Unmet Surgical Need among Adults in A Mixed Urban-Rural Community in Nigeria: A Survey of 1,993 Adults Using the Sosas Survey Tool.

INTRODUCTION: Community-based prevalence studies are known to be more accurate than hospital-based records. However, such community-based prevalence studies are uncommon in low- and middle-income countries including Nigeria. Allocation of resources and prioritization of health care needs by policy makers require data from such community-based studies to be meaningful and sustainable. This study aims to assess the prevalence of common surgical conditions amongst adults in Nigeria. METHODS: A descriptive cross-sectional community-based study to determine the prevalence of congenital and acquired surgical conditions in adults in a mixed rural-urban area of Lagos was conducted. The study population comprised resident members in the Ikorodu Local Government Area (LGA) of Lagos State. Data was collected using a modified version of the interviewer-administered questionnaire, the Surgeons OverSeas Assessment of Surgical Need (SOSAS) survey tool. Data was analysed using the REDCap analytic tool. RESULTS: Eight hundred and fifty-six households were surveyed with a yield of 1,992 adults. There were 95 adults who complained of surgical conditions giving a prevalence rate of 5%. Vast majority of reported conditions were acquired deformities (n=94) while only 1 congenital deformity was reported. Others included breast lumps, anterior neck swelling, and groin swellings. CONCLUSION: The most common surgical complaints in our setting among adults were acquired conditions of the extremities and open wounds/sores. With an estimated population of 90 million adults and approximately 1,200 orthopaedic and general surgeons respectively, the surgeon-to-affected population ratio is 1:10,000. There is a large gap to be filled in terms of surgical manpower development.

INTRODUCTION: Les études de prévalence communautaires sont connues pour être plus précises que les dossiers hospitaliers. Cependant, de telles études de prévalence communautaires sont rares dans les pays à revenu faible et intermédiaire, y compris le Nigeria. L'allocation des ressources et la priorisation des besoins de santé par les décideurs nécessitent des données issues de telles études communautaires pour être significatives et durables. Cette étude vise à évaluer la prévalence des affections chirurgicales courantes chez les adultes au Nigeria. MÉTHODES: Une étude descriptive transversale basée sur la communauté pour déterminer la prévalence des conditions chirurgicales congénitales et acquises chez les adultes dans une zone rurale-urbaine mixte de Lagos a été menée. La population étudiée comprenait des membres résidents de la zone de gouvernement local (LGA) d'Ikorodu, dans l'État de Lagos. Les données ont été collectées à l'aide d'une version modifiée du questionnaire administré par un enquêteur, l'outil d'enquête Surgeons OverSeas Assessment of Surgical Need (SOSAS). Les données ont été analysées à l'aide de l'outil analytique REDCap. RÉSULTATS: Huit cent cinquante-six ménages ont été enquêtés, ce qui a donné 1 992 adultes. Quatre-vingt-quinze adultes se sont plaints de conditions chirurgicales, donnant un taux de prévalence de 5 %. La grande majorité des conditions rapportées étaient des déformations acquises (n=94) tandis qu'une seule déformation congénitale a été signalée. Les autres incluaient des nodules mammaires, des gonflements antérieurs du cou et des gonflements inguinaux. CONCLUSION: Les plaintes chirurgicales les plus courantes dans notre cadre parmi les adultes étaient des conditions acquises des extrémités et des plaies ouvertes/ulcères. Avec une population estimée à 90 millions d'adultes et environ 1 200 chirurgiens orthopédiques et généralistes respectivement, le ratio chirurgien-population affectée est de 1:10,000. Il y a un grand écart à combler en termes de développement de la main-d'œuvre chirurgicale. MOTS CLÉS: Prévalence, Charge de morbidité, Chirurgie, Plaies.

Optimising nucleic acid recovery from rapid antigen tests for whole genome sequencing of respiratory viruses.

