Screening for Cervical Cancer With High-Risk Human Papillomavirus Testing: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Cervical cancer can be prevented with detection and treatment of precancerous cell changes caused primarily by high-risk types of human papillomavirus (hrHPV), the causative agents in more than 90% of cervical cancers. Objective: To systematically review benefits and harms of cervical cancer screening for hrHPV to inform the US Preventive Services Task Force. Data Sources: MEDLINE, PubMed, PsycINFO, and the Cochrane Collaboration Registry of Controlled Trials from January 2011 through February 15, 2017; surveillance through May 25, 2018. Study Selection: Randomized clinical trials (RCTs) and cohort studies comparing primary hrHPV screening alone or hrHPV cotesting (both hrHPV testing and cytology) with cytology (Papanicolaou [Pap] test) screening alone. Data Extraction and Synthesis: Two investigators independently reviewed abstracts and full-text articles and quality rated included studies; data were qualitatively synthesized. Main Outcomes and Measures: Invasive cervical cancer; cervical intraepithelial neoplasia (CIN); false-positive, colposcopy, and biopsy rates; psychological harms. Results: Eight RCTs (n = 410 556), 5 cohort studies (n = 402 615), and 1 individual participant data (IPD) meta-analysis (n = 176 464) were included. Trials were heterogeneous for screening interval, number of rounds, and protocol. For primary hrHPV screening, evidence was consistent across 4 trials demonstrating increased detection of CIN 3 or worse (CIN 3+) in round 1 (relative risk [RR] range, 1.61 [95% CI, 1.09-2.37] to 7.46 [95% CI, 1.02-54.66]). Among 4 hrHPV cotesting trials, first-round CIN 3+ detection was not significantly different between screening groups; RRs for cumulative CIN 3+ detection over 2 screening rounds ranged from 0.91 to 1.13. In first-round screening, false-positive rates for primary hrHPV screening ranged from 6.6% to 7.4%, compared with 2.6% to 6.5% for cytology. For cotesting, false-positives ranged from 5.8% to 19.9% in the first round of screening, compared with 2.6% to 10.9% for cytology. First-round colposcopy rates were also higher, ranging 1.2% to 7.9% for primary hrHPV testing, compared with 1.1% to 3.1% for cytology alone; colposcopy rates for cotesting ranged from 6.8% to 10.9%, compared with 3.3% to 5.2% for cytology alone. The IPD meta-analysis of data from 4 cotesting trials and 1 primary hrHPV screening trial found lower risk of invasive cervical cancer with any hrHPV screening compared with cytology alone (pooled RR, 0.60 [95% CI, 0.40-0.89]). Conclusions and Relevance: Primary hrHPV screening detected higher rates of CIN 3+ at first-round screening compared with cytology. Cotesting trials did not show initial increased CIN 3+ detection. Both hrHPV screening strategies had higher false-positive and colposcopy rates than cytology, which could lead to more treatments with potential harms.

Bleeding Risks With Aspirin Use for Primary Prevention in Adults: A Systematic Review for the U.S. Preventive Services Task Force.

BACKGROUND: The balance between potential aspirin-related risks and benefits is critical in primary prevention. PURPOSE: To evaluate the risk for serious bleeding with regular aspirin use in cardiovascular disease (CVD) primary prevention. DATA SOURCES: PubMed, MEDLINE, Cochrane Central Register of Controlled Trials (2010 through 6 January 2015), and relevant references from other reviews. STUDY SELECTION: Randomized, controlled trials; cohort studies; and meta-analyses comparing aspirin with placebo or no treatment to prevent CVD or cancer in adults. DATA EXTRACTION: One investigator abstracted data, another checked for accuracy, and 2 assessed study quality. DATA SYNTHESIS: In CVD primary prevention studies, very-low-dose aspirin use (≤100 mg daily or every other day) increased major gastrointestinal (GI) bleeding risk by 58% (odds ratio [OR], 1.58 [95% CI, 1.29 to 1.95]) and hemorrhagic stroke risk by 27% (OR, 1.27 [CI, 0.96 to 1.68]). Projected excess bleeding events with aspirin depend on baseline assumptions. Estimated excess major bleeding events were 1.39 (CI, 0.70 to 2.28) for GI bleeding and 0.32 (CI, -0.05 to 0.82) for hemorrhagic stroke per 1000 person-years of aspirin exposure using baseline bleeding rates from a community-based observational sample. Such events could be greater among older persons, men, and those with CVD risk factors that also increase bleeding risk. LIMITATIONS: Power to detect effects on hemorrhagic stroke was limited. Harms other than serious bleeding were not examined. CONCLUSION: Consideration of the safety of primary prevention with aspirin requires an individualized assessment of aspirin's effects on bleeding risks and expected benefits because absolute bleeding risk may vary considerably by patient. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Aspirin for the Prevention of Cancer Incidence and Mortality: Systematic Evidence Reviews for the U.S. Preventive Services Task Force.

