Eligibility Rates among Racially and Ethnically Diverse US Participants in Phase 2 and Phase 3 Placebo-Controlled, Double-Blind, Randomized Trials of Lecanemab and Elenbecestat in Early Alzheimer Disease.

OBJECTIVE: Many factors contribute to inadequate diversity in Alzheimer disease (AD) clinical trials. We evaluated eligibility rates among racial and ethnic groups at US sites in large global multisite trials in early AD. METHODS: Using screening data from 4 randomized, double-blind, placebo-controlled clinical trials in early AD, we assessed rates of eligibility among racial and ethnic groups controlling for other demographic covariates. Each trial incorporated positron emission tomography and/or cerebrospinal fluid to evaluate brain amyloid pathology, as well as typical eligibility criteria used in early AD trials. RESULTS: Across the trials, 10,804 US participants were screened: 193 (2%) were of Hispanic ethnicity and Black race, 2,624 (25%) were of Hispanic ethnicity and White race, 118 (1%) were of non-Hispanic ethnicity (NH) and Asian race, 696 (7%) were of NH ethnicity and Black race, and 7,017 (65%) were of NH ethnicity and White race. Data from 156 participants who did not fit into these categories were excluded. Accounting for age, sex, and trial and using NH White participants as a reference group, we observed higher probabilities of ineligibility for amyloid biomarker criteria among Hispanic Black (odds ratio [OR] = 3.20, 95% confidence interval [CI] = 2.11-4.88), Hispanic White (OR = 4.15, 95% CI = 3.58-4.83), NH Asian (OR = 2.35, 95% CI = 1.23-4.55), and NH Black (OR = 3.75, 95% CI = 2.80-5.06) participants. INTERPRETATION: Differential eligibility may contribute to underrepresentation of some minoritized racial and ethnic groups in early AD trials. Amyloid biomarker eligibility is a requirement to confirm the diagnosis of AD and for treatment with amyloid-lowering drugs and differed among racial and ethnic groups. ANN NEUROL 2024;95:288-298.

A digitally driven manufacturing process for high resolution patterning of cell formations.

This paper presents the engineering and validation of an enabling technology that facilitates new capabilities in in vitro cell models for high-throughput screening and tissue engineering applications. This is conducted through a computerized system that allows the design and deposition of high-fidelity microscale patterned coatings that selectively alter the chemical and topographical properties of cell culturing surfaces. Significantly, compared to alternative methods for microscale surface patterning, this is a digitally controlled and automated process thereby allowing scientists to rapidly create and explore an almost infinite range of cell culture patterns. This new capability is experimentally validated across six different cell lines demonstrating how the precise microscale deposition of these patterned coatings can influence spatiotemporal growth and movement of endothelial, fibroblast, neuronal and macrophage cells. To further demonstrate this platform, more complex patterns are then created and shown to guide the behavioral response of colorectal carcinoma cells.

To Expand the Evidence Base About Harms from Tests and Treatments.

Rigorous evidence about the broad range of harms that might be experienced by a patient in the course of testing and treatment is sparse. We aimed to generate recommendations for how researchers might more comprehensively evaluate potential harms of healthcare interventions, to allow clinicians and patients to better include this evidence in clinical decision-making. We propose seven domains of harms of tests and treatments that are relevant to patients: (1) physical impairment, (2) psychological distress, (3) social disruption, (4) disruption in connection to healthcare, (5) labeling, (6) financial impact, and (7) treatment burden. These domains will include a range of severity of harms and variation in timing after testing or treatment, attributable to the service itself or a resulting care cascade. Although some new measures may be needed, diverse data and tools are available to allow the assessment of harms comprehensively across these domains. We encourage researchers to evaluate harms in sub-populations, since the harms experienced may differ importantly by demographics, social determinants, presence of comorbid illness, psychological state, and other characteristics. Regulators, funders, and editors might require either assessment or reporting of harms in each domain or require justification for inclusion and exclusion of different domains.

