Course Of Illness Research Articles

Reported race-associated differences in control and schizophrenia post-mortem brain transcriptomes implicate stress-related and neuroimmune pathways

BackgroundThe molecular mechanisms underlying racial disparities in schizophrenia (SCZ) illness courses and outcomes are poorly understood. While these differences are thought to arise partly through stressful social gradients, little is known about how these differences are reflected in the brain, nor how they might underlie disparate psychiatric outcomes.MethodsTo better understand the neuro-molecular correlates of social gradients, SCZ, and their overlap, we analyzed post-mortem dorsolateral prefrontal cortex (DLPFC) RNAseq data from two racially diverse cohorts in the CommonMind Consortium (235 reported Black and 546 White, 322 SCZ cases and 459 controls) using differential expression and gene set variation analyses.ResultsWe observed differences in brain gene expression that were consistent across cohorts and reported race. A combined mega-analysis identified 1,514 genes with differential expression (DE) between reported race groups after accounting for diagnosis and other covariates. Functional enrichment analyses identified upregulation of genes involved in stress and immune response, highlighting the potential role of environmental differences between reported race groups. In a race-by-diagnosis interaction analysis, no individual genes passed statistical significance. However, 109 gene sets showed statistically significant differences, implicating metabolic and immune pathways.ConclusionOur results suggest molecular mechanisms uniquely perturbed across reported race groups and identify several candidate pathways associated with SCZ in a reported race-dependent manner. Our results underscore the importance of diverse cohort ascertainment to better capture population-level differences in SCZ pathogenesis.

QOL-02. SOCIAL NETWORKS CAN BE QUANTITATIVELY MEASURED AND NETWORKS WITH GREATER STRUCTURAL DIVERSITY ARE ASSOCIATED WITH HIGHER HUMAN FLOURISHING

Abstract BACKGROUND In patients with glioblastoma, the predicted progressive deterioration in physical and cognitive abilities leads to decreased quality of life for patients and their caregivers. Research has shown that one’s social environment is a major contributor to health outcomes. However, in this population, study of the social environment is a gap in the literature. METHODS We examined the personal social networks of 25 adult glioblastoma patients at one time between initial diagnosis and first cycle of adjuvant chemotherapy from March to September 2023. We additionally collected demographic, tumor measures, and the European Organization for Research and Treatment of Cancer Quality-of-Life for Patients with Brain Tumors (EORTC QLQ-BN20) and the Harvard Human Flourishing Index (HFI) measures. RESULTS The average age was 64.5 years old, 56% were female, and 84% had a Karnofsky Performance Status (KPS) of 70 or higher. Patients had large network sizes (mean of 8.8). Patients reported high levels of flourishing despite the challenging diagnosis. Flourishing was statistically significantly associated with lower network constraint (networks in which alters are less likely to be connected to each other) in a patient’s social network (p=0.046) and less lower extremity weakness (p=0.025), controlling for age, gender, income, tumor at size of diagnosis, and KPS. CONCLUSION Our study indicates personal social networks with more contacts who are not connected to each other are associated with greater flourishing. Quantifying the social networks of patients with glioblastoma has implications as an objective measure for supportive care trials. Moreover, standard quality-of-life measures may not adequately capture what it means to meaningfully live and flourish. Therefore, future studies should include how social networks and flourishing change over the course of illness and how this may also impact overall survival.

