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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

The role of cytoreductive nephrectomy in patients with metastatic renal cell carcinoma is a subject of debate. We report a durable complete response in a 62-year-old man Jehovah’s Witness with metastatic clear cell renal cell carcinoma who received two cycles of nivolumab/ipilimumab followed by radical nephrectomy and metastasectomy of known pulmonary disease site, both without a clinical need for perioperative blood transfusions. The patient continues to be without evidence of disease and without additional need for systemic therapy over a year after his radical nephrectomy. The case highlights that cytoreductive nephrectomy continues to play a role in the era of immune checkpoint inhibitors.

ImportanceMenopause 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.ObjectiveTo 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 reviewThe 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.FindingsAlthough 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 recommendationThe 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).

Abstract Dementia has a devastating impact on the quality of life of patients and families and comes with a huge cost to society. Dementia prevention is considered a public health priority by the World Health Organization. Delaying the onset of dementia by treating associated risk factors will bring huge individual and societal benefit. Empirical evidence suggests that, in higher-income countries, dementia incidence is decreasing as a result of healthier lifestyles. This observation supports the notion that preventing dementia is possible and that a certain degree of prevention is already in action. Further reduction of dementia incidence through deliberate prevention plans is needed to counteract its growing prevalence due to increasing life expectancy. An increasing number of individuals with normal cognitive performance seek help in the current memory clinics asking an evaluation of their dementia risk, preventive interventions, or interventions to ameliorate their cognitive performance. Consistent evidence suggests that some of these individuals are indeed at increased risk of dementia. This new health demand asks for a shift of target population, from patients with cognitive impairment to worried but cognitively unimpaired individuals. However, current memory clinics do not have the programs and protocols in place to deal with this new population. We envision the development of new services, henceforth called Brain Health Services, devoted to respond to demands from cognitively unimpaired individuals concerned about their risk of dementia. The missions of Brain Health Services will be (i) dementia risk profiling, (ii) dementia risk communication, (iii) dementia risk reduction, and (iv) cognitive enhancement. In this paper, we present the organizational and structural challenges associated with the set-up of Brain Health Services.

Abstract Although prevention of dementia and late-life cognitive decline is a major public health priority, there are currently no generally established prevention strategies or operational models for implementing such strategies into practice. This article is a narrative review of available evidence from multidomain dementia prevention trials targeting several risk factors and disease mechanisms simultaneously, in individuals without dementia at baseline. Based on the findings, we formulate recommendations for implementing precision risk reduction strategies into new services called Brain Health Services. A literature search was conducted using medical databases (MEDLINE via PubMed and SCOPUS) to select relevant studies: non-pharmacological multidomain interventions (i.e., combining two or more intervention domains), target population including individuals without dementia, and primary outcomes including cognitive/functional performance changes and/or incident cognitive impairment or dementia. Further literature searches covered the following topics: sub-group analyses assessing potential modifiers for the intervention effect on cognition in the multidomain prevention trials, dementia risk scores used as surrogate outcomes in multidomain prevention trials, dementia risk scores in relation to brain pathology markers, and cardiovascular risk scores in relation to dementia. Multidomain intervention studies conducted so far appear to have mixed results and substantial variability in target populations, format and intensity of interventions, choice of control conditions, and outcome measures. Most trials were conducted in high-income countries. The differences in design between the larger, longer-term trials that met vs. did not meet their primary outcomes suggest that multidomain intervention effectiveness may be dependent on a precision prevention approach, i.e., successfully identifying the at-risk groups who are most likely to benefit. One such successful trial has already developed an operational model for implementing the intervention into practice. Evidence on the efficacy of risk reduction interventions is promising, but not yet conclusive. More long-term multidomain randomized controlled trials are needed to fill the current evidence gaps, especially concerning low- and middle-income countries and integration of dementia prevention with existing cerebrovascular prevention programs. A precision risk reduction approach may be most effective for dementia prevention. Such an approach could be implemented in Brain Health Services.

Abstract Brain Health Services are a novel approach to the personalized prevention of dementia. In this paper, we consider how such services can best reflect their social, cultural, and economic context and, in doing so, deliver fair and equitable access to risk reduction. We present specific areas of challenge associated with the social context for dementia prevention. The first concentrates on how Brain Health Services engage with the “at-risk“ individual, recognizing the range of factors that shape an individual’s risk of dementia and the efficacy of risk reduction measures. The second emphasizes the social context of Brain Health Services themselves and their ability to provide equitable access to risk reduction. We then elaborate proposals for meeting or mitigating these challenges. We suggest that considering these challenges will enable Brain Health Services to address two fundamental questions: the balance between an individualized “high-risk” and population focus for public health prevention and the ability of services to meet ethical standards of justice and health equity.

Abstract We envisage the development of new Brain Health Services to achieve primary and secondary dementia prevention. These services will complement existing memory clinics by targeting cognitively unimpaired individuals, where the focus is on risk profiling and personalized risk reduction interventions rather than diagnosing and treating late-stage disease. In this article, we review key potentially modifiable risk factors and genetic risk factors and discuss assessment of risk factors as well as additional fluid and imaging biomarkers that may enhance risk profiling. We then outline multidomain measures and risk profiling and provide practical guidelines for Brain Health Services, with consideration of outstanding uncertainties and challenges. Users of Brain Health Services should undergo risk profiling tailored to their age, level of risk, and availability of local resources. Initial risk assessment should incorporate a multidomain risk profiling measure. For users aged 39–64, we recommend the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) Dementia Risk Score, whereas for users aged 65 and older, we recommend the Brief Dementia Screening Indicator (BDSI) and the Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI). The initial assessment should also include potentially modifiable risk factors including sociodemographic, lifestyle, and health factors. If resources allow, apolipoprotein E ɛ4 status testing and structural magnetic resonance imaging should be conducted. If this initial assessment indicates a low dementia risk, then low intensity interventions can be implemented. If the user has a high dementia risk, additional investigations should be considered if local resources allow. Common variant polygenic risk of late-onset AD can be tested in middle-aged or older adults. Rare variants should only be investigated in users with a family history of early-onset dementia in a first degree relative. Advanced imaging with 18-fluorodeoxyglucose positron emission tomography (FDG-PET) or amyloid PET may be informative in high risk users to clarify the nature and burden of their underlying pathologies. Cerebrospinal fluid biomarkers are not recommended for this setting, and blood-based biomarkers need further validation before clinical use. As new technologies become available, advances in artificial intelligence are likely to improve our ability to combine diverse data to further enhance risk profiling. Ultimately, Brain Health Services have the potential to reduce the future burden of dementia through risk profiling, risk communication, personalized risk reduction, and cognitive enhancement interventions.

