The role of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence and prognosis: a meta-analysis of prospective cohort studies

Background

The impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis.

Methods

We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models.

Results

The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR) = 1.87, 95% confidence interval (CI): 1.15–2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39–2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13–1.48) risk of death from all-causes and 91% increased (95%CI: 1.41–2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12–3.33) compared with non-diabetic patients.

Conclusion

The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes have a poorer prognosis relative to their non-diabetic counterparts.     

Initial presentations predict mortality in pulmonary tuberculosis patients--a prospective observational study

Background

Despite effective anti-TB treatments, tuberculosis remains a serious threat to public health and is associated with high mortality. Old age and multiple co-morbidities are known risk factors for death. The association of clinical presentations with mortality in pulmonary tuberculosis patients remains an issue of controversy.

Methods

This prospective observational study enrolled newly diagnosed, culture-proven pulmonary tuberculosis patients from five medical centers and one regional hospital, which were referral hospitals of TB patients. Radiographic findings and clinical symptoms were determined at the time of diagnosis. Patients who died for any reason during the course of anti-TB treatment were defined as mortality cases and death that occurred within 30 days of initiating treatment was defined as early mortality. Clinical factors associated with overall mortality and early mortality were investigated.

Results

A total of 992 patients were enrolled and 195 (19.7%) died. Nearly one-third (62/195, 31.8%) of the deaths occurred before or within 30 days of treatment initiation. Older age (RR = 1.04, 95%CI: 1.03–1.05), malignancy (RR = 2.42, 95%CI: 1.77–3.31), renal insufficiency (RR = 1.77, 95%CI: 1.12–2.80), presence of chronic cough (RR = 0.63, 95%CI: 0.47–0.84), fever (RR = 1.45, 95%CI: 1.09–1.94), and anorexia (RR = 1.49, 95%CI: 1.07–2.06) were independently associated with overall mortality. Kaplan-Meier survival analysis demonstrated significantly higher mortality in patients present with fever (p<0.001), anorexia (p = 0.005), and without chronic cough (p<0.001). Among patients of mortality, those with respiratory symptoms of chronic cough (RR = 0.56, 95%CI: 0.33–0.98) and dyspnea (HR = 0.51, 95%CI: 0.27–0.98) were less likely to experience early mortality. The radiological features were comparable between survivors and non-survivors.

Conclusions

In addition to demographic characteristics, clinical presentations including the presence of fever, anorexia, and the absence of chronic cough, were also independent predictors for on-treatment mortality in pulmonary tuberculosis patients.     

Marital status and mortality among middle age and elderly men and women in urban Shanghai

Background

Previous studies have suggested that marital status is associated with mortality, but few studies have been conducted in China where increasing aging population and divorce rates may have major impact on health and total mortality.

Methods

We examined the association of marital status with mortality using data from the Shanghai Women''s Health Study (1996–2009) and Shanghai Men''s Health Study (2002–2009), two population-based cohort studies of 74,942 women aged 40–70 years and 61,500 men aged 40–74 years at the study enrollment. Deaths were identified by biennial home visits and record linkage with the vital statistics registry. Marital status was categorized as married, never married, divorced, widowed, and all unmarried categories combined. Cox regression models were used to derive hazard ratios (HR) and 95% confidence interval (CI).

Results

Unmarried and widowed women had an increased all-cause HR = 1.11, 95% CI: 1.03, 1.21 and HR = 1.10, 95% CI: 1.02, 1.20 respectively) and cancer (HR = 1.17, 95% CI: 1.04, 1.32 and HR = 1.18, 95% CI: 1.04, 1.34 respectively) mortality. Never married women had excess all-cause mortality (HR = 1.46, 95% CI: 1.03, 2.09). Divorce was associated with elevated cardiovascular disease (CVD) mortality in women (HR = 1.47, 95% CI: 1.01, 2.13) and elevated all-cause mortality (HR = 2.45, 95% CI: 1.55, 3.86) in men. Amongst men, not being married was associated with excess all-cause (HR = 1.45, 95% CI: 1.12, 1.88) and CVD (HR = 1.65, 95% CI: 1.07, 2.54) mortality.

