Association of total cerebral small vessel disease burden with the cavitation of recent small subcortical infarcts

Background Recent small subcortical infarcts (RSSIs) could evolve into cavitation (lacunes) or non-cavitation (white matter hyperintensities or disappearance) during the chronic period, but the factors involved remain unclear. Purpose To explore the association between total cerebral small vessel disease (CSVD) burden and lesion cavitation. Material and Methods We retrospectively selected 202 inpatients with an isolated RSSI who underwent baseline and follow-up magnetic resonance imaging (median interval = 16.6 months; interquartile range [IQR]=8.2–30.1). Inpatients were divided into cavitation and non-cavitation groups depending on whether a fluid-filled cavity formed. Data including demographic, clinical, and radiological features were collected and analyzed. To determine total CSVD burden, four imaging markers, including lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces, were rated and summed as a final practical score between 0 and 4. Results Overall, 137 (67.8%) patients progressed to cavitation and 65 (32.2%) to non-cavitation. Binary multivariable regression analysis showed that the baseline total CSVD burden ( P = 0.005) and infarct diameter ( P = 0.002) were independent risk factors for cavitation. A severe total burden (scores of 3–4) at baseline was independently related to cavitation ( P = 0.001). Moreover, the total CSVD burden score varied from 2 (IQR=1–3) at baseline to 3 (IQR=2–4) at follow-up. The extent of the increase in total burden was correlated with cavitation ( r = 0.201; P = 0.004). Conclusion Total CSVD burden, both the baseline value and extent of increase, was positively associated with cavitation. RSSIs with severe total CSVD burden at baseline have a greater potential to become cavitated.

Experience with open schools and preschools in periods of high community transmission of COVID-19 in Norway during the academic year of 2020/2021.

Background: Schools and preschools have largely remained open in Norway throughout the pandemic, with flexible mitigation measures in place. This contrasts with many other high-income countries that closed schools for long periods of time. Here we describe cases and outbreaks of COVID-19 in schools and preschools during the academic year 2020/2021, to evaluate the strategy of keeping these open with infection prevention control measures in place. Methods: In this descriptive study, the Norwegian Institute of Public Health initiated systematic surveillance for COVID-19 cases and outbreaks in schools and preschools in October 2020. Data was compiled from the national outbreak alert system VESUV, municipality websites, and media scanning combined with the national emergency preparedness register Beredt C-19. An outbreak was defined as ≥2 cases among pupils or staff within 14 days at the same educational setting. Settings were categorized as preschool (1-5-years), primary school (6-12-years), lower secondary school (13-15-years) and upper secondary school (16-18- years). We reported the incidence rate among preschool and school-aged pupils and gave a descriptive overview of outbreaks and included cases per educational setting. Results: During the whole academic year, a total of 1203 outbreaks in preschools and school settings were identified, out of a total of 8311 preschools and schools nationwide. The incidence of COVID-19 in preschool- and school-aged children and the rates of outbreaks in these settings largely followed the community trend. Most of the outbreaks occurred in primary schools (40%) and preschools (25%). Outbreaks across all settings were mostly small (median 3 cases, range 2 to 72), however, 40 outbreaks (3% of total) included 20 or more cases. The larger outbreaks were predominantly seen in primary schools (43%). Conclusions: We observed few large outbreaks in open schools and preschools in Norway during the academic year of 2020/2021, also when the Alpha variant was predominant. This illustrates that it is possible to keep schools and preschools open even during periods of high community transmission of COVID-19. Adherence to targeted IPC measures adaptable to the local situation has been essential to keep educational settings open, and thus reduce the total burden on children and adolescents. Keywords: SARS-Cov 2, COVID-19, Schools, Preschools, Children, Pupils, Outbreaks, Educational settings, Prevention, Adolescents

