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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]

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: 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: 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]

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]

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]

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]

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]

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]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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 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]

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Young people account for more than a quarter of new HIV infections in the US, with the majority of cases among young men who have sex with men; young transgender women are also vulnerable to infection. Substance use, particularly alcohol misuse, is a driver of sexual transmission and a potential barrier to engagement in the HIV prevention and care continuum, however vulnerable youth are difficult to reach for substance use services due, in part, to complex social and structural factors and limited access to health care. The Community Prevention Services Task Force recommends electronic screening and brief intervention as an evidence-based intervention for the prevention of excessive alcohol consumption; however, no prior studies have extended this model to community-based populations of youth that are susceptible to HIV infection. This paper describes the study protocol for an electronic screening and brief intervention to reduce alcohol misuse among adolescents and young adults vulnerable to HIV infection in community-based settings.Methods: This study, Step Up, Test Up, is a randomized controlled trial of an electronic alcohol screening and brief intervention among youth, ages 16-25, who are vulnerable to HIV infection. Individuals who present for HIV testing at one of three community-based locations are recruited for study participation. Eligibility includes those aged 16-25 years, HIV-negative or unknown HIV status, male or trans female with a history of sex with men, and English-speaking. Participants who screen at moderate to high risk for alcohol misuse on the Alcohol Use Disorders Identification Test (AUDIT) are randomized (1:1) to either an electronic brief intervention to reduce alcohol misuse or a time-and attention-matched control. The primary outcome is change in the frequency/quantity of recent alcohol use at 1, 3, 6 and 12-month follow-up.Discussion: Testing of evidence-based interventions to reduce alcohol misuse among youth vulnerable to HIV infection are needed. This study will provide evidence to determine feasibility and efficacy of a brief electronically-delivered intervention to reduce alcohol misuse for this population.Trial Registration: ClinicalTrials.gov number, NCT02703116, registered March 9, 2016. [ABSTRACT FROM AUTHOR]

Objective: The use of relative and absolute effect estimates has important implications for the interpretation of study findings. Likewise, examining additive and multiplicative interaction can lead to differing conclusions about the joint effects of two exposure variables. The aim of this paper is to examine the relationship between BMI and mortality on the relative and absolute scales and investigate interaction between BMI and age.Methods: Data from 68,132 participants in the Women's Health Initiative (WHI) study were used. The risk ratio and risk difference of BMI on mortality were estimated. A product term was also included to examine interaction between BMI and age on the multiplicative scale, and the relative excess risk of interaction was calculated to measure additive interaction.Results: Results demonstrated that the mortality risk ratio decreased as women aged, but the mortality risk difference increased as women aged. Evidence of additive and multiplicative interaction between age and BMI was found.Conclusions: In postmenopausal women, the relative mortality risk associated with high BMI decreased with increasing age, but the absolute risk of high BMI increased with increasing age. This indicates the importance of considering the interaction between age and BMI to understand mortality risk in older women. [ABSTRACT FROM AUTHOR]

Purpose: There is a considerable body of literature relating to trabeculectomy, however there are no data representative of the national experience of trabeculectomy in the United Kingdom (UK). The Department of Health funded a national survey of trabeculectomy to establish current practice patterns and the outcome of trabeculectomy in the National Health Service (NHS). In this paper we present the reported complications of first-time trabeculectomy from a nationally representative cohort of patients with chronic open angle glaucoma.Methods: Cross-sectional study of consultant ophthalmologists performing trabeculectomy in the NHS. Participants recruited their four most recent consecutive first-time trabeculectomy cases with chronic open angle glaucoma according to study eligibility criteria and data were collected by self-administered questionnaire.Follow-up: one year post-trabeculectomy.Main Outcome Measures: occurrence of early and late complications.Results: Clinical outcome data were available for 1240 (85.3%) of cases. Early complications were reported in 578 (46.6%) cases and late complications in 512 (42.3%) cases. Some cases had more than one complication. The most frequent early complications were hyphaema (n = 304, 24.6%), shallow anterior chamber (n = 296, 23.9%), hypotony (n = 296, 24.3%), wound leak (n = 216, 17.8%) and choroidal detachment (n = 175, 14.1%). The most frequent late complications were cataract (n = 251, 20.2%), visual loss (n = 230, 18.8%) and encapsulated bleb (n = 42, 3.4%). The occurrence of most complications was not associated with a consultant's specialist interest, level of activity, type of hospital or region. Encapsulated bleb was reported more frequently in a university hospital setting.Conclusions: The complication rates reported in this paper represent the national experience of first-time trabeculectomy for open angle glaucoma in the UK. These are similar to previous published studies and highlight in particular, the impact of trabeculectomy on visual acuity in the first year following surgery. This survey provides valid and clinically relevant data on the complications of trabeculectomy for the production of guidelines and standards for audit at regional, local and individual level. [ABSTRACT FROM AUTHOR]

