Five million years of Antarctic Circumpolar Current strength variability.

The Antarctic Circumpolar Current (ACC) represents the world's largest ocean-current system and affects global ocean circulation, climate and Antarctic ice-sheet stability1-3. Today, ACC dynamics are controlled by atmospheric forcing, oceanic density gradients and eddy activity4. Whereas palaeoceanographic reconstructions exhibit regional heterogeneity in ACC position and strength over Pleistocene glacial-interglacial cycles5-8, the long-term evolution of the ACC is poorly known. Here we document changes in ACC strength from sediment cores in the Pacific Southern Ocean. We find no linear long-term trend in ACC flow since 5.3 million years ago (Ma), in contrast to global cooling9 and increasing global ice volume10. Instead, we observe a reversal on a million-year timescale, from increasing ACC strength during Pliocene global cooling to a subsequent decrease with further Early Pleistocene cooling. This shift in the ACC regime coincided with a Southern Ocean reconfiguration that altered the sensitivity of the ACC to atmospheric and oceanic forcings11-13. We find ACC strength changes to be closely linked to 400,000-year eccentricity cycles, probably originating from modulation of precessional changes in the South Pacific jet stream linked to tropical Pacific temperature variability14. A persistent link between weaker ACC flow, equatorward-shifted opal deposition and reduced atmospheric CO2 during glacial periods first emerged during the Mid-Pleistocene Transition (MPT). The strongest ACC flow occurred during warmer-than-present intervals of the Plio-Pleistocene, providing evidence of potentially increasing ACC flow with future climate warming.

Patagonian dust, Agulhas Current, and Antarctic ice-rafted debris contributions to the South Atlantic Ocean over the past 150,000 years.

Disentangling inputs of aeolian dust, ice-rafted debris (IRD), and eroded continental detritus delivered by ocean currents to marine sediments provide important insights into Earth System processes and climate. This study uses Sr-Nd-Pb isotope ratios of the continent-derived (lithogenic) fraction in deep-sea core TN057-6 from the subantarctic Southern Ocean southwest of Africa over the past 150,000 y to identify source regions and quantify their relative contributions and fluxes utilizing a mixing model set in a Bayesian framework. The data are compared with proxies from parallel core Ocean Drilling Program Site 1090 and newly presented data from potential South America aeolian dust source areas (PSAs), allowing for an integrated investigation into atmospheric, oceanic, and cryospheric dynamics. PSA inputs varied on glacial/interglacial timescales, with southern South American sources dominating up to 88% of the lithogenic fraction (mainly Patagonia, which provided up to 68%) during cold periods, while southern African sources were more important during interglacials. During the warmer Marine Isotope Stage (MIS) 3 of the last glacial period, lithogenic fluxes were twice that of colder MIS2 and MIS4 at times, and showed unique isotope ratios best explained by Antarctic-derived IRD, likely from the Weddell Sea. The IRD intrusions contributed up to 41% at times and followed Antarctic millennial warming events that raised temperatures, causing instability of icesheet margins. High IRD was synchronous with increased bioavailable iron, nutrient utilization, high biological productivity, and decreased atmospheric CO2. Overall, TN057-6 sediments record systematic Southern Hemisphere climate shifts and cryospheric changes that impacted biogeochemical cycling on both glacial/interglacial and subglacial timescales.

Family Medicine Resident Scholarly Activity Infrastructure, Output, and Dissemination: A CERA Survey.

PURPOSE: Meeting scholarly activity requirements continues to be a challenge in many family medicine (FM) residency programs. Studies comprehensively describing FM resident scholarship have been limited. We sought to identify institutional factors associated with increased scholarly output and meeting requirements of the Accreditation Council for Graduate Medical Education (ACGME). OBJECTIVES: Our goals were to: (1) describe scholarly activity experiences among FM residents compared with ACGME requirements; (2) classify experiences by Boyer's domains of scholarship; and (3) associate experiences with residency program characteristics and scholarly activity infrastructure. METHODS: This was a cross-sectional survey. The survey questions were part of an omnibus survey to FM residency program directors conducted by the Council of Academic Family Medicine Educational Research Alliance (CERA). All ACGME-accredited US FM residency program directors, identified by the Association of Family Medicine Residency Directors, were sampled. RESULTS: Of the 691 eligible program directors, 298 (43%) completed the survey. The respondents reported that 25% or more residents exceeded ACGME minimum output, 17% reported that 25% or more residents published their work, and 50% reported that 25% or more residents delivered conference presentations. Programs exceeding ACGME scholarship requirements exhibit robust infrastructure characterized by access to faculty mentorship, scholarly activity curricula, Institutional Review Board, medical librarian, and statistician. CONCLUSIONS: These findings suggest the need for codified ACGME requirements for scholarly activity infrastructure to ensure access to resources in FM residency programs. By fostering FM resident engagement in scholarly activity, programs help to create a culture of inquiry, and address discrepancies in funding and output among FM residency programs.

