Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.

We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).

Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta β = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta β = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.

Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome.

Venovenous collaterals are abnormal connections between the systemic and pulmonary venous systems. They are commonly seen in the Fontan circulation and may lead to significant hypoxaemia. Transcatheter closure of venovenous collaterals is a potential but controversial treatment as the long-term benefits and outcomes are not well understood.

This retrospective cohort study utilised data from the Australian and New Zealand Fontan Registry. Patients who underwent transcatheter venovenous collateral occlusion for hypoxemia from the year 2000 onwards were included. Atriopulmonary and Kawashima-type Fontan circulations were excluded to reflect a more contemporary Fontan cohort.

Nineteen patients (age 19.3 ± 7.8 years, 53% female) underwent transcatheter venovenous collateral occlusion. Compared to baseline, mean oxygen saturation was improved at latest follow-up (90.5% vs 87.0%; p = 0.003). Nine patients achieved a clinically significant response (defined as an increase of at least 5% to 90% or greater), and this was associated with lower baseline Fontan pressures (12.9 v 15.6 mmHg; p = 0.02). No heart failure hospitalisations, arrhythmia, transplant referrals, or mortality were observed during the median follow-up period of 4 years. Two patients experienced thromboembolic events and five patients underwent re-intervention.

Transcatheter occlusion of venovenous collaterals in Fontan patients with chronic hypoxaemia resulted in a modest increase in oxygenation over a median follow-up of 4 years and longer-term prognosis did not appear to be adversely affected. Lower Fontan pressures at baseline were associated with a greater improvement in oxygenation.

To characterize the relationship between chlorhexidine gluconate (CHG) skin concentration and skin microbial colonization.

Serial cross-sectional study.

Adult patients in medical intensive care units (ICUs) from 7 hospitals; from 1 hospital, additional patients colonized with carbapenemase-producing Enterobacterales (CPE) from both ICU and non-ICU settings. All hospitals performed routine CHG bathing in the ICU.

Skin swab samples were collected from adjacent areas of the neck, axilla, and inguinal region for microbial culture and CHG skin concentration measurement using a semiquantitative colorimetric assay. We used linear mixed effects multilevel models to analyze the relationship between CHG concentration and microbial detection. We explored threshold effects using additional models.

We collected samples from 736 of 759 (97%) eligible ICU patients and 68 patients colonized with CPE. On skin, gram-positive bacteria were cultured most frequently (93% of patients), followed by Candida species (26%) and gram-negative bacteria (20%). The adjusted odds of microbial recovery for every twofold increase in CHG skin concentration were 0.84 (95% CI, 0.80–0.87; P < .001) for gram-positive bacteria, 0.93 (95% CI, 0.89–0.98; P = .008) for Candida species, 0.96 (95% CI, 0.91–1.02; P = .17) for gram-negative bacteria, and 0.94 (95% CI, 0.84–1.06; P = .33) for CPE. A threshold CHG skin concentration for reduced microbial detection was not observed.

On a cross-sectional basis, higher CHG skin concentrations were associated with less detection of gram-positive bacteria and Candida species on the skin, but not gram-negative bacteria, including CPE. For infection prevention, targeting higher CHG skin concentrations may improve control of certain pathogens.

Various water-based heater-cooler devices (HCDs) have been implicated in nontuberculous mycobacteria outbreaks. Ongoing rigorous surveillance for healthcare-associated M. abscessus (HA-Mab) put in place following a prior institutional outbreak of M. abscessus alerted investigators to a cluster of 3 extrapulmonary M. abscessus infections among patients who had undergone cardiothoracic surgery.

Investigators convened a multidisciplinary team and launched a comprehensive investigation to identify potential sources of M. abscessus in the healthcare setting. Adherence to tap water avoidance protocols during patient care and HCD cleaning, disinfection, and maintenance practices were reviewed. Relevant environmental samples were obtained. Patient and environmental M. abscessus isolates were compared using multilocus-sequence typing and pulsed-field gel electrophoresis. Smoke testing was performed to evaluate the potential for aerosol generation and dispersion during HCD use. The entire HCD fleet was replaced to mitigate continued transmission.

Clinical presentations of case patients and epidemiologic data supported intraoperative acquisition. M. abscessus was isolated from HCDs used on patients and molecular comparison with patient isolates demonstrated clonality. Smoke testing simulated aerosolization of M. abscessus from HCDs during device operation. Because the HCD fleet was replaced, no additional extrapulmonary HA-Mab infections due to the unique clone identified in this cluster have been detected.

