Predisposing Risk Factors for Delirium in Living Donor Liver Transplantation Patients in Intensive Care Units

Background

Delirium is one of the main causes of increased length of intensive care unit (ICU) stay among patients who have undergone living donor liver transplantation (LDLT). We aimed to evaluate risk factors for delirium after LDLT as well as to investigate whether delirium impacts the length of ICU and hospital stay.

Methods

Seventy-eight patients who underwent LDLT during the period January 2010 to December 2012 at a single medical center were enrolled. The Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scale was used to diagnose delirium. Preoperative, postoperative, and hematologic factors were included as potential risk factors for developing delirium.

Results

During the study period, delirium was diagnosed in 37 (47.4%) patients after LDLT. The mean onset of symptoms occurred 7.0±5.5 days after surgery and the mean duration of symptoms was 5.0±2.6 days. The length of stay in the ICU for patients with delirium (39.8±28.1 days) was significantly longer than that for patients without delirium (29.3±19.0 days) (p<0.05). Risk factors associated with delirium included history of alcohol abuse [odds ratio (OR) = 6.40, 95% confidence interval (CI): 1.85–22.06], preoperative hepatic encephalopathy (OR = 4.45, 95% CI: 1.36–14.51), APACHE II score ≥16 (OR = 1.73, 95% CI: 1.71–2.56), and duration of endotracheal intubation ≥5 days (OR = 1.81, 95% CI: 1.52–2.23).

Conclusions

History of alcohol abuse, preoperative hepatic encephalopathy, APACHE II scores ≥16 and endotracheal intubation ≥5 days were predictive of developing delirium in the ICU following liver transplantation surgery and were associated with increased length of ICU and hospital stay.     

Impact of statins and ACE inhibitors on mortality after COPD exacerbations

Background

The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.

Methods

We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation. Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.

Results

We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation. In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB). After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40–0.64) and ACE inhibitor/ARB use (0.55, 0.46–0.66) were significantly associated with decreased 90-day mortality.

Conclusion

Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation. Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations.     

Host Factors and Biomarkers Associated with Poor Outcomes in Adults with Invasive Pneumococcal Disease

BackgroundInvasive pneumococcal disease (IPD) causes considerable morbidity and mortality. We aimed to identify host factors and biomarkers associated with poor outcomes in adult patients with IPD in Japan, which has a rapidly-aging population.MethodsIn a large-scale surveillance study of 506 Japanese adults with IPD, we investigated the role of host factors, disease severity, biomarkers based on clinical laboratory data, treatment regimens, and bacterial factors on 28-day mortality.ResultsOverall mortality was 24.1%, and the mortality rate increased from 10.0% in patients aged ˂50 years to 33.1% in patients aged ≥80 years. Disease severity also increased 28-day mortality, from 12.5% among patients with bacteraemia without sepsis to 35.0% in patients with severe sepsis and 56.9% with septic shock. The death rate within 48 hours after admission was high at 54.9%. Risk factors for mortality identified by multivariate analysis were as follows: white blood cell (WBC) count <4000 cells/μL (odds ratio [OR], 6.9; 95% confidence interval [CI], 3.7–12.8, p < .001); age ≥80 years (OR, 6.5; 95% CI, 2.0–21.6, p = .002); serum creatinine ≥2.0 mg/dL (OR, 4.5; 95% CI, 2.5–8.1, p < .001); underlying liver disease (OR, 3.5; 95% CI, 1.6–7.8, p = .002); mechanical ventilation (OR, 3.0; 95% CI, 1.7–5.6, p < .001); and lactate dehydrogenase ≥300 IU/L (OR, 2.4; 95% CI, 1.4–4.0, p = .001). Pneumococcal serotype and drug resistance were not associated with poor outcomes.ConclusionsHost factors, disease severity, and biomarkers, especially WBC counts and serum creatinine, were more important determinants of mortality than bacterial factors.     

