Carilion Clinic

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on the management of chronic insomnia disorder in adults. METHODS: This guideline is based on a systematic review of randomized, controlled trials published in English from 2004 through September 2015. Evaluated outcomes included global outcomes assessed by questionnaires, patient-reported sleep outcomes, and harms. The target audience for this guideline includes all clinicians, and the target patient population includes adults with chronic insomnia disorder. This guideline grades the evidence and recommendations by using the ACP grading system, which is based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RECOMMENDATION 1: ACP recommends that all adult patients receive cognitive behavioral therapy for insomnia (CBT-I) as the initial treatment for chronic insomnia disorder. (Grade: strong recommendation, moderate-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians use a shared decision-making approach, including a discussion of the benefits, harms, and costs of short-term use of medications, to decide whether to add pharmacological therapy in adults with chronic insomnia disorder in whom cognitive behavioral therapy for insomnia (CBT-I) alone was unsuccessful. (Grade: weak recommendation, low-quality evidence).

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).

Importance: The number of deaths from cervical cancer in the United States has decreased substantially since the implementation of widespread cervical cancer screening and has declined from 2.8 to 2.3 deaths per 100 000 women from 2000 to 2015. Objective: To update the US Preventive Services Task Force (USPSTF) 2012 recommendation on screening for cervical cancer. Evidence Review: The USPSTF reviewed the evidence on screening for cervical cancer, with a focus on clinical trials and cohort studies that evaluated screening with high-risk human papillomavirus (hrHPV) testing alone or hrHPV and cytology together (cotesting) compared with cervical cytology alone. The USPSTF also commissioned a decision analysis model to evaluate the age at which to begin and end screening, the optimal interval for screening, the effectiveness of different screening strategies, and related benefits and harms of different screening strategies. Findings: Screening with cervical cytology alone, primary hrHPV testing alone, or cotesting can detect high-grade precancerous cervical lesions and cervical cancer. Screening women aged 21 to 65 years substantially reduces cervical cancer incidence and mortality. The harms of screening for cervical cancer in women aged 30 to 65 years are moderate. The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone in women aged 21 to 29 years substantially outweigh the harms. The USPSTF concludes with high certainty that the benefits of screening every 3 years with cytology alone, every 5 years with hrHPV testing alone, or every 5 years with both tests (cotesting) in women aged 30 to 65 years outweigh the harms. Screening women older than 65 years who have had adequate prior screening and women younger than 21 years does not provide significant benefit. Screening women who have had a hysterectomy with removal of the cervix for indications other than a high-grade precancerous lesion or cervical cancer provides no benefit. The USPSTF concludes with moderate to high certainty that screening women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer, screening women younger than 21 years, and screening women who have had a hysterectomy with removal of the cervix for indications other than a high-grade precancerous lesion or cervical cancer does not result in a positive net benefit. Conclusions and Recommendation: The USPSTF recommends screening for cervical cancer every 3 years with cervical cytology alone in women aged 21 to 29 years. (A recommendation) The USPSTF recommends screening every 3 years with cervical cytology alone, every 5 years with hrHPV testing alone, or every 5 years with hrHPV testing in combination with cytology (cotesting) in women aged 30 to 65 years. (A recommendation) The USPSTF recommends against screening for cervical cancer in women younger than 21 years. (D recommendation) The USPSTF recommends against screening for cervical cancer in women older than 65 years who have had adequate prior screening and are not otherwise at high risk for cervical cancer. (D recommendation) The USPSTF recommends against screening for cervical cancer in women who have had a hysterectomy with removal of the cervix and do not have a history of a high-grade precancerous lesion or cervical cancer. (D recommendation).

IMPORTANCE: Based 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 CONSIDERATIONS: Although 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). OBJECTIVE: To update the 2010 US Preventive Services Task Force (USPSTF) recommendation on screening for obesity in children 6 years and older. EVIDENCE REVIEW: The USPSTF reviewed the evidence on screening for obesity in children and adolescents and the benefits and harms of weight management interventions. FINDINGS: Comprehensive, 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 RECOMMENDATION: The 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).

