Epidemiology and Outcome of Severe Sepsis and Septic Shock in Intensive Care Units in Mainland China

Introduction

Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality.

Methods

We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included.

Results

A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027–1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691–4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142–5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141–4.420) were significantly associated with mortality.

Conclusions

Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these 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.     

Long-Term Results after Proximal Thoracic Aortic Redo Surgery

Objective

To evaluate early and mid-term results in patients undergoing proximal thoracic aortic redo surgery.

Methods

We analyzed 60 patients (median age 60 years, median logistic EuroSCORE 40) who underwent proximal thoracic aortic redo surgery between January 2005 and April 2012. Outcome and risk factors were analyzed.

Results

In hospital mortality was 13%, perioperative neurologic injury was 7%. Fifty percent of patients underwent redo surgery in an urgent or emergency setting. In 65%, partial or total arch replacement with or without conventional or frozen elephant trunk extension was performed. The preoperative logistic EuroSCORE I confirmed to be a reliable predictor of adverse outcome- (ROC 0.786, 95%CI 0.64–0.93) as did the new EuroSCORE II model: ROC 0.882 95%CI 0.78–0.98. Extensive individual logistic EuroSCORE I levels more than 67 showed an OR of 7.01, 95%CI 1.43–34.27. A EuroSCORE II larger than 28 showed an OR of 4.44 (95%CI 1.4–14.06). Multivariate logistic regression analysis identified a critical preoperative state (OR 7.96, 95%CI 1.51–38.79) but not advanced age (OR 2.46, 95%CI 0.48–12.66) as the strongest independent predictor of in-hospital mortality. Median follow-up was 23 months (1–52 months). One year and five year actuarial survival rates were 83% and 69% respectively. Freedom from reoperation during follow-up was 100%.

Conclusions

Despite a substantial early attrition rate in patients presenting with a critical preoperative state, proximal thoracic aortic redo surgery provides excellent early and mid-term results. Higher EuroSCORE I and II levels and a critical preoperative state but not advanced age are independent predictors of in-hospital mortality. As a consequence, age alone should no longer be regarded as a contraindication for surgical treatment in this particular group of patients.     

Higher Adenoma Detection Rates with Endocuff-Assisted Colonoscopy – A Randomized Controlled Multicenter Trial

Objectives

The Endocuff is a device mounted on the tip of the colonoscope to help flatten the colonic folds during withdrawal. This study aimed to compare the adenoma detection rates between Endocuff-assisted (EC) colonoscopy and standard colonoscopy (SC).

Methods

This randomized prospective multicenter trial was conducted at four academic endoscopy units in Germany. Participants: 500 patients (235 males, median age 64[IQR 54–73]) for colon adenoma detection purposes were included in the study. All patients were either allocated to EC or SC. The primary outcome measure was the determination of the adenoma detection rates (ADR).

Results

The ADR significantly increased with the use of the Endocuff compared to standard colonoscopy (35.4%[95% confidence interval{CI} 29–41%] vs. 20.7%[95%CI 15–26%], p<0.0001). Significantly more sessile polyps were detected by EC. Overall procedure time and withdrawal time did not differ. Caecal and ileum intubation rates were similar. No major adverse events occurred in both groups. In multivariate analysis, age (odds ratio [OR] 1.03; 95%[CI] 1.01–1.05), male sex (OR 1.74; 95%CI 1.10–2.73), withdrawal time (OR 1.16; 95%CI 1.05–1.30), procedure time (OR 1.07; 95%CI 1.04–1.10), colon cleanliness (OR 0.60; 95%CI 0.39–0.94) and use of Endocuff (OR 2.09; 95%CI 1.34–3.27) were independent predictors of adenoma detection rates.

Conclusions

EC increases the adenoma detection rate by 14.7%(95%CI 6.9–22.5%). EC is safe, effective, easy to handle and might reduce colorectal interval carcinomas.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02034929","term_id":"NCT02034929"}}NCT02034929.     

Nucleated Red Blood Cells as Predictors of All-Cause Mortality in Cardiac Intensive Care Unit Patients: A Prospective Cohort Study

Background

The presence of nucleated red blood cells (NRBCs) in the peripheral blood of critically ill patients is associated with a poorer prognosis, though data on cardiovascular critical care patients is lacking. The aim of the present study was to assess the role of NRBCs as a predictor of intensive care unit (ICU) and in hospital all-cause mortality among cardiologic patients.

