Speech and language therapy versus placebo or no intervention for speech problems in Parkinson's disease

Parkinson's disease patients commonly suffer from speech and vocal problems including dysarthric speech, reduced loudness and loss of articulation. These symptoms increase in frequency and intensity with progression of the disease). Speech and language therapy (SLT) aims to improve the intelligibility of speech with behavioural treatment techniques or instrumental aids

Pressor and Sympathetic Responses to Graded Skeletal Muscle Metaboreflex Activation in Females with Relapsing-Remitting Multiple Sclerosis

Multiple sclerosis (MS) is a progressive disease characterized by demyelination in the central nervous system which disproportionately impacts females. Previous studies suggest MS-related exercise intolerance may be due to abnormal control of arterial blood pressure (BP) via the skeletal muscle metaboreflex. However, few studies have been performed and equivocal results reported. Discontinuity in prior data may be due to limited perturbation of metaboreflex activation using only low and moderate intensity exercise. PURPOSE: The purpose of this investigation was to test the hypothesis that females with MS have blunted BP and sympathetic responses to graded static handgrip (HG) exercise and isolated metaboreflex activation during postexercise ischemia (PEI) compared to healthy controls. METHODS: In 7 females with relapsing-remitting MS and 9 healthy female controls beat-to-beat BP (finometer) and muscle sympathetic nerve activity (MSNA; peroneal microneurography) were recorded at rest and during two minutes of handgrip performed at 30% and 40% maximum voluntary contraction followed by two minutes of PEI to isolate the muscle metaboreflex. RESULTS: There were no differences in resting mean arterial pressure (MAP; P= 0.16) or MSNA burst frequency (P= 0.15) between MS and controls. MAP and MSNA increased during 30% HG (MS: Δ19.8 ± 9.1 mmHg vs. Con: Δ17.8 ± 5.4 mmHg; P= 0.30 and MS: Δ17 ± 12 bursts/min vs. Con: Δ18 ± 17 bursts/min; P= 0.46) and 40% HG (MS: Δ29.3 ± 8.0 mmHg vs. Con: Δ30.0 ± 6.9 mmHg; P= 0.43 and MS: Δ36 ± 16 bursts/min vs. Con: Δ40 ± 9 bursts/min; P= 0.30) with no differences between groups. Likewise, MAP and MSNA responses were also not different during PEI post 30% HG (MS: Δ15.8 ± 7.6 mmHg vs. Con: Δ15.8 ± 6.4 mmHg; P= 0.50 and MS: Δ15 ± 9 bursts/min vs. Con: Δ11 ± 7 bursts/min; P= 0.19) or PEI post 40% HG (MS: Δ25.8 ± 6.3 mmHg vs. Con: Δ22.6 ± 8.2 mmHg; P= 0.43 and MS: Δ23 ± 13 bursts/min vs. Con: Δ24 ± 7 bursts/min; P= 0.46) between MS and controls. CONCLUSION: These preliminary data suggest intact skeletal muscle metaboreflex control of arterial BP in females with MS

Rofecoxib and cardiovascular adverse events in adjuvant treatment of colorectal cancer

Background Selective cyclooxygenase inhibitors may retard the progression of cancer, but they have enhanced thrombotic potential. We report on cardiovascular adverse events in patients receiving rofecoxib to reduce rates of recurrence of colorectal cancer. Methods All serious adverse events that were cardiovascular thrombotic events were reviewed in 2434 patients with stage II or III colorectal cancer participating in a randomized, placebo-controlled trial of rofecoxib, 25 mg daily, started after potentially curative tumor resection and chemotherapy or radiotherapy as indicated. The trial was terminated prematurely owing to worldwide withdrawal of rofecoxib. To examine possible persistent risks, we examined cardiovascular thrombotic events reported up to 24 months after the trial was closed. Results The median duration of active treatment was 7.4 months. The 1167 patients receiving rofecoxib and the 1160 patients receiving placebo were well matched, with a median follow-up period of 33.0 months (interquartile range, 27.6 to 40.1) and 33.4 months (27.7 to 40.4), respectively. Of the 23 confirmed cardiovascular thrombotic events, 16 occurred in the rofecoxib group during or within 14 days after the treatment period, with an estimated relative risk of 2.66 (from the Cox proportional-hazards model; 95% confidence interval [CI], 1.03 to 6.86; P = 0.04). Analysis of the Antiplatelet Trialists’ Collaboration end point (the combined incidence of death from cardiovascular, hemorrhagic, and unknown causes; of nonfatal myocardial infarction; and of nonfatal ischemic and hemorrhagic stroke) gave an unadjusted relative risk of 1.60 (95% CI, 0.57 to 4.51; P = 0.37). Fourteen more cardiovascular thrombotic events, six in the rofecoxib group, were reported within the 2 years after trial closure, with an overall unadjusted relative risk of 1.50 (95% CI, 0.76 to 2.94; P = 0.24). Four patients in the rofecoxib group and two in the placebo group died from thrombotic causes during or within 14 days after the treatment period, and during the follow-up period, one patient in the rofecoxib group and five patients in the placebo group died from cardiovascular causes. Conclusions Rofecoxib therapy was associated with an increased frequency of adverse cardiovascular events among patients with a median study treatment of 7.4 months’ duration. (Current Controlled Trials number, ISRCTN98278138.

