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Background: Classroom-based interprofessional education (IPE) has been shown to improve medical students’ understanding of IPE competencies, but less is known about how those skills apply in clinical environments. This study assesses an IPE session’s influence on medical students’ interactions with cross-disciplinary colleagues during their pediatrics clerkship. Methods: Medical, nursing, and pharmacy students in pediatrics clinical rotations participated in an hour-long, virtual classroom-based smallgroup IPE activity in which they answered questions about a hypothetical case of a febrile neonate’s course of hospitalization. Each student received answers to these questions given to students from other professions, such that answering the questions from the perspective of their own profession required the students to share and gather information from other students in their group. After the session, students completed retrospective pre- and postsession self-assessments of their achievement of IPE session objectives, which were analyzed using the Wilcoxon signed-rank test. They also participated in focused interviews that were analyzed qualitatively to explore the session’s influence on their clinical experiences. Results: Medical students’ retrospective pre- and postsession selfassessment ratings differed significantly, indicating improvement in students’ IPE competencies. However, interviews revealed that less than one-third of medical students applied IPE skills during their clerkship due to lack of autonomy and confidence. Conclusions: The IPE session’s influence on medical students’ interprofessional collaboration was minimal and suggests that classroom-based IPE has limited impact on students’ interprofessional collaboration in the clinical learning environment. This finding suggests the need for intentional, clinically integrated IPE activities. [ABSTRACT FROM AUTHOR]

Increasing reliance on statistics for treatment and clinical risk assessment not only leads to the reductive interpretation of disease but also obscures ambiguities, distrust, and profound emotions that are important parts of a patient's lived experience of illness and that should be regarded as clinically and ethically relevant. Enabling critique of the limitations of statistics and illustrating their hegemonic impact on the patient's experience of illness, graphic medicine emerges as a democratic platform where marginalized perspectives on illness experiences are vindicated. Through a close reading of two carer narratives, Mom's Cancer (2006) and Janet & Me: An Illustrated Story of Love and Loss (2004), we illustrate how graphic pathographies represent experiential features of illness that are obscured by overreliance on statistical data. [ABSTRACT FROM AUTHOR]

Firearm violence is a significant and increasing cause of mortality. Although physicians view firearm counseling as their professional obligation, few engage in the practice. This study examines medical education and firearm counseling among physicians in North Carolina. While 65 percent of physicians reported knowing how to counsel patients about gun safety, only 25 percent reported having conversations with patients about firearms or firearm safety often or very often. Physicians reporting continuing medical education (CME) attendance on gun safety, however, were more likely to report providing patients with firearm safety counseling and asking patients with depression about firearms. Increasing availability of and physician participation in firearm violence prevention CME could significantly increase physicians' knowledge of and engagement in firearm counseling. [ABSTRACT FROM AUTHOR]

Importance: While guidance on statistical principles for clinical trials exists, there is an absence of guidance covering the required content of statistical analysis plans (SAPs) to support transparency and reproducibility.Objective: To develop recommendations for a minimum set of items that should be addressed in SAPs for clinical trials, developed with input from statisticians, previous guideline authors, journal editors, regulators, and funders.Design: Funders and regulators (n = 39) of randomized trials were contacted and the literature was searched to identify existing guidance; a survey of current practice was conducted across the network of UK Clinical Research Collaboration-registered trial units (n = 46, 1 unit had 2 responders) and a Delphi survey (n = 73 invited participants) was conducted to establish consensus on SAPs. The Delphi survey was sent to statisticians in trial units who completed the survey of current practice (n = 46), CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guideline authors (n = 16), pharmaceutical industry statisticians (n = 3), journal editors (n = 9), and regulators (n = 2) (3 participants were included in 2 groups each), culminating in a consensus meeting attended by experts (N = 12) with representatives from each group. The guidance subsequently underwent critical review by statisticians from the surveyed trial units and members of the expert panel of the consensus meeting (N = 51), followed by piloting of the guidance document in the SAPs of 5 trials.Findings: No existing guidance was identified. The registered trials unit survey (46 responses) highlighted diversity in current practice and confirmed support for developing guidance. The Delphi survey (54 of 73, 74% participants completing both rounds) reached consensus on 42% (n = 46) of 110 items. The expert panel (N = 12) agreed that 63 items should be included in the guidance, with an additional 17 items identified as important but may be referenced elsewhere. Following critical review and piloting, some overlapping items were combined, leaving 55 items.Conclusions and Relevance: Recommendations are provided for a minimum set of items that should be addressed and included in SAPs for clinical trials. Trial registration, protocols, and statistical analysis plans are critically important in ensuring appropriate reporting of clinical trials. [ABSTRACT FROM AUTHOR]

Importance: The extent of dorsolateral prefrontal cortex (DLPFC) plasticity in Alzheimer disease (AD) and its association with working memory are not known.Objectives: To determine whether participants with AD had impaired DLPFC plasticity compared with healthy control participants, to compare working memory between participants with AD and controls, and to determine whether DLPFC plasticity was associated with working memory.Design, Setting, and Participants: This cross-sectional study included 32 participants with AD who were 65 years or older and met diagnostic criteria for dementia due to probable AD with a score of at least 17 on the Mini-Mental State Examination and 16 age-matched control participants. Participants were recruited from a university teaching hospital from May 2013 to October 2016.Main Outcomes and Measures: Plasticity of the DLPFC measured as potentiation of cortical-evoked activity using paired associative stimulation (a combination of peripheral nerve electrical stimulation and transcranial magnetic stimulation) combined with electroencephalography. Working memory was assessed with the n-back task (1- and 2-back) and measured using the A' statistic.Results: Among the 32 participants with AD, 17 were women and 15 were men (mean [SD] age, 76.3 [6.3] years); among the 16 controls, 8 were men and 8 were women (mean [SD] age, 76.4 [5.1] years). Participants with AD had impaired DLPFC plasticity (mean [SD] potentiation, 1.18 [0.25]) compared with controls (mean [SD] potentiation, 1.40 [0.35]; F1,44 = 5.90; P = .02; between-group comparison, Cohen d = 0.77; P = .01). Participants with AD also had impaired performances on the 1-back condition (mean [SD] A' = 0.47 [0.30]) compared with controls (mean [SD] A' = 0.96 [0.01]; Cohen d = 1.86; P < .001), with similar findings for participants with AD on the 2-back condition (mean [SD] A' = 0.29 [0.2]) compared with controls (mean [SD], A' = 0.85 [0.18]; Cohen d = 2.83; P < .001). Plasticity of DLPFC was positively associated with working memory performance on the 1-back A' (parameter estimate B [SE] = 0.32 [0.13]; standardized β = 0.29; P = .02) and 2-back A' (B [SE] = 0.43 [0.15]; β = 0.39; P = .006) across both groups after controlling for age, education, and attention.Conclusions and Relevance: This study demonstrated impaired in vivo DLPFC plasticity in patients with AD. The findings support the use of DLPFC plasticity as a measure of DLPFC function and a potential treatment target to enhance DLPFC function and working memory in patients with AD. [ABSTRACT FROM AUTHOR]

Importance: Changes in behavior and personality are 1 criterion for the diagnosis of dementia. It is unclear, however, whether such changes begin before the clinical onset of the disease.Objective: To determine whether increases in neuroticism, declines in conscientiousness, and changes in other personality traits occur before the onset of mild cognitive impairment or dementia.Design, Setting, and Participants: A cohort of 2046 community-dwelling older adults who volunteered to participate in the Baltimore Longitudinal Study of Aging were included. The study examined personality and clinical assessments obtained between 1980 and July 13, 2016, from participants with no cognitive impairment at first assessment who were followed up for as long as 36 years (mean [SD], 12.05 [9.54] years). The self-report personality scales were not considered during consensus diagnostic conferences.Main Outcomes and Measures: Change in self-rated personality traits assessed in the preclinical phase of Alzheimer disease and other dementias with the Revised NEO Personality Inventory, a 240-item questionnaire that assesses 30 facets, 6 for each of the 5 major dimensions: neuroticism, extraversion, openness, agreeableness, and conscientiousness.Results: Of the 2046 participants, 931 [45.5%] were women; mean (SD) age at first assessment was 62.56 (14.63) years. During 24 569 person-years, mild cognitive impairment was diagnosed in 104 (5.1%) individuals, and all-cause dementia was diagnosed in 255 (12.5%) participants, including 194 (9.5%) with Alzheimer disease. Multilevel modeling that accounted for age, sex, race, and educational level found significant differences on the intercept of several traits: individuals who developed dementia scored higher on neuroticism (β = 2.83; 95% CI, 1.44 to 4.22; P < .001) and lower on conscientiousness (β = -3.34; 95% CI, -4.93 to -1.75; P < .001) and extraversion (β = -1.74; 95% CI, -3.23 to -0.25; P = .02). Change in personality (ie, slope), however, was not significantly different between the nonimpaired and the Alzheimer disease groups (eg, neuroticism: β = 0.00; 95% CI, -0.08 to 0.08; P = .91; conscientiousness: β = -0.06; 95% CI, -0.16 to 0.04; P = .24). Slopes for individuals who developed mild cognitive impairment (eg, neuroticism: β = 0.00; 95% CI, -0.12 to 0.12; P = .98; conscientiousness: β = -0.09; 95% CI, -0.23 to 0.05; P = .18) and all-cause dementia (eg, neuroticism: β = 0.02; 95% CI, -0.06 to 0.10; P = .49; conscientiousness: β = -0.08; 95% CI, -0.16 to 0.00; P = .07) were also similar to those for nonimpaired participants.Conclusions and Relevance: No evidence for preclinical change in personality before the onset of mild cognitive impairment or dementia was identified. These findings provide evidence against the reverse causality hypothesis and strengthen evidence for personality traits as a risk factor for dementia. [ABSTRACT FROM AUTHOR]