A meta-analysis of data-driven cognitive subgroups in bipolar disorder

The delineation of cognitive subgroups of bipolar disorder (BD) might be helpful for identifying biologically valid subtypes of this disorder. This meta-analysis identified peer-reviewed literature on studies investigating cognitive subgroups of BD with data-driven clustering methods. Relevant studies were searched in PubMed, Scopus, and Web of Science. Random-effects meta-analysis was performed using R software. A total of 14 cross-sectional studies including euthymic or mildly symptomatic patients with BD were included in the current meta-analysis. The available studies have consistently supported a 3-cluster solution. The pooled prevalence of the severe-impairment, moderate-impairment, and major good-functioning groups were 23.1 % (95%CI, 18.5 %–27.7 %), 42.5 % (95%CI, 36.3 %–48.8 %), and 33.5 % (95%CI, 25.9 %–41.1 %) respectively. Compared to healthy controls, both the severe-impairment (g=−1.40 to −1.73) and moderate-impairment groups (g=−0.59 to −0.96) had significant deficits in all six cognitive domains (verbal memory, visual memory, executive functions, working memory, attention and processing speed). The good-performance subgroup had a small increase in the performance of executive functions (g=0.23) and normal functioning in all other domains. Compared to the good-performance subgroup, the severe-impairment subgroup was characterized by more severe functional impairment, more hospital admissions, a higher percentage of type I BD and antipsychotic use. The characteristics of the moderate-impairment subgroup were lying between the other two subgroups for most of the measures. The current findings support the existence of 3 cognitive subgroups in BD including severe-impairment and moderate-impairment groups which are associated with a more severe course of illness.

060. Chronic Megacolon with Recto Vaginal Fistulo Associated with Atresia Ani: A 26-Year History and Case Report

Background: Large bowel obstruction and megacolon formation with rectovaginal fistule ascociated with atresia ani is rare. abnormal colon dilatation that falls into one of three categories: toxic, chronic, or acute. Acute megacolon, sometimes called Ogilvie syndrome, is a condition that frequently affects sick or postoperative individuals and is linked to autonomic nervous system dysfunction. Its source is unknown. On the other hand, intestinal dysfunction brought on by neurological or muscle conditions is the cause of chronic megacolon. The symptoms of all three kinds include bloating, stomach pain, and constipation. Case: We present a case of an 26-year-old woman surviving large bowel obstruction and mega-megacolon formation secondary atresia ani and fistulo rectovagina for 26years alive, with an presentation of abdominal distention. Results The patient’s symptoms, laboratory test results, and imaging were consistent with large bowel obstruction. The patient underwent urgent exploratory laparotomy. Upon entry in the abdomen, it was unexpected that the extreme colonic wall thickening, indicating the longtime course of illness. In this instance, we performed a number of procedures, including ligation of the obstructed colon, anus repair, and vaginal fistula repair. Conclusion: This report aims to point out the atypical and in-extremes presentation of an otherwise common disease.

Community-Associated MRSA—Not So Innocent Sibling per Se: A Case Report

Background: Methicillin-resistant S. aureus (MRSA) is a major healthcare burden and is classified as healthcare-associated (HA-MRSA) and community-associated (CA-MRSA). While HA-MRSA is clinically feared, CA-MRSA is often considered less pathogenic. This case report highlights the serious course of illness due to CA-MRSA infection and provides a treatment strategy for the management of such cases. Case description: A 41-year-old male presented with fever and breathlessness for five days. Upon admission, he was provided empirical treatment for atypical infections and vasopressor support for hypotension. His condition deteriorated, necessitating ventilator support. Although the initial tracheal Bio Fire test indicated MRSA, his clinical manifestations did not match MRSA pneumonia symptoms; however, CA-MRSA was confirmed within 12 h. Skin legions developed within 16 h and progressed gradually from ecchymosis, petechial, and palpable purpura to bullous lesions over 72 h. The antibiotic regimen was modified and optimized with the addition of Clindamycin, Vancomycin, and Meropenem–Colistin. Owing to high IL-6 levels, dual vasopressor support, and acute kidney failure, he was started on early (within 12 h) continuous renal replacement therapy (CRRT) with CytoSorb filter (for 3 days) for cytokine removal. IL-6 levels decreased after two days of CytoSorb use. Subsequently, the patient stabilized with reduced dependence on vasopressor and ventilator assistance. Discussion: Early diagnosis of CA-MRSA and management with CRRT using CytoSorb may help improve patient outcomes. To our knowledge, this is the first report of clinical management of CA-MRSA with CytoSorb therapy in India that resulted in positive outcomes.

