Clinical effectiveness of a rehabilitation program integrating exercise, self-management, and active coping strategies for chronic knee pain: a cluster randomized trial.

OBJECTIVE: Chronic knee pain is a major cause of disability and health care expenditure, but there are concerns about efficacy, cost, and side effects associated with usual primary care. Conservative rehabilitation may offer a safe, effective, affordable alternative. We compared the effectiveness of a rehabilitation program integrating exercise, self-management, and active coping strategies (Enabling Self-management and Coping with Arthritic Knee Pain through Exercise [ESCAPE-knee pain]) with usual primary care in improving functioning in persons with chronic knee pain. METHODS: We conducted a single-blind, pragmatic, cluster randomized controlled trial. Participants age >/=50 years, reporting knee pain for >6 months, were recruited from 54 inner-city primary care practices. Primary care practices were randomized to continued usual primary care (i.e., whatever intervention a participant's primary care physician deemed appropriate), usual primary care plus the rehabilitation program delivered to individual participants, or usual primary care plus the rehabilitation program delivered to groups of 8 participants. The primary outcome was self-reported functioning (Western Ontario and McMaster Universities Osteoarthritis Index physical functioning [WOMAC-func]) 6 months after completing rehabilitation. RESULTS: A total of 418 participants were recruited; 76 (18%) withdrew, only 5 (1%) due to adverse events. Rehabilitated participants had better functioning than participants continuing usual primary care (-3.33 difference in WOMAC-func score; 95% confidence interval [95% CI] -5.88, -0.78; P = 0.01). Improvements were similar whether participants received individual rehabilitation (-3.53; 95% CI -6.52, -0.55) or group rehabilitation (-3.16; 95% CI -6.55, -0.12). CONCLUSION: ESCAPE-knee pain provides a safe, relatively brief intervention for chronic knee pain that is equally effective whether delivered to individuals or groups of participants

Patient-reported outcomes of pain and physical functioning in neurofibromatosis clinical trials.

ObjectiveTumors and other disease complications of neurofibromatosis (NF) can cause pain and negatively affect physical functioning. To document the clinical benefit of treatment in NF trials targeting these manifestations, patient-reported outcomes (PROs) assessing pain and physical functioning should be included as study endpoints. Currently, there is no consensus on the selection and use of such measures in the NF population. This article presents the recommendations of the PRO group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration for assessing the domains of pain and physical functioning for NF clinical trials.MethodsThe REiNS PRO group reviewed and rated existing PRO measures assessing pain intensity, pain interference, and physical functioning using their systematic method. Final recommendations are based primarily on 4 main criteria: patient characteristics, item content, psychometric properties, and feasibility for clinical trials.ResultsThe REiNS PRO group chose the Numeric Rating Scale-11 (≥8 years) to assess pain intensity, the Pain Interference Index (6-24 years) and the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Scale (≥18 years) to evaluate pain interference, and the PROMIS Physical Functioning Scale to measure upper extremity function and mobility (≥5 years) for NF clinical trials.ConclusionsThe REiNS Collaboration currently recommends these PRO measures to assess the domains of pain and physical functioning for NF clinical trials; however, further research is needed to evaluate their use in individuals with NF. A final consensus recommendation for the pain interference measure will be disseminated in a future publication based on findings from additional published research

Neurocognitive outcomes in neurofibromatosis clinical trials

Neurofibromatosis type 1 (NF1) is associated with neurocognitive deficits that can impact everyday functioning of children, adolescents, and adults with this disease. However, there is little agreement regarding measures to use as cognitive endpoints in clinical trials. This article describes the work of the Neurocognitive Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. The goal of this committee is to identify standardized and specific cognitive assessment tools for use in NF clinical trials. The committee first identified cognitive domains relevant to NF1 and prioritized attention as the first domain of focus given prior and current trends in NF1 cognitive clinical trials. Performance measures and behavioral rating questionnaires of attention were reviewed by the group using established criteria to assess patient characteristics, psychometric properties, and feasibility. The highest rated tests underwent side-by-side comparison. The Digit Span subtest from the Wechsler scales was given the highest ratings of the performance measures due to its good psychometrics, feasibility, utility across a wide age range, and extensive use in previous research. The Conners scales achieved the highest ratings of the behavioral questionnaires for similar reasons. Future articles will focus on other cognitive domains, with the ultimate goal of achieving agreement for cognitive endpoints that can be used across NF clinical trials

Gaps in detailed knowledge of human papillomavirus (HPV) and the HPV vaccine among medical students in Scotland

<p>Background: A vaccination programme targeted against human papillomavirus (HPV) types16 and 18 was introduced in the UK in 2008, with the aim of decreasing incidence of cervical disease. Vaccine roll out to 12–13 year old girls with a catch-up programme for girls aged up to 17 years and 364 days was accompanied by a very comprehensive public health information (PHI) campaign which described the role of HPV in the development of cervical cancer.</p> <p>Methods: A brief questionnaire, designed to assess acquisition of knowledge of HPV infection and its association to cervical cancer, was administered to two different cohorts of male and female 1st year medical students (school leavers: 83% in age range 17–20) at a UK university. The study was timed so that the first survey in 2008 immediately followed a summer's intensive PHI campaign and very shortly after vaccine roll-out (150 students). The second survey was exactly one year later over which time there was a sustained PHI campaign (213 students).</p> <p>Results: We addressed three research questions: knowledge about three specific details of HPV infection that could be acquired from PHI, whether length of the PHI campaign and/or vaccination of females had any bearing on HPV knowledge, and knowledge differences between men and women regarding HPV. No female student in the 2008 cohort had completed the three-dose vaccine schedule compared to 58.4% of female students in 2009. Overall, participants’ knowledge regarding the sexually transmitted nature of HPV and its association with cervical cancer was high in both year groups. However, in both years, less than 50% of students correctly identified that HPV causes over 90% of cases of cervical cancer. Males gave fewer correct answers for these two details in 2009. In 2008 only around 50% of students recognised that the current vaccine protects against a limited subset of cervical cancer-causing HPV sub-types, although there was a significant increase in correct response among female students in the 2009 cohort compared to the 2008 cohort.</p> <p>onclusions: This study highlights a lack of understanding regarding the extent of protection against cervical cancer conferred by the HPV vaccine, even among an educated population in the UK who could have a vested interest in acquiring such knowledge. The intensive PHI campaign accompanying the first year of HPV vaccination seemed to have little effect on knowledge over time. This is one of the first studies to assess detailed knowledge of HPV in both males and females. There is scope for continued improvements to PHI regarding the link between HPV infection and cervical cancer.</p&gt

