Dipesh Mistry

The risks of red cell transfusion for hip fracture surgery in the elderly

Background and Objectives  The benefits and indications for blood transfusion among surgical patients are controversial. There is evidence which suggests that blood transfusion is associated with poor clinical outcomes and risks of infection, but there are few data in the elderly population.

Group cognitive behavioural interventions for low back pain in primary care: extended follow-up of the Back Skills Training Trial (ISRCTN54717854).

Summary Long‐term follow‐up of a randomised controlled trial of a cognitive behavioural intervention for low back pain indicates that effects on disability and pain are maintained to at least 34 months. Abstract Group cognitive behavioural intervention (CBI) is effective in reducing low back pain and disability over a 12‐month period, in comparison to best practice advice in primary care. The aim was to study the effects of this CBI beyond 12 months. We undertook an extended follow‐up of our original randomised, controlled trial of a group CBI and best practice advice in primary care, in comparison to best practice advice alone. Participants were mailed a questionnaire including measures of disability, pain, health services resource use, and health‐related quality of life. The time of extended follow‐up ranged between 20 and 50 months (mean 34 months). Fifty‐six percent (395 of 701) of the original cohort provided extended follow‐up. Those who responded were older and had less disability and pain at baseline than did the original trial cohort. After 12 months, the improvements in pain and disability observed with CBI were sustained. For disability measures, the treatment difference in favour of CBI persisted (mean difference 1.3 Roland and Morris Disability Questionnaire points, 95% confidence interval 0.27 to 2.26; 5.5 Modified von Korff Scale disability points, 95% confidence interval 0.27 to 10.64). There was no between‐group difference in Modified von Korff Scale pain outcomes. The results suggest that the effects of a group CBI are maintained up to an average of 34 months. Although pain improves in response to best practice advice, longer‐term recovery of disability remains substantially less.

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

Importance Ankle fractures cause substantial morbidity in older persons. Surgical fixation is the contemporary intervention but is associated with infection and other healing complications. Objective To 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. Design, Setting, and Participants This 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. Interventions Participants were randomly assigned to surgery (n = 309) or casting (n = 311). Casts were applied in the operating room under general or spinal anesthesia by a trained surgeon. Main Outcomes and Measures The 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. Results Among 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 equivalence = .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. Conclusions and Relevance Among 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. Trial Registration isrctn.com Identifier: ISRCTN04180738.

Identifying potential moderators for response to treatment in low back pain: A systematic review

BACKGROUND Identifying which patients with non-specific low back pain are likely to gain the greatest benefit from different treatments is an important research priority. Few studies are large enough to produce data on sub-group effects from different treatments. Data from existing large studies may help identify potential moderators to use in future individual patient data meta-analyses. OBJECTIVE To systematically review papers of therapist delivered interventions for low back pain to identify potential moderators to inform an individual patient data meta-analysis. DATA SOURCES We searched MEDLINE, EMBASE, Web of Science and Citation Index and Cochrane Register of Controlled Trials (CENTRALhttp://www.cochrane.org/editorial-and-publishing-policy-resource/cochrane-central-register-controlled-trials-central) for relevant papers. DATA EXTRACTION AND DATA SYNTHESIS We screened for randomised controlled trials with ≥500 or more participants, and cohort studies of ≥1000 or more participants. We examined all publications related to these studies for any reported moderator analyses. Two reviewers independently did risk of bias assessment of main results and quality assessment of any moderator analyses. RESULTS We included four randomised trials (n=7208). Potential moderators with strong evidence (p<0.05) in one or more studies were age, employment status and type, back pain status, narcotic medication use, treatment expectations and education. Potential moderators with weaker evidence (0.05<p≤0.20) included gender, psychological distress, pain/disability and quality of life. CONCLUSION There are insufficient robust data on moderators to be useful in clinical practice. This review has identified some important potential moderators of treatment effect worthy of testing in future confirmatory analyses.

The Beta Agonist Lung Injury TrIal (BALTI) - prevention trial protocol

BackgroundAcute lung injury complicates approximately 25-30% of subjects undergoing oesophagectomy. Experimental studies suggest that treatment with beta agonists may prevent the development of acute lung injury by decreasing inflammatory cell infiltration, activation and inflammatory cytokine release, enhancing basal alveolar fluid clearance and improving alveolar capillary barrier function.Methods/DesignThe Beta Agonist Lung Injury TrIal (prevention) is a multi-centre, randomised, double blind, placebo-controlled trial. The aim of the trial is to determine in patients undergoing elective transthoracic oesphagectomy, if treatment with inhaled salmeterol 100 mcg twice daily started at induction of anaesthesia and continued for 72 hours thereafter compared to placebo affect the incidence of early acute lung injury and other clinical, resource and patient focused outcomes. The primary outcome will be the development of acute lung injury within 72 hours of oesophagectomy. The trial secondary outcomes are the development of acute lung injury during the first 28 days post operatively; PaO2: FiO2 ratio; the number of ventilator and organ failure free days, 28 and 90 day survival; health related quality of life and resource utilisation. The study aims to recruit 360 patients from 10 UK centres.Trial registration numberCurrent Controlled Trials ISRCTN47481946