Measuring social environment factors of depressed inpatients: A cross-sectional study

Abstract The course and management of mental illness are both influenced by social contextual factors. Standardised questionnaires are required to monitor inpatients’ social environment and to design interventions. This study aims to describe the social environment of inpatients with depression using standardised instruments, and to analyse the instrument’s applicability. This cross-sectional study included depressed adult inpatients admitted to a German psychiatric hospital. We used three standardised questionnaires to evaluate social risk factors: the Lubben Social Network Scale (LSNS), the WHO Disability Assessment Schedule (WHODAS) and the Social Cohesion and Trust Scale (SCTS). The appropriateness of the questionnaires was assessed with a context-specific quality appraisal. Our study included 196 patients with depression having a mean age of 38.8 (SD = 13.7) years of whom 50% were female. A total of 164 (85%) of patients reported a family history of mental health problems, and 31 (38.8%) had experienced discrimination. Analyses of the LSNS and WHODAS showed that the prevalence of social isolation and disability was significantly higher among inpatients compared to the general population. The WHODAS scores were highest in patients aged 18-30, while social isolation was elevated but stable among different age groups (range 18.7- 19.4%). Both, the WHODAS and LSNS showed good clinical applicability, comparability, and test properties. A lack of validation in a young population of the LSNS was considered a weakness. The SCTS showed imperfections in its applicability and comparability. Depressed inpatients have a limited social network compared to the general population. We emphasise the importance of assessing the applicability of questionnaires representing social environment as the basis for developing interventions. We recommend systematic monitoring of social characteristics to identify potential targets of intervention and thereby facilitate the management of depression. Key messages • Hospitalised patients with depression have a decreased social functioning and a smaller social network compared to the general population. • Standardised social environment questionnaires should be consented and used to plan and enrich depression management.

Subtypes of Childhood Trauma Exposure Associated with Earlier Onset and Delayed Treatment in Rapid Cycling Bipolar Disorder: A CaseControl Study

ABSTRACT Studies on bipolar disorder (BD) have suggested that exposure to childhood trauma (CT) and rapid cycling BD (RC-BD) are associated with earlier onset and overall worse prognosis. The association between CT exposure and RC-BD in patients from low/middle-income countries has not been sufficiently characterized. Therefore, we performed a case–control study of patients with RC-BD (n = 35), patients without RC-BD (n = 35), and healthy controls (HC) (n = 105) in a low/middle-income country, Colombia, to evaluate CT exposure and RC-BD for clinical associations. We reported a significant number of patients with RC-BD exposed to physical abuse and/or sexual abuse compared with patients without RC-BD during the course of illness. In addition, CT exposure and RC-BD were associated with an earlier age of onset and delayed diagnosis and treatment. In the future, recognition of early CT exposure in populations at risk for BD may help tailor precise interventions and thus change the course of illness and worse prognosis.

Long-term courses of major depressive disorder : Characteristics, risk factors and the definitional challenge of treatment response

The definition of long-term courses of depression is heterogeneous. Chronic and treatment-resistant courses, in particular, represent ahigh-cost factor and greatly reduce the quality of life. Based on the pharmacotherapeutic treatment-resistant depression (TRD), more and more systemic approaches are becoming important. This narrative review provides an overview of the long-term course of depressive disorders, including various definitions and influencing factors. In addition, an overview of biomarker research on treatment response with afocus on neuroimaging is presented. Aselective literature search was conducted in PubMed and Google Scholar for anarrative review. Particular attention was given to larger cohort studies, systematic reviews, meta-analyses and studies on the prediction of treatment response. Chronic and treatment-resistant courses mean arelevant reduction in the quality of life and increased health risks. The assessment of treatment response is adefinitional challenge: An alternative to TRD is the systemically oriented difficult to treat depression (DTD). The focus is thus moving away from symptom reduction towards controlling the level of functioning. Biomarker research for treatment response offers potential but currently mainly serves to gain theoretical knowledge. Recording the long-term course of depressive illnesses is important, but also complex. Clinical interventions should therefore include acontinuous monitoring and the focus on maintaining the quality of life.

Rocky Mountain Spotted Fever in Children along the US‒Mexico Border, 2017-2023.