This paper reviews the foundation for a role of the human anterior insular cortex (AIC) in emotional awareness, defined as the conscious experience of emotions. We first introduce the neuroanatomical features of AIC and existing findings on emotional awareness. Using empathy, the awareness and understanding of other people's emotional states, as a test case, we then present evidence to demonstrate: 1) AIC and anterior cingulate cortex (ACC) are commonly coactivated as revealed by a meta-analysis, 2) AIC is functionally dissociable from ACC, 3) AIC integrates stimulus-driven and top-down information, and 4) AIC is necessary for emotional awareness. We propose a model in which AIC serves two major functions: integrating bottom-up interoceptive signals with top-down predictions to generate a current awareness state and providing descending predictions to visceral systems that provide a point of reference for autonomic reflexes. We argue that AIC is critical and necessary for emotional awareness.

The field of behavioral economics has made important inroads into the understanding of substance use disorders through the concept of reinforcer pathology. Reinforcer pathology refers to the joint effects of (a) the persistently high valuation of a reinforcer, broadly defined to include tangible commodities and experiences, and/or (b) the excessive preference for the immediate acquisition or consumption of a commodity despite long-term negative outcomes. From this perspective, reinforcer pathology results from the recursive interactions of endogenous person-level variables and exogenous environment-level factors. The current review describes the basic principles of behavioral economics that are central to reinforcer pathology, the processes that engender reinforcer pathology, and the approaches and procedures that can repair reinforcement pathologies. The overall goal of this review is to present a new understanding of substance use disorders as viewed by recent advances in behavioral economics.

Importance: By 2020, approximately 12.3 million individuals in the United States older than 50 years are expected to have osteoporosis. Osteoporotic fractures, particularly hip fractures, are associated with limitations in ambulation, chronic pain and disability, loss of independence, and decreased quality of life, and 21% to 30% of patients who experience a hip fracture die within 1 year. The prevalence of primary osteoporosis (ie, osteoporosis without underlying disease) increases with age and differs by race/ethnicity. With the aging of the US population, the potential preventable burden is likely to increase in future years. Objective: To update the 2011 US Preventive Services Task Force (USPSTF) recommendation on screening for osteoporosis. Evidence Review: The USPSTF reviewed the evidence on screening for and treatment of osteoporotic fractures in men and women, as well as risk assessment tools, screening intervals, and efficacy of screening and treatment in subgroups. The screening population was postmenopausal women and older men with no known previous osteoporotic fractures and no known comorbid conditions or medication use associated with secondary osteoporosis. Findings: The USPSTF found convincing evidence that bone measurement tests are accurate for detecting osteoporosis and predicting osteoporotic fractures in women and men. The USPSTF found adequate evidence that clinical risk assessment tools are moderately accurate in identifying risk of osteoporosis and osteoporotic fractures. The USPSTF found convincing evidence that drug therapies reduce subsequent fracture rates in postmenopausal women. The USPSTF found that the evidence is inadequate to assess the effectiveness of drug therapies in reducing subsequent fracture rates in men without previous fractures. Conclusions and Recommendation: The USPSTF recommends screening for osteoporosis with bone measurement testing to prevent osteoporotic fractures in women 65 years and older. (B recommendation) The USPSTF recommends screening for osteoporosis with bone measurement testing to prevent osteoporotic fractures in postmenopausal women younger than 65 years at increased risk of osteoporosis, as determined by a formal clinical risk assessment tool. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis to prevent osteoporotic fractures in men. (I statement).

