Cancer Incidence and Mortality in Patients with Type 2 Diabetes Treated with Human Insulin: A Cohort Study in Shanghai

Aim

The aim was to investigate the association between human insulin and cancer incidence and mortality in Chinese patients with type 2 diabetes.

Methods

We recruited 8,774 insulin-naïve diabetes patients from the Shanghai Diabetes Registry (SDR). The follow-up rate was 85.4%. All subjects were divided into the insulin use cohort (n = 3,639) and the non-insulin use cohort (n = 5,135). The primary outcome was the first diagnosis of any cancer. The secondary outcome was all-cause mortality. Cox proportional hazards model was used to estimate the relative risk (RR) of cancer and mortality.

Results

We observed 98 cancer events in the insulin use cohort and 170 in the non-insulin use cohort. Cancer incidence rates were 78.6 and 74.3 per 10,000 patients per year in the insulin users and the non-insulin users, respectively. No significant difference in cancer risk was observed between the two cohorts (adjusted RR = 1.20, 95% CI 0.89–1.62, P = 0.228). Regarding site-specific cancers, only the risk of liver cancer was significantly higher in the insulin users compared to that in the non-insulin users (adjusted RR = 2.84, 95% CI 1.12–7.17, P = 0.028). The risks of overall mortality (adjusted RR = 1.89, 95% CI 1.47–2.43, P<0.0001) and death from cancer (adjusted RR = 2.16, 95% CI 1.39–3.35, P = 0.001) were all significantly higher in the insulin users than in the non-insulin users.

Conclusion

There was no excess risk of overall cancer in patients with type 2 diabetes who were treated with human insulin. However, a significantly higher risk of liver cancer was found in these patients. Moreover, insulin users showed higher risks of overall and cancer mortality. Considering that individuals treated with insulin were more likely to be advanced diabetic patients, caution should be used in interpreting these results.     

Mortality Predictors in Renal Transplant Recipients with Severe Sepsis and Septic Shock

Introduction

The growing number of renal transplant recipients in a sustained immunosuppressive state is a factor that can contribute to increased incidence of sepsis. However, relatively little is known about sepsis in this population. The aim of this single-center study was to evaluate the factors associated with hospital mortality in renal transplant patients admitted to the intensive care unit (ICU) with severe sepsis and septic shock.

Methods

Patient demographics and transplant-related and ICU stay data were retrospectively collected. Multiple logistic regression was conducted to identify the independent risk factors associated with hospital mortality.

Results

A total of 190 patients were enrolled, 64.2% of whom received kidneys from deceased donors. The mean patient age was 51±13 years (males, 115 [60.5%]), and the median APACHE II was 20 (16–23). The majority of patients developed sepsis late after the renal transplantation (2.1 [0.6–2.3] years). The lung was the most common infection site (59.5%). Upon ICU admission, 16.4% of the patients had ≤1 systemic inflammatory response syndrome criteria. Among the patients, 61.5% presented with ≥2 organ failures at admission, and 27.9% experienced septic shock within the first 24 hours of ICU admission. The overall hospital mortality rate was 38.4%. In the multivariate analysis, the independent determinants of hospital mortality were male gender (OR = 5.9; 95% CI, 1.7–19.6; p = 0.004), delta SOFA 24 h (OR = 1.7; 95% CI, 1.2–2.3; p = 0.001), mechanical ventilation (OR = 30; 95% CI, 8.8–102.2; p<0.0001), hematologic dysfunction (OR = 6.8; 95% CI, 2.0–22.6; p = 0.002), admission from the ward (OR = 3.4; 95% CI, 1.2–9.7; p = 0.02) and acute kidney injury stage 3 (OR = 5.7; 95% CI,1.9–16.6; p = 0.002).

Conclusions

Hospital mortality in renal transplant patients with severe sepsis and septic shock was associated with male gender, admission from the wards, worse SOFA scores on the first day and the presence of hematologic dysfunction, mechanical ventilation or advanced graft dysfunction.     

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.     

