15 research outputs found

    Structure and dynamics of the Gulf of Maine humpback whale population

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    Population structure and vital rates of Gulf of Maine (GOM) humpback whales, Megaptera novaeangliae, were studied by a combination of longitudinal data, region-wide surveys and modern mark-recapture statistical methods. Demography and rates of exchange were examined among six GOM areas. Juveniles and females were preferentially encountered in southern GOM habitats, including at the Studds Stellwagen Bank National Marine Sanctuary (SBNMS). Multi-state modelling also revealed unequal probabilities of movement between areas that was not explained by inter-area distance, adjacency, whale density or dominant prey type. Aerial surveys and photo-identification data indicated that the population was likely closed to migration between June and September. Otherwise, seasonal trends in population composition were consistent the demographically staggered migration reported in other oceans. Over-wintering occurred,but there was little evidence that a significant number of humpback whales failed to undertake or complete migration each year. Vital rates varied with sex, age and time. Juveniles exhibited lower and more variable survival than adults and so were a potential source of downward bias in “non-calf” survival estimates. Males exhibited higher survival than females and achieved maximal survival at age five, the estimated age at male puberty. By contrast, females did not reach peak survival until the current average age at first birth (8.78 years, s = 2.33). The latter was significantly higher than previous estimates and females that recruited by age seven had a lower likelihood of subsequent survival than those that recruited late. Costs of reproduction persisted into adulthood, with breeders exhibiting lower survival than nonbreeders. Calves born during years of low fecundity exhibited lower survival than those born when fecundity was high, possibly due to lower maternal investment. Costs of reproduction have not previously been described in cetaceans, but are consistent with the risks potentially associated with capital breeding

    'Septrin psychosis' among renal transplant patients with Pneumocystis jirovecii pneumonia

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    Objectives To report on the temporal relationship between administration of trimethoprim/sulfamethoxazole to medically immunosuppressed HIV-negative renal patients with Pneumocystis jirovecii pneumonia (PCP) and the development of an acute psychosis. Methods We investigated a retrospective case series of renal transplant and immunosuppressed patients with PCP within an ongoing outbreak in the northwest of England since 2009. Four patients with PCP developed psychosis following treatment with trimethoprim/sulfamethoxazole. Results Four of twenty patients developed acute psychoses following administration of trimethoprim/sulfamethoxazole, including one accidental re-challenge. Symptoms resolved within 24 h of changing the therapy. The striking temporal relationship between the initiation and discontinuation of the drug and the behavioural changes suggests a causal relationship. Conclusions With increasing solid organ transplantation and the use of immunosuppressants, vigilance regarding trimethoprim/sulfamethoxazole dose modification is required and the routine use of therapeutic drug monitoring should be considered</p

    Comparative evaluation of ten lateral flow immunoassays to detect SARS-CoV-2 antibodies

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    Background: Rapid mobilisation from industry and academia following the outbreak of the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), led to the development and availability of SARS-CoV-2 lateral flow immunoassays (LFAs). High quality LFAs are urgently needed at the point of care to add to currently available diagnostic tools. In this study, we provide evaluation data for ten LFAs suitable for use at the point of care. Methods: : COVID-19 positive patients (N=45), confirmed by reverse transcription – quantitative polymerase chain reaction (RT-qPCR), were recruited through the International Severe Acute Respiratory and Emerging Infection Consortium - Coronavirus Clinical Characterisation Consortium (ISARIC4C) study. Sera collected from patients with influenza A (N=20), tuberculosis (N=5), individuals with previous flavivirus exposure (N=21), and healthy sera (N=4), collected pre-pandemic, were used as negative controls. Ten LFAs manufactured or distributed by ASBT Holdings Ltd, Cellex, Fortress Diagnostics, Nantong Egens Biotechnology, Mologic, NG Biotech, Nal von Minden and Suzhou Herui BioMed Co. were evaluated. Results: : Compared to RT-qPCR, sensitivity of LFAs ranged from 87.0-95.7%. Specificity against pre-pandemic controls ranged between 92.0-100%. Compared to IgG ELISA, sensitivity and specificity ranged between 90.5-100% and 93.2-100%, respectively. Percentage agreement between LFAs and IgG ELISA ranged from 89.6-92.7%. Inter-test agreement between LFAs and IgG ELISA ranged between kappa=0.792-0.854. Conclusions: : LFAs may serve as a useful tool for rapid confirmation of ongoing or previous infection in conjunction with clinical suspicion of COVID-19 in patients attending hospital. Impartial validation prior to commercial sale provides users with data that can inform best use settings

    Absenteeism among public health nurses : does commitment matter?

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    Includes bibliographical references (leaves 69-73)This study explored the relationship between absenteeism and commitment (affective, continuance and normative commitment) as directed towards the organisation, co-workers and the nursing profession. Job satisfaction, job involvement, career stage and the absence culture were examined as moderators of the relationship between absenteeism and commitment. The sample comprised of 227 public sector nurses (54% response rate) from 11 day clinics and hospitals within the Western Cape Metropolitan District Health Services of South Africa. Affective, continuance and normative commitment to the organisation were not directly related to absenteeism, although interactions between these commitment components were significant predictors of absenteeism. Affective commitment to co-workers did not significantly explain absenteeism. However, affective commitment to the nursing profession explained significant variance in nurse absenteeism both directly and through the moderation effects of the absence culture of the workplace and the profession. Job satisfaction, job involvement and career stage of the nurses did not moderate the absenteeism-commitment relationship. The contributions of the study are discussed and recommendations for future research are made

