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1.

Aims/Hypothesis

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

Methods

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

Results

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

Conclusions/Interpretation

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

2.

Background

Multiple studies have investigated the effect of perioperative blood transfusion (PBT) for patients with radical cystectomy (RC), but the results have been inconsistent. We conducted a systematic review and meta-analysis to investigate the relationship between PBT and the clinical outcomes of RC patients.

Methods

We searched MEDLINE, EMBASE, the Cochrane library and BIOSIS previews to identify relevant literature for studies that focused on the relationship of PBT and outcomes of patients undergoing RC. A fixed or random effects model was used in this meta-analysis to calculate the pooled hazard ratio (HR) with 95% confidence intervals (CIs).

Results

A total of 7080 patients in 6 studies matched the selection criteria. Aggregation of the data suggested that PBT in patients who underwent RC correlated with increased all-cause mortality, cancer-specific mortality and cancer recurrence. The combined HRs were 1.19 (n = 6 studies, 95% CI: 1.11–1.27, Z = 4.71, P<0.00001), 1.17 (n = 4 studies, 95% CI: 1.06–1.30, Z = 3.06, P = 0.002), 1.14 (n = 3 studies, 95% CI: 1.03–1.27, Z = 2.50, P = 0.01), respectively. The all-cause mortality associated with PBT did not vary by the characteristics of the study, including number of study participants, follow-up period and the median blood transfusion ratio of the study.

Conclusion

Our data showed that PBT significantly increased the risks of all-cause mortality, cancer-specific mortality and cancer recurrence in patients undergoing RC for bladder cancer.  相似文献   

3.

Background

Markers that can discriminate between indolent and aggressive prostate tumours are needed. We studied gene methylation in non-neoplastic tissue adjacent to prostate tumour (NTAT) in association with prostate cancer mortality.

Methods

From two cohorts of consecutive prostate cancer patients diagnosed at one pathology ward in Turin, Italy, we selected 157 patients with available NTAT and followed them up for more than 14 years. We obtained DNA from NTAT in paraffin-embedded prostate tumour tissues and used probe real-time PCR to analyse methylation of the glutathione S-transferase (GSTP1) and adenomatous polyposis coli (APC) gene promoters.

Results

Prevalence of APC and GSTP1 methylation in the NTAT was between 40 and 45%. It was associated with methylation in prostate tumour tissue for the same two genes as well as with a high Gleason score. The hazard ratio (HR) of prostate cancer mortality was 2.38 (95% confidence interval: 1.23–4.61) for APC methylation, and 2.92 (1.49–5.74) for GSTP1 methylation in NTAT. It changed to 1.91 (1.03–3.56) and 1.60 (0.80–3.19) after adjusting for Gleason score and methylation in prostate tumour tissue. Comparison of 2 vs. 0 methylated genes in NTAT revealed a HR of 4.30 (2.00–9.22), which decreased to 2.40 (1.15–5.01) after adjustment. Results were stronger in the first 5 years of follow-up (adjusted HR: 3.29, 95% CI: 1.27–8.52).

Conclusions

Changes in gene methylation are an early event in prostate carcinogenesis and may play a role in cancer progression. Gene methylation in NTAT is a possible prognostic marker to be evaluated in clinical studies.  相似文献   

4.

Background and Objectives

In previous studies, obesity (measured according to the body mass index) has correlated inconsistently with the risk of biopsy-measured prostate cancer, and specifically high-grade prostate cancer. This meta-analysis aimed to clarify these correlations.

Methods

A comprehensive literature search of the MEDLINE and EMBASE databases was conducted for relevant studies published through January 2014. The pooled estimates of odds ratios (OR) and confidence intervals (CI) were computed, and the meta-analysis was performed with the STATA software according to a random effects approach.