Background: Globally it is estimated that 480 000 people developed multidrug-resistant tuberculosis (MDR-TB) in 2014 and 190 000 people died from the disease. Successful treatment outcomes are achieved in only 50 % of patients with MDR-TB, compared to 86 % for drug susceptible disease. It is widely held that delay in time to initiation of treatment for MDR-TB is an important predictor of treatment outcome. The objective of this review was to assess the existing evidence on the outcomes of multidrug- and extensively drug-resistant tuberculosis patients treated early (≤4 weeks) versus late (>4 weeks) after diagnosis of drug resistance.Methods: Eight sources providing access to 17 globally representative electronic health care databases, indexes, sources of evidence-based reviews and grey literature were searched using terms incorporating time to treatment and MDR-TB. Two-stage sifting in duplicate was employed to assess studies against pre-specified inclusion and exclusion criteria. Only those articles reporting WHO-defined treatment outcomes were considered for inclusion. Articles reporting on fewer than 10 patients, published before 1990, or without a comparison of outcomes in patient groups experiencing different delays to treatment initiation were excluded.Results: The initial search yielded 1978 references, of which 1475 unique references remained after removal of duplicates and 28 articles published pre-1990. After title and abstract sifting, 64 papers underwent full text review. None of these articles fulfilled the criteria for inclusion in the review.Conclusions: Whilst there is an inherent logic in the theory that treatment delay will lead to poorer treatment outcomes, no published evidence was identified in this systematic review to support this hypothesis. Reports of programmatic changes leading to reductions in treatment delay exist in the literature, but attribution of differences in outcomes specifically to treatment delay is confounded by other contemporaneous changes. Further primary research on this question is not considered a high priority use of limited resources, though where data are available, improved reporting of outcomes by time to treatment should be encouraged. [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]

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Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Anxiety is a common concern of cancer survivors during the transition from active cancer treatment to cancer survivorship (the re-entry phase). This paper presents the study protocol for a novel group-based behavioral intervention to improve mental health, well-being, and medical use outcomes among anxious cancer survivors at re-entry.Methods/design: This two-armed, prospective randomized controlled trial will randomize a minimum of 100 re-entry-phase cancer survivors with moderate to high anxiety to the intervention or a usual care control condition. The intervention is delivered in a group format over 7 weeks; content is based on Acceptance and Commitment Therapy (ACT), an acceptance, mindfulness, and values-based intervention. Participants will be recruited from community cancer care centers and the intervention will be led by the onsite clinical social workers. Participants will be assessed at baseline, mid-intervention, post-intervention, and 3- and 6-month follow-up. ACT participants will complete process measures before the beginning of group sessions 2, 4, and 6; all participants will complete the process measures during the regular assessments. The primary outcome is anxiety symptoms; secondary outcomes include anxiety disorder severity, fear of recurrence, depressive symptoms, cancer-related trauma symptoms, sense of life meaning, vitality/fatigue, and medical utilization.Discussion: This clinical trial will provide valuable evidence regarding the efficacy of the group ACT intervention in community oncology settings.Trial Registration: Clinicaltrials.gov NCT02550925 . [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]