Shorter versus longer duration antibiotic regimens for treatment of culture-positive neonatal sepsis.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the safety and effectiveness of shorter versus longer duration antibiotic regimens for the treatment of culture-positive neonatal sepsis with or without meningitis.

Shorter versus longer duration antibiotic regimens for treatment of suspected neonatal sepsis.

OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the safety and effectiveness of shorter versus longer duration antibiotic regimens for the treatment of suspected neonatal sepsis.

Screening for Speech and Language Delay and Disorders in Children 5 Years or Younger: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Children with speech and language difficulties are at risk for learning and behavioral problems. Objective: To review the evidence on screening for speech and language delay or disorders in children 5 years or younger to inform the US Preventive Services Task Force. Data Sources: PubMed/MEDLINE, Cochrane Library, PsycInfo, ERIC, Linguistic and Language Behavior Abstracts (ProQuest), and trial registries through January 17, 2023; surveillance through November 24, 2023. Study Selection: English-language studies of screening test accuracy, trials or cohort studies comparing screening vs no screening; randomized clinical trials (RCTs) of interventions. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, study quality, and data extraction; results were narratively summarized. Main Outcomes and Measures: Screening test accuracy, speech and language outcomes, school performance, function, quality of life, and harms. Results: Thirty-eight studies in 41 articles were included (N = 9006). No study evaluated the direct benefits of screening vs no screening. Twenty-one studies (n = 7489) assessed the accuracy of 23 different screening tools that varied with regard to whether they were designed to be completed by parents vs trained examiners, and to screen for global (any) language problems vs specific skills (eg, expressive language). Three studies assessing parent-reported tools for expressive language skills found consistently high sensitivity (range, 88%-93%) and specificity (range, 88%-85%). The accuracy of other screening tools varied widely. Seventeen RCTs (n = 1517) evaluated interventions for speech and language delay or disorders, although none enrolled children identified by routine screening in primary care. Two RCTs evaluating relatively intensive parental group training interventions (11 sessions) found benefit for different measures of expressive language skills, and 1 evaluating a less intensive intervention (6 sessions) found no difference between groups for any outcome. Two RCTs (n = 76) evaluating the Lidcombe Program of Early Stuttering Intervention delivered by speech-language pathologists featuring parent training found a 2.3% to 3.0% lower proportion of syllables stuttered at 9 months compared with the control group when delivered in clinic and via telehealth, respectively. Evidence on other interventions was limited. No RCTs reported on the harms of interventions. Conclusions and Relevance: No studies directly assessed the benefits and harms of screening. Some parent-reported screening tools for expressive language skills had reasonable accuracy for detecting expressive language delay. Group parent training programs for speech delay that provided at least 11 parental training sessions improved expressive language skills, and a stuttering intervention delivered by speech-language pathologists reduced stuttering frequency.

Folic Acid Supplementation to Prevent Neural Tube Defects: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Neural tube defects are among the most common birth defects in the US. Objective: To review new evidence on the benefits and harms of folic acid supplementation for the prevention of neural tube defects to inform the US Preventive Services Task Force. Evidence Review: Sources included PubMed, Cochrane Library, Embase, and trial registries from July 1, 2015, through July 2, 2021; references; and experts, with surveillance through February 10, 2023. Two investigators independently reviewed English-language randomized studies and nonrandomized cohort studies in very highly developed countries that focused on the use of folic acid supplementation for the prevention of neural tube defect-affected pregnancies; methodological quality was dually and independently assessed. Findings: Twelve observational studies (reported in 13 publications) were eligible for this limited update (N = 1 244 072). Of these, 3 studies (n = 990 372) reported on the effect of folic acid supplementation on neural tube defects. For harms, 9 studies were eligible: 1 randomized clinical trial (n = 431) reported on variations in twin delivery, 7 observational studies (n = 761 125) reported on the incidence of autism spectrum disorder, and 1 observational study (n = 429 004) reported on maternal cancer. Two cohort studies and 1 case-control study newly identified in this update reported on the association between folic acid supplementation and neural tube defects (n = 990 372). One cohort study reported a statistically significant reduced risk of neural tube defects associated with folic acid supplementation taken before pregnancy (adjusted relative risk [aRR], 0.54 [95% CI, 0.31-0.91]), during pregnancy (aRR, 0.62 [95% CI, 0.39-0.97]), and before and during pregnancy (aRR, 0.49 [95% CI, 0.29-0.83]), but this association occurred for only the later of 2 periods studied (2006-2013 and not 1999-2005). No other statistically significant benefits were reported overall. No study reported statistically significant harms (multiple gestation, autism, and maternal cancer) associated with pregnancy-related folic acid exposure. Conclusions and Relevance: New evidence from observational studies provided additional evidence of the benefit of folic acid supplementation for preventing neural tube defects and no evidence of harms related to multiple gestation, autism, or maternal cancer. The new evidence was consistent with previously reviewed evidence on benefits and harms.

