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Background: Coronary artery disease is the leading cause of death in the United States. At-risk asymptomatic adults are eligible for screening with electrocardiogram-gated coronary artery calcium (CAC) CT, which aids in risk stratification and management decision-making. Incidental CAC (iCAC) is easily quantified on chest CT in patients imaged for noncardiac indications; however, radiologists do not routinely report the finding., Objective: To determine the clinical significance of CAC identified incidentally on routine chest CT performed for noncardiac indications., Design: An informationist developed search strategies in MEDLINE, Embase, and SCOPUS, and two reviewers independently screened results at both the abstract and full text levels. Data extracted from eligible articles included age, rate of iCAC identification, radiologist reporting frequency, impact on downstream medical management, and association of iCAC with patient outcomes., Results: From 359 unique citations, 83 research publications met inclusion criteria. The percentage of patients with iCAC ranged from 9% to 100%. Thirty-one investigations measured association(s) between iCAC and cardiovascular morbidity and mortality, and 29 identified significant correlations, including nonfatal myocardial infarction, fatal myocardial infarction, major adverse cardiovascular event, cardiovascular death, and all-cause death. iCAC was present in 20% to 100% of the patients in these cohorts, but when present, iCAC was reported by radiologists in only 31% to 44% of cases. Between 18% and 77% of patients with iCAC were not on preventive medications in studies that reported these data. Seven studies measured the effect of reporting on guideline directed medical therapy, and 5 (71%) reported an increase in medication prescriptions after diagnosis of iCAC, with one confirming reductions in low-density lipoprotein levels. Twelve investigations reported good concordance between CAC grade on noncardiac CT and Agatston score on electrocardiogram-gated cardiac CT, and 10 demonstrated that artificial intelligence tools can reliably calculate an Agatston score on noncardiac CT., Conclusion: A body of evidence demonstrates that patients with iCAC on routine chest CT are at risk for cardiovascular disease events and death, but they are often undiagnosed. Uniform reporting of iCAC in the chest CT impression represents an opportunity for radiology to contribute to early identification of high-risk individuals and potentially reduce morbidity and mortality. AI tools have been validated to calculate Agatston score on routine chest CT and hold the best potential for facilitating broad adoption., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) updates the KDIGO 2012 guideline and has been developed with patient partners, clinicians, and researchers around the world, using robust methodology. This update, based on a substantially broader base of evidence than has previously been available, reflects an exciting time in nephrology. New therapies and strategies have been tested in large and diverse populations that help to inform care; however, this guideline is not intended for people receiving dialysis nor those who have a kidney transplant. The document is sensitive to international considerations, CKD across the lifespan, and discusses special considerations in implementation. The scope includes chapters dedicated to the evaluation and risk assessment of people with CKD, management to delay CKD progression and its complications, medication management and drug stewardship in CKD, and optimal models of CKD care. Treatment approaches and actionable guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations which followed the "Grading of Recommendations Assessment, Development, and Evaluation" (GRADE) approach. The limitations of the evidence are discussed. The guideline also provides practice points, which serve to direct clinical care or activities for which a systematic review was not conducted, and it includes useful infographics and describes an important research agenda for the future. It targets a broad audience of people with CKD and their healthcare, while being mindful of implications for policy and payment., (Copyright © 2023 Kidney Disease: Improving Global Outcomes (KDIGO). Published by Elsevier Inc. All rights reserved.)

Objectives: Epilepsy treatment decision making is complex and understanding what informs caregiver decision making about treatment for childhood epilepsy is crucial to better support caregivers and their children. We synthesised evidence on caregivers' perspectives and experiences of treatments for childhood epilepsy., Design: Systematic review of qualitative studies using a best-fit framework and Grading of Recommendations Assessment, Development and Evaluation Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERQual) approach., Data Sources: Searched Embase, PubMed, CINAHL, PsycINFO, SocINDEX and Web of Science from 1 January 1999 to 19 August 2021., Eligibility Criteria: We included qualitative studies examining caregiver's perspectives on antiseizure medication, diet or surgical treatments for childhood epilepsy. We excluded studies not reported in English., Data Extraction and Synthesis: We extracted qualitative evidence into 1 of 14 domains defined by the Theoretical Domains Framework (TDF). One reviewer extracted study data and methodological characteristics, and two reviewers extracted qualitative findings. The team verified all extractions. We identified themes within TDF domains and synthesised summary statements of these themes. We assessed our confidence in our summary statements using GRADE-CERQual., Results: We identified five studies (in six reports) of good methodological quality focused on parent perceptions of neurosurgery; we found limited indirect evidence on parents' perceptions of medications or diet. We identified themes within 6 of the 14 TDF domains relevant to treatment decisions: knowledge, emotion; social/professional role and identity; social influence; beliefs about consequences; and environmental context and resources., Conclusions: Parents of children with epilepsy navigate a complex process to decide whether to have their child undergo surgery. Educational resources, peer support and patient navigators may help support parents through this process. More qualitative studies are needed on non-surgical treatments for epilepsy and among caregivers from different cultural and socioeconomic backgrounds to fully understand the diversity of perspectives that informs treatment decision making., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Parkinson's disease (PD) is the fastest-growing neurological disease in the world. A key challenge in PD is tracking disease severity, progression, and medication response. Existing methods are semisubjective and require visiting the clinic. In this work, we demonstrate an effective approach for assessing PD severity, progression, and medication response at home, in an objective manner. We used a radio device located in the background of the home. The device detected and analyzed the radio waves that bounce off people's bodies and inferred their movements and gait speed. We continuously monitored 50 participants, with and without PD, in their homes for up to 1 year. We collected over 200,000 gait speed measurements. Cross-sectional analysis of the data shows that at-home gait speed strongly correlates with gold-standard PD assessments, as evaluated by the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III subscore and total score. At-home gait speed also provides a more sensitive marker for tracking disease progression over time than the widely used MDS-UPDRS. Further, the monitored gait speed was able to capture symptom fluctuations in response to medications and their impact on patients' daily functioning. Our study shows the feasibility of continuous, objective, sensitive, and passive assessment of PD at home and hence has the potential of improving clinical care and drug clinical trials.

