Randomised, placebo-controlled, double-blind, double-dummy, multicentre trial comparing electronic cigarettes with nicotine to varenicline and to electronic cigarettes without nicotine: the ECSMOKE trial protocol.

Electronic cigarettes (EC) mainly with nicotine content are widely used worldwide. Although the number of publications about its use is increasing exponentially, evidence-based, unbiased, conclusive, head-to-head comparisons about its efficacy and safety as an aid for smoking cessation are lacking. METHODS AND ANALYSIS: Design: randomised, placebo and reference treatment-controlled, multicentre, double-blind, double-dummy, parallel-group trial. Participants: smokers smoking at least 10 cigarettes/day in the past year and motivated to quit, aged 18-70 years. Interventions: (A) EC without nicotine (ECwoN) plus placebo tablets of varenicline administered by oral route: placebo condition, (B) EC with nicotine (ECwN) plus placebo tablets of varenicline: ECwN condition. Voltage regulated EC will be used with liquid containing 12 mg/mL of nicotine for ad libitum use. Flavour: blond tobacco. (C) Reference: ECwoN plus 0.5 mg varenicline tablets: varenicline condition. Varenicline administered according to the marketing authorisationauthorisation. Treatment duration: 1 week+3 months. Primary outcome: continuous smoking abstinence rate (CAR) (abstinence from conventional/combustible cigarettes) during the last 4 weeks (weeks 9-12) of the treatment period defined as self-report of no smoking during the previous 2 weeks and expired air carbon monoxide ≤8 at visit 4 at week 10 after target quit date (TQD), that is, 11 weeks after treatment initiation AND at visit 5, week 12 after TQD, that is, 13 weeks after treatment initiation. Secondary outcomes: safety profile; point prevalence abstinence rate; CAR confirmed by urinary anabasine concentration; changes in cigarettes/day consumption; craving for tobacco and withdrawal symptoms with respect of baseline. The ethics committee approval was obtained on 17 April 2018. All data collected about the study participants will be anonymised. Investigators will communicate trial results to participants, health authorities, healthcare professionals, the public and other relevant groups without any publication restrictions. NCT03630614; Pre-results

Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials.

BACKGROUND: Treatment efficacy of physical agents in osteoarthritis of the knee (OAK) pain has been largely unknown, and this systematic review was aimed at assessing their short-term efficacies for pain relief. METHODS: Systematic review with meta-analysis of efficacy within 1-4 weeks and at follow up at 1-12 weeks after the end of treatment. RESULTS: 36 randomised placebo-controlled trials (RCTs) were identified with 2434 patients where 1391 patients received active treatment. 33 trials satisfied three or more out of five methodological criteria (Jadad scale). The patient sample had a mean age of 65.1 years and mean baseline pain of 62.9 mm on a 100 mm visual analogue scale (VAS). Within 4 weeks of the commencement of treatment manual acupuncture, static magnets and ultrasound therapies did not offer statistically significant short-term pain relief over placebo. Pulsed electromagnetic fields offered a small reduction in pain of 6.9 mm [95% CI: 2.2 to 11.6] (n = 487). Transcutaneous electrical nerve stimulation (TENS, including interferential currents), electro-acupuncture (EA) and low level laser therapy (LLLT) offered clinically relevant pain relieving effects of 18.8 mm [95% CI: 9.6 to 28.1] (n = 414), 21.9 mm [95% CI: 17.3 to 26.5] (n = 73) and 17.7 mm [95% CI: 8.1 to 27.3] (n = 343) on VAS respectively versus placebo control. In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to 22.2 mm [95% CI: 18.1 to 26.3] for TENS, and 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS. Follow-up data up to 12 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of LLLT, EA and TENS treatment was stopped. CONCLUSION: TENS, EA and LLLT administered with optimal doses in an intensive 2-4 week treatment regimen, seem to offer clinically relevant short-term pain relief for OAK

Risk factors for sickness absence due to low back pain and prognostic factors for return to work in a cohort of shipyard workers

