Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.

To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.

We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.

Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.

We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.

Cefazolin is the preferred antimicrobial for the prevention of surgical site infections (SSIs) in many procedures. The presence of penicillin allergies can influence prescribing of alternative agents like vancomycin. In April 2022, Nebraska Medicine implemented a suppression of alerts for non-IgE-mediated and nonsevere penicillin allergies in the electronic medical record (EMR) upon cephalosporin prescribing. The objective of this study was to evaluate changes in perioperative cefazolin for SSI prophylaxis.

This was a quasi-experimental study of patients undergoing procedures for which cefazolin was the preferred agent per institutional guidance. Education on the change was distributed via e-mail to surgical staff and pharmacists. Pre- and post-intervention data were collected from April 2021 through March 2022 and April 11, 2022, through October 2022, respectively. Chart review was performed on patients with reported penicillin allergies for the top surgical procedures with <50% cefazolin utilization pre-intervention. The primary outcome was the administration of perioperative cefazolin in patients with penicillin allergies, including unknown reactions.

A total of 6,676 patients underwent surgical procedures (pre-intervention n = 4,147, post-intervention n = 2,529). Documented penicillin allergies were similar between the pre- and post-intervention group (12.3% vs. 12.6%). In individuals with documented penicillin allergies, cefazolin prescribing increased from 49.6% to 74.3% (p < 0.01). Chart review for safety outcomes identified no difference in new severe reactions, rescue medication, SSIs, acute kidney injury, postoperative Clostridioides difficile infection, or methicillin-resistant Staphylococcus aureus infections.

Following the suppression of EMR alerts for non-IgE-mediated and nonsevere penicillin allergies, cefazolin prescribing rates for SSI prophylaxis significantly improved.

With persistent incidence, incomplete vaccination rates, confounding respiratory illnesses, and few therapeutic interventions available, COVID-19 continues to be a burden on the pediatric population. During a surge, it is difficult for hospitals to direct limited healthcare resources effectively. While the overwhelming majority of pediatric infections are mild, there have been life-threatening exceptions that illuminated the need to proactively identify pediatric patients at risk of severe COVID-19 and other respiratory infectious diseases. However, a nationwide capability for developing validated computational tools to identify pediatric patients at risk using real-world data does not exist.

HHS ASPR BARDA sought, through the power of competition in a challenge, to create computational models to address two clinically important questions using the National COVID Cohort Collaborative: (1) Of pediatric patients who test positive for COVID-19 in an outpatient setting, who are at risk for hospitalization? (2) Of pediatric patients who test positive for COVID-19 and are hospitalized, who are at risk for needing mechanical ventilation or cardiovascular interventions?

This challenge was the first, multi-agency, coordinated computational challenge carried out by the federal government as a response to a public health emergency. Fifty-five computational models were evaluated across both tasks and two winners and three honorable mentions were selected.

This challenge serves as a framework for how the government, research communities, and large data repositories can be brought together to source solutions when resources are strapped during a pandemic.

Although trauma-focused cognitive behavior therapy (TF-CBT) is the frontline treatment for post-traumatic stress disorder (PTSD), one-third of patients are treatment non-responders. To identify neural markers of treatment response to TF-CBT when participants are reappraising aversive material.

This study assessed PTSD patients (n = 37) prior to TF-CBT during functional magnetic brain resonance imaging (fMRI) when they reappraised or watched traumatic images. Patients then underwent nine sessions of TF-CBT, and were then assessed for symptom severity on the Clinician-Administered PTSD Scale. FMRI responses for cognitive reappraisal and emotional reactivity contrasts of traumatic images were correlated with the reduction of PTSD severity from pretreatment to post-treatment.

Symptom improvement was associated with decreased activation of the left amygdala during reappraisal, but increased activation of bilateral amygdala and hippocampus during emotional reactivity prior to treatment. Lower connectivity of the left amygdala to the subgenual anterior cingulate cortex, pregenual anterior cingulate cortex, and right insula, and that between the left hippocampus and right amygdala were also associated with symptom improvement.

These findings provide evidence that optimal treatment response to TF-CBT involves the capacity to engage emotional networks during emotional processing, and also to reduce the engagement of these networks when down-regulating emotions.