Importance: More than 35% of men and 40% of women in the United States are obese. Obesity is associated with health problems such as increased risk for coronary heart disease, type 2 diabetes, various types of cancer, gallstones, and disability. Obesity is also associated with an increased risk for death, particularly among adults younger than 65 years. Objective: To update the US Preventive Services Task Force (USPSTF) 2012 recommendation on screening for obesity in adults. Evidence Review: The USPSTF reviewed the evidence on interventions (behavioral and pharmacotherapy) for weight loss or weight loss maintenance that can be provided in or referred from a primary care setting. Surgical weight loss interventions and nonsurgical weight loss devices (eg, gastric balloons) are considered to be outside the scope of the primary care setting. Findings: The USPSTF found adequate evidence that intensive, multicomponent behavioral interventions in adults with obesity can lead to clinically significant improvements in weight status and reduce the incidence of type 2 diabetes among adults with obesity and elevated plasma glucose levels; these interventions are of moderate benefit. The USPSTF found adequate evidence that behavior-based weight loss maintenance interventions are of moderate benefit. The USPSTF found adequate evidence that the harms of intensive, multicomponent behavioral interventions (including weight loss maintenance interventions) in adults with obesity are small to none. Therefore, the USPSTF concludes with moderate certainty that offering or referring adults with obesity to intensive behavioral interventions or behavior-based weight loss maintenance interventions has a moderate net benefit. Conclusions and Recommendation: The USPSTF recommends that clinicians offer or refer adults with a body mass index of 30 or higher to intensive, multicomponent behavioral interventions. (B recommendation).

This paper broadly reviews the study of mild traumatic brain injury (mTBI), across the spectrum of neuroimaging modalities. Among the range of imaging methods, however, magnetic resonance imaging (MRI) is unique in its applicability to studying both structure and function. Thus we additionally performed meta-analyses of MRI results to examine 1) the issue of anatomical variability and consistency for functional MRI (fMRI) findings, 2) the analogous issue of anatomical consistency for white-matter findings, and 3) the importance of accounting for the time post injury in diffusion weighted imaging reports. As we discuss, the human neuroimaging literature consists of both small and large studies spanning acute to chronic time points that have examined both structural and functional changes with mTBI, using virtually every available medical imaging modality. Two key commonalities have been used across the majority of imaging studies. The first is the comparison between mTBI and control populations. The second is the attempt to link imaging results with neuropsychological assessments. Our fMRI meta-analysis demonstrates a frontal vulnerability to mTBI, demonstrated by decreased signal in prefrontal cortex compared to controls. This vulnerability is further highlighted by examining the frequency of reported mTBI white matter anisotropy, in which we show a strong anterior-to-posterior gradient (with anterior regions being more frequently reported in mTBI). Our final DTI meta-analysis examines a debated topic arising from inconsistent anisotropy findings across studies. Our results support the hypothesis that acute mTBI is associated with elevated anisotropy values and chronic mTBI complaints are correlated with depressed anisotropy. Thus, this review and set of meta-analyses demonstrate several important points about the ongoing use of neuroimaging to understand the functional and structural changes that occur throughout the time course of mTBI recovery. Based on the complexity of mTBI, however, much more work in this area is required to characterize injury mechanisms and recovery factors and to achieve clinically-relevant capabilities for diagnosis.

Psychedelic drugs produce profound changes in consciousness, but the underlying neurobiological mechanisms for this remain unclear. Spontaneous and induced oscillatory activity was recorded in healthy human participants with magnetoencephalography after intravenous infusion of psilocybin--prodrug of the nonselective serotonin 2A receptor agonist and classic psychedelic psilocin. Psilocybin reduced spontaneous cortical oscillatory power from 1 to 50 Hz in posterior association cortices, and from 8 to 100 Hz in frontal association cortices. Large decreases in oscillatory power were seen in areas of the default-mode network. Independent component analysis was used to identify a number of resting-state networks, and activity in these was similarly decreased after psilocybin. Psilocybin had no effect on low-level visually induced and motor-induced gamma-band oscillations, suggesting that some basic elements of oscillatory brain activity are relatively preserved during the psychedelic experience. Dynamic causal modeling revealed that posterior cingulate cortex desynchronization can be explained by increased excitability of deep-layer pyramidal neurons, which are known to be rich in 5-HT2A receptors. These findings suggest that the subjective effects of psychedelics result from a desynchronization of ongoing oscillatory rhythms in the cortex, likely triggered by 5-HT2A receptor-mediated excitation of deep pyramidal cells.

