Current practice in methodology and reporting of the sample size calculation in randomised trials of hip and knee osteoarthritis: a protocol for a systematic review

Background A key aspect of the design of randomised controlled trials (RCTs) is determining the sample size. It is important that the trial sample size is appropriately calculated. The required sample size will differ by clinical area, for instance, due to the prevalence of the condition and the choice of primary outcome. Additionally, it will depend upon the choice of target difference assumed in the calculation. Focussing upon the hip and knee osteoarthritis population, this study aims to systematically review how the trial size was determined for trials of osteoarthritis, on what basis, and how well these aspects are reported. Methods Several electronic databases (Medline, Cochrane library, CINAHL, EMBASE, PsycINFO, PEDro and AMED) will be searched to identify articles on RCTs of hip and knee osteoarthritis published in 2016. Articles will be screened for eligibility and data extracted independently by two reviewers. Data will be extracted on study characteristics (design, population, intervention and control treatments), primary outcome, chosen sample size and justification, parameters used to calculate the sample size (including treatment effect in control arm, level of variability in primary outcome, loss to follow-up rates). Data will be summarised across the studies using appropriate summary statistics (e.g. n and %, median and interquartile range). The proportion of studies which report each key component of the sample size calculation will be presented. The reproducibility of the sample size calculation will be tested. Discussion The findings of this systematic review will summarise the current practice for sample size calculation in trials of hip and knee osteoarthritis. It will also provide evidence on the completeness of the reporting of the sample size calculation, reproducibility of the chosen sample size and the basis for the values used in the calculation. Trial registration As this review was not eligible to be registered on PROSPERO, the summary information was uploaded to Figshare to make it publicly accessible in order to avoid unnecessary duplication amongst other benefits (https://doi.org/10.6084/m9.figshare.5009027.v1); Registered January 17, 2017

The meaning of participation to stroke survivors: a qualitative study

Background/Aims: The effect of stroke can be all encompassing, and has an impact on significant roles in life. Assessing someone's level of participation is seen as essential to understanding the social impact of a disability on a person's life, and tailoring support accordingly. This study aimed to examine the meaning of participation to stroke survivors, in order to provide insight into the meaning of participation in the context of a stroke. Methods: A qualitative approach drawing on methods of phenomenology was used, with data collected via semi-structured interviews and a follow-up focus group. Analysis was undertaken using techniques of interpretative phenomenological analysis. Findings: Six stroke survivors and six carers were interviewed, and four stroke survivors attended a focus group. Three main themes in relation to the meaning of participation were identified in the data: ‘being actively involved’; ‘making meaningful choices’; and ‘being me’. Conclusions: The work confirms the findings of previous studies on participation, and adds to current understandings by developing the meaning of ‘involvement’ beyond a social concept. It highlights that ‘involvement’ can include active engagement in life through being alone. It also identifies a specific link between stroke survivors’ sense of self, and participation

Problems persist in reporting of methods and results for the WOMAC measure in hip and knee osteoarthritis trials

Purpose The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a commonly used outcome measure for osteoarthritis. There are different versions of the WOMAC (Likert, visual analogue or numeric scales). A previous review of trials published before 2010 found poor reporting and inconsistency in how the WOMAC was used. This review explores whether these problems persist. Methods This systematic review included randomised trials of hip and/or knee osteoarthritis published in 2016 that used the WOMAC. Data were extracted on the version used, score range, analysis and results of the WOMAC, and whether these details were clearly reported. Results This review included 62 trials and 41 reported the WOMAC total score. The version used and item range for the WOMAC total score were unclear in 44% (n = 18/41) and 24% (n = 10/41) of trials, respectively. The smallest total score range was 0–10 (calculated by averaging 24 items scored 0–10); the largest was 0–2400 (calculated by summing 24 items scored 0–100). All trials reported the statistical analysis methods but only 29% reported the between-group mean difference and 95% confidence interval. Conclusion Details on the use and scoring of the WOMAC were often not reported. We recommend that trials report the version of the WOMAC and the score range used. The between-group treatment effect and corresponding confidence interval should be reported. If all the items of the WOMAC are collected, the total score and individual subscale scores should be presented. Better reporting would facilitate the interpretation, comparison and synthesis of the WOMAC score in trials

