Intravenous methylprednisolone pulse therapy and the risk of in-hospital mortality among acute COVID-19 patients: Nationwide clinical cohort study.

BACKGROUND: Steroids are widely used to modulate the inflammatory reactions associated with coronavirus disease 2019 (COVID-19); however, the optimal upper limit dose of steroid use for acute COVID-19 care remains unclear and currently available data may suffer from a time-dependent bias of no effectiveness or reversed causation given the desperate situation of treatment during this pandemic. Accordingly, the aim of this study was to elucidate the impact of intravenous pulse therapy with methylprednisolone (500 mg or greater per day) on the risk of in-hospital mortality among patients with COVID-19 by controlling for time-dependent bias. METHODS: We performed a prospective cohort study with 67,348 hospitalised acute COVID-19 patients at 438 hospitals during 2020-2021 in Japan. The impact of intravenous methylprednisolone pulse therapy on the risk of in-hospital mortality was examined based on hazard ratios (HRs) and 95% confidence intervals (95% CIs), with stratification according to the status of invasive mechanical ventilation (iMV). Time-dependent bias was controlled for in a marginal structural model analysis, with reference to patients without methylprednisolone therapy. RESULTS: During the study period, 2400 patients died. In-hospital mortality rates of iMV-free patients without or with methylprednisolone pulse therapy were 2.3% and 19.5%, and the corresponding values for iMV-receiving patients were 24.7% and 28.6%, respectively. The marginal structural model analysis showed that intravenous pulse therapy with methylprednisolone was associated with a lower risk of in-hospital mortality among patients receiving-iMV (HR 0.59; 95% CI 0.52-0.68). In contrast, pulse therapy with methylprednisolone increased the risk of in-hospital mortality among iMV-free patients (HR 3.38; 95% CI 3.02-3.79). The benefits of pulse therapy for iMV-receiving patients were greater than in those treated with intermediate/higher doses (40-250 mg intravenously) of methylprednisolone (HR 0.80; 95% CI 0.71-0.89). CONCLUSION: The results of our study suggest that intravenous methylprednisolone showed dose-response efficiencies, and pulse therapy may benefit critically ill patients with acute COVID-19, such as those requiring iMV.

Long-term Weight Loss as a Predictor of Mortality in Hemodialysis Patients.

BACKGROUND: Serial weight decrease can be a prognostic predictor in chronic hemodialysis (HD) patients. We investigated the impact of long-term post-HD body weight (BW) changes on all-cause mortality among HD patients. METHODS: This longitudinal cohort study and post-hoc analysis evaluated participants of a previous randomized controlled trial conducted between 2006 and 2011 who were followed up until 2018. Weight change slopes were generated with repeated measurements every 6 months during the trial for patients having ≥5 BW measurements. Participants were categorized into four groups based on quartiles of weight change slopes; the median weight changes per 6 months were -1.02 kg, -0.25 kg, +0.26 kg, and +0.86 kg for first, second, third, and fourth quartile, respectively. Cox proportional hazard regression was used to evaluate differences in subsequent survival among the four groups. BW trajectories were plotted with a backward time-scale and multilevel regression analysis to visualize the difference in BW trajectories between survivors and non-survivors. RESULTS: Among the 461 patients, 404 were evaluated, and 168 (41.6%) died within a median follow-up period of 10.2 years. The Cox proportional hazard regression adjusted for covariates and baseline BW showed that a higher rate of weight loss was associated with higher mortality. The hazard ratios were 2.02 (95% confidence interval [CI], 1.28-3.20), 1.77 (95% CI, 1.10-2.85), 1.00 (reference), and 1.11 (95% CI, 0.67-1.83) for the first, second, third (reference), and fourth quartiles, respectively. BW trajectories revealed a significant decrease in BW in non-survivors. CONCLUSION: Weight loss elucidated via serial BW measurements every 6 months is significantly associated with higher mortality among HD patients.

Pre-Extubation Cuffed Tube Leak Test and Subsequent Post-Extubation Laryngeal Edema: Prospective, Single-Center Evaluation of PICU Patients.

OBJECTIVES: We performed our standard air leak, leak percentage, and cuff leak percentage tests in pediatric patients intubated with microcuff pediatric tracheal tubes (MPTTs) just before extubation. We examined the association between test findings and the subsequent occurrence of post-extubation laryngeal edema (PLE). DESIGN: Prospective, single-center, observational study. SETTING: PICU (June 1, 2020 to May 31, 2021). PATIENTS: Pediatric patients intubated and scheduled for extubation during the day shift in the PICU. INTERVENTIONS: Multiple pre-extubation leak tests were performed on each patient immediately before extubation. In our center, the standard leak test is positive if a leak is audible at 30 cm H 2 O applied pressure with the MPTT cuff deflated. Two other tests were calculated in the pressure control-assist control ventilator mode using the following formulas: leak percentage with deflated cuff = (inspiratory tidal volume [V t ]-expiratory V t ) × 100/inspiratory V t ; cuff leak percentage = (expiratory V t with inflated cuff-expiratory V t with deflated cuff) × 100/expiratory V t with inflated cuff. MEASUREMENTS AND MAIN RESULTS: The diagnostic criteria for PLE was made by at least two healthcare professionals and included upper airway stricture with stridor-requiring nebulized epinephrine. Eighty-five pediatric patients (< 15 yr) who had been intubated for at least 12 hours using the MPTT were included. Positive rates for the standard leak, leak percentage (cutoff 10%), and cuff leak percentage (cutoff 10%) tests were 0.27, 0.20, and 0.64, respectively. The standard leak, leak percentage, and cuff leak tests showed sensitivities of 0.36, 0.27, and 0.55, respectively; and specificities of 0.74, 0.81, and 0.35, respectively. PLE occurred in 11 of 85 patients (13%), and there were no instances of needing reintubation. CONCLUSIONS: The pre-extubation leak tests in current practice for intubated pediatric patients in the PICU all lack diagnostic accuracy for PLE.