Tacrolimus-Based versus Cyclosporine-Based Immunosuppression in Hepatitis C Virus-Infected Patients after Liver Transplantation: A Meta-Analysis and Systematic Review

Background

Most liver transplant recipients receive calcineurin inhibitors (CNIs), especially tacrolimus and cyclosporine, as immunosuppressant agents to prevent rejection. A controversy exists as to whether the outcomes of hepatitis C virus (HCV)-infected liver transplant patients differ based on the CNIs used. This meta-analysis compares the clinical outcomes of tacrolimus-based and cyclosporine-based immunosuppression, especially cases of HCV recurrence in liver transplant patients with end-stage liver disease caused by HCV infection.

Methods

Related articles were identified from the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, and Embase. Meta-analyses were performed for the results of homogeneous studies.

Results

Nine randomized or quasi-randomized controlled trials were included. The total effect size of mortality (RR = 0.98, 95% CI: 0.77–1.25, P = 0.87) and graft loss (RR = 1.05, 95% CI: 0.83–1.33, P = 0.67) showed no significant difference between the two groups irrespective of duration of immunosuppressant therapy after liver transplantation. In addition, the HCV recurrence-induced mortality (RR = 1.11, 95% CI: 0.66–1.89, P = 0.69), graft loss (RR = 1.62, 95% CI: 0.64–4.07, P  = 0.31) and retransplantation (RR = 1.40, 95% CI: 0.48–4.09, P = 0.54), as well as available biopsies, confirmed that histological HCV recurrences (RR =  0.92, 95% CI: 0.71–1.19, P = 0.51) were similar.

Conclusion

These results suggested no difference in posttransplant HCV recurrence-induced mortality, graft loss and retransplantation, as well as histological HCV recurrence in patients treated with tacrolimus-based and cyclosporine-based immunosuppresion.     

Extravascular lung water correlates multiorgan dysfunction syndrome and mortality in sepsis

Background

This study was designated to investigate whether increased extravascular lung water index (EVLWI) may correlate multiple organ dysfunction syndrome (MODS) and mortality in sepsis.

Methods

We designed a prospective cohort study in an intensive care unit of a tertiary care hospital. Sixty-seven patients with severe sepsis were included. Data were used to determine an association between EVLWI and the development of MODS and mortality. These connections were determined by the multiple logistic regression, plotting the receiver operating characteristic (ROC) curve and by Spearman test.

Results

EVLWI levels were higher in MODS patients on day 1 (median (IQR), 18(12.8–23.9) ml/kg, n = 38, p<0.0001) than in those without (median (IQR), 12.4 (7.9–16.3) ml/kg, n = 29) and day 3 (median (IQR), 17.8 (11.2–22.8) ml/kg, n = 29, p = 0.004) than in those without (median (IQR), 12.4 (8.0–16.3) ml/kg, n = 29). EVLWI was used as an independent predictor of the development of MODS (odds ratio, 1.6; p = 0.005; 95% confidence interval, 1.2∼2.2) during ICU stay. The area under the ROC curve showed that EVLWI levels could predict MODS (0.866) and mortality (0.881) during ICU stay. Meanwhile, the higher of SOFA score, the more EVLWI was found on day 1 (r = 0.7041, p<0.0001) and day 3 (r = 0.7732, p<0.0001).

Conclusions

Increased EVLWI levels correlates development of MODS and mortality during the patients'' ICU stay. Further more, the potential of novel treatment in severe sepsis with lung injury may develop.     

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.     

Phenotype and Functions of Natural Killer Cells in Critically-Ill Septic Patients

Rationale

Natural killer cells, as a major source of interferon-γ, contribute to the amplification of the inflammatory response as well as to mortality during severe sepsis in animal models.

Objective

We studied the phenotype and functions of circulating NK cells in critically-ill septic patients.

Methods

Blood samples were taken <48 hours after admission from 42 ICU patients with severe sepsis (n = 15) or septic shock (n = 14) (Sepsis group), non-septic SIRS (n = 13) (SIRS group), as well as 21 healthy controls. The immuno-phenotype and functions of NK cells were studied by flow cytometry.