Importance: Patients with attention-deficit/hyperactivity disorder (ADHD) are at an increased risk of attempting suicide. Stimulants, such as methylphenidate hydrochloride, are the most common treatment for ADHD, but the association between their therapeutic use and suicide is unclear.Objective: To investigate the association between methylphenidate and the risk of suicide attempts.Design, Setting, and Participants: A population-based, electronic medical records database from the Hong Kong Clinical Data Analysis & Reporting System was used to identify 25 629 individuals aged 6 to 25 years who were treated with methylphenidate between January 1, 2001, and December 31, 2015. Those who had attempted suicide were included in the analysis. A self-controlled case series design was used to control for time-invariant characteristics of the patients.Main Outcomes and Measures: Relative incidence of suicide attempt during periods when patients were exposed to methylphenidate compared with nonexposed periods.Results: Among 25 629 patients with methylphenidate prescriptions, 154 had their first recorded suicide attempt within the study period; of these individuals, 111 (72.1%) were male; mean (SD) age at baseline was 7.15 (2.19) years. The overall incidence of suicide attempts during methylphenidate treatment was 9.27 per 10 000 patient-years. An increased risk of suicide attempts was detected during the 90-day period before methylphenidate was initiated, with an incidence rate ratio (IRR) of 6.55 (95% CI, 3.37-12.72). The IRR remained elevated during the first 90 days of treatment (IRR, 3.91; 95% CI, 1.62-9.42) before returning to baseline levels during ongoing treatment (IRR, 1.35; 95% CI, 0.77-2.38). When the risk during the first 90 days of treatment was compared with the 90 days preceding first treatment, the incidence of suicide attempts was not elevated (IRR, 0.78; 95% CI, 0.26-2.35).Conclusions and Relevance: The incidence of suicide attempts was higher in the period immediately before the start of methylphenidate treatment. The risk remained elevated immediately after the start of methylphenidate treatment and returned to baseline levels during continuation of methylphenidate treatment. The observed higher risk of suicide attempts before treatment may reflect emerging psychiatric symptoms that trigger medical consultations that result in a decision to begin ADHD treatment. Therefore, this study's results do not support a causal association between methylphenidate treatment and suicide attempts. [ABSTRACT FROM AUTHOR]

The article examines changes in access to care for adults on the basis of mental health status using statistics obtained from national sample in the U.S. The authors identified adults between the 5-point and 12-point threshold to be suffering from moderate mental illness and those at thirteen-point threshold or higher to be suffering from severe mental illness.

Importance: Chronic respiratory diseases are an important cause of death and disability in the United States.Objective: To estimate age-standardized mortality rates by county from chronic respiratory diseases.Design, Setting, and Participants: Validated small area estimation models were applied to deidentified death records from the National Center for Health Statistics and population counts from the US Census Bureau, National Center for Health Statistics, and Human Mortality Database to estimate county-level mortality rates from 1980 to 2014 for chronic respiratory diseases.Exposure: County of residence.Main Outcomes and Measures: Age-standardized mortality rates by county, year, sex, and cause.Results: A total of 4 616 711 deaths due to chronic respiratory diseases were recorded in the United States from January 1, 1980, through December 31, 2014. Nationally, the mortality rate from chronic respiratory diseases increased from 40.8 (95% uncertainty interval [UI], 39.8-41.8) deaths per 100 000 population in 1980 to a peak of 55.4 (95% UI, 54.1-56.5) deaths per 100 000 population in 2002 and then declined to 52.9 (95% UI, 51.6-54.4) deaths per 100 000 population in 2014. This overall 29.7% (95% UI, 25.5%-33.8%) increase in chronic respiratory disease mortality from 1980 to 2014 reflected increases in the mortality rate from chronic obstructive pulmonary disease (by 30.8% [95% UI, 25.2%-39.0%], from 34.5 [95% UI, 33.0-35.5] to 45.1 [95% UI, 43.7-46.9] deaths per 100 000 population), interstitial lung disease and pulmonary sarcoidosis (by 100.5% [95% UI, 5.8%-155.2%], from 2.7 [95% UI, 2.3-4.2] to 5.5 [95% UI, 3.5-6.1] deaths per 100 000 population), and all other chronic respiratory diseases (by 42.3% [95% UI, 32.4%-63.8%], from 0.51 [95% UI, 0.48-0.54] to 0.73 [95% UI, 0.69-0.78] deaths per 100 000 population). There were substantial differences in mortality rates and changes in mortality rates over time among counties, and geographic patterns differed by cause. Counties with the highest mortality rates were found primarily in central Appalachia for chronic obstructive pulmonary disease and pneumoconiosis; widely dispersed throughout the Southwest, northern Great Plains, New England, and South Atlantic for interstitial lung disease; along the southern half of the Mississippi River and in Georgia and South Carolina for asthma; and in southern states from Mississippi to South Carolina for other chronic respiratory diseases.Conclusions and Relevance: Despite recent declines in mortality from chronic respiratory diseases, mortality rates in 2014 remained significantly higher than in 1980. Between 1980 and 2014, there were important differences in mortality rates and changes in mortality by county, sex, and particular chronic respiratory disease type. These estimates may be helpful for informing efforts to improve prevention, diagnosis, and treatment. [ABSTRACT FROM AUTHOR]

Importance: Motor vehicle crashes (MVCs) are a major public health problem. Research has demonstrated that individuals with attention-deficit/hyperactivity disorder (ADHD) are more likely to experience MVCs, but the effect of ADHD medication treatment on the risk of MVCs remains unclear.Objective: To explore associations between ADHD medication use and risk of MVCs in a large cohort of patients with ADHD.Design, Setting, and Participants: For this study, a US national cohort of patients with ADHD (n = 2 319 450) was identified from commercial health insurance claims between January 1, 2005, and December 31, 2014, and followed up for emergency department visits for MVCs. The study used within-individual analyses to compare the risk of MVCs during months in which patients received ADHD medication with the risk of MVCs during months in which they did not receive ADHD medication.Exposures: Dispensed prescription of ADHD medications.Main Outcomes and Measures: Emergency department visits for MVCs.Results: Among 2 319 450 patients identified with ADHD, the mean (SD) age was 32.5 (12.8) years, and 51.7% were female. In the within-individual analyses, male patients with ADHD had a 38% (odds ratio, 0.62; 95% CI, 0.56-0.67) lower risk of MVCs in months when receiving ADHD medication compared with months when not receiving medication, and female patients had a 42% (odds ratio, 0.58; 95% CI, 0.53-0.62) lower risk of MVCs in months when receiving ADHD medication. Similar reductions were found across all age groups, across multiple sensitivity analyses, and when considering the long-term association between ADHD medication use and MVCs. Estimates of the population-attributable fraction suggested that up to 22.1% of the MVCs in patients with ADHD could have been avoided if they had received medication during the entire follow-up.Conclusions and Relevance: Among patients with ADHD, rates of MVCs were lower during periods when they received ADHD medication. Considering the high prevalence of ADHD and its association with MVCs, these findings warrant attention to this prevalent and preventable cause of mortality and morbidity. [ABSTRACT FROM AUTHOR]

