Search

Background: Early language delay is exacerbated by social disadvantage. Factors such as parents' low levels of literacy, confidence and self‐perception can affect the capacity to act on advice received, critical to empowerment. Methods used to achieve successful health outcomes in socially disadvantaged clinical populations may need enhancing. Aims: To compare the impact of standard parent‐based intervention (PBI) to enhanced PBI for young children with speech, language and communication needs (SCLN) and their families living in more socially disadvantaged populations. Methods and Procedures: A multicentre clustered blind randomised controlled trial was used to compare the effect of parent‐based group interventions to improve early language development with children (mean age 27.5 months) from more socially disadvantaged populations with an expressive vocabulary of 40 or less single words. Intervention sessions were delivered by a speech and language therapist, over a 20‐week period. Participants received one of two interventions: (1) Standard Care – indirect group PBI – (PBI) (2) Enhanced Care: indirect group enhanced PBI – (EPBI). Both standardised and non‐standardised measures were used as outcomes. Parent engagement in the intervention was captured through analysis of attendance and the Parent Activation Measure – Speech & Language Therapy (PAM‐SLT) (Insignia Health, 2014). The PAM measures a person's knowledge, skills and confidence to manage their own health and well‐being (NHS England, 2018). In this study, activation referred to parents' knowledge, skills and confidence to manage their child's language development. Outcomes and Results: One hundred fifty‐five participants were randomised at baseline. Children in both groups made significant improvements in the outcome on MacArthur‐Bates Communicative Development Inventories Sentence Length, from pre‐intervention to post‐intervention and 6 months post‐intervention (p < 0.05). Changes in vocabulary and expressive language skills were more equivocal, showing wide variation in confidence intervals for both groups. Where parents attended at least one intervention session almost all effect sizes were in favour of the EPBI intervention. Parents' activation levels significantly increased for both groups (EPBI p < 0.001, PBI p = 0.003), with a moderate effect size in favour of EPBI (Hedges' G 0.37, confidence interval –0.02 to 0.76), although wide variation was found. Conclusions and Implications: This trial provides some evidence of facilitating the language development of children with SLCN from more socially disadvantaged areas through supporting caregivers. However, we found variation in outcomes; some children made excellent progress, whilst others did not. Further exploration of parent engagement and its relationship to child language outcomes will be valuable to understanding more about mechanisms of change in interventions that involve parents. WHAT THIS PAPER ADDS: What is already known on the subject: Speech, language and communication needs (SLCN) have a knock‐on effect on emotional well‐being, school readiness, literacy and school attainment, putting children at increased risk of long‐term consequences such as poor literacy, mental health problems and unemployment. In disadvantaged areas, the prevalence of language difficulties is higher than elsewhere. Factors such as parents' low levels of literacy, confidence and self‐perception can affect the capacity to act on advice received, critical to empowerment. What this paper adds to existing knowledge: Children with SLCN from more socially disadvantaged areas can make improvements in their language development through parent intervention, although wide individual variation was found. There was some evidence that children achieve better outcomes with EPBI, which employed an interagency collaborative approach. Parent's engagement (activation levels) increased significantly over time with intervention, with the increase twice as big for EPBI. What are the potential or actual clinical implications of this work?: This trial provides some evidence that it is possible to facilitate the language development of children from more socially disadvantaged areas through supporting their caregivers. Further research would be useful to determine whether increases in parent engagement are related to adherence to intervention and change in child outcomes. [ABSTRACT FROM AUTHOR]

Background: Very young children from lower socioeconomic status (SES) backgrounds often show poorer language development. Whilst there have been attempts to provide early intervention programmes, these sometimes miss the most disadvantaged groups. Aims: This report presents preliminary feasibility and effectiveness data for a novel language intervention designed for parents of toddlers in the United Kingdom. Methods and Procedures: In total, 43 UK families of 2–4‐year‐olds were recruited to the study, half of whom completed an 8‐week course (Tots Talking) focussed on parent interaction, and half of whom acted as wait‐list controls. Results and Outcomes: Results suggest that such programmes are feasible for families with 86% staying in the intervention. In addition, greater changes in underlying communication skills such as joint attention and gesture were evident compared to wait‐list controls. Conclusions and Implications: We conclude that pre‐verbal skills may be more important to measure as initial outcomes than language or vocabulary change in this population. What This Paper Adds: What is already known on the subject: Children from lower socioeconomic status (SES) backgrounds are at higher risk of communication difficulties and there is a need for community intervention programmes for very young children. What this study adds: This study suggests that such programmes can be feasible and effective, but that very early/basic communicative skills (such as joint attention) may be boosted first rather than language or vocabulary. What are the clinical implications of this work?: Children's centres and other community services could feasibly run short parent facing courses emphasising contingent communication in low SES families and other diverse groups. These may be more successful run with younger preschoolers. Joint attention may be a better focus of intervention before expecting vocabulary or language change. Community health professionals may find this information useful in referring and supporting families in need. [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.)

Aim: To examine the efficacy of Hand-Arm Bimanual Intensive Therapy (HABIT) on daily functioning, unimanual dexterity, and bimanual performance of children with bilateral cerebral palsy (CP) compared with customary care.Method: Forty-one children with bilateral CP, aged 4 to 16 years, classified in levels I to III of the Manual Ability Classification System, were randomly assigned to HABIT (90h) (n=21) or to customary care (4.5h) (n=20). Participants' daily functioning (Pediatric Evaluation of Disability Inventory [PEDI], Canadian Occupational Performance Measure [COPM]), unimanual dexterity (Jebsen-Taylor Test of Hand Function, Box and Blocks Test [BBT]), and bimanual performance (Both Hands Assessment) were assessed pre-, post-, and 6 months after the intervention. Linear mixed-effects models were used for inferential analysis.Results: Children participating in HABIT showed greater improvements in daily functioning (COPMperformance : χ12 =9.50, p<0.01; COPMsatisfaction : χ12 =5.07, p<0.05; PEDIfunctional skills : χ12 =6.81, p<0.01; PEDIcaregiver assistance : χ12 =6.23, p<0.05) and in the dexterity of the dominant hand (BBT: χ12 =3.99, p<0.05) compared with children maintaining customary care. Group or time effects did not explain any variance in bimanual performance or in the dexterity of the non-dominant hand.Interpretation: HABIT may be beneficial for children with bilateral CP, with benefits evidenced for daily functioning outcomes.What This Paper Adds: Hand-Arm Bimanual Intensive Therapy (HABIT) improved daily functioning of children with bilateral cerebral palsy (CP). Bimanual performance, measured by the Both Hands Assessment, did not change after HABIT in children with bilateral CP. Children with asymmetric and symmetric hand use exhibited similar improvements after HABIT. [ABSTRACT FROM AUTHOR]

We investigated the effects of readymade versus self‐generated graphic organizers (GOs) on learning, comparing the performances of undergraduates (N = 81) tasked with learning a multimedia document. This document was either presented on its own (control group), with a readymade GO, or with a blank GO that students had to fill in either before or during the learning of the document. In line with previous research, adding a readymade GO increased students' memorization and transfer scores, compared with controls. By displaying the main ideas in the text and their hierarchical relations, GOs act as visual aids to learning. Results showed that self‐generating a GO was no more beneficial than viewing a readymade GO when students were placed in a dual‐task situation (generation + learning). However, when the students' information processing was guided by sequencing these tasks (generation then learning), they outperformed the control and readymade groups on memorization and comprehension. Lay Description: What is already known about this topic: Graphic organizers (GOs) consist in visual displays showing the main ideas of a text and their interrelations.Adding GOs to pedagogical document have been shown to improve students' learning.However, self‐generating GOs has been proven to be detrimental for learning in several studies. What this paper adds: In previous studies, self‐generation of graphic organizers (GOs) have often been carried out while learning, however this task should be separated from the learning task.In the present study, students' learning performances increased when the self‐generated task was separated from the learning task compared to a condition with a readymade GO.These benefits on learning were not observed when the self‐generated activity was not guided. Implications for practitioners: Graphic organizers gathering all the key elements of a multimedia document and highlighting the structure of this document should be used in order to increase students' learning.Students should not be placed in double‐task situation when learning from a pedagogical document.In‐task guidance should be provided when self‐generative tasks are performed. [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.)

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.)

