Muscle energy technique for chronic obstructive pulmonary disease: A feasibility study.

OBJECTIVE: This study aimed to investigate the feasibility of implementing a manual therapy technique (muscle energy technique, MET) protocol in a hospital pulmonary rehabilitation (PR) program for patients with moderate to severe chronic obstructive pulmonary disease (COPD). Please cite this article as: Baxter DA, Coyle ME, Hill CJ, Worsnop C, Shergis JL. Muscle energy technique for chronic obstructive pulmonary disease: A feasibility study. J Integr Med. 2023; 21(3): 245-253. METHODS: Participants aged 40 years and over, with moderate to severe COPD, were recruited into this 12-week study. The primary outcome measures were feasibility (acceptability of the intervention and attendance/adherence to the trial) and safety (adverse events, AEs). All participants received the MET and PR therapies. Participants and assessors were unblinded. Semi-standardized MET was delivered on 6 occasions (a maximum of once per week) at the hospital directly before a PR session. Participants undertook PR sessions as per the hospital program at a frequency of two days per week for 8 weeks. Participants were contacted 4 weeks after their final MET treatment via a telephone call to assess acceptability of the intervention. RESULTS: Thirty-three participants were enrolled, with a median age of 74 years (range 45-89 years). The median number of MET sessions that participants attended was 5 (range 0-6) out of a possible 6 sessions (83% attendance). At follow-up, participants overwhelmingly enjoyed the MET treatment with some subjectively reporting improved breathing. There were no major AEs related to the intervention, with the majority of AEs classified as expected events related to COPD exacerbations. CONCLUSION: It is feasible to implement a manual therapy protocol using MET as an adjunct to PR in a hospital setting. Recruitment rates were satisfactory and there were no AEs related to the MET component of the intervention.

The burden of low back pain and its association with socio-demographic variables in the Middle East and North Africa region, 1990-2019.

BACKGROUND: Low back pain (LBP) is the most common musculoskeletal disorder globally. Providing region- and national-specific information on the burden of low back pain is critical for local healthcare policy makers. The present study aimed to report, compare, and contextualize the prevalence, incidence and years lived with disability (YLDs) of low back pain in the Middle East and North Africa (MENA) region by age, sex and sociodemographic index (SDI), from 1990 to 2019. METHODS: Publicly available data were obtained from the Global Burden of Disease (GBD) study 2019. The burden of LBP was reported for the 21 countries located in the MENA region, from 1990 to 2019. All estimates were reported as counts and age-standardised rates per 100,000 population, together with their corresponding 95% uncertainty intervals (UIs). RESULTS: In 2019, the age-standardised point prevalence and incidence rate per 100,000 in MENA were 7668.2 (95% UI 6798.0 to 8363.3) and 3215.9 (95%CI 2838.8 to 3638.3), which were 5.8% (4.3 to 7.4) and 4.4% (3.4 to 5.5) lower than in 1990, respectively. Furthermore, the regional age-standardised YLD rate in 2019 was 862.0 (605.5 to 1153.3) per 100,000, which was 6.0% (4.2 to 7.7) lower than in 1990. In 2019, Turkey [953.6 (671.3 to 1283.5)] and Lebanon [727.2 (511.5 to 966.0)] had the highest and lowest age-standardised YLD rates, respectively. There was no country in the MENA region that showed increases in the age-standardised prevalence, incidence or YLD rates of LBP over the measurement period. Furthermore, in 2019 the number of prevalent cases were highest in the 35-39 age group, with males having a higher number of cases in all age groups. In addition, the age-standardised YLD rates for males in the MENA region were higher than the global estimates in almost all age groups, in both 1990 and 2019. Furthermore, the burden of LBP was not associated with the level of socio-economic development during the measurement period. CONCLUSION: The burden attributable to LBP in the MENA region decreased slightly from 1990 to 2019. Furthermore, the burden among males was higher than the global average. Consequently, more integrated healthcare interventions are needed to more effectively alleviate the burden of low back pain in this region.

Using the derived 28-joint disease activity score patient-reported components (DAS28-P) index as a discriminatory measure of response to disease-modifying anti-rheumatic drug therapy in early rheumatoid arthritis.