Association between hospital internal medicine physician workforce and patient admissions during the COVID-19 pandemic in Japan.

BACKGROUND: Hospital physician workforce in Japan is the lowest among developed countries. Many patients with novel coronavirus disease 2019 (COVID-19) with high risk of mortality could not be hospitalized during case surges in Japan and only about 5% of total acute care beds were used as COVID-19 beds nationwide. However, the relationship between the number of hospital physicians and patient admissions remains unclear. Thus, we aimed to evaluate this relationship in areas with the highest incidences during the surges. METHODS: Data collection was performed for teaching hospitals accredited with the specialty of internal medicine in three prefectures which experienced the highest COVID-19 incidences in Japan (Tokyo, Osaka, Okinawa). Association was examined between the number of full-time physicians (internal medicine staff physicians and residents) and admissions of internal medicine patients through ambulance transport from April 2020 to March 2021. Analysis was conducted separately for community hospitals and university hospitals because the latter have roles as research institutions in Japan. Community hospitals included private, public, and semi-public hospitals. RESULTS: Of 117 teaching hospitals in three prefectures, data from 108 teaching hospitals (83 community hospitals and 25 university hospitals) were available. A total of 102,400 internal medicine patients were admitted to these hospitals during the one-year period. Private hospitals received the greatest mean number of patient admissions (290 per 100 beds), followed by public hospitals (227) and semi-public hospitals (201), and university hospitals (94). Among community hospitals, a higher number of resident physicians per 100 beds was significantly associated with a greater number of patient admissions per 100 beds with beta coefficient of 11.6 (95% CI, 1.5 to 21.2, p = 0.025) admissions by one physician increase per 100 beds. There was no such association among university hospitals. CONCLUSIONS: Community hospitals with many resident physicians accepted more internal medicine admissions through ambulance transport during the COVID-19 pandemic. An effective policy to counter physician shortage in hospitals in Japan may be to increase internal medicine resident physicians among community hospitals to save more lives.

Risk Factors of Preterm Birth in Okinawa Prefecture, the Southernmost Island Prefecture of Japan.

OBJECTIVES: A high rate of preterm birth has been reported in Okinawa Prefecture, the southernmost island prefecture of Japan. Hence, this study aimed to identify the risk factors for preterm birth in this prefecture. METHODS: This retrospective study included data from January 2013 to December 2019 from three facilities in Okinawa Prefecture. Of 13,468 cases of preterm birth at ≥ 22 weeks of gestation, 11,868 were included in this study. Stillbirth and multiparity cases were excluded. First, we compared the overall preterm and full-term birth groups by categorizing the patient background, obstetric, and fetal risk factors. Further, we categorized preterm births into three groups (22-27, 28-33, and 34-36 weeks of gestation) and examined patient background factors to identify potential risk factors for the occurrence of preterm birth in each group. RESULTS: Preterm births accounted for 21.2% (2,521 cases) of all cases, with the rates of 2.6% (317 cases), 6.7% (800 cases), and 11.8% (1,404 cases) at 22-27, 28-33, and 34-36 weeks of gestation, respectively. To prevent preterm birth in Okinawa Prefecture, the present study specifically focused on patient background characteristics. In the multinomial logistic regression, the risk factors for preterm birth at 22-27 weeks of gestation were previous preterm birth (P < 0.0001) and lower age (P = 0.026); at 28-33 weeks of gestation, the risk factors were previous preterm birth (P < 0.0001) and history of cervical conization (P = 0.009); and at 34-36 weeks of gestation, only previous preterm birth (P < 0.0001) was a risk factor. CONCLUSIONS FOR PRACTICE: Previous preterm birth, younger age, and history of cervical conization were risk factors for Preterm birth in Okinawa. To reduce premature births in Okinawa Prefecture, it is important to pick up women with these risk factors and provide them with appropriate guidance and education on an ongoing basis.

Predictors of Survival in Chronic Hemodialysis Patients: A 10-Year Longitudinal Follow-Up Analysis.

