Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study

This article from the UK Obstetric Surveillance System SARS-CoV-2 Infection in Pregnancy Collaborative Group was published online in the BMJ (Clinical research ed.) at the end of June 2020.
Objectives:  To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants.
Design:  Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS).
Setting:  All 194 obstetric units in the UK.
Participants:  427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020.
Main Outcome Measures:  Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission.
Results:  The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth.
Conclusions:  Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation.
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Incidence, clinical outcomes, and transmission dynamics of severe coronavirus disease 2019 in California and Washington: prospective cohort study.

This article by Lewnard and colleagues was first published in the BMJ in May 2020.
Objective:  To understand the epidemiology and burden of severe coronavirus disease 2019 (covid-19) during the first epidemic wave on the west coast of the United States.
Design:  Prospective cohort study.
Setting:  Kaiser Permanente integrated healthcare delivery systems serving populations in northern California, southern California, and Washington state.
Participants:  1840 people with a first acute hospital admission for confirmed covid-19 by 22 April 2020, among 9 596 321 healthcare plan enrollees. Analyses of hospital length of stay and clinical outcomes included 1328 people admitted by 9 April 2020 (534 in northern California, 711 in southern California, and 83 in Washington).
Main Outcome Measures:  Cumulative incidence of first acute hospital admission for confirmed covid-19, and subsequent probabilities of admission to an intensive care unit (ICU) and mortality, as well as duration of hospital stay and ICU stay. The effective reproduction number (RE ) describing transmission dynamics was estimated for each region.
Results:  As of 22 April 2020, cumulative incidences of a first acute hospital admission for covid-19 were 15.6 per 100 000 cohort members in northern California, 23.3 per 100 000 in southern California, and 14.7 per 100 000 in Washington. Accounting for censoring of incomplete hospital stays among those admitted by 9 April 2020, the estimated median duration of stay among survivors was 9.3 days (with 95% staying 0.8 to 32.9 days) and among non-survivors was 12.7 days (1.6 to 37.7 days). The censoring adjusted probability of ICU admission for male patients was 48.5% (95% confidence interval 41.8% to 56.3%) and for female patients was 32.0% (26.6% to 38.4%). For patients requiring critical care, the median duration of ICU stay was 10.6 days (with 95% staying 1.3 to 30.8 days). The censoring adjusted case fatality ratio was 23.5% (95% confidence interval 19.6% to 28.2%) among male inpatients and 14.9% (11.8% to 18.6%) among female inpatients; mortality risk increased with age for both male and female patients. Reductions in RE were identified over the study period within each region.
Conclusions:  Among residents of California and Washington state enrolled in Kaiser Permanente healthcare plans who were admitted to hospital with covid-19, the probabilities of ICU admission, of long hospital stay, and of mortality were identified to be high. Incidence rates of new hospital admissions have stabilized or declined in conjunction with implementation of social distancing interventions.
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Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study