Patients’ use of information about medicine side effects in relation to experiences of suspected adverse drug reactions

Background Adverse drug reactions (ADRs) are common, and information about medicines is increasingly widely available to the public. However, relatively little work has explored how people use medicines information to help them assess symptoms that may be suspected ADRs. Objective Our objective was to determine how patients use patient information leaflets (PILs) or other medicines information sources and whether information use differs depending on experiences of suspected ADRs. Method This was a cross-sectional survey conducted in six National Health Service (NHS) hospitals in North West England involving medical in-patients taking at least two regular medicines prior to admission. The survey was administered via a questionnaire and covered use of the PIL and other medicines information sources, perceived knowledge about medicines risks/ADRs, experiences of suspected ADRs, plus demographic information. Results Of the 1,218 respondents to the survey, 18.8 % never read the PIL, whilst 6.5 % only do so if something unexpected happens. Educational level was related to perceived knowledge about medicines risks, but not to reading the PIL or seeking further information about medicines risks. Over half the respondents (56.0 %) never sought more information about possible side effects of medicines. A total of 57.2 % claimed they had experienced a suspected ADR. Of these 85.9 % were either very sure or fairly sure this was a reaction to a medicine. Over half of those experiencing a suspected ADR (53.8 %) had read the PIL, of whom 36.2 % did so before the suspected ADR occurred, the remainder afterwards. Reading the PIL helped 84.8 % of these respondents to decide they had experienced an ADR. Educational level, general knowledge of medicines risks and number of regular medicines used all increased the likelihood of experiencing an ADR. Conclusion More patients should be encouraged to read the PIL supplied with medicines. The results support the view that most patients feel knowledgeable about medicines risks and suspected ADRs and value information about side effects, but that reading about side effects in PILs or other medicines information sources does not lead to experiences of suspected ADRs

Effect of lifestyle intervention plus rosiglitazone or placebo therapy on left ventricular mass assessed with cardiovascular magnetic resonance in the metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>To evaluate the effect of lifestyle intervention in conjunction with rosiglitazone or placebo therapy on left ventricular (LV) mass, using cardiovascular magnetic resonance (CMR) in the metabolic syndrome.</p> <p>Methods</p> <p>The present study was a pre-specified substudy of a double-blind randomized controlled trial evaluating the effect of lifestyle intervention in conjunction with rosiglitazone or placebo therapy on carotid artery atherosclerosis in the metabolic syndrome. From this original study population, 10 subjects from the placebo group and 10 from the rosiglitazone group were randomly selected. At baseline and follow-up (52 weeks), clinical and laboratory measurements were assessed and a CMR-examination was performed to evaluate LV mass indexed for body surface area (LV mass-I). Subsequently, the effect of therapy (rosiglitazone vs. placebo) and clinical and laboratory variables on LV mass-I was evaluated.</p> <p>Results</p> <p>In both groups, body mass index, waist circumference, systolic and diastolic blood pressure significantly decreased during follow-up. Interestingly, LV mass-I significantly decreased in the placebo group (48.9 ± 5.3 g/m²vs. 44.3 ± 5.6 g/m², p < 0.001) indicating reverse remodeling, whereas LV mass-I remained unchanged in the rosiglitazone group (54.7 ± 9.9 g/m²vs. 53.7 ± 9.2 g/m², p = 0.3). After correction for systolic and diastolic blood pressure and triglyceride, the kind of therapy (rosiglitazone vs. placebo) remained the only significant predictor of LV mass-I reduction.</p> <p>Conclusions</p> <p>Lifestyle intervention resulted in a reduction of LV mass-I in the metabolic syndrome, indicating reverse remodeling. However, rosiglitazone therapy may have inhibited this positive reverse remodeling.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.controlled-trials.com/ISRCTN54951661">ISRCTN54951661</a>.</p