Screening for Eating Disorders in Adolescents and Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Eating disorders are associated with adverse health and social outcomes. Objective: To review the evidence on screening for eating disorders in adolescents and adults to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, PsycINFO, and trial registries through December 19, 2020; surveillance through January 1, 2022. Study Selection: English-language studies of screening test accuracy, randomized clinical trials (RCTs) of screening or interventions for eating disorders in populations with screen-detected or previously untreated eating disorders (trials limited to populations who are underweight were ineligible). Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality. Meta-analysis of test accuracy studies and intervention trials. Main Outcomes and Measures: Test accuracy, eating disorder symptom severity, quality of life, depression, and harms. Results: Fifty-seven studies were included (N = 10 773); 3 (n = 1073) limited to adolescents (mean or median age, 14-15 years). No study directly evaluated the benefits and harms of screening. Seventeen studies (n = 6804) evaluated screening test accuracy. The SCOFF questionnaire (cut point ≥2) had a pooled sensitivity of 84% (95% CI, 74% to 90%) and pooled specificity of 80% (95% CI, 65% to 89%) in adults (10 studies, n = 3684). Forty RCTs (n = 3969) evaluated interventions for eating disorders; none enrolled a screen-detected population. Lisdexamfetamine for binge eating disorder (4 RCTs; n = 900) was associated with larger reductions in eating disorder symptom severity on the Yale-Brown Obsessive Compulsive Scale modified for binge eating (YBOCS-BE) than placebo (pooled mean difference, -5.75 [95% CI, -8.32 to -3.17]). Two RCTs (n = 465) of topiramate for binge eating disorder found larger reductions in YBOCS-BE scores associated with topiramate than placebo, from -6.40 (95% CI, -8.16 to -4.64) to -2.55 (95% CI, -4.22 to -0.88). Nine pharmacotherapy trials (n = 2006) reported on harms. Compared with placebo, lisdexamfetamine was associated with higher rates of dry mouth, headache, and insomnia, and topiramate was associated with higher rates of paresthesia, taste perversion, confusion, and concentration difficulty. Twenty-four trials (n = 1644) assessed psychological interventions. Guided self-help for binge eating disorder improved eating disorder symptom severity more than control (pooled standardized mean difference, -0.96 [95% CI, -1.26 to -0.67]) (5 studies, n = 391). Evidence on other interventions was limited. Conclusions and Relevance: No studies directly assessed the benefits and harms of screening. The SCOFF questionnaire had adequate accuracy for detecting eating disorders among adults. No treatment trials enrolled screen-detected populations; guided self-help, lisdexamfetamine, and topiramate were effective for reducing eating disorder symptom severity among referred populations with binge eating disorder, but pharmacotherapies were also associated with harms.