"Post-GDM support would be really good for mothers": A qualitative interview study exploring how to support a healthy diet and physical activity after gestational diabetes.

BACKGROUND: Women with a history of gestational diabetes mellitus (GDM) are at high risk of developing type 2 diabetes mellitus (T2DM). They are therefore recommended to follow a healthy diet and be physically active in order to reduce that risk. However, achieving and maintaining these behaviours in the postpartum period is challenging. This study sought to explore women's views on suggested practical approaches to achieve and maintain a healthy diet and physical activity to reduce T2DM risk. METHODS: Semi-structured interviews with 20 participants in Cambridgeshire, UK were conducted at three to 48 months after GDM. The participants' current diet and physical activity, intentions for any changes, and views on potential interventions to help manage T2DM risk through these behaviours were discussed. Framework analysis was used to analyse the transcripts. The interview schedule, suggested interventions, and thematic framework were based on a recent systematic review. RESULTS: Most of the participants wanted to eat more healthily and be more active. A third of the participants considered that postpartum support for these behaviours would be transformative, a third thought it would be beneficial, and a third did not want additional support. The majority agreed that more information about the impact of diet and physical activity on diabetes risk, support to exercise with others, and advice about eating healthily, exercising with a busy schedule, monitoring progress and sustaining changes would facilitate a healthy diet and physical activity. Four other suggested interventions received mixed responses. It would be acceptable for this support to be delivered throughout pregnancy and postpartum through a range of formats. Clinicians were seen to have important roles in giving or signposting to support. CONCLUSIONS: Many women would appreciate more support to reduce their T2DM risk after GDM and believe that a variety of interventions to integrate changes into their daily lives would help them to sustain healthier lifestyles.RAD was funded by a PhD studentship from the National Institute for Health Research (NIHR) School for Primary Care Research (SPCR; SPCR-S-S102). This paper presents independent research funded by the NIHR SPCR. The views expressed are those of the author(s) and not necessarily those of the NIHR, the NHS or the Department of Health. JAUS was funded by a Cancer Research UK Cancer Prevention Fellowship (C55650/A21464). SJG is supported by the Medical Research Council (MC_UU_12015/4). The University of Cambridge has received salary support in respect of SJG from the NHS in the East of England through the Clinical Academic Reserve. CEA is supported by an Action Medical Research Grant (GN2778) and a Medical Research Council New Investigator Research Grant (MR/T016701/1). CLM is supported by the Diabetes UK Harry Keen Intermediate Clinical Fellowship (DUK-HKF 17/0005712) and the European Foundation for the Study of Diabetes – Novo Nordisk Foundation Future Leaders’ Award (NNF19SA058974). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Phase I Clinical Trials in Acute Myeloid Leukemia: 23-Year Experience From Cancer Therapy Evaluation Program of the National Cancer Institute

Therapy for acute myeloid leukemia (AML) has largely remained unchanged, and outcomes are unsatisfactory. We sought to analyze outcomes of AML patients enrolled in phase I studies to determine whether overall response rates (ORR) and mortality rates have changed over time

A comparison of the development of audiovisual integration in children with autism spectrum disorders and typically developing children

This study aimed to investigate the development of audiovisual integration in children with Autism Spectrum Disorder (ASD). Audiovisual integration was measured using the McGurk effect in children with ASD aged 7–16 years and typically developing children (control group) matched approximately for age, sex, nonverbal ability and verbal ability. Results showed that the children with ASD were delayed in visual accuracy and audiovisual integration compared to the control group. However, in the audiovisual integration measure, children with ASD appeared to ‘catch-up’ with their typically developing peers at the older age ranges. The suggestion that children with ASD show a deficit in audiovisual integration which diminishes with age has clinical implications for those assessing and treating these children

