Office of Disease Prevention

Importance: Approximately 80% of US adults and adolescents are insufficiently active. Physical activity fosters normal growth and development and can make people feel, function, and sleep better and reduce risk of many chronic diseases. Objective: To summarize key guidelines in the Physical Activity Guidelines for Americans, 2nd edition (PAG). Process and Evidence Synthesis: The 2018 Physical Activity Guidelines Advisory Committee conducted a systematic review of the science supporting physical activity and health. The committee addressed 38 questions and 104 subquestions and graded the evidence based on consistency and quality of the research. Evidence graded as strong or moderate was the basis of the key guidelines. The Department of Health and Human Services (HHS) based the PAG on the 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Recommendations: The PAG provides information and guidance on the types and amounts of physical activity to improve a variety of health outcomes for multiple population groups. Preschool-aged children (3 through 5 years) should be physically active throughout the day to enhance growth and development. Children and adolescents aged 6 through 17 years should do 60 minutes or more of moderate-to-vigorous physical activity daily. Adults should do at least 150 minutes to 300 minutes a week of moderate-intensity, or 75 minutes to 150 minutes a week of vigorous-intensity aerobic physical activity, or an equivalent combination of moderate- and vigorous-intensity aerobic activity. They should also do muscle-strengthening activities on 2 or more days a week. Older adults should do multicomponent physical activity that includes balance training as well as aerobic and muscle-strengthening activities. Pregnant and postpartum women should do at least 150 minutes of moderate-intensity aerobic activity a week. Adults with chronic conditions or disabilities, who are able, should follow the key guidelines for adults and do both aerobic and muscle-strengthening activities. Recommendations emphasize that moving more and sitting less will benefit nearly everyone. Individuals performing the least physical activity benefit most by even modest increases in moderate-to-vigorous physical activity. Additional benefits occur with more physical activity. Both aerobic and muscle-strengthening physical activity are beneficial. Conclusions and Relevance: The Physical Activity Guidelines for Americans, 2nd edition, provides information and guidance on the types and amounts of physical activity that provide substantial health benefits. Health professionals and policy makers should facilitate awareness of the guidelines and promote the health benefits of physical activity and support efforts to implement programs, practices, and policies to facilitate increased physical activity and to improve the health of the US population.

BACKGROUND: The effect of screening with prostate-specific-antigen (PSA) testing and digital rectal examination on the rate of death from prostate cancer is unknown. This is the first report from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial on prostate-cancer mortality. METHODS: From 1993 through 2001, we randomly assigned 76,693 men at 10 U.S. study centers to receive either annual screening (38,343 subjects) or usual care as the control (38,350 subjects). Men in the screening group were offered annual PSA testing for 6 years and digital rectal examination for 4 years. The subjects and health care providers received the results and decided on the type of follow-up evaluation. Usual care sometimes included screening, as some organizations have recommended. The numbers of all cancers and deaths and causes of death were ascertained. RESULTS: In the screening group, rates of compliance were 85% for PSA testing and 86% for digital rectal examination. Rates of screening in the control group increased from 40% in the first year to 52% in the sixth year for PSA testing and ranged from 41 to 46% for digital rectal examination. After 7 years of follow-up, the incidence of prostate cancer per 10,000 person-years was 116 (2820 cancers) in the screening group and 95 (2322 cancers) in the control group (rate ratio, 1.22; 95% confidence interval [CI], 1.16 to 1.29). The incidence of death per 10,000 person-years was 2.0 (50 deaths) in the screening group and 1.7 (44 deaths) in the control group (rate ratio, 1.13; 95% CI, 0.75 to 1.70). The data at 10 years were 67% complete and consistent with these overall findings. CONCLUSIONS: After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups. (ClinicalTrials.gov number, NCT00002540.)