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Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Developmental Medicine & Child Neurology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Type 2 diabetes mellitus is associated with cognitive dysfunction and an increased risk of dementia. Linagliptin is a glucose-lowering agent of the dipeptidyl peptidase-IV (DPP-IV) inhibitor class that is of particular interest for the prevention of accelerated cognitive decline, because it may potentially benefit the brain through pleiotropic effects, beyond glucose lowering. This paper presents the design of a study that aims to establish if linagliptin is superior to the sulfonylurea glimepiride in the prevention of accelerated cognitive decline in patients with type 2 diabetes mellitus.Methods: The cognition substudy is an integral part of the ongoing event-driven, randomised, double blind CARdiOvascular safety of LINAgliptin (CAROLINA®) trial, which evaluates the effect of treatment with linagliptin versus glimepiride on cardiovascular outcomes. CAROLINA® includes patients with type 2 diabetes mellitus with sub-optimal glycaemic control at elevated cardiovascular risk. The substudy will evaluate patients randomised and treated who have a baseline Mini Mental State Examination (MMSE) score ≥ 24, documented years of formal education with at least one valid cognitive assessment at baseline and during follow-up. The primary cognitive outcome is the occurrence of accelerated cognitive decline at the end of follow-up. The two treatment groups will be compared by using a logistic regression. Accelerated cognitive decline is defined as a rate of cognitive decline that falls at or below the 16th percentile of decline for the whole cohort on either the MMSE or a combined score of the trail making and verbal fluency test. Potential confounders are taken into account at an individual patient level, using a regression based index.Discussion: Between December 2010 and December 2012, 6042 patients were randomised and treated with either linagliptin (5 mg) or glimepiride (1-4 mg) once daily in CAROLINA®. Cognitive tests were conducted in nearly 4500 participants at baseline and are scheduled for two subsequent assessments, after 160 weeks of follow-up and end of follow-up. This substudy of the ongoing CAROLINA® trial will establish if linagliptin is superior to glimepiride in the prevention of accelerated cognitive decline in patients with type 2 diabetes mellitus. Final results are expected in 2019.Trial Registration: ClinicalTrials.gov Identifier: NCT 01243424 . [ABSTRACT FROM AUTHOR]

Background: Recruitment of participants is particularly challenging in primary care, with less than a third of randomised controlled trials (RCT) achieving their target within the original time frame. Participant identification, consent, randomisation and data collection can all be time-consuming. Trials recruiting an incident, as opposed to a prevalent, population may be particularly affected. This paper describes the impact of a deferred recruitment model in a RCT of antibiotics for children with infected eczema in primary care, which required the recruitment of cases presenting acutely.Methods: Eligible children were identified by participating general practitioners (GPs) and referred to a study research nurse, who then visited them at home. This allowed the consent and recruitment processes to take place outside the general practice setting. Information was recorded about patients who were referred and recruited, or if not, the reasons for non-recruitment. Data on recruitment challenges were collected through semi-structured interviews and questionnaires with a sample of participating GPs. Data were thematically analysed to identify key themes.Results: Of the children referred to the study 34% (58/171) were not recruited - 48% (28/58) because of difficulties arranging a baseline visit within the defined time frame, 31% (18/58) did not meet the study inclusion criteria at the time of nurse assessment, and 21% (12/58) declined participation. GPs had positive views about the recruitment process, reporting that parents valued and benefitted from additional contact with a nurse. GPs felt that the deferred recruitment model did not negatively impact on the study.Conclusions: GPs and parents recognised the benefits of deferred recruitment, but these did not translate into enhanced recruitment of participants. The model resulted in the loss of a third of children who were identified by the GP as eligible, but not subsequently recruited to the study. If the potential for improving outcomes in primary care through complex studies is to be realised, new approaches to recruitment into primary care trials need to be developed and evaluated.Trial Registration: International Standard Randomised Controlled Trials, ISRCTN96705420 . Registered on 27 June 2012. [ABSTRACT FROM AUTHOR]

