A National Registry for People With All Stages of Kidney Disease: The National Kidney Foundation (NKF) Patient Network.

RATIONALE & OBJECTIVE: The National Kidney Foundation (NKF) launched the first national US kidney disease patient registry, the NKF Patient Network, that is open to patients throughout the continuum of chronic kidney disease (CKD). The Network provides individualized education and will facilitate patient-centered research, clinical care, and health policy decisions. Here, we present the overall design and the results of a feasibility study that was conducted July through December 2020. STUDY DESIGN: Longitudinal observational cohort study of patient-entered data with or without electronic health care record (EHR) linkage in collaboration with health systems. SETTING & PARTICIPANTS: People with CKD, age≥18 years, are invited through their provider, NKF communications, or national outreach campaign. People self-enroll and share their data through a secure portal that offers individualized education and support. The first health system partner is Geisinger. EXPOSURE: Any cause and stage of CKD, including dialysis and kidney transplant recipients. OUTCOME: Feasibility of the EHR data transfer, participants' characteristics, and their perspectives on usability and content. ANALYTICAL APPROACH: Data were collected and analyzed through the registry portal powered by the Pulse Infoframe healthie 2.0 platform. RESULTS: During the feasibility study, 80 participants completed their profile, and 42 completed a satisfaction survey. Mean age was 57.5 years, 51% were women, 83% were White, and 89% were non-Hispanic or Latino. Of the participants, 60% were not aware of their level of estimated glomerular filtration rate and 91% of their urinary albumin-creatinine ratio. LIMITATIONS: Challenges for the Network are lack of awareness of kidney disease for many with CKD, difficulty in recruiting vulnerable populations or those with low digital readiness, and loss to follow-up, all leading to selection bias. CONCLUSIONS: The Network is positioned to become a national and international platform for real-world data that can inform the development of patient-centered research, care, and treatments.

EGFR mutation prevalence, real-world treatment patterns, and outcomes among patients with resected, early-stage, non-small cell lung cancer in Canada.

OBJECTIVES: The ADAURA trial demonstrated the benefit of adjuvant osimertinib among patients with resected, early-stage, epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). To understand the potential population impact, it is critical to deduce the prevalence, management, and outcomes of this patient population in the real-world setting before use of adjuvant osimertinib. MATERIALS AND METHODS: Using PALEOS (Pan-cAnadian Lung cancEr Observational Study) data (2012-2019), a retrospective, multi-center, observational cohort study was conducted among patients with early-stage (IB-IIIA) resected NSCLC who had not received neoadjuvant therapy. Study outcomes included EGFRm prevalence, treatment patterns, recurrence outcomes, and overall and disease-free survival (OS/DFS). RESULTS: Among patients undergoing reflexive EGFRm testing by a pathologist at time of diagnosis irrespective of disease stage (N = 535), 23 % were EGFRm-positive; 15.9 % had common mutations and 5.6 % had uncommon mutations. Within the EGFRm-positive cohort (N = 156), mean age at diagnosis was 68 years, 65 % of patients were female, and 35 % were of Asian descent. At diagnosis, 48 %, 31 %, and 21 % had stage IB, II, or IIIA disease, respectively; 46 % received adjuvant therapy after resection. Half of patients experienced disease recurrence, typically involving distant sites; central nervous system metastasis varied from 12 % to 15.0 % across disease stages. EGFR tyrosine kinase inhibitors were the most commonly received therapy after first metastatic recurrence. Median OS (DFS) was not reached, 71.2 (22.8) months, and 50.1 (18.0) months among stage IB, II, and IIIA patients. Patients with uncommon EGFRm had a lower probability of survival than those with common EGFRm (2 years: 87 % vs 91 %-94 %; 4 years: 56 % vs 73 %-82 %). CONCLUSION: Approximately-one-quarter of patients with resected, early-stage NSCLC were EGFRm-positive in this study. These patients had high recurrence rates and suboptimal long-term survival after treatment with current therapies. New adjuvant treatments are warranted.

Severity Assessment in CDKL5 Deficiency Disorder.