STUDY OF ROLE OF CIRCULATING ANTIOXIDANTS IN DEVELOPMENT OF SENILE CATARACT

Introduction: Senile cataract is the commonest worldwide cause of treatable blindness, most often due to excess reactive oxygen species [ROS]. Anti-oxidant vitamins namely beta-carotene, ascorbate and tocopherol and enzymes like superoxide dismutase (SOD), constitute rst line defenses against ROS assault, while malondialdehyde (MDA) levels indicate the total burden of lipid peroxidation in-vivo. Objectives: We aimed to compare the levels of above ve analytes in senile cataract patients in contrast to apparently healthy controls and also among smoking and non-smoking sub groups of both cases and controls. Methods: A hospital-based case-control study, was conducted with 102 cases of senile cataract and 102 control subjects, following strict inclusion and exclusion criteria. Recruited individuals were sub-categorized into smokers and non-smokers. After overnight fasting (12 hours), 10 ml blood was drawn aseptically. Serum and plasma were separated and used for biochemical estimations of all ve analytes, following established protocols. Levels were compared between cases and controls as well as between the smoking and non-smoking sub-sections of both groups. Results: Signicantly lower levels of plasma ascorbate and serum tocopherol were seen in cases as compared to controls (P=0.0078 and P<0.0001 respectively). Signicantly lower levels of serum beta carotene (P<0.0001), tocopherol (P<0.0001), plasma ascorbate (P<0.0001), and SOD (P<0.0001). Signicantly higher level of serum MDA (P= 0.0494) was seen in the smokers, as compared to non-smokers Conclusions: Lowered serum tocopherol and plasma ascorbate were signicant factors leading to senile cataract. Furthermore, smoking was found crucial in loss of anti-oxidant defenses and subsequent development of cataract.

Cerebral Small Vessel Disease Burden Related to Carotid Intraplaque Hemorrhage Serves as an Imaging Marker for Clinical Symptoms in Carotid Stenosis

Objectives: In patients with carotid stenosis, to investigate the relationship between carotid intraplaque hemorrhage (IPH) and total burden of cerebral small vessel disease (CSVD) and preliminarily explore whether the total CSVD burden as an imaging marker can distinguish the severity of clinical symptoms.Methods: A total of 108 patients (the mean age was 66 ± 7 years, and 85.2% were male) with unilateral carotid stenosis ≥50% underwent brain MRI and high-resolution MRI for carotid plaque characterization. The total burden of CSVD was calculated by accumulating one point according to the presence or severity of each of the four MRI markers: white matter hyperintensities, lacunes, perivascular spaces, and cerebral microbleeds. Recent clinical symptoms including transient ischemic attack, amaurosis fugax, and ischemic stroke were recorded. The association between intraplaque hemorrhage (IPH) and total CSVD burden was examined adjusted for other risk factors. The symmetry of CSVD burdens between the ipsilateral and contralateral hemispheres of IPH was tested. Imaging features (CSVD score, IPH, degree of stenosis, and completeness of the circle of Willis) were correlated with clinical symptoms by Kruskal–Wallis H test, Chi-square test, and Fisher's exact test.Results: Multivariable logistic regression analysis showed that IPH (OR = 2.98, 95% CI [1.39, 6.40], p = 0.005) was independently associated with a higher CSVD score. The presence of unilateral IPH was associated with the inter-hemispheric CSVD score difference (p = 0.004). Patients with stroke had a higher ipsilateral CSVD score than asymptomatic patients (p = 0.004) and those with transient ischemic attack/amaurosis fugax (p = 0.008). The statistical difference was marginally significant between symptoms and IPH (p = 0.057). No statistical difference was found between the symptoms and degree of stenosis and the completeness of the circle of Willis (p &gt; 0.05).Conclusions: Carotid IPH is associated with an elevated total burden of CSVD in patients with carotid stenosis. Compared with the degree of stenosis, primary collaterals, and IPH, the total CSVD score might be a more effective imaging marker linked with clinical symptoms.