Results

The absolute number of peripheral blood CD3–CD56⁺ NK cells was similarly reduced in all groups of ICU patients, but with a normal percentage of NK cells. When NK cell cytotoxicity was evaluated with degranulation assays (CD107 expression), no difference was observed between Sepsis patients and healthy controls. Under antibody-dependent cell cytotoxicity (ADCC) conditions, SIRS patients exhibited increased CD107 surface expression on NK cells (62.9[61.3–70]%) compared to healthy controls (43.5[32.1–53.1]%) or Sepsis patients (49.2[37.3–62.9]%) (p = 0.002). Compared to healthy (10.2[6.3–13.1]%), reduced interferon-γ production by NK cells (K562 stimulation) was observed in Sepsis group (6.2[2.2–9.9]%, p<0.01), and especially in patients with septic shock. Conversely, SIRS patients exhibited increased interferon-γ production (42.9[30.1–54.7]%) compared to Sepsis patients (18.4[11.7–35.7]%, p<0.01) or healthy controls (26.8[19.3–44.9]%, p = 0.09) in ADCC condition.

Conclusions

Extensive monitoring of the NK-cell phenotype and function in critically-ill septic patients revealed early decreased NK-cell function with impaired interferon-γ production. These results may aid future NK-based immuno-interventions.

Trial Registration

NTC00699868.     

Sedentary Behavior and Incident Cancer: A Meta-Analysis of Prospective Studies

Background

Sedentary behavior is ubiquitous in modern adults'' daily lives and it has been suggested to be associated with incident cancer. However, the results have been inconsistent. In this study, we performed a systematic review and meta-analysis of prospective cohort studies to clarify the association between sedentary behavior and incident cancer.

Method

PubMed and Embase databases were searched up to March 2014. All prospective cohort studies on the association between sedentary behavior and incident cancer were included. The summary relative risks (RRs) with 95% confidence intervals (CIs) were estimated using random effect model.

Results

A total of 17 prospective studies from 14 articles, including a total of 857,581 participants and 18,553 cases, were included in the analysis for sedentary behavior and risk of incident cancer. The overall meta-analysis suggested that sedentary behavior increased risk of cancer (RR = 1.20, 95%CI = 1.12–1.28), with no evidence of heterogeneity between studies (I ² = 7.3%, P = 0.368). Subgroup analyses demonstrated that there were statistical associations between sedentary behavior and some cancer types (endometrial cancer: RR = 1.28, 95% CI = 1.08–1.53; colorectal cancer: RR = 1.30, 95%CI = 1.12–1.49; breast cancer: RR = 1.17, 95%CI = 1.03–1.33; lung cancer: RR = 1.27, 95%CI = 1.06–1.52). However, there was no association of sedentary behavior with ovarian cancer (RR = 1.26, 95%CI = 0.87–1.82), renal cell carcinoma (RR = 1.11, 95%CI = 0.87–1.41) or non-Hodgkin lymphoid neoplasms (RR = 1.09, 95%CI = 0.82–1.43).

Conclusion

The present meta-analysis suggested that prolonged sedentary behavior was independently associated with an increased risk of incident endometrial, colorectal, breast, and lung cancers, but not with ovarian cancer, renal cell carcinoma or non-Hodgkin lymphoid neoplasms.     

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     

Nutritional Support for Patients Sustaining Traumatic Brain Injury: A Systematic Review and Meta-Analysis of Prospective Studies

Background

In traumatic brain injury (TBI), the appropriate timing and route of feeding, and the efficacy of immune-enhancing formulae have not been well established. We performed this meta-analysis aiming to compare the effects of different nutritional support modalities on clinical outcomes of TBI patients.

Methods

We systematically searched Pubmed, Embase, and the Cochrane Library until October, 2012. All randomized controlled trials (RCTs) and non-randomized prospective studies (NPSs) that compared the effects of different routes, timings, or formulae of feeding on outcomes in TBI patients were selected. The primary outcomes included mortality and poor outcome. The secondary outcomes included the length of hospital stay, the length of ventilation days, and the rate of infectious or feeding-related complications.

