Effect of diuretic use on 30-day postdialysis mortality in critically ill patients receiving acute dialysis

Background

The impact of diuretic usage and dosage on the mortality of critically ill patients with acute kidney injury is still unclear.

Methods and Results

In this prospective, multicenter, observational study, 572 patients with postsurgical acute kidney injury receiving hemodialysis were recruited and followed daily. Thirty-day postdialysis mortality was analyzed using Cox''s proportional hazards model with time-dependent covariates. The mean age of the 572 patients was 60.8±16.6 years. Patients with lower serum creatinine (p = 0.031) and blood lactate (p = 0.033) at ICU admission, lower predialysis urine output (p = 0.001) and PaO₂/FiO₂ (p = 0.039), as well as diabetes (p = 0.037) and heart failure (p = 0.049) were more likely to receive diuretics. A total of 280 (49.0%) patients died within 30 days after acute dialysis initiation. The analysis of 30-day postdialysis mortality by fitting propensity score-adjusted Cox''s proportional hazards models with time-dependent covariates showed that higher 3-day accumulated diuretic doses after dialysis initiation (HR = 1.449, p = 0.021) could increase the hazard rate of death. Moreover, higher time-varying 3-day accumulative diuretic doses were associated with hypotension (p<0.001) and less intense hemodialysis (p<0.001) during the acute dialysis period.

Background and Significance

Higher time-varying 3-day accumulative diuretic dose predicts mortality in postsurgical critically ill patients requiring acute dialysis. Higher diuretic doses are associated with hypotension and a lower intensity of dialysis. Caution should be employed before loop diuretics are administered to postsurgical patients during the acute dialysis period.     

Risk factors associated with increased mortality among HIV infected children initiating antiretroviral therapy (ART) in South Africa

Objective

To identify demographic and clinical risk factors associated with mortality after initiation of antiretroviral therapy (ART) in a cohort of human immunodeficiency (HIV) infected children in KwaZulu-Natal, South Africa.

Methods

We performed a retrospective cohort study of 537 children initiating antiretroviral therapy at McCord Hospital in KwaZulu-Natal, South Africa. Data were extracted from electronic medical records and risk factors associated with mortality were assessed using Cox regression analysis.

Results

Overall there were 47 deaths from the cohort of 537 children initiating ART with over 991 child-years of follow-up (median 22 months on ART), yielding a mortality rate of 4.7 deaths per 100 child years on ART. Univariate analysis indicated that mortality was significantly associated with lower weight-for-age Z-score (p<0.0001), chronic diarrhea (p = 0.0002), lower hemoglobin (p = 0.002), age <3 years (p = 0.003), and CD4% <10% (p = 0.005). The final multivariable Cox proportional hazards mortality model found age less than 3 years (p = 0.004), CD4 <10% (p = 0.01), chronic diarrhea (p = 0.03), weight-for-age Z-score (<0.0001) and female gender as a covariate varying with time (p = 0.03) all significantly associated with mortality.

Conclusion

In addition to recognized risk factors such as young age and advanced immunosuppression, we found female gender to be significantly associated with mortality in this pediatric ART cohort. Future studies are needed to determine whether intrinsic biologic differences or socio-cultural factors place female children with HIV at increased risk of death following initiation of ART.     

Prediction of emergent heart failure death by semi-quantitative triage risk stratification

Objectives

Generic triage risk assessments are widely used in the emergency department (ED), but have not been validated for prediction of short-term risk among patients with acute heart failure (HF). Our objective was to evaluate the Canadian Triage Acuity Scale (CTAS) for prediction of early death among HF patients.

Methods

We included patients presenting with HF to an ED in Ontario from Apr 2003 to Mar 2007. We used the National Ambulatory Care Reporting System and vital statistics databases to examine care and outcomes.