The design of clinical trials in hepatocellular carcinoma (HCC) is complex because many patients have concurrent liver disease, which can confound the assessment of clinical benefit. There is an urgent need for high-quality trials in this disease. An expert panel was convened by the American Association for the Study of Liver Diseases to develop guidelines that provide a common framework for designing trials to facilitate comparability of results. According to these guidelines, randomized phase 2 trials with a time-to-event primary endpoint, such as time to progression, are pivotal in clinical research on HCC. Survival remains the main endpoint to measure effectiveness in phase 3 studies, whereas time to recurrence is proposed as an appropriate endpoint in the adjuvant setting. Because progression-free survival and disease-free survival are composite endpoints, they are more vulnerable than others in HCC clinical studies and may not be able to capture clinical benefits. Selection of the target population should be based on the Barcelona Clinic Liver Cancer staging system. New drugs should be tested in patients with well-preserved liver function (Child-Pugh A class). Patients assigned to the control arm should receive standard-of-care therapy, that is, chemoembolization for patients with intermediate-stage disease and sorafenib for patients with advanced-stage disease. Further research is needed to incorporate biomarkers and molecular imaging into clinical research in HCC. These surrogate markers may help to enrich study populations and maximize the cost-benefit ratio of trial execution. Design and conduct of phase 3 trials should be coordinated by centers with appropriate expertise in HCC.

PURPOSE: Physical activity (PA) is known to improve cognitive and brain function, but debate continues regarding the consistency and magnitude of its effects, populations and cognitive domains most affected, and parameters necessary to achieve the greatest improvements (e.g., dose). METHODS: In this umbrella review conducted in part for the 2018 Health and Human Services Physical Activity Guidelines for Americans Advisory Committee, we examined whether PA interventions enhance cognitive and brain outcomes across the life span, as well as in populations experiencing cognitive dysfunction (e.g., schizophrenia). Systematic reviews, meta-analyses, and pooled analyses were used. We further examined whether engaging in greater amounts of PA is associated with a reduced risk of developing cognitive impairment and dementia in late adulthood. RESULTS: Moderate evidence from randomized controlled trials indicates an association between moderate- to vigorous-intensity PA and improvements in cognition, including performance on academic achievement and neuropsychological tests, such as those measuring processing speed, memory, and executive function. Strong evidence demonstrates that acute bouts of moderate- to vigorous-intensity PA have transient benefits for cognition during the postrecovery period after exercise. Strong evidence demonstrates that greater amounts of PA are associated with a reduced risk of developing cognitive impairment, including Alzheimer's disease. The strength of the findings varies across the life span and in individuals with medical conditions influencing cognition. CONCLUSIONS: There is moderate-to-strong support that PA benefits cognitive functioning during early and late periods of the life span and in certain populations characterized by cognitive deficits.

BACKGROUND: The benefits of endoscopic testing for colorectal-cancer screening are uncertain. We evaluated the effect of screening with flexible sigmoidoscopy on colorectal-cancer incidence and mortality. METHODS: From 1993 through 2001, we randomly assigned 154,900 men and women 55 to 74 years of age either to screening with flexible sigmoidoscopy, with a repeat screening at 3 or 5 years, or to usual care. Cases of colorectal cancer and deaths from the disease were ascertained. RESULTS: Of the 77,445 participants randomly assigned to screening (intervention group), 83.5% underwent baseline flexible sigmoidoscopy and 54.0% were screened at 3 or 5 years. The incidence of colorectal cancer after a median follow-up of 11.9 years was 11.9 cases per 10,000 person-years in the intervention group (1012 cases), as compared with 15.2 cases per 10,000 person-years in the usual-care group (1287 cases), which represents a 21% reduction (relative risk, 0.79; 95% confidence interval [CI], 0.72 to 0.85; P<0.001). Significant reductions were observed in the incidence of both distal colorectal cancer (479 cases in the intervention group vs. 669 cases in the usual-care group; relative risk, 0.71; 95% CI, 0.64 to 0.80; P<0.001) and proximal colorectal cancer (512 cases vs. 595 cases; relative risk, 0.86; 95% CI, 0.76 to 0.97; P=0.01). There were 2.9 deaths from colorectal cancer per 10,000 person-years in the intervention group (252 deaths), as compared with 3.9 per 10,000 person-years in the usual-care group (341 deaths), which represents a 26% reduction (relative risk, 0.74; 95% CI, 0.63 to 0.87; P<0.001). Mortality from distal colorectal cancer was reduced by 50% (87 deaths in the intervention group vs. 175 in the usual-care group; relative risk, 0.50; 95% CI, 0.38 to 0.64; P<0.001); mortality from proximal colorectal cancer was unaffected (143 and 147 deaths, respectively; relative risk, 0.97; 95% CI, 0.77 to 1.22; P=0.81). CONCLUSIONS: Screening with flexible sigmoidoscopy was associated with a significant decrease in colorectal-cancer incidence (in both the distal and proximal colon) and mortality (distal colon only). (Funded by the National Cancer Institute; PLCO ClinicalTrials.gov number, NCT00002540.).