Rocky mountain spotted fever (RMSF) causes significant illness and death in children. Although historically rare in California, USA, RMSF is endemic in areas of northern Mexico that border California. We describe 7 children with RMSF who were hospitalized at a tertiary pediatric referral center in California during 2017-2023. Five children had recent travel to Mexico with presumptive exposure, but 2 children did not report any travel outside of California. In all 7 patients, Rickettsia rickettsii DNA was detected by plasma microbial cell-free next-generation sequencing, which may be a useful diagnostic modality for RMSF, especially early in the course of illness, when standard diagnostic tests for RMSF are of limited sensitivity. A high index of suspicion and awareness of local epidemiologic trends remain most critical to recognizing the clinical syndrome of RMSF and initiating appropriate antimicrobial therapy in a timely fashion.

Efficacy of human interleukin-11 analogs for treating dengue fever-associated thrombocytopenia: a prospective cohort

AimDengue fever (DF), carried by Aedes mosquitoes, affects millions worldwide. Platelet-inducing human IL-11 analogues may be effective in treating DF-associated thrombocytopenia.MethodologyA prospective study was done at Dr. Ziauddin Hospital, a tertiary care hospital in Karachi, Pakistan, from September 2023 to April 30, 2024.ResultsThis study recruited 300 DF patients characterized by thrombocytopenia (platelet count < 30,000), including 159 in the treatment and 141 in the control group. The median age of patients was 34 ± 11.05 years, with 187 males (62.3%) and 113 females (37.7%). The treatment group had a higher proportion of fever (80%, p < 0.0001) and headache (96%, p = 0.012) compared to the control group; however, no significant changes were observed in other clinical parameters between the two groups. Following treatment for 5 days, platelet counts of the treatment group increased significantly in response to IL-11 treatment compared to the control group at all time intervals (day 0, day 1, day 2, day 3, day 4, and day 5). Following treatment, males consistently exhibited higher platelet counts than females (all p < 0.05). In addition, patients admitted on day 3 of their course of illness showed a significantly slow response to the treatment compared to those admitted on day 5. Although young individuals exhibited a significant increase in platelet count, the age showed no significant intergroup differences.ConclusionsIL-11 analogs have promising potential for treating DF-associated thrombocytopenia. Additional investigation is necessary to refine administration protocols and examine the wider therapeutic ramifications of IL-11 in managing DF.

Multi-Way adaptive Time Aware LSTM for irregularly collected sequential ICU data

In personalized predictive medicine, accurately modeling a patient’s illness and care processes is essential, given their inherent long-term temporal dependencies. However, electronic medical records contain episodic and irregularly timed data due to patients visiting hospitals based on treatment needs, resulting in unique patterns for each hospital stay. Consequently, when constructing a personalized predictive model, it is crucial to consider these factors in order to accurately capture the patient’s health journey.To address this challenge, we present a novel deep dynamic memory neural network called Multi-Way adaptive Time Aware LSTM (MWTA-LSTM). The primary objective of MWTA-LSTM is to leverage medical records, memorize illness trajectories and care processes, estimate current illness states, and predict future risks, thereby providing a high level of precision and predictive power. To enhance its capabilities, MWTA-LSTM extends the conventional Long Short-Term Memory (LSTM) model in two key ways. Firstly, it incorporates frequency measurement and the most recent observation(last observation) to enhance personalized predictive modeling of patient illnesses, enabling a more accurate understanding of the patient’s condition. Secondly, it parameterizes the cell state to handle irregular timing effectively, utilizing both frequency measurement and elapsed times. Furthermore, the model capitalizes on both to comprehend the impact of interventions on the course of illness on the cell state, facilitating the memorization of illness courses and improving its ability to capture the temporal dynamics of healthcare data, accommodating variations and irregularities in event and observation timing. Lastly, we introduce a novel adaptive pooling strategy that specifically targets and resolves outlier issues that can potentially occur during the analysis of EHR data. By incorporating these features, MWTA-LSTM significantly improves its ability to capture the temporal dynamics of healthcare data, accommodating variations and irregularities in event and observation timing.We validate the effectiveness of our proposed model through empirical experiments conducted on two real-world clinical datasets and three real-world time series datasets. Our results demonstrate the superiority of MWTA-LSTM over current state-of-the-art models and other robust baselines. This showcases the potential of MWTA-LSTM in advancing personalized predictive medicine by offering a more accurate and comprehensive approach to modeling patient health trajectories.