BACKGROUND: Cancer is the second leading cause of death in the United States. PURPOSE: To conduct systematic reviews of aspirin and 1) total cancer mortality and incidence in persons eligible for primary prevention of cardiovascular disease (CVD) and 2) colorectal cancer (CRC) mortality and incidence in persons at average CRC risk. DATA SOURCES: MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials through January 2015 and relevant references from other reviews. STUDY SELECTION: Trials comparing oral aspirin versus placebo or no treatment in adults aged 40 years or older were included. Two investigators independently reviewed abstracts and articles against inclusion and quality criteria. DATA EXTRACTION: Data from 20 good- or fair-quality trials were abstracted by one reviewer and checked by another. DATA SYNTHESIS: In CVD primary prevention trials, cancer mortality (relative risk [RR], 0.96 [95% CI, 0.87 to 1.06]) (10 trials; n = 103 787) and incidence (RR, 0.98 [CI, 0.93 to 1.04]) (6 trials; n = 72 926) were similar in aspirin and control groups over 3.6 to 10.1 years. In CVD primary and secondary prevention trials, 20-year CRC mortality was reduced among persons assigned to aspirin therapy (RR, 0.67 [CI, 0.52 to 0.86]) (4 trials; n = 14 033). Aspirin appeared to reduce CRC incidence beginning 10 to 19 years after initiation (RR, 0.60 [CI, 0.47 to 0.76]) (3 trials; n = 47 464). LIMITATIONS: Most data were from clinically and methodologically heterogeneous CVD prevention trials. Outcome assessment and follow-up length varied across studies. Data on non-CRC cancer types and subgroups were limited. CONCLUSION: In CVD primary prevention populations, aspirin's effect on total cancer mortality and incidence was not clearly established. Evidence from CVD primary and secondary prevention studies suggested that aspirin therapy reduces CRC incidence and perhaps mortality approximately 10 years after initiation. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Preeclampsia Screening: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Preeclampsia is a complex disease of pregnancy with sometimes serious effects on maternal and infant morbidity and mortality. It is defined by hypertension after 20 weeks' gestation and proteinuria or other evidence of multisystem involvement. OBJECTIVE: To systematically review the benefits and harms of preeclampsia screening and risk assessment for the US Preventive Services Task Force. DATA SOURCES: MEDLINE, PubMed, and Cochrane Central Register of Controlled Trials databases from 1990 through September 1, 2015. Surveillance for new evidence in targeted publications was conducted through October 5, 2016. STUDY SELECTION: English-language trials and observational studies, including externally validated prediction models, of screening effectiveness, benefits, and harms from routine preeclampsia screening during pregnancy. DATA EXTRACTION AND SYNTHESIS: Independent dual review of article abstracts and full texts against a priori inclusion criteria. Meta-analysis was not performed because of clinical and statistical heterogeneity of included studies. MAIN OUTCOMES AND MEASURES: Maternal and infant health outcomes, including eclampsia, stroke, stillbirth, preterm birth, and low birth weight; screening and risk prediction test performance; harms of screening and risk assessment. RESULTS: Twenty-one studies (13 982 participants) were included. No studies directly compared the effectiveness of preeclampsia screening in a screened population vs an unscreened population; 1 US trial (n = 2764) found no difference in benefits or harms with fewer prenatal visits but was underpowered for rare, serious outcomes. For harms, a before-after comparison cohort noninferiority study of urine protein screening for specific indications compared with routine screening (n = 1952) did not identify harms with fewer urine screening tests. Four studies (n = 7123) reported external validation performance of 16 risk prediction models, 5 of which had good or better discrimination (c statistic >0.80) for prediction of preeclampsia, and positive predictive values of 4% in the largest, most applicable validation cohorts. Calibration was not reported despite being a key model performance measure. There were no studies of urine screening test performance conducted in asymptomatic primary care populations; 14 studies of protein urine test performance among women being evaluated for suspected preeclampsia (n = 1888) had wide-ranging test accuracy (sensitivity, 22%-100%; specificity, 36%-100%) and high statistical and clinical heterogeneity in tests used, eligibility criteria, and proteinuria prevalence (8.7%-93.8%). CONCLUSIONS AND RELEVANCE: Evidence to estimate benefits and harms of preeclampsia screening and the test performance of different screening approaches over the course of pregnancy was limited. Externally validated risk prediction models had limited applicability and lacked calibration and clinical implementation data needed to support routine use. Further research is needed to better inform risk-based screening approaches and improve screening strategies, given the complex pathophysiology and clinical unpredictability of preeclampsia.