As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a novel purified reconstituted bilayer membrane (PRBM) to the standard of care (SOC) in the treatment of non‐healing DFUs. This study included 105 patients who were randomized to either of two treatment groups (n = 54 PRBM; n = 51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n = 47 PRBM; n = 33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing, quality of life, and cost to closure. The DFUs that had been treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, p = 0.00004, PP: 92% vs. 67%, p = 0.005). Wounds treated with PRBM also healed significantly faster than those treated with SOC with a mean of 42 versus 62 days for SOC (p = 0.00074) and achieved a mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p = 0.0023). There were no adverse events or serious adverse events that were related to either the PRBM or the SOC. In comparison to the SOC, DFUs healed faster when treated with PRBM. Thus, the use of this PRBM is an effective option for the treatment of chronic DFUs. [ABSTRACT FROM AUTHOR]

Background: Micrographia occurs in approximately 60% of people with Parkinson's disease (PD). Although handwriting is an important task in daily life, it is not clear whether relearning and consolidation (ie the solid storage in motor memory) of this skill is possible in PD. The objective was to conduct for the first time a controlled study into the effects of intensive motor learning to improve micrographia in PD.Methods: In this placebo-controlled study, 38 right-handed people with PD were randomized into 2 groups, receiving 1 of 2 equally time-intensive training programs (30 min/day, 5 days/week for 6 weeks). The experimental group (n = 18) performed amplitude training focused at improving writing size. The placebo group (n = 20) received stretch and relaxation exercises. Participants' writing skills were assessed using a touch-sensitive writing tablet and a pen-and-paper test, pre- and posttraining, and after a 6-week retention period. The primary outcome was change in amplitude during several tests of consolidation: (1) transfer, using trained and untrained sequences performed with and without target zones; and (2) automatization, using single- and dual-task sequences.Results: The group receiving amplitude training significantly improved in amplitude and variability of amplitude on the transfer and automatization task. Effect sizes varied between 7% and 17%, and these benefits were maintained after the 6-week retention period. Moreover, there was transfer to daily life writing.Conclusions: These results show automatization, transfer, and retention of increased writing size (diminished micrographia) after intensive amplitude training, indicating that consolidation of motor learning is possible in PD. © 2016 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Resistance exercise training is effective to counteract the adverse effects of androgen deprivation therapy (ADT) on body composition, muscle mass and leg strength in prostate cancer patients (PCa). However, it is unknown whether these effects can be autonomously maintained after cessation of the supervised program. Sixty‐eight PCa patients on ADT were included. The exercise intervention group (EX, n = 37) performed 20 weeks of supervised resistance exercise training. Thereafter, patients were advised to autonomously continue exercise training. The control group (CON, n = 31) only received usual care. Outcome measures were compared between baseline and after 1 year. Changes during the intervention (baseline vs. 20 weeks) and follow‐up period (20 weeks vs. 1 year) were descriptively explored. In EX, 83% reported to have continued exercise training themselves. After 1 year, fat mass gains were attenuated in EX compared to CON (1.2 ± 2.6 and 2.8 ± 1.9 kg, respectively; time × treatment effect p = 0.032). The fat percentage increased, and lean mass and quadriceps muscle cross‐sectional area decreased over time, with no differences between groups (overall 1.6 ± 2.1%, −0.7 ± 2.3 kg and −2.2 ± 2.9 cm2, respectively; time effects, all p < 0.05). For muscle strength, an increase of ∼5% in EX was observed, significantly different from the ∼10% decrease in CON (p < 0.001). Subsequent analyses showed that the initial exercise training‐obtained gains in lean mass, muscle mass and strength in EX compared to CON, declined during the follow‐up period. In conclusion, PCa patients on ADT are not capable to autonomously maintain the exercise‐obtained gains of a 20‐week supervised training program over a subsequent 1‐year period. Highlights: ADT for prostate cancer results in many side effects, including muscle mass lossA supervised resistance exercise training program can counteract many side effectsAfter cessation of the supervised program, exercise benefits are not effectively preservedMore focus on sustainability of exercise programs during ADT is required [ABSTRACT FROM AUTHOR]

A novel autologous heterogeneous skin construct (AHSC) was previously shown to be effective versus standard of care (SOC) treatment in facilitating complete wound healing of Wagner 1 diabetic foot ulcers in an interim analysis of 50 patients previously published. We now report the final analysis of 100 patients (50 per group), which further supports the interim analysis findings. Forty‐five subjects in the AHSC treatment group received only one application of the autologous heterogeneous skin construct, and five received two applications. For the primary endpoint at 12 weeks, there were significantly more diabetic wounds closed in the AHSC treatment group (35/50, 70%) than in the SOC control group (17/50, 34%) (p = 0.00032). A significant difference in percentage area reduction between groups was also demonstrated over 8 weeks (p = 0.009). Forty‐nine subjects experienced 148 adverse events: 66 occurred in 21 subjects (42%) in the AHSC treatment group versus 82 in 28 SOC control group subjects (56.0%). Eight subjects were withdrawn due to serious adverse events. Autologous heterogeneous skin construct was shown to be an effective adjunctive therapy for healing Wagner 1 diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

To evaluate the status of a 7‐month phase 3 study conducted to test the effect of intramuscular injections of VM202 (ENGENSIS), a plasmid DNA encoding human hepatocyte growth factor, into the calf muscles of chronic nonhealing diabetic foot ulcers with concomitant peripheral artery disease. The phase 3 study, originally aimed to recruit 300 subjects, was discontinued because of slow patient recruitment. An unprespecified interim analysis was performed for the 44 subjects enrolled to assess the status and determine the future direction. Statistical analyses were carried out for the Intent‐to‐Treat (ITT) population and separately for subjects with neuroischemic ulcers, using a t‐test and Fisher's exact test. A logistic regression analysis was also conducted. VM202 was safe and potentially should have benefits. In the ITT population (N = 44), there was a positive trend toward closure in the VM202 group from 3 to 6 months but with no statistical significance. Levels of ulcer volume or area were found to be highly skewed between the placebo and VM202 groups. Forty subjects, excluding four outliers in both arms, showed significant wound‐closing effects at month 6 (P =.0457). In 23 patients with neuroischemic ulcers, the percentage of subjects reaching complete ulcer closure was significantly higher in the VM202 group at months 3, 4, and 5 (P =.0391,.0391, and.0361). When two outliers were excluded, a significant difference was evident in months 3, 4, 5, and 6 (P =.03 for all points). A potentially clinically meaningful 0.15 increase in Ankle‐Brachial Index was observed in the VM202 group at day 210 in the ITT population (P =.0776). Intramuscular injections of VM202 plasmid DNA to calf muscle may have promise in the treatment of chronic neuroischemic diabetic foot ulcers (DFUs). Given the safety profile and potential healing effects, continuing a larger DFU study is warranted with modifications of the current protocol and expansion of enrolling sites. [ABSTRACT FROM AUTHOR]

Summary: Objectives: Childhood obesity increases risk factors related to metabolic diseases. Watermelon's bioactive components can help reduce these risk factors. However, no study has investigated the effects of whole watermelon including both the flesh and rind or have assessed the impacts of any form of watermelon on children with overweight or obesity. The goal of this study was to examine the effects of whole‐blenderized watermelon (BWM) consumption on cardiometabolic risk factors. Methods: A randomized, cross‐over clinical design was implemented. Boys and girls ages 10–17 years with overweight or obesity (BMI ≥ 85th percentile) consumed one cup of BWM or an isocaloric sugar‐sweetened beverage (control) every day for 8 weeks with a 4‐week washout between trials. Anthropometrics, dietary, biochemical and clinical measures were obtained before and at the end of each trial. Results: A total of 17 participants completed the study. Eight weeks of BWM intake significantly decreased BMI (p = 0.032), BMI percentile (BMIP) (p = 0.038), body fat percentage (p = 0.036), and haemoglobin A1c (HbA1c) (p = 0.012) compared to the sugar‐sweetened beverage. Sugar‐sweetened beverage consumption increased BMIP (p = 0.014) compared to baseline. No significant differences were observed for inflammation, blood glucose, insulin, lipids, liver function enzymes, and satiety hormones. Conclusions: The results support that BWM consumption improved some cardiometabolic risk factors including BMI, BMIP, body fat, and HbA1c. Watermelon is a potential alternative to unhealthful snacks for improving anthropometry and some risk factors related to obesity in children. [ABSTRACT FROM AUTHOR]

Background: 5%–10% children and young people (CYP) experience specific phobias that impact daily functioning. Cognitive Behaviour Therapy (CBT) is recommended but has limitations. One Session Treatment (OST), a briefer alternative incorporating CBT principles, has demonstrated efficacy. The Alleviating Specific Phobias Experienced by Children Trial (ASPECT) investigated the non‐inferiority of OST compared to multi‐session CBT for treating specific phobias in CYP. Methods: ASPECT was a pragmatic, multi‐center, non‐inferiority randomized controlled trial in 26 CAMHS sites, three voluntary agency services, and one university‐based CYP well‐being service. CYP aged 7–16 years with specific phobia were randomized to receive OST or CBT. Clinical non‐inferiority and a nested cost‐effectiveness evaluation was assessed 6‐months post‐randomization using the Behavioural Avoidance Task (BAT). Secondary outcome measures included the Anxiety Disorder Interview Schedule, Child Anxiety Impact Scale, Revised Children's Anxiety Depression Scale, goal‐based outcome measure, and EQ‐5DY and CHU‐9D, collected blind at baseline and six‐months. Results: 268 CYPs were randomized to OST (n = 134) or CBT (n = 134). Mean BAT scores at 6 months were similar across groups in both intention‐to‐treat (ITT) and per‐protocol (PP) populations (CBT: 7.1 (ITT, n = 76), 7.4 (PP, n = 57), OST: 7.4 (ITT, n = 73), 7.6 (PP, n = 56), on the standardized scale‐adjusted mean difference for CBT compared to OST ‐0.123, 95% CI −0.449 to 0.202 (ITT), mean difference −0.204, 95% CI −0.579 to 0.171 (PP)). These findings were wholly below the standardized non‐inferiority limit of 0.4, suggesting that OST is non‐inferior to CBT. No between‐group differences were found on secondary outcomes. OST marginally decreased mean service use costs and maintained similar mean Quality Adjusted Life Years compared to CBT. Conclusions: One Session Treatment has similar clinical effectiveness to CBT for specific phobias in CYP and may be a cost‐saving alternative. [ABSTRACT FROM AUTHOR]