Results

Among 68,380 patients (76±12 years, 49.4% men), early mortality was stratified with death rates of 9.9%, 1.9%, 0.9%, and 0.5% at 1-day, and 17.2%, 5.9%, 3.8%, and 2.5% at 7-days, for CTAS 1, 2, 3, and 4–5, respectively. Compared to lower acuity (CTAS 4–5) patients, adjusted odds ratios (aOR) for 1-day death were 1.32 (95%CI; 0.93–1.88; p = 0.12) for CTAS 3, 2.41 (95%CI; 1.71–3.40; p<0.001) for CTAS 2, and highest for CTAS 1: 9.06 (95%CI; 6.28–13.06; p<0.001). Predictors of triage-critical (CTAS 1) status included oxygen saturation <90% (aOR 5.92, 95%CI; 3.09–11.81; p<0.001), respiratory rate >24 breaths/minute (aOR 1.96, 95%CI; 1.05–3.67; p = 0.034), and arrival by paramedic (aOR 3.52, 95%CI; 1.70–8.02; p = 0.001). While age/sex-adjusted CTAS score provided good discrimination for ED (c-statistic = 0.817) and 1-day (c-statistic = 0.724) death, mortality prediction was improved further after accounting for cardiac and non-cardiac co-morbidities (c-statistics 0.882 and 0.810, respectively; both p<0.001).

Conclusions

A semi-quantitative triage acuity scale assigned at ED presentation and based largely on respiratory factors predicted emergent death among HF patients.     

The effects of age on inflammatory and coagulation-fibrinolysis response in patients hospitalized for pneumonia

Objective

To determine whether inflammatory and hemostasis response in patients hospitalized for pneumonia varies by age and whether these differences explain higher mortality in the elderly.

Methods

In an observational cohort of subjects with community-acquired pneumonia (CAP) recruited from emergency departments (ED) in 28 hospitals, we divided subjects into 5 age groups (<50, 51–64, 65–74, 75–84, and ≥85). We measured circulating levels of inflammatory (TNF, IL-6, and IL-10), hemostasis (D-dimer, Factor IX, thrombin-antithrombin complex, antithrombin and plasminogen-activator inhibitor-1), and cell-surface markers (TLR-2, TLR-4, and HLA-DR) during the first week of hospitalization and at discharge and compared 90-day mortality. We used logistic regression to compare odds ratios (OR) for 90-day mortality between age groups, adjusting for differences in pre-infection factors alone and then additionally adjusting for immune markers.

Results

Of 2,183 subjects, 495, 444, 403, 583, and 258 subjects were <50, 51–64, 65–74, 75–84, and ≥85 years of age, respectively. Large age-related differences were observed in 90-day mortality (0.82% vs. 3.2% vs. 6.4% vs. 12.8% vs. 13.6%, p<0.01). No age-related differences in inflammatory and cell surface markers occurred during the first week. Older subjects had higher pro-coagulant markers on ED presentation and over first week (p≤0.03), but these differences were modest (1.0–1.7-fold differences). Odds of death for older adults changed minimally in models incorporating differences in hemostasis and inflammatory markers (for subjects ≥85 compared to those <50, OR = 4.36, when adjusted for pre-infection factors and OR = 3.49 when additionally adjusted for hemostasis markers). At discharge, despite clinical recovery as evidenced by normal vital signs in >85% subjects, older subjects had modestly increased hemostasis markers and IL-6 levels (p<0.01).

Conclusions

Modest age-related increases in coagulation response occur during hospitalization for CAP; however these differences do not explain the large differences in mortality. Despite clinical recovery, immune resolution may be delayed in older adults at discharge.     

Identification of chronic heart failure patients with a high 12-month mortality risk using biomarkers including plasma C-terminal pro-endothelin-1

Objectives

We hypothesised that assessment of plasma C-terminal pro-endothelin-1 (CT-proET-1), a stable endothelin-1 precursor fragment, is of prognostic value in patients with chronic heart failure (CHF), beyond other prognosticators, including N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Methods

We examined 491 patients with systolic CHF (age: 63±11 years, 91% men, New York Heart Association [NYHA] class [I/II/III/IV]: 9%/45%/38%/8%, 69% ischemic etiology). Plasma CT-proET-1 was detected using a chemiluminescence immunoassay.