Findings

13 RCTs and 3 NPSs were included. The pooled data demonstrated that, compared with delayed feeding, early feeding was associated with a significant reduction in the rate of mortality (relative risk [RR] = 0.35; 95% CI, 0.24–0.50), poor outcome (RR = 0.70; 95% CI, 0.54–0.91), and infectious complications (RR = 0.77; 95% CI, 0.59–0.99). Compared with enteral nutrition, parenteral nutrition showed a slight trend of reduction in the rate of mortality (RR = 0.61; 95% CI, 0.34–1.09), poor outcome (RR = 0.73; 95% CI, 0.51–1.04), and infectious complications (RR = 0.89; 95% CI, 0.66–1.22), whereas without statistical significances. The immune-enhancing formula was associated with a significant reduction in infection rate compared with the standard formula (RR = 0.54; 95% CI, 0.35–0.82). Small-bowel feeding was found to be with a decreasing rate of pneumonia compared with nasogastric feeding (RR = 0.41; 95% CI, 0.22–0.76).

Conclusion

After TBI, early initiation of nutrition is recommended. It appears that parenteral nutrition is superior to enteral nutrition in improving outcomes. Our results lend support to the use of small-bowel feeding and immune-enhancing formulae in reducing infectious complications.     

Moderate Hyponatremia Is Associated with Increased Risk of Mortality: Evidence from a Meta-Analysis

Background

Hyponatremia is the most common electrolyte disorder in clinical practice, and evidence to date indicates that severe hyponatremia is associated with increased morbidity and mortality. The aim of our study was to perform a meta-analysis that included the published studies that compared mortality rates in subjects with or without hyponatremia of any degree.

Methods and Findings

An extensive Medline, Embase and Cochrane search was performed to retrieve the studies published up to October 1^st 2012, using the following words: “hyponatremia” and “mortality”. Eighty-one studies satisfied inclusion criteria encompassing a total of 850222 patients, of whom 17.4% were hyponatremic. The identification of relevant abstracts, the selection of studies and the subsequent data extraction were performed independently by two of the authors, and conflicts resolved by a third investigator. Across all 81 studies, hyponatremia was significantly associated with an increased risk of overall mortality (RR = 2.60[2.31–2.93]). Hyponatremia was also associated with an increased risk of mortality in patients with myocardial infarction (RR = 2.83[2.23–3.58]), heart failure (RR = 2.47[2.09–2.92]), cirrhosis (RR = 3.34[1.91–5.83]), pulmonary infections (RR = 2.49[1.44–4.30]), mixed diseases (RR = 2.59[1.97–3.40]), and in hospitalized patients (RR = 2.48[2.09–2.95]). A mean difference of serum [Na⁺] of 4.8 mmol/L was found in subjects who died compared to survivors (130.1±5.6 vs 134.9±5.1 mmol/L). A meta-regression analysis showed that the hyponatremia-related risk of overall mortality was inversely correlated with serum [Na⁺]. This association was confirmed in a multiple regression model after adjusting for age, gender, and diabetes mellitus as an associated morbidity.

Conclusions

This meta-analysis shows for the first time that even a moderate serum [Na⁺] decrease is associated with an increased risk of mortality in commonly observed clinical conditions across large numbers of patients.     

Serum Levels of Caspase-Cleaved Cytokeratin-18 and Mortality Are Associated in Severe Septic Patients: Pilot Study

Objective

Apoptosis is increased in sepsis. Cytokeratin 18 (CK-18), a protein of the intermediate filament group present in most epithelial and parenchymal cells, is cleaved by the action of caspases and released into the blood as caspase-cleaved CK (CCCK)-18 during apoptosis. Circulating levels of CCCK-18 have scarcely been explored in septic patients. In one study with 101 severe septic patients, the authors reported higher serum CCCK-18 levels in non-survivors than in survivors; however, the sample size was too small to demonstrate an association between serum CCCK-18 levels and early mortality and whether they could be used as a biomarker to predict outcomes in septic patients. Thus, these were the objectives of this study with a large series of patients.

Methods

We performed a prospective, multicenter, observational study in six Spanish Intensive Care Units with 224 severe septic patients. Blood samples were collected at the time that severe sepsis was diagnosed to determine serum levels of CCCK-18, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-10. The end point was 30-day mortality.

