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Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools.
To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics.
Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts.
Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = −0.34 years, s.e. = 0.08), major depression (β = −0.34 years, s.e. = 0.08), schizophrenia (β = −0.39 years, s.e. = 0.08), and educational attainment (β = −0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.
AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
In 2020 a group of U.S. healthcare leaders formed the National Organization to Prevent Hospital-Acquired Pneumonia (NOHAP) to issue a call to action to address non–ventilator-associated hospital-acquired pneumonia (NVHAP). NVHAP is one of the most common and morbid healthcare-associated infections, but it is not tracked, reported, or actively prevented by most hospitals. This national call to action includes (1) launching a national healthcare conversation about NVHAP prevention; (2) adding NVHAP prevention measures to education for patients, healthcare professionals, and students; (3) challenging healthcare systems and insurers to implement and support NVHAP prevention; and (4) encouraging researchers to develop new strategies for NVHAP surveillance and prevention. The purpose of this document is to outline research needs to support the NVHAP call to action. Primary needs include the development of better models to estimate the economic cost of NVHAP, to elucidate the pathophysiology of NVHAP and identify the most promising pathways for prevention, to develop objective and efficient surveillance methods to track NVHAP, to rigorously test the impact of prevention strategies proposed to prevent NVHAP, and to identify the policy levers that will best engage hospitals in NVHAP surveillance and prevention. A joint task force developed this document including stakeholders from the Veterans’ Health Administration (VHA), the U.S. Centers for Disease Control and Prevention (CDC), The Joint Commission, the American Dental Association, the Patient Safety Movement Foundation, Oral Health Nursing Education and Practice (OHNEP), Teaching Oral-Systemic Health (TOSH), industry partners and academia.
Congenital heart disease (CHD) is the most common birth defect for infants born in the United States, with approximately 36,000 affected infants born annually. While mortality rates for children with CHD have significantly declined, there is a growing population of individuals with CHD living into adulthood prompting the need to optimise long-term development and quality of life. For infants with CHD, pre- and post-surgery, there is an increased risk of developmental challenges and feeding difficulties. Feeding challenges carry profound implications for the quality of life for individuals with CHD and their families as they impact short- and long-term neurodevelopment related to growth and nutrition, sensory regulation, and social-emotional bonding with parents and other caregivers. Oral feeding challenges in children with CHD are often the result of medical complications, delayed transition to oral feeding, reduced stamina, oral feeding refusal, developmental delay, and consequences of the overwhelming intensive care unit (ICU) environment. This article aims to characterise the disruptions in feeding development for infants with CHD and describe neurodevelopmental factors that may contribute to short- and long-term oral feeding difficulties.
To determine whether the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) Clostridioides difficile infection (CDI) severity criteria adequately predicts poor outcomes.
Retrospective validation study.
Setting and participants:
Patients with CDI in the Veterans’ Affairs Health System from January 1, 2006, to December 31, 2016.
For the 2010 criteria, patients with leukocytosis or a serum creatinine (SCr) value ≥1.5 times the baseline were classified as severe. For the 2018 criteria, patients with leukocytosis or a SCr value ≥1.5 mg/dL were classified as severe. Poor outcomes were defined as hospital or intensive care admission within 7 days of diagnosis, colectomy within 14 days, or 30-day all-cause mortality; they were modeled as a function of the 2010 and 2018 criteria separately using logistic regression.
We analyzed data from 86,112 episodes of CDI. Severity was unclassifiable in a large proportion of episodes diagnosed in subacute care (2010, 58.8%; 2018, 49.2%). Sensitivity ranged from 0.48 for subacute care using 2010 criteria to 0.73 for acute care using 2018 criteria. Areas under the curve were poor and similar (0.60 for subacute care and 0.57 for acute care) for both versions, but negative predictive values were >0.80.
Model performances across care settings and criteria versions were generally poor but had reasonably high negative predictive value. Many patients in the subacute-care setting, an increasing fraction of CDI cases, could not be classified. More work is needed to develop criteria to identify patients at risk of poor outcomes.