Despite adhering to HCD cleaning and disinfection strategies beyond manufacturer instructions for use, HCDs became colonized with and ultimately transmitted M. abscessus to 3 patients. Design modifications to better contain aerosols or filter exhaust during device operation are needed to prevent NTM transmission events from water-based HCDs.

To assess whether measurement and feedback of chlorhexidine gluconate (CHG) skin concentrations can improve CHG bathing practice across multiple intensive care units (ICUs).

A before-and-after quality improvement study measuring patient CHG skin concentrations during 6 point-prevalence surveys (3 surveys each during baseline and intervention periods).

The study was conducted across 7 geographically diverse ICUs with routine CHG bathing.

Adult patients in the medical ICU.

CHG skin concentrations were measured at the neck, axilla, and inguinal region using a semiquantitative colorimetric assay. Aggregate unit-level CHG skin concentration measurements from the baseline period and each intervention period survey were reported back to ICU leadership, which then used routine education and quality improvement activities to improve CHG bathing practice. We used multilevel linear models to assess the impact of intervention on CHG skin concentrations.

We enrolled 681 (93%) of 736 eligible patients; 92% received a CHG bath prior to survey. At baseline, CHG skin concentrations were lowest on the neck, compared to axillary or inguinal regions (P < .001). CHG was not detected on 33% of necks, 19% of axillae, and 18% of inguinal regions (P < .001 for differences in body sites). During the intervention period, ICUs that used CHG-impregnated cloths had a 3-fold increase in patient CHG skin concentrations as compared to baseline (P < .001).

Routine CHG bathing performance in the ICU varied across multiple hospitals. Measurement and feedback of CHG skin concentrations can be an important tool to improve CHG bathing practice.

To determine the proportion of hospitals that implemented 6 leading practices in their antimicrobial stewardship programs (ASPs). Design: Cross-sectional observational survey.

Acute-care hospitals.

ASP leaders.

Advance letters and electronic questionnaires were initiated February 2020. Primary outcomes were percentage of hospitals that (1) implemented facility-specific treatment guidelines (FSTG); (2) performed interactive prospective audit and feedback (PAF) either face-to-face or by telephone; (3) optimized diagnostic testing; (4) measured antibiotic utilization; (5) measured C. difficile infection (CDI); and (6) measured adherence to FSTGs.

Of 948 hospitals invited, 288 (30.4%) completed the questionnaire. Among them, 82 (28.5%) had <99 beds, 162 (56.3%) had 100–399 beds, and 44 (15.2%) had ≥400+ beds. Also, 230 (79.9%) were healthcare system members. Moreover, 161 hospitals (54.8%) reported implementing FSTGs; 214 (72.4%) performed interactive PAF; 105 (34.9%) implemented procedures to optimize diagnostic testing; 235 (79.8%) measured antibiotic utilization; 258 (88.2%) measured CDI; and 110 (37.1%) measured FSTG adherence. Small hospitals performed less interactive PAF (61.0%; P = .0018). Small and nonsystem hospitals were less likely to optimize diagnostic testing: 25.2% (P = .030) and 21.0% (P = .0077), respectively. Small hospitals were less likely to measure antibiotic utilization (67.8%; P = .0010) and CDI (80.3%; P = .0038). Nonsystem hospitals were less likely to implement FSTGs (34.3%; P < .001).

Significant variation exists in the adoption of ASP leading practices. A minority of hospitals have taken action to optimize diagnostic testing and measure adherence to FSTGs. Additional efforts are needed to expand adoption of leading practices across all acute-care hospitals with the greatest need in smaller hospitals.

To describe the epidemiology of complex colon surgical procedures (COLO), stratified by present at time of surgery (PATOS) surgical-site infections (SSIs) and non-PATOS SSIs and their impact on the epidemiology of colon-surgery SSIs.

Retrospective cohort study.

SSI data were prospectively collected from patients undergoing colon surgical procedures (COLOs) as defined by the National Healthcare Safety Network (NHSN) at 34 community hospitals in the southeastern United States from January 2015 to June 2019. Logistic regression models identified specific characteristics of complex COLO SSIs, complex non-PATOS COLO SSIs, and complex PATOS COLO SSIs.