The most common pressure ulcer associated with medical devices in the ICU is pressure injury associated with the endotracheal tube. We aimed to scrutinise the effects of two different techniques of endotracheal tube securement used in the ICU on the occurrence of pressure ulcers. This randomised clinical trial was conducted in 60 patients, 30 of which were intervention and 30 experimental, admittedin the ICU of a training and research hospitaldata were collected using the descriptive and clinical characteristics from the Braden Scale for predicting Pressure Sore Risk, the Pressure Ulcer Scale for healing, The International Staging System for Pressure Injuries and the Eilers Oral Assessment Guide. Based on the Braden Scale scores of the patients, we found that 98.3% of the cases were in the high‐risk group before and after the intervention. We also found that the recovery was higher among patients in whom the bandage fixation method was applied compared to those in whom the fixation was done with an endotracheal tube holder. [ABSTRACT FROM AUTHOR]

Background: Pain is one of the main reasons to present to emergency departments (EDs). Opioids are indispensable for acute pain management but are associated with side effects, misuse, and dependence. The aim of this study was to test whether a single dose of intravenous (IV) acetaminophen (paracetamol) can reduce the use of morphine for pain relief and/or morphine‐related adverse events (AEs). Methods: ED patients >18 years with acute pain (i.e., Numeric Rating Scale [NRS] > 4) were screened for eligibility. Patients with analgesia in the past 6 h, chronic pain, or clinical instability were excluded. Patients were randomized in a 1:1 ratio to receive either morphine 0.1 mg/kg and 1 g acetaminophen IV or morphine 0.1 mg/kg and placebo IV. The intervention was double‐blinded. Additional morphine 0.05 mg/kg IV was administered every 15 minutes until pain relief (defined as NRS < 4) and whether the pain recurred. The primary outcome was the mean morphine dose for pain relief. Secondary outcomes were the total amount of morphine given, time to achieve pain relief, and AEs. Results: A total of 220 patients were randomized and 202 evaluated for the primary outcome. The mean morphine dose for pain relief was similar in both groups (acetaminophen 0.15 mg ± 0.07 mg/kg, placebo 0.16 ± 0.07 mg/kg). There were no differences in the total amount of morphine given (acetaminophen 0.19 ± 0.09 mg/kg, placebo 0.19 ± 0.1 mg/kg), the time to achieve pain relief (acetaminophen 30 min [95% CI 17–31 min], placebo 30 min [95% CI 30–35 min]), and the frequency of AEs (overall 27.4%). Time to pain recurrence did not differ significantly between the groups (hazard ratio 1.23 [0.76–1.98], p = 0.40). Conclusions: In ED patients, acetaminophen had no additional effect on pain control or morphine‐sparing effect at the time of first morphine administration. Titrated morphine with the algorithm used was highly effective, with 80% of all patients reporting pain relief within 60 min of starting therapy. [ABSTRACT FROM AUTHOR]

Background: Neurofeedback is considered a promising intervention for the treatment of attention‐deficit hyperactivity disorder (ADHD). NEWROFEED is a prospective, multicentre, randomized (3:2), reference drug‐controlled trial in children with ADHD aged between 7 and 13 years. The main objective of NEWROFEED was to demonstrate the noninferiority of personalized at‐home neurofeedback (NF) training versus methylphenidate in the treatment of children with ADHD. Methods: The NF group (n = 111) underwent eight visits and two treatment phases of 16 to 20 at‐home sessions with down‐training of the theta/beta ratio (TBR) for children with high TBR and enhancing the sensorimotor rhythm (SMR) for the others. The control group (n = 67) received optimally titrated long‐acting methylphenidate. The primary endpoint was the change between baseline and endpoint in the Clinician ADHD‐RS‐IV total score in the per‐protocol population (90 NF/59 controls). Trial registration: US National Institute of Health, ClinicalTrials.gov #NCT02778360. Results: Our study failed to demonstrate noninferiority of NF versus methylphenidate (mean between‐group difference 8.09 90% CI [8.09; 10.56]). However, both treatment groups showed significant pre–post improvements in core ADHD symptoms and in a broader range of problems. Reduction in the Clinician ADHD‐RS‐IV total score between baseline and final visit (D90) was 26.7% (SMD = 0.89) in the NF and 46.9% (SMD = 2.03) in the control group. NF effects increased whereas those of methylphenidate were stable between intermediate and final visit. Conclusions: Based on clinicians' reports, the effects of at‐home NF were inferior to those of methylphenidate as a stand‐alone treatment. [ABSTRACT FROM AUTHOR]

Buprenorphine was registered in Australia as a maintenance and detoxification agent for the management of opioid dependence in November, 2000, and became widely available in August, 2001. This paper provides an overview of key developments in the introduction of buprenorphine treatment in Australia, with an emphasis upon the delivery of services in community-based (primary care) settings. A central study in this work was the Buprenorphine Implementation Trial (BIT), a randomized, controlled trial comparing buprenorphine and methadone maintenance treatment delivered under naturalistic conditions by specialist and community-based service providers (general practitioners and community pharmacists) in 139 subjects across nineteen treatment sites. In addition to conventional patient outcome measures (treatment retention, drug use, psychosocial functioning, and cost effectiveness), the BIT study also involved the development and evaluation of clinical guidelines, training programs for clinicians, and client literature, which are described here. Integration of treatment systems (methadone with buprenorphine, specialist and primary-care programs) and factors thought to be important in the uptake of buprenorphine treatment in Australia since registration are discussed. [ABSTRACT FROM AUTHOR]

Background: Federal exception from informed consent (EFIC) procedures allow studies to enroll patients with time‐sensitive, life‐threatening conditions when written consent is not feasible. Our objective was to compare enrollment rates with and without EFIC in a trial of tranexamic acid (TXA) for children with hemorrhagic injuries. Methods: We conducted a four‐center randomized controlled pilot and feasibility trial evaluating TXA in children with severe hemorrhagic brain and/or torso injuries. We initiated the trial enrolling patients without EFIC. After 3 months of enrollment, we met our a priori futility threshold and paused the trial to incorporate EFIC procedures and obtain regulatory approval. We then restarted the trial allowing EFIC if the guardian was unable to provide timely written consent. We used descriptive statistics to compare characteristics of eligible patients approached with and without EFIC procedures. We also calculated the time delay to restart the trial using EFIC. Results: We enrolled one of 15 (6.7%) eligible patients (0.17 per site per month) prior to using EFIC procedures. Of the 14 missed eligible patients, seven (50%) were not enrolled because guardians were not present or were injured and unable to provide written consent. After obtaining approval for EFIC, we enrolled 30 of 48 (62.5%) eligible patients (1.34 per site per month). Of these 30 patients, 22 (73.3%) were enrolled with EFIC. Of the 22, no guardians refused written consent after randomization. There were no significant differences in the eligibility rate and patient characteristics enrolled with and without EFIC procedures. Across all sites, the mean delay to restart the trial using EFIC procedures was 12 months. Conclusions: In a multicenter trial of severely injured children, the use of EFIC procedures greatly increased the enrollment rate and was well accepted by guardians. Initiating the trial without EFIC procedures led to a significant delay in enrollment. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the chronic effects of green tea (GT) extract and resistance training (RT) on ambulatory and office blood pressure (BP), heart rate (HR), and rate-pressure product (RPP) in a sample of Iranian women with high-normal/stage 1 hypertension. Forty-four middle-aged sedentary women participated in this randomized, double-blind, placebo-controlled study. They were randomly assigned to one of four groups: GT and RT (GR, n = 11), RT (n = 10), GT (n = 10), or control (n = 13). Three weeks of GT consumption were followed by six weeks of the interaction with RT. GR and RT groups performed two circuits of RT at %50 of 1RM two days per week. RT and control groups also received placebo (maltodextrin) with the same timing. The changes of each variable from baseline to post-intervention were compared between the groups using the ANOVA test, and effect size (ES) statistic was also calculated. In comparison with the control group, significant reductions were found for office systolic BP (SBP, 8%, ES = 1.22), and 24 h-SBP (5%, ES = 1.2) in the RT group. However, GR group showed significant decreases in office SBP (10.5%, ES = 1.45), mean BP (8%, ES = 1.11), RPP (13%, ES = 1.47), 24 h-SBP (5%, ES = 1.21), and 24 h-RPP (10%, ES = 1.15). The interaction of regular RT and GT consumption seems to induce more beneficial effects on some important parameters including MBP and RPP when compared to RT or GT alone. [ABSTRACT FROM AUTHOR]