Benefits of Bifidobacterium breve M-16V Supplementation in Preterm Neonates - A Retrospective Cohort Study

Background

Systematic reviews of randomised controlled trials report that probiotics reduce the risk of necrotising enterocolitis (NEC) in preterm neonates.

Aim

To determine whether routine probiotic supplementation (RPS) to preterm neonates would reduce the incidence of NEC.

Methods

The incidence of NEC ≥ Stage II and all-cause mortality was compared for an equal period of 24 months ‘before’ (Epoch 1) and ‘after’ (Epoch 2) RPS with Bifidobacterium breve M-16V in neonates <34 weeks. Multivariate logistic regression analysis was conducted to adjust for relevant confounders.

Results

A total of 1755 neonates (Epoch I vs. II: 835 vs. 920) with comparable gestation and birth weights were admitted. There was a significant reduction in NEC ≥ Stage II: 3% vs. 1%, adjusted odds ratio (aOR) = 0.43 (95%CI: 0.21–0.87); ‘NEC ≥ Stage II or all-cause mortality’: 9% vs. 5%, aOR = 0.53 (95%CI: 0.32–0.88); but not all-cause mortality alone: 7% vs. 4%, aOR = 0.58 (95% CI: 0.31–1.06) in Epoch II. The benefits in neonates <28 weeks did not reach statistical significance: NEC ≥ Stage II: 6% vs. 3%, aOR 0.51 (95%CI: 0.20–1.27), ‘NEC ≥ Stage II or all-cause mortality’, 21% vs. 14%, aOR = 0.59 (95%CI: 0.29–1.18); all-cause mortality: 17% vs. 11%, aOR = 0.63 (95%CI: 0.28–1.41). There was no probiotic sepsis.

Conclusion

RPS with Bifidobacterium breve M-16V was associated with decreased NEC≥ Stage II and ‘NEC≥ Stage II or all-cause mortality’ in neonates <34 weeks. Large sample size is required to assess the potential benefits of RPS in neonates <28 weeks.     

Thrombocytopenia Is Associated with Acute Respiratory Distress Syndrome Mortality: An International Study

Background

Early detection of the Acute Respiratory Distress Syndrome (ARDS) has the potential to improvethe prognosis of critically ill patients admitted to the intensive care unit (ICU). However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions.

Objectives

This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies.

Methods

We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA.

Results

Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70–18.3), pulmonary injury (OR: 3.22; 95% CI: 1.60–6.47), and thrombocytopenia, defined as platelet count <80×10³/µL, (OR: 2.67; 95% CI: 1.27–5.62)were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07–1.57) but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96–1.62). The presence of both thrombocytopenia and ARDS substantially increased 60-daymortality. Sensitivity analyses showed that a platelet count of <100×10³/µLin combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients.

Conclusions

This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality.     

Intentional Weight Loss and All-Cause Mortality: A Meta-Analysis of Randomized Clinical Trials

Background

Obesity is associated with increased mortality, and weight loss trials show rapid improvement in many mortality risk factors. Yet, observational studies typically associate weight loss with higher mortality risk. The purpose of this meta-analysis of randomized controlled trials (RCTs) of weight loss was to clarify the effects of intentional weight loss on mortality.

Methods

2,484 abstracts were identified and reviewed in PUBMED, yielding 15 RCTs reporting (1) randomization to weight loss or non-weight loss arms, (2) duration of ≥18 months, and (3) deaths by intervention arm. Weight loss interventions were all lifestyle-based. Relative risks (RR) and 95% confidence intervals (95% CI) were estimated for each trial. For trials reporting at least one death (n = 12), a summary estimate was calculated using the Mantel-Haenszel method. Sensitivity analysis using sparse data methods included remaining trials.