Efforts to identify meaningful functional imaging-based biomarkers are limited by the ability to reliably characterize inter-individual differences in human brain function. Although a growing number of connectomics-based measures are reported to have moderate to high test-retest reliability, the variability in data acquisition, experimental designs, and analytic methods precludes the ability to generalize results. The Consortium for Reliability and Reproducibility (CoRR) is working to address this challenge and establish test-retest reliability as a minimum standard for methods development in functional connectomics. Specifically, CoRR has aggregated 1,629 typical individuals' resting state fMRI (rfMRI) data (5,093 rfMRI scans) from 18 international sites, and is openly sharing them via the International Data-sharing Neuroimaging Initiative (INDI). To allow researchers to generate various estimates of reliability and reproducibility, a variety of data acquisition procedures and experimental designs are included. Similarly, to enable users to assess the impact of commonly encountered artifacts (for example, motion) on characterizations of inter-individual variation, datasets of varying quality are included.

Importance: Perinatal depression, which is the occurrence of a depressive disorder during pregnancy or following childbirth, affects as many as 1 in 7 women and is one of the most common complications of pregnancy and the postpartum period. It is well established that perinatal depression can result in adverse short- and long-term effects on both the woman and child. Objective: To issue a new US Preventive Services Task Force (USPSTF) recommendation on interventions to prevent perinatal depression. Evidence Review: The USPSTF reviewed the evidence on the benefits and harms of preventive interventions for perinatal depression in pregnant or postpartum women or their children. The USPSTF reviewed contextual information on the accuracy of tools used to identify women at increased risk of perinatal depression and the most effective timing for preventive interventions. Interventions reviewed included counseling, health system interventions, physical activity, education, supportive interventions, and other behavioral interventions, such as infant sleep training and expressive writing. Pharmacological approaches included the use of nortriptyline, sertraline, and omega-3 fatty acids. Findings: The USPSTF found convincing evidence that counseling interventions, such as cognitive behavioral therapy and interpersonal therapy, are effective in preventing perinatal depression. Women with a history of depression, current depressive symptoms, or certain socioeconomic risk factors (eg, low income or young or single parenthood) would benefit from counseling interventions and could be considered at increased risk. The USPSTF found adequate evidence to bound the potential harms of counseling interventions as no greater than small, based on the nature of the intervention and the low likelihood of serious harms. The USPSTF found inadequate evidence to assess the benefits and harms of other noncounseling interventions. The USPSTF concludes with moderate certainty that providing or referring pregnant or postpartum women at increased risk to counseling interventions has a moderate net benefit in preventing perinatal depression. Conclusions and Recommendation: The USPSTF recommends that clinicians provide or refer pregnant and postpartum persons who are at increased risk of perinatal depression to counseling interventions. (B recommendation).

PURPOSE: Moral distress is a phenomenon affecting many professionals across healthcare settings. Few studies have used a standard measure of moral distress to assess and compare differences among professions and settings. DESIGN: A descriptive, comparative design was used to study moral distress among all healthcare professionals and all settings at one large healthcare system in January 2011. METHODS: Data were gathered via a web-based survey of demographics, the Moral Distress Scale-Revised (MDS-R), and a shortened version of Olson's Hospital Ethical Climate Scale (HECS-S). FINDINGS: Five hundred ninety-two (592) clinicians completed usable surveys (22%). Moral distress was present in all professional groups. Nurses and other professionals involved in direct patient care had significantly higher moral distress than physicians (p = .001) and other indirect care professionals (p < .001). Moral distress was negatively correlated with ethical workplace climate (r = -0.516; p < .001). Watching patient care suffer due to lack of continuity and poor communication were the highest-ranked sources of moral distress for all professional groups, but the groups varied in other identified sources. Providers working in adult or intensive care unit (ICU) settings had higher levels of moral distress than did clinicians in pediatric or non-ICU settings (p < .001). Providers who left or considered leaving a position had significantly higher moral distress levels than those who never considered leaving (p < .001). Providers who had training in end-of-life care had higher average levels of moral distress than those without this training (p = .005). CONCLUSIONS: Although there may be differences in perspectives and experiences, moral distress is a common experience for clinicians, regardless of profession. CLINICAL RELEVANCE: Moral distress is associated with burnout and intention to leave a position. By understanding its root causes, interventions can be tailored to minimize moral distress with the ultimate goal of enhancing patient care, staff satisfaction, and retention.

