Five-year survival prognosis of young, middle-aged, and elderly adult female invasive breast cancer patients by clinical and lifestyle characteristics.

PURPOSE: Early-onset breast cancer incidence has been increasing globally and in Taiwan. However, previous studies have not comprehensively examined how clinical and lifestyle characteristics influence the 5-year survival of breast cancer diagnosed at different stages of adulthood. METHODS: We analyzed the Taiwan National Cancer Registry and Cause of Death datasets to understand how clinical factors (including tumor and treatment characteristics) and lifestyle factors (including body mass index, cigarette smoking, and alcohol consumption) were associated with the 5-year survival of 8471 young, 57,695 middle-aged, and 14,074 elderly female adult invasive breast cancer patients respectively diagnosed at age 20-39, 40-64, and ≥ 65 years between 2002 and 2015, with mortality follow-up to 2020. Poisson regression was used for obtaining the crude and adjusted 5-year survival risk ratios. RESULTS: Clinical and lifestyle characteristics were distributed differently but had mostly similar direction of association with 5-year survival for the three age groups. Receiving any treatment was associated with better survival, especially for elderly patients. Being underweight at initial cancer treatment was associated with worse survival than having normal weight, especially for elderly patients. Current smokers had worse survival than never smokers for middle-aged and elderly patients. The 5-year breast cancer-specific survival was not significantly higher for those of age 45-49 years than 40-44 years, despite the recommended starting screening age is 45 years in Taiwan. CONCLUSION: Our findings contribute to the understanding of early-onset and later-onset female breast cancer characteristics and prognosis, which may inform surveillance and treatment strategies to achieve better breast cancer prognosis.

Risk of circulatory diseases associated with proton-pump inhibitors: a retrospective cohort study using electronic medical records in Thailand.

Background: Proton-pump inhibitors (PPIs) are prescribed to treat gastric acid-related diseases, while they may also have potential risks to population health. Recent studies suggested that a potential mechanism explaining the association between PPIs and cardiovascular diseases (CVD) includes the inhibition of the nitrate-nitrite-nitric oxide (NO) pathway. However, previous observational studies showed controversial results of the association. In addition, the inhibition of the NO pathway due to PPIs use may lead to peripheral vascular diseases (PVD); however, none of the studies explore the PPI-PVD association. Therefore, this study aimed to evaluate the association of PPIs with circulatory diseases (CVD, ischemic strokes or IS, and PVD). Methods: We conducted a retrospective hospital-based cohort study from Oct 2010 to Sep 2017 in Songkhla province, Thailand. PPIs and histamine 2-receptor antagonists (H2RAs) prescriptions were collected from electronic pharmacy records, while diagnostic outcomes were retrieved from electronic medical records at Songklanagarind hospital. Patients were followed up with an on-treatment approach. Cox proportional hazard models were applied to measure the association comparing PPIs vs H2RAs after 1:1 propensity-score-matching. Sub-group analysis, multi-bias E-values, and array-based sensitivity analysis for some covariates were used to assess the robustness of associations. Results: A total of 3,928 new PPIs and 3,928 H2RAs users were included in the 1:1 propensity score-matched cohort. As compared with H2RAs, the association of PPIs with CVD, IS, and PVD, the hazard ratios were 1.76 95% CI = [1.40-2.20] for CVD, 3.53 95% CI = [2.21-5.64] for ischemic strokes, and 17.07 95% CI = [13.82-76.25] for PVD. The association between PPIs and each outcome was significant with medication persistent ratio of over 50%. In addition, the association between PPIs and circulatory diseases was robust to unmeasured confounders (i.e., smoking and alcohol). Conclusion: PPIs were associated with circulatory diseases, particularly ischemic strokes in this hospital-based cohort study, whereas, the strength of associations was robust to unmeasured confounders.

Young adult cancer incidence trends in Taiwan and the U.S. from 2002 to 2016.