Screening for Prediabetes and Type 2 Diabetes: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Type 2 diabetes is common and is a leading cause of morbidity and disability. Objective: To review the evidence on screening for prediabetes and diabetes to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through September 2019; references; and experts; literature surveillance through May 21, 2021. Study Selection: English-language controlled studies evaluating screening or interventions for prediabetes or diabetes that was screen detected or recently diagnosed. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when at least 3 similar studies were available. Main Outcomes and Measures: Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. Results: The review included 89 publications (N = 68 882). Two randomized clinical trials (RCTs) (25 120 participants) found no significant difference between screening and control groups for all-cause or cause-specific mortality at 10 years. For harms (eg, anxiety or worry), the trials reported no significant differences between screening and control groups. For recently diagnosed (not screen-detected) diabetes, 5 RCTs (5138 participants) were included. In the UK Prospective Diabetes Study, health outcomes were improved with intensive glucose control with sulfonylureas or insulin. For example, for all-cause mortality the relative risk (RR) was 0.87 (95% CI, 0.79 to 0.96) over 20 years (10-year posttrial assessment). For overweight persons, intensive glucose control with metformin improved health outcomes at the 10-year follow-up (eg, all-cause mortality: RR, 0.64 [95% CI, 0.45 to 0.91]), and benefits were maintained longer term. Lifestyle interventions (most involving >360 minutes) for obese or overweight persons with prediabetes were associated with reductions in the incidence of diabetes (23 RCTs; pooled RR, 0.78 [95% CI, 0.69 to 0.88]). Lifestyle interventions were also associated with improved intermediate outcomes, such as reduced weight, body mass index, systolic blood pressure, and diastolic blood pressure (pooled weighted mean difference, -1.7 mm Hg [95% CI, -2.6 to -0.8] and -1.2 mm Hg [95% CI, -2.0 to -0.4], respectively). Metformin was associated with a significant reduction in diabetes incidence (pooled RR, 0.73 [95% CI, 0.64 to 0.83]) and reduction in weight and body mass index. Conclusions and Relevance: Trials of screening for diabetes found no significant mortality benefit but had insufficient data to assess other health outcomes; evidence on harms of screening was limited. For persons with recently diagnosed (not screen-detected) diabetes, interventions improved health outcomes; for obese or overweight persons with prediabetes, interventions were associated with reduced incidence of diabetes and improvement in other intermediate outcomes.

Screening for Lung Cancer With Low-Dose Computed Tomography: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Lung cancer is the leading cause of cancer-related death in the US. Objective: To review the evidence on screening for lung cancer with low-dose computed tomography (LDCT) to inform the US Preventive Services Task Force (USPSTF). Data Sources: MEDLINE, Cochrane Library, and trial registries through May 2019; references; experts; and literature surveillance through November 20, 2020. Study Selection: English-language studies of screening with LDCT, accuracy of LDCT, risk prediction models, or treatment for early-stage lung cancer. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Data were not pooled because of heterogeneity of populations and screening protocols. Main Outcomes and Measures: Lung cancer incidence, lung cancer mortality, all-cause mortality, test accuracy, and harms. Results: This review included 223 publications. Seven randomized clinical trials (RCTs) (N = 86 486) evaluated lung cancer screening with LDCT; the National Lung Screening Trial (NLST, N = 53 454) and Nederlands-Leuvens Longkanker Screenings Onderzoek (NELSON, N = 15 792) were the largest RCTs. Participants were more likely to benefit than the US screening-eligible population (eg, based on life expectancy). The NLST found a reduction in lung cancer mortality (incidence rate ratio [IRR], 0.85 [95% CI, 0.75-0.96]; number needed to screen [NNS] to prevent 1 lung cancer death, 323 over 6.5 years of follow-up) with 3 rounds of annual LDCT screening compared with chest radiograph for high-risk current and former smokers aged 55 to 74 years. NELSON found a reduction in lung cancer mortality (IRR, 0.75 [95% CI, 0.61-0.90]; NNS to prevent 1 lung cancer death of 130 over 10 years of follow-up) with 4 rounds of LDCT screening with increasing intervals compared with no screening for high-risk current and former smokers aged 50 to 74 years. Harms of screening included radiation-induced cancer, false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, and increases in distress. For every 1000 persons screened in the NLST, false-positive results led to 17 invasive procedures (number needed to harm, 59) and fewer than 1 person having a major complication. Overdiagnosis estimates varied greatly (0%-67% chance that a lung cancer was overdiagnosed). Incidental findings were common, and estimates varied widely (4.4%-40.7% of persons screened). Conclusions and Relevance: Screening high-risk persons with LDCT can reduce lung cancer mortality but also causes false-positive results leading to unnecessary tests and invasive procedures, overdiagnosis, incidental findings, increases in distress, and, rarely, radiation-induced cancers. Most studies reviewed did not use current nodule evaluation protocols, which might reduce false-positive results and invasive procedures for false-positive results.

