Monitoring adherence to drug treatment by using change in cholesterol concentration: Secondary analysis of trial data

Objective: To estimate the accuracy of monitoring cholesterol concentration for detecting non-adherence to lipid lowering treatment. Design: Secondary analysis of data on cholesterol concentration in the LIPID (long term intervention with pravastatin in ischaemic disease) study by using three measures of non-adherence: discontinuation of treatment, allocation to placebo arm, less than 80% of pills taken. Setting: Randomised placebo controlled trial in Australia and New Zealand. Participants: 9014 patients with previous coronary heart disease. Interventions: Pravastatin 40 mg or placebo daily. Main outcome measures: Sensitivity, specificity, area under the receiver operating characteristics (ROC) curve, post-test probability. Results: Monitoring of cholesterol concentration had modest ability for detecting complete non-adherence. One year after the start of treatment, half (1957/3937) of the non-adherent patients and 6% (253/3944) of adherent patients had a rise in concentration of low density lipoprotein cholesterol. Accuracy was reasonable (area under the curve 0.89). Cholesterol monitoring, however, had weak ability for detecting partial non-adherence. One year after the start of treatment,16%(34/213) of partially adherent and 4% (155/3585) of fully adherent patients had a rise in concentration of low density lipoprotein cholesterol. Accuracy was poor (area under the curve 0.65). For typical pre-test probabilities of non-adherence ranging from low (25%) to high (75%), the post-test probabilities indicate continuing uncertainty after lipid testing. A patient with no change in low density lipoprotein cholesterol concentration has a post-test probability of being completely non-adherent of between 67% and 95% and a post-test probability of being partially non-adherent of between 48% and 89%. A patient with a decrease in concentration of 1.0 mmol/L has a post-test probability of being completely non-adherent of between 7% and 40% and a post-test probability of being partially non-adherent of between 21% and 71%. Conclusions: Monitoring concentration of low density lipoprotein (or total) cholesterol has modest ability to detect complete non-adherence or non-persistence with pravastatin treatment and weak ability to detect partial non-adherence. Results of monitoring should be considered as no more than an adjunct to careful discussion with patients about adherence

Early CRT monitoring using time-domain optical coherence tomography does not add to visual acuity for predicting visual loss in patients with central retinal vein occlusion treated with intravitreal ranibizumab:A secondary analysis of trial data

Our primary purpose was to assess the clinical (predictive) validity of central retinal thickness (CRT) and best corrected visual acuity (BCVA) at 1 week and 1 month after starting treatment with ranibizumab for central retinal vein occlusion. The authors also assessed detectability of response to treatment

When to remeasure cardiovascular risk in untreated people at low and intermediate risk: Observational study

Objective: To estimate the probability of becoming high risk for cardiovascular disease among people at low and intermediate risk and not being treated for high blood pressure or lipid levels. Design: Observational study. Setting: General communities in Japan and the United States. Participants: 13 757 participants of the Tokyo health check-up study and 3855 of the Framingham studies aged 30-74 years with complete data on risk equation covariates, not receiving blood pressure or cholesterol lowering treatment, and with an estimated risk of cardiovascular disease 20% using the Framingham equation. Results: At baseline most participants had 10% probability of crossing the treatment threshold at one year for the 15-<20% baseline risk group. Conclusions: Decisions on the frequency of remeasuring for cardiovascular risk should be made on the basis of baseline risk. Repeat risk estimation before 8-10 years is not warranted for most people initially not requiring treatment. However, remeasurement within a year seems warranted in those with an initial 15-<20% risk

Follow-up of early stage melanoma: specialist clinician perspectives on the functions of follow-up and implications for extending follow-up intervals

BACKGROUND: There is limited evidence on the relative effectiveness of different follow-up schedules for patients with AJCC stage I or II melanoma, but less frequent follow-up than is currently recommended has been proposed. OBJECTIVES: To describe melanoma clinicians' perspectives on the functions of follow-up, factors that influence follow-up intervals, and important considerations for extending intervals. METHODS: Qualitative interviews with 16 clinicians (surgical oncologists, dermatologists, melanoma unit physicians) who conduct follow-up at two of Australia's largest specialist centers. RESULTS: Follow-up is conducted for early detection of recurrences or new primary melanomas, to manage patient anxiety, support patient self-care, and as part of shared care. Recommended intervals are based on guidelines but account for each patient's clinical risk profile, level of anxiety, patient education requirements, capacity to engage in skin self-examination, and how the clinician prefers to manage any suspicious lesions. CONCLUSIONS: To revise guidelines and implement change it is important to understand the rationale underpinning existing practice. Extended follow-up intervals for early stage melanoma are more likely to be adopted after the first year when patients are less anxious and sufficiently prepared to conduct self-examination. Clinicians may retain existing schedules for highly anxious patients or those unable to examine themselves