BACKGROUND: The 28-joint disease activity score (DAS28) is a widely used measure to assess disease activity in rheumatoid arthritis (RA). The DAS28-P index, a derived proportion of the patient-reported components (joint tenderness and patient global assessment) within the DAS28, has been utilized as a discriminatory measure of non-inflammatory pain mechanisms in RA. This study aimed to evaluate the use of the DAS28-P index as a predictor of treatment response in early RA. METHODS: Patients with early RA enrolled in a supplemental fish oil clinical trial received a combination of disease-modifying anti-rheumatic drugs (DMARDs) according to a 'treat-to-target' protocol. First, consecutive measures of the DAS28-P index, derived from the DAS28-erythrocyte sedimentation rate (DAS28-ESR), at each visit over a 1-year period were estimated for each patient. Then, distinct subgroups of treatment responders based on the trajectories of the DAS28-P indices were identified using bivariate k-means cluster analysis. Data on baseline predictors as well as longitudinal outcomes of disease impact and DMARD use over a 1-year period and radiographic progression over a 3-year period were collected and analyzed using a random intercept, population-averaged generalized estimating equation model. RESULTS: 121 patients were included (74% female; mean age of 57; median of 16 weeks of active disease) and a 3-cluster model was identified-the 'Responders' group (n = 58; 48%), the 'Partial Responders' group (n = 32; 26%), and the 'Non-Responders' group (n = 31; 26%). The 'Partial Responders' group had consistently higher proportions of the DAS28-P index throughout the study period and had minimal radiographic progression over time, with the lowest joint erosion score of 0.9 [95% confidence interval (CI) 0.2, 1.6], observed at the 3-year follow-up. At 52 weeks, the methotrexate dose was higher for both 'Partial Responders' and 'Non-Responders' groups (18.5 mg [95% CI 15.5, 21.5] and 18.6 mg [95% CI 15.3, 21.8] respectively), when compared with the 'Responders' group (12.8 mg [95% CI 14.7, 20.9]). CONCLUSIONS: Persistently high DAS28-P index scores are useful to distinguish poor patient global assessment and excessive treatment escalation in early RA, suggestive of underlying non-inflammatory pain contributing to higher disease activity score. Early identification of patients with discordant subjective and objective components of composite disease activity measures may allow better tailoring of treatment in RA.

Krill oil improved osteoarthritic knee pain in adults with mild to moderate knee osteoarthritis: a 6-month multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Osteoarthritis (OA) is a major cause of chronic pain and disability worldwide. Treatment generally focuses on symptom relief through nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics, which may incur side effects. Krill oil, rich in anti-inflammatory long-chain (LC) omega-3 ( ω-3) PUFAs and astaxanthin, may be a safe and effective alternative treatment. OBJECTIVES: This study sought to investigate the effects of a commercially available krill oil supplement on knee pain in adults with mild to moderate knee OA. Secondary outcomes were knee stiffness; physical function; NSAID use; Omega-3 Index; and lipid, inflammatory, and safety markers. METHODS: Healthy adults (n = 235, 40-65 y old, BMI >18.5 to <35 kg/m2), clinically diagnosed with mild to moderate knee OA, regular knee pain, and consuming <0.5 g/d LC ω-3 PUFAs, participated in a 6-mo double-blind, randomized, placebo-controlled, multicenter trial. Participants consumed either 4 g krill oil/d (0.60 g EPA/d, 0.28 g DHA/d, 0.45 g astaxanthin/d) or placebo (mixed vegetable oil). Knee outcomes were assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) numeric scale (normalized to scores of 0-100). Outcomes were assessed at baseline, 3 mo, and 6 mo. RESULTS: Omega-3 Index increased with the krill oil supplement compared with placebo (from 6.0% to 8.9% compared with from 5.5% to 5.4%, P < 0.001). Knee pain score improved in both groups with greater improvements for krill oil than for placebo (difference in adjusted mean change between groups at 6 mo: -5.18; 95% CI: -10.0, -0.32; P = 0.04). Knee stiffness and physical function also had greater improvements with krill oil than with placebo (difference in adjusted mean change between groups at 6 mo: -6.45; 95% CI: -12.1, -0.9 and -4.67; 95% CI: -9.26, -0.05, respectively; P < 0.05). NSAID use, serum lipids, and inflammatory and safety markers did not differ between groups. CONCLUSIONS: Krill oil was safe to consume and resulted in modest improvements in knee pain, stiffness, and physical function in adults with mild to moderate knee OA.This trial was registered at clinicaltrials.gov as NCT03483090.

Effect of omega-three supplementation on serum urate and gout flares in people with gout; a pilot randomized trial.