Conclusions

Marriage is associated with decreased all cause mortality and CVD mortality, in particular, among both Chinese men and women.     

Five-year prognosis in an incident cohort of people presenting with acute myocardial infarction

Background

Following an AMI, it is important for patients and their physicians to appreciate the subsequent risk of death, and the potential benefits of invasive cardiac procedures and secondary preventive therapy. Studies, to-date, have focused largely on high-risk populations. We wished to determine the risk of death in a population-derived cohort of 2,887 patients after a first acute myocardial infarction (AMI).

Methods

Logistic regression and survival analysis were conducted to investigate the effect of different baseline characteristics, pharmacological therapies and revascularization procedures on coronary heart disease (CHD) and all-cause mortality outcomes.

Results

Within five years 44.4% of patients died (27.1% short-term [<30 days] and 23.7% longer-term [≥30 days]). Percutaneous transluminal coronary angioplasty (Adjusted Hazards Ratio (AHR) = 0.49, 95% Confidence Interval (CI) 0.26–0.93), β-blockers (AHR = 0.58, 95%CI 0.46–0.74) and statins (AHR = 0.60, 95%CI 0.47–0.77) were all associated with significant reductions in longer-term CHD-related mortality. However, not all patients received secondary preventive therapy (8.7%). Diabetes (AHR = 1.83, 95%CI 1.43–2.34), stroke (AHR = 1.73, 95%CI 1.35–2.22), heart failure (AHR = 1.69, 95%CI 1.28–2.22), smoking (AHR = 1.72, 95%CI 1.18–2.51) and obesity (>30 kg/m2; AHR = 1.39, 95%CI 1.01–1.90) increased the risk of longer-term mortality independent of other risk factors.

Conclusions

It is encouraging that the coronary procedure PTCA and pharmacological secondary prevention therapies were found to be strongly associated with an important reduced risk of subsequent death, although not all patients received these interventions. Smoking, being obese and having cardiovascular related disease at baseline were also associated with an increased likelihood of longer-term mortality, independent of other baseline characteristics. Thus, the provision of smoking cessation, advice on diet (for obese patients) and optimal treatment is likely to be crucial for reducing mortality in all patients after AMI.     

Renal function and risk factors of moderate to severe chronic kidney disease in Golestan Province, northeast of Iran

Introduction

The incidence of end-stage renal disease is increasing worldwide. Earlier studies reported high prevalence rates of obesity and hypertension, two major risk factors of chronic kidney disease (CKD), in Golestan Province, Iran. We aimed to investigate prevalence of moderate to severe CKD and its risk factors in the region.

Methods

Questionnaire data and blood samples were collected from 3591 participants (≥18 years old) from the general population. Based on serum creatinine levels, glomerular filtration rate (GFR) was estimated.

Results

High body mass index (BMI) was common: 35.0% of participants were overweight (BMI 25–29.9) and 24.5% were obese (BMI ≥30). Prevalence of CKD stages 3 to 5 (CKD–S3-5), i.e., GFR <60 mL/min/1.73 m², was 4.6%. The odds ratio (OR) and 95% confidence interval (95% CI) for the risk of CKD–S3-5 associated with every year increase in age was 1.13 (1.11–1.15). Men were at lower risk of CKD–S3-5 than women (OR = 0.28; 95% CI 0.18–0.45). Obesity (OR = 1.78; 95% CI 1.04–3.05) and self-reported diabetes (OR = 1.70; 95% CI 1.00–2.86), hypertension (OR = 3.16; 95% CI 2.02–4.95), ischemic heart disease (OR = 2.73; 95% CI 1.55–4.81), and myocardial infarction (OR = 2.69; 95% CI 1.14–6.32) were associated with increased risk of CKD–S3-5 in the models adjusted for age and sex. The association persisted for self-reported hypertension even after adjustments for BMI and history of diabetes (OR = 2.85; 95% CI 1.77–4.59).

Conclusion

A considerable proportion of inhabitants in Golestan have CKD–S3-5. Screening of individuals with major risk factors of CKD, in order to early detection and treatment of impaired renal function, may be plausible. Further studies on optimal risk prediction of future end-stage renal disease and effectiveness of any screening program are warranted.     