This article by Docherty and other members of the ISARIC4C investigators group was first published in BMJ during May 2020.
Objective:  To characterise the clinical features of patients admitted to hospital with coronavirus disease 2019 (covid-19) in the United Kingdom during the growth phase of the first wave of this outbreak who were enrolled in the International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) World Health Organization (WHO) Clinical Characterisation Protocol UK (CCP-UK) study, and to explore risk factors associated with mortality in hospital.
Design:  Prospective observational cohort study with rapid data gathering and near real time analysis.
Setting:  208 acute care hospitals in England, Wales, and Scotland between 6 February and 19 April 2020. A case report form developed by ISARIC and WHO was used to collect clinical data. A minimal follow-up time of two weeks (to 3 May 2020) allowed most patients to complete their hospital admission.
Participants:  20 133 hospital in-patients with covid-19.
Main Outcome Measures:  Admission to critical care (high dependency unit or intensive care unit) and mortality in hospital.
Results:  The median age of patients admitted to hospital with covid-19, or with a diagnosis of covid-19 made in hospital, was 73 years (interquartile range 58-82, range 0-104). More men were admitted than women (men 60%, n=12 068; women 40%, n=8065). The median duration of symptoms before admission was 4 days (interquartile range 1-8). The commonest co-morbidities were chronic cardiac disease (31%, 5469/17 702), uncomplicated diabetes (21%, 3650/17 599), non-asthmatic chronic pulmonary disease (18%, 3128/17 634), and chronic kidney disease (16%, 2830/17 506); 23% (4161/18 525) had no reported major comorbidity. Overall, 41% (8199/20 133) of patients were discharged alive, 26% (5165/20 133) died, and 34% (6769/20 133) continued to receive care at the reporting date. 17% (3001/18 183) required admission to high dependency or intensive care units; of these, 28% (826/3001) were discharged alive, 32% (958/3001) died, and 41% (1217/3001) continued to receive care at the reporting date. Of those receiving mechanical ventilation, 17% (276/1658) were discharged alive, 37% (618/1658) died, and 46% (764/1658) remained in hospital. Increasing age, male sex, and comorbidities including chronic cardiac disease, non-asthmatic chronic pulmonary disease, chronic kidney disease, liver disease and obesity were associated with higher mortality in hospital.
Conclusions:  ISARIC WHO CCP-UK is a large prospective cohort study of patients in hospital with covid-19. The study continues to enrol at the time of this report. In study participants, mortality was high, independent risk factors were increasing age, male sex, and chronic comorbidity, including obesity. This study has shown the importance of pandemic preparedness and the need to maintain readiness to launch research studies in response to outbreaks.
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Low serum albumin levels and new-onset atrial fibrillation in the ICU a prospective cohort study

This research by van Beek et others was published on line in the Journal of Critical Care during November 2019.
Purpose:  The aim was to determine if a low serum albumin (SA) level was associated with the occurrence of new onset atrial fibrillation (NOAF) during the first 48 h of intensive care unit (ICU) admission.
Methods:  Overall, 97 patients admitted to the ICU were included in this prospective study. NOAF during the first 48 h was defined as irregularity and absence of p-waves on the continuous electrocardiogram, lasting longer than 2 min. Association were analysed using logistic regression with correction for confounding variables in multivariable analysis.
Results:  The incidence of NOAF during the first 48 h of ICU admission was 18%. SA levels at ICU admission were significantly associated with NOAF after correction for confounders (odds ratio [OR] 0.86, 95%CI 0.77–0.97, p = .010). SA levels were also significantly associated with the number of episodes of NOAF in multivariate analysis (−0.09 episodes, 95%CI [−0.15/−0.04], p = .001), but not with the presence of sinus rhythm at 48 h (OR 1.05, 95%CI [0.93–1.12], p = .46).
Conclusion:  In this small hypothesis generating study low levels of SA were associated with the occurrence of NOAF. It remains to be shown if increasing SA levels lowers the incidence of NOAF.
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Gender differences in mortality and quality of life after septic shock: A post-hoc analysis of the ARISE study

This article by Luethi and others was published online in the Journal of Critical Care during November 2019.
Purpose:  To assess the impact of gender and pre-menopausal state on short- and long-term outcomes in patients with septic shock.
Material and methods:  Cohort study of the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial, an international randomized controlled trial comparing early goal-directed therapy (EGDT) to usual care in patients with early septic shock, conducted between October 2008 and April 2014. The primary exposure in this analysis was legal gender and the secondary exposure was pre-menopausal state defined by chronological age (≤ 50 years).
Results:  641 (40.3%) of all 1591 ARISE trial participants in the intention-to-treat population were females and overall, 337 (21.2%) (146 females) patients were 50 years of age or younger. After risk-adjustment, we could not identify any survival benefit for female patients at day 90 in the younger (≤50 years) (adjusted Odds Ratio (aOR): 0.91 (0.46–1.89), p = .85) nor in the older (>50 years) age-group (aOR: 1.10 (0.81–1.49), p = .56). Similarly, there was no gender-difference in ICU, hospital, 1-year mortality nor quality of life measures.
Conclusions:  This post-hoc analysis of a large multi-center trial in early septic shock has shown no short- or long-term survival effect for women overall as well as in the pre-menopausal age-group.
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Association of negative fluid balance during the de-escalation phase of sepsis management on mortality: A cohort study