Detection of Massive Forming Galaxies at Redshifts Greater than One

The complex problem of when and how galaxies formed has not until recently been susceptible of direct attack. It has been known for some time that the excessive number of blue galaxies counted at faint magnitudes implies that a considerable fraction of the massive star formation in the universe occurred at z < 3, but, surprisingly, spectroscopic studies of galaxies down to a B magnitude of 24 found little sign of the expected high-z progenitors of current massive galaxies, but rather, in large part, small blue galaxies at modest redshifts z \sim 0.3. This unexpected population has diverted attention from the possibility that early massive star-forming galaxies might also be found in the faint blue excess. From KECK spectroscopic observations deep enough to encompass a large population of z > 1 field galaxies, we can now show directly that in fact these forming galaxies are present in substantial numbers at B \sim 24, and that the era from redshifts 1 to 2 was clearly a major period of galaxy formation. These z > 1 galaxies have very unusual morphologies as seen in deep HST WFPC2 images.Comment: 10 pages LaTeX + 5 PostScript figures in uuencoded gzipped tar file; aasms4.sty, flushrt.sty, overcite.sty (the two aastex4.0 and overcite.sty macros are available from xxx.lanl.gov) Also available (along with style files) via anonymous ftp to ftp://hubble.ifa.hawaii.edu/pub/preprints . E-print version of paper adds citation cross-references to other archived e-prints, where available. To appear in Nature October 19, 199

Pauli problem for a spin of arbitrary length: A simple method to determine its wave function

The problem of determining a pure state vector from measurements is investigated for a quantum spin of arbitrary length. Generically, only a finite number of wave functions is compatible with the intensities of the spin components in two different spatial directions, measured by a Stern-Gerlach apparatus. The remaining ambiguity can be resolved by one additional well-defined measurement. This method combines efficiency with simplicity: only a small number of quantities have to be measured and the experimental setup is elementary. Other approaches to determine state vectors from measurements, also known as the ‘‘Pauli problem,’’ are reviewed for both spin and particle systems

Does oral sodium bicarbonate therapy improve function and quality of life in older patients with chronic kidney disease and low-grade acidosis (the BiCARB trial)? Study protocol for a randomized controlled trial

Date of acceptance: 01/07/2015 © 2015 Witham et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements UK NIHR HTA grant 10/71/01. We acknowledge the financial support of NHS Research Scotland in conducting this trial.Peer reviewedPublisher PD

Exceptional river gorge formation from unexceptional floods

An understanding of rates and mechanisms of incision and knickpoint retreat in bedrock rivers is fundamental to perceptions of landscape response to external drivers, yet only sparse field data are available. Here we present eye witness accounts and quantitative surveys of rapid, amphitheatre-headed gorge formation in unweathered granite from the overtopping of a rock-cut dam spillway by small-moderate floods (~100–1,500 m3 s−1). The amount of erosion demonstrates no relationship with flood magnitude or bedload availability. Instead, structural pattern of the bedrock through faults and joints appears to be the primary control on landscape change. These discontinuities facilitate rapid erosion (>270 m headward retreat; ~100 m incision; and ~160 m widening over 6 years) principally through fluvial plucking and block topple. The example demonstrates the potential for extremely rapid transient bedrock erosion even when rocks are mechanically strong and flood discharges are moderate. These observations are relevant to perceived models of gorge formation and knickpoint retreat

The optical counterpart to gamma-ray burst GRB970228 observed using the Hubble Space Telescope

Although more than 2,000 astronomical gamma-ray bursts (GRBs) have been detected, and numerous models proposed to explain their occurrence, they have remained enigmatic owing to the lack of an obvious counterpart at other wavelengths. The recent ground-based detection of a transient source in the vicinity of GRB 970228 may therefore have provided a breakthrough. The optical counterpart appears to be embedded in an extended source which, if a galaxy as has been suggested, would lend weight to those models that place GRBs at cosmological distances. Here we report the observations using the Hubble Space Telescope of the transient counterpart and extended source 26 and 39 days after the initial gamma-ray outburst. We find that the counterpart has faded since the initial detection (and continues to fade), but the extended source exhibits no significant change in brightness between the two dates of observations reported here. The size and apparent constancy between the two epochs of HST observations imply that it is extragalactic, but its faintness makes a definitive statement about its nature difficult. Nevertheless, the decay profile of the transient source is consistent with a popular impulsive-fireball model, which assumes a merger between two neutron stars in a distant galaxy.Comment: 11 pages + 2 figures. To appear in Nature (29 May 1997 issue