Results

Non-surviving patients (n = 80) showed higher serum CCCK-18 levels (P<0.001) than survivors (n = 144). Multiple logistic regression analysis showed that serum CCCK-18 levels>391 u/L were associated with 30-day survival (Odds ratio = 2.687; 95% confidence interval = 1.449–4.983; P = 0.002), controlling for SOFA score, serum lactic acid levels and age. Kaplan-Meier survival analysis showed that the risk of death in septic patients with serum CCCK-18 levels >391 u/L was higher than in patients with lower values (Hazard Ratio = 3.1; 95% CI = 1.96–4.84; P<0.001). Serum CCCK-18 levels were positively associated with serum levels of IL-6 and lactic acid, and with SOFA and APACHE scores.

Conclusions

The major novel finding of our study, the largest cohort of septic patients providing data on circulating CCCK-18 levels, was that serum CCCK-18 levels are associated with mortality in severe septic patients.     

Association between Plasminogen Activator Inhibitor-1 -675 4G/5G Polymorphism and Sepsis: A Meta-Analysis

Background

Several studies have evaluated the association between plasminogen activator inhibitor-1 (PAI-1) -675 4G/5G polymorphism and sepsis in different populations. However, the available results are conflicting.

Methods

A search of Pubmed and EMBASE databases was performed to identify relevant studies for inclusion in the meta-analysis. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were determined using a random-effects model.

Results

Twelve case-control studies and three cohort studies were included. Overall, a significant association between 4G/5G polymorphism and sepsis risk was observed for 4G/4G vs. 4G/5G +5G/5G (OR = 1.30, 95% CI 1.08–1.56, P = 0.006). In addition, there was a significant association between PAI-1 4G/5G polymorphism and sepsis-related mortality (OR = 1.72, 95% CI 1.27–2.33, P = 0.0005). In subgroup analyses, increased sepsis risk and mortality risk were found in Caucasians and in patients with sepsis.

Conclusions

This meta-analysis suggested that the PAI-1 -675 4G/5G polymorphism was a risk factor for sepsis and sepsis mortality.     

Reproductive and Exogenous Hormone Factors in Relation to Risk of Meningioma in Women: A Meta-Analysis

Background and Objective

A number of studies have focused on the association between oral contraceptive (OC), hormonal replacement therapy (HRT) and reproductive factors and meningioma risk, but the results were inconsistent. Thus, a meta-analysis was performed to obtain more precise estimates of risk.

Methods

We conducted a literature search using PubMed and EMBASE databases to July2013, without any limitations. Random effects models were used to summarize results.

Results

Twelve case-control and six cohort studies were included in this meta-analysis. We found that an increased risk of meningioma was associated with HRT use(RR = 1.19, 95% CI = 1.01–1.40), postmenopausal women(RR = 1.32, 95% CI = 1.07–1.64) and parity(RR = 1.18, 95% CI = 1.00–1.40).No significant associations were observed for OC use (RR = 0.93, 95% CI = 0.83–1.03), age at menarche(RR = 1.06, 95% CI = 0.92–1.21), age at menopause(RR = 1.03, 95% CI = 0.81–1.30), or age at first birth(RR = 0.94, 95% CI = 0.80–1.10).

Conclusion

In conclusion, the results of our study support the hypothesis that longer exposure to effect of female sex hormones may increase the risk of meningioma in women, yet additional studies are warranted to confirm our findings and identify the underlying biological mechanisms.     

The Continuum of Maternal Sepsis Severity: Incidence and Risk Factors in a Population-Based Cohort Study

Objective

To investigate the incidence and risk factors associated with uncomplicated maternal sepsis and progression to severe sepsis in a large population-based birth cohort.

Methods

This retrospective cohort study used linked hospital discharge and vital statistics records data for 1,622,474 live births in California during 2005–2007. Demographic and clinical factors were adjusted using multivariable logistic regression with robust standard errors.