Screening for Obesity and Intervention for Weight Management in Children and Adolescents: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Obesity is common in children and adolescents in the United States, is associated with negative health effects, and increases the likelihood of obesity in adulthood. OBJECTIVE: To systematically review the benefits and harms of screening and treatment for obesity and overweight in children and adolescents to inform the US Preventive Services Task Force. DATA SOURCES: MEDLINE, PubMed, PsycINFO, Cochrane Collaboration Registry of Controlled Trials, and the Education Resources Information Center through January 22, 2016; references of relevant publications; government websites. Surveillance continued through December 5, 2016. STUDY SELECTION: English-language trials of benefits or harms of screening or treatment (behavior-based, orlistat, metformin) for overweight or obesity in children aged 2 through 18 years, conducted in or recruited from health care settings. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles, then extracted data from fair- and good-quality trials. Random-effects meta-analysis was used to estimate the benefits of lifestyle-based programs and metformin. MAIN OUTCOMES AND MEASURES: Weight or excess weight (eg, body mass index [BMI]; BMI z score, measuring the number of standard deviations from the median BMI for age and sex), cardiometabolic outcomes, quality of life, other health outcomes, harms. RESULTS: There was no direct evidence on the benefits or harms of screening children and adolescents for excess weight. Among 42 trials of lifestyle-based interventions to reduce excess weight (N = 6956), those with an estimated 26 hours or more of contact consistently demonstrated mean reductions in excess weight compared with usual care or other control groups after 6 to 12 months, with no evidence of causing harm. Generally, intervention groups showed absolute reductions in BMI z score of 0.20 or more and maintained their baseline weight within a mean of approximately 5 lb, while control groups showed small increases or no change in BMI z score, typically gaining a mean of 5 to 17 lb. Only 3 of 26 interventions with fewer contact hours showed a benefit in weight reduction. Use of metformin (8 studies, n = 616) and orlistat (3 studies, n = 779) were associated with greater BMI reductions compared with placebo: -0.86 (95% CI, -1.44 to -0.29; 6 studies; I2 = 0%) for metformin and -0.50 to -0.94 for orlistat. Groups receiving lifestyle-based interventions offering 52 or more hours of contact showed greater improvements in blood pressure than control groups: -6.4 mm Hg (95% CI, -8.6 to -4.2; 6 studies; I2 = 51%) for systolic blood pressure and -4.0 mm Hg (95% CI, -5.6 to -2.5; 6 studies; I2 = 17%) for diastolic blood pressure. There were mixed findings for insulin or glucose measures and no benefit for lipids. Medications showed small or no benefit for cardiometabolic outcomes, including fasting glucose level. Nonserious harms were common with medication use, although discontinuation due to adverse effects was usually less than 5%. CONCLUSIONS AND RELEVANCE: Lifestyle-based weight loss interventions with 26 or more hours of intervention contact are likely to help reduce excess weight in children and adolescents. The clinical significance of the small benefit of medication use is unclear.