Importance: Excessive alcohol use is one of the most common causes of premature mortality in the United States. From 2006 to 2010, an estimated 88 000 alcohol-attributable deaths occurred annually in the United States, caused by both acute conditions (eg, injuries from motor vehicle collisions) and chronic conditions (eg, alcoholic liver disease). Alcohol use during pregnancy is also one of the major preventable causes of birth defects and developmental disabilities. Objective: To update the US Preventive Services Task Force (USPSTF) 2013 recommendation on screening for unhealthy alcohol use in primary care settings. Evidence Review: The USPSTF commissioned a review of the evidence on the effectiveness of screening to reduce unhealthy alcohol use (defined as a spectrum of behaviors, from risky drinking to alcohol use disorder, that result in increased risk for health consequences) morbidity, mortality, or risky behaviors and to improve health, social, or legal outcomes; the accuracy of various screening approaches; the effectiveness of counseling interventions to reduce unhealthy alcohol use, morbidity, mortality, or risky behaviors and to improve health, social, or legal outcomes; and the harms of screening and behavioral counseling interventions. Findings: The net benefit of screening and brief behavioral counseling interventions for unhealthy alcohol use in adults, including pregnant women, is moderate. The evidence is insufficient to assess the balance of benefits and harms of screening and brief behavioral counseling interventions for unhealthy alcohol use in adolescents. Conclusions and Recommendation: The USPSTF recommends screening for unhealthy alcohol use in primary care settings in adults 18 years or older, including pregnant women, and providing persons engaged in risky or hazardous drinking with brief behavioral counseling interventions to reduce unhealthy alcohol use. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening and brief behavioral counseling interventions for alcohol use in primary care settings in adolescents aged 12 to 17 years. (I statement).

IMPORTANCE: Tobacco use is the leading preventable cause of disease, disability, and death in the US. In 2014, it was estimated that 480 000 deaths annually are attributed to cigarette smoking, including second hand smoke exposure. Smoking during pregnancy can increase the risk of numerous adverse pregnancy outcomes (eg, miscarriage and congenital anomalies) and complications in the offspring (including sudden infant death syndrome and impaired lung function in childhood). In 2019, an estimated 50.6 million US adults (20.8% of the adult population) used tobacco; 14.0% of the US adult population currently smoked cigarettes and 4.5% of the adult population used electronic cigarettes (e-cigarettes). Among pregnant US women who gave birth in 2016, 7.2% reported smoking cigarettes while pregnant. OBJECTIVE: To update its 2015 recommendation, the USPSTF commissioned a review to evaluate the benefits and harms of primary care interventions on tobacco use cessation in adults, including pregnant persons. POPULATION: This recommendation statement applies to adults 18 years or older, including pregnant persons. EVIDENCE ASSESSMENT: The USPSTF concludes with high certainty that the net benefit of behavioral interventions and US Food and Drug Associated (FDA)-approved pharmacotherapy for tobacco smoking cessation, alone or combined, in nonpregnant adults who smoke is substantial. The USPSTF concludes with high certainty that the net benefit of behavioral interventions for tobacco smoking cessation on perinatal outcomes and smoking cessation in pregnant persons is substantial. The USPSTF concludes that the evidence on pharmacotherapy interventions for tobacco smoking cessation in pregnant persons is insufficient because few studies are available, and the balance of benefits and harms cannot be determined. The USPSTF concludes that the evidence on the use of e-cigarettes for tobacco smoking cessation in adults, including pregnant persons, is insufficient, and the balance of benefits and harms cannot be determined. The USPSTF has identified the lack of well-designed, randomized clinical trials on e-cigarettes that report smoking abstinence or adverse events as a critical gap in the evidence. RECOMMENDATIONS: The USPSTF recommends that clinicians ask all adults about tobacco use, advise them to stop using tobacco, and provide behavioral interventions and FDA-approved pharmacotherapy for cessation to nonpregnant adults who use tobacco. (A recommendation) The USPSTF recommends that clinicians ask all pregnant persons about tobacco use, advise them to stop using tobacco, and provide behavioral interventions for cessation to pregnant persons who use tobacco. (A recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of pharmacotherapy interventions for tobacco cessation in pregnant persons. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of e-cigarettes for tobacco cessation in adults, including pregnant persons. The USPSTF recommends that clinicians direct patients who use tobacco to other tobacco cessation interventions with proven effectiveness and established safety. (I statement).