BACKGROUND: Previous studies have not examined young adult cancer incidence trends in Taiwan, or comprehensively compared these trends at two nations with different population genetics, environmental exposures, and health care. Therefore, we compared the incidence rates and trends of the most common young adult cancers diagnosed at 20-39 years of age in Taiwan and the U.S. METHODS: Incidence rates from 2002 to 2016 were calculated from the Taiwan National Health Insurance Research Datasets and the U.S. Surveillance, Epidemiology, and End Results Program. For trend assessment, average annual percent change (AAPC) values were calculated from 15 years of data using Joinpoint Regression Program. We also obtained sex or age of diagnosis stratified estimates. RESULTS: The age-standardized overall young adult cancer incidence rate significantly increased from 2002 to 2016 in both Taiwan (AAPC=1.1%, 95% CI: 0.8-1.5%) and the U.S. (AAPC=1.8%, 95% CI: 1.1-2.4%). Cancers with significantly decreasing trends in Taiwan included cancers of the nasopharynx, liver, and tongue, which were not among the most common young adult cancers in the U.S. Cancers with significantly increasing trends in both Taiwan and the U.S. included colorectal, thyroid, and female breast cancers. Lymphoma, ovarian cancer, and lung and bronchus cancer had significantly increasing trends in Taiwan but not in the U.S. Although cervical cancer had significantly decreasing trends in both nations among those 30-39 years of age, its trend was significantly increasing in Taiwan but decreasing in the U.S. among those 20-29 years of age. CONCLUSION: The types of common young adult cancers as well as their incidence rates and trends differed in Taiwan and the U.S. Future studies should further understand the etiological factors driving these trends.

Incidence of hospitalization for infection among patients with hepatitis B or C virus infection without cirrhosis in Taiwan: A cohort study.

BACKGROUND: Infection is a major complication in liver cirrhosis and causes major morbidity and mortality. However, the incidence and mortality related to these conditions in patients infected with hepatitis C virus (HCV) are unclear, as is whether antiviral therapy could change their infection risk. METHODS AND FINDINGS: In this community-based cohort study, a total of 115,336 adults (mean age 52.2 years; 35.6% men) without cirrhosis participating in the New Taipei City Health Screening in 2005-2008 were classified as having noncirrhotic HCV (NC-HCV) (n = 2,839), noncirrhotic hepatitis B virus (NC-HBV) (n = 8,316), or no HBV or HCV infection (NBNC) (n = 104,181). Participants were followed to their first hospitalization for infection or death after data linkage with the Taiwan National Health Insurance Research Database (NHIRD) and Death Registry. A Cox proportional hazard regression model, adjusted for age, sex, body mass index (BMI), smoking, alcohol consumption, education level, diabetes, renal function, systemic steroids, and history of hospitalization, was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for overall and individual sites of infection and infection-related mortality. The reference group was NBNC participants with normal to mildly elevated alanine aminotransferase (ALT) (<1.5 times upper normal limit [UNL]) levels. To further address the impact of antiviral treatment on infection risk, we conducted analyses of data from the nationwide NHIRD and compared the risks for hospitalization because of infections and infection-related deaths between patients with HCV who received antiviral therapy (n = 20,264) and those who remained untreated (n = 104,360). During a median 8.2-year follow-up, the incidence of hospitalization for infection was substantially higher in NC-HCV patients. Compared to the reference group, NC-HCV was associated with a significantly higher risk for hospitalization because of overall infections (adjusted HR: 1.22; 95% CI: 1.12-1.33), but we observed no increased risk for patients in the NC-HBV (adjusted HR: 0.94; 95% CI: 0.88-1.01) or NBNC group with moderate to markedly elevated ALT levels (adjusted HR: 1.03; 95% CI: 0.93-1.14). For specific sites of infection, the NC-HCV group had increased risks for septicemia and lower respiratory tract, reproductive, and urinary tract infections. We noted no increased risk for infection-related death among patients with NC-HCV. Patients with HCV who received antiviral therapy had significantly reduced infection-related hospitalization and death risks (adjusted HR: 0.79; 95% CI: 0.73-0.84 for infection-related hospitalization and adjusted HR: 0.08; 95% CI: 0.04-0.16 for infection-related deaths). Study limitations include the exclusion of patients with cirrhosis from the cohort, the possibility of unmeasured confounding, and the lack of information on direct-acting antiviral agents (DAAs). CONCLUSIONS: In this study, patients with NC-HCV were at increased risk for hospitalization for infection, while no increased risk was observed for NC-HBV-infected patients.

Thiazolidinediones and reduced risk of incident bacterial abscess in adults with type 2 diabetes: A population-based cohort study.