OBJECTIVES: To determine the effect of omega-three supplementation with fish oil on serum urate, weight and body mass index (BMI) in people with gout. METHODS: A pilot 6-month, randomized, open-label clinical trial was undertaken in people with gout with serum urate ≥ 0.36 mmol/l. Forty participants were randomized to receive 6.2 g omega-3 fish oil daily or no fish oil for 24 weeks. Blood was obtained monthly for serum urate and red cell EPA (20:5n-3) DHA (22:6n-3) were measured using a blood spot collection system. RESULTS: There was no statistically significant difference in the mean (SEM) decrease in serum urate between baseline and week 24 between randomized groups: fish oil - 0.021 (0.02) mmol/l versus control - 0.006 (0.02) mmol/l. There was no significant difference in change in weight or BMI between baseline and week 24 between randomized groups. There was a statistically significant correlation between red cell omega-three concentrations and the total number of flares per participant between week 12 and week 24; total omega-three r = - 0.75 (p ≤ 0.001), EPA r = - 0.75 (p ≤ 0.001) and DHA r = -0.76 (p ≤ 0.001). In the omega-three fish oil group four participants reported gastrointestinal adverse effects definitely or probably related to the omega-three supplementation. CONCLUSIONS: The lack of untoward effect of omega three fish oil supplementation on serum urate and BMI together with the relationship between higher omega-three concentrations and lower gout flares supports the development of further adequately powered clinical trials to determine the role of omega-three supplements as prophylaxis against gout flares in people starting urate lowering therapy. Clinical trial registration ACTRN12617000539336p Registered 13/04/2017.

Perceptions and experiences of a manual therapy trial: a qualitative study of people with moderate to severe COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) presents with physical, emotional and social difficulties that affect quality of life. Multimodal management includes both pharmacological and non-pharmacological strategies, and pulmonary rehabilitation (PR) plays an important role. Recent research has suggested that manual therapies may improve perceptions of dyspnea for people with COPD. METHODS: Focus group interviews were conducted as part of a mixed methods study to assess the feasibility of implementing a manual therapy technique-muscle energy technique (MET)-as an adjunct to PR for people with moderate to severe COPD. Focus group interviews were conducted to examine trial participants views of the intervention and the trial design. A thematic analysis was undertaken to explore the data. RESULTS: Twelve participants with moderate to severe COPD participated in three focus groups. Participants were motivated to participate in the trial to be proactive about their health. They perceived MET to be a gentle, comfortable form of stretching that allowed them to 'breathe easier' and prepared them for PR. A small number of participants reported mild muscular discomfort during MET, but this was short-lasting and was not bothersome. Participants enjoyed the one-on-one contact with researchers and learned more about their breathing while performing spirometric testing. Most participants wanted longer and more frequent MET sessions, and some requested 'homework' stretching exercises. CONCLUSIONS: The findings of this study show that a manual therapy intervention was received well by participants in a clinical trial setting. A small number of participants reported mild musculoskeletal discomfort in relation to the MET treatment. Participant preferences for additional and longer treatment sessions should be carefully considered against available resources in future clinical trials. TRIAL REGISTRATION: ANZCTR, ACTRN12618000801213. Registered 11 May 2018 - Retrospectively registered. http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374643&isReview=true.

Effect of Foot Reflexology and Aromatherapy on Anxiety and Pain During Brachytherapy for Cervical Cancer.

OBJECTIVES: To determine if the addition of aromatherapy and foot reflexology to the standard of care improves pain and anxiety in patients receiving brachytherapy for cervical cancer. SAMPLE & SETTING: 41 women with locally advanced cervical cancer who received intracavitary brachytherapy as part of their treatment. METHODS & VARIABLES: Participants were randomized to either the control group, which received the standard-of-care management during brachytherapy, or the intervention group, which received the addition of aromatherapy and foot reflexology to standard of care. Participants rated their pain on a numeric rating scale and anxiety on the State-Trait Anxiety Inventory (STAI) and a numeric rating scale at five different time points. RESULTS: All average pain and anxiety scores were equal or lower at each key time point for the intervention group. Statistically significant differences were found for the intervention group for anxiety on the numeric rating scale and on the STAI, but only post-reflexology. IMPLICATIONS FOR NURSING: Nurses and other healthcare providers can be trained to provide reflexology during painful, anxiety-producing procedures to increase patient tolerance of these treatments and overall quality of life.