Background and Objectives: To recruit and characterize a national cohort of individuals who have a genetic variant ( LRRK2 G2019S) that increases risk of Parkinson disease (PD), assess participant satisfaction with a decentralized, remote research model, and evaluate interest in future clinical trials., Methods: In partnership with 23andMe, Inc., a personal genetics company, LRRK2 G2019S carriers with and without PD were recruited to participate in an ongoing 36-month decentralized, remote natural history study. We examined concordance between self-reported and clinician-determined PD diagnosis. We applied the Movement Disorder Society Prodromal Parkinson's Disease Criteria and asked investigators to identify concern for parkinsonism to distinguish participants with probable prodromal PD. We compared baseline characteristics of LRRK2 G2019S carriers with PD, with prodromal PD, and without PD., Results: Over 15 months, we enrolled 277 LRRK2 G2019S carriers from 34 states. At baseline, 60 had self-reported PD (mean [SD] age 67.8 years [8.4], 98% White, 52% female, 80% Ashkenazi Jewish, and 67% with a family history of PD), and 217 did not (mean [SD] age 53.7 years [15.1], 95% White, 59% female, 73% Ashkenazi Jewish, and 57% with a family history of PD). Agreement between self-reported and clinician-determined PD status was excellent (κ = 0.94, 95% confidence interval 0.89-0.99). Twenty-four participants had prodromal PD; 9 met criteria for probable prodromal PD and investigators identified concern for parkinsonism in 20 cases. Compared with those without prodromal PD, participants with prodromal PD were older (63.9 years [9.0] vs 51.9 years [15.1], p < 0.001), had higher modified Movement Disorders Society-Unified Parkinson's Disease Rating Scale motor scores (5.7 [4.3] vs 0.8 [2.1], p < 0.001), and had higher Scale for Outcomes in PD for Autonomic Symptoms scores (11.5 [6.2] vs 6.9 [5.7], p = 0.002). Two-thirds of participants enrolled were new to research, 97% were satisfied with the overall study, and 94% of those without PD would participate in future preventive clinical trials., Discussion: An entirely remote national cohort of LRRK2 G2019S carriers was recruited from a single site. This study will prospectively characterize a large LRRK2 G2019S cohort, refine a new model of clinical research, and engage new research participants willing to participate in future therapeutic trials., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Appropriate models of survivorship care for the growing number of adult survivors of childhood cancer are unclear. We conducted a realist review to describe how models of care that include primary care and relevant resources (eg, tools, training) could be effective for adult survivors of childhood cancer. We first developed an initial program theory based on qualitative literature (studies, commentaries, opinion pieces) and stakeholder consultations. We then reviewed quantitative evidence and consulted stakeholders to refine the program theory and develop and refine context-mechanism-outcome hypotheses regarding how models of care that include primary care could be effective for adult survivors of childhood cancer. Effectiveness for both resources and models is defined by survivors living longer and feeling better through high-value care. Intermediate measures of effectiveness evaluate the extent to which survivors and providers understand the survivor's history, risks, symptoms and problems, health-care needs, and available resources. Thus, the models of care and resources are intended to provide information to survivors and/or primary care providers to enable them to obtain/deliver appropriate care. The variables from our program theory found most consistently in the literature include oncology vs primary care specialty, survivor and provider knowledge, provider comfort treating childhood cancer survivors, communication and coordination between and among providers and survivors, and delivery/receipt of prevention and surveillance of late effects. In turn, these variables were prominent in our context-mechanism-outcome hypotheses. The findings from this realist review can inform future research to improve childhood cancer survivorship care and outcomes., (© The Author(s) 2022. Published by Oxford University Press.)

Objective: Ineligibility for and refusal to participate in randomized controlled trials (RCTs) can potentially lead to unrepresentative study samples and limited generalizability of findings. We examined the rates of exclusion and refusal in RCTs that have studied impact on suicide-related outcomes in the US., Data Sources: PubMed, the Cochrane Library, the Campbell Collaboration Library of Systematic Reviews, CINAHL, PsycINFO, and Education Resources Information Center were searched from January 1990 to May 2020 using the terms ( suicide prevention ) AND ( clinical trial )., Study Selection: Of 8,403 studies retrieved, 36 RCTs assessing effectiveness on suicide-related outcomes in youth (≤ 25 years old) conducted in the US were included., Data Extraction: Study-level data were extracted by 2 independent investigators for a random-effects meta-analysis and meta-regression., Results: The study participants (N = 13,264) had a mean (SD) age of 14.87 (1.58) years and were 50% male, 23% African American, and 24% Hispanic. The exclusion rate was 36.4%, while the refusal rate was 25.5%. The exclusion rate was significantly higher in the studies excluding individuals not exceeding specified cutoff points of suicide screening tools (51.2%; adjusted linear coefficient [β] = 1.30, standard error [SE] = 0.15; P  = .041) and individuals not meeting the age or school grade criterion (45.9%; β = 1.37, SE = 0.13; P  = .005)., Conclusions: The rates of exclusion and refusal in youth prevention interventions studying impact on suicide-related outcomes were not as high compared to the rates found in other mental and behavioral interventions. While there was strong racial/ethnic group representation in RCTs examining youth suicide-related outcomes, suicide severity and age limited eligibility., (© Copyright 2022 Physicians Postgraduate Press, Inc.)

Purpose: To perform a mixed methods review to evaluate the effectiveness and implementation of models for integrating palliative care into ambulatory care for US adults with noncancer serious chronic illness., Methods: We searched 3 electronic databases from January 2000 to May 2020 and included qualitative, mixed methods studies and randomized and nonrandomized controlled trials. For each study, 2 reviewers abstracted data and independently assessed for quality. We conducted meta-analyses as appropriate and graded strength of evidence (SOE) for quantitative outcomes., Results: Quantitative analysis included 14 studies of 2,934 patients. Compared to usual care, models evaluated were not more effective for improving patient health-related quality of life (HRQOL) (standardized mean difference [SMD] of 4 of 8 studies, 0.19; 95% CI, ‒0.03 to 0.41) (SOE: moderate) or for patient depressive symptom scores (SMD of 3 of 9 studies, ‒0.09; 95% CI, ‒0.35 to 0.16) (SOE: moderate). Models might have little to no effect on patient satisfaction (SOE: low) but were more effective for increasing advance directive (AD) documentation (relative risk, 1.62; 95% CI, 1.35 to 1.94) (SOE: moderate). Qualitative analysis included 5 studies of 146 patients. Patient preferences for appropriate timing of palliative care varied; costs, additional visits, and travel were considered barriers to implementation., Conclusion: Models might have little to no effect on decreasing overall symptom burden and were not more effective than usual care for improving HRQOL or depressive symptom scores but were more effective for increasing AD documentation. Additional research should focus on identifying and addressing characteristics and implementation factors critical to integrating models to improve ambulatory, patient-centered outcomes., (© 2022 Annals of Family Medicine, Inc.)

New models of primary care include patient-reported outcome measures (PROMs) to promote patient-centered care. PROMs provide information on patient functional status and well-being, can be used to enhance care quality, and are proposed for use in assessing performance. Our objective was to identify a short list of candidate PROMs for use in primary care practice and to serve as a basis for performance measures (PMs). We used qualitative and quantitative methods to identify relevant patient-reported outcome (PRO) domains for use in performance measurement (PRO-PM) and their associated PROMs. We collected data from key informant groups: patients (n = 13; one-on-one and group interviews; concept saturation analysis), clinical thought leaders (n = 9; group discussions; thematic analysis), primary care practices representatives (n = 37; six focus groups; thematic analysis), and primary care payer representatives (n = 10; 12-question survey; frequencies of responses). We merged the key informant group information with findings from environmental literature scans. We conducted a targeted evidence review of measurement properties for candidate PROMs. We used a scoping review and key informant groups to identify PROM evaluation criteria, which were linked to the National Quality Forum measure evaluation criteria. We developed a de novo schema to score candidate PROMs against our criteria. We identified four PRO domains and 10 candidate PROMs: 3 for depressive symptoms, 2 for physical function, 3 for self-efficacy, 2 for ability to participate. Five PROMs met ≥ 70% of the evidence criteria for three PRO domains: PHQ-9 or PROMIS Depression (depression), PF-10 or PROMIS-PF (physical functioning), and PROMIS Self-Efficacy for Managing Treatments and Medications (self-efficacy). The PROMIS Ability to Participate in Social Roles and Activities met 68% of our criteria and might be considered for inclusion. Existing evidence and key informant data identified 5 candidate PROMs to use in primary care. These instruments can be used to develop PRO-PMs.

