This study examines hospitalizations and deaths associated with the SARS-CoV-2 Omicron variant compared with matched patients infected with the Delta variant.
AbstractObjectiveTo estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death).DesignTest negative design ...study.SettingOntario, Canada between 14 December 2020 and 19 April 2021.Participants324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2.InterventionsBNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine.Main outcome measuresLaboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes.ResultsOf 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation.ConclusionsTwo doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.
Unperturbed fetal development is essential for future health of an individual. Previous studies have linked diseases of aging to harmful alterations that happen during fetal development. Given the ...significant long‐term impact that intrauterine environment has on an individual's life, it was hypothesized that maternal stress during pregnancy will have negative effects on the offspring's bone density and cross‐sectional area. To test this, twenty‐eight female and seven male Wistar rats (Rattus norvegicus) were purchased and bred to produce 176 offspring. During pregnancy, dams were randomly divided into four groups (n=7, per group) and immobilization stress induced as follows; Group 1 (GW1): immobilization stress on days 1–7 of pregnancy, Group 2 (GW2): on days 8–14, Group 3 (GW3): on days 15–21, Group 4 (Controls): left undisturbed. Maternal cortisol hormone, food intake, and weight gain were monitored during pregnancy. Pups were raised under normal laboratory conditions and sacrificed at ages: 4, 8, 12, and 16 weeks to determine the effect of prenatal stress. At necropsy, the femur was removed and preserved for image analysis.
Differences among groups were determined by T‐test or analysis of variance (ANOVA). P values ≤ 0.05 were considered significant. Cortisol hormone levels in controls were lower than those of stressed animals. Stressed dams consumed 12.5% less food per day compared to controls. Animals in GW1 and GW2 gained less weight during pregnancy but had larger litters than did GW3 or the control group. Offspring born to GW3 were heavier compared to all other groups. The femurs were scanned using the XCT Research SA+ peripheral Quantitative Computed Tomography (pQCT). Preliminary analysis of cortical bone shows the GW1 males as having a significantly lower cortical thickness compared to the controls at the age of 8, 12 and 16 weeks. The GW1 males also had a significantly lower periosteal perimeter and endosteal perimeter compared to controls at the age of 8 weeks. There was no significant difference in cortical thickness, periosteal perimeter and endosteal perimeter of females. This preliminary analysis shows that bone development in males was significantly impacted when fetuses in this study were exposed to high levels of cortisol in‐utero during the first week of gestation. Analysis of the remaining data is ongoing.
IMPORTANCE: As a result of low numbers of pediatric cases early in the COVID-19 pandemic, pediatric household transmission of SARS-CoV-2 remains an understudied topic. OBJECTIVE: To determine whether ...there are differences in the odds of household transmission by younger children compared with older children. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study took place between June 1 and December 31, 2020, in Ontario, Canada. Private households in which the index case individual of laboratory-confirmed SARS-CoV-2 infection was younger than 18 years were included. Individuals were excluded if they resided in apartments missing suite information, in households with multiple index cases, or in households where the age of the index case individual was missing. EXPOSURES: Age group of pediatric index cases categorized as 0 to 3, 4 to 8, 9 to 13, and 14 to 17 years. MAIN OUTCOMES AND MEASURES: Household transmission, defined as households where at least 1 secondary case occurred 1 to 14 days after the pediatric index case. RESULTS: A total of 6280 households had pediatric index cases, and 1717 households (27.3%) experienced secondary transmission. The mean (SD) age of pediatric index case individuals was 10.7 (5.1) years and 2863 (45.6%) were female individuals. Children aged 0 to 3 years had the highest odds of transmitting SARS-CoV-2 to household contacts compared with children aged 14 to 17 years (odds ratio, 1.43; 95% CI, 1.17-1.75). This association was similarly observed in sensitivity analyses defining secondary cases as 2 to 14 days or 4 to 14 days after the index case and stratified analyses by presence of symptoms, association with a school/childcare outbreak, or school/childcare reopening. Children aged 4 to 8 years and 9 to 13 years also had increased odds of transmission (aged 4-8 years: odds ratio, 1.40; 95% CI, 1.18-1.67; aged 9-13 years: odds ratio, 1.13; 95% CI, 0.97-1.32). CONCLUSIONS AND RELEVANCE: This study suggests that younger children may be more likely to transmit SARS-CoV-2 infection compared with older children, and the highest odds of transmission was observed for children aged 0 to 3 years. Differential infectivity of pediatric age groups has implications for infection prevention within households, as well as schools/childcare, to minimize risk of household secondary transmission. Additional population-based studies are required to establish the risk of transmission by younger pediatric index cases.
This study determined the spread of the B.1.1.7 SARs-CoV-2 variant in the Greater Toronto Area over 4 months by tracking S-gene target failure as marker.
The US Food and Drug Administration (FDA) Amendments Act of 2007 authorized the FDA to require risk evaluation and mitigation strategy (REMS) programs for drugs with important safety concerns. REMS ...can have elements to assure safe use (ETASU), such as patient registries, dispensing restrictions, and physician training and certification requirements. We aimed to understand physician experiences with and perceptions of a selection of ETASU REMS.
Physicians prescribing 1 of 4 ETASU REMS-covered drugs: natalizumab, riociguat, sodium oxybate, and vigabatrin.
Descriptive phenomenological study based on semi-structured phone interviews.
Qualitative content analysis to summarize physician responses to open-ended questions.
