, concerns were usually resolved remotely, but 19 (10.1%) were seen at a secondary care clinic and 14 (7.4%) referred to their GP. 49 (25.9%) of concerns were not completely resolved due to partial non-compliance with DNP follow-up.Conclusion: Melanoma patients randomized to the ASICA intervention were able to report skin-related concerns that could be resolved remotely through interaction with a DNP. Feasibility issues highlighted by ASICA will support further development and optimization of this digital tool.Trial Registration: Clinical Trials.gov , NCT03328247 . Registered on 1 November 2017. [ABSTRACT FROM AUTHOR]

Purpose: Age, sex, and type of fracture have traditionally been described as prognostic factors for proximal humeral fractures (PHFs). Some non-medical patient-related factors may play a role in the outcome. This paper evaluates the association of comorbidities and socioeconomic factors with clinical outcomes for PHF.Methods: A total of 217 patients with PHF were evaluated according to Neer's classification with X-ray. Comorbidities were assessed through the Charlson comorbidity index and, non-medical patient-related factors were determined with a 52-item questionnaire concerning personal behaviors such as social activities, family support, economic solvency, and leisure-time activities. The clinical outcome was assessed with the Constant-Murley Score (CMS), with a minimum 1-year follow-up. The minimal clinically relevant difference for the CMS was set at 10 points. A multivariable analysis was performed to adjust for comorbidities and non-medical patient-related factors, such as age, sex, fracture classification, and treatment.Results: One hundred and eighty-three patients completed the initial research protocol, while 126 of them completed the 1-year follow-up. The mean age was 71.6 years (SD ± 13.3), and 79.3% of the patients were women. In the bivariable analysis, age and comorbidities were correlated with the CMS (correlation coefficient: - 0.34 [- 0.49, 0.17] and 0.35 [0.18, 0.50], respectively), as well as non-medical patient-related factors and the fracture pattern (p value ANOVA < 0.001). In the multivariable regression model, the effects of considering oneself socially active, without economic problems, and self-sufficient were associated with a higher CMS than the effect of the fracture pattern (beta coefficient: 11.69 [6.09-17.30], 15.54 [8.32-22.75], and 10.61 [3.34-17.88], respectively).Conclusion: Socioeconomic status had a higher impact on functional outcomes than fracture pattern in patients with PHF. [ABSTRACT FROM AUTHOR]

Objective: To compare clinical and imaging findings between extreme lateral lumbar interbody fusion (XLIF) and posterior fusion (PF) via meta-analysis for the treatment of lumbar degenerative diseases.Methods: English papers reporting clinical and imaging findings for the treatment of lumbar degenerative diseases with XLIF and PF published electronically in the PubMed, Embase, Cochrane Library, and Web of Science databases from January 2006 to August 2019 were retrieved. Two authors independently extracted data and evaluated the quality of the included literature. Meta-analysis of outcome measures was performed using Stata 14 and RevMan 5.3 software.Results: This meta-analysis included 744 patients from nine studies, two of which were prospective studies, while the others were retrospective studies. The quality of each study was determined to be high. The meta-analysis showed no significant differences in the operative time, length of hospital stay, clinical effectiveness, and improvement in postoperative global sagittal alignment between two approaches (P > 0.05). However, XLIF was significantly better than PF in reducing intraoperative blood loss and recovery of local sagittal alignment (P < 0.05). Moreover, the high incidence of postoperative complications were detected in XLIF group (P < 0.05).Conclusions: Both surgical approaches have equally promising clinical effectiveness for the treatment of lumbar degenerative diseases. Although XLIF can reduce intraoperative blood loss and obtain better postoperative local sagittal alignment than PF, the high incidence of postoperative complications should prompt us to consider why XLIF procedure is still being offered to our patients and how we can reduce these complications. In addition, any conclusions should be taken with caution because of the mix of prospective and retrospective studies, and the high heterogeneity and bias. [ABSTRACT FROM AUTHOR]

Clinical relevance: Home-based videogame treatments are increasingly popular for amblyopia treatment. However, at-home treatments tend to be done in short sessions and with frequent disruptions, which may reduce the effectiveness of binocular visual stimulation. These treatment adherence patterns need to be accounted for when considering dose-response relationships and treatment effectiveness.Background: Home-based videogame treatments are increasingly being used for various sensory conditions, including amblyopia ('lazy eye'), but treatment adherence continues to limit success. To examine detailed behavioural patterns associated with home-based videogame treatment, we analysed in detail the videogame adherence data from the Binocular tReatment of Amblyopia with VideOgames (BRAVO) clinical trial (ACTRN12613001004752).Methods: Children (7-12 years), teenagers (13-17 years) and adults (≥ 18 years) with unilateral amblyopia were loaned iPod Touch devices with either an active treatment or placebo videogame and instructed to play for a total of 1-2 hours/day for six weeks at home. Objectively-recorded adherence data from device software were used to analyse adherence patterns such as session length, daily distribution of gameplay, use of the pause function, and differences between age groups. Objectively-recorded adherence was also compared to subjectively-reported adherence from paper-based diaries.Results: One hundred and five of the 115 randomised participants completed six weeks of videogame training. Average adherence was 65% (SD 37%) of the minimum hours prescribed. Game training was generally performed in short sessions (mean 21.5, SD 11.2 minutes), mostly in the evening, with frequent pauses (median every 4.1 minutes, IQR 6.1). Children played in significantly shorter sessions and paused more frequently than older age groups (p < 0.0001). Participants tended to over-report adherence in subjective diaries compared to objectively-recorded gameplay time.Conclusion: Adherence to home-based videogame treatment was characterised by short sessions interspersed with frequent pauses, suggesting regular disengagement. This complicates dose-response calculations and may interfere with the effectiveness of treatments like binocular treatments for amblyopia, which require sustained visual stimulation. [ABSTRACT FROM AUTHOR]

Background: Though home-based human immunodeficiency virus (HIV) counseling and testing (HBHCT) is implemented in many sub-Saharan African countries as part of their HIV programs, linkage to HIV care remains a challenge. The purpose of this study is to test an intervention to enhance linkage to HIV care and improve HIV viral suppression among individuals testing HIV positive during HBHCT in rural Uganda.Methods: The PATH (Providing Access To HIV Care)/Ekkubo Study is a cluster-randomized controlled trial which compares the efficacy of an enhanced linkage to HIV care intervention vs. standard-of-care (paper-based referrals) at achieving individual and population-level HIV viral suppression, and intermediate outcomes of linkage to care, receipt of opportunistic infection prophylaxis, and antiretroviral therapy initiation following HBHCT. Approximately 600 men and women aged 18-59 who test HIV positive during district-wide HBHCT in rural Uganda will be enrolled in this study. Villages (clusters) are pair matched by population size and then randomly assigned to the intervention or standard-of-care arm. Study teams visit households and participants complete a baseline questionnaire, receive HIV counseling and testing, and have blood drawn for HIV viral load and CD4 testing. At baseline, standard-of-care arm participants receive referrals to HIV care including a paper-based referral and then receive their CD4 results via home visit 2 weeks later. Intervention arm participants receive an intervention counseling session at baseline, up to three follow-up counseling sessions at home, and a booster session at the HIV clinic if they present for care. These sessions each last approximately 30 min and consist of counseling to help clients: identify and reduce barriers to HIV care engagement, disclose their HIV status, identify a treatment supporter, and overcome HIV-related stigma through links to social support resources in the community. Participants in both arms complete interviewer-administered questionnaires at six and 12 months follow-up, HIV viral load and CD4 testing at 12 months follow-up, and allow access to their medical records.Discussion: The findings of this study can inform the integration of a potentially cost-effective approach to improving rates of linkage to care and HIV viral suppression in HBHCT. If effective, this intervention can improve treatment outcomes, reduce mortality, and through its effect on individual and population-level HIV viral load, and decrease HIV incidence.Trial Registration: NCT02545673. [ABSTRACT FROM AUTHOR]