Aims: To review systematically the use of intravenous (IV) inotropic agents acting through the adrenergic signalling pathway, compared with placebo or an active agent, in patients with heart failure.Methods: Studies investigating the use of intravenous inotropes in patients with heart failure published between 1966 and 2000 were identified using MEDLINE, the Cochrane register and Embase databases. Reference lists from relevant papers and reviews were hand searched for further papers. In total, 21 trials, that included 632 patients receiving IV inotropic drugs, placebo or non-treatment control, were identified. Drugs of the following classes were included, the beta-agonists; dobutamine, high-dose (>2.5 microg/kg/min) dopamine, dopexamine and the phosphodiesterase (PDE) inhibitors; amrinone, milrinone, enoximone and toborinone. Sixteen trials (474 patients) contributed data from acute invasive haemodynamic studies of symptomatically severe heart failure. Five trials (158 patients) were based on intermittent inotropic therapy in an outpatient context.Results: With few exceptions, trials of intravenous inotropic agents were small and often failed to report clinically important outcomes. Compared to placebo, intravenous inotropic agents acting through the adrenergic system tended to increase mortality (odds ratio 1.50 (95% CI=0.51 to 3.92) but this did not reach significance and insufficient data were available to determine whether symptoms improved. There appeared to be little difference in the effect of beta-agonists compared to PDE inhibitors on patient outcomes but this could be attributed to the paucity of data.Conclusions: Intravenous inotropic agents acting through the adrenergic pathway are often used in patients with worsening heart failure to achieve arbitrary haemodynamic targets. Our analyses show that there is very little evidence that such treatment improves symptoms or patient outcomes and may not be safe. This highlights the need for further well designed randomised clinical trials. [ABSTRACT FROM AUTHOR]

Background: The efficacy of ALO-02, an abuse-deterrent formulation containing extended-release oxycodone and sequestered naltrexone, in the treatment of chronic low back pain (CLBP) was studied in a 12-week randomized controlled trial. Primary efficacy endpoint results have been published previously (Rauck et al., 2015). The current paper focuses on patient-reported outcomes for health-related quality of life (HRQL), work productivity, and activity impairment that were assessed during this study.Methods: This was a double-blind, placebo-controlled, randomized withdrawal study in patients with moderate-to-severe CLBP. After a screening period (≤2 weeks), patients entered an open-label titration period (4-6 weeks). Treatment responders were then randomized to a double-blind placebo-controlled treatment period (12 weeks). HRQL was assessed using changes in the Short Form-36 v2 Health Survey (SF-36v2) and the EuroQol-5 Dimensions Health Questionnaire 3-Level version (EQ-5D-3L). Work productivity and regular activities were evaluated using the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP).Results: A total of 410 patients received ALO-02 during the open-label titration period, of which 280 (intent-to-treat (ITT) population) were treated during the double-blind placebo-controlled treatment period (placebo, n = 134; ALO-02, n = 146). Significant improvement was observed for all SF-36v2 subscales and component scores (p < 0.005) and the EQ-5D-3L summary index and visual analog scale (p < 0.0001) during the titration period. Improvement was also significant (p < 0.0001) for all WPAI:SHP outcomes except 'work time missed due to CLBP' for the titration period. Significant differences favoring ALO-02 compared with placebo were only observed for the SF-36v2 Bodily Pain subscale (p ≤ 0.0232; ITT population) during the double-blind treatment period and the overall study period (screening to the end of the double-blind treatment period). The percentage change in activity impairment due to low back pain subscale of the WPAI:SHP significantly favored ALO-02 compared with placebo for the ITT population when considering the overall study period (p = 0.0040).Conclusions: HRQL, work productivity, and activity impairment may be improved with ALO-02 treatment.Trial Registration: ClinicalTrials.gov NCT01571362 , registered April 3, 2012. [ABSTRACT FROM AUTHOR]

