Surface Chemistry in Environmental Degradation of Polymeric Solids.

Microplastics (MPs) cause significant adverse environmental effects. To address this issue, a scientific approach for understanding the formation of MPs is essential. In this Perspective, we summarize the three typical degradation behaviors of polymeric solids from a surface chemistry perspective: chemical degradation, biodegradation, and mechanical degradation. These three degradation processes can occur consecutively or simultaneously in poorly managed polymeric materials, ultimately resulting in their disintegration into the environment. This Perspective provides valuable insights into controlling the degradation of polymeric solids and designing eco-friendly polymers for a sustainable future.

Conservative versus Surgical Treatment of Pneumatosis Intestinalis: Experience from a Multidisciplinary Center.

BACKGROUND Pneumatosis intestinalis (PI) is an uncommon condition that is not specific to any particular disease. Currently, there is no specific clinical guideline for treating and diagnosing PI. Furthermore, there are numerous causes of PI, which makes it difficult for clinicians - internal medicine physicians as well as surgeons - to take a clinical approach to diagnosis and treatment. CASE REPORT We present 3 clinical scenarios with PI. In the first patient there was a solitary image of PI, which was treated successfully with parenteral nutrition and intravenous antibiotics, and he was discharged after 5 days. The other 2 cases, which involve gas in the hepatic portal vein (HPVG), were handled in 2 distinct ways: surgically and conservatively. One needed diagnostic laparoscopy with necrotic segmentectomy and was discharged from the hospital on postoperative day 16. The last patient, received resuscitation treatment due to severe comorbidities and inability to tolerate surgery. After 3 days, abdominal CT scan revealed no signs of remaining PI. However, the patient was terminally discharged after 7 weeks of treatment due to septic shock caused by sacrococcygeal ulcer and urinary tract infection. By drawing comparisons among these 3 scenarios, we aim to highlight certain indicators for conservative treatment success. CONCLUSIONS PI with HPVG is a sign of severe prognosis, which often requires surgical intervention. However, the decision to manage conservatively or surgically depends on the patient's condition and other criteria such as peritonitis, free fluid in the abdominal cavity, and the presence of shock. Physicians should also weigh the benefits and risks of surgical intervention in critically ill patients.

Clonal gene signatures predict prognosis in mesothelioma and lung adenocarcinoma.

Malignant pleural mesothelioma (MPM) is a rare but lethal pleural cancer with high intratumor heterogeneity (ITH). A recent study in lung adenocarcinoma has developed a clonal gene signature (ORACLE) from multiregional transcriptomic data and demonstrated high prognostic values and reproducibility. However, such a strategy has not been tested in other types of cancer with high ITH. We aimed to identify biomarkers from multi-regional data to prognostically stratify MPM patients. We generated a multiregional RNA-seq dataset for 78 tumor samples obtained from 26 MPM patients, each with one sample collected from a superior, lateral, and inferior region of the tumor. By integrating this dataset with the Cancer Genome Atlas MPM RNA-seq data, we selected 29 prognostic genes displaying high variability across different tumors but low ITH, which named PRACME (Prognostic Risk Associated Clonal Mesothelioma Expression). We evaluated PRACME in two independent MPM datasets and demonstrated its prognostic values. Patients with high signature scores are associated with poor prognosis after adjusting established clinical factors. Interestingly, the PRACME and the ORACLE signatures defined respectively from MPM and lung adenocarcinoma cross-predict prognosis between the two cancer types. Further investigation indicated that the cross-prediction ability might be explained by the high similarity between the two cancer types in their genomic regions with copy number variation, which host many clonal genes. Overall, our clonal signature PRACME provided prognostic stratification in MPM and this study emphasized the importance of multi-regional transcriptomic data for prognostic stratification based on clonal genes.

Spyglass: a framework for reproducible and shareable neuroscience research.

