The largest genome-wide association study for breast cancer in Taiwanese Han population.

PURPOSE: Breast cancer is a molecularly heterogeneous disease, and multiple genetic variants contribute to its development and prognosis. Most of previous genome-wide association studies (GWASs) and polygenic risk scores (PRSs) analyses focused on studying breast cancers of Caucasian populations, which may not be applicable to other population. Therefore, we conducted the largest breast cancer cohort of Taiwanese population to fill in the knowledge gap. METHODS: A total of 152,534 Participants recruited by China Medical University Hospital between 2003 and 2019 were filtered by several patient selection criteria and GWAS quality control steps, resulting in the inclusion of 2496 cases and 9984 controls for this study. We then conducted GWAS for all breast cancers and PRS analyses for all breast cancers and the four breast cancer subtypes, including luminal A, luminal B, basal-like, and HER2-enriched. RESULTS: The GWAS analyses identified 113 SNPs, 50 of which were novel. The PRS models for all breast cancers and the luminal A subtype showed positively correlated trends between the PRS and the risk of developing breast cancer. The odds ratios (95% confidence intervals) for the groups with the highest PRS in all breast cancers and the luminal A subtype were 5.33 (3.79-7.66) and 3.55 (2.13-6.14), respectively. CONCLUSION: In summary, we explored the association of genetic variants with breast cancer in the largest Taiwanese cohort and developed two PRS models that can predict the risk of developing any breast cancer and the luminal A subtype in Taiwanese women.

Dyslipidemia and coronary artery calcium: From association to development of a risk-prediction nomogram.

BACKGROUND AND AIMS: The associations between dyslipidemia and coronary artery calcium (CAC) are controversial. We investigated their cross-sectional relationships and developed a predictive scoring system for prognostically significant coronary calcification (PSCC). METHODS AND RESULTS: This study evaluated the lipid profiles and the CAC score (CACS) measured through multidetector computed tomography (MDCT) among Taiwanese adult patients in a tertiary hospital between 2011 and 2016. Patients with CACS higher than 100 were classified as having PSCC. Dyslipidemia for each lipid component was defined based on the clinical cutoffs or the use of the lipid-lowering agents. Multivariable logistic regression was used to assess the association between dyslipidemia and PSCC and the model performance was assessed using calibration plot, discrimination, and a decision curve analysis. Of the 3586 eligible patients, 364 (10.2%) had PSCC. Increased age, male sex, higher body mass index (BMI), and higher level of triglyceride (TG) were associated with PSCC. The adjusted odds ratios (95% confidence intervals) of PSCC was 1.15 (0.90-1.47) for dyslipidemia defined by total cholesterol (TC) ≥200 mg/dL, 1.06 (0.83-1.35) for low-density-lipoprotein-cholesterol (LDL-C) ≥130 mg/dL, and 1.36 (1.06-1.75) for TG ≥ 200 mg/dL. The positive association between TG ≥ 200 mg/dL and PSCC was not modified by sex. Incorporating hypertriglyceridemia did not significantly improve the predictive performance of the base model comprising of age, sex, BMI, smoking, hypertension, diabetes, estimated glomerular filtration rate, and fasting glucose. CONCLUSIONS: Hypertriglyceridemia was significantly associated with the prevalent odds of PSCC. Our proposed predictive model may be a useful screening tool for PSCC.

Association between statin use and second cancer risk in breast cancer patients: a nationwide population-based cohort study.

