Potential impact of annual vaccination with reformulated COVID-19 vaccines: Lessons from the US COVID-19 scenario modeling hub.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) continues to cause significant hospitalizations and deaths in the United States. Its continued burden and the impact of annually reformulated vaccines remain unclear. Here, we present projections of COVID-19 hospitalizations and deaths in the United States for the next 2 years under 2 plausible assumptions about immune escape (20% per year and 50% per year) and 3 possible CDC recommendations for the use of annually reformulated vaccines (no recommendation, vaccination for those aged 65 years and over, vaccination for all eligible age groups based on FDA approval). METHODS AND FINDINGS: The COVID-19 Scenario Modeling Hub solicited projections of COVID-19 hospitalization and deaths between April 15, 2023 and April 15, 2025 under 6 scenarios representing the intersection of considered levels of immune escape and vaccination. Annually reformulated vaccines are assumed to be 65% effective against symptomatic infection with strains circulating on June 15 of each year and to become available on September 1. Age- and state-specific coverage in recommended groups was assumed to match that seen for the first (fall 2021) COVID-19 booster. State and national projections from 8 modeling teams were ensembled to produce projections for each scenario and expected reductions in disease outcomes due to vaccination over the projection period. From April 15, 2023 to April 15, 2025, COVID-19 is projected to cause annual epidemics peaking November to January. In the most pessimistic scenario (high immune escape, no vaccination recommendation), we project 2.1 million (90% projection interval (PI) [1,438,000, 4,270,000]) hospitalizations and 209,000 (90% PI [139,000, 461,000]) deaths, exceeding pre-pandemic mortality of influenza and pneumonia. In high immune escape scenarios, vaccination of those aged 65+ results in 230,000 (95% confidence interval (CI) [104,000, 355,000]) fewer hospitalizations and 33,000 (95% CI [12,000, 54,000]) fewer deaths, while vaccination of all eligible individuals results in 431,000 (95% CI: 264,000-598,000) fewer hospitalizations and 49,000 (95% CI [29,000, 69,000]) fewer deaths. CONCLUSIONS: COVID-19 is projected to be a significant public health threat over the coming 2 years. Broad vaccination has the potential to substantially reduce the burden of this disease, saving tens of thousands of lives each year.

ClinGen variant curation expert panel recommendations for classification of variants in GAMT, GATM and SLC6A8 for cerebral creatine deficiency syndromes.

Cerebral creatine deficiency syndromes (CCDS) are inherited metabolic phenotypes of creatine synthesis and transport. There are two enzyme deficiencies, guanidinoacetate methyltransferase (GAMT), encoded by GAMT and arginine-glycine amidinotransferase (AGAT), encoded by GATM, which are involved in the synthesis of creatine. After synthesis, creatine is taken up by a sodium-dependent membrane bound creatine transporter (CRTR), encoded by SLC6A8, into all organs. Creatine uptake is very important especially in high energy demanding organs such as the brain, and muscle. To classify the pathogenicity of variants in GAMT, GATM, and SLC6A8, we developed the CCDS Variant Curation Expert Panel (VCEP) in 2018, supported by The Clinical Genome Resource (ClinGen), a National Institutes of Health (NIH)-funded resource. We developed disease-specific variant classification guidelines for GAMT-, GATM-, and SLC6A8-related CCDS, adapted from the American College of Medical Genetics/Association of Molecular Pathology (ACMG/AMP) variant interpretation guidelines. We applied specific variant classification guidelines to 30 pilot variants in each of the three genes that have variants associated with CCDS. Our CCDS VCEP was approved by the ClinGen Sequence Variant Interpretation Working Group (SVI WG) and Clinical Domain Oversight Committee in July 2022. We curated 181 variants including 72 variants in GAMT, 45 variants in GATM, and 64 variants in SLC6A8 and submitted these classifications to ClinVar, a public variant database supported by the National Center for Biotechnology Information. Missense variants were the most common variant type in all three genes. We submitted 32 new variants and reclassified 34 variants with conflicting interpretations. We report specific phenotype (PP4) using a points system based on the urine and plasma guanidinoacetate and creatine levels, brain magnetic resonance spectroscopy (MRS) creatine level, and enzyme activity or creatine uptake in fibroblasts ranging from PP4, PP4_Moderate and PP4_Strong. Our CCDS VCEP is one of the first panels applying disease specific variant classification algorithms for an X-linked disease. The availability of these guidelines and classifications can guide molecular genetics and genomic laboratories and health care providers to assess the molecular diagnosis of individuals with a CCDS phenotype.

