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Clinical Infectious Diseases : An... Oct 2022Households have emerged as important venues for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Little is known, however, regarding the...
BACKGROUND
Households have emerged as important venues for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Little is known, however, regarding the magnitude and determinants of household transmission in increasingly vaccinated populations.
METHODS
From September 2020 to January 2022, symptomatic nonhospitalized individuals with SARS-CoV-2 infection by RNA detection were identified within 5 days of symptom onset; all individuals resided with at least 1 other SARS-CoV-2-uninfected household member. These infected persons (cases) and their household members (contacts) were subsequently followed with questionnaire-based measurement and serial nasal specimen collection. The primary outcome was SARS-CoV-2 infection among contacts.
RESULTS
We evaluated 42 cases and their 74 household contacts. Among the contacts, 32 (43%) became infected, of whom 5 (16%) were asymptomatic; 81% of transmissions occurred by 5 days after the case's symptom onset. From 21 unvaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection among contacts was 18/40 (45% [95% confidence interval {CI}, 29%-62%]), most of whom were unvaccinated. From 21 vaccinated cases, 14-day cumulative incidence of SARS-CoV-2 infection was 14/34 (41% [95% CI, 25%-59%]) among all contacts and 12/29 (41% [95% CI, 24%-61%]) among vaccinated contacts. At least 1 comorbid condition among cases and 10 or more days of RNA detection in cases were associated with increased risk of infection among contacts.
CONCLUSIONS
Among households including individuals with symptomatic SARS-CoV-2 infection, both vaccinated-to-vaccinated and unvaccinated-to-unvaccinated transmission of SARS-CoV-2 to household contacts was common. Because vaccination alone did not notably reduce risk of infection, household contacts will need to employ additional interventions to avoid infection.
Topics: COVID-19; Cohort Studies; Humans; Longitudinal Studies; RNA; SARS-CoV-2
PubMed: 35788827
DOI: 10.1093/cid/ciac545 -
Alzheimer's & Dementia (Amsterdam,... 2023Apathy is one of the most common neuropsychiatric symptoms (NPS) and is associated with poor clinical outcomes. Research that helps define the apathy phenotype is...
UNLABELLED
Apathy is one of the most common neuropsychiatric symptoms (NPS) and is associated with poor clinical outcomes. Research that helps define the apathy phenotype is urgently needed, particularly for clinical and biomarker studies. We used latent class analysis (LCA) with two independent cohorts to understand how apathy and depression symptoms co-occur statistically. We further explored the relationship between latent class membership, demographics, and the presence of other NPS. The LCA identified a four-class solution (no symptoms, apathy, depression, and combined apathy/depression), reproducible over both cohorts, providing robust support for an apathy syndrome distinct from depression and confirming that an apathy/depression syndrome exists, supported by the model fit test with the four-class solution scores evidencing better fitting (Bayesian information criterion adjusted and entropy ). Using a data-driven method, we show distinct and statistically meaningful co-occurrence of apathy and depressive symptoms. There was evidence that these classes have different clinical associations, which may help inform diagnostic categories for research studies and clinical practice.
HIGHLIGHTS
We found four classes: no symptoms, apathy, depression and apathy/depression.Apathy conferred a higher probability for agitation.Apathy diagnostic criteria should include accompanying neuropsychiatric symptoms.
PubMed: 36777092
DOI: 10.1002/dad2.12398 -
Journal of Clinical Research in... Aug 2023Mutations in the gene result in rare inherited syndromes causing insulin resistance, such as leprechaunism (Donohue syndrome), Rabson-Mendenhall syndrome and insulin...