Oral Complementary Medicine Use among People with Inflammatory Arthritis: An Australian Rheumatology Association Database Analysis.

OBJECTIVES: To describe oral complementary medicine (CM) use in people with inflammatory arthritis, associations with use, and changes in use over time. METHODS: Demographic, clinical, and patient-reported outcome data from 5,630 participants with rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and juvenile idiopathic arthritis (JIA) were extracted from the Australian Rheumatology Association Database (ARAD), a national observational database. CM use at entry into ARAD was ascertained for participants recruited between 2002 and 2018. CM was categorised according to the NIH/Cochrane schema (fatty acids, herbs, or supplements). Logistic regression was used to assess associations between demographic characteristics and CM use. Change in CM use between 2006 and 2016 was investigated using a nonparametric test for trend of rate by year. RESULTS: 2,156 (38.3%) ARAD participants were taking CM at enrolment (RA: 1,502/3,960 (37.9%), AS: 281/736 (38.2%), PsA: 334/749 (44.6%), and JIA: 39/185 (21.1%)). CM use was more prevalent in women (OR 1.3; 95% CI: 1.13-1.50), those with tertiary education (OR 1.32; 95% CI: 1.13-1.55), private health insurance (OR 1.26; (95% CI: 1.10-1.44), drinking alcohol sometimes (OR 1.22; 95% CI: 1.05-1.43), poorer function (HAQ) (OR 1.13; 95% CI: 1.02-1.24), use of NSAID (OR 1.32; 95% CI 1.17-1.50), weak (OR 1.21; 95% CI 1.05-1.41) but not strong opioids, and less prevalent in current smokers (OR 0.76; 95%: CI 0.63-0.91). CM use was not associated with pain, disease activity, or quality of life. The most common CMs were fish oils (N = 1,489 users) followed by glucosamine (N = 605). Both declined in use over time between 2006 and 2016 (27.5% to 21.4%, trend p = 0.85 and 15.5% to 6.4%, trend p < 0.01), respectively. CONCLUSION: Oral CM use is common among Australians with inflammatory arthritis. Its use is greater among women and those with tertiary education. Fish oil and glucosamine, the most common CMs, both declined in use over time.

Modifiable Lifestyle Factors Associated With Response to Treatment in Early Rheumatoid Arthritis.

OBJECTIVE: We aimed to evaluate the associations between response to algorithm-directed treat-to-target conventional synthetic disease-modifying antirheumatic drug therapy and potentially modifiable lifestyle factors, including dietary fish oil supplementation, body mass index (BMI), and smoking history in a rheumatoid arthritis (RA) inception cohort. METHODS: Patients with RA with a duration of less than 12 months were reviewed every 3 to 6 weeks to adjust therapy according to disease response. All patients received advice to take fish oil supplements, and omega-3 status was measured as plasma levels of eicosapentaenoic acid (EPA). Lifestyle factors and other variables potentially prognostic for 28-joint Disease Activity Score (DAS28) remission and DAS28 low disease activity (LDA) at the 12-month visit were included in multivariable logistic regression models. RESULTS: Of 300 participants, 57.7% reached DAS28 LDA, and 43.7% were in DAS28 remission at 1 year. Increase in plasma EPA was associated with an increase in the odds of being in LDA (adjusted odds ratio [OR] = 1.27; P < 0.0001) and remission (adjusted OR = 1.21; P < 0.001). There was some evidence that the effect of BMI on LDA might be modified by smoking history. An increase in BMI was associated with a decrease in the odds of being in LDA in current and former smokers but had no impact on LDA in patients who had never smoked. There were no meaningful associations between BMI or smoking history and remission. CONCLUSION: Omega-3 status, BMI, and smoking history are potential predictors of outcome in early RA. The possibility of an effect modification by smoking on the predictive value of BMI merits further investigation.

Treatment of cancer-associated venous thromboembolism: 12-month outcomes of the placebo versus rivaroxaban randomization of the SELECT-D Trial (SELECT-D: 12m).