Objective: To determine the effects on weight loss of three abbreviated behavioral weight loss interventions with and without coaching and mobile technology.Methods: A randomized controlled efficacy study of three 6-month weight loss treatments was conducted in 96 adults with obesity: 1) self-guided (SELF), 2) standard (STND), or 3) technology-supported (TECH). STND and TECH received eight in-person group treatment sessions. SELF and STND used paper diaries to self-monitor diet, activity, and weight; TECH used a smartphone application with social networking features and wireless accelerometer.Results: Weight loss was greater for TECH and STND than SELF at 6 months (-5.7 kg [95% confidence interval: -7.2 to -4.1] vs. -2.7 kg [95% confidence interval: -5.1 to -0.3], P < 0.05) but not 12 months. TECH and STND did not differ except that more STND (59%) than TECH (34%) achieved ≥ 5% weight loss at 6 months (P < 0.05). Self-monitoring adherence was greater in TECH than STND (P < 0.001), greater in both interventions than SELF (P < 0.001), and covaried with weight loss (r(84) = 0.36-0.51, P < 0.001).Conclusions: Abbreviated behavioral counseling can produce clinically meaningful weight loss regardless of whether self-monitoring is performed on paper or smartphone, but long-term superiority over standard of care self-guided treatment is challenging to maintain. [ABSTRACT FROM AUTHOR]

Background: Dissociative seizures (DSs), also called psychogenic non-epileptic seizures, are a distressing and disabling problem for many patients in neurological settings with high and often unnecessary economic costs. The COgnitive behavioural therapy versus standardised medical care for adults with Dissociative non-Epileptic Seizures (CODES) trial is an evaluation of a specifically tailored psychological intervention with the aims of reducing seizure frequency and severity and improving psychological well-being in adults with DS. The aim of this paper is to report in detail the quantitative and economic analysis plan for the CODES trial, as agreed by the trial steering committee.Methods: The CODES trial is a multicentre, pragmatic, parallel group, randomised controlled trial performed to evaluate the clinical effectiveness and cost-effectiveness of 13 sessions of cognitive behavioural therapy (CBT) plus standardised medical care (SMC) compared with SMC alone for adult outpatients with DS.Discussion: The objectives and design of the trial are summarised, and the aims and procedures of the planned analyses are illustrated. The proposed analysis plan addresses statistical considerations such as maintaining blinding, monitoring adherence with the protocol, describing aspects of treatment and dealing with missing data. The formal analysis approach for the primary and secondary outcomes is described, as are the descriptive statistics that will be reported. This paper provides transparency to the planned inferential analyses for the CODES trial prior to the extraction of outcome data. It also provides an update to the previously published trial protocol and guidance to those conducting similar trials.Trial Registration: ISRCTN registry ISRCTN05681227 (registered on 5 March 2014); ClinicalTrials.gov NCT02325544 (registered on 15 December 2014). [ABSTRACT FROM AUTHOR]

Background: Placebo medications, by definition, are composed of inactive ingredients that have no physiological effect on symptoms. Nonetheless, administration of placebo in randomized controlled trials (RCTs) and in clinical settings has been demonstrated to have significant impact on many physical and psychological complaints. Until recently, conventional wisdom has suggested that patients must believe that placebo pills actually contain (or, at least, might possibly contain) active medication in order to elicit a response to placebo. However, several recent RCTs, including patients with irritable bowel syndrome (IBS), chronic low back pain, and episodic migraine, have demonstrated that individuals receiving open-label placebo (OLP) can still experience symptomatic improvement and benefit from honestly described placebo treatment.Methods and Design: This paper describes an innovative multidisciplinary trial design (n = 280) that attempts to replicate and expand upon an earlier IBS OLP study. The current study will compare OLP to double-blind placebo (DBP) administration which is made possible by including a nested, double-blind RCT comparing DBP and peppermint oil. The study also examines possible genetic and psychological predictors of OLP and seeks to better understand participants' experiences with OLP and DBP through a series of extensive interviews with a randomly selected subgroup.Discussion: OLP treatment is a novel strategy for ethically harnessing placebo effects. It has potential to re-frame theories of placebo and to influence how physicians can optimize watch-and-wait strategies for common, subjective symptoms. The current study aims to dramatically expand what we know about OLP by comparing, for the first time, OLP and DBP administration. Adopting a unique, multidisciplinary approach, the study also explores genetic, psychological and experiential dimensions of OLP. The paper ends with an extensive discussion of the "culture" of the trial as well as potential mechanisms of OLP and ethical implications.Trial Registration: ClinicalTrials.gov, identifier: NCT02802241 . Registered on 14 June 2016. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of viscosupplementation with single-injection hylan G-F20 (Synvisc-One) in knee osteoarthritis (OA), during routine clinical care, in a 52 week observational study.Research Design and Methods: The LOBRAS study involved a 1 year long, multi-center, quasi-experimental, repeated measures, observational study. Consenting patients in Australia fulfilling inclusion/exclusion criteria under the care of a medical specialist in routine clinical practice were enrolled. Prior to, and for 52 weeks following, intra-articular single-injection hylan G-F20, patients were repeatedly evaluated using the WOMAC NRS4.1 Index and the SF-36 questionnaire. The WOMAC NRS4.1 was administered by mobile phone (with paper back-up), and the SF-36 was administered on paper. Patients were monitored for adverse events.Main Outcome Measures: Western Ontario and McMaster (WOMAC) OA Index, and the Short Form 36 questionnaire (SF-36 v2).Results: A total of 131 patients with knee OA were enrolled, of whom 119 provided both pre- and post-intervention WOMAC data. Statistically significant improvements (with a maximum of p ≤ .025) from baseline to Week 12, Month 6 and Week 52 were detected, by intention-to-treat (ITT) and per-protocol (PP) analyses, in WOMAC Pain, Stiffness, Function, PGA, and Total Score, SF-36 PCS, and WOMAC-derived HUI3. Adverse event (AE) monitoring detected treatment-related AEs in 5.3% of patients.Conclusions: The effectiveness of single-injection hylan G-F20 in routine clinical care is supported by the detection of statistically significant, clinically important improvements in WOMAC Pain, Stiffness, Function, Total, and PGA outcomes, and statistically significant improvements in SF-36 PCS and WOMAC-derived HUI3 outcomes at multiple time points. Limitations of this study include lack of a control group or blinding. No predictive indicators of the response to treatment were identified. In general single-injection hylan G-F20 was well tolerated with very few patients experiencing any treatment-related adverse events. Collectively, these observations attest to the effectiveness of single-injection hylan G-F20 and complement previous observations in routine clinical care. [ABSTRACT FROM AUTHOR]

