Scaling up Quality Improvement for Surgical Teams (QIST)-avoiding surgical site infection and anaemia at the time of surgery: a cluster randomised controlled trial of the effectiveness of quality improvement collaboratives to introduce change in the NHS.

BACKGROUND: The aim of this trial was to assess the effectiveness of quality improvement collaboratives to implement large-scale change in the National Health Service (NHS) in the UK, specifically for improving outcomes in patients undergoing primary, elective total hip or knee replacement. METHODS: We undertook a two-arm, cluster randomised controlled trial comparing the roll-out of two preoperative pathways: methicillin-sensitive Staphylococcus aureus (MSSA) decolonisation (infection arm) and anaemia screening and treatment (anaemia arm). NHS Trusts are public sector organisations that provide healthcare within a geographical area. NHS Trusts (n = 41) in England providing primary, elective total hip and knee replacements, but that did not have a preoperative anaemia screening or MSSA decolonisation pathway in place, were randomised to one of the two parallel collaboratives. Collaboratives took place from May 2018 to November 2019. Twenty-seven Trusts completed the trial (11 anaemia, 16 infection). Outcome data were collected for procedures performed between November 2018 and November 2019. Co-primary outcomes were perioperative blood transfusion (within 7 days of surgery) and deep surgical site infection (SSI) caused by MSSA (within 90 days post-surgery) for the anaemia and infection trial arms, respectively. Secondary outcomes were deep and superficial SSIs (any organism), length of hospital stay, critical care admissions and unplanned readmissions. Process measures included the proportion of eligible patients receiving each preoperative initiative. RESULTS: There were 19,254 procedures from 27 NHS Trusts included in the results (6324 from 11 Trusts in the anaemia arm, 12,930 from 16 Trusts in the infection arm). There were no improvements observed for blood transfusion (anaemia arm 183 (2.9%); infection arm 302 (2.3%) transfusions; adjusted odds ratio 1.20, 95% CI 0.52-2.75, p = 0.67) or MSSA deep SSI (anaemia arm 8 (0.13%); infection arm 18 (0.14%); adjusted odds ratio 1.01, 95% CI 0.42-2.46, p = 0.98). There were no significant improvements in any secondary outcome. This is despite process measures showing the preoperative pathways were implemented for 73.7% and 61.1% of eligible procedures in the infection and anaemia arms, respectively. CONCLUSIONS: Quality improvement collaboratives did not result in improved patient outcomes in this trial; however, there was some evidence they may support successful implementation of new preoperative pathways in the NHS. TRIAL REGISTRATION: Prospectively registered on 15 February 2018, ISRCTN11085475.

Effectiveness of pre-operative anaemia screening and increased Tranexamic acid dose policies on outcomes following unilateral primary, elective total hip or knee replacement: a statistical analysis plan for an interrupted time series and regression discontinuity study.

Perioperative blood transfusion is associated with poorer postoperative outcomes following hip and knee replacement surgery. Evidence for the effectiveness of some measures aimed at reducing blood transfusions in this setting are limited and often rely on weak pre-post study designs. Quasi-experimental study designs such as interrupted time series (ITS) and regression discontinuity design (RDD) address many of the weaknesses of the pre-post study design. In addition, a priori publication of statistical analysis plans for such studies increases their transparency and likely validity, as readers are able to distinguish between pre-planned and exploratory analyses. As such, this article, written prospective of any analysis, provides the statistical analysis plan for an ITS and RDD study based on a data set of 20,772 primary elective hip and knee replacement patients in a single English NHS Trust. The primary aim is to evaluate the impact of a preoperative anaemia optimisation service on perioperative blood transfusion (within 7 days of surgery) using both ITS and RDD methods. A secondary aim is to evaluate the impact of a policy of increased tranexamic acid dose given at the time of surgery, using ITS methods.

The impact of lung function case-finding tests on smoking behaviour: A nested randomised trial within a case-finding cohort.