Abstract Background The Japanese Association of Dialysis Physicians, the Japanese Society for Dialysis Therapy, and the Japanese Society of Nephrology jointly established COVID-19 Task Force Committee and began surveying the number of newly infected patients. Methods This registry of the COVID-19 Task Force Committee was used to collect data of dialysis patients; a total of 1010 dialysis patients with COVID-19 were included in the analysis. Overall survival of patients was investigated with stratification by age group, complication status, and treatment. In addition, predictive factors for mortality were also investigated. The overall survival was estimated by Kaplan–Meier methods and compared by using log-rank test. Multivariate analysis was performed to identify the risk factor of mortality. For all statistical analyses, p

Abstract Background People with disabilities (PwD) have been facing multiple health, social, and economic disparities during the COVID-19 pandemic, stemming from structural disparities experienced for long time. This paper aims to present the PREparedness, RESponse and SySTemic transformation (PRE-RE-SyST): a model for a disability-inclusive pandemic responses and systematic disparities reduction. Methods Scoping review with a thematic analysis was conducted on the literature published up to mid-September 2020, equating to the initial stages of the COVID-19 pandemic. Seven scientific databases and three preprint databases were searched to identify empirical or perspective papers addressing health and socio-economic disparities experienced by PwD as well as reporting actions to address them. Snowballing searches and experts’ consultation were also conducted. Two independent reviewers made eligibility decisions and performed data extractions on any action or recommended action to address disparities. A thematic analysis was then used for the model construction, informed by a systems-thinking approach (i.e., the Iceberg Model). Results From 1027 unique references, 84 were included in the final analysis. The PRE-RE-SyST model articulates a four-level strategic action to: 1) Respond to prevent or reduce disability disparities during a pandemic crisis; 2) Prepare ahead for pandemic and other crises responses; 3) Design systems and policies for a structural disability-inclusiveness; and 4) Transform society’s cultural assumptions about disability. ‘Simple rules’ and literature-based examples on how these strategies can be deployed are provided. Conclusion The PRE-RE-SyST model articulates main strategies, ‘simple rules’ and possible means whereby public health authorities, policy-makers, and other stakeholders can address disability disparities in pandemic crises, and beyond. Beyond immediate pandemic responses, disability-inclusiveness is needed to develop everyday equity-oriented policies and practices that can transform societies towards greater resiliency, as a whole, to pandemic and other health and social emergencies.

This study employs a survey of undergraduate business school freshmen to examine factors that influence their decision to study business and whether these factors differ by gender. Specifically, the study examines internal factors, such as students' perceived aptitudes and interests in the subject; external factors, such as compensation and job availability; and social/interpersonal influences, such as input of teachers, school counselors, parents, and friends. This paper follows up on the authors' earlier work, which found that despite an increase in the number of male students enrolled in business programs across the nation during the period between 2003 and 2011, female representation declined--an enrollment trend with significant consequences for colleges of business, industry, and the national economy. This study is an attempt to understand this trend by identifying those factors that may influence women to choose business as an undergraduate major.

Host genetics is a key determinant of COVID-19 outcomes. Previously, the COVID-19 Host Genetics Initiative genome-wide association study used common variants to identify multiple loci associated with COVID-19 outcomes. However, variants with the largest impact on COVID-19 outcomes are expected to be rare in the population. Hence, studying rare variants may provide additional insights into disease susceptibility and pathogenesis, thereby informing therapeutics development. Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease (95% CI: 2.75-10.05, p = 5.41x10-7). This association was consistent across sexes. These results further support TLR7 as a genetic determinant of severe disease and suggest that larger studies on rare variants influencing COVID-19 outcomes could provide additional insights.

An investigation on fatty acid, triacylglycerol, tocopherol, and xanthophyll contents and thermal properties of pecan (Carya illinoinensis) kernel oils from two cultivars was carried out. The main fatty acids were oleic acid, followed by linoleic and palmitic acids. The predominant triacylglycerols were OOL, OOO, and OLL (where O stands for oleoyl and L for linoleoyl). Pecan kernel oil is a rich source of tocopherols, mainly γ-tocopherol. Two xanthophylls (lutein and zeaxanthin) were investigated, and lutein was found to be the major one. Thermal behavior was studied by differential scanning calorimetry (DSC). Pecan nut oil displayed melting and crystallization transitions at low-temperature zones. The difference between DSC parameter values provides a path for distinguishing among cultivars. These data promote pecan kernel oil as a potential source of bioactive compounds with nutraceutical properties (monounsaturated fatty acids, tocopherols, and xanthophylls) and reveal, for the first time, the thermal properties of Carya illinoinensis oil.

Abstract Background Despite remarkable achievements in antiretroviral therapy (ART), losses to follow-up (LTFU) might prevent the long-term success of HIV treatment and might delay the achievement of the 90–90-90 objectives. This scoping review is aimed at the description and analysis of the strategies used in high-income countries to reengage LTFU in HIV care, their implementation and impact. Methods A scoping review was done following Arksey & O′Malley’s methodological framework and recommendations from Joanna Briggs Institute. Peer reviewed articles were searched for in Pubmed, Scopus and Web of Science; and grey literature was searched for in Google and other sources of information. Documents were charted according to the information presented on LTFU, the reengagement procedures used in HIV units in high-income countries, published during the last 15 years. In addition, bibliographies of chosen articles were reviewed for additional articles. Results Twenty-eight documents were finally included, over 80% of them published in the United States later than 2015. Database searches, phone calls and/or mail contacts were the most common strategies used to locate and track LTFU, while motivational interviews and strengths-based techniques were used most often during reengagement visits. Outcomes like tracing activities efficacy, rates of reengagement and viral load reduction were reported as outcome measures. Conclusions This review shows a recent and growing trend in developing and implementing patient reengagement strategies in HIV care. However, most of these strategies have been implemented in the United States and little information is available for other high-income countries. The procedures used to trace and contact LTFU are similar across reviewed studies, but their impact and sustainability are widely different depending on the country studied.