Clinical symptoms and psychosocial functioning in patients with schizophrenia spectrum disorders testing seropositive for anti-NMDAR antibodies: a case–control comparison with patients testing negative

Antibodies against the N-methyl-D-aspartate receptor (NMDAR) have been described in the serum of people with schizophrenia spectrum disorders (schizophrenia). However, the prevalence and clinical relevance of these antibodies in schizophrenia is unclear. This knowledge gap includes the possibility of such antibodies being associated with a distinct clinical profile, which in turn might warrant a distinct treatment approach. We aimed to assess the seroprevalence of anti-NMDAR antibodies in schizophrenia, and compare symptoms and psychosocial functioning between patients with schizophrenia who were seropositive and seronegative for these antibodies. In this case-control comparison, by combining new and existing studies, we included patients diagnosed with schizophrenia from four independent cohorts for whom anti-NMDAR serostatus had been assessed (or could be assessed by us) with live cell-based assays. Included cohorts were from the EULAST study (a trial conducted across 15 European countries and Israel), the OPTiMiSE study (an interventional study in Europe), and the PPiP1 and PPiP2 studies (conducted in the UK). Patients from these cohorts were analysed if they had complete Positive and Negative Syndrome Scale (PANSS) data. No participant had been diagnosed with autoimmune encephalitis or received treatment for this condition. After calculating the prevalence of serum anti-NMDAR antibodies, we examined possible differences in PANSS scores (negative, positive, and general symptom subscales, and total score) between anti-NMDAR-seropositive and anti-NMDAR-seronegative patients. Psychosocial functioning as measured by Personal Social Performance (PSP) score was also compared. All analyses were exploratory and no adjustment was done for multiple testing. People with lived experience were not involved in the conduct of this study. We collected individual patient data from 1114 patients with schizophrenia across the four cohorts. The study population had a mean age of 28·6 years (SD 7·6) and comprised 382 (34·3%) women and 732 (65·7%) men, including patients of White (929 [83·4%]), Asian (54 [4·8%]), Black (68 [6·1%]), and other (62 [5·6%]) ethnicities. Overall, 41 (3·7%) participants (range 3·1-4·0% across cohorts) tested positive for serum anti-NMDAR antibodies. Lower symptom severity on the negative symptoms PANSS subscale was observed for anti-NMDAR-seropositive patients (mean score 15·8 [SD 6·4]) than for anti-NMDAR-seronegative patients (18·2 [6·8]; Cohen's d=0·36; p=0·026), as well as on the general symptoms PANSS subscale (32·9 [8·9] vs 36·1 [10·1]; d=0·33; p=0·029) and total PANSS score (65·5 [18·5] vs 72·6 [19·3]; d=0·37; p=0·013). Mean PSP score was better in anti-NMDAR-positive patients (62·0 [17·0]) than in anti-NMDAR-negative patients (53·5 [16·3]; d=0·52; p=0·014). Serum NMDAR antibodies are present in 3-4% of patients with schizophrenia and are associated with relatively low severity of negative symptoms and relatively good psychosocial functioning. Thus, although the findings await replication in cohorts from other geographical regions, serum anti-NMDAR antibodies might be associated with a different form of psychotic illness. These findings could inform future prognostic and interventional studies examining whether anti-NMDAR antibodies are associated with a specific course of illness or with treatment response. None.

Role of Biomarkers Diagnostic Tools in Patients with COVID-19: Stratification Made Easy.