Invited Commentary: Beyond Overdiagnosis-Diagnosis Without Benefit.

In an accompanying article, Hofmann (Am J Epidemiol. 2019;188(10):1812-1817) seeks to clarify the concept of overdiagnosis by screening. He makes a helpful suggestion to reconnect diagnosis with patient suffering, pointing out the underlying issue in overdiagnosis of prognostic uncertainty. He then divides prognostic uncertainty into developmental and progression uncertainty, using a categorical model of disease progression through indicators to manifest disease. This model could be improved by considering the heterogeneity of patient-condition combinations. This leads to an understanding of the probabilistic nature of the connection between any indicator in a specific individual and patient suffering. The model also needs to consider the time span over which the patient-condition combination leads to patient suffering. I propose a simpler approach that goes further to focus not only on overdiagnosis but also on the broader problem of diagnosis without benefit and diagnosis without net benefit. This makes measurement easier and focuses attention where it belongs: on the harm caused by overly aggressive screening programs.

Management of Acute and Recurrent Gout: A Clinical Practice Guideline From the American College of Physicians.

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of gout. Methods: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials; systematic reviews; and large observational studies published between January 2010 and March 2016. Clinical outcomes evaluated included pain, joint swelling and tenderness, activities of daily living, patient global assessment, recurrence, intermediate outcomes of serum urate levels, and harms. Target Audience and Patient Population: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute or recurrent gout. Recommendation 1: ACP recommends that clinicians choose corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or colchicine to treat patients with acute gout. (Grade: strong recommendation, high-quality evidence). Recommendation 2: ACP recommends that clinicians use low-dose colchicine when using colchicine to treat acute gout. (Grade: strong recommendation, moderate-quality evidence). Recommendation 3: ACP recommends against initiating long-term urate-lowering therapy in most patients after a first gout attack or in patients with infrequent attacks. (Grade: strong recommendation, moderate-quality evidence). Recommendation 4: ACP recommends that clinicians discuss benefits, harms, costs, and individual preferences with patients before initiating urate-lowering therapy, including concomitant prophylaxis, in patients with recurrent gout attacks. (Grade: strong recommendation, moderate-quality evidence).

Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians.

Description: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on noninvasive treatment of low back pain. Methods: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials and systematic reviews published through April 2015 on noninvasive pharmacologic and nonpharmacologic treatments for low back pain. Updated searches were performed through November 2016. Clinical outcomes evaluated included reduction or elimination of low back pain, improvement in back-specific and overall function, improvement in health-related quality of life, reduction in work disability and return to work, global improvement, number of back pain episodes or time between episodes, patient satisfaction, and adverse effects. Target Audience and Patient Population: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute, subacute, or chronic low back pain. Recommendation 1: Given that most patients with acute or subacute low back pain improve over time regardless of treatment, clinicians and patients should select nonpharmacologic treatment with superficial heat (moderate-quality evidence), massage, acupuncture, or spinal manipulation (low-quality evidence). If pharmacologic treatment is desired, clinicians and patients should select nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants (moderate-quality evidence). (Grade: strong recommendation). Recommendation 2: For patients with chronic low back pain, clinicians and patients should initially select nonpharmacologic treatment with exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction (moderate-quality evidence), tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, low-level laser therapy, operant therapy, cognitive behavioral therapy, or spinal manipulation (low-quality evidence). (Grade: strong recommendation). Recommendation 3: In patients with chronic low back pain who have had an inadequate response to nonpharmacologic therapy, clinicians and patients should consider pharmacologic treatment with nonsteroidal anti-inflammatory drugs as first-line therapy, or tramadol or duloxetine as second-line therapy. Clinicians should only consider opioids as an option in patients who have failed the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients. (Grade: weak recommendation, moderate-quality evidence).