Abstract Background Survivors of severe COVID-19 are at risk of impaired health-related quality of life (HRQoL) and persistent physical and psychological disability after ICU and hospital discharge. The subsequent social burden is a major concern. We aimed to assess the short-term HRQoL, physical function and prevalence of post-traumatic stress symptoms of invasively mechanically ventilated COVID-19 patients treated in our ICU. Methods Prospective, observational cohort study in a follow-up clinic. Patients completed a 6-min walking test (6MWT) to assess their cardio-pulmonary function around 2 months (early follow-up) from hospital discharge, the EQ-5D-5L questionnaire for quality of life assessment around 2 months and at 6 months from hospital discharge and an anonymous web-based Impact of Event Scale-Revised (IES-R) questionnaire for Post-Traumatic Stress symptoms at 2 months. Results 47 patients attended our follow-up program, mean age 59 ± 10 years, median pre-morbid Clinical Frailty Scale (CFS) 2 [2–3]. The median distance walked in 6 min was 470 [406–516] m, 83 [67–99]% of the predicted value. Overall 1 out 3 patients and 4/18 (22%) among those with a good functional baseline prior to COVID-19 (CFS of 1 or 2) had lower (84%) than predicted 6MWT. EQ-5D-5L quality of life VAS was 80 [70–90] out of 100 at early follow-up with a slight improvement to 85 [77.5–90] at 6 months. Mobility, self-care and usual activities improved between the two timepoints, while pain/discomfort and depression/anxiety did not improve or got worse. The IES-R total score was greater than the threshold for concern of 1.6 in 27/41(66%) respondents. Conclusions Patients recovering from severe COVID-19 requiring invasive mechanical ventilation surviving hospital discharge present with early mild to moderate functional impairment, mildly reduced quality of life from hospital discharge with an overall improvement of mobility, self-care and the ability of performing usual activities, while a worsening of pain and depression/anxiety symptoms at 6 months and a large proportion of symptoms of post-traumatic distress soon after hospital discharge.

Background: Myanmar has one of the largest malaria burdens in Southeast Asia. Along the border with Thailand, Plasmodium falciparum parasites are increasingly showing reduced sensitivity to artemisinin combination therapies. Given that there are no current alternative treatment therapies, one proposed solution to the threat of untreatable P. falciparum malaria is to eliminate the parasite from the region. Several small-scale elimination projects have been piloted along the Myanmar-Thailand border. Following their success, this operational research aimed to scale up the elimination to a broad area of Eastern Kayin State, Myanmar. Methods: The project relied on geographic reconnaissance and a geographic information system, community engagement, generalized access to community-based early diagnosis and treatment, near real-time epidemiological surveillance, cross sectional malaria prevalence surveys and targeted mass drug administration in villages with high prevalence of P. falciparum malaria. Molecular markers of drug resistance were also monitored in individuals with symptomatic and asymptomatic infections. Discussion: This project illustrates the establishment of an elimination project and operational research in a remote, rural area encompassing several armed groups, multiple political organizations and a near-absent health care infrastructure. The establishment of the project relied on a strong rapport with the target community, on-the-ground knowledge (through geographic surveys and community engagement), rapid decision making and an approach that was flexible enough to quickly adapt to a complex landscape. The elimination project is ongoing, now over three years in operation, and assessment of the impact of this operational research will follow. This project has relevance not only for other malaria elimination projects but also for operational research aimed at eliminating other diseases.

Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content. Using genome-wide association, we identified Tnni3k as one gene that influences variation in this composition and demonstrated that Tnni3k knockout resulted in elevated MNDCM content and increased cardiomyocyte proliferation after injury. Reciprocally, overexpression of Tnni3k in zebrafish promoted cardiomyocyte polyploidization and compromised heart regeneration. Our results corroborate the relevance of MNDCMs in heart regeneration. Moreover, they imply that intrinsic heart regeneration is not limited nor uniform in all individuals, but rather is a variable trait influenced by multiple genes.

ImportanceOne 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 considerationsStudies 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.ObjectiveTo update the 2011 US Preventive Services Task Force (USPSTF) recommendation on screening for amblyopia and its risk factors in children.Evidence reviewThe 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.FindingsTreatment 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 recommendationsThe 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).

ImportanceAdults who adhere to national guidelines for a healthful diet and physical activity have lower rates of cardiovascular morbidity and mortality than those who do not. All persons, regardless of their risk status for cardiovascular disease (CVD), can gain health benefits from healthy eating behaviors and appropriate physical activity.ObjectiveTo update the 2012 US Preventive Services Task Force (USPSTF) recommendation on behavioral counseling to promote a healthful diet and physical activity for cardiovascular disease prevention among adults without obesity who do not have cardiovascular risk factors (hypertension, dyslipidemia, abnormal blood glucose levels, or diabetes).Evidence reviewThe USPSTF reviewed the evidence on whether primary care-relevant counseling interventions to promote a healthful diet, physical activity, or both improve health outcomes, intermediate outcomes associated with CVD, or dietary or physical activity behaviors in adults; interventions to reduce sedentary behaviors; and the harms of behavioral counseling interventions.FindingsCounseling interventions result in improvements in healthful behaviors and small but potentially important improvements in intermediate outcomes, including reductions in blood pressure and low-density lipoprotein cholesterol levels and improvements in measures of adiposity. The overall magnitude of benefit related to these interventions is positive but small. The potential harms are at most small, leading the USPSTF to conclude that these interventions have a small net benefit for adults without obesity who do not have CVD risk factors.Conclusions and recommendationThe USPSTF recommends that primary care professionals individualize the decision to offer or refer adults without obesity who do not have hypertension, dyslipidemia, abnormal blood glucose levels, or diabetes to behavioral counseling to promote a healthful diet and physical activity. Existing evidence indicates a positive but small benefit of behavioral counseling for the prevention of CVD in this population. Persons who are interested and ready to make behavioral changes may be most likely to benefit from behavioral counseling. (C recommendation).