Results

1598 mothers developed sepsis; incidence of all sepsis was 10 per 10,000 live births (95% CI = 9.4–10.3). Women had significantly increased adjusted odds (aOR) of developing sepsis if they were older (25–34 years: aOR = 1.29; ≥35 years: aOR = 1.41), had ≤high-school education (aOR = 1.63), public/no-insurance (aOR = 1.22) or a cesarean section (primary: aOR = 1.99; repeat: aOR = 1.25). 791 women progressed to severe sepsis; incidence of severe sepsis was 4.9 per 10,000 live births (95% CI = 4.5–5.2). Women had significantly increased adjusted odds of progressing to severe sepsis if they were Black (aOR = 2.09), Asian (aOR = 1.59), Hispanic (aOR = 1.42), had public/no-insurance (aOR = 1.52), delivered in hospitals with <1,000 births/year (aOR = 1.93), were primiparous (aOR = 2.03), had a multiple birth (aOR = 3.5), diabetes (aOR = 1.47), or chronic hypertension (aOR = 8.51). Preeclampsia and postpartum hemorrhage were also significantly associated with progression to severe sepsis (aOR = 3.72; aOR = 4.18). For every cumulative factor, risk of uncomplicated sepsis increased by 25% (95% CI = 17.4–32.3) and risk of progression to severe sepsis/septic shock increased by 57% (95% CI = 40.8–74.4).

Conclusions

The rate of severe sepsis was approximately twice the 1991–2003 national estimate. Risk factors identified are relevant to obstetric practice given their cumulative risk effect and the apparent increase in severe sepsis incidence.     

Effect of Statin Therapy in the Outcome of Bloodstream Infections Due to Staphylococcus aureus: A Prospective Cohort Study

Introduction

Statins have pleiotropic effects that could influence the prevention and outcome of some infectious diseases. There is no information about their specific effect on Staphylococcus aureus bacteremia (SAB).

Methods

A prospective cohort study including all SAB diagnosed in patients aged ≥18 years admitted to a 950-bed tertiary hospital from March 2008 to January 2011 was performed. The main outcome variable was 14-day mortality, and the secondary outcome variables were 30-day mortality, persistent bacteremia (PB) and presence of severe sepsis or septic shock at diagnosis of SAB. The effect of statin therapy at the onset of SAB was studied by multivariate logistic regression and Cox regression analysis, including a propensity score for statin therapy.

Results

We included 160 episodes. Thirty-three patients (21.3%) were receiving statins at the onset of SAB. 14-day mortality was 21.3%. After adjustment for age, Charlson index, Pitt score, adequate management, and high risk source, statin therapy had a protective effect on 14-day mortality (adjusted OR = 0.08; 95% CI: 0.01–0.66; p = 0.02), and PB (OR = 0.89; 95% CI: 0.27–1.00; p = 0.05) although the effect was not significant on 30-day mortality (OR = 0.35; 95% CI: 0.10–1.23; p = 0.10) or presentation with severe sepsis or septic shock (adjusted OR = 0.89; CI 95%: 0.27–2.94; p = 0.8). An effect on 30-day mortality could neither be demonstrated on Cox analysis (adjusted HR = 0.5; 95% CI: 0.19–1.29; p = 0.15).

Conclusions

Statin treatment in patients with SAB was associated with lower early mortality and PB. Randomized studies are necessary to identify the role of statins in the treatment of patients with SAB.     

Cardiac Complications Associated with Short-Term Mortality in Schizophrenia Patients Hospitalized for Pneumonia: A Nationwide Case-Control Study

Background

Pneumonia is one of most prevalent infectious diseases worldwide and is associated with considerable mortality. In comparison to general population, schizophrenia patients hospitalized for pneumonia have poorer outcomes. We explored the risk factors of short-term mortality in this population because the information is lacking in the literature.

Methods

In a nationwide schizophrenia cohort, derived from the National Health Insurance Research Database in Taiwan, that was hospitalized for pneumonia between 2000 and 2008 (n = 1,741), we identified 141 subjects who died during their hospitalizations or shortly after their discharges. Based on risk-set sampling in a 1∶4 ratio, 468 matched controls were selected from the study cohort (i.e., schizophrenia cohort with pneumonia). Physical illnesses were categorized as pre-existing and incident illnesses that developed after pneumonia respectively. Exposures to medications were categorized by type, duration, and defined daily dose. We used stepwise conditional logistic regression to explore the risk factors for short-term mortality.