Treatment of Low Bone Density or Osteoporosis to Prevent Fractures in Men and Women: A Clinical Practice Guideline Update From the American College of Physicians.

Description: This guideline updates the 2008 American College of Physicians (ACP) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women. This guideline is endorsed by the American Academy of Family Physicians. Methods: The ACP Clinical Guidelines Committee based these recommendations on a systematic review of randomized controlled trials; systematic reviews; large observational studies (for adverse events); and case reports (for rare events) that were published between 2 January 2005 and 3 June 2011. The review was updated to July 2016 by using a machine-learning method, and a limited update to October 2016 was done. Clinical outcomes evaluated were fractures and adverse events. This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density, including pharmaceutical prescriptions, calcium, vitamin D, and estrogen. Evidence was graded according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Target Audience and Patient Population: The target audience for this guideline includes all clinicians. The target patient population includes men and women with low bone density and osteoporosis. Recommendation 1: ACP recommends that clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis. (Grade: strong recommendation; high-quality evidence). Recommendation 2: ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. (Grade: weak recommendation; low-quality evidence). Recommendation 3: ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinically recognized osteoporosis. (Grade: weak recommendation; low-quality evidence). Recommendation 4: ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women. (Grade: weak recommendation; low-quality evidence). Recommendation 5: ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women. (Grade: strong recommendation; moderate-quality evidence). Recommendation 6: ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. (Grade: weak recommendation; low-quality evidence).

A pre-post study testing a lung cancer screening decision aid in primary care.

BACKGROUND: The United States Preventive Services Task Force (USPSTF) issued recommendations for older, heavy lifetime smokers to complete annual low-dose computed tomography (LDCT) scans of the chest as screening for lung cancer. The USPSTF recommends and the Centers for Medicare and Medicaid Services require shared decision making using a decision aid for lung cancer screening with annual LDCT. Little is known about how decision aids affect screening knowledge, preferences, and behavior. Thus, we tested a lung cancer screening decision aid video in screening-eligible primary care patients. METHODS: We conducted a single-group study with surveys before and after decision aid viewing and medical record review at 3 months. Participants were active patients of a large US academic primary care practice who were current or former smokers, ages 55-80 years, and eligible for screening based on current screening guidelines. Outcomes assessed pre-post decision aid viewing were screening-related knowledge score (9 items about screening-related harms of false positives and overdiagnosis, likelihood of benefit; score range = 0-9) and preference (preferred screening vs. not). Screening behavior measures, assessed via chart review, included provider visits, screening discussion, LDCT ordering, and LDCT completion within 3 months. RESULTS: Among 50 participants, knowledge increased from pre- to post-decision aid viewing (mean = 2.6 vs. 5.5, difference = 2.8; 95% CI 2.1, 3.6, p < 0.001). Preferences across the overall sample remained similar such that 54% preferred screening at baseline and 50% after viewing; however, 28% of participants changed their preference (to or away from screening) from baseline to after viewing. We assessed screening behavior for 36 participants who had a primary care visit during the 3-month period following enrollment. Eighteen of 36 preferred screening after decision aid viewing. Of these 18, 10 discussed screening, 8 had a test ordered, and 6 completed LDCT. Among the 18 who preferred no screening, 7 discussed screening, 5 had a test ordered, and 4 completed LDCT. CONCLUSIONS: In primary care patients, a lung cancer screening decision aid improved knowledge regarding screening-related benefits and harms. Screening preferences and behavior were heterogeneous. TRIAL REGISTRATION: This study is registered at www.clinicaltrials.gov . NCT03077230 (registered retrospectively,November 22, 2016).

Design of a randomized clinical trial of a colorectal cancer screening decision aid to promote appropriate screening in community-dwelling older adults.