BACKGROUND: Pathologic mutations in cyclin-dependent kinase-like 5 cause CDKL5 deficiency disorder, a genetic syndrome associated with severe epilepsy and cognitive, motor, visual, and autonomic disturbances. This disorder is a relatively common genetic cause of early-life epilepsy. A specific severity assessment is lacking, required to monitor the clinical course and needed to define the natural history and for clinical trial readiness. METHODS: A severity assessment was developed based on clinical and research experience from the International Foundation for CDKL5 Research Centers of Excellence consortium and the National Institutes of Health Rett and Rett-Related Disorders Natural History Study consortium. An initial draft severity assessment was presented and reviewed at the annual CDKL5 Forum meeting (Boston, 2017). Subsequently it was iterated through four cycles of a modified Delphi process by a group of clinicians, researchers, industry, patient advisory groups, and parents familiar with this disorder until consensus was achieved. The revised version of the severity assessment was presented for review, comment, and piloting to families at the International Foundation for CDKL5 Research-sponsored family meeting (Colorado, 2018). Final revisions were based on this additional input. RESULTS: The final severity assessment comprised 51 items that comprehensively describe domains of epilepsy; motor; cognition, behavior, vision, and speech; and autonomic functions. Parental ratings of therapy effectiveness and child and family functioning are also included. CONCLUSIONS: A severity assessment was rapidly developed with input from multiple stakeholders. Refinement through ongoing validation is required for future clinical trials. The consensus methods employed for the development of severity assessment may be applicable to similar rare disorders.

Barriers to technology use among older heart failure individuals in managing their symptoms after hospital discharge.

BACKGROUND: In North America, heart failure (HF) is the leading cause for hospital readmission. Supportive technology, such as computers and tablets, could potentially assist patients with self-care to manage their condition after hospital discharge; however, older individuals have difficulties in adopting technology to manage their condition. METHOD: This study used a mixed methods design to identify barriers to technology use in HF self-care. In the qualitative phase, semi-structured interviews were conducted with 18 HF patients and 10 informal caregivers or care partners (CP). In the quantitative phase, five questionnaires were administered to 15 patients and 8 CP: Montreal Cognitive Assessment; Short Literacy Survey and Subjective Numeracy Scale; Self-Care of HF Index; Knowledge Assessment Questionnaire; and Patient Activation Measure. RESULTS: In the qualitative phase, five themes emerged regarding engagement in self care and technology use: knowledge level of HF; level of willingness to ask questions related to HF; confidence level in making health-related decisions individually; level of technology usage in daily activities; and self-recording of health measurements. Quantitative analysis found that most HF patients had mild cognitive impairment (MCI), adequate health numeracy levels to understand and manage their health condition, high confidence levels in managing their condition and willingness to engage in self-care. There was variation in willingness to adopt technology. CONCLUSION: Patients were willing to engage in HF self-care however they relied on CPs who were more willing to ask questions about HF. Technology tools may assist in HF self-care, but they must be tailored for use among older individuals.

Post-pyloric versus gastric tube feeding for preventing pneumonia and improving nutritional outcomes in critically ill adults.