Previous lung diseases and lung cancer risk: a systematic review and meta-analysis

Background

In order to review the epidemiologic evidence concerning previous lung diseases as risk factors for lung cancer, a meta-analysis and systematic review was conducted.

Methods

Relevant studies were identified through MEDLINE searches. Using random effects models, summary effects of specific previous conditions were evaluated separately and combined. Stratified analyses were conducted based on smoking status, gender, control sources and continent.

Results

A previous history of COPD, chronic bronchitis or emphysema conferred relative risks (RR) of 2.22 (95% confidence interval (CI): 1.66, 2.97) (from 16 studies), 1.52 (95% CI: 1.25, 1.84) (from 23 studies) and 2.04 (95% CI: 1.72, 2.41) (from 20 studies), respectively, and for all these diseases combined 1.80 (95% CI: 1.60, 2.11) (from 39 studies). The RR of lung cancer for subjects with a previous history of pneumonia was 1.43 (95% CI: 1.22–1.68) (from 22 studies) and for subjects with a previous history of tuberculosis was 1.76 (95% CI = 1.49, 2.08), (from 30 studies). Effects were attenuated when restricting analysis to never smokers only for COPD/emphysema/chronic bronchitis (RR = 1.22, 0.97–1.53), however remained significant for pneumonia 1.36 (95% CI: 1.10, 1.69) (from 8 studies) and tuberculosis 1.90 (95% CI: 1.45, 2.50) (from 11 studies).

Conclusions

Previous lung diseases are associated with an increased risk of lung cancer with the evidence among never smokers supporting a direct relationship between previous lung diseases and lung cancer.     

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     

Intake of Gnetum Africanum and Dacryodes Edulis, Imbalance of Oxidant/Antioxidant Status and Prevalence of Diabetic Retinopathy in Central Africans

Objective

To estimate the prevalence of DR and to correlate cardiometabolic, sociodemographic, and oxidant/antioxidant imbalance data to the prevalence of DR.

Design

This case-control study included type 2 DM (T2 DM) patients with DR (n = 66), T2 DM patients without DR (N = 84), and healthy controls (n = 45) without DR, in Kinshasa town. Diet, albuminemia, serum vitamins, and 8-isoprostane were examined.

Results

No intake of safou (OR = 2.7 95% CI 1.2–5.8; P = 0.014), low serum albumin <4.5 g/dL (OR-2.9 95% CI 1.4–5.9; P = 0.003), no intake of fumbwa (OR = 2.8 95% CI 1.2–6.5; P = 0.014), high 8-isoprostane (OR = 14.3 95% CI 4.5–46; P<0.0001), DM duration ≥5 years (OR = 3.8 95% CI 1.6–9.1; P = 0.003), and low serum vitamin C (OR = 4.5 95% CI 1.3–15.5; P = 0.016) were identified as the significant independent determinants of DR.

Conclusion

The important role of oxidant/antioxidant status imbalance and diet is demonstrated in DR.     

Body iron stores and heme-iron intake in relation to risk of type 2 diabetes: a systematic review and meta-analysis

Background and Objective

Emerging evidence from biological and epidemiological studies has suggested that body iron stores and heme-iron intake may be related to the risk of type 2 diabetes (T2D). We aimed to examine the association of body iron stores and heme-iron intake with T2D risk by conducting a systematic review and meta-analysis of previously published studies.

Research Design and Methods

Systematic review and subsequent meta-analysis were conducted by searching MEDLINE database up to June 22, 2012 to identify studies that analyzed the association of body iron stores or dietary heme-iron intake with T2D risk. The meta-analysis was performed using the effect estimates and 95% confidence intervals (CIs) to calculate the pooled risk estimates, while the heterogeneity among studies was examined using the I² and Q statistic.