Screening for Depression and Suicide Risk in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Depression, suicidal ideation, and self-harm behaviors in youth are associated with functional impairment and suicide. Objective: To review the evidence on screening for depression or suicide risk in children and adolescents to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed, Cochrane Library, PsycINFO, CINAHL, and trial registries through July 19, 2021; references, experts, and surveillance through June 1, 2022. Study Selection: English-language, randomized clinical trials (RCTs) of screening for depression or suicide risk; diagnostic test accuracy studies; RCTs of psychotherapy and first-line pharmacotherapy; RCTs, observational studies, and systematic reviews reporting harms. Data Extraction and Synthesis: Two reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Test accuracy, symptoms, response, remission, loss of diagnosis, mortality, functioning, suicide-related events, and adverse events. Results: Twenty-one studies (N = 5433) were included for depression and 19 studies (N = 6290) for suicide risk. For depression, no studies reported on the direct effects of screening on health outcomes, and 7 studies (n = 3281) reported sensitivity of screening instruments ranging from 0.59 to 0.94 and specificity from 0.38 to 0.96. Depression treatment with psychotherapy was associated with improved symptoms (Beck Depression Inventory pooled standardized mean difference, -0.58 [95% CI, -0.83 to -0.34]; n = 471; 4 studies; and Hamilton Depression Scale pooled mean difference, -2.25 [95% CI, -4.09 to -0.41]; n = 262; 3 studies) clinical response (3 studies with statistically significant results using varying thresholds), and loss of diagnosis (relative risk, 1.73 [95% CI, 1.00 to 3.00; n = 395; 4 studies). Pharmacotherapy was associated with improvement on symptoms (Children's Depression Rating Scale-Revised mean difference, -3.76 [95% CI, -5.95 to -1.57; n = 793; 3 studies), remission (relative risk, 1.20 [95% CI, 1.00 to 1.45]; n = 793; 3 studies) and functioning (Children's Global Assessment Scale pooled mean difference, 2.60 (95% CI, 0.78 to 4.42; n = 793; 3 studies). Other outcomes were not statistically significantly different. Differences in suicide-related outcomes and adverse events for pharmacotherapy when compared with placebo were not statistically significant. For suicide risk, no studies reported on the direct benefits of screening on health outcomes, and 2 RCTs (n = 2675) reported no harms of screening. One study (n = 581) reported on sensitivity of screening, ranging from 0.87 to 0.91; specificity was 0.60. Sixteen RCTs (n = 3034) reported on suicide risk interventions. Interventions were associated with lower scores for the Beck Hopelessness Scale (pooled mean difference, -2.35 [95% CI, -4.06 to -0.65]; n = 644; 4 RCTs). Findings for other suicide-related outcomes were mixed or not statistically significantly different. Conclusion and Relevance: Indirect evidence suggested that some screening instruments were reasonably accurate for detecting depression. Psychotherapy and pharmacotherapy were associated with some benefits and no statistically significant harms for depression, but the evidence was limited for suicide risk screening instruments and interventions.

Screening for Anxiety in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Anxiety in children and adolescents is associated with impaired functioning, educational underachievement, and future mental health conditions. Objective: To review the evidence on screening for anxiety in children and adolescents to inform the US Preventive Services Task Force. Data Sources: PubMed, Cochrane Library, PsycINFO, CINAHL, and trial registries through July 19, 2021; references, experts, and surveillance through June 1, 2022. Study Selection: English-language, randomized clinical trials (RCTs) of screening; diagnostic test accuracy studies; RCTs of cognitive behavioral therapy (CBT) or US Food and Drug Administration-approved pharmacotherapy; RCTs, observational studies, and systematic reviews reporting harms. Data Extraction and Synthesis: Two reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Test accuracy, symptoms, response, remission, loss of diagnosis, all-cause mortality, functioning, suicide-related symptoms or events, adverse events. Results: Thirty-nine studies (N = 6065) were included. No study reported on the direct benefits or harms of screening on health outcomes. Ten studies (n = 3260) reported the sensitivity of screening instruments, ranging from 0.34 to 1.00, with specificity ranging from 0.47 to 0.99. Twenty-nine RCTs (n = 2805) reported on treatment: 22 on CBT, 6 on pharmacotherapy, and 1 on CBT, sertraline, and CBT plus sertraline. CBT was associated with gains on several pooled measures of symptom improvement (magnitude of change varied by outcome measure), response (pooled relative risk [RR], 1.89 [95% CI, 1.17 to 3.05]; n = 606; 6 studies), remission (RR, 2.68 [95% CI, 1.48 to 4.88]; n = 321; 4 studies), and loss of diagnosis (RR range, 3.02-3.09) when compared with usual care or wait-list controls. The evidence on functioning for CBT was mixed. Pharmacotherapy, when compared with placebo, was associated with gains on 2 pooled measures of symptom improvement-mean difference (Pediatric Anxiety Rating Scale mean difference, -4.0 [95% CI, -5.5 to -2.5]; n = 726; 5 studies; and Clinical Global Impression-Severity scale mean difference, -0.84 [95% CI, -1.13 to -0.55]; n = 550; 4 studies) and response (RR, 2.11 [95% CI, 1.58 to 2.98]; n = 370; 5 studies)-but was mixed on measures of functioning. Eleven RCTs (n = 1293) reported harms of anxiety treatments. Suicide-related harms were rare, and the differences were not statistically significantly different. Conclusions and Relevance: Indirect evidence suggested that some screening instruments were reasonably accurate. CBT and pharmacotherapy were associated with benefits; no statistically significant association with harms was reported.