Importance: Individuals who self-harm may have an increased risk of aggression toward others, but this association has been insufficiently investigated. More conclusive evidence may affect assessment, treatment interventions, and clinical guidelines.Objective: To investigate the association between nonfatal self-harm and violent crime.Design, Setting, and Participants: This population-based longitudinal cohort study, conducted from January 1, 1997, through December 31, 2013, studied all Swedish citizens born between 1982 and 1998 who were 15 years and older (N = 1 850 252). Individuals who emigrated from Sweden before the age of 15 years (n = 104 051) or immigrated to Sweden after the age of 13 years (ie, <2 years before the beginning of the follow-up; n = 22 009) were excluded. Data analysis was performed from April 21, 2016, to June 4, 2016.Exposures: Receipt of self-harm-associated clinical care.Main Outcomes and Measures: Conviction of a violent crime according to the Swedish penal code.Results: The study cohort consisted of 1 850 525 individuals (950 382 males and 900 143 females), and the mean (SD) follow-up time was 8.1 (4.7) years (range, 0-17.0 years; minimum age, 15 years; maximum age, 32 years). During a mean follow-up period of 8.1 years, 55 185 individuals (3.0%) received clinical care for self-harm. The crude hazard ratio was 4.9 (95% CI, 4.8-5.0) for violent crime conviction in exposed individuals compared with the unexposed group. Women who self-harm were at particularly high risk for expressing violent behaviors. After adjustment for relevant psychiatric comorbidities and socioeconomic status, an almost doubled hazard of violent offense remained (hazard ratio, 1.8; 95% CI, 1.8-1.9).Conclusions and Relevance: Self-harm is associated with an increased risk of conviction for a violent offense in both sexes. The risk of violence, as well as the risk of suicide and self-harm, should be assessed among offending and self-harming individuals. [ABSTRACT FROM AUTHOR]

Importance: The fear conditioning and extinction neurocircuitry has been extensively studied in healthy and clinical populations, with a particular focus on posttraumatic stress disorder. Despite significant overlap of symptoms between posttraumatic stress disorder and anxiety disorders, the latter has received less attention. Given that dysregulated fear levels characterize anxiety disorders, examining the neural correlates of fear and extinction learning may shed light on the pathogenesis of underlying anxiety disorders.Objectives: To investigate the psychophysiological and neural correlates of fear conditioning and extinction recall in anxiety disorders and to document how these features differ as a function of multiple diagnoses or anxiety severity.Design, Setting, and Participants: This investigation was a cross-sectional, case-control, functional magnetic resonance imaging study at an academic medical center. Participants were healthy controls and individuals with at least 1 of the following anxiety disorders: generalized anxiety disorder, social anxiety disorder, specific phobia, and panic disorder. The study dates were between March 2013 and May 2015.Exposures: Two-day fear conditioning and extinction paradigm.Main Outcomes and Measures: Skin conductance responses, blood oxygenation level-dependent responses, trait anxiety scores from the State Trait Anxiety Inventory-Trait Form, and functional connectivity.Results: This study included 21 healthy controls (10 women) and 61 individuals with anxiety disorders (36 women). P values reported for the neuroimaging results are all familywise error corrected. Skin conductance responses during extinction recall did not differ between individuals with anxiety disorders and healthy controls (ηp2 = 0.001, P = .79), where ηp2 is partial eta squared. The anxiety group had lower activation of the ventromedial prefrontal cortex (vmPFC) during extinction recall (ηp2 = 0.178, P = .02). A similar hypoactive pattern was found during early conditioning (ηp2 = 0.106, P = .009). The vmPFC hypoactivation was associated with anxiety symptom severity (r = -0.420, P = .01 for conditioning and r = -0.464, P = .004 for extinction recall) and the number of co-occuring anxiety disorders diagnosed (ηp2 = 0.137, P = .009 for conditioning and ηp2 = 0.227, P = .004 for extinction recall). Psychophysiological interaction analyses revealed that the fear network connectivity differed between healthy controls and the anxiety group during fear learning (ηp2 range between 0.088 and 0.176 and P range between 0.02 and 0.003) and extinction recall (ηp2 range between 0.111 and 0.235 and P range between 0.02 and 0.002).Conclusions and Relevance: Despite no skin conductance response group differences during extinction recall, brain activation patterns between anxious and healthy individuals differed. These findings encourage future studies to examine the conditions longitudinally and in the context of treatment trials to improve and guide therapeutics via advanced neurobiological understanding of each disorder. [ABSTRACT FROM AUTHOR]

Importance: Despite long-standing interest in the association of psychiatric disorders with intelligence, few population-based studies of psychiatric disorders have assessed intelligence.Objective: To investigate the association of fluid intelligence with past-year and lifetime psychiatric disorders, disorder age at onset, and disorder severity in a nationally representative sample of US adolescents.Design, Setting, and Participants: National sample of adolescents ascertained from schools and households from the National Comorbidity Survey Replication-Adolescent Supplement, collected 2001 through 2004. Face-to-face household interviews with adolescents and questionnaires from parents were obtained. The data were analyzed from February to December 2016. DSM-IV mental disorders were assessed with the World Health Organization Composite International Diagnostic Interview, and included a broad range of fear, distress, behavior, substance use, and other disorders. Disorder severity was measured with the Sheehan Disability Scale.Main Outcomes and Measures: Fluid IQ measured with the Kaufman Brief Intelligence Test, normed within the sample by 6-month age groups.Results: The sample included 10 073 adolescents (mean [SD] age, 15.2 [1.50] years; 49.0% female) with valid data on fluid intelligence. Lower mean (SE) IQ was observed among adolescents with past-year bipolar disorder (94.2 [1.69]; P = .004), attention-deficit/hyperactivity disorder (96.3 [0.91]; P = .002), oppositional defiant disorder (97.3 [0.66]; P = .007), conduct disorder (97.1 [0.82]; P = .02), substance use disorders (alcohol abuse, 96.5 [0.67]; P < .001; drug abuse, 97.6 [0.64]; P = .02), and specific phobia (97.1 [0.39]; P = .001) after adjustment for a wide range of potential confounders. Intelligence was not associated with posttraumatic stress disorder, eating disorders, and anxiety disorders other than specific phobia, and was positively associated with past-year major depression (mean [SE], 100 [0.5]; P = .01). Associations of fluid intelligence with lifetime disorders that had remitted were attenuated compared with past-year disorders, with the exception of separation anxiety disorder. Multiple past-year disorders had a larger proportion of adolescents less than 1 SD below the mean IQ range than those without a disorder. Across disorders, higher disorder severity was associated with lower fluid intelligence. For example, among adolescents with specific phobia, those with severe disorder had a mean (SE) of 4.4 (0.72) points lower IQ than those without severe disorder (P < .001), and those with alcohol abuse had a mean (SE) of 5.6 (1.2) points lower IQ than those without severe disorder (P < .001).Conclusions and Relevance: Numerous psychiatric disorders were associated with reductions in fluid intelligence; associations were generally small in magnitude. Stronger associations of current than past disorders with intelligence suggest that active symptoms of psychiatric disorders interfere with cognitive functioning. Early identification and treatment of children with mental disorders in school settings is critical to promote academic achievement and long-term success. [ABSTRACT FROM AUTHOR]

Importance: Little is understood about how the symptoms of posttraumatic stress develop over time into the syndrome of posttraumatic stress disorder (PTSD).Objective: To use a network analysis approach to identify the nature of the association between PTSD symptoms in the acute phase after trauma and the chronic phase.Design, Setting, and Participants: A prospective cohort study enrolled 1138 patients recently admitted with traumatic injury to 1 of 4 major trauma hospitals across Australia from March 13, 2004, to February 26, 2006. Participants underwent assessment during hospital admission (n = 1388) and at 12 months after injury (n = 852). Networks of symptom associations were analyzed in the acute and chronic phases using partial correlations, relative importance estimates, and centrality measures of each symptom in terms of its association strengths, closeness to other symptoms, and importance in connecting other symptoms to each other. Data were analyzed from March 3 to September 5, 2016.Main Outcomes and Measures: Severity of PTSD was assessed at each assessment with the Clinician-Administered PTSD Scale.Results: Of the 1138 patients undergoing assessment at admission (837 men [73.6%] and 301 women [26.4%]; mean [SD] age, 37.90 [13.62] years), strong connections were found in the acute phase. Reexperiencing symptoms were central to other symptoms in the acute phase, with intrusions and physiological reactivity among the most central symptoms in the networks in terms of the extent to which they occur between other symptoms (mean [SD], 1.2 [0.7] and 1.0 [0.9], respectively), closeness to other symptoms (mean [SD], 0.9 [0.3] and 1.1 [0.9], respectively), and strength of the associations (mean [SD], 1.6 [0.3] and 1.5 [0.3] respectively) among flashbacks, intrusions, and avoidance of thoughts, with moderately strong connections between intrusions and nightmares, being upset by reminders, and physiological reactivity. Intrusions and physiological reactivity were central in the acute phase. Among the 852 patients (73.6%) who completed the 12-month assessment, overall network connectivity was significantly stronger at 12 months than in the acute phase (global strength values, 6.57 vs 7.60; paired difference, 1.03; P < .001). The network associations among the reexperiencing symptoms were strengthened at 12 months, and physiological reactivity was strongly associated with the startle response, which was also associated with hypervigilance. Strong connectivity among emotional numbing, detachment from others, and disinterest in activities as well as moderately strong links among irritability (anger), concentration deficits, and sleep disturbance were found.Conclusions and Relevance: As time elapses after trauma, fear circuitry and dysphoric PTSD symptoms appear to emerge as connected networks. Intrusive memories and reactivity are centrally associated with other symptoms in the acute phase, potentially pointing to the utility of addressing these symptoms in early intervention strategies. [ABSTRACT FROM AUTHOR]