BACKGROUND: Risk factors of mortality in chronic hemodialysis patients have not yet been sufficiently evaluated. In particular, chronological transits and interactions of the impact of risk factors have rarely been described. METHODS: This study is a post hoc analysis of the participants in the Olme-sartan Clinical Trial in Okinawan Patients under OKIDS (OCTOPUS) study conducted between June 2006 and June 2011. We additionally followed up on the prognosis of the participants until July 31, 2018. Standardized univariable and multivariable Cox regression analyses were used to evaluate the influences of the participants' baseline characteristics on all-cause mortality. We also evaluated chronological changes in the impacts of risk factors, interactions among predictors, and the influence of missing values using sensitivity analyses. RESULTS: Of the 469 original trial participants, 461 participants were evaluated. The median time of follow-up was 10.2 years. A total of 211 (45.8%) participants were deceased. The leading causes of death were infection (n = 72, 34.1%) and cardiovascular disease (n = 66, 31.3%). Univariate and multivariate Cox regression analyses revealed that the impact of diabetes mellitus, history of coronary intervention, and hypoalbuminemia were significant risk factors for mortality during the whole follow-up period. During the early follow-up period (≤3 years), standardized univariate Cox regression analyses revealed that history of amputation (hazard ratio [HR] = 4.61, p < 0.001), lower dry weight, higher cardiothoracic ratio, and lower potassium levels were statistically significant risks. In those who survived for longer than 3 years, a history of stroke (HR = 1.73, p = 0.006), higher systolic blood pressure, lower serum sodium levels, and higher levels of hemoglobin, and serum phosphate were significant risks. We also observed a stable interaction between the impacts of serum phosphate and albumin on all-cause mortality. CONCLUSION: In chronic hemodialysis patients, targets to improve the short-term prognosis and long-term prognosis are not equivalent. Hyperphosphatemia was a significant risk factor for the all-cause mortality among patients with normal serum albumin levels but not among patients with compromised albumin levels.

The association between frailty and chronic kidney disease; cross-sectional analysis of the Nambu Cohort Study.

BACKGROUND: Both frailty and chronic kidney disease (CKD) increase with age and share many similarities. Many studies have demonstrated an association between frailty and chronic kidney disease (CKD), but an association with dipstick proteinuria is limited. METHODS: This is the cross-sectional analysis of the Nambu Cohort Study at the beginning of observation. Frailty was diagnosed using Kihon Checklist. Logistic analysis was used to evaluate the association between frailty and CKD or dipstick proteinuria. RESULTS: Among a total of 630 outpatients [age, 78 (70-84) years, men, 50%], the prevalence of patients with pre-frailty and frailty was 32% and 40%, respectively. The proportion of patients with pre-frailty and frailty increased with decreasing estimated glomerular filtration rate (eGFR) and increasing dipstick proteinuria levels. The odds ratios (95% confidence intervals) for CKD stage of 60 < eGFR ≤ 45 ml/min/1.73 m2, and 45 ml/min/1.73 m2 < eGFR for frailty was 0.87 (0.56-1.35) and 2.54 (1.46-4.53), respectively, compared with non-CKD as a reference. Furthermore, the odds ratios for the frailty of dipstick proteinuria with ± and + or over were 1.36 (0.88-2.09) and 1.78 (1.00-3.17), respectively, when dipstick proteinuria-was used as a reference. Moreover, the combination of eGFR and dipstick proteinuria levels increased the odds ratio for pre-frailty and frailty. CONCLUSION: Elderly patients with CKD had a higher prevalence of pre-frailty and frailty. By adding urinary protein information to eGFR, the link between CKD and frailty becomes even more robust.

Nucleated red blood cells, critical illness survivors and postdischarge outcomes: a cohort study.

BACKGROUND: Little is known about risk factors associated with out-of-hospital outcomes in survivors of critical illness. We hypothesized that the presence of nucleated red blood cells in patients who survived critical care would be associated with adverse outcomes following hospital discharge. METHODS: We performed a two-center observational cohort study of patients treated in medical and surgical intensive care units in Boston, Massachusetts. All data were obtained from the Research Patient Data Registry at Partners HealthCare. We studied 2878 patients, age ≥ 18 years, who received critical care between 2011 and 2015 and survived hospitalization. The exposure of interest was nucleated red blood cells occurring from 2 days prior to 7 days after critical care initiation. The primary outcome was mortality in the 90 days following hospital discharge. Secondary outcome was unplanned 30-day hospital readmission. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both nucleated red blood cells and outcome. Adjustment included age, race (white versus nonwhite), gender, Deyo-Charlson Index, patient type (medical versus surgical), sepsis and acute organ failure. RESULTS: In patients who received critical care and survived hospitalization, the absolute risk of 90-day postdischarge mortality was 5.9%, 11.7%, 15.8% and 21.9% in patients with 0/µl, 1-100/µl, 101-200/µl and more than 200/µl nucleated red blood cells respectively. Nucleated red blood cells were a robust predictor of postdischarge mortality and remained so following multivariable adjustment. The fully adjusted odds of 90-day postdischarge mortality in patients with 1-100/µl, 101-200/µl and more than 200/µl nucleated red blood cells were 1.77 (95% CI, 1.23-2.54), 2.51 (95% CI, 1.36-4.62) and 3.72 (95% CI, 2.16-6.39) respectively, relative to patients without nucleated red blood cells. Further, the presence of nucleated red blood cells is a significant predictor of the odds of unplanned 30-day hospital readmission. CONCLUSION: In critically ill patients who survive hospitalization, the presence of nucleated red blood cells is a robust predictor of postdischarge mortality and unplanned hospital readmission.

Derivation and validation of the acute organ failure score to predict outcome in critically ill patients: a cohort study.