BACKGROUND: Whole genome sequencing (WGS) of respiratory viruses from rapid antigen tests (RAT-WGS) is a novel approach to expanding genomic surveillance of respiratory infections. To date however, there are limited data on the genomic stability of these viruses on RATs. In this study, we investigated the effect of storage conditions and nucleic acid preservatives on the ability to enhance stability and improve recovery of respiratory virus genomes from RATs. METHODS: A mixture of common respiratory viruses was used to inoculate RATs at different environmental temperatures (4°C, 20°C and 36°C), with two preservative reagents (RNALater and DNA/RNA shield) Nucleic acid was extracted from RATs at two different timepoints (72 h and seven days) and subject to real-time multiplex respiratory PCR to detect a range of respiratory viruses. WGS was performed using target-enrichment with the TWIST Comprehensive Viral Research Panel. Defined metrics from an automated in-house bioinformatic pipeline were used to assess and compare viral genome recovery under different conditions. RESULTS: Nucleic acid degradation (indicated by relative change in PCR cycle threshold and WGS-based metrics) was most notable at 20 °C and 36 °C. Storage in either RNALater or DNA / RNA shield improved genome recovery for respiratory viruses across all temperature conditions, although this was most pronounced for RNALater. Subtyping of Influenza viruses demonstrated the applicability of RAT-WGS in downstream genomic epidemiological surveillance. CONCLUSIONS: Under simulated conditions, RAT-WGS demonstrated that (i) viral genomes were generally stable at 4°C at 72 h and 1 week, (ii) RNALater has a more significant preservation of nucleic acids compared to DNA/RNA Shield and (iii) genome recovery can be achieved using a sequencing depth of 500,000 reads per sample in RNALater, across all respiratory viruses and conditions.

CEACAM5-Targeted Immuno-PET in Androgen Receptor-Negative Prostate Cancer.

The incidence of androgen receptor (AR)-negative (AR-) prostate cancer, including aggressive neuroendocrine prostate cancer (NEPC), has more than doubled in the last decade, but its timely diagnosis is difficult as it lacks typical prostate cancer hallmarks. The carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) has recently been identified as an upregulated surface antigen in NEPC. We developed an immuno-PET agent targeting CEACAM5 and evaluated its ability to delineate AR- prostate cancer in vivo. Methods: CEACAM5 expression was evaluated in a panel of prostate cancer cell lines by immunohistochemistry and Western blotting. The CEACAM5-targeting antibody labetuzumab was conjugated with the chelator desferrioxamine (DFO) and radiolabeled with 89Zr. The in vivo distribution of the radiolabeled antibody was evaluated in xenograft prostate cancer models by PET imaging and ex vivo organ distribution. Results: The NEPC cell line H660 exhibited strong CEACAM5 expression, whereas expression was limited in the AR- cell lines PC3 and DU145 and absent in the AR-positive cell line LNCaP. [89Zr]Zr-DFO-labetuzumab imaging was able to clearly delineate both neuroendocrine H660 xenografts and AR- DU145 in vivo but could not detect the AR-positive xenograft LNCaP. Conclusion: Immuno-PET imaging with [89Zr]Zr-DFO-labetuzumab is a promising diagnostic tool for AR- prostate cancer.

A Cost-Effectiveness Analysis of Population-Level Dental Caries Prevention Strategies in US Children.

OBJECTIVE: To improve oral health disparities and outcomes among US children impacted by dental caries, there is a need to understand the cost-effectiveness of a targeted, risk-based versus universal-based approach for caries prevention. METHODS: Health and economic outcomes were simulated in a cohort of 50,000 US children aged 1-18 years, comparing current practice (CP) to risk-based-prevention (RBP) and prevention-for-all (PFA) strategies using health care sector and limited societal perspectives. Prevention included biannual oral health exams and fluoride varnish application, and one-time dental sealant placement. The primary outcome is the cost-effectiveness ratio (ICER), defined as the additional cost per quality-adjusted life year (QALY) gained when comparing each strategy to the next least costly one. RESULTS: For RBP compared to CP, the ICER was US$83,000/QALY from the health care sector perspective; for PFA compared to RBP the ICER was US$154,000/QALY. Using a limited societal perspective that includes caregiver time spent attending dental or medical setting visits, RBP compared to CP yielded a ratio of $119,000/QALY and PFA compared to RBP was $235,000/QALY. Results were most sensitive to changes in the probability of pain from an episode of dental caries, costs for prevention and restoration, and the loss in health-related quality of life due to dental caries pain. Scenario analyses evaluating a reduced intensity of prevention services yielded lower ICERs. CONCLUSION: Using a risk-based approach that identifies and targets children at increased risk for dental caries to guide the delivery of prevention services represents an economic value similar to other pediatric prevention programs.

