the validity of drug effects on proteinuria albuminuria serum creatinine and estimated gfr as surrogate end points for eskd a systematic review

Rationale & Objective Proteinuria, albuminuria, and serum creatinine level are widely used as surrogate end point measures of end-stage kidney disease (ESKD). We evaluated the correlation between antihypertensive drug effects on surrogate renal end points and ESKD. Study Design Systematic review. Setting & Participants Randomized controlled trials of blood pressure–lowering therapy. Selection Criteria for Studies Trials of pharmacological blood pressure–lowering strategies reporting drug effects on albuminuria, proteinuria, or serum creatinine level and ESKD through March 26, 2018. Analytical Approach Bayesian bivariate meta-analysis to calculate correlations between drug effects on surrogate end points and drug effects on ESKD. Risks of bias were adjudicated using the Cochrane tool. Results 22 randomized controlled trials involving 69,642 participants were eligible. Risks of bias in the included trials were frequently unclear due to incomplete reporting. Relative risk for ESKD was statistically significant in 1 of 29 (3.4%) treatment comparisons. There appeared to be little or no correlation between antihypertensive drug effects on serum creatinine level, albuminuria, proteinuria, and the corresponding effects on ESKD. All correlations had wide 95% credible intervals that included the null effect. Limitations Low power due to infrequent outcomes of ESKD and incomplete data reporting in primary trials. Conclusions The association between antihypertensive drug effects on doubling of serum creatinine level and albuminuria or proteinuria with ESKD in treatment trials is not sufficiently certain to enable the confident use of these markers to guide clinical or regulatory decision making

Value of routine monitoring of bone mineral density after starting bisphosphonate treatment: secondary analysis of trial data

Objective: To assess the value of monitoring response to bisphosphonate treatment by means of measuring bone mineral density

Cochrane diagnostic test accuracy reviews

In 1996, shortly after the founding of The Cochrane Collaboration, leading figures in test evaluation research established a Methods Group to focus on the relatively new and rapidly evolving methods for the systematic review of studies of diagnostic tests. Seven years later, the Collaboration decided it was time to develop a publication format and methodology for Diagnostic Test Accuracy (DTA) reviews, as well as the software needed to implement these reviews in The Cochrane Library. A meeting hosted by the German Cochrane Centre in 2004 brought together key methodologists in the area, many of whom became closely involved in the subsequent development of the methodological framework for DTA reviews. DTA reviews first appeared in The Cochrane Library in 2008 and are now an integral part of the work of the Collaboration

Psychosocial outcomes of three triage methods for the management of borderline abnormal cervical smears: an open randomised trial

Objective To assess which of three triage strategies for women with borderline abnormal cervical smear results in the best psychosocial outcomes

Association of Drug Effects on Serum Parathyroid Hormone, Phosphorus, and Calcium Levels With Mortality in CKD: A Meta-analysis

Background Serum parathyroid hormone (PTH), phosphorus, and calcium levels are surrogate outcomes that are central to the evaluation of drug treatments in chronic kidney disease (CKD). This systematic review evaluates the evidence for the correlation between drug effects on biochemical (PTH, phosphorus, and calcium) and all-cause and cardiovascular mortality end points in adults with CKD. Study Design Systematic review and meta-analysis. Setting & Population Adults with CKD. Selection Criteria for Studies Randomized trials reporting drug effects on biochemical and mortality end points. Intervention Drug interventions with effects on serum PTH, phosphorus, and calcium levels, including vitamin D compounds, phosphate binders, cinacalcet, bisphosphonates, and calcitonin. Outcomes Correlation between drug effects on biochemical and all-cause and cardiovascular mortality. Results 28 studies (6,999 participants) reported both biochemical and mortality outcomes and were eligible for analysis. Associations between drug effects on surrogate biochemical end points and corresponding effects on mortality were weak and imprecise. All correlation coefficients were less than 0.70, and 95% credible intervals were generally wide and overlapped with zero, consistent with the possibility of no association. The exception was an inverse correlation between drug effects on serum PTH levels and all-cause mortality, which was nominally significant (−0.64; 95% credible interval, −0.85 to −0.15), but the strength of this association was very imprecise. Risk of bias within available trials was generally high, further reducing confidence in the summary correlations. Findings were robust to adjustment for age, baseline serum PTH level, allocation concealment, CKD stage, and drug class. Limitations Low power in analyses and combining evidence from many different drug comparisons with incomplete data across studies. Conclusions Drug effects on serum PTH, phosphorus, and calcium levels are weakly and imprecisely correlated with all-cause and cardiovascular death in the setting of CKD. Risks of mortality (patient-level outcome) cannot be inferred from treatment-induced changes in biochemical outcomes in people with CKD. Similarly, existing data do not exclude a mortality benefit with treatment. Trials need to address patient-centered outcomes to evaluate drug effectiveness in this setting