Results

Trials enrolled 17,186 participants (53% female, mean age at randomization = 52 years). Mean body mass indices ranged from 30–46 kg/m², follow-up times ranged from 18 months to 12.6 years (mean: 27 months), and average weight loss in reported trials was 5.5±4.0 kg. A total of 264 deaths were reported in weight loss groups and 310 in non-weight loss groups. The weight loss groups experienced a 15% lower all-cause mortality risk (RR = 0.85; 95% CI: 0.73–1.00). There was no evidence for heterogeneity of effect (Cochran’s Q = 5.59 (11 d.f.; p = 0.90); I² = 0). Results were similar in trials with a mean age at randomization ≥55 years (RR = 0.84; 95% CI 0.71–0.99) and a follow-up time of ≥4 years (RR = 0.85; 95% CI 0.72–1.00).

Conclusions

In obese adults, intentional weight loss may be associated with approximately a 15% reduction in all-cause mortality.     

Blood Pressure Variability and Cardiovascular Risk in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects.     

Adjunctive steroid in HIV-negative patients with severe Pneumocystis pneumonia

Background

High-dose steroid therapy has been proven effective in AIDS-related Pneumocystis pneumonia (PCP) but not in non-AIDS-related cases. We evaluated the effects on survival of steroids in HIV-negative patients with PCP.

Methods

Retrospective study patients admitted to the ICU with hypoxemic PCP. We compared patients receiving HDS (≥1 mg/Kg/day prednisone equivalent), low-dose steroids (LDS group, <1 mg/Kg/day prednisone equivalent), and no steroids (NS group). Variables independently associated with ICU mortality were identified.

Results

139 HIV-negative patients with PCP were included. Median age was 48 [40–60] years. The main underlying conditions were hematological malignancies (n=55, 39.6%), cancer (n=11, 7.9%), and solid organ transplantation (n=73, 52.2%). ICU mortality was 26% (36 deaths). The HDS group had 72 (51.8%) patients, the LDS group 35 (25%) patients, and the NS group 32 (23%) patients. Independent predictors of ICU mortality were SAPS II at ICU admission (odds ratio [OR], 1.04/point; [95%CI], 1.01-1.08, P=0.01), non-hematological disease (OR, 4.06; [95%CI], 1.19-13.09, P=0.03), vasopressor use (OR, 20.31; 95%CI, 6.45-63.9, P<0.001), and HDS (OR, 9.33; 95%CI, 1.97-44.3, P=0.02). HDS was not associated with the rate of ICU-acquired infections.

Conclusions

HDS were associated with increased mortality in HIV-negative patients with PCP via a mechanism independent from an increased risk of infection.     

Impact of Preexisting Interstitial Lung Disease on Acute,Extensive Radiation Pneumonitis: Retrospective Analysis of Patients with Lung Cancer

IntroductionThis study investigated the clinical characteristics and predictive factors for developing acute extended radiation pneumonitis with a focus on the presence and radiological characteristics of preexisting interstitial lung disease.MethodsOf 1429 irradiations for lung cancer from May 2006 to August 2013, we reviewed 651 irradiations involving the lung field. The presence, compatibility with usual interstitial pneumonia, and occupying area of preexisting interstitial lung disease were retrospectively evaluated by pretreatment computed tomography. Cases of non-infectious, non-cardiogenic, acute respiratory failure with an extended bilateral shadow developing within 30 days after the last irradiation were defined as acute extended radiation pneumonitis.ResultsNine (1.4%) patients developed acute extended radiation pneumonitis a mean of 6.7 days after the last irradiation. Although preexisting interstitial lung disease was found in 13% of patients (84 patients), 78% of patients (7 patients) with acute extended radiation pneumonitis cases had preexisting interstitial lung disease, which resulted in incidences of acute extended radiation pneumonitis of 0.35 and 8.3% in patients without and with preexisting interstitial lung disease, respectively. Multivariate logistic analysis indicated that the presence of preexisting interstitial lung disease (odds ratio = 22.6; 95% confidence interval = 5.29–155; p < 0.001) and performance status (≥2; odds ratio = 4.22; 95% confidence interval = 1.06–20.8; p = 0.049) were significant predictive factors. Further analysis of the 84 patients with preexisting interstitial lung disease revealed that involvement of more than 10% of the lung field was the only independent predictive factor associated with the risk of acute extended radiation pneumonitis (odds ratio = 6.14; 95% confidence interval = 1.0–37.4); p = 0.038).ConclusionsPretreatment computed tomography evaluations of the presence of and area size occupied by preexisting interstitial lung disease should be assessed for safer irradiation of areas involving the lung field.     