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

Importance: Obstructive sleep apnea (OSA) is associated with adverse health outcomes. Objective: To review the evidence on screening for OSA in asymptomatic adults or those with unrecognized OSA symptoms to inform the US Preventive Services Task Force. Data Sources: PubMed/MEDLINE, Cochrane Library, Embase, and trial registries through August 23, 2021; surveillance through September 23, 2022. Study Selection: English-language studies of screening test accuracy, randomized clinical trials (RCTs) of screening or treatment of OSA reporting health outcomes or harms, and systematic reviews of treatment reporting changes in blood pressure and apnea-hypopnea index (AHI) scores. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality. Meta-analysis of intervention trials. Main Outcomes and Measures: Test accuracy, excessive daytime sleepiness, sleep-related and general health-related quality of life (QOL), and harms. Results: Eighty-six studies were included (N = 11 051). No study directly compared screening with no screening. Screening accuracy of the Multivariable Apnea Prediction score followed by unattended home sleep testing for detecting severe OSA syndrome (AHI ≥30 and Epworth Sleepiness Scale [ESS] score >10) measured as the area under the curve in 2 studies (n = 702) was 0.80 (95% CI, 0.78 to 0.82) and 0.83 (95% CI, 0.77 to 0.90). Five studies assessing the accuracy of other screening tools were heterogeneous and results were inconsistent. Compared with inactive control, positive airway pressure was associated with a significant improvement in ESS score from baseline (pooled mean difference, -2.33 [95% CI, -2.75 to -1.90]; 47 trials; n = 7024), sleep-related QOL (standardized mean difference, 0.30 [95% CI, 0.19 to 0.42]; 17 trials; n = 3083), and general health-related QOL measured by the 36-Item Short Form Health Survey (SF-36) mental health component summary score change (pooled mean difference, 2.20 [95% CI, 0.95 to 3.44]; 15 trials; n = 2345) and SF-36 physical health component summary score change (pooled mean difference, 1.53 [95% CI, 0.29 to 2.77]; 13 trials; n = 2031). Use of mandibular advancement devices was also associated with a significantly larger ESS score change compared with controls (pooled mean difference, -1.67 [95% CI, 2.09 to -1.25]; 10 trials; n = 1540). Reporting of other health outcomes was sparse; no included trial found significant benefit associated with treatment on mortality, cardiovascular events, or motor vehicle crashes. In 3 systematic reviews, positive airway pressure was significantly associated with reduced blood pressure; however, the difference was relatively small (2-3 mm Hg). Conclusions and Relevance: The accuracy and clinical utility of OSA screening tools that could be used in primary care settings were uncertain. Positive airway pressure and mandibular advancement devices reduced ESS score. Trials of positive airway pressure found modest improvement in sleep-related and general health-related QOL but have not established whether treatment reduces mortality or improves most other health outcomes.

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

Importance: Of youths diagnosed with type 2 diabetes, many develop microvascular complications by young adulthood. Objective: To review the evidence on benefits and harms of screening children and adolescents for prediabetes and type 2 diabetes to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through May 3, 2021; references; experts; literature surveillance through July 22, 2022. Study Selection: English-language controlled studies evaluating screening or interventions for prediabetes or type 2 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. Main Outcomes and Measures: Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. Results: This review included 8 publications (856 participants; mean age, 14 years [range, 10-17 years]). Of those, 6 were from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. No eligible studies directly evaluated the benefits or harms of screening. One randomized clinical trial (RCT) (TODAY; n = 699 adolescents with obesity; mean age, 14 years) comparing metformin, metformin plus rosiglitazone, and metformin plus lifestyle intervention reported that 2 youths with recently diagnosed diabetes developed kidney impairment (0 vs 1 vs 1, respectively; P > .99) and 11 developed diabetic ketoacidosis (5 vs 3 vs 3, respectively; P = .70). One RCT of 75 adolescents (mean age, 13 years) with obesity with prediabetes compared an intensive lifestyle intervention with standard care and reported that no participants in either group developed diabetes, although follow-up was only 6 months. Regarding harms of interventions, 2 RCTs assessing different comparisons enrolled youths with recently diagnosed diabetes. Major hypoglycemic events were reported by less than 1% of participants. Minor hypoglycemic events were more common among youths treated with metformin plus rosiglitazone than among those treated with metformin or metformin plus lifestyle intervention in TODAY (8.2% vs 4.3% vs 3.4%, P = .05). In 1 study, gastrointestinal adverse events were more commonly reported by those taking metformin than by those taking placebo (abdominal pain: 25% vs 12%; nausea/vomiting: 17% vs 10%; P not reported). Conclusions and Relevance: No eligible studies directly evaluated the benefits or harms of screening for prediabetes and type 2 diabetes in children and adolescents. For youths with prediabetes or recently diagnosed (not screen-detected) diabetes, the only eligible trials reported few health outcomes and found no difference between groups, although evidence was limited by substantial imprecision and a duration of follow-up likely insufficient to assess health outcomes.

Identification of Cardiac Magnetic Resonance Imaging Thresholds for Risk Stratification in Pulmonary Arterial Hypertension.