Results

A total of 11 studies that included 29,464 individuals were identified. A 5-kg/m2 increase in body mass index was associated with a 15% (OR, 1.15; 95% CI, 0.98–1.34) higher risk of prostate cancer detection and a 37% (OR, 1.37; 95% CI, 1.19–1.57) higher risk of high-grade prostate cancer detection at biopsy. There were no differences among the results of studies conducted in the USA, Europe or Asia. We also found that studies that had adjusted for prostate-specific antigen levels, digital rectal examination results, and prostate volumes obtained positive significant outcomes (OR, 1.27; 95% CI, 1.12–1.44), whereas studies that did not adjust for the above-mentioned confounding variables obtained negative results (OR, 0.92; 95% CI, 0.68–1.25). Moreover, the positive correlation between body mass index and the detection of both prostate cancer and high-grade diseases tended to be stronger as the number of biopsy cores increased.

Conclusion

The present meta-analysis demonstrated that a high body mass index correlated positively with prostate cancer detection, especially high-grade prostate cancer detection. The adoption of a modified and possibly more aggressive biopsy strategy was suggested for obese populations.  相似文献   

5.
Noto H  Goto A  Tsujimoto T  Noda M 《PloS one》2012,7(3):e33411

Background

A growing body of evidence has suggested that metformin potentially reduces the risk of cancer. Our objective was to enhance the precision of estimates of the effect of metformin on the risk of any-site and site-specific cancers in patients with diabetes.

Methods/Principal Findings

We performed a search of MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for pertinent articles published as of October 12, 2011, and included them in a systematic review and meta-analysis. We calculated pooled risk ratios (RRs) for overall cancer mortality and cancer incidence. Of the 21,195 diabetic patients reported in 6 studies (4 cohort studies, 2 RCTs), 991 (4.5%) cases of death from cancer were reported. A total of 11,117 (5.3%) cases of incident cancer at any site were reported among 210,892 patients in 10 studies (2 RCTs, 6 cohort studies, 2 case-control studies). The risks of cancer among metformin users were significantly lower than those among non-metformin users: the pooled RRs (95% confidence interval) were 0.66 (0.49–0.88) for cancer mortality, 0.67 (0.53–0.85) for all-cancer incidence, 0.68 (0.53–0.88) for colorectal cancer (n = 6), 0.20 (0.07–0.59) for hepatocellular cancer (n = 4), 0.67 (0.45–0.99) for lung cancer (n = 3).

Conclusion/Significance

The use of metformin in diabetic patients was associated with significantly lower risks of cancer mortality and incidence. However, this analysis is mainly based on observational studies and our findings underscore the more need for long-term RCTs to confirm this potential benefit for individuals with diabetes.  相似文献   

6.

Objective

To examine whether fish and fish oil consumption across the lifespan is associated with a lower risk of prostate cancer.

Design

The study was nested among 2268 men aged 67–96 years in the AGES-Reykjavik cohort study. In 2002 to 2006, dietary habits were assessed, for early life, midlife and later life using a validated food frequency questionnaire. Participants were followed for prostate cancer diagnosis and mortality through 2009 via linkage to nationwide cancer- and mortality registers. Adjusting for potential confounders, we used regression models to estimate odds ratios (ORs) and hazard ratios (HRs) for prostate cancer according to fish and fish oil consumption.

Results

Among the 2268 men, we ascertained 214 prevalent and 133 incident prostate cancer cases, of which 63 had advanced disease. High fish consumption in early- and midlife was not associated with overall or advanced prostate cancer. High intake of salted or smoked fish was associated with a 2-fold increased risk of advanced prostate cancer both in early life (95% CI: 1.08, 3.62) and in later life (95% CI: 1.04, 5.00). Men consuming fish oil in later life had a lower risk of advanced prostate cancer [HR (95%CI): 0.43 (0.19, 0.95)], no association was found for early life or midlife consumption.

Conclusions

Salted or smoked fish may increase risk of advanced prostate cancer, whereas fish oil consumption may be protective against progression of prostate cancer in elderly men. In a setting with very high fish consumption, no association was found between overall fish consumption in early or midlife and prostate cancer risk.  相似文献   

7.

Background

Deletions of the glutathione S-transferase genes M1 and T1 (GSTM1 and GSTT1) have been studied as potential risk factors for prostate cancer. Conflicting results have been obtained. Moreover, most such studies could not discriminate heterozygous from homozygous carriers of the non-deleted alleles.