Methods

NRBCs were measured daily in consecutive cardiac ICU patients, including individuals with both coronary and non-coronary acute cardiac care. We excluded patients younger than 18 years, with cancer or hematological disease, on glucocorticoid therapy, those that were readmitted after hospital discharge and patients who died in the first 24 hours after admission. We performed a multiple logistic analysis to identify independent predictors of mortality.

Results

We included 152 patients (60.6 ± 16.8 years, 51.8% female, median ICU stay of 7 [4–11] days). The prevalence of NRBCs was 54.6% (83/152). The presence of NRBC was associated with a higher ICU mortality (49.4% vs 21.7%, P<0.001) as well as in-hospital mortality (61.4% vs 33.3%, p = 0.001). NRBC were equally associated with mortality among coronary disease (64.71% vs 32.5% [OR 3.80; 95%CI: 1.45–10.0; p = 0.007]) and non-coronary disease patients (61.45% vs 33.3% [OR 3.19; 95%CI: 1.63–6.21; p<0.001]). In a multivariable model, the inclusion of NRBC to the APACHE II score resulted in a significant improvement in the discrimination (p = 0.01).

Conclusions

NRBC are predictors of all-cause in-hospital mortality in patients admitted to a cardiac ICU. This predictive value is independent and complementary to the well validated APACHE II score.     

Fixed Effects Modelling for Provider Mortality Outcomes: Analysis of the Australia and New Zealand Intensive Care Society (ANZICS) Adult Patient Data-Base

Background

Risk adjusted mortality for intensive care units (ICU) is usually estimated via logistic regression. Random effects (RE) or hierarchical models have been advocated to estimate provider risk-adjusted mortality on the basis that standard estimators increase false outlier classification. The utility of fixed effects (FE) estimators (separate ICU-specific intercepts) has not been fully explored.

Methods

Using a cohort from the Australian and New Zealand Intensive Care Society Adult Patient Database, 2009–2010, the model fit of different logistic estimators (FE, random-intercept and random-coefficient) was characterised: Bayesian Information Criterion (BIC; lower values better), receiver-operator characteristic curve area (AUC) and Hosmer-Lemeshow (H-L) statistic. ICU standardised hospital mortality ratios (SMR) and 95%CI were compared between models. ICU site performance (FE), relative to the grand observation-weighted mean (GO-WM) on odds ratio (OR), risk ratio (RR) and probability scales were assessed using model-based average marginal effects (AME).

Results

The data set consisted of 145355 patients in 128 ICUs, years 2009 (47.5%) & 2010 (52.5%), with mean(SD) age 60.9(18.8) years, 56% male and ICU and hospital mortalities of 7.0% and 10.9% respectively. The FE model had a BIC = 64058, AUC = 0.90 and an H-L statistic P-value = 0.22. The best-fitting random-intercept model had a BIC = 64457, AUC = 0.90 and H-L statistic P-value = 0.32 and random-coefficient model, BIC = 64556, AUC = 0.90 and H-L statistic P-value = 0.28. Across ICUs and over years no outliers (SMR 95% CI excluding null-value = 1) were identified and no model difference in SMR spread or 95%CI span was demonstrated. Using AME (OR and RR scale), ICU site-specific estimates diverged from the GO-WM, and the effect spread decreased over calendar years. On the probability scale, a majority of ICUs demonstrated calendar year decrease, but in the for-profit sector, this trend was reversed.

Conclusions

The FE estimator had model advantage compared with conventional RE models. Using AME, between and over-year ICU site-effects were easily characterised.     

Association between Statin Use and Short-Term Outcome Based on Severity of Ischemic Stroke: A Cohort Study

Background

Statins reportedly improve clinical outcomes for ischemic stroke patients. However, it is unclear whether the contribution of statin treatment varies depending on the severity of stroke. We sought to investigate the relationship between statin use and the outcome of acute first-ever ischemic stroke patients stratified by stroke severity.

Methods

A total of 7,455 acute first-ever ischemic stroke patients without statin treatment before onset were eligible from the China National Stroke Registry. A National Institutes of Health Stroke Scale (NIHSS) score of 0 to 4 was defined as minor stroke, and a NIHSS score of >4 was defined as non-minor stroke. We analyzed the association between statin use during hospitalization and mortality as well as functional outcome (measured by a modified Rankin Scale score of 0–5) at 3 months after onset using multivariable logistic regression models.