Early Hepatic Dysfunction Is Associated with a Worse Outcome in Patients Presenting with Acute Respiratory Distress Syndrome: A Post-Hoc Analysis of the ACURASYS and PROSEVA Studies

Introduction

Bilirubin is well-recognized marker of hepatic dysfunction in intensive care unit (ICU) patients. Multiple organ failure often complicates acute respiratory distress syndrome (ARDS) evolution and is associated with high mortality. The effect of early hepatic dysfunction on ARDS mortality has been poorly investigated. We evaluated the incidence and the prognostic significance of increased serum bilirubin levels in the initial phase of ARDS.

Methods

The data of 805 patients with ARDS were retrospectively analysed. This population was extracted from two recent multicenter, prospective and randomised trials. Patients presenting with ARDS with a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen < 150 mmHg measured with a PEEP ≥ 5 cm of water were included. The total serum bilirubin was measured at inclusion and at days 2, 4, 7 and 14. The primary objective was to analyse the bilirubin at inclusion according to the 90-day mortality rate.

Results

The 90-day mortality rate was 33.8% (n = 272). The non-survivors were older, had higher Sepsis-related Organ Failure Assessment (SOFA) score and were more likely to have a medical diagnosis on admission than the survivors. At inclusion, the SOFA score without the liver score (10.3±2.9 vs. 9.0±3.0, p<0.0001) and the serum bilirubin levels (36.1±57.0 vs. 20.5±31.5 μmol/L, p<0.0001) were significantly higher in the non-survivors than in the survivors. Age, the hepatic SOFA score, the coagulation SOFA score, the arterial pH level, and the plateau pressure were independently associated with 90-day mortality in patients with ARDS.

Conclusion

Bilirubin used as a surrogate marker of hepatic dysfunction and measured early in the course of ARDS was associated with the 90-day mortality rate.     

The Gender-Dependent Association between Obesity and Age-Related Cataracts in Middle-Aged Korean Adults

The aim of this study was to investigate the association of central and abdominal obesity with the prevalence of cataracts in a middle-aged Korean population. This retrospective cross-sectional study was based on the data collected from the Korea National Health and Nutrition Examination Survey 2008–2009, in which 4,914 subjects were examined. Ophthalmological examinations were performed to determine the presence of a nuclear, cortical, or posterior subcapsular cataract. Both general obesity (a body mass index ≥25 kg/m²) and abdominal obesity (a waist circumference ≥90 cm for men and ≥80 cm for women) were significantly associated with the occurrence of cataracts among middle-aged women [adjusted odds ratio (aOR), 1.32; 95% confidence interval (CI), 1.03–1.69; and aOR, 1.40; 95% CI, 1.06–1.85, respectively], while abdominal obesity was significantly inversely associated with the occurrence of cataracts among middle-aged men (aOR, 0.76; 95% CI, 0.58–1.01; and aOR, 0.66; 95% CI, 0.49–0.89, respectively). We report a difference in the association between obesity and the prevalence of cataracts based on gender.     