Spatial Analysis of Drug-Susceptible and Multidrug-Resistant Cases of Tuberculosis, Ho Chi Minh City, Vietnam, 2020-2023.

We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.

Survival impact of post-operative immunotherapy in resected stage III cutaneous melanomas in the checkpoint era.

BACKGROUND: Checkpoint inhibitors have shown improvement in recurrence-free survival in the post-operative setting for node-positive melanoma and were first approved in late 2015. However, single-agent checkpoint therapies have yet to show benefit to overall survival (OS) for lower-risk stage III cancers. We evaluated the OS benefit of post-operative immunotherapy in the National Cancer Database (NCDB). PATIENTS AND METHODS: Patient cases were selected from the NCDB 2020 Participant Use File. Patients diagnosed with stage III cutaneous melanoma between 2016 and 2019 who underwent definitive resection for their melanoma were included. OS between those who received post-operative immunotherapy within 84 days of surgery and those who did not was analyzed by the Kaplan-Meier method. Demographic and clinical characteristics between the two groups were compared via Cox proportional hazard models. RESULTS: 14 978 patients with stage III melanoma were included. Of those, 34.9% (n = 5234) received post-operative immunotherapy and 65.1% (n = 9744) did not. Using the American Joint Committee on Cancer version 8 (AJCCv8) staging, 36-month survival was significantly higher in patients who received post-operative immunotherapy compared to no post-operative systemic therapy in those diagnosed with stage IIIB (88.0% versus 84.7%, P = 0.011), IIIC (75.6% versus 68.1%, P < 0.001), or IIID (59.2% versus 48.4%, P = 0.002). No significant improvement in 36-month survival was seen in patients who received post-operative immunotherapy in patients with stage IIIA disease (93.0% versus 92.2%, P = 0.218). CONCLUSIONS: Post-operative immunotherapy had an OS benefit in patients with AJCCv8 stage IIIB, IIIC, and IIID disease, but had no significant survival benefit for patients with stage IIIA melanomas.

Estimating Transition Probabilities for Modeling Major Depression in Adolescents by Sex and Race or Ethnicity Combinations in the USA.

OBJECTIVE: About one-fifth of US adolescents experienced major depressive symptoms, but few studies have examined longitudinal trends of adolescents developing depression or recovering by demographic factors. We estimated new transition probability inputs, and then used them in a simulation model to project the epidemiologic burden and trajectory of depression of diverse adolescents by sex and race or ethnicity combinations. METHODS: Transition probabilities were first derived using parametric survival analysis of data from the National Longitudinal Study of Adolescent to Adult Health and then calibrated to cross-sectional data from the National Survey on Drug Use and Health. We developed a cohort state-transition model to simulate age-specific depression outcomes of US adolescents. A hypothetical adolescent cohort was modeled from 12-22 years with annual transitions. Model outcomes included proportions of youth experiencing depression, recovery, or depression-free cases and were reported for a US adolescent population by sex, race or ethnicity, and sex and race or ethnicity combinations. RESULTS: At 22 years of age, approximately 16% of adolescents had depression, 12% were in recovery, and 72% had never developed depression. Depression prevalence peaked around 16-17 years-old. Adolescents of multiracial or other race or ethnicity, White, American Indian or Alaska Native, and Hispanic, Latino, or Spanish descent were more likely to experience depression than other racial or ethnic groups. Depression trajectories generated by the model matched well with historical observational studies by sex and race or ethnicity, except for individuals from American Indian or Alaska Native and multiracial or other race or ethnicity backgrounds. CONCLUSIONS: This study validated new transition probabilities for future use in decision models evaluating adolescent depression policies or interventions. Different sets of transition parameters by demographic factors (sex and race or ethnicity combinations) were generated to support future health equity research, including distributional cost-effectiveness analysis. Further data disaggregated with respect to race, ethnicity, religion, income, geography, gender identity, sexual orientation, and disability would be helpful to project accurate estimates for historically minoritized communities.

Parent Perceptions of Telemedicine for Acute Pediatric Respiratory Tract Infections: Sequential Mixed Methods Study.