Importance: An international task force recently redefined the concept of sepsis. This task force recommended the use of the quick Sequential Organ Failure Assessment (qSOFA) score instead of systemic inflammatory response syndrome (SIRS) criteria to identify patients at high risk of mortality. However, these new criteria have not been prospectively validated in some settings, and their added value in the emergency department remains unknown.Objective: To prospectively validate qSOFA as a mortality predictor and compare the performances of the new sepsis criteria to the previous ones.Design, Settings, and Participants: International prospective cohort study, conducted in France, Spain, Belgium, and Switzerland between May and June 2016. In the 30 participating emergency departments, for a 4-week period, consecutive patients who visited the emergency departments with suspected infection were included. All variables from previous and new definitions of sepsis were collected. Patients were followed up until hospital discharge or death.Exposures: Measurement of qSOFA, SOFA, and SIRS.Main Outcomes and Measures: In-hospital mortality.Results: Of 1088 patients screened, 879 were included in the analysis. Median age was 67 years (interquartile range, 47-81 years), 414 (47%) were women, and 379 (43%) had respiratory tract infection. Overall in-hospital mortality was 8%: 3% for patients with a qSOFA score lower than 2 vs 24% for those with qSOFA score of 2 or higher (absolute difference, 21%; 95% CI, 15%-26%). The qSOFA performed better than both SIRS and severe sepsis in predicting in-hospital mortality, with an area under the receiver operating curve (AUROC) of 0.80 (95% CI, 0.74-0.85) vs 0.65 (95% CI, 0.59-0.70) for both SIRS and severe sepsis (P < .001; incremental AUROC, 0.15; 95% CI, 0.09-0.22). The hazard ratio of qSOFA score for death was 6.2 (95% CI, 3.8-10.3) vs 3.5 (95% CI, 2.2-5.5) for severe sepsis.Conclusions and Relevance: Among patients presenting to the emergency department with suspected infection, the use of qSOFA resulted in greater prognostic accuracy for in-hospital mortality than did either SIRS or severe sepsis. These findings provide support for the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria in the emergency department setting.Trial Registration: clinicaltrials.gov Identifier: NCT02738164. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding variations in the ratio of physician charges to Medicare payments by specialty and region.

Importance: Elevated systolic blood (SBP) pressure is a leading global health risk. Quantifying the levels of SBP is important to guide prevention policies and interventions.Objective: To estimate the association between SBP of at least 110 to 115 mm Hg and SBP of 140 mm Hg or higher and the burden of different causes of death and disability by age and sex for 195 countries and territories, 1990-2015.Design: A comparative risk assessment of health loss related to SBP. Estimated distribution of SBP was based on 844 studies from 154 countries (published 1980-2015) of 8.69 million participants. Spatiotemporal Gaussian process regression was used to generate estimates of mean SBP and adjusted variance for each age, sex, country, and year. Diseases with sufficient evidence for a causal relationship with high SBP (eg, ischemic heart disease, ischemic stroke, and hemorrhagic stroke) were included in the primary analysis.Main Outcomes and Measures: Mean SBP level, cause-specific deaths, and health burden related to SBP (≥110-115 mm Hg and also ≥140 mm Hg) by age, sex, country, and year.Results: Between 1990-2015, the rate of SBP of at least 110 to 115 mm Hg increased from 73 119 (95% uncertainty interval [UI], 67 949-78 241) to 81 373 (95% UI, 76 814-85 770) per 100 000, and SBP of 140 mm Hg or higher increased from 17 307 (95% UI, 17 117-17 492) to 20 526 (95% UI, 20 283-20 746) per 100 000. The estimated annual death rate per 100 000 associated with SBP of at least 110 to 115 mm Hg increased from 135.6 (95% UI, 122.4-148.1) to 145.2 (95% UI 130.3-159.9) and the rate for SBP of 140 mm Hg or higher increased from 97.9 (95% UI, 87.5-108.1) to 106.3 (95% UI, 94.6-118.1). For loss of DALYs associated with systolic blood pressure of 140 mm Hg or higher, the loss increased from 95.9 million (95% uncertainty interval [UI], 87.0-104.9 million) to 143.0 million (95% UI, 130.2-157.0 million) [corrected], and for SBP of 140 mm Hg or higher, the loss increased from 5.2 million (95% UI, 4.6-5.7 million) to 7.8 million (95% UI, 7.0-8.7 million). The largest numbers of SBP-related deaths were caused by ischemic heart disease (4.9 million [95% UI, 4.0-5.7 million]; 54.5%), hemorrhagic stroke (2.0 million [95% UI, 1.6-2.3 million]; 58.3%), and ischemic stroke (1.5 million [95% UI, 1.2-1.8 million]; 50.0%). In 2015, China, India, Russia, Indonesia, and the United States accounted for more than half of the global DALYs related to SBP of at least 110 to 115 mm Hg.Conclusions and Relevance: In international surveys, although there is uncertainty in some estimates, the rate of elevated SBP (≥110-115 and ≥140 mm Hg) increased substantially between 1990 and 2015, and DALYs and deaths associated with elevated SBP also increased. Projections based on this sample suggest that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mm Hg and 874 million adults had SBP of 140 mm Hg or higher. [ABSTRACT FROM AUTHOR]

Importance: Differences in cardiovascular autonomic activity between individuals with psychiatric disorders and healthy controls have been observed, but whether cardiovascular autonomic abnormalities are associated with subsequent psychiatric disorders is unknown.Objective: To investigate whether differences in cardiac autonomic function as indexed by resting heart rate and blood pressure are associated with psychiatric disorders during the lifetime of men in Sweden.Design, Setting, and Participants: We conducted a longitudinal register-based study of Swedish men whose resting heart rate (n = 1 039 443) and blood pressure (n = 1 555 979) were measured at military conscription at a mean (SD) age of 18.3 (0.6) years during the period from 1969 to 2010, with register-based follow-up data available until the end of 2013. Analyses were performed from November 18, 2015, to June 9, 2016.Main Outcomes and Measures: Dates of inpatient/outpatient diagnoses of anxiety disorders, obsessive-compulsive disorder, posttraumatic stress disorder, depressive disorders, bipolar disorder, schizophrenia, and substance use disorders and convictions for violent crimes, between 1973 and 2013, were obtained from nationwide registers. Adjustments were made for height, weight, body mass index, cardiorespiratory fitness, cognitive ability, and socioeconomic covariates.Results: After adjustment for covariates, Cox regression models with up to 45 years of follow-up data showed that men (mean [SD] age of 18.3 [0.6] years at conscription) with resting heart rates above 82 beats per minute had a 69% (95% CI, 46%-94%) increased risk for obsessive-compulsive disorder, a 21% (95% CI, 11%-33%) increased risk for schizophrenia, and an 18% (95% CI, 13%-22%) increased risk for anxiety disorders compared with men with resting heart rates below 62 beats per minute. Similar associations were observed with systolic/diastolic blood pressure. In contrast, lower resting heart rate and lower systolic blood pressure were associated with substance use disorders and violent criminality.Conclusions and Relevance: Our results suggest that for men, differences in heart rate and blood pressure in late adolescence are associated with lifetime major psychiatric disorders, with higher levels associated with obsessive-compulsive disorder, schizophrenia, and anxiety disorders and lower levels associated with substance use disorders and violent behavior. Differences in autonomic nervous system functioning may predate or represent an early marker of psychiatric disorders. [ABSTRACT FROM AUTHOR]