OBJECTIVES: Prediction models for ICU mortality rely heavily on physiologic variables that may not be available in large retrospective studies. An alternative approach when physiologic variables are absent stratifies mortality risk by acute organ failure classification. DESIGN: Retrospective cohort study. SETTING: Two large teaching hospitals in Boston, MA. SUBJECTS: Ninety-two thousand eight hundred eighty-six patients aged 18 years old or older admitted between November 3, 1997, and February 25, 2011, who received critical care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The derivation cohort consisted of 35,566 patients from Brigham and Women's Hospital, and the validation cohort comprised 57,320 patients from Massachusetts General Hospital. Acute organ failure was determined for each patient based on International Classification of Diseases, 9th Revision, Clinical Modification code combinations. The main outcome measure was 30-day mortality. A clinical prediction model was created based on a logistic regression model describing the risk of 30-day mortality as a function of age, medical versus surgical patient type, Deyo-Charlson index, sepsis, and type acute organ failure (respiratory, renal, hepatic, hematologic, metabolic, and neurologic) after ICU admission. We computed goodness-of fit statistics and c-statistics as measures of model calibration and 30-day mortality discrimination, respectively. Thirty-day mortality occurred in 5,228 of 35,566 patients (14.7%) assigned to the derivation cohort. The clinical prediction model was predictive for 30-day mortality. The c-statistic for the clinical prediction model was 0.7447 (95% CI, 0.74-0.75) in the derivation cohort and 0.7356 (95% CI, 0.73-0.74) in the validation cohort. For both the derivation and validation cohorts, the Hosmer-Lemeshow chi-square p values indicated good model fit. In a smaller cohort of 444 patients with Acute Physiologic and Chronic Health Evaluation II scores determined, differences in model discrimination of 30-day mortality between the clinical prediction model and Acute Physiologic and Chronic Health Evaluation II were not significant (chi-square=0.76; p=0.38). CONCLUSIONS: An acute organ failure-based clinical prediction model shows good calibration and discrimination for 30-day mortality in the critically ill. The clinical prediction model compares favorably to Acute Physiologic and Chronic Health Evaluation II score in the prediction of 30-day mortality in the critically ill. This score may be useful for severity of illness risk adjustment in observational studies where physiologic data are unavailable.

The association of acute kidney injury in the critically ill and postdischarge outcomes: a cohort study*.

OBJECTIVE: Hospital readmissions contribute significantly to the cost of inpatient care and are targeted as a marker for quality of care. Little is known about risk factors associated with hospital readmission in survivors of critical illness. We hypothesized that acute kidney injury in patients who survived critical care would be associated with increased risk of 30-day postdischarge hospital readmission, postdischarge mortality, and progression to end-stage renal disease. DESIGN: Two center observational cohort study. SETTING: Medical and surgical ICUs at the Brigham and Women's Hospital and the Massachusetts General Hospital in Boston, Massachusetts. PATIENTS: We studied 62,096 patients, 18 years old and older, who received critical care between 1997 and 2012 and survived hospitalization. INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: : All data was obtained from the Research Patient Data Registry at Partners HealthCare. The exposure of interest was acute kidney injury defined as meeting Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease Risk, Injury or Failure criteria occurring 3 days prior to 7 days after critical care initiation. The primary outcome was hospital readmission in the 30 days following hospital discharge. The secondary outcome was mortality in the 30 days following hospital discharge. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both acute kidney injury and readmission status. Adjustment included age, race (white vs nonwhite), gender, Deyo-Charlson Index, patient type (medical vs surgical) and sepsis. Additionally, long-term progression to End Stage Renal Disease in patients with acute kidney injury was analyzed with a risk-adjusted Cox proportional hazards regression model. The absolute risk of 30-day readmission was 12.3%, 19.0%, 21.2%, and 21.1% in patients with No Acute Kidney Injury, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Injury, and Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Failure, respectively. In patients who received critical care and survived hospitalization, acute kidney injury was a robust predictor of hospital readmission and post-discharge mortality and remained so following multivariable adjustment. The odds of 30-day post-discharge hospital readmission in patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, or Failure fully adjusted were 1.44 (95% CI, 1.25-1.66), 1.98 (95% CI, 1.66-2.36), and 1.55 (95% CI, 1.26-1.91) respectively, relative to patients without acute kidney injury. Further, the odds of 30-day post-discharge mortality in patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, or Failure fully adjusted per our primary analysis were 1.39 (95% CI, 1.28-1.51), 1.46 (95% CI, 1.30-1.64), and 1.42 (95% CI, 1.26-1.61) respectively, relative to patients without acute kidney injury. The addition of the propensity score to the multivariable model did not change the point estimates significantly. Finally, taking into account age, gender, race, Deyo-Charlson Index, and patient type, we observed a relationship between acute kidney injury and development of end-stage renal disease. Patients with Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease class Risk, Injury, Failure experienced a significantly higher risk of end-stage renal disease during follow-up than patients without acute kidney injury (hazard ratio, 2.03; 95% CI, 1.56-2.65; hazard ratio, 3.99; 95% CI, 3.04-5.23; hazard ratio, 10.40; 95% CI, 8.54-12.69, respectively). CONCLUSIONS: Patients who suffer acute kidney injury are among a high-risk group of ICU survivors for adverse outcomes. In patients treated with critical care who survive hospitalization, acute kidney injury is a robust predictor of subsequent unplanned hospital readmission. In critical illness survivors, acute kidney injury is also associated with the odds of 30-day postdischarge mortality and the risk of subsequent end-stage renal disease.

Nutritional Status and Mortality in the Critically Ill.