Results

Pre-existing arrhythmia was associated with short-term mortality (adjusted risk ratio [RR] = 4.99, p<0.01). Several variables during hospitalization were associated with increased mortality risk, including incident arrhythmia (RR = 7.44, p<0.01), incident heart failure (RR = 5.49, p = 0.0183) and the use of hypoglycemic drugs (RR = 2.32, p<0.01). Furthermore, individual antipsychotic drugs (such as clozapine) known to induce pneumonia were not significantly associated with the risk.

Conclusions

Incident cardiac complications following pneumonia are associated with increased short-term mortality. These findings have broad implications for clinical intervention and future studies are needed to clarify the mechanisms of the risk factors.     

HIV Incidence and Risk Factors in Chinese Young Men Who Have Sex with Men—A Prospective Cohort Study

Objectives

To assess HIV incidence and its associated risk factors among young men who have sex with men (YMSM) in urban areas, China.

Design

The study used a prospective cohort study design and standard diagnostic tests.

Methods

A twelve-month prospective cohort study was conducted among YMSM (18–25 years old) in 8 large cities in China. The participants were recruited via snowball sampling. A total of 1102 HIV-negative YMSM completed baseline assessment, 878 YMSM participants completed 6-month follow-up, and 902 completed 12-month follow-up. HIV was screened by an enzyme-linked immunosorbent assay and confirmed with Western Blot. Syphilis was screened via rapid plasma reagent and confirmed by treponema pallidum particle agglutination assay.

Results

78 HIV seroconversions were identified within 1168.4 person-year observations yielding an incidence rate of 6.7 per 100 person-years. HIV seroconversion was associated with non-student status (RR = 2.61, 90% CI = 1.3–5.26), low HIV transmission knowledge (RR = 8.87, 90% CI = 2.16–36.43), and syphilis infection (RR = 5.04, 90% CI = 2.57–9.90).

Conclusions

Incidence of HIV among YMSM is high in urban areas of China. Interventions measures are required to contain the HIV epidemic within this population.     

Shorter Men Live Longer: Association of Height with Longevity and FOXO3 Genotype in American Men of Japanese Ancestry

Objectives

To determine the relation between height, FOXO3 genotype and age of death in humans.

Methods

Observational study of 8,003 American men of Japanese ancestry from the Honolulu Heart Program/Honolulu-Asia Aging Study (HHP/HAAS), a genetically and culturally homogeneous cohort followed for over 40 years. A Cox regression model with age as the time scale, stratified by year of birth, was used to estimate the effect of baseline height on mortality during follow-up. An analysis of height and longevity-associated variants of the key regulatory gene in the insulin/IGF-1 signaling (IIS) pathway, FOXO3, was performed in a HHP-HAAS subpopulation. A study of fasting insulin level and height was conducted in another HHP-HAAS subpopulation.

Results

A positive association was found between baseline height and all-cause mortality (RR = 1.007; 95% CI 1.003–1.011; P = 0.002) over the follow-up period. Adjustments for possible confounding variables reduced this association only slightly (RR = 1.006; 95% CI 1.002–1.010; P = 0.007). In addition, height was positively associated with all cancer mortality and mortality from cancer unrelated to smoking. A Cox regression model with time-dependent covariates showed that relative risk for baseline height on mortality increased as the population aged. Comparison of genotypes of a longevity-associated single nucleotide polymorphism in FOXO3 showed that the longevity allele was inversely associated with height. This finding was consistent with prior findings in model organisms of aging. Height was also positively associated with fasting blood insulin level, a risk factor for mortality. Regression analysis of fasting insulin level (mIU/L) on height (cm) adjusting for the age both data were collected yielded a regression coefficient of 0.26 (95% CI 0.10–0.42; P = 0.001).

Conclusion

Height in mid-life is positively associated with mortality, with shorter stature predicting longer lifespan. Height was, moreover, associated with fasting insulin level and the longevity genotype of FOXO3, consistent with a mechanistic role for the IIS pathway.     

Effectiveness of Influenza Vaccination in Patients with End-Stage Renal Disease Receiving Hemodialysis: A Population-Based Study

Background

Little is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.

Methods

We used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.

Results

The age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72–0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75–0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64–1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12–0.33) and mortality (adjusted HR 0.50, 95% CI 0.41–0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26–0.35) after counting vaccination for multi-years.

Conclusions

ESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly.