Changes over time in characteristics, resource use and outcomes among ICU patients with COVID-19-A nationwide, observational study in Denmark

BACKGROUND: Characteristics and care of intensive care unit (ICU) patients with COVID‐19 may have changed during the pandemic, but longitudinal data assessing this are limited. We compared patients with COVID‐19 admitted to Danish ICUs in the first wave with those admitted later. METHODS: Among all Danish ICU patients with COVID‐19, we compared demographics, chronic comorbidities, use of organ support, length of stay and vital status of those admitted 10 March to 19 May 2020 (first wave) versus 20 May 2020 to 30 June 2021. We analysed risk factors for death by adjusted logistic regression analysis. RESULTS: Among all hospitalised patients with COVID‐19, a lower proportion was admitted to ICU after the first wave (13% vs. 8%). Among all 1374 ICU patients with COVID‐19, 326 were admitted during the first wave. There were no major differences in patient's characteristics or mortality between the two periods, but use of invasive mechanical ventilation (81% vs. 58% of patients), renal replacement therapy (26% vs. 13%) and ECMO (8% vs. 3%) and median length of stay in ICU (13 vs. 10 days) and in hospital (20 vs. 17 days) were all significantly lower after the first wave. Risk factors for death were higher age, larger burden of comorbidities (heart failure, pulmonary disease and kidney disease) and active cancer, but not admission during or after the first wave. CONCLUSIONS: After the first wave of COVID‐19 in Denmark, a lower proportion of hospitalised patients with COVID‐19 were admitted to ICU. Among ICU patients, use of organ support was lower and length of stay was reduced, but mortality rates remained at a relatively high level

The clinical, biochemical and genetic features associated with RMND1-related mitochondrial disease

Background Mutations in the RMND1 (Required for Meiotic Nuclear Division protein 1) gene have recently been linked to infantile onset mitochondrial disease characterised by multiple mitochondrial respiratory chain defects. Methods We summarised the clinical, biochemical and molecular genetic investigation of an international cohort of affected individuals with RMND1 mutations. In addition, we reviewed all the previously published cases to determine the genotype–phenotype correlates and performed survival analysis to identify prognostic factors. Results We identified 14 new cases from 11 pedigrees that harbour recessive RMND1 mutations, including 6 novel variants: c.533C>A, p.(Thr178Lys); c.565C>T, p.(Gln189*); c.631G>A, p.(Val211Met); c.1303C>T, p.(Leu435Phe); c.830+1G>A and c.1317+1G>T. Together with all previously published cases (n=32), we show that congenital sensorineural deafness, hypotonia, developmental delay and lactic acidaemia are common clinical manifestations with disease onset under 2 years. Renal involvement is more prevalent than seizures (66% vs 44%). In addition, median survival time was longer in patients with renal involvement compared with those without renal disease (6 years vs 8 months, p=0.009). The neurological phenotype also appears milder in patients with renal involvement. Conclusions The clinical phenotypes and prognosis associated with RMND1 mutations are more heterogeneous than that were initially described. Regular monitoring of kidney function is imperative in the clinical practice in light of nephropathy being present in over 60% of cases. Furthermore, renal replacement therapy should be considered particularly in those patients with mild neurological manifestation as shown in our study that four recipients of kidney transplant demonstrate good clinical outcome to date

Determination of the Form Factors for the Decay B0 --> D*-l+nu_l and of the CKM Matrix Element |Vcb|