Mutations in the gene result in rare inherited syndromes causing insulin resistance, such as leprechaunism (Donohue syndrome), Rabson-Mendenhall syndrome and insulin resistance type A. Leprechaunism is an autosomal recessive disorder associated with extreme insulin resistance that leads to hyperinsulinemia, impaired glucose homeostasis, fasting hypoglycemia and postprandial hyperglycemia. Impaired insulin action causes prenatal and postnatal growth retardation. Lipoatrophy, dysmorphic facies, hypertrichosis, macrogenitosomia and hypertrophy of internal organs are also present. A male infant with congenital insulin resistance was born at term after a normal pregnancy with a weight of 1905 g (<3 c), a length of 48 cm (<3 c), and an Apgar score of 10. Intrauterine growth retardation, transient hypoglycemia, pneumonia, urinary tract infection and heart defects [patent foramen ovale (PFO); patent ductus arteriosus (PDA)] were diagnosed after birth. At 5 weeks of age, he was admitted to the regional hospital with severe fever, diarrhea and dehydration. Hyperglycemia was observed (672 mg/dL), and insulin was administered. He was referred to a hospital at 7 weeks of age for suspected neonatal diabetes and hypertrophic cardiomyopathy. The physical examination revealed a loud systolic heart murmur, tachycardia, tachypnea, dysmorphic facies, hypertrichosis, acanthosis nigricans, hypotonia, swollen nipples and enlarged testicles. Glycemic fluctuations (50-250 mg/dL) were observed. The serum insulin concentration was high (maximum 1200 IU/mL) at normoglycemia. Ultrasound of the heart confirmed progressive hypertrophic cardiomyopathy. Leprechaunism was confirmed by genetic analysis of , in which a novel c.320C>G; p. Thr107Arg homozygous missense mutation was found in exon 2.
Topics: Female; Humans; Infant; Infant, Newborn; Male; Antigens, CD; Cardiomyopathy, Hypertrophic; Diabetes Mellitus; Donohue Syndrome; Facies; Hyperglycemia; Hypertrichosis; Hypoglycemia; Insulin; Insulin Resistance; Mutation; Receptor, Insulin
PubMed: 34965699
DOI: 10.4274/jcrpe.galenos.2021.2021.0256 -
BMJ (Clinical Research Ed.) Aug 2020To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2... (Observational Study)
Observational Study
OBJECTIVE
To characterise the clinical features of children and young people admitted to hospital with laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK and explore factors associated with admission to critical care, mortality, and development of multisystem inflammatory syndrome in children and adolescents temporarily related to coronavirus disease 2019 (covid-19) (MIS-C).
DESIGN
Prospective observational cohort study with rapid data gathering and near real time analysis.
SETTING
260 hospitals in England, Wales, and Scotland between 17 January and 3 July 2020, with a minimum follow-up time of two weeks (to 17 July 2020).
PARTICIPANTS
651 children and young people aged less than 19 years admitted to 138 hospitals and enrolled into the International Severe Acute Respiratory and emergency Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK study with laboratory confirmed SARS-CoV-2.
MAIN OUTCOME MEASURES
Admission to critical care (high dependency or intensive care), in-hospital mortality, or meeting the WHO preliminary case definition for MIS-C.
RESULTS
Median age was 4.6 (interquartile range 0.3-13.7) years, 35% (225/651) were under 12 months old, and 56% (367/650) were male. 57% (330/576) were white, 12% (67/576) South Asian, and 10% (56/576) black. 42% (276/651) had at least one recorded comorbidity. A systemic mucocutaneous-enteric cluster of symptoms was identified, which encompassed the symptoms for the WHO MIS-C criteria. 18% (116/632) of children were admitted to critical care. On multivariable analysis, this was associated with age under 1 month (odds ratio 3.21, 95% confidence interval 1.36 to 7.66; P=0.008), age 10-14 years (3.23, 1.55 to 6.99; P=0.002), and black ethnicity (2.82, 1.41 to 5.57; P=0.003). Six (1%) of 627 patients died in hospital, all of whom had profound comorbidity. 11% (52/456) met the WHO MIS-C criteria, with the first patient developing symptoms in mid-March. Children meeting MIS-C criteria were older (median age 10.7 (8.3-14.1) 1.6 (0.2-12.9) years; P<0.001) and more likely to be of non-white ethnicity (64% (29/45) 42% (148/355); P=0.004). Children with MIS-C were five times more likely to be admitted to critical care (73% (38/52) 15% (62/404); P<0.001). In addition to the WHO criteria, children with MIS-C were more likely to present with fatigue (51% (24/47) 28% (86/302); P=0.004), headache (34% (16/47) 10% (26/263); P<0.001), myalgia (34% (15/44) 8% (21/270); P<0.001), sore throat (30% (14/47) (12% (34/284); P=0.003), and lymphadenopathy (20% (9/46) 3% (10/318); P<0.001) and to have a platelet count of less than 150 × 10/L (32% (16/50) 11% (38/348); P<0.001) than children who did not have MIS-C. No deaths occurred in the MIS-C group.