Results

Increasing CT-proET-1 was a predictor of increased cardiovascular mortality at 12-months of follow-up (standardized hazard ratio 1.42, 95% confidence interval [CI] 1.04–1.95, p = 0.03) after adjusting for NT-proBNP, left ventricular ejection fraction (LVEF), age, creatinine, NYHA class. In receiver operating characteristic curve analysis, areas under curve for 12-month follow-up were similar for CT-proET-1 and NT-proBNP (p = 0.40). Both NT-proBNP and CT-proET-1 added prognostic value to a base model that included LVEF, age, creatinine, and NYHA class. Adding CT-proET-1 to the base model had stronger prognostic power (p<0.01) than adding NT-proBNP (p<0.01). Adding CT-proET-1 to NT-proBNP in this model yielded further prognostic information (p = 0.02).

Conclusions

Plasma CT-proET-1 constitutes a novel predictor of increased 12-month cardiovascular mortality in patients with CHF. High CT-proET-1 together with high NT-proBNP enable to identify patients with CHF and particularly unfavourable outcomes.     

Serum 25(OH)D Is a 2-Year Predictor of All-Cause Mortality, Cardiac Death and Sudden Cardiac Death in Chest Pain Patients from Northern Argentina

Background

Several studies have shown an association between vitamin D deficiency and cardiovascular risk. Vitamin D status is assessed by determination of 25-hydroxyvitamin D [25(OH)D] in serum.

Methods

We assessed the prognostic utility of 25(OH)D in 982 chest-pain patients with suspected acute coronary syndrome (ACS) from Salta, Northern Argentina. 2-year follow-up data including all-cause mortality, cardiac death and sudden cardiac death were analyzed in quartiles of 25(OH)D, applying univariate and multivariate analysis.

Results

There were statistically significant changes in seasonal 25(OH)D levels. At follow-up, 119 patients had died. The mean 25(OH)D levels were significantly lower among patients dying than in long-term survivors, both in the total population and in patients with a troponin T (TnT) release (n = 388). When comparing 25(OH)D in the highest quartile to the lowest quartile in a multivariable Cox regression model for all-cause mortality, the hazard ratio (HR) for cardiac death and sudden cardiac death in the total population was 0.37 (95% CI, 0.19–0.73), p = 0.004, 0.23 (95% CI, 0.08–0.67), p = 0.007, and 0.32 (95% CI, 0.11–0.94), p = 0.038, respectively. In patients with TnT release, the respective HR was 0.24 (95% CI, 0.10–0.54), p = 0.001, 0.18 (95% CI, 0.05–0.60), p = 0.006 and 0.25 (95% CI, 0.07–0.89), p = 0.033. 25(OH)D had no prognostic value in patients with no TnT release.

Conclusion

Vitamin D was shown to be a useful biomarker for prediction of mortality when obtained at admission in chest pain patients with suspected ACS.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01377402","term_id":"NCT01377402"}}NCT01377402     

Asymmetric dimethylarginine, endothelial nitric oxide bioavailability and mortality in sepsis

Background

Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are raised in patients with chronic vascular disease, causing increased cardiovascular risk and endothelial dysfunction, but the role of ADMA in acute inflammatory states is less well defined.

Methods and Results

In a prospective longitudinal study in 67 patients with acute sepsis and 31 controls, digital microvascular reactivity was measured by peripheral arterial tonometry and blood was collected at baseline and 2–4 days later. Plasma ADMA and L-arginine concentrations were determined by high performance liquid chromatography. Baseline plasma L-arginine: ADMA ratio was significantly lower in sepsis patients (median [IQR] 63 [45–103]) than in hospital controls (143 [123–166], p<0.0001) and correlated with microvascular reactivity (r = 0.34, R² = 0.12, p = 0.02). Baseline plasma ADMA was independently associated with 28-day mortality (Odds ratio [95% CI] for death in those in the highest quartile (≥0.66 µmol/L) = 20.8 [2.2–195.0], p = 0.008), and was independently correlated with severity of organ failure. Increase in ADMA over time correlated with increase in organ failure and decrease in microvascular reactivity.

