Sallie Lamb

Changes in muscle torque following anterior cruciate ligament reconstruction: A comparison between hamstrings and patella tendon graft procedures on 45 patients

We designed a prospective study to examine the influence of graft type (hamstring or patella tendon) on thigh muscle torque recovery after anterior cruciate ligament reconstruction. 60 patients undergoing ACL reconstruction, using a hamstring or patella tendon graft, were studied and 45 were followed up to 1 year. Concentric and eccentric quadriceps and hamstring torque were recorded, using an isokinetic dynamometer preoperatively, 6 and 12 months after ACL reconstruction. We found an improvement in all muscle functions in both the operated and unoperated legs during the recovery period. Graft type had no effect on recovery. During the first 6 months, torque was restored to preoperative levels and continued to improve in all muscles and actions between 6 months and 1 year.

The OPERA trial: protocol for a randomised trial of an exercise intervention for older people in residential and nursing accommodation

AbstractBackgroundDepression is common in residents of Residential and Nursing homes (RNHs). It is usually undetected and often undertreated. Depression is associated with poor outcomes including increased morbidity and mortality. Exercise has potential to improve depression, and has been shown in existing trials to improve outcomes among younger and older people. Existing evidence comes from trials that are short, underpowered and not from RNH settings. The aim of the OPERA trial is to establish whether exercise is effective in reducing the prevalence of depression among older RNH residents.MethodOPERA is a cluster randomised controlled trial. RNHs are randomised to one of two groups with interventions lasting 12 monthsnIntervention group: a depression awareness and physical activity training session for care home staff, plus a whole home physical activation programme including twice weekly physiotherapist-led exercise groups. The intervention lasts for one year from randomisation, ornControl group: a depression awareness training session for care home staff.Participants are people aged 65 or over who are free of severe cognitive impairment and willing to participate in the study. Our primary outcome is the prevalence of depressive symptoms, a GDS-15 score of five or more, in all participants at the end of the one year intervention period. Our secondary depression outcomes include remission of depressive symptoms and change in GDS-15 scores in those with depressive symptoms prior to randomisation. Other secondary outcomes include, fear of falling, mobility, fractures, pain, cognition, costs and health related quality of life. We aimed to randomise 77 RNHs.DiscussionHome recruitment was completed in May 2010; 78 homes have been randomised. Follow up will finish in May 2011 and results will be available late 2011.Trial Registration[ISRCTN: ISRCTN43769277]

Functional recovery in patients with nonunion treated with the Ilizarov technique.

There are few reports on function after limb salvage surgery using the Ilizarov technique, and none that document the pattern of recovery or predict when maximum function returns. This prospective, longitudinal study documents the baseline functional abilities of 40 consecutive patients with nonunion of a fracture in the lower limb. Patients were studied for at least two and a half years following the completion of surgery. Function was measured by timed tests of functional performance and by the Toronto Extremity Salvage Score self-reported patient questionnaire. Recovery was slowest in the early stages after removal of the frame and greatest between six months and one year. Statistically significant improvement continued up to, but not beyond two years. This observation has important implications for the length of follow-up incorporated into the rehabilitation programmes for patients, predictions of patient status in regard to compensation and for the design of future studies to evaluate functional outcome.

Predicting response to a cognitive–behavioral approach to treating low back pain: Secondary analysis of the BeST data set

Identifying factors that predict who is likely to gain the greatest benefit from different treatments for low back pain is an important research priority. Here we report moderator analyses of the Back Skills Training Trial (BeST) that tested a cognitive–behavioral approach for low back pain.