Objective

We investigated whether copy number variation (CNV) of the GSTM1 and/or GSTT1 genes contribute to the risk of prostate cancer in the Caribbean population of African descent of Guadeloupe.

Methods

In a population-based case-control study, we compared 629 prostate cancer patients and 622 control subjects. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Exact copy numbers of GSTM1 and GSTT1 were determined by real-time PCR.

Results

A higher copy number of GSTM1 was marginally associated with prostate cancer risk. Men with 2 and 3 or more GSTT1 genes were at higher risk of prostate cancer (OR: 1.55, 95% CI: 1.11–2.16 and OR: 4.89, 95% CI: 1.71–13.99, respectively; Ptrend<0.001). Men with 3, 4 and 5 or more copies of both GSTM1 and GSTT1 genes were at higher risk of prostate cancer (OR: 2.18, 95% CI: 1.21–3.91, OR: 3.24, 95% CI: 1.63–6.46, and OR: 5.77, 95% CI: 1.40–23.84, respectively; Ptrend<0.001).

Conclusions

Copy number of GSTT1 and combined GSTM1/GSTT1 appear to be associated with prostate cancer risk in our population study with gene dose relationship. Our results support the hypothesis that variations in copy number of GSTT1 modulate the risk of prostate cancer.  相似文献   

8.

Objective

To evaluate the risk of cancer among patients with generalized anxiety disorder (GAD) in a nationwide population-based dataset.

Methods

We recruited newly-diagnosed GAD patients aged 20 years or older without antecedent cancer from the Taiwan National Health Insurance Research database between 2000–2010. Standardized incidence ratios (SIRs) of cancers were calculated in GAD patients, and the subgroup of GAD patients diagnosed by psychiatric specialists.

Results

A total of 559 cancers developed among 19,793 GAD patients with a follow-up of 89,485 person-years (median follow-up of 4.34 years), leading to a significantly increased SIR of 1.14 [95% confidence interval (CI) 1.05–1.24]. Male GAD patients had a significantly increased SIR overall (1.30, 95% CI 1.15–1.46) and for lung and prostate cancer (1.77, 95% CI 1.33–2.30 and 2.17, 95% CI 1.56–2.93, respectively). Patients over 80 years of age also had a significantly increased SIR (1.56, 95% CI 1.25–1.92), especially in males. However, psychiatrist-diagnosed GAD patients did not show increased cancer risk relative to the general population, perhaps due to having fewer physical comorbidities than non-psychiatrist-diagnosed GAD patients.

Conclusion

This study found that overall cancer risk is elevated among patients with GAD. The risk of lung and prostate cancer also increased in male patients with GAD. This increased cancer risk may be due to physical comorbidities and surveillance bias. Further prospective study is necessary to confirm these findings.  相似文献   

9.
Va P  Yang WS  Nechuta S  Chow WH  Cai H  Yang G  Gao S  Gao YT  Zheng W  Shu XO  Xiang YB 《PloS one》2011,6(11):e26600

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.  相似文献   

10.

Objective

The aim was to examine if long-term psychiatric sickness absence was associated with all-cause and diagnosis-specific (cardiovascular disease (CVD), cancer and suicide) mortality for the period 1990–2007. An additional aim was to examine these associations for psychiatric sickness absence in 1990 and 2000, with follow-up on mortality during 1991–1997 and 2001–2007, separately.

Methods

Employees within municipalities and county councils, 244,990 individuals in 1990 and 764,137 individuals in 2000, were followed up to 2007 through register linkages. Analyses were conducted with flexible parametric survival models comparing sickness absentees due to psychiatric diagnoses (>90 days) with those not receiving sick leave benefit.