Conclusions

Impaired endothelial and microvascular function due to decreased endothelial NO bioavailability is a potential mechanism linking increased plasma ADMA with organ failure and death in sepsis.     

Safety and clinical outcome of thrombolysis in ischaemic stroke using a perfusion CT mismatch between 3 and 6 hours

Objective

It may be possible to thrombolyse ischaemic stroke (IS) patients up to 6 h by using penumbral imaging. We investigated whether a perfusion CT (CTP) mismatch can help to select patients for thrombolysis up to 6 h.

Methods

A cohort of 254 thrombolysed IS patients was studied. 174 (69%) were thrombolysed at 0–3 h by using non-contrast CT (NCCT), and 80 (31%) at 3–6 h (35 at 3–4.5 h and 45 at 4.5–6 h) by using CTP mismatch criteria. Symptomatic intracerebral haemorrhage (SICH), the mortality and the modified Rankin Score (mRS) were assessed at 3 months. Independent determinants of outcome in patients thrombolysed between 3 and 6 h were identified.

Results

The baseline characteristics were comparable in the two groups. There were no differences in SICH (3% v 4%, p = 0.71), any ICH (7% v 9%, p = 0.61), or mortality (16% v 9%, p = 0.15) or mRS 0–2 at 3 months (55% v 54%, p = 0.96) between patients thrombolysed at 0–3 h (NCCT only) or at 3–6 h (CTP mismatch). There were no significant differences in outcome between patients thrombolysed at 3–4.5 h or 4.5–6 h. The NIHSS score was the only independent determinant of a mRS of 0–2 at 3 months (OR 0.89, 95% CI 0.82–0.97, p = 0.007) in patients treated using CTP mismatch criteria beyond 3 h.

Conclusions

The use of a CTP mismatch model may help to guide thrombolysis decisions up to 6 h after IS onset.     

Elderly subjects have a delayed antibody response and prolonged viraemia following yellow fever vaccination: a prospective controlled cohort study

Background

Yellow fever vaccination (YF-17D) can cause serious adverse events (SAEs). The mechanism of these SAEs is poorly understood. Older age has been identified as a risk factor. We tested the hypothesis that the humoral immune response to yellow fever vaccine develops more slowly in elderly than in younger subjects.

Method

We vaccinated young volunteers (18–28 yrs, N = 30) and elderly travelers (60–81 yrs, N = 28) with YF-17D and measured their neutralizing antibody titers and plasma YF-17D RNA copy numbers before vaccination and 3, 5, 10, 14 and 28 days after vaccination.

Results

Ten days after vaccination seroprotection was attained by 77% (23/30) of the young participants and by 50% (14/28) of the elderly participants (p = 0.03). Accordingly, the Geometric Mean Titer of younger participants was higher than the GMT of the elderly participants. At day 10 the difference was +2.9 IU/ml (95% CI 1.8–4.7, p = 0.00004) and at day 14 +1.8 IU/ml (95% CI 1.1–2.9, p = 0.02, using a mixed linear model. Viraemia was more common in the elderly (86%, 24/28) than in the younger participants (60%, 14/30) (p = 0.03) with higher YF-17D RNA copy numbers in the elderly participants.

Conclusions

We found that elderly subjects had a delayed antibody response and higher viraemia levels after yellow fever primovaccination. We postulate that with older age, a weaker immune response to yellow fever vaccine allows the attenuated virus to cause higher viraemia levels which may increase the risk of developing SAEs. This may be one piece in the puzzle of the pathophysiology of YEL-AVD.

Trial Registration

Trialregitser.nl NTR1040     

Risk of all-cause mortality in HIV infected patients is associated with clinical, immunologic predictors and the CCR5 Δ32 deletion

Objective

Investigation of the interplay between the CCR5 Δ32/wt genotype and demographic, epidemiological, clinical and immunological factors associated with mortality in the cART era.

Design

Longitudinal data from 507 HIV-infected patients following the Δ32 allele detection were analyzed.