Objective: To participate in shared decision making (SDM), patients need to understand their options and develop trust in their own decision‐making abilities. Two experiments investigated the potential of decision aids (DAs) in preparing patients for SDM by raising awareness of preference‐sensitivity (Study 1) and showing possible personal motives for decision making (Study 2) in addition to providing information about the treatment options. Methods: Participants (Study 1: N = 117; Study 2: N = 217) were put into two scenarios (Study 1: cruciate ligament rupture; Study 2: contraception), watched a consultation video and were randomized into one of three groups where they received additional information in the form of (a) narrative patient testimonials; (b) non‐narrative decision strategies; and (c) an unrelated text (control group). Results: Participants who viewed the patient testimonials or decision strategies felt better prepared for a decision (Study 1: P <.001, ηP2 = 0.43; Study 2: P <.001, ηP2 = 0.57) and evaluated the decision‐making process more positively (Study 2: P <.001, ηP2 = 0.13) than participants in the control condition. Decision certainty (Study 1: P <.001, ηP2 = 0.05) and satisfaction (Study 1: P <.001, ηP2 = 0.11; Study 2: P =.003, d = 0.29) were higher across all conditions after watching the consultation video, and certainty and satisfaction were lower in the control condition (Study 2: P <.001, ηP2 = 0.05). Discussion: Decision aids that explain preference‐sensitivity and personal motives can be beneficial for improving people's feelings of being prepared and their perception of the decision‐making process. To reach decision certainty and satisfaction, being well informed of one's options is particularly relevant. We discuss the implications of our findings for future research and the design of DAs. [ABSTRACT FROM AUTHOR]

Background and aims: Culturally relevant and feasible interventions are needed to address limited professional resources in sub‐Saharan Africa for behaviorally treating the dual epidemics of HIV and alcohol use disorder. This study tested the efficacy of a cognitive–behavioral therapy (CBT) intervention to reduce alcohol use among HIV‐infected outpatients in Eldoret, Kenya. Design Randomized clinical trial. Setting: A large HIV outpatient clinic in Eldoret, Kenya, affiliated with the Academic Model Providing Access to Healthcare collaboration. Participants: A total of 614 HIV‐infected outpatients [312 CBT; 302 healthy life‐styles (HL); 48.5% male; mean age: 38.9 years; mean education 7.7 years] who reported a minimum of hazardous or binge drinking. Intervention and comparator: A culturally adapted six‐session gender‐stratified group CBT intervention compared with HL education, each delivered by paraprofessionals over six weekly 90‐minute sessions with a 9‐month follow‐up. Measurements Primary outcome measures were percentage of drinking days (PDD) and mean drinks per drinking day (DDD) computed from retrospective daily number of drinks data obtained by use of the time‐line follow‐back from baseline to 9 months post‐intervention. Exploratory analyses examined unprotected sex and number of partners. Findings Median attendance was six sessions across condition. Retention at 9 months post‐intervention was high and similar by condition: CBT 86% and HL 83%. PDD and DDD marginal means were significantly lower in CBT than HL at all three study phases. Maintenance period, PDD – CBT = 3.64 (0.696), HL = 5.72 (0.71), mean difference 2.08, 95% confidence interval (CI) = 0.13 – 4.04; DDD – CBT = 0.66 (0.96), HL = 0.98 (0.098), mean difference = 0.31, 95% CI = 0.05 – 0.58. Risky sex decreased over time in both conditions, with a temporary effect for CBT at the 1‐month follow‐up. Conclusions: A cognitive–behavioral therapy intervention was more efficacious than healthy lifestyles education in reducing alcohol use among HIV‐infected Kenyan outpatient drinkers. [ABSTRACT FROM AUTHOR]

Background: This study was conducted to assess the clinical, immunological, and patient-centered outcomes of microcurrent electrotherapy on palatal wound healing.Methods: This was a parallel, double-masked randomized clinical trial, in which 53 patients with ridge preservation indications were selected and randomly assigned to one of two groups. In the control (sham) group (n = 27), palatal wounds, after free gingival grafts (FGG) harvest, received sham application of electrotherapy. In the test (electrotherapy treatment [EE]) group (n = 26), palatal wounds, after FGG harvest, received application of microcurrent electrotherapy protocol. Clinical parameters, patient-centered outcomes, and inflammatory markers were evaluated, up to 90 days postoperatively.Results: The EE group achieved earlier wound closure (P <0.001) and epithelialization (P <0.05; P = 0.03) at 7 and 14 days after harvest when compared with the sham group. Painful symptomatology was reported less frequently in the EE group than in the sham group at 3-day follow-up (P = 0.008). Likewise, an improvement in Oral Health Impact Profile was reported 2 days after the procedure by the EE group (P = 0.04). In addition, favorable modulation of inflammatory wound healing markers occurred when electrotherapy was applied.Conclusion: Within the limits of the present study, it can be concluded that the use of a low-intensity electrotherapy protocol may accelerate palatal wound healing and decrease patient discomfort after FGG harvest. [ABSTRACT FROM AUTHOR]

The rapid emergence of expensive anticancer therapies is leading to exponential growth in healthcare expenses. In clinical trials, most investigational drugs are provided free of charge by industrial and academic sponsors. This results in drug cost savings for healthcare payers, who are no longer charged with the cost of the standard-of-care treatment, which would have been administered outside the trial. This study aims to estimate drug cost savings resulting from patient enrolment in hematological oncology clinical trials, from a public payer perspective. Retrospective screening identified all patients with hematological malignancies included from 2011 to 2016 in a phase III trial and having received at least one sponsor-provided cycle. Drug cost savings were defined as the standard treatment costs not charged to the payer due to sponsor provision of treatment. For each patient, cost savings were determined by the number of cycles received in the trial and the cost of standard (control arm) treatment. Of the 345 patients included in eligible trials during study period, 272 received sponsor-provided drugs. Drug cost savings could be estimated for 177 patients (65.1%) included in 27 trials. Total cost savings were €5218 million (US$ 6804 million) for 1720 sponsor-provided cycles. Mean cost saving per patient was €19 182.7 ± 29 865.7 ($25 015.24 ± 39 478.25). Most cost-saving trials were industry-sponsored (77.8%), although academic trials generated 40.15% of total cost savings. Enrolling patients in clinical trials, whether industry-sponsored or academic, leads to substantial drug cost savings for payers. Implications are significant for public payers facing increasing financial constraints, as savings can be reallocated to patient care. [ABSTRACT FROM AUTHOR]

Objective: Troublesome hot flushes and night sweats (HFNS) are experienced by many women after treatment for breast cancer, impacting significantly on sleep and quality of life. Cognitive behavioural therapy (CBT) is known to be effective for the alleviation of HFNS. However, it is not known if it can effectively be delivered by specialist nurses. We investigated whether group CBT, delivered by breast care nurses (BCNs), can reduce the impact of HFNS.Methods: We recruited women with primary breast cancer following primary treatment with seven or more HFNS/week (including 4/10 or above on the HFNS problem rating scale), from six UK hospitals to an open, randomised, phase 3 effectiveness trial. Participants were randomised to Group CBT or usual care (UC). The primary endpoint was HFNS problem rating at 26 weeks after randomisation. Secondary outcomes included sleep, depression, anxiety and quality of life.Results: Between 2017 and 2018, 130 participants were recruited (CBT:63, control:67). We found a 46% (6.9-3.7) reduction in the mean HFNS problem rating score from randomisation to 26 weeks in the CBT arm and a 15% (6.5-5.5) reduction in the UC arm (adjusted mean difference -1.96, CI -3.68 to -0.23, P = .039). Secondary outcomes, including frequency of HFNS, sleep, anxiety and depression all improved significantly.Conclusion: Our results suggest that specialist nurses can be trained to deliver CBT effectively to alleviate troublesome menopausal hot flushes in women following breast cancer in the NHS setting. [ABSTRACT FROM AUTHOR]