Background: The National Institute for Health and Care Excellence (NICE) recommends evidence-based parenting programmes as a first-line intervention for conduct disorders (CD) in children aged 5-11 years. As these are not effective in 25-33% of cases, NICE has requested research into second-line interventions. Child and Adolescent Psychotherapists (CAPTs) address highly complex problems where first-line treatments have failed and there have been small-scale studies of Psychoanalytic Child Psychotherapy (PCP) for CD. A feasibility trial is needed to determine whether a confirmatory trial of manualised PCP (mPCP) versus Treatment as Usual (TaU) for CD is practicable or needs refinement. The aim of this paper is to publish the abridged protocol of this feasibility trial.Methods and Design: TIGA-CUB (Trial on improving Inter-Generational Attachment for Children Undergoing Behaviour problems) is a two-arm, pragmatic, parallel-group, multicentre, individually randomised (1:1) controlled feasibility trial (target n = 60) with blinded outcome assessment (at 4 and 8 months), which aims to develop an optimum practicable protocol for a confirmatory, pragmatic, randomised controlled trial (RCT) (primary outcome: child's behaviour; secondary outcomes: parental reflective functioning and mental health, child and parent quality of life), comparing mPCP and TaU as second-line treatments for children aged 5-11 years with treatment-resistant CD and inter-generational attachment difficulties, and for their primary carers. Child-primary carer dyads will be recruited following a referral to, or re-referral within, National Health Service (NHS) Child and Adolescent Mental Health Services (CAMHS) after an unsuccessful first-line parenting intervention. PCP will be delivered by qualified CAPTs working in routine NHS clinical practice, using a trial-specific PCP manual (a brief version of established PCP clinical practice). Outcomes are: (1) feasibility of recruitment methods, (2) uptake and follow-up rates, (3) therapeutic delivery, treatment retention and attendance, intervention adherence rates, (4) follow-up data collection, and (5) statistical, health economics, process evaluation, and qualitative outcomes.Discussion: TIGA-CUB will provide important information on the feasibility and potential challenges of undertaking a confirmatory RCT to evaluate the effectiveness and cost-effectiveness of mPCP.Trial Registration: Current Controlled Trials, ID: ISRCTN86725795 . Registered on 31 May 2016. [ABSTRACT FROM AUTHOR]

Background: Adults with co-occurring mental and substance use disorders (CODs) are overrepresented in jails. In-custody barriers to treatment, including a lack of evidence-based treatment options and the often short periods of incarceration, and limited communication between jails and community-based treatment agencies that can hinder immediate enrollment into community care once released have contributed to a cycle of limited treatment engagement, unaddressed criminogenic risks, and (re)arrest among this vulnerable and high-risk population. This paper describes a study that will develop research and communication protocols and adapt two evidence-based treatments, dual-diagnosis motivational interviewing (DDMI) and integrated group therapy (IGT), for delivery to adults with CODs across a jail-to-community treatment continuum.Methods/design: Adaptations to DDMI and IGT were guided by the Risk-Need-Responsivity model and the National Institute of Corrections' implementation competencies; the development of the implementation framework and communication protocols were guided by the Evidence-Based Interagency Implementation Model for community corrections and the Inter-organizational Relationship model, respectively. Implementation and evaluation of the protocols and adapted interventions will occur via an open trial and a pilot randomized trial. The clinical intervention consists of two in-jail DDMI sessions and 12 in-community IGT sessions. Twelve adults with CODs and four clinicians will participate in the open trial to evaluate the acceptability and feasibility of, and fidelity to, the interventions and research and communication protocols. The pilot controlled trial will be conducted with 60 inmates who will be randomized to either DDMI-IGT or treatment as usual. A baseline assessment will be conducted in jail, and four community-based assessments will be conducted during a 6-month follow-up period. Implementation, clinical, public health, and treatment preference outcomes will be evaluated.Discussion: Findings have the potential to improve both jail- and community-based treatment services for adults with CODs as well as inform methods for conducting rigorous pilot implementation and evaluation research in correctional settings and as inmates re-enter the community. Findings will contribute to a growing area of work focused on interrupting the cycle of limited treatment engagement, unaddressed criminogenic risks, and (re)arrest among adults with CODs.Trial Registration: ClinicalTrials.gov, NCT02214667 . Registered on 10 August 2014. [ABSTRACT FROM AUTHOR]