Diagnostic and predictive accuracy of blood pressure screening methods with consideration of rescreening intervals: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Elevated blood pressure (BP) is the largest contributing risk factor to all-cause and cardiovascular mortality. PURPOSE: To update a systematic review on the benefits and harms of screening for high BP in adults and to summarize evidence on rescreening intervals and diagnostic and predictive accuracy of different BP methods for cardiovascular events. DATA SOURCES: Selected databases searched through 24 February 2014. STUDY SELECTION: Fair- and good-quality trials and diagnostic accuracy and cohort studies conducted in adults and published in English. DATA EXTRACTION: One investigator abstracted data, and a second checked for accuracy. Study quality was dual-reviewed. DATA SYNTHESIS: Ambulatory BP monitoring (ABPM) predicted long-term cardiovascular outcomes independently of office BP (hazard ratio range, 1.28 to 1.40, in 11 studies). Across 27 studies, 35% to 95% of persons with an elevated BP at screening remained hypertensive after nonoffice confirmatory testing. Cardiovascular outcomes in persons who were normotensive after confirmatory testing (isolated clinic hypertension) were similar to outcomes in those who were normotensive at screening. In 40 studies, hypertension incidence after rescreening varied considerably at each yearly interval up to 6 years. Intrastudy comparisons showed at least 2-fold higher incidence in older adults, those with high-normal BP, overweight and obese persons, and African Americans. LIMITATION: Few diagnostic accuracy studies of office BP methods and protocols in untreated adults. CONCLUSION: Evidence supports ABPM as the reference standard for confirming elevated office BP screening results to avoid misdiagnosis and overtreatment of persons with isolated clinic hypertension. Persons with BP in the high-normal range, older persons, those with an above-normal body mass index, and African Americans are at higher risk for hypertension on rescreening within 6 years than are persons without these risk factors. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Primary Care Screening for and Treatment of Depression in Pregnant and Postpartum Women: Evidence Report and Systematic Review for the US Preventive Services Task Force.

IMPORTANCE: Depression is a source of substantial burden for individuals and their families, including women during the pregnant and postpartum period. OBJECTIVE: To systematically review the benefits and harms of depression screening and treatment, and accuracy of selected screening instruments, for pregnant and postpartum women. Evidence for depression screening in adults in general is available in the full report. DATA SOURCES: MEDLINE, PubMed, PsycINFO, and the Cochrane Collaboration Registry of Controlled Trials through January 20, 2015; references; and government websites. STUDY SELECTION: English-language trials of benefits and harms of depression screening, depression treatment in pregnant and postpartum women with screen-detected depression, and diagnostic accuracy studies of depression screening instruments in pregnant and postpartum women. DATA EXTRACTION AND SYNTHESIS: Two investigators independently reviewed abstracts and full-text articles and extracted data from fair- and good-quality studies. Random-effects meta-analysis was used to estimate the benefit of cognitive behavioral therapy (CBT) in pregnant and postpartum women. MAIN OUTCOMES AND MEASURES: Depression remission, prevalence, symptoms, and related measures of depression recovery or response; sensitivity and specificity of selected screening measures to detect depression; and serious adverse effects of antidepressant treatment. RESULTS: Among pregnant and postpartum women 18 years and older, 6 trials (n = 11,869) showed 18% to 59% relative reductions with screening programs, or 2.1% to 9.1% absolute reductions, in the risk of depression at follow-up (3-5 months) after participation in programs involving depression screening, with or without additional treatment components, compared with usual care. Based on 23 studies (n = 5398), a cutoff of 13 on the English-language Edinburgh Postnatal Depression Scale demonstrated sensitivity ranging from 0.67 (95% CI, 0.18-0.96) to 1.00 (95% CI, 0.67-1.00) and specificity consistently 0.87 or higher. Data were sparse for Patient Health Questionnaire instruments. Pooled results for the benefit of CBT for pregnant and postpartum women with screen-detected depression showed an increase in the likelihood of remission (pooled relative risk, 1.34 [95% CI, 1.19-1.50]; No. of studies [K] = 10, I2 = 7.9%) compared with usual care, with absolute increases ranging from 6.2% to 34.6%. Observational evidence showed that second-generation antidepressant use during pregnancy may be associated with small increases in the risks of potentially serious harms. CONCLUSIONS AND RELEVANCE: Direct and indirect evidence suggested that screening pregnant and postpartum women for depression may reduce depressive symptoms in women with depression and reduce the prevalence of depression in a given population. Evidence for pregnant women was sparser but was consistent with the evidence for postpartum women regarding the benefits of screening, the benefits of treatment, and screening instrument accuracy.

Primary care behavioral interventions to prevent or reduce illicit drug use and nonmedical pharmaceutical use in children and adolescents: a systematic evidence review for the U.S. Preventive Services Task Force.

BACKGROUND: Drug use among youths is associated with negative health and social consequences. Even infrequent use increases the risk for serious adverse events by increasing risk-taking behaviors in intoxicated or impaired persons. PURPOSE: To systematically review the benefits and harms of primary care-relevant interventions designed to prevent or reduce illicit drug use or the nonmedical use of prescription drugs among youths. DATA SOURCES: PubMed, PsycINFO, and the Cochrane Central Register of Controlled Trials through 4 June 2013; MEDLINE through 31 August 2013; and manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently reviewed 2253 abstracts and 144 full-text articles. English-language trials of primary care-relevant behavioral interventions that reported drug use, health outcomes, or harms were included. DATA EXTRACTION: One investigator abstracted data from good- and fair-quality trials into prespecified evidence tables, and a second investigator checked these data. DATA SYNTHESIS: Six trials were included, 4 of which examined the effect of the intervention on a health or social outcome. One trial found no effect of the intervention on marijuana-related consequences or driving under the influence of marijuana; 3 trials generally found no reduction in depressed mood at 12 or 24 months. Four of the 5 trials assessing self-reported marijuana use found statistically significant differences favoring the intervention group participants (such as a between-group difference of 0.10 to 0.17 use occasions in the past month). Three trials also reported positive outcomes in nonmedical prescription drug use occasions. LIMITATIONS: The body of evidence was small, and there were heterogeneous measures of outcomes of limited clinical applicability. Trials primarily included adolescents with little or no substance use. CONCLUSION: Evidence is inadequate on the benefits of primary care-relevant behavioral interventions in reducing self-reported illicit and pharmaceutical drug use among adolescents. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Behavioral sexual risk-reduction counseling in primary care to prevent sexually transmitted infections: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Sexually transmitted infections (STIs) are common and preventable. PURPOSE: To update a previous systematic review about the benefits and harms of sexual risk-reduction counseling to prevent STIs for the U.S. Preventive Services Task Force. DATA SOURCES: Selected databases from January 2007 through October 2013, manual searches of references lists and gray literature, and studies from the previous review. STUDY SELECTION: English-language fair- or good-quality trials conducted in adolescents or adults. DATA EXTRACTION: One investigator abstracted data and a second checked the abstraction. Study quality was dual-reviewed. DATA SYNTHESIS: 31 trials were included: 16 (n=56,110) were newly published and 15 (n=14,214) were from the previous review. Most trials targeted persons at increased risk for STIs based on sociodemographic characteristics, risky sexual behavior, or history of an STI. High-intensity (>2 hours) interventions reduced STI incidence in adolescents (odds ratio, 0.38 [95% CI, 0.24 to 0.60]) and adults (odds ratio, 0.70 [CI, 0.56 to 0.87]). Lower-intensity interventions were generally not effective in adults, but some approaches were promising. Although moderate-intensity interventions may be effective in adolescents, data were very sparse. Reported behavioral outcomes were heterogeneous and most likely to show a benefit with high-intensity interventions at 6 months or less. No consistent evidence was found that sexual risk-reduction counseling was harmful. LIMITATIONS: Low-risk populations and male adolescents were underrepresented. Reliability of self-reported behavioral outcomes was unknown. CONCLUSION: High-intensity counseling on sexual risk reduction can reduce STIs in primary care and related settings, especially in sexually active adolescents and in adults at increased risk for STIs. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Vitamin and mineral supplements in the primary prevention of cardiovascular disease and cancer: An updated systematic evidence review for the U.S. Preventive Services Task Force.

