Pemetrexed and immunotherapies (e.g., pembrolizumab) are approved for first-line maintenance (1LM) treatment of nonsquamous advanced/metastatic non-small-cell lung cancer (NSCLC), but real-world data on their use are limited. The objective of this study was to assess 1LM clinical outcomes, safety, and treatment patterns of immunotherapy versus immunotherapy+pemetrexed among patients with advanced/metastatic NSCLC from the EU4 (France, Germany, Italy, Spain)+UK.

Data from patients in the US, Canada, and EU4+UK with nonsquamous advanced/metastatic NSCLC without targetable mutations were collected via electronic case report form. Physician-identified patients (≥18 y) in the EU4+UK were eligible for this subgroup analysis if they achieved stable disease or complete or partial response with first-line platinum-based chemotherapy+immunotherapy (January 2019 to March 2021) and received 1LM immunotherapy or immunotherapy+pemetrexed. Patients were followed from index (1LM initiation) until last physician contact or death. Outcomes were overall survival (OS), progression-free survival (PFS), treatment patterns and duration, and adverse events.

Among the selected 367 patients (male, 71.9%; mean±StDev age, 63.4±7.2 y; current/former smokers, 85.8%), 203 (55.3%) received immunotherapies, most commonly pembrolizumab (n=173; 85.2%), and 164 (44.7%) received immunotherapy+pemetrexed. Patients receiving immunotherapy had longer median adjusted OS and PFS compared to those receiving immunotherapy+pemetrexed (OS hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.36, 0.90; PFS HR: 0.58; 95% CI: 0.38, 0.79). Patients receiving immunotherapy versus patients receiving immunotherapy+pemetrexed had longer median treatment duration (14.0 vs 10.3 mo; p<0.001) and were less likely to experience anemia (19.7% vs 33.5%; p<0.01). Results were similar in the overall study population.

In this real-world study, among the selected patients with nonsquamous advanced/metastatic NSCLC who achieved stable disease or complete or partial response with first-line therapy, the addition of pemetrexed to immunotherapy in 1LM did not appear to confer a clinical benefit. Identifying treatments that can improve clinical outcomes for these patients remains an area of unmet need.

COVID-19 lockdowns increased the risk of mental health problems, especially for children with autism spectrum disorder (ASD). However, despite its importance, little is known about the protective factors for ASD children during the lockdowns.

Based on the Shanghai Autism Early Developmental Cohort, 188 ASD children with two visits before and after the strict Omicron lockdown were included; 85 children were lockdown-free, while 52 and 51 children were under the longer and the shorter durations of strict lockdown, respectively. We tested the association of the lockdown group with the clinical improvement and also the modulation effects of parent/family-related factors on this association by linear regression/mixed-effect models. Within the social brain structures, we examined the voxel-wise interaction between the grey matter volume and the identified modulation effects.

Compared with the lockdown-free group, the ASD children experienced the longer duration of strict lockdown had less clinical improvement (β = 0.49, 95% confidence interval (CI) [0.19–0.79], p = 0.001) and this difference was greatest for social cognition (2.62 [0.94–4.30], p = 0.002). We found that this association was modulated by parental agreeableness in a protective way (−0.11 [−0.17 to −0.05], p = 0.002). This protective effect was enhanced in the ASD children with larger grey matter volumes in the brain's mentalizing network, including the temporal pole, the medial superior frontal gyrus, and the superior temporal gyrus.

This longitudinal neuroimaging cohort study identified that the parental agreeableness interacting with the ASD children's social brain development reduced the negative impact on clinical symptoms during the strict lockdown.

Inflammation plays a crucial role in the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). This study aimed to examine whether the dysregulation of complement components contributes to brain structural defects in patients with mood disorders.

A total of 52 BD patients, 35 MDD patients, and 53 controls were recruited. The human complement immunology assay was used to measure the levels of complement factors. Whole brain-based analysis was performed to investigate differences in gray matter volume (GMV) and cortical thickness (CT) among the BD, MDD, and control groups, and relationships were explored between neuroanatomical differences and levels of complement components.