Scientific progress depends on reliable and reproducible results. Progress can also be accelerated when data are shared and re-analyzed to address new questions. Current approaches to storing and analyzing neural data typically involve bespoke formats and software that make replication, as well as the subsequent reuse of data, difficult if not impossible. To address these challenges, we created Spyglass, an open-source software framework that enables reproducible analyses and sharing of data and both intermediate and final results within and across labs. Spyglass uses the Neurodata Without Borders (NWB) standard and includes pipelines for several core analyses in neuroscience, including spectral filtering, spike sorting, pose tracking, and neural decoding. It can be easily extended to apply both existing and newly developed pipelines to datasets from multiple sources. We demonstrate these features in the context of a cross-laboratory replication by applying advanced state space decoding algorithms to publicly available data. New users can try out Spyglass on a Jupyter Hub hosted by HHMI and 2i2c: https://spyglass.hhmi.2i2c.cloud/.

Frequency of HLA-DR+CD38hi T cells identifies and quantifies T-cell activation in hemophagocytic lymphohistiocytosis, hyperinflammation, and immune regulatory disorders.

BACKGROUND: Quantifying T-cell activation is essential for the diagnosis and evaluation of treatment response in various hyperinflammatory and immune regulatory disorders, including hemophagocytic lymphohistiocytosis. Plasma soluble IL-2 receptor (sIL-2R) is a well-established biomarker for evaluating systemic T-cell activation. However, the limited availability of sIL-2R testing could result in delayed diagnosis. Furthermore, high sIL-2R levels may not always reflect T-cell activation. OBJECTIVES: To address these limitations, this study investigated whether cell surface markers of T-cell activation, HLA-DR, and CD38, as assessed by flow cytometry, could be used to quantify systemic T-cell activation in a variety of inflammatory disease states and examine its correlation with sIL-2R levels. METHODS: Results for sIL-2R, CXCL9, and ferritin assays were obtained from patient's medical records. Frequency of HLA-DR+CD38high(hi) T-cells was assessed in different T-cell subsets using flow cytometry. RESULTS: In this study's cohort, activation in total CD8+ T (r = 0.65; P < .0001) and CD4+ (r = 0.42; P < .0001) T-cell subsets significantly correlated with plasma sIL-2R levels. At the disease onset, the frequency of HLA-DR+CD38hi T cells in CD8+ T (r = 0.65, P < .0001) and CD4+ T (r = 0.77; P < .0001) effector memory (TEM) compartments correlated strongly with sIL-2R levels. Evaluation of T-cell activation markers in follow-up samples also revealed a positive correlation for both CD4+ TEM and CD8+ TEM activation with sIL-2R levels; thus, attesting its utility in initial diagnosis and in evaluating treatment response. The frequency of HLA-DR+CD38hi T-cells in the CD8+ TEM compartment also correlated with plasma CXCL9 (r = 0.42; P = .0120) and ferritin levels (r = 0.32; P = .0037). CONCLUSIONS: This study demonstrates that flow cytometry-based direct T-cell activation assessed by HLA-DR+CD38hi T cells accurately quantifies T-cell activation and strongly correlates with sIL-2R levels across a spectrum of hyperinflammatory and immune dysregulation disorders.

Outcomes for pregnant women with Borderline Personality Disorder who attended a specialist antenatal service.

OBJECTIVE: Our study focussed on the obstetric and psychosocial outcomes of pregnant women with Borderline Personality Disorder (BPD) who received care via a specialist antenatal clinic in Western Australia. METHOD: This study is a retrospective examination of outcomes for 80 women with a confirmed diagnosis of BPD, with findings compared with published population outcome data for the state. RESULTS: Pregnant women with BPD appeared to be at a risk of complications including pre-eclampsia and special care nursery admission for their newborns when compared to population data. Furthermore, the studied women had elevated rates of psychiatric admissions during pregnancy, child protection involvement, and domestic violence. Polypharmacy exposure was frequent, with the likely impact on obstetric and neonatal outcomes requiring further study. CONCLUSION: The findings reinforced the notion that pregnant women with BPD experience complex multifaceted vulnerabilities and require enhanced multidisciplinary care. Our study further calls for the development of clinical practice guidelines for managing BPD in the perinatal period.