ImportanceBased on year 2000 Centers for Disease Control and Prevention growth charts, approximately 17% of children and adolescents aged 2 to 19 years in the United States have obesity, and almost 32% of children and adolescents are overweight or have obesity. Obesity in children and adolescents is associated with morbidity such as mental health and psychological issues, asthma, obstructive sleep apnea, orthopedic problems, and adverse cardiovascular and metabolic outcomes (eg, high blood pressure, abnormal lipid levels, and insulin resistance). Children and adolescents may also experience teasing and bullying behaviors based on their weight. Obesity in childhood and adolescence may continue into adulthood and lead to adverse cardiovascular outcomes or other obesity-related morbidity, such as type 2 diabetes.Subpopulation considerationsAlthough the overall rate of child and adolescent obesity has stabilized over the last decade after increasing steadily for 3 decades, obesity rates continue to increase in certain populations, such as African American girls and Hispanic boys. These racial/ethnic differences in obesity prevalence are likely a result of both genetic and nongenetic factors (eg, socioeconomic status, intake of sugar-sweetened beverages and fast food, and having a television in the bedroom).ObjectiveTo update the 2010 US Preventive Services Task Force (USPSTF) recommendation on screening for obesity in children 6 years and older.Evidence reviewThe USPSTF reviewed the evidence on screening for obesity in children and adolescents and the benefits and harms of weight management interventions.FindingsComprehensive, intensive behavioral interventions (≥26 contact hours) in children and adolescents 6 years and older who have obesity can result in improvements in weight status for up to 12 months; there is inadequate evidence regarding the effectiveness of less intensive interventions. The harms of behavioral interventions can be bounded as small to none, and the harms of screening are minimal. Therefore, the USPSTF concluded with moderate certainty that screening for obesity in children and adolescents 6 years and older is of moderate net benefit.Conclusions and recommendationThe USPSTF recommends that clinicians screen for obesity in children and adolescents 6 years and older and offer or refer them to comprehensive, intensive behavioral interventions to promote improvements in weight status. (B recommendation).

ImportanceThe incidence of thyroid cancer detection has increased by 4.5% per year over the last 10 years, faster than for any other cancer, but without a corresponding change in the mortality rate. In 2013, the incidence rate of thyroid cancer in the United States was 15.3 cases per 100 000 persons. Most cases of thyroid cancer have a good prognosis; the 5-year survival rate for thyroid cancer overall is 98.1%.ObjectiveTo update the US Preventive Services Task Force (USPSTF) recommendation on screening for thyroid cancer.Evidence reviewThe USPSTF reviewed the evidence on the benefits and harms of screening for thyroid cancer in asymptomatic adults, the diagnostic accuracy of screening (including neck palpation and ultrasound), and the benefits and harms of treatment of screen-detected thyroid cancer.FindingsThe USPSTF found inadequate direct evidence on the benefits of screening but determined that the magnitude of the overall benefits of screening and treatment can be bounded as no greater than small, given the relative rarity of thyroid cancer, the apparent lack of difference in outcomes between patients who are treated vs monitored (for the most common tumor types), and observational evidence showing no change in mortality over time after introduction of a mass screening program. The USPSTF found inadequate direct evidence on the harms of screening but determined that the overall magnitude of the harms of screening and treatment can be bounded as at least moderate, given adequate evidence of harms of treatment and indirect evidence that overdiagnosis and overtreatment are likely to be substantial with population-based screening. The USPSTF therefore determined that the net benefit of screening for thyroid cancer is negative.Conclusions and recommendationThe USPSTF recommends against screening for thyroid cancer in asymptomatic adults. (D recommendation).

ImportancePreeclampsia affects approximately 4% of pregnancies in the United States. It is the second leading cause of maternal mortality worldwide and may lead to serious maternal complications, including stroke, eclampsia, and organ failure. Adverse perinatal outcomes for the fetus and newborn include intrauterine growth restriction, low birth weight, and stillbirth. Many of the complications associated with preeclampsia lead to early induction of labor or cesarean delivery and subsequent preterm birth.Subpopulation considerationsPreeclampsia is more prevalent among African American women than among white women. Differences in prevalence may be, in part, due to African American women being disproportionally affected by risk factors for preeclampsia. African American women also have case fatality rates related to preeclampsia 3 times higher than rates among white women. Inequalities in access to adequate prenatal care may contribute to poor outcomes associated with preeclampsia in African American women.ObjectiveTo update the 1996 US Preventive Services Task Force (USPSTF) recommendation on screening for preeclampsia.Evidence reviewThe USPSTF reviewed the evidence on the accuracy of screening and diagnostic tests for preeclampsia, the potential benefits and harms of screening for preeclampsia, the effectiveness of risk prediction tools, and the benefits and harms of treatment of screen-detected preeclampsia.FindingsGiven the evidence that treatment can reduce maternal and perinatal morbidity and mortality, and the well-established accuracy of blood pressure measurements, the USPSTF found adequate evidence that screening for preeclampsia results in a substantial benefit for the mother and infant. In addition, there is adequate evidence to bound the harms of screening for and treatment of preeclampsia as no greater than small. Therefore, the USPSTF concludes with moderate certainty that there is a substantial net benefit of screening for preeclampsia in pregnant women.Conclusions and recommendationThe USPSTF recommends screening for preeclampsia in pregnant women with blood pressure measurements throughout pregnancy. (B recommendation).

ImportanceMany conditions that can affect women's health are often evaluated through pelvic examination. Although the pelvic examination is a common part of the physical examination, it is unclear whether performing screening pelvic examinations in asymptomatic women has a significant effect on disease morbidity and mortality.ObjectiveTo issue a new US Preventive Services Task Force (USPSTF) recommendation on screening for gynecologic conditions with pelvic examination for conditions other than cervical cancer, gonorrhea, and chlamydia, for which the USPSTF has already made specific recommendations.Evidence reviewThe USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women 18 years and older who are not at increased risk for any specific gynecologic condition.FindingsOverall, the USPSTF found inadequate evidence on screening pelvic examinations for the early detection and treatment of a range of gynecologic conditions in asymptomatic, nonpregnant adult women.Conclusions and recommendationThe USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of performing screening pelvic examinations in asymptomatic, nonpregnant adult women. (I statement) This statement does not apply to specific disorders for which the USPSTF already recommends screening (ie, screening for cervical cancer with a Papanicolaou smear, screening for gonorrhea and chlamydia).