Importance: Emotional and behavioral symptoms in cognitively normal older people may be direct manifestations of Alzheimer disease (AD) pathophysiology at the preclinical stage, prior to the onset of mild cognitive impairment. Loneliness is a perceived state of social and emotional isolation that has been associated with cognitive and functional decline and an increased risk of incident AD dementia. We hypothesized that loneliness might occur in association with elevated cortical amyloid burden, an in vivo research biomarker of AD.Objective: To determine whether cortical amyloid burden is associated with greater loneliness in cognitively normal older adults.Design, Setting, and Participants: Cross-sectional analyses using data from the Harvard Aging Brain Study of 79 cognitively normal, community-dwelling participants. A continuous, aggregate measure of cortical amyloid burden, determined by Pittsburgh Compound B-positron emission tomography (PiB-PET), was examined in association with loneliness in linear regression models adjusting for age, sex, apolipoprotein E ε4 (APOEε4), socioeconomic status, depression, anxiety, and social network (without and with the interaction of amyloid and APOEε4). We also quantified the association of high amyloid burden (amyloid-positive group) to loneliness (lonely group) using logistic regression, controlling for the same covariates, with the amyloid-positive group and the lonely group, each composing 32% of the sample (n = 25).Main Outcomes and Measures: Loneliness, as determined by the 3-item UCLA Loneliness Scale (possible range, 3-12, with higher score indicating greater loneliness).Results: The 79 participants included 43 women and 36 men with a mean (SD) age of 76.4 (6.2) years. Mean (SD) cortical amyloid burden via PiB-PET was 1.230 (0.209), and the mean (SD) UCLA-3 loneliness score was 5.3 (1.8). Twenty-two (28%) had positive APOEε4 carrier status, and 25 (32%) were in the amyloid-positive group with cortical PiB distribution volume ratio greater than 1.2. Controlling for age, sex, APOEε4, socioeconomic status, depression, anxiety, and social network, we found that higher amyloid burden was significantly associated with greater loneliness: compared with individuals in the amyloid-negative group, those in the amyloid-positive group were 7.5-fold (95% CI, 1.7-fold to 34.0-fold) more likely to be classified as lonely than nonlonely (β = 3.3, partial r = 0.4, P = .002). Furthermore, the association of high amyloid burden and loneliness was stronger in APOEε4 carriers than in noncarriers.Conclusions and Relevance: We report a novel association of loneliness with cortical amyloid burden in cognitively normal older adults, suggesting that loneliness is a neuropsychiatric symptom relevant to preclinical AD. This work will inform new research into the neural underpinnings and disease mechanisms involved in loneliness and may enhance early detection and intervention research in AD. [ABSTRACT FROM AUTHOR]

Importance: Millions of women worldwide use hormonal contraception. Despite the clinical evidence of an influence of hormonal contraception on some women's mood, associations between the use of hormonal contraception and mood disturbances remain inadequately addressed.Objective: To investigate whether the use of hormonal contraception is positively associated with subsequent use of antidepressants and a diagnosis of depression at a psychiatric hospital.Design, Setting, and Participants: This nationwide prospective cohort study combined data from the National Prescription Register and the Psychiatric Central Research Register in Denmark. All women and adolescents aged 15 to 34 years who were living in Denmark were followed up from January 1, 2000, to December 2013, if they had no prior depression diagnosis, redeemed prescription for antidepressants, other major psychiatric diagnosis, cancer, venous thrombosis, or infertility treatment. Data were collected from January 1, 1995, to December 31, 2013, and analyzed from January 1, 2015, through April 1, 2016.Exposures: Use of different types of hormonal contraception.Main Outcomes and Measures: With time-varying covariates, adjusted incidence rate ratios (RRs) were calculated for first use of an antidepressant and first diagnosis of depression at a psychiatric hospital.Results: A total of 1 061 997 women (mean [SD] age, 24.4 [0.001] years; mean [SD] follow-up, 6.4 [0.004] years) were included in the analysis. Compared with nonusers, users of combined oral contraceptives had an RR of first use of an antidepressant of 1.23 (95% CI, 1.22-1.25). Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34 (95% CI, 1.27-1.40); users of a patch (norgestrolmin), 2.0 (95% CI, 1.76-2.18); users of a vaginal ring (etonogestrel), 1.6 (95% CI, 1.55-1.69); and users of a levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42). For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 (95% CI, 1.75-1.84) and those using progestin-only pills, 2.2 (95% CI, 1.99-2.52). Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4 (95% CI, 1.34-1.46). When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71).Conclusions and Relevance: Use of hormonal contraception, especially among adolescents, was associated with subsequent use of antidepressants and a first diagnosis of depression, suggesting depression as a potential adverse effect of hormonal contraceptive use. [ABSTRACT FROM AUTHOR]

Importance: Self-directed and interpersonal violence share some common risk factors such as a parental history of mental illness. However, relationships between the full spectrum of parental psychiatric disease and these 2 related outcomes are unclear.Objective: To examine associations between the full spectrum of parental psychiatric disease and risks of attempted suicide and violent offending among offspring.Design, Setting, and Participants: Population-based cohort study of all persons born in Denmark 1967 through 1997, followed up from their 15th birthday until occurrence of adverse outcome or December 31, 2012, whichever came first.Exposures: Array of parental psychiatric disorders and parental suicide attempt, delineated from records of secondary care treatments.Main Outcomes and Measures: Using survival analyses techniques, incidence rate ratios were estimated for offspring suicide attempt and violent offending.Results: We examined 1 743 525 cohort members (48.7% female; total follow-up, 27.2 million person-years). Risks for offspring suicide attempt and violent offending were elevated across virtually the full spectrum of parental psychiatric disease. Incidence rate ratios were the most elevated for parental diagnoses of antisocial personality disorder (suicide attempt, 3.96; 95% CI, 3.72-4.21; violent offending, 3.62; 95% CI, 3.41-3.84) and cannabis misuse (suicide attempt, 3.57; 95% CI, 3.25-3.92; violent offending, 4.05; 95% CI, 3.72-4.39), and for parental suicide attempt (suicide attempt, 3.42; 95% CI, 3.29-3.55; violent offending, 3.31; 95% CI, 3.19-3.44). Parental mood disorders (and bipolar disorder in particular) conferred more modest risk increases. A history of mental illness or suicide attempt in both parents was associated with double the risks compared with having just 1 affected parent. Associations between parental psychiatric disease and offspring violent offending were stronger for female than for male offspring, whereas little sex difference in risk was found for offspring suicide attempt.Conclusions and Relevance: The similarities in risk patterns observed between the 2 outcomes may evidence a shared etiology. Early interventions to tackle parental mental disorders may be beneficial to both parents and children. [ABSTRACT FROM AUTHOR]

This JAMA Guide to Statistics and Methods discusses the CONSERVE guidelines, which address how to report extenuating circumstances that lead to a modification in trial design, conduct, or analysis. [ABSTRACT FROM AUTHOR]

Importance: Findings suggest that infections might be linked to the development of psychiatric disorders and suicidal behavior. Large-scale studies are needed to investigate the effect of infection on the risk of suicide.Objective: To estimate the association between hospitalization with infection and the risk of death by suicide.Design, Setting, and Participants: Nationwide, population-based, prospective cohort study with more than 149 million person-years of follow-up. Data were analyzed with survival analysis techniques and were adjusted for sex, age, calendar period, cohabitation status, socioeconomic status, and the Charlson Comorbidity Index. Individual data were drawn from Danish longitudinal registers. A total of 7.22 million individuals 15 years or older living in Denmark between January 1, 1980, and December 31, 2011, were observed during a 32-year follow-up period.Main Outcomes and Measures: The risk of death by suicide was identified in the Danish Cause of Death Register. Incidence rate ratios (IRRs) and accompanying 95% CIs were used as measures of relative risk.Results: In 7 221 578 individuals (3 601 653 men and 3 619 925 women) observed for a total of 149 061 786 person-years, 32 683 suicides were observed during the follow-up period. Among the suicides, 7892 (24.1%) individuals had previously been diagnosed as having an infection during a hospitalization. Hospitalization with infection was linked to an elevated risk of suicide, with an IRR of 1.42 (95% CI, 1.38-1.46) compared with those without prior infection. Dose-response relationships were observed with respect to the number of hospital contacts for different infections. For example, having 7 or more infections was linked to an IRR of 2.90 (95% CI, 2.14-3.93). The number of days of treatment for infections was associated with an elevated risk of suicide in a dose-response relationship. More than 3 months of hospital treatment was linked to an IRR of 2.38 (95% CI, 2.05-2.76). The population-attributable risk associated with hospitalization with infection accounted for 10.1% of suicides.Conclusions and Relevance: An increased risk of death by suicide was found among individuals hospitalized with infection in prospective and dose-response relationships. These findings indicate that infections may have a relevant role in the pathophysiological mechanisms of suicidal behavior. [ABSTRACT FROM AUTHOR]