PURPOSE: This article reviews and updates the evidence on the associations between physical activity and risk for cancer, and for mortality in persons with cancer, as presented in the 2018 Physical Activity Guidelines Advisory Committee Scientific Report. METHODS: Systematic reviews of meta-analyses, systematic reviews, and pooled analyses were conducted through December 2016. An updated systematic review of such reports plus original research through February 2018 was conducted. This article also identifies future research needs. RESULTS: In reviewing 45 reports comprising hundreds of epidemiologic studies with several million study participants, the report found strong evidence for an association between highest versus lowest physical activity levels and reduced risks of bladder, breast, colon, endometrial, esophageal adenocarcinoma, renal, and gastric cancers. Relative risk reductions ranged from approximately 10% to 20%. Based on 18 systematic reviews and meta-analyses, the report also found moderate or limited associations between greater amounts of physical activity and decreased all-cause and cancer-specific mortality in individuals with a diagnosis of breast, colorectal, or prostate cancer, with relative risk reductions ranging almost up to 40% to 50%. The updated search, with five meta-analyses and 25 source articles reviewed, confirmed these findings. CONCLUSIONS: Levels of physical activity recommended in the 2018 Guidelines are associated with reduced risk and improved survival for several cancers. More research is needed to determine the associations between physical activity and incidence for less common cancers and associations with survival for other cancers. Future studies of cancer incidence and mortality should consider these associations for population subgroups, to determine dose-response relationships between physical activity and cancer risk and prognosis, and to establish mechanisms to explain these associations.

Since the World Health Organization launched its commission on the social determinants of health (SDOH) over a decade ago, a large body of research has proven that social determinants-defined as the conditions in which people are born, grow, live, work, and age-are significant drivers of disease risk and susceptibility within clinical care and public health systems. Unfortunately, the term has lost meaning within systems of care because of misuse and lack of context. As many disparate health outcomes remain, including higher risk of maternal mortality among Black women, a deeper understanding of the SDOH-and what forces underlie their distribution-is needed. In this article, we will expand our review of social determinants of maternal health to include the terms "structural determinants of health" and "root causes of inequities" as we assess the literature on this topic. We hypothesize that the addition of structural determinants and root causes will identify racism as a cause of inequities in maternal health outcomes, as many of the social and political structures and policies in the United States were born out of racism, classism, and gender oppression. We will conclude with proposed practice and policy solutions to end inequities in maternal health outcomes.

