The effect of paternal psoriasis on neonatal outcomes: a nationwide population-based study.

Background: Psoriasis is a chronic autoimmune disease involving both environmental and genetic risk factors. Maternal psoriasis often results in poor pregnancies that influence both mothers and newborns. However, the influence of paternal psoriasis on the newborn remains unknown. The aim of this study was to investigate whether paternal psoriasis is associated with increased risk of adverse neonatal outcomes, within a nationwide population-based data setting. Methods: Singleton pregnancies were identified in the Taiwan National Health Insurance database and National Birth Registry between 2004-2011 and classified into four study groups according to whether mothers and spouses had psoriasis (paternal(-)/maternal(-), paternal(+)/maternal(-), paternal(-)/maternal(+), and paternal(+)/maternal(+)). Data were analyzed retrospectively. Adjusted odds ratios (aOR) or hazard ratios (aHR) were calculated to evaluate the risk of neonatal outcomes between groups. Results: A total of 1,498,892 singleton pregnancies were recruited. Newborns of fathers with psoriasis but not of mothers with psoriasis were associated with an aHR (95% CI) of 3.69 (1.65-8.26) for psoriasis, 1.13 (1.06-1.21) for atopic dermatitis and 1.05 (1.01-1.10) for allergic rhinitis. Newborns of mothers with psoriasis but not of fathers with psoriasis were associated with an aOR (95% CI) of 1.26 (1.12-1.43) for low birth weight (<2500 g) and 1.64 (1.10-2.43) for low Apgar scores, and an aHR of 5.70 (2.71-11.99) for psoriasis. Conclusion: Newborns of fathers with psoriasis are associated with significantly higher risk of developing atopic dermatitis, allergic rhinitis and psoriasis. Caution is advised for adverse neonatal outcomes when either or both parents have psoriasis.

Fetal-neonatal and maternal pregnancy outcomes in women with rheumatoid arthritis: a population-based cohort study.

OBJECTIVES: Rheumatoid arthritis (RA) may adversely influence pregnancy and lead to adverse birth outcomes. This study estimated the risk of adverse fetal-neonatal and maternal pregnancy outcomes in women with RA. DESIGN: This was a retrospective cohort study. SETTING: We used both the National Health Insurance database and the Taiwan Birth Reporting System, between 2004 and 2014. PARTICIPANTS: We identified 2 100 143 singleton pregnancies with 922 RA pregnancies, either live births or stillbirths, delivered by 1 468 318 women. OUTCOME MEASURES: ORs with 95% CIs for fetal-neonatal and maternal outcomes were compared between pregnancies involving mothers with and without RA using an adjusted generalised estimating equation model. RESULTS: Covariates including age, infant sex, Charlson Comorbidity Index, urbanisation, income, occupation, birth year and maternal nationality were adjusted. Compared with pregnancies in women without RA, pregnancies in women with RA showed that the fetuses/neonates had adjusted ORs (95% CI) of 2.03 (1.66 to 2.50) for low birth weight (n=123), 1.99 (1.64 to 2.40) for prematurity (n=141), 1.77 (1.46 to 2.15) for small for gestational age (n=144) and 1.35 (1.03 to 1.78) for fetal distress (n=60). Pregnancies in women with RA had adjusted ORs (95% CI) of 1.24 (1.00 to 1.52) for antepartum haemorrhage (n=106), 1.32 (1.15 to 1.51) for caesarean delivery (n=398), and 3.33 (1.07 to 10.34) for disseminated intravascular coagulation (n=3), compared with women without RA. Fetuses/neonates born to mothers with RA did not have a higher risk of being stillborn or having fetal abnormalities. Pregnant women with RA did not have increased risks of postpartum death, cardiovascular complications, surgical complications or systemic organ dysfunction. CONCLUSIONS: Pregnancies in women with RA were associated with higher risks of multiple adverse fetal-neonatal and maternal outcomes; however, most pregnancies in these women were successful.