ImportanceCeliac disease is caused by an immune response in persons who are genetically susceptible to dietary gluten, a protein complex found in wheat, rye, and barley. Ingestion of gluten by persons with celiac disease causes immune-mediated inflammatory damage to the small intestine.ObjectiveTo issue a new US Preventive Services Task Force (USPSTF) recommendation on screening for celiac disease.Evidence reviewThe USPSTF reviewed the evidence on the accuracy of screening in asymptomatic adults, adolescents, and children; the potential benefits and harms of screening vs not screening and targeted vs universal screening; and the benefits and harms of treatment of screen-detected celiac disease. The USPSTF also reviewed contextual information on the prevalence of celiac disease among patients without obvious symptoms and the natural history of subclinical celiac disease.FindingsThe USPSTF found inadequate evidence on the accuracy of screening for celiac disease, the potential benefits and harms of screening vs not screening or targeted vs universal screening, and the potential benefits and harms of treatment of screen-detected celiac disease.Conclusions and recommendationThe USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for celiac disease in asymptomatic persons. (I statement).

Background: Myanmar has one of the largest malaria burdens in the Greater Mekong Subregion (GMS). Throughout the GMS, Plasmodium falciparum parasites are increasingly resistant to artemisinin combination therapies. Given that there are no current alternative treatment therapies, one proposed solution to the threat of untreatable P. falciparum malaria is to eliminate the parasite from the region. Several small-scale elimination projects have been piloted in the GMS, including along the Myanmar-Thailand border. Following the success of the pilot elimination project along the Myanmar-Thailand border, there was a scale up to a broad area of Eastern Kayin State, Myanmar. Here we describe the establishment of the scale up elimination project in Easter Kayin State. Methods: The scale up relied on geographic reconnaissance and a geographic information system, community engagement, generalized access to community-based early diagnosis and treatment, near real-time epidemiological surveillance, cross sectional malaria prevalence surveys and targeted mass drug administration in villages with high prevalence of P. falciparum malaria. Molecular markers of drug resistance were also monitored in individuals with symptomatic and asymptomatic infections. Discussion: This protocol illustrates the establishment of an elimination project and operational research in a remote, rural area encompassing several armed groups, multiple political organizations and a near-absent health care infrastructure. The establishment of the project relied on a strong rapport with the target community, on-the-ground knowledge (through geographic surveys and community engagement), rapid decision making and an approach that was flexible enough to quickly adapt to a complex landscape. The elimination project is ongoing, now over three years in operation, and assessment of the impact of this operational research will follow. This project has relevance not only for other malaria elimination projects but also for operational research aimed at eliminating other diseases.

ImportanceBased on data from the 1990s, estimated prevalence of obstructive sleep apnea (OSA) in the United States is 10% for mild OSA and 3.8% to 6.5% for moderate to severe OSA; current prevalence may be higher, given the increasing prevalence of obesity. Severe OSA is associated with increased all-cause mortality, cardiovascular disease and cerebrovascular events, diabetes, cognitive impairment, decreased quality of life, and motor vehicle crashes.ObjectiveTo issue a new US Preventive Services Task Force (USPSTF) recommendation on screening for OSA in asymptomatic adults.Evidence reviewThe USPSTF reviewed the evidence on the accuracy, benefits, and potential harms of screening for OSA in asymptomatic adults seen in primary care, including those with unrecognized symptoms. The USPSTF also evaluated the evidence on the benefits and harms of treatment of OSA on intermediate and final health outcomes.FindingsThe USPSTF found insufficient evidence on screening for or treatment of OSA in asymptomatic adults or adults with unrecognized symptoms. Therefore, the USPSTF was unable to determine the magnitude of the benefits or harms of screening for OSA or whether there is a net benefit or harm to screening.Conclusions and recommendationThe USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for OSA in asymptomatic adults. (I statement).

ImportanceNeural tube defects are among the most common major congenital anomalies in the United States and may lead to a range of disabilities or death. Daily folic acid supplementation in the periconceptional period can prevent neural tube defects. However, most women do not receive the recommended daily intake of folate from diet alone.ObjectiveTo update the 2009 US Preventive Services Task Force (USPSTF) recommendation on folic acid supplementation in women of childbearing age.Evidence reviewIn 2009, the USPSTF reviewed the effectiveness of folic acid supplementation in women of childbearing age for the prevention of neural tube defects in infants. The current review assessed new evidence on the benefits and harms of folic acid supplementation.FindingsThe USPSTF assessed the balance of the benefits and harms of folic acid supplementation in women of childbearing age and determined that the net benefit is substantial. Evidence is adequate that the harms to the mother or infant from folic acid supplementation taken at the usual doses are no greater than small. Therefore, the USPSTF reaffirms its 2009 recommendation.Conclusions and recommendationThe USPSTF recommends that all women who are planning or capable of pregnancy take a daily supplement containing 0.4 to 0.8 mg (400-800 µg) of folic acid. (A recommendation).

ImportanceGenital herpes is a prevalent sexually transmitted infection in the United States, occurring in almost 1 in 6 persons aged 14 to 49 years. Infection is caused by 2 subtypes of the herpes simplex virus (HSV), HSV-1 and HSV-2. Antiviral medications may provide symptomatic relief from outbreaks but do not cure HSV infection. Neonatal herpes infection, while uncommon, can result in substantial morbidity and mortality.ObjectiveTo update the 2005 US Preventive Services Task Force (USPSTF) recommendation on screening for genital herpes.Evidence reviewThe USPSTF reviewed the evidence on the accuracy, benefits, and harms of serologic screening for HSV-2 infection in asymptomatic persons, including those who are pregnant, as well as the effectiveness and harms of preventive medications and behavioral counseling interventions to reduce future symptomatic episodes and transmission to others.FindingsBased on the natural history of HSV infection, its epidemiology, and the available evidence on the accuracy of serologic screening tests, the USPSTF concluded that the harms outweigh the benefits of serologic screening for genital HSV infection in asymptomatic adolescents and adults, including those who are pregnant.Conclusions and recommendationThe USPSTF recommends against routine serologic screening for genital HSV infection in asymptomatic adolescents and adults, including those who are pregnant. (D recommendation).