BACKGROUND: Since 2020, parents have had increasing opportunities to use telemedicine for their children, but how parents decide whether to use telemedicine for acute pediatric care relative to alternative sites of care is not clear. One of the most common reasons parents seek acute care for their children is for acute respiratory tract infections (ARTIs). OBJECTIVE: This study aims to examine parental expectations of care via telemedicine for pediatric ARTIs, contrasting expectations of care delivered via primary care telemedicine and direct-to-consumer (DTC) telemedicine. METHODS: We performed a sequential mixed methods analysis to examine how parents assess telemedicine for their children's acute care. We used ARTIs as a case study for examining parent perceptions of telemedicine. First, we analyzed semistructured interviews focused on parent responses about the use of telemedicine. Each factor discussed by parents was coded to reflect whether parents indicated it incentivized or disincentivized their preferences for telemedicine versus in-person care. Results were organized by a 7-dimension framework of parental health care seeking that was generated previously, which included dimensions related to care sites (expected access, affordability, clinical quality, and site quality) and dimensions related to child or family factors (perceived illness severity, perceived child susceptibility, and parent self-efficacy). Second, we analyzed responses to a national survey, which inquired about parental expectations of primary care telemedicine, commercial DTC telemedicine, and 3 in-person sites of care (primary care, urgent care, and emergency department) across 21 factors identified through prior qualitative work. To assess whether parents had different expectations of different telemedicine models, we compared survey responses for primary care telemedicine and commercial DTC telemedicine using weighted logistic regression. RESULTS: Interview participants (n=40) described factors affecting their perceptions of telemedicine as a care modality for pediatric ARTIs. Generally, factors aligned with access and affordability (eg, decreased wait time and lower out-of-pocket cost) were discussed as potential incentives for telemedicine use, while factors aligned with perceived illness severity, child susceptibility, and clinician quality (eg, trustworthiness) were discussed as potential disincentives for telemedicine use. In survey responses (n=1206), primary care and commercial DTC telemedicine were rated similarly on items related to expected accessibility and affordability. In contrast, on items related to expected quality of care, primary care telemedicine was viewed similarly to in-person primary care, while commercial DTC telemedicine was rated lower. For example, 69.7% (weighted; 842/1197) of respondents anticipated their children would be comfortable and cooperative with primary care telemedicine versus 49.7% (weighted; 584/1193) with commercial DTC telemedicine (P<.001). CONCLUSIONS: In a mixed methods analysis focused on telemedicine for ARTIs, parents expressed more concerns about telemedicine quality in commercial DTC models compared with primary care-based telemedicine. These results could help health systems better design telemedicine initiatives to support family-centered care.

Involvement of superior colliculus in complex figure detection of mice.

Object detection is an essential function of the visual system. Although the visual cortex plays an important role in object detection, the superior colliculus can support detection when the visual cortex is ablated or silenced. Moreover, it has been shown that superficial layers of mouse SC (sSC) encode visual features of complex objects, and that this code is not inherited from the primary visual cortex. This suggests that mouse sSC may provide a significant contribution to complex object vision. Here, we use optogenetics to show that mouse sSC is involved in figure detection based on differences in figure contrast, orientation, and phase. Additionally, our neural recordings show that in mouse sSC, image elements that belong to a figure elicit stronger activity than those same elements when they are part of the background. The discriminability of this neural code is higher for correct trials than for incorrect trials. Our results provide new insight into the behavioral relevance of the visual processing that takes place in sSC.

[Creation and evaluation of a triage survey for ophthalmology emergencies]. / Élaboration et évaluation d'un autoquestionnaire de triage pour les demandes de soins non programmés en ophtalmologie.