General practitioner perceptions and experiences of managing perinatal mental health: a scoping review.

BACKGROUND: General Practitioners (GPs) are involved in preconception, pregnancy, and postnatal care. Overall, mental health remains a significant contributor to disease burden affecting 1 in 4 pregnant women. Psychotropic medication prescribing occurs in almost 1 in 12 pregnancies, and appears to be increasing, along with the prevalence of mental health disorders in women of reproductive age. Perinatal mental health management is therefore not an unlikely scenario within their clinical practice. This scoping review aims to map current research related to GPs perceptions and experiences of managing perinatal mental health. METHOD: A comprehensive search strategy using nine electronic databases, and grey literature was undertaken between December 2021 and February 2023. Relevant studies were sourced from peer review databases using key terms related to perinatal mental health and general practitioners. Search results were screened on title, abstract and full text to assess those meeting inclusion criteria and relevance to the research question. RESULTS: After screening, 16 articles were included in the scoping review. The majority focused on perinatal depression. Findings support that GPs express confidence with diagnosing perinatal depression but report issues of stigma navigating a diagnosis. Over the last two decades, prescribing confidence in perinatal mental health remains variable with concerns for the safety profile of medication, low level of confidence in providing information and a strong reliance on personal experience. Despite the establishment of perinatal guidelines by countries, the utilisation of these and other existing resources by GPs appears from current literature to be infrequent. Many challenges exist for GPs around time pressures, a lack of information and resources, and difficulty accessing referral to services. CONCLUSION: Recommendations following this scoping review include targeted perinatal education programs specific for GPs and embedded within training programs and the development of practice guidelines and resources specific to general practice that recognises time, services, and funding limitations. To achieve this future research is first needed on how guidelines and resources can be developed and best delivered to optimise GP engagement to improve knowledge and enhance patient care.

A multi-institutional pediatric dataset of clinical radiology MRIs by the Children's Brain Tumor Network.

Pediatric brain and spinal cancers remain the leading cause of cancer-related death in children. Advancements in clinical decision-support in pediatric neuro-oncology utilizing the wealth of radiology imaging data collected through standard care, however, has significantly lagged other domains. Such data is ripe for use with predictive analytics such as artificial intelligence (AI) methods, which require large datasets. To address this unmet need, we provide a multi-institutional, large-scale pediatric dataset of 23,101 multi-parametric MRI exams acquired through routine care for 1,526 brain tumor patients, as part of the Children's Brain Tumor Network. This includes longitudinal MRIs across various cancer diagnoses, with associated patient-level clinical information, digital pathology slides, as well as tissue genotype and omics data. To facilitate downstream analysis, treatment-naïve images for 370 subjects were processed and released through the NCI Childhood Cancer Data Initiative via the Cancer Data Service. Through ongoing efforts to continuously build these imaging repositories, our aim is to accelerate discovery and translational AI models with real-world data, to ultimately empower precision medicine for children.

Retraction: A new polymer lab-on-a-chip (LOC) based on a microfluidic capillary flow assay (MCFA) for detecting unbound cortisol in saliva.

Retraction of 'A new polymer lab-on-a-chip (LOC) based on a microfluidic capillary flow assay (MCFA) for detecting unbound cortisol in saliva' by Vinitha T. U. et al., Lab Chip, 2020, 20, 1961-1974, DOI: https://doi.org/10.1039/D0LC00071J.

Exclusive waterpipe smoking and the risk of nasopharynx cancer in Vietnamese men, a prospective cohort study.