Background: The sample size required to power a study to a nominal level in a paired comparative diagnostic accuracy study, i.e. studies in which the diagnostic accuracy of two testing procedures is compared relative to a gold standard, depends on the conditional dependence between the two tests - the lower the dependence the greater the sample size required. A priori, we usually do not know the dependence between the two tests and thus cannot determine the exact sample size required. One option is to use the implied sample size for the maximal negative dependence, giving the largest possible sample size. However, this is potentially wasteful of resources and unnecessarily burdensome on study participants as the study is likely to be overpowered. A more accurate estimate of the sample size can be determined at a planned interim analysis point where the sample size is re-estimated.Methods: This paper discusses a sample size estimation and re-estimation method based on the maximum likelihood estimates, under an implied multinomial model, of the observed values of conditional dependence between the two tests and, if required, prevalence, at a planned interim. The method is illustrated by comparing the accuracy of two procedures for the detection of pancreatic cancer, one procedure using the standard battery of tests, and the other using the standard battery with the addition of a PET/CT scan all relative to the gold standard of a cell biopsy. Simulation of the proposed method illustrates its robustness under various conditions.Results: The results show that the type I error rate of the overall experiment is stable using our suggested method and that the type II error rate is close to or above nominal. Furthermore, the instances in which the type II error rate is above nominal are in the situations where the lowest sample size is required, meaning a lower impact on the actual number of participants recruited.Conclusion: We recommend multinomial model maximum likelihood estimation of the conditional dependence between paired diagnostic accuracy tests at an interim to reduce the number of participants required to power the study to at least the nominal level.Trial Registration: ISRCTN ISRCTN73852054 . Registered 9th of January 2015. Retrospectively registered. [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: A pragmatic, stepped wedge trial design can be an appealing design to evaluate complex interventions in real-life settings. However, there are certain pitfalls that need to be considered. This paper reports on the experiences and lessons learned from the conduct of a cluster randomized, stepped wedge trial evaluating the effect of the Hospital Elder Life Program (HELP) in a Dutch hospital setting to prevent older patients from developing delirium.Methods: We evaluated our trial which was conducted in eight departments in two hospitals in hospitalized patients aged 70 years or older who were at risk for delirium by reflecting on the assumptions that we had and on what we intended to accomplish when we started, as compared to what we actually realized in the different phases of our study. Lessons learned on the design, the timeline, the enrollment of eligible patients and the use of routinely collected data are provided accompanied by recommendations to address challenges.Results: The start of the trial was delayed which caused subsequent time schedule problems. The requirement for individual informed consent for a quality improvement project made the inclusion more prone to selection bias. Most units experienced major difficulties in including patients, leading to excluding two of the eight units from participation. This resulted in failing to include a similar number of patients in the control condition versus the intervention condition. Data on outcomes routinely collected in the electronic patient records were not accessible during the study, and appeared to be often missing during analyses.Conclusions: The stepped wedge, cluster randomized trial poses specific risks in the design and execution of research in real-life settings of which researchers should be aware to prevent negative consequences impacting the validity of their results. Valid conclusions on the effectiveness of the HELP in the Dutch hospital setting are hampered by the limited quantity and quality of routine clinical data in our pragmatic trial. Executing a stepped wedge design in a daily practice setting using routinely collected data requires specific attention to ethical review, flexibility, a spacious time schedule, the availability of substantial capacity in the research team and early checks on the data availability and quality.Trial Registration: Netherlands Trial Register, identifier: NTR3842 . Registered on 24 January 2013. [ABSTRACT FROM AUTHOR]