Background: Despite strong evidence giving guidance for effective fall prevention interventions in community-residing older people, there is currently no clear model for engaging general medical practitioners in fall prevention and routine use of allied health professionals in fall prevention has been slow, limiting widespread dissemination. This protocol paper outlines an implementation-effectiveness study of the Integrated Solutions for Sustainable Fall Prevention (iSOLVE) intervention which has developed integrated processes and pathways to identify older people at risk of falls and engage a whole of primary care approach to fall prevention.Methods/design: This protocol paper presents the iSOLVE implementation processes and change strategies and outlines the study design of a blended type 2 hybrid design. The study consists of a two-arm cluster randomized controlled trial in 28 general practices and recruiting 560 patients in Sydney, Australia, to evaluate effectiveness of the iSOLVE intervention in changing general practitioner fall management practices and reducing patient falls and the cost effectiveness from a healthcare funder perspective. Secondary outcomes include change in medications known to increase fall risk. We will simultaneously conduct a multi-methodology evaluation to investigate the workability and utility of the implementation intervention. The implementation evaluation includes in-depth interviews and surveys with general practitioners and allied health professionals to explore acceptability and uptake of the intervention, the coherence of the proposed changes for those in the work setting, and how to facilitate the collective action needed to implement changes in practice; social network mapping will explore professional relationships and influences on referral patterns; and, a survey of GPs in the geographical intervention zone will test diffusion of evidence-based fall prevention practices. The project works in partnership with a primary care health network, state fall prevention leaders, and a community of practice of fall prevention advocates.Discussion: The design is aimed at providing clear direction for sustainability and informing decisions about generalization of the iSOLVE intervention processes and change strategies. While challenges exist in hybrid designs, there is a potential for significant outcomes as the iSOLVE pathways project brings together practice and research to collectively solve a major national problem with implications for policy service delivery.Trial Registration: Australian New Zealand Clinial Trials Registry ACTRN12615000401550. [ABSTRACT FROM AUTHOR]

Background: The efficacy of many cognitive behavioral component interventions has not been examined, with worry outcome monitoring among them.Methods: To address this issue, 51 participants with clinical levels of generalized anxiety disorder were randomly assigned to a treatment or control condition for 10 days. The treatment condition consisted of a brief ecological momentary intervention termed the Worry Outcome Journal (WOJ). WOJ participants recorded worries and tracked their outcomes, rating worry distress, interference, and expected outcome probabilities. Thought log (TL) control participants completed a record of their everyday thoughts and rated associated distress. All participants made four entries on paper each day when randomly prompted by text message. They then entered their paper contents online each night. After 30 days they reviewed their contents electronically and completed follow-up measures.Results: Primary results revealed significant reductions in worry for WOJ users compared to TL users at postintervention. A marginally significant difference was found at 20-day follow-up and treatment gains were maintained. Secondary analyses showed no harmful increases in worry beliefs for WOJ users, as well as preliminary evidence for decreases in beliefs about the uncontrollability of thoughts in both groups.Conclusion: The WOJ may be a viable therapist-independent treatment for reducing worry, even after only 10 days of use. [ABSTRACT FROM AUTHOR]

Background: Psychotherapy for borderline personality disorder is often extensive and resource-intensive. Mentalisation-based therapy is a psychodynamically oriented treatment option for borderline personality disorder, which includes a case formulation, psychoeducation, and group and individual therapy. The evidence on short-term compared with long-term mentalisation-based therapy is currently unknown.Methods/design: The Short-Term MBT Project (MBT-RCT) is a single-centre, parallel-group, investigator-initiated, randomised clinical superiority trial in which short-term (20 weeks) will be compared with long-term (14 months) mentalisation-based therapy for outpatients with subthreshold or diagnosed borderline personality disorder. Outcome assessors, data managers, the data safety and monitoring committee, statisticians, and decision-makers will be blinded to treatment allocation. Participants will be assessed before randomisation and at 8, 16, and 24 months after randomisation. The primary outcome will be the severity of borderline symptomatology assessed with the Zanarini Rating Scale for Borderline Personality Disorder. Secondary outcomes will be functional impairment (Work and Social Adjustment Scale), quality of life (Short-Form Health Survey 36-mental component), global functioning (Global Assessment of Functioning), and proportion of participants with severe self-harm. In this paper, we present a detailed statistical analysis plan including a comprehensive explanation of the planned statistical analyses, methods to handle missing data, and assessments of the underlying statistical assumptions. Final statistical analyses will be conducted independently by two statisticians following the present plan.Discussion: We have developed this statistical analysis plan before unblinding of the trial results in line with the Declaration of Helsinki and the International Conference on Harmonization of Good Clinical Practice Guidelines, which should increase the validity of the MBT-RCT trial by mitigation of analysis bias.Trial Registration: ClinicalTrials.gov NCT03677037 . Registered on 19 September 2018. [ABSTRACT FROM AUTHOR]

Background: Although tenotomy and tenodesis are frequently used for long head of the biceps tendon lesions, controversies remain as to which technique is superior regarding pain, functionality, complications, and cosmetic appearance.Questions/purposes: (1) For long head of biceps tendon lesions, does tenotomy or tenodesis result in greater improvements in VAS score for pain? (2) Which approach has superior results when evaluating function outcome (Constant) scores? (3) Does tenotomy or tenodesis have fewer complications? (4) Does tenotomy or tenodesis result in better cosmesis (Popeye sign)?Methods: A systematic review was performed in the Cochrane Library, Embase, PubMed, and Literatura Latino Americana e do Caribe em Ciências da Saúde (LILACS) using the keywords "long head of the biceps tendon," "biceps tenodesis," and "tenotomy." We completed the search in June 2020. The inclusion criteria were randomized controlled trials and quasirandomized controlled trials that investigated tenodesis and tenotomy with no language restriction and evaluation of adult patients who presented with a long head of the biceps tendon lesion, associated with other lesions or not, without previous shoulder surgeries and who had no response to nonoperative treatment. The initial search yielded 239 studies, 40 of which were duplicates. We assessed the titles and abstracts of 199 articles and excluded all studies that were not randomized controlled trials (literature reviews) or that compared different techniques. We assessed the full text of 14 articles and excluded the ones that were protocols and cohort studies. We evaluated the risk of bias using the Cochrane Collaboration tool. We included eight studies in this systematic review and meta-analysis, with a total of 615 participants, 306 of whom were treated with tenotomy and 309 with tenodesis. The median duration of follow-up was 2 years. Overall, the included studies had a low risk of bias. The complications evaluated were adhesive capsulitis, biceps brachii tear, cramps, and a subsequent second surgical procedure. We used a random model in this meta-analysis so that we could generalize the results beyond the included studies. In this study, we only reported differences between the groups if they were both statistically valid and larger than the minimum clinically important difference (MCID).Results: Comparing tenotomy and tenodesis, we observed no difference between the groups regarding pain in the long term (mean difference 0.25 [95% confidence interval -0.29 to 0.80]; p = 0.36). There was no difference in Constant score in the long-term (mean difference -1.45 [95% CI -2.96 to 0.06]; p = 0.06). There were no differences when evaluating for major complications (odds ratio 1.37 [95% CI 0.29 to 6.56]; p = 0.70). There were not enough papers evaluating adhesive capsulitis, cramping, and risk of revision surgery. Popeye sign was more frequent in the tenotomy group than in the tenodesis group (OR 4.70 [95% CI 2.71 to 8.17]; p < 0.001).Conclusion: This systematic review demonstrated that tenotomy and tenodesis offer satisfactory treatment for long head of the biceps tendon lesions. In terms of pain improvement and Constant score, there was no difference between the techniques, but patients undergoing tenotomy have worse cosmetic results. Therefore, surgeons should choose the technique based on their skills and the patient's expectations of surgery, such as cosmesis and time to recovery. More studies are needed to evaluate complications such as adhesive capsulitis and cramping, as well as to compare duration of surgery and recovery time for each technique.Level Of Evidence: Level I, therapeutic study. [ABSTRACT FROM AUTHOR]