Results

The meta-analysis included 16 high-quality studies: 12 studies analyzed ferritin levels (4,366 T2D patients and 41,091 controls) and 4 measured heme-iron intake (9,246 T2D patients and 179,689 controls). The combined relative risk (RR) comparing the highest and lowest category of ferritin levels was 1.66 (95% CI: 1.15–2.39) for prospective studies, 2.29 (95% CI: 1.48–3.54) for cross-sectional studies with heterogeneity (Q = 14.84, p = 0.01, I² = 66.3%; Q = 44.16, p<0.001, I² = 88.7%). The combined RR comparing the highest and lowest category of heme-iron intake was 1.31 (95% CI: 1.21–1.43) with heterogeneity (Q = 1.39, p = 0.71, I² = 0%). No publication bias was found. Additional 15 studies that were of good quality, had significant results, and analyzed the association between body iron stores and T2D risk were qualitatively included in the systematic review.

Conclusions

The meta-analysis and systematic review suggest that increased ferritin levels and heme-iron intake are both associated with higher risk of T2D.     

Epicardial Adipose Tissue in Patients with Chronic Obstructive Pulmonary Disease

Rationale

Epicardial Adipose Tissue (EAT) volume as determined by chest computed tomography (CT) is an independent marker of cardiovascular events in the general population. COPD patients have an increased risk of cardiovascular disease, however nothing is known about the EAT volume in this population.

Objectives

To assess EAT volume in COPD and explore its association with clinical and physiological variables of disease severity.

Methods

We measured EAT using low-dose CT in 171 stable COPD patients and 70 controls matched by age, smoking history and BMI. We determined blood pressure, cholesterol, glucose and HbA1c levels, microalbuminuria, lung function, BODE index, co-morbidity index and coronary artery calcium score (CAC). EAT volume were compared between groups. Uni and multivariate analyses explored the relationship between EAT volume and the COPD related variables.

Results

COPD patients had a higher EAT volume [143.7 (P_25–75, 108.3–196.6) vs 129.1 (P_25–75, 91.3–170.8) cm³, p = 0.02)] and the EAT volume was significantly associated with CAC (r = 0.38, p<0.001) and CRP (r = 0.32, p<0.001) but not with microalbuminuria (r = 0.12, p = 0.13). In COPD patients, EAT volume was associated with: age, pack-years, BMI, gender, FEV₁%, 6 MWD, MMRC and HTN. Multivariate analysis showed that only pack-years (B = 0.6, 95% CI: 0.5–1.3), BMI (B = 7.8, 95% CI: 5.7–9.9) and 6 MWD (B = −0.2, 95% CI: −0.3–−0.1), predicted EAT volume.

Conclusions

EAT volume is increased in COPD patients and is independently associated with smoking history, BMI and exercise capacity, all modifiable risk factors of future cardiovascular events. EAT volume could be a non-invasive marker of COPD patients at high risk for future cardiovascular events.     

Widowhood and mortality: a meta-analysis

Background

While the "widowhood effect" is well known, there is substantial heterogeneity in the magnitude of effects reported in different studies. We conducted a meta-analysis of widowhood and mortality, focusing on longitudinal studies with follow-up from the time of bereavement.

Methods and Findings

A random-effects meta-analysis was conducted to calculate the overall relative risk (RR) for subsequent mortality among 2,263,888 subjects from 15 prospective cohort studies. We found a statistically significant positive association between widowhood and mortality, but the widowhood effect was stronger in the period earlier than six months since bereavement (overall RR = 1.41, 95% CI: 1.26, 1.57) compared to the effect after six months (overall RR = 1.14, 95% CI: 1.10, 1.18). Meta-regression showed that the widowhood effect was not different for those aged younger than 65 years compared to those older than 65 (P = 0.25). There was, however, a difference in the magnitude of the widowhood effect by gender; for women the RR was not statistically significantly different from the null (overall RR = 1.04, 95% CI: 1.00, 1.08), while it was for men (overall RR = 1.23, 95% CI: 1.18, 1.28).

Conclusions

The results suggest that further studies should focus more on the mechanisms that generate this association especially among men.     

Mortality burden and socioeconomic status in India

Background

The dimensions along which mortality is patterned in India remains unclear. We examined the specific contribution of social castes, household income, assets, and monthly per capita consumption to mortality differentials in India.