Importance: The inclusion of authors from diverse backgrounds and with different lived experiences is critical to ensuring the questions addressed in systematic reviews (SRs), as well as the subsequent conclusions and recommendations made, are representative of the global community., Objective: To assess the gender and geographic diversity of authors among all Cochrane SRs in eyes and vision as compared with a random sample of non-Cochrane SRs of interventions in the field of eyes and vision., Design: The Cochrane Eyes and Vision US Satellite maintains a database of SRs in the field of eyes and vision. We selected all (n = 313) eyes and vision intervention SRs published in The Cochrane Library and a random sample of 313 eyes and vision intervention SRs published elsewhere for this study. We determined gender of the first and corresponding authors ("woman," "man," or "unknown") using a previously developed algorithm and their location based on institution country and the World Health Organization region., Results: From the 626 reviews included in our sample, we identified 751 unique authors who comprised 887 author positions (i.e., first and/or corresponding authors). We were able to ascertain the gender of 647/751 (86%) authors: 276 women and 371 men. Among Cochrane eyes and vision SRs, the proportions of women in first and/or corresponding author positions were consistent and approximately equal to men. Among non-Cochrane eyes and vision SRs, the representation of women was markedly lower as corresponding authors than other positions. Most authors of Cochrane eyes and vision SRs were from the UK (31%) and USA (26%), whereas most authors of non-Cochrane SRs were from China (34%)., Conclusions and Relevance: Compared with authors of non-Cochrane SRs in eyes and vision, authors of Cochrane SRs appear to have approximately equal representation of women and men among perceived important author positions and be located in European and North American countries, possibly due to the locations of the Cochrane editorial teams. Cochrane Eyes and Vision should continue to recruit authors from around the world in locations that reflect the global burden of eye disease.

Background: The rise of direct-to-consumer genetic testing has enabled many to learn of their possible increased risk for rare diseases, some of which may be suitable for gene-targeted therapies. However, recruiting a large and representative population for rare diseases or genetically defined sub-populations of common diseases is slow, difficult, and expensive., Objective: To assess the feasibility of recruiting and retaining a cohort of individuals who carry a genetic mutation linked to Parkinson's disease (G2019S variant of LRRK2); to characterize this cohort relative to the characteristics of traditional, in-person studies; and to evaluate this model's ability to create an engaged study cohort interested in future clinical trials of gene-directed therapies., Methods: This single-site,3-year national longitudinal observational study will recruit between 250 to 350 LRRK2 carriers without Parkinson's disease and approximately 50 with the condition. Participants must have undergone genetic testing by the personal genetics company, 23andMe, Inc., have knowledge of their carrier status, and consent to be contacted for research studies. All participants undergo standardized assessments, including video-based cognitive and motor examination, and complete patient-reported outcomes on an annual basis., Results: 263 individuals living in 33 states have enrolled. The cohort has a mean (SD) age of 56.0 (15.9) years, 59% are female, and 76% are of Ashkenazi Jewish descent. 233 have completed the baseline visit: 47 with self-reported Parkinson's disease and 186 without., Conclusions: This study establishes a promising model for developing a geographically dispersed and well-characterized cohort ready for participation in future clinical trials of gene-directed therapies.

Objectives: The benefits and harms of diabetes treatments need to be carefully weighed in people with type II diabetes mellitus (DM) and multiple chronic conditions (MCCs). Our objective was to quantitatively assess the benefits and harms of the addition of basal insulin (insulin) vs. sulfonylurea (SU) to metformin in people with DM and MCCs., Study Design and Setting: Data inputs into the benefit-harms analysis included (1) baseline risks of patient-centered outcomes (death, myocardial infarction, stroke, severe hypoglycemia, diarrhea, nausea) from cohorts and trials; (2) treatment effects for the addition of insulin vs. SU from a network meta-analysis; and (3) patient preference survey for outcome weights. Statistical analysis calculated the probability that adding insulin has greater benefits than harms, when compared with an SU, overall and by prespecified subgroups., Results: Including the six outcomes, the probability of net benefit for insulin compared with SU was similar, across subgroups by age and diabetes duration (probability range, using conditional logit weights: 0.44-0.56). Adding patient preferences for treatment burden associated with insulin injections shifted the probability to favor SU over insulin (probability range, using conditional logit weights: 0.01-0.12)., Conclusion: In people with DM and MCCs, we demonstrated incomplete evidence to conclude if basal insulin or SU should be added in people with DM and MCCs on metformin alone. The benefit-harm balance was sensitive to treatment preferences, that is., perceived treatment burden, indicating the importance of shared-decision making in caring for people with MCCs who are at high risk for experiencing harms associated with diabetes management., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Context: The National Academy of Medicine recommends childhood obesity prevention efforts making healthier options the passive choice. This review evaluated the effectiveness of population-level policies and programs from natural experiments for childhood obesity prevention., Evidence Acquistion: The search included PubMed, CINAHL, PsycINFO, and EconLit from 2000 to 2017 for policies evaluated by natural experiments reporting childhood BMI outcomes. The studies were analyzed in 2017-2018. Interventions were classified by environmental focus (food/beverage, physical activity, or both) and stratified by setting (school, community, both). Risk of bias was evaluated for each study., Evidence Synthesis: Of 33 natural experiments, most (73%) took place in the school setting only. The most common environmental focus in any setting was food/beverage (48%). All four studies that focused on both food/beverage and physical activity in schools demonstrated decreased prevalence of overweight/obesity or BMI z-score by 0.04-0.17. BMI decreased in all four studies in both school and community settings. The largest effect size was a decrease in BMI z-score of 0.5, but most were <0.25. The risk of bias was high for most (76%) studies. Most (63%) of the eight studies with low/medium risk of bias took place in the school setting focused on the food/beverage environment; effects on BMI were mixed., Conclusions: Natural experiments evaluating school-based policies focusing on both the food/beverage and physical activity environments (versus targeting only one) consistently showed improvement in BMI. However, most studies had high risk of bias, highlighting the need for improved methods for evaluation of natural experiments for childhood obesity prevention., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Suicide is now the second leading cause of death among persons between the ages of adolescents and emerging adults and rates have increased despite more funding and broader implementation of youth suicide-prevention programs. A systematic review was conducted focusing on identifying youth suicide-prevention studies within the United States. This paper reports on the methods utilized for understanding possible moderators of suicide-prevention program outcomes., Methods: We searched six databases from 1990 through August 2017 to identify studies of suicide-preventive interventions among those under age 26 years. Two independent team members screened search results and sequentially extracted information related to statistical methods of moderation analyses., Results: 69 articles were included in the systematic review of which only 17 (24.6%) explored treatment effect heterogeneity using moderation analysis. The most commonly used analytic tool was regression with an interaction term. The moderators studied included demographic characteristics such as gender and ethnicity as well as individual characteristics such as traumatic stress exposure and multiple prior suicide attempts., Conclusions: With a greater emphasis from the federal government and funding agencies on precision prevention, understanding which prevention programs work for specific subgroups is essential. Only a small percentage of the reviewed articles assessed moderation effects. This is a substantial research gap driven by sample size or other limitations which have impeded the identification of intervention effect heterogeneity.