Results

A total of 3,231 (43.3%) patients received statin treatment during hospitalization. Multivariable analysis showed that statin use during hospitalization decreased mortality of ischemic stroke patients (OR, 0.51; 95%CI, 0.38–0.67), but did not improve poor functional outcomes (OR, 0.95; 95CI%, 0.81–1.11) at 3 months. The interaction between statin use and stroke severity was significant both in dependence and death outcome (P = 0.04 for dependence outcome, P = 0.03 for death outcome). After stratification by stroke severity, statin use during hospitalization decreased the mortality of stroke (OR, 0.44; 95%CI, 0.31–0.62) and poor functional outcome (OR, 0.73; 95%CI, 0.57–0.92) at 3 months in the non-minor stroke group.

Conclusions

Statin use during hospitalization may improve the clinical outcome of acute first-ever ischemic stroke depending on the severity of stroke. Non-minor stroke patients may obtain benefit from statin treatment with improvements in poor functional outcomes and mortality.     

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.     

Nicotinic acetylcholine receptor variants associated with susceptibility to chronic obstructive pulmonary disease: a meta-analysis

Background

Only 10-15% of smokers develop chronic obstructive pulmonary disease (COPD) which indicates genetic susceptibility to the disease. Recent studies suggested an association between COPD and polymorphisms in CHRNA coding subunits of nicotinic acetylcholine receptor. Herein, we performed a meta-analysis to clarify the impact of CHRNA variants on COPD.

Methods

We searched Web of Knowledge and Medline from 1990 through June 2011 for COPD gene studies reporting variants on CHRNA. Pooled odds ratios (ORs) were calculated using the major allele or genotype as reference group.

Results

Among seven reported variants in CHRNA, rs1051730 was finally analyzed with sufficient studies. Totally 3460 COPD and 11437 controls from 7 individual studies were pooled-analyzed. A-allele of rs1051730 was associated with an increased risk of COPD regardless of smoking exposure (pooled OR = 1.26, 95% CI 1.18-1.34, p < 10^-5). At the genotypic level, the ORs gradually increased per A-allele (OR = 1.27 and 1.50 for GA and AA respectively, p < 10^-5). Besides, AA genotype exhibited an association with reduced FEV1% predicted (mean difference 3.51%, 95%CI 0.87-6.16%, p = 0.009) and increased risk of emphysema (OR 1.93, 95%CI 1.29-2.90, p = 0.001).

Conclusions

Our findings suggest that rs1051730 in CHRNA is a susceptibility variant for COPD, in terms of both airway obstruction and parenchyma destruction.     

Metformin Therapy and Risk of Cancer in Patients with Type 2 Diabetes: Systematic Review

Aims/Hypothesis

Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes.

Methods

Data source: MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers.

Results

Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74–0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36–0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76–0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83–0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma.

Conclusions/Interpretation

Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.     

C-Reactive Protein/Albumin Ratio Predicts 90-Day Mortality of Septic Patients

Introduction

Residual inflammation at ICU discharge may have impact upon long-term mortality. However, the significance of ongoing inflammation on mortality after ICU discharge is poorly described. C-reactive protein (CRP) and albumin are measured frequently in the ICU and exhibit opposing patterns during inflammation. Since infection is a potent trigger of inflammation, we hypothesized that CRP levels at discharge would correlate with long-term mortality in septic patients and that the CRP/albumin ratio would be a better marker of prognosis than CRP alone.

Methods

We evaluated 334 patients admitted to the ICU as a result of severe sepsis or septic shock who were discharged alive after a minimum of 72 hours in the ICU. We evaluated the performance of both CRP and CRP/albumin to predict mortality at 90 days after ICU discharge. Two multivariate logistic models were generated based on measurements at discharge: one model included CRP (Model-CRP), and the other included the CRP/albumin ratio (Model-CRP/albumin).

Results

There were 229 (67%) and 111 (33%) patients with severe sepsis and septic shock, respectively. During the 90 days of follow-up, 73 (22%) patients died. CRP/albumin ratios at admission and at discharge were associated with a poor outcome and showed greater accuracy than CRP alone at these time points (p = 0.0455 and p = 0.0438, respectively). CRP levels and the CRP/albumin ratio were independent predictors of mortality at 90 days (Model-CRP: adjusted OR 2.34, 95% CI 1.14–4.83, p = 0.021; Model-CRP/albumin: adjusted OR 2.18, 95% CI 1.10–4.67, p = 0.035). Both models showed similar accuracy (p = 0.2483). However, Model-CRP was not calibrated.

Conclusions

Residual inflammation at ICU discharge assessed using the CRP/albumin ratio is an independent risk factor for mortality at 90 days in septic patients. The use of the CRP/albumin ratio as a long-term marker of prognosis provides more consistent results than standard CRP values alone.     

Predictive Value of Ionized Calcium in Critically Ill Patients: An Analysis of a Large Clinical Database MIMIC II

Background and Objective

ionized calcium (iCa) has been investigated for its association with mortality in intensive care unit (ICU) patients in many studies. However, these studies are small in sample size and the results are conflicting. The present study aimed to establish the association of iCa with mortality by using a large clinical database.

Methods

Multiparameter Intelligent Monitoring in Intensive Care II (MIMIC II) database was used for analysis. Patients older than 15 years were eligible, and patients without iCa measured during their ICU stay were excluded. Demographic data and clinical characteristics were extracted and compared between survivors and non-survivors. iCa measure on ICU admission was defined as Ca₀; Ca_max was the maximum iCa during ICU stay; Ca_min was the minimum value of iCa during the ICU stay; Ca_mean was the arithmetic mean iCa during ICU stay.

Main results

A total of 15409 ICU admissions satisfied our inclusion criteria and were included in our analysis. The prevalence of hypocalcemia on ICU entry was 62.06%. Ca₀ was significantly lower in non-survivors than in survivors (1.11±0.14 vs 1.13±0.10 mmol/l, p<0.001). In multivariate analysis, moderate hypocalcemia in Ca0 was significantly associated with increased risk of death (OR: 1.943; 95% CI: 1.340–2.817), and mild hypercalcemia was associated with lower mortality (OR: 0.553, 95% CI: 0.400–0.767). While moderate and mild hypocalcemia in Ca_mean is associated with increased risk of death (OR: 1.153, 95% CI: 1.006–1.322 and OR: 2.520, 95% CI: 1.485–4.278), hypercalcemia in Ca_mean is not significantly associated with ICU mortality.

Conclusion

The relationship between Ca₀ and clinical outcome follows an “U” shaped curve with the nadir at the normal range, extending slightly to hypercalcemia. Mild hypercalcemia in Ca₀ is protective, whereas moderate and mild hypocalcemia in Ca_mean is associated with increased risk of death.     

Factors Associated with Myopia in School Children in China: The Beijing Childhood Eye Study

Purpose

To assess factors associated with myopia in school children in rural and urban parts of Greater Beijing.

Methods

The Beijing Pedriatic Eye Study was a population-based cross-sectional study, in which one school of each level (primary, junior high, senior high) was randomly selected from nine randomly selected districts out of 18 districts of Greater Beijing. The children underwent non-cylcoplegic refractometry and their parents an interview.

Results

Of 16,771 eligible students, 15,066 (89.8%) children (7,769 (51.6%) girls) participated, with 8,860 (58.8%) participants living in the rural region. Mean age was 13.2±3.4 years (range:7–18 years). In multivariate analysis, prevalence of myopia (defined as ≤−1.00 diopters) was associated with higher age (Odds ratio(OR):1.37; 95% confidence interval(CI):1.35,1.39), female gender (OR:1.35;95%CI:1.25,1.47), key school type (OR:0.77;95%CI: 0.70,0.85), higher family income (OR:1.04;95%CI:1.01,1.07), parental myopia (OR:1.46;95%CI:1.40,1.53), dim reading illumination (OR:0.93;95%CI: 0.88,0.98), longer daily studying duration (OR:1.10;95%CI:1.06,1.15), shorter duration of watching television (or computer) (OR:0.93;95%CI:0.89,0.97), higher self-reported protein intake (OR:0.94;95%CI:0.90,0.99), feeling well about life and status (OR:0.93;95%CI:0.89,0.98), and feeling tired or dizzy (OR:0.94;95%CI:0.91,0.97). Prevalence of high myopia (defined as ≤−6.00 diopters) was associated with higher age (OR:1.43;95%CI:1.38, 1.48), key school type (OR:0.61;95%CI:0.49,0.74), family income (OR:1.07;95%CI:1.02,1.13), parental myopia (OR:1.65;95%CI:1.54,1.76), dim reading illumination (OR:0.86;95%CI:0.77,0.96), less rest during studying (OR:1.18;95%CI:1.10,1.27), feeling well about life and studying (OR:0.88;95%CI: 0.81,0.96) and feeling dizzy or tired (OR:0.93;95%CI:0.87,0.99). Prevalence of high myopia (defined as ≤−8.00 diopters) was significantly associated with higher age (OR:1.39;95%CI:1.31,1.48;), key school type (OR:0.61;95%CI:0.42,0.88) and parental myopia (OR:1.87;95%CI:1.66,2.12).

