Interventions to Prevent Falls in Older Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Falls are the most common cause of injury-related morbidity and mortality in older adults. Objective: To systematically review evidence on the effectiveness and harms of fall prevention interventions in community-dwelling older adults. Data Sources: MEDLINE, Cumulative Index for Nursing and Allied Health Literature, and Cochrane Central Register of Controlled Clinical Trials for relevant English-language literature published between January 1, 2016, and May 8, 2023, with ongoing surveillance through March 22, 2024. Study Selection: Randomized clinical trials of interventions to prevent falls in community-dwelling adults 65 years or older. Data Extraction and Synthesis: Critical appraisal and data abstraction by 2 independent reviewers. Random-effects meta-analyses with Knapp-Hartung adjustment. Main Outcomes and Measures: Falls, injurious falls, fall-related fractures, hospitalizations or emergency department visits, people with 1 or more falls, people with injurious falls, people with fall-related fractures, and harms. Results: Eighty-three fair- to good-quality randomized clinical trials (n = 48 839) examined the effectiveness of 6 fall prevention interventions in older adults. This article focuses on the 2 most studied intervention types: multifactorial (28 studies; n = 27 784) and exercise (37 studies; n = 16 117) interventions. Multifactorial interventions were associated with a statistically significant reduction in falls (incidence rate ratio [IRR], 0.84 [95% CI, 0.74-0.95]) but not a statistically significant reduction in individual risk of 1 or more falls (relative risk [RR], 0.96 [95% CI, 0.91-1.02]), injurious falls (IRR, 0.92 [95% CI, 0.84-1.01]), fall-related fractures (IRR, 1.01 [95% CI, 0.81-1.26]), individual risk of injurious falls (RR, 0.92 [95% CI, 0.83-1.02]), or individual risk of fall-related fractures (RR, 0.86 [95% CI, 0.60-1.24]). Exercise interventions were associated with statistically significant reductions in falls (IRR, 0.85 [95% CI, 0.75-0.96]), individual risk of 1 or more falls (RR, 0.92 [95% CI, 0.87-0.98]), and injurious falls (IRR, 0.84 [95% CI, 0.74-0.95]) but not individual risk of injurious falls (RR, 0.90 [95% CI, 0.79-1.02]). Harms associated with multifactorial and exercise interventions were not well reported and were generally rare, minor musculoskeletal symptoms associated with exercise. Conclusions and Relevance: Multifactorial and exercise interventions were associated with reduced falls in multiple good-quality trials. Exercise demonstrated the most consistent statistically significant benefit across multiple fall-related outcomes.

Aspirin Use to Prevent Cardiovascular Disease and Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Low-dose aspirin is used for primary cardiovascular disease prevention and may have benefits for colorectal cancer prevention. Objective: To review the benefits and harms of aspirin in primary cardiovascular disease prevention and colorectal cancer prevention to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, Embase, and the Cochrane Central Register of Controlled Trials through January 2021; literature surveillance through January 21, 2022. Study Selection: English-language randomized clinical trials (RCTs) of low-dose aspirin (≤100 mg/d) compared with placebo or no intervention in primary prevention populations. Data Extraction and Synthesis: Single extraction, verified by a second reviewer. Quantitative synthesis using Peto fixed-effects meta-analysis. Main Outcomes and Measures: Cardiovascular disease events and mortality, all-cause mortality, colorectal cancer incidence and mortality, major bleeding, and hemorrhagic stroke. Results: Eleven RCTs (N = 134 470) and 1 pilot trial (N = 400) of low-dose aspirin for primary cardiovascular disease prevention were included. Low-dose aspirin was associated with a significant decrease in major cardiovascular disease events (odds ratio [OR], 0.90 [95% CI, 0.85-0.95]; 11 RCTs [n = 134 470]; I2 = 0%; range in absolute effects, -2.5% to 0.1%). Results for individual cardiovascular disease outcomes were significant, with similar magnitude of benefit. Aspirin was not significantly associated with reductions in cardiovascular disease mortality or all-cause mortality. There was limited trial evidence on benefits for colorectal cancer, with the findings highly variable by length of follow-up and statistically significant only when considering long-term observational follow-up beyond randomized trial periods. Low-dose aspirin was associated with significant increases in total major bleeding (OR, 1.44 [95% CI, 1.32-1.57]; 10 RCTs [n = 133 194]; I2 = 4.7%; range in absolute effects, 0.1% to 1.0%) and in site-specific bleeding, with similar magnitude. Conclusions and Relevance: Low-dose aspirin was associated with small absolute risk reductions in major cardiovascular disease events and small absolute increases in major bleeding. Colorectal cancer results were less robust and highly variable.