GMV in the medial orbital frontal cortex (mOFC) and middle cingulum was lower in both patient groups than in controls, while the CT of the left precentral gyrus and left superior frontal gyrus were affected differently in the two disorders. Concentrations of C1q, C4, factor B, factor H, and properdin were higher in both patient groups than in controls, while concentrations of C3, C4 and factor H were significantly higher in BD than in MDD. Concentrations of C1q, factor H, and properdin showed a significant negative correlation with GMV in the mOFC at the voxel-wise level.

BD and MDD are associated with shared and different alterations in levels of complement factors and structural impairment in the brain. Structural defects in mOFC may be associated with elevated levels of certain complement factors, providing insight into the shared neuro-inflammatory pathogenesis of mood disorders.

We aimed to examine how public health policies influenced the dynamics of coronavirus disease 2019 (COVID-19) time-varying reproductive number (Rt) in South Carolina from February 26, 2020, to January 1, 2021.

COVID-19 case series (March 6, 2020, to January 10, 2021) were shifted by 9 d to approximate the infection date. We analyzed the effects of state and county policies on Rt using EpiEstim. We performed linear regression to evaluate if per-capita cumulative case count varies across counties with different population size.

Rt shifted from 2-3 in March to <1 during April and May. Rt rose over the summer and stayed between 1.4 and 0.7. The introduction of statewide mask mandates was associated with a decline in Rt (−15.3%; 95% CrI, −13.6%, −16.8%), and school re-opening, an increase by 12.3% (95% CrI, 10.1%, 14.4%). Less densely populated counties had higher attack rates (P < 0.0001).

The Rt dynamics over time indicated that public health interventions substantially slowed COVID-19 transmission in South Carolina, while their relaxation may have promoted further transmission. Policies encouraging people to stay home, such as closing nonessential businesses, were associated with Rt reduction, while policies that encouraged more movement, such as re-opening schools, were associated with Rt increase.

Grey matter (GM) reduction is a consistent observation in established late stages of schizophrenia, but patients in the untreated early stages of illness display an increase as well as a decrease in GM distribution relative to healthy controls (HC). The relative excess of GM may indicate putative compensatory responses, though to date its relevance is unclear.

343 first-episode treatment-naïve patients with schizophrenia (FES) and 342 HC were recruited. Multivariate source-based morphometry was performed to identify covarying ‘networks' of grey matter concentration (GMC). Neurocognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and symptom burden using the Positive and Negative Symptoms Scale (PANSS) were obtained. Bivariate linear relationships between GMC and cognition/symptoms were studied.

Compared to healthy subjects, FES had prominently lower GMC in two components; the first consists of the anterior insula, inferior frontal gyrus, anterior cingulate and the second component with the superior temporal gyrus, precuneus, inferior/superior parietal lobule, cuneus, and lingual gyrus. Higher GMC was seen in adjacent areas of the middle and superior temporal gyrus, middle frontal gyrus, inferior parietal cortex and putamen. Greater GMC of this component was associated with lower duration of untreated psychosis, less severe positive symptoms and better performance on cognitive tests.

In untreated stages of schizophrenia, both a distributed lower and higher GMC is observable. While the higher GMC is relatively modest, it occurs across frontoparietal, temporal and subcortical regions in association with reduced illness burden suggesting a compensatory role for higher GMC in the early stages of schizophrenia.

Deficits in event-related potential (ERP) including duration mismatch negativity (MMN) and P3a have been demonstrated widely in chronic schizophrenia (SZ) but inconsistent findings were reported in first-episode patients. Psychotropic medications and diagnosis might contribute to different findings on MMN/P3a ERP in first-episode patients. The present study examined MMN and P3a in first episode drug naïve SZ and bipolar disorder (BPD) patients and explored the relationships among ERPs, neurocognition and global functioning.

Twenty SZ, 24 BPD and 49 age and sex-matched healthy controls were enrolled in this study. Data of clinical symptoms [Positive and Negative Symptoms Scale (PANSS), Young Manic Rating Scale (YMRS), Hamilton Depression Rating Scale (HAMD)], neurocognition [Wechsler Adult Intelligence Scale (WAIS), Cattell's Culture Fair Intelligence Test (CCFT), Delay Matching to Sample (DMS), Rapid Visual Information Processing (RVP)], and functioning [Functioning Assessment Short Test (FAST)] were collected. P3a and MMN were elicited using a passive auditory oddball paradigm.