This article by Dhondup and others was published online in the Journal of Critical Care during October 2019.
Purpose:  We aimed to evaluate the impact of negative fluid balance during the fluid de-escalation phase of sepsis management.
Material and methods:  This is a historical cohort study of adult intensive care units (ICU) patients with septic shock and severe sepsis in a quaternary medical center, from January 2007 through December 2009. We used regression modeling to assess the impact of negative volume balance on mortality after adjustments for age, comorbidities, and illness severity.
Results:  Among 633 enrolled patients, 387 patients reached negative fluid balance who in comparison with others had a lower 90-day mortality rate (36% vs. 44%; P = .048), despite higher severity of illness. Each 1-L negative daily fluid balance was associated with reduced ICU, hospital, 90-day and 1-year mortality (hazard ratio [HR] 0.39[95%CI, 0.28–0.57], 0.76[95%CI, 0.63–0.94], 0.69[95%CI, 0.59–0.81], 0.67 [0.58–0.78], respectively; P < .05). This protective effect of negative volume balance was maintained when cumulative ICU fluid balance was utilized.
Conclusions:  There is not only a significant association between outcomes of patients who were resuscitated for sepsis and achieving negative fluid balance, but also the amount of daily or cumulative negative fluid balance is associated with lower mortality of these patients. Prospective clinical trials are needed to validate this finding.
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Intensive care unit occupancy and premature discharge rates: A cohort study assessing the reporting of quality indicators

This paper by Blayney and colleagues was first published online in the Journal of Critical Care during October 2019.
Purpose:  ICU occupancy fluctuates. High levels may disadvantage patients. Currently, occupancy is benchmarked annually which may inaccurately reflect strained units. Outcomes potentially sensitive to occupancy include premature (early) ICU discharge and non-clinical transfer (NCT). This study assesses the association between daily occupancy and these outcomes, and evaluates benchmarking care across Scotland using daily occupancy.
Materials and methods:  Population: all Scottish ICU patients, 2006–2014. Exposure: bed occupancy per unit-day; Outcomes: proportion of early discharges and NCTs. Design: Retrospective cohort study. Outcome rates were calculated above various occupancy thresholds. Polynomial regression visualised associations, and inflection points between occupancy and outcomes. Spearman’s rho correlations between occupancy measures and outcomes were reported.
Results:  65,472 discharges occurred over 57,812 unit-days. 1954(3.0%) discharges were early; 429 (0.7%) were NCTs. Early discharge rates above 70%, 80% and 90% occupancy were 3.9%, 5.0% and 7.5% respectively. Occupancies at which outcome rates greatly increased were near 80% for early discharge, and 90% for NCT. Mean annual occupancy was not correlated with outcomes; annual proportion of days ≥90% occupancy correlated most strongly (early discharge rho = 0.46,p < .001; NCT rho = 0.31, p < .001).
Conclusions:  We demonstrate a clear association between daily ICU occupancy and early discharge/NCT. Daily occupancy may better benchmark care quality than mean annual occupancy.
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Association between acute kidney injury and neurological outcome or death at 6 months in out-of-hospital cardiac arrest: A prospective, multicenter, observational cohort study