Conclusions

Myopia in school children in Greater Beijing was associated with higher age, female gender, school type, parental myopia, higher socioeconomic background, dim reading illumination, longer daily studying duration, less rest during study, shorter duration of watching television (or computer), higher self-reported protein intake, feeling well about life and status, and feeling tired and dizzy.     

Pneumocystis Pneumonia in HIV-Infected and Immunocompromised Non-HIV Infected Patients: A Retrospective Study of Two Centers in China

Background

Pneumocystis pneumonia (PCP) is an emerging infectious disease in immunocompromised hosts. However, the clinical characteristics of these patients are poorly understood in mainland China.

Methods

We performed a retrospective study of PCP from 2008 to 2012. Information was collected regarding clinical manifestations, hospitalization, and outcome. A prognostic analysis was performed using a Cox regression model.

Results

151 cases of PCP were included; 46 non-HIV and 105 HIV cases. All-cause mortality (15.2% vs. 12.4%, p = 0.64) and the results of time-to-event analysis (log-rank test, p = 0.62) were similar between non-HIV and HIV infected cases, respectively. From 2008 to 2012, time from admission to initial treatment in non-HIV infected PCP patients showed declining trend [median (range) 20 (9–44) vs. 12 (4–24) vs. 9 (2–23) vs. 7 (2–22) vs. 7 (1–14) days]. A similar trend was observed for all-cause mortality (33.3% vs. 20.0% vs.14.3% vs. 14.3% vs. 6.7%). Patients with four or more of the following clinical manifestations (cough, dyspnea, fever, chest pain, and weight loss) [adjusted HR (AHR) 29.06, 95% CI 2.13–396.36, P = 0.01] and admission to intensive care unit (ICU) [AHR 22.55, 95% CI 1.36–375.06, P = 0.03] were independently associated with all-cause mortality in non-HIV infected PCP patients. Variables associated with mortality in HIV infected PCP patients were admission to ICU (AHR 72.26, 95% CI 11.76–443.87, P<0.001) and albumin ≤30 g/L (AHR 9.93 95% CI 1.69–58.30, P = 0.01).

Conclusions

Upon admission comprehensive clinical assessment including assessment of four or more clinical manifestations (cough, dyspnea, fever, chest pain, and weight loss) in non-HIV infected PCP patients and albumin ≤30 g/L in HIV infected patients might improve prognosis.     

Potential Risk Factors of Persistent Low Back Pain Developing from Mild Low Back Pain in Urban Japanese Workers

Study Design

Two-year, prospective cohort data from the Japan epidemiological research of occupation-related back pain study in urban settings were used for this analysis.

Objective

To examine the association between aggravated low back pain and psychosocial factors among Japanese workers with mild low back pain.

Summary of Background Data

Although psychosocial factors are strongly indicated as yellow flags of low back pain (LBP) leading to disability, the association between aggravated LBP and psychosocial factors has not been well assessed in Japanese workers.

Methods

At baseline, 5,310 participants responded to a self-administered questionnaire including questions about individual characteristics, ergonomic work demands, and work-related psychosocial factors (response rate: 86.5%), with 3,811 respondents completing the 1-year follow-up questionnaire. The target outcome was aggravation of mild LBP into persistent LBP during the follow-up period. Incidence was calculated for the participants with mild LBP during the past year at baseline. Logistic regression was used to explore risk factors associated with persistent LBP.