Anticholinergic deprescribing: A case report demonstrating improved cognition and function with minimal adverse withdrawal effects.

Anticholinergic-induced cognitive impairment may be partially reversible upon cessation. A barrier to deprescribing of anticholinergics is the unknown risk of anticholinergic adverse drug withdrawal events (ADWE), with only limited information available on the incidence, timing and severity of anticholinergic ADWE. We report the case of a 76-year-old woman who experienced significant cognitive improvement following deprescribing long-term use of a strong anticholinergic drug, doxepin, and dose reduction of another possible anticholinergic agent. The patient decided to abruptly stop taking doxepin, despite a planned careful taper with twice weekly monitoring, but did not experience any severe anticholinergic ADWE and subsequently had significantly improved cognitive function. Future research should focus on better understanding the risk of anticholinergic ADWE so that anticholinergic deprescribing decisions, including how often and by how much to taper, can be made confidently and safely.

Comorbid depression among adults with heart failure in Ethiopia: a hospital-based cross-sectional study.

BACKGROUND: Depression is a common comorbidity in adults with heart failure. It is associated with poor clinical outcomes, including decreased health-related quality of life and increased morbidity and mortality. There is a lack of data concerning the extent of this issue in Ethiopia. Consequently, this study aimed to assess the prevalence of comorbid depression and associated factors among adults living with heart failure in Ethiopia. METHODS: A hospital-based cross-sectional study was conducted at the cardiac outpatient clinics of two selected specialist public hospitals in Addis Ababa, Ethiopia: St. Paul's Hospital Millennium Medical College and St. Peter Specialized Hospital. An interviewer-administered questionnaire was used to collect data from 383 adults with heart failure who attended the clinics and met the inclusion criteria. Depression was measured using the Patient Health Questionnaire (PHQ-9). A binary logistic regression model was fitted to identify factors associated with depression. All statistical analyses were conducted using STATA version 17 software. RESULTS: The mean age of the participants was 55 years. On average, participants had moderate depression, as indicated by the mean PHQ-9 score of 11.02 ± 6.14, and 217 (56.6%, 95%CI 51.53-61.68) had comorbid depression. Significant associations with depression were observed among participants who were female (AOR: 2.31, 95%CI:1.30-4.08), had comorbid diabetes mellitus (AOR: 3.16, 95%CI: 1.47-6.82), were classified as New York Heart Association (NYHA) class IV (AOR: 3.59, 95%CI: 1.05-12.30), reported poor levels of social support (AOR: 6.04, 95%CI: 2.97-12.32), and took more than five medications per day (AOR: 5.26, 95%CI: 2.72-10.18). CONCLUSIONS: This study indicates that over half of all adults with heart failure in Ethiopia have comorbid depression, influenced by several factors. The findings have significant implications in terms of treatment outcomes and quality of life. More research in the area, including interventional and qualitative studies, and consideration of multifaceted approaches, such as psychosocial interventions, are needed to reduce the burden of comorbid depression in this population.

Human adenovirus-associated health risk in the recreational waters of the Yal-ku lagoon in the Mexican Caribbean.

The study objective was to evaluate human faecal contamination impacts in the Yal-ku lagoon in the Mexican Caribbean and to estimate adenovirus infection and illness risks associated with recreational exposure during water activities. A total of 20 water samples (10 from each site × two sites) (50 L) were collected monthly over a period of 12 months from two selected sampling sites in the swimming area of the Yal-ku lagoon. The occurrence of faecal-associated viruses was explored, and human adenovirus (HAdV) and pepper mild mottle virus (PMMoV) concentrations were quantified. A quantitative microbial risk assessment (QMRA) model was used to estimate exposure and subsequent adenovirus infection and illness risk for 1 h of swimming or snorkelling. Somatic and F + -specific coliphages occurred in 100% of the samples. Both HAdV and PMMoV were detected at a 60% frequency thereby indicating persistent faecal inputs. PMMoV concentrations (44-370 GC/L) were relatively lower than the concentrations of HAdV (64-1,000 GC/L). Estimated mean adenovirus risks were greater for snorkelling than for swimming by roughly one to two orders of magnitude and estimated mean illness risks for snorkelling were >32/1,000. Human faecal contamination is frequent in the Yal-ku lagoon, which is associated with human gastrointestinal illness.