Background: Pregnant women with depression and/or anxiety prior to pregnancy are at higher risk of preterm birth, breastfeeding problems, postpartum depression, and disruption of the mother-infant attachment. It is well documented that exercise improves psychological well-being in nonpregnant subjects with symptoms of depression. However, in only a few small studies have researchers examined the effect of exercise on symptoms of depression among pregnant women. We hypothesize that physiotherapist-supervised group exercise for pregnant women at risk of antenatal depression increases their psychological well-being. This paper describes the study protocol of a randomized controlled trial (RCT) on a supervised group exercise intervention for pregnant women with a current or previous history of depression and/or anxiety.Methods/design: The RCT is being carried out at the Department of Obstetrics, Rigshospitalet, Copenhagen University Hospital, in the period 2016-2019. The inclusion criteria are pregnant women ≥18 years of age with depression and/or anxiety requiring treatment by a psychiatrist or a psychologist within the last 10 years and/or intake of antidepressants in the 3 months prior to conception and/or during pregnancy. The women must have appropriate Danish language skills, be pregnant with a single fetus, give written informed consent, and be at 17-22 gestational weeks when the intervention begins. The primary outcome is psychological well-being (the five-item World Health Organization Well-being Index). Secondary outcomes are symptoms of depression (Edinburgh Postnatal Depression Scale), functional ability (General Health Questionnaire), clinical symptoms of anxiety (State-Trait Anxiety Inventory), sleep quality and sleep disturbances (Pittsburgh Sleep Quality Index), and pregnancy and delivery outcomes. The intervention is supervised group exercise twice weekly for 12 weeks. The control group will receive standard antenatal care. On the basis of sample size calculation, a total of 300 women will be randomly assigned to either the intervention or the control group in a ratio of 1:1.Discussion: The trial is expected to contribute to the body of knowledge used in planning antenatal care for pregnant women at risk of depression.Trial Registration: ClinicalTrials.gov, NCT02833519 . Registered on 19 May 2016. [ABSTRACT FROM AUTHOR]

Background: Patient-Reported Outcome (PRO) measurement is a method for measuring perceptions of patients on their health and quality of life. The aim of this paper is to present the results of PRO measurements in total hip and knee replacement as routinely collected during 20 years of surgery in a university hospital setting.Methods: Data of consecutive patients between 1993 and 2014 were collected. Health outcomes were measured pre-surgery and at 3, 6, and 12 months post-surgery. Outcomes for hip replacement were measured with the Harris Hip Score (HHS) and Oxford Hip Score (OHS). Outcomes for knee replacement were measured with the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the Knee Society Score (KSS). A Visual Analog Scale (VAS) for pain was used. Absolute and relative Minimal Clinically Important Differences (MCID) were estimated. Generalized estimating equation analysis was used for estimating mean outcomes. Trends over time were analyzed.Results: The database contained 2,089 patients with hip replacement, and 704 patients with knee replacement. Mean HHS and OHS scores in primary hip replacement at 12 months post-surgery were 86.7 (SD: 14.5) and 41.1 (SD: 7.5) respectively. Improvements on the HHS based on absolute MCID was lower for revisions compared to primary hip replacements, with 72.4% and 87.0% respectively. Mean WOMAC and KSS scores in knee replacement at 12 months post-surgery were 21.5 (SD: 18.2) and 67.0 (SD: 26.4) respectively. Improvements based on absolute MCID were lowest for the KSS (62.6%) and highest for VAS pain (85.6%). Trend analysis showed a difference in 1 out of 24 comparisons in hip replacement and in 2 out of 9 comparisons in knee replacement.Conclusions: The functional status of a large cohort of patients significantly improved after hip and knee replacement based on routine data collection. Our study shows the feasibility of the routine collection of PRO data in patients with total hip and knee replacement. The use of PRO data provides opportunities for continuous quality improvement. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a common complication in the critically ill patients and associated with a substantial morbidity and mortality. Severe AKI may be associated with up to 60% hospital mortality. Over the years, renal replacement therapy (RRT) has emerged as the mainstay of the treatment for AKI. However, the exact timing of initiation of RRT for better patient outcome is still debatable with conflicting data from randomized controlled trials. Thus, a systematic review and meta-analysis was performed to assess the impact of "early" versus "late" initiation of RRT.Methods: All the published literature through the major databases including Medline/Pubmed, Embase, and Google Scholar were searched from 1970 to October 2016. Reference lists from the articles were reviewed to identify additional pertinent articles. Retrieved papers concerning the effect of "early/prophylactic" RRT versus "late/as and when required" RRT were reviewed by the authors, and the data were extracted using a standardized data collection tool. Randomized trials (RCTs) comparing early initiation of RRT or prophylactic RRT with late or as and when required RRT were included. The primary outcome measures were all cause mortality and dialysis dependence on day 90. The secondary outcome measures were: length of ICU stay, length of hospital stay, recovery of renal function and adverse events.Results: Of the 547 citation retrieved, full text of 44 articles was assessed for eligibility. Of these a total of 10 RCTs with 1,636 participants were included. All the trials were open label; six trials have unclear or high risk of bias for allocation concealment while four trials have low risk of bias for allocation concealment. There was a variable definition of early versus late in different studies. Thus, the definition of early or late was taken according to individual study definition. Compared to late RRT, there was no significant benefit of early RRT on day 30 mortality [6 studies; 1301 participants; RR, 0.92;95% CI: 0.76, 1.12); day 60 mortality [3 trials;1075 participants; RR, 0.94; 95% CI: 0.78, 1.14)]; day 90 mortality [3 trials; 555 participants; RR,0.94;95% CI: 0.67, 1.33)]; overall ICU or hospital mortality; dialysis dependence on day 90 [3 trials; (RR, 1.06; 95% CI:0.53, 2.12)]. There was no significant difference between length of ICU or hospital stay or recovery of renal functions. A subgroup analysis based on modality of RRT or mixed medical and surgical vs. surgical or based on severity of illness showed no difference in outcome measure. The trials with high or unclear risk of bias for allocation concealment showed benefit of early RRT (RR, 0.74; 95% CI: 0.59, 0.91) while the trials with low risk of bias for allocation concealment showed no difference in the mortality (RR, 1.02; 95% CI: 0.89, 1.17). Grade evidence generated for most of the outcomes was "low quality".Conclusion: This updated meta-analysis showed no added benefit of early initiation of RRT for patients with AKI. The grade evidence generated was of "low quality" and there was a high heterogeneity in the included trials.Prospero Registration Number: CRD42016043092 . [ABSTRACT FROM AUTHOR]

