Alex R. Kemper

An evidence development process for newborn screening

SUMMARY This article describes the background, development, and ini-tial implementation of new procedures for the systematic reviewof key issues in newborn screening. Building on the work ofother systematic review efforts, the ERG described here hasaimed to develop consistent and transparent strategies for evi-dence review. This process has helped to strengthen a complexanalysis and decision system by providing balanced evi-dence, taking into account available high-quality data, expertopinion, and other levels of evidence, in a transparent man-ner. The methods developed and the identification of areas ofmissing data may also help investigators begin to standardizethe clinical and laboratory data they collect pertaining to thenewborn screening and diagnosis of rare disorders and theiroutcomes and focus future research efforts in the mostneeded areas.ACKNOWLEDGEMENTSThis review was made possible by subcontract number SC-07-028 to Massachusetts General Hospital, Center for Child andAdolescent Health Policy under prime contract numberHHSP23320045014XI to Altarum Institute, from the Maternaland Child Health Bureau (MCHB) (Title V, Social SecurityAct), Health Resources and Services Administration (HRSA),U.S. Department of Health and Human Services (DHHS).REFERENCES

Screening for prostate cancer USPreventive servicestaskforcerecommendation statement

Importance In the United States, the lifetime risk of being diagnosed with prostate cancer is approximately 13%, and the lifetime risk of dying of prostate cancer is 2.5%. The median age of death from prostate cancer is 80 years. Many men with prostate cancer never experience symptoms and, without screening, would never know they have the disease. African American men and men with a family history of prostate cancer have an increased risk of prostate cancer compared with other men. Objective To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on prostate-specific antigen (PSA)–based screening for prostate cancer. Evidence Review The USPSTF reviewed the evidence on the benefits and harms of PSA-based screening for prostate cancer and subsequent treatment of screen-detected prostate cancer. The USPSTF also commissioned a review of existing decision analysis models and the overdiagnosis rate of PSA-based screening. The reviews also examined the benefits and harms of PSA-based screening in patient subpopulations at higher risk of prostate cancer, including older men, African American men, and men with a family history of prostate cancer. Findings Adequate evidence from randomized clinical trials shows that PSA-based screening programs in men aged 55 to 69 years may prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 men screened. Screening programs may also prevent approximately 3 cases of metastatic prostate cancer per 1000 men screened. Potential harms of screening include frequent false-positive results and psychological harms. Harms of prostate cancer treatment include erectile dysfunction, urinary incontinence, and bowel symptoms. About 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 men will experience long-term erectile dysfunction. Adequate evidence shows that the harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false-positive results, diagnostic harms from biopsies, and harms from treatment. The USPSTF concludes with moderate certainty that the net benefit of PSA-based screening for prostate cancer in men aged 55 to 69 years is small for some men. How each man weighs specific benefits and harms will determine whether the overall net benefit is small. The USPSTF concludes with moderate certainty that the potential benefits of PSA-based screening for prostate cancer in men 70 years and older do not outweigh the expected harms. Conclusions and Recommendation For men aged 55 to 69 years, the decision to undergo periodic PSA-based screening for prostate cancer should be an individual one and should include discussion of the potential benefits and harms of screening with their clinician. Screening offers a small potential benefit of reducing the chance of death from prostate cancer in some men. However, many men will experience potential harms of screening, including false-positive results that require additional testing and possible prostate biopsy; overdiagnosis and overtreatment; and treatment complications, such as incontinence and erectile dysfunction. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the balance of benefits and harms on the basis of family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening and treatment-specific outcomes, and other health needs. Clinicians should not screen men who do not express a preference for screening. (C recommendation) The USPSTF recommends against PSA-based screening for prostate cancer in men 70 years and older. (D recommendation)

Interventions to prevent falls in community-dwelling older adults us Preventive Services Task Force recommendation statement