AIM: Previous research has suggested that peroxisome proliferator-activated receptor-gamma (PPAR-γ) may play an important role in immunomodulation. We aimed to examine the association between thiazolidinediones, PPAR-γ agonists and incidence of bacterial abscess among patients with type 2 diabetes. MATERIALS AND METHODS: This retrospective cohort study between 2000 and 2010 included 46 986 propensity (PS)-matched patients diagnosed with type 2 diabetes. We compared the incidence of bacterial abscess, including liver and non-liver abscesses, between patients treated with metformin plus a thiazolidinedione (M + T, N = 7831) or metformin plus a sulfonylurea (M + S, N = 39 155). Data were retrieved from a population-based Taiwanese database. We applied Cox proportional hazard regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), comparing M + T and M + S after PS matching. RESULTS: During a median follow-up of 4.5 years, the incidence rate of bacterial abscess was lower with M + T than with M + S treatment (1.89 vs 3.15 per 1000 person-years) in the PS-matched cohort. M + T was associated with a reduced risk of bacterial abscess (HRs after PS matching, 0.58; 95% CI, 0.42-0.80 for total bacterial abscess; 0.54; 95% CI, 0.28-1.07 for liver abscess; 0.59; 95% CI, 0.41-0.85 for non-liver abscess). Results did not change materially after accounting for unmeasured confounding factors using high-dimenional PS matching and differential censoring between regimen groups. Rosiglitazone and pioglitazone, in combination with metformin, produced similar reductions in risk of all abscess outcomes. CONCLUSION: We found that M + T may provide a protective benefit in reducing the incidence of bacterial abscesses. These findings merit further investigation.

Risk of mortality with concomitant use of tamoxifen and selective serotonin reuptake inhibitors: multi-database cohort study.

OBJECTIVE:  To compare differences in mortality between women concomitantly treated with tamoxifen and selective serotonin reuptake inhibitors (SSRIs) that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) versus tamoxifen and other SSRIs. DESIGN:  Population based cohort study. SETTING:  Five US databases covering individuals enrolled in private and public health insurance programs from 1995 to 2013. PARTICIPANTS:  Two cohorts of women who started taking tamoxifen. In cohort 1, women started taking an SSRI during tamoxifen treatment. In cohort 2, women were already taking an SSRI when they started taking tamoxifen. MAIN OUTCOME MEASURES:  All cause mortality in each cohort in women taking SSRIs that are potent inhibitors of CYP2D6 (paroxetine, fluoxetine) versus other SSRIs. Propensity scores were used to match exposure groups in a variable ratio fashion. Results were measured separately for each cohort and combined hazard ratios calculated from Cox regression models across the two cohorts with random effects meta-analysis. RESULTS:  There were 6067 and 8465 new users of tamoxifen in cohorts 1 and 2, respectively. Mean age was 55. A total of 991 and 1014 deaths occurred in cohorts 1 and 2 during a median follow-up of 2.2 (interquartile range 0.9-4.5) and 2.0 (0.8-3.9) years, respectively. The pooled hazard ratio for death for potent inhibitors (rate 58.6/1000 person years) compared with other SSRIs (rate 57.9/1000 person years) across cohorts 1 and 2 was 0.96 (95% confidence interval 0.88 to 1.06). Results were consistent across sensitivity analyses. CONCLUSION:  Concomitant use of tamoxifen and potent CYP2D6 inhibiting SSRIs versus other SSRIs was not associated with an increased risk of death.

Risk factors of ifosfamide-related encephalopathy in adult patients with cancer: A retrospective analysis.

