There is emerging evidence of heterogeneity within treatment-resistance schizophrenia (TRS), with some people not responding to antipsychotic treatment from illness onset and a smaller group becoming treatment-resistant after an initial response period. It has been suggested that these groups have different aetiologies. Few studies have investigated socio-demographic and clinical differences between early and late onset of TRS.

This study aims to investigate socio-demographic and clinical correlates of late-onset of TRS.

Using data from the electronic health records of the South London and Maudsley, we identified a cohort of people with TRS. Regression analyses were conducted to identify correlates of the length of treatment to TRS. Analysed predictors include gender, age, ethnicity, positive symptoms severity, problems with activities of daily living, psychiatric comorbidities, involuntary hospitalisation and treatment with long-acting injectable antipsychotics.

We observed a continuum of the length of treatment until TRS presentation. Having severe hallucinations and delusions at treatment start was associated shorter duration of treatment until the presentation of TRS.

Our findings do not support a clear cut categorisation between early and late TRS, based on length of treatment until treatment resistance onset. More severe positive symptoms predict earlier onset of treatment resistance.

DFdF, GKS, EF and IR have received research funding from Janssen and H. Lundbeck A/S. RDH and HS have received research funding from Roche, Pfizer, Janssen and Lundbeck. SES is employed on a grant held by Cardiff University from Takeda Pharmaceutical Comp

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.

To evaluate whether a series of quality improvement interventions to promote safe perioperative use of cephalosporins in penicillin-allergic patients improved use of first-line antibiotics and decreased costs.

Before-and-after trial following several educational interventions.

Academic medical center.

This study included patients undergoing a surgical procedure involving receipt of a perioperative antibiotic other than a penicillin or carbapenem between January 1, 2017, and August 31, 2019. Patients with and without a penicillin allergy label in their electronic medical record were compared with respect to the percentage who received a cephalosporin and average antibiotic cost per patient.

A multidisciplinary team from infectious diseases, allergy, anesthesiology, surgery, and pharmacy surveyed anesthesiology providers about their use of perioperative cephalosporins in penicillin-allergic patients. Using findings from that survey, the team designed a decision-support algorithm for safe utilization and provided 2 educational forums to introduce this algorithm, emphasizing the safety of cefazolin or cefuroxime in penicillin-allergic patients without history of a severe delayed hypersensitivity reaction.

The percentage of penicillin-allergic patients receiving a perioperative cephalosporin improved from ∼34% to >80% following algorithm implementation and the associated educational interventions. This increase in cephalosporin use was associated with a ∼50% reduction in antibiotic cost per penicillin-allergic patient. No significant adverse reactions were reported.

An educational antibiotic stewardship intervention produced a significant change in clinician behavior. A simple intervention can have a significant impact, although further study is needed regarding whether this response is sustained and whether an educational intervention is similarly effective in other healthcare systems.

The benefit of late window endovascular treatment (EVT) for anterior circulation ischemic stroke has been demonstrated using perfusion-based neuroimaging. We evaluated whether non-contrast CT (NCCT) and CT-angiogram (CTA) alone can select late-presenting patients for EVT.

We performed a retrospective comparison of all patients undergoing EVT at a single comprehensive stroke center from January 2016 to April 2017. Patients planned for EVT were divided into early (<6 hours from onset) and late (≥6 hours from onset or last time seen normal) window groups. Incidence of symptomatic hemorrhagic transformations (sHTs) at 24 hours and 3-month modified Rankin scores (mRSs) were compared.

During the study period, 204 (82%) patients underwent EVT in the early and 44 (18%) in the late window. Median (interquartile range) NIH Stroke Scale Score was similar between groups (early: 18 [15–23] vs. late: 17 [13–21]), as were median ASPECT scores (early: 9 [8–10] vs. late: 9 [7–9]). In the late window, 42 (95%) strokes were of unknown onset. Similar proportions of sHT occurred at 24 hours (early: 12 [6%] vs. late: 4 [9%], p = 0.43). At 3 months, the proportion of patients achieving functional independence (mRS 0–2) were comparable in the early (80/192 [42%]) and late (16/41 [39%]) windows (p = 0.76).

NCCT- and CTA-based patient selection led to similar functional independence outcomes and low proportions of sHT in the early and late windows. In centers without access to perfusion-based neuroimaging, this pragmatic approach could be safe, particularly for strokes of unknown onset.

Retinoblastoma is the most common primary intraocular tumor of childhood with >95% survival rates in the US. Traditional therapy for retinoblastoma often included enucleation (removal of the eye). While much is known about the visual, physical, and cognitive ramifications of enucleation, data are lacking about survivors' perception of how this treatment impacts overall quality of life.