BACKGROUND: Vitamin and mineral supplements are commonly used to prevent chronic diseases. PURPOSE: To systematically review evidence for the benefit and harms of vitamin and mineral supplements in community-dwelling, nutrient-sufficient adults for the primary prevention of cardiovascular disease (CVD) and cancer. DATA SOURCES: MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Database of Abstracts of Reviews of Effects were searched from January 2005 to 29 January 2013, with manual searches of reference lists and gray literature. STUDY SELECTION: Two investigators independently selected and reviewed fair- and good-quality trials for benefit and fair- and good-quality trials and observational studies for harms. DATA EXTRACTION: Dual quality assessments and data abstraction. DATA SYNTHESIS: Two large trials (n = 27 658) reported lower cancer incidence in men taking a multivitamin for more than 10 years (pooled unadjusted relative risk, 0.93 [95% CI, 0.87 to 0.99]). The study that included women showed no effect in that group. High-quality studies (k = 24; n = 324 653) of single and paired nutrients (such as vitamins A, C, or D; folic acid; selenium; or calcium) were scant and heterogeneous and showed no clear evidence of benefit or harm. Neither vitamin E nor ß-carotene prevented CVD or cancer, and ß-carotene increased lung cancer risk in smokers. LIMITATIONS: The analysis included only primary prevention studies in adults without known nutritional deficiencies. Studies were conducted in older individuals and included various supplements and doses under the set upper tolerable limits. Duration of most studies was less than 10 years. CONCLUSION: Limited evidence supports any benefit from vitamin and mineral supplementation for the prevention of cancer or CVD. Two trials found a small, borderline-significant benefit from multivitamin supplements on cancer in men only and no effect on CVD. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Screening for and treatment of suicide risk relevant to primary care: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: In 2009, suicide accounted for 36 897 deaths in the United States. PURPOSE: To review the accuracy of screening instruments and the efficacy and safety of screening for and treatment of suicide risk in populations and settings relevant to primary care. DATA SOURCES: Citations from MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, and CINAHL (2002 to 17 July 2012); gray literature; and a surveillance search of MEDLINE for additional screening trials (July to December 2012). STUDY SELECTION: Fair- or good-quality English-language studies that assessed the accuracy of screening instruments in primary care or similar populations and trials of suicide prevention interventions in primary or mental health care settings. DATA EXTRACTION: One investigator abstracted data; a second checked the abstraction. Two investigators rated study quality. DATA SYNTHESIS: Evidence was insufficient to determine the benefits of screening in primary care populations; very limited evidence identified no serious harms. Minimal evidence suggested that screening tools can identify some adults at increased risk for suicide in primary care, but accuracy was lower in studies of older adults. Minimal evidence limited to high-risk populations suggested poor performance of screening instruments in adolescents. Trial evidence showed that psychotherapy reduced suicide attempts in high-risk adults but not adolescents. Most trials were insufficiently powered to detect effects on deaths. LIMITATION: Treatment evidence was derived from high-risk rather than screening-detected populations. Evidence relevant to adolescents, older adults, and racial or ethnic minorities was limited. CONCLUSION: Primary care-feasible screening tools might help to identify some adults at increased risk for suicide but have limited ability to detect suicide risk in adolescents. Psychotherapy may reduce suicide attempts in some high-risk adults, but effective interventions for high-risk adolescents are not yet proven. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Risk factors and other epidemiologic considerations for cervical cancer screening: a narrative review for the U.S. Preventive Services Task Force.

Despite the success of cervical cancer screening programs, questions remain about the appropriate time to begin and end screening. This review explores epidemiologic and contextual data on cervical cancer screening to inform decisions about when screening should begin and end. Cervical cancer is rare among women younger than 20 years. Screening for cervical cancer in this age group is complicated by lower rates of detection and higher rates of false-positive results than in older women. Methods used to diagnose and treat cervical intraepithelial neoplasia have important potential adverse effects. High-risk human papillomavirus infections and abnormalities on cytologic and histologic examination have relatively high rates of regression. Accordingly, cervical cancer screening in women younger than 20 years may be harmful. The incidence of, and mortality rates from, cervical cancer and the proportion of U.S. women aged 65 years or older who have had a Papanicolaou smear within 3 years have decreased since 2000. Available evidence supports discontinuation of cervical cancer screening among women aged 65 years or older who have had adequate screening and are not otherwise at high risk. Further reductions in the burden of cervical cancer in older women are probably best achieved by focusing on screening those who have not been adequately screened.

Liquid-based cytology and human papillomavirus testing to screen for cervical cancer: a systematic review for the U.S. Preventive Services Task Force.