Diabetic Foot Complications and Their Risk Factors from a Large Retrospective Cohort Study

BackgroundFoot complications are considered to be a serious consequence of diabetes mellitus, posing a major medical and economical threat. Identifying the extent of this problem and its risk factors will enable health providers to set up better prevention programs. Saudi National Diabetes Registry (SNDR), being a large database source, would be the best tool to evaluate this problem.MethodsThis is a cross-sectional study of a cohort of 62,681 patients aged ≥25 years from SNDR database, selected for studying foot complications associated with diabetes and related risk factors.ResultsThe overall prevalence of diabetic foot complications was 3.3% with 95% confidence interval (95% CI) of (3.16%–3.44%), whilst the prevalences of foot ulcer, gangrene, and amputations were 2.05% (1.94%–2.16%), 0.19% (0.16%–0.22%), and 1.06% (0.98%–1.14%), respectively. The prevalence of foot complications increased with age and diabetes duration predominantly amongst the male patients. Diabetic foot is more commonly seen among type 2 patients, although it is more prevalent among type 1 diabetic patients. The Univariate analysis showed Charcot joints, peripheral vascular disease (PVD), neuropathy, diabetes duration ≥10 years, insulin use, retinopathy, nephropathy, age ≥45 years, cerebral vascular disease (CVD), poor glycemic control, coronary artery disease (CAD), male gender, smoking, and hypertension to be significant risk factors with odds ratio and 95% CI at 42.53 (18.16–99.62), 14.47 (8.99–23.31), 12.06 (10.54–13.80), 7.22 (6.10–8.55), 4.69 (4.28–5.14), 4.45 (4.05–4.89), 2.88 (2.43–3.40), 2.81 (2.31–3.43), 2.24 (1.98–2.45), 2.02 (1.84–2.22), 1.54 (1.29–1.83), and 1.51 (1.38–1.65), respectively.ConclusionsRisk factors for diabetic foot complications are highly prevalent; they have put these complications at a higher rate and warrant primary and secondary prevention programs to minimize morbidity and mortality in addition to economic impact of the complications. Other measurements, such as decompression of lower extremity nerves, should be considered among diabetic patients.     

Acute Respiratory Failure in Critically Ill Patients with Interstitial Lung Disease

Background

Patients with chronic known or unknown interstitial lung disease (ILD) may present with severe respiratory flares that require intensive management. Outcome data in these patients are scarce.

Patients and Methods

Clinical and radiological features were collected in 83 patients with ILD-associated acute respiratory failure (ARF). Determinants of hospital mortality and response to corticosteroid therapy were identified by logistic regression.

Results

Hospital and 1-year mortality rates were 41% and 54% respectively. Pulmonary hypertension, computed tomography (CT) fibrosis and acute kidney injury were independently associated with mortality (odds ratio (OR) 4.55; 95% confidence interval (95%CI) (1.20–17.33); OR, 7.68; (1.78–33.22) and OR 10.60; (2.25–49.97) respectively). Response to steroids was higher in patients with shorter time from hospital admission to corticosteroid therapy. Patients with fibrosis on CT had lower response to steroids (OR, 0.03; (0.005–0.21)). In mechanically ventilated patients, overdistension induced by high PEEP settings was associated with CT fibrosis and hospital mortality.

Conclusion

Mortality is high in ILD-associated ARF. CT and echocardiography are valuable prognostic tools. Prompt corticosteroid therapy may improve survival.     

Aspiration-Related Acute Respiratory Distress Syndrome in Acute Stroke Patient

Background

Aspiration of oral or gastric contents into the larynx and lower respiratory tract is a common problem in acute stroke patients, which significantly increases the incidence of acute respiratory distress syndrome (ARDS). However, little is known about the clinical characteristics of aspiration-related ARDS in acute stroke patients.

Methods

Over 17-month period a retrospective cohort study was done on 1495 consecutive patients with acute stroke. The data including demographic characteristics, clinical manifestations, laboratory examinations, chest imaging, and hospital discharge status were collected to analysis.