Methods

Cumulative 15 years mortality was calculated using Kaplan-Meyer methodology. Hazard ratios were estimated using univariate Cox models. Basing on Akakie information criteria and statistical significance multivariate Cox model was constructed and effect plots presenting adjusted hazard ratio time-dependency were drawn. Analysis of the association of all-cause mortality and CCR5 Δ32/wt genotype prior to the antiretroviral treatment (cART) initiation (n = 507) and on the therapy (n = 422) was also performed.

Results

A mortality rate of 2.66 (CI 2.57–3.19) per 100 person-years was observed. Univariate analysis factors modifying the risk of death included the CCR5 genotype, gender, history of cART, AIDS diagnosis and also CD4 lymphocyte nadir, zenith, the latest CD4 count and stable levels >500 cells/µl. For multivariate analysis the following predictors were selected: CCR5 genotype (HR for wt/wt 2.53, CI 1.16–5.53, p = 0.02), gender (HR for males 1.91, 95%CI 1.1–3.36, p = 0.023), introduction of combined antiretroviral treatment (HR 4.85, CI 3.0–7.89, if untreated or treated <1 month, p<0.0001) CD4 count of 500 cells/µl for six months or more (HR 4.16, CI 1.95–8.88 if not achieved, p = 0.028), the latest CD4 count (HR 5.44, CI 3.39–8.74 for <100 cells/µl, p<0.0001) and history of AIDS (HR 1.69, CI 1.03–2.79, p = 0.039). Among untreated individuals the Δ32/wt genotype was associated with notably better survival (p = 0.026), while among cART treated individuals the Δ32 mutation did not correlate significantly with higher survival rates (p = 0.23).

Conclusions

The Δ32 CCR5 allele is associated with a reduction of the risk of all-cause mortality in HIV (+) patients alongside clinical and immunologic predictors such as AIDS, history of cART, lymphocyte CD4 cell count and gender.     

Asthma prevalence associated with geographical latitude and regional insolation in the United States of America and Australia

Background

It has been proposed that vitamin D deficiency may be responsible for an increase in the prevalence of allergic diseases and asthma worldwide. Human ability to generate physiologically required quantities of vitamin D through sun exposure is decreasing with increasing geographical latitude.

Objectives

Considering that vitamin D deficiency is usually due to lack of outdoor sun exposure, this study is designed to test the hypothesis that a higher prevalence of asthma should be expected at high relative to low geographical latitudes.

Methods

Linear regression analyses are performed on asthma prevalence in the U.S. adult population vs. geographical latitude, insolation, air temperature, and air pollution (PM_2.5) for 97 major metropolitan/micropolitan statistical areas of the continental United States of America and on general population asthma prevalence vs. geographical latitude in eight metropolitan areas of Australia.

Results

A 10° change in geographical latitude from southern to northern regions of the Eastern Seaboard is associated with a 2% increase in adult asthma prevalence (p<0.001). Total insolation in winter months is almost as strong as latitude in its ability to explain the observed spatial variation in the prevalence of asthma (r² = 0.43; p<0.001). Similar results are obtained using the Australian data (r² = 0.73; p<0.01), suggesting a consistent association between the latitude/insolation and asthma prevalence worldwide.

Conclusions

The results of this study suggest that, as a known modulator of the immune response closely linked with the geographical latitude and erythemal UV irradiation, vitamin D may play an important role in the development/exacerbation of asthma.     

Phagocytic activity is impaired in type 2 diabetes mellitus and increases after metabolic improvement

Objective

1) To evaluate whether peripheral blood mononuclear cells (PBMCs) from type 2 diabetic patients present an impairment of phagocytic activity; 2) To determine whether the eventual impairment in phagocytic activity is related to glycemic control and can be reversed by improving blood glucose levels.

Methods

21 type 2 diabetic patients and 21 healthy volunteers were prospectively recruited for a case-control study. In addition, those patients in whom HbA1c was higher than 8% (n = 12) were hospitalized in order to complete a 5-day intensification treatment of blood glucose. Phagocytic activity was assessed by using a modified flow cytometry procedure developed in our laboratory based on DNA/RNA viable staining to discriminate erythrocytes and debris. This method is simple, highly sensitive and reproducible and it takes advantage of classic methods that are widely used in flow cytometry.