Methods and Findings

Cross-sectional data on 217 363 individuals from 41 554 households from the 2004–2005 India Human Development Survey was analyzed using multiple logistic regressions. Mortality differentials across social castes were attenuated after adjusting for household economic factors such as income and assets. Individuals living in the lowest income and assets quintiles had an increased risk of mortality with odds ratio (OR) of 1.66 (95% CI  = 1.23–2.24) in the bottom income quintile and OR of 2.94 (95% CI  = 1.66–5.22) in the bottom asset quintile. Counter-intuitively, individuals living in households with lowest monthly consumption per capita had significantly lower probability of death (OR  = 0.27, 95% CI  = 0.20–0.38).

Conclusions

Mortality burden in India is largely patterned on economic dimensions as opposed to caste dimensions, though caste may play an important role in predicting economic opportunities.     

Impact of small body weight on tenofovir-associated renal dysfunction in HIV-infected patients: a retrospective cohort study of Japanese patients

Background

Treatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight.

Methods

In a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis.

Results

The median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10–1.37; p<0.001)(per 1 kg/m² decrement, HR = 1.14; 95% CI, 1.05–1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01–1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00–1.16; p = 0.058).

Conclusion

The incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight was identified as an independent risk factor for tenofovir-associated renal dysfunction. Close monitoring of renal function is advocated for patients with small body weight treated with tenofovir.     

Neighborhood socioeconomic deprivation and mortality: NIH-AARP diet and health study

Purpose

Residing in deprived areas may increase risk of mortality beyond that explained by a person''s own SES-related factors and lifestyle. The aim of this study was to examine the relation between neighborhood socioeconomic deprivation and all-cause, cancer- and cardiovascular disease (CVD)-specific mortality for men and women after accounting for education and other important person-level risk factors.

Methods

In the longitudinal NIH-AARP Study, we analyzed data from healthy participants, ages 50–71 years at study baseline (1995–1996). Deaths (n = 33831) were identified through December 2005. Information on census tracts was obtained from the 2000 US Census. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for quintiles of neighborhood deprivation.

Results

Participants in the highest quintile of deprivation had elevated risks for overall mortality (HR_men = 1.17, 95% CI: 1.10, 1.24; HR_women = 1.13, 95% CI: 1.05, 1.22) and marginally increased risk for cancer deaths (HR_men = 1.09, 95% CI: 1.00, 1.20; HR_women = 1.09, 95% CI: 0.99, 1.22). CVD mortality associations appeared stronger in men (HR = 1.33, 95% CI: 1.19, 1.49) than women (HR = 1.18, 95% CI: 1.01, 1.38). There was no evidence of an effect modification by education.

Conclusion

Higher neighborhood deprivation was associated with modest increases in all-cause, cancer- and CVD-mortality after accounting for many established risk factors.     

Differential white blood cell count and type 2 diabetes: systematic review and meta-analysis of cross-sectional and prospective studies

Objective

Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated.

Research Design and Methods

Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored.

Results

The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10⁻¹⁸). Substantial heterogeneity was present (I² = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10⁻⁴), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10⁻¹³), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10⁻⁵). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference.

Conclusions

A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate.     

Social class differences in secular trends in established coronary risk factors over 20 years: a cohort study of British men from 1978-80 to 1998-2000

Background

Coronary heart disease (CHD) mortality in the UK since the late 1970s has declined more markedly among higher socioeconomic groups. However, little is known about changes in coronary risk factors in different socioeconomic groups. This study examined whether changes in established coronary risk factors in Britain over 20 years between 1978–80 and 1998–2000 differed between socioeconomic groups.

Methods and Findings

A socioeconomically representative cohort of 7735 British men aged 40–59 years was followed-up from 1978–80 to 1998–2000; data on blood pressure (BP), cholesterol, body mass index (BMI) and cigarette smoking were collected at both points in 4252 survivors. Social class was based on longest-held occupation in middle-age. Compared with men in non-manual occupations, men in manual occupations experienced a greater increase in BMI (mean difference = 0.33 kg/m²; 95%CI 0.14–0.53; p for interaction = 0.001), a smaller decline in non-HDL cholesterol (difference in mean change = 0.18 mmol/l; 95%CI 0.11–0.25, p for interaction≤0.0001) and a smaller increase in HDL cholesterol (difference in mean change = 0.04 mmol/l; 95%CI 0.02–0.06, p for interaction≤0.0001). However, mean systolic BP declined more in manual than non-manual groups (difference in mean change = 3.6; 95%CI 2.1–5.1, p for interaction≤0.0001). The odds of being a current smoker in 1978–80 and 1998–2000 did not differ between non-manual and manual social classes (p for interaction = 0.51).