BACKGROUND: Clinical trials have demonstrated that the second-generation cobalt-chromium everolimus-eluting stent (CoCr-EES) is superior to the first-generation paclitaxel-eluting stent (PES) and is noninferior or superior to the sirolimus-eluting stent (SES) in terms of safety and efficacy. It remains unclear whether vascular responses to CoCr-EES are different from those to SES and PES because the pathology of CoCr-EES has not been described in humans. METHODS AND RESULTS: A total of 204 lesions (SES=73; PES=85; CoCr-EES=46) from 149 autopsy cases with duration of implantation >30 days and ≤3 years were pathologically analyzed, and comparison of vascular responses was corrected for duration of implantation. The observed frequency of late and very late stent thrombosis was less in CoCr-EES (4%) versus SES (21%; P=0.029) and PES (26%; P=0.008). Neointimal thickness was comparable among the groups, whereas the percentage of uncovered struts was strikingly lower in CoCr-EES (median=2.6%) versus SES (18.0%; P<0.0005) and PES (18.7%; P<0.0005). CoCr-EES showed a lower inflammation score (with no hypersensitivity) and less fibrin deposition versus SES and PES. The observed frequency of neoatherosclerosis, however, did not differ significantly among the groups (CoCr-EES=29%; SES=35%; PES=19%). CoCr-EES had the least frequency of stent fracture (CoCr-EES=13%; SES=40%; PES=19%; P=0.007 for CoCr-EES versus SES), whereas fracture-related restenosis or thrombosis was comparable among the groups (CoCr-EES=6.5%; SES=5.5%; PES=1.2%). CONCLUSIONS: CoCr-EES demonstrated greater strut coverage with less inflammation, less fibrin deposition, and less late and very late stent thrombosis compared with SES and PES in human autopsy analysis. Nevertheless, the observed frequencies of neoatherosclerosis and fracture-related adverse pathological events were comparable in these devices, indicating that careful long-term follow-up remains important even after CoCr-EES placement.