OBJECTIVES: The association between nutritional status and mortality in critically ill patients is unclear based on the current literature. To clarify this relation, we analyzed the association between nutrition and mortality in a large population of critically ill patients and hypothesized that mortality would be impacted by nutritional status. DESIGN: Retrospective observational study. SETTING: Single academic medical center. PATIENTS: Six thousand five hundred eighteen adults treated in medical and surgical ICUs between 2004 and 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All cohort patients received a formal, in-person, standardized evaluation by a registered dietitian. The exposure of interest, malnutrition, was categorized as nonspecific malnutrition, protein-energy malnutrition, or well nourished and determined by data related to anthropometric measurements, biochemical indicators, clinical signs of malnutrition, malnutrition risk factors, and metabolic stress. The primary outcome was all-cause 30-day mortality determined by the Social Security Death Master File. Associations between nutrition groups and mortality were estimated by bivariable and multivariable logistic regression models. Adjusted odds ratios were estimated with inclusion of covariate terms thought to plausibly interact with both nutrition status and mortality. We used propensity score matching on baseline characteristics to reduce residual confounding of the nutrition status category assignment. In the cohort, nonspecific malnutrition was present in 56%, protein-energy malnutrition was present in 12%, and 32% were well nourished. The 30-day and 90-day mortality rates for the cohort were 19.1% and 26.6%, respectively. Nutritional status is a significant predictor of 30-day mortality following adjustment for age, gender, race, medical versus surgical patient type, Deyo-Charlson index, acute organ failure, vasopressor use, and sepsis: nonspecific malnutrition 30-day mortality odds ratio, 1.17 (95% CI, 1.01-1.37); protein-energy malnutrition 30-day mortality odds ratio, 2.10 (95% CI, 1.70-2.59), all relative to patients without malnutrition. In the matched cohort, the adjusted odds of 30-day mortality in the group of propensity score-matched patients with protein-energy malnutrition was two-fold greater than that of patients without malnutrition. CONCLUSION: In a large population of critically ill adults, an association exists between nutrition status and mortality.

The relationship among obesity, nutritional status, and mortality in the critically ill.

INTRODUCTION: The association between obesity and mortality in critically ill patients is unclear based on the current literature. To clarify this relationship, we analyzed the association between obesity and mortality in a large population of critically ill patients and hypothesized that mortality would be impacted by nutritional status. METHODS: We performed a single-center observational study of 6,518 adult patients treated in medical and surgical ICUs between 2004 and 2011. All patients received a formal, in-person, and standardized evaluation by a registered dietitian. Body mass index was determined at the time of dietitian consultation from the estimated dry weight or hospital admission weight and categorized a priori as less than 18.5 kg/m (underweight), 18.5-24.9 kg/m (normal/referent), 25-29.9 kg/m (overweight), 30-39.9 kg/m (obesity class I and II), and more than or equal to 40.0 kg/m (obesity class III). Malnutrition diagnoses were categorized as nonspecific malnutrition, protein-energy malnutrition, or well nourished. The primary outcome was all-cause 30-day mortality determined by the Social Security Death Master File. Associations between body mass index groups and mortality were estimated by bivariable and multivariable logistic regression models. Adjusted odds ratios were estimated with inclusion of covariate terms thought to plausibly interact with both body mass index and mortality. We utilized propensity score matching on baseline characteristics and nutrition status to reduce residual confounding of the body mass index category assignment. RESULTS: In the cohort, 5% were underweight, 36% were normal weight, 31% were overweight, 23% had class I/II obesity, and 5% had class III obesity. Nonspecific malnutrition was present in 56%, protein-energy malnutrition was present in 12%, and 32% were well nourished. The 30-day and 90-day mortality rate for the cohort was 19.1 and 26.6%, respectively. Obesity is a significant predictor of improved 30-day mortality following adjustment for age, gender, race, medical versus surgical patient type, Deyo-Charlson index, acute organ failure, vasopressor use, and sepsis: underweight odds ratio 30-day mortality is 1.09 (95% CI, 0.80-1.48), overweight 30-day mortality odds ratio is 0.93 (95% CI, 0.80-1.09), class I/II obesity 30-day mortality odds ratio is 0.80 (95% CI, 0.67-0.96), and class III obesity 30-day mortality odds ratio is 0.69 (95% CI, 0.49-0.97), all relative to patients with body mass index 18.5-24.9 kg/m. Importantly, there is confounding of the obesity-mortality association on the basis of malnutrition. Adjustment for only nutrition status attenuates the obesity-30-day mortality association: underweight odds ratio is 0.74 (95% CI, 0.54-1.00), overweight odds ratio is 1.05 (95% CI, 0.90-1.23), class I/II obesity odds ratio is 0.96 (95% CI, 0.81-1.15), and class III obesity odds ratio is 0.81 (95% CI, 0.59-1.12), all relative to patients with body mass index 18.5-24.9 kg/m. In a subset of patients with body mass index more than or equal to 30.0 kg/m (n = 1,799), those with either nonspecific or protein-energy malnutrition have increased mortality relative to well-nourished patients with body mass index more than or equal to 30.0 kg/m: odds ratio of 90-day mortality is 1.67 (95% CI, 1.29-2.15; p < 0.0001), fully adjusted. In a cohort of propensity score matched patients (n = 3,554), the body mass index-mortality association was not statistically significant, likely from matching on nutrition status. CONCLUSIONS: In a large population of critically ill adults, the association between improved mortality and obesity is confounded by malnutrition status. Critically ill obese patients with malnutrition have worse outcomes than obese patients without malnutrition.

Association of low serum 25-hydroxyvitamin D levels and sepsis in the critically ill.