BACKGROUND: Nutritional support is an essential component of critical care. Malnutrition has been associated with poor outcomes among patients in intensive care units (ICUs). Evidence suggests that in patients with a functional gut, nutrition should be administered through the enteral route. One of the main concerns regarding use of the enteral route is the reduction in gastric motility that is often responsible for limited caloric intake. This increases the risk of aspiration pneumonia as well. Post-pyloric feeding, in which the feed is delivered directly into the duodenum or the jejunum, could solve these issues and provide additional benefits over routine gastric administration of the feed. OBJECTIVES: To evaluate the effectiveness and safety of post-pyloric feeding versus gastric feeding for critically ill adults who require enteral tube feeding. SEARCH METHODS: We searched the following databases: Cochrane Central Register of Controlled Trials (CENTRAL;2013 Issue 10), MEDLINE (Ovid) (1950 to October 2013), EMBASE (Ovid) (1980 to October 2013) and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO host (1982 to October 2013). We reran the search on 4 February 2015 and will deal with the one study of interest when we update the review. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials comparing post-pyloric versus gastric tube feeding in critically ill adults. DATA COLLECTION AND ANALYSIS: We extracted data using the standard methods of the Cochrane Anaesthesia, Critical and Emergency Care Group and separately evaluated trial quality and data extraction as performed by each review author. We contacted trials authors to request missing data. MAIN RESULTS: We pooled data from 14 trials of 1109 participants in a meta-analysis. Moderate quality evidence suggests that post-pyloric feeding is associated with low rates of pneumonia compared with gastric tube feeding (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.51 to 0.84). Low-quality evidence shows an increase in the percentage of total nutrient delivered to the patient by post-pyloric feeding (mean difference (MD) 7.8%, 95% CI 1.43 to 14.18).Evidence of moderate quality revealed no differences in duration of mechanical ventilation or in mortality. Intensive care unit (ICU) length of stay was similar between the two groups. The effect on the time required to achieve the full nutrition target was uncertain (MD -1.99 hours 95% CI -10.97 to 6.99) (very low-quality evidence). We found no evidence suggesting an increase in the rate of complications during insertion or maintenance of the tube in the post-pyloric group (RR 0.51, 95% CI 0.19 to 1.364; RR1.63, 95% CI 0.93 to 2.86, respectively); evidence was assessed as being of low quality for both.Risk of bias was generally low in most studies, and review authors expressed concern regarding lack of blinding of the caregiver in most trials. AUTHORS' CONCLUSIONS: We found moderate-quality evidence of a 30% lower rate of pneumonia associated with post-pyloric feeding and low-quality evidence suggesting an increase in the amount of nutrition delivered to these participants. We do not have sufficient evidence to show that other clinically important outcomes such as duration of mechanical ventilation, mortality and length of stay were affected by the site of tube feeding.Low-quality evidence suggests that insertion of a post-pyloric feeding tube appears to be safe and was not associated with increased complications when compared with gastric tube insertion. Placement of the post-pyloric tube can present challenges; the procedure is technically difficult, requiring expertise and sophisticated radiological or endoscopic assistance.We recommend that use of a post-pyloric feeding tube may be preferred for ICU patients for whom placement of the post-pyloric feeding tube is feasible. Findings of this review preclude recommendations regarding the best method for placing the post-pyloric feeding tube. The clinician is left with this decision, which should be based on the policies of institutional facilities and should be made on a case-by-case basis. Protocols and training for bedside placement by physicians or nurses should be evaluated.

A hybrid manifold learning algorithm for the diagnosis and prognostication of Alzheimer's disease.

The diagnosis of Alzheimer's disease (AD) requires a variety of medical tests, which leads to huge amounts of multivariate heterogeneous data. Such data are difficult to compare, visualize, and analyze due to the heterogeneous nature of medical tests. We present a hybrid manifold learning framework, which embeds the feature vectors in a subspace preserving the underlying pairwise similarity structure, i.e. similar/dissimilar pairs. Evaluation tests are carried out using the neuroimaging and biological data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) in a three-class (normal, mild cognitive impairment, and AD) classification task using support vector machine (SVM). Furthermore, we make extensive comparison with standard manifold learning algorithms, such as Principal Component Analysis (PCA), Principal Component Analysis (PCA), Multidimensional Scaling (MDS), and isometric feature mapping (Isomap). Experimental results show that our proposed algorithm yields an overall accuracy of 85.33% in the three-class task.

An Internet-Based Counseling Intervention With Email Reminders that Promotes Self-Care in Adults With Chronic Heart Failure: Randomized Controlled Trial Protocol.