BACKGROUND: Appropriate colorectal cancer screening in older adults should be aligned with the likelihood of net benefit. In general, patient decision aids improve knowledge and values clarity, but in older adults, they may also help patients identify their individual likelihood of benefit and foster individualized decision-making. We report on the design of a randomized clinical trial to understand the effects of a patient decision aid on appropriate colorectal cancer screening. This report includes a description of the baseline characteristics of participants. METHODS: English-speaking primary care patients aged 70-84 years who were not currently up to date with screening were recruited into a randomized clinical trial comparing a tailored colorectal cancer screening decision aid with an attention control. The intervention group received a decision aid that included a values clarification exercise and individualized decision-making worksheet, while the control group received an educational pamphlet on safe driving behaviors. The primary outcome was appropriate screening at 6 months based on chart review. We used a composite measure to define appropriate screening as screening for participants in good health, a discussion about screening for patients in intermediate health, and no screening for patients in poor health. Health state was objectively determined using patients' Charlson Comorbidity Index score and age. RESULTS: A total of 14 practices in central North Carolina participated as part of a practice-based research network. In total, 424 patients were recruited to participate and completed a baseline visit. Overall, 79% of participants were White and 58% female, with a mean age of 76.8 years. Patient characteristics between groups were similar by age, gender, race, education, insurance coverage, or work status. Overall, 70% had some college education or more, 57% were married, and virtually all had Medicare insurance (90%). The three primary medical conditions among the cohort were a history of diabetes, pneumonia, and cancer (28%, 26%, and 21%, respectively). CONCLUSION: We designed a randomized clinical trial to test a novel use of a patient decision aid to promote appropriate colorectal cancer screening and have recruited a diverse study population that seems similar between the intervention and control groups. The study should be able to determine the ability of a patient decision aid to increase individualized and appropriate colorectal cancer screening.

Screening for Obstructive Sleep Apnea in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Many adverse health outcomes are associated with obstructive sleep apnea (OSA). Objective: To review primary care-relevant evidence on screening adults for OSA, test accuracy, and treatment of OSA, to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through October 2015, references, and experts, with surveillance of the literature through October 5, 2016. Study Selection: English-language randomized clinical trials (RCTs); studies evaluating accuracy of screening questionnaires or prediction tools, diagnostic accuracy of portable monitors, or association between apnea-hypopnea index (AHI) and health outcomes among community-based participants. Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles. When multiple similar studies were available, random-effects meta-analyses were conducted. Main Outcomes and Measures: Sensitivity, specificity, area under the curve (AUC), AHI, Epworth Sleepiness Scale (ESS) scores, blood pressure, mortality, cardiovascular events, motor vehicle crashes, quality of life, and harms. Results: A total of 110 studies were included (N = 46 188). No RCTs compared screening with no screening. In 2 studies (n = 702), the screening accuracy of the multivariable apnea prediction score followed by home portable monitor testing for detecting severe OSA syndrome (AHI ≥30 and ESS score >10) was AUC 0.80 (95% CI, 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90), respectively, but the studies oversampled high-risk participants and those with OSA and OSA syndrome. No studies prospectively evaluated screening tools to report calibration or clinical utility for improving health outcomes. Meta-analysis found that continuous positive airway pressure (CPAP) compared with sham was significantly associated with reduction of AHI (weighted mean difference [WMD], -33.8 [95% CI, -42.0 to -25.6]; 13 trials, 543 participants), excessive sleepiness assessed by ESS score (WMD, -2.0 [95% CI, -2.6 to -1.4]; 22 trials, 2721 participants), diurnal systolic blood pressure (WMD, -2.4 points [95% CI, -3.9 to -0.9]; 15 trials, 1190 participants), and diurnal diastolic blood pressure (WMD, -1.3 points [95% CI, -2.2 to -0.4]; 15 trials, 1190 participants). CPAP was associated with modest improvement in sleep-related quality of life (Cohen d, 0.28 [95% CI, 0.14 to 0.42]; 13 trials, 2325 participants). Mandibular advancement devices (MADs) and weight loss programs were also associated with reduced AHI and excessive sleepiness. Common adverse effects of CPAP and MADs included oral or nasal dryness, irritation, and pain, among others. In cohort studies, there was a consistent association between AHI and all-cause mortality. Conclusions and Relevance: There is uncertainty about the accuracy or clinical utility of all potential screening tools. Multiple treatments for OSA reduce AHI, ESS scores, and blood pressure. Trials of CPAP and other treatments have not established whether treatment reduces mortality or improves most other health outcomes, except for modest improvement in sleep-related quality of life.

3D printed fluidics with embedded analytic functionality for automated reaction optimisation.