OBJECTIVE: We hypothesized that deficiency in 25-hydroxyvitamin D prior to hospital admission would be associated with sepsis in the critically ill. DESIGN: Two-center observational study of patients treated in medical and surgical ICUs. SETTING: Two hundred nine medical and surgical intensive care beds in two teaching hospitals in Boston, MA. PATIENTS: Three thousand three hundred eighty-six patients, 18 years old or older, in whom 25-hydroxyvitamin D was measured prior to hospitalization between 1998 and 2011. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: : Preadmission 25-hydroxyvitamin D was categorized as deficiency in 25-hydroxyvitamin D (≤ 15 ng/mL), insufficiency (15-30 ng/mL), and sufficiency (≥ 30 ng/mL). The primary outcome was sepsis as defined by International Classification of Diseases, 9th Edition, Clinical Modification and validated by the 2001 Society of Critical Care Medicine/European Society of Intensive Care Medicine, American College of Chest Physicians, American Thoracic Society, and Surgical Infection Society international sepsis definitions conference guidelines. Logistic regression examined the presence of sepsis 3 days prior to critical care initiation to 7 days after critical care initiation. Adjusted odds ratios were estimated by multivariable logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive for the risk of sepsis. In the full cohort, 25-hydroxyvitamin D deficiency is a significant predictor for the risk of International Classification of Diseases, 9th Edition, Clinical Modification-defined sepsis following multivariable adjustment, including age, gender, race, type (surgical vs medical), and Deyo-Charlson index (adjusted odds ratio, 1.51 [95% CI, 1.17-1.94]; p = 0.001) relative to patients with 25-hydroxyvitamin D sufficiency. In a subset of cohort patients enriched for those with International Classification of Diseases, 9th Edition, Clinical Modification-diagnosed sepsis (n = 444), preadmission 25-hydroxyvitamin D deficiency is a significant predictor for the risk of conference guideline-defined sepsis following multivariable adjustment, including age, gender, race, type (surgical vs medical), and Acute Physiology and Chronic Health Evaluation II (adjusted odds ratio, 2.05 [95% CI, 1.19-3.52]; p = 0.009) relative to patients with 25-hydroxyvitamin D sufficiency. Furthermore, in cohort patients with International Classification of Diseases, 9th Edition, Clinical Modification-defined sepsis (n = 568), the multivariable adjusted risk of 90-day mortality was 1.6-fold higher in those with preadmission 25-hydroxyvitamin D values in the insufficient and deficient range, compared with those with preadmission vitamin D sufficiency (adjusted odds ratio, 1.63 [95% CI, 1.11-2.39]; p = 0.01). CONCLUSION: 25-hydroxyvitamin D deficiency prior to hospital admission is a significant predictor of sepsis in the critically ill. Additionally, patients with sepsis who are not vitamin D sufficient have an increased risk of mortality following critical care initiation.

The association of red cell distribution width at hospital discharge and out-of-hospital mortality following critical illness*.

OBJECTIVES: Red cell distribution width is associated with mortality and bloodstream infection risk in the critically ill. In hospitalized patients with critical illness, it is not known if red cell distribution width can predict subsequent risk of all-cause mortality following hospital discharge. We hypothesized that an increase in red cell distribution width at hospital discharge in patients who survived to discharge following critical care would be associated with increased postdischarge mortality. DESIGN: Two-center observational cohort study SETTING: : All medical and surgical ICUs at the Brigham and Women's Hospital and Massachusetts General Hospital. PATIENTS: We studied 43,212 patients, who were 18 years old or older and received critical care between 1997 and 2007 and survived hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was red cell distribution width within 24 hours of hospital discharge and categorized a priori in quintiles as less than or equal to 13.3%, 13.3-14.0%, 14.0-14.7%, 14.7-15.8%, and more than 15.8%. The primary outcome was all-cause mortality in the 30 days following hospital discharge. Secondary outcomes included 90-day and 365-day mortality following hospital discharge. Mortality was determined using the U.S. Social Security Administration Death Master File, and 365-day follow-up was present in all cohort patients. Adjusted odds ratios were estimated by multivariable logistic regression models with inclusion of covariate terms thought to plausibly interact with both red cell distribution width and mortality. Adjustment included age, race, gender, Deyo-Charlson Index, patient type (medical vs surgical), sepsis, and number of organs with acute failure. In patients who received critical care and survived hospitalization, the discharge red cell distribution width was a robust predictor of all-cause mortality and remained so following multivariable adjustment. Patients with a discharge red cell distribution width of 14.0-14.7%, 14.7-15.8%, and more than 15.8% have an odds ratio for mortality in the 30 days following hospital discharge of 2.86 (95% CI, 2.25-3.62), 4.57 (95% CI, 3.66-5.72), and 8.80 (95% CI, 7.15-10.83), respectively, all relative to patients with a discharge red cell distribution width less than or equal to 13.3%. Following multivariable adjustment, patients with a discharge red cell distribution width of 14.0-14.7%, 14.7-15.8%, and more than 15.8% have an odds ratio for mortality in the 30 days following hospital discharge of 1.63 (95% CI, 1.27-2.07), 2.36 (95% CI, 1.87-2.97), and 4.18 (95% CI, 3.36-5.20), respectively, all relative to patients with a discharge red cell distribution width less than or equal to 13.3%. Similar significant robust associations post multivariable adjustments are seen with death by days 90 and 365 postdischarge. Estimating the receiver-operating characteristic area under the curve shows that discharge red cell distribution width has moderate discriminative power for mortality 30 days following hospital discharge (area under the curve = 0.70; SE 0.006; 95% CI, 0.69-0.71; p < 0.0001). CONCLUSION: In patients treated with critical care who survive hospitalization, an elevated red cell distribution width at the time of discharge is a robust predictor of subsequent all-cause patient mortality. Increased discharge red cell distribution width likely reflects the presence of proinflammatory state, oxidative stress, arterial underfilling, or a combination, thereof which may explain the observed impact on patient survival following discharge. Elevated red cell distribution width at hospital discharge may identify ICU survivors who are at risk for adverse outcomes following hospital discharge.