Comparing alternating pressure mattresses and high-specification foam mattresses to prevent pressure ulcers in high-risk patients: the PRESSURE 2 RCT

Background: Pressure ulcers (PUs) are a burden to patients, carers and health-care providers. Specialist mattresses minimise the intensity and duration of pressure on vulnerable skin sites in at-risk patients. Primary objective: Time to developing a new PU of category ≥ 2 in patients using an alternating pressure mattress (APM) compared with a high-specification foam mattress (HSFM). Design: A multicentre, Phase III, open, prospective, planned as an adaptive double-triangular group sequential, parallel-group, randomised controlled trial with an a priori sample size of 2954 participants. Randomisation used minimisation (incorporating a random element). Setting: The trial was set in 42 secondary and community inpatient facilities in the UK. Participants: Adult inpatients with evidence of acute illness and at a high risk of PU development. Interventions and follow-up: APM or HSFM – the treatment phase lasted a maximum of 60 days; the final 30 days were post-treatment follow-up. Main outcome measures: Time to event. Results: From August 2013 to November 2016, 2029 participants were randomised to receive either APM (n = 1016) or HSFM (n = 1013). Primary end point – 30-day final follow-up: of the 2029 participants in the intention-to-treat population, 160 (7.9%) developed a new PU of category ≥ 2. There was insufficient evidence of a difference between groups for time to new PU of category ≥ 2 [Fine and Gray model HR 0.76, 95% confidence interval (CI) 0.56 to 1.04; exact p-value of 0.0890 and 2% absolute difference]. Treatment phase sensitivity analysis: 132 (6.5%) participants developed a new PU of category ≥ 2 between randomisation and end of treatment phase. There was a statistically significant difference in the treatment phase time-to-event sensitivity analysis (Fine and Gray model HR 0.66, 95% CI 0.46 to 0.93; p = 0.0176 and 2.6% absolute difference). Secondary end points – 30-day final follow-up: new PUs of category ≥ 1 developed in 350 (17.2%) participants, with no evidence of a difference between mattress groups in time to PU development, (Fine and Gray model HR 0.83, 95% CI 0.67 to 1.02; p-value = 0.0733 and absolute difference 3.1%). New PUs of category ≥ 3 developed in 32 (1.6%) participants with insufficient evidence of a difference between mattress groups in time to PU development (Fine and Gray model HR 0.81, 95% CI 0.40 to 1.62; p = 0.5530 and absolute difference 0.4%). Of the 145 pre-existing PUs of category 2, 89 (61.4%) healed – there was insufficient evidence of a difference in time to healing (Fine and Gray model HR 1.12, 95% CI 0.74 to 1.68; p = 0.6122 and absolute difference 2.9%). Health economics – the within-trial and long-term analysis showed APM to be cost-effective compared with HSFM; however, the difference in costs models are small and the quality-adjusted life-year gains are very small. There were no safety concerns. Blinded photography substudy – the reliability of central blinded review compared with clinical assessment for PUs of category ≥ 2 was ‘very good’ (kappa statistic 0.82, prevalence- and bias-adjusted kappa 0.82). Quality-of-life substudy – the Pressure Ulcer Quality of Life – Prevention (PU-QoL-P) instrument meets the established criteria for reliability, construct validity and responsiveness. Limitations: A lower than anticipated event rate. Conclusions: In acutely ill inpatients who are bedfast/chairfast and/or have a category 1 PU and/or localised skin pain, APMs confer a small treatment phase benefit that is diminished over time. Overall, the APM patient compliance, very low PU incidence rate observed and small differences between mattresses indicate the need for improved indicators for targeting of APMs and individualised decision-making. Decisions should take into account skin status, patient preferences (movement ability and rehabilitation needs) and the presence of factors that may be potentially modifiable through APM allocation, including being completely immobile, having nutritional deficits, lacking capacity and/or having altered skin/category 1 PU. Future work: Explore the relationship between mental capacity, levels of independent movement, repositioning and PU development. Explore ‘what works for whom and in what circumstances’. Trial registration: Current Controlled Trials ISRCTN01151335. Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 52. See the NIHR Journals Library website for further project information