Results

Long-term sickness absence for psychiatric disorders was associated with an increased risk of mortality due to all causes; CVD; cancer (smoking and non-smoking related); and suicide during the period 1990–2007. After full adjustment for socio-demographic covariates and previous inpatient care due to somatic and psychiatric diagnoses, these associations remained significant for all-cause mortality (Hazard ratios (HR) and 95% confidence interval (CI)): HR 1.56, 95% CI 1.3–1.8; CVD: HR 1.35, 95% CI 1.0–1.9, and suicide: HR 3.84, 95% CI 2.4–6.1. For both cohorts 1990 and 2000 estimates point in the same direction. For the time-period 2000–2007, we found increased risks of mortality in the fully adjusted model due to all causes: HR 1.47, 95% CI 1.2–1.7; CVD: HR 1.83, 95% CI 1.2–2.7; overall cancer: HR 1.33, 95% CI 1.0–1.7; and suicide: HR 2.15, 95% CI 1.3–3.7.

Conclusion

Long-term sickness absence for psychiatric disorders predicted premature mortality from all-causes, cardiovascular disease, cancer, and suicide.  相似文献   

11.
Yang WS  Va P  Bray F  Gao S  Gao J  Li HL  Xiang YB 《PloS one》2011,6(12):e27326

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.  相似文献   

12.

Background

Interleukin-6 (IL-6) may have a protective role in acute liver disease but a detrimental effect in chronic liver disease. It is unknown whether IL-6 is associated with risk of liver-related mortality in humans.

Aims

To determine if IL-6 is associated with an increased risk of all-cause, cardiovascular disease (CVD), cancer, and liver-related mortality.

Methods

A prospective cohort study included 1843 participants who attended a research visit in 1984–87. Multiple covariates were ascertained including serum IL-6. Multivariable-adjusted Cox proportional hazards regression analyses were used to examine the association between serum IL-6 as a continuous (log transformed) variable with all-cause, CVD, cancer, and liver-related mortality. Patients with prevalent CVD, cancer and liver disease were excluded for cause-specific mortality.

Results

The mean (± standard deviation) age and body-mass-index (BMI) of participants was 68 (±10.6) years and 25 (±3.7) Kg/m2, respectively. During the 25,802 person-years of follow-up, the cumulative all-cause, CVD, cancer, and liver-related mortality were 53.1% (N = 978), 25.5%, 11.3%, and 1.3%, respectively. The median (±IQR) length of follow-up was 15.3±10.6 years. In multivariable analyses, adjusted for age, sex, alcohol, BMI, diabetes, hypertension, total cholesterol, HDL, and smoking, one-SD increment in log-transformed serum IL-6 was associated with increased risk of all-cause, CVD, cancer, and liver-related mortality, with hazard ratios of 1.48 (95% CI, 1.33–1.64), 1.38 (95% CI, 1.16–1.65), 1.35 (95% CI, 1.02–1.79), and 1.88 (95% CI, 0.97–3.67), respectively. CRP adjustment attenuated the effects but the association between IL-6 and all-cause and CVD mortality remained statistically significant, independent of CRP levels.

Conclusions

In community-dwelling older adults, serum IL-6 is associated with all-cause, CVD, cancer, and liver-related mortality.  相似文献   

13.

Background

Studies have reported inconsistent findings regarding the association between obstructive sleep apnea (OSA) and future risks of cardiovascular and all-cause mortality. We conducted a meta-analysis to investigate whether OSA is an independent predictor for future cardiovascular and all-cause mortality using prospective observational studies.

Methods

Electronic literature databases (Medline and Embase) were searched for prospective observational studies published prior to December 2012. Only observational studies that assessed baseline OSA and future risk of cardiovascular and all-cause mortality were selected. Pooled hazard risk (HR) and corresponding 95% confidence intervals (CI) were calculated for categorical risk estimates. Subgroup analyses were based on the severity of OSA.

Results

Six studies with 11932 patients were identified and analyzed, with 239 reporting cardiovascular mortality, and 1397 all-cause mortality. Pooled HR of all-cause mortality was 1.19 (95% CI, 1.00 to 1.41) for moderate OSA and 1.90 (95% CI, 1.29 to 2.81) for severe OSA. Pooled HR of cardiovascular mortality was 1.40 (95% CI, 0.77 to 2.53) for moderate OSA and 2.65 (95% CI, 1.82 to 3.85) for severe OSA. There were no differences in cardiovascular mortality in continuous positive airway pressure (CPAP) treatment compared with healthy subjects (HR 0.82; 95% CI, 0.50 to 1.33).