Aim: To evaluate an innovative paediatric neurorehabilitation model in relation to improving quality of neurorehabilitation and reducing length of stay (LOS) for children with acquired brain injury.Method: A process evaluation approach was conducted in line with Medical Research Council evaluation of complex interventions guidance. Analysis was conducted on routinely collected patient data from 2017 to 2018, including LOS and family feedback. Descriptive and inferential statistics were used for quantitative analysis and qualitative data was analysed thematically.Results: Outcomes for 70 children (0-16y, median age 5y, IQR 1-11y, 46 males, 24 females) referred to the service indicated improved function and reduced complexity of need. The mean LOS was 10.6 days compared to baseline mean LOS of 41 days (2011-2012). High satisfaction from the families was recorded; however, ongoing needs and service gaps regarding long-term support were identified.Interpretation: This service model is effective in delivering quality paediatric neurorehabilitation, demonstrating a sustained impact on LOS, and positive patient outcome data and family feedback for this group of patients. What this paper adds Investment in early intensive neurorehabilitation and supported discharge impacts length of stay (LOS) for children with acquired brain injury. Early intensive neurorehabilitation and supported discharge is effective. This is demonstrated by a sustained reduction in LOS, positive patient outcomes, and family feedback. [ABSTRACT FROM AUTHOR]

Conventionally, pediatric patients with major burns need frozen cadaveric allografts to save their lives. However, these allografts are insufficient in many burn units because of cultural and local governmental laws in China. This paper reported 22 pediatric patients with major burns who received fresh scalp allografts from their parents, siblings, or relatives from January 2011 to December 2017. These 22 pediatric patients sustained deep partial-thickness to full-thickness burns involving 40% total body surface area (TBSA) on average. Wounds were covered with fresh scalp allografts alone or with postage stamp autografts and fresh scalp allografts post excision. Data were collected from medical files of the treated patients, including sex, age, etiology of burn injury, abbreviated burn severity index (ABSI), and TBSA. Postoperative variables included early survival rate of skin grafts, mean time to rejection, length of hospital stay (LHS), healing time of donor sites, and follow-up complications of donors. The 1-year survival rate of the 22 pediatric patients included into the study was 100%. The early survival rate of the scalp allografts was similar to the autografts. The mean time to rejection was 15.5 ± 3.60 days. The average LHS was 58 days. All donor sites healed within 7.6 days on average, without scar formation, alopecia areata, or folliculitis. Following up data of the donors revealed a full psychological sense of accomplishment and no regrets of donating the scalp to save the burned children. Therefore, the use of fresh scalp allografts is a feasible alternative to save pediatric patients with major burns when frozen allografts are unavailable. [ABSTRACT FROM AUTHOR]

Background: Core outcome sets (COS) help to minimise bias in trials and facilitate evidence synthesis. Delphi surveys are increasingly being used as part of a wider process to reach consensus about what outcomes should be included in a COS. Qualitative research can be used to inform the development of Delphi surveys. This is an advance in the field of COS development and one which is potentially valuable; however, little guidance exists for COS developers on how best to use qualitative methods and what the challenges are. This paper aims to provide early guidance on the potential role and contribution of qualitative research in this area. We hope the ideas we present will be challenged, critiqued and built upon by others exploring the role of qualitative research in COS development. This paper draws upon the experiences of using qualitative methods in the pre-Delphi stage of the development of three different COS. Using these studies as examples, we identify some of the ways that qualitative research might contribute to COS development, the challenges in using such methods and areas where future research is required.Results: Qualitative research can help to identify what outcomes are important to stakeholders; facilitate understanding of why some outcomes may be more important than others, determine the scope of outcomes; identify appropriate language for use in the Delphi survey and inform comparisons between stakeholder data and other sources, such as systematic reviews. Developers need to consider a number of methodological points when using qualitative research: specifically, which stakeholders to involve, how to sample participants, which data collection methods are most appropriate, how to consider outcomes with stakeholders and how to analyse these data. A number of areas for future research are identified.Conclusions: Qualitative research has the potential to increase the research community's confidence in COS, although this will be dependent upon using rigorous and appropriate methodology. We have begun to identify some issues for COS developers to consider in using qualitative methods to inform the development of Delphi surveys in this article. [ABSTRACT FROM AUTHOR]

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor-in-Chief. The editorial board has raised concerns regarding the integrity of this paper and remaining in the public domain. It is by far the largest trial of corticosteroids for this indication, overwhelming other similar trials in Cochrane and other systematic reviews and is likely leading to widespread prescription of this drug, which may have serious side effects on fetal brain development. If the data is unreliable, women and babies are being harmed. As we have not received the original dataset or a satisfactory response from Dr Nada for an explanation regarding our concerns after giving them a month to respond, we have decided to retract this paper. [ABSTRACT FROM AUTHOR]

Background: E-mental health is a promising medium to keep mental health affordable and accessible. For consumers with severe mental illness the evidence of the effectiveness of e-health is limited. A number of difficulties and barriers have to be addressed concerning e-health for consumers with severe mental illness. One possible solution might be to blend e-health with face-to-face delivery of a recovery-oriented treatment, like the Illness Management & Recovery (IMR) programme. This paper describes the development of an e-health application for the IMR programme and the design of an early clustered randomized controlled trial.Method/design: We developed the e-IMR intervention according to the six-step protocol of Intervention Mapping. Consumers joined the development group to address important and relevant issues for the target group. Decisions during the six-step development process were based on qualitative evaluations of the Illness Management & Recovery programme, structured interviews, discussion in the development group, and literature reviews on qualitative papers concerning consumers with severe mental illness, theoretical models, behavioural change techniques, and telemedicine for consumers with severe mental illness. The aim of the e-IMR intervention is to help consumers with severe mental illness to involve others, manage achieving goals, and prevent relapse. The e-IMR intervention consists of face-to-face delivery of the Illness Management & Recovery programme and an e-health application containing peer-testimonials on videos, follow up on goals and coping strategies, monitoring symptoms, solving problems, and communication opportunities. We designed an early cluster randomized controlled trial that will evaluate the e-IMR intervention. In the control condition the Illness Management & Recovery programme is provided. The main effect-study parameters are: illness management, recovery, psychiatric symptoms severity, self-management, quality of life, and general health. The process of the IMR program will be evaluated on fidelity and feasibility in semi-structured interviews with participants and trainers.Discussion: Intervention Mapping provided a systematic procedure for the development of this e-health intervention for consumers with severe mental illness and the preparation of an early randomized controlled trial.Trial Registration: The trial is registered in the Dutch Trial Register: NTR4772 . [ABSTRACT FROM AUTHOR]

Purpose: Postmicturition dribbling (PMD) is a stressful symptom in middle-aged men characterized by urinary leakage after the completion of normal voiding. Appropriate treatments have not yet been introduced. This study assessed the efficacy of treatment of PMD with 75 mg udenafil daily.Materials and Methods: The study included 138 men with regular sexual lifestyles. The Hallym PMD questionnaire (HPMDQ) was used to assess PMD symptoms. After all basic examinations, patients were randomly assigned to either udenafil or placebo. Patients completed the surveys, uroflowmetry (UFM), a bladder scan, and the paper test during the follow-up visit.Results: The mean age of the patients was 57.6 years. PMD with one of every three urinations was experienced by 59 patients (42.8%), whereas 45 patients (32.6%) experienced PMD with two of every three urinations. PMD with every urination was experienced by 34 patients (24.6%). More than half of the patients (89 patients, 65.4%) indicated that persistent PMD symptoms would likely result in moderate to severe discomfort in their daily activities. As time passed, the udenafil group showed significant improvement in PMD symptoms (p = 0.001).Conclusion: Udenafil 75 mg once daily can be an effective treatment for patients with PMD symptoms. [ABSTRACT FROM AUTHOR]