Tobacco smoking is carcinogenic to humans. Besides cigarettes, the most common form of tobacco smoking, there was sparse evidence of waterpipe's carcinogenicity-induced nasopharyngeal cancer (NPC). This study investigated the association between waterpipe smoking and NPC mortality. Our study followed up with 20,144 eligible man participants from nine northern Vietnam communes between 2007 and 2019. Face-to-face interviews were conducted to gather data on exclusive waterpipe and cigarette smoking and dietary intake using structured semi-quantitative food frequency and lifestyle questionnaires. Nasopharyngeal cancer was determined by accessing the medical records at the state health facilities. We estimated the Cox proportional hazard ratio and 95% confidence intervals, HR (95% CI). The proportion of never smokers, exclusive waterpipe, exclusive cigarette, and dual waterpipe and cigarette smokers was 55.8%, 14.5%, 16.6%, and 13.1%, respectively. Exclusively waterpipe smokers increased the risk of NPC death compared to exclusively cigarette smokers, HR (95% CI): 4.51 (1.25, 16.31), p = 0.022. A dose-dependent positive relationship between NPC and exclusive waterpipe smoking was significantly seen for higher intensity HR (95% CI): 1.35 (1.07, 1.71), earlier age of smoking initiation HR (95% CI): 1.26 (1.06, 1.50), longer duration HR (95% CI): 1.31 (1.04, 1.66), and the cumulative number of a smoke lifetime HR (95% CI): 1.37 (1.08, 1.74). We observed a significant positive association between exclusive waterpipe smoking and NPC in men. The findings suggested that waterpipe smoking is likely more harmful than cigarettes in developing this cancer. A firm tobacco control against waterpipe smoking is highly recommended.

User-Centered Design and Evaluation of Clinical Decision Support to Improve Early Peanut Introduction: Formative Study.

BACKGROUND: Peanut allergy has recently become more prevalent. Peanut introduction recommendations have evolved from suggesting peanut avoidance until the age of 3 years to more recent guidelines encouraging early peanut introduction after the Learning Early about Peanut Allergy (LEAP) study in 2015. Guideline adherence is poor, leading to missed care opportunities. OBJECTIVE: In this study, we aimed to develop a user-centered clinical decision support (CDS) tool to improve implementation of the most recent early peanut introduction guidelines in the primary care clinic setting. METHODS: We edited the note template of the well-child check (WCC) visits at ages 4 and 6 months with CDS prompts and point-of-care education. Formative and summative usability testing were completed with pediatric residents in a simulated electronic health record (EHR). We estimated task completion rates and perceived usefulness of the CDS in summative testing, comparing a test EHR with and without the CDS. RESULTS: Formative usability testing with the residents provided qualitative data that led to improvements in the build for both the 4-month and 6-month WCC note templates. During summative usability testing, the CDS tool significantly improved discussion of early peanut introduction at the 4-month WCC visit compared to scenarios without the CDS tool (9/15, 60% with CDS and 0/15, 0% without CDS). All providers except one at the 4-month WCC scenario gave at least an adequate score for the ease of use of the CDS tool for the history of present illness and assessment and plan sections. During the summative usability testing with the 6-month WCC new build note template, providers more commonly provided comprehensive care once obtaining a patient history concerning for an immunoglobulin E-mediated peanut reaction by placing a referral to allergy/immunology (P=.48), prescribing an epinephrine auto-injector (P=.07), instructing on how to avoid peanut products (P<.001), and providing an emergency treatment plan (P=.003) with CDS guidance. All providers gave at least an adequate score for ease of use of the CDS tool in the after-visit summary. CONCLUSIONS: User-centered CDS improved application of early peanut introduction recommendations and comprehensive care for patients who have symptoms concerning for peanut allergy in a simulation.

Fetal SSRI antidepressant exposure and infant sleep: Findings from the MPEWS pregnancy cohort study.