Conclusions

Severe OSA is a strong independent predictor for future cardiovascular and all-cause mortality. CPAP treatment was associated with decrease cardiovascular mortality.  相似文献   

14.

Background

Aflibercept is a human recombinant fusion protein with antiangiogenic effects that functions as a decoy receptor to bind vascular endothelial growth factor A. Proteinuria is one of its major adverse effects with a substantial variation in the incidence rate, and the overall risk of proteinuria has not been systematically studied. We performed a meta-analysis of published clinical trials to quantify the incidence and relative risk of proteinuria in cancer patients treated with aflibercept.

Methods

The electronic databases were searched, including PubMed, Embase, Cochrane databases, and ASCO (American Society of Clinical Oncology) abstracts. Eligible studies were phase II and III prospective clinical trials of cancer patients treated with aflibercept with toxicity data on proteinuria. Overall incidence rates, relative risk (RR), and 95% confidence intervals (CI) were calculated using fixed or random effects models depending on the heterogeneity of the included studies.

Results

A total of 4,596 patients with a variety of solid tumors from 16 prospective clinical trials were included for the meta-analysis. The overall incidences of all-grade and high-grade proteinuria in cancer patients were 33.9% (95% CI: 27.3–42.1%) and 7.9% (95% CI: 6.1–10.2%). The relative risks of proteinuria of aflibercept compared to control were increased for all-grade (RR = 1.41, 95% CI: 1.13–1.77) and high-grade (RR = 6.18, 95% CI: 3.78–10.12) proteinuria. The risk of developing all-grade and high-grade proteinuria with aflibercept was substantially higher than that of bevacizumab (all-grade: RR 1.85, 95% CI: 1.63–2.11; high-grade: RR 2.37, 95% CI: 1.84–3.05).

Conclusions

Aflibercept is associated with an increased risk of developing proteinuria. Appropriate monitoring and treatment is strongly recommended to prevent potential renal damage. Future studies are still needed to investigate the risk reduction and possible use of aflibercept in cancer patients.  相似文献   

15.

Purpose

Several epidemiologic studies have evaluated the association between nonsteroidal anti-inflammatory drugs (NSAIDs) and bladder cancer risk and the results were varied. Thus, we conducted a comprehensive meta-analysis of studies exclusively dedicated to the relationship between the 3 most commonly used analgesics and bladder cancer risk.

Methods

A systematic literature search up to November 2012 was performed in PubMed database for 3 categories of analgesics: acetaminophen, aspirin or non-aspirin NSAIDs. Study-specific risk estimates were pooled using a random-effects model.

Results

Seventeen studies (8 cohort and 9 case-control studies), involving a total of 10,618 bladder cancer cases, were contributed to the analysis. We found that acetaminophen (relative risk [RR] 1.01, 95% confidence interval [CI] 0.88–1.17) and aspirin (RR 1.02, 95% CI 0.91–1.14) were not associated with bladder cancer risk. Although non-aspirin NSAIDs was statistically significantly associated with reduced risk of bladder cancer among case-control studies (but not cohort studies), the overall risk was not statistically significant (RR 0.87, 95% CI 0.73–1.05). Furthermore, we also found that non-aspirin NSAIDs use was significantly associated with a 43% reduction in bladder cancer risk among nonsmokers (RR 0.57, 95% CI 0.43–0.76), but not among current smokers.

Conclusion

The results of our meta-analysis suggest that there is no association between use of acetaminophen, aspirin or non-aspirin NSAIDs and bladder cancer risk. However, non-aspirin NSAIDs use might be associated with a reduction in risk of bladder cancer for nonsmokers.  相似文献   

16.

Background

Despite the magnitude and increase of sickness absence due to mental diagnoses, little is known regarding long-term health outcomes. The aim of this nationwide population-based, prospective cohort study was to investigate the association between sickness absence due to specific mental diagnoses and the risk of all-cause and cause-specific mortality.