There is a dearth of robust methods to estimate the causal effects of multiple treatments when the outcome is binary. This paper uses two unique sets of simulations to propose and evaluate the use of Bayesian additive regression trees in such settings. First, we compare Bayesian additive regression trees to several approaches that have been proposed for continuous outcomes, including inverse probability of treatment weighting, targeted maximum likelihood estimator, vector matching, and regression adjustment. Results suggest that under conditions of non-linearity and non-additivity of both the treatment assignment and outcome generating mechanisms, Bayesian additive regression trees, targeted maximum likelihood estimator, and inverse probability of treatment weighting using generalized boosted models provide better bias reduction and smaller root mean squared error. Bayesian additive regression trees and targeted maximum likelihood estimator provide more consistent 95% confidence interval coverage and better large-sample convergence property. Second, we supply Bayesian additive regression trees with a strategy to identify a common support region for retaining inferential units and for avoiding extrapolating over areas of the covariate space where common support does not exist. Bayesian additive regression trees retain more inferential units than the generalized propensity score-based strategy, and shows lower bias, compared to targeted maximum likelihood estimator or generalized boosted model, in a variety of scenarios differing by the degree of covariate overlap. A case study examining the effects of three surgical approaches for non-small cell lung cancer demonstrates the methods. [ABSTRACT FROM AUTHOR]

Background: As the novel SARS-CoV-2 pandemic occurred, no specific treatment was yet available. Inflammatory response secondary to viral infection might be the driver of severe diseases. We report the safety and efficacy (in terms of overall survival and hospital discharge) of the anti-IL6 tocilizumab (TCZ) in subjects with COVID-19.Methods: This retrospective, single-center analysis included all the patients consecutively admitted to our Hospital with severe or critical COVID-19 who started TCZ treatment from March 13th to April 03rd, 2020. A 1:2 matching to patients not treated with TCZ was performed according to age, sex, severity of disease, P/F, Charlson Comorbidity Index and length of time between symptoms onset and hospital admittance. Descriptive statistics and non-parametric tests to compare the groups were applied. Kaplan Meier probability curves and Cox regression models for survival, hospital discharge and orotracheal intubation were used.Results: Seventy-four patients treated with TCZ were matched with 148 matched controls. They were mainly males (81.5%), Caucasian (82.0%) and with a median age of 59 years. The majority (69.8%) showed critical stage COVID-19 disease. TCZ use was associated with a better overall survival (HR 0.499 [95% CI 0.262-0.952], p = 0.035) compared to controls but with a longer hospital stay (HR 1.658 [95% CI 1.088-2.524], p = 0.019) mainly due to biochemical, respiratory and infectious adverse events.Discussion: TCZ use resulted potentially effective on COVID-19 in terms of overall survival. Caution is warranted given the potential occurrence of adverse events.Financial Support: Some of the tocilizumab doses used in the subjects included in this analysis were provided by the "Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia" (EudraCT Number: 2020-001110-38) supported by the Italian National Agency for Drugs (AIFA). No specific funding support was planned for study design, data collection and analysis and manuscript writing of this paper. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of nutrition education program on hemodialysis patients' quality of life (QoL) and serum electrolytes levels.Methods: This study was a randomized controlled trial in which 94 eligible hemodialysis patients were randomly assigned to intervention (n = 48) and control (n = 46) groups. In the intervention group, the patients were trained in healthy nutrition for four weeks. After two months, samples of both groups completed the Kidney Disease Quality of Life Instrument (KDQOL) and Na, K, P, Ca and Mg levels were also measured and compared.Results: There were no significant differences in QoL scores and electrolytes between the two groups before intervention (p > 0.05). After intervention the QoL scores in the intervention group were significantly higher than in the control group (p < 0.05). However, after intervention the levels of Na, K, P and Mg in the intervention group were significantly lower than in the control group (p < 0.05). Calcium level was not significantly different between the two groups after intervention (p = 0.16).Conclusion: The results showed that e-learning is effective in improving the QoL and serum electrolytes of hemodialysis patients.Practice Implications: This paper could serve as support for clinical healthcare professionals to improve patient knowledge and QoL through virtual education methods. [ABSTRACT FROM AUTHOR]

Background: Previous research has shown an association between burnout and low emotional competence (EC), defined as the ability to adequately regulate the intensity and expression of emotions. EC might also play a maintaining role in depression. The current paper aimed at studying the effect of improved EC on the course of burnout and depression.Methods: 113 psychiatric inpatients completed a set of standardized self-report questionnaires at intake, discharge and three months after treatment, assessing EC, burnout, and depression. Multi-level analyses investigated the effect of improved EC on burnout and depression.Results: Improved EC including a better emotion regulation during treatment predicted favourable treatment outcomes regarding burnout and depression symptoms.Limitations: The present results should be considered in light of some methodological limitations. Most importantly, the patient sample consists of patients of one inpatient ward and is therefore not representative of all burnout patients.Conclusions: This study supports EC as a putative mechanism of change in the multimodal treatment of inpatients with a stress-related depressive disorder and burnout. Clinical and research consequences of the findings will be discussed. [ABSTRACT FROM AUTHOR]

Constructing causal inference methods to handle longitudinal data in observational studies is of high interest. In an observational setting, treatment assignment at each clinical visit follows a decision strategy where the treating clinician selects treatment based on current and past clinical measurements as well as treatment histories. These time-dependent structures, coupled with inherent correlations between and within each visit, add on to the data complexity. Despite recent interest in Bayesian causal methods, only a limited literature has explored approaches to handle longitudinal data and no method handles repeatedly measured outcomes. In this paper, we extended two Bayesian approaches: Bayesian estimation of marginal structural models and two-stage Bayesian propensity score analysis to handle a repeatedly measured outcome. Our proposed methods permit causal estimation of treatment effects at each visit. Time-dependent inverse probability of treatment weights are obtained from the Markov chain Monte Carlo samples of the posterior treatment assignment model for each follow-up visit. We use a simulation study to validate and compare the proposed methods and illustrate our approaches through a study of intravenous immunoglobulin therapy in treating newly diagnosed juvenile dermatomyositis. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy, safety, and tolerability of oromucosal nabiximols cannabinoid medicine as adjunct therapy for children with spasticity due to cerebral palsy/traumatic central nervous system injury with inadequate response to existing treatment.Method: Overall, 72 patients (mean [SD] age 12y 4mo [3y 1mo], range 8-18y) were randomized at a ratio of 2:1 to receive nabiximols (n=47; 29 males, 18 females) or placebo (n=25; 15 males, 10 females) for 12 weeks (12 sprays/day max. based on clinical response/tolerability). The primary outcome was change from baseline in level of spasticity on a 0 to 10 Numerical Rating Scale (NRS), assessed by the primary caregiver at 12 weeks. Secondary outcomes included additional measures for spasticity, sleep quality, pain, health-related quality of life, comfort, depression, and safety.Results: There was no significant difference in the spasticity 0 to 10 NRS between nabiximols versus placebo groups after 12 weeks. No statistically significant differences were observed for any secondary endpoint. Adverse events were predominantly mild or moderate in severity; however, three cases of hallucinations were reported.Interpretation: Nabiximols was generally well tolerated; however, neuropsychiatric adverse events were observed. No significant reduction in spasticity with nabiximols treatment versus placebo was observed.What This Paper Adds: Oromucosal nabiximols is generally well tolerated by paediatric patients. However, three cases of hallucinations were observed, one of which involved auditory hallucinations and a suicide attempt. Oromucosal nabiximols versus placebo did not reduce cerebral palsy/central nervous system injury-related spasticity. [ABSTRACT FROM AUTHOR]