PURPOSE: Many studies have revealed that statin therapy reduced mortality in cancer patients, especially in breast cancer, but the effect for second cancer was unclear. We, therefore, performed a comparable cohort study to determine the risk of second cancer in breast cancer patients with statin therapy. METHODS: Using claims data from Taiwan's National Health Insurance Program, this study enrolled newly diagnosed breast cancer patients from 2000 to 2007 with and without statin therapy as the statin (n = 1222) and nonstatin (n = 4888) cohorts, respectively. The nonstatin cohort was propensity score matched by cohort entry year, age, and randomly selected comorbidities. These two cohorts were followed up until the diagnosis of second cancer, death, or the end of 2011. Cox proportional hazard models were used to estimate the hazard ratios. RESULTS: The statin cohort had a lower incidence rate than the nonstatin cohort for second cancer (7.37 vs. 8.36 per 1000 person-years), although the difference was not significant (adjusted hazard ratio [aHR] 0.90, 95% confidence interval [CI] 0.65-1.26). Compared with the nonstatin cohort, the second cancer risk was significantly higher for patients taking pravastatin (aHR 2.71, 95% CI 1.19-6.19) but lower for those receiving multiple statin treatment (aHR 0.45, 95% CI 0.25-0.81) and combined lipophilic and hydrophilic type of statin (aHR 0.42, 95% CI 0.20-0.89). The risk was lower for patients receiving a cumulative defined daily dose (cDDD) of > 430 (aHR 0.41, 95% CI 0.19-0.86). CONCLUSION: This study showed that there is little association between statin use and second cancer risk in breast cancer patients.

Hypoglycaemic episodes increase the risk of ventricular arrhythmia and sudden cardiac arrest in patients with type 2 diabetes-A nationwide cohort study.

BACKGROUND: The impact of hypoglycaemic episode (HE) on the risk of ventricular arrhythmia (VA) and sudden cardiac arrest (SCA) remains unclear. We hypothesized that HE increases the risk of both VA and SCA and that glucose-lowering agents causing HE also increase the risk of VA/SCA in patients with type 2 diabetes (T2D). METHODS: Patients aged 20 years or older with newly diagnosed T2D were identified using the Taiwan National Health Insurance Database. HE was defined as the presentation of hypoglycaemic coma or specified/unspecified hypoglycaemia. The control group consisted of T2D patients without HE. The primary outcome was the occurrence of VA (including ventricular tachycardia and fibrillation) and SCA during the defined follow-up periods. A multivariate Cox hazards regression model was used to evaluate the hazard ratio (HR) for VA or SCA. RESULTS: A total of 54 303 patients were screened, with 1037 patients with HE assigned to the HE group and 4148 frequency-matched patients without HE constituting the control group. During a mean follow-up period of 3.3 ± 2.5 years, 29 VA/SCA events occurred. Compared with the control group, HE group had a higher incidence of VA/SCA (adjusted HR: 2.42, P = .04). Patients who had used insulin for glycaemic control showed an increased risk of VA/SCA compared with patients who did not receive insulin (adjusted HR: 3.05, P = .01). CONCLUSIONS: The HEs in patients with T2D increased the risk of VA/SCA, compared with those who did not experience HEs. Use of insulin also independently increased the risk of VA/SCA.

Non-alcoholic fatty liver disease among patients with sleep disorders: a Nationwide study of Taiwan.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. Studies have shown that sleep apnea is associated with NAFLD. However, studies on the association between sleep disorders in general and NAFLD are limited. We conducted a nationwide population-based longitudinal study to evaluate this potential association. METHODS: We identified patients diagnosed with sleep disorders in the years 2000 through 2005 in Taiwan using the National Health Insurance Research Database and selected an equal number of patients without sleep disorders from the same database as the comparison cohort. The patients were followed from the index date to the diagnosis of NAFLD or the end of 2013. We used Cox proportional hazards models to estimate the risk of NAFLD associated with sleep disorders. RESULTS: A total of 33,045 patients with sleep disorders were identified. The incidence of NAFLD was 14.0 per 10,000 person-year in patients with sleep disorders and 6.2 per 10,000 person-year in the comparison cohort. The adjusted hazard ratio (AHR) of NAFLD associated with sleep disorders was 1.78 (95% confidence interval [95%CI]: 1.46-2.16), and other independent risk factors included male sex (AHR = 1.31, 95%CI: 1.12-1.54), age 40-59 years (AHR = 1.49, 95%CI: 1.21-1.82), and dyslipidemia (AHR = 2.51, 95%CI: 2.08-3.04). In the subgroup analyses, both patients with (AHR = 2.24, 95%CI: 1.05-4.77) and without (AHR = 1.77, 95%CI: 1.46-2.15) sleep apnea had an increased risk of NAFLD. CONCLUSIONS: Sleep disorders are associated with NAFLD, even in patients without sleep apnea. Further studies are warranted to explore the mechanisms of the association.