Results

Aspiration-related ARDS was diagnosed in 54 patients (3.6%). The most common presenting symptom was tachypnea (respiratory rate ≥25 breaths/min) in 50 cases. Computed tomography (CT) images usually demonstrated diffuse ground-glass opacities (GGOs) and inhomogeneous patchy consolidations involving the low lobes. Age, NIHSS score, GCS score, dysphagia, dysarthria, hemoglobin concentration, serum aspertate aminotransferase (AST), serum albumin, serum sodium, and admission glucose level were independently associated with aspiration-related ARDS (odds ratio (OR) 1.05, 95% confidence interval (CI) (1.04–1.07); OR 2.87, (2.68–3.63); OR 4.21, (3.57–5.09); OR 2.18, (1.23–3.86); OR 1.67, (1.31–2.14); OR 2.31, (1.11–4.84); OR 1.68, (1.01–2.80); OR 2.15, (1.19–3.90); OR 1.92, (1.10–3.36) and OR 1.14, (1.06–1.21) respectively).

Conclusions

Aspiration-related ARDS frequently occurs in acute stroke patient with impairment consciousness. It is advisable that performing chest CT timely may identify disease early and prompt treatment to rescue patients.     

Prognostic Value of Obesity on Both Overall Mortality and Cardiovascular Disease in the General Population

Background

Obesity represents an important health problem and its association with cardiovascular risk factors is well-known. The aim of this work was to assess the correlation between obesity and mortality (both, all-cause mortality and the combined variable of all-cause mortality plus the appearance of a non-fatal first cardiovascular event) in a general population sample from the south-east of Spain.

Materials and Methods

This prospective cohort study used stratified and randomized two-stage sampling. Obesity [body mass index (BMI) ≥30 kg/m²] as a predictive variable of mortality and cardiovascular events was assessed after controlling for age, sex, cardiovascular disease history, high blood pressure, diabetes mellitus, hypercholesterolemia, high-density lipoprotein/triglycerides ratio, total cholesterol and smoking with the Cox regression model.

Results

The mean follow-up time of the 1,248 participants was 10.6 years. The incidence of all-cause mortality during this period was 97 deaths for every 10,000 person/years (95% CI: 80–113) and the incidence of all-cause mortality+cardiovascular morbidity was 143 cases for every 10,000 person/years (95% CI: 124–163). A BMI ≥35 kg/m² yielded a hazard ratio for all-cause mortality of 1.94 (95% CI: 1.11–3.42) in comparison to non-obese subjects (BMI <30 kg/m²). For the combination of cardiovascular morbidity plus all-cause mortality, a BMI ≥35 kg/m² had a hazard ratio of 1.84 (95% CI: 1.15–2.93) compared to non-obese subjects.

Conclusions

A BMI ≥35 kg/m² is an important predictor of both overall mortality and of the combination of cardiovascular morbidity plus all-cause mortality.     

Anticoagulation Management Practices and Outcomes in Elderly Patients with Acute Venous Thromboembolism: A Clinical Research Study

Whether anticoagulation management practices are associated with improved outcomes in elderly patients with acute venous thromboembolism (VTE) is uncertain. Thus, we aimed to examine whether practices recommended by the American College of Chest Physicians guidelines are associated with outcomes in elderly patients with VTE. We studied 991 patients aged ≥65 years with acute VTE in a Swiss prospective multicenter cohort study and assessed the adherence to four management practices: parenteral anticoagulation ≥5 days, INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulation, early start with vitamin K antagonists (VKA) ≤24 hours of VTE diagnosis, and the use of low-molecular-weight heparin (LMWH) or fondaparinux. The outcomes were all-cause mortality, VTE recurrence, and major bleeding at 6 months, and the length of hospital stay (LOS). We used Cox regression and lognormal survival models, adjusting for patient characteristics. Overall, 9% of patients died, 3% had VTE recurrence, and 7% major bleeding. Early start with VKA was associated with a lower risk of major bleeding (adjusted hazard ratio 0.37, 95% CI 0.20–0.71). Early start with VKA (adjusted time ratio [TR] 0.77, 95% CI 0.69–0.86) and use of LMWH/fondaparinux (adjusted TR 0.87, 95% CI 0.78–0.97) were associated with a shorter LOS. An INR ≥2.0 for ≥24 hours before stopping parenteral anticoagulants was associated with a longer LOS (adjusted TR 1.2, 95% CI 1.08–1.33). In elderly patients with VTE, the adherence to recommended anticoagulation management practices showed mixed results. In conclusion, only early start with VKA and use of parenteral LMWH/fondaparinux were associated with better outcomes.     