Endometrial Adenocarcinomas With No Specific Molecular Profile: Morphologic Features and Molecular Alterations of "Copy-number Low" Tumors.

The study evaluated morphologic patterns, mutational profiles, and ß-catenin immunohistochemistry (IHC) in copy-number low (CNL) endometrial adenocarcinomas (EAs). CNL EAs (n=19) with next-generation or whole genome sequencing results and available tissue for IHC were identified from our institutional database. Clinical data and histologic slides were reviewed. IHC for ß-catenin was performed and correlated with mutation status. Images of digital slides of CNL EAs from The Cancer Genome Atlas (TCGA) database (n=90) were blindly reviewed by 4 pathologists, and morphology was correlated with mutation status. Categorical variables were analyzed using the Fisher exact test, and agreement was assessed using Fleiss κ. CTNNB1 mutations were present in 63% (12/19) of CNL EAs. ß-catenin nuclear localization was present in 83% of CTNNB1-mutated tumors (10/12) and in 0% (0/7) of CTNNB1-wildtype tumors (sensitivity 0.83, specificity 1.00). Squamous differentiation (SD) was present in 47% (9/19) and was more often observed in CTNNB1-mutated tumors (P=0.02). Mucinous differentiation (MD) was associated with KRAS mutations (P<0.01). Digital image review of TCGA CNL EAs revealed that pathologist agreement on SD was strong (κ=0.82), whereas agreement on MD was weak (κ=0.48). Pathologists identified SD in 22% (20/90), which was significantly associated with the presence of CTNNB1 mutations (P<0.01). CNL EAs demonstrate several morphologies with divergent molecular profiles. SD was significantly associated with CTNNB1 mutations and nuclear localization of ß-catenin in these tumors. Nuclear expression of ß-catenin is a sensitive and specific IHC marker for CTNNB1 mutations in CNL EAs. CNL EAs with KRAS mutations often displayed MD.

Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the US. Objective: To systematically review the effectiveness, test accuracy, and harms of screening for CRC to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2015, to December 4, 2019; surveillance through March 26, 2021. Study Selection: English-language studies conducted in asymptomatic populations at general risk of CRC. Data Extraction and Synthesis: Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted. Main Outcomes and Measures: Colorectal cancer incidence and mortality, test accuracy in detecting cancers or adenomas, and serious adverse events. Results: The review included 33 studies (n = 10 776 276) on the effectiveness of screening, 59 (n = 3 491 045) on the test performance of screening tests, and 131 (n = 26 987 366) on the harms of screening. In randomized clinical trials (4 trials, n = 458 002), intention to screen with 1- or 2-time flexible sigmoidoscopy vs no screening was associated with a decrease in CRC-specific mortality (incidence rate ratio, 0.74 [95% CI, 0.68-0.80]). Annual or biennial guaiac fecal occult blood test (gFOBT) vs no screening (5 trials, n = 419 966) was associated with a reduction of CRC-specific mortality after 2 to 9 rounds of screening (relative risk at 19.5 years, 0.91 [95% CI, 0.84-0.98]; relative risk at 30 years, 0.78 [95% CI, 0.65-0.93]). In observational studies, receipt of screening colonoscopy (2 studies, n = 436 927) or fecal immunochemical test (FIT) (1 study, n = 5.4 million) vs no screening was associated with lower risk of CRC incidence or mortality. Nine studies (n = 6497) evaluated the test accuracy of screening computed tomography (CT) colonography, 4 of which also reported the test accuracy of colonoscopy; pooled sensitivity to detect adenomas 6 mm or larger was similar between CT colonography with bowel prep (0.86) and colonoscopy (0.89). In pooled values, commonly evaluated FITs (14 studies, n = 45 403) (sensitivity, 0.74; specificity, 0.94) and stool DNA with FIT (4 studies, n = 12 424) (sensitivity, 0.93; specificity, 0.85) performed better than high-sensitivity gFOBT (2 studies, n = 3503) (sensitivity, 0.50-0.75; specificity, 0.96-0.98) to detect cancers. Serious harms of screening colonoscopy included perforations (3.1/10 000 procedures) and major bleeding (14.6/10 000 procedures). CT colonography may have harms resulting from low-dose ionizing radiation. It is unclear if detection of extracolonic findings on CT colonography is a net benefit or harm. Conclusions and Relevance: There are several options to screen for colorectal cancer, each with a different level of evidence demonstrating its ability to reduce cancer mortality, its ability to detect cancer or precursor lesions, and its risk of harms.