We present a combined measurement of the Cabibbo-Kobayashi-Maskawa matrix element $|V_{cb}|$ and of the parameters $\rho^2$, $R_1$, and $R_2$, which fully characterize the form factors of the $B^0 \to D^{*-}\ell^{+}\nu_\ell$ decay in the framework of HQET, based on a sample of about 52,800 $B^0 \to D^{*-}\ell^{+}\nu_\ell$ decays recorded by the BABAR detector. The kinematical information of the fully reconstructed decay is used to extract the following values for the parameters (where the first errors are statistical and the second systematic): $\rho^2 = 1.156 \pm 0.094 \pm 0.028$, $R_1 = 1.329 \pm 0.131 \pm 0.044$, $R_2 = 0.859 \pm 0.077 \pm 0.022$, $\mathcal{F}(1)|V_{cb}| = (35.03 \pm 0.39 \pm 1.15) \times 10^{-3}$. By combining these measurements with the previous BABAR measurements of the form factors which employs a different technique on a partial sample of the data, we improve the statistical accuracy of the measurement, obtaining: $\rho^2 = 1.179 \pm 0.048 \pm 0.028, R_1 = 1.417 \pm 0.061 \pm 0.044, R_2 = 0.836 \pm 0.037 \pm 0.022,$ and $\mathcal{F}(1)|V_{cb}| = (34.68 \pm 0.32 \pm 1.15) \times 10^{-3}.$ Using the lattice calculations for the axial form factor $\mathcal{F}(1)$, we extract $|V_{cb}| =(37.74 \pm 0.35 \pm 1.25 \pm ^{1.23}_{1.44}) \times 10^{-3}$, where the third error is due to the uncertainty in $\mathcal{F}(1)$

Study of the Exclusive Initial-State Radiation Production of the DDˉD \bar D System

A study of exclusive production of the $D \bar D$ system through initial-state r adiation is performed in a search for charmonium states, where $D=D^0$ or $D^+$. The $D^0$ mesons are reconstructed in the $D^0 \to K^- \pi^+$, $D^0 \to K^- \pi^+ \pi^0$, and $D^0 \to K^- \pi^+ \pi^+ \pi^-$ decay modes. The $D^+$ is reconstructed through the $D^+ \to K^- \pi^+ \pi^+$ decay mode. The analysis makes use of an integrated luminosity of 288.5 fb$^{-1}$ collected by the BaBar experiment. The $D \bar D$ mass spectrum shows a clear $\psi(3770)$ signal. Further structures appear in the 3.9 and 4.1 GeV/$c^2$ regions. No evidence is found for Y(4260) decays to $D \bar D$, implying an up per limit \frac{\BR(Y(4260)\to D \bar D)}{\BR(Y(4260)\to J/\psi \pi^+ \pi^-)} < 7.6 (95 % confidence level)

Genetic, Phenotypic, and Interferon Biomarker Status in ADAR1-Related Neurological Disease

We investigated the genetic, phenotypic, and interferon status of 46 patients from 37 families with neurological disease due to mutations in ADAR1. The clinicoradiological phenotype encompassed a spectrum of Aicardi–Goutières syndrome, isolated bilateral striatal necrosis, spastic paraparesis with normal neuroimaging, a progressive spastic dystonic motor disorder, and adult-onset psychological difficulties with intracranial calcification. Homozygous missense mutations were recorded in five families. We observed a p.Pro193Ala variant in the heterozygous state in 22 of 23 families with compound heterozygous mutations. We also ascertained 11 cases from nine families with a p.Gly1007Arg dominant-negative mutation, which occurred de novo in four patients, and was inherited in three families in association with marked phenotypic variability. In 50 of 52 samples from 34 patients, we identified a marked upregulation of type I interferon-stimulated gene transcripts in peripheral blood, with a median interferon score of 16.99 (interquartile range [IQR]: 10.64–25.71) compared with controls (median: 0.93, IQR: 0.57–1.30). Thus, mutations in ADAR1 are associated with a variety of clinically distinct neurological phenotypes presenting from early infancy to adulthood, inherited either as an autosomal recessive or dominant trait. Testing for an interferon signature in blood represents a useful biomarker in this context

Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C.