Importance Falls are the leading cause of injury-related morbidity and mortality among older adults in the United States. In 2014, 28.7% of community-dwelling adults 65 years or older reported falling, resulting in 29 million falls (37.5% of which needed medical treatment or restricted activity for a day or longer) and an estimated 33 000 deaths in 2015. Objective To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on the prevention of falls in community-dwelling older adults. Evidence Review The USPSTF reviewed the evidence on the effectiveness and harms of primary care–relevant interventions to prevent falls and fall-related morbidity and mortality in community-dwelling older adults 65 years or older who are not known to have osteoporosis or vitamin D deficiency. Findings The USPSTF found adequate evidence that exercise interventions have a moderate benefit in preventing falls in older adults at increased risk for falls and that multifactorial interventions have a small benefit. The USPSTF found adequate evidence that vitamin D supplementation has no benefit in preventing falls in older adults. The USPSTF found adequate evidence to bound the harms of exercise and multifactorial interventions as no greater than small. The USPSTF found adequate evidence that the overall harms of vitamin D supplementation are small to moderate. Conclusions and Recommendation The USPSTF recommends exercise interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. (B recommendation) The USPSTF recommends that clinicians selectively offer multifactorial interventions to prevent falls in community-dwelling adults 65 years or older who are at increased risk for falls. Existing evidence indicates that the overall net benefit of routinely offering multifactorial interventions to prevent falls is small. When determining whether this service is appropriate for an individual, patients and clinicians should consider the balance of benefits and harms based on the circumstances of prior falls, presence of comorbid medical conditions, and the patient’s values and preferences. (C recommendation) The USPSTF recommends against vitamin D supplementation to prevent falls in community-dwelling adults 65 years or older. (D recommendation) These recommendations apply to community-dwelling adults who are not known to have osteoporosis or vitamin D deficiency.

Behavioral Counseling to Prevent Skin Cancer: US Preventive Services Task Force Recommendation Statement

Importance Skin cancer is the most common type of cancer in the United States. Although invasive melanoma accounts for only 2% of all skin cancer cases, it is responsible for 80% of skin cancer deaths. Basal and squamous cell carcinoma, the 2 predominant types of nonmelanoma skin cancer, represent the vast majority of skin cancer cases. Objective To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on behavioral counseling for the primary prevention of skin cancer and the 2009 recommendation on screening for skin cancer with skin self-examination. Evidence Review The USPSTF reviewed the evidence on whether counseling patients about sun protection reduces intermediate outcomes (eg, sunburn or precursor skin lesions) or skin cancer; the link between counseling and behavior change, the link between behavior change and skin cancer incidence, and the harms of counseling or changes in sun protection behavior; and the link between counseling patients to perform skin self-examination and skin cancer outcomes, as well as the harms of skin self-examination. Findings The USPSTF determined that behavioral counseling interventions are of moderate benefit in increasing sun protection behaviors in children, adolescents, and young adults with fair skin types. The USPSTF found adequate evidence that behavioral counseling interventions result in a small increase in sun protection behaviors in adults older than 24 years with fair skin types. The USPSTF found inadequate evidence on the benefits and harms of counseling adults about skin self-examination to prevent skin cancer. Conclusions and Recommendation The USPSTF recommends counseling young adults, adolescents, children, and parents of young children about minimizing exposure to UV radiation for persons aged 6 months to 24 years with fair skin types to reduce their risk of skin cancer. (B recommendation) The USPSTF recommends that clinicians selectively offer counseling to adults older than 24 years with fair skin types about minimizing their exposure to UV radiation to reduce risk of skin cancer. Existing evidence indicates that the net benefit of counseling all adults older than 24 years is small. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the presence of risk factors for skin cancer. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of counseling adults about skin self-examination to prevent skin cancer. (I statement)

Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: US Preventive Services Task Force Recommendation Statement

Importance Menopause occurs at a median age of 51.3 years, and the average US woman who reaches menopause is expected to live another 30 years. The prevalence and incidence of most chronic conditions, such as coronary heart disease, dementia, stroke, fractures, and breast cancer, increase with age; however, the excess risk for these conditions that can be attributed to menopause alone is uncertain. Since the publication of findings from the Women’s Health Initiative that hormone therapy use is associated with serious adverse health effects in postmenopausal women, use of menopausal hormone therapy has declined. Objective To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on the use of menopausal hormone therapy for the primary prevention of chronic conditions. Evidence Review The USPSTF reviewed the evidence on the benefits and harms of systemic (ie, oral or transdermal) hormone therapy for the prevention of chronic conditions in postmenopausal women and whether outcomes vary among women in different subgroups or by timing of intervention after menopause. The review did not address hormone therapy for preventing or treating menopausal symptoms. Findings Although the use of hormone therapy to prevent chronic conditions in postmenopausal women is associated with some benefits, there are also well-documented harms. The USPSTF determined that the magnitude of both the benefits and the harms of hormone therapy in postmenopausal women is small to moderate. Therefore, the USPSTF concluded with moderate certainty that combined estrogen and progestin has no net benefit for the primary prevention of chronic conditions for most postmenopausal women with an intact uterus and that estrogen alone has no net benefit for the primary prevention of chronic conditions for most postmenopausal women who have had a hysterectomy. Conclusions and Recommendation The USPSTF recommends against the use of combined estrogen and progestin for the primary prevention of chronic conditions in postmenopausal women. (D recommendation) The USPSTF recommends against the use of estrogen alone for the primary prevention of chronic conditions in postmenopausal women who have had a hysterectomy. (D recommendation)