Legacy effects of statins on cardiovascular and all-cause mortality: A meta-analysis

© Author(s) (or their employer(s)) 2018. Objectives To assess evidence for 'legacy' (post-trial) effects on cardiovascular disease (CVD) mortality and all-cause mortality among adult participants of placebocontrolled randomised controlled trials (RCTs) of statins. Design Meta-analysis of aggregate data. Setting/Participants Placebo-controlled statin RCTS for primary and secondary CVD prevention. Methods Data sources: PubMed, Embase from inception and forward citations of Cholesterol Treatment Trialists' Collaborators RCTs to 16 June 2016. Study selection: Two independent reviewers identified all statin RCT follow-up reports including ≥1000 participants, and cardiovascular and all-cause mortality. Data extraction and synthesis: Two independent reviewers extracted data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Main outcomes: Post-trial CVD and all-cause mortality. Results We included eight trials, with mean post-trial follow-up ranging from 1.6 to 15.1 years, and including 13 781 post-trial deaths (6685 CVD). Direct effects of statins within trials were greater than legacy effects posttrials. The pooled data from all eight studies showed no evidence overall of legacy effects on CVD mortality, but some evidence of legacy effects on all-cause mortality (p=0.01). Exploratory subgroup analysis found possible differences in legacy effect for primary prevention trials compared with secondary prevention trials for both CVD mortality (p=0.15) and all-cause mortality (p=0.02). Pooled post-trial HR for the three primary prevention studies demonstrated possible post-trial legacy effects on CVD mortality (HR=0.87; 95% CI 0.79 to 0.95) and on all-cause mortality (HR=0.90; 95% CI 0.85 to 0.96). Conclusions Possible post-trial statin legacy effects on all-cause mortality appear to be driven by the primary prevention studies. Although these relative benefits were smaller than those observed within the trial, the absolute benefits may be similar for the two time periods. Analysis of individual patient data from follow-up studies after placebo-controlled statin RCTs in lower-risk populations may provide more definitive evidence on whether early treatment of subclinical atherosclerosis is likely to be beneficial

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

Early prediction of pathologic response to neoadjuvant therapy in breast cancer: Systematic review of the accuracy of MRI

Abstract Magnetic resonance imaging (MRI) has been proposed to have a role in predicting final pathologic response when undertaken early during neoadjuvant chemotherapy (NAC) in breast cancer. This paper examines the evidence for MRI's accuracy in early response prediction. A systematic literature search (to February 2011) was performed to identify studies reporting the accuracy of MRI during NAC in predicting pathologic response, including searches of MEDLINE, PREMEDLINE, EMBASE, and Cochrane databases. 13 studies were eligible (total 605 subjects, range 16–188). Dynamic contrast-enhanced (DCE) MRI was typically performed after 1–2 cycles of anthracycline-based or anthracycline/taxane-based NAC, and compared to a pre-NAC baseline scan. MRI parameters measured included changes in uni- or bidimensional tumour size, three-dimensional volume, quantitative dynamic contrast measurements (volume transfer constant [Ktrans], exchange rate constant [ k ep ], early contrast uptake [ECU]), and descriptive patterns of tumour reduction. Thresholds for identifying response varied across studies. Definitions of response included pathologic complete response (pCR), near-pCR, and residual tumour with evidence of NAC effect (range of response 0–58%). Heterogeneity across MRI parameters and the outcome definition precluded statistical meta-analysis. Based on descriptive presentation of the data, sensitivity/specificity pairs for prediction of pathologic response were highest in studies measuring reductions in Ktrans (near-pCR), ECU (pCR, but not near-pCR) and tumour volume (pCR or near-pCR), at high thresholds (typically >50%); lower sensitivity/specificity pairs were evident in studies measuring reductions in uni- or bidimensional tumour size. However, limitations in study methodology and data reporting preclude definitive conclusions. Methods proposed to address these limitations include: statistical comparison between MRI parameters, and MRI vs other tests (particularly ultrasound and clinical examination); standardising MRI thresholds and pCR definitions; and reporting changes in NAC based on test results. Further studies adopting these methods are warranted