Background: Lateral elbow pain (LEP) due to tendinosis is one of the most common musculoskeletal pains of the upper limbs, yet there is no satisfactory treatment. This study was an international, prospective, multi-centre, randomized, controlled, clinical trial to evaluate the efficacy of acupuncture compared to sham laser in the treatment of LEP.Methods: The study used a parallel and stratified design (1:1 allocation using a computer-generated sequence) and was participant-, outcome assessor- and statistician-blinded. Subjects from 18 to 80 years with unilateral chronic LEP (minimum three months) were recruited at four centres in Australia, China, Hong Kong and Italy. The treatment group received manual acupuncture at acupoints LI 10 and LI 11 on the affected side whereas the control group received sham laser acupuncture at the same acupoints. The primary endpoint was disabilities of the arm, shoulder, and hand (DASH) questionnaire score at the three-week post-treatment follow-up visit. Three VAS scales (pain at rest, pain on motion and pain during exertion) were secondary outcomes measures. Ninety-six subjects were allocated to either the treatment group (n = 47) or control group (n = 49) and were all included in the analysis.Results: At the follow-up visit, we found significant differences in DASH score between the two groups (p = .015). The median change to baseline for the treatment group was -11.7 (interval: -50.83 to 23.33), and for the control group -7.50 (interval: -36.67 to 29.10). The estimated effect size was 0.47, indicating a medium effect. Significant differences were also found for secondary outcome measures for VAS of pain. There were no severe adverse events. Our findings suggest that acupuncture has a moderate efficacy in the treatment of LEP.Conclusions: Acupuncture was shown to be efficacious in improving the function of the arm associated with lateral elbow tendinosis. Both the DASH score and the pain VAS on two occasions (at rest and during motion) showed a significant change over time indicating acupuncture as a potential treatment for LEP due to tendinosis. [ABSTRACT FROM AUTHOR]

Background: The objective of this trial is to optimize the transmuscular quadratus lumborum (TQL) block, by investigating the minimal effective volume (MEV90 ) of ropivacaine 0.75% for single-shot TQL block in percutaneous nephrolithotomy (PNL) patients.Methods: This double-blind, randomized and controlled dose-finding trial is based on a biased coin up-and-down sequential design, where the volume of local anaesthetic administered to each patient depends on the response from the previous one. Investigating the TQL block, the first patient recruited receives 20 ml ropivacaine 0.75% preoperatively. In case of block failure, the next patient will receive the same volume with an increment of 2 ml. Given a successful block for the first patient, the next patient will be randomized to either a lower volume (previous volume with a reduction of 2 ml), or the same volume as the previous patient. The respective probabilities being b = 0.11 for a reduced volume and 1-b = 0.89 for the same volume. Block success is defined as patient reported pain score numeric rated scale (NRS) ≤3 (0-10/10) 30 minutes after arrival in the post anaesthesia care unit (PACU). The NRS pain score is our primary and only outcome for block success. A minimum of 25 eligible patients are needed to achieve precise estimation of MEV90 with narrow 95% confidence intervals derived by bootstrapping.Discussion: Recruiting will begin June 2020 and is expected to finish November 2020. Data analysis will be performed at interims during and after the study. Results will be published in an international peer-reviewed medical journal. [ABSTRACT FROM AUTHOR]

Objective: The aim of this article is to describe the incidence and characteristics of pregnancy-related death in low- and middle-resource settings, in relation to the availability of key obstetric resources.Design: This is a secondary analysis of a stepped-wedge cluster randomised controlled trial.Setting: This trial was undertaken at ten sites across eight low- and middle-income countries in sub-Saharan Africa, India and Haiti.Population: Institutional-level consent was obtained and all women presenting for maternity care were eligible for inclusion.Methods: Pregnancy-related deaths were collected prospectively from routine data sources and active case searching.Main Outcome Measures: Pregnancy-related death, place, timing and age of maternal death, and neonatal outcomes in women with this outcome.Results: Over 20 months, in 536 233 deliveries there were 998 maternal deaths (18.6/10 000, range 28/10 000-630/10 000). The leading causes of death were obstetric haemorrhage (36.0%, n = 359), hypertensive disorders of pregnancy (20.6%, n = 206), sepsis (14.1%, n = 141) and other (26.5%, n = 264). Approximately a quarter of deaths occurred prior to delivery (28.4%, n = 283), 35.7% (n = 356) occurred on the day of delivery and 35.9% (n = 359) occurred after delivery. Half of maternal deaths (50.6%; n = 505) occurred in women aged 20-29 years, 10.3% (n = 103) occurred in women aged under 20 years, 34.5% (n = 344) occurred in women aged 30-39 years and 4.6% (n = 46) occurred in women aged ≥40 years. There was no measured association between the availability of key obstetric resources and the rate of pregnancy-related death.Conclusions: The large variation in the rate of pregnancy-related death, irrespective of resource availability, emphasises that inequality and inequity in health care persists.Tweetable Abstract: Inequality and inequity in pregnancy-related death persists globally, irrespective of resource availability. [ABSTRACT FROM AUTHOR]

Aims: This trial was conducted to explore the protective effect on β-cell function of adding vitamin D3 to DPP-4 inhibitors to treat patients with latent autoimmune diabetes in adults (LADA).Methods: 60 LADA patients were randomized to group A (n = 21) - conventional therapy with metformin (1-1.7 g/day) and/or insulin treatment; group B (n = 20) - saxagliptin (5 mg/day) plus conventional therapy; and group C (n = 19) - vitamin D3 (2000 IU/day) plus saxagliptin and conventional therapy for 12 months. Fasting and 2-hour postprandial blood samples were collected to measure blood glucose, glycosylated hemoglobin and C-peptide levels at baseline and after 3, 6 and 12 months of treatment.Results: During the 12 months of follow-up, the levels of fasting C-peptide (FCP), 2-hour postprandial C-peptide (PCP) and the C-peptide index (CPI, serum C-peptide-to-plasma glucose level ratio) were maintained in group C. In contrast to those in group A and group B, FCP levels decreased significantly in group B, and CPI levels declined significantly in group A during the 1-year treatment (P < .05). Additionally, the levels of GADA titers in group C significantly decreased compared with those at baseline (P < .05), but no significant differences in GADA titers levels were detected in group A and group B. No significant differences were found among the three groups in the levels of FCP, PCP, the CPI or GADA titers.Conclusions: The data suggested that adding 2000 IU/day vitamin D3 to saxagliptin might preserve β-cell function in patients with LADA. [ABSTRACT FROM AUTHOR]

Background: IRL752 is a novel small-molecule compound that acts to regioselectively enhance norepinephrine, dopamine, and acetylcholine neurotransmission in the cerebral cortex.Objective: The primary objective of the trial was to investigate the safety and tolerability of IRL752 in patients with Parkinson's disease and dementia.Methods: Patients with Parkinson's disease and dementia were randomized to IRL752 or placebo treatment (3:1 ratio) for 28 days. The study drug was given as an adjunct treatment to the patients' regular stable antiparkinsonian medication. Dosing was individually titrated for 14 days after which the dose was kept stable for an additional 14 days.Results: A total of 32 patients were randomized to treatment, and 29 patients completed the 4-week treatment. Adverse events were generally mild and transient and were mostly reported during the dose titration phase. There were 2 serious adverse events, and none of them were related to the experimental treatment. The average dose achieved in the stable dose phase was 600 mg daily, yielding a 2-hour postdose plasma concentration of about 4 μM on day 28. Exploratory assessment of secondary outcomes indicated efficacy for symptoms and signs known to be poorly responsive to levodopa.Conclusions: IRL752 appears to be safe and well tolerated for a 4-week treatment in patients with Parkinson's disease and dementia. © 2020 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Understanding genetic factors that contribute to cannabis use disorder (CUD) is important, but to date, findings have been equivocal. Single-nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 gene (CNR1; rs1049353 and rs806378) and fatty acid amide hydrolase (FAAH) gene (rs324420) have been implicated in CUD. Their relationship to addiction endophenotypes such as cannabis-related state satiety, the salience of appetitive cues, and craving after acute cannabinoid administration has not been investigated. Forty-eight cannabis users participated in a double-blind, placebo-controlled, four-way crossover experiment where they were administered treatments in a randomized order via vaporization: placebo, Δ9 -tetrahydrocannabinol (THC) (8 mg), THC + cannabidiol (THC + CBD) (8 + 16 mg), and CBD (16 mg). Cannabis-related state satiety, appetitive cue salience (cannabis and food), and cannabis craving were assessed each day. Participants were genotyped for rs1049353, rs806378, and rs324420. Results indicated that CNR1 rs1049353 GG carriers showed increased state satiety after THC/THC + CBD administration in comparison with placebo and reduced the salience of appetitive cues after THC in comparison with CBD administration; A carriers did not vary on either of these measures indicative of a vulnerability to CUD. CNR1 rs806378 CC carriers showed greater salience to appetitive cues in comparison with T carriers, but there was no evidence for changes in state satiety. FAAH rs324420 A carriers showed greater bias to appetitive cues after THC, in comparison with CC carriers. FAAH CC carriers showed reduced bias after THC in comparison with CBD. No SNPs modulated craving. These findings identify candidate neurocognitive mechanisms through which endocannabinoid system genetics may influence vulnerability to CUD. [ABSTRACT FROM AUTHOR]