The purpose of this study was to determine risk factors for the occurrence of sickness absence due to low back pain (LBP) and to evaluate prognostic factors for return to work. A longitudinal study with 1-year follow-up was conducted among 853 shipyard workers. The cohort was drawn around January 2004 among employees in the shipyard industry. Baseline information was obtained by questionnaire on physical and psychosocial work load, need for recovery, perceived general health, musculoskeletal complaints, sickness absence, and health care use during the past year. During the 1-year follow-up for each subject medical certifications were retrieved for information on the frequency and duration of spells of sickness absence and associated diagnoses. Cox regression analyses were conducted on occurrence and on duration of sickness absence with hazard ratios (HR) with 95% confidence interval (95% CI) as measure of association. During the 1-year follow-up period, 14% of the population was on sick leave at least once with LBP while recurrence reached 41%. The main risk factors for sickness absence were previous absence due to a health problem other than LBP (HR 3.07; 95%CI 1.66–5.68) or previous sickness absence due to LBP (HR 6.52; 95%CI 3.16–13.46). Care seeking for LBP and lower educational level also hold significant influences (HR 2.41; 95%CI 1.45–4.01 and HR 2.46; 95%CI 1.19–5.07, respectively). Living with others, night shift and supervising duties were associated with less absenteeism due to LBP. Workers with a history of herniated disc had a significantly decreased rate of returning to work, whereas those who suffered from hand-wrist complaints and LBP returned to work faster. Prior sick leave due to LBP partly captured the effects of work-related physical and psychosocial factors on occurrence of sick leave. Our study showed that individual and job characteristics (living alone, night shift, lower education, sick leave, or care seeking during the last 12 months) influenced the decision to take sick leave due to LBP. An increased awareness of those frequently on sick leave and additional management after return to work may have a beneficial effect on the sickness absence pattern

Identifying placebo responders and predictors of response in osteoarthritis: a protocol for individual patient data meta-analysis

Background: The management of osteoarthritis (OA) is unsatisfactory, as most treatments are not clinically effective over placebo and most drugs have considerable side effects. On average, 75 % of the analgesic effect from OA treatments in clinical trials can be attributed to a placebo response, and this response varies greatly from patient to patient. This individual patient data (IPD) meta-analysis aims to identify placebo responders and the potential determinants of the placebo response in OA. Methods: This study is undertaken in conjunction with the OA Trial Bank, an ongoing international consortium aiming to collect IPD from randomised controlled trials (RCTs) for all treatments of OA. RCTs for each treatment of OA have been systematically searched for, and authors of the relevant trials have been contacted to request the IPD. We will use the IPD of placebo-controlled RCTs held by the OA Trial Bank for this project. The IPD in placebo groups will be used to investigate the placebo response according to the minimum clinically important difference (MCID) threshold (e.g. 20 % pain reduction). Responders to placebo will be compared with non-responders to identify predictors of response. The quality of the trials will be assessed and potential determinants will be examined using multilevel logistic regression analyses. Discussion: This study explores the varying magnitude of the placebo response and the proportion of participants that experience a clinically important placebo effect in OA RCTs. Potential determinants of the placebo response will also be investigated. These determinants may be useful for future studies as it may allow participants to be stratified into groups based on their likely response to placebo. The results of this study may also be useful for pharmaceutical companies, who could improve the design of their studies in order to separate the specific treatment from the non-specific contextual (i.e. placebo) effects

Self-management for osteoarthritis of the knee: Does mode of delivery influence outcome?