When establishing an effective treatment with binary data in a two-stage design, one-sided tests for a proportion p are employed. Researchers use the parameter configuration at the boundary of the null hypothesis space to determine a rejection region and an optimal design. However, it is unclear whether the (maximum) Type I error rate is achieved at the boundary especially when the sample size in stage 2 varies. In this paper, we first prove that this is true for a large family of tests in adaptive two-stage designs by showing that any test in the family has a nondecreasing power in p and then derive optimal designs. Second, similar results are established for m-stage designs with m > 2. Supplementary materials for this article are available online. [ABSTRACT FROM AUTHOR]

It has long been recognized that sample size calculations for cluster randomized trials require consideration of the correlation between multiple observations within the same cluster. When measurements are taken at anything other than a single point in time, these correlations depend not only on the cluster but also on the time separation between measurements and additionally, on whether different participants (cross-sectional designs) or the same participants (cohort designs) are repeatedly measured. This is particularly relevant in trials with multiple periods of measurement, such as the cluster cross-over and stepped-wedge designs, but also to some degree in parallel designs. Several papers describing sample size methodology for these designs have been published, but this methodology might not be accessible to all researchers. In this article we provide a tutorial on sample size calculation for cluster randomized designs with particular emphasis on designs with multiple periods of measurement and provide a web-based tool, the Shiny CRT Calculator, to allow researchers to easily conduct these sample size calculations. We consider both cross-sectional and cohort designs and allow for a variety of assumed within-cluster correlation structures. We consider cluster heterogeneity in treatment effects (for designs where treatment is crossed with cluster), as well as individually randomized group-treatment trials with differential clustering between arms, for example designs where clustering arises from interventions being delivered in groups. The calculator will compute power or precision, as a function of cluster size or number of clusters, for a wide variety of designs and correlation structures. We illustrate the methodology and the flexibility of the Shiny CRT Calculator using a range of examples. [ABSTRACT FROM AUTHOR]

Objectives: This paper is aimed to explore the value of double source CT angiography (DS-CTA) for diagnosing in-stent restenosis in lower limb artery.Methods: From January 2016 to October 2018, all patients with stent in lower limb artery in our hospital were investigated by both DS-CTA and digital subtraction angiography. We measured the minimum lumen diameter and the diameter of the proximal normal vessels under each stent placement. The in-stent restenosis is defined as restenosis when the lumen area decreased by more than 50%. Digital subtraction angiography was performed within 1 week after DS-CT scan. Relationship between DS-CTA and digital subtraction angiography for diagnosing in-stent restenosis in lower limb artery was analyzed. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DS-CTA for diagnosis of in-stent restenosis were analyzed with digital subtraction angiography as the reference standard. A total of 68 stents were placed in 51 patients. Among these patients, 27 cases were diagnosed as in-stent restenosis, presenting as endovascular contrast agent bias or crescent filling defect with the lumen area reducing over 50%, 6 cases of which had no significant in-stent restenosis by digital subtraction angiography analysis. Furthermore, 12 cases were occlusion, in which there was no high density contrast agent in stents; the remaining 41 stents were unobstructed and the contrast agent was filled well, 8 cases of which had significant in-stent restenosis by digital subtraction angiography analysis. In addition, four stents were deformed or distorted. Statistical analysis demonstrated the concentrations of DS-CTA and digital subtraction angiography in diagnosing in-stent restenosis for lower limb artery were closely related, and the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DS-CTA were 72.4%, 84.6%, 77.8%, 80.5%, and 79.4%, respectively.Conclusion: DS-CTA has a potential reliability for diagnosis of in-stent restenosis in lower limb artery, which may be further improved to be used for clinical interventional treatment of vascular diseases. [ABSTRACT FROM AUTHOR]

Child birth order (CBO) in the family has received little attention in the field of prevention science. CBO is relevant to early interventionists from a public health perspective, as the most widely disseminated home-visiting program has traditionally targeted mothers and their first-born children. The current paper revisits a previous publication by Shaw et al. (2009) on the effectiveness of the Family Check-Up (FCU) to evaluate CBO (firstborn vs. middle vs. youngest) as a moderator of treatment effects of the FCU in relation to improvements in parenting, maternal depressive symptoms, and child outcomes from ages 2 to 4 in a sample of low-income, ethnically diverse families (N = 709) with multiple children. Results suggest that the FCU elicited improvements in observed parenting from ages 2 to 3 primarily for target children who were the youngest or middle children, but not for firstborns. Findings are discussed in the context of implications for prevention science research, dissemination, and public policy. [ABSTRACT FROM AUTHOR]

Aims: The TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8 °C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and exploratory outcomes will be collected. We also present the explorative outcome analyses which will focus on neurocognitive function and societal participation in OHCA-survivors.Methods: Blinded outcome-assessors will perform follow-up at 30-days after the OHCA with a telephone interview, including the modified Rankin Scale (mRS) and the Glasgow Outcome Scale Extended (GOSE). Face-to-face meetings will be performed at 6 and 24-months, and include reports on outcome from several sources of information: clinician-reported: mRS, GOSE; patient-reported: EuroQol-5 Dimensions-5 Level responses version (EQ-5D-5L), Life satisfaction, Two Simple Questions; observer-reported: Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest version (IQCODE-CA) and neurocognitive performance measures: Montreal Cognitive Assessment, (MoCA), Symbol Digit Modalities Test (SDMT). Exploratory analyses will be performed with an emphasis on brain injury in the survivors, where the two intervention groups will be compared for potential differences in neuro-cognitive function (MoCA, SDMT) and societal participation (GOSE). Strategies to increase inter-rater reliability and decrease missing data are described.Discussion: The TTM2-trial follow-up is a pragmatic yet detailed pre-planned and standardised assessment of patient's outcome designed to ensure data-quality, decrease missing data and provide optimal conditions to investigate clinically relevant effects of TTM, including OHCA-survivors' neurocognitive function and societal participation. [ABSTRACT FROM AUTHOR]

Aim: To examine the impact of engagement in a self-chosen community-based activity on three relevant body functions (motor, cognitive, and affective) as well as on the performance of the selected activity.Method: An individual-based interrupted time series design with multiple baselines was used. Seven young people (four males, three females) aged 15 to 25 years (median 18y; interquartile range 17-20y) with physical disabilities participated in an 8-week community activity of choice (e.g. swimming, playing piano). Change in three relevant body functions, underpinning the specific chosen activity, including motor (e.g. Functional Reach Test, Trunk Impairment Scale, dynamometers), cognitive and affective (Behavior Assessment System for Children), as well as activity performance (Canadian Occupational Performance Measure) were measured repeatedly, providing individual outcome trajectories. Linear and mixed-effects models were used.Results: Significant improvements in at least one aspect of motor function (6 out of 6), cognition (3 out of 3), affect (5 out of 7), and performance (7 out of 7) were observed. Specifically, the intervention had a moderate to large effect on hyperactivity (1.45, 95% confidence interval [CI] 1.0-1.9) with a smaller effect on anxiety (0.21, 95% CI 0.10-0.32) and inadequacy (0.21, 95% CI 0.02-0.39). Concurrently, a notable effect size for activity performance (4.61, 95% CI 0.76-8.46) was observed. Average change across motor outcomes was substantial (3.7 SDs from baseline), yet non-significant.Interpertation: Findings provide initial evidence of the benefits resulting from participation-based interventions, emphasizing the merit of meaningful 'real-life' young people-engaging therapy.What This Paper Adds: Participation-based interventions can impact body-function level outcomes. Significant improvements in the performance of chosen activities were observed. Significant improvements were also seen in cognitive and affective body functions. Improvements in motor-related outcomes were substantial but not statistically significant. [ABSTRACT FROM AUTHOR]