Background: This study compared clinical and patient-centered outcomes of subepithelial connective tissue graft (CTG) with and without enamel matrix derivative (EMD) in the treatment of multiple Class III-IV Miller periodontal recession (REC) defects on mandibular anterior teeth.Methods: This randomized clinical study evaluated 41 patients at 3 years follow-up. One hundred and fifty-six teeth were divided into two groups: test (CTG-EMD, 79 teeth) and control (CTG only, 77 teeth). Clinical REC, keratinized tissue (KT) width, percentage of root coverage, patient-centered outcomes were compared between the two groups.Results: At 36 months follow-up, patient level analysis showed that REC in the test group reduced significantly (5.71 ± 0.58 mm to 1.57 ± 0.85 mm) compared with the control group (5.94 ± 0.46 mm to 2.51 ± 0.62 mm) (P < 0.001), while KT width increased in the test group (1.51 ± 0.26 mm to 4.18 ± 0.34 mm) and was significantly greater than the control group (1.65 ± 0.21 mm to 2.90 ± 0.20 mm) (P < 0.001). At 36 months, tooth level analysis (Class III and Class IV groups) found less residual REC and increased KT in the test group compared with the control group (P < 0.01). Significantly less pain was reported at 2, 7, and 14 days follow-up post-surgery in the test group (P < 0.001).Conclusions: The addition of EMD to CTG results in improved root coverage outcomes and higher amounts of KT width 36 months after treatment of Class III-IV REC on mandibular anterior teeth. The adjunctive use of EMD also resulted in significantly reduced pain 14 days post-surgery. [ABSTRACT FROM AUTHOR]

Background: A reliable central venous access device is a cornerstone in the treatment of cancer. Both peripherally inserted central catheters (PICC) and totally implanted chest ports (PORT) are commonly used for the delivery of chemotherapy. Both types of catheter can cause adverse events such as catheter-related deep venous thrombosis (CR-DVT), infection and mechanical complications.Method: We conducted a randomized controlled trial including 399 patients with cancer and performed a health economic evaluation investigating the cost related to PICCs and PORTs using several clinically relevant dimensions from a healthcare perspective. The cost was determined using process and cost estimate models.Result: PICCs are associated with a higher total cost when compared with PORTs. Combining the costs of all categories, the prize per inserted device was 824.58 EUR for PICC and 662.34 EUR for PORT. When adjusting for total catheter dwell time the price was 6.58 EUR/day for PICC and 3.01 EUR/day for PORT. The difference in CR-DVT was the main contributor to the difference in cost. The daily cost of PICC is approximately twice to that of PORT.Conclusion: We have demonstrated that the cost from a healthcare perspective is higher in cancer patients receiving a PICC than to those with a PORT. The difference is driven mainly by the cost related to the management of adverse events. Our findings are relevant to anaesthetists, oncologists and vascular access clinicians and should be considered when choosing vascular access device prior to chemotherapy. [ABSTRACT FROM AUTHOR]

Objective: Unselected population-based BRCA testing provides the opportunity to apply genomics on a population-scale to maximise primary prevention for breast-and-ovarian cancer. We compare long-term outcomes of population-based and family-history (FH)/clinical-criteria-based BRCA testing on psychological health and quality of life.Design: Randomised controlled trial (RCT) (ISRCTN73338115) GCaPPS, with two-arms: (i) population-screening (PS); (ii) FH/clinical-criteria-based testing.Setting: North London Ashkenazi-Jewish (AJ) population.Population/sample: AJ women/men.Methods: Population-based RCT (1:1). Participants were recruited through self-referral, following pre-test genetic counselling from the North London AJ population.Inclusion Criteria: AJ women/men >18 years old; exclusion-criteria: prior BRCA testing or first-degree relatives of BRCA-carriers.Interventions: Genetic testing for three Jewish BRCA founder-mutations: 185delAG (c.68_69delAG), 5382insC (c.5266dupC) and 6174delT (c.5946delT), for (i) all participants in PS arm; (ii) those fulfilling FH/clinical criteria in FH arm. Linear mixed models and appropriate contrast tests were used to analyse the impact of BRCA testing on psychological and quality-of-life outcomes over 3 years.Main Outcome Measures: Validated questionnaires (HADS/MICRA/HAI/SF12) used to analyse psychological wellbeing/quality-of-life outcomes at baseline/1-year/2-year/3-year follow up.Results: In all, 1034 individuals (691 women, 343 men) were randomised to PS (n = 530) or FH (n = 504) arms. There was a statistically significant decrease in anxiety (P = 0.046) and total anxiety-&-depression scores (P = 0.0.012) in the PS arm compared with the FH arm over 3 years. No significant difference was observed between the FH and PS arms for depression, health-anxiety, distress, uncertainty, quality-of-life or experience scores associated with BRCA testing. Contrast tests showed a decrease in anxiety (P = 0.018), health-anxiety (P < 0.0005) and quality-of-life (P = 0.004) scores in both PS and FH groups over time. Eighteen of 30 (60%) BRCA carriers identified did not fulfil clinical criteria for BRCA testing. Total BRCA prevalence was 2.9% (95% CI 1.97-4.12%), BRCA1 prevalence was 1.55% (95% CI 0.89-2.5%) and BRCA2 prevalence was 1.35% (95% CI 0.74-2.26%).Conclusion: Population-based AJ BRCA testing does not adversely affect long-term psychological wellbeing or quality-of-life, decreases anxiety and could identify up to 150% additional BRCA carriers.Tweetable Abstract: Population BRCA testing in Ashkenazi Jews reduces anxiety and does not adversely affect psychological health or quality of life. [ABSTRACT FROM AUTHOR]

Given the importance of heavy menstrual bleeding (HMB), we investigated the effect of plantain syrup on HMB. This randomized clinical trial was performed on 68 women with HMB who were referred to the traditional medicine clinics of Mashhad University of Medical Sciences. The intervention group received placebo capsule and plantain syrup, whereas the control group received mefenamic acid capsule and placebo syrup in the first 5 days of menstruation for three menstruation cycles. Patients were asked to complete pictorial blood assessment chart one cycle before the intervention and three intervention cycles. Hemoglobin was measured at the beginning and at the end of the study. The results showed that the bleeding duration and severity diminished in both groups. No significant difference was observed between two groups in severity of bleeding after intervention (Cohen's d = .24), but duration of bleeding in mefenamic acid group was reduced significantly in comparison with plantain group (Cohen's d = .57). Although mean hemoglobin alterations in mefenamic acid group had a significant difference before and after the intervention, there was no significant difference between the two groups in mean hemoglobin alterations postintervention. Plantain syrup could be suggested as a complementary treatment for HMB, but further studies are required. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the efficacy of a problem-solving intervention for the prevention of suicidal risk in Brazilian adolescents with elevated suicidal potential and depressive symptoms.Methods: A randomized controlled trial was conducted involving 100 participants (mean age 17.2 years, 60% women, 46% mixed race), allocated to the problem-solving intervention (n = 50) or the usual care control group (n = 50). Blinded interviewers conducted assessments at pretreatment, posttreatment, 1, 3, and 6 months of follow-up. The main outcome was suicidal orientation; secondary outcomes were suicidal risk, suicidal plans and attempts, depressive symptoms, and problem-solving skills.Results: At posttreatment and up to 6-month follow-up, there was lower suicidal orientation and suicidal risk in the problem-solving group compared to the control group. There were lower suicidal plans and attempts (0.0% participants vs 2.2% with a suicide plan and 2.2% with both suicide plan and attempt); risk difference was 0.04 (95% CI: 0.01-0.09) and the number needed to treat was 25 (95% CI: 11-70). Significant effects of the intervention on depressive symptoms were found at posttreatment and maintained for 6 months. The change in global and functional problem-solving skills mediated the reduction in suicide orientation.Conclusions: Thus, suicidal risk can be successfully prevented in adolescents. [ABSTRACT FROM AUTHOR]