This longitudinal study examines the association between fetal Selective Serotonergic Reuptake Inhibitor antidepressant exposure and infant sleep behaviours at six and 12 months of age and focus on three of the most commonly prescribed antidepressants in pregnancy. This study utilises data on 698 women recruited at less than 20 weeks of pregnancy and are followed up at six and 12 months postpartum. Women were recruited into one of three groups: those taking either sertraline, citalopram or escitalopram antidepressants in pregnancy (n = 85); women with a depressive disorder who were not taking antidepressants (non-medicated depressed, NMD; n = 82); and, and a control group of women (n = 531). At six and 12 months, data were collected on breastfeeding and sleep location and infant sleep was measured using the Brief Infant Sleep Questionnaire. Antidepressants sertraline, escitalopram and citalopram were not associated with increased infant waking or time awake. However, sertraline was associated with longer time for an infant to go to sleep. This study provides reassurance that SSRI antidepressants and, in particular, sertraline, escitalopram and citalopram are not associated with infant sleep behaviours that are commonly regarded as problematic including night waking. Further replication of these findings, including with direct measures of infant sleep, are recommended.

Immune Infiltration in Tumor and Adjacent Non-Neoplastic Regions Codetermines Patient Clinical Outcomes in Early-Stage Lung Cancer.

INTRODUCTION: In recent years, the proportion of patients with NSCLC diagnosed at an early stage has increased continuously. METHODS: In this study, we analyzed samples and data collected from 119 samples from 67 early stage patients with NSCLC, including 52 pairs of tumor and adjacent non-neoplastic samples, and performed RNA-sequencing analysis with high sequencing depth. RESULTS: We found that immune-related genes were highly enriched among the differentially expressed genes and observed significantly higher inferred immune infiltration levels in adjacent non-neoplastic samples than in tumor samples. In survival analysis, the infiltration of certain immune cell types in tumor, but not adjacent non-neoplastic, samples were associated with overall patient survival, and excitingly, the differential infiltration between paired samples (tumor minus non-neoplastic) was more prognostic than expression in either non-neoplastic or tumor tissues. We also performed B cell receptor (BCR) and T cell receptor (TCR) repertoire analysis and observed more BCR/TCR clonotypes and increased BCR clonality in tumor than in non-neoplastic samples. Finally, we carefully quantified the fraction of the five histologic subtypes in our adenocarcinoma samples and found that higher histologic pattern complexity was associated with higher immune infiltration and low TCR clonality in the tumor-proximal regions. CONCLUSIONS: Our results indicated significantly differential immune characteristics between tumor and adjacent non-neoplastic samples and suggested that the two regions provided complementary prognostic values in early-stage NSCLCs.

Dynamic indoor free-space optical communication enabled by beam steering and beam shaping.

Indoor free-space optical communication (FSO) provides orders of magnitude larger usable bandwidth compared to radio-frequency links but suffers from an intrinsic trade-off between areal coverage and received power. In this paper, we report a dynamic indoor FSO system enabled by a line-of-sight optical link featuring advanced beam control capabilities. The optical link herein utilizes a passive target acquisition scheme by combining a beam steering and beam shaping transmitter with a receiver adorned with a ring-shaped retroreflector. When controlled by an efficient beam scanning algorithm, the transmitter is capable of locating the receiver with millimeter-scale accuracy over a distance of 3 m with a full viewing angle of ±11.25∘ in the vertical direction and ±18.75∘ in the horizontal direction within 1.162±0.005s, regardless of the receiver's positions. We also demonstrate 1 Gbit/s data rate with bit error rates below 4×10-7 using an 850 nm laser diode with only 2 mW of output power.

DNA-PKcs as an upstream mediator of OCT4-induced MYC activation in small cell lung cancer.