Close contact casting vs surgery for initial treatment of unstable ankle fractures in older adults: A randomized clinical trial

ImportancenAnkle fractures cause substantial morbidity in older persons. Surgical fixation is the contemporary intervention but is associated with infection and other healing complications.nnnObjectivenTo determine whether initial fracture treatment with close contact casting, a molded below-knee cast with minimal padding, offers outcome equivalent to that with immediate surgery, with fewer complications and less health resource use.nnnDesign, Setting, and ParticipantsnThis was a pragmatic, equivalence, randomized clinical trial with blinded outcome assessors. A pilot study commenced in May 2004, followed by multicenter recruitment from July 2010 to November 2013; follow-up was completed May 2014. Recruitment was from 24 UK major trauma centers and general hospitals. Participants were 620 adults older than 60 years with acute, overtly unstable ankle fracture. Exclusions were serious limb or concomitant disease or substantial cognitive impairment.nnnInterventionsnParticipants were randomly assigned to surgery (nu2009=u2009309) or casting (nu2009=u2009311). Casts were applied in the operating room under general or spinal anesthesia by a trained surgeon.nnnMain Outcomes and MeasuresnThe primary 6-month, per-protocol outcome was the Olerud-Molander Ankle Score at 6 months (OMAS; range, 0-100; higher scores indicate better outcomes and fewer symptoms), equivalence prespecified as ±6 points. Secondary outcomes were quality of life, pain, ankle motion, mobility, complications, health resource use, and patient satisfaction.nnnResultsnAmong 620 adults (mean age, 71 years; 460 [74%] women) who were randomized, 593 (96%) completed the study. Nearly all participants (579/620; 93%) received allocated treatment; 52 of 275 (19%) who initially received casting later converted to surgery, which was allowable in the casting treatment pathway to manage early loss of fracture reduction. At 6 months, casting resulted in ankle function equivalent to that with surgery (OMAS score, 66.0 [95% CI, 63.6-68.5] for surgery vs 64.5 [95% CI, 61.8-67.2] for casting; mean difference, -0.6 [95% CI, -3.9 to 2.6]; P for equivalenceu2009=u2009.001). Infection and wound breakdown were more common with surgery (29/298 [10%] vs 4/275 [1%]; odds ratio [OR], 7.3 [95% CI, 2.6-20.2]), as were additional operating room procedures (18/298 [6%] for surgery and 3/275 [1%] for casting; OR, 5.8 [95% CI, 1.8-18.7]). Radiologic malunion was more common in the casting group (38/249 [15%] vs 8/274 [3%] for surgery; OR, 6.0 [95% CI, 2.8-12.9]). Casting required less operating room time compared with surgery (mean difference [minutes/participant], -54 [95% CI, -58 to -50]). There were no significant differences in other secondary outcomes: quality of life, pain, ankle motion, mobility, and patient satisfaction.nnnConclusions and RelevancenAmong older adults with unstable ankle fracture, the use of close contact casting compared with surgery resulted in similar functional outcomes at 6 months. Close contact casting may be an appropriate treatment for such patients.nnnTrial Registrationnisrctn.com Identifier: ISRCTN04180738.

Development of a core outcome set for disease modification trials in mild to moderate dementia: a systematic review, patient and public consultation and consensus recommendations.