BACKGROUND: Chronic heart failure (CHF) is a public health priority. Its age-standardized prevalence has increased over the past decade. A major challenge for the management of CHF is to promote long-term adherence to self-care behaviors without overtaxing available health care resources. Counseling by multidisciplinary health care teams helps to improve adherence to self-care behaviors and to reduce the rate of death and hospitalization. In the absence of intervention, adherence to self-care is below recommended standards. OBJECTIVE: This trial aims to establish and evaluate a Canadian e-platform that will provide a core, standardized protocol of behavioral counseling and education to facilitate long-term adherence to self-care among patients with CHF. METHODS: Canadian e-Platform to Promote Behavioral Self-Management in Chronic Heart Failure (CHF-CePPORT) is a multi-site, double blind, randomized controlled trial with a 2 parallel-group (e-Counseling + Usual Care vs e-Info Control + Usual Care) by 3 assessments (baseline, 4-, and 12-month) design. We will identify subjects with New York Heart Association Class II or III systolic heart failure from collaborating CHF clinics and then recruit them (n=278) by phone. Subjects will be randomized in blocks within each site (Toronto, Montreal, and Vancouver). The primary outcome will be improved quality of life, defined as an increased number of subjects with an improvement of ≥5 points on the summary score of the Kansas City Cardiomyopathy Questionnaire. We will also assess the following secondary outcomes: (1) diet habits, depression, anxiety, smoking history, stress level, and readiness for change using self-report questionnaires, (2) physical activity level, current smoking status, and vagal-heart rate modulation by physiological tests, and (3) exercise capacity, prognostic indicators of cardiovascular functioning, and medication adherence through medical chart review. The primary outcome will be analyzed using generalized estimation equations with repeated measures on an intention-to-treat basis. Secondary outcomes will be analyzed using repeated-measures linear mixed models with a random effects intercept. All significant main effects or interactions in the statistical models will be followed up with post hoc contrasts using a Bonferroni correction with a 2-sided statistical significance criterion of P<.05. RESULTS: This 3.5-year, proof-of-principle trial will establish the e-infrastructure for a pan-Canadian e-platform for CHF that is comprised of a standardized, evidence-based protocol of e-Counseling. CONCLUSIONS: CHF-CePPORT is designed to improve long-term adherence to self-care behaviors and quality of life among patients with CHF. It will demonstrate a distinct Canadian initiative to build capacity for preventive eHealth services for patients with CHF. TRIAL REGISTRATION: ClinicalTrials.gov NCT01864369; http://clinicaltrials.gov/ct2/show/NCT01864369 (Archived by WebCite at http://www.webcitation.org/6Iiv6so7E).

CMR imaging with rapid visual T1 assessment predicts mortality in patients suspected of cardiac amyloidosis.

OBJECTIVES: This study tested the diagnostic and prognostic utility of a rapid, visual T1 assessment method for identification of cardiac amyloidosis (CA) in a "real-life" referral population undergoing cardiac magnetic resonance for suspected CA. BACKGROUND: In patients with confirmed CA, delayed-enhancement cardiac magnetic resonance (DE-CMR) frequently shows a diffuse, global hyperenhancement (HE) pattern. However, imaging is often technically challenging, and the prognostic significance of diffuse HE is unclear. METHODS: Ninety consecutive patients referred for suspected CA and 64 hypertensive patients with left ventricular hypertrophy (LVH) were prospectively enrolled and underwent a modified DE-CMR protocol. After gadolinium administration a method for rapid, visual T1 assessment was used to identify the presence of diffuse HE during the scan, allowing immediate optimization of settings for the conventional DE-CMR that followed. The primary endpoint was all-cause mortality. RESULTS: Among patients with suspected CA, 66% (59 of 90) demonstrated HE, with 81% (48 of 59) of these meeting pre-specified visual T1 assessment criteria for diffuse HE. Among hypertensive LVH patients, 6% (4 of 64) had HE, with none having diffuse HE. During 29 months of follow-up (interquartile range: 12 to 44 months), there were 50 (56%) deaths in patients with suspected CA and 4 (6%) in patients with hypertensive LVH. Multivariable analysis demonstrated that the presence of diffuse HE was the most important predictor of death in the group with suspected CA (hazard ratio: 5.5, 95% confidence interval: 2.7 to 11.0; p < 0.0001) and in the population as a whole (hazard ratio: 6.0, 95% confidence interval 3.0 to 12.1; p < 0.0001). Among 25 patients with myocardial histology obtained during follow-up, the sensitivity, specificity, and accuracy of diffuse HE in the diagnosis of CA were 93%, 70%, and 84%, respectively. CONCLUSIONS: Among patients suspected of CA, the presence of diffuse HE by visual T1 assessment accurately identifies patients with histologically-proven CA and is a strong predictor of mortality.