Importance: Previous studies have linked suicide risk with religious participation, but the majority have used ecologic, cross-sectional, or case-control data.Objective: To examine the longitudinal association between religious service attendance and suicide and the joint associations of suicide with service attendance and religious affiliation.Design, Setting, and Participants: We evaluated associations between religious service attendance and suicide from 1996 through June 2010 in a large, long-term prospective cohort, the Nurses' Health Study, in an analysis that included 89 708 women. Religious service attendance was self-reported in 1992 and 1996. Data analysis was conducted from 1996 through 2010.Main Outcomes and Measures: Cox proportional hazards regression models were used to examine the association between religious service attendance and suicide, adjusting for demographic covariates, lifestyle factors, medical history, depressive symptoms, and social integration measures. We performed sensitivity analyses to examine the influence of unmeasured confounding.Results: Among 89 708 women aged 30 to 55 years who participated in the Nurses' Health Study, attendance at religious services once per week or more was associated with an approximately 5-fold lower rate of suicide compared with never attending religious services (hazard ratio, 0.16; 95% CI, 0.06-0.46). Service attendance once or more per week vs less frequent attendance was associated with a hazard ratio of 0.05 (95% CI, 0.006-0.48) for Catholics but only 0.34 (95% CI, 0.10-1.10) for Protestants (P = .05 for heterogeneity). Results were robust in sensitivity analysis and to exclusions of persons who were previously depressed or had a history of cancer or cardiovascular disease. There was evidence that social integration, depressive symptoms, and alcohol consumption partially mediated the association among those occasionally attending services, but not for those attending frequently.Conclusions and Relevance: In this cohort of US women, frequent religious service attendance was associated with a significantly lower rate of suicide. [ABSTRACT FROM AUTHOR]

Importance: Psychotic disorders are characterized by attenuated activity in the brain's valuation system in key reward processing areas, such as the ventral striatum (VS), as measured with functional magnetic resonance imaging.Objective: To examine whether common risk variants for psychosis are associated with individual variation in the VS.Design, Setting, and Participants: A cross-sectional study of a large cohort of adolescents from the IMAGEN study (a European multicenter study of reinforcement sensitivity in adolescents) was performed from March 1, 2008, through December 31, 2011. Data analysis was conducted from October 1, 2015, to January 9, 2016. Polygenic risk profile scores (RPSs) for psychosis were generated for 1841 healthy adolescents. Sample size and characteristics varied across regression analyses, depending on mutual information available (N = 1524-1836).Main Outcomes and Measures: Reward-related brain function was assessed with blood oxygen level dependency (BOLD) in the VS using the monetary incentive delay (MID) task, distinguishing reward anticipation and receipt. Behavioral impulsivity, IQ, MID task performance, and VS BOLD were regressed against psychosis RPS at 4 progressive P thresholds (P < .01, P < .05, P < .10, and P < .50 for RPS models 1-4, respectively).Results: In a sample of 1841 healthy adolescents (mean age, 14.5 years; 906 boys and 935 girls), we replicated an association between increasing psychosis RPS and reduced IQ (matrix reasoning: corrected P = .003 for RPS model 2, 0.4% variance explained), supporting the validity of the psychosis RPS models. We also found a nominally significant association between increased psychosis RPS and reduced MID task performance (uncorrected P = .03 for RPS model 4, 0.2% variance explained). Our main finding was a positive association between psychosis RPS and VS BOLD during reward anticipation at all 4 psychosis RPS models and for 2 P thresholds for reward receipt (RPS models 1 and 3), correcting for the familywise error rate (0.8%-1.9% variance explained).Conclusions and Relevance: These findings support an association between psychosis RPS and VS BOLD in adolescents. Genetic risk for psychosis may shape an individual's response to rewarding stimuli. [ABSTRACT FROM AUTHOR]

Importance: Despite the well-established role of striatal dopamine in psychosis, current views generally agree that cortical dysfunction is likely necessary for the emergence of psychotic symptoms. The topographic organization of striatal-cortical connections is central to gating and integration of higher-order information, so a disruption of such topography via dysregulated dopamine could lead to cortical dysfunction in schizophrenia. However, this hypothesis remains to be tested using multivariate methods ascertaining the global pattern of striatal connectivity and without the confounding effects of antidopaminergic medication.Objectives: To examine whether the pattern of brain connectivity across striatal subregions is abnormal in unmedicated patients with schizophrenia and whether this abnormality relates to psychotic symptoms and extrastriatal dopaminergic transmission.Design, Setting, and Participants: In this multimodal, case-control study, we obtained resting-state functional magnetic resonance imaging data from 18 unmedicated patients with schizophrenia and 24 matched healthy controls from the New York State Psychiatric Institute. A subset of these (12 and 17, respectively) underwent positron emission tomography with the dopamine D2 receptor radiotracer carbon 11-labeled FLB457 before and after amphetamine administration. Data were acquired between June 16, 2011, and February 25, 2014. Data analysis was performed from September 1, 2014, to January 11, 2016.Main Outcomes and Measures: Group differences in the striatal connectivity pattern (assessed via multivariable logistic regression) across striatal subregions, the association between the multivariate striatal connectivity pattern and extrastriatal baseline D2 receptor binding potential and its change after amphetamine administration, and the association between the multivariate connectivity pattern and the severity of positive symptoms evaluated with the Positive and Negative Syndrome Scale.Results: Of the patients with schizophrenia (mean [SEM] age, 35.6 [11.8] years), 9 (50%) were male and 9 (50%) were female. Of the controls (mean [SEM] age, 33.7 [8.8] years), 10 (42%) were male and 14 (58%) were female. Patients had an abnormal pattern of striatal connectivity, which included abnormal caudate connections with a distributed set of associative cortex regions (χ229 = 53.55, P = .004). In patients, more deviation from the multivariate pattern of striatal connectivity found in controls correlated specifically with more severe positive symptoms (ρ = -0.77, P = .002). Striatal connectivity also correlated with baseline binding potential across cortical and extrastriatal subcortical regions (t25 = 3.01, P = .01, Bonferroni corrected) but not with its change after amphetamine administration.Conclusions and Relevance: Using a multimodal, circuit-level interrogation of striatal-cortical connections, it was demonstrated that the functional topography of these connections is globally disrupted in unmedicated patients with schizophrenia. These findings suggest that striatal-cortical dysconnectivity may underlie the effects of dopamine dysregulation on the pathophysiologic mechanism of psychotic symptoms. [ABSTRACT FROM AUTHOR]

Importance: Excess alcohol consumption and alcohol use disorders (AUDs) are associated with substantially increased mortality. Efforts to reduce this toll require an understanding of their causes.Objective: To clarify the degree to which the excess mortality associated with AUDs arises (1) from the predispositions of the person who develops AUD (and which would likely be shared by close relatives) and (2) as a direct result of AUD itself.Design, Setting, and Participants: A prospective cohort and co-relative design study involving all individuals born in Sweden from 1940 to 1965 who had neither died nor migrated prior to 1973 or age 15 years (N = 2 821 036). They were followed up from January 1, 1973, until December 31, 2010. Alcohol use disorder was assessed from medical, criminal, and pharmacy registries. Half-siblings, full-siblings, and monozygotic twin pairs discordant for AUD were obtained from the Multi-Generation and Twin Register.Main Outcome and Measure: Death obtained from the Swedish Death registry.Results: Our cohort (1 447 887 males and 1 373 149 females) included 131 895 males and 42 163 females registered with AUD. The mean (SD) age at first AUD registration was 39 (13.4) years. We ascertained 127 347 and 76 325 deaths in the male and female subsamples, respectively. Controlling for sex, educational status, and year of birth, the mortality hazard ratio associated with AUD was 5.83 (95% CI, 5.76-5.90) and varied-with an inverted U-shaped function-by age. Examining the AUD-mortality association in the general population and in relative pairs discordant for AUD exposure demonstrated substantial familial confounding in early to mid-adulthood: the AUD-associated mortality hazard ratio was much lower in discordant close relatives than in the general population. In middle to late adulthood, evidence for familial confounding decreased with increasing evidence for a direct effect of AUD on elevated mortality. In the oldest age group (65-70 years), the mortality hazard ratios were similar across the population and all relative pairs, suggesting that the excess mortality was largely a result of having AUD. Adding years since onset of AUD to the model showed that both increasing age and increasing years of duration of AUD contributed to the reduction of familial confounding in the association between AUD and elevated mortality.Conclusions and Relevance: Excess mortality associated with AUD arises both from the predispositions of the person who develops AUD and the direct result of having AUD. The effect of predisposition is more prominent early in the life course and in the early years of AUD. The direct effect of AUD becomes progressively more important later in life and with longer duration of AUD. These results have implications for interventions seeking to reduce the elevated AUD-associated mortality. [ABSTRACT FROM AUTHOR]