Methods

A cohort of all 4 857 943 individuals living in Sweden on 31.12.2004 (aged 16–64 years, not sickness absent, or on retirement or disability pension), was followed from 01.01.2005 through 31.12.2008 for all-cause and cause-specific mortality (suicide, cancer, circulatory disease) through linkage of individual register data. Individuals with at least one new sick-leave spell with a mental diagnosis in 2005 were compared to individuals with no sickness absence. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox regression, adjusting for age, sex, education, country of birth, family situation, area of residence, and pre-existing morbidity (diagnosis-specific hospital inpatient (2000–2005) and outpatient (2001–2005) care).

Results

In the multivariate analyses, mental sickness absence in 2005 was associated with an increased risk for all-cause mortality: HR: 1.65, 95% CI: 1.47–1.86 in women and in men: 1.73, 1.57–1.91; for suicide, cancer (both smoking and non-smoking related) as well as mortality due to circulatory disease only in men. Estimates for cause-specific mortality ranged from 1.48 to 3.37. Associations with all-cause mortality were found for all mental sickness absence diagnostic groups studied.

Conclusions

Knowledge about the prognosis of patients sickness absent with specific mental diagnoses is of crucial clinical importance in health care. Sickness absence due to specific mental diagnoses may here be used as a risk indictor for subsequent mortality.  相似文献   

17.

Background

Recent studies suggest that cancer increases risk of atrial fibrillation. Whether atrial fibrillation is a marker for underlying occult cancer is unknown.

Methods

We conducted a cohort study (1980–2011) of all Danish patients with new-onset atrial fibrillation. To examine cancer risk, we computed absolute risk at 3 months and standardized incidence ratios (SIRs) by comparing observed cancer incidence among patients newly diagnosed with atrial fibrillation with that expected based on national cancer incidence during the period.

Results

Median follow-up time was 3.4 years among 269 742 atrial fibrillation patients. Within 3 months of follow-up, 6656 cancers occurred (absolute risk, 2.5%; 95% confidence intervals [CI], 2.4%–2.5%) versus 1302 expected, yielding a SIR of 5.11; 95% CI, 4.99–5.24. Associations were particularly strong for cancers of the lung, kidney, colon, ovary, and for non-Hodgkin''s lymphoma. The SIR within 3 months of follow-up was 7.02; 95% CI, 6.76–7.28 for metastatic and 3.53; 95% CI, 3.38–3.68 for localized cancer. Beyond 3 months of follow-up, overall cancer risk was modestly increased (SIR, 1.13; 95% CI, 1.12–1.15).

Conclusion

Patients with new-onset atrial fibrillation had a markedly increased relative risk of a cancer diagnosis within the next three months, however, corresponding absolute risk was small.  相似文献   

18.

Background

The UK Prospective Diabetes Study showed that metformin decreases mortality compared to diet alone in overweight patients with type 2 diabetes mellitus. Since then, it has been the first-line treatment in overweight patients with type 2 diabetes. However, metformin-sulphonylurea bitherapy may increase mortality.

Methods and Findings

This meta-analysis of randomised controlled trials evaluated metformin efficacy (in studies of metformin versus diet alone, versus placebo, and versus no treatment; metformin as an add-on therapy; and metformin withdrawal) against cardiovascular morbidity or mortality in patients with type 2 diabetes. We searched Medline, Embase, and the Cochrane database. Primary end points were all-cause mortality and cardiovascular death. Secondary end points included all myocardial infarctions, all strokes, congestive heart failure, peripheral vascular disease, leg amputations, and microvascular complications. Thirteen randomised controlled trials (13,110 patients) were retrieved; 9,560 patients were given metformin, and 3,550 patients were given conventional treatment or placebo. Metformin did not significantly affect the primary outcomes all-cause mortality, risk ratio (RR) = 0.99 (95% CI: 0.75 to 1.31), and cardiovascular mortality, RR = 1.05 (95% CI: 0.67 to 1.64). The secondary outcomes were also unaffected by metformin treatment: all myocardial infarctions, RR = 0.90 (95% CI: 0.74 to 1.09); all strokes, RR = 0.76 (95% CI: 0.51 to 1.14); heart failure, RR = 1.03 (95% CI: 0.67 to 1.59); peripheral vascular disease, RR = 0.90 (95% CI: 0.46 to 1.78); leg amputations, RR = 1.04 (95% CI: 0.44 to 2.44); and microvascular complications, RR = 0.83 (95% CI: 0.59 to 1.17). For all-cause mortality and cardiovascular mortality, there was significant heterogeneity when including the UK Prospective Diabetes Study subgroups (I 2 = 41% and 59%). There was significant interaction with sulphonylurea as a concomitant treatment for myocardial infarction (p = 0.10 and 0.02, respectively).

