Association of Serum C-Peptide Concentrations with Cancer Mortality Risk in Pre-Diabetes or Undiagnosed Diabetes

Background: Known associations between diabetes and cancer could logically be attributed to hyperglycemia, hypersecretion of insulin, and/or insulin resistance. This study examined the relationship between initial glycemic biomarkers among men and women with impaired fasting glucose or undiagnosed diabetes and cancer mortality during follow up. Methods: The cohort included subjects aged 40 years and above from the Third National Health and Nutrition Examination Survey (NHANES III) with fasted serum glucose >100 mg/dl without the aid of pharmaceutical intervention (insulin or oral hypoglycemics). Cancer mortality was obtained from the NHANES III-linked follow-up database (up to December 31, 2006). A Cox regression model was applied to test for the associations between cancer mortality and fasting serum glucose, insulin, glycosylated hemoglobin (HbA1c), C-peptide, insulin like growth factor (IGF-1), IGF binding protein 3 (IGFBP3) and estimated insulin resistance. Results: A total of 158 and 100 cancer deaths were recorded respectively from 1,348 men and 1,161 women during the mean 134-month follow-up. After adjusting for the effect of age and smoking in women, all-cause cancer deaths (HR: 1.96 per pmol/ml, 95% CI: 1.02-3.77) and lung cancer deaths (HR: 2.65 per pmol/ml, 95% CI: 1.31-5.36) were specifically associated with serum C-peptide concentrations. Similar associations in men were not statistically significant. Serum glucose, HbA1c, IGF-1, IGFBP3 and HOMA were not independently related to long-term cancer mortality. Conclusion: C-peptide analyses suggest a modest association with both all-cause and lung cancer mortality in women but not in men. Further studies will be required to explore the mechanisms

Anaemia and related nutrient deficiencies after Roux-en-Y gastric bypass surgery: a systematic review and meta-analysis

Objective: To obtain a pooled risk estimate on the long-term impact of anaemia and related nutritional deficiencies in patients receiving Roux-en-Y gastric bypass (RYGB) surgery. Design: Systematic review and meta-analysis. Data sources: MEDLINE, EMBASE and Cochrane databases were searched to identify English reports published before 16 May 2014. Eligibility criteria: Articles with case numbers >100, follow-up period >12 months, and complete data from both before and after surgery were selected. Outcomes of interest were changes in baseline measurements of proportion of patients with anaemia, by haemoglobin, haematocrit, ferritin, iron, vitamin B-12 and folate levels. Data collection and analysis: Two reviewers independently reviewed data and selected six prospective and nine retrospective studies with a total of 5909 patients. A random effect model with inverse variance weighting was used to calculate summary estimates of outcomes at 6, 12, 24 and 36 months postoperatively. Results: Proportion of patients with anaemia was 12.2% at baseline, which, respectively, increased to 20.9% and 25.9% at 12 and 24 months follow-up, consistent with decreases in haemoglobin and haematocrit levels. Although the serum iron level did not change substantially after surgery, the frequency of patients with ferritin deficiency increased from 7.9% at baseline to 13.4% and 23.0% at 12 and 24 months, respectively, postoperation. Vitamin B-12 deficiency increased from 2.3% at baseline to 6.5% at 12 months after surgery in those subjects receiving RYGB. There was no obvious increase in folate deficiency. Conclusions: RYGB surgery is associated with an increased risk of anaemia and deficiencies of iron and vitamin B-12, but not folate. Ferritin is more sensitive when serum iron level is within normal range

Gefitinib與以鉑金為主化學治療在無法開刀非小細胞肺癌患者第一線治療之療效與安全性評估 - 統合分析

Background: To evaluate the risk/benefit profiles of gefitinib in comparison with platinum-based doublets chemotherapy as a first-tine treatment for chemonaive patients with advanced non-small-cell lung cancer in East Asia. Methods: We searched MEDLINE, EMBASE, Cochrane Library , and ClinicalTrials.gov to identify randomized and non- randomized phase II or III clinical trials of gefitinib or chemotherapy treatment in East Asian patients published before 4/30/2007. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. Treatment arms with gefitinib 250 mg/day and platinum-based doublets chemotherapy irrespective of dosage and schedule were combined to calculate the pooled estimates for efficacy and safety outcomes of interest. Results: We identified 7 gefitinib and 41 platinum-based doublets chemotherapy trials with nearly 3000 enrolled patients for planned comparison. The pooled response rate ( 95% confidence interval) to gefitinib for unselected chemonaive population was 31% (23-38%), not substantially different from 34% (31-38%) reported by platinum-based doublets chemotherapy trials. Patients with certain characteristics were more likely to benefit from gefitinib treatment, with pooled response rates as high as 75% (60-90% ) for patients with epidermal growth factor receptor (EGFR) exon 18-21 mutations; 56% (38-74%) for never smokers; 55% ( 41-69%) for female; and 43% (30-57%) for adenocarcinoma or bronchioalveolar carcinoma. Severe hematological adverse events related to gefitinib treatment were not observed in any of the included trials. However, the risks of severe liver and lung injury related to gefitinib treatment were both approximately 6%, significantly higher than 1% and 0.2 % reported by platinum-based doublets chemotherapy trials. Conclusion: Our data suggest that one third of chemonaive NSCLC patients in East Asia would respond to oral gefitinib monotherapy white 6% would develop severe liver and lung injury. Although patients with EGFR gene mutations, female gender, non-smokers, or adenocarcinoma were more likely to respond to gefitinib, further study with valid comparison groups are needed to identify the optimal treatment strategy in these subpopulations

Severe hepatic injury associated with different statins in patients with chronic liver disease: A nationwide population-based cohort study

Background and AimThe hepatotoxicity of statins in patients with chronic liver diseases remains unclear. In this study, we aimed to estimate the risk of severe hepatic injury associated with different statins in patients with chronic liver disease. MethodsA nationwide population-based cohort study was conducted by analyzing the Taiwan National Health Insurance database. A total of 37929 subjects with chronic liver disease who started statin therapy were identified during the period of January 1, 2005 to December 31, 2009. Outcome was defined as hospitalization due to liver injury. ResultsDuring a total of 118772 person-years of follow-up, 912 incident cases of hospitalization due to hepatic injury are identified. The incidence rate was 2.95, 2.49, 2.92, 1.94, 2.65, and 2.52 per 100000 person-days for atorvastatin, lovastatin, fluvastatin, pravastatin, simvastatin, and rosuvastatin initiators, respectively. Overall, there was no difference in the incidence associated with different statins. However, when each statin was further categorized to high (0.5 defined daily dose) or low (<0.5 defined daily dose) mean daily dose, only high-dose atorvastatin was significantly associated with increased risk of hospitalization due to hepatic injury (hazard ratio, 1.62; 95% confidence interval, 1.29, 2.03) as compared with low-dose atorvastatin. ConclusionThe overall incidence of hospitalization due to severe hepatic injury was low among statin initiators with chronic liver disease. Only high-dose atorvastatin was associated with increased risk

實證醫學共識對於減少內視鏡交感神 經切除術的影響 全國性調查

BACKGROUND Endoscopic thoracic sympathectomy (ETS) was overused for treating patients with hyperhidrosis in Taiwan. OBJECTIVES To determine whether use of evidence and a consensus-building exercise can reduce rates of surgery. METHODS We invited all surgeons in Taiwan who performed five or more ETSs per year for treating patients with hyperhidrosis to join this study. A structured questionnaire was mailed to surgeons asking about their management decisions based on clinical scenarios. Then we provided surgeons with evidence synopses and used the Delphi method to reach consensus. We analyzed healthcare utilization data during 2000 to 2005 and calculated total numbers of ETSs performed per 12 months to examine the effect on surgeons' behavior. RESULTS Of 155 surgeons invited, 61 (40%) completed this study. They agreed that observation or topical therapy was appropriate for patients with mild palmar hyperhidrosis, whereas ETS was appropriate for children, adolescents, and young and middle-aged adults who had severe symptoms. Surgeons became more willing to recommend botulinum toxin injection after we provided evidence synopses. We found a 52% reduction in mean total ETSs per 12 months in surgeons receiving evidence synopses. A higher percentage of reduction occurred in patients younger than 12 and aged 60 and older. CONCLUSION Evidence- based consensus development is helpful in decreasing overuse of ETS in treating patients with hyperhidrosis in Taiwan

Increased Risk of Active Tuberculosis following Acute Kidney Injury: A Nationwide, Population-Based Study

Background: Profound alterations in immune responses associated with uremia and exacerbated by dialysis increase the risk of active tuberculosis (TB). Evidence of the long-term risk and outcome of active TB after acute kidney injury (AKI) is limited. Methods: This population-based-cohort study used claim records retrieved from the Taiwan National Health Insurance database. We retrieved records of all hospitalized patients, more than 18 years, who underwent dialysis for acute kidney injury (AKI) during 1999-2008 and validated using the NSARF data. Time-dependent Cox proportional hazards model to adjust for the ongoing effect of end-stage renal disease (ESRD) was conducted to predict long-term de novo active TB after discharge from index hospitalization. Results: Out of 2,909 AKI dialysis patients surviving 90 days after index discharge, 686 did not require dialysis after hospital discharge. The control group included 11,636 hospital patients without AKI, dialysis, or history of TB. The relative risk of active TB in AKI dialysis patients, relative to the general population, after a mean follow-up period of 3.6 years was 7.71. Patients who did (hazard ratio [HR], 3.84; p<0.001) and did not (HR, 6.39; p<0.001) recover from AKI requiring dialysis had significantly higher incidence of TB than patients without AKI. The external validated data also showed nonrecovery subgroup (HR = subgroup (HR = 4.37; p = 0.049) had high risk of developing active TB compared with non-AKI. Additionally, active TB was; p = 0.049) had high risk of developing active TB compared with non-AKI. Additionally, active TB was associated with long-term all-cause mortality after AKI requiring dialysis (HR, 1.34; p = 0.032). Conclusions: AKI requiring dialysis seems to independently increase the long-term risk of active TB, even among those who weaned from dialysis at discharge. These results raise concerns that the increasing global burden of AKI will in turn increase the incidence of active TB

Risk of Parkinson's disease following severe constipation: A nationwide population-based cohort study

Introduction: Constipation is a non-motor symptom of Parkinson's disease (PD). We investigated the association between the severity of constipation and subsequent risk of PD in a population-based sample. Methods: 551,324 participants free of PD, dementia, and stroke were retrospectively ascertained between January 1, 2005 and December 31, 2005 using the Taiwan National Health Insurance Research Database. The association between constipation at the beginning of the study and the incidence of PD was examined using a Cox regression model. Information regarding comorbidities and concomitant medications use was adjusted in the proportional hazards models. Results: After an average follow-up of 5.5 years, 2336 incident PD cases were diagnosed. The crude incidence rate of PD per 1,000,000 person-days was 1.57 for subjects without constipation and 4.04, 5.28, and 12.67 for mild, moderate, and severe constipation, respectively. After adjusting for age, sex, comorbidities, and concomitant medication use, patients with constipation were more likely to develop PD than subjects without constipation; the adjusted hazard ratio (aHR) was 3.28 (95% CI: 2.14-5.03), 3.83 (2.51-5.84), and 4.22 (2.95-6.05) for individual constipation severity categories. Constipation severity was also associated with an increased likelihood of PD in the time-varying analysis; the aHR was 2.84 (2.43-333), 5.22 (4.61-5.92), and 10.47 (9.46-11.58) for mild, moderate, and severe constipation, respectively (P < 0.0001). After excluding PD patients diagnosed within 3 years of constipation, the association remained significant. Conclusions: Our study suggests that the severity of constipation is associated with a future diagnosis of PD in a dose-dependent manner. (C) 2014 Elsevier Ltd. All rights reserved

Meta-Analysis: Ribavirin-Induced Haemolytic Anaemia in Patients with Chronic Hepatitis C

Aim: To use meta-analysis to study the risk of aemiarelated to ribavirin therapy for chronic hepatitis C. Methods: The MEDLINE database up to January 2001 was searched for randomized controlled trials of ribavirin ( monotherapy or combined with interferon) for chronic hepatitis C. The outcomes evaluated were withdrawal from the study due to anaemia, ribavirin dosage reduction due to a decrease in haemoglobin and haemoglobin levels below 10 g/dL. Results: Based on 17 studies, the overall risk difference (ribavirin vs. no ribavirin) for anaemia was 0.09 [95% confidence interval (CI), 0.04-0.13]. Two Asian studies reported risk differences of 0.29 and 0.22, greater than the pooled risk difference of 0.07 (95% CI, 0.03-0.12) for 15 non-Asian studies. The risk associated with 1 g or more of ribavirin per day was higher (risk difference, 0.09; 95% CI, 0.04-0.14 ) than that for 0.8 g of ribavirin per day (risk difference, 0.01; 95% CI, -0.04-0.06). Conclusions: Chronic hepatitis C patients treated with 1 g or more of ribavirin per day were at a higher risk of developing anaemia. Reported risks were higher among Asian studies , which may be due to differences in study entrance criteria, dosage titration strategy or ethnic vulnerability