INTRODUCTION: The American College of Sports Medicine convened an International Multidisciplinary Roundtable on Exercise and Cancer in March 2018 to evaluate and translate the evidence linking physical activity and cancer prevention, treatment, and control. This article discusses findings from the Roundtable in relation to the biologic and epidemiologic evidence for the role of physical activity in cancer prevention and survival. RESULTS: The evidence supports that there are a number of biologically plausible mechanisms, whereby physical activity can influence cancer risk, and that physical activity is beneficial for the prevention of several types of cancer including breast, colon, endometrial, kidney, bladder, esophageal, and stomach. Minimizing time spent in sedentary behavior may also lower risk of endometrial, colon and lung cancers. Conversely, physical activity is associated with higher risk of melanoma, a serious form of skin cancer. Further, physical activity before and after a cancer diagnosis is also likely to be relevant for improved survival for those diagnosed with breast and colon cancer; with data suggesting that postdiagnosis physical activity provides greater mortality benefits than prediagnosis physical activity. CONCLUSIONS: Collectively, there is consistent, compelling evidence that physical activity plays a role in preventing many types of cancer and for improving longevity among cancer survivors, although the evidence related to higher risk of melanoma demonstrates the importance of sun safe practices while being physically active. Together, these findings underscore the importance of physical activity in cancer prevention and control. Fitness and public health professionals and health care providers worldwide are encouraged to spread the message to the general population and cancer survivors to be physically active as their age, abilities, and cancer status will allow.

Maintaining or improving quality of life (QoL) and well-being is a universal goal across the lifespan. Being physically active has been suggested as one way to enhance QoL and well-being. In this systematic review, conducted in part for the 2018 U.S. Health and Human Services Physical Activity Guidelines for Americans Scientific Advisory Committee Report, we examined the relationship between physical activity (PA) and QoL and well-being experienced by the general population across the lifespan and by persons with psychiatric and neurologic conditions. Systematic reviews, meta-analyses, and pooled analyses from 2006 to 2018 were used for the evidence base. Strong evidence (predominantly from randomized controlled trials [RCTs]) demonstrated that, for adults aged 18-65 years and older adults (primarily 65 years and older), PA improves QoL and well-being when compared with minimal or no-treatment controls. Moderate evidence indicated that PA improves QoL and well-being in individuals with schizophrenia and Parkinson's disease, and limited evidence indicated that PA improves QoL and well-being for youth and for adults with major clinical depression or bipolar disorder. Insufficient evidence existed for individuals with dementia because of a small number of studies with mixed results. Future high-quality research designs should include RCTs involving longer interventions testing different modes and intensities of PA in diverse populations of healthy people and individuals with cognitive (e.g., dementia) and mental health conditions (e.g., schizophrenia) to precisely characterize the effects of different forms of PA on aspects of QoL and well-being.

Current methods for developing practice guidelines include informal consensus development, formal consensus development, evidence-based guideline development, and explicit guideline development. Informal consensus development is the oldest and most common approach, but guidelines produced in this manner are often of poor quality and lack adequate documentation of methods. Formal consensus development uses a systematic approach to assess expert opinion and to reach agreement on recommendations. Evidence-based guideline development links recommendations directly to scientific evidence of effectiveness; rules of evidence are emphasized over expert opinion in making recommendations. Explicit guideline development clarifies the rationale by specifying the potential benefits, harms, and costs of available interventions; estimating the possibility of the outcomes; and comparing the desirability of the outcomes based on patient preferences. Steps in the development of practice guidelines include introductory decisions (selection of topic and panel members, clarification of purpose); assessments of clinical appropriateness (review of scientific evidence and expert opinion); assessment of public policy issues (resource limitations, feasibility issues); and guideline document development and evaluation (drafting of document, peer review, and pretesting).