Impact of interventions on medication adherence and blood pressure control in patients with essential hypertension: a systematic review by the ISPOR medication adherence and persistence special interest group.

OBJECTIVES: To systematically review the evidence on the impact of interventions to improve medication adherence in adults prescribed antihypertensive medications. METHODS: An electronic search was undertaken of articles published between 1979 and 2009, without language restriction, that focused on interventions to improve antihypertensive medication adherence among patients (≥18 years) with essential hypertension. Studies must have measured adherence as an outcome of the intervention. We followed standard guidelines for the conduct and reporting of the review and conducted a narrative synthesis of reported data. RESULTS: Ninety-seven articles were identified for inclusion; 35 (35 of 97, 36.1%) examined interventions to directly improve medication adherence, and the majority (58 of 97, 59.8%) were randomized controlled trials. Thirty-four (34 of 97, 35.1%) studies reported a statistically significant improvement in medication adherence. DISCUSSION/CONCLUSIONS: Interventions aimed at improving patients' knowledge of medications possess the greatest potential clinical value in improving adherence with antihypertensive therapy. However, we identified several limitations of these studies, and advise future researchers to focus on using validated adherence measures, well-designed randomized controlled trials with relevant adherence and clinical outcomes, and guidelines on the appropriate design and analysis of adherence research.

Antihypertensive medication use, adherence, stops, and starts in Canadians with hypertension.

BACKGROUND: Some of the greatest barriers to achieving blood pressure control are perceived to be failure to prescribe antihypertensive medication and lack of adherence to medication prescriptions. METHODS: Self-reported data from 6017 Canadians with diagnosed hypertension who responded to the 2008 Canadian Community Health Survey and the 2009 Survey on Living with Chronic Diseases in Canada were examined. RESULTS: The majority (82%) of individuals with diagnosed hypertension reported using antihypertensive medications. The main reasons for not taking medications were either that they were not prescribed (42%) or that blood pressure had been controlled without medications (45%). Of those not taking antihypertensive medications in 2008 (n = 963), 18% had started antihypertensive medications by 2009, and of those initially taking medications (n = 5058), 5% had stopped. Of those taking medications in 2009, 89% indicated they took the medication as prescribed, and 10% indicated they occasionally missed a dose. Participants who were recently diagnosed, not measuring blood pressure at home, not having a plan to control blood pressure, or not receiving instructions on how to take medications were less likely to be taking antihypertensive medications; similar factors tended to be associated with stopping antihypertensive medication use. CONCLUSIONS: Compatible with high rates of hypertension control, most Canadians diagnosed with hypertension take antihypertensive medications and report adherence. Widespread implementation of self-management strategies for blood pressure control and standardized instructions on antihypertensive medication may further optimize drug treatment.

Health behaviour advice from health professionals to Canadian adults with hypertension: results from a national survey.

BACKGROUND: Health professionals play an important role in providing health information to patients. The objectives of this study were to examine the type of advice that Canadians with hypertension recall receiving from health professionals to manage their condition, and to assess if there is an association between health behaviour advice provided by health professionals and self-reported engagement in health behaviour modification. METHODS: Respondents of the 2009 Survey on Living with Chronic Diseases in Canada (N = 6142) were asked about sociodemographic characteristics, health care utilization, and health behaviour modification to control hypertension. Association between receipt of advice from health professional and ever engaging, continuing to engage, and not engaging in health behaviour modification was quantified by prevalence rate ratios. RESULTS: Most participants (90.9%; 95% confidence interval [CI], 89.6-92.2) reported that the health professional most responsible for treating their high blood pressure was their general practitioner. Approximately 9% reported that they had not received or do not recall receiving any advice for blood pressure control. The most commonly reported advice received from a health professional was to participate in physical activity or exercise (70.0%). Respondents who had received advice on health behaviour change to manage their high blood pressure were more likely to report engaging in the behaviour compared with those who did not receive such advice. CONCLUSIONS: Many Canadians with hypertension receive health behaviour change advice from their health professionals. Receiving this advice was associated with a greater likelihood of attempting health behaviour change and attempting to sustain that change.

Moving beyond the stigma: systematic review of video games and their potential to combat obesity.