Importance: Autism spectrum disorder (ASD) is marked by social disability and is associated with dysfunction in brain circuits supporting social cue perception. The degree to which neural functioning reflects individual-level behavioral phenotype is unclear, slowing the search for functional neuroimaging biomarkers of ASD.Objective: To examine whether quantified neural function in social perception circuits may serve as an individual-level marker of ASD in children and adolescents.Design, Setting, and Participants: The cohort study was conducted at the Yale Child Study Center and involved children and adolescents diagnosed as having ASD and typically developing participants. Participants included a discovery cohort and a larger replication cohort. Individual-level social perception circuit functioning was assessed as functional magnetic resonance imaging brain responses to point-light displays of coherent vs scrambled human motion.Main Outcomes and Measures: Outcome measures included performance of quantified brain responses in affected male and female participants in terms of area under the receiver operating characteristic curve (AUC), sensitivity and specificity, and correlations between brain responses and social behavior.Results: Of the 39 participants in the discovery cohort aged 4 to 17 years, 22 had ASD and 30 were boys. Of the 75 participants in the replication cohort aged 7 to 20 years, 37 had ASD and 52 were boys. A relative reduction in social perception circuit responses was identified in discovery cohort boys with ASD at an AUC of 0.75 (95% CI, 0.52-0.89; P = .01); however, typically developing girls and girls with ASD could not be distinguished (P = .54). The results were confirmed in the replication cohort, where brain responses were identified in boys with ASD at an AUC of 0.79 (95% CI, 0.64-0.91; P < .001) and failed to distinguish affected and unaffected girls (P = .82). Across both cohorts, boys were identified at an AUC of 0.77 (95% CI, 0.64-0.86) with corresponding sensitivity and specificity of 76% each. Additionally, brain responses were associated with social behavior in boys but not in girls.Conclusions and Relevance: Quantified social perception circuit activity is a promising individual-level candidate neural marker of the male ASD behavioral phenotype. Our findings highlight the need to better understand effects of sex on social perception processing in relation to ASD phenotype manifestations. [ABSTRACT FROM AUTHOR]

Importance: Although deficits in emotional processing are prominent in schizophrenia, it has been difficult to identify neural mechanisms related to the genetic risk for this highly heritable illness. Prior studies have not found consistent regional activation or connectivity alterations in first-degree relatives compared with healthy controls, suggesting that a more comprehensive search for connectomic biomarkers is warranted.Objectives: To identify a potential systems-level intermediate phenotype linked to emotion processing in schizophrenia and to examine the psychological association, task specificity, test-retest reliability, and clinical validity of the identified phenotype.Design, Setting, and Participations: The study was performed in university research hospitals from June 1, 2008, through December 31, 2013. We examined 58 unaffected first-degree relatives of patients with schizophrenia and 94 healthy controls with an emotional face-matching functional magnetic resonance imaging paradigm. Test-retest reliability was analyzed with an independent sample of 26 healthy participants. A clinical association study was performed in 31 patients with schizophrenia and 45 healthy controls. Data analysis was performed from January 1 to September 30, 2014.Main Outcomes and Measures: Conventional amygdala activity and seeded connectivity measures, graph-based global and local network connectivity measures, Spearman rank correlation, intraclass correlation, and gray matter volumes.Results: Among the 152 volunteers included in the relative-control sample, 58 were unaffected first-degree relatives of patients with schizophrenia (mean [SD] age, 33.29 [12.56]; 38 were women), and 94 were healthy controls without a first-degree relative with mental illness (mean [SD] age, 32.69 [10.09] years; 55 were women). A graph-theoretical connectivity approach identified significantly decreased connectivity in a subnetwork that primarily included the limbic cortex, visual cortex, and subcortex during emotional face processing (cluster-level P corrected for familywise error = .006) in relatives compared with controls. The connectivity of the same subnetwork was significantly decreased in patients with schizophrenia (F = 6.29, P = .01). Furthermore, we found that this subnetwork connectivity measure was negatively correlated with trait anxiety scores (P = .04), test-retest reliable (intraclass correlation coefficient = 0.57), specific to emotional face processing (F = 17.97, P < .001), and independent of gray matter volumes of the identified brain areas (F = 1.84, P = .18). Replicating previous results, no significant group differences were found in face-related amygdala activation and amygdala-anterior cingulate cortex connectivity (P corrected for familywise error =.37 and .11, respectively).Conclusions and Relevance: Our results indicate that altered connectivity in a visual-limbic subnetwork during emotional face processing may be a functional connectomic intermediate phenotype for schizophrenia. The phenotype is reliable, task specific, related to trait anxiety, and associated with manifest illness. These data encourage the further investigation of this phenotype in clinical and pharmacologic studies. [ABSTRACT FROM AUTHOR]

Importance: Military sexual trauma (MST) is associated with adverse physical and mental health outcomes following military separation. Recent research suggests that MST may be a determinant in several factors associated with postdeployment homelessness.Objective: To evaluate MST as an independent risk factor for homelessness and to determine whether risk varies by sex.Design, Setting, and Participants: A retrospective cohort study of US veterans who used Veterans Health Administration (VHA) services between fiscal years 2004 and 2013 was conducted using administrative data from the Department of Defense and VHA. Included in the study were 601 892 US veterans deployed in Iraq or Afghanistan who separated from the military between fiscal years 2001 and 2011 and subsequently used VHA services.Exposure: Positive response to screen for MST administered in VHA facilities.Main Outcomes and Measures: Administrative evidence of homelessness within 30 days, 1 year, and 5 years following the first VHA encounter after last deployment.Results: The mean (SD) age of the 601 892 participants was 38.9 (9.4) years, 527 874 (87.7%) were male, 310 854 (51.6%) were white, and 382 361 (63.5%) were enlisted in the Army. Among veterans with a positive screen for MST, rates of homelessness were 1.6% within 30 days, 4.4% within 1 year, and 9.6% within 5 years, more than double the rates of veterans with a negative MST screen (0.7%, 1.8%, and 4.3%, respectively). A positive screen for MST was significantly and independently associated with postdeployment homelessness. In regression models adjusted for demographic and military service characteristics, odds of experiencing homelessness were higher among those who screened positive for MST compared with those who screened negative (30-day: adjusted odds ratio [AOR], 1.89; 95% CI, 1.58-2.24; 1-year: AOR, 2.27; 95% CI, 2.04-2.53; and 5-year: AOR, 2.63; 95% CI, 2.36-2.93). Military sexual trauma screen status remained independently associated with homelessness after adjusting for co-occurring mental health and substance abuse diagnoses in follow-up regression models (30-day: AOR, 1.62; 95% CI, 1.36-1.93; 1-year: AOR, 1.49; 95% CI, 1.33-1.66; and 5-year: AOR, 1.39; 95% CI, 1.24-1.55). In the fully adjusted models, the interaction between MST status and sex was significant in the 30-day and 1-year cohorts (30-day: AOR, 1.54; 95% CI, 1.18-2.02; and 1-year: AOR, 1.46; 95% CI, 1.23-1.74), denoting higher risk for homelessness among males with a positive screen for MST.Conclusions and Relevance: A positive screen for MST was independently associated with postdeployment homelessness, with male veterans at greater risk than female veterans. These results underscore the importance of the MST screen as a clinically important marker of reintegration outcomes among veterans. These findings demonstrate significant long-term negative effects and inform our understanding of the public health implications of sexual abuse and harassment. [ABSTRACT FROM AUTHOR]

Importance: Disrupted autonomic nervous system functioning as measured by heart rate variability (HRV) has been associated with posttraumatic stress disorder (PTSD). It is not clear, however, whether reduced HRV before trauma exposure contributes to the risk for development of PTSD.Objective: To examine whether HRV before combat deployment is associated with increased risk of a PTSD diagnosis after deployment when accounting for deployment-related combat exposure.Design, Setting, and Participants: Between July 14, 2008, and May 24, 2012, active-duty Marines were assessed 1 to 2 months before a combat deployment and again 4 to 6 months after their return. The first phase of the Marine Resiliency Study (MRS-I) included 1415 male Marines, 59 of whom developed PTSD after deployment. Participants in the second phase of the Marine Resiliency Study (MRS-II) included 745 male Marines, 25 of whom developed PTSD after deployment. Analysis was conducted from November 25, 2013, to April 16, 2015.Main Outcomes and Measures: Predeployment HRV was measured via finger photoplethysmography during a 5-minute period of rest. Frequency-domain measures of HRV were generated. Diagnosis of PTSD was determined using the Clinician-Administered PTSD Scale.Results: After accounting for deployment-related combat exposure, lower HRV before deployment as measured by an increased low-frequency (LF) to high-frequency (HF) ratio of HRV was associated with risk of PTSD diagnosis after deployment (combined MRS-I and MRS-II cohort meta-analysis odds ratio, 1.47; 95% CI, 1.10-1.98; P = .01). The prevalence of postdeployment PTSD was higher in participants with high predeployment LF:HF ratios (15.8% [6 of 38 participants]) compared with participants who did not have high LF:HF ratios (3.7% [78 of 2122 participants]).Conclusions and Relevance: This prospective longitudinal study provides initial and modest evidence that an altered state of autonomic nervous system functioning contributes to PTSD vulnerability, taking into account other key risk factors. If these findings are replicated, interventions that change autonomic nervous system function may open novel opportunities for prevention and treatment of PTSD. [ABSTRACT FROM AUTHOR]