BACKGROUND: Screening programs using conventional cytology have successfully reduced cervical cancer, but newer tests might enhance screening. PURPOSE: To systematically review the evidence on liquid-based cytology (LBC) and high-risk human papillomavirus (HPV) screening for U.S. Preventive Services Task Force use in updating its 2003 recommendation. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, and PsycINFO from January 2000 through September 2010. STUDY SELECTION: Two independent reviewers selected fair- to good-quality English-language studies that compared LBC or HPV-enhanced primary screening with conventional cytology in countries with developed population-based screening for cervical cancer. DATA EXTRACTION: At least 2 independent reviewers critically appraised and rated the quality of studies and used standardized abstraction forms to extract data about test performance for detecting cervical intraepithelial neoplasia (CIN) and cancer and screening-related harms. DATA SYNTHESIS: On the basis of 4 fair- to good-quality studies (141 566 participants), LBC had equivalent sensitivity and specificity to conventional cytology. Six fair- to good-quality diagnostic accuracy studies showed that 1-time HPV screening was more sensitive than cytology for detecting CIN3+/CIN2+ but was less specific. On the basis of 2 fair- to good-quality randomized, controlled trials (RCTs) (120 533 participants), primary HPV screening detected more cases of CIN3 or cancer in women older than 30 years. Four fair- to good-quality diagnostic accuracy studies and 4 fair- to good-quality RCTs showed mixed results of cotesting (HPV plus cytology) in women aged 30 years or older compared with cytology alone, with no clear advantage over primary HPV screening. Incomplete reporting of results for all screening rounds, including detection of disease and colposcopies, limits our ability to determine the net benefit of HPV-enhanced testing strategies. LIMITATION: Resources were insufficient to gather unpublished data, short-term trial data showed possible ascertainment bias, and most RCTs used protocols that differed from current U.S. practice. CONCLUSION: Evidence supports the use of LBC or conventional cytology for cervical cancer screening, but more complete evidence is needed before HPV-enhanced primary screening is widely adopted for women aged 30 years or older.

Characteristics of physicians receiving large payments from pharmaceutical companies and the accuracy of their disclosures in publications: an observational study.

BACKGROUND: Financial relationships between physicians and industry are extensive and public reporting of industry payments to physicians is now occurring. Our objectives were to describe physician recipients of large total payments from these seven companies, and to examine discrepancies between these payments and conflict of interest (COI) disclosures in authors' concurrent publications. METHODS: The investigative journalism organization, ProPublica, compiled the Dollars for Docs database of payments to individuals from publically available data from seven US pharmaceutical companies during the period 2009 to 2010. We examined the cohort of 373 physicians in this database who each received USD $100,000 or more in the reporting period 2009 to 2010. RESULTS: These physicians received a total of $52,600,624 during this period (mean payment per physician $141,020). The predominant specialties were internal medicine and psychiatry. 147 of these physicians authored a total of 134 publications in the first quarter of 2011 and 77% (103) of these publications provided a COI disclosure. 69% of the 103 publications did not contain disclosures of the payment listed in the Dollars for Docs database. CONCLUSIONS: With increased public reporting of industry payments to physicians, it is apparent that large sums are being paid for services such as consulting and peer education. In over two-thirds of publications where COI disclosures were provided, the disclosures by physician authors did not include industry payments that were documented in the Dollars for Docs database.

Estimating data from figures with a Web-based program: Considerations for a systematic review.

BACKGROUND: Systematic reviewers often encounter incomplete or missing data, and the information desired may be difficult to obtain from a study author. Thus, systematic reviewers may have to resort to estimating data from figures with little or no raw data in a study's corresponding text or tables. METHODS: We discuss a case study in which participants used a publically available Web-based program, called webplotdigitizer, to estimate data from 2 figures. We evaluated and used the intraclass coefficient and the accuracy of the estimates to the true data to inform considerations when using estimated data from figures in systematic reviews. RESULTS: The estimates for both figures were consistent, although the distribution of estimates in the figure of a continuous outcome was slightly higher. For the continuous outcome, the percent difference ranged from 0.23% to 30.35% while the percent difference of the event rate ranged from 0.22% to 8.92%. For both figures, the intraclass coefficient was excellent (>0.95). CONCLUSIONS: Systematic reviewers should consider and be transparent when estimating data from figures when the information cannot be obtained from study authors and perform sensitivity analyses of pooled results to reduce bias.

Limitations of A Measurement Tool to Assess Systematic Reviews (AMSTAR) and suggestions for improvement.

A Measurement Tool to Assess Systematic Reviews (AMSTAR) is a commonly used tool to assess the quality of systematic reviews; however, modifications are needed to improve its usability, reliability, and validity. In this commentary, we summarize our experience and the experiences of others who have used AMSTAR and provide suggestions for its improvement. We propose that AMSTAR should modify a number of individual items and their instructions and responses to make them more congruent with an assessment of the methodologic quality of systematic reviews. We recommend adding new items and modifying existing items to assess the quality of the body of evidence and to address subgroup and sensitivity analyses. More detailed instructions are needed for scoring individual items across multiple reviewers, and we recommend that a total score should not be calculated. These suggestions need to be empirically tested prior to implementation.