Results

Of 1,675 participants who had mild LBP during the preceding year, 43 (2.6%) developed persistent LBP during the follow-up year. Multivariate analyses adjusted for individual factors and an ergonomic factor found statistically significant or almost significant associations of the following psychosocial factors with persistent LBP: interpersonal stress at work [adjusted odds ratio (OR): 1.96 and 95% confidence interval (95%CI): 1.00–3.82], job satisfaction (OR: 2.34, 95%CI: 1.21–4.54), depression (OR: 1.92, 95%CI: 1.00–3.69), somatic symptoms (OR: 2.78, 95%CI: 1.44–5.40), support from supervisors (OR: 2.01, 95%CI: 1.05–3.85), previous sick-leave due to LBP (OR: 1.94, 95%CI: 0.98–3.86) and family history of LBP with disability (OR: 1.98, 95%CI: 1.04–3.78).

Conclusions

Psychosocial factors are important risk factors for persistent LBP in urban Japanese workers. It may be necessary to take psychosocial factors into account, along with physical work demands, to reduce LBP related disability.     

Naloxone for Severe Traumatic Brain Injury: A Meta-Analysis

Objective

The efficiency of naloxone for the management of secondary brain injury after severe traumatic brain injury (sTBI) remains undefined. The aim of this study is to evaluate the current evidence regarding the clinical efficiency and safety of naloxone as a treatment for sTBI in mainland China.

Methodology/Principal Findings

A systematic search of the China Biology Medicine disc (CBM), China Science and Technology Journal Database (VIP), China National Knowledge Internet (CNKI), and Wan Fang Database was performed to identify randomized controlled trials (RCTs) of naloxone treatment for patients with sTBI in mainland China. The quality of the included trials was assessed, and the RevMan 5.1 software was employed to conduct this meta-analysis. Nineteen RCTs including 2332 patients were included in this study. The odds ratio (OR) showed statistically significant differences between the naloxone group and the control group (placebo) in terms of mortality at 18 months after treatment (OR, 0.51, 95%CI: 0.38–0.67; p<0.00001), prevalence of abnormal heart rates (OR, 0.30, 95%CI: 0.21–0.43; p<0.00001), abnormal breathing rate (OR, 0.25, 95%CI: 0.17–0.36; p<0.00001) at discharge, the level of intracranial pressure at discharge (OR, 2.00, 95%CI: 1.41–2.83; p = 0.0001), verbal or physical dysfunction rate (OR, 0.65, 95%CI: 0.43–0.98; p = 0.04), and severe disability rate (OR, 0.47, 95%CI: 0.30–0.73; p = 0.0001) at 18 months after the treatment. The mean difference (MD) showed statistically significant differences in awakening time at discharge (MD, −4.81, 95%CI: −5.49 to −4.12; p<0.00001), and GCS at 3 days (MD, 1.00, 95%CI: 0.70–1.30; p<0.00001) and 10 days (MD, 1.76, 95%CI: 1.55–1.97; p<0.00001) after treatment comparing naloxone with placebo group.

Conclusions/Significance

This study indicated that applying naloxone in the early stage for sTBI patients might effectively reduce mortality, control intracranial pressure (ICP), and significantly improve the prognosis.     

Incidence and Risk of Cardiotoxicity Associated with Bortezomib in the Treatment of Cancer: A Systematic Review and Meta-Analysis

Background

We conducted a systematic review and meta-analysis to clarify the incidence and risk of cardiotoxicity associated with bortezomib in cancer patients.

Methods

Databases from PubMed, Web of Science and abstracts presented at ASCO meeting up to July 31, 2013 were searched to identify relevant studies. Eligible studies included prospective phase II and III trials evaluating bortezomib in cancer patients with adequate data on cardiotoxicity. Statistical analyses were conducted to calculate the summary incidence, odds ratio (OR) and 95% confidence intervals (CIs) by using either random effects or fixed effect models according to the heterogeneity of included studies.