Background: This systematic review identifies programs, policies, and built-environment changes targeting prevention and control of adult obesity and evaluates their effectiveness., Methods: We searched PubMed, CINAHL, PsycINFO, and EconLit from January 2000 to March 2018. We included natural experiment studies evaluating a program, policy, or built-environment change targeting adult obesity and reporting weight/body mass index (BMI). Studies were categorized by primary intervention target: physical activity/built environment, food/beverage, messaging, or multiple. Two reviewers independently assessed the risk of bias for each study using the Effective Public Health Practice Project tool., Results: Of 158 natural experiments targeting obesity, 17 reported adult weight/BMI outcomes. Four of 9 studies reporting on physical activity/built environment demonstrated reduced weight/BMI, although effect sizes were small with low strength of evidence and high risk of bias. None of the 5 studies targeting the food/beverage environment decreased weight/BMI; strength of evidence was low, and 2 studies were rated high risk of bias., Discussion: We identified few natural experiments reporting on the effectiveness of programs, policies, and built-environment changes on adult obesity. Overall, we found no evidence that policies intending to promote physical activity and healthy eating had beneficial effects on weight/BMI and most studies had a high risk of bias. Limitations include few studies met our inclusion criteria; excluded studies in children and those not reporting on weight/BMI outcomes; weight/BMI reporting was very heterogeneous. More high-quality research, including natural experiments studies, is critical for informing the population-level effectiveness of obesity prevention and control initiatives in adults.

Context: Assessment tools are data collection instruments that are completed by or with patients or caregivers and which collect data at the individual patient or caregiver level., Objectives: The objectives of this study are to 1) summarize palliative care assessment tools completed by or with patients or caregivers and 2) identify needs for future tool development and evaluation., Methods: We completed 1) a systematic review of systematic reviews; 2) a supplemental search of previous reviews and Web sites, and/or 3) a targeted search for primary articles when no tools existed in a domain. Paired investigators screened search results, assessed risk of bias, and abstracted data. We organized tools by domains from the National Consensus Project Clinical Practice Guidelines for Palliative Care and selected the most relevant, recent, and highest quality systematic review for each domain., Results: We included 10 systematic reviews and identified 152 tools (97 from systematic reviews and 55 from supplemental sources). Key gaps included no systematic review for pain and few tools assessing structural, cultural, spiritual, or ethical/legal domains, or patient-reported experience with end-of-life care. Psychometric information was available for many tools, but few studies evaluated responsiveness (sensitivity to change) and no studies compared tools., Conclusion: Few to no tools address the spiritual, ethical, or cultural domains or patient-reported experience with end-of-life care. While some data exist on psychometric properties of tools, the responsiveness of different tools to change and/or comparisons between tools have not been evaluated. Future research should focus on developing or testing tools that address domains for which few tools exist, evaluating responsiveness, and comparing tools., (Copyright © 2017 American Academy of Hospice and Palliative Medicine. All rights reserved.)

Background: Having more than one chronic condition is common and is associated with greater health care utilization, higher medication burden and complexity of treatment. However, clinical practice guidelines (CPGs) do not routinely address the balance between harms and benefits of treatments for people with multiple chronic conditions (MCCs)., Objective: To partner with the Kaiser Permanente Integrated Cardiovascular Health (ICVH) program to engage multiple stakeholders in a mixed-methods approach in order to: 1) identify two high-priority clinical questions related to MCCs, and 2) understand patients' and family caregivers' perceptions of meaningful outcomes to inform benefit/harm assessments for these two high-priority questions. These clinical questions and outcomes will be used to inform CPG recommendations for people with MCCs. DESIGN AND PARTICIPANTS: The ICVH program provided 130 topics rank-ordered by the potential for finding evidence that would change clinical recommendations regarding the topic. We used a modified Delphi method to identify and reword topics into questions relevant to people with MCCs. We used two sets of focus groups (n = 27) to elicit patient and caregiver perspectives on two important research questions and relevant patient-important outcomes on benefit/harm balance for people with MCCs., Key Results: Co-investigators, patients and caregivers identified "optimal blood pressure goals" and "diabetes medication management" as important clinical topics for CPGs related to people with MCCs. Stakeholders identified a list of relevant outcomes to be addressed in future CPG development including 1) physical function and energy, 2) emotional health and well-being, 3) avoidance of treatment burden, side effects and risks, 4) interaction with providers and health care system, and 5) prevention of adverse long-term health outcomes., Conclusions: Through the application of a mixed-methods process, we identified the questions regarding optimal blood pressure goals and diabetes medication management, along with related patient-centered outcomes, to inform novel evidence syntheses for those with MCCs. This study provides the lessons learned and a generalizable process for CPG developers to engage patient and caregivers in priority-setting for the translation of evidence into future CPGs. Ultimately, engaging patient and stakeholders around MCCs could improve the relevance of CPGs for the care of people with MCCs.

Background: The Agency for Health Care Research and Quality Patient Safety Indicators (PSIs) and Centers for Medicare and Medicaid Services Hospital-acquired Conditions (HACs) are increasingly being used for pay-for-performance and public reporting despite concerns over their validity. Given the potential for these measures to misinform patients, misclassify hospitals, and misapply financial and reputational harm to hospitals, these need to be rigorously evaluated. We performed a systematic review and meta-analysis to assess PSI and HAC measure validity., Methods: We searched MEDLINE and the gray literature from January 1, 1990 through January 14, 2015 for studies that addressed the validity of the HAC measures and PSIs. Secondary outcomes included the effects of present on admission (POA) modifiers, and the most common reasons for discrepancies. We developed pooled results for measures evaluated by ≥3 studies. We propose a threshold of 80% for positive predictive value or sensitivity for pay-for-performance and public reporting suitability., Results: Only 5 measures, Iatrogenic Pneumothorax (PSI 6/HAC 17), Central Line-associated Bloodstream Infections (PSI 7), Postoperative hemorrhage/hematoma (PSI 9), Postoperative deep vein thrombosis/pulmonary embolus (PSI 12), and Accidental Puncture/Laceration (PSI 15), had sufficient data for pooled meta-analysis. Only PSI 15 (Accidental Puncture and Laceration) met our proposed threshold for validity (positive predictive value only) but this result was weakened by considerable heterogeneity. Coding errors were the most common reasons for discrepancies between medical record review and administrative databases. POA modifiers may improve the validity of some measures., Conclusion: This systematic review finds that there is limited validity for the PSI and HAC measures when measured against the reference standard of a medical chart review. Their use, as they currently exist, for public reporting and pay-for-performance, should be publicly reevaluated in light of these findings.