OBJECTIVES: The authors developed an "off-the-shelf" source of health-related quality of life (HRQL) scores for cost-effectiveness analysts unable to collect primary data. METHODS: The authors derived and conducted preliminary validation on a set of health-related quality of life scores for chronic conditions using nationally representative data from the National Health Interview Survey (NHIS) and the Healthy People 2000 Years of Healthy Life measure developed to monitor the health (longevity and health-related quality of life) of Americans during this decade. The measure comprises two domains, role function and self-rated health, and is scaled from 0 (death) to 1 (best health state). Health-related quality of life scores for chronic conditions were calculated using the Years of Healthy Life scores associated with chronic conditions reported in the 1987-1992 National Health Interview Survey. Preliminary validation was examined by comparing the health-related quality of life scores with those obtained in two other studies. RESULTS: Tables provide health-related quality of life scores for persons with and without conditions. The scores had reasonable face validity, ranging from 0.87 for allergic rhinitis to 0.27 for hemiplegia. Correlations of the health-related quality of life condition weight scores with those from two other studies were 0.78 and 0.86. CONCLUSIONS: These condition weights may prove useful to investigators conducting cost-effectiveness analyses using secondary data, where community ratings of health-related quality of life for chronic conditions are required. Use of a standard set of health-related quality of life weights gathered from a national sample can enhance the comparability of cost-effectiveness analyses. Improvements in national data collection techniques, with empirical gathering of preferences, will further strengthen this measure.

Type 1 diabetes is considered to be an autoimmune disease in which T lymphocytes infiltrate the islets of pancreas and destroy the insulin producing beta cell population. Besides antigen specificity, the quality of immune reactivity against islet cell antigen(s) is an important determinant of the beta cell destruction. Much evidence indicates that the function of the gut immune system is central in the pathogenesis, as the regulation of the gut immune system may be aberrant in type 1 diabetes. The role of virus infections in the pathogenesis of type 1 diabetes has been supported by substantial new evidence suggesting that one virus group, enteroviruses, may trigger the beta-cell damaging process in a considerable proportion of patients. The latest evidence comes from studies indicating the presence of viral genome in diabetic patients and from prospective studies confirming epidemiological risk effect. If this association holds still true in ongoing large-scale studies, intervention trials should be considered to confirm causality. Of the dietary putative etiological factors, cow's milk proteins have received the main attention. Many studies indicate an association between early exposure to dietary cow's milk proteins and an increased risk of type 1 diabetes. The question will be answered by a large scale, prospective, randomized, international intervention trial. Another dietary factor in need of more studies is the deficiency of vitamin D. Among toxins, N-nitroso compounds are the main candidates. An interaction of genetic and environmental factors is important in evaluating the possible role of a certain environmental factor in the etiology of type 1 diabetes.

There is growing interest in the use of practice guidelines for physicians as a means of reducing inappropriate care, controlling geographic variations in practice patterns, and making more effective use of health care resources. Recent developments at the national health policy level suggest that practice guidelines will play an increasingly prominent role in the practice of medicine. The federal government has created a new US Public Health Service agency with responsibility for practice guidelines. Guidelines have been developed by more than 35 physician organizations and specialty societies. The American Medical Association and the Council of Medical Specialty Societies have endorsed practice guidelines and are organizing specialty societies to set policy on the subject. Academic medical centers have formed a research consortium on practice guidelines. Independent research centers (eg, the RAND Corporation and the Institute of Medicine) are developing methods for assessing appropriateness and setting guidelines. Other groups, such as hospitals, insurers, managed care plans, and private enterprises, are also directly involved. The implications of these developments are far reaching.

BACKGROUND: Few evaluations of school health programs measure academic outcomes. K-12 education needs evidence for academic achievement to implement school programs. This article presents a systematic review of the literature to examine evidence that school health programs aligned with the Coordinated School Health Program (CSHP) model improve academic success. METHODS: A multidisciplinary panel of health researchers searched the literature related to academic achievement and elements of the CSHP model (health services, counseling/social services, nutrition services, health promotion for staff, parent/family/community involvement, healthy school environment, physical education, and health education) to identify scientifically rigorous studies of interventions. Study designs were classified according to the analytic framework provided in the Guide developed by the Community Preventive Services Task Force. RESULTS: The strongest evidence from scientifically rigorous evaluations exists for a positive effect on some academic outcomes from school health programs for asthmatic children that incorporate health education and parental involvement. Strong evidence also exists for a lack of negative effects of physical education programs on academic outcomes. Limited evidence from scientifically rigorous evaluations support the effect of nutrition services, health services, and mental health programs, but no such evidence is found in the literature to support the effect of staff health promotion programs or school environment interventions on academic outcomes. CONCLUSIONS: Scientifically rigorous evaluation of school health programs is challenging to conduct due to issues related to sample size, recruitment, random assignment to condition, implementation fidelity, costs, and adequate follow-up time. However, school health programs hold promise for improving academic outcomes for children.