PURPOSE: The demand for eye care is growing continuously. We created a triage survey system, based on categories of severity, to optimize first line patient care in an ophthalmology emergency department. METHODS: This cross-sectional study was carried out from July 7th, 2021 to October 10th, 2021. During this period, a survey was taken by patients upon arrival to the emergency department. Patients completed the survey by ticking boxes that best fitted their situation. The survey classified patients into three categories of severity: GREEN, ORANGE and RED. A chart review was performed to record the final diagnoses. The severity of each diagnosis was rated according to the Base Score. This score was then compared to the level of severity as determined by our survey to calculate the agreement between the two methods. RESULTS: We collected 767 survey forms, with an 80% response rate. We noted 78 different diagnoses. We scored 564 patients as GREEN, 107 as ORANGE and 96 as RED. The sensitivity rates for the green, orange and red categories were 90%, 70% and 96% respectively. The specificity rates were 90% for the green category, 95% for orange and 94% for red, with good agreement (kappa coefficient=0.70). CONCLUSION: Our results suggest that a self-administered survey could be useful as a triage tool for common ocular emergencies. This survey could be performed better if complete by the patients with the assistance of emergency staff. Potentially helpful for high flow structures such as university-based hospitals, this triage survey might also help in comprehensive clinics or emergency departments.

Synthesis and Characteristics of Polymer-Mediated Curcumin Molecular Imprinting for Quantitative Determination of Curcumin in Food Samples.

In this study, a molecularly imprinted polymer (MIP)-based extraction process for determining curcumin in food samples was carried out. MIP and NIP were thermally synthesized in acetonitrile solvent (porogen) using methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as a cross-linking agent, azobisisobutyronitrile as an initiator, and curcumin as a template molecule. Parameters affecting the synthesis process, such as temperature, the ratio of the components in the reaction, and the extraction solvent, were investigated. The characteristics of the synthesized material were examined using infrared spectroscopy and scanning electron microscopy. The maximum adsorption capacity of the material was found to be 1.34 mg/g MIP with an adsorption efficiency of 89.96% for MIP and 12.35% for NIP. The MIP material exhibited high selectivity for curcumin compared to other compounds such as quercetin (18.00%), rutin (14.74%), and ketoconazole (0.00%). The analysis method for curcumin using the MIP material was performed with validated parameters including linear range (1 - 25 mg/L, r2 = 0.9997), accuracy (recovery rate of 90.90 %), precision (RSDR = 0.338 %, RSDr = 1.591 %), detection limit (0.051 mg/L), and quantification limit (0.156 mg/L). The validation results indicated that the HPLC-DAD method was entirely suitable for analyzing the curcumin content in food samples.

A (Sub)field Guide to Quality Control in Hippocampal Subfield Segmentation on Highresolution T2-weighted MRI.

Inquiries into properties of brain structure and function have progressed due to developments in magnetic resonance imaging (MRI). To sustain progress in investigating and quantifying neuroanatomical details in vivo, the reliability and validity of brain measurements are paramount. Quality control (QC) is a set of procedures for mitigating errors and ensuring the validity and reliability of brain measurements. Despite its importance, there is little guidance on best QC practices and reporting procedures. The study of hippocampal subfields in vivo is a critical case for QC because of their small size, inter-dependent boundary definitions, and common artifacts in the MRI data used for subfield measurements. We addressed this gap by surveying the broader scientific community studying hippocampal subfields on their views and approaches to QC. We received responses from 37 investigators spanning 10 countries, covering different career stages, and studying both healthy and pathological development and aging. In this sample, 81% of researchers considered QC to be very important or important, and 19% viewed it as fairly important. Despite this, only 46% of researchers reported on their QC processes in prior publications. In many instances, lack of reporting appeared due to ambiguous guidance on relevant details and guidance for reporting, rather than absence of QC. Here, we provide recommendations for correcting errors to maximize reliability and minimize bias. We also summarize threats to segmentation accuracy, review common QC methods, and make recommendations for best practices and reporting in publications. Implementing the recommended QC practices will collectively improve inferences to the larger population, as well as have implications for clinical practice and public health.

Clinical evaluation of hysterectomy for the treatment of invasive mole in Southern Vietnam.

