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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.
We surveyed infectious disease specialists about early COVID-19 vaccination preparedness. Almost all respondents’ institutions rated their facility’s preparedness plan as either excellent or adequate. Vaccine hesitancy and concern about adverse reactions were the most common anticipated barriers to COVID-19 vaccination. Only 60% believed currently that COVID-19 vaccination should be mandatory.
To describe epidemiologic and genomic characteristics of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in a large skilled-nursing facility (SNF), and the strategies that controlled transmission.
Design, setting, and participants:
This cohort study was conducted during March 22–May 4, 2020, among all staff and residents at a 780-bed SNF in San Francisco, California.
Contact tracing and symptom screening guided targeted testing of staff and residents; respiratory specimens were also collected through serial point prevalence surveys (PPSs) in units with confirmed cases. Cases were confirmed by real-time reverse transcription–polymerase chain reaction testing for SARS-CoV-2, and whole-genome sequencing (WGS) was used to characterize viral isolate lineages and relatedness. Infection prevention and control (IPC) interventions included restricting from work any staff who had close contact with a confirmed case; restricting movement between units; implementing surgical face masking facility-wide; and the use of recommended PPE (ie, isolation gown, gloves, N95 respirator and eye protection) for clinical interactions in units with confirmed cases.
Of 725 staff and residents tested through targeted testing and serial PPSs, 21 (3%) were SARS-CoV-2 positive: 16 (76%) staff and 5 (24%) residents. Fifteen cases (71%) were linked to a single unit. Targeted testing identified 17 cases (81%), and PPSs identified 4 cases (19%). Most cases (71%) were identified before IPC interventions could be implemented. WGS was performed on SARS-CoV-2 isolates from 4 staff and 4 residents: 5 were of Santa Clara County lineage and the 3 others were distinct lineages.
Early implementation of targeted testing, serial PPSs, and multimodal IPC interventions limited SARS-CoV-2 transmission within the SNF.
Background: There is little empirical research into lay definitions of frailty. Objectives: (1) To explore the definitions of frailty among older men, and (2) to explore if these definitions match commonly used clinical definitions of frailty. Methods: Analysis of open-ended questions to survey data from a prospective cohort study of older airmen. The definitions of frailty were elicited, and grouped according to themes. Results: 147 men responded (mean age: 93). There was considerable heterogeneity in older men’s’ definitions of frailty, and no theme of frailty was predominant. The most common theme was impairment in activities of daily living. Older men’s’ definition of frailty was not consistent with any commonly used medical theory of frailty. Conclusions: Most older men think frailty is important, but their definitions are not consistent. Frailty may be a heterogeneous experience, which different people experience differently.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
For most common infections requiring hospitalization, antibiotic treatment is completed after hospital discharge. Postdischarge therapy is often unnecessarily broad spectrum and prolonged. We developed an intervention to improve antibiotic selection and shorten treatment durations.
Single center, quasi-experimental retrospective cohort study
Patients prescribed oral antibiotics at hospital discharge before (July 2012–June 2013) and after (October 2014–February 2015) an intervention consisting of (1) institutional guidance for oral step-down antibiotic selection and duration of therapy and (2) pharmacy audit of discharge prescriptions with real-time prescribing recommendations to providers. The primary outcomes measured were total prescribed duration of therapy and use of antibiotics with broad gram-negative activity (ie, fluoroquinolones or amoxicillin-clavulanate).
Overall, 300 cases from the preintervention period and 200 cases from the intervention period were included. Compared with the preintervention period, the use of antibiotics with broad gram-negative activity decreased during the intervention (51% vs 40%; P=.02), particularly fluoroquinolones (38% vs 25%; P=.002). The total duration of therapy decreased from a median of 10 days (interquartile range [IQR], 7–13 days) to 9 days (IQR, 6–13 days) but did not reach statistical significance (P=.13). However, the duration prescribed at discharge declined from 6 days (IQR, 4–10 days) to 5 days (IQR, 3–7 days) (P=.003). During the intervention, there was a nonsignificant increase in the overall appropriateness of discharge prescriptions from 52% to 66% (P=.15).
A multifaceted intervention to optimize antibiotic prescribing at hospital discharge was associated with less frequent use of antibiotics with broad gram-negative activity and shorter postdischarge treatment durations.
Adult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children.
Pediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitals
Patients ≤18 years old ventilated for ≥1 day
We identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models.
In total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on “pediatric VAC with antimicrobial use” (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test (“pediatric PVAP”) occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls.
We propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes.
To assess an intervention to limit community-associated methicillin-resistant Staphylococcus aureus (MRSA) dissemination.
Randomized, controlled trial.
County Jail, Dallas, Texas.
A total of 4,196 detainees in 68 detention tanks.
Tanks were randomly assigned to 1 of 3 groups: in group 1, detainees received cloths that contained chlorhexidine gluconate (CHG) to clean their entire skin surface 3 times per week for 6 months; group 2 received identical cloths containing only water; and group 3 received no skin treatment. During the study, all newly arrived detainees were invited to enroll. Nares and hand cultures were obtained at baseline and from all current enrollees at 2 and 6 months.
At baseline, S. aureus was isolated from 41.2% and MRSA from 8.0% (nares and/or hand) of 947 enrollees. The average participation rate was 47%. At 6 months, MRSA carriage was 10.0% in group 3 and 8.7% in group 1 tanks (estimated absolute risk reduction [95% confidence interval (CI)], 1.4% [−4.8% to 7.1%]; P = .655). At 6 months, carriage of any S. aureus was 51.1% in group 3, 40.7% in group 1 (absolute risk reduction [95% CI], 10.4% [0.01%–20.1%]; P = .047), and 42.8% (absolute risk reduction [95% CI], 8.3% [−1.4% to 18.0%]; P = .099) in group 2.
Skin cleaning with CHG for 6 months in detainees, compared with no intervention, significantly decreased carriage of S. aureus, and use of water cloths produced a nonsignificant but similar decrease. A nonsignificant decrease in MRSA carriage was found with CHG cloth use.
This white paper identifies knowledge gaps and new challenges in healthcare epidemiology research, assesses the progress made toward addressing research priorities, provides the Society for Healthcare Epidemiology of America (SHEA) Research Committee's recommendations for high-priority research topics, and proposes a road map for making progress toward these goals. It updates the 2010 SHEA Research Committee document, “Charting the Course for the Future of Science in Healthcare Epidemiology: Results of a Survey of the Membership of SHEA,” which called for a national approach to healthcare-associated infections (HAIs) and a prioritized research agenda. This paper highlights recent studies that have advanced our understanding of HAIs, the establishment of the SHEA Research Network as a collaborative infrastructure to address research questions, prevention initiatives at state and national levels, changes in reporting and payment requirements, and new patterns in antimicrobial resistance.