Glitazones and alpha-glucosidase inhibitors as the second-line oral anti-diabetic agents added to metformin reduce cardiovascular risk in Type 2 diabetes patients: a nationwide cohort observational study.

OBJECTIVE: Metformin is the standard first-line drug for patients with Type 2 diabetes (T2DM). However, the optimal second-line oral anti-diabetic agent (ADA) remains unclear. We investigated the cardiovascular risk of various ADAs used as add-on medication to metformin in T2DM patients from a nationwide cohort. METHODS: T2DM patients using different add-on oral ADAs after an initial metformin therapy of > 90 days were identified from the Taiwan National Health Insurance Database. Five classes of ADAs, including sulphonylureas (SU), glinides, thiazolidinediones (TZD), alpha-glucosidase inhibitors (AGI), and dipeptidyl peptidase-4 inhibitors (DPP-4I) were selected for analysis. The reference group was the SU added to metformin. Patients were excluded if aged < 20 years, had a history of stroke or acute coronary syndrome (ACS), or were receiving insulin treatment. The primary outcomes included any major adverse cardiovascular event (MACE) including ACS, ischemic/hemorrhagic stroke, and death. A Cox regression model was used to estimate the hazard ratio (HR) for MACE. RESULTS: A total of 26,742 patients receiving their add-on drug to metformin of either SU (n = 24,277), glinides (n = 962), TZD (n = 581), AGI (n = 808), or DPP-4I (n = 114) were analyzed. After a mean follow-up duration of 6.6 ± 3.4 years, a total of 4775 MACEs occurred. Compared with the SU+metformin group (reference), the TZD+metformin (adjusted HR: 0.66; 95% CI 0.50-0.88, p = 0.004) and AGI+metformin (adjusted HR: 0.74; 95% CI 0.59-0.94, p = 0.01) groups showed a significantly lower risk of MACE. CONCLUSION: Both TZD and AGI, when used as an add-on drug to metformin were associated with lower MACE risk when compared with SU added to metformin in this retrospective cohort study. Trial registration CE13152B-3. Registered 7 Mar, 2013, retrospectively registered.

Hypothyroidism is associated with all-cause mortality in a national cohort of chronic haemodialysis patients.

AIM: The prevalence of hypothyroidism is high in haemodialysis (HD) patients and hypothyroidism increases all-cause mortality in HD patients. Comorbidities are common in HD patients and are associated with both mortality and hypothyroidism. The aim of the study is to explore the effect of the interactions of comorbidities and hypothyroidism on all-cause mortality in HD patients. METHOD: Patients with hypothyroidism (ICD-9-CM 244.0, 244.1, and 244.9) and matched patients without hypothyroidism in the Registry for Catastrophic Illness Patient Database of Taiwan Health Insurance from 2000 to 2010 were analyzed. The association of hypothyroidism and risk of all-cause mortality was analyzed using Cox proportional hazard regression. RESULT: Nine hundred and eight HD patients with hypothyroidism and 3632 sex-, age-, gender- matched HD patients without hypothyroidism were analyzed. Hypothyroidism was associated with increased all-cause mortality with an adjusted hazard ratio of 1.22 [95% confidence interval (CI): 1.10-1.36, P < 0.001]. TRT may decrease mortality associated with hypothyroidism (P < 0.001). There was a significant interaction (P = 0.04) between diabetes and hypothyroidism. There was no significant interaction found in hypothyroidism and the following comorbidities: hyperlipidaemia, hypertension, chronic obstructive pulmonary disease, coronary artery disease, stroke, peripheral arterial disease, asthma, congestive heart failure and cancer. CONCLUSION: Hypothyroidism is associated with increased all-cause mortality in chronic HD patients. The interaction of hypothyroidism and diabetes, but not other common comorbidities in HD patients, has an effect on mortality risks.

Disability benefits as an incentive for hysterectomy: Uterine fibroid patients in Taiwan.