Circulating Mitochondrial DNA in Patients in the ICU as a Marker of Mortality: Derivation and Validation

Background

Mitochondrial DNA (mtDNA) is a critical activator of inflammation and the innate immune system. However, mtDNA level has not been tested for its role as a biomarker in the intensive care unit (ICU). We hypothesized that circulating cell-free mtDNA levels would be associated with mortality and improve risk prediction in ICU patients.

Methods and Findings

Analyses of mtDNA levels were performed on blood samples obtained from two prospective observational cohort studies of ICU patients (the Brigham and Women''s Hospital Registry of Critical Illness [BWH RoCI, n = 200] and Molecular Epidemiology of Acute Respiratory Distress Syndrome [ME ARDS, n = 243]). mtDNA levels in plasma were assessed by measuring the copy number of the NADH dehydrogenase 1 gene using quantitative real-time PCR. Medical ICU patients with an elevated mtDNA level (≥3,200 copies/µl plasma) had increased odds of dying within 28 d of ICU admission in both the BWH RoCI (odds ratio [OR] 7.5, 95% CI 3.6–15.8, p = 1×10⁻⁷) and ME ARDS (OR 8.4, 95% CI 2.9–24.2, p = 9×10⁻⁵) cohorts, while no evidence for association was noted in non-medical ICU patients. The addition of an elevated mtDNA level improved the net reclassification index (NRI) of 28-d mortality among medical ICU patients when added to clinical models in both the BWH RoCI (NRI 79%, standard error 14%, p<1×10⁻⁴) and ME ARDS (NRI 55%, standard error 20%, p = 0.007) cohorts. In the BWH RoCI cohort, those with an elevated mtDNA level had an increased risk of death, even in analyses limited to patients with sepsis or acute respiratory distress syndrome. Study limitations include the lack of data elucidating the concise pathological roles of mtDNA in the patients, and the limited numbers of measurements for some of biomarkers.

Conclusions

Increased mtDNA levels are associated with ICU mortality, and inclusion of mtDNA level improves risk prediction in medical ICU patients. Our data suggest that mtDNA could serve as a viable plasma biomarker in medical ICU patients. Please see later in the article for the Editors'' Summary     

Separating parental and treatment contributions to perinatal health after fresh and frozen embryo transfer in assisted reproduction: A cohort study with within-sibship analysis