Efficacy of Pharmacotherapy for Seasonal Influenza in Young and Middle-aged Adults: A Systematic Review and Network Meta-analysis.

Background Seasonal influenza affects healthcare demand. However, the efficacy of anti-influenza drugs, particularly among young patients at a low risk of complications, has rarely been evaluated. Therefore, we evaluated the efficacy of anti-influenza drugs against seasonal influenza in healthy young and middle-aged adults. Methods A systematic review and network meta-analysis were conducted. The Cochrane Central Register of Controlled Trials and Medical Literature Analysis and Retrieval System Online were searched for original articles reporting double-blind, randomized controlled trials published up to the end of July 2023. Clinical trials that tested the efficacy of anti-influenza drugs in young and middle-aged patients with seasonal influenza were also included. The primary outcome was time to fever alleviation. The efficacy and adverse effects of these treatments were estimated using a Bayesian hierarchical random-effects model and a Markov chain Monte Carlo simulation. Results In total, 24 articles with 34 treatments and 8,949 individuals were included. Oseltamivir (300 mg/day for 5 days) showed the largest reduction in time to fever alleviation by -19.1 (95% confidence interval [CI]: -29.4, -10.7) h compared with a placebo. Baloxavir marboxil (40 mg/day) reduced the time to symptom alleviation by -28.2 (95% CI: -42.7, -13.7) h, and peramivir (300 mg/day) administered by intravenous infusion for 1 day reduced the time to resumption of usual activities by -43.5 (95% CI: -72.8, -14.2) h. Conclusion Several pharmaceutical treatments were able to reduce the recovery time for fever and symptom alleviation and resumption of usual activities in young and middle-aged adults with seasonal influenza without increasing the risk of complications.

Association of low serum 25-hydroxyvitamin D levels and acute kidney injury in the critically ill.

OBJECTIVE: Given the importance of inflammation in acute kidney injury and the relationship between vitamin D and inflammation, we sought to elucidate the effect of vitamin D on acute kidney injury. We hypothesized that deficiency in 25-hydroxyvitamin D prior to hospital admission would be associated with acute kidney injury in the critically ill. DESIGN: Two-center observational study of patients treated in medical and surgical intensive care units. SETTING: Two hundred nine medical and surgical intensive care beds in two teaching hospitals in Boston, Massachusetts. PATIENTS: Two thousand seventy-five patients, aged ≥ 18 yrs, in whom serum 25-hydroxyvitamin D was measured prior to hospitalization between 1998 and 2009. INTERVENTIONS: : None. MEASUREMENTS AND MAIN RESULTS: The exposure of interest was preadmission serum 25-hydroxyvitamin D and categorized a priori as deficiency (25-hydroxyvitamin D <15 ng/mL), insufficiency (25-hydroxyvitamin D 15-30 ng/mL), or sufficiency (25-hydroxyvitamin D ≥ 30 ng/mL). The primary outcome was acute kidney injury defined as meeting Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) Injury or Failure criteria. Logistic regression examined the RIFLE criteria outcome. Adjusted odds ratios were estimated by multivariate logistic regression models. Preadmission 25-hydroxyvitamin D deficiency is predictive of acute kidney injury. Patients with 25-hydroxyvitamin D deficiency have an odds ratio for acute kidney injury of 1.73 (95% confidence interval 1.30-2.30; p < .0001) relative to patients with 25-hydroxyvitamin D sufficiency. 25-Hydroxyvitamin D deficiency remains a significant predictor of acute kidney injury following multivariable adjustment (adjusted odds ratio 1.50; 95% confidence interval 1.42-2.24; p < .0001). Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for acute kidney injury of 1.49 (95% confidence interval 1.15-1.94; p = .003) and an adjusted odds ratio of 1.23 (95% confidence interval 1.12-1.72; p = .003) relative to patients with 25-hydroxyvitamin D sufficiency. In addition, preadmission 25-hydroxyvitamin D deficiency is predictive of mortality. Patients with 25-hydroxyvitamin D insufficiency have an odds ratio for 30-day mortality of 1.60 (95% confidence interval 1.18-2.17; p = .003) and an adjusted odds ratio of 1.61 (95% confidence interval 1.06-1.57; p = .004) relative to patients with 25-hydroxyvitamin D sufficiency. CONCLUSION: Deficiency of 25-hydroxyvitamin D prior to hospital admission is a significant predictor of acute kidney injury and mortality in a critically ill patient population.

Effects of Electrocardiographic Monitoring Education on Nurses' Confidence and Psychological Stress: An Online Cross-Sectional Survey in Japan.