Worker compensation insurance in Taiwan ensures that a woman under the age of 45 years who has her uterus removed can receive disability compensation benefits. The present study investigated whether such a compensation policy was related to a woman's inclination to have a hysterectomy. We extracted the records of 16,030 women diagnosed with uterine fibroids (UF) between 2000 and 2010 from the Longitudinal Taiwan Health Insurance Database. Each younger and older age group had a significantly lower hysterectomy rate compared to that of the 44-year-old age group. Moreover, significantly more patients with lower monthly wages had had hysterectomies than those with higher monthly wages. Policy makers should be aware that worker compensation regulations in Taiwan might encourage women with economic need to undergo hysterectomy surgery when approaching the age of 45 years.

Association between allergic disease, sleep-disordered breathing, and childhood nocturnal enuresis: a population-based case-control study.

BACKGROUND: Little is known about the associations between allergic disease, sleep-disordered breathing (SDB), and childhood nocturnal enuresis (NE). We examined whether allergic disease and SDB were associated with childhood NE. METHODS: Data were assessed from the 2007-2012 Taiwan National Health Insurance Research Database. We enrolled 4308 children aged 5-18 years having NE diagnosis and age- and sex-matched 4308 children as the control group. The odds ratios of NE were calculated to determine an association with preexisting allergic disease and SDB. RESULTS: A total of 8616 children were included in the analysis. Prevalence of allergic diseases and SDB was significantly higher for the NE group than the control group (all p < 0.001). After adjusting odds ratios for potential confounding factors, except asthma, children with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and obstructive sleep apnea (OSA) had significantly higher odds of NE compared with children never diagnosed. With stratification for sex, girls with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, OSA, and snoring had significantly higher odds of NE, compared with girls never diagnosed. Only boys with allergic rhinitis and OSA were associated with increased odds of NE. With stratification for age, children aged 5-12 years with allergic rhinitis, atopic dermatitis, allergic conjunctivitis, and OSA had significantly higher odds of NE compared with those never diagnosed. Odds of NE increased with the number of comorbid allergic diseases. CONCLUSIONS: Allergic diseases and SDB are associated with increased odds of childhood NE. The odds of NE increased with the number of comorbid allergic diseases present.

Tourette syndrome increases risk of bone fractures: a population-based cohort study.

This study assesses the risk of fractures among children with Tourette syndrome (TS), and identifies the effects of comorbidities and antipsychotics. We randomly sampled the claims data of 1 million enrollees in the National Health Insurance program of Taiwan, and identified 1258 children with TS diagnosed between 2000 and 2010. Additionally, 12,580 children without TS who were frequency matched for sex, age, residential area, parental occupation, and index year were identified for comparison. The children's cases were followed until December 31, 2010, or censored to ascertain incident fractures cases and associations with comorbidities of attention-deficit/hyperactivity disorder (ADHD) or obsessive-compulsive disorder (OCD) and treatments with antipsychotics, antidepressants, or clonidine. The TS cohort had a 1.27-fold higher incidence of fractures than did the comparison cohort (190.37 vs. 149.94 per 10,000 person-years), with an adjusted hazard ratio (HR) of 1.28 [95% confidence interval (CI) 1.06-1.55] based on multivariable Cox regression analysis. This increased risk of fractures was apparent for fractures of the skull, neck, and spine. Comorbid ADHD and OCD did not result in an additional risk of fractures. The children without both ADHD and OCD were also at a higher risk of fractures, indicating that TS alone increases the risk of fractures. The children taking antipsychotics had a reduced risk of fractures, and the adjusted HR decreased to 1.17 (95% CI 0.90-1.52). Children with TS have an increased risk of fractures. ADHD and OCD do not increase the risk further.

Risk of epilepsy in type 1 diabetes mellitus: a population-based cohort study.