Rationale: Pulmonary arterial hypertension (PAH) is a life-shortening condition. The European Society of Cardiology and European Respiratory Society and the REVEAL (North American Registry to Evaluate Early and Long-Term PAH Disease Management) risk score calculator (REVEAL 2.0) identify thresholds to predict 1-year mortality.Objectives: This study evaluates whether cardiac magnetic resonance imaging (MRI) thresholds can be identified and used to aid risk stratification and facilitate decision-making.Methods: Consecutive patients with PAH (n = 438) undergoing cardiac MRI were identified from the ASPIRE (Assessing the Spectrum of Pulmonary Hypertension Identified at a Referral Center) MRI database. Thresholds were identified from a discovery cohort and evaluated in a test cohort.Measurements and Main Results: A percentage-predicted right ventricular end-systolic volume index threshold of 227% or a left ventricular end-diastolic volume index of 58 ml/m2 identified patients at low (<5%) and high (>10%) risk of 1-year mortality. These metrics respectively identified 63% and 34% of patients as low risk. Right ventricular ejection fraction >54%, 37-54%, and <37% identified 21%, 43%, and 36% of patients at low, intermediate, and high risk, respectively, of 1-year mortality. At follow-up cardiac MRI, patients who improved to or were maintained in a low-risk group had a 1-year mortality <5%. Percentage-predicted right ventricular end-systolic volume index independently predicted outcome and, when used in conjunction with the REVEAL 2.0 risk score calculator or a modified French Pulmonary Hypertension Registry approach, improved risk stratification for 1-year mortality.Conclusions: Cardiac MRI can be used to risk stratify patients with PAH using a threshold approach. Percentage-predicted right ventricular end-systolic volume index can identify a high percentage of patients at low-risk of 1-year mortality and, when used in conjunction with current risk stratification approaches, can improve risk stratification. This study supports further evaluation of cardiac MRI in risk stratification in PAH.

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.

Re-thinking How We Teach Quality Improvement: Adding Meaning to an ACGME Requirement.

BACKGROUND: Many residency programs have struggled to meaningfully meet the ACGME quality improvement (QI) requirements. Similarly, our residents were receiving limited QI education, and their longitudinal projects were ineffective. AIM: Create an integrated didactic and experiential learning environment that equips residents to become leaders of QI. SETTING AND PARTICIPANTS: Internal medicine (IM) residency program of 45 residents in a large community hospital. PROGRAM DESCRIPTION: This curriculum included eight content areas. Games, real-life application, and project celebrations cultivated engagement. Sessions occurred during residents' 2-week outpatient rotations. Project development was standardized. PROGRAM EVALUATION: The QI Knowledge Application Tool-Revised (QIKAT-R) and separate surveys were used before and after the curriculum's implementation to evaluate resident QI knowledge and confidence, respectively. We also tracked QI scholarship and faculty engagement. Mean QIKAT-R scores improved significantly from 7.0 (SD 2.9) at baseline to 16.6 (SD 4.7) post-curriculum (n = 37 pairs, p = 0.043). Residents' adverse event reporting increased from 44% (19/43) at baseline to 90% (28/31) post-curriculum. Seven presentations were accepted for local, regional, and national conferences, compared with one presentation the preceding year. DISCUSSION: A QI curriculum can be successfully integrated in a "4 + 2" program.

Screening for Atrial Fibrillation With Electrocardiography: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Atrial fibrillation is the most common arrhythmia and increases the risk of stroke. Objective: To review the evidence on screening for nonvalvular atrial fibrillation with electrocardiography (ECG) and stroke prevention treatment in asymptomatic adults 65 years or older to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, and trial registries through May 2017; references; experts; literature surveillance through June 6, 2018. Study Selection: English-language randomized clinical trials (RCTs), prospective cohort studies evaluating detection rates of atrial fibrillation or harms of screening, and systematic reviews evaluating stroke prevention treatment. Eligible treatment studies compared warfarin, aspirin, or novel oral anticoagulants (NOACs) with placebo or no treatment. Studies were excluded that focused on persons with a history of cardiovascular disease. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality. When at least 3 similar studies were available, random-effects meta-analyses were conducted. Main Outcomes and Measures: Detection of previously undiagnosed atrial fibrillation, mortality, stroke, stroke-related morbidity, and harms. Results: Seventeen studies were included (n = 135 300). No studies evaluated screening compared with no screening and focused on health outcomes. Systematic screening with ECG identified more new cases of atrial fibrillation than no screening (absolute increase, from 0.6% [95% CI, 0.1%-0.9%] to 2.8% [95% CI, 0.9%-4.7%] over 12 months; 2 RCTs, n = 15 803), but a systematic approach using ECG did not detect more cases than an approach using pulse palpation (2 RCTs, n = 17 803). For potential harms, no eligible studies compared screening with no screening. Warfarin (mean, 1.5 years) was associated with a reduced risk of ischemic stroke (relative risk [RR], 0.32 [95% CI, 0.20-0.51]) and all-cause mortality (RR, 0.68 [95% CI, 0.50-0.93]) and with increased risk of bleeding (5 trials, n = 2415). Participants in treatment trials were not screen detected, and most had long-standing persistent atrial fibrillation. A network meta-analysis reported that NOACs were associated with a significantly lower risk of a composite outcome of stroke and systemic embolism (adjusted odds ratios compared with placebo or control ranged from 0.32-0.44); the risk of bleeding was increased (adjusted odds ratios, 1.4-2.2), but confidence intervals were wide and differences between groups were not statistically significant. Conclusions and Relevance: Although screening with ECG can detect previously unknown cases of atrial fibrillation, it has not been shown to detect more cases than screening focused on pulse palpation. Treatments for atrial fibrillation reduce the risk of stroke and all-cause mortality and increase the risk of bleeding, but trials have not assessed whether treatment of screen-detected asymptomatic older adults results in better health outcomes than treatment after detection by usual care or after symptoms develop.