Results

Type 2 diabetic patients showed a lower percentage of activated macrophages in comparison with non-diabetic subjects (54.00±18.93 vs 68.53±12.77%; p = 0.006) Significant negative correlations between phagocytic activity and fasting glucose (r = −0.619, p = 0.004) and HbA1c (r = −0.506, p = 0.019) were detected. In addition, multiple linear regression analyses showed that either fasting plasma glucose or HbA1c were independently associated with phagocytic activity. Furthermore, in the subset of patients who underwent metabolic optimization a significant increase in phagocytic activity was observed (p = 0.029).

Conclusions

Glycemic control is related to phagocytic activity in type 2 diabetes. Our results suggest that improvement in phagocytic activity can be added to the beneficial effects of metabolic optimization.     

Seeking clarity within cloudy effluents: differentiating fungal from bacterial peritonitis in peritoneal dialysis patients

Background

Fungal peritonitis is a serious complication of peritoneal dialysis (PD) therapy with the majority of patients ceasing PD permanently. The aims of this study were to identify risk factors and clinical associations that may discriminate between fungal from bacterial peritonitis.

Methods

We retrospectively identified episodes of fungal peritonitis from 2001–2010 in PD patients at Liverpool and Westmead Hospitals (Australia). Fungal peritonitis cases were matched in a 1∶2 ratio with patients with bacterial peritonitis from each institution''s dialysis registry, occurring closest in time to the fungal episode. Patient demographic, clinical and outcome data were obtained from the medical records.

Results

Thirty-nine episodes of fungal peritonitis (rate of 0.02 episodes per patient-year of dialysis) were matched with 78 episodes of bacterial peritonitis. Candida species were the commonest pathogens (35/39; 90% episodes) with Candida albicans (37%), Candida parapsilosis (32%) and Candida glabrata (13%) the most frequently isolated species. Compared to bacterial peritonitis, fungal peritonitis patients had received PD for significantly longer (1133 vs. 775 catheter-days; p = 0.016), were more likely to have had previous episodes of bacterial peritonitis (51% vs. 10%; p = 0.01), and to have received prior antibacterial therapy (51% vs. 10%; p = 0.01). Patients with fungal peritonitis were less likely to have fever and abdominal pain on presentation, but had higher rates of PD catheter removal (79% vs. 22%; p<0.005), and permanent transfer to haemodialysis (87% vs. 24%; p<0.005). Hospital length of stay was significantly longer in patients with fungal peritonitis (26.1 days vs. 12.6 days; p = 0.017), but the all-cause 30-day mortality rate was similar in both groups. Fluconazole was a suitable empiric antifungal agent; with no Candida resistance detected.

Conclusion

Prompt recognition of clinical risk factors, initiation of antifungal therapy and removal of PD catheters are key considerations in optimising outcomes.     

Impact of definitive therapy with beta-lactam monotherapy or combination with an aminoglycoside or a quinolone for Pseudomonas aeruginosa bacteremia

Background

Bacteremia by Pseudomonas aeruginosa represents one severe infection. It is not clear whether beta-lactam monotherapy leads to similar rates of treatment success compared to combinations of beta-lactams with aminoglycosides or quinolones.

Methods

Retrospective cohort study from 3 tertiary hospitals (2 in Greece and 1 in Italy). Pseudomonas aeruginosa isolates were susceptible to a beta-lactam and an aminoglycoside or a quinolone. Patients received appropriate therapy for at least 48 hours. Primary outcome of interest was treatment success in patients with definitive beta-lactam combination therapy compared to monotherapy. Secondary outcomes were treatment success keeping the same empirical and definitive regimen, mortality, and toxicity.