Background Self-management has become increasingly popular in the management of chronic diseases. There are many different self-management models. Meta analyses of arthritis self-management have concluded that it is difficult to recommend any one program in preference to another due to inconsistencies in the study designs used to evaluate different programs. The Stanford Arthritis Self-Management Program (ASMP), most commonly delivered by trained lay leaders, is a generic program widely used for people with rheumatological disorders. We have developed a more specific program expressly for people with osteoarthritis of the knee (OAKP). It includes information designed to be delivered by health professionals and results in improvements in pain, function and quality of life. Aim: To determine whether, for people with osteoarthritis (OA) of the knee, the OAKP implemented in a primary health care setting can achieve and maintain clinically meaningful improvements in more participants than ASMP delivered in the same environment. Methods/Design The effectiveness of the programs will be compared in a single-blind randomized study. Participants: 146 participants with established OA knee will be recruited. Volunteers with coexistent inflammatory joint disease or serious co-morbidities will be excluded. Interventions: Participants will be randomised into either OAKP or ASMP groups and followed for 6 months. Measurements: Assessments will be immediately before and after the intervention and at 6 months. Primary outcome measures will be WOMAC and SF-36 questionnaires and a VAS for pain. Secondary outcomes will include balance, tested using a timed single leg balance test and a timed step test and self-efficacy. Data will be analysed using repeated measures ANOVA. Discussion With an aging population the health care costs for people with arthritis are ever increasing. Although cost analysis is beyond the scope of this study, it is reasonable to expect that costs will be greater when health professionals deliver self-management programs as opposed to lay leaders. Consequently it is critical to examine the relative effectiveness of the primary care management strategies available for OA

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Relative efficacy of topical non-steroidal anti-inflammatory drugs and topical capsaicin in osteoarthritis: protocol for an individual patient data meta-analysis

Background Pain is the most troubling issue to patients with osteoarthritis (OA), yet current pharmacological treatments offer only small-to-moderate pain reduction. Current guidelines therefore emphasise the need to identify predictors of treatment response. In line with these recommendations, an individual patient data (IPD) meta-analysis will be conducted. The study aims to investigate the relative treatment effects of topical non-steroidal anti-inflammatory drugs (NSAIDs) and topical capsaicin in OA and to identify patient-level predictors of treatment response. Methods IPD will be collected from randomised controlled trials (RCTs) of topical NSAIDs and capsaicin in OA. Multilevel regression modelling will be conducted to determine predictors for the specific and the overall treatment effect. Discussion Through the identification of treatment responders, this IPD meta-analysis may improve the current understanding of the pain mechanisms in OA and guide clinical decision-making. Identifying and prescribing the treatment most likely to be beneficial for an individual with OA will improve the efficiency of patient management

Interference with work in fibromyalgia - effect of treatment with pregabalin and relation to pain response

BACKGROUND: Clinical trials in chronic pain often collect information about interference with work as answers to component questions of commonly used questionnaires but these data are not normally analysed separately. METHODS: We performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks. We analysed data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey, Sheehan Disability Scale, and Multidimensional Assessment of Fatigue, including "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from FIQ. Analyses were performed according to randomised treatment group (pregabalin 150-600 mg daily or placebo), pain improvement (0-10 numerical pain rating scale scores at trial beginning vs. end), and end of trial pain state (100 mm visual analogue pain scale [VAS]). RESULTS: Comparing treatment group average outcomes revealed modest improvement over the duration of the trials, more so with active treatment than with placebo. For the 'work missed' question from FIQ the change for patients on placebo was from 2.2 (standard deviation [SD] 2.3) days of work lost per week at trial beginning to 1.9 (SD 2.1) days lost at trial end (p < 0.01). For patients on 600 mg pregabalin the change was from 2.1 (SD 2.2) days to 1.6 (SD 2.0) days (p < 0.001). However, the change in days of work lost was substantial in patients with a good pain response: from 2.0 (SD 2.2) days to 0.97 (SD 1.6) days (p < 0.0001) for those experiencing >/= 50% pain improvement and from 1.9 (SD 2.2) days to 0.73 (SD 1.4) days (p < 0.0001) for those achieving a low level of pain at trial end (<30 mm on the VAS). Patients achieving both >/= 50% pain improvement and a pain score <30 mm on the VAS had the largest improvement, from 2.0 (SD 2.2) days to 0.60 (SD 1.3) days (p < 0.0001). Analysing answers to the other questions yielded qualitatively similar results. CONCLUSIONS: Effective pain treatment goes along with benefit regarding work. A reduction in time off work >1 day per week can be achieved in patients with good pain responses