Significant MMN and P3a deficits and impaired neurocognition were found in both SZ and BPD patients. In SZ, MMN was significantly correlated with FAST (r = 0.48) and CCFT (r = −0.31). In BPD, MMN was significantly correlated with DMS (r = −0.54). For P3a, RVP and FAST scores were significant predictors in SZ, whereas RVP, WAIS and FAST were significant predictors in BPD.

The present study found deficits in MMN, P3a, neurocognition in drug naïve SZ and BPD patients. These deficits appeared to link with levels of higher-order cognition and functioning.

People with serious mental illness are at great risk of suicide, but little is known about the suicide rates among this population. We aimed to quantify the suicide rates among people with serious mental illness (bipolar disorder, major depression, or schizophrenia).

PubMed and Web of Science were searched to identify studies published from 1 January 1975 to 10 December 2020. We assessed English-language studies for the suicide rates among people with serious mental illness. Random-effects meta-analysis was used. Changes in follow-up time and the suicide rates were presented by a locally weighted scatter-plot smoothing (LOESS) curve. Suicide rate ratio was estimated for assessments of difference in suicide rate by sex.

Of 5014 identified studies, 41 were included in this analysis. The pooled suicide rate was 312.8 per 100 000 person-years (95% CI 230.3–406.8). Europe was reported to have the highest pooled suicide rate of 335.2 per 100 000 person-years (95% CI 261.5–417.6). Major depression had the highest suicide rate of 534.3 per 100 000 person-years (95% CI 30.4–1448.7). There is a downward trend in suicide rate estimates over follow-up time. Excess risk of suicide in males was found [1.90 (95% CI 1.60–2.25)]. The most common suicide method was poisoning [21.9 per 100 000 person-years (95% CI 3.7–50.4)].

The suicide rates among people with serious mental illness were high, highlighting the requirements for increasing psychological assessment and monitoring. Further study should focus on region and age differences in suicide among this population.

We aimed to explore and create an evaluation model to assess hospital response capability for a public health emergency (PHE).

Grounded theory was used to construct a comprehensive evaluation index system. Combining with the index system and previous studies and policy documents, we investigated surge capability of hospitals in a PHE. The factor analysis method was used to establish the model.

The comprehensive evaluation system with 11 primary and 30 secondary indicators was constructed. A total of 89 secondary and tertiary hospitals were surveyed in China. The evaluation model (C = 0.587C1 + 0.151C2 + 0.140C3 + 0.122C4) was established. Four factors were identified, namely, preparation factor, treatment factor, emergency awareness factor, and prehospital first-aid factor.

A public health emergency could bring huge losses and a capable hospital response was necessary. There was an urgent need to evaluate hospital capability for a PHE.

To determine the effect of graft choice (allograft, bone-patellar tendon-bone autograft, or hamstring autograft) on deep tissue infections following anterior cruciate ligament (ACL) reconstructions.

Retrospective cohort study.

Patients from 6 US health plans who underwent ACL reconstruction from January 1, 2000, through December 31, 2008.

We identified ACL reconstructions and potential postoperative infections using claims data. A hierarchical stratified sampling strategy was used to identify patients for medical record review to confirm ACL reconstructions and to determine allograft vs autograft tissue implanted, clinical characteristics, and infection status. We estimated infection rates overall and by graft type. We used logistic regression to assess the association between infections and patients’ demographic characteristics, comorbidities, and choice of graft.

On review of 1,452 medical records, we found 55 deep wound infections. With correction for sampling weights, infection rates varied by graft type: 0.5% (95% CI, 0.3%-0.8%) with allografts, 0.6% (0.1%–1.5%) with bone-patellar tendon-bone autografts, and 2.5% (1.9%–3.1%) with hamstring autograft. After adjusting for potential confounders, we found an increased infection risk with hamstring autografts compared with allografts (odds ratio, 5.9; 95% CI, 2.8–12.8). However, there was no difference in infection risk among bone-patellar tendon-bone autografts vs allografts (odds ratio, 1.2; 95% CI, 0.3–4.8).

The overall risk for deep wound infections following ACL reconstruction is low but it does vary by graft type. Infection risk was highest in hamstring autograft recipients compared with allograft recipients and bone-patellar tendon-bone autograft recipients.

Infect Control Hosp Epidemiol 2016;37:827–833