Results

Out of 92 bacteremias there were 54 evaluable episodes for the primary outcome (20 received monotherapy). Treatment success was higher with combination therapy (85%) compared to beta-lactam monotherapy (65%), however not statistically significantly [Odds ratio (OR) 3.1; 95% Confidence Interval (CI) 0.69–14.7, p = 0.1]. Very long (>2 months) hospitalisation before bacteremia was the only factor independently associated with treatment success (OR 0.73; 95% CI 0.01–0.95, p = 0.046), however this result entailed few episodes. All-cause mortality did not differ significantly between combination therapy [6/31 (19%)] and monotherapy [8/19 (42%)], p = 0.11. Only Charlson comorbidity index was associated with excess mortality (p = 0.03).

Conclusion

Our study, in accordance with previous ones, indicates that the choice between monotherapy and combination therapy may not affect treatment success significantly. However, our study does not have statistical power to identify small or moderate differences. A large randomized controlled trial evaluating this issue is justified.     

Bronchial responsiveness is related to increased exhaled NO (FE(NO)) in non-smokers and decreased FE(NO) in smokers

Rationale

Both atopy and smoking are known to be associated with increased bronchial responsiveness. Fraction of nitric oxide (NO) in the exhaled air (FE_NO), a marker of airways inflammation, is decreased by smoking and increased by atopy. NO has also a physiological bronchodilating and bronchoprotective role.

Objectives

To investigate how the relation between FE_NO and bronchial responsiveness is modulated by atopy and smoking habits.

Methods

Exhaled NO measurements and methacholine challenge were performed in 468 subjects from the random sample of three European Community Respiratory Health Survey II centers: Turin (Italy), Gothenburg and Uppsala (both Sweden). Atopy status was defined by using specific IgE measurements while smoking status was questionnaire-assessed.

Main Results

Increased bronchial responsiveness was associated with increased FE_NO levels in non-smokers (p = 0.02) and decreased FE_NO levels in current smokers (p = 0.03). The negative association between bronchial responsiveness and FE_NO was seen only in the group smoking less <10 cigarettes/day (p = 0.008). Increased bronchial responsiveness was associated with increased FE_NO in atopic subjects (p = 0.04) while no significant association was found in non-atopic participants. The reported interaction between FE_NO and smoking and atopy, respectively were maintained after adjusting for possible confounders (p-values<0.05).

Conclusions

The present study highlights the interactions of the relationship between FE_NO and bronchial responsiveness with smoking and atopy, suggesting different mechanisms behind atopy- and smoking-related increases of bronchial responsiveness.     

An ecological study of the determinants of differences in 2009 pandemic influenza mortality rates between countries in Europe

Background

Pandemic A (H1N1) 2009 mortality rates varied widely from one country to another. Our aim was to identify potential socioeconomic determinants of pandemic mortality and explain between-country variation.

Methodology

Based on data from a total of 30 European countries, we applied random-effects Poisson regression models to study the relationship between pandemic mortality rates (May 2009 to May 2010) and a set of representative environmental, health care-associated, economic and demographic country-level parameters. The study was completed by June 2010.

Principal Findings

Most regression approaches indicated a consistent, statistically significant inverse association between pandemic influenza-related mortality and per capita government expenditure on health. The findings were similar in univariable [coefficient: –0.00028, 95% Confidence Interval (CI): –0.00046, –0.00010, p = 0.002] and multivariable analyses (including all covariates, coefficient: –0.00107, 95% CI: –0.00196, –0.00018, p = 0.018). The estimate was barely insignificant when the multivariable model included only significant covariates from the univariate step (coefficient: –0.00046, 95% CI: –0.00095, 0.00003, p = 0.063).

Conclusions

Our findings imply a significant inverse association between public spending on health and pandemic influenza mortality. In an attempt to interpret the estimated coefficient (–0.00028) for the per capita government expenditure on health, we observed that a rise of 100 international dollars was associated with a reduction in the pandemic influenza mortality rate by approximately 2.8%. However, further work needs to be done to unravel the mechanisms by which reduced government spending on health may have affected the 2009 pandemic influenza mortality.     