In coronavirus disease 2019 (COVID-19) patients, several serum biomarkers have been identified. Upon intensive care unit (ICU) admission, these laboratory markers become more crucial to distinguish between patients with severe cases of COVID-19. It might assist doctors in predicting the course of illnesses and treating patients appropriately. This work was to investigate the role of biomarkers in patients with COVID-19 classification admitted to the hospital and identified by reverse transcription polymerase chain reaction (RT-PCR). Peripheral blood sample was taken from COVID-19 cases isolated on admission to determine C-reactive protein (CRP), D-dimer, Fibrinogen, neutrophil-lymphocyte ratio (NLR), leukocytes CRP ratio (LeCR), lymphocyte-CRP ratio (LCR), interleukin-6 (IL6), leukocytes interleukin 6 ratio (LeIL6), systemic inflammatory index (SII), platelet-to-lymphocyte ratio (PLR), and tissue plasminogen activator inhibitor one (tPAI-1). Follow-up for IL6, Ferritin, D-dimer, and tPAI-1 were determined on the 3rd and 7th days. Comparisons of severity revealed that hypertension, chronic obstructive pulmonary disease (COPD), and Ischemia were major risk factors in COVID-19 patients. There was a statistically significant difference between the test groups for fibrinogen (p < 0.000), IL6 (p < 0.009), LeCR (p < 0.006), and LCR (p < 0.011). Based on laboratory test findings at the time of ICU admission, we can distinguish severe cases of COVID-19.

Health of Saudi Women in the Post-Pandemic Era: Candidiasis Incidence and Post COVID-19 and COVID-19-Vaccination.

Candidiasis, commonly known as yeast infection, affects people worldwide due to the overgrowth of Candida species. Of several types, genital candidiasis, particularly vulvovaginal candidiasis (VVC), primarily caused by C. albicans is frequently observed in females of reproductive age. Candidiasis has also become a serious issue in the post-pandemic era, as it occurs as a secondary infection in COVID-19 patients during or after the course of viral illness. Therefore, this study investigated the incidence of C. albicans infections in women of reproductive age, and its relationship with the incidence of COVID-19 and vaccination in Saudi Arabia. Additionally, this study aimed to determine the awareness of women on candidiasis and its subsequent impact on the occurrence of infection. A survey-based quantitative study was conducted in which primary data were collected from participants using a self-reported questionnaire. A total of 200 women aged 18-45 were selected through random sampling. Apart from their sociodemographic characteristics, the history of COVID-19 incidence, COVID-19 vaccination, and candidiasis occurrences among respondents were recorded. Their level of awareness and knowledge of candidiasis, along with their perceptions of strategies for mitigating the risk of incidence, were also evaluated. The collected data were analysed using different statistical tools. The findings of this study revealed a positive correlation between candidiasis, viral infection, and vaccination, regardless of the type and dosage of vaccine administered. Furthermore, both COVID-19 incidence and vaccination had a positive and significant impact on the occurrence of candidiasis among Saudi women. Despite certain limitations, this study has theoretical and managerial implications for improved management of candidiasis in the post-COVID era.

Association between the lactate-albumin ratio and microcirculation changes in Pediatric Septic patients

A lactate/albumin ratio (LAR) greater than 0.5 measured early in the course of pediatric critical illness is associated with greater mortality. Whether the elevated LAR can be explained by microcirculation disorders in children with sepsis is not known. In this longitudinal retrospective study (January 2021-January 2024), serum albumin and lactate were measured on admission to the pediatric intensive care unit (PICU), with sublingual video microscopy performed simultaneously to measure microcirculation. A total of 178 children were included, 37% of whom had septic shock measured with the Phoenix Sepsis Score. Patients with remote sepsis had greater odds of an elevated LAR (aOR 6.87: 95% CI 1.98–23.73; p < 0.01). Children with an elevated LAR had more microvascular blood flow abnormalities (aOR 1.31 95% CI 1.08–1.58; p < 0.01), lower 4-6-micron capillary density (aOR 1.03 95% CI 1.01–1.05; p < 0.01) and greater odds of dying (aOR 3.55 95% CI 1.21–10.38; p = 0.02) compared to those with a low LAR. We found no association between LAR and endothelial glycocalyx degradation. A normal LAR is associated with less risk of microcirculatory injury (aOR 0.77 95% CI 0.65–0.93; p < 0.01). In children with sepsis, an elevated LAR is associated with microcirculation abnormalities (microvascular density and flow). The lactate/albumin ratio is a potentially useful biomarker for microcirculatory injury in sepsis.