Increasing epidemic proportions of overweight children in the United States presents formidable challenges for education and healthcare. Given the popularity and pervasiveness of video gaming culture in North American children, the perfect opportunity arises to investigate the potential of video games to promote healthful behaviour. Our objective was to systematically review the literature for possible benefits of active and educational video games targeting diet and physical activity in children. A review of English-language journal articles from 1998 to 2011 using EMBASE and PubMed was conducted. Thirty-four studies concerned with children, video games, physical, and/or nutritional outcomes were included. Results of these studies that showed some benefit (increased physical activity and nutritional knowledge as a result of gaming) demonstrate the possibility of video games to combat childhood obesity-looking beyond the stigma attached to gaming.

Hitting the ground running: Healthgrid deployment and adoption.

We consider the issues of healthgrid development, deployment and adoption in health care and research environments. While healthgrid technology could be deployed to support advanced medical research, we are not seeing its wide adoption. Understanding why this technology is not being exploited is one purpose of this paper. We do so in light of the seminal Healthgrid White Paper and the SHARE roadmap. We also address barriers to adoption and successes by presenting experiences in North America and Europe. By critically appraising where we are, we hope that we can hit the ground running in the near future.

Stopping randomized trials early for benefit and estimation of treatment effects: systematic review and meta-regression analysis.

CONTEXT: Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping. OBJECTIVE: To compare the treatment effect from truncated RCTs with that from meta-analyses of RCTs addressing the same question but not stopped early (nontruncated RCTs) and to explore factors associated with overestimates of effect. DATA SOURCES: Search of MEDLINE, EMBASE, Current Contents, and full-text journal content databases to identify truncated RCTs up to January 2007; search of MEDLINE, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects to identify systematic reviews from which individual RCTs were extracted up to January 2008. STUDY SELECTION: Selected studies were RCTs reported as having stopped early for benefit and matching nontruncated RCTs from systematic reviews. Independent reviewers with medical content expertise, working blinded to trial results, judged the eligibility of the nontruncated RCTs based on their similarity to the truncated RCTs. DATA EXTRACTION: Reviewers with methodological expertise conducted data extraction independently. RESULTS: The analysis included 91 truncated RCTs asking 63 different questions and 424 matching nontruncated RCTs. The pooled ratio of relative risks in truncated RCTs vs matching nontruncated RCTs was 0.71 (95% confidence interval, 0.65-0.77). This difference was independent of the presence of a statistical stopping rule and the methodological quality of the studies as assessed by allocation concealment and blinding. Large differences in treatment effect size between truncated and nontruncated RCTs (ratio of relative risks <0.75) occurred with truncated RCTs having fewer than 500 events. In 39 of the 63 questions (62%), the pooled effects of the nontruncated RCTs failed to demonstrate significant benefit. CONCLUSIONS: Truncated RCTs were associated with greater effect sizes than RCTs not stopped early. This difference was independent of the presence of statistical stopping rules and was greatest in smaller studies.

Stopping randomized trials early for benefit: a protocol of the Study Of Trial Policy Of Interim Truncation-2 (STOPIT-2).

BACKGROUND: Randomized clinical trials (RCTs) stopped early for benefit often receive great attention and affect clinical practice, but pose interpretational challenges for clinicians, researchers, and policy makers. Because the decision to stop the trial may arise from catching the treatment effect at a random high, truncated RCTs (tRCTs) may overestimate the true treatment effect. The Study Of Trial Policy Of Interim Truncation (STOPIT-1), which systematically reviewed the epidemiology and reporting quality of tRCTs, found that such trials are becoming more common, but that reporting of stopping rules and decisions were often deficient. Most importantly, treatment effects were often implausibly large and inversely related to the number of the events accrued. The aim of STOPIT-2 is to determine the magnitude and determinants of possible bias introduced by stopping RCTs early for benefit. METHODS/DESIGN: We will use sensitive strategies to search for systematic reviews addressing the same clinical question as each of the tRCTs identified in STOPIT-1 and in a subsequent literature search. We will check all RCTs included in each systematic review to determine their similarity to the index tRCT in terms of participants, interventions, and outcome definition, and conduct new meta-analyses addressing the outcome that led to early termination of the tRCT. For each pair of tRCT and systematic review of corresponding non-tRCTs we will estimate the ratio of relative risks, and hence estimate the degree of bias. We will use hierarchical multivariable regression to determine the factors associated with the magnitude of this ratio. Factors explored will include the presence and quality of a stopping rule, the methodological quality of the trials, and the number of total events that had occurred at the time of truncation.Finally, we will evaluate whether Bayesian methods using conservative informative priors to "regress to the mean" overoptimistic tRCTs can correct observed biases. DISCUSSION: A better understanding of the extent to which tRCTs exaggerate treatment effects and of the factors associated with the magnitude of this bias can optimize trial design and data monitoring charters, and may aid in the interpretation of the results from trials stopped early for benefit.