Conclusions

Although metformin is considered the gold standard, its benefit/risk ratio remains uncertain. We cannot exclude a 25% reduction or a 31% increase in all-cause mortality. We cannot exclude a 33% reduction or a 64% increase in cardiovascular mortality. Further studies are needed to clarify this situation. Please see later in the article for the Editors'' Summary  相似文献   

19.

Background

An association between male fertility and risk of prostate cancer has been suggested, possibly through lower androgen levels in subfertile men. We evaluated male fertility in relation to risk of prostate cancer by assessing the frequency of fathering of dizygotic twins, a marker of high fertility, among cases of prostate cancer and controls.

Methods

We performed a case-control study in Prostate Cancer data Base Sweden (PCBaSe), a nationwide, population-based cohort. PCBaSe was linked to the Swedish twin register for information on zygosity for same-sex twins and to other nationwide health care registers and demographic databases for information on socioeconomic factors, comorbidity, and tumor characteristics for 96 301 prostate cancer cases and 378 583 matched controls. To account for the influence of in vitro fertilization on dizygotic twinning, analyses were restricted to men who had fathered children before 1991, when in vitro fertilization was still uncommon in Sweden.

Results

1 112 cases and 4 538 controls had fathered dizygotic twins. Men with dizygotic twins had no increased risk of prostate cancer compared to fathers of singletons; neither for total prostate cancer odds ratio (OR) 0.95(95% CI 0.89–1.02), nor for any risk category, OR 0.97 (95% CI 0.84–1.12) for low-risk disease, and OR 1.04 (95% CI 0.90–1.22) for metastatic disease.

Conclusion

The lack of association between fathering of dizygotic twins and prostate cancer risk give no support for an association between male fertility and prostate cancer risk.  相似文献   

20.

Background and Aims

MET, the hepatocyte growth factor receptor, is a receptor tyrosine kinase overexpressed and activated in a subset of gastric cancer. Several studies investigated the relationship between MET amplification and expression with the clinical outcome in patients with gastric cancer, but yielded conflicting results. We performed a systematic review and meta-analysis to determine the influence of MET amplification and expression on prognosis in gastric cancer.

Methods

MEDLINE and EMBASE were searched for studies that explored the association between MET amplification and expression with survival in patients with gastric cancer up to 1 April, 2013. Data of individual hazard ratios (HRs) and 95% confidence intervals (CIs) for meta-analyses were extracted from the publications and combined in pooled HRs.

Results

Fourteen studies involving 2,258 patients with gastric cancer were included. It was suggested that MET overexpression had an unfavorable impact on survival of patients with gastric cancer, with HRs (95% CIs) of 2.57 (95% CI: 1.97–3.35) overall, 2.82 (95% CI: 1.86–4.27) among studies using amplification for measure scale of MET and 2.42 (95% CI: 1.66–3.54) for expression. The magnitude of association was reduced whereas remained statistically significant in high quality studies or in larger sample size studies and corresponding HRs were 2.18(1.76, 2.70) and 2.35(1.93, 2.87), respectively, without significant heterogeneity.

Conclusion

The findings from present study indicated that higher MET gene amplification and expression in gastric cancer was an indicator of poor prognosis.  相似文献   

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