Additive manufacturing or '3D printing' is being developed as a novel manufacturing process for the production of bespoke micro- and milliscale fluidic devices. When coupled with online monitoring and optimisation software, this offers an advanced, customised method for performing automated chemical synthesis. This paper reports the use of two additive manufacturing processes, stereolithography and selective laser melting, to create multifunctional fluidic devices with embedded reaction monitoring capability. The selectively laser melted parts are the first published examples of multifunctional 3D printed metal fluidic devices. These devices allow high temperature and pressure chemistry to be performed in solvent systems destructive to the majority of devices manufactured via stereolithography, polymer jetting and fused deposition modelling processes previously utilised for this application. These devices were integrated with commercially available flow chemistry, chromatographic and spectroscopic analysis equipment, allowing automated online and inline optimisation of the reaction medium. This set-up allowed the optimisation of two reactions, a ketone functional group interconversion and a fused polycyclic heterocycle formation, via spectroscopic and chromatographic analysis.

A value framework for cancer screening: advice for high-value care from the American College of Physicians.

Experts, professional societies, and consumer groups often recommend different strategies for cancer screening. These strategies vary in the intensity of their search for asymptomatic lesions and in their value. This article outlines a framework for thinking about the value of varying intensities of cancer screening. The authors conclude that increasing intensity beyond an optimal level leads to low-value screening and speculate about pressures that encourage overly intensive, low-value screening.

Screening for cancer: advice for high-value care from the American College of Physicians.

BACKGROUND: Cancer screening is one approach to reducing cancer-related morbidity and mortality rates. Screening strategies vary in intensity. Higher-intensity strategies are not necessarily higher value. High-value strategies provide a degree of benefits that clearly justifies the harms and costs incurred; low-value screening provides limited or no benefits to justify the harms and costs. When cancer screening leads to benefits, an optimal intensity of screening maximizes value. Some aspects of screening practices, especially overuse and underuse, are low value. METHODS: Screening strategies for asymptomatic, average-risk adults for 5 common types of cancer were evaluated by reviewing clinical guidelines and evidence syntheses from the American College of Physicians (ACP), U.S. Preventive Services Task Force, American Academy of Family Physicians, American Cancer Society, American Congress of Obstetricians and Gynecologists, American Gastroenterological Association, and American Urological Association. "High value" was defined as the lowest screening intensity threshold at which organizations agree about screening recommendations for each type of cancer and "low value" as agreement about not recommending overly intensive screening strategies. This information is supplemented with additional findings from randomized, controlled trials; modeling studies; and studies of costs or resource use, including information found in the National Cancer Institute's Physician Data Query and UpToDate. The ACP provides high-value care screening advice for 5 common types of cancer; the specifics are outlined in this article. The ACP strongly encourages clinicians to adopt a cancer screening strategy that focuses on reaching all eligible persons with these high-value screening options while reducing overly intensive, low-value screening.

Serologic Screening for Genital Herpes: An Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Genital herpes simplex virus (HSV) infection is a prevalent sexually transmitted infection. Vertical transmission of HSV can lead to fetal morbidity and mortality. Objective: To assess the evidence on serologic screening and preventive interventions for genital HSV infection in asymptomatic adults and adolescents to support the US Preventive Services Task Force for an updated recommendation statement. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through March 31, 2016. Surveillance for new evidence in targeted publications was conducted through October 31, 2016. Study Selection: English-language randomized clinical trials (RCTs) comparing screening with no screening in persons without past or current symptoms of genital herpes; studies evaluating accuracy and harms of serologic screening tests for HSV-2; RCTs assessing preventive interventions in asymptomatic persons seropositive for HSV-2. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; pooled sensitivities and specificities of screening tests using a hierarchical summary receiver operating characteristic curve analysis when at least 3 similar studies were available. Main Outcomes and Measures: Accuracy of screening tests, benefits of screening, harms of screening, reduction in genital herpes outbreaks. Results: A total of 17 studies (n = 9736 participants; range, 24-3290) in 19 publications were included. No RCTs compared screening with no screening. Most studies of the accuracy of screening tests were from populations with high HSV-2 prevalence (greater than 40% based on Western blot). Pooled estimates of sensitivity and specificity of the most commonly used test at the manufacturer's cutpoint were 99% (95% CI, 97%-100%) and 81% (95% CI, 68%-90%), respectively (10 studies; n = 6537). At higher cutpoints, pooled estimates were 95% (95% CI, 91%-97%) and 89% (95% CI, 82%-93%), respectively (7 studies; n = 5516). Use of this test at the manufacturer's cutpoint in a population of 100 000 with a prevalence of HSV-2 of 16% (the seroprevalence in US adults with unknown symptom status) would result in 15 840 true-positive results and 15 960 false-positive results (positive predictive value, 50%). Serologic screening for genital herpes was associated with psychosocial harms, including distress and anxiety related to positive test results. Four RCTs compared preventive medications with placebo, 2 in nonpregnant asymptomatic adults who were HSV-2 seropositive and 2 in HSV-2-serodiscordant couples. Results in both populations were heterogeneous and inconsistent. Conclusions and Relevance: Serologic screening for genital herpes is associated with a high rate of false-positive test results and potential psychosocial harms. Evidence from RCTs does not establish whether preventive antiviral medication for asymptomatic HSV-2 infection has benefit.