Research gaps and priorities for quantitative microbial risk assessment (QMRA).

The coronavirus disease 2019 pandemic highlighted the need for more rapid and routine application of modeling approaches such as quantitative microbial risk assessment (QMRA) for protecting public health. QMRA is a transdisciplinary science dedicated to understanding, predicting, and mitigating infectious disease risks. To better equip QMRA researchers to inform policy and public health management, an Advances in Research for QMRA workshop was held to synthesize a path forward for QMRA research. We summarize insights from 41 QMRA researchers and experts to clarify the role of QMRA in risk analysis by (1) identifying key research needs, (2) highlighting emerging applications of QMRA; and (3) describing data needs and key scientific efforts to improve the science of QMRA. Key identified research priorities included using molecular tools in QMRA, advancing dose-response methodology, addressing needed exposure assessments, harmonizing environmental monitoring for QMRA, unifying a divide between disease transmission and QMRA models, calibrating and/or validating QMRA models, modeling co-exposures and mixtures, and standardizing practices for incorporating variability and uncertainty throughout the source-to-outcome continuum. Cross-cutting needs identified were to: develop a community of research and practice, integrate QMRA with other scientific approaches, increase QMRA translation and impacts, build communication strategies, and encourage sustainable funding mechanisms. Ultimately, a vision for advancing the science of QMRA is outlined for informing national to global health assessments, controls, and policies.

Do the teaching, practice and assessment of clinical communication skills align?

BACKGROUND: Evidence indicates that communication skills teaching learnt in the classroom are not often readily transferable to the assessment methods that are applied nor to the clinical environment. An observational study was conducted to objectively evaluate students' communication skills in different learning environments. The study sought to investigate the extent to which the communication skills demonstrated by students in classroom, clinical, and assessment settings align. METHOD: A mixed methods study was conducted to observe and evaluate students during the fourth year of a five-year medical program. Participants were videorecorded during structured classroom 'interactional skills' sessions, as well as clinical encounters with real patients and an OSCE station calling upon communication skills. The Calgary Cambridge Observational Guides was used to evaluate students at different settings. RESULT: This study observed 28 students and findings revealed that while in the classroom students were able to practise a broad range of communication skills, in contrast in the clinical environment, information-gathering and relationship-building with patients became the focus of their encounters with patients. In the OSCEs, limited time and high-pressure scenarios caused the students to rush to complete the task which focussed solely on information-gathering and/or explanation, diminishing opportunity for rapport-building with the patient. CONCLUSION: These findings indicate a poor alignment that can develop between the skills practiced across learning environments. Further research is needed to investigate the development and application of students' skills over the long term to understand supports for and barriers to effective teaching and learning of communication skills in different learning environments.

Preliminary Analysis of Fall Concern Among Family Caregivers of Older Adults Discharged From the Hospital: A Psychometric Evaluation of the Carers' Fall Concern Instrument.

PURPOSE: To provide a preliminary descriptive analysis of the change in fall concern among family caregiver-care recipient dyads during hospitalization and after discharge as part of a prospective study exploring the psychometric properties of the Carers' Fall Concern Instrument. METHOD: Using a prospective cohort design, an interviewer-administered survey was completed by dyads at 48 hours before discharge and 1 week and 30 days after discharge. RESULTS: Of family caregivers, 76.9% thought their care recipient was at risk of falling and 61.5% were afraid of them falling. However, only 34.6% of older adults thought that they were at risk of falling and only 42.3% were afraid of falling. Family caregivers reported significantly less concern about falls after their care recipients were discharged. CONCLUSION: This study provided greater insight into caregiver-care recipient dyads' fall concern during their transition from hospital to home that may guide post-discharge fall prevention education on falls. [Journal of Gerontological Nursing, 50(5), 14-18.].