BACKGROUND/PURPOSE: Ifosfamide, a widely used chemotherapeutic agent, has been frequently associated with encephalopathy. A larger-scale study was conducted to identify risk factors of ifosfamide-related encephalopathy, including hepatic function. METHODS: Adult patients who had completed at least one cycle of ifosfamide between January 2008 and December 2010 were included. Those with renal failure or liver failure were excluded. Data were collected through chart review. Patients with encephalopathy and patients without encephalopathy were compared on age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), baseline serum creatinine (SCr) level, albumin level, white blood cell count, liver function, brain metastasis, and dosage of ifosfamide. Chi-square test or Fisher's exact test, Student t test, and univariate and multivariate logistic regressions were used for analysis. RESULTS: This study enrolled 337 patients. Thirty-eight patients (11%) had ifosfamide-related encephalopathy. They had poorer ECOG PS; higher SCr level, white blood cell count, and aspartate aminotransferase level; and lower serum albumin level compared with patients without encephalopathy. Ifosfamide dosage, brain metastasis, and age were not significant risk factors. Multivariate analysis indicated that only ECOG PS, SCr level, and albumin level contributed significantly to the risk. CONCLUSION: To date, this is the largest-scale study to have analyzed the risk factors of ifosfamide-related encephalopathy. This study confirms that an ECOG PS of 2-4 and increased SCr level are significant risk factors of ifosfamide-related encephalopathy, whereas increased albumin level decreases the risk, consistent with previous reports. Higher aspartate aminotransferase levels have no significant impact. In contrast to previous studies, ifosfamide dosage and brain metastasis are not significant contributing factors.

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 B12 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 B12 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 B12, but not folate. Ferritin is more sensitive when serum iron level is within normal range.

Examining the association between statins and lung cancer incidence in patients with type 2 diabetes mellitus.

BACKGROUND/PURPOSE: The relationship between statin use and lung cancer remains unclear. Patients with diabetes mellitus, who are at higher risks for both cancer and atherosclerosis, are usually indicated for statin use. The objective was to explore the relationship between statins, lung squamous cell carcinoma (SCC), and lung adenocarcinoma incidence in diabetic patients. METHODS: A cohort of 596,812 type 2 diabetic patients was identified from the Taiwan National Health Insurance claims database in the year 2000, and followed until the earliest of lung cancer diagnosis, death, or December 31, 2007. A Cox regression model with time-varying statin use was applied to estimate the hazard ratio (HR) of lung cancer incidence comparing use and nonuse of statins. A sensitivity analysis was applied to examine the association after adjustment for smoking effect. RESULTS: In the original diabetic cohort, 60,969 statin users and 535,843 statin nonusers were identified. In a median follow-up time of 7.9 years, a total of 1182 incident SCC cases and 2345 adenocarcinoma cases developed. Initial analysis showed a decreased risk of SCC if statins were ever used (HR, 0.69; 95% confidence interval, 0.60-0.81). However, the relative risk would be 0.92 for males and 0.90 for females for statins after adjusting for smoking effect. There was no association between statin use and adenocarcinoma (HR, 0.97; 95% confidence interval, 0.88-1.07), with similar findings after controlling for smoking effect. CONCLUSION: There is no statistically significant association between statin use with lung cancer incidence in diabetic patients after adjustment for the confounding effect attributed to cigarette smoking.

Development and validation of a pharmacy-based comorbidity measure in a population-based automated health care database.

STUDY OBJECTIVE: To develop the Pharmacy-Based Disease Indicator (PBDI), and to evaluate its performance versus the diagnosis-based Deyo version of the Charlson Index in predicting subsequent-year hospitalization in adults. DESIGN: Retrospective cohort analysis. DATA SOURCE: Longitudinal health insurance database derived from the national health insurance system in Taiwan. PATIENTS: Two adult populations were identified: 697,823 individuals who were at least 18 years of age on January 1, 2005 (dataset 2005), and 714,072 who were at least 18 years of age on January 1, 2006 (dataset 2006). MEASUREMENTS AND MAIN RESULTS: Based on the Chronic Disease Score framework and the Anatomical Therapeutic Chemical classification system, we developed the PBDI, a comorbidity measure that is a function of 37 drug categories that correspond to major diseases in Taiwan. The relationship between individuals' PBDI score and subsequent-year hospitalization was evaluated by use of logistic regression models. Covariates in the models included age group, sex, PBDI score, and Deyo score. Using the two overlapping adult populations, we calculated both the PBDI score and the Deyo score for each individual in each year. Using subsequent-year hospitalization as the outcome and each comorbidity measure as the predictor, we demonstrated that the c statistic of the PBDI versus the Deyo version of the Charlson Index was 0.72 versus 0.69 for both the 2005 and 2006 populations. The Akaike information criterion, Bayesian information criterion, model calibration, and reclassification measures also confirmed the utility of the PBDI. CONCLUSION: The PBDI demonstrated acceptable predictive performance for subsequent-year hospitalization. It can be used as a general comorbidity measure to describe the health status of populations based on data derived from population-based automated health care databases.