Update on the Methods of the U.S. Preventive Services Task Force: Methods for Understanding Certainty and Net Benefit When Making Recommendations

Since the 1980s, the U.S. Preventive Services Task Force (USPSTF) has developed and used rigorous methods to make evidence-based recommendations about preventive services to promote health and well-being for all Americans. Recommendations are based on the evidence of magnitude of net benefit (benefits minus harms). Expert opinion is not substituted when evidence is lacking. Evidence gaps are common. Few preventive services are supported by high-quality studies that directly and comprehensively determine the overall magnitude of benefits and harms in the same study. When assessing the body of evidence, studies may not have been conducted in primary care settings, studies may not have sufficiently included populations of interest, and long-term outcomes may not have been directly assessed. When direct evidence is not available, the USPSTF uses the methodologies of applicability to determine whether evidence can be generalized to an asymptomatic primary care population; coherence to link bodies of evidence and create an indirect evidence pathway; extrapolation to make inferences across the indirect evidence pathway, extend evidence to populations not specifically studied, consider service delivery intervals, and infer long-term outcomes; and conceptual bounding to set theoretical lower or upper limits for plausible benefits or harms. The USPSTF extends the evidence only so far as to maintain at least moderate certainty that its findings are preserved. This manuscript details with examples of how the USPSTF uses these methods to make recommendations that truly reflect the evidence.

Vision Screening in Children Aged 6 Months to 5 Years: US Preventive Services Task Force Recommendation Statement

Importance One of the most important causes of vision abnormalities in children is amblyopia (also known as “lazy eye”). Amblyopia is an alteration in the visual neural pathway in a child’s developing brain that can lead to permanent vision loss in the affected eye. Among children younger than 6 years, 1% to 6% have amblyopia or its risk factors (strabismus, anisometropia, or both). Early identification of vision abnormalities could prevent the development of amblyopia. Subpopulation Considerations Studies show that screening rates among children vary by race/ethnicity and family income. Data based on parent reports from 2009-2010 indicated identical screening rates among black non-Hispanic children and white non-Hispanic children (80.7%); however, Hispanic children were less likely than non-Hispanic children to report vision screening (69.8%). Children whose families earned 200% or more above the federal poverty level were more likely to report vision screening than families with lower incomes. Objective To update the 2011 US Preventive Services Task Force (USPSTF) recommendation on screening for amblyopia and its risk factors in children. Evidence Review The USPSTF reviewed the evidence on the accuracy of vision screening tests and the benefits and harms of vision screening and treatment. Surgical interventions were considered to be out of scope for this review. Findings Treatment of amblyopia is associated with moderate improvements in visual acuity in children aged 3 to 5 years, which are likely to result in permanent improvements in vision throughout life. The USPSTF concluded that the benefits are moderate because untreated amblyopia results in permanent, uncorrectable vision loss, and the benefits of screening and treatment potentially can be experienced over a child’s lifetime. The USPSTF found adequate evidence to bound the potential harms of treatment (ie, higher false-positive rates in low-prevalence populations) as small. Therefore, the USPSTF concluded with moderate certainty that the overall net benefit is moderate for children aged 3 to 5 years. Conclusions and Recommendations The USPSTF recommends vision screening at least once in all children aged 3 to 5 years to detect amblyopia or its risk factors. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of vision screening in children younger than 3 years. (I statement)

The Gateway to Journal Improvements

* Abbreviation:n AAP — : American Academy of PediatricsnnA year ago we heralded the start of a new Congress and the 65th anniversary of Pediatrics with an enormous amount of optimism for continued improvement in health care reform and care for children and families. Although many would question our optimism regarding the work of our federal government as it ground to a halt for a few weeks last fall, we hope no one would say the same is true for our journal. Not only did we initiate a number of changes in our publication last year—we are again implementing some changes this upcoming year as part of our process of ongoing quality improvement to make our journal as responsive to the needs of our readers and the children and families who benefit from what we publish every month. As we look toward 2014, our Editorial Board and Managing Editorial Staff wish to share with you what you can expect in terms of those additional changes that should get you excited not just about the journal, but about the field of pediatrics and where it’s going.nnThe number of American Academy of Pediatrics (AAP) members using mobile devices to discover and read scholarly articles is growing rapidly. In fact, 60% of our readers are now using a tablet … nnAddress correspondence to Lewis R. First, MD, MS, Editor-in-Chief, Pediatrics Editorial Office, University of Vermont College of Medicine, 89 Beaumont Ave, Given Courtyard S250, Burlington, VT 05405. E-mail: lewis.first{at}uvm.edu