PROBLEM/CONDITION: Since 1971, CDC, the U.S. Environmental Protection Agency, and the Council of State and Territorial Epidemiologists have maintained a collaborative surveillance system for collecting and periodically reporting data related to occurrences and causes of waterborne-disease outbreaks (WBDOs). This surveillance system is the primary source of data concerning the scope and effects of waterborne disease outbreaks on persons in the United States. REPORTING PERIOD COVERED: This summary includes data on WBDOs associated with drinking water that occurred during January 2001-December 2002 and on three previously unreported outbreaks that occurred during 2000. DESCRIPTION OF SYSTEM: Public health departments in the states, territories, localities, and the Freely Associated States are primarily responsible for detecting and investigating WBDOs and voluntarily reporting them to CDC on a standard form. The surveillance system includes data for outbreaks associated with both drinking water and recreational water; only outbreaks associated with drinking water are reported in this summary. RESULTS: During 2001-2002, a total of 31 WBDOs associated with drinking water were reported by 19 states. These 31 outbreaks caused illness among an estimated 1,020 persons and were linked to seven deaths. The microbe or chemical that caused the outbreak was identified for 24 (77.4%) of the 31 outbreaks. Of the 24 identified outbreaks, 19 (79.2%) were associated with pathogens, and five (20.8%) were associated with acute chemical poisonings. Five outbreaks were caused by norovirus, five by parasites, and three by non-Legionella bacteria. All seven outbreaks involving acute gastrointestinal illness of unknown etiology were suspected of having an infectious cause. For the first time, this MMWR Surveillance Summary includes drinking water-associated outbreaks of Legionnaires disease (LD); six outbreaks of LD occurred during 2001-2002. Of the 25 non-Legionella associated outbreaks, 23 (92.0%) were reported in systems that used groundwater sources; nine (39.1%) of these 23 groundwater outbreaks were associated with private noncommunity wells that were not regulated by EPA. INTERPRETATION: The number of drinking water-associated outbreaks decreased from 39 during 1999-2000 to 31 during 2001-2002. Two (8.0%) outbreaks associated with surface water occurred during 2001-2002; neither was associated with consumption of untreated water. The number of outbreaks associated with groundwater sources decreased from 28 during 1999-2000 to 23 during 2001-2002; however, the proportion of such outbreaks increased from 73.7% to 92.0%. The number of outbreaks associated with untreated groundwater decreased from 17 (44.7%) during 1999-2000 to 10 (40.0%) during 2001-2002. Outbreaks associated with private, unregulated wells remained relatively stable, although more outbreaks involving private, treated wells were reported during 2001-2002. Because the only groundwater systems that are required to disinfect their water supplies are public systems under the influence of surface water, these findings support EPA's development of a groundwater rule that specifies when corrective action (including disinfection) is required. PUBLIC HEALTH ACTION: CDC and EPA use surveillance data 1) to identify the types of water systems, their deficiencies, and the etiologic agents associated with outbreaks and 2) to evaluate the adequacy of technologies for providing safe drinking water. Surveillance data are used also to establish research priorities, which can lead to improved water-quality regulations. CDC and EPA recently completed epidemiologic studies that assess the level of waterborne illness attributable to municipal drinking water in nonoutbreak conditions. The decrease in outbreaks in surface water systems is attributable primarily to implementation of provisions of EPA rules enacted since the late 1980s. Rules under development by EPA are expected to protect the public further from microbial contaminants while addressing risk tradeoffs of disinfection byproducts in drinking water.