Of 31 physicians (14 female), 6 prescribed riociguat, 6 vigabatrin, 7 sodium oxybate, and 12 natalizumab (5 for Crohn's disease, 7 for multiple sclerosis), most demonstrated good understanding of the rationale for and requirements of the ETASU REMS but believed that the programs had limited effect on clinical practice. Some physicians reported that the ETASU REMS made them more comfortable with prescribing covered drugs due to heightened oversight, facilitated discussions about treatment, and were likely more beneficial for non-specialists. Concerns were raised about the administrative effort needed to comply with the programs and the potential misuse of patient health information transmitted to manufacturers.
Physicians are generally aware of ETASU REMS and get reassurance from the additional oversight, but the programs can be better integrated into clinical workflows and can be designed to better protect patient health information.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Numerous studies in humans link a nonsynonymous genetic polymorphism (I148M) in adiponutrin (ADPN) to various forms of fatty liver disease and liver cirrhosis. Despite its high clinical relevance, ...the molecular function of ADPN and the mechanism by which I148M variant affects hepatic metabolism are unclear. Here we show that ADPN promotes cellular lipid synthesis by converting lysophosphatidic acid (LPA) into phosphatidic acid. The ADPN-catalyzed LPA acyltransferase (LPAAT) reaction is specific for LPA and long-chain acyl-CoAs. Wild-type mice receiving a high-sucrose diet exhibit substantial upregulation of Adpn in the liver and a concomitant increase in LPAAT activity. In Adpn-deficient mice, this diet-induced increase in hepatic LPAAT activity is reduced. Notably, the I148M variant of human ADPN exhibits increased LPAAT activity leading to increased cellular lipid accumulation. This gain of function provides a plausible biochemical mechanism for the development of liver steatosis in subjects carrying the I148M variant.
► Adiponutrin acts as a lysophosphatidic acid acyltransferase ► I148M variant of ADPN represents a gain-of-function mutation ► Adpn-deficient mice on high-sucrose diet exhibit diminished hepatic LPAAT activity ► Overexpression of I148M-ADPN causes increased FFA incorporation into glycerolipids
Candida auris
is an emerging infectious agent with limited antimicrobial susceptibilities. An outbreak was identified in a neurosciences ICU in the United Kingdom and was linked to reusable ...temperature probes.
•As well as embryotrophic cytokines, the maternal reproductive tract can secrete embryotoxic cytokines including TNF, TRAIL and IFNG.•Embryotoxic cytokines can be elevated in reproductive and ...systemic inflammatory conditions including infection, diabetes, obesity, PCOS and endometriosis.•Embryotoxic cytokines may contribute to unexplained infertility, as well as embryonic programming of fetal growth restriction and metabolic disorder in offspring.
Cytokines in the reproductive tract environment at conception mediate a dialogue between the embryo and maternal tissues to profoundly influence embryo development and implantation success. Through effects on gene expression and the cell stress response, cytokines elicit an epigenetic impact with consequences for placental development and fetal growth, which in turn affect metabolic phenotype and long-term health of offspring. There is substantial evidence demonstrating that pro-survival cytokines, such as GM-CSF, CSF1, LIF, HB-EGF and IGFII, support embryos to develop optimally. Less attention has been paid to cytokines that adversely impact embryo development, including the pro-inflammatory cytokines TNF, TRAIL and IFNG. These agents elicit cell stress, impair cell survival and retard blastocyst development, and at sufficiently high concentrations, can cause embryo demise. Experiments in mice suggest these so-called ‘embryotoxic’ cytokines can harm embryos through pro-apoptotic and adverse programming effects, as well as indirectly suppressing uterine receptivity through the maternal immune response. Embryotrophic factors may mitigate against and protect from these adverse effects. Thus, the balance between embryotrophic and embryotoxic cytokines can impart effects on embryo development and implantation, and has the potential to contribute to endometrial ‘biosensor’ function to mediate embryo selection. Embryotoxic cytokines can be elevated in plasma and reproductive tract tissues in inflammatory conditions including infection, diabetes, obesity, PCOS and endometriosis. Studies are therefore warranted to investigate whether excessive embryotoxic cytokines contribute to infertility and recurrent implantation failure in women, and compromised reproductive performance in livestock animals.
Protecting healthcare workers (HCWs) from Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a priority to maintain a safe and functioning healthcare system. Our objective was to ...describe and compare the epidemiology, clinical characteristics, and lethality of SARS-CoV-2 infections among HCWs compared to non-HCWs.
Using reportable disease data at Public Health Ontario, we conducted a population-based cross-sectional study comparing demographic, exposure, and clinical variables between HCWs and non-HCWs with SARS-CoV-2 infections as of 30 September 2020. We calculated rates of infections over time and determined the frequency of within household transmissions using natural language processing based on residential address. We evaluated the risk of death using a multivariable logistic regression model adjusting for age, sex, comorbidities, symptoms, and long-term care home exposure.
There were 7,050 (12.5%) HCW SARS-CoV-2 infections in Ontario, Canada, of whom 24.9% were nurses, 2.3% were physicians, and the remaining 72.8% other specialties, including personal support workers. Overall HCWs had an infection rate of 1,276 per 100,000 compared to non-HCWs of 346 per 100,000 (3.7 times higher). This difference decreased from a 7 times higher rate in April to no difference in September 2020. Twenty-six percent of HCWs had a household member with SARS-CoV-2 infection; 6.8% were probable acquisitions, 12.3% secondary transmissions, and 6.9% unknown direction of transmission. Death among HCWs was 0.2% compared to 6.1% of non-HCWs. The risk of death in HCWs remained significantly lower than non-HCWs after adjustment (adjusted odds ratio 0.09; 95%CI 0.05-0.17).
HCWs represent a disproportionate number of diagnosed SARS-CoV-2 infections in Ontario, however this discrepancy is at least partially explained by limitations in testing earlier in the pandemic for non-HCWs. We observed a low risk of death in HCWs which could not be completely explained by other factors.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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