Molecular diagnostic yield of genome sequencing versus targeted gene panel testing in racially and ethnically diverse pediatric patients.

PURPOSE: Adoption of genome sequencing (GS) as a first-line test requires evaluation of its diagnostic yield. We evaluated the GS and targeted gene panel (TGP) testing in diverse pediatric patients (probands) with suspected genetic conditions. METHODS: Probands with neurologic, cardiac, or immunologic conditions were offered GS and TGP testing. Diagnostic yield was compared using a fully paired study design. RESULTS: A total of 645 probands (median age 9 years) underwent genetic testing, and 113 (17.5%) received a molecular diagnosis. Among 642 probands with both GS and TGP testing, GS yielded 106 (16.5%) and TGPs yielded 52 (8.1%) diagnoses (P < .001). Yield was greater for GS vs TGPs in Hispanic/Latino(a) (17.2% vs 9.5%, P < .001) and White/European American (19.8% vs 7.9%, P < .001) but not in Black/African American (11.5% vs 7.7%, P = .22) population groups by self-report. A higher rate of inconclusive results was seen in the Black/African American (63.8%) vs White/European American (47.6%; P = .01) population group. Most causal copy number variants (17 of 19) and mosaic variants (6 of 8) were detected only by GS. CONCLUSION: GS may yield up to twice as many diagnoses in pediatric patients compared with TGP testing but not yet across all population groups.

Identification of copy number variants with genome sequencing: Clinical experiences from the NYCKidSeq program.

Copy number variations (CNVs) play a significant role in human disease. While chromosomal microarray has traditionally been the first-tier test for CNV detection, use of genome sequencing (GS) is increasing. We report the frequency of CNVs detected with GS in a diverse pediatric cohort from the NYCKidSeq program and highlight specific examples of its clinical impact. A total of 1052 children (0-21 years) with neurodevelopmental, cardiac, and/or immunodeficiency phenotypes received GS. Phenotype-driven analysis was used, resulting in 183 (17.4%) participants with a diagnostic result. CNVs accounted for 20.2% of participants with a diagnostic result (37/183) and ranged from 0.5 kb to 16 Mb. Of participants with a diagnostic result (n = 183) and phenotypes in more than one category, 5/17 (29.4%) were solved by a CNV finding, suggesting a high prevalence of diagnostic CNVs in participants with complex phenotypes. Thirteen participants with a diagnostic CNV (35.1%) had previously uninformative genetic testing, of which nine included a chromosomal microarray. This study demonstrates the benefits of GS for reliable detection of CNVs in a pediatric cohort with variable phenotypes.

Biallelic variants in TUBGCP6 result in microcephaly and chorioretinopathy 1: Report of four cases and a literature review.

Autosomal recessive microcephaly and chorioretinopathy-1 (MCCRP1) is a rare Mendelian disorder resulting from biallelic loss of function variants in Tubulin-Gamma Complex Associated Protein 6 (TUBGCP6, MIM#610053). Clinical features of this disorder include microcephaly, cognitive impairment, dysmorphic features, and variable ophthalmological anomalies including chorioretinopathy. Microcephaly can be recognized prenatally and visual impairment becomes evident during the first year of life. The clinical presentation resembles the findings in some acquired conditions such as congenital toxoplasmosis and cytomegalovirus infections; thus, it is important to recognize and diagnose this syndrome in view of its impact on patient health management and familial reproductive plans. To date, only seven molecularly confirmed patients from five unrelated families have been reported. We report an additional four unrelated patients with TUBGCP6 variants including one prenatal diagnosis and review the clinical phenotypes and genotypes of all the known cases. This report expands the molecular and phenotypic spectrum of TUBGCP6 and includes additional prenatal findings associated with MCCRP1.

Detection of mosaic variants using genome sequencing in a large pediatric cohort.