Background: Mothers In Motion (MIM), a community-based lifestyle behavioral intervention, was designed and conducted to help low-income overweight and obese young mothers prevent further weight gain via promotion of stress management, healthy eating, and physical activity. This paper presents intervention effect on body weight (primary outcome) and summarizes lessons learned.Methods: Participants (N = 612) were recruited from 7 Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) offices in Michigan and were individually randomized to an intervention n= 410) or a comparison (n =202) group (2: 1 ratio). During the 16-week intervention, intervention participants watched theory-based culturally sensitive videos (in DVD format) featuring peers from the target audience to learn skills for managing stress, eating healthier, and being more physically active. They also dialed into peer support group teleconferences to enhance skills learned in the videos and increase motivation for lifestyle behavioral changes. Body weight, the primary outcome, was measured at baseline, immediately after the 16-week intervention, and 3 months after the 16-week intervention. Intervention effect was tested via general linear mixed model for repeated measures, using baseline measures as adjusting covariates.Results: At baseline, the mean age of the participants was 28.5 ± 5.0 years (intervention: 28.4 ± 5.0, comparison: 28.9 ± 5.0); the mean body weight was 190.2 ± 1.4 lbs (intervention: 191.8 ± 30.0, comparison: 188.5 ± 29.1); and the mean body mass index (BMI) was 32.2 ± 4.4 (intervention: 32.2 ± 4.4, comparison: 31.7 ± 4.2). Of sample, 64.7% were obese. At 3 months after the 16-week intervention, no significant weight differences were found between the intervention (188.3 ± 10.6 lbs, BMI: 31.6 ± 1.8) and comparison groups (187.7 ± 10.6 lbs, BMI: 31.53 ± 1.8) when controlling for baseline body weight.Conclusions: This lifestyle behavioral intervention that focused on stress management, healthy eating and physical activity was not effective in helping low-income overweight and obese young mothers prevent further weight gain.Trial Registration: Clinical Trials NCT01839708 . This trial was registered retrospectively on February 28, 2013. [ABSTRACT FROM AUTHOR]