BACKGROUND: The Anticoagulation Therapy in Selected Cancer Patients at Risk of Recurrence of Venous Thromboembolism (SELECT-D) trial demonstrated reduction in recurrent venous thromboembolism (VTE) but increased bleeding with rivaroxaban compared with dalteparin for treatment of acute VTE in cancer patients, at 6 months. Uncertainty remains around optimal duration of anticoagulation. OBJECTIVES: To assess VTE recurrence and bleeding, with anticoagulation or not, beyond 6 months. PATIENTS/METHODS: In SELECT-D, after 6 months of trial treatment for VTE, patients with active cancer and residual deep vein thrombosis (RDVT) or index pulmonary embolism (PE) were eligible for randomization to a further 6 months of rivaroxaban or placebo. Patients with no RDVT stopped anticoagulation. Primary outcome was VTE recurrence at 12 months. The second randomization closed prematurely because of low recruitment when 92 of the planned 300 patients were recruited. RESULTS: Ninety-two of 136 eligible patients were randomized to rivaroxaban or placebo. The cumulative VTE recurrence after 6 months from the second randomization was 14% with placebo and 4% with rivaroxaban (hazard ratio, 0.32; 95% confidence interval [CI], 0.06-1.58). The major and clinically relevant non-major bleeding rates were 0% and 0% with placebo; and 5% (95% CI, 1-18) and 4% (95% CI, 1-17) with rivaroxaban. In an exploratory analysis, 7 (15%) of 46 placebo patients with RDVT or an index PE experienced recurrent VTE compared to none in the 35 patients in the RDVT-negative cohort (P = .03). CONCLUSION: The SELECT-D trial was underpowered to detect a statistically significant reduction in recurrent VTE with extended anticoagulation. The absence of RDVT and/or index PE, defined a population at low risk of recurrence.

Home-based pulmonary rehabilitation for COPD using minimal resources: An economic analysis.

BACKGROUND AND OBJECTIVE: This study aimed to compare the cost-effectiveness and cost-utility of home and centre-based pulmonary rehabilitation for adults with stable chronic obstructive pulmonary disease (COPD). METHODS: Prospective economic analyses were undertaken from a health system perspective alongside a randomized controlled equivalence trial in which participants referred to pulmonary rehabilitation undertook a standard 8-week outpatient centre-based or a new home-based programme. Participants underwent clinical assessment prior to programme commencement, immediately following completion and 12 months following programme completion. They provided data for utility (quality-adjusted life years (QALY) determined using SF6D (utility scores for health states) calculated from 36-Item Short Form Health Survey version 2) and effectiveness (change in distance walked on 6-min walk test (Δ6MWD) following pulmonary rehabilitation ). Individual-level cost data for the 12 months following programme completion was sourced from healthcare administration and government databases. RESULTS: Between-group mean difference point estimates for cost (-$4497 (95% CI: -$12 250 to $3257), utility (0.025 (-0.038 to 0.086) QALY) and effectiveness (14 m (-11 to 39) Δ6MWD) favoured the home-based group. Cost-utility analyses demonstrated 63% of estimates falling in the dominant southeast quadrant and the probability that the new home-based model was cost-effective at a $0 threshold for willingness to pay was 78%. Results were robust to a range of sensitivity analyses. Programme completion was associated with significantly lower healthcare costs in the following 12 months. CONCLUSION: Home-based pulmonary rehabilitation provides a cost-effective alternative model for people with COPD who cannot access traditional centre-based programmes.

Participation in Physical Activity During Center and Home-Based Pulmonary Rehabilitation for People With COPD: A SECONDARY ANALYSIS OF A RANDOMIZED CONTROLLED TRIAL.

PURPOSE: To compare levels of physical activity during center and home-based pulmonary rehabilitation (PR) in people with chronic obstructive pulmonary disease. METHODS: Forty-five consecutive participants (23 male, n = 20, in the home-based group) with mean age of 68 ± 8 yr and forced expiratory volume in the first second of expiration (FEV1) 53 ± 18% predicted undertook physical activity monitoring using the SenseWear Armband during the final week of the interventions of center or home-based PR. Differences in time spent in total physical activity (≥1.5 METs), time spent in moderate to vigorous intensity physical activity (≥3 METs), and steps were compared. RESULTS: Home participants spent a median and interquartile range of 310 (199-328) min/d engaged in total physical activity (29% moderate to vigorous intensity physical activity) compared with 300 (204-370) min/d for the center group (28% moderate to vigorous intensity physical activity, P = .98). Daily step count did not differ between groups (home-based median 5232 [2067-7718] versus center-based median 4049 [1983-6040], P = .66). Of note, center-based participants took 38% more steps on days of program attendance compared with nonattendance days (mean difference: 761 steps/d; 95% CI, -56 to 1579, P = .06). CONCLUSION: For people with chronic obstructive pulmonary disease undertaking PR, no differences in physical activity levels between center and home-based programs were demonstrated. Understanding the impact of the indirect supervision and motivational interviewing technique utilized during home-based PR on levels of physical activity in people with chronic obstructive pulmonary disease may support clinical implementation of the model as an alternative option to traditional care.