This Guide to Statistics and Methods describes how confidence intervals can be used to help in the interpretation of nonsignificant findings across all study designs. [ABSTRACT FROM AUTHOR]

This JAMA Guide to Statistics and Methods takes a look at estimands, estimators, and estimates in the context of randomized clinical trials and suggests several qualities that make for good estimands, including their scope, ability to summarize treatment effects, external validity, and ability to provide good estimates. [ABSTRACT FROM AUTHOR]

This JAMA Guide to Statistics and Methods describes how intention-to-treat, per-protocol, and as-treated approaches to analysis differ with regard to the patient population and treatment assignments and their implications for interpretation of treatment effects in clinical trials. [ABSTRACT FROM AUTHOR]

Importance: Systematic reviews and meta-analyses of individual participant data (IPD) aim to collect, check, and reanalyze individual-level data from all studies addressing a particular research question and are therefore considered a gold standard approach to evidence synthesis. They are likely to be used with increasing frequency as current initiatives to share clinical trial data gain momentum and may be particularly important in reviewing controversial therapeutic areas.Objective: To develop PRISMA-IPD as a stand-alone extension to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) Statement, tailored to the specific requirements of reporting systematic reviews and meta-analyses of IPD. Although developed primarily for reviews of randomized trials, many items will apply in other contexts, including reviews of diagnosis and prognosis.Design: Development of PRISMA-IPD followed the EQUATOR Network framework guidance and used the existing standard PRISMA Statement as a starting point to draft additional relevant material. A web-based survey informed discussion at an international workshop that included researchers, clinicians, methodologists experienced in conducting systematic reviews and meta-analyses of IPD, and journal editors. The statement was drafted and iterative refinements were made by the project, advisory, and development groups. The PRISMA-IPD Development Group reached agreement on the PRISMA-IPD checklist and flow diagram by consensus.Findings: Compared with standard PRISMA, the PRISMA-IPD checklist includes 3 new items that address (1) methods of checking the integrity of the IPD (such as pattern of randomization, data consistency, baseline imbalance, and missing data), (2) reporting any important issues that emerge, and (3) exploring variation (such as whether certain types of individual benefit more from the intervention than others). A further additional item was created by reorganization of standard PRISMA items relating to interpreting results. Wording was modified in 23 items to reflect the IPD approach.Conclusions and Relevance: PRISMA-IPD provides guidelines for reporting systematic reviews and meta-analyses of IPD. [ABSTRACT FROM AUTHOR]

An editorial is presented which addresses the use of big data to determine chronic respiratory disease-related mortality patterns, trends, and associations, and it mentions the identification of potential public health interventions. An article in the journal dealing with mortality in U.S. counties is examined, along with deaths due to chronic obstructive pulmonary disease (COPD), tobacco use, and asthma. Asbestosis- and pneumoconiosis-related deaths are also assessed.

This JAMA Guide to Statistics and Methods explains worst-rank score methods, a nonparametric statistical technique that assigns worst-case outcomes for patients with missing data to account for missingness that may reflect an adverse change in patient status (informative rather than random missingness). [ABSTRACT FROM AUTHOR]

The article focuses on a study that analyzes the results obtained from Surveillance, Epidemiology, and End Results (SEER) database of the U.S. National Cancer Institute, which suggests that the incidence of advanced breast cancer in young women Is Increasing in the U.S. The data spanning 1973-2009, 1992-2009, and 2000-2009 for breast cancer was analyzed. It further mentions that disease confined to the breast, regional to contiguous and adjacent organ spread such as lymph nodes or chest wall were considered localized, while those that spread to other parts such as bones, brain or lungs were considered distant. A significant increase in breast cancer with distant involvement was observed between 1976 and 2009 for women aged 25 to 39 years.

The article offers a comparison between the robotically assisted and laparoscopic hysterectomy in women with benign gynecologic disease. This study aims to analyze the association between robotic surgery and rates of abdominal and laparoscopic hysterectomy. A cohort analysis of 264,758 women who underwent hysterectomy for benign gynecologic disorders at several hospitals across the U.S. from 2007 to 2010 was conducted. Several parameters that were considered for comparison include post operative complications, deaths occurred and cost for patients who underwent robotic hysterectomy compared with both abdominal and laparoscopic procedures. Further it states that even though similar morbidity profiles were observed in both cases, but robotic technology involves higher cost inputs.

The CONSORT (Consolidated Standards of Reporting Trials) Statement, which includes a checklist and a flow diagram, is a guideline developed to help authors improve the reporting of the findings from randomized controlled trials. It was updated most recently in 2010. Its primary focus is on individually randomized trials with 2 parallel groups that assess the possible superiority of one treatment compared with another. The CONSORT Statement has been extended to other trial designs such as cluster randomization, and recommendations for noninferiority and equivalence trials were made in 2006. In this article, we present an updated extension of the CONSORT checklist for reporting noninferiority and equivalence trials, based on the 2010 version of the CONSORT Statement and the 2008 CONSORT Statement for the reporting of abstracts, and provide illustrative examples and explanations for those items that differ from the main 2010 CONSORT checklist. The intent is to improve reporting of noninferiority and equivalence trials, enabling readers to assess the reliability of their results and conclusions. [ABSTRACT FROM AUTHOR]

The article intends to develop a clinical prediction rule for severe disability and death from acute ischemic stroke during hospital admission. It offers information on the methods used in the study including population, data collection and definition of variables, and statistical analysis. It concludes that the PLAN clinical prediction rule need further studies in various settings and population groups.

The article presents a meta-analysis to assess the role of omega-3 supplementation on major cardiovascular outcomes. It is concluded that omega-3 polyunsaturated fatty acids (PUFAs) supplementation is not associated with a lower risk of all-cause mortality, cardiac death and myocardial infarction. The findings justifies that the use of omega-3 as a structured intervention in clinical practice do not support dietary omega-3 PUFA administration.

The article investigates how end-stage renal disease sufferers in the U.S. can be made more aware of the promising potential that peritoneal dialysis (PD) therapy holds for them, despite the low rates of preference that it holds compared to hemodialysis (HD). It offers general information about the study, the research method and study population that was selected, and the statistical method that was employed to analyze the results. Results showed that PD was often not selected by ESRD patients, and that trend should be reversed in PD's favor.

The article reports on the results of the National Health and Aging Trends Study (NHATS) on the trends of digital health technology usage by seniors in the U.S. Topics discussed include the exemption from review of the study by the Partners HealthCare Human Research Committee, reference to the seniors as the sickest and fastest growing segment of the U.S. population as well as the desired improvement on the socioeconomic disparities in the study. Also mentioned was the suggestion for usability.

The article focuses on the study regarding the association of sleep characteristics and risks of falls among older women. To estimate the objective characteristics of sleep, wrist antigraphs were worn by patients for a minimum of 72 hours. A piezolectric bimorph-ceramic cantilver are used to detect the movements. The height and body mass index of the subjects were also measured. Information on the statistical analysis and results of the study is presented. The use of benzodiazepines in insomia and its association with an increased risk of falls are also taken into account.

The article discusses a study on medical resident students' comprehension of biostatistics and complicated data that is reported in medical literature. Most physicians continue to access clinical studies in order to stay current with evidence-based medicine. Information summaries are most helpful in providing the clinical information and practice guidelines. Some medical schools include statistical concepts within the curriculum to prepare students for on the job understanding. The design, setting, participants, outcome measure, results and conclusions are detailed.

This article presents the results of a study to evaluate the cost-effectiveness of bone densitometry followed by 5 years of oral bisphosphonate therapy in older men to prevent fractures for those found to have osteoporosis compared with no intervention. The study used a Markov cost-utility model using Data Pro Healthcare software. Background mortality was estimated from 2003 U.S. vital statistics. The probabilities of each type of fracture were established as functions of age, presence of osteoporosis and other factors from data gathered by the Rochester Epidemiology Project. The study found lifetime costs gained for the densitometry and follow up treatment were less than $50,000 for men aged 65 and older with a prior fracture. The study concludes that the densitometry and bisphosphonate therapy may be cost-effective for men as young as 70.

This article presents the results of a study looking at how meta-analysis of clinical trials which used different means of measurement, can be transformed into a uniform scale; the standardized mean difference (SMD) scale. Further, the study wanted to see how reliable the resulting meta-analyses are from the SMD. The high proportion of meta-analyses based on SMDs that showed errors indicated that data extraction was the probable cause for error rates and this can negate or even reverse the findings of a study. The authors say that all readers and policy makers need to take note and approach meta-analyses with caution.