Background: Photoactivated disinfection (PAD) could support the periodontal treatment outcome. The effect of the light emitting diode (LED) as an innovative light source in PAD is under discussion. The aim of this study was to evaluate the clinical and microbiological effect of adjunctive PAD in the treatment of periodontitis with a red LED as light source.Methods: Twenty patients with periodontitis completed this split-mouth study. The left and right side of the jaws were randomly assigned to either test or control group. After conservative periodontal treatment in both groups, the test group received two sessions of adjunctive PAD (red LED, 635 nm, photosensitive dye, 0.01% tolonium chloride), whereas the control group received no adjunctive PAD. The parameters of clinical periodontal examination-including probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP) and microbiological assays (PCR) were evaluated before and after treatment.Results: After 3 months, both treatment groups showed significant improvements regarding BOP, PD, and CAL compared to baseline, with no significant difference between control and treatment group. The recolonization of Porphyromonas gingivalis and Treponema denticola was reduced after adjuvant treatment, but not significantly.Conclusions: The positive effect of adjunctive PAD regarding clinical parameters was reported in recent trials. In this study and with the current settings, both treatment groups showed similar clinical results after initial periodontal treatment, without beneficial effect of adjunctive PAD. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate whether the intake of the 1975 Japanese diet (JD) could reduce the amount of abdominal fat in people with overweight.Methods: Using a single-blind randomized controlled trial, the modern diet (MD) was compared with the 1975-type JD, which is based on the MD but includes five characteristics of the 1975 JD in an enhanced form. Overweight people were randomly assigned to an MD group (n = 30) and a JD group (n = 30). The participants consumed test diets that were provided three times a day for 28 days. Body composition measurements and blood biochemical examinations were performed before and after the test diet intake, and the proportions of change were compared.Results: Those in the JD group had significantly decreased BMI, fat mass, and levels of low-density lipoprotein cholesterol, glycated hemoglobin, and C-reactive protein (P = 0.002, 0.015, 0.014, 0.012, and 0.039, respectively) and significantly increased high-density lipoprotein cholesterol levels compared with those in the MD group (P = 0.020).Conclusions: The intake of a diet with the characteristics of the 1975 JD may have beneficial effects on lipid metabolism in people with overweight and reduce the onset risk of metabolism-related disorders, such as obesity and diabetes. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the effects of sustained morning fasting or breakfast consumption on metabolism, energy intake, and appetite in healthy adults with obesity.Methods: An independent-measures randomized controlled trial with baseline and follow-up laboratory assessment days separated by a 6-week intervention of either morning fasting (0 kcal until 12:00 pm) or daily breakfast (> 700 kcal by 11:00 am) was performed. Measures included metabolic outcomes (glucose, insulin, nonesterified fatty acids), hormones regulating appetite (total/acylated ghrelin, peptide YY, leptin), and energy expenditure (diet-induced thermogenesis) parameters throughout a laboratory test day and ad libitum intake following a fixed breakfast.Results: Allocation to fasting versus breakfast resulted in minimal adaptation as reflected by the metabolic outcomes or the majority of appetite regulatory outcomes for either area under curve or time-course-based measures (P > 0.05). Ad libitum lunch intake was not different (P = 0.13), nor was diet-induced thermogenesis or a composite appetite score (both P > 0.10). However, there was a reduced total area under the curve for peptide YY (P = 0.05) and increased postprandial hunger ratings (P = 0.05) in the breakfast group.Conclusions: There was little evidence of metabolic adaptation to acute feeding or negative consequences from sustained morning fasting. This indicates that previously observed differences between breakfast consumers and skippers may be acute effects of feeding or may have resulted from other lifestyle factors. [ABSTRACT FROM AUTHOR]

Objective: To explore physiotherapists' perceptions before and after delivering exercise advice via telephone to patients with knee osteoarthritis (OA).Methods: We performed a descriptive qualitative study (based on interpretivist methodology) embedded within a randomized controlled trial. Before and after providing exercise therapy to patients with knee OA, all 8 physiotherapists who were involved in the trial participated in semi-structured interviews via telephone. Interviews were audio recorded, transcribed verbatim, and thematically analyzed.Results: Prior to delivering the intervention, physiotherapists thought that the telephone should be used only for follow-up rather than as the primary mode of providing care. They believed that telephone-delivered care would be convenient and cost-saving for patients, would provide increased opportunity for patient education, and also increase access to services, but that the lack of visual and physical contact with patients would be problematic. After delivering the intervention, physiotherapists reflected that telephone-delivered care exceeded their expectations, noting positive patient outcomes including improved pain, function, and confidence. The focus on communication allowed more personal conversations with patients and shifted patient expectations of care away from manual therapies and toward self-management. Numerous implementation considerations were identified, including the need for clinician training in communication skills, written resources for patients to supplement telephone calls, and careful deliberation of how to schedule telephone consultations during the usual in-person consultations in the clinic.Conclusion: Although physiotherapists were initially skeptical about the effectiveness of telephone-delivered service models to patients with knee OA, perceptions shifted once they experienced delivery of care via this nontraditional method. Our findings suggest that firsthand experience may be necessary for physiotherapists to embrace new models of service delivery. [ABSTRACT FROM AUTHOR]

Background and Objectives: Neuroactive steroids (NAS) may play a role in addiction, with observed increases in response to acute stress and drug use, but decreases with chronic substance use, suggesting that NAS neuroadaptations may occur with chronic substance use. However, levels of NAS in addicted individuals have not been systematically examined. Here, we evaluated a panel of NAS in men and women with cocaine use disorder (CUD) who participated in a clinical laboratory study of progesterone.Methods: Forty six CUD individuals were enrolled in a randomized placebo-controlled laboratory study to evaluate progesterone effects on levels of various NAS. On day 5 of a 7-day inpatient treatment regimen of 400 mg/day progesterone (15M/8F) or placebo (14M/9F), plasma levels of NAS known to be downstream of progesterone (allopregnanolone, pregnanolone), and NAS not in the progesterone synthesis pathway (androstanediol, testosterone, dehydroepiandrosterone [DHEA] and the NAS precursor, pregnenolone) were analyzed using highly sensitive gas chromatography/mass spectrometry (GC/MS). The relationship between each of the NAS and chronicity of cocaine use was also assessed.Results: Progesterone versus placebo significantly increased the GABAergic NAS allopregnanolone and pregnanolone in both CUD men and women. Levels of pregnenolone, testosterone, its GABAergic metabolite androstanediol, and the non-GABAergic DHEA were unaffected by progesterone treatment, and testosterone and androstanediol levels were significantly higher in men than women. Importantly, lower pregnenolone and androstanediol levels were associated with greater years of cocaine use.Scientific Significance: GABAergic NAS that are upstream from the progesterone synthesis pathway appear susceptible to chronic effects of cocaine use. (Am J Addict 2019;28:16-21). [ABSTRACT FROM AUTHOR]

Although weight loss improves blood pressure (BP), its association with mortality remains unclear. In the Trials of Hypertension Prevention (TOHP), individuals aged 30-54 years with high normal BP were randomized to weight loss, usual care or other intervention over 18 months (TOHP I) or 3-4 years (TOHP II), with average 23-year mortality follow-up. We examined mortality and (a) randomized weight loss and (b) observed weight change among all with high baseline weight. Among 2964 randomized participants, 227 deaths occurred, with no intervention difference (hazard ratio (HR) = 0.97, 95% confidence interval (CI) = 0.75-1.26, P = 0.84). Among 3828 high-weight participants, weight change was directly related to mortality (HR = 1.14 per 5% change, 95% CI = 1.02-1.28, P = 0.019). During the trial 15% lost >5% (HR = 0.82), 29% lost 0-<=5% (HR = 0.94), 41% gained 0-<5% (reference), and 16% gained >5% (HR = 1.29) (P-trend = 0.046). This is consistent with a long-term beneficial effect of presumed intentional weight loss on mortality. [ABSTRACT FROM AUTHOR]

Objective: To test the hypothesis that patient-initiated follow up reduces the fear of cancer recurrence (FCR) and healthcare use when compared with traditional hospital-based follow up.Design: Pragmatic, multicentre randomised trial.Setting: Four Danish departments of gynaecology between May 2013 and May 2016.Population: One hundred and fifty-six women diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I low-intermediate risk endometrial carcinoma.Methods: Women allocated to the control group attended hospital-based follow up consisting of regular outpatient visits for 3 years after primary treatment. Women in the intervention group were instructed in patient-initiated follow up, which included careful instruction in alarm symptoms and options for self-referral rather than a schedule of examinations.Main Outcome Measures: The primary end point was FCR as measured by the Fear of Cancer Recurrence Inventory (FCRI) after 10 months of follow up. Secondary end points included cancer-related use of primary and secondary health care during the first 10 months after treatment.Results: In the primary analysis, FCR decreased significantly more in the control group from baseline to 10 months of follow up (difference -5.9, 95% CI -10.9 to -0.9). The majority of this improvement happened after only 3 months of follow up. Women receiving the intervention had fewer examinations at the department compared with the control group (0 versus 2 median visits, P < 0.01) and 58% of these examinations were scheduled because of vaginal bleeding.Conclusions: Hospital-based follow up alleviates FCR significantly more than patient-initiated follow up, though the estimated difference was small. Patient-initiated follow up is a feasible, potentially cost-reducing follow-up approach in a population of endometrial cancer survivors with low risk of recurrence. The decision to use patient-initiated follow up should balance these benefits and harms.Tweetable Abstract: Patient-initiated follow up reduces healthcare use but maintains fear of recurrence in endometrial cancer.Plain Language Summary: Why and how was the study carried out? Follow up of women with endometrial cancer is resource consuming and previous research suggests that it is not effective. Even though the women benefit from reassurance at follow up, routine examinations may also remind the women of the disease and induce fear of cancer recurrence. Furthermore, routine follow up may delay recurrence diagnosis, because the women do not report their symptoms until the next scheduled visit. In the research explained in this article, patient-initiated follow up was evaluated as an alternative to traditional follow up. The women were randomly assigned to one of two follow-up programmes: regular gynaecological examinations at the department of gynaecology or self-referral with careful instruction in alarm symptoms, that is, patient-initiated follow up. The level of fear of cancer recurrence in the two groups was obtained by questionnaires. Information on healthcare use was obtained by questionnaires and a chart review. What were the main findings? Regular examinations at the department of gynaecology reduced the fear of cancer recurrence significantly more than patient-initiated follow up, though the difference was small. Women who were instructed in alarm symptoms, under self-referral, were able to monitor their symptoms, and this approach significantly reduced the number of examinations at the department of gynaecology. What are the limitations of the work? Participants in the self-referral group knew that they were examined less than other women, and this may have induced fear of cancer recurrence. Similarly, the regular completion of questionnaires regarding fear of cancer recurrence may have reminded the women of the disease and diminished the difference between the two groups. What are the implications for patients Patient-initiated follow up reduced healthcare use but maintained fear of cancer recurrence in women who had survived early-stage endometrial cancer. Future analyses on quality of life and cost-effectiveness are needed to balance the benefits and harms of patient-initiated follow up. [ABSTRACT FROM AUTHOR]