A framework for planning and critiquing medication compliance and persistence research using prospective study designs.

BACKGROUND: Medication compliance and persistence are important determinants of clinical outcomes. With the application of evidence-based therapy, it is increasingly important to ensure that studies that use compliance or persistence as a primary or secondary outcome are designed suitably and employ appropriate analyses to support the inferences made. OBJECTIVE: The aim of this work was to describe the designs of medication compliance/persistence studies and provide guidance on appropriate analyses, with the ultimate goal of helping health providers and payers of health care understand the impact of compliance and persistence on health outcomes. METHODS: MEDLINE, CINAHL, EMBASE, and all EBM Reviews databases were searched to locate key research articles about prospective medication compliance and persistence studies. Articles published between 1978 and 2008 were included in the search. Inclusion criteria included a focus on medication compliance and persistence, and prospective research designs. Articles that largely focused on retrospective study designs or were based on opinion rather than evidence were excluded. RESULTS: A systematic framework was developed that comprised a prospective checklist and a quantitative tool to assess the quality of studies. The key elements of the checklist included the following: title and abstract, introduction or background, objectives, methods and study design, statistical analysis and results, discussion, conclusions, and disclosure of conflicts of interest. For each element, examples are provided to help readers make an informed decision about the design, value, and quality of a particular prospective study. CONCLUSIONS: The checklist and quantitative tool can be used to provide objective validation of the rigor of prospective research designs. It is anticipated that future research will follow a uniform approach to presentation and evaluation of data, thereby facilitating a clear understanding of the impact of compliance and persistence on health outcomes.

TEACH: Trial of Education And Compliance in Heart dysfunction chronic disease and heart failure (HF) as an increasing problem.

UNLABELLED: In this manuscript we outline the development of a randomized control trial. INTRODUCTION: Heart failure (HF) is one of the leading causes of hospitalization in North America. While great advances have been made in the treatment of this disease, many factors limit the effectiveness of treatment. The objective of this Trial of Education And Compliance in Heart failure patients (TEACH) was to measure in patients with heart failure who were hospitalized and then discharged into the community, the impact of a comprehensive outpatient educational intervention on: 1) a composite endpoint of mortality, readmissions and visits to the emergency room for all causes, 2) the impact of the intervention on health-related quality of life, 3) the impact of the intervention on compliance to medication and 4) the economic impact of providing such an intervention to patients. RESEARCH DESIGN: This was a prospective cluster randomized controlled clinical trial in patients who were admitted to hospital with a diagnosis of heart failure (HF). Patients were stratified by reason for admission to hospital. Stratum 1 included patients whose primary reason for admission was HF and stratum 2 included patients whose primary reason for hospital admission was not HF. HYPOTHESIS: HF patients who receive an enhanced educational intervention from their community pharmacist will 1) have an absolute risk reduction in the number of events of 20%, 2) be more compliant, 3) will demonstrate less health-related quality of life (HRQoL) impairment as measured by disease-specific and generic HRQoL instruments and 4) will lower costs/Quality Adjusted Life Years (QALY) due to fewer total events per patient. OUTCOMES: Outcomes were collected every 3 months from baseline to the end of 1 year. Events were tracked using a comprehensive database that we developed and validated. In order to measure compliance we used electronic measures known as Track Caps (MEMS). We also used pharmacy refill data that was provided to us from all community pharmacies the patient used. This data was analyzed and interpreted using a validated formula developed by Steiner et al. (1996).