Vitamin D, Calcium, or Combined Supplementation for the Primary Prevention of Fractures in Community-Dwelling Adults: US Preventive Services Task Force Recommendation Statement

Importance Because of the aging population, osteoporotic fractures are an increasingly important cause of morbidity and mortality in the United States. Approximately 2 million osteoporotic fractures occurred in the United States in 2005, and annual incidence is projected to increase to more than 3 million fractures by 2025. Within 1 year of experiencing a hip fracture, many patients are unable to walk independently, more than half require assistance with activities of daily living, and 20% to 30% of patients will die. Objective To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on vitamin D supplementation, with or without calcium, to prevent fractures. Evidence Review The USPSTF reviewed the evidence on vitamin D, calcium, and combined supplementation for the primary prevention of fractures in community-dwelling adults (defined as not living in a nursing home or other institutional care setting). The review excluded studies conducted in populations with a known disorder related to bone metabolism (eg, osteoporosis or vitamin D deficiency), taking medications known to be associated with osteoporosis (eg, long-term steroids), or with a previous fracture. Findings The USPSTF found inadequate evidence to estimate the benefits of vitamin D, calcium, or combined supplementation to prevent fractures in community-dwelling men and premenopausal women. The USPSTF found adequate evidence that daily supplementation with 400 IU or less of vitamin D and 1000 mg or less of calcium has no benefit for the primary prevention of fractures in community-dwelling, postmenopausal women. The USPSTF found inadequate evidence to estimate the benefits of doses greater than 400 IU of vitamin D or greater than 1000 mg of calcium to prevent fractures in community-dwelling postmenopausal women. The USPSTF found adequate evidence that supplementation with vitamin D and calcium increases the incidence of kidney stones. Conclusions and Recommendation The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of vitamin D and calcium supplementation, alone or combined, for the primary prevention of fractures in community-dwelling, asymptomatic men and premenopausal women. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of the benefits and harms of daily supplementation with doses greater than 400 IU of vitamin D and greater than 1000 mg of calcium for the primary prevention of fractures in community-dwelling, postmenopausal women. (I statement) The USPSTF recommends against daily supplementation with 400 IU or less of vitamin D and 1000 mg or less of calcium for the primary prevention of fractures in community-dwelling, postmenopausal women. (D recommendation) These recommendations do not apply to persons with a history of osteoporotic fractures, increased risk for falls, or a diagnosis of osteoporosis or vitamin D deficiency.

Screening for Adolescent Idiopathic Scoliosis: US Preventive Services Task Force Recommendation Statement

Importance Adolescent idiopathic scoliosis, a lateral curvature of the spine of unknown cause with a Cobb angle of at least 10°, occurs in children and adolescents aged 10 to 18 years. Idiopathic scoliosis is the most common form and usually worsens during adolescence before skeletal maturity. Severe spinal curvature may be associated with adverse long-term health outcomes (eg, pulmonary disorders, disability, back pain, psychological effects, cosmetic issues, and reduced quality of life). Early identification and effective treatment of mild scoliosis could slow or stop curvature progression before skeletal maturity, thereby improving long-term outcomes in adulthood. Objective To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for idiopathic scoliosis in asymptomatic adolescents. Evidence Review The USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of adolescent idiopathic scoliosis. Findings The USPSTF found no direct evidence on screening for adolescent idiopathic scoliosis and health outcomes and no evidence on the harms of screening. The USPSTF found inadequate evidence on treatment with exercise and surgery. It found adequate evidence that treatment with bracing may slow curvature progression in adolescents with mild or moderate curvature severity (Cobb angle <40° to 50°); however, evidence on the association between reduction in spinal curvature in adolescence and long-term health outcomes in adulthood is inadequate. The USPSTF found inadequate evidence on the harms of treatment. Therefore, the USPSTF concludes that the current evidence is insufficient and that the balance of benefits and harms of screening for adolescent idiopathic scoliosis cannot be determined. Conclusions and Recommendation The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for adolescent idiopathic scoliosis in children and adolescents aged 10 to 18 years. (I statement)