CONCLUSIONS
Children and young people have less severe acute covid-19 than adults. A systemic mucocutaneous-enteric symptom cluster was also identified in acute cases that shares features with MIS-C. This study provides additional evidence for refining the WHO MIS-C preliminary case definition. Children meeting the MIS-C criteria have different demographic and clinical features depending on whether they have acute SARS-CoV-2 infection (polymerase chain reaction positive) or are post-acute (antibody positive).
STUDY REGISTRATION
ISRCTN66726260.
Topics: Adolescent; Age Factors; Betacoronavirus; COVID-19; Child; Child, Preschool; Cohort Studies; Coronavirus Infections; Critical Care; Female; Hospital Mortality; Hospitalization; Humans; Infant; Infant, Newborn; Male; Pandemics; Pneumonia, Viral; Respiration, Artificial; SARS-CoV-2; Systemic Inflammatory Response Syndrome; United Kingdom; Young Adult
PubMed: 32960186
DOI: 10.1136/bmj.m3249 -
Journal of Addiction MedicineState Medicaid programs are the largest single provider of healthcare for pregnant persons with opioid use disorder (OUD). Our objective was to provide comparable,...
OBJECTIVES
State Medicaid programs are the largest single provider of healthcare for pregnant persons with opioid use disorder (OUD). Our objective was to provide comparable, multistate measures estimating the burden of OUD in pregnancy, medication for OUD (MOUD) in pregnancy, and related neonatal and child outcomes.
METHODS
Drawing on the Medicaid Outcomes Distributed Research Network (MODRN), we accessed administrative healthcare data for 1.6 million pregnancies and 1.3 million live births in 9 state Medicaid populations from 2014 to 2017. We analyzed within- and between-state prevalences and time trends in the following outcomes: diagnosis of OUD in pregnancy, initiation, and continuity of MOUD in pregnancy, Neonatal Opioid Withdrawal Syndrome (NOWS), and well-child visit utilization among children with NOWS.
RESULTS
OUD diagnosis increased from 49.6 per 1000 to 54.1 per 1000 pregnancies, and the percentage of those with any MOUD in pregnancy increased from 53.4% to 57.9%, during our study time period. State-specific percentages of 180-day continuity of MOUD ranged from 41.2% to 84.5%. The rate of neonates diagnosed with NOWS increased from 32.7 to 37.0 per 1000 live births. State-specific percentages of children diagnosed with NOWS who had the recommended well-child visits in the first 15 months ranged from 39.3% to 62.5%.
CONCLUSIONS
Medicaid data, which allow for longitudinal surveillance of care across different settings, can be used to monitor OUD and related pregnancy and child health outcomes. Findings highlight the need for public health efforts to improve care for pregnant persons and children affected by OUD.
Topics: Analgesics, Opioid; Delivery of Health Care; Female; Humans; Infant, Newborn; Medicaid; Opiate Substitution Treatment; Opioid-Related Disorders; Pregnancy; Pregnant Women; United States
PubMed: 33560699
DOI: 10.1097/ADM.0000000000000780 -
BMC Pediatrics May 2024Donohue syndrome (DS), also referred to as leprechaunism, is a remarkably uncommon autosomal recessive disorder that primarily affects the endocrine system. Its...
INTRODUCTION
Donohue syndrome (DS), also referred to as leprechaunism, is a remarkably uncommon autosomal recessive disorder that primarily affects the endocrine system. Its incidence rate is exceedingly low, with only 1 case reported per 4 million live births. The syndrome is distinguished by a series of characteristic clinical features.