Secular Trends in the Incidence, Prevalence, and Medications for Epilepsy from 2007 to 2015 in Taiwan: A Nationwide Population-Based Study.

BACKGROUND: Patients with epilepsy have a higher mortality rate than the general population. Up-to-date estimates of epilepsy incidence, prevalence, and medication use are critical to assist policymaking. METHODS: Using the National Taiwan Insurance Research Database, the standardized incidence and prevalence of epilepsy were estimated in each calendar year from 2007 to 2015. We used the incident cases of epilepsy to analyze the change in prescribing patterns from 2007 to 2015. Joinpoint regression was used to estimate secular trends. RESULTS: From 2007 to 2015, the age- and sex-standardized incidence decreased from 0.72 (95% confidence interval [CI] 0.70-0.73) to 0.54 (95% CI 0.53-0.55) per 1,000 person-years, giving an annual percentage change (APC) of -2.73 (p < 0.05). Among patients younger than 20 years, the incidence did not change significantly. The age- and sex-standardized prevalence decreased from 6.94 (95% CI 6.90-6.98) to 6.86 (95% CI, 6.82-6.89) per 1,000 people, giving an APC of -0.31 (p < 0.05). However, the prevalence increased in the 35- to 49- and 50- to 64-year age-groups. The most common first-line anticonvulsant was phenytoin in 2007 and valproate in 2015. The use of levetiracetam, clobazam, and valproate increased during the study period, with APCs of 25.48% (95% CI 19.97-31.24), 6.41 (3.09-9.85), and 2.83 (1.51-4.16), respectively. The use of carbamazepine, phenytoin, and topiramate decreased; the APCs were -23.86% (95% CI -25.25 to -22.44), -6.61 (-8.40 to -4.79), and -4.29% (-7.87 to -0.57), respectively. CONCLUSIONS: The overall prevalence and incidence of epilepsy decreased slightly from 2007 to 2015. The prescribed first-line anticonvulsant also changed over time.

The Temporal Relationships and Associations between Cutaneous Manifestations and Inflammatory Bowel Disease: A Nationwide Population-Based Cohort Study.

The temporal relationships between inflammatory bowel disease (IBD)-associated cutaneous manifestations and IBD remain uncertain, with existing evidence mostly from separate cross-sectional studies. We sought to determine the risks of IBD-related dermatologic diseases before and after the diagnosis of IBD. We identified 2847 cases of IBD and 14,235 matched controls from the Taiwan National Health Insurance Research Database between 2003 and 2014. The risks of cutaneous manifestations before and after the diagnosis of IBD were estimated with multivariable-adjusted analyses. At diagnosis, IBD was associated with atopic dermatitis (odds ratio (OR) = 1.61; 95% confidence interval (CI), 1.14-2.28), erythema nodosum (OR = 7.44; 95%CI, 3.75-14.77), aphthous stomatitis (OR = 2.01; 95%CI, 1.72-2.35), polyarteritis nodosa (OR = 5.67; 95%CI, 2.69-11.98), rosacea (OR = 1.67, 95%CI = 1.19-2.35), and cutaneous T cell lymphoma (OR = 21.27; 95%CI, 2.37-191.00). IBD was associated with the subsequent development of pyoderma gangrenosum (hazard ratio (HR) = 17.79; 95%CI, 6.35-49.86), erythema nodosum (HR = 6.54; 95%CI, 2.83-15.13), polyarteritis nodosa (HR = 2.69; 95%CI, 1.05-6.90), hidradenitis suppurativa (HR = 2.48; 95%CI, 1.03-5.97), psoriasis (HR = 2.19; 95%CI, 1.27-3.79), rosacea (HR = 1.92; 95%CI, 1.39-2.65), and aphthous stomatitis (HR = 1.45; 95%CI, 1.22-1.72). This study clarified the associations and temporal relationships between cutaneous manifestations and IBD, highlighting the need for interdisciplinary care in the patient with specific dermatologic diseases presenting with abdominal symptoms, or the IBD patients with cutaneous lesions.