Comparison of an Oral Factor Xa Inhibitor With Low Molecular Weight Heparin in Patients With Cancer With Venous Thromboembolism: Results of a Randomized Trial (SELECT-D).

Purpose Venous thromboembolism (VTE) is common in patients with cancer. Long-term daily subcutaneous low molecular weight heparin has been standard treatment for such patients. The purpose of this study was to assess if an oral factor Xa inhibitor, rivaroxaban, would offer an alternative treatment for VTE in patients with cancer. Patient and Methods In this multicenter, randomized, open-label, pilot trial in the United Kingdom, patients with active cancer who had symptomatic pulmonary embolism (PE), incidental PE, or symptomatic lower-extremity proximal deep vein thrombosis (DVT) were recruited. Allocation was to dalteparin (200 IU/kg daily during month 1, then 150 IU/kg daily for months 2-6) or rivaroxaban (15 mg twice daily for 3 weeks, then 20 mg once daily for a total of 6 months). The primary outcome was VTE recurrence over 6 months. Safety was assessed by major bleeding and clinically relevant nonmajor bleeding (CRNMB). A sample size of 400 patients would provide estimates of VTE recurrence to within ± 4.5%, assuming a VTE recurrence rate at 6 months of 10%. Results A total of 203 patients were randomly assigned to each group, 58% of whom had metastases. Twenty-six patients experienced recurrent VTE (dalteparin, n = 18; rivaroxaban, n = 8). The 6-month cumulative VTE recurrence rate was 11% (95% CI, 7% to 16%) with dalteparin and 4% (95% CI, 2% to 9%) with rivaroxaban (hazard ratio [HR], 0.43; 95% CI, 0.19 to 0.99). The 6-month cumulative rate of major bleeding was 4% (95% CI, 2% to 8%) for dalteparin and 6% (95% CI, 3% to 11%) for rivaroxaban (HR, 1.83; 95% CI, 0.68 to 4.96). Corresponding rates of CRNMB were 4% (95% CI, 2% to 9%) and 13% (95% CI, 9% to 19%), respectively (HR, 3.76; 95% CI, 1.63 to 8.69). Conclusion Rivaroxaban was associated with relatively low VTE recurrence but higher CRNMB compared with dalteparin.

Telerehabilitation versus traditional centre-based pulmonary rehabilitation for people with chronic respiratory disease: protocol for a randomised controlled trial.

BACKGROUND: Pulmonary rehabilitation is an effective therapeutic intervention for people with chronic respiratory disease. However, fewer than 5% of eligible individuals receive pulmonary rehabilitation on an annual basis, largely due to limited availability of services and difficulties associated with travel and transport. The Rehabilitation Exercise At Home (REAcH) study is an assessor-blinded, multi-centre, randomised controlled equivalence trial designed to compare the efficacy of home-based telerehabilitation and traditional centre-based pulmonary rehabilitation in people with chronic respiratory disease. METHODS: Participants will undertake an 8-week group-based pulmonary rehabilitation program of twice-weekly supervised exercise training, either in-person at a centre-based pulmonary rehabilitation program or remotely from their home via the Internet. Supervised exercise training sessions will include 30 min of aerobic exercise (cycle and/or walking training). Individualised education and self-management training will be delivered. All participants will be prescribed a home exercise program of walking and strengthening activities. Outcomes will be assessed by a blinded assessor at baseline, after completion of the intervention, and 12-months post intervention. The primary outcome is change in dyspnea score as measured by the Chronic Respiratory Questionnaire - dyspnea domain (CRQ-D). Secondary outcomes will evaluate the efficacy of telerehabilitation on 6-min walk distance, endurance cycle time during a constant work rate test, physical activity and quality of life. Adherence to pulmonary rehabilitation between the two models will be compared. A full economic analysis from a societal perspective will be undertaken to determine the cost-effectiveness of telerehabilitation compared to centre-based pulmonary rehabilitation. DISCUSSION: Alternative models of pulmonary rehabilitation are required to improve both equity of access and patient-related outcomes. This trial will establish whether telerehabilitation can achieve equivalent improvement in outcomes compared to traditional centre-based pulmonary rehabilitation. If efficacious and cost-effective, the proposed telerehabilitation model is designed to be rapidly deployed into clinical practice. TRIAL REGISTRATION: Clinical trial registered with the Australian and New Zealand Clinical Trials Register at ( ACTRN12616000360415 ). Registered 21 March 2016.