CASE PRESENTATION
We present a case of a twenty-month-old male with DS who experienced a range of dysmorphic and clinical features with the involvement of multiple systems. These features include skin hyperpigmentation, hypertrichosis, distinct facial features, abdominal distension, and microcephaly, with the involvement of the endocrine, renal, respiratory, and cardiac systems.
CONCLUSION
The primary features of DS involve severe insulin resistance and growth abnormalities, the association with pulmonary hypertension (PHTN) has not been reported before. This finding adds more complexity to the condition. To the best of the author's knowledge, this is the first report for a patient with DS who has PHTN. Further investigation is required since the mechanisms behind the development of PHTN in DS are not entirely understood. Shedding light on this association will contribute to better management strategies and outcomes for affected patients.
Topics: Humans; Male; Hypertension, Pulmonary; Infant; Donohue Syndrome
PubMed: 38773407
DOI: 10.1186/s12887-024-04714-1 -
Frontiers in Endocrinology 2021Defects in the insulin receptor () gene cause various severe insulin resistance conditions, including Donohue syndrome (DS), Rabson-Mendenhall syndrome (RMS) and type A...
OBJECTIVE
Defects in the insulin receptor () gene cause various severe insulin resistance conditions, including Donohue syndrome (DS), Rabson-Mendenhall syndrome (RMS) and type A insulin resistance (type A-IR). This study aimed to investigate the clinical characterization and molecular defects in three Chinese children with -related insulin resistance syndrome.
METHODS
We reviewed the clinical data of three Chinese children with -related insulin resistance syndrome from two unrelated kindreds. Genetic analysis was performed using whole-exome sequencing and the effects of the novel variants were further assessed by functional assays.
RESULTS
The proband with type A-IR presented with acanthosis nigricans, hypertrichosis, and euglycemia with mild insulin resistance in early childhood. His sister presented with features typical of type A-IR and was diagnosed with diabetes mellitus with severe insulin resistance at the age of 9.8 years. The proband with DS showed typical dysmorphic characteristics, severe intrauterine growth retardation, extreme insulin resistance, fasting hypoglycemia and postprandial hyperglycemia from birth. The heterozygote variants c.[3670G>A]; c.[3614C>T] were identified in both siblings with type A-IR; and c.[749_751del]; c.[3355C>T] in the patient with DS. studies showed that the novel variant c.749_751del [p.(Thr250del)] in the α-subunit, reduced expression of the mature INSR protein and severely impaired INSR function. In contrast, the novel variant c.3670G>A [p.(Val1224Met)] in the β-subunit had no effect on total protein expression and phosphorylation of INSR and Akt, suggesting that the variant p.Val1224Met appeared to be tolerated and was not responsible for the severe insulin resistance.
CONCLUSION
Our study detailed the clinical features of three patients with type A-IR and DS, and identified two novel variants in the gene. Functional assays indicated the novel variant p.Thr250del was pathogenic. In contrast, the novel variant p.Val1224Met was suggested to be tolerated by our experimental data, even though bioinformatics analyses predicted the variant as deleterious.
Topics: Acanthosis Nigricans; Animals; Antigens, CD; CHO Cells; Child; Child, Preschool; China; Cricetulus; DNA Mutational Analysis; Diabetes Complications; Donohue Syndrome; Family; Female; Humans; Insulin Resistance; Male; Metabolic Syndrome; Mutation, Missense; Patient Acuity; Pedigree; Receptor, Insulin; Syndrome
PubMed: 33995269
DOI: 10.3389/fendo.2021.606964 -
The Journal of Infectious Diseases Jun 2023From 2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission studies (enrolling April 2020 to January 2022) with rapid enrollment and...
From 2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) household transmission studies (enrolling April 2020 to January 2022) with rapid enrollment and specimen collection for 14 days, 61% (43/70) of primary cases had culturable virus detected ≥6 days post-onset. Risk of secondary infection among household contacts tended to be greater when primary cases had culturable virus detected after onset. Regardless of duration of culturable virus, most secondary infections (70%, 28/40) had serial intervals <6 days, suggesting early transmission. These data examine viral culture as a proxy for infectiousness, reaffirm the need for rapid control measures after infection, and highlight the potential for prolonged infectiousness (≥6 days) in many individuals.