Conclusion

Several key risk factors for CHD and type 2 diabetes showed less favourable changes in men in manual occupations. Continuing priority is needed to improve adverse cardiovascular risk profiles in socially disadvantaged groups in the UK.     

Multiple Sclerosis and CCSVI: A Population-Based Case Control Study

Background

Chronic cerebrospinal venous insufficiency (CCSVI) has been associated to multiple sclerosis (MS).

Objective

To evaluate the possible association between CCSVI and MS, using a population-based control design.

Methods

A random cohort of 148 incident MS patients were enrolled in the study. We have also studied 20 patients with clinically isolated syndrome (CIS), 40 patients with other neurological diseases (OND), and 172 healthy controls. Transcranial (TCC) and Echo Color Doppler (ECD) were carried out in 380 subjects. A subject was considered CCSVI positive if ≥2 venous hemodynamic criteria were fulfilled.

Results

CCSVI was present in 28 (18.9%) of the MS patients, in 2 (10%) of CIS patients, in 11 (6.4%) of the controls, and in 2 (5%) of the OND patients. A significant association between MS and CCSVI was found with an odds ratio of 3.41 (95% confidence interval 1.63–7.13; p = 0.001). CCSVI was significantly more frequent among MS subjects with a disease duration longer than 144 months (26.1% versus 12.6% of patients with duration shorter than 144 months; p = 0.03) and among patients with secondary progressive (SP) and primary progressive (PP) forms (30.2% and 29.4, respectively) than in patients with relapsing remitting (RR) MS (14.3%). A stronger association was found considering SP and PP forms (age adjusted OR = 4.7; 95% CI 1.83–12.0, p = 0.001); the association was weaker with the RR patients (age adjusted OR = 2.58; 95%CI 1.12–5.92; p = 0.02) or not significant in CIS group (age adjusted OR = 2.04; 95%CI 0.40–10.3; p = 0.4).

Conclusions

A higher frequency of CCSVI has been found in MS patients; it was more evident in patients with advanced MS, suggesting that CCSVI could be related to MS disability.     

Diabetes with hypertension as risk factors for adult dengue hemorrhagic fever in a predominantly dengue serotype 2 epidemic: a case control study

Background

Dengue hemorrhagic fever (DHF) is a severe form of dengue, characterized by bleeding and plasma leakage. A number of DHF risk factors had been suggested. However, these risk factors may not be generalized to all populations and epidemics for screening and clinical management of patients at risk of developing DHF. This study explored demographic and comorbidity risk factors for DHF in adult dengue epidemics in Singapore in year 2006 (predominantly serotype 1) and in year 2007–2008 (predominantly serotype 2).

Methods

A retrospective case-control study was conducted with 149 DHF and 326 dengue fever (DF) patients from year 2006, and 669 DHF and 1,141 DF patients from year 2007–2008. Demographic and reported comorbidity data were collected from patients previously. We performed multivariate logistic regression to assess the association between DHF and demographic and co-morbidities for year 2006 and year 2007–2008, respectively.

Results

Only Chinese (adjusted odds ratio [AOR] = 1.90; 95% confidence interval [CI]: 1.01–3.56) was independently associated with DHF in year 2006. In contrast, age groups of 30–39 years (AOR = 1.41; 95% CI:1.09–1.81), 40–49 years (AOR = 1.34; 95% CI:1.09–1.81), female (AOR = 1.57; 95% CI:1.28–1.94), Chinese (AOR = 1.67; 95% CI:1.24–2.24), diabetes (AOR = 1.78; 95% CI:1.06–2.97), and diabetes with hypertension (AOR = 2.16; 95%CI:1.18–3.96) were independently associated with DHF in year 2007–2008. Hypertension was proposed to have effect modification on the risk of DHF outcome in dengue patients with diabetes. Chinese who had diabetes with hypertension had 2.1 (95% CI:1.07–4.12) times higher risk of DHF compared with Chinese who had no diabetes and no hypertension.