AIMS/HYPOTHESIS: Type 1 diabetes mellitus is a major public health problem of increasing global concern, with potential neurological complications. A possible association exists between type 1 diabetes and subsequent epilepsy. This study evaluated the relationship between type 1 diabetes and epilepsy in Taiwan. METHODS: Claims data from the Taiwan National Health Insurance Research Database were used to conduct retrospective cohort analyses. The study cohort contained 2568 patients with type 1 diabetes, each of whom was frequency-matched by sex, urbanisation of residence area and index year with ten patients without type 1 diabetes. Cox proportional hazard regression analysis was conducted to estimate the effects of type 1 diabetes on epilepsy risk. RESULTS: In patients with type 1 diabetes, the risk of developing epilepsy was significantly higher than that in patients without type 1 diabetes (p < 0.0001 for logrank test). After adjustment for potential confounders, the type 1 diabetes cohort was 2.84 times as likely to develop epilepsy than the control cohort was (HR 2.84 [95% CI 2.11, 3.83]). CONCLUSIONS/INTERPRETATION: Patients with type 1 diabetes are at an increased risk of developing epilepsy. Metabolic abnormalities of type 1 diabetes, such as hyperglycaemia and hypoglycaemia, may have a damaging effect on the central nervous system and be associated with significant long-term neurological sequelae. The causative factors between type 1 diabetes and the increased risk of epilepsy require further investigation.

Cancer risk in East Asian patients associated with acquired haemolytic anaemia: a nationwide population-based cohort study.

BACKGROUND: This study investigated whether patients with acquired haemolytic anaemia (AHA) would have elevated cancer risk including that for non-haematological solid tumours. We further examined whether the cancer risk would be different between patients with autoimmune type AHA (AIHA) and patients of non-AIHA. METHODS: Using nationwide population-based insurance claims data of Taiwan we identified a cohort of patients with AHA with no pre-existing cancer, (n = 3902) and a comparison cohort (n = 39020) without AHA, frequency-matched by gender, age, urbanization of residency and diagnosis date. Incidence and Cox method estimated adjusted hazard ratios (aHR) of cancers controlling covariates by the end of 2010 were calculated. Risks between patients with AIHA and non-AIHA were compared. Sensitivity analysis was carried out to measure the risk of cancer between patients with and without AHA by follow-up years. RESULTS: Patients with AHA had a 90% greater incidence of cancer than controls, with an aHR of 1.78 (95% confidence interval (CI), 1.50-2.12)]. The overall aHRs of cancer for patients with AIHA and non-AIHA were 2.01 (95% CI, 1.56-2.59) and 1.87 (95% CI, 1.53-2.29), respectively, compared with the comparison cohort. The aHRs for lymphatic-haematopoietic malignancy were 19.5 and 9.59 in the AIHA and non-AIHA cohorts, respectively. No hazard of colorectal, lung, liver or breast cancer was significant. CONCLUSIONS: There is a near 2-fold elevated risk for subsequent cancer in patients with AHA, particularly for lymphatic-haematopoietic malignancy, which is much greater for patients with AIHA than non-AIHA. These findings can help clinicians decide patient-centred personalized long-term management.

Increased incidence of gastrointestinal cancers among patients with pyogenic liver abscess: a population-based cohort study.

BACKGROUND & AIMS: The relationship between pyogenic liver abscess (PLA) and gastrointestinal (GI) cancer was first reported more than 20 years ago, yet little is known about this connection. We evaluated this association in a population-based, retrospective, cohort study. METHODS: Using Taiwan National Health Insurance claims data, we collected data on a cohort of 14,690 patients with PLA diagnosed from 2000 to 2007. A reference cohort of 58,760 persons without PLA (controls) was selected from the same database, frequency matched by age, sex, and index year. Both cohorts were followed up until the end of 2009, and incidences of GI cancer were calculated. RESULTS: The incidence of GI cancer was 4.30-fold higher among patients with PLA compared with controls (10.8 vs 2.51/1000 person-years). Site-specific analysis showed that the highest incidence of colorectal cancer was among patients with PLA and diabetes mellitus, followed by patients with PLA without diabetes and controls with diabetes (9.58, 5.76, and 1.49/10,000 person-years, respectively). The PLA cohort also had a high risk of small intestine cancer (adjusted hazard ratio [aHR], 12.7; 95% confidence interval [CI], 5.79-27.7) and biliary tract cancer (aHR, 9.56; 95% CI, 6.68-13.7). Their risk of pancreatic cancer (aHR, 2.51; 95% CI, 1.68-3.76) was also significant. However, patients with PLA did not have an increased risk of gastric cancer compared with controls. CONCLUSIONS: In a population-based study, we found that the incidence of GI cancer is increased more than 4-fold among patients with PLA compared with controls. PLA might therefore be an indicator of GI cancer. Patients with PLA had the highest incidence of colorectal cancer, followed by cancers of the biliary tract, pancreas, and small intestine.