Topics: Humans; SARS-CoV-2; COVID-19; Tennessee; Family Characteristics; California
PubMed: 36705269
DOI: 10.1093/infdis/jiad018 -
The Journal of Clinical Endocrinology... Feb 2022Rabson-Mendenhall syndrome (RMS) is caused by biallelic pathogenic variants in the insulin receptor gene (INSR) leading to insulin-resistant diabetes, microvascular...
CONTEXT
Rabson-Mendenhall syndrome (RMS) is caused by biallelic pathogenic variants in the insulin receptor gene (INSR) leading to insulin-resistant diabetes, microvascular complications, and growth hormone resistance with short stature. Small, uncontrolled studies suggest that 1-year treatment with recombinant leptin (metreleptin) improves glycemia in RMS.
OBJECTIVE
This study aimed to determine effects of long-term metreleptin in RMS on glycemia, anthropometrics, the growth hormone axis, and kidney function.
METHODS
We compared RMS patients during nonrandomized open-label treatment with metreleptin (≥ 0.15 mg/kg/day) vs no metreleptin over 90 months (5 subjects in both groups at different times, 4 only in metreleptin group, 2 only in control group). Main outcome measures were A1c; glucose; insulin; 24-hour urine glucose; standard deviation scores (SDS) for height, weight, body mass index (BMI), and insulin-like growth factor 1 (IGF-1); growth hormone; and estimated glomerular filtration rate.
RESULTS
Over time, metreleptin-treated subjects maintained 1.8 percentage point lower A1c vs controls (P = 0.007), which remained significant after accounting for changes in insulin doses. Metreleptin-treated subjects had a reduction in BMI SDS, which predicted decreased A1c. Growth hormone increased after metreleptin treatment vs control, with no difference in SDS between groups for IGF-1 or height. Reduced BMI predicted higher growth hormone, while reduced A1c predicted higher IGF-1.
CONCLUSION
Metreleptin alters the natural history of rising A1c in RMS, leading to lower A1c throughout long-term follow-up. Improved glycemia with metreleptin is likely attributable to appetite suppression and lower BMI SDS. Lower BMI after metreleptin may also worsen growth hormone resistance in RMS, resulting in a null effect on IGF-1 and growth despite improved glycemia.
Topics: Antigens, CD; Blood Glucose; Body Height; Body Mass Index; Body Weight; Donohue Syndrome; Glomerular Filtration Rate; Glycated Hemoglobin; Human Growth Hormone; Humans; Insulin; Insulin-Like Growth Factor I; Kidney; Leptin; Receptor, Insulin; Treatment Outcome
PubMed: 34718628
DOI: 10.1210/clinem/dgab782 -
Frontiers in Neuroscience 2022Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing...
Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing the brain to asymmetric perfusion. Though ECMO patients frequently experience brain injury, neurologic exams and imaging are difficult to obtain. Diffuse correlation spectroscopy (DCS) non-invasively measures relative cerebral blood flow (rBF) at the bedside using an optical probe on each side of the forehead. In this study we observed interhemispheric rBF differences in response to mean arterial pressure (MAP) changes in adult ECMO recipients. We recruited 13 subjects aged 21-78 years (7 with cardiac arrest, 4 with acute heart failure, and 2 with acute respiratory distress syndrome). They were dichotomized Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; = 4) and non-comatose (GCS-M > 4; = 9) groups. Comatose patients had greater interhemispheric rBF asymmetry (ASYM) vs. non-comatose patients over a range of MAP values (29 vs. 11%, = 0.009). ASYM in comatose patients resolved near a MAP range of 70-80 mmHg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Correlations between post-oxygenator pCO or pH vs. ASYM were significantly different between comatose and non-comatose groups. Our findings indicate that comatose patients are more likely to have asymmetric cerebral perfusion.
PubMed: 35478849
DOI: 10.3389/fnins.2022.858404