Adult Patients' Perspectives on the Benefits and Harms of Overused Screening Tests: a Qualitative Study.

BACKGROUND: In recent years, there has been a growing interest in reducing the overuse of healthcare services. However, little is known about how patients conceptualize the benefits and harms of overused screening tests or how patients make decisions regarding these tests. OBJECTIVE: To determine how patients think about the harms and benefits of overused screening tests and how they consider these and other factors when making decisions. DESIGN: Semi-structured, qualitative interviews. PARTICIPANTS: The study comprised 50 patients, ages 50-84, who had previously received or not received any of four overused screening services: 1) prostate cancer screening (men ages 50-69), 2) colon cancer screening (men and women ages 76-85), 3) osteoporosis screening (low-risk women ages 50-64), or 4) cardiovascular disease screening (low-risk men and women ages 50-85). APPROACH: We conducted a thematic analysis, using a hybrid inductive-deductive approach. Two independent coders analyzed interview transcriptions to identify themes and exemplifying quotes. KEY RESULTS: Many patients could not name a harm of screening. When they did name harms, patients often focused on only the harms of the screening test itself and rarely mentioned harms further along the screening cascade (e.g., from follow-up testing and treatment). In contrast, patients could easily name benefits of screening, although many seemed to misunderstand or overestimate the magnitude of the benefits. Furthermore, patients described many additional factors they considered when making screening decisions, including their clinicians' recommendations, their age, family or friends' experiences with disease, and insurance coverage. CONCLUSIONS: This study highlights the need to help adults recognize and understand the benefits and harms of screening and make appropriate decisions about overused screening tests.

The psychological harms of screening: the evidence we have versus the evidence we need.

BACKGROUND: Systematic reviews for the US Preventive Services Task Force have found less high-quality evidence on psychological than physical harms of screening. To understand the extent of evidence on psychological harms, we developed an evidence map that quantifies the distribution of evidence on psychological harms for five adult screening services. We also note gaps in the literature and make recommendations for future research. METHODS: We systematically searched PubMed, PsycInfo, and CINAHL from 2002 to 2012 for studies of any research design that assessed the burden or frequency of psychological harm associated with screening for: prostate and lung cancers, osteoporosis, abdominal aortic aneurysm (AAA) and carotid artery stenosis (CAS). We also searched for studies that estimated rates of overdiagnosis (a marker for unnecessary labeling). We included studies published in English and used dual independent review to determine study inclusion and to abstract information on design, types of measures, and outcomes assessed. RESULTS: Sixty-eight studies assessing psychological harms met our criteria; 62 % concerned prostate cancer and 16 % concerned lung cancer. Evidence was scant for the other three screening services. Overall, only about one-third of the studies used both longitudinal designs and condition-specific measures (ranging from 0 % for AAA and CAS to 78 % for lung cancer), which can provide the best evidence on harms. An additional 20 studies that met our criteria estimated rates of overdiagnosis in lung or prostate cancer. No studies estimated overdiagnosis for the non-cancer screening services. DISCUSSION: Evidence on psychological harms varied markedly across screening services in number and potential usefulness. We found important evidence gaps for all five screening services. The evidence that we have on psychological harms is inadequate in number of studies and in research design and measures. Future research should focus more clearly on the evidence that we need for decision making about screening.