Monitoring the implementation of a program being evaluated can improve the interpretability of data collected and help evaluators to avoid committing a Type III error: evaluating a program that has not been adequately implemented. This article describes an evaluation that analyzed the implementation of a school health education curriculum, assessed cognitive learning outcomes attributable to the curriculum, and examined the relationship between classroom implementation and changes in students' knowledge. Five fifth-grade classes (n = 101) participated in the curriculum, and five classes (n = 84) served as a comparison group. Data collection procedures involved a pretest and posttest of all students' health-related knowledge, daily monitoring of classroom implementation by the five teachers participating, and questionnaires completed by principals and teachers. Analysis methods included descriptive statistics, parametric and nonparametric tests of significance, and qualitative assessment procedures. Results indicated that the curriculum had a positive effect on learning in students; curriculum implementation varied considerably among the five classes participating; teaching/learning activities that were most and least likely to be implemented could be identified and described; both teachers and principals perceived the program favorably; some health instruction was occurring in the comparison classes, so it was not appropriate to consider them as pure controls; and no statistically significant relationship between curriculum implementation and cognitive outcomes was observed. This study provides evidence of the need for and value of measuring implementation of programs being evaluated. Implications for developing implementation measures and the role of formative evaluation in health education practice are considered.

BACKGROUND: Two large-scale prostate cancer screening trials using prostate-specific antigen (PSA) have given conflicting results in terms of the efficacy of such screening. One of those trials, the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, previously reported outcomes with 13 years of follow-up. This study presents updated findings from the PLCO trial. METHODS: The PLCO trial randomized subjects from 1993 to 2001 to an intervention or control arm. Intervention-arm men received annual PSA tests for 6 years and digital rectal examinations for 4 years. This study used a linkage with the National Death Index to extend mortality follow-up to a maximum of 19 years after randomization. RESULTS: Men were randomized to the intervention arm (n = 38,340) or the control arm (n = 38,343). The median follow-up time was 14.8 years (25th/75th, 12.7/16.5 years) in the intervention arm and 14.7 years (25th/75th, 12.6/16.4 years) in the control arm. There were 255 deaths from prostate cancer in the intervention arm and 244 deaths from prostate cancer in the control arm; this meant a rate ratio (RR) of 1.04 (95% confidence interval [CI], 0.87-1.24). The RR for all-cause mortality was 0.977 (95% CI, 0.950-1.004). It was estimated that 86% of the men in the control arm and 99% of the men in the intervention arm received any PSA testing during the trial, and the estimated yearly screening-phase PSA testing rates were 46% and 84%, respectively. CONCLUSIONS: Extended follow-up of the PLCO trial over a median of 15 years continues to indicate no reduction in prostate cancer mortality for the intervention arm versus the control arm. Because of the high rate of control-arm PSA testing, this finding can be viewed as showing no benefit of organized screening versus opportunistic screening. Cancer 2017;123:592-599. © 2016 American Cancer Society.