An evolutionary concept analysis: stigma among women living with hepatitis C

BackgroundStigma is a complex social phenomenon that leads to marginalization and influences the course of illness. In the context of hepatitis C virus (HCV), stigma is a well-documented barrier to accessing care, treatment, and cure. In recent years, HCV rates among women have increased, resulting in an urgent need to address stigma and its harmful effects. The purpose of this concept analysis was to investigate stigma in the context of women living with HCV using Rodgers’ evolutionary method.MethodsPubMed, CINAHL, Scopus, Medline, PsycINFO, and Nursing and Allied Health were used to identify articles describing HCV stigma among women. Articles from peer-reviewed journals and geographic locations, published between 2002–2023, were included in the analysis. As specified in Rodgers’ evolutionary method, articles were analyzed with a focus on the concept’s context, surrogate and related terms, antecedents, attributes, examples, and consequences.ResultsFollowing screening, 33 articles were selected for inclusion in the analysis. Discrimination and marginalization were identified as surrogate and related terms to stigma; and antecedents of stigma were identified as limited knowledge, fear of diagnosis, and disclosure. Prevalent attributes of stigma in the literature were described as feelings of decreased self-worth, negative stereotyping, and fear of transmission. Importantly, HCV stigma among women is unique in comparison to other forms of infectious disease-related stigma, primarily due its impact on women’s identity as mothers and caregivers. Stigmatization of women living with HCV resulted in negative consequences to personal relationships and healthcare access due to decreased health-seeking behaviours. Although access to HCV treatment has changed considerably over time, a temporal analysis could not be completed due to the limited number of articles.ConclusionsStigma in the context of women living with HCV has its own unique antecedents, attributes, and consequences. This enhanced understanding of stigma among women living with HCV has the potential to inform improved and more effective approaches to care, which will be required to reach HCV elimination. Furthermore, this analysis identifies stigma layering and stigma in the direct-acting antiviral treatment era as areas for more in-depth future inquiry.

Biallelic Mismatch Repair Deficiency in Children and Adolescents: A Review of Published and Unpublished Data from India—Need for an Indian Consortium

Abstract Introduction Biallelic mismatch repair deficiency or constitutional mismatch repair deficiency (CMMRD) is a rare and aggressive pediatric cancer predisposition syndrome that occurs as a result of homozygous (biallelic) pathogenic variants in mismatch repair genes. The primary malignancies that occur in CMMRD are mainly hematological and brain malignancies. Most published data are from the western populations and the Middle East. Data from India are limited to case reports. We performed an analysis to determine the prevalence of CMMRD in the Indian population. Materials and Methods All children aged less than 18 years with a diagnosis of CMMRD from various centers in India were included. CMMRD confirmed using genetic, molecular, and clinical criteria by an international consensus was included in the analysis. Literature search and data submitted by individual centers were reviewed. Results The analysis revealed that 22 children had genetically confirmed CMMRD. The median age of the cohort was 6.5 years, with a male predominance (male:female, 2:1). The classical phenotype of café-au-lait macules was observed in 72.7 % of subjects. The most common pathological variant was found in the PMS2 gene, which accounted for 77.3 % of children. Hematological malignancy (T cell acute lymphoblastic leukemia) was the most common primary malignancy in our study that occurred at a median age of 5 years (interquartile range 4–6 years) followed by brain tumors. The age at initial presentation for CMMRD with mutations in MSH2, MSH6, and PMS2 was 5.4, 4, and 7.5 years, respectively. Conclusion The diagnosis of CMMRD requires a high index of suspicion for the early diagnosis, management, surveillance, counseling, and testing of family members. The awareness about CMMRD in clinicians is important so that diagnosis is made early, and a second malignancy is detected and treated early. The need for an Indian consortium to determine the actual burden of the disease, genetic characteristics, and course of illness in our country has been emphasized.

Trajectories of daily antipsychotic use and weight gain in people hospitalized for the first episode of psychosis.