The aim of this study was to determine what clinically important events occur in ST-elevation myocardial infarction (STEMI) patients transported for primary percutaneous coronary intervention (PCI) via a primary care paramedic (PCP) crew, and what proportion of such events could only be treated by advanced care paramedic (ACP) protocols.

We conducted a health record review of STEMI transports by PCP-only crews and those transferred from PCP to ACP crews (ACP-intercept) from 2011 to 2015. A piloted data collection form was used to extract clinically important events, interventions during transport, and mortality.

We identified 214 STEMI bypass cases (118 PCP-only and 96 ACP-intercept). Characteristics were mean age 61.4 years; 44.4% inferior infarcts; mean response time 6 minutes, 19 seconds; total paramedic contact time 29 minutes, 40 seconds; and, in cases of ACP-intercept, 7 minutes, 46 seconds of PCP-only contact time. A clinically important event occurred in 127 (59.3%) of cases: SBP < 90 mm Hg (26.2%), HR < 60 (30.4%), HR > 100 (20.6%), arrhythmias 7.5%, altered mental status 6.5%, airway intervention 2.3%. Two patients (0.9%) arrested, both survived. Of the events identified, 42.5% could be addressed differently by ACP protocols. The majority related to fluid boluses for hypotension (34.6%). In the ACP-intercept group, ACPs acted on 51.6% of events. There were six (2.8%) in-hospital deaths.

Although clinically important events are common in STEMI bypass patients, a smaller proportion of events would be addressed differently by ACP compared with PCP protocols. The majority of clinically important events were transient and of limited clinical significance. PCP-only crews can safely transport STEMI patients directly to primary PCI.

Little is known about the relationship between adolescent affective problems (anxiety and depression) and mortality.

To examine whether adolescent affective symptoms are associated with premature mortality, and to assess whether this relationship is independent of other developmental factors.

Data (n = 3884) was from Britain's oldest birth cohort study – the National Survey of Health and Development. Adolescent affective symptoms were rated by teachers at ages 13 and 15 years: scores were summed and classified into three categories: mild or no, moderate and severe symptoms (1st–50th, 51st–90th and 91st–100th percentiles, respectively). Mortality data were obtained from national registry data up to age 68 years. Potential confounders were parental social class, childhood cognition and illness, and adolescent externalising behaviour.

Over the 53-year follow-up period, 12.2% (n = 472) of study members died. Severe adolescent affective symptoms were associated with an increased rate of mortality compared with those with mild or no symptoms (gender adjusted hazard ratio 1.76, 95% CI 1.33–2.33). This association was only partially attenuated after adjustment for potential confounders (fully adjusted hazard ratio 1.61, 95% CI 1.20–2.15). There was suggestive evidence of an association across multiple causes of death. Moderate symptoms were not associated with mortality.

Severe adolescent affective symptoms are associated with an increased rate of premature mortality over a 53-year follow-up period, independent of potential confounders. These findings underscore the importance of early mental health interventions.

None.

The aim of this study was to explore perinatal and early postnatal outcomes in fetuses with prenatally diagnosed d-transposition of the great arteries and impacts of standardised prenatal consultation.

All fetuses with prenatally diagnosed d-transposition of the great arteries prospectively enrolled at South China cardiac centre from 2011 to 2015. Standardised prenatal consultation was introduced in 2013 and comprehensive measures were implemented, such as establishing fetal CHD Outpatient Consultation Service, performing standard prenatal consultation according to specifications, and establishing a multidisciplinary team with senior specialists performing in-person consultations. Continuous follow-up investigation was conducted. Perinatal and postnatal outcomes were compared before and after consultation including live birth, elective termination of pregnancy, spontaneous fetal death, stillbirths, referral for surgery, and survival.

In all, 146 fetuses were enrolled with 41 (28%) lost to follow-up. Among 105 remaining fetuses, 29 (28%) were live births and 76 (72%) were terminated. After consultation, live birth rate was higher (50 versus 33%) and termination rate was lower (50 versus 76%), although there was no statistical significance. Excluding three live births without postnatal d-transposition of the great arteries, 65% (17/26) underwent arterial switch operation within 30 days. A total of three in-hospital deaths occurred and during the 10-month follow-up period, one death was observed. In one case, the switch procedure was performed at 13 months and the infant survived. Out of eight infants without arterial switch operation, two died.