Addressing Racism in Preventive Services: Methods Report to Support the US Preventive Services Task Force.

Importance: In January 2021, the US Preventive Services Task Force (USPSTF) issued a values statement that acknowledged systemic racism and included a commitment to address racism and health equity in recommendations for clinical preventive services. Objectives: To articulate the definitional and conceptual issues around racism and health inequity and to describe how racism and health inequities are currently addressed in preventive health. Methods: An audit was conducted assessing (1) published literature on frameworks or policy and position statements addressing racism, (2) a subset of cancer and cardiovascular topics in USPSTF reports, (3) recent systematic reviews on interventions to reduce health inequities in preventive health or to prevent racism in health care, and (4) health care-relevant professional societies, guideline-making organizations, agencies, and funding bodies to gather information about how they are addressing racism and health equity. Findings: Race as a social category does not have biological underpinnings but has biological consequences through racism. Racism is complex and pervasive, operates at multiple interrelated levels, and exerts negative effects on other social determinants and health and well-being through multiple pathways. In its reports, the USPSTF has addressed racial and ethnic disparities, but not racism explicitly. The systematic reviews to support the USPSTF include interventions that may mitigate health disparities through cultural tailoring of behavioral interventions, but reviews have not explicitly addressed other commonly studied interventions to increase the uptake of preventive services or foster the implementation of preventive services. Many organizations have issued recent statements and commitments around racism in health care, but few have provided substantive guidance on operational steps to address the effects of racism. Where guidance is unavailable regarding the proposed actions, it is principally because work to achieve them is in very early stages. The most directly relevant and immediately useful guidance identified is that from the GRADE working group. Conclusions and Relevance: This methods report provides a summary of issues around racism and health inequity, including the status of how these are being addressed in preventive health.

NCCN Guidelines Insights: Cervical Cancer, Version 1.2020.

The NCCN Guidelines for Cervical Cancer provide recommendations for diagnostic workup, staging, and treatment of patients with the disease. These NCCN Guidelines Insights focus on recent updates to the guidelines, including changes to first- and second-line systemic therapy recommendations for patients with recurrent or metastatic disease, and emerging evidence on a new histopathologic classification system for HPV-related endocervical adenocarcinoma.