Systematic Review of Skin-to-Skin Care for Full-Term, Healthy Newborns.

OBJECTIVE: To determine the effect of skin-to-skin mother-infant holding, touch, and/or massage on full-term, healthy newborns and their primary caregivers. DATA SOURCES: A seven-member scientific advisory panel searched the databases PubMed, CINAHL, and Scopus using the search terms massage, skin-to-skin contact, kangaroo care, touch, therapeutic touch, and full-term newborns for research with human participants published in English with no date parameters. STUDY SELECTION: The initial search yielded 416 articles. After reviewing titles and retaining only articles that met the review criteria, 280 articles remained. The panel co-chairs reviewed and discussed the abstracts of these articles and retained 90 for review. DATA EXTRACTION: Each article was assigned to one panel member and one co-chair for review. Members of the panel met via teleconference to present articles and to determine whether they had scientific merit and addressed the research question. Articles that did not meet these standards were eliminated. Forty articles included relevant evidence: 33 articles on skin-to-skin holding and 7 on infant massage. DATA SYNTHESIS: We created a table that included the purpose, design, and findings of each study. This information was synthesized into a feasibility report by the co-chairs. CONCLUSION: Evidence supports recommendations for skin-to-skin care for all full-term, healthy newborns. Although there is inadequate evidence to recommend massage as standard care for all newborns, massage has been shown to help consolidate sleep patterns and reduce jaundice.

Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose.

OBJECTIVES: To determine whether high-dose fish oil is superior to low-dose supplementation for symptomatic and structural outcomes in knee osteoarthritis (OA). METHODS: A randomised, double-blind, multicentre trial enrolled 202 patients with knee OA and regular knee pain. They were randomised 1:1 to high-dose fish oil (4.5 g omega-3 fatty acids) 15 mL/day or (2) low-dose fish oil (blend of fish oil and sunola oil; ratio of 1:9, 0.45 g omega-3 fatty acids) 15 mL/day. The primary endpoints were Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain score at 3, 6, 12 and 24 months, and change in cartilage volume at 24 months. Secondary outcomes included WOMAC function, quality of life, analgesic and non-steroidal anti-inflammatory drug use and bone marrow lesion score. RESULTS: Although there was improvement in both groups, the low-dose fish oil group had greater improvement in WOMAC pain and function scores at 2 years compared with the high-dose group, whereas between-group differences at 1 year did not reach statistical significance. There was no difference between the two groups in cartilage volume loss at 2 years. For other secondary endpoints, there was no difference between the two groups at 2 years. CONCLUSIONS: In people with symptomatic knee OA, there was no additional benefit of a high-dose fish oil compared with low-dose fish oil. The combination comparator oil appeared to have better efficacy in reducing pain at 2 years, suggesting that this requires further investigation. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN 12607000415404).

Dopamine receptor antagonists as new mode-of-action insecticide leads for control of Aedes and Culex mosquito vectors.

BACKGROUND: New mode-of-action insecticides are sought to provide continued control of pesticide resistant arthropod vectors of neglected tropical diseases (NTDs). We previously identified antagonists of the AaDOP2 D1-like dopamine receptor (DAR) from the yellow fever mosquito, Aedes aegypti, with toxicity to Ae. aegypti larvae as leads for novel insecticides. To extend DAR-based insecticide discovery, we evaluated the molecular and pharmacological characteristics of an orthologous DAR target, CqDOP2, from Culex quinquefasciatus, the vector of lymphatic filariasis and West Nile virus. METHODS/RESULTS: CqDOP2 has 94.7% amino acid identity to AaDOP2 and 28.3% identity to the human D1-like DAR, hD1. CqDOP2 and AaDOP2 exhibited similar pharmacological responses to biogenic amines and DAR antagonists in cell-based assays. The antagonists amitriptyline, amperozide, asenapine, chlorpromazine and doxepin were between 35 to 227-fold more selective at inhibiting the response of CqDOP2 and AaDOP2 in comparison to hD1. Antagonists were toxic to both C. quinquefasciatus and Ae. aegypti larvae, with LC50 values ranging from 41 to 208 µM 72 h post-exposure. Orthologous DOP2 receptors identified from the African malaria mosquito, Anopheles gambiae, the sand fly, Phlebotomus papatasi and the tsetse fly, Glossina morsitans, had high sequence similarity to CqDOP2 and AaDOP2. CONCLUSIONS: DAR antagonists represent a putative new insecticide class with activity against C. quinquefasciatus and Ae. aegypti, the two most important mosquito vectors of NTDs. There has been limited change in the sequence and pharmacological properties of the DOP2 DARs of these species since divergence of the tribes Culicini and Aedini. We identified antagonists selective for mosquito versus human DARs and observed a correlation between DAR pharmacology and the in vivo larval toxicity of antagonists. These data demonstrate that sequence similarity can be predictive of target potential. On this basis, we propose expanded insecticide discovery around orthologous DOP2 targets from additional dipteran vectors.