Objectives: Linking national, State, and community data systems, such as those used for medical service billing, to existing data from suicide prevention efforts could facilitate the assessment of longer term outcomes. Our objective was to identify and describe data systems that can be linked to data from studies of youth suicide prevention interventions and to identify analytic approaches to advance youth suicide prevention research., Data Sources: We conducted a systematic review to identify studies of suicide prevention interventions and three types of searches to identify data systems providing suicide-related outcomes: (1) a literature search, (2) an environmental scan of gray literature, and (3) a targeted search, through contact with relevant individuals, in six States, two cities, and one tribal community., Review Methods: Two independent reviewers screened all results. Studies and data systems had to be based in the United States; include individuals between 0 and 25 years of age; and include suicide, suicide attempt, or suicide ideation as an outcome., Results: Of the 47 studies (described in 59 articles) of suicide prevention interventions identified in our systematic review, only 6 studied outcomes by linking to external data systems and only 12 explored treatment heterogeneity through the effects of moderators such as gender or race/ethnicity. We identified 153 unique and potentially linkable external data systems, 66 of which we classified as "fairly accessible" with data dictionaries available., Conclusions: There is potential for linking existing data systems with suicide prevention efforts to assess the broader and extended impact of suicide prevention interventions. However, sparse availability of data dictionaries and lack of adherence to standard data elements limit the potential utility of linking prevention efforts with data systems., Competing Interests: None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report., (This publication is in the public domain.)

Objectives: To assess whether persons with amyotrophic lateral sclerosis (ALS) are at risk of a therapeutic misconception (TM) in which they misconceive research as treatment or overestimate the likelihood of its benefit., Methods: 72 patients with ALS recruited via academic and patient organisations were surveyed using a hypothetical first-in-human intervention study scenario. We elicited their understanding of the purpose of the study ('purpose-of-research question') and then asked how they interpreted the question. We then asked for an estimate of the likelihood that their ALS would improve by participating and asked them to explain the meaning of their estimates., Results: Although 10 of 72 (14%) subjects incorrectly said that the intervention study was 'mostly intending to help [me]' in response to the purpose-of-research question, 7 of those 10 thought that the question was asking them about their own motivations for participating. Overall, only one of 72 respondents (1.4%) both understood the purpose-of-research question as intended and gave the incorrect response. Subjects' mean estimate of likelihood of benefit was 31% (SD 26). This was due to 29 of 72 of respondents providing high estimates (50%-54% likelihood), which they said were expressions of hope and need for a positive attitude; among those who said their estimates meant 'those are the facts' or 'there is a lot of uncertainty', the estimates were much lower (12.6% and 18.5%, respectively)., Conclusions: In this group of patients with ALS considering a hypothetical first-in-human intervention study, apparent TM responses have alternative explanations and the risk of true TM appears low., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Iodine contrast media are essential components of many imaging procedures. An important potential side effect is contrast-induced nephropathy (CIN)., Purpose: To compare CIN risk for contrast media within and between osmolality classes in patients receiving diagnostic or therapeutic imaging procedures., Data Sources: PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Scopus through June 2015., Study Selection: Randomized, controlled trials that reported CIN-related outcomes in patients receiving low-osmolar contrast media (LOCM) or iso-osmolar contrast media for imaging., Data Extraction: Independent study selection and quality assessment by 2 reviewers and dual extraction of study characteristics and results., Data Synthesis: None of the 5 studies that compared types of LOCM reported a statistically significant or clinically important difference among study groups, but the strength of evidence was low. Twenty-five randomized, controlled trials found a slight reduction in CIN risk with the iso-osmolar contrast media agent iodixanol compared with a diverse group of LOCM that just reached statistical significance in a meta-analysis (pooled relative risk, 0.80 [95% CI, 0.65 to 0.99]; P = 0.045). This comparison's strength of evidence was moderate. In a meta regression of randomized, controlled trials of iodixanol, no relationship was found between route of administration and comparative CIN risk., Limitations: Few studies compared LOCM. Procedural details about contrast administration were not uniformly reported. Few studies specified clinical indications or severity of baseline renal impairment., Conclusion: No differences were found in CIN risk among types of LOCM. Iodixanol had a slightly lower risk for CIN than LOCM, but the lower risk did not exceed a criterion for clinical importance., Primary Funding Source: Agency for Healthcare Research and Quality.

Background: Desire for improvement in one's illness and having one's own doctor functioning as a researcher are thought to promote therapeutic misconception (TM), a phenomenon in which research subjects are said to conflate research with treatment., Purpose: To examine whether subjects' therapeutic motivation and own doctor functioning as researcher are associated with TM., Methods: We interviewed 90 persons with advanced Parkinson's disease (PD) enrolled or intending to enrol in sham surgery controlled neurosurgical trials, using qualitative interviews. Subjects were compared by motivation (primarily therapeutic vs primarily altruistic or dually motivated by altruistic and therapeutic motivation), and by doctor status (own doctor as site investigator vs not) on the following: understanding of purpose of study; understanding of research procedures; perception of chance of direct benefit; and recollection and perceptions concerning the risks., Results: 60% had primarily therapeutic motivation and 44% had their own doctor as the site investigator, but neither were generally associated with increased TM responses. Overall level of understanding of purpose and procedures of research were high. Subjects responded with generally high estimates of probability of direct benefit, but their rationales were personal and complex. The therapeutic-motivation group was more sensitive to risks. Five (5.6%) subjects provided incorrect answers to the question about purpose of research, and yet, showed excellent understanding of research procedures., Conclusions: In persons with PD involved in sham surgery clinical trials, being primarily motivated by desire for direct benefit to one's illness or having one's own doctor as the site investigator were not associated with greater TM responses., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Context: A Healthy People 2020 objective is to increase the prevalence of healthy-weight adults in the U.S. A systematic review of the effectiveness and safety of strategies to prevent weight gain in adults was performed., Evidence Acquisition: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, PsycINFO, and ClinicalTrials.gov were searched through June 2012. Two reviewers independently reviewed titles, abstracts, and articles. Trials and observational studies with at least 1 year of follow-up that reported on strategies to prevent weight gain or maintain weight were included. Data were abstracted on weight, adherence, safety, and quality-of-life outcomes. The quantity, quality, and consistency of the evidence were graded, with a focus on studies' risks of bias, consistency of results across studies, how directly the question of interest was addressed, and precision of results. A meaningful difference and a significant threshold (p<0.05) were used to identify effective strategies. Evidence was synthesized qualitatively., Evidence Synthesis: Twenty-two studies (11 trials and 11 observational studies) involving 480,142 participants were included. The strength of evidence is low for all strategies, but effective approaches may include low-fat diets, eating fewer meals prepared away from home, eating more fruits and vegetables, monitoring heart rate during exercise, and participation in group lifestyle sessions with reminder text messages. Safety and quality of life were rarely reported., Conclusions: Although the evidence is not strong, there may be effective strategies to prevent weight gain., (© 2013 American Journal of Preventive Medicine Published by American Journal of Preventive Medicine All rights reserved.)