Behavioral Counseling Interventions to Prevent Sexually Transmitted Infections: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Increasing rates of preventable sexually transmitted infections (STIs) in the US pose substantial burdens to health and well-being. Objective: To update evidence for the US Preventive Services Task Force (USPSTF) on effectiveness of behavioral counseling interventions for preventing STIs. Data Sources: Studies from the previous USPSTF review (2014); literature published January 2013 through May 31, 2019, in MEDLINE, PubMed (for publisher-supplied records only), PsycINFO, and Cochrane Central Register of Controlled Trials. Ongoing surveillance through May 22, 2020. Study Selection: Good- and fair-quality randomized and nonrandomized controlled intervention studies of behavioral counseling interventions for adolescents and adults conducted in primary care settings were included. Studies with active comparators only or limited to individuals requiring specialist care for STI risk-related comorbidities were excluded. Data Extraction and Synthesis: Dual risk of bias assessment, with inconsistent ratings adjudicated by a third team member. Study data were abstracted into prespecified forms. Pooled odds ratios (ORs) were estimated using the DerSimonian and Laird method or the restricted maximum likelihood method with Knapp-Hartung adjustment. Main Outcomes and Measures: Differences in STI diagnoses, self-reported condom use, and self-reported unprotected sex at 3 months or more after baseline. Results: The review included 37 randomized trials and 2 nonrandomized controlled intervention studies (N = 65 888; 13 good-quality, 26 fair-quality) recruited from primary care settings in the US. Study populations were composed predominantly of heterosexual adolescents and young adults (12 to 25 years), females, and racial and ethnic minorities at increased risk for STIs. Nineteen trials (n = 52 072) reported STI diagnoses as outcomes (3 to 17 months' follow-up); intervention was associated with reduced STI incidence (OR, 0.66 [95% CI, 0.54-0.81; I2 = 74%]). Absolute differences in STI acquisition between groups varied widely depending on baseline population STI risk and intervention effectiveness, ranging from 19% fewer to 4% more people acquiring STI. Thirty-four trials (n = 21 417) reported behavioral change outcomes. Interventions were associated with self-reported behavioral change (eg, increased condom use) that reduce STI risk (OR, 1.31 [95% CI, 1.10-1.56; I2 = 40%, n = 5253). There was limited evidence on persistence of intervention effects beyond 1 year. No harms were identified in 7 studies (n = 3458) reporting adverse outcomes. Conclusions and Relevance: Behavioral counseling interventions for individuals seeking primary health care were associated with reduced incidence of STIs. Group or individual counseling sessions lasting more than 2 hours were associated with larger reductions in STI incidence, and interventions of shorter duration also were associated with STI prevention, although evidence was limited on whether the STI reductions associated with these interventions persisted beyond 1 year.

The association between progesterone receptor expression and survival in women with adult granulosa cell tumors.

BACKGROUND: Granulosa cell tumors (GCT) variably express estrogen receptors (ER) and progesterone receptors (PR). The goal of this study is to evaluate the relationship between ER and PR expression patterns and clinical outcomes in women with GCT. METHODS: A multicenter, retrospective analysis was performed of all cases of GCT diagnosed between 1989 and 2012. Immunohistochemical staining for ER and PR was performed on formalin-fixed paraffin embedded (FFPE) tumor tissue and interpreted using a semiquantitative scoring system that incorporated tumor cell staining proportion and intensity. Demographics, disease status, and survival information were collected. Associations between ER and PR staining scores and recurrence-free and overall survival were assessed using univariate Cox proportional hazards models. RESULTS: FFPE tumor blocks were available for 149/186 GCT patients. The majority of the women had clinical stage I disease (76%). ER and PR expression was present in 52% and 98% of subjects, respectively. The median composite scores of ER and PR staining were 1 (range 0-8) and 9 (range 0-15), respectively. In univariate analysis, PR composite score >9 was strongly associated with decreased recurrence-free survival (HR = 2.9, 95% CI = 1.5-5.5) and decreased overall survival (HR = 3.7, CI 1.3-10.2). ER composite score was not a significant predictor of recurrence-free survival or overall survival (p = 0.7, HR = 1.1, 95% CI 0.6-2.0 and p = 0.06, HR = 1.1, 95% CI 0.4-2.9, respectively). CONCLUSIONS: Our results reveal that high PR composite score (≥9) was associated with both decreased recurrence-free and overall survival in patients with GCT while ER expression was not associated with survival outcomes.

Cervical Cancer, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology.

Cervical cancer is a malignant epithelial tumor that forms in the uterine cervix. Most cases of cervical cancer are preventable through human papilloma virus (HPV) vaccination, routine screening, and treatment of precancerous lesions. However, due to inadequate screening protocols in many regions of the world, cervical cancer remains the fourth-most common cancer in women globally. The complete NCCN Guidelines for Cervical Cancer provide recommendations for the diagnosis, evaluation, and treatment of cervical cancer. This manuscript discusses guiding principles for the workup, staging, and treatment of early stage and locally advanced cervical cancer, as well as evidence for these recommendations. For recommendations regarding treatment of recurrent or metastatic disease, please see the full guidelines on NCCN.org.