CONTEXT: 4H or POLR3-related leukodystrophy is an autosomal recessive disorder typically characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism, caused by biallelic pathogenic variants in POLR3A, POLR3B, POLR1C, and POLR3K. The endocrine and growth abnormalities associated with this disorder have not been thoroughly investigated to date. OBJECTIVE: To systematically characterize endocrine abnormalities of patients with 4H leukodystrophy. DESIGN: An international cross-sectional study was performed on 150 patients with genetically confirmed 4H leukodystrophy between 2015 and 2016. Endocrine and growth abnormalities were evaluated, and neurological and other non-neurological features were reviewed. Potential genotype/phenotype associations were also investigated. SETTING: This was a multicenter retrospective study using information collected from 3 predominant centers. PATIENTS: A total of 150 patients with 4H leukodystrophy and pathogenic variants in POLR3A, POLR3B, or POLR1C were included. MAIN OUTCOME MEASURES: Variables used to evaluate endocrine and growth abnormalities included pubertal history, hormone levels (estradiol, testosterone, stimulated LH and FSH, stimulated GH, IGF-I, prolactin, ACTH, cortisol, TSH, and T4), and height and head circumference charts. RESULTS: The most common endocrine abnormalities were delayed puberty (57/74; 77% overall, 64% in males, 89% in females) and short stature (57/93; 61%), when evaluated according to physician assessment. Abnormal thyroid function was reported in 22% (13/59) of patients. CONCLUSIONS: Our results confirm pubertal abnormalities and short stature are the most common endocrine features seen in 4H leukodystrophy. However, we noted that endocrine abnormalities are typically underinvestigated in this patient population. A prospective study is required to formulate evidence-based recommendations for management of the endocrine manifestations of this disorder

Measurements of Branching Fractions, Polarizations, and Direct CP-Violation Asymmetries in B→ρK∗ and B→f0(980)K∗ Decays

We report searches for B -meson decays to the charmless final states ρ K ∗ and f 0 ( 980 ) K ∗ with a sample of 232 × 10 6 B ¯¯¯ B pairs collected with the BABAR detector at the PEP-II e + e − collider. We measure in units of 10 − 6 the following branching fractions, where the first error quoted is statistical and the second systematic, or upper limits are given at the 90% confidence level : B ( B + → ρ 0 K * + ) < 6.1 , B ( B + → ρ + K * 0 ) = 9.6 ± 1.7 ± 1.5 , B ( B 0 → ρ − K * + ) < 12.0 , B ( B 0 → ρ 0 K * 0 ) = 5.6 ± 0.9 ± 1.3 , B ( B + → f 0 ( 980 ) K * + ) = 5.2 ± 1.2 ± 0.5 , and B ( B 0 → f 0 ( 980 ) K * 0 ) < 4.3 . For the significant modes, we also measure the fraction of longitudinal polarization and the charge asymmetry: f L ( B + → ρ + K * 0 ) = 0.52 ± 0.10 ± 0.04 , f L ( B 0 → ρ 0 K * 0 ) = 0.57 ± 0.09 ± 0.08 , A C P ( B + → ρ + K * 0 ) = − 0.01 ± 0.16 ± 0.02 , A C P ( B 0 → ρ 0 K * 0 ) = 0.09 ± 0.19 ± 0.02 , and A C P ( B + → f 0 ( 980 ) K * + ) = − 0.34 ± 0.21 ± 0.03

Isolation and genotyping of Toxoplasma gondii from different areas in Gabon.

International audienc

Exploring the knowledge and attitudes of Cameroonian medical students towards global surgery: A web-based survey.

INTRODUCTION:Global surgery is a growing field studying the determinants of safe and affordable surgical care and advocating to gain the global health community's attention. In Cameroon, little is known about the level of knowledge and attitudes of students. Our survey aimed to describe the knowledge and attitudes of Cameroonian medical students towards global surgery. MATERIALS AND METHODS:We performed an anonymous online survey of final-year Cameroonian medical students. Mann-Whitney U test and Spearman correlation analysis were used for bivariate analysis, and the alpha value was set at 0.05. Odds ratios and their 95% confidence intervals were calculated. RESULTS:204 respondents with a mean age of 24.7 years (±2.0) participated in this study. 58.3% were male, 41.6% had previously heard or read about global surgery, 36.3% had taken part in a global surgery study, and 10.8% had attended a global surgery event. Mercy Ships was well known (46.5%), and most students believed that surgical interventions were more costly than medical treatments (75.0%). The mean score of the global surgery evaluation was 47.4% (±29.6%), and being able to recognize more global surgery organizations was correlated with having assumed multiple roles during global surgery studies (p = 0.008) and identifying more global surgery indicators (p = 0.04). Workforce, infrastructure, and funding were highlighted as the top priorities for the development of global surgery in Cameroon. CONCLUSION:Medical students are conscious of the importance of surgical care. They lack the opportunities to nurture their interest and should be taught global surgery concepts and skills