Over the 4.5-year study period, we identified 720 complex COLO SSIs following 28,188 COLO surgeries (prevalence rate, 2.55 per 100 procedures). Overall, 544 complex COLO SSIs (76%) were complex non-PATOS COLO SSIs (prevalence rate [PR], 1.93 per 100 procedures) and 176 (24%) complex PATOS COLO SSIs (PR, 0.62 per 100 procedures). Age >75 years and operation duration in the >75th percentile were independently associated with non-PATOS SSIs but not PATOS SSIs. Conversely, emergency surgery and hospital volume for COLO procedures were independently associated with PATOS SSIs but not non-PATOS SSIs. The proportion of polymicrobial SSIs was significantly higher for non-PATOS SSIs compared with PATOS SSIs.

Complex PATOS COLO SSIs have distinct features from complex non-PATOS COLO SSIs. Removal of PATOS COLO SSIs from public reporting allows more accurate comparisons among hospitals that perform different case mixes of colon surgeries.

Sparse recent data are available on the epidemiology of surgical site infections (SSIs) in community hospitals. Our objective was to provide updated epidemiology data on complex SSIs in community hospitals and to characterize trends of SSI prevalence rates over time.

Retrospective cohort study.

SSI data were collected from patients undergoing 26 commonly performed surgical procedures at 32 community hospitals in the southeastern United States from 2013 to 2018. SSI prevalence rates were calculated for each year and were stratified by procedure and causative pathogen.

Over the 6-year study period, 3,561 complex (deep incisional or organ-space) SSIs occurred following 669,467 total surgeries (prevalence rate, 0.53 infections per 100 procedures). The overall complex SSI prevalence rate did not change significantly during the study period: 0.58 of 100 procedures in 2013 versus 0.53 of 100 procedures in 2018 (prevalence rate ratio [PRR], 0.84; 95% CI, 0.66–1.08; P = .16). Methicillin-sensitive Staphylococcus aureus (MSSA) complex SSIs (n = 480, 13.5%) were more common than complex SSIs caused by methicillin-resistant S. aureus (MRSA; n = 363, 10.2%).

The complex SSI rate did not decrease in our cohort of community hospitals from 2013 to 2018, which is a change from prior comparisons. The reason for this stagnation is unclear. Additional research is needed to determine the proportion of or remaining SSIs that are preventable and what measures would be effective to further reduce SSI rates.

Airway management is a controversial topic in modern Emergency Medical Services (EMS) systems. Among many concerns regarding endotracheal intubation (ETI), unrecognized esophageal intubation and observations of unfavorable neurologic outcomes in some studies raise the question of whether alternative airway techniques should be first-line in EMS airway management protocols. Supraglottic airway devices (SADs) are simpler to use, provide reliable oxygenation and ventilation, and may thus be an alternative first-line airway device for paramedics. In 2019, Alachua County Fire Rescue (ACFR; Alachua, Florida USA) introduced a novel protocol for advanced airway management emphasizing first-line use of a second-generation SAD (i-gel) for patients requiring medication-facilitated airway management (referred to as “rapid sequence airway” [RSA] protocol).

This was a one-year quality assurance review of care provided under the RSA protocol looking at compliance and first-pass success rate of first-line SAD use.

Records were obtained from the agency’s electronic medical record (EMR), searching for the use of the RSA protocol, advanced airway devices, or either ketamine or rocuronium. If available, hospital follow-up data regarding patient condition and emergency department (ED) airway exchange were obtained.

During the first year, 33 advanced airway attempts were made under the protocol by 23 paramedics. Overall, compliance with the airway device sequence as specified in the protocol was 72.7%. When ETI was non-compliantly used as first-line airway device, the first-pass success rate was 44.4% compared to 87.5% with adherence to first-line SAD use. All prehospital SADs were exchanged in the ED in a delayed fashion and almost exclusively per physician preference alone. In no case was the SAD exchanged for suspected dislodgement evidenced by lack of capnography.

First-line use of a SAD was associated with a high first-pass attempt success rate in a real-life cohort of prehospital advanced airway encounters. No SAD required emergent exchange upon hospital arrival.

An ‘ethnic’ or ‘group’ density effect in psychosis has been observed, whereby the risk of psychosis in minority group individuals is inversely related to neighbourhood-level proportions of others belonging to the same group. However, there is conflicting evidence over whether this effect differs between minority groups and limited investigation into other moderators.

To conduct a comprehensive systematic review and meta-analysis of the group density effect in psychosis and examine moderators.