Angiotensin-converting enzyme inhibitors and bacterial pneumonia in patients with Parkinson disease.

BACKGROUND: To evaluate the association of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with pneumonia development in patients with Parkinson's disease (PD). METHODS: The study cohort consisted of patients aged 50 years or older who were initially diagnosed with PD and had hypertension. We assessed the patients' exposure statuses and accumulated doses of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. We then evaluated the risk of pneumonia development in the patients who were exposed to these drugs and those who were not. RESULTS: We examined 2,310 patients. During the observation period, 608 patients developed pneumonia. Angiotensin-converting enzyme inhibitors were associated with a lower risk of pneumonia. This association was dose-dependent. CONCLUSION: Angiotensin-converting enzyme inhibitor use was associated with a dose-dependent reduction in the risk of pneumonia in patients with PD and hypertension.

Association between zolpidem use and glaucoma risk: a Taiwanese population-based case-control study.

BACKGROUND: To date, the relationship between zolpidem use and subsequent risk of glaucoma in a Taiwanese population has not been assessed. METHODS: We used data from the National Health Insurance system to investigate whether zolpidem use was related to glaucoma risk. A 1:4 matched case-control study was conducted. The cases were patients newly diagnosed with glaucoma from 2001 to 2010. The controls were randomly selected non-glaucoma subjects matched by sex and age (± 5 years). Zolpidem exposure and/or the average dosage of zolpidem used (mg/year) were evaluated. Medical comorbidities were considered as confounding factors. Multiple logistic regression models were used to evaluate the potential risk of zolpidem exposure on glaucoma with/without adjustment for the effects of confounding variables. RESULTS: The exposure rate of zolpidem use in the glaucoma group was significantly higher than that of the control group (2.8% vs. 2.0%, P < 0.0001). The adjusted odds ratio (OR) of the risk of glaucoma for those with zolpidem use vs. those without was 1.19 (95% confidence interval [CI], 1.02-1.38). Compared to non-zolpidem users, zolpidem users with an average dose of more than 200 mg/year had significantly increased risk of glaucoma (OR 1.31, 95% CI 1.03-1.68). CONCLUSIONS: This study suggests that the use of zolpidem might increase the risk of subsequent glaucoma. Further confirmatory studies are recommended to clarify this important issue.

The association between occupational characteristics and hysterectomies for treating uterine fibroids in Taiwan.

This study examined the relationship between the occupational characteristics of women with uterine fibroids (UFs) and the decision to have a hysterectomy. Data from the Longitudinal Taiwan Health Insurance Database (LTHID) from 2000 to 2009 were analyzed to investigate the association between occupation and hysterectomies. Multivariable logistic regression analysis showed that, compared with white-collar UF patients, the odds ratio (OR) for hysterectomy surgery was 1.21 (95% confidence interval (CI) = 1.11-1.32) for blue-collar UF patients. Moreover, non-government employees with UFs also had significantly increased odds of having a hysterectomy compared to government employees with UFs (OR = 1.19, 95% CI = 1.04-1.36). This study provides information regarding the extent to which differences in occupation and decision-making processes might affect the marked variations in the use of hysterectomies for UFs.

Injury Location and Mechanism for Complex Regional Pain Syndrome: A Nationwide Population-Based Case-Control Study in Taiwan.