Psychiatric disorders and self-harm across 26 adult cancers: cumulative burden, temporal variation, excess years of life lost and unnatural causes of deaths

Background Cancer is a life-altering event causing considerable psychological distress. However, population-representative variations in the total burden of psychiatric episodes across cancer types and treatment modalities have not been examined. We sought to estimate the risk of self-harm after incident psychiatric disorder diagnosis in patients with cancer, and the risk of unnatural deaths after self-harm. Design, Setting, Participants Population-based cohort study with multiphase study designs. Population-based linked patient records in England (1998-2020) from primary care practices, hospitals, cancer registry and death registry were employed. We identified 459,542 individuals age ≥ 18 years with an incident diagnosis of a site-specific cancer of interest. Main outcome measures Using outpatient and inpatient records, we identified patients with five psychiatric disorders of interest: depression, anxiety disorder, schizophrenia, bipolar disorder and personality disorder. Cumulative burden for all psychiatric events was estimated using the mean cumulative count method. We considered 10 cancer treatment regimens, 11 chemotherapy drug classes, deprivation status and 21 non-cancer comorbidities in stratified analyses. Propensity score matching was employed to identify controls who did not have any record of a psychiatric disorder of interest. For each psychiatric disorder category, we fitted a Cox regression model to estimate the risk of self-harm. We also estimated the risk of all-cause mortality and excess years of life lost comparing patients with and without psychiatric disorders. A separate matched cohort was generated to explore the risk of suicide and unnatural deaths following self-harm. Results Depression was the most common psychiatric disorder in patients with cancer, where some of the highest cumulative burdens were observed in patients with testicular cancer (98.05 per 100 individuals [CI: 83.08-127.25]), cervical cancer (78.74 [73.61-90.14]) and Hodgkin lymphoma (69.87 [61.05-69.48]) by age 60. Patients who received chemotherapy, radiotherapy and surgery had the highest cumulative burden of psychiatric disorders, while patients who received radiotherapy alone had the lowest burden. Patients treated with alkylating agent chemotherapeutics had the highest burden of psychiatric disorders while those treated with kinase inhibitors had the lowest burden. Among patients with cancer, 5,683 individuals were identified as having an incident self-harm episode. A previous diagnosis of psychiatric disorder before self-harm was at least twice as prevalent than a subsequent diagnosis of psychiatric disorder where the prevalence ratio was the highest in patients with brain tumours (5.36, CI: 4.57-6.14). Younger individuals were more likely to be diagnosed with mental illness before the first self-harm episode. However, individuals from more deprived regions (2.46, CI: 2.32-2.60) and individuals with ≥4 pre-existing comorbidities (2.19, CI: 1.92-2.46) were less likely to be diagnosed with mental illness before self-harm. Patients with mental illness had a higher cumulative burden of self-harm events compared with matched controls. All mental illnesses were associated with an increased risk of subsequent self-harm, where the highest risk was observed within 12 months of the mental illness diagnosis. Risks of self-harm during the first year in matched cohorts were as follow: depression (adjusted HR 44.1, CI: 34.0-57.1), anxiety disorder (HR 21.1, CI: 16.4-27.0) and schizophrenia (HR 7.5, CI: 5.0-11.2). Patients with cancer and psychiatric disorder experienced excess years of life lost. Patients who harmed themselves were 6.8 times more likely to die of unnatural causes of death compared with controls within 12 months of self-harm (HR 6.8, CI: 4.3-10.7). The risk of unnatural death after 12 months was markedly lower (HR 2.0, CI: 1.5-2.7). Conclusions This study quantifies the total burden of psychiatric events and self-harm in patients with cancer. The cumulative burden of psychiatric events varies across cancer type, treatment regimen and chemotherapy type. Incident psychiatric disorder diagnoses were significantly associated with increased risk of subsequent self-harm, where risks varied across psychiatric diagnostic categories and follow-up periods. Patients who harm themselves experienced the highest risk of dying from unnatural deaths within the first year of self-harm. We provide an extensive knowledge base to help inform collaborative cancer-psychiatric care initiatives by prioritising patients who are most at risk.

Benchmarking gambling screens to health-state utility: The PGSI and the SGHS estimate similar levels of population gambling-harm