    Risk stratification of patients admitted to hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: development and validation of the 4C Mortality Score

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    Objectives To develop and validate a pragmatic risk score to predict mortality for patients admitted to hospital with covid-19. Design Prospective observational cohort study: ISARIC WHO CCP-UK study (ISARIC Coronavirus Clinical Characterisation Consortium [4C]). Model training was performed on a cohort of patients recruited between 6 February and 20 May 2020, with validation conducted on a second cohort of patients recruited between 21 May and 29 June 2020. Setting 260 hospitals across England, Scotland, and Wales. Participants Adult patients (≥18 years) admitted to hospital with covid-19 admitted at least four weeks before final data extraction. Main outcome measures In-hospital mortality. Results There were 34 692 patients included in the derivation dataset (mortality rate 31.7%) and 22 454 in the validation dataset (mortality 31.5%). The final 4C Mortality Score included eight variables readily available at initial hospital assessment: age, sex, number of comorbidities, respiratory rate, peripheral oxygen saturation, level of consciousness, urea, and C-reactive protein (score range 0-21 points). The 4C risk stratification score demonstrated high discrimination for mortality (derivation cohort: AUROC 0.79; 95% CI 0.78 − 0.79; validation cohort 0.78, 0.77-0.79) with excellent calibration (slope = 1.0). Patients with a score ≥15 (n = 2310, 17.4%) had a 67% mortality (i.e., positive predictive value 67%) compared with 1.0% mortality for those with a score ≤3 (n = 918, 7%; negative predictive value 99%). Discriminatory performance was higher than 15 pre-existing risk stratification scores (AUROC range 0.60-0.76), with scores developed in other covid-19 cohorts often performing poorly (range 0.63-0.73). Conclusions We have developed and validated an easy-to-use risk stratification score based on commonly available parameters at hospital presentation. This outperformed existing scores, demonstrated utility to directly inform clinical decision making, and can be used to stratify inpatients with covid-19 into different management groups. The 4C Mortality Score may help clinicians identify patients with covid-19 at high risk of dying during current and subsequent waves of the pandemic. Study registration ISRCTN6672626

    Prospective validation of the 4C prognostic models for adults hospitalised with COVID-19 using the ISARIC WHO Clinical Characterisation Protocol

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    Purpose To prospectively validate two risk scores to predict mortality (4C Mortality) and in-hospital deterioration (4C Deterioration) among adults hospitalised with COVID-19. Methods Prospective observational cohort study of adults (age ≥18 years) with confirmed or highly suspected COVID-19 recruited into the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) WHO Clinical Characterisation Protocol UK (CCP-UK) study in 306 hospitals across England, Scotland and Wales. Patients were recruited between 27 August 2020 and 17 February 2021, with at least 4 weeks follow-up before final data extraction. The main outcome measures were discrimination and calibration of models for in-hospital deterioration (defined as any requirement of ventilatory support or critical care, or death) and mortality, incorporating predefined subgroups. Results 76 588 participants were included, of whom 27 352 (37.4%) deteriorated and 12 581 (17.4%) died. Both the 4C Mortality (0.78 (0.77 to 0.78)) and 4C Deterioration scores (pooled C-statistic 0.76 (95% CI 0.75 to 0.77)) demonstrated consistent discrimination across all nine National Health Service regions, with similar performance metrics to the original validation cohorts. Calibration remained stable (4C Mortality: pooled slope 1.09, pooled calibration-in-the-large 0.12; 4C Deterioration: 1.00, –0.04), with no need for temporal recalibration during the second UK pandemic wave of hospital admissions. Conclusion Both 4C risk stratification models demonstrate consistent performance to predict clinical deterioration and mortality in a large prospective second wave validation cohort of UK patients. Despite recent advances in the treatment and management of adults hospitalised with COVID-19, both scores can continue to inform clinical decision making

    Delayed Mucosal Antiviral Responses Despite Robust Peripheral Inflammation in Fatal COVID-19

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    Background. While inflammatory and immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in peripheral blood are extensively described, responses at the upper respiratory mucosal site of initial infection are relatively poorly defined. We sought to identify mucosal cytokine/chemokine signatures that distinguished coronavirus disease 2019 (COVID-19) severity categories, and relate these to disease progression and peripheral inflammation. Methods. We measured 35 cytokines and chemokines in nasal samples from 274 patients hospitalized with COVID-19. Analysis considered the timing of sampling during disease, as either the early (0-5 days after symptom onset) or late (6-20 days after symptom onset) phase. Results. Patients that survived severe COVID-19 showed interferon (IFN)-dominated mucosal immune responses (IFN-γ, CXCL10, and CXCL13) early in infection. These early mucosal responses were absent in patients who would progress to fatal disease despite equivalent SARS-CoV-2 viral load. Mucosal inflammation in later disease was dominated by interleukin 2 (IL-2), IL-10, IFN-γ, and IL-12p70, which scaled with severity but did not differentiate patients who would survive or succumb to disease. Cytokines and chemokines in the mucosa showed distinctions from responses evident in the peripheral blood, particularly during fatal disease. Conclusions. Defective early mucosal antiviral responses anticipate fatal COVID-19 but are not associated with viral load. Early mucosal immune responses may define the trajectory of severe COVID-19

    Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

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    One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

    Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission

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    Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11–1.70] ng/mL vs 0.24 [0.10–0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51–.60])
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