The increased use of next-generation sequencing has expanded our understanding of the involvement and prevalence of mosaicism in genetic disorders. We describe a total of eleven cases: nine in which mosaic variants detected by genome sequencing (GS) and/or targeted gene panels (TGPs) were considered to be causative for the proband's phenotype, and two of apparent parental mosaicism. Variants were identified in the following genes: PHACTR1, SCN8A, KCNT1, CDKL5, NEXMIF, CUX1, TSC2, GABRB2, and SMARCB1. In addition, we identified one large duplication including three genes, UBE3A, GABRB3, and MAGEL2, and one large deletion including deletion of ARFGAP1, EEF1A2, CHRNA4, and KCNQ2. All patients were enrolled in the NYCKidSeq study, a research program studying the communication of genomic information in clinical care, as well as the clinical utility and diagnostic yield of GS for children with suspected genetic disorders in diverse populations in New York City. We observed variability in the correlation between reported variant allele fraction and the severity of the patient's phenotype, although we were not able to determine the mosaicism percentage in clinically relevant tissue(s). Although our study was not sufficiently powered to assess differences in mosaicism detection between the two testing modalities, we saw a trend toward better detection by GS as compared with TGP testing. This case series supports the importance of mosaicism in childhood-onset genetic conditions and informs guidelines for laboratory and clinical interpretation of mosaic variants detected by GS.

Malignant Catatonia: A Review for the Intensivist.

Catatonia is a clinical syndrome characterized by psychomotor, neurological and behavioral changes. The clinical picture of catatonia ranges from akinetic stupor to severe motoric excitement. Catatonia can occur in the setting of a primary psychiatric condition such as bipolar disorder or secondary to a general medical illness like autoimmune encephalitis. Importantly, it can co-occur with delirium or coma. Malignant catatonia describes catatonia that presents with clinically significant autonomic abnormalities including change in temperature, blood pressure, heart rate, and respiratory rate. It is a life-threatening form of acute brain dysfunction that has several motoric manifestations and occurs secondary to a primary psychiatric condition or a medical cause. Many of the established predisposing and precipitating factors for catatonia such as exposure to neuroleptic medications or withdrawal states are common in the setting of critical illness. Catatonia typically improves with benzodiazepines and treatment of its underlying psychiatric or medical conditions, with electroconvulsive therapy reserved for catatonia refractory to benzodiazepines or for malignant catatonia. However, some forms of catatonia, such as catatonia secondary to a general medical condition or catatonia comorbid with delirium, may be less responsive to traditional treatments. Prompt recognition and treatment of catatonia are crucial because malignant catatonia may be fatal without treatment. Given the high morbidity and mortality associated with malignant catatonia, intensivists should familiarize themselves with this important and under-recognized condition.

A Confounding Discourse Analysis of Vietnamese Sex Workers' Talk in the City of Kaiyuan, China.

BACKGROUND: Vietnamese female sex workers (VFSWs) cross the border into Kaiyuan City, Yunnan Province yearly. However, very little is known about both the health and psychological issues VFSWs experience. The objectives of this study were to explore the dominant discourses that emerged from the VFSWs' talk. The interviews occurred between May 2018 and June 2018 with 20 VFSWs who worked in Kaiyuan City, China. The English translated transcripts were analyzed using an eclectic feminist method of discourse analysis. Two discourses emerged. First, "Agency when working in Karaoke Bars and other Indoor Venues", and second, "Negative Impacts on Psychological Well-being and Other Problems from Migration." As for Discourse 1, the VFSWs positioned themselves as having agency over choosing their clientele as well as agency over what they were willing to negotiate with their clients to establish boundaries of their bodies. As for the Discourse 2, while there was a discourse of agency in their work there was also a contrasting, confounding discourse around the negative impact on psychological well-being and reports of stress as a migrant worker. Discourse 1 and Discourse 2 are confounding. When analyzed together, the discourses suggest that the impacts on psychological well-being may be more related to the migrant status of the women, supporting the notion of systemically influenced agency.

Health-related quality of life of people with heart failure in low- and middle-income countries: a systematic review and meta-analysis.