Objective: To determine whether oral clindamycin reduces the risk of preterm birth (PTB) in women with abnormal vaginal microflora as evidenced by a vaginal pH ≥5.0.Design: Randomised double-blind placebo-controlled trial.Setting: Rural southern India.Population: Pregnant women with a singleton fetus between 13+0/7 weeks and 20+6/7 weeks.Methods: Pregnant women were recruited during prenatal visits in Karnataka, India, from October 2013 to July 2015. Women were required to have a singleton fetus between 13+0/7 weeks and 20+6/7 weeks and an elevated vaginal pH (≥5.0) by colorimetric assessment. Participants were randomised to either oral clindamycin 300 mg twice daily for 5 days or an identical-appearing placebo.Main Outcome Measures: The primary outcome was the incidence of PTB, defined as delivery before 37+0/7 weeks.Results: Of the 6476 screened women, 1727 women were randomised (block randomised in groups of six; clindamycin n = 866, placebo n = 861). The demographic, reproductive, and anthropomorphometric characteristics of the study groups were similar. Compliance was high, with over 94% of capsules being taken. The rate of PTB before 37 weeks was comparable between the two groups [clindamycin 115/826 (13.9%) versus placebo 111/806 (13.8%), between-group difference 0.2% (95% CI -3.2 to 3.5%, P = 0.93)], as was PTB at less than 34 weeks [clindamycin 40/826 (4.8%) versus placebo group 37/806 (4.6%), between-group difference 0.3% (95% CI -1.8 to 2.3%, P = 0.81)]. No differences were detected in the incidence of birthweight of<2500 g, <1500 g, miscarriage, stillbirth or neonatal death.Conclusion: In this setting, oral clindamycin did not decrease PTB among women with vaginal pH ≥5.0.Tweetable Abstract: Oral clindamycin between 13+0/7 and 20+6/7 weeks does not prevent preterm birth in women with a vaginal pH ≥5.0. [ABSTRACT FROM AUTHOR]

Results of the SPRINT study have been disputed, based on the assumption that unattended BP measurements do not correlate with usual BP measurements. In this study, the authors investigated the correlation of unattended SPRINT-like measurements with other conventional measurements. All BP measurements were taken with the patient seated in a comfortable chair with the legs uncrossed and not speaking during the procedure. For the purpose of this study, sixty-five patients, mostly male (93%), were recruited from our hypertension clinic and all were on antihypertensive medication (av 3.0 ± 1.1). Patients were at high cardiovascular risk with high rates of comorbidities, av age 68 ± 12 years, 49% with diabetes, 34% with mild CKD (CKD 1-3, average eGFR 55.0 ± 13 mL/min/1.73 m2 ), and 20% with history of stable coronary artery disease. All BP measurements were similar with no statistically significant difference (one-way ANOVA, P = 0.621). Compared to unattended SPRINT BP values (139.77 ± 19.22/75.42 ± 11.72 mm Hg), the clinic BP measurements were numerically slightly higher but with a NS P value (P = 0.163). Similarly, unattended BP measurements were similar to values taken by the clinic physician. In a smaller cohort of 11 patients, the authors compared unobserved vs observed SPRINT-like BP measurements, and in 13 patients, the authors compared unobserved SPRINT-like BP measurements to average home BP measurements (Table 3). There were no significant differences between any of the subgroups (one-way ANOVA, P = 0.816 for systolic and P = 0.803 for diastolic). The authors conclude that unattended BP measurements taken (the SPRINT way) are similar to other conventional office blood pressure measurements. [ABSTRACT FROM AUTHOR]

We report the rationale and design of a community PHARMacy-based prospective randomized controlled interdisciplinary study for ambulatory patients with Chronic Heart Failure (PHARM-CHF) and results of its pilot study. The pilot study randomized 50 patients to a pharmacy-based intervention or usual care for 12 months. It demonstrated the feasibility of the design and showed reduced systolic blood pressure in the intervention group as indicator for improved medication adherence. The main study will randomize patients ≥60 years on stable pharmacotherapy including at least one diuretic and a history of heart failure hospitalization within 12 months. The intervention group will receive a medication review at baseline followed by regular dose dispensing of the medication, counselling regarding medication use and symptoms of heart failure. The control patients are unknown to the pharmacy and receive usual care. The primary efficacy endpoint is medication adherence, pre-specified as a significant difference of the proportion of days covered between the intervention and control group within 365 days following randomization using pharmacy claims data for three CHF medications (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid receptor antagonists). The primary composite safety endpoint is days lost due to blindly adjudicated unplanned cardiovascular hospitalizations or death. Overall, 248 patients shall be randomized. The minimum follow-up is 12 months with an expected mean of 24 months. Based on the feasibility demonstrated in the pilot study, the randomized PHARM-CHF trial will test whether an interdisciplinary pharmacy-based intervention can safely improve medication adherence and will estimate the potential impact on clinical endpoints. ClinicalTrials.gov Identifier: NCT01692119. [ABSTRACT FROM AUTHOR]

Objective: To assess whether a combination of Internet-based and postal survey methods (mixed-mode) compared to postal-only survey methods (postal-only) leads to improved response rates in a physician survey, and to compare the cost implications of the different recruitment strategies.Data Sources/study Setting: All primary care gynecologists in Bremen and Lower Saxony, Germany, were invited to participate in a cross-sectional survey from January to July 2014.Study Design: The sample was divided into two strata (A; B) depending on availability of an email address. Within each stratum, potential participants were randomly assigned to mixed-mode or postal-only group.Principal Findings: In Stratum A, the mixed-mode group had a lower response rate compared to the postal-only group (12.5 vs. 20.2 percent; RR = 0.61, 95 percent CI: 0.44-0.87). In stratum B, no significant differences were found (15.6 vs. 16.2 percent; RR = 0.95, 95 percent CI: 0.62-1.44). Total costs (in €) per valid questionnaire returned (Stratum A: 399.72 vs. 248.85; Stratum B: 496.37 vs. 455.15) and per percentage point of response (Stratum A: 1,379.02 vs. 861.02; Stratum B 1,116.82 vs. 1,024.09) were higher, whereas variable costs were lower in mixed-mode compared to the respective postal-only groups (Stratum A cost ratio: 0.47, Stratum B cost ratio: 0.71).Conclusions: In this study, primary care gynecologists were more likely to participate by traditional postal-only than by mixed-mode survey methods that first offered an Internet option. However, the lower response rate for the mixed-mode method may be partly due to the older age structure of the responding gynecologists. Variable costs per returned questionnaire were substantially lower in mixed-mode groups and indicate the potential for cost savings if the sample population is sufficiently large. [ABSTRACT FROM AUTHOR]

Aim: Sudden unexpected death in infancy (SUDI) rates for Māori and Pacific infants remain higher than for other ethnic groups in New Zealand and bed-sharing is a major risk factor when there is smoking exposure in pregnancy. Sleep space programmes of education and Pēpi-Pod baby beds require evaluation.Methods: Two hundred and forty Māori and Pacific women and infants were randomised 1:1, to the Pēpi-Pod sleep space programme, or to a control group with 'usual care'. When infants were under 2 weeks of age, baseline interviews occurred, followed up by interviews at 2 and 4 months of age to assess safe sleep knowledge, infant care practices and Pēpi-Pod use and acceptability. All participants were offered a New Zealand Standard approved portable cot.Results: At baseline, 25% of babies did not have a baby bed. Knowledge of smoking and bed-sharing as SUDI risks improved at follow-up in both groups. One quarter regularly bed-shared at follow-up in both groups. Intention to bed-share was a strong predictor of subsequent behaviour. Pēpi-Pods were regularly used by 46% at 2 months and 16% at 4 months follow-up.Conclusions: Bed-sharing and knowledge improvement were similar irrespective of group. It is likely that the impact of the intervention was reduced because the control group received better support than 'usual care' and all participants had a baby bed. New Zealand SUDI rates have declined since sleep space programmes have been available. Sleep space programmes should be prioritised for those with modifiable SUDI risk. [ABSTRACT FROM AUTHOR]