Evaluation of AaDOP2 receptor antagonists reveals antidepressants and antipsychotics as novel lead molecules for control of the yellow fever mosquito, Aedes aegypti.

The yellow fever mosquito, Aedes aegypti, vectors disease-causing agents that adversely affect human health, most notably the viruses causing dengue and yellow fever. The efficacy of current mosquito control programs is challenged by the emergence of insecticide-resistant mosquito populations, suggesting an urgent need for the development of chemical insecticides with new mechanisms of action. One recently identified potential insecticide target is the A. aegypti D1-like dopamine receptor, AaDOP2. The focus of the present study was to evaluate AaDOP2 antagonism both in vitro and in vivo using assay technologies with increased throughput. The in vitro assays revealed AaDOP2 antagonism by four distinct chemical scaffolds from tricyclic antidepressant or antipsychotic chemical classes, and elucidated several structure-activity relationship trends that contributed to enhanced antagonist potency, including lipophilicity, halide substitution on the tricyclic core, and conformational rigidity. Six compounds displayed previously unparalleled potency for in vitro AaDOP2 antagonism, and among these, asenapine, methiothepin, and cis-(Z)-flupenthixol displayed subnanomolar IC50 values and caused rapid toxicity to A. aegypti larvae and/or adults in vivo. Our study revealed a significant correlation between in vitro potency for AaDOP2 antagonism and in vivo toxicity, suggesting viability of AaDOP2 as an insecticidal target. Taken together, this study expanded the repertoire of known AaDOP2 antagonists, enhanced our understanding of AaDOP2 pharmacology, provided further support for rational targeting of AaDOP2, and demonstrated the utility of efficiency-enhancing in vitro and in vivo assay technologies within our genome-to-lead pipeline for the discovery of next-generation insecticides.

Vitamin D levels in an Australian population.

BACKGROUND: Levels of vitamin D in the population have come under increasing scrutiny, however there are only a few studies in Australia which measure levels in the general population. The aim of this study was to measure the levels of vitamin D within a large population cohort and examine the association with seasons and selected demographic and health risk factors. METHODS: A longitudinal cohort study of 2413 participants in the northwest suburbs of Adelaide, South Australia conducted between 2008 and 2010 was used to examine serum levels of 25-hydroxy vitamin D (25(OH)D) in relation to demographic characteristics (age, sex, income, education and country of birth), seasons, the use of vitamin D supplements and selected health risk factors (physical activity, body mass index and smoking). Both unadjusted and adjusted mean levels of serum 25(OH)D were examined, as were the factors associated with the unadjusted and adjusted prevalence of serum 25(OH)D levels below 50 and 75 nmol/L. RESULTS: Overall, the mean level of serum 25(OH)D was 69.2 nmol/L with 22.7% of the population having a serum 25(OH)D level below 50 nmol/L, the level which is generally recognised as vitamin D deficiency. There were significantly higher levels of 25(OH)D among males compared to females (t = 4.65, p < 0.001). Higher levels of 25(OH)D were also measured in summer and autumn compared with winter and spring. Generally, mean levels of 25(OH)D were lower in those classified as obese. Smokers and those undertaking no or less than 150 minutes/week of physical activity also had lower levels of serum vitamin D. Obesity (as classified by body mass index), season and undertaking an insufficient level of physical activity to obtain a health benefit were significantly associated with the prevalence of vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency is prevalent in South Australia, affecting almost one quarter of the population and levels are related to activity, obesity and season even when adjusted for confounding factors. Improved methods of addressing vitamin D levels in population are required.