PURPOSE: Heart failure is a global health concern and associated with poor health-related quality of life and increased mortality. There is a disproportionate burden on patients and health systems in low- and middle-income countries. This systematic review and meta-analysis estimates the health-related quality of life of people with heart failure in low- and middle-income countries. METHODS: A systematic literature search was conducted to identify relevant studies from January 2012 to November 2022 using the following databases: MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science, Scopus and JBI EBP database. Study screening, quality appraisal and data extraction were conducted using JBI methodology. A random-effects model was used to perform the meta-analysis. Heterogeneity was assessed using the I2 statistic. All statistical analyses were done in STATA version 17. RESULTS: A total of 33 studies with 5612 participants were included in this review. The Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Short-Form-36 questionnaire (SF-36) were the most used instruments across 19 and 8 studies, respectively. The pooled mean MLHFQ and SF-36 scores using the random-effects model were 46.08 (95% CI 35.06, 57.10) and 41.23 (95% CI 36.63, 45.83), respectively. In a subgroup analysis using both instruments, the highest health-related quality-of-life scores occurred in studies with inpatient participants. CONCLUSION: The overall health-related quality of life of people with heart failure in low- and middle-income countries is poor. Strategies should be strategically developed to improve the health-related quality of life of people with heart failure in these countries. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022377781.

Mapping associations between anxiety and sleep problems among outpatients in high-altitude areas: a network analysis.

BACKGROUND: Anxiety and sleep problems are common comorbidities among outpatients living in high-altitude areas. Network analysis is a novel method to investigate the interaction and the association between symptoms across diverse disorders. This study used network analysis to investigate the network structure symptoms of anxiety and sleep problems among outpatients in high-altitude areas, and to explore the differences in symptom associations in various sex, age, educational levels and employment groups. METHODS: The data was collected from the Sleep Medicine Center of The First People's Hospital of Yunnan Province from November 2017 to January 2021 with consecutive recruitment (N = 11,194). Anxiety and sleep problems were measured by the Chinese version of the seven-item Generalized Anxiety Disorder Scale (GAD-7) and the Pittsburgh Sleep Quality Index (PSQI) respectively. Central symptoms were identified based on centrality indices and bridge symptoms were identified with bridge indices. The difference of network structures in various sex, age, educational levels and employment groups were also explored. RESULTS: Among all the cases, 6,534 (58.37%; 95% CI: 57.45-59.29%) reported experiencing anxiety (GAD-7 total scores ≥ 5), and 7,718 (68.94%; 95% CI: 68.08-69.80%) reported experiencing sleep problems (PSQI total scores ≥ 10). Based on the results of network analysis, among participants, "Nervousness", "Trouble relaxing", "Uncontrollable worry" were the most critical central symptoms and bridge symptoms within the anxiety and sleep problems network structure. The adjusted network model after controlling for covariates was significantly correlated with the original (r = 0.75, P = 0.46). Additionally, there were significant differences in edge weights in the comparisons between sex, age and educational levels groups (P < 0.001), while the employed and unemployed groups did not show significant differences in edge weights (P > 0.05). CONCLUSIONS: In the anxiety and sleep problems network model, among outpatients living in high-altitude areas, nervousness, uncontrollable worry, and trouble relaxing were the most central symptoms and bridge symptoms. Moreover, there were significant differences between various sex, age and educational levels. These findings can be used to provide clinical suggestions for psychological interventions and measures targeting to reduce symptoms that exacerbate mental health.

School health systems under strain: an example of COVID-19 experiences & burnout among school health staff in Pima County, Arizona.

BACKGROUND: School health staff lead and provide a variety of care for children in schools. As school districts have navigated the COVID-19 pandemic, school health staff have faced unprecedented challenges in protecting the health of students and school staff. Our objective was to qualitatively characterize these pandemic challenges and experiences of school health staff in Pima County, Arizona to identify gaps in school health staff support for improving future emergency preparedness. METHODS: We conducted two focus group discussions (FGDs) with 48 school health staff in Pima County, Arizona in two school districts using a discussion guide including ten open-ended questions. The FGDs were audio recorded and transcribed verbatim. We used the socioecological model (SEM) to organize the thematic analysis and generate codes and themes; data were analyzed using Atlas.ti software. FINDINGS: The pandemic has significantly challenged school health staff with new pandemic-related job tasks: managing isolation, vaccination, and developing/implementing new and evolving COVID-19 guidelines. School health staff also reported increased stress related to interactions with parents and school administration as well as frustrations with rapid changes to guidance from the health department and policy makers. A common issue was not having enough staff or resources to complete regular job responsibilities, such as providing care for students with non-COVID-19 related health issues. CONCLUSIONS: Increased workload for school health staff resulted in physical burnout, mental distress, and disruption of core functions with long term implications for children's health. These focus groups highlight the need for improved emergency preparedness in schools during pandemics or infectious disease outbreaks. These include basic infrastructure changes (e.g., personnel support from health departments for tasks such as contact tracing to enable school nurses to continue core functions), and increased funding to allow for hazard pay and more school health personnel during emergency situations. In addition, basic school health infrastructure is lacking, and we should include a licensed school health nurse in every school.