BACKGROUND: Few studies have investigated the relationship between injury location, mechanism and their association with complex regional pain syndrome (CRPS). We conducted a nationwide database survey to explore this issue. METHODS: This was a population-based case-control study. Five hundred and eighty-nine patients with at least one ambulatory visit or admission with a principal diagnosis of CRPS from 2004 to 2009 were selected. For each CRPS patient, ten age- and sex-matched non-CRPS subjects were randomly selected. The odds ratios (PLoS One. 2013;8:e57205) and 95% confidence intervals (95% CIs) of risk factors for CRPS were derived from multivariate logistic regression models. RESULTS: Injury was a risk factor for CRPS (OR, 2.96; 95% CI, 2.18 to 4.02) independent of age and sex. In adjusted models, open wound on the upper limbs (OR 1.25, 95% CI 1.02 to 1.54) conferred higher CRPS risk. Injury mechanisms including nerve and spinal cord injury (OR 2.42, 95% CI 1.44 to 4.08), muscle and joint sprain and strain (OR 1.69, 95% CI 1.40 to 2.03), superficial injury (OR 1.23, 95% CI 1.00 to 1.51), and contusion (OR 1.44, 95% CI 1.20 to 1.74), but not fracture, increased the risk of CRPS. CONCLUSION: Injury in the extremities rather than the trunk is an important risk factor for CRPS. Certain injury mechanisms confer higher risk of CRPS. This nationwide study demonstrated that injury increased CRPS nearly threefold. Open wound, sprain and strain, superficial injury, contusion, and nerve and spinal cord injury are main injury mechanisms. Injury in the extremities confers a higher risk of CRPS.

Association between colonic diverticular disease and colorectal cancer: a nationwide population-based study.

BACKGROUND & AIMS: We investigated whether a diagnosis of colonic diverticular disease is associated with an increased risk for subsequent development of colorectal cancer (CRC) in a nationwide population-based retrospective study. METHODS: We identified 41,359 individuals diagnosed with colonic diverticular disease as inpatients from 2000 through 2009 from the Taiwan National Health Insurance Research Database (study cohort) and collected data for 165,436 randomly selected additional subjects, matched by sex, age, and baseline year (comparison cohort). Data were collected until individuals developed CRC or withdrew from the National Health Insurance system, or until December 31, 2010. Cumulative incidences and hazard ratios (HRs) of CRC development were determined. To assess for ascertainment bias, we conducted an analysis excluding the first 12 months of follow-up evaluation. RESULTS: The risk of CRC was significantly higher in the study cohort than in the comparison cohort (HR adjusted for age, sex, and comorbidities, 4.54; 95% confidence interval, 4.19-4.91; P < .0001). In a sensitivity analysis, we excluded the first 12 months of follow-up evaluation after a diagnosis of colonic diverticular disease; subsequent incidence rates for CRC in the study and comparison cohorts were 15.13 and 15.74 per 10,000 person-years, respectively (adjusted HR, 0.96; 95% confidence interval, 0.83-1.11). CONCLUSIONS: Colonic diverticular disease is not associated with an increased risk of subsequent CRC after the first year of diagnosis of colonic diverticular disease. An increased risk was observed in the first year, possibly owing to misclassification and screening effects.

Attention-deficit-hyperactivity disorder increases risk of bone fracture: a population-based cohort study.

AIM: Attention-deficit-hyperactivity disorder (ADHD) is a disorder that is associated with accidental injuries. The aim of this study was to evaluate the relationship between ADHD and bone fracture in children. METHOD: The study cohort comprised 3640 children (2874 males, 766 females; mean age 8y 5mo, SD 3y) with ADHD (International Classification of Diseases, Ninth Revision) who were matched to children without ADHD at a ratio of 1:4 (n=14 560; 11 496 males, 3064 females; mean age 8y 5mo, SD 3y). A Cox proportional hazard regression analysis was conducted to estimate how ADHD affected the risk of bone fracture. RESULTS: The incidence of fracture among the ADHD cohort was 197.67 per 10,000 person-years, and was 1.3-fold greater than in the comparison cohort (147.54 per 10,000 person-years). The risk in children with ADHD was higher than that in children without ADHD (p value for log-rank test < 0.001). After adjusting for potential confounding factors, the ADHD cohort was 1.32 times more likely to have bone fracture accidents than the comparison cohort (hazard ratio, 1.32; 95% confidence interval 1.17-1.49). INTERPRETATION: Children with ADHD have a higher risk of experiencing bone fracture accidents than do children without ADHD.