Results

A total of 5718 patients with a variety of malignancies from 25 clinical trials were included in our analysis. The incidence of all-grade and high-grade cardiotoxicity associated with bortezomib was 3.8% (95%CI: 2.6–5.6%) and 2.3% (1.6–3.5%), with a mortality of 3.0% (1.4–6.5%). Patients treated with bortezomib did not significantly increase the risk of all-grade (OR 1.15, 95%CI: 0.82–1.62, p = 0.41) and high-grade (OR 1.13, 95%CI: 0.58–2.24, p = 0.72) cardiotoxicity compared with patients treated with control medication. Sub-group analysis showed that the incidence of cardiotoxicity varied with tumor types, treatment regimens and phases of trials. No evidence of publication bias was observed.

Conclusions

The use of bortezomib does not significantly increase the risk of cardiotoxicity compared to control patients. Further studies are recommended to investigate this association and risk differences among different tumor types, treatment regimens and phases of trials.     

The Synergistic Effect of Functional Status and Comorbidity Burden on Mortality: A 16-Year Survival Analysis

Objectives

The relationship between disability and comorbidity on mortality is widely perceived as additive in clinical models of frailty.

Design

National data were retrospectively extracted from medical records of community hospital.

Data Sources

There were of 12,804 acutely-disabled patients admitted for inpatient rehabilitation in Singapore rehabilitation community hospitals from 1996 through 2005 were followed up for death till 31 December 2011.

Outcome Measure

Cox proportional-hazards regression to assess the interaction of comorbidity and disability at discharge on all-cause mortality.

Results

During a median follow-up of 10.9 years, there were 8,565 deaths (66.9%). The mean age was 73.0 (standard deviation: 11.5) years. Independent risk factors of mortality were higher comorbidity (p<0.001), severity of disability at discharge (p<0.001), being widowed (adjusted hazard ratio [aHR]: 1.38, 95% confidence interval [CI]:1.25–1.53), low socioeconomic status (aHR:1.40, 95%CI:1.29–1.53), discharge to nursing home (aHR:1.14, 95%CI:1.05–1.22) and re-admission into acute care (aHR:1.54, 95%CI:1.45–1.65). In the main effects model, those with high comorbidity had an aHR = 2.41 (95%CI:2.13–2.72) whereas those with total disability had an aHR = 2.28 (95%CI:2.12–2.46). In the interaction model, synergistic interaction existed between comorbidity and disability (p<0.001) where those with high comorbidity and total disability had much higher aHR = 6.57 (95%CI:5.15–8.37).

Conclusions

Patients with greater comorbidity and disability at discharge, discharge to nursing home or re-admission into acute care, lower socioeconomic status and being widowed had higher mortality risk. Our results identified predictive variables of mortality that map well onto the frailty cascade model. Increasing comorbidity and disability interacted synergistically to increase mortality risk.     

The Impact of Renal Impairment on Long-Term Safety and Effectiveness of Drug-Eluting Stents

Background

Renal impairment (RI) is associated with impaired prognosis in patients with coronary artery disease. Clinical and angiographic outcomes of patients undergoing percutaneous coronary intervention (PCI) with the use of drug-eluting stents (DES) in this patient population are not well established.

Methods

We pooled individual data for 5,011 patients from 3 trials with the exclusive and unrestricted use of DES (SIRTAX - N = 1,012, LEADERS - N = 1,707, RESOLUTE AC - N = 2,292). Angiographic follow-up was available for 1,544 lesions. Outcomes through 2 years were stratified according to glomerular filtration rate (normal renal function: GFR≥90 ml/min; mild RI: 90<GFR≥60 ml/min; moderate/severe RI GFR<60 ml/min).

Results

Patients with moderate/severe RI had an increased risk of cardiac death or myocardial infarction ([MI], OR 2.14, 95%CI 1.36–3.36), cardiac death (OR 2.21, 95%CI 1.10–4.46), and MI (OR 2.02, 95%CI 1.19–3.43) compared with patients with normal renal function at 2 years follow-up. There was no difference in cardiac death or MI between patients with mild RI compared to those with normal renal function (OR 1.10, 95%CI 0.75–1.61). The risk of target-lesion revascularization was similar for patients with moderate/severe RI (OR 1.17, 95%CI 0.70–1.95) and mild RI (OR 1.16, 95%CI 0.81–1.64) compared with patients with normal renal function. In-stent late loss and in-segment restenosis were not different for patients with moderate/severe RI, mild RI, and normal renal function.

Conclusions

Renal function does not affect clinical and angiographic effectiveness of DES. However, prognosis remains impaired among patients with moderate/severe RI.