Gestational Trophoblastic Neoplasia, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Gestational trophoblastic neoplasia (GTN), a subset of gestational trophoblastic disease (GTD), occurs when tumors develop in the cells that would normally form the placenta during pregnancy. The NCCN Guidelines for Gestational Trophoblastic Neoplasia provides treatment recommendations for various types of GTD including hydatidiform mole, persistent post-molar GTN, low-risk GTN, high-risk GTN, and intermediate trophoblastic tumor.

Screening for Asymptomatic Bacteriuria in Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Screening for asymptomatic bacteriuria can identify patients for whom treatment might be beneficial for preventing symptomatic infection and other health outcomes. Objective: To systematically review benefits and harms of asymptomatic bacteriuria screening and treatment in adults, including during pregnancy, to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed (publisher-supplied records), and Cochrane Collaboration Central Registry of Controlled Trials; surveillance through May 24, 2019. Study Selection: Randomized clinical trials (RCTs) and observational studies on benefits and harms of screening for asymptomatic bacteriuria; RCTs on benefits and harms of asymptomatic bacteriuria treatment. Eligible populations included unselected, asymptomatic individuals without known urinary tract conditions. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Random-effects meta-analysis was conducted to estimate benefits of the interventions. Main Outcomes and Measures: Symptomatic infection; function, morbidity, mortality; pregnancy complications and birth outcomes. Results: Nineteen studies (N = 8443) meeting inclusion criteria were identified. Two cohort studies (n = 5289) found fewer cases of pyelonephritis in the cohorts of screened pregnant women (0.5%) than within retrospective comparisons of unscreened cohorts (2.2% and 1.8%); the larger study estimated a statistically significant relative risk of 0.30 (95% CI, 0.15-0.60). No studies examined screening in nonpregnant populations. Among 12 trials of asymptomatic bacteriuria screening and treatment during pregnancy (n = 2377; 1 conducted within past 30 years), there were reduced rates of pyelonephritis (range, 0%-16.5% for the intervention group and 2.2%-36.4% for the control group; pooled risk ratio [RR], 0.24 [95% CI, 0.14-0.40]; 12 trials) and low birth weight (range, 2.5%-14.8% for the intervention group and 6.7%-21.4% for the control group; pooled RR, 0.64 [95% CI, 0.46-0.90]; 7 trials). There was no significant difference in infant mortality (pooled RR, 0.98 [95% CI, 0.29-3.26]; 6 trials). Five RCTs of asymptomatic bacteriuria treatment in nonpregnant adults (n = 777) did not report any significant differences in risk of infection, mobility, or mortality. Limited evidence on harms of screening or treatment was available, and no statistically significant differences were identified. Conclusions and Relevance: Screening and treatment for asymptomatic bacteriuria during pregnancy was associated with reduced rates of pyelonephritis and low birth weights, but the available evidence was not current, with only 1 study conducted in the past 30 years. Benefits of asymptomatic bacteriuria treatment in nonpregnant adult populations were not found. Trial evidence on harms of asymptomatic bacteriuria antibiotic treatment was limited.

Evolving Roles of Histologic Evaluation and Molecular/Genomic Profiling in the Management of Endometrial Cancer.

Endometrial cancers are the most common gynecologic malignancies. The staging of endometrial cancer has evolved from a clinical-based system to a comprehensive surgical-pathologic approach that allows for better risk stratification and treatment planning. Over the past few years, use of NCCN's sentinel lymph node (SLN) mapping algorithm for the surgical staging of endometrial cancer has gained significant acceptance and is now commonly applied in many practices. However, pathologic evaluation of prognostic factors is beset by challenges, including the reproducibility of histologic classification and FIGO's grading, as well as the questionable clinical significance of low-volume tumor in SLNs. With the revelation of major genomic classes of endometrial cancer comes the potential for improved, reproducible, and prognostically relevant classification schemes, which integrate traditional pathologic parameters with genomic findings, to aid in treatment decisions. Pathologic identification of new variants of endometrial cancer, such as undifferentiated carcinoma, continues to advance the phenotypic spectrum of these tumors, spurring genomic and functional studies to further characterize their mechanistic underpinnings and potentially reveal new avenues for treatment. In the era of precision medicine, pathologic assessment of biomarkers (eg, mismatch repair proteins) and recognition of phenotypes that are amenable to specific targeted therapies (such as POLE-mutated tumors) have become integral to the management of women with endometrial carcinoma.