Conflicts of interest among authors of clinical practice guidelines for glycemic control in type 2 diabetes mellitus.

BACKGROUND: Conflict of interest (COI) is an important potential source of bias in the development of clinical practice guidelines (CPGs). OBJECTIVES: To examine rates of disclosure of COI, including financial interests in companies that manufacture drugs that are recommended in CPGs on glycemic control in type 2 diabetes mellitus, and to explore the relationship between recommendations for specific drugs in a guideline and author COI. METHODS: We identified a cohort of relevant guidelines from the National Guideline Clearinghouse (NGC) and abstracted COI disclosures from all guideline authors for this observational, cross-sectional study. We determined which hypoglycemic drugs were recommended in each guideline, and explored the relationship between specific disclosures and whether a drug was recommended. RESULTS: Among 13 included guidelines, the percentage of authors with one or more financial disclosures varied from 0 to 94% (mean 44.2%), and was particularly high for two US-based guidelines (91% and 94%). Three guidelines disclosed no author financial COI. The percentage of authors with disclosures of financial interests in manufacturers of recommended drugs was also high (mean 30%). On average, 56% of manufacturers of patented drugs recommended in each guideline had one or more authors with a financial interest in their company. We did not find a significant relationship between financial interests and whether a drug was recommended in our sample; US-based guidelines were more likely to make recommendations for a specific drug compared to non-US based guidelines. DISCUSSION: Authors of this cohort of guidelines have financial interests directly related to the drugs that they are recommending. Although we did not find an association between author COI and drugs recommended in these guidelines and we cannot draw conclusions about the validity of the recommendations, the credibility of many of these guidelines is in doubt.

Quality of clinical practice guidelines for glycemic control in type 2 diabetes mellitus.

BACKGROUND: Several studies have reported that clinical practice guidelines (CPGs) in a variety of clinical areas are of modest or variable quality. The objective of this study was to evaluate the quality of an international cohort of CPGs that provide recommendations on pharmaceutical management of glycemic control in patients with type 2 diabetes mellitus (DM2). METHODS AND FINDINGS: We searched the National Guideline Clearinghouse (NGC) on February 15th and June 4th, 2012 for CPGs meeting inclusion criteria. Two independent assessors rated the quality of each CPG using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. Twenty-four guidelines were evaluated, and most had high scores for clarity and presentation. However, scope and purpose, stakeholder involvement, rigor of development, and applicability domains varied considerably. The majority of guidelines scored low on editorial independence, and only seven CPGs were based on an underlying systematic review of the evidence. CONCLUSIONS: The overall quality of CPGs for glycemic control in DM2 is moderate, but there is substantial variability among quality domains within and across guidelines. Guideline users need to be aware of this variability and carefully appraise and select the guidelines that they apply to patient care.

Conflict of interest policies for organizations producing a large number of clinical practice guidelines.

BACKGROUND: Conflict of interest (COI) of clinical practice guideline (CPG) sponsors and authors is an important potential source of bias in CPG development. The objectives of this study were to describe the COI policies for organizations currently producing a significant number of CPGs, and to determine if these policies meet 2011 Institute of Medicine (IOM) standards. METHODOLOGY/PRINCIPAL FINDINGS: We identified organizations with five or more guidelines listed in the National Guideline Clearinghouse between January 1, 2009 and November 5, 2010. We obtained the COI policy for each organization from publicly accessible sources, most often the organization's website, and compared those polices to IOM standards related to COI. 37 organizations fulfilled our inclusion criteria, of which 17 (46%) had a COI policy directly related to CPGs. These COI policies varied widely with respect to types of COI addressed, from whom disclosures were collected, monetary thresholds for disclosure, approaches to management, and updating requirements. Not one organization's policy adhered to all seven of the IOM standards that were examined, and nine organizations did not meet a single one of the standards. CONCLUSIONS/SIGNIFICANCE: COI policies among organizations producing a large number of CPGs currently do not measure up to IOM standards related to COI disclosure and management. CPG developers need to make significant improvements in these policies and their implementation in order to optimize the quality and credibility of their guidelines.