Qualitative analysis of an open-ended response describing how much the removal of an eye had affected retinoblastoma survivors' lives and in what ways in free text, narrative form.

Four hundred and four retinoblastoma survivors who had undergone enucleation (bilateral disease = 214; 52% female; mean age = 44, SD = 11) completed the survey. Survivors reported physical problems (n = 205, 50.7%), intrapersonal problems (n = 77, 19.1%), social and relational problems (n = 98, 24.3%), and affective problems (n = 34, 8.4%) at a mean of 42 years after diagnosis. Three key themes emerged from survivors' responses; specifically, they (1) continue to report physical and intrapersonal struggles with appearance and related self-consciousness due to appearance; (2) have multiple social and relational problems, with teasing and bullying being prominent problems; and (3) reported utilization of active coping strategies, including developing more acceptance and learning compensatory skills around activities of daily living.

This study suggests that adult retinoblastoma survivors treated with enucleation continue to struggle with a unique set of psychosocial problems. Future interventions can be designed to teach survivors more active coping skills (e.g., for appearance-related issues, vision-related issues, and teasing/bullying) to optimize survivors' long-term quality of life.

Aquaculture is one of the fastest-growing food production sectors in many low-income and food-deficit countries with aquatic ecozones. Yet its specific impact on nutrition and livelihood in local communities, where commercial and/or export-orientated aquaculture activities are developed, is largely unknown.

The present narrative and argumentative review aims to provide an overview of our current understanding of the connections between aquaculture agroecosystems, local and national fish production, fish consumption patterns and nutrition and health outcomes.

The agroecological dynamic in a coastal-estuarine zone, where the aquatic environment ranges from fully saline to freshwater, is complex, with seasonal and annual fluctuations in freshwater supply creating a variable salinity gradient which impacts on aquatic food production and on food production more generally. The local communities living in these dynamic aquatic ecozones are vulnerable to poverty, poor diet and health, while these ecosystems produce highly valuable and nutritious aquatic foods. Policies addressing the specific challenges of risk management of these communities are limited by the sectoral separation of aquatic food production – the fisheries and aquaculture sector, the broader food sector – and public health institutions.

Here we provide an argument for the integration of these factors to improve aquaculture value chains to better address the nutritional challenges in Bangladesh.

Major depressive disorder (MDD) is a leading cause of disease burden worldwide, with lifetime prevalence in the United States of 17%. Here we present the results of the first prospective, large-scale, patient- and rater-blind, randomized controlled trial evaluating the clinical importance of achieving congruence between combinatorial pharmacogenomic (PGx) testing and medication selection for MDD.

1,167 outpatients diagnosed with MDD and an inadequate response to ≥1 psychotropic medications were enrolled and randomized 1:1 to a Treatment as Usual (TAU) arm or PGx-guided care arm. Combinatorial PGx testing categorized medications in three groups based on the level of gene-drug interactions: use as directed, use with caution, or use with increased caution and more frequent monitoring. Patient assessments were performed at weeks 0 (baseline), 4, 8, 12 and 24. Patients, site raters, and central raters were blinded in both arms until after week 8. In the guided-care arm, physicians had access to the combinatorial PGx test result to guide medication selection. Primary outcomes utilized the Hamilton Depression Rating Scale (HAM-D17) and included symptom improvement (percent change in HAM-D17 from baseline), response (50% decrease in HAM-D17 from baseline), and remission (HAM-D17<7) at the fully blinded week 8 time point. The durability of patient outcomes was assessed at week 24. Medications were considered congruent with PGx test results if they were in the ‘use as directed’ or ‘use with caution’ report categories while medications in the ‘use with increased caution and more frequent monitoring’ were considered incongruent. Patients who started on incongruent medications were analyzed separately according to whether they changed to congruent medications by week8.

At week 8, symptom improvement for individuals in the guided-care arm was not significantly different than TAU (27.2% versus 24.4%, p=0.11). However, individuals in the guided-care arm were more likely than those in TAU to achieve remission (15% versus 10%; p<0.01) and response (26% versus 20%; p=0.01). Remission rates, response rates, and symptom reductions continued to improve in the guided-treatment arm until the 24week time point. Congruent prescribing increased to 91% in the guided-care arm by week 8. Among patients who were taking one or more incongruent medication at baseline, those who changed to congruent medications by week 8 demonstrated significantly greater symptom improvement (p<0.01), response (p=0.04), and remission rates (p<0.01) compared to those who persisted on incongruent medications.

Combinatorial PGx testing improves short- and long-term response and remission rates for MDD compared to standard of care. In addition, prescribing congruency with PGx-guided medication recommendations is important for achieving symptom improvement, response, and remission for MDD patients.

Funding Acknowledgements: This study was supported by Assurex Health, Inc.