Small cell lung cancer (SCLC) is a neuroendocrine tumor noted for the rapid development of both metastases and resistance to chemotherapy. High mutation burden, ubiquitous loss of TP53 and RB1, and a mutually exclusive amplification of MYC gene family members contribute to genomic instability and make the development of new targeted agents a challenge. Previously, we reported a novel OCT4-induced MYC transcriptional activation pathway involving c-MYC, pOCT4S111, and MAPKAPK2 in progressive neuroblastoma, also a neuroendocrine tumor. Using tumor microarray analysis of clinical samples and preclinical models, we now report a correlation in expression between these proteins in SCLC. In correlating c-MYC protein expression with genomic amplification, we determined that some SCLC cell lines exhibited high c-MYC without genomic amplification, implying amplification-independent MYC activation. We then confirmed direct interaction between OCT4 and DNA-PKcs and identified specific OCT4 and DNA-PKcs binding sites. Knock-down of both POU5F1 (encoding OCT4) and PRKDC (encoding DNA-PKcs) resulted in decreased c-MYC expression. Further, we confirmed binding of OCT4 to the promoter/enhancer region of MYC. Together, these data establish the presence of a DNA-PKcs/OCT4/c-MYC pathway in SCLCs. We then disruptively targeted this pathway and demonstrated anticancer activity in SCLC cell lines and xenografts using both DNA-PKcs inhibitors and a protein-protein interaction inhibitor of DNA-PKcs and OCT4. In conclusion, we demonstrate here that DNA-PKcs can mediate high c-MYC expression in SCLCs, and that this pathway may represent a new therapeutic target for SCLCs with high c-MYC expression.

Calcium Intake Contributed by Whole Foods and Gastric Cancer in Viet Nam: A Case­Control Study.

BACKGROUND: Recent studies revealed the potential tumor-suppressive effects of calcium. We aimed to investigate the association between dietary calcium intake contributed by whole foods and gastric cancer. METHODS: 466 gastric cancer cases and 1531 controls were extracted from the completed case-control studies in hospitals in Hanoi from 2017 to 2019. A validated semi-quantitative food frequency questionnaire was used to obtain data via face-to-face interviews with the trained interviewer. Calcium intake was calculated based on the food frequency intake per year. Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were calculated. RESULTS: The study participants consumed less than 50% of 700 mg/day compared to the recommended calcium intake. With increasing calcium intake, we found a reduction in gastric cancer in both genders, men and women (adjusted OR and 95%CI, 5th vs. 1st quintile: 0.50 (0.36, 0.70), p_trend 0.000; 0.62 (0.42, 0.92), p_trend 0.019; and 0.30 (0.16, 0.57), p_trend 0.000, respectively). The inverse association remained in the subgroups of never-smokers and those with positive H. pylori infection. CONCLUSION: We observed substantial benefits of calcium intake from whole foods against gastric cancer in the Vietnamese population with a low nutritious status.

Transvaginal Ultrasound Diagnosis of Ovarian Ectopic Pregnancy.

Primary ovarian pregnancies are rare and comprise less than one percent of all ectopic pregnancies. Diagnosis can be difficult as an ovarian ectopic pregnancy may share similar features on ultrasound with those of a corpus luteal cyst. Findings on transvaginal ultrasound, including a hyperechoic ring, may denote the presence of a gestational sac and therefore an ovarian ectopic pregnancy. Ultrasonographic findings, as well as a strong suspicion of an ovarian ectopic pregnancy, are critical. The report reviews the case of a 23-year-old primigravida with first trimester bleeding, an elevated human chorionic gonadotropin, an ovarian cyst, and no intrauterine pregnancy detected on ultrasound. The evaluation, diagnosis, and surgical management of an ovarian ectopic pregnancy are discussed.

Indigenous peoples and inclusion in clinical and genomic research: Understanding the history and navigating contemporary engagement.

Despite significant improvements in pediatric cancer survival outcomes, there remain glaring disparities in under-represented racial and ethnic groups that warrant mitigation by the scientific and clinical community. To address and work towards eliminating such disparities, the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and Children's Brain Tumor Network (CBTN) established a Diversity, Equity, and Inclusion (DEI) working group in 2020. The DEI working group is dedicated to improving access to care for all pediatric patients with central nervous system (CNS) tumors, broadening diversity within the research community, and providing sustainable data-driven solutions. To this end, the DEI working group aims to coordinate regular educational sessions centered on critical DEI topics in pediatric research and clinical care of pediatric patients, with a focus on pediatric neuro-oncology. In April 2022, the group led a moderated panel of experts on Indigenous Peoples' rights and participation in clinical research activities. The following paper serves to provide the scientific community a perspective on how to prioritize the inclusion of Indigenous Peoples in research with cultural sensitivity and with the intent of improving not only representation, but patient outcomes regardless of patient race, ethnicity, or socioeconomic background.