Live birth rate increased after consultation; however, termination remained high. Combining termination, patients without arterial switch operation, and operative mortality, outcomes of d-transposition of the great arteries infants can be improved. Standard consultation, multidisciplinary collaboration, and improved perinatal care are important to improve outcomes.

To determine whether real-time availability of rapid molecular results of Staphylococcus aureus would impact emergency department clinician antimicrobial selection for adults with cutaneous abscesses.

We performed a prospective, randomized controlled trial comparing a rapid molecular test with standard of care culture-based testing. Follow-up telephone calls were made at between 2 and 7 days, 1 month, and 3 months after discharge.

Two urban, academic emergency departments.

Patients at least 18 years old presenting with a chief complaint of abscess, cellulitis, or insect bite and receiving incision and drainage were eligible. Seven hundred seventy-eight people were assessed for eligibility and 252 met eligibility criteria.

Clinician antibiotic selection and clinical outcomes were evaluated. An ad hoc outcome of test performance was performed.

We enrolled 252 patients and 126 were randomized to receive the rapid test. Methicillin-susceptible S. aureus–positive patients receiving rapid test results were prescribed beta-lactams more often than controls (absolute difference, 14.5% [95% CI, 1.1%–30.1%]) whereas methicillin-resistant S. aureus–positive patients receiving rapid test results were more often prescribed anti–methicillin-resistant S. aureus antibiotics (absolute difference, 21.5% [95% CI, 10.1%–33.0%]). There were no significant differences between the 2 groups in 1-week or 3-month clinical outcomes.

Availability of rapid molecular test results after incision and drainage was associated with more-targeted antibiotic selection.

clinicaltrials.gov Identifier: NCT01523899

Infect. Control Hosp. Epidemiol. 2015;36(12):1423–1430

Pseudoprogression (psPD) is now recognised following radiotherapy with concurrent temozolomide (RT/TMZ) for glioblastoma multiforme (GBM). The aim of this study was to determine the incidence of psPD following RT/TMZ and the effect of psPD on prognosis.

All patients receiving RT/TMZ for newly diagnosed GBM were identified from a prospective database. Clinical and radiographic data were retrospectively reviewed. Early progression was defined as radiological progression (RECIST criteria) during or within eight weeks of completing RT/TMZ. Pseudoprogression was defined as early progression with subsequent disease stabilization, without salvage therapy, for at least six months from completion of RT/TMZ. The primary outcome was overall survival (Kaplan-Meier) and log rank analysis was used to compare groups.

Out of 111 patients analyzed, 104 were evaluable for radiological response. Median age was 58 years and median follow-up 55 weeks. Early progression was confirmed in 26% and within this group 32% had psPD. Median survival for the whole cohort was 56.7 weeks [95% CI (51.0, 71.3)]. Median survival for patients with psPD was significantly higher than for patients with true early progression (124.9 weeks versus 36.0 weeks, p=0.0286).

Approximately one third of patients with early progression were found to have psPD which was associated with a favourable prognosis. Maintenance TMZ should not be abandoned on the basis of seemingly discouraging imaging features identified within the first three months after RT/TMZ.

It is controversial if distant recurrence of glioblastoma is more common after temozolomide (TMZ) concurrent with radiotherapy (RT). Optimal therapy for patients with recurrent disease after RT/TMZ is unclear. Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival.

We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003-2007. Statistical analyses included Kaplan-Meier method for survival, and multivariate Cox proportional hazards model for the effect of salvage treatment on survival.

58 patients (86.6%) recurred locally; 9 patients (13.4%) had a distant non-contiguous focus of new disease. Median survival(MS) was 17 months; median time-to-progression(TTP) 6.8 months. The local and distant groups had comparable prognostic factors. There was no difference in MS(p=0.35) or TTP(p=0.95) by location of recurrence. At relapse, 26 patients(38.8%) received continuous, dose-intense TMZ, 24(35.8%) other therapy(4.5% RT; 20.9% lomustine+/-procarbazine; 4.5% etoposide; 1.5% conventional TMZ; 4.5% TMZ then lomustine), and 17(25.4%) were untreated. Dose-intense TMZ was associated with prolonged MS compared to all other patients(21.5 months vs. 12.4 months, p=0.019, HR=3.86, 95%CI: 1.81-8.22) and similar to MS with other chemotherapy regimens(18.8 months, p=0.40, HR=1.30, 95% CI: 0.65-2.61).