OBJECTIVE: This study aimed to determine the rate of salvage chemotherapy and review associated factors in invasive mole patients treated by primary or delayed hysterectomy. PATIENTS AND METHODS: This study was carried out at the Tu Du Hospital, where a total of 189 patients were diagnosed with invasive mole based on histologic examination by hysterectomy between 01/2016 to 12/2020. We used the life table method to estimate the cumulative rate. We applied the Cox proportional hazard model to determine the factors associated with the need for salvage chemotherapy. RESULTS: At 12-month follow-up, 47 patients had required salvage chemotherapy. The incidence was 24.87% (95% CI: 18.88-31.66). Applying the multivariate model, prophylactic chemotherapy (HR = 2.75, 95% Cl: 1.20-6.30) and two weeks postoperative hCG value greater than 1,900 mIU/mL (HR = 4.30, 95% Cl: 2.08-8.87) increased the risk of requiring salvage chemotherapy. Postoperative chemotherapy decreased the risk of requiring salvage chemotherapy (HR = 0.43, 95% Cl: 0.22-0.83). CONCLUSIONS: Hysterectomy can be considered safe and effective in treating invasive mole patients. Although patients were treated by hysterectomy, 24.87% of patients needed salvage chemotherapy to achieve remission. This study affirms the malignant nature of invasive mole, a subtype of gestational trophoblastic neoplasia (GTN). It is not purely a local invasion of molar villi. Postoperative chemotherapy plays an essential role in reducing the risk of requiring salvage chemotherapy.

Preferences and experiences of pediatricians on implementing national guidelines on universal routine screening of adolescents for major depressive disorder: A qualitative study.

BACKGROUND: To explore the preferences of pediatricians for key factors around the implementation of universal routine screening guidelines for major depressive disorder in adolescent patients in a primary care setting. METHOD: Semi-structured qualitative interviews were conducted with U.S. pediatricians. Participants were recruited by convenience sampling and snowball sampling. Qualitive data were summarized using thematic analysis to identify themes relevant to preferences around implementing screening strategies for adolescent patients. Recruitment ended upon reaching thematic saturation when no new themes were revealed. RESULTS: Of the 14 participants, 11 identified as female, 3 male, 10 white, and 4 Asian. Top themes among pediatrician participants were around the screening modality (14/14 participants), screening validity (14/14), time barriers (14/14), and confidentiality barriers (12/14). Less frequently mentioned themes by pediatricians were workplace coordination and logistics (7/14), alternative starting ages for screening (7/14), more frequent screenings than annual screenings (3/14), and additional clinical training regarding depression diagnosis and treatment (2/14). LIMITATIONS: Pool of interviewed participants was limited by diversity in terms of geography, race/ethnicity, or practice settings. CONCLUSIONS: To promote the uptake of universal routine screening of adolescent major depression, pediatricians expressed it was important to address key implementation factors regarding the screening modality, screening validity, time constraints, and confidential care concerns in a primary care delivery context. Findings could be used to inform the development of implementation strategies to facilitate depression screening in primary care. Future research is needed to quantitively assess decisions and tradeoffs that pediatricians make when implementing universal screening to support adolescent mental health.

Click Chemistry and Radiochemistry: An Update.

The term "click chemistry" describes a class of organic transformations that were developed to make chemical synthesis simpler and easier, in essence allowing chemists to combine molecular subunits as if they were puzzle pieces. Over the last 25 years, the click chemistry toolbox has swelled from the canonical copper-catalyzed azide-alkyne cycloaddition to encompass an array of ligations, including bioorthogonal variants, such as the strain-promoted azide-alkyne cycloaddition and the inverse electron-demand Diels-Alder reaction. Without question, the rise of click chemistry has impacted all areas of chemical and biological science. Yet the unique traits of radiopharmaceutical chemistry have made it particularly fertile ground for this technology. In this update, we seek to provide a comprehensive guide to recent developments at the intersection of click chemistry and radiopharmaceutical chemistry and to illuminate several exciting trends in the field, including the use of emergent click transformations in radiosynthesis, the clinical translation of novel probes synthesized using click chemistry, and the advent of click-based in vivo pretargeting.

Multi-omics analysis of mucosal and systemic immunity to SARS-CoV-2 after birth.

The dynamics of immunity to infection in infants remain obscure. Here, we used a multi-omics approach to perform a longitudinal analysis of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in infants and young children by analyzing blood samples and weekly nasal swabs collected before, during, and after infection with Omicron and non-Omicron variants. Infection stimulated robust antibody titers that, unlike in adults, showed no sign of decay for up to 300 days. Infants mounted a robust mucosal immune response characterized by inflammatory cytokines, interferon (IFN) α, and T helper (Th) 17 and neutrophil markers (interleukin [IL]-17, IL-8, and CXCL1). The immune response in blood was characterized by upregulation of activation markers on innate cells, no inflammatory cytokines, but several chemokines and IFNα. The latter correlated with viral load and expression of interferon-stimulated genes (ISGs) in myeloid cells measured by single-cell multi-omics. Together, these data provide a snapshot of immunity to infection during the initial weeks and months of life.