Satellite Tracking Reveals Long Distance Coastal Travel and Homing by Translocated Estuarine Crocodiles, Crocodylus porosus

Crocodilians have a wide distribution, often in remote areas, are cryptic, secretive and are easily disturbed by human presence. Their capacity for large scale movements is poorly known. Here, we report the first study of post-release movement patterns in translocated adult crocodiles, and the first application of satellite telemetry to a crocodilian. Three large male Crocodylus porosus (3.1–4.5 m) were captured in northern Australia and translocated by helicopter for 56, 99 and 411 km of coastline, the last across Cape York Peninsula from the west coast to the east coast. All crocodiles spent time around their release site before returning rapidly and apparently purposefully to their capture locations. The animal that circumnavigated Cape York Peninsula to return to its capture site, travelled more than 400 km in 20 days, which is the longest homeward travel yet reported for a crocodilian. Such impressive homing ability is significant because translocation has sometimes been used to manage potentially dangerous C. porosus close to human settlement. It is clear that large male estuarine crocodiles can exhibit strong site fidelity, have remarkable navigational skills, and may move long distances following a coastline. These long journeys included impressive daily movements of 10–30 km, often consecutively

Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial

<p>Abstract</p> <p>Background</p> <p>Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants.</p> <p>Methods/Design</p> <p>The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis.</p> <p>Discussion</p> <p>This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants.</p> <p>Trial registration number</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2768">NTR2768</a></p

A pilot study to assess the feasibility and impact of a brief motivational intervention on problem drug and alcohol use in adult mental health inpatient units: study protocol for a randomized controlled trial.

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly creditedBACKGROUND: Substance misuse in those with severe mental health problems is common and associated with poor engagement in treatment and treatment outcomes. Up to 44% of those admitted into psychiatric inpatient facilities have coexisting substance-misuse problems. However, this is not routinely addressed as part of their treatment plan. A mental health admission may present a window of opportunity for inpatients to reevaluate the impact of their substance use. This study will aim to evaluate the effectiveness of a targeted brief motivational intervention in improving engagement in treatment and to assess how feasible and acceptable this intervention is to inpatients and staff as a routine intervention. METHODS/DESIGN: This randomized controlled trial will use concealed randomization; blind, independent assessment of outcome at 3 months; characterization of refusers and dropouts; and be analyzed according to the intention-to-treat principle. After baseline assessments, eligible participants will be randomized either to the Brief Integrated Motivational Intervention plus Treatment As Usual, or Treatment as Usual alone. Eligible participants will be those who are new admissions; >18 years; ICD-10 diagnosis of -schizophrenia or related disorder, bipolar affective disorder, recurrent depressive disorder, and DSM-IV diagnosis of substance abuse or dependence over the last 3 months. The primary outcome is engagement in treatment for substance misuse, and secondary outcomes include readiness to change substance misuse together with a cost-effectiveness analysis. Qualitative interviews with staff and participants will assess the acceptability of the intervention. DISCUSSION: This pilot randomized trial will provide the first robust evidence base for inpatient care of people with severe mental health problems and co-morbid substance misuse and provide the groundwork for confirmatory trials to evaluate a potentially feasible, cost-effective, and easy-to-implement treatment option that may be readily integrated into standard inpatient and community-based care. TRIAL REGISTRATION: ISRCTN43548483 Date of ISRCTN assignation: 4/17/2014.This study is funded by the National Institute for Health Research (NIHR) Research for Patient Benefit Programme: PB-PG-1010-23138. It is sponsored by Birmingham & Solihull Mental Health NHS Foundation Trust and the University of Birmingham. This manuscript presents independent research funded by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (number PB-PG-1010-23138)

High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers

BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly proliferative triple-negative breast cancer (TNBC) cell lines with compromised spindle assembly checkpoint activity. BOS172722 synergizes with paclitaxel to induce gross chromosomal segregation defects caused by MPS1 inhibitor-mediated abrogation of the mitotic delay induced by paclitaxel treatment. In in vivo pharmacodynamic experiments, BOS172722 potently inhibits the spindle assembly checkpoint induced by paclitaxel in human tumor xenograft models of TNBC, as measured by inhibition of the phosphorylation of histone H3 and the phosphorylation of the MPS1 substrate, KNL1. This mechanistic synergy results in significant in vivo efficacy, with robust tumor regressions observed for the combination of BOS172722 and paclitaxel versus either agent alone in long-term efficacy studies in multiple human tumor xenograft TNBC models, including a patient-derived xenograft and a systemic metastasis model. The current target indication for BOS172722 is TNBC, based on their high sensitivity to MPS1 inhibition, the well-defined clinical patient population with high unmet need, and the synergy observed with paclitaxel