Objective: To compare the effectiveness of self-management, dietary, physical activity, and/or environmental strategies for the prevention of weight gain among adults in work and college settings., Method: We conducted a systematic review of work/college-based studies that intervened on adults using one or more of the above strategies with follow up over at least a 12-month period. We excluded studies with a weight loss component. Our weight outcomes included body mass index (BMI), weight, and waist circumference., Results: We included 7 work- and 2 college-based interventional studies, which all used combinations of different strategies. There was moderate strength of evidence that work/college-based combination interventions prevented weight gain of ≥0.5kg over 12months as compared to control; however, we were unable to perform meta-analysis due to substantial heterogeneity in the intervention strategies and study populations. These programs did not prevent BMI gain or waist circumference increase., Conclusion: While we found limited evidence that work/college-based interventions employing a combination of strategies prevent adult weight gain, the combination of personalized diet and physical activity counseling for the individual along with the promotion of healthy lifestyle changes in the environment may be a promising strategy to explore in future research., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To systematically review the evidence on the effectiveness of health care and palliative care interventions to improve outcomes for patients with advanced and serious illness., Data Sources: We searched MEDLINE®, CINAHL, PsycINFO, Cochrane, and DARE from 2000 through 2011. We identified additional studies from reference lists of eligible articles and relevant reviews, as well as from technical experts., Review Methods: We developed questions in collaboration with technical experts. We excluded retrospective and uncontrolled studies. Two investigators independently screened search results and abstracted data from eligible studies. We adapted previous frameworks to categorize included studies (e.g., by improvement target, setting). Because many studies did not report effect sizes and almost all studies were small (lt 200 studies), in order to be able to quantitatively describe the literature, we calculated the percentage of studies with a significant improvement in outcomes with the intervention compared to control group for each category. We also checked that all other studies did not report significant results in the opposite direction and checked that there were not differences between larger and smaller studies., Results: We included 90 studies described in 96 articles. Of the 23 studies targeting continuity, coordination, and transitions, 33 percent of studies that evaluated quality of life as an outcome, 67 percent that evaluated patient satisfaction, and 31 percent that evaluated health care utilization (admissions and length of stay) found a statistically significant improvement with the intervention. Of the 21 studies targeting pain, almost all focused on patient education and self-management; 48 percent of them found a statistically significant improvement with the intervention. Findings for larger (>100) and smaller (le 100) studies were similar. For distress, only 29 percent of the seven included studies found a statistically significant impact. Of the 20 studies in communication and decisionmaking, only 22 percent of studies addressing patient or family satisfaction found a statistically significant improvement for this outcome, compared to 73 percent for the outcome of health care utilization. We found only two studies within hospice programs, both of which found a statistically significant improvement in at least one outcome; nine studies were in nursing homes, 78 percent of which demonstrated a significant improvement with the intervention. In terms of types of quality improvement, for the target of continuity, studies including patient-centered quality improvement types, such as education and self-management, had the strongest evidence of effectiveness on patient- and family-centered domains such as satisfaction and quality of life. Studies of provider-focused interventions (e.g., education, reminders) were more likely to have an impact on health care utilization. Only one of five studies addressing multiple targets and focusing on facilitated relay of clinical data to providers demonstrated a statistically significant improvement in either quality of life or satisfaction. In terms of consultative and integrative interventions, for the target of communication and decisionmaking, three-quarters of consultative interventions showed a statistically significant improvement with the intervention, compared to half of integrative interventions. The literature was too heterogeneous and effect sizes were too infrequently reported for quantitative synthesis. There was moderate strength of evidence for the target of continuity, coordination, and transitions and the outcome of patient and caregiver satisfaction but low strength of evidence for other outcomes. For the target of pain, there was moderate strength of evidence for pain as an outcome. For the target of communication and decisionmaking, there was moderate strength of evidence for the outcome of health care utilization but low strength of evidence for other outcomes., Conclusions: We found that evidence was strongest (moderate strength of evidence) for interventions for pain, and for the targets of communication and decisionmaking and continuity for selected outcomes. While a few high- and medium-quality, well-designed health care and palliative care interventions have been conducted to improve outcomes for patients with advanced and serious illness, this report highlights the continued presence of variable findings, quality deficiencies, vaguely defined interventions, and variable outcome measurement tools and reporting in much of this intervention literature. The evidence has a number of gaps, including few studies in the hospice setting or pediatrics. Future research needs include techniques for improving recruitment and retention to assure adequate sample size, better development and description of interventions, and further development and standardization of outcome measures and tools.

Objectives: The main objective of the report is to review the evidence on the impact of health information technology (IT) that supports patient-centered care (PCC) on: health care processes; clinical outcomes; intermediate outcomes (patient or provider satisfaction, health knowledge and behavior, and cost); responsiveness to needs and preferences of patients; shared decisionmaking and patient-clinician communication; and access to information. Additional objectives were to identify barriers and facilitators for using health IT to deliver PCC, and to identify gaps in evidence and information needed by patients, providers, payers, and policymakers., Data Sources: MEDLINE®, Embase®, Cochrane Library, Scopus, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, INSPEC, and Compendex databases through July 31, 2010., Methods: Paired members of our team reviewed citations to identify randomized controlled trials of PCC-related health IT interventions and studies that addressed barriers and facilitators for health IT for delivery of PCC. Independent assessors rated studies for quality. Paired reviewers abstracted data., Results: The search identified 327 eligible articles, including 184 articles on the impact of health IT applications implemented to support PCC and 206 articles addressing barriers or facilitators for such health IT applications. Sixty-three articles addressed both questions. The study results suggested positive effects of PCC-related health IT interventions on health care process outcomes, disease-specific clinical outcomes (for diabetes mellitus, heart disease, cancer, and other health conditions), intermediate outcomes, responsiveness to the needs and preferences of patients, shared decisionmaking, patient-clinician communication, and access to medical information. Studies reported a number of barriers and facilitators for using health IT applications to enable PCC. Barriers included: lack of usability; problems with access to the health IT application due to older age, low income, education, cognitive impairment, and other factors; low computer literacy in patients and clinicians; insufficient basic formal training in health IT applications; physicians' concerns about more work; workflow issues; problems related to new system implementation, including concerns about confidentiality of patient information; depersonalization; incompatibility with current health care practices; lack of standardization; and problems with reimbursement. Facilitators for the utilization of health IT included ease of use, perceived usefulness, efficiency of use, availability of support, comfort in use, and site location., Conclusions: Despite marked heterogeneity in study characteristics and quality, substantial evidence exists confirming that health IT applications with PCC-related components have a positive effect on health care outcomes. positive effect on health care outcomes.