We aimed to investigate the association between nurses' electrocardiographic (ECG) monitoring education and their confidence and psychological stress regarding ECG monitoring. In 2019, a web-based cross-sectional study was conducted among Japanese nurses. A multivariable logistic regression analysis was performed to evaluate the effects of education on nurses' confidence and psychological stress regarding ECG monitoring. In total, 1652 nurses were included in the study. Factors significantly associated with nurses' confidence were post-graduate education experience (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.6-3.6), ≥11 post-graduate years (OR, 2.2; 95% CI, 1.5-3.1), male gender (OR, 4.4; 95% CI, 2.9-6.6), ≥5 helpful experiences with ECG monitoring (OR, 10.7; 95% CI, 6.0-19.1), work experience in an intensive care unit (OR, 2.3; 95% CI, 1.5-3.7), and work experience in a cardiology department (OR, 1.7; 95% CI, 1.2-2.4). Factors significantly associated with nurses' psychological stress were male gender (OR, 1.9; 95% CI, 1.2-2.9), ≥5 helpful experiences with ECG monitoring (OR, 1.9; 95% CI, 1.2-2.9), and work experience in an emergency room (OR, 2.4; 95% CI, 1.3-4.8). These results suggest that nurses' post-graduate ECG monitoring education enhanced their confidence, but did not reduce psychological stress regarding ECG monitoring.

Blood pressure, frailty status, and all-cause mortality in elderly hypertensives; The Nambu Cohort Study.

Antihypertensive therapy is pivotal for reducing cardiovascular events. The 2019 Guidelines for the Management of Hypertension set a target blood pressure (BP) of <140/90 mmHg for persons older than 75 years of age. Optimal BP levels for older persons with frailty, however, are controversial because evidence for the relationship between BP level and prognosis by frailty status is limited. Here, we evaluated the relationship between systolic BP and frailty status with all-cause mortality in ambulatory older hypertensive patients using data from the Nambu Cohort study. A total of 535 patients (age 78 [70-84] years, 51% men, 37% with frailty) were prospectively followed for a mean duration of 41 (34-43) months. During the follow-up period, 49 patients died. Mortality rates stratified by systolic BP and frailty status were lowest in patients with systolic BP < 140 mmHg and non-frailty, followed by those with systolic BP ≥ 140 mmHg and non-frailty. Patients with frailty had the highest mortality regardless of the BP level. The adjusted hazard ratios (95% confidence intervals) of each category for all-cause mortality were as follows: ≥140 mmHg/Non-frailty 3.19 (1.12-11.40), <140 mmHg/Frailty 4.72 (1.67-16.90), and ≥140 mmHg/Frailty 3.56 (1.16-13.40) compared with <140 mmHg/Non-frailty as a reference. These results indicated that frail patients have a poor prognosis regardless of their BP levels. Non-frail patients, however, with systolic BP levels <140 mmHg had a better prognosis. Frailty may be a marker to differentiate patients who are likely to gain benefit from antihypertensive medication among older hypertensives.

Prevalence and characteristics of antibiotic prescription for acute COVID-19 patients in Japan.

COVID-19 is a viral infection and does not require antibiotics. The study aimed to elucidate a prescribing pattern of antibiotics for COVID-19. A nationwide cross-sectional study was conducted in Japan. The Diagnosis and Procedure Combinations (DPC) data was used to collect information, covering 25% of all acute care hospitals in the country. In 140,439 COVID-19 patients, 18,550 (13.21%) patients received antibiotics. Antibiotics were prescribed more often in inpatients (10,809 out of 66,912, 16.15%) than outpatients (7741 out of 73,527, 10.53%) (p < 0.001). Outpatient prescription was significantly associated with older patients (odds ratio [OR], 4.66; 95% confidence interval [CI] 4.41-4.93) and a greater Charlson index (OR with one-point index increase, 1.22; 95% CI 1.21-1.23). Inpatient prescription was significantly associated with older patients (OR 2.10; 95% CI 2.01-2.21), male gender (OR 1.12, 95% CI 1.07-1.18), a greater Charlson index (OR with one-point increase, 1.06; 95% CI 1.05-1.07), requirement of oxygen therapy (OR 3.44; 95% CI 3.28-3.60) and mechanical ventilation (OR 15.09; 95% CI 13.60-16.74). The most frequently prescribed antibiotic among outpatients was cefazolin, while that among inpatients was ceftriaxone. Antibiotic prescription is relatively low for acute COVID-19 in Japan. Antibiotic prescription was associated with older age, multi-morbidity, severe disease, and winter season.

Frequency of night shift and menstrual cycle characteristics in Japanese nurses working under two or three rotating shifts.

OBJECTIVES: In Japan, the prevalence of irregular menstrual cycles and its association with the frequency of night shifts have scarcely assessed. The present study aimed to evaluate the relationship between irregular menstrual cycles and the frequency of night shifts in Japanese female nurses. METHODS: We conducted a cross-sectional web-based self-administered questionnaire survey in 2019. An irregular menstrual cycle was defined as a cycle length of ≤21 days or ≥39 days at least a few times over the past year or amenorrhea for at least 3 months. We used Poison regression analysis with a robust error variance to calculate the prevalence ratios adjusted for age, body mass index, hospital size, and the department in which they worked. RESULTS: A total of 1249 women were included, and 679 (54.4%) and 195 (15.6%) of them worked under two and three rotating shifts. The prevalence of irregular menstrual cycles was 24.8%, 37.4%, and 35.9% in the no night, two rotating, and three rotating shifts groups, respectively. While the frequency of night shifts had a dose-responsive relationship with irregular menstrual cycles in the two rotating shifts group, it was not observed in the three rotating shifts group. However, the risk of work getting affected by dysmenorrhea or premenstrual symptoms increased in the three rotating shifts group. CONCLUSIONS: Over 30% of Japanese female nurses working under night shifts had irregular menstrual cycles. The high frequency of night shifts increased the risk of irregular menstrual cycles and secondary amenorrhea in the two rotating shifts group.