Aim: To determine whether epilepsy surgery improved health-related quality of life (HRQoL) and whether seizure freedom after surgery mediated the improvement in HRQoL.Method: This multicenter cohort study compared HRQoL after epilepsy surgery to pharmacological management in children with drug-resistant epilepsy (DRE). HRQoL was measured using the Quality of Life in Childhood Epilepsy (QOLCE) questionnaire at baseline and 1-year follow-up. The mediator between treatment type and HRQoL was seizure freedom.Results: Two hundred and thirty-seven patients were recruited (surgery group: n=147 [92 males, 45 females]; pharmacological group: n=90 [53 males, 37 females]). Mean age at seizure onset was 6 years (SD 4y 4mo) in the surgical group and 6 years 1 month (SD 4y) in the pharmacological group. The odds ratio of seizure freedom was higher for the surgery versus pharmacological group (β=4.24 [95% confidence interval {CI}: 2.26-7.93], p<0.001). Surgery had no direct effect on total QOLCE score at 1-year (β=0.24 [95% CI -2.04 to 2.51], p=0.839) compared to pharmacological management, but had an indirect effect on total QOLCE that was mediated by seizure freedom (β=0.92 [95% CI 0.19-1.65], p=0.013), adjusting for baseline total QOLCE score. Surgery had a direct effect on improving social function (p=0.043), and an indirect effect on improving physical function (p=0.016), cognition (p=0.042), social function (p=0.012) and behavior (p=0.032), mediated by seizure freedom.Interpretation: Greater seizure freedom achieved through epilepsy surgery mediated the improvement in HRQoL compared to pharmacological management in children with DRE.What This Paper Adds: Seizure freedom is higher after pediatric epilepsy surgery compared to pharmacologically managed epilepsy. Surgery indirectly improves health-related quality of life (HRQoL) mediated by seizure freedom compared to pharmacological management. Surgery has a direct effect on improving social function relative to pharmacological management. Baseline HRQoL was an important predictor of HRQoL after treatment. [ABSTRACT FROM AUTHOR]

Surrogate endpoints play an important role in drug development when they can be used to measure treatment effect early compared to the final clinical outcome and to predict clinical benefit or harm. Such endpoints are assessed for their predictive value of clinical benefit by investigating the surrogate relationship between treatment effects on the surrogate and final outcomes using meta-analytic methods. When surrogate relationships vary across treatment classes, such validation may fail due to limited data within each treatment class. In this paper, two alternative Bayesian meta-analytic methods are introduced which allow for borrowing of information from other treatment classes when exploring the surrogacy in a particular class. The first approach extends a standard model for the evaluation of surrogate endpoints to a hierarchical meta-analysis model assuming full exchangeability of surrogate relationships across all the treatment classes, thus facilitating borrowing of information across the classes. The second method is able to relax this assumption by allowing for partial exchangeability of surrogate relationships across treatment classes to avoid excessive borrowing of information from distinctly different classes. We carried out a simulation study to assess the proposed methods in nine data scenarios and compared them with subgroup analysis using the standard model within each treatment class. We also applied the methods to an illustrative example in colorectal cancer which led to obtaining the parameters describing the surrogate relationships with higher precision. [ABSTRACT FROM AUTHOR]

Aim: To assess the responsiveness, concurrent validity, and feasibility of the Dyskinesia Impairment Scale (DIS) in non-ambulatory patients with dyskinetic cerebral palsy (CP).Method: The study is a secondary analysis of data collected in the IDYS trial, a randomized controlled trial on the effects of intrathecal baclofen (ITB). The DIS and Barry-Albright Dystonia Scale (BADS) were conducted at baseline and after 3 months of ITB or placebo treatment. Responsiveness was assessed by comparing the effect sizes and correlation of change after treatment between the DIS and BADS. Concurrent validity was evaluated by assessing the correlations between scales. Feasibility was evaluated for each DIS item by the number of participants who successfully accomplished the item.Results: Thirty-three non-ambulatory patients (9 females, 24 males) with dyskinetic CP (ITB-treated: n=17, mean [SD] age: 14y 1mo [4y 1mo]; placebo-treated: n=16, mean [SD] age: 14y 7mo [4y]) were included in the study. The effect sizes for BADS and DIS were similar in The ITB-treated group (-0.29 and -0.22 respectively). Changes after treatment on the DIS dystonia subscale correlated with changes on the BADS (r=0.64; p<0.001). The DIS dystonia subscale and BADS correlated at baseline and follow-up (r=0.78; p<0.001 and r=0.79; p<0.001). Not all DIS activity items could be performed in this sample of patients.Interpretation: For non-ambulatory patients with dyskinetic CP, the responsiveness of the DIS equalled the responsiveness of BADS. Concurrent validity was adequate. Feasibility for activity items was restricted in patients with severe dyskinetic CP.What This Paper Adds: The Dyskinesia Impairment Scale (DIS) and Barry-Albright Dystonia Scale showed similar responsiveness in non-ambulatory patients with dyskinetic cerebral palsy (CP). No floor or ceiling effect was observed for DIS in non-ambulatory participants. The concurrent validity of DIS was adequate in non-ambulatory participants. Patients with dyskinetic CP in Gross Motor Function Classification System levels IV and V could not perform all DIS activity items. [ABSTRACT FROM AUTHOR]

Background: Accessing quality mental health care poses significant challenges for persons affected by adversity, especially in low- and middle-income countries where resources are scarce. To mitigate this, the World Health Organization has developed group problem management plus (gPM+), a low-intensity psychological intervention for adults experiencing psychological distress. gPM+ is a group-based intervention consisting of five-sessions, and can be delivered by non-specialist providers. This paper outlines the study protocol for a trial of gPM+ in Jordan.Methods: We will conduct a single-blind, two-arm, randomized controlled trial in a Syrian refugee camp in Jordan. We aim to enrol 480 adults into the trial. Participants will be eligible for the trial if they screen positive for levels of psychological distress. Following screening, those eligible will be randomly assigned to receive the gPM+ intervention or enhanced treatment as usual. The primary outcome is reduction in levels of psychological distress at 3-months post-treatment. Secondary outcomes include anxiety, depression, prodromal psychotic symptoms, posttraumatic stress disorder, prolonged grief, daily functioning, economic effectiveness, and change in parenting behaviour. Secondary outcomes also include the reduction in psychological distress of the participant's child.Discussion: The trial aims to deliver a template for affordable and scalable psychosocial interventions that can readily be implemented in refugee settings, and that can benefit both the participant and their child.Trial Registration: Australian New Zealand Clinical Trials Registry, ACTRN12619001386123. Registered prospectively on 10/10/2019. [ABSTRACT FROM AUTHOR]

