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Aims White matter hyperintensities (WMH) progress with age and hypertension, but the key period of exposure to elevated blood pressure (BP), and the relative role of systolic BP (SBP) vs. diastolic BP (DBP), remains unclear. This study aims to determine the relationship between WMH and concurrent vs. past BP. Methods and results UK Biobank is a prospective community-based cohort of 40–69-year olds from 22 centres, with magnetic resonance imaging in a subgroup of over 40 000 people at 4–12 years after baseline assessment. Standardized associations between WMH load (WMH volume normalized by total white matter volume and logit-transformed) and concurrent vs. past BP were determined using linear models, adjusted for age, sex, cardiovascular risk factors, BP source, assessment centre, and time since baseline. Associations adjusted for regression dilution bias were determined between median WMH and usual SBP or DBP, stratified by age and baseline BP. In 37 041 eligible participants with WMH data and BP measures, WMH were more strongly associated with concurrent SBP [DBP: β = 0.064, 95% confidence interval (CI) 0.050–0.078; SBP: β = 0.076, 95% CI 0.062–0.090], but the strongest association was for past DBP (DBP: β = 0.087, 95% CI 0.064–0.109; SBP: β = 0.045, 95% CI 0.022–0.069), particularly under the age of 50 (DBP: β = 0.103, 95% CI 0.055–0.152; SBP: β = 0.012, 95% CI −0.044 to 0.069). Due to the higher prevalence of elevated SBP, median WMH increased 1.126 (95% CI 1.107–1.146) per 10 mmHg usual SBP and 1.106 (95% CI 1.090–1.122) per 5 mmHg usual DBP, whilst the population attributable fraction of WMH in the top decile was greater for elevated SBP (19.1% for concurrent SBP; 24.4% for past SBP). Any increase in BP, even below 140 for SBP and below 90 mmHg for DBP, and especially if requiring antihypertensive medication, was associated with increased WMH. Conclusions WMH were strongly associated with concurrent and past elevated BP with the population burden of severe WMH greatest for SBP. However, before the age of 50, DBP was more strongly associated with WMH. Long-term prevention of WMH may require control of even mildly elevated midlife DBP.

Supplemental material, sj-pdf-2-jcb-10.1177_0271678X211058803 for White matter damage due to pulsatile versus steady blood pressure differs by vascular territory: A cross-sectional analysis of the UK Biobank cohort study by Karolina A Wartolowska and Alastair JS Webb in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X211058803 for White matter damage due to pulsatile versus steady blood pressure differs by vascular territory: A cross-sectional analysis of the UK Biobank cohort study by Karolina A Wartolowska and Alastair JS Webb in Journal of Cerebral Blood Flow & Metabolism

Supplemental material, sj-docx-1-eso-10.1177_23969873221143570 for The EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases (TREAT-SVDs) trial: Study protocol for a randomised crossover trial by Anna Kopczak, Michael S Stringer, Hilde van den Brink, Danielle Kerkhofs, Gordon W Blair, Maud van Dinther, Laurien Onkenhout, Karolina A Wartolowska, Michael J Thrippleton, Marco Duering, Julie Staals, Martin Middeke, Elisabeth André, Bo Norrving, Marie-Germaine Bousser, Ulrich Mansmann, Peter M Rothwell, Fergus N Doubal, Robert van Oostenbrugge, Geert Jan Biessels, Alastair JS Webb, Joanna M Wardlaw and Martin Dichgans in European Stroke Journal

ObjectiveTo evaluate the impact of the Quintet Recruitment Intervention (QRI) on recruitment in challenging randomized controlled trials (RCTs) that have applied the intervention. The QRI aims to understand recruitment difficulties, and then implements ‘QRI-actions’ to address these as recruitment proceeds.Study Design and SettingA mixed-methods study, comprising: a) before-and-after comparisons of recruitment rates and numbers of patients approached, and b) qualitative case studies, including documentary analysis and interviews with RCT investigators.ResultsFive UK-based publicly-funded RCTs were included in the evaluation. All recruited to target. RCT2 and RCT5 both received up-front pre-recruitment training before the intervention was applied. RCT2 did not encounter recruitment issues and recruited above target from its outset. Recruitment difficulties, particularly communication issues, were identified and addressed through QRI-actions in RCTs 1, 3, 4 and 5. Randomization rates significantly improved post-QRI-action in RCTs 1,3, and 4. QRI-actions addressed issues with approaching eligible patients in RCTs 3 and 5, which both saw significant increases in patients approached. Trial investigators reported that the QRI had unearthed issues they had been unaware of, and reportedly changed their practices post QRI-action.ConclusionThere is promising evidence to suggest the QRI can support recruitment to difficult RCTs. This needs to be substantiated with future controlled evaluations.