Uterine Neoplasms, Version 1.2018, NCCN Clinical Practice Guidelines in Oncology.

Endometrial carcinoma is a malignant epithelial tumor that forms in the inner lining, or endometrium, of the uterus. Endometrial carcinoma is the most common gynecologic malignancy. Approximately two-thirds of endometrial carcinoma cases are diagnosed with disease confined to the uterus. The complete NCCN Guidelines for Uterine Neoplasms provide recommendations for the diagnosis, evaluation, and treatment of endometrial cancer and uterine sarcoma. This manuscript discusses guiding principles for the diagnosis, staging, and treatment of early-stage endometrial carcinoma as well as evidence for these recommendations.

Screening for Syphilis Infection in Pregnant Women: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: The incidence of syphilis and congenital syphilis in the United States has increased after reaching historic lows in the early 2000s. Objective: To systematically review literature on the effectiveness and harms of screening for syphilis in pregnancy and the harms of penicillin treatment in pregnancy to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant English-language literature, published from January 1, 2008, to June 2, 2017. Ongoing surveillance was conducted through November 22, 2017. Study Selection: Studies conducted in countries categorized as "high" or "very high" on the Human Development Index that explicitly addressed 1 of 3 a priori-defined key questions. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Data from included studies were narratively synthesized without pooling data. Main Outcomes and Measures: Incidence of congenital syphilis; any harms of screening or penicillin treatment in pregnancy. Results: Seven studies in 8 publications were included. One observational study evaluated the implementation of syphilis screening in pregnancy in 2 441 237 women in China. From 2002 to 2012, screening for syphilis in all pregnant women increased from 89.8% to 97.2%, and the incidence of congenital syphilis decreased from 109.3 to 9.4 cases per 100 000 live births. Five studies (n = 21 795) evaluated the false-positive findings of treponemal tests and 1 study (n = 318) evaluated the false-negative findings of nontreponemal tests. These studies found that false-positives with treponemal-specific enzyme or chemiluminescent immunoassays were common (46.5%-88.2%), therefore warranting reflexive (automatic confirmatory) testing for all positive test findings. One study (n = 318) found no false-negatives with treponemal tests, and 1 study (n = 139) demonstrated the prozone phenomenon (false-negative response from high antibody titer) with rapid plasma reagin screening using undiluted samples (2.9%). No studies were identified for harms of penicillin in pregnancy. Conclusions and Relevance: Screening for syphilis infection in pregnant women is associated with reduced incidence of congenital syphilis, and available evidence supports the need for reflexive testing for positive test results.