RATIONALE AIMS AND OBJECTIVES: Increasing awareness of people's lung health through the use of lung function tests or symptom-based questionnaires is a potential method to aid smoking cessation. We investigated the impact of case-finding lung function tests for chronic obstructive pulmonary disease on smoking behaviour. METHODS: Our trial used a novel waiting list randomised controlled trial design, nested within a case-finding cohort study. The cohort comprised current smokers aged 35 years or more, from general practices in Yorkshire and Humberside, who were randomised to receive lung function tests (spirometry, microspirometry, peak flow meter measurement, and a WheezoMeter) and case-finding questionnaires either immediately ("tests now") or later ("waiting list" control). Outcome measures included self-reported smoking cessation and number of cigarettes smoked at follow-up (at 2, 3, or 6 months after randomisation, depending on study site), with 409 participants included in the primary analysis. RESULTS: Six hundred seventy-four participants were randomised using stratified block randomisation to the 2 groups (340 to "tests now" and 334 to "waiting list"), with 409 included in the primary analysis (194 in "tests now" and 215 in "waiting list" groups). Smoking cessation at follow-up was very similar across groups (8.8% in the "tests now" group, compared with 9.2% in the "waiting list" group). Completing case-finding lung function tests did not significantly impact smoking cessation (OR 1.00, 95% CI, 0.57-1.77, adjusting for age, sex, baseline number of cigarettes smoked, and study site). A sensitivity analysis, assuming that participants with missing data were still smoking, gave similar results (OR 0.86, 95% CI, 0.47-1.56). Analysis of the number of cigarettes smoked at follow-up using negative binomial regression adjusting for the same factors above gave an incidence rate ratio of 0.95 (95% CI, 0.88-1.03). CONCLUSIONS: There is no evidence from this trial of an effect of lung function tests on smoking cessation among a population of smokers aged 35 years or over. Indeed, when assuming that those with missing data were smokers, a slightly lower odds of smoking cessation was observed in the "test now" group compared with the "waiting list" group.

Missing data in randomized controlled trials testing palliative interventions pose a significant risk of bias and loss of power: a systematic review and meta-analyses.

OBJECTIVES: To assess the risk posed by missing data (MD) to the power and validity of trials evaluating palliative interventions. STUDY DESIGN AND SETTING: A systematic review of MD in published randomized controlled trials (RCTs) of palliative interventions in participants with life-limiting illnesses was conducted, and random-effects meta-analyses and metaregression were performed. CENTRAL, MEDLINE, and EMBASE (2009-2014) were searched with no language restrictions. RESULTS: One hundred and eight RCTs representing 15,560 patients were included. The weighted estimate for MD at the primary endpoint was 23.1% (95% confidence interval [CI] 19.3, 27.4). Larger MD proportions were associated with increasing numbers of questions/tests requested (odds ratio [OR], 1.19; 95% CI 1.05, 1.35) and with longer study duration (OR, 1.09; 95% CI 1.02, 1.17). Meta-analysis found evidence of differential rates of MD between trial arms, which varied in direction (OR, 1.04; 95% CI 0.90, 1.20; I(2) 35.9, P = 0.001). Despite randomization, MD in the intervention arms (vs. control) were more likely to be attributed to disease progression unrelated to the intervention (OR, 1.31; 95% CI 1.02, 1.69). This was not the case for MD due to death (OR, 0.92; 95% CI 0.78, 1.08). CONCLUSION: The overall proportion and differential rates and reasons for MD reduce the power and potentially introduce bias to palliative care trials.

Prior notification of trial participants by newsletter increased response rates: a randomized controlled trial.

OBJECTIVE: To assess the effectiveness of prenotification using a newsletter to increase questionnaire response rates within a randomized controlled trial (RCT). STUDY DESIGN AND SETTING: An RCT set within the context of the Medical Research Council's SCOOP trial of screening older women for fracture risk. RESULTS: A subsample of SCOOP participants were randomized in equal numbers to receive a newsletter approximately 6 weeks before the follow-up questionnaire or no newsletter. Of the 1,342 participants in the newsletter group, 1,291 (96.2%) returned their 24-month follow-up questionnaire compared with 1,271 of the 1,344 participants who were not allocated to receive the newsletter (94.6%). The difference of 1.6% was statistically significant (P=0.05), with an odds ratio (OR) of 1.45 (95% confidence interval [CI]: 1.01, 2.10). The newsletter and no newsletter groups required a similar number of reminders (OR 0.88, 95% CI: 0.73, 1.06), had a similar number with a complete primary outcome (OR 0.95, 95% CI: 0.57, 1.58), and took a similar time to respond (log rank 1.30, P=0.25). CONCLUSIONS: This study supports previous research that suggests that prenotification increases survey response rate: albeit a small absolute increase. No previous study has shown this to be so within the context of patients enrolled within an RCT. Trials that use newsletters to keep their participants informed of the study's progress should use the newsletter as a prenotification device as this will increase overall response rates.

Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial).