Reasons for Encounters and Comorbidities in Adolescents with Intellectual Disability in General Practice: A Retrospective Analysis of Data from the Ask Study.

Adolescents with intellectual disability have substantial health needs. This retrospective analysis of data from the Ask Study describes reasons for primary care encounters and the prevalence and incidence of chronic physical and mental conditions among a cohort of community-dwelling adolescents with intellectual disability. Participants attended secondary schools in southern Queensland, Australia. Primary care data were extracted from primary care records. Demographic and health information was collected using carer-completed questionnaires. Reasons for primary care encounters, disease prevalence at age 16 years, and disease incidence through adolescence were reported. Data were obtained for 432 adolescents with intellectual disability (median follow-up: 4.1 years). Skin problems (29.4 per 100 encounters) were the most common reason patients presented for primary care, followed by psychological and behavioural problems (14.4 per 100 encounters) and musculoskeletal problems (13.8 per 100 encounters). Conditions with the highest prevalence were autism spectrum disorder (18.6%) and asthma (18.1%). The prevalence of epilepsy, visual impairment, and cerebral palsy were 14.7, 11.1, and 8.0%, respectively. Gastroesophageal reflux had the highest incidence (9.4 cases per 1000 person-years). Adolescents with intellectual disability have significant healthcare needs, which general practitioners need to be aware of and address. Study findings should inform the development of training programs for general practitioners.

Severe falciparum malaria in pregnancy in Southeast Asia: a multi-centre retrospective cohort study.

BACKGROUND: Severe malaria in pregnancy causes maternal mortality, morbidity, and adverse foetal outcomes. The factors contributing to adverse maternal and foetal outcomes are not well defined. We aimed to identify the factors predicting higher maternal mortality and to describe the foetal mortality and morbidity associated with severe falciparum malaria in pregnancy. METHODS: A retrospective cohort study was conducted of severe falciparum malaria in pregnancy, as defined by the World Health Organization severe malaria criteria. The patients were managed prospectively by the Shoklo Malaria Research Unit (SMRU) on the Thailand-Myanmar border or were included in hospital-based clinical trials in six Southeast Asian countries. Fixed-effects multivariable penalised logistic regression was used for analysing maternal mortality. RESULTS: We included 213 (123 SMRU and 90 hospital-based) episodes of severe falciparum malaria in pregnancy managed between 1980 and 2020. The mean maternal age was 25.7 (SD 6.8) years, and the mean gestational age was 25.6 (SD 8.9) weeks. The overall maternal mortality was 12.2% (26/213). Coma (adjusted odds ratio [aOR], 7.18, 95% CI 2.01-25.57, p = 0.0002), hypotension (aOR 11.21, 95%CI 1.27-98.92, p = 0.03) and respiratory failure (aOR 4.98, 95%CI 1.13-22.01, p = 0.03) were associated with maternal mortality. Pregnant women with one or more of these three criteria had a mortality of 29.1% (25/86) (95%CI 19.5 to 38.7%) whereas there were no deaths in 88 pregnant women with hyperparasitaemia (> 10% parasitised erythrocytes) only or severe anaemia (haematocrit < 20%) only. In the SMRU prospective cohort, in which the pregnant women were followed up until delivery, the risks of foetal loss (23.3% by Kaplan-Meier estimator, 25/117) and small-for-gestational-age (38.3%, 23/60) after severe malaria were high. Maternal death, foetal loss and preterm birth occurred commonly within a week of diagnosis of severe malaria. CONCLUSIONS: Vital organ dysfunction in pregnant women with severe malaria was associated with a very high maternal and foetal mortality whereas severe anaemia or hyperparasitaemia alone were not associated with poor prognosis, which may explain the variation of reported mortality from severe malaria in pregnancy. Access to antenatal care must be promoted to reduce barriers to early diagnosis and treatment of both malaria and anaemia.