Scientific software registries and repositories improve software findability and research transparency, provide information for software citations, and foster preservation of computational methods in a wide range of disciplines. Registries and repositories play a critical role by supporting research reproducibility and replicability, but developing them takes effort and few guidelines are available to help prospective creators of these resources. To address this need, the FORCE11 Software Citation Implementation Working Group convened a Task Force to distill the experiences of the managers of existing resources in setting expectations for all stakeholders. In this article, we describe the resultant best practices which include defining the scope, policies, and rules that govern individual registries and repositories, along with the background, examples, and collaborative work that went into their development. We believe that establishing specific policies such as those presented here will help other scientific software registries and repositories better serve their users and their disciplines.

Background: Torus (buckle) fractures of the wrist are the most common fractures in children involving the distal radius and/or ulna. It is unclear if children require rigid immobilisation and follow-up or would recover equally as well by being discharged without any immobilisation or a bandage. Given the large number of these injuries, identifying the optimal treatment strategy could have important effects on the child, the number of days of school absence and NHS costs. Objectives: To establish whether or not treating children with a distal radius torus fracture with the offer of a soft bandage and immediate discharge (i.e. offer of a bandage) provides the same recovery, in terms of pain, function, complications, acceptability, school absence and resource use, as treatment with rigid immobilisation and follow-up as per usual practice (i.e. rigid immobilisation). Design: A pragmatic, multicentre, randomised controlled equivalence trial. Setting: Twenty-three UK emergency departments. Participants: A total of 965 children (aged 4–15 years) with a distal radius torus fracture were randomised from January 2019 to July 2020 using a secure, centralised, online-encrypted randomisation service. Exclusion criteria included presentation > 36 hours after injury, multiple injuries and an inability to complete follow-up. Interventions: A bandage was offered to 489 participants and applied to 458, and rigid immobilisation was carried out in 476 participants. Participants and clinicians were not blinded to the treatment allocation. Main outcome measures: The pain at 3 days post randomisation was measured using the Wong–Baker FACES Pain Rating Scale. Secondary outcomes were the patient-reported outcomes measurement system upper extremity limb score for children, health-related quality of life, complications, school absence, analgesia use and resource use collected up to 6 weeks post randomisation. Results: A total of 94% of participants provided primary outcome data. At 3 days, the primary outcome of pain was equivalent in both groups. With reference to the prespecified equivalence margin of 1.0, the adjusted difference in the intention-to-treat population was –0.10 (95% confidence interval –0.37 to 0.17) and the per-protocol population was –0.06 (95% confidence interval –0.34 to 0.21). There was equivalence of pain in both age subgroups (i.e. 4–7 years and 8–15 years). There was no difference in the rate of complications, with five complications (1.0%) in the offer of a bandage group and three complications (0.6%) in the rigid immobilisation group. There were no differences between treatment groups in functional recovery, quality of life or school absence at any point during the follow-up. Analgesia use was marginally higher at day 1 in the offer of a bandage group than it was in the rigid immobilisation group (83% vs. 78% of participants), but there was no difference at other time points. The offer of a bandage significantly reduced the cost of treatment and had a high probability of cost-effectiveness at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year. Limitations: Families had a strong pre-existing preference for the rigid immobilisation treatment. Given this, and the inability to blind families to the treatment allocation, observer bias was a concern. However, there was clear evidence of equivalence. Conclusions: The study findings support the offer of a bandage in children with a distal radius torus fracture. Future work: A clinical decision tool to determine which children require radiography is an important next step to prevent overtreatment of minor wrist fractures. There is also a need to rationalise interventions for other common childhood injuries (e.g. ‘toddler’s fractures’ of the tibia). Trial registration: This trial is registered as ISRCTN13955395 and UKCRN Portfolio 39678. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 33. See the NIHR Journals Library website for further project information.

Abstract Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic affecting a variety of medical treatments, including hemodialysis. This study aims to investigate the implementation of infection control measures, to examine the shortage of personal protective equipment (PPE) and disinfectants, and to quantify the number of nosocomial COVID-19 transmissions in hemodialysis facilities in Japan during the pandemic. Methods We conducted a nationwide questionnaire survey between 20 October and 16 November 2020 (i.e., between the “second wave” and “third wave” in Japan) in the 4198 dialysis facilities of the Japanese Association of Dialysis Physicians and the Japanese Society for Dialysis Therapy. A total of 2227 facilities (53.0%) responded. The questionnaire consisted of (i) characteristics of facilities, (ii) infection prevention measures in routine dialysis practices, (iii) shortage of PPE, (iv) feasibility of various isolation measures, and (v) nosocomial transmission. Results Half of the responding facilities were hospitals with multiple departments, and the other half were clinics specialized in dialysis. Several infection prevention measures such as health checks of staff and patients, donning of masks before and after hemodialysis, and disinfection of frequently contacted areas were implemented during the COVID-19 pandemic. There was a significant improvement in the implementation rate of these measures during the pandemic, compared to before it, which reached over 90%. More than half of the facilities reported a shortage of disposable masks (67.2%) and hand sanitizer alcohol (56.7%). Isolation of COVID-19 patients in private rooms was possible only in 52.7% of the facilities. The majority of facilities (73.3%) could not accept COVID-19 dialysis patients due to lack of space and manpower. Nosocomial transmission of COVID-19 occurred in 4.0% of the facilities. Of those infected, 51.9% were staff. Conclusions This survey revealed that most hemodialysis facilities in Japan had improved implementation of infection control measures and had shortage of PPEs and disinfectants, though some facilities did not implement infection prevention measures adequately, mainly due to the limited space of the facility. It may be recommended that each facility immediately establishes isolation measures to prepare for the pandemic of COVID-19.