Importance: Potentially harmful mutations of the breast cancer susceptibility 1 and 2 genes (BRCA1/2) are associated with increased risk for breast, ovarian, fallopian tube, and peritoneal cancer. For women in the United States, breast cancer is the most common cancer after nonmelanoma skin cancer and the second leading cause of cancer death. In the general population, BRCA1/2 mutations occur in an estimated 1 in 300 to 500 women and account for 5% to 10% of breast cancer cases and 15% of ovarian cancer cases. Objective: To update the 2013 US Preventive Services Task Force (USPSTF) recommendation on risk assessment, genetic counseling, and genetic testing for BRCA-related cancer. Evidence Review: The USPSTF reviewed the evidence on risk assessment, genetic counseling, and genetic testing for potentially harmful BRCA1/2 mutations in asymptomatic women who have never been diagnosed with BRCA-related cancer, as well as those with a previous diagnosis of breast, ovarian, tubal, or peritoneal cancer who have completed treatment and are considered cancer free. In addition, the USPSTF reviewed interventions to reduce the risk for breast, ovarian, tubal, or peritoneal cancer in women with potentially harmful BRCA1/2 mutations, including intensive cancer screening, medications, and risk-reducing surgery. Findings: For women whose family or personal history is associated with an increased risk for harmful mutations in the BRCA1/2 genes, or who have an ancestry associated with BRCA1/2 gene mutations, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are moderate. For women whose personal or family history or ancestry is not associated with an increased risk for harmful mutations in the BRCA1/2 genes, there is adequate evidence that the benefits of risk assessment, genetic counseling, genetic testing, and interventions are small to none. Regardless of family or personal history, the USPSTF found adequate evidence that the overall harms of risk assessment, genetic counseling, genetic testing, and interventions are small to moderate. Conclusions and Recommendation: The USPSTF recommends that primary care clinicians assess women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer or who have an ancestry associated with BRCA1/2 gene mutations with an appropriate brief familial risk assessment tool. Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. (B recommendation) The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmful BRCA1/2 gene mutations. (D recommendation).

BACKGROUND: Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether. RESULTS: Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a "leaky" gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner. CONCLUSIONS: This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupus-associated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.

DESCRIPTION: The American College of Physicians (ACP) developed this guideline with the American College of Cardiology Foundation (ACCF), American Heart Association (AHA), American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, and Society of Thoracic Surgeons to present the available evidence on the management of stable known or suspected ischemic heart disease. METHODS: Literature on this topic published before November 2011 was identified by using MEDLINE, Embase, Cochrane CENTRAL, PsychINFO, AMED, and SCOPUS. Searches were limited to human studies published in English. This guideline grades the evidence and recommendations according to a translation of the ACCF/AHA grading system into ACP's clinical practice guidelines grading system. RECOMMENDATIONS: The guideline includes 48 specific recommendations that address the following issues: patient education, management of proven risk factors (dyslipidemia, hypertension, diabetes, physical activity body weight, and smoking), risk factor reduction strategies of unproven benefit, medical therapy to prevent myocardial infarction and death and to relieve symptoms, alternative therapy, revascularization to improve survival and symptoms, and patient follow-up.

Importance: Pancreatic cancer is an uncommon cancer with an age-adjusted annual incidence of 12.9 cases per 100 000 person-years. However, the death rate is 11.0 deaths per 100 000 person-years because the prognosis of pancreatic cancer is poor. Although its incidence is low, pancreatic cancer is the third most common cause of cancer death in the United States. Because of the increasing incidence of pancreatic cancer, along with improvements in early detection and treatment of other types of cancer, it is estimated that pancreatic cancer may soon become the second-leading cause of cancer death in the United States. Objective: To update the 2004 US Preventive Services Task Force (USPSTF) recommendation on screening for pancreatic cancer. Evidence Review: The USPSTF reviewed the evidence on the benefits and harms of screening for pancreatic cancer, the diagnostic accuracy of screening tests for pancreatic cancer, and the benefits and harms of treatment of screen-detected or asymptomatic pancreatic cancer. Findings: The USPSTF found no evidence that screening for pancreatic cancer or treatment of screen-detected pancreatic cancer improves disease-specific morbidity or mortality, or all-cause mortality. The USPSTF found adequate evidence that the magnitude of the benefits of screening for pancreatic cancer in asymptomatic adults can be bounded as no greater than small. The USPSTF found adequate evidence that the magnitude of the harms of screening for pancreatic cancer and treatment of screen-detected pancreatic cancer can be bounded as at least moderate. The USPSTF reaffirms its previous conclusion that the potential benefits of screening for pancreatic cancer in asymptomatic adults do not outweigh the potential harms. Conclusions and Recommendation: The USPSTF recommends against screening for pancreatic cancer in asymptomatic adults. (D recommendation).