CONTEXT: Vitamin D or calcium supplementation may have effects on vascular disease and cancer. OBJECTIVE: Our objective was to investigate whether vitamin D or calcium supplementation affects mortality, vascular disease, and cancer in older people. DESIGN AND SETTING: The study included long-term follow-up of participants in a two by two factorial, randomized controlled trial from 21 orthopedic centers in the United Kingdom. PARTICIPANTS: Participants were 5292 people (85% women) aged at least 70 yr with previous low-trauma fracture. INTERVENTIONS: Participants were randomly allocated to daily vitamin D(3) (800 IU), calcium (1000 mg), both, or placebo for 24-62 months, with a follow-up of 3 yr after intervention. MAIN OUTCOME MEASURES: All-cause mortality, vascular disease mortality, cancer mortality, and cancer incidence were evaluated. RESULTS: In intention-to-treat analyses, mortality [hazard ratio (HR) = 0.93; 95% confidence interval (CI) = 0.85-1.02], vascular disease mortality (HR = 0.91; 95% CI = 0.79-1.05), cancer mortality (HR = 0.85; 95% CI = 0.68-1.06), and cancer incidence (HR = 1.07; 95% CI = 0.92-1.25) did not differ significantly between participants allocated vitamin D and those not. All-cause mortality (HR = 1.03; 95% CI = 0.94-1.13), vascular disease mortality (HR = 1.07; 95% CI = 0.92-1.24), cancer mortality (HR = 1.13; 95% CI = 0.91-1.40), and cancer incidence (HR = 1.06; 95% CI = 0.91-1.23) also did not differ significantly between participants allocated calcium and those not. In a post hoc statistical analysis adjusting for compliance, thus with fewer participants, trends for reduced mortality with vitamin D and increased mortality with calcium were accentuated, although all results remain nonsignificant. CONCLUSIONS: Daily vitamin D or calcium supplementation did not affect mortality, vascular disease, cancer mortality, or cancer incidence.

The quality of trials in operative surgery.

OBJECTIVE: This study aimed to assess the reported quality of trials in operative surgery. SUMMARY BACKGROUND DATA: Randomized controlled trials (RCTs) in operative surgery have previously been criticized for using weak methodology despite no evidence to suggest their quality is any different from nonsurgical trials. STUDY DESIGN: All surgical RCTs published in the British Medical Journal, the Journal of the American Medical Association, The Lancet, and the New England Journal of Medicine between 1998 and 2004 were identified. The adequacy of the reported methodology used to perform the randomization, power calculation, and recruitment was assessed for each trial using predefined criteria. The results from the surgical trials were compared with a randomly selected control group of nonsurgical RCTs, which were matched for journal and year of publication. RESULTS: Sixty-six surgical RCTs were identified. Adequate reporting of randomization sequence generation was seen in 42% (n = 28) of surgical trials and 30% (n = 20) of nonsurgical trials, and adequate allocation concealment was recorded in 46% (n = 30) and 47% (n = 31), respectively. When combining these 2 interrelated steps of randomization, only 26% (n = 17) of surgical trials and 23% (n = 15) of nonsurgical trials reported both adequately. Adequate recruitment was recorded in 52% (n = 33 of 63) surgical and 55% (n = 33 of 60) nonsurgical trials, with approximately a quarter (n = 17 and n = 16, respectively) of the trials in both the surgical and nonsurgical categories reporting an adequate power calculation. CONCLUSIONS: There was no evidence that the reported quality of surgical trials was different to nonsurgical trials. However, approximately half or less of all the trials reviewed reported adequate methodology.

Resource use data by patient report or hospital records: do they agree?

BACKGROUND: Economic evaluations alongside clinical trials are becoming increasingly common. Cost data are often collected through the use of postal questionnaires; however, the accuracy of this method is uncertain. We compared postal questionnaires with hospital records for collecting data on physiotherapy service use. METHODS: As part of a randomised trial of orthopaedic medicine compared with orthopaedic surgery we collected physiotherapy use data on a group of patients from retrospective postal questionnaires and from hospital records. RESULTS: 315 patients were referred for physiotherapy. Hospital data on attendances was available for 30% (n = 96), compared with 48% (n = 150) of patients completing questionnaire data (95% Cl for difference = 10% to 24%); 19% (n = 59) had data available from both sources. The two methods produced an intraclass correlation coefficient of 0.54 (95% Cl 0.31 to 0.70). However, the two methods produced significantly different estimates of resource use with patient self report recalling a mean of 1.3 extra visits (95% Cl 0.4 to 2.2) compared with hospital records. CONCLUSIONS: Using questionnaires in this study produced data on a greater number of patients compared with examination of hospital records. However, the two data sources did differ in the quantity of physiotherapy used and this should be taken into account in any analysis.