Prognostic factors for chronic headache : a systematic review

Objective: To identify predictors of prognosis and trial outcomes in prospective studies of people with chronic headache. Methods: This was a systematic review of published literature in peer-reviewed journals. We included (1) randomized controlled trials (RCTs) of interventions for chronic headache that reported subgroup analyses and (2) prospective cohort studies, published in English, since 1980. Participants included adults with chronic headache (including chronic headache, chronic migraine, and chronic tension-type headache with or without medication overuse headache). We searched key databases using free text and MeSH terms. Two reviewers independently extracted data and assessed the methodologic quality of studies and overall quality of evidence identified using appropriate published checklists. Results: We identified 16,556 titles, removed 663 duplicates, and reviewed 199 articles, of which 27 were included in the review—17 prospective cohorts and 10 RCTs with subgroup analyses reported. There was moderate-quality evidence indicating that depression, anxiety, poor sleep and stress, medication overuse, and poor self-efficacy for managing headaches are potential prognostic factors for poor prognosis and unfavorable outcomes from preventive treatment in chronic headache. There was inconclusive evidence about treatment expectations, age, age at onset, body mass index, employment, and several headache features. Conclusions: This review identified several potential predictors of poor prognosis and worse outcome postinterventions in people with chronic headache. The majority of these are modifiable. The findings also highlight the need for more longitudinal high-quality research of prognostic factors in chronic headache.

Evaluating the quality of subgroup analyses in randomized controlled trials of therapist-delivered interventions for nonspecific low back pain: a systematic review.

Study Design. Systematic review. Objective. To evaluate the quality, conduct, and reporting of subgroup analyses performed in randomized controlled trials of therapist-delivered interventions for nonspecific low back pain (NSLBP). Summary of Background Data. Randomized controlled trials of therapist-delivered interventions for NSLBP to date have, at best, shown small to moderate positive effects. Identifying subgroups is an important research priority. This review evaluates the quality, conduct, and reporting of subgroup analyses performed in the NSLBP literature. Methods. Multiple electronic databases were searched for randomized controlled trials of therapist-delivered interventions for NSLBP. Of the identified articles, only articles reporting subgroup analyses (confirmatory or exploratory) were included in the final review. Methodological criteria were used to evaluate the quality of subgroup analyses. The quality of conduct and reporting was also evaluated. Results. Thirty-nine articles were included in the final review. Of these, only 3 (8%) tested hypotheses about moderators (confirmatory findings), 18 (46%) generated hypotheses about moderators to inform future research (exploratory findings), and 18 (46%) provided insufficient findings. The appropriate statistical test for interaction was performed in 27 of the articles, of which 10 reported results from interaction tests, 4 incorrectly reported results within individual subgroups, and the remaining articles reported either P values or nothing at all. Conclusion. Subgroup analyses performed in NSLBP trials have been severely underpowered, are only able to provide exploratory or insufficient findings, and have rather poor quality of reporting. Using current approaches, few definitive trials of subgrouping in back pain are very likely to be performed. There is a need to develop new approaches to subgroup identification in back pain research. Level of Evidence: 1

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

OBJECTIVE Follow-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. STUDY DESIGN AND SETTING A large clinical trial of lower back pain. RESULTS About 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. CONCLUSION Researchers 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.

Dementia And Physical Activity (DAPA) trial of moderate to high intensity exercise training for people with dementia: randomised controlled trial

Abstract Objective To estimate the effect of a moderate to high intensity aerobic and strength exercise training programme on cognitive impairment and other outcomes in people with mild to moderate dementia. Design Multicentre, pragmatic, investigator masked, randomised controlled trial. Setting National Health Service primary care, community and memory services, dementia research registers, and voluntary sector providers in 15 English regions. Participants 494 people with dementia: 329 were assigned to an aerobic and strength exercise programme and 165 were assigned to usual care. Random allocation was 2:1 in favour of the exercise arm. Interventions Usual care plus four months of supervised exercise and support for ongoing physical activity, or usual care only. Interventions were delivered in community gym facilities and NHS premises. Main outcome measures The primary outcome was score on the Alzheimer’s disease assessment scale-cognitive subscale (ADAS-cog) at 12 months. Secondary outcomes included activities of daily living, neuropsychiatric symptoms, health related quality of life, and carer quality of life and burden. Physical fitness (including the six minute walk test) was measured in the exercise arm during the intervention. Results The average age of participants was 77 (SD 7.9) years and 301/494 (61%) were men. By 12 months the mean ADAS-cog score had increased to 25.2 (SD 12.3) in the exercise arm and 23.8 (SD 10.4) in the usual care arm (adjusted between group difference −1.4, 95% confidence interval −2.6 to −0.2, P=0.03). This indicates greater cognitive impairment in the exercise group, although the average difference is small and clinical relevance uncertain. No differences were found in secondary outcomes or preplanned subgroup analyses by dementia type (Alzheimer’s disease or other), severity of cognitive impairment, sex, and mobility. Compliance with exercise was good. Over 65% of participants (214/329) attended more than three quarters of scheduled sessions. Six minute walking distance improved over six weeks (mean change 18.1 m, 95% confidence interval 11.6 m to 24.6 m). Conclusion A moderate to high intensity aerobic and strength exercise training programme does not slow cognitive impairment in people with mild to moderate dementia. The exercise training programme improved physical fitness, but there were no noticeable improvements in other clinical outcomes. Trial registration Current Controlled Trials ISRCTN10416500.