BACKGROUND: The benefit of screening for prostate cancer using prostate-specific antigen (PSA) testing and digital rectal examination (DRE) is uncertain and is under evaluation in a randomized prospective trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Although the final results are several years away, the initial round of screening is complete. We describe the population enrolled in the PLCO trial, their baseline PSA and DRE screening results, and diagnostic follow-up results during the first year of follow-up. METHODS: A total of 38,350 men were randomly assigned to the screening arm of the PLCO trial from November 1993 through June 2001. Men were advised to seek diagnostic follow-up from their primary care provider if their DRE was suspicious for cancer and/or if their serum PSA level was higher than 4 ng/mL. PLCO trial staff obtained records related to diagnostic follow-up. RESULTS: Compliance with both screening tests was high (more than 89%). At screening, 7.5% of men had a positive DRE (i.e., suspicious for cancer) and 7.9% had a PSA level higher than 4 ng/mL. Of the men with positive screening tests, 74.2% underwent additional diagnostic testing, and 31.5% underwent a prostatic biopsy within 1 year. Overall, 1.4% of the men in the screening arm were diagnosed with prostate cancer, the majority of whom had clinically localized cancer. These compliance, biopsy, and cancer detection rates appear to be representative of contemporary practice patterns. CONCLUSION: The PLCO trial is evaluating PSA- and DRE-based screening for prostate cancer in a clinically valid manner. Whether such screening will result in a reduction of prostate cancer mortality cannot be answered until the randomized comparison is completed.

INTRODUCTION: We conducted a systematic umbrella review to evaluate the literature relating to effects of physical activity on pain, physical function, health-related quality of life, comorbid conditions and osteoarthritis (OA) structural disease progression in individuals with lower-extremity OA. METHODS: Our primary search encompassed 2011 to February 2018 for existing systematic reviews (SR), meta-analyses (MA) and pooled analyses dealing with physical activity including exercise (not mixed with any other intervention and compared to a no-activity control group). A supplementary search encompassed 2006 to February 2018 for original research related to physical activity (including exercise) and lower limb OA progression. Study characteristics were abstracted, and risk of bias was assessed. RESULTS: Physical activity decreased pain and improved physical function (strong evidence) and improved health-related quality of life (moderate evidence) among people with hip or knee OA relative to less active adults with OA. There was no evidence to suggest accelerated OA progression for physical activity below 10,000 steps per day. Both physical activity equivalent to the 2008 Physical Activity Guidelines for Americans (150 min·wk of moderate-intensity exercise in bouts ≥10 min) and lower levels of physical activity (at least 45 total minutes per week of moderate-intensity) were associated with improved or sustained high function. No SR/MA addressing comorbid conditions in OA were found. Measurable benefits of physical activity appeared to persist for periods of up to 6 months following cessation of a defined program. CONCLUSIONS: People with lower-extremity OA should be encouraged to engage in achievable amounts of physical activity, of even modest intensities. They can choose to accrue minutes of physical activity throughout the entire day, irrespective of bout duration, and be confident in gaining some health and arthritis-related benefits.

Background: Preexposure prophylaxis (PrEP) is highly effective for preventing human immunodeficiency virus (HIV) infection, but risk compensation (RC) in men who have sex with men (MSM) raises concerns about increased sexually transmitted infections (STIs). The Center for Disease Control and Prevention's (CDC's) PrEP guidelines recommend biannual STI screening, which may reduce incidence by treating STIs that would otherwise remain undiagnosed. We investigated these two counteracting phenomena. Methods: With a network-based mathematical model of HIV, Neisseria gonorrhoeae (NG), and Chlamydia trachomatis (CT) transmission dynamics among MSM in the United States, we simulated PrEP uptake following the prescription indications and HIV/STI screening recommendations in the CDC guidelines. Scenarios varied PrEP coverage (the proportion of MSM indicated for PrEP who received it), RC (a reduction in the per-act probability of condom use), and the STI screening interval. Results: In our reference scenario (40% coverage, 40% RC), 42% of NG and 40% of CT infections would be averted over the next decade. A doubling of RC would still result in net STI prevention relative to no PrEP. STIs declined because PrEP-related STI screening resulted in a 17% and 16% absolute increase in the treatment of asymptomatic and rectal STIs, respectively. Screening and timely treatment at quarterly vs biannual intervals would reduce STI incidence an additional 50%. Conclusions: Implementation of the CDC PrEP guidelines while scaling up PrEP coverage could result in a significant decline in STI incidence among MSM. Our study highlights the design of PrEP not only as antiretroviral medication but as combination HIV/STI prevention incorporating STI screening.