BACKGROUNDnThere is currently no disease-modifying treatment available to halt or delay the progression of the disease pathology in dementia. An agreed core set of the best-available and most appropriate outcomes for disease modification would facilitate the design of trials and ensure consistency across disease modification trials, as well as making results comparable and meta-analysable in future trials.nnnOBJECTIVESnTo agree a set of core outcomes for disease modification trials for mild to moderate dementia with the UK dementia research community and patient and public involvement (PPI).nnnDATA SOURCESnWe included disease modification trials with quantitative outcomes of efficacy from (1) references from related systematic reviews in workstream 1; (2) searches of the Cochrane Dementia and Cognitive Improvement Group study register, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, EMBASE, Latin American and Caribbean Health Sciences Literature and PsycINFO on 11 December 2015, and clinical trial registries [International Standard Randomised Controlled Trial Number (ISRCTN) and clinicaltrials.gov] on 22 and 29 January 2016; and (3) hand-searches of reference lists of relevant systematic reviews from database searches.nnnREVIEW METHODSnThe project consisted of four workstreams. (1) We obtained related core outcome sets and work from co-applicants. (2) We systematically reviewed published and ongoing disease modification trials to identify the outcomes used in different domains. We extracted outcomes used in each trial, recording how many used each outcome and with how many participants. We divided outcomes into the domains measured and searched for validation data. (3) We consulted with PPI participants about recommended outcomes. (4) We presented all the synthesised information at a conference attended by the wider body of National Institute for Health Research (NIHR) dementia researchers to reach consensus on a core set of outcomes.nnnRESULTSnWe included 149 papers from the 22,918 papers screened, referring to 125 individual trials. Eighty-one outcomes were used across trials, including 72 scales [31 cognitive, 12 activities of daily living (ADLs), 10 global, 16 neuropsychiatric and three quality of life] and nine biological techniques. We consulted with 18 people for PPI. The conference decided that only cognition and biological markers are core measures of disease modification. Cognition should be measured by the Mini Mental State Examination (MMSE) or the Alzheimers Disease Assessment Scale - Cognitive subscale (ADAS-Cog), and brain changes through structural magnetic resonance imaging (MRI) in a subset of participants. All other domains are important but not core. We recommend using the Neuropsychiatric Inventory for neuropsychiatric symptoms: the Disability Assessment for Dementia for ADLs, the Dementia Quality of Life Measure for quality of life and the Clinical Dementia Rating scale to measure dementia globally.nnnLIMITATIONSnMost of the trials included participants with Alzheimers disease, so recommendations may not apply to other types of dementia. We did not conduct economic analyses. The PPI consultation was limited to members of the Alzheimers Society Research Network.nnnCONCLUSIONSnCognitive outcomes and biological markers form the core outcome set for future disease modification trials, measured by the MMSE or ADAS-Cog, and structural MRI in a subset of participants.nnnFUTURE WORKnWe envisage that the core set may be superseded in the future, particularly for other types of dementia. There is a need to develop an algorithm to compare scores on the MMSE and ADAS-Cog.nnnSTUDY REGISTRATIONnThe project was registered with Core Outcome Measures in Effectiveness Trials [ www.comet-initiative.org/studies/details/819?result=true (accessed 7 April 2016)]. The systematic review protocol is registered as PROSPERO CRD42015027346.nnnFUNDINGnThe National Institute for Health Research Health Technology Assessment programme.

A randomised controlled trial and cost-effectiveness analysis of high-frequency oscillatory ventilation against conventional artificial ventilation for adults with acute respiratory distress syndrome. The OSCAR (OSCillation in ARDS) study.

BACKGROUNDnPatients with the acute respiratory distress syndrome (ARDS) require artificial ventilation but this treatment may produce secondary lung damage. High-frequency oscillatory ventilation (HFOV) may reduce this damage.nnnOBJECTIVESnTo determine the clinical benefit and cost-effectiveness of HFOV in patients with ARDS compared with standard mechanical ventilation.nnnDESIGNnA parallel, randomised, unblinded clinical trial.nnnSETTINGnUK intensive care units.nnnPARTICIPANTSnMechanically ventilated patients with a partial pressure of oxygen in arterial blood/fractional concentration of inspired oxygen (P : F) ratio of 26.7 kPa (200 mmHg) or less and an expected duration of ventilation of at least 2 days at recruitment.nnnINTERVENTIONSnTreatment armu2002HFOV using a Novalung R100(®) ventilator (Metran Co. Ltd, Saitama, Japan) ventilator until the start of weaning. Control armu2002Conventional mechanical ventilation using the devices available in the participating centres.nnnMAIN OUTCOME MEASURESnThe primary clinical outcome was all-cause mortality at 30 days after randomisation. The primary health economic outcome was the cost per quality-adjusted life-year (QALY) gained.nnnRESULTSnOne hundred and sixty-six of 398 patients (41.7%) randomised to the HFOV group and 163 of 397 patients (41.1%) randomised to the conventional mechanical ventilation group died within 30 days of randomisation (p = 0.85), for an absolute difference of 0.6% [95% confidence interval (CI) -6.1% to 7.5%]. After adjustment for study centre, sex, Acute Physiology and Chronic Health Evaluation II score, and the initial P : F ratio, the odds ratio for survival in the conventional ventilation group was 1.03 (95% CI 0.75 to 1.40; p = 0.87 logistic regression). Survival analysis showed no difference in the probability of survival up to 12 months after randomisation. The average QALY at 1 year in the HFOV group was 0.302 compared to 0.246. This gives an incremental cost-effectiveness ratio (ICER) for the cost to society per QALY of £88,790 and an ICER for the cost to the NHS per QALY of £ 78,260.nnnCONCLUSIONSnThe use of HFOV had no effect on 30-day mortality in adult patients undergoing mechanical ventilation for ARDS and no economic advantage. We suggest that further research into avoiding ventilator-induced lung injury should concentrate on ventilatory strategies other than HFOV.nnnTRIAL REGISTRATIONnCurrent Controlled Trials ISRCTN10416500.