Impact of repeated micro and macro blood sampling on clinical chemistry and haematology in rats for toxicokinetic studies.

Non-clinical rodent safety studies are essential in the development of new medicines to assess for potential adverse effects. Typically, toxicokinetic samples are collected from a satellite group. AstraZeneca implemented repeated microsampling of main study animals as standard in the one-month small molecule regulatory toxicology studies. A retrospective analysis of the clinical chemistry and haematology data collected in 52 independent studies from the adult rat controls explored the impact of micro and macro sampling of main study animals. For the majority of variables, the blood sampling technique had no significant impact on the mean or range. For microsampling, a few variables had statistically significant effects on the mean signal but these were considered to have limited biological relevance and would therefore not introduce a meaningful bias to any toxicological evaluation. The macrosampling had the expected effects on the red cell parameters of haemoglobin, haematocrit and red blood count due to the larger blood volume draw. In contrast, microsampling showed no such changes. In conclusion, this large-scale retrospective analysis supports the use of microsampling, for toxicokinetics, of main study animals and enables us to conduct rodent toxicology studies without satellite animals and further reduce the number of animals used in toxicological assessments.

Multiple Mental Health Literacies in a Traditional Temple Site in Kerala: The Intersection Between Beliefs, Spiritual and Healing Regimes.

The notion of 'mental health literacy' has been proposed as a way of improving mental health problem recognition, service utilisation and reducing stigma. Yet, the idea embodies a number of medical-model assumptions which are often at odds with diverse communities' spiritual traditions and local belief systems. Twenty participants were recruited to this study consisting of mental health service users (N = 7), family carers (N = 8) and community members (N = 5) in a temple town in Kerala, South India participated in semi-structured interviews exploring the variety of beliefs and practices relating to mental health. Our findings indicate that the issue may be better understood in terms of multiple mental health literacies which people deploy in different circumstances. Even those sceptical of traditional and spiritual approaches are knowledgeable about them, and the traditional practices themselves often involve detailed regimes of activities aimed at effecting an improvement in the person's mood or condition. Therefore, we argue it is appropriate to consider mental health literacy not as a unitary universal phenomenon but instead as a mosaic of different literacies which may be deployed in different settings and in line with different experiences and which may operate in synergy with each other to enable treatment but also facilitate a sense of meaning and purpose in life.

Exposure frequency, intensity, and duration: What we know about work-related asthma risks for healthcare workers from cleaning and disinfection.

The objective of this review was to scope the current evidence base related to three exposure assessment concepts: frequency, intensity, and duration (latency) for cleaning and disinfection exposures in healthcare and subsequent work-related asthma risks. A search strategy was developed addressing intersections of four main concepts: (1) work-related asthma; (2) occupation (healthcare workers/nurses); (3) cleaning and disinfection; and (4) exposure. Three databases were searched: Embase, PubMed, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) database. Data were extracted related to three main components of risk assessment: (1) exposure frequency, (2) exposure intensity, and (3) exposure duration. Latency data were analyzed using an exponential distribution fit, and extracted concentration data were compared to occupational exposure limits. The final number of included sources from which data were extracted was 133. Latency periods for occupational asthma were exponentially distributed, with a mean waiting time (1/λ) of 4.55 years. No extracted concentration data were above OELs except for some formaldehyde and glutaraldehyde concentrations. Data from included sources also indicated some evidence for a dose-response relationship regarding increased frequency yielding increased risk, but this relationship is unclear due to potential confounders (differences in role/task and associated exposure) and the healthy worker effect. Data priority needs to include linking concentration data to health outcomes, as most current literature does not include both types of measurements in a single study, leading to uncertainty in dose-response relationships.