Four databases were systematically searched. A narrative review was conducted and a three-level meta-analysis was performed. The potential moderating effect of crudely and specifically defined minority groups was assessed. Country, time, area size and whether studies used clinical or non-clinical outcomes were also tested as moderators.

Thirty-two studies were included in the narrative review and ten in the meta-analysis. A 10 percentage-point decrease in own-group density was associated with a 20% increase in psychosis risk (OR = 1.20, 95% CI 1.09−1.32, P < 0.001). This was moderated by crudely defined minority groups (F6,68 = 6.86, P < 0.001), with the strongest associations observed in Black populations, followed by a White Other sample. Greater heterogeneity was observed when specific minority groups were assessed (F25,49 = 7.26, P < 0.001).

This is the first review to provide meta-analytic evidence that the risk of psychosis posed by lower own-group density varies across minority groups, with the strongest associations observed in Black individuals. Heterogeneity in effect sizes may reflect distinctive social experiences of specific minority groups. Potential mechanisms are discussed, along with the implications of findings and suggestions for future research.

Evaluate the safety and tolerability of aripiprazole once-monthly (ARI-OM) initiation in patients stabilized on oral antipsychotics other than aripiprazole. Previous pivotal Phase III trials have evaluated initiating ARI-OM in patients stabilized on oral aripiprazole1.

Eligible patients were treated with oral atypical antipsychotics other than aripiprazole with a history of oral aripiprazole tolerability. The study included a screening phase (30 days) and a treatment phase (28 days). Patients were stabilized per investigator's judgment for ≥14 days on risperidone, olanzapine, quetiapine, or ziprasidone, before administration of ARI-OM (400 mg). Current oral antipsychotic was co-administered with ARI-OM for 2 weeks to determine safety and tolerability of a single ARI-OM dose following treatment initiation. Safety assessments were adverse events (AEs); extrapyramidal symptoms (EPSs) using standard objective rating scales; Columbia-Suicide Severity Rating Scale; clinical laboratory measures; and weight changes.

60 patients initiated ARI-OM, while continuing treatment for ≤2 weeks with oral risperidone (n=24), quetiapine (n=28), ziprasidone (n=5) or olanzapine (n=3). Treatment-emergent (TE) AEs (≥5%) were fatigue, injection-site pain, and restlessness (risperidone); insomnia, dystonia, injection-site pain, and toothache (quetiapine); and muscle spasm, tooth abscess, and toothache (ziprasidone). Prior olanzapine did not cause any AEs. Incidence of TE-EPSs were similar in all groups (< 5%). There were no unusual changes in objective EPS rating scales, suicidality, weight, laboratory values or fasting metabolic parameters across all groups.

The AE profile of patients receiving ARI-OM concomitant with oral atypical antipsychotics other than aripiprazole was consistent with prior reports1.

To evaluate efficacy and safety of aripiprazole once-monthly 400mg (AOM-400mg), an extended release injectable suspension of aripiprazole, in obese (BMI =30kg/m2) and non-obese (BMI <30kg/m2) patients with schizophrenia.

Data from a 38-week, double-blind, active-controlled, non-inferiority study (NCT00706654); randomisation (2:2:1) to AOM-400mg, oral aripiprazole (10-30mg/day) (ARI), or aripiprazole once-monthly 50mg (AOM-50mg) assessing the efficacy and safety of AOM in patients requiring chronic antipsychotic treatment were used for this post-hoc analysis. We report the overall relapse rates in the 38-week randomized phase. Comparisons of overall relapse rates were analyzed using the Chi-squared test.

662 patients were randomized to: AOM-400mg (n=265); ARI (n=266); or AOM-50mg (n=131). Of these, the following were obese: AOM- 400mg: n=95; ARI: n=95; AOM-50mg: n=43. In the obese patients, the overall relapse rate was significantly (p=0.0012) lower with AOM-400mg (7.4%) than with AOM-50mg (27.9%). The difference between AOM-400mg and ARI (8.4%) was not significantly different. In the non-obese patients, the overall relapse was significantly (p=0.0153) lower with AOM-400mg (8.8%) than with AOM-50mg (19.3%). The difference between AOM-400mg and ARI (7.6%) was not significantly different. For patients treated with AOM-400mg, the most common TEAEs (>10% in any group) are presented in Table 1.

Table 1.

The efficacy and tolerability of aripiprazole once-monthly 400mg were similar in both the obese and non-obese subgroups.

Supported by Otsuka Pharmaceutical Development & Commercialization, Inc., and H. Lundbeck A/S