The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local. Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma. Overall survival is similar to other conventional salvage regimens; however TMZ may be better tolerated. This study is limited by its retrospective nature and potential selection bias. Prospective controlled studies are needed.

To explore current practices and decision making regarding antimicrobial prescribing among emergency department (ED) clinical providers.

We conducted a survey of ED providers recruited from 8 sites in 3 cities. Using purposeful sampling, we then recruited 21 providers for in-depth interviews. Additionally, we observed 10 patient-provider interactions at one of the ED sites. SAS 9.3 was used for descriptive and predictive statistics. Interviews were audio recorded, transcribed, and analyzed using a thematic, constructivist approach with consensus coding using NVivo 10.0. Field and interview notes collected during the observational study were aligned with themes identified through individual interviews.

Of 150 survey respondents, 76% agreed or strongly agreed that antibiotics are overused in the ED, while half believed they personally did not overprescribe. Eighty-nine percent used a smartphone or tablet in the ED for antibiotic prescribing decisions. Several significant differences were found between attending and resident physicians. Interview analysis identified 42 codes aggregated into the following themes: (1) resource and environmental factors that affect care; (2) access to and quality of care received outside of the ED consult; (3) patient-provider relationships; (4) clinical inertia; and (5) local knowledge generation. The observational study revealed limited patient understanding of antibiotic use. Providers relied heavily upon diagnostics and provided limited education to patients. Most patients denied a priori expectations of being prescribed antibiotics.

Patient, provider, and healthcare system factors should be considered when designing interventions to improve antimicrobial stewardship in the ED setting.

Infect Control Hosp Epidemiol 2014;35(9):1114-1125

To validate the utility of a previously published scoring model (Italian) to identify patients infected with community-onset extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-EKP) and develop a new model (Duke) based on local epidemiology.

This case-control study included patients 18 years of age or more admitted to Duke University Hospital between January 1, 2008, and December 31, 2010, with culture-confirmed infection due to an ESBL-EKP (cases). Uninfected controls were matched to cases (3 : 1). The Italian model was applied to our patient population for validation. The Duke model was developed through logistic-regression-based prediction scores calculated on variables independently associated with ESBL-EKP isolation. Sensitivities and specificities at various point cutoffs were determined, and determination of the area under the receiver operating characteristic curve (ROC AUC) was performed.

A total of 123 cases and 375 controls were identified. Adjusted odds ratios and 95% confidence intervals for variables previously identified in the Italian model were as follows: hospitalization (3.20 [1.62–6.55]), transfer (4.31 [2.15–8.78]), urinary catheterization (5.92 [3.09–11.60]), β-lactam and/or fluoroquinolone therapy (3.76 [2.06–6.95]), age 70 years or more (1.55 [0.79–3.01]), and Charlson Comorbidity Score of 4 or above (1.06 [0.55–2.01]). Sensitivity and specificity were, respectively, more than or equal to 95% and less than or equal to 47% for scores 3 or below and were less than or equal to 50% and more than or equal to 96% for scores 8 or above. The ROC AUC was 0.88. Variables identified in the Duke model were as follows: hospitalization (2.63 [1.32–5.41]), transfer (5.30 [2.67–10.71]), urinary catheterization (6.89 [3.62–13.38]), β-lactam and/or fluoroquinolone therapy (3.47 [1.91–6.41]), and immunosuppression (2.34 [1.14–4.80]). Sensitivity and specificity were, respectively, more than or equal to 94% and less than or equal to 65% for scores 3 or below and were less than or equal to 58% and more than or equal to 95% for scores 8 or above. The ROC AUC was 0.89.

While the previously reported model was an excellent predictor of community-onset ESBL-EKP infection, models utilizing factors based on local epidemiology may be associated with improved performance.