Screening to Prevent Osteoporotic Fractures: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Osteoporotic fractures cause significant morbidity and mortality. Objective: To update the evidence on screening and treatment to prevent osteoporotic fractures for the US Preventive Services Task Force. Data Sources: PubMed, the Cochrane Library, EMBASE, and trial registries (November 1, 2009, through October 1, 2016) and surveillance of the literature (through March 23, 2018); bibliographies from articles. Study Selection: Adults 40 years and older; screening cohorts without prevalent low-trauma fractures or treatment cohorts with increased fracture risk; studies assessing screening, bone measurement tests or clinical risk assessments, pharmacologic treatment. Data Extraction and Synthesis: Dual, independent review of titles/abstracts and full-text articles; study quality rating; random-effects meta-analysis. Main Outcomes and Measures: Incident fractures and related morbidity and mortality, diagnostic and predictive accuracy, harms of screening or treatment. Results: One hundred sixty-eight fair- or good-quality articles were included. One randomized clinical trial (RCT) (n = 12 483) comparing screening with no screening reported fewer hip fractures (2.6% vs 3.5%; hazard ratio [HR], 0.72 [95% CI, 0.59-0.89]) but no other statistically significant benefits or harms. The accuracy of bone measurement tests to identify osteoporosis varied (area under the curve [AUC], 0.32-0.89). The pooled accuracy of clinical risk assessments for identifying osteoporosis ranged from AUC of 0.65 to 0.76 in women and from 0.76 to 0.80 in men; the accuracy for predicting fractures was similar. For women, bisphosphonates, parathyroid hormone, raloxifene, and denosumab were associated with a lower risk of vertebral fractures (9 trials [n = 23 690]; relative risks [RRs] from 0.32-0.64). Bisphosphonates (8 RCTs [n = 16 438]; pooled RR, 0.84 [95% CI, 0.76-0.92]) and denosumab (1 RCT [n = 7868]; RR, 0.80 [95% CI, 0.67-0.95]) were associated with a lower risk of nonvertebral fractures. Denosumab reduced the risk of hip fracture (1 RCT [n = 7868]; RR, 0.60 [95% CI, 0.37-0.97]), but bisphosphonates did not have a statistically significant association (3 RCTs [n = 8988]; pooled RR, 0.70 [95% CI, 0.44-1.11]). Evidence was limited for men: zoledronic acid reduced the risk of radiographic vertebral fractures (1 RCT [n = 1199]; RR, 0.33 [95% CI, 0.16-0.70]); no studies demonstrated reductions in clinical or hip fractures. Bisphosphonates were not consistently associated with reported harms other than deep vein thrombosis (raloxifene vs placebo; 3 RCTs [n = 5839]; RR, 2.14 [95% CI, 0.99-4.66]). Conclusions and Relevance: In women, screening to prevent osteoporotic fractures may reduce hip fractures, and treatment reduced the risk of vertebral and nonvertebral fractures; there was not consistent evidence of treatment harms. The accuracy of bone measurement tests or clinical risk assessments for identifying osteoporosis or predicting fractures varied from very poor to good.