Screening and Behavioral Counseling Interventions to Reduce Unhealthy Alcohol Use in Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Unhealthy alcohol use is common, increasing, and a leading cause of premature mortality. Objective: To review literature on the effectiveness and harms of screening and counseling for unhealthy alcohol use to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, PsycINFO, and the Cochrane Central Register of Controlled Trials through October 12, 2017; literature surveillance through August 1, 2018. Study Selection: Test accuracy studies and randomized clinical trials of screening and counseling to reduce unhealthy alcohol use. Data Extraction and Synthesis: Independent critical appraisal and data abstraction by 2 reviewers. Counseling trials were pooled using random-effects meta-analyses. Main Outcomes and Measures: Sensitivity, specificity, drinks per week, exceeding recommended limits, heavy use episodes, abstinence (for pregnant women), and other health, family, social, and legal outcomes. Results: One hundred thirteen studies (N = 314 466) were included. No studies examined benefits or harms of screening programs to reduce unhealthy alcohol use. For adolescents (10 studies [n = 171 363]), 1 study (n = 225) reported a sensitivity of 0.73 (95% CI, 0.60 to 0.83) and specificity of 0.81 (95% CI, 0.74 to 0.86) using the AUDIT-C (Alcohol Use Disorders Identification Test-Consumption) to detect the full spectrum of unhealthy alcohol use. For adults (35 studies [n = 114 182]), brief screening instruments commonly reported sensitivity and specificity between 0.70 and 0.85. Two trials of the effects of interventions to reduce unhealthy alcohol use in adolescents (n = 588) found mixed results: one reported a benefit in high-risk but not moderate-risk drinkers, and the other reported a statistically significant reduction in drinking frequency for boys but not girls; neither reported health or related outcomes. Across all populations (68 studies [n = 36 528]), counseling interventions were associated with a decrease in drinks per week (weighted mean difference, -1.6 [95% CI, -2.2 to -1.0]; 32 studies [37 effects; n = 15 974]), the proportion exceeding recommended drinking limits (odds ratio [OR], 0.60 [95% CI, 0.53 to 0.67]; 15 studies [16 effects; n = 9760]), and the proportion reporting a heavy use episode (OR, 0.67 [95% CI, 0.58 to 0.77]; 12 studies [14 effects; n = 8108]), and an increase in the proportion of pregnant women reporting abstinence (OR, 2.26 [95% CI, 1.43 to 3.56]; 5 studies [n = 796]) after 6 to 12 months. Health outcomes were sparsely reported and generally did not demonstrate group differences in effect. There was no evidence that these interventions could be harmful. Conclusions and Relevance: Among adults, screening instruments feasible for use in primary care are available that can effectively identify people with unhealthy alcohol use, and counseling interventions in those who screen positive are associated with reductions in unhealthy alcohol use. There was no evidence that these interventions have unintended harmful effects.

Screening for Syphilis Infection in Nonpregnant Adults and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

This systematic review to support the 2022 US Preventive Services Task Force Recommendation Statement on screening for syphilis infection summarizes published evidence on the benefits and harms of screening for syphilis infection in asymptomatic, nonpregnant adults and adolescents at increased risk for syphilis infection.

Prognostic significance of differential expression of angiogenic genes in women with high-grade serous ovarian carcinoma.

OBJECTIVES: To identify angiogenic biomarkers associated with tumor angiogenesis and clinical outcome in high-grade serous ovarian cancer (HGSC). METHODS: 51 HGSC samples were analyzed using Affymetrix HG-U133A microarray. Microvessel density (MVD) counts were determined using CD31 and CD105. Associations between mRNA expression levels and overall survival were assessed using rank score statistic. Effect size was estimated as a hazard ratio (HR) under a proportional hazard model. The Storey q-value method was used to account for multiple testing within the false-discovery rate (FDR) framework. Publicly available databases including TCGA and GSE were used for external confirmation. RESULTS: Thirty-one angiogenic-related genes were significantly associated with survival (q≤0.05). Of these 31 genes, 4 were also associated with outcome in the TCGA data: AKT1 (q=0.02; TCGA p=0.01, HR=0.8), CD44 (q=0.003; TCGA p=0.05, HR=0.9), EPHB2 (q=0.01; TCGA p=0.05, HR=1.2), and ERBB2 (q=0.02; TCGA p=0.05, HR=1.2). While 5 were associated with outcome in the GSE database: FLT1 (q=0.03; GSE26712 p=0.01, HR=3.1); PF4 (q=0.02; GSE26712 p=0.01, HR=3.0); NRP1 (q=0.02; GSE26712 p<0.04, HR>1.4); COL4A3 (q=0.04; GSE26712 p=0.03, HR=1.3); and ANGPTL3 (q=0.02; GSE14764 p=0.02, HR=1.5). High AKT1 and CD44 were associated with longer survival. In contrast, high expression of EPHB2, ERBB2, FLT1; PF4, NRP1, COL4A3, and ANGPTL3 were associated with shorter survival. CD105-MVD and CD31-MVD were not significantly associated with angiogenic gene expression. CONCLUSIONS: Thirty-one angiogenic-related genes were associated with survival in advanced HGSC and nine of these genes were confirmed in independent publicly available databases.