BackgroundCompared to naturally conceived children, adverse perinatal outcomes are more common among children born after assisted reproductive technology with fresh embryo transfer (fresh-ET) or frozen embryo transfer (frozen-ET). However, most previous studies could not adequately control for family confounding factors such as subfertility. We compared birth size and duration of pregnancy among infants born after fresh-ET or frozen-ET versus natural conception, using a within-sibship design to account for confounding by maternal factors.Methods and findingsThis registry-based cohort study with nationwide data from Denmark (1994–2014), Norway (1988–2015), and Sweden (1988–2015) consisted of 4,510,790 live-born singletons, 4,414,703 from natural conception, 78,095 from fresh-ET, and 17,990 from frozen-ET. We identified 33,056 offspring sibling groups with the same mother, conceived by at least 2 different conception methods. Outcomes were mean birthweight, small and large for gestational age, mean gestational age, preterm (<37 weeks, versus ≥37), and very preterm birth (<32 weeks, versus ≥32). Singletons born after fresh-ET had lower mean birthweight (−51 g, 95% CI −58 to −45, p < 0.001) and increased odds of small for gestational age (odds ratio [OR] 1.20, 95% CI 1.08 to 1.34, p < 0.001), while those born after frozen-ET had higher mean birthweight (82 g, 95% CI 70 to 94, p < 0.001) and increased odds of large for gestational age (OR 1.84, 95% CI 1.56 to 2.17, p < 0.001), compared to naturally conceived siblings. Conventional population analyses gave similar results. Compared to naturally conceived siblings, mean gestational age was lower after fresh-ET (−1.0 days, 95% CI −1.2 to −0.8, p < 0.001), but not after frozen-ET (0.3 days, 95% CI 0.0 to 0.6, p = 0.028). There were increased odds of preterm birth after fresh-ET (OR 1.27, 95% CI 1.17 to 1.37, p < 0.001), and in most models after frozen-ET, versus naturally conceived siblings, with somewhat stronger associations in population analyses. For very preterm birth, population analyses showed increased odds for both fresh-ET (OR 2.03, 95% CI 1.90 to 2.12, p < 0.001) and frozen-ET (OR 1.66, 95% CI 1.42 to 1.94, p < 0.001) compared with natural conception, but results were notably attenuated within siblings (OR 1.18, 95% CI 1.0 to 1.41, p = 0.059, and OR 0.92, 95% CI 0.67 to 1.27, p = 0.6, for fresh-ET and frozen-ET, respectively). Sensitivity analyses in full siblings, in siblings born within 3-year interval, by birth order, and restricting to single embryo transfers and blastocyst transfers were consistent with the main analyses. Main limitations were high proportions of missing data on maternal body mass index and smoking.ConclusionsWe found that infants conceived by fresh-ET had lower birthweight and increased odds of small for gestational age, and those conceived by frozen-ET had higher birthweight and increased odds of large for gestational age. Conception by either fresh-ET or frozen-ET was associated with increased odds of preterm birth. That these findings were observed within siblings, as well as in conventional multivariable population analyses, reduces the likelihood that they are explained by confounding or selection bias.Trial registrationClinicalTrials.gov ISRCTN11780826.

Kjersti Westvik-Johari and co-workers report on perinatal outcomes following fresh and frozen embryo transfer.     

Albuminuria as a Risk Factor for Anemia in Chronic Kidney Disease: Result from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD)

Background

Anemia is a common complication among patients with chronic kidney disease (CKD), and it is associated with unfavorable clinical outcomes in patients with CKD independent of the estimated glomerular filtration rate (eGFR). We assessed the association of the urinary albumin-to-creatinine ratio (ACR) and eGFR with anemia in CKD patients.

Methods

We conducted a cross-sectional study using baseline data from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). Multiple regression analysis was performed to identify the independent association of albuminuria with anemia. Furthermore, odds ratios for anemia were calculated by cross-categorization of ACR and eGFR.

Results

Among 1,456 patients, the mean age was 53.5 ± 12.4 years, and the mean eGFR and ACR were 51.9 ± 30.5 mL/min per 1.73 m² and 853.2 ± 1,330.3 mg/g, respectively. Anemia was present in 644 patients (40.5%). Multivariate analysis showed that the odds ratio of anemia increased according to ACR levels, after adjusting for age, sex, eGFR, body mass index, pulse pressure, cause of CKD, use of erythropoiesis stimulating agents, serum calcium and ferritin (ACR < 30 mg/g as a reference group; 30–299 mg/g, adjusted odds ratio (OR) = 1.43, 95% confidence interval (CI) = 0.88–2.33; ≥300 mg/g, adjusted OR = 1.86, 95% CI = 1.12–3.10). In addition, graded associations were observed in cross-categorized groups of a higher ACR and eGFR compared to the reference group with an ACR <30 mg/g and eGFR ≥60 mL/min per 1.73 m².

Conclusion

The present study demonstrated that albuminuria was a significant risk factor for anemia in CKD patients independent of the eGFR.