Background and aims: Both the Problem Gambling Severity Index (PGSI) and the Short Gambling Harms Screen (SGHS) purport to identify individuals harmed by gambling. However, there is dispute as to how much individuals are harmed, conditional on their scores from these instruments. We used an experienced utility framework to estimate the magnitude of implied impacts on health and wellbeing.Methods: We measured health utility using the Short Form Six-Dimension (SF-6D), and used this as a benchmark. All 2603 cases were propensity score weighted, to balance the affected group (i.e., SGHS 1+ or PGSI 1+ vs 0) with a reference group of gamblers with respect to risk factors for gambling harm. Weighted regression models estimated decrements to health utility scores attributable to gambling, whilst controlling for key comorbidities.Results: We found significant attributable decrements to health utility for all non-zero SGHS scores, as well as moderate-risk and problem gamblers, but not for PGSI low-risk gamblers. Applying these coefficients to population data, we find a similar total burden for both instruments, although the SGHS more specifically identified the subpopulation of harmed individuals. For both screens, outcomes on the SF-6D implies that about two-thirds of the ‘burden of harm’ is attributable to gamblers outside of the most severe categories.Discussion and Conclusions: Gambling screens have hitherto provided nominal category membership, and population surveys typically focus on problem gambling prevalence. These results quantify the health utility decrement for each category, allowing for tracking of the aggregate population impact based on all affected gamblers.

The contribution of hospital-acquired infections to the COVID-19 epidemic in England in the first half of 2020

BackgroundSARS-CoV-2 spreads in hospitals, but the contribution of these settings to the overall COVID-19 burden at a national level is unknown.MethodsWe used comprehensive national English datasets and simulation modelling to determine the total burden (identified and unidentified) of symptomatic hospital-acquired infections. Those unidentified would either be 1) discharged before symptom onset (“missed”), or 2) have symptom onset 7 days or fewer from admission (“misclassified”). We estimated the contribution of “misclassified” cases and transmission from “missed” symptomatic infections to the English epidemic before 31st July 2020.FindingsIn our dataset of hospitalised COVID-19 patients in acute English Trusts with a recorded symptom onset date (n = 65,028), 7% were classified as hospital-acquired (with symptom onset 8 or more days after admission and before discharge). We estimated that only 30% (range across weeks and 200 simulations: 20-41%) of symptomatic hospital-acquired infections would be identified. Misclassified cases and onward transmission from missed infections could account for 15% (mean, 95% range over 200 simulations: 14·1%-15·8%) of cases currently classified as community-acquired COVID-19.From this, we estimated that 26,600 (25,900 to 27,700) individuals acquired a symptomatic SARS-CoV-2 infection in an acute Trust in England before 31st July 2020, resulting in 15,900 (15,200-16,400) or 20.1% (19.2%-20.7%) of all identified hospitalised COVID-19 cases.ConclusionsTransmission of SARS-CoV-2 to hospitalised patients likely caused approximately a fifth of identified cases of hospitalised COVID-19 in the “first wave”, but fewer than 1% of all SARS-CoV-2 infections in England. Using symptom onset as a detection method for hospital-acquired SARS-CoV-2 likely misses a substantial proportion (>60%) of hospital-acquired infections.FundingNational Institute for Health Research, UK Medical Research Council, Society for Laboratory Automation and Screening, UKRI, Wellcome Trust, Singapore National Medical Research Council.Research in contextEvidence before this studyWe searched PubMed with the terms “((national OR country) AND (contribution OR burden OR estimates) AND (“hospital-acquired” OR “hospital-associated” OR “nosocomial”)) AND Covid-19” for articles published in English up to July 1st 2021. This identified 42 studies, with no studies that had aimed to produce comprehensive national estimates of the contribution of hospital settings to the COVID-19 pandemic. Most studies focused on estimating seroprevalence or levels of infection in healthcare workers only, which were not our focus. Removing the initial national/country terms identified 120 studies, with no country level estimates. Several single hospital setting estimates exist for England and other countries, but the percentage of hospital-associated infections reported relies on identified cases in the absence of universal testing.Added value of this studyThis study provides the first national-level estimates of all symptomatic hospital-acquired infections with SARS-CoV-2 in England up to the 31st July 2020. Using comprehensive data, we calculate how many infections would be unidentified and hence can generate a total burden, impossible from just notification data. Moreover, our burden estimates for onward transmission suggest the contribution of hospitals to the overall infection burden.Implications of all the available evidenceLarge numbers of patients may become infected with SARS-CoV-2 in hospitals though only a small proportion of such infections are identified. Further work is needed to better understand how interventions can reduce such transmission and to better understand the contributions of hospital transmission to mortality.