Abstract Background Rapid and simple serological assays for characterizing antibody responses are important in the current COVID-19 pandemic caused by SARS-CoV-2. Multiplex immunoblot (IB) assays termed COVID-19 IB assays were developed for detecting IgG and IgM antibodies to SARS-CoV-2 virus proteins in COVID-19 patients. Methods Recombinant nucleocapsid protein and the S1, S2 and receptor binding domain (RBD) of the spike protein of SARS-CoV-2 were used as target antigens in the COVID-19 IBs. Specificity of the IB assay was established with 231 sera from persons with allergy, unrelated viral infections, autoimmune conditions and suspected tick-borne diseases, and 32 goat antisera to human influenza proteins. IgG and IgM COVID-19 IBs assays were performed on 84 sera obtained at different times after a positive RT-qPCR test from 37 COVID-19 patients with mild symptoms. Results Criteria for determining overall IgG and IgM antibody positivity using the four SARS-CoV-2 proteins were developed by optimizing specificity and sensitivity in the COVID-19 IgG and IgM IB assays. The estimated sensitivities and specificities of the COVID-19 IgG and IgM IBs for IgG and IgM antibodies individually or for either IgG or IgM antibodies meet the US recommendations for laboratory serological diagnostic tests. The proportion of IgM-positive sera from the COVID-19 patients following an RT-qPCR positive test was maximal at 83% before 10 days and decreased to 0% after 100 days, while the proportions of IgG-positive sera tended to plateau between days 11 and 65 at 78–100% and fall to 44% after 100 days. Detection of either IgG or IgM antibodies was better than IgG or IgM alone for assessing seroconversion in COVID-19. Both IgG and IgM antibodies detected RBD less frequently than S1, S2 and N proteins. Conclusions The multiplex COVID-19 IB assays offer many advantages for simultaneously evaluating antibody responses to different SARS-CoV-2 proteins in COVID-19 patients.

Associations between of omega-3 fatty acids and mortality are not clear. Here the authors report that, based on a pooled analysis of 17 prospective cohort studies, higher blood omega-3 fatty acid levels correlate with lower risk of all-cause mortality.

(1) Background: Preventive measures taken in response to the coronavirus disease 2019 (COVID-19) pandemic have adversely affected an entire range of cancer-related medical activities. The reallocation of medical resources, staff, and ambulatory services, as well as critical shortages in pharmaceutical and medical supplies have compelled healthcare professionals to prioritize patients with cancer to treatment and screening services based on a set of classification criteria in cancer-related guidelines. Cancer patients themselves have been affected on multiple levels, and addressing their concerns poses another challenge to the oncology community. (2) Methods: We conducted a Canada-wide search of cancer-related clinical practice guidelines on the management and prioritization of individuals into treatment and screening services. We also outlined the resources provided by Canadian cancer charities and patient advocacy groups to provide cancer patients, or potential cancer patients, with useful information and valuable support resources. (3) Results: The identified provincial guidelines emphasized cancer care (i.e., treatment) more than cancer control (i.e., screening). For cancer-related resources, a clear significance was placed on knowledge & awareness and supportive resources, mainly relating to mental health. (4) Conclusion: We provided a guidance document outlining cancer-related guidelines and resources that are available to healthcare providers and patients across Canada during the COVID-19 pandemic.

Abstract Background and purpose Coronavirus disease 2019 (COVID-19) is associated with a small but clinically significant risk of stroke, the cause of which is frequently cryptogenic. In a large multinational cohort of consecutive COVID-19 patients with stroke, we evaluated clinical predictors of cryptogenic stroke, short-term functional outcomes and in-hospital mortality among patients according to stroke etiology. Methods We explored clinical characteristics and short-term outcomes of consecutively evaluated patients 18 years of age or older with acute ischemic stroke (AIS) and laboratory-confirmed COVID-19 from 31 hospitals in 4 countries (3/1/20–6/16/20). Results Of the 14.483 laboratory-confirmed patients with COVID-19, 156 (1.1%) were diagnosed with AIS. Sixty-one (39.4%) were female, 84 (67.2%) white, and 88 (61.5%) were between 60 and 79 years of age. The most frequently reported etiology of AIS was cryptogenic (55/129, 42.6%), which was associated with significantly higher white blood cell count, c-reactive protein, and D-dimer levels than non-cryptogenic AIS patients (p

Introduction: Health systems worldwide are challenged to address the health-care needs of persons with COVID-19. After the immediate need to mitigate the spread of COVID-19 and scale up relevant health-care capacities, one major challenge has emerged – scaling up rehabilitation to address the functioning limitations experienced by COVID-19 patients/survivors. To meet this challenge, the International Society of Physical and Rehabilitation Medicine (ISPRM) endeavors to develop a tool for the assessment and reporting of functioning of COVID-19 patients/survivors – “ClinFIT COVID- 19” to assist health professionals to optimally address patients' health-care needs. The first step in the development process is identifying the International Classification of Functioning, Disability, and Health (ICF) categories that ClinFIT COVID-19 should cover for acute, postacute, and long-term settings. Methods: The multistep process to develop the ClinFIT COVID-19 category list involved the development of a proposed list of ICF categories, a survey of ISPRM members worldwide about the proposed category list, and a postsurvey consultation with the ISPRM ClinFIT Task Force. Results: The final category list for the acute care context contains the seven categories provided to the survey participants (energy/drive functions, sleep, emotional functions, pain, exercise tolerance functions, carrying out daily routine, and walking) plus six categories related to respiration, mobility, and cognition. The postacute and long-term care versions also contain the seven categories plus additional categories relevant for the specific context. The postacute version contains 15 categories and the long-term 16 categories. Conclusions: To advance the next steps, the leaders of ISPRM and the Task Force call national and international societies of rehabilitation professionals to join this coordinated effort.

Abstract Objective To identify possible socio-demographic and clinical factors associated with Good Outcome (GO) as compared with Poor Outcome (PO) in adult patients diagnosed with Bipolar Disorder (BD) who received long-term treatment with lithium. Methods A comprehensive search of major electronic databases was performed to identify relevant studies that included adults patients (18 years or older) with a diagnosis of BD and reported sociodemographic and/or clinical variables associated with treatment response and/or with illness outcome during long-term treatment to lithium (> = 6 months). The quality of the studies was scored using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies from the National Institute of Health. Results Following review, 34 publications (from 31 independent datasets) were eligible for inclusion in this review. Most of them (n = 25) used a retrospective design. Only 11 studies were graded as good or borderline good quality. Forty-three potential predictors of outcome to lithium were identified. Four factors were associated with PO to lithium: alcohol use disorder; personality disorders; higher lifetime number of hospital admissions and rapid cycling pattern. Two factors were associated with GO in patients treated with lithium: good social support and episodic evolution of BD. However, when the synthesis of findings was limited to the highest (good or borderline good) quality studies (11 studies), only higher lifetime number of hospitalization admissions remained associated with PO to lithium and no associations remained for GO to lithium. Conclusion Despite decades of research on lithium and its clinical use, besides lifetime number of hospital admissions, no factor being consistently associated with GO or PO to lithium was identified. Hence, there remains a substantial gap in our understanding of predictors of outcome of lithium treatment indicating there is a need of high quality research on large representative samples.