We need to better understand the risk factors and predictors of medication-related weight gain to improve metabolic health of individuals with schizophrenia. This study explores how trajectories of antipsychotic medication (AP) use impact body weight early in the course of schizophrenia. We recruited 92 participants with first-episode psychosis (FEP, n=92) during their first psychiatric hospitalization. We prospectively collected weight, body mass index (BMI), metabolic markers, and exact daily medication exposure during 6-week hospitalization. We quantified the trajectory of AP medication changes and AP polypharmacy using a novel approach based on meta-analytical ranking of medications and tested it as a predictor of weight gain together with traditional risk factors. Most people started treatment with risperidone (n=57), followed by olanzapine (n=29). Then, 48% of individuals remained on their first prescribed medication, while 33% of people remained on monotherapy. Almost half of the individuals (39/92) experienced escalation of medications, mostly switch to AP polypharmacy (90%). Only baseline BMI was a predictor of BMI change. Individuals in the top tercile of weight gain, compared to those in the bottom tercile, showed lower follow-up symptoms, a trend for longer prehospitalization antipsychotic treatment, and greater exposure to metabolically problematic medications. Early in the course of illness, during inpatient treatment, baseline BMI is the strongest and earliest predictor of weight gain on APs and is a better predictor than type of medication, polypharmacy, or medication switches. Baseline BMI predicted weight change over a period of weeks, when other traditional predictors demonstrated a much smaller effect.

Trauma History in a Medium-Secure Adult Male Forensic Mental Health Setting

Forensic services have shifted their focus to the importance of forensic practice becoming more trauma informed. Trauma exposure is pervasive in forensic mental health populations and has been found to negatively impact the course of severe mental illness (SMI) and increase risk of violence. This study aimed to explore the trauma histories of adult male inpatients in a medium-secure psychiatric hospital, and examine childhood and adulthood trauma as predictors of diagnoses, self-harm, suicidality, hospital re-admissions, substance use, and nature of offense. The case files of 85 male patients in a medium secure unit in the UK were reviewed. Eighty-seven percent of patients had a schizophrenia diagnosis and 86% had extensive trauma histories, the most common trauma type being physical violence in childhood (44.7%). One patient had a PTSD diagnosis. Logistic regressions demonstrated that cumulative childhood and adulthood trauma significantly increased the odds of self-harm. Cumulative childhood trauma exposure was found to decrease the likelihood of having a schizophrenia diagnosis. There is a serious under-recognition of the extent and consequences of trauma exposure; trauma histories are likely greater than the findings of this study and existing literature suggests. Implications for clinical practice, trauma-informed care (TiC), and future research are proposed.

B - 104 Cognition, Stigma, and Social and Occupational Functioning in First Episode Psychosis

Abstract Objective Among the many challenges faced by individuals experiencing their first episode of psychosis (FEP), commencement of public, self-, and structural stigma regarding their symptoms contributes to internalized shame, social exclusion, and discrimination. Individuals with FEP may experience rejection from friends, family, and community members due to misconceptions and fear surrounding mental illness, which can worsen mental health outcomes and hinder recovery. The aim of this study was to evaluate the extent of self-reported stigma and predictors in adults with a first episode of psychosis. Method We measured IQ, stigma, social and occupational functioning, race, sex, and symptoms of psychosis in a sample of 77 individuals with FEP (29% female, mean age 31.8 years). Results Multiple regression analysis indicated that psychotic symptoms delusions were significant predictors of stigma in the model, while race, IQ, sex, and functioning were not significant predictors. The model was statistically significant for symptoms of delusions (p &amp;lt; 0.05). Conclusions Initial findings indicate increased stigma is predicted by increased severity of delusional symptoms among individuals experiencing their first episode of psychosis. Surprisingly, other factors associated with stigma in more chronic illness were not significant predictors in the regression model. It may be that early in the course of psychotic illness, symptoms differentially contribute individuals’ perceptions of stigma by others. While these results offer preliminary insight, further research is necessary to explore additional factors uniquely associated with stigma in FEP, including contributors to internalized, public, and structural stigma, as well as interventions for decreasing negative impacts of stigma.