Delay in filling the initial prescription for a statin: a potential early indicator of medication nonpersistence.

BACKGROUND: Identification of early predictors of medication nonpersistence may allow timely adherence-promoting interventions and potentially reduce the risk of negative health outcomes. OBJECTIVE: This study was conducted to determine whether delay in filling an initial statin prescription predicts subsequent nonpersistence with medication. METHODS: This observational study of a cohort of adult patients (>18 years) who newly initiated statin therapy between December 1997 and June 2000 employed data from the administrative claims database of a large US managed care organization. Patients initiating statin therapy had to have at least 18 months of continuous eligibility and no statin use in the 6-month period before the index prescription. A new measure, dispensation delay, was measured as the gap between the most recent physician or hospital visit and the fill date of the index prescription. Five categories of dispensation delay were created--no delay, 1 to 7 days, 8 to 30 days, 31 to 183 days, and >183 days. Nonpersistence was defined as a gap of >or=30 days in the statin prescription supply during the follow-up period. Cox proportional hazards regression was used to model the risk of the initial dispensation delay on the time to discontinuation, controlling for such variables as demographic characteristics, comorbidities, physician specialty, and previous health care utilization. RESULTS: The final sample included 19,038 patients. Among all variables studied, the dispensation-delay variables were the most significant predictors of non-persistence, with a longer delay predicting a higher risk of early discontinuation. Patients with delays in filling the initial prescription of >30 days but <183 days were 30% more likely to discontinue therapy than those without delays (hazard ratio=1.30; 95% CI=1.20-1.40). CONCLUSIONS: The delay in filling the first statin prescription significantly predicted future non-persistence. Use of this measure may allow early identification of patients at high risk for early discontinuation.

A checklist for medication compliance and persistence studies using retrospective databases.

The increasing number of retrospective database studies related to medication compliance and persistence (C&P), and the inherent variability within each, has created a need for improvement in the quality and consistency of medication C&P research. This article stems from the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) efforts to develop a checklist of items that should be either included, or at least considered, when a retrospective database analysis of medication compliance or persistence is undertaken. This consensus document outlines a systematic approach to designing or reviewing retrospective database studies of medication C&P. Included in this article are discussions on data sources, measures of C&P, results reporting, and even conflict of interests. If followed, this checklist should improve the consistency and quality of C&P analyses, which in turn will help providers and payers understand the impact of C&P on health outcomes.

Pilot study to determine the impact of a multidisciplinary educational intervention in patients hospitalized with heart failure.

BACKGROUND: Patients with heart failure (HF) face challenges complying with multidrug regimens. OBJECTIVES: To examine the impact of a compliance enhancing intervention on medication compliance and morbidity in HF. DESIGN: Patients were randomized to either usual care or an inhospital educational intervention delivered by a multidisciplinary team (Intervention). SETTING: Acute medical and surgical units at a teaching hospital. PATIENTS: One hundred thirty four patients with a clinical diagnosis of HF and a left ventricular ejection fraction of < 40% requiring long-term medical treatment. MAIN OUTCOME MEASURES: A validated HF-specific instrument provided a measure of knowledge. We characterized patients as noncompliant if pharmacy refill data suggested they had taken < or = 0.80 of their medication. We measured quality of life using the Minnesota Living with Heart Failure Questionnaire and the Short Form 36 and conducted a time to first event analysis of a composite end point including mortality, readmissions, and emergency department visits. RESULTS: The Intervention group showed higher knowledge scores at discharge and 1 year (P = .05). The risk of noncompliance in Intervention patients varied from 0.78 (95% CI 0.33-1.89) for ACE-I (13% Intervention, 17% Control) to 1.02 (0.49-2.12) for diuretics (23% Intervention, 23% Control). Quality of life improved in both groups over time; the only difference between groups favored the Intervention (Minnesota Living with Heart Failure Questionnaire, P = .04). The composite end point occurred in 67% of control and 60% of Intervention patients (hazard ratio 0.85, 95% CI 0.55-1.30). CONCLUSIONS: An inhospital educational intervention improved knowledge and, possibly, quality of life and may be useful as part of a comprehensive compliance enhancing strategy in patients with HF.