The problem of how to best select variables for confounding adjustment forms one of the key challenges in the evaluation of exposure or treatment effects in observational studies. Routine practice is often based on stepwise selection procedures that use hypothesis testing, change-in-estimate assessments or the lasso, which have all been criticised for - amongst other things - not giving sufficient priority to the selection of confounders. This has prompted vigorous recent activity in developing procedures that prioritise the selection of confounders, while preventing the selection of so-called instrumental variables that are associated with exposure, but not outcome (after adjustment for the exposure). A major drawback of all these procedures is that there is no finite sample size at which they are guaranteed to deliver treatment effect estimators and associated confidence intervals with adequate performance. This is the result of the estimator jumping back and forth between different selected models, and standard confidence intervals ignoring the resulting model selection uncertainty. In this paper, we will develop insight into this by evaluating the finite-sample distribution of the exposure effect estimator in linear regression, under a number of the aforementioned confounder selection procedures. We will show that by making clever use of propensity scores, a simple and generic solution is obtained in the context of generalized linear models, which overcomes this concern (under weaker conditions than competing proposals). Specifically, we propose to use separate regularized regressions for the outcome and propensity score models in order to construct a doubly robust 'g-estimator'; when these models are sufficiently sparse and correctly specified, standard confidence intervals for the g-estimator implicitly incorporate the uncertainty induced by the variable selection procedure. [ABSTRACT FROM AUTHOR]

Non-adherence to assigned treatment is a common issue in cluster randomised trials. In these settings, the efficacy estimand may also be of interest. Many methodological contributions in recent years have advocated using instrumental variables to identify and estimate the local average treatment effect. However, the clustered nature of randomisation in cluster randomised trials adds to the complexity of such analyses. In this paper, we show that the local average treatment effect can be estimated via two-stage least squares regression using cluster-level summaries of the outcome and treatment received under certain assumptions. We propose the use of baseline variables to adjust the cluster-level summaries before performing two-stage least squares in order to improve efficiency. Implementation needs to account for the reduced sample size, as well as the possible heteroscedasticity, to obtain valid inferences. Simulations are used to assess the performance of two-stage least squares of cluster-level summaries under cluster-level or individual-level non-adherence, with and without weighting and robust standard errors. The impact of adjusting for baseline covariates and of appropriate degrees of freedom correction for inference is also explored. The methods are then illustrated by re-analysing a cluster randomised trial carried out in a specific UK primary care setting. Two-stage least squares estimation using cluster-level summaries provides estimates with small to negligible bias and coverage close to nominal level, provided the appropriate small sample degrees of freedom correction and robust standard errors are used for inference. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate tolerability of and response to rituximab in children with myelin oligodendrocyte glycoprotein (MOG) antibody-positive relapsing neuroinflammatory disease. This was an observational study of prospectively collected data on 12 consecutive children (eight females, four males; median age at onset 10y 6mo [interquartile range {IQR} 7y 2mo-12y 5mo], median follow-up 2y 1mo [IQR 1y 7mo-2y 6mo]) with central nervous system inflammation and persistent serum MOG immunoglobulin G positivity more than 12 weeks after clinical presentation. Patients received a standardized rituximab treatment protocol. MOG antibody testing was performed following standardized cell-based methods. Median clinical follow-up after rituximab induction was 2 years (IQR 1y 7mo-2y 10mo). The relapse rate in the first 12 months posttreatment was 0 (IQR 0-0). After rituximab, two patients relapsed during B-cell suppression and four showed clinical or radiological disease recurrences at B-cell reconstitution. Mild-to-moderate infusion related adverse events occurred in two patients. Leukopenia developed in seven patients and serum immunoglobulin suppression in five patients with no significant age effect on the risk of their development. None developed severe life-threatening events. Rituximab-induced B-cell suppression was associated with absence of relapses in 10 patients who were MOG-positive with recurrent disease. Rituximab was well tolerated. The most frequent adverse effects were hypogammaglobulinemia and leukopenia. We recommend monitoring of complete blood counts and immunoglobulins in this population. WHAT THIS PAPER ADDS: Rituximab appears to control disease in most anti-myelin oligodendrocyte glycoprotein-positive patients with relapsing neuroinflammatory disease. Rituximab was associated with transitory, mild-to-moderate infusion-related effects. Half of patients treated with rituximab developed leukopenia or hypogammaglobulinemia. No opportunistic infections were observed. [ABSTRACT FROM AUTHOR]

Background: Displaced mid-third clavicle fractures are common, and their management remains unclear. Although several meta-analyses have compared specific operative techniques with nonoperative management, it is not possible to compare different operative constructs with one another using a standard meta-analysis. Conversely, a network meta-analysis allows comparisons among more than two treatment arms, using both direct and indirect comparisons between interventions across many trials. To our knowledge, no network meta-analysis has been performed to compare the multiple treatment options for displaced clavicle fractures.Questions/purposes: We performed a network meta-analysis of randomized, controlled trials (RCTs) to determine from among the approaches used to treat displaced midshaft clavicle fractures: (1) the intervention with the highest chance of union at 1 year, (2) the intervention with the lowest risk of revision surgery, and (3) the intervention with the highest functional outcome scores. Secondarily, we also (4) compared the surgical subtypes in the available RCTs on the same above endpoints.Methods: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were reviewed for relevant randomized controlled trials published up to July 25, 2018. Two hundred and eighty four papers were reviewed, with 22 meeting inclusion criteria of RCTs with appropriate randomization techniques, adult population, minimum of 1 year follow-up and including at least one operative treatment arm. In total, 1002 patients were treated with a plate construct, 378 with an intramedullary device, and 585 patients were managed nonoperatively. Treatment subtypes included locked intramedullary devices (56), unlocked intramedullary devices (322), anterior plating (89), anterosuperior plating (150), superior plating (449) or plating not otherwise specified (314). We performed a network meta-analysis to compare and rank the treatments for displaced clavicle fractures. We considered the following outcomes: union achievement, revision surgery risk and functional outcomes (DASH and Constant Scores). The minimal clinically important difference (MCID) was considered for both Constant and DASH scores to be at 8 points, representing the average of MCID scores reported for both DASH and Constant in the evidence, respectively.Results: Union achievement was lower in patients treated nonoperatively (88.9%), and higher in patients treated operatively (96.7%, relative risk [RR] 1.128 [95% CI 1.1 to 1.17]; p < 0.001), Number needed to treat (NNT) = 10). Union achievement increased with any plate construct (97.8%, RR 1.13 [95% CI 1.1 to 1.7]; p < 0.0001, NNT = 9) and with anterior or anterosuperior plates (99.3%, RR 1.14 [95% CI 1.1 to 1.8]; p < 0.0001, NNT = 8). Risk of reoperation, when considering planned removal of hardware, was similar across all treatment arms. Lastly, operative treatment outperformed nonoperative treatment with minor improvements in DASH and Constant scores, though not approaching the MCID. At the subtype level, anterosuperior plating ranked highest in DASH and Constant functional scores with mean differences reaching 10-point improvement for Constant scores (95% CI 4.4 to 2.5) and 7.6 point improvement for DASH (95% CI 5.2 to 20).Conclusions: We found that surgical treatment led to a greater likelihood of union at 1 year of follow-up among adult patients with displaced mid-third clavicle fractures. In aggregate, surgical treatment did not increase functional scores by amounts that patients were likely to consider clinically important. Use of specific subtypes of plating (anterior, anterosuperior) resulted in improvements in the Constant score that were slightly above the MCID but did not reach the MCID for the DASH score, suggesting that any outcomes-score benefits favoring surgery were likely to be imperceptible or small. In light of these findings, we believe patients can be informed that surgery for this injury can increase the likelihood of union incrementally (about 10 patients would need to undergo surgery to avoid one nonunion), but they should not expect better function than they would achieve without surgery; most patients can avoid surgery altogether with little absolute risk of nonunion. Patients who opt for surgery must be told that the decision should be weighed against complications and the possibility of undergoing a second procedure for hardware removal. Patients opting not to have surgery for acute midshaft clavicle fractures can be told that nonunion occurs in slightly more than 10% of patients, and that these can be more difficult to manage than acute fractures.Level Of Evidence: Level I, therapeutic study. [ABSTRACT FROM AUTHOR]