Relationship between minimally invasive hysterectomy, pelvic cytology, and lymph vascular space invasion: a single institution study of 458 patients.

OBJECTIVE: The aim of this study is to determine whether a minimally invasive approach to hysterectomy is associated with an increased rate of lymph vascular space invasion (LVSI) and/or malignant pelvic peritoneal cytology in endometrial cancer. METHODS: We performed a single institution analysis of 458 women with endometrial cancer who underwent either total abdominal hysterectomy (TAH) or minimally invasive hysterectomy (MIH) with use of a disposable uterine manipulator. All patients had endometrial cancer diagnosed by endometrial biopsy at a single academic institution between 2002 and 2012. Exclusion criteria were pre-operative D&C and/or hysteroscopy, uterine perforation or morcellation, and conversion to laparotomy. Multivariate logistic regression models to determine if type of hysterectomy predicts either LVSI or presence of abnormal cytology were controlled for grade, stage, depth of invasion, tumor size, cervical and adnexal involvement. RESULTS: LVSI was identified in 39/214 (18%) MIH and 44/242 (18%) TAH (p=0.99). Pelvic washings were malignant in 14/203 (7%) MIH and 16/241 (7%) TAH (p=1.0). Washings were atypical or inconclusive in 16/203 (8%) MIH and 6/241 (2.5%) TAH (p=0.014). In multivariate analyses, type of hysterectomy was not a significant predictor of either LVSI (p=0.29) or presence of malignant washings (p=0.66), but was a predictor of atypical or inconclusive washings (p=0.03). CONCLUSION: Minimally invasive hysterectomy with use of a uterine manipulator for endometrial cancer is not associated with LVSI or malignant cytology. Algorithms that better determine the etiology and implications of inconclusive or atypical pelvic cytology are needed to inform the possible additional risk associated with a minimally invasive approach to endometrial cancer.

Obesity is associated with worse overall survival in women with low-grade papillary serous epithelial ovarian cancer.

OBJECTIVE: The objective of this study was to evaluate prognostic risk factors for survival in women with low-grade serous epithelial ovarian cancer (LGSC). METHODS: A multicenter retrospective analysis of patients with LGSC was conducted. Potential epidemiologic risk factors evaluated included obesity, age, parity, race, smoking, oral contraceptive pill and/or hormonal replacement therapy use, and previous hysterectomy or surgery on fallopian tubes and/or ovaries. Additional factors included stage, extent of debulking, residual disease, and disease status. RESULTS: Eighty-one patients were identified, and pathologic diagnosis was independently confirmed. Median age at diagnosis was 56 years (range, 21-86 years). Thirty-four percent were obese, and 80% had optimally debulked disease. Forty-six percent were alive, 14% with disease, whereas 25% were dead of disease, 2% died of intercurrent disease, and 27% had an unknown status. In a univariate analysis, optimal surgical debulking was associated with improved progression-free survival (P = 0.01), disease-specific survival (P = 0.03), and overall survival (OS) (P < 0.001) and body mass index with worse OS (P = 0.05). On multivariate analysis, obesity (hazard ratio, 2.8; 95% confidence interval, 1.05-7.3; P = 0.04) and optimal tumor debulking (hazard ratio, 0.05; 95% confidence interval, 0.008-0.29; P = 0.001) were a significant predictor of OS. CONCLUSIONS: In a multivariate analysis, obesity and optimal tumor cytoreduction were significant predictors of OS. However, obesity was not associated with worse disease-specific survival, suggesting that mortality of obese patients with LGSC may result from other comorbidities. Interventions addressing obesity may improve survival for women diagnosed with LGSC, and further study is warranted to address the role of obesity in LGSC.

Lesions of the Bartholin gland: a review.

Most lesions of the Bartholin gland are cysts or abscesses. Clinicians are taught that lesions of the Bartholin gland occurring in older women should raise the differential diagnosis of malignancy, although these are uncommon. A variety of more unusual and rare lesions of the Bartholin gland have been reported. This review focuses on these less common entities, which must be considered as well when encountering pathology of the Bartholin gland.