Gender difference in 2-year mortality and immunological response to ART in an HIV-infected Chinese population, 2006-2008

Background

Since it was initiated in 2002, the China Free Antiretroviral Treatment (ART) Program has been progressing from an emergency response to a standardized treatment and care system. As of December 31, 2009, a total of 81,880 patients in 31 provinces, autonomous regions, and special municipalities received free ART. Gender differences, however, in mortality and immunological response to ART in this cohort have never been described.

Objective

To understand whether women and men who enrolled in the China National Free ART Program responded equally well to the treatment.

Methods

A retrospective analysis of the national free ART databases from June 2006–December 2008 was performed. HIV-infected subjects who were 18 years or older, ART naïve at baseline, and on a 3TC regimen enrolled in the program from June 1 to December 31, 2006, were included in this study, then followed up to 2 years.

Results

Among 3457 enrolled subjects who met the inclusion criteria, 59.2% were male and 40.8% female. The majority of the subjects were 19–44 years old (77%) and married (72%). Over the full 24 months of follow-up, the mortality rate was 19.0% in males and 11.4% in females (p = 0.0014). Males on therapy for 3–24 months were more likely to die than females (HR = 1.46, 95% CI: 1.04–2.06, p = 0.0307) after adjusting for baseline characteristics. Compared to men, women had higher CD4+ counts over time after initiating ART (p<0.0001).

Conclusions

Our study showed that women had an overall lower mortality and higher CD4+ counts than men in response to ART treatment, which may be attributed to adherence, biological factors, social, cultural and economic reasons. Further study is needed to explore these factors that might contribute to the gender differences in mortality and immunological response to ART.     

Impact of genetic variation in SORCS1 on memory retention

Objective

We previously reported that genetic variants in SORCS1 increase the risk of AD, that over-expression of SorCS1 reduces γ-secretase activity and Aβ levels, and that SorCS1 suppression increases γ-secretase processing of APP and Aβ levels. We now explored the effect of variation in SORCS1 on memory.

Methods

We explored associations between SORCS1-SNPs and memory retention in the NIA-LOAD case control dataset (162 cases,670 controls) and a cohort of Caribbean Hispanics (549 cases,544 controls) using single marker and haplotype analyses.

Results

Three SNPs in intron 1, were associated with memory retention in the NIA-LOAD dataset or the Caribbean Hispanic dataset (rs10884402(A allele:β = −0.15,p = 0.008), rs7078098(C allele:β = 0.18,p = 0.007) and rs950809(C allele:β = 0.17,p = 0.008)) and all three SNPs were significant in a meta-analysis of both datasets (0.002ConclusionsVariation in intron 1 in SORCS1 is associated with memory changes in AD.     

Increased prevalence of albuminuria in HIV-infected adults with diabetes

Objective

HIV and type 2 diabetes are known risk factors for albuminuria, but no previous reports have characterized albuminuria in HIV-infected patients with diabetes.

Research Design and Methods

We performed a cross-sectional study including 73 HIV-infected adults with type 2 diabetes, 82 HIV-infected non-diabetics, and 61 diabetic control subjects without HIV. Serum creatinine >1.5 mg/dL was exclusionary. Albuminuria was defined as urinary albumin/creatinine ratio >30 mg/g.

Results

The prevalence of albuminuria was significantly increased among HIV-infected diabetics (34% vs. 13% of HIV non-diabetic vs. 16% diabetic control, p = 0.005). HIV status and diabetes remained significant predictors of albuminuria after adjusting for age, race, BMI, and blood pressure. Albumin/creatinine ratio correlated significantly with HIV viral load (r = 0.28, p = 0.0005) and HIV-infected subjects with albuminuria had significantly greater cumulative exposure to abacavir (p = 0.01). In an adjusted multivariate regression analysis of HIV-infected subjects, the diagnosis of diabetes (p = 0.003), higher HIV viral load (p = 0.03) and cumulative exposure to abacavir (p = 0.0009) were significant independent predictors of albuminuria.

Conclusions

HIV and diabetes appear to have additive effects on albuminuria which is also independently associated with increased exposure to abacavir and HIV viral load. Future research on the persistence, progression and management of albuminuria in this unique at-risk population is needed.