Adverse pregnancy outcomes in women with Behçet's disease: population-based registry linkage study in Taiwan.

OBJECTIVES: To estimate the risks of adverse pregnancy outcomes in women with Behçet's disease (BD) METHODS: Data collected by the Taiwan National Health Insurance Administration between 2001 and 2012 was used for our study. A total of 2,350,339 pregnancies from the Taiwan National Health Insurance database and birth registry were identified. Maternal history of BD in women was ascertained. A comparison was made to determine whether BD increased the risk of health issues associated with pregnancy and fetal outcomes. Using an adjusted generalized estimating equation model, we estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for fetal-neonatal and maternal outcomes. RESULTS: There were 99 pregnancies in women with BD and 2,350,240 pregnancies in women without BD. The OR and 95% CI of puerperal cerebrovascular disorders were 12.08 (1.7-85.9), and those of gestational diabetes were 1.89 (1.1-3.25). Both were higher than the values in general pregnant women after adjusting for age, infant sex, urban residence, income, occupation, birth year, and Charlson Comorbidity Index. However, there were no adverse fetal outcomes in pregnant women with BD. CONCLUSIONS: Patients with BD have no significant risks of multiple complications except for puerperal cerebrovascular disease and gestational diabetes during pregnancy. Close monitoring of blood sugar is suggested. Furthermore, neonatal outcomes were not influenced by BD. Key Points • Patients with Behçet's disease are at a risk of puerperal cerebrovascular disease and gestational diabetes during pregnancy. • The odds ratio and 95% confidence interval for puerperal cerebrovascular disorders were 12.08 (1.7-85.9), and those for gestational diabetes were 1.89 (1.1-3.25). • Pregnant patients with Behçet's disease have no risks of neonatal outcomes.

A Machine Learning Model for Predicting Unscheduled 72 h Return Visits to the Emergency Department by Patients with Abdominal Pain.

Seventy-two-hour unscheduled return visits (URVs) by emergency department patients are a key clinical index for evaluating the quality of care in emergency departments (EDs). This study aimed to develop a machine learning model to predict 72 h URVs for ED patients with abdominal pain. Electronic health records data were collected from the Chang Gung Research Database (CGRD) for 25,151 ED visits by patients with abdominal pain and a total of 617 features were used for analysis. We used supervised machine learning models, namely logistic regression (LR), support vector machine (SVM), random forest (RF), extreme gradient boosting (XGB), and voting classifier (VC), to predict URVs. The VC model achieved more favorable overall performance than other models (AUROC: 0.74; 95% confidence interval (CI), 0.69-0.76; sensitivity, 0.39; specificity, 0.89; F1 score, 0.25). The reduced VC model achieved comparable performance (AUROC: 0.72; 95% CI, 0.69-0.74) to the full models using all clinical features. The VC model exhibited the most favorable performance in predicting 72 h URVs for patients with abdominal pain, both for all-features and reduced-features models. Application of the VC model in the clinical setting after validation may help physicians to make accurate decisions and decrease URVs.

Fetal-neonatal and maternal outcomes in women with psoriasis vulgaris: A nationwide population-based registry linkage study in Taiwan.