Informing efficient randomised controlled trials: Exploration of challenges in developing progression criteria for internal pilot studies

Objectives Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or ‘progression’ criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase. Design A structured literature review and exploration of stakeholders opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders. Results There is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decision-making process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented. Conclusions Systematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials.

Recovery of muscle strength and power after limb-lengthening surgery.

OBJECTIVEnTo report muscle strength, power, and function after limb-lengthening surgery performed by using the Ilizarov technique.nnnDESIGNnProspective, longitudinal observational study of a cohort of consecutive patients who underwent limb-lengthening distraction followed up for 2 years after surgery.nnnSETTINGnNational Health Service hospital specializing in orthopedic surgery.nnnPARTICIPANTSnPatients (N=16) who had undergone limb-lengthening surgery performed by using the Ilizarov method (11 men, 5 women; mean age=27 y; range, 13-56 y).nnnINTERVENTIONSnNone.nnnMAIN OUTCOME MEASURESnMuscle strength and power were assessed by using 2 validated measures: isokinetic concentric strength of the quadriceps and hamstrings measured by using a dynamometer and leg extensor power. Measures were recorded preoperatively and at 6, 12, and 24 months after the completion of lengthening. Function was measured by 2 timed tests of functional performance: stair climbing and sit-to-stand.nnnRESULTSnOverall results were good with high reports of function and satisfactory clinical examination. Both concentric muscle strength and leg power showed a clear pattern of decreased muscle strength at 6 months after frame removal, improving throughout the study period until it was within 3% of the preoperative value at 2 years. By 2 years, self-reported function and ability to complete timed functional tests had returned to or improved on the preoperative values. Muscle strength remained slightly below the preoperative value; this was more pronounced in the quadriceps than the hamstrings. There was no association between muscle strength and the amount of lengthening that had been undertaken.nnnCONCLUSIONSnThis study suggests that there is a small residual decrease in muscle strength and power after limb-lengthening surgery but that these do not adversely impact on a patients ability to perform everyday functional activities.

Telephone interviews can be used to collect follow-up data subsequent to no response to postal questionnaires in clinical trials.

OBJECTIVEnFollow-up data were collected using postal questionnaires and if participants did not respond, then data was collected using telephone interviews. The objectives of this study were to examine, for the two methods, how respondents differed in characteristics and whether the observed treatment difference varied.nnnSTUDY DESIGN AND SETTINGnA large clinical trial of lower back pain.nnnRESULTSnAbout 60% (98/163) of the nonresponders to postal questionnaire provided data by telephone, which increased the overall response rate by 14% (from 71% to 85%). A consistent treatment difference was found across the methods for the outcome measures at 12 months, implying that the observed treatment effect had not been modified. There were some differences between the participants: responders of postal questionnaire were older, likely to be female, white (ethnic origin), not working, with less disability of back pain, compared with those who responded by a telephone interview. At 12 months, there was greater improvement in back pain, disability, and general health for those who responded by postal questionnaires.nnnCONCLUSIONnResearchers should consider the use of more than one method of collecting data as this increases response rate, participant representativeness, and enhances precision of effect estimates.