Objectives: To systematically review the evidence on the use of inhaled nitric oxide (iNO) in preterm infants born at or before 34 weeks gestation age who receive respiratory support., Data Sources: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Studies (CENTRAL) and PsycInfo in June 2010. We also searched the proceedings of the 2009 and 2010 Pediatric Academic Societies Meeting and ClinicalTrials.gov. We identified additional studies from reference lists of eligible articles and relevant reviews, as well as from technical experts., Review Methods: Questions were developed in collaboration with technical experts, including the chair of the upcoming National Institutes of Health Office of Medical Applications of Research Consensus Development Conference. We limited our review to randomized controlled trials (RCTs) for the question of survival or occurrence of bronchopulmonary dysplasia (BPD) and for the question on short-term risks. All study designs were considered for long-term pulmonary or neurodevelopmental outcomes, and for questions about whether outcomes varied by subpopulation or by intervention characteristics. Two investigators independently screened search results, and abstracted data from eligible articles., Results: We identified a total of 14 RCTs, reported in 23 articles, and eight observational studies. Mortality rates in the NICU did not differ for infants treated with iNO versus those not treated with iNO (RR 0.97 (95% CI 0.82, 1.15)). BPD at 36 weeks for iNO and control groups also did not differ (RR 0.93 (0.86, 1.003) for survivors). A small difference was found between iNO and control infants in the composite outcome of death or BPD (RR 0.93 (0.87, 0.99)). There was inconsistent evidence about the risk of brain injury from individual RCTs, but meta-analyses showed no difference between iNO and control groups. We found no evidence of differences in other short term risks. There was no evidence to suggest a difference in the incidence of cerebral palsy (RR 1.36 (0.88, 2.10)), neurodevelopmental impairment (RR 0.91 (0.77, 1.12)), or cognitive impairment (RR 0.72 (0.35, 1.45)). Evidence was limited on whether the effect of iNO varies by subpopulation or by characteristics of the therapy (timing, dose and duration, mode of delivery, or concurrent therapies)., Conclusions: There was a seven percent reduction in the risk of the composite outcome of death or BPD at 36 weeks PMA for infants treated with iNO compared to controls, but no reduction in death or BPD alone. Further studies are needed to explore particular subgroups of infants and to assess long term outcomes including function in childhood. There is currently no evidence to support the use of iNO in preterm infants with respiratory failure outside the context of rigorously conducted randomized clinical trials.

Objective: The objective of the report is to review the evidence on the impact of consumer health informatics (CHI) applications on health outcomes, to identify the knowledge gaps and to make recommendations for future research., Data Sources: We searched MEDLINE, EMBASE, The Cochrane Library, Scopus, and CINAHL databases, references in eligible articles and the table of contents of selected journals; and query of experts., Methods: Paired reviewers reviewed citations to identify randomized controlled trials (RCTs) of the impact of CHI applications, and all studies that addressed barriers to use of CHI applications. All studies were independently assessed for quality. All data was abstracted, graded, and reviewed by 2 different reviewers., Results: One hundred forty-six eligible articles were identified including 121 RCTs. Studies were very heterogeous and of variable quality. Four of five asthma care studies found significant positive impact of a CHI application on at least one healthcare process measure. In terms of the impact of CHI on intermediate health outcomes, significant positive impact was demonstrated in at least one intermediate health outcome of; all three identified breast cancer studies, 89 percent of 32 diet, exercise, physical activity, not obesity studies, all 7 alcohol abuse studies, 58 percent of 19 smoking cessation studies, 40 percent of 12 obesity studies, all 7 diabetes studies, 88 percent of 8 mental health studies, 25 percent of 4 asthma/COPD studies, and one of two menopause/HRT utilization studies. Thirteen additional single studies were identified and each found evidence of significant impact of a CHI application on one or more intermediate outcomes. Eight studies evaluated the effect of CHI on the doctor patient relationship. Five of these studies demonstrated significant positive impact of CHI on at least one aspect of the doctor patient relationship. In terms of the impact of CHI on clinical outcomes, significant positive impact was demonstrated in at least one clinical outcome of; one of three breast cancer studies, four of five diet, exercise, or physical activity studies, all seven mental health studies, all three identified diabetes studies. No studies included in this review found any evidence of consumer harm attributable to a CHI application. Evidence was insufficient to determine the economic impact of CHI applications., Conclusions: Despite study heterogeneity, quality variability, and some data paucity, available literature suggests that select CHI applications may effectively engage consumers, enhance traditional clinical interventions, and improve both intermediate and clinical health outcomes.

Objectives: To synthesize the published literature on the efficacy, effectiveness, and toxicity of hydroxyurea (HU) when used for treatment of sickle cell disease (SCD); and to review the evidence regarding barriers to its use., Data Sources: Articles cited in MEDLlNE, EMBASE, TOXLine, and CINAHL through June 30, 2007., Review Methods: Paired reviewers reviewed each title, abstract, and article to assess eligibility. They abstracted data sequentially and then independently graded the evidence., Results: In one small, randomized trial of HU in children with SCD; the yearly hospitalization rate was lower with HU than placebo (1.1 versus 2.8, p=0.002). The absolute increase in fetal hemoglobin (Hb F%) was 10.7 percent. Twenty observational studies of HU in children reported similar increases in Hb F%, while hemoglobin concentration increased by roughly 1 g/dl. One large randomized trial tested the efficacy of HU in adults with SCD and found that after 2 years of treatment, Hb F% increased by 3.2 percent and hemoglobin increased by 0.6 g/dl, The median number of painful crises was 44 percent (p<0.001) lower among patients treated with HU. The 12 observational studies of HU enrolling adults with SCD supported these findings. Panelists from the Center for the Evaluation of Risks to Human Reproduction reviewed the literature for potential toxicities of HU. They concluded that HU does not cause a growth delay in children 5-15 years old. There were no data on the effects on subsequent generations following exposure of developing germ cells to HU in utero. Some evidence supported impaired spermatogenesis with use of HU. Although we identified six patients taking HU who developed leukemia, the evidence did not support causality. Similarly, the evidence suggested no association between HU and leg ulcers in patients with SCD, although there was in patients with other illnesses. The literature supported neutropenia, skin rashes and nail changes associated with use of HU, but was sparse regarding skin neoplasms or other secondary malignancies in SCD. Only two studies investigated barriers to use of HU. Perceived efficacy and perceived safety of HU had the largest influence on patients' (or parents' ) choice to use HU. Providers reported barriers to be patient concerns about side effects; and their own concerns about HU in older patients, patient compliance, lack of contraception, side effects and carcinogenic potential, doubts about effectiveness, and concern about costs., Conclusions: HU is efficacious in children and adults with SCD; with an increase in Hb F%, and reduction in hospitalizations and pain crises. However, few studies have measured the effectiveness of HU for SCD in usual practice. The paucity of long-term studies limits conclusions about toxicities and about mortality. Future studies of interventions to overcome the barriers to use of HU in patients with SCD are necessary.