Conclusions

Adult dengue patients in Singapore who were 30–49 years, Chinese, female, had diabetes or diabetes with hypertension were at greater risk of developing DHF during epidemic of predominantly serotype 2. These risk factors can be used to guide triaging of patients who require closer clinical monitoring and early hospitalization in Singapore, when confirmed in more studies.     

Anterior Cervical Discectomy with Arthroplasty versus Arthrodesis for Single-Level Cervical Spondylosis: A Systematic Review and Meta-Analysis

Objective

To estimate the effectiveness of anterior cervical discectomy with arthroplasty (ACDA) compared to anterior cervical discectomy with fusion (ACDF) for patient-important outcomes for single-level cervical spondylosis.

Data sources

Electronic databases (MEDLINE, EMBASE, Cochrane Register for Randomized Controlled Trials, BIOSIS and LILACS), archives of spine meetings and bibliographies of relevant articles.

Study selection

We included RCTs of ACDF versus ACDA in adult patients with single-level cervical spondylosis reporting at least one of the following outcomes: functionality, neurological success, neck pain, arm pain, quality of life, surgery for adjacent level degeneration (ALD), reoperation and dysphonia/dysphagia. We used no language restrictions. We performed title and abstract screening and full text screening independently and in duplicate.

Data synthesis

We used random-effects model to pool data using mean difference (MD) for continuous outcomes and relative risk (RR) for dichotomous outcomes. We used GRADE to evaluate the quality of evidence for each outcome.

Results

Of 2804 citations, 9 articles reporting on 9 trials (1778 participants) were eligible. ACDA is associated with a clinically significant lower incidence of neurologic failure (RR  = 0.53, 95% CI  = 0.37–0.75, p = 0.0004) and improvement in the Neck pain visual analogue scale (VAS) (MD  = 6.56, 95% CI  = 3.22–9.90, p = 0.0001; Minimal clinically important difference (MCID)  = 2.5. ACDA is associated with a statistically but not clinically significant improvement in Arm pain VAS and SF-36 physical component summary. ACDA is associated with non-statistically significant higher improvement in the Neck Disability Index Score and lower incidence of ALD requiring surgery, reoperation, and dysphagia/dysphonia.

Conclusions

There is no strong evidence to support the routine use of ACDA over ACDF in single-level cervical spondylosis. Current trials lack long-term data required to assess safety as well as surgery for ALD. We suggest that ACDA in patients with single level cervical spondylosis is an option although its benefits and indication over ACDF remain in question.     

C-reactive protein, interleukin 6 and lung cancer risk: a meta-analysis

Purpose

Epidemiologic findings are inconsistent concerning the associations between C-reactive protein (CRP), interleukin 6 (IL-6) and lung cancer risk. We conducted a meta-analysis of epidemiologic studies to examine these associations.

Methods

A systematic literature search up to October 2011 was performed in MEDLINE and EMBASE. Study-specific risk estimates were pooled using a random-effects model.

Results

The 10 studies on CRP involved a total of 1918 lung cancer cases. The pooled RR of lung cancer for one unit change in natural logarithm (ln) CRP was 1.28 (95% CI 1.17–1.41). There was no statistically significant heterogeneity among studies (P = 0.116; I² = 36.6%). We also found that CRP was significantly associated with increased risk of lung cancer among men (RR 1.18, 95% CI 1.09–1.28) but not among women. The 5 studies on IL-6 involved a total of 924 lung cancer cases. The pooled RR of lung cancer for one unit change in ln IL-6 was 1.28 (95% CI 0.92–1.79), however, statistically significant heterogeneity was found. After excluding the study contributing most to the heterogeneity, the summary estimate was essentially unchanged.

Conclusion

CRP was associated with increased risk of lung cancer, especially among men. There was no significant association between IL-6 and lung cancer risk.