Background: There is a problem with the visibility of retractions, and many retracted papers continue to be cited as if they were still valid. It has been suggested that authors citing retracted papers should be contacted about it, but this has been deemed too challenging and has never been attempted.Design: This is a randomised controlled trial.Methods: All eligible retracted papers will be randomised either to the intervention (an email notifying authors of the citing papers about the fact that they have cited a retracted publication) or the control group (no notification email).Outcomes: The primary outcome will be the rate of citation of retracted papers during 12 months follow-up. The secondary outcomes will be a 24-month follow-up and the qualitative analysis of feedback from the authors in response to the intervention email.Conclusions: Our trial will investigate whether the number of citations of retracted papers can be reduced by notifying researchers that they cited a retracted paper.

Chapters describing changes in pain-related brain activation after anti-TNF treatment in patients with severe rheumatoid arthritis.The chapter describing differences in brain structure between patients and age- and sex-matched healthy controls has been published separately (Wartolowska K, Hough MG, Jenkinson M, et al. Structural changes of the brain in rheumatoid arthritis. Arthritis Rheum 2012;64.)

A poster presented at the

A poster presented at the EFIC conference in 2011

This is description of an software tool notifying authors that they cited a retracted paper and a protocol for a proposed randomised trial investigating the impact of notifying authors that they have cited a retracted paper.

Search terms: list of search terms used to systematically search literature. (DOCX 79 kb)

All identified RCTs: list of all surgical RCTs with a placebo arm identified during the systematic review. (PDF 40 kb)

Risk of bias: table summarizing possible list of bias items in each included trial. (PDF 27 kb)

PRISMA checklist. (DOC 61 kb)

Background Arthroscopic subacromial decompression (ASAD) is a commonly performed surgical intervention for shoulder pain. The rationale is that removal of a bony acromial spur relieves symptoms by decompressing rotator cuff tendons passing through the subacromial space. However, the efficacy of this procedure is uncertain. The objective of this trial was to compare the efficacy and cost-effectiveness of ASAD in patients with subacromial pain using appropriate control groups, including placebo intervention. Methods/Design The trial is a three-group, parallel design, pragmatic, randomised controlled study. The intervention content for each group (ASAD, active monitoring with specialist reassessment (AMSR) and investigational shoulder arthroscopy only (AO)) enables assessment of (1) the efficacy of the surgery against no surgery; (2) the need for a specific component of the surgery—namely, removal of the bony spur; and (3) quantification of the placebo effect. Concealed allocation was performed using a 1:1:1 randomisation ratio and using age, sex, baseline Oxford Shoulder Score (OSS) and centre as minimisation criteria. The primary outcome measure is the OSS at 6 months post randomisation. A total of 300 patients recruited over 24 months from a minimum of 14 UK shoulder units over 24 months were required to detect a difference of 4.5 points on the OSS (standard deviation, 9) with 90% power and to allow for 15% loss to follow-up. Secondary outcomes include cost-effectiveness, pain, complications and patient satisfaction. A substantial qualitative research component is included. The primary analysis will be conducted on the modified intention-to-treat analysis. Sensitivity analysis will be used to assess the robustness of the results with regard to the underlying assumptions about missing data using multiple imputation. Discussion This trial uses an innovative design to account for the known placebo effects of surgery, but it also will delineate the mechanism for any benefit from surgery. The investigational AO group is considered a placebo intervention (not sham surgery), as it includes all components of subacromial decompression except the critical surgical element. Some discussion is also dedicated to the challenges of conducting placebo surgery trials. Trial registrations UK Clinical Research Network UKCRN12104. Registered 22 May 2012. International Standard Randomised Controlled Trial ISRCTN33864128. Registered 22 June 2012. ClinicalTrials.gov NCT01623011. Registered 15 June 2012. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-0725-y) contains supplementary material, which is available to authorized users.