Screening for Cardiovascular Disease Risk With Resting or Exercise Electrocardiography: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Cardiovascular disease (CVD) is the leading cause of death in the United States. Objective: To review the evidence on screening asymptomatic adults for CVD risk using electrocardiography (ECG) to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, and trial registries through May 2017; references; experts; literature surveillance through April 4, 2018. Study Selection: English-language randomized clinical trials (RCTs); prospective cohort studies reporting reclassification, calibration, or discrimination that compared risk assessment using ECG plus traditional risk factors vs traditional risk factors alone. For harms, additional study designs were eligible. Studies of persons with symptoms or a CVD diagnosis were excluded. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings. Main Outcomes and Measures: Mortality, cardiovascular events, reclassification, calibration, discrimination, and harms. Results: Sixteen studies were included (N = 77 140). Two RCTs (n = 1151) found no significant improvement for screening with exercise ECG (vs no screening) in adults aged 50 to 75 years with diabetes for the primary cardiovascular composite outcomes (hazard ratios, 1.00 [95% CI, 0.59-1.71] and 0.85 [95% CI, 0.39-1.84] for each study). No RCTs evaluated screening with resting ECG. Evidence from 5 cohort studies (n = 9582) showed that adding exercise ECG to traditional risk factors such as age, sex, current smoking, diabetes, total cholesterol level, and high-density lipoprotein cholesterol level produced small improvements in discrimination (absolute improvements in area under the curve [AUC] or C statistics, 0.02-0.03, reported by 3 studies); whether calibration or appropriate risk classification improves is uncertain. Evidence from 9 cohort studies (n = 66 407) showed that adding resting ECG to traditional risk factors produced small improvements in discrimination (absolute improvement in AUC or C statistics, 0.001-0.05) and appropriate risk classification for prediction of multiple cardiovascular outcomes, although evidence was limited by imprecision, quality, considerable heterogeneity, and inconsistent use of risk thresholds used for clinical decision making. Total net reclassification improvements ranged from 3.6% (2.7% event; 0.6% nonevent) to 30% (17% event; 19% nonevent) for studies using the Framingham Risk Score or Pooled Cohort Equations base models. Evidence on potential harms (eg, from subsequent angiography or revascularization) in asymptomatic persons was limited. Conclusions and Relevance: RCTs of screening with exercise ECG found no improvement in health outcomes, despite focusing on higher-risk populations with diabetes. The addition of resting ECG to traditional risk factors accurately reclassified persons, but evidence for this finding had many limitations. The frequency of harms from screening is uncertain.

Screening for Intimate Partner Violence, Elder Abuse, and Abuse of Vulnerable Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Intimate partner violence (IPV), elder abuse, and abuse of vulnerable adults are common and result in adverse health outcomes. Objective: To review the evidence on screening and interventions for IPV, elder abuse, and abuse of vulnerable adults to inform the US Preventive Services Task Force. Data Sources: MEDLINE, Cochrane Library, EMBASE, and trial registries through October 4, 2017; references; experts; literature surveillance through August 1, 2018. Study Selection: English-language randomized clinical trials (RCTs), studies evaluating test accuracy, and cohort studies with a concurrent control group assessing harms. Data Extraction and Synthesis: Dual review of titles and abstracts, full-text articles, and study quality; qualitative synthesis of findings. Data were not pooled, primarily because of heterogeneity of populations, interventions, and outcomes. Main Outcomes and Measures: Abuse or neglect, morbidity caused by abuse, test accuracy, and harms. Results: Thirty studies were included (N = 14 959). Three RCTs (n = 3759) compared IPV screening with no screening; none found significant improvements in outcomes (eg, IPV or quality of life) over 3 to 18 months and 2 (n = 935) reported no harms of screening. Nine studies assessed tools to detect any past-year or current IPV in women; for past-year IPV (5 studies [n = 6331]), sensitivity of 5 tools ranged from 65% to 87% and specificity ranged from 80% to 95%. The accuracy of 5 tools (4 studies [n = 1795]) for detecting current abuse varied widely; sensitivity ranged from 46% to 94% and specificity ranged from 38% to 95%. Eleven RCTs (n = 6740) evaluated interventions for women with screen-detected IPV. Two enrolling pregnant women (n = 575) found significantly less IPV among women in the intervention group: 1 home visiting intervention (standardized mean difference [SMD], -0.34 [95% CI, -0.59 to -0.08]) and 1 behavioral counseling intervention for multiple risks (IPV, smoking, depression, tobacco exposure) (SMD, -0.40 [95% CI, -0.68 to -0.12]). No studies evaluated screening or interventions for elder abuse or abuse of vulnerable adults. One study assessing a screening tool for elder abuse had poor accuracy (sensitivity, 46% and specificity, 73% for detecting physical or verbal abuse). Conclusions and Relevance: Although available screening tools may reasonably identify women experiencing IPV, trials of IPV screening in adult women did not show a reduction in IPV or improvement in quality of life over 3 to 18 months. Limited evidence suggested that home visiting and behavioral counseling interventions that address multiple risk factors may lead to reduced IPV among pregnant or postpartum women. No studies assessed screening or treatment for elder abuse and abuse of vulnerable adults.