The accuracy of clinical symptoms and signs for the diagnosis of serious bacterial infection in young febrile children: prospective cohort study of 15 781 febrile illnesses

Objectives To evaluate current processes by which young children presenting with a febrile illness but suspected of having serious bacterial infection are diagnosed and treated, and to develop and test a multivariable model to distinguish serious bacterial infections from self limiting non-bacterial illnesses

Randomised controlled trial to assess the impact of a lifestyle intervention (ActWELL) in women invited to NHS breast screening

Peer reviewedPublisher PD

Red flags to screen for malignancy and fracture in patients with low back pain: Systematic review

Abstract Objective To review the evidence on diagnostic accuracy of red flag signs and symptoms to screen for fracture or malignancy in patients presenting with low back pain to primary, secondary, or tertiary care. Design Systematic review. Data sources Medline, OldMedline, Embase, and CINAHL from earliest available up to 1 October 2013. Inclusion criteria Primary diagnostic studies comparing red flags for fracture or malignancy to an acceptable reference standard, published in any language. Review methods Assessment of study quality and extraction of data was conducted by three independent assessors. Diagnostic accuracy statistics and post-test probabilities were generated for each red flag. Results We included 14 studies (eight from primary care, two from secondary care, four from tertiary care) evaluating 53 red flags; only five studies evaluated combinations of red flags. Pooling of data was not possible because of index test heterogeneity. Many red flags in current guidelines provide virtually no change in probability of fracture or malignancy or have untested diagnostic accuracy. The red flags with the highest post-test probability f

A novel approach to increasing community capacity for weight management a volunteer-delivered programme (ActWELL) initiated within breast screening clinics:a randomised controlled trial

Background: It is estimated that around 30% of breast cancers in post-menopausal women are related to lifestyle. The breast cancer-pooling project demonstrated that sustained weight loss of 2 to 4.5 kg is associated with an 18% lower risk of breast cancer, highlighting the importance of small changes in body weight. Our study aimed to assess the effectiveness a volunteer-delivered, community based, weight management programme (ActWELL) for women with a BMI > 25 kg/m2 attending NHS Scotland Breast Screening clinics. Methods: A multicentre, 1:1 parallel group, randomised controlled trial was undertaken in 560 women aged 50 to 70 years with BMI > 25 kg/m2. On completion of baseline measures, all participants received a breast cancer prevention leaflet. Intervention group participants received the ActWELL intervention which focussed on personalised diet advice and pedometer walking plans. The programme was delivered in leisure centres by (the charity) Breast Cancer Now volunteer coaches. Primary outcomes were changes between groups at 12 months in body weight (kg) and physical activity (accelerometer measured step count). Results: Two hundred seventy-nine women were allocated to the intervention group and 281 to the comparison group. Twelve-month data were available from 240 (81%) intervention and 227 (85%) comparison group participants. Coaches delivered 523 coaching sessions and 1915 support calls to 279 intervention participants. Mean weight change was − 2.5 kg (95% CI − 3.1 to − 1.9) in the intervention group and − 1.2 kg (− 1.8 to 0.6) in the comparison group. The adjusted mean difference was − 1.3 kg (95% CI − 2.2 to − 0.4, P = 0.003). The odds ratio for losing 5% weight was 2.20 (95% CI 1.4 to 3.4, p = 0.0005) in favour of the intervention. The adjusted mean difference in step counts between groups was 483 steps/day (95% CI − 635 to 1602) (NS). Conclusions: A community weight management intervention initiated at breast screening clinics and delivered by volunteer coaches doubled the likelihood of clinically significant weight loss at 12 months (compared with usual care) offering significant potential to decrease breast cancer risk

Correction to:A novel approach to increasing community capacity for weight management a volunteer-delivered programme (ActWELL) initiated within breast screening clinics: a randomised controlled trial

Acknowledgements Our thanks to Elizabeth Banks who advised and assisted with many aspects of the study and also to the many women who commented on the development and design of this study including those on our Public Advisory Team (Pamela Deponio, Maggie Taylor and Mary Wotherspoon). Funding This work was supported by The Scottish Government, grant number BC/Screening/17/01. The funders provided independent referee reports which guided the final study design. The funders have read this manuscript. In-kind support was given by Breast Cancer Now for facilitating this study.Peer reviewedPublisher PD