This paper by Oh and colleagues was first published online in the Journal of Critical Care during August 2019.
Purpose:  This study aimed to evaluate the association between acute kidney injury (AKI) and 6 months neurological outcome after out-of-hospital cardiac arrest (OHCA).
Materials and methods:  Prospective multi-center observational cohort included adult OHCA patients treated with targeted temperature management (TTM) across 20 hospitals in the South Korea between October 2015 and October 2017. The diagnosis of AKI was made using the Kidney Disease: Improving Global Outcomes criteria. The outcome was neurological outcome at 6 months evaluated using the modified Rankin scale (MRS).
Results:  Among 5676 patients with OHCA, 583 patients were enrolled. AKI developed in 348 (60%) patients. Significantly more non-AKI patients had good neurological outcome at 6 months (MRS 0–3) than AKI patients (134/235 [57%] vs. 69/348 [20%], P < .001). AKI was associated with poor neurological outcome at six months in multivariate logistic regression analysis (adjusted odds ratio: 0.206 [95% confidence interval: 0.099–0.426], P < .001]). Cox regression analysis with time-varying covariate of AKI showed that patients with AKI had a higher risk of death than those without AKI (hazard ratio: 2.223; 95% confidence interval: 1.630–3.030, P < .001).
Conclusions:  AKI is associated with poor neurological outcome (MRS 4–6) at 6 months in OHCA patients treated with TTM.

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Intensive care use and mortality among patients with ST elevation myocardial infarction: retrospective cohort study.

This research by Valley and others was published in the BMJ in June 2019.
Objective:  To evaluate the effect of intensive care unit (ICU) admission on mortality among patients with ST elevation myocardial infarction (STEMI).
Design:  Retrospective cohort study.
Setting: 1727 acute care hospitals in the United States. Participants:  Medicare beneficiaries (aged 65 years or older) admitted with STEMI to either an ICU or a non-ICU unit (general/telemetry ward or intermediate care) between January 2014 and October 2015.
Main Outcome Measure:  30 day mortality. An instrumental variable analysis was done to account for confounding, using as an instrument the additional distance that a patient with STEMI would need to travel beyond the closest hospital to arrive at a hospital in the top quarter of ICU admission rates for STEMI.
Results:  The analysis included 109 375 patients admitted to hospital with STEMI. Hospitals in the top quarter of ICU admission rates admitted 85% or more of STEMI patients to an ICU. Among patients who received ICU care dependent on their proximity to a hospital in the top quarter of ICU admission rates, ICU admission was associated with lower 30 day mortality than non-ICU admission (absolute decrease 6.1 (95% confidence interval -11.9 to -0.3) percentage points). In a separate analysis among patients with non-STEMI, a group for whom evidence suggests that routine ICU care does not improve outcomes, ICU admission was not associated with differences in mortality (absolute increase 1.3 (-0.9 to 3.4) percentage points).
Conclusions:  ICU care for STEMI is associated with improved mortality among patients who could be treated in an ICU or non-ICU unit. An urgent need exists to identify which patients with STEMI benefit from ICU admission and what about ICU care is beneficial.
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Time of admission to intensive care unit, strained capacity, and mortality: A retrospective cohort study

This research by Cardoso and colleagues was published online in June 2019 in the Journal of Critical Care.
Purpose:  We sought to study the association between afterhours ICU admission and ICU mortality considering measures of strained ICU capacity.
Materials and methods:  Retrospective analysis of 4141 admissions to 2 ICUs in Lisbon, Portugal (06/2016–06/2018). Primary exposure was ICU admission on 20:00 h–07:59 h. Primary outcome was ICU mortality. Measures of strained ICU capacity were: bed occupancy rate ≥ 90% and cluster of ICU admissions 2 h before or following index admission.
Results:  There were 1581 (38.2%) afterhours ICU admissions. Median APACHE II score (19 vs. 20) was similar between patients admitted afterhours and others (P = .27). Patients admitted afterhours had higher crude ICU mortality (15.4% vs. 21.9%; P < .001), but similar adjusted ICU mortality (aOR [95%CI] = 1.15 [0.97–1.38]; P = .12). While bed occupancy rate ≥ 90% was more frequent in patients admitted afterhours (23.1% vs. 29.1%) or deceased in ICU (23.6% vs. 33.7%), cluster of ICU admissions was more frequent in patients admitted during daytime hours (75.2% vs. 58.9%) or that survived the ICU stay (70.1% vs. 63.9%; P ≤ .001 for all). These measures of strained ICU capacity were not associated with adjusted ICU mortality (P ≥ .10 for both).
Conclusions:  Afterhours ICU admission and measures of strained ICU capacity were associated with crude but not adjusted ICU mortality.
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