Adjuvant 5-Fluorouracil/leucovorin, capecitabine, and oxaliplatin-related regimens for stage II/III colon cancer patients 66 years or older.

Adjuvant chemotherapy of leucovorin-modulated 5-fluorouracil (5-FU/LV), capecitabine, and adding oxaliplatin to 5-FU/LV or capecitabine (FLOX/OX) have been standard regimens for high-risk stage II or III colon cancer (CC). We aimed to evaluate their patterns of use, association with survival, and rate of emergency room visit (ER) or hospitalization during the treatment period. High-risk stage II or III patients aged >65 years diagnosed between 2007 and 2015, underwent colectomy, and received any of these three regimens were selected from SEER and Texas Cancer Registry (TC) linked with Medicare data. Chi-square test, Kaplan-Meier survival curves, Cox regression, and logistic regression were used in data analysis. A total of 5621 (1080 stage II and 4541 stage III) patients with median age of 72 years were included in this study. For stage II, 24.4% used 5-FU/LV, 31.2% used capecitabine, and 44.4% used FLOX/OX; the respective numbers for stage III were 13.8%, 17.9%, and 68.3%. Patients aged <70 years, not in the West region, not in Medicare state-buy-in program, and with no comorbidity were more likely to use FLOX/OX. FLOX/OX was associated with improved overall survival (OS) in stage II and III patients and improved cancer-specific survival in stage III patients compared with 5-FU/LV. The survival benefit of FLOX/OX was sustained in stage III patients aged ≥70 years. Capecitabine had the lowest ER/hospitalization rate with 19.2% in stage II and 28.9% in III. The use of FLOX/OX was associated with improved survival compared with 5-FU/LV among CC patients. Capecitabine was associated with the lowest ER/hospitalization rate.

Clozapine Therapy and COVID-19: A Systematic Review of the Prevalence Rates, Health Outcomes, Hematological Markers, and Patient Perspectives.

BACKGROUND/OBJECTIVES: There have been concerns that clozapine treatment may undermine the capacity of the body to fight infection and increase the vulnerability to contracting COVID-19. This review of recent cohort studies investigated (1) whether people with a severe psychiatric disorder are at increased risk of COVID-19 and complications, (2) the immunological response of clozapine-users who contract COVID-19, and (3) patients' perspectives on COVID-19 and the pandemic response. METHODS: A systematic search of EMBASE, Medline, Pubmed, and PsycINFO databases using PRISMA guidelines using "COVID-19", "clozapine", and "vaccination" terms. RESULTS: 18 studies (out of 330 identified) met all criteria (N = 119 054 including 8045 on clozapine). There was no strong evidence that clozapine users may be at increased risk of contracting COVID-19 or developing complications after adjusting for medical comorbidities. Hematological studies showed temporary reductions in neutrophils in COVID-19-positive patients and vaccination suggesting a clozapine effect in defence against infection. Vaccination studies did not report major adverse effects. Increased plasma levels of clozapine and neutropenia however point to COVID-19-related interference of clozapine metabolism. Patient surveys reported limited impact on mental health and positive attitudes regarding pandemic response. CONCLUSION: This review did not find compelling evidence that the immune system of clozapine users put them at risk of COVID-19 and further complications. Evidence of drug-infection interactions however points to the importance of adhering to consensus guidelines about clozapine therapy during the pandemic. More evidence using longitudinal designs is required to examine the longer-term effects of COVID-19 and vaccination in this vulnerable population.