Abstract Background Personalized cancer vaccines are emerging as one of the most promising approaches to immunotherapy of advanced cancers. However, only a small proportion of the neoepitopes generated by somatic DNA mutations in cancer cells lead to tumor rejection. Since it is impractical to experimentally assess all candidate neoepitopes prior to vaccination, developing accurate methods for predicting tumor-rejection mediating neoepitopes (TRMNs) is critical for enabling routine clinical use of cancer vaccines. Results In this paper we introduce Positive-unlabeled Learning using AuTOml (PLATO), a general semi-supervised approach to improving accuracy of model-based classifiers. PLATO generates a set of high confidence positive calls by applying a stringent filter to model-based predictions, then rescores remaining candidates by using positive-unlabeled learning. To achieve robust performance on clinical samples with large patient-to-patient variation, PLATO further integrates AutoML hyper-parameter tuning, classification threshold selection based on spies, and support for bootstrapping. Conclusions Experimental results on real datasets demonstrate that PLATO has improved performance compared to model-based approaches for two key steps in TRMN prediction, namely somatic variant calling from exome sequencing data and peptide identification from MS/MS data.

Abstract We monitored the burden of cancer in Italy and its trends over the last three decades, providing estimates of cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs), for cancer overall and 30 cancer sites using data from the Global Burden of Disease study 2017. An overview of mortality trends between 1990 and 2017 was also provided. In 2017, there were 254,336 new cancer cases in men and 214,994 in women, corresponding to an age-standardized incidence rate (ASIR) of 438 and 330/100,000, respectively. Between 1990 and 2017, incident cancer cases, and, to a lesser extent, ASIRs significantly increased overall and for almost all cancer sites, but ASIRs significantly declined for lung and other tobacco-related neoplasms. In 2017, there were 101,659 cancer deaths in men (age-standardized death rate, ASDR, 158.5/100,000) and 78,918 in women (ASDR 93.9/100,000). Cancer deaths significantly increased between 1990 and 2017 (+ 18%), but ASDR significantly decreased (− 28%). Deaths significantly increased for many cancer sites, but decreased for stomach, esophageal, laryngeal, Hodgkin lymphoma, and testicular cancer. ASDRs significantly decreased for most neoplasms, with the main exceptions of cancer of the pancreas and uterus, and multiple myeloma. In 2017, cancer caused 3,204,000 DALYs. Between 1990 and 2017, DALYs and age-standardized DALY rates significantly declined (-3.4% and -33%, respectively). Age-standardized mortality rates in Italy showed favorable patterns over the last few decades. However, the absolute number of cancer cases and, to a lower extent, of cancer deaths increased likely due to the progressive ageing of the population, this calling for a continuous effort in cancer prevention, early diagnosis, and treatment.

ImportanceCardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States, accounting for 1 of every 3 deaths among adults.ObjectiveTo update the 2008 US Preventive Services Task Force (USPSTF) recommendation on screening for lipid disorders in adults.Evidence reviewThe USPSTF reviewed the evidence on the benefits and harms of screening for and treatment of dyslipidemia in adults 21 years and older; the benefits and harms of statin use in reducing CVD events and mortality in adults without a history of CVD events; whether the benefits of statin use vary by subgroup, clinical characteristics, or dosage; and the benefits of various treatment strategies in adults 40 years and older without a history of CVD events.Conclusions and recommendationsThe USPSTF recommends initiating use of low- to moderate-dose statins in adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors (dyslipidemia, diabetes, hypertension, or smoking) and a calculated 10-year CVD event risk of 10% or greater (B recommendation). The USPSTF recommends that clinicians selectively offer low- to moderate-dose statins to adults aged 40 to 75 years without a history of CVD who have 1 or more CVD risk factors and a calculated 10-year CVD event risk of 7.5% to 10% (C recommendation). The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of initiating statin use in adults 76 years and older (I statement).

ImportanceThere is convincing evidence that breastfeeding provides substantial health benefits for children. However, nearly half of all US mothers who initially breastfeed stop doing so by 6 months, and there are significant disparities in breastfeeding rates among younger mothers and in disadvantaged communities.ObjectiveTo update the 2008 US Preventive Services Task Force (USPSTF) recommendation on primary care interventions to promote breastfeeding.Evidence reviewThe USPSTF reviewed the evidence on the effectiveness of interventions to support breastfeeding on breastfeeding initiation, duration, and exclusivity. The USPSTF also briefly reviewed the literature on the effects of these interventions on child and maternal health outcomes.FindingsThe USPSTF found adequate evidence that interventions to support breastfeeding, including professional support, peer support, and formal education, change behavior and that the harms of these interventions are no greater than small. The USPSTF concludes with moderate certainty that interventions to support breastfeeding have a moderate net benefit.Conclusions and recommendationThe USPSTF recommends providing interventions during pregnancy and after birth to support breastfeeding. (B recommendation).

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.

ImportanceTuberculosis remains an important preventable disease in the United States. An effective strategy for reducing the transmission, morbidity, and mortality of active disease is the identification and treatment of latent tuberculosis infection (LTBI) to prevent progression to active disease.ObjectiveTo issue a current US Preventive Services Task Force (USPSTF) recommendation on screening for LTBI.Evidence reviewThe USPSTF reviewed the evidence on screening for LTBI in asymptomatic adults seen in primary care, including evidence dating from the inception of searched databases.FindingsThe USPSTF found adequate evidence that accurate screening tests for LTBI are available, treatment of LTBI provides a moderate health benefit in preventing progression to active disease, and the harms of screening and treatment are small. The USPSTF has moderate certainty that screening for LTBI in persons at increased risk for infection provides a moderate net benefit.Conclusions and recommendationThe USPSTF recommends screening for LTBI in populations at increased risk. (B recommendation).