Objectives: To assess the evidence that three marketed gene expression-based assays improve prognostic accuracy, treatment choice, and health outcomes in women diagnosed with early stage breast cancer., Review Methods: We evaluated the evidence for three gene expression assays on the market; Oncotype DX, MammaPrint and the Breast Cancer Profiling (BCP or H/I ratio) test, and for gene expression signatures underlying the assays. We sought evidence on: analytic performance of tests, clinical validity (i.e., prognostic accuracy and discrimination), clinical utility (i.e., prediction of treatment benefit), harms, impact on clinical decision making and health care costs., Results: Few papers were found on the analytic validity of the Oncotype DX and MammaPrint tests, but these showed reasonable within-laboratory replicability. Pre-analytic issues related to sample storage and preparation may play a larger role than within-laboratory variation. For clinical validity, studies differed according to whether they examined the actual test that is currently being offered to patients or the underlying gene signature. Almost all of the Oncotype DX evidence was for the marketed test, the strongest validation study being from one arm of a randomized controlled trial (NSABP-14) with a clinically homogeneous population. This study showed that the test, added in a clinically meaningful manner to standard prognostic indices. The MammaPrint signature and test itself was examined in studies with clinically heterogeneous populations (e.g., mix of ER positivity and tamoxifen treatment) and showed a clinically relevant separation of patients into risk categories, but it was not clear exactly how many predictions would be shifted across decision thresholds if this were used in combination with traditional indices. The BCP test itself was examined in one study, and the signature was tested in a variety of formulations in several studies. One randomized controlled trial provided high quality retrospective evidence of the clinical utility of Oncotype DX to predict chemotherapy treatment benefit, but evidence for clinical utility was not found for MammaPrint or the H/I ratio. Three decision analyses examined the cost-effectiveness of breast cancer gene expression assays, and overall were inconclusive., Conclusions: Oncotype DX is furthest along the validation pathway, with strong retrospective evidence that it predicts distant spread and chemotherapy benefit to a clinically relevant extent over standard predictors, in a well-defined clinical subgroup with clear treatment implications. The evidence for clinical implications of using MammaPrint was not as clear as with Oncotype DX, and the ability to predict chemotherapy benefit does not yet exist. The H/I ratio test requires further validation. For all tests, the relationship of predicted to observed risk in different populations still needs further study, as does their incremental contribution, optimal implementation, and relevance to patients on current therapies.

Objectives: To review and synthesize published literature on the efficacy of multivitamin/mineral supplements and certain single nutrient supplements in the primary prevention of chronic disease in the general adult population, and on the safety of multivitamin/mineral supplements and certain single nutrient supplements, likely to be included in multivitamin/mineral supplements, in the general population of adults and children., Data Sources: All articles published through February 28, 2006, on MEDLINE, EMBASE, and the Cochrane databases., Review Methods: Each article underwent double reviews on title, abstract, and inclusion eligibility. Two reviewers performed data abstraction and quality assessment. Differences in opinion were resolved through consensus adjudication., Results: Few trials have addressed the efficacy of multivitamin/mineral supplement use in chronic disease prevention in the general population of the United States. One trial on poorly nourished Chinese showed supplementation with combined Beta-carotene, vitamin E and selenium reduced gastric cancer incidence and mortality, and overall cancer mortality. In a French trial, combined vitamin C, vitamin E, Beta-carotene, selenium, and zinc reduced cancer risk in men but not in women. No cardiovascular benefit was evident in both trials. Multivitamin/mineral supplement use had no benefit for preventing cataract. Zinc/antioxidants had benefits for preventing advanced age-related macular degeneration in persons at high risk for the disease. With few exceptions, neither Beta-carotene nor vitamin E had benefits for preventing cancer, cardiovascular disease, cataract, and age-related macular degeneration. Beta-carotene supplementation increased lung cancer risk in smokers and persons exposed to asbestos. Folic acid alone or combined with vitamin B12 and/or vitamin B6 had no significant effects on cognitive function. Selenium may confer benefit for cancer prevention but not cardiovascular disease prevention. Calcium may prevent bone mineral density loss in postmenopausal women, and may reduce vertebral fractures, but not non-vertebral fractures. The evidence suggests dose-dependent benefits of vitamin D with/without calcium for retaining bone mineral density and preventing hip fracture, non-vertebral fracture and falls. We found no consistent pattern of increased adverse effects of multivitamin/mineral supplements except for skin yellowing by Beta-carotene., Conclusions: Multivitamin/mineral supplement use may prevent cancer in individuals with poor or suboptimal nutritional status. The heterogeneity in the study populations limits generalization to United States population. Multivitamin/mineral supplements conferred no benefit in preventing cardiovascular disease or cataract, and may prevent advanced age-related macular degeneration only in high-risk individuals. The overall quality and quantity of the literature on the safety of multivitamin/mineral supplements is limited.

Objectives: To systematically review evidence on definitions of the periodic health evaluation (PHE), its associated benefits and harms, and system-level interventions to improve its delivery., Data Sources: Electronic searches in MEDLINE, and other databases; hand searching of 24 journals and bibliographies through February 2006., Review Methods: Paired investigators abstracted data and judged study quality using standard criteria. We reported effect sizes for mean differences and proportions in randomized controlled trials (RCTs). We adapted GRADE Working Group criteria to assess quantity, quality and consistency of the best evidence pertaining to each outcome, assigning grades of "high," "medium," "low," or "very low.", Results: Among 36 identified studies (11 RCTs), definitions of the PHE varied widely. In studies assessing benefits, the PHE consistently improved (over usual care) the delivery/receipt of the gynecological exam/Pap smear (2 RCTs, small effect (Cohen's d (95% confidence interval (CI)):0.07 (0.07,0.07)) to large effect (Cohen's d (CI):1.71 (1.69, 1.73)), strength and consistency graded "high"); cholesterol screening (1 RCT, small effect (Cohen's d (CI):0.02 (0.00,0.04)) with large associations in 4 observational studies, graded "medium"); fecal occult blood testing (2 RCTs, large effects (Cohen's d (CI): 1.19 (1.17, 1.21) and 1.07 (1.05, 1.08)), graded "high"). Effects of the PHE were mixed among studies assessing delivery/receipt of counseling (graded "low"), immunizations (graded "medium"), and mammography (graded "low"). In one RCT, the PHE led to a smaller increase in patient "worry" (13%) compared to usual care (23%) (graded "medium"). The PHE had mixed effects on serum cholesterol (graded "low"), blood pressure, body mass index, disease detection, health habits and health status (graded "medium"), hospitalization (graded "high"), and costs, disability, and mortality (graded "medium"). No studies assessed harms. Delivery of the PHE was improved by scheduling of appointments for PHE (1 RCT, medium effects (Cohen's d (CI): 0.69 (0.68, 0.70)) and offering a free PHE (1 non-RCT, 22% increase) (graded "medium")., Conclusions: The evidence suggests delivery of some recommended preventive services are improved by the PHE and may be more directly affected by the PHE than intermediate or long-term clinical outcomes and costs. Descriptions of the PHE and outcomes were heterogeneous, and some trials were performed before dissemination of recommendations by the U.S. Preventive Services Task Force, limiting interpretations of findings. Efforts are needed to clarify the long-term benefits of receiving multiple preventive services in the context of the PHE. Future studies assessing the PHE should incorporate diverse populations, carefully define comparisons to "usual care," and comprehensively assess intermediate outcomes, harms, and costs.