OBJECTIVES/SPECIFIC AIMS: Objectives/goals: Describe the process used to develop leveled competencies and associated examples. Discuss the final leveled competencies and their potential use in clinical research professional workforce initiatives. METHODS/STUDY POPULATION: The revised JTFCTC Framework 2.0 has 51 competency statements, representing 8 domains. Each competency statement has now been refined to delineate fundamental, skilled or advanced levels of knowledge and capability. Typically, the fundamental level describes the competency for a professional that requires some coaching and oversight, but is able to understand and identify basic concepts. The skilled level of the competency reflects the professional’s solid understanding of the competency and use of the information to take action independently in most situations. The advanced level embodies high level thinking, problem solving, and the ability to guide others in the competency. The process for developing both the three levels and examples involved 5 workgroups, each chaired by a content expert and comprising of national/international clinical research experts, including representatives from research sites, professional associations, government, and industry and academic sponsors. RESULTS/ANTICIPATED RESULTS: The committee developed 51 specific competencies arrayed across 3 levels and examples of each to demonstrate an appropriate application of the competency. The competencies and examples, and potential utilization, will be described. DISCUSSION/SIGNIFICANCE OF IMPACT: The use of competencies in the context of workforce development and training initiatives is helping to create standards for the clinical research profession. These leveled competencies allow for an important refinement to the standards that can be used to enhance the quality and safety of the clinical research enterprise and guide workforce development.
We examined the prospective associations of objective and subjective measures of stress during pregnancy with infant stress reactivity and regulation, an early-life predictor of psychopathology. In a racially and ethnically diverse low-income sample of 151 mother–infant dyads, maternal reports of stressful life events (SLE) and perceived stress (PS) were collected serially over gestation and the early postpartum period. Infant reactivity and regulation at 6 months of age was assessed via maternal report of temperament (negativity, surgency, and regulation) and infant parasympathetic nervous system physiology (respiratory sinus arrhythmia [RSA]) during the Still Face Paradigm. Regression models predicting infant temperament showed higher maternal prenatal PS predicted lower surgency and self-regulation but not negativity. Regression models predicting infant physiology showed higher numbers of SLE during gestation predicted greater RSA reactivity and weaker recovery. Tests of interactions revealed SLE predicted RSA reactivity only at moderate to high levels of PS. Thus, findings suggest objective and subjective measures of maternal prenatal stress uniquely predict infant behavior and physiology, adjusting for key pre- and postnatal covariates, and advance the limited evidence for such prenatal programming within high-risk populations. Assessing multiple levels of maternal stress and offspring stress reactivity and regulation provides a richer picture of intergenerational transmission of adversity.
To examine variation in antibiotic coverage and detection of resistant pathogens in community-onset pneumonia.
A total of 128 hospitals in the Veterans Affairs health system.
Hospitalizations with a principal diagnosis of pneumonia from 2009 through 2010.
We examined proportions of hospitalizations with empiric antibiotic coverage for methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PAER) and with initial detection in blood or respiratory cultures. We compared lowest- versus highest-decile hospitals, and we estimated adjusted probabilities (AP) for patient- and hospital-level factors predicting coverage and detection using hierarchical regression modeling.
Among 38,473 hospitalizations, empiric coverage varied widely across hospitals (MRSA lowest vs highest, 8.2% vs 42.0%; PAER lowest vs highest, 13.9% vs 44.4%). Detection rates also varied (MRSA lowest vs highest, 0.5% vs 3.6%; PAER lowest vs highest, 0.6% vs 3.7%). Whereas coverage was greatest among patients with recent hospitalizations (AP for anti-MRSA, 54%; AP for anti-PAER, 59%) and long-term care (AP for anti-MRSA, 60%; AP for anti-PAER, 66%), detection was greatest in patients with a previous history of a positive culture (AP for MRSA, 7.9%; AP for PAER, 11.9%) and in hospitals with a high prevalence of the organism in pneumonia (AP for MRSA, 3.9%; AP for PAER, 3.2%). Low hospital complexity and rural setting were strong negative predictors of coverage but not of detection.
Hospitals demonstrated widespread variation in both coverage and detection of MRSA and PAER, but probability of coverage correlated poorly with probability of detection. Factors associated with empiric coverage (eg, healthcare exposure) were different from those associated with detection (eg, microbiology history). Providing microbiology data during empiric antibiotic decision making could better align coverage to risk for resistant pathogens and could promote more judicious use of broad-spectrum antibiotics.
Miscarriage is the most common complication of early pregnancy. This chapter summarizes the risk factors for first-trimester miscarriage. There is a strong relationship between infertility and miscarriage. Studies have shown that risk of miscarriage varies by socio-economic position, but the trends are unclear and most probably relate to exposure to environmental, occupational or behavioral risk factors. A very clear finding from the National Women's Health Study (NWHS) was the impact of stressful life events, a stressful job situation, and feelings of anxiety and depression on the risk of miscarriage. Most people seek an explanation of the cause of their miscarriage and treatment or guidance to prevent a recurrence. Efforts to gather research evidence have been hampered in the past by methodological difficulties and the lack of understanding by health professionals that at least a proportion of miscarriages are preventable.