Interdisciplinary care involving dermatologists and obstetricians is important for pregnant women with psoriasis. However, well-controlled risk estimates and detailed outcome measurements for adverse pregnancy and fetal outcomes are rare and inconsistent. The aim of the present study was to investigate maternal and fetal outcomes of mothers with psoriasis by using a population-based nationwide health registrar database. We identified 2 350 330 singleton pregnancies, of which 4058 singleton pregnancies were psoriatic patients using the Taiwan National Health Insurance database and birth registry from 2001 to 2012. Odds ratios (OR) and 95% confidence intervals (CI) for pregnancy outcomes were calculated using an adjusted generalized estimating equation model. Pregnancies in psoriatic patients were associated with an adjusted OR (95% CI) of 1.57 (1.31-1.89) for pre-eclampsia, 1.5 (1.28-1.75) for pregnancy-related hypertension and 1.57 (1.36-1.82) for severe post-partum hemorrhage. Offspring of women with psoriasis were associated with an adjusted OR (95% CI) of 1.48 (1.11-1.96) for stillbirth, 1.27 (1.14-1.41) for low birthweight of less than 2500 g, 1.13 (1.02-1.25) for preterm labor, 1.12 (1.02-1.23) for small for gestational age and 1.09 (0.96-1.25) for fetal distress. Lower Apgar scores were also observed in babies born to mothers with psoriasis. In conclusion, pregnancies in women with psoriasis have a significantly higher risk of adverse pregnancy outcome compared with unaffected mothers.

Association of pregnancy outcomes in women with type 2 diabetes treated with metformin versus insulin when becoming pregnant.

BACKGROUND: Metformin use in pregnancy is controversial because metformin crosses the placenta and the safety on the fetus has not been well-established. This retrospective study aimed to compare pregnancy outcomes in women with preexisting type 2 diabetes receiving metformin or standard insulin treatment. METHODS: The cohort of this population-based study includes women of age 20-44 years with preexisting type 2 diabetes and singleton pregnancies in Taiwan between 2003 and 2014. Subjects were classified into three mutually exclusive groups according to glucose-lowering treatments received before and after becoming pregnant: insulin group, switching group (metformin to insulin), and metformin group. A generalized estimating equation model adjusted for patient age, duration of type 2 diabetes, hypertension, hyperlipidemia, retinopathy, and aspirin use was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of adverse pregnancy outcomes. RESULTS: A total of 1166 pregnancies were identified in the insulin group (n = 222), the switching group (n = 318) and the metformin group (n = 626). The insulin group and the switching group had similar pregnancy outcomes for both the mother and fetus, including risk of primary cesarean section, pregnancy-related hypertension, preeclampsia, preterm birth (< 37 weeks), very preterm birth (< 32 weeks), low birth weight (< 2500 g), high birth weight (> 4000 g), large for gestational age, and congenital malformations. The metformin group had a lower risk of primary cesarean section (aOR = 0.57; 95% CI, 0.40-0.82) and congenital malformations (aOR, 0.51; 95% CI; 0.27-0.94) and similar risk for the other outcomes as compared with the insulin group. CONCLUSIONS: Metformin therapy was not associated with increased adverse pregnancy outcomes in women with type 2 diabetes as compared with standard insulin therapy.

Impact of Metformin Use on Survival in Patients with Gastric Cancer and Diabetes Mellitus Following Gastrectomy.

Studies have shown the anticancer effects of metformin in vitro. However, whether metformin can prevent cancer recurrence or prolong survival in patients with gastric cancer (GC) and diabetes mellitus (DM) post-gastrectomy remains unknown. We evaluated the beneficial effects of metformin in patients with GC and DM post-gastrectomy. We recruited 2400 patients with GC (1749 without DM, 651 with DM) who underwent surgery between 1997 and 2010. Patients with DM were stratified into metformin (group 1) and non-metformin (group 2) users. Their clinicopathological data were recorded prospectively, and demographics, recurrence-free survival (RFS), and cancer-specific survival (CSS) were compared. Tumour recurrence risk and cause of death were analysed between groups 1 and 2 among patients with DM stratified by tumour stage. We also compared RFS and overall survival among patients with and without DM. Tumour recurrence occurred in 201 patients with GC: 57 (25%) in group 1 and 144 (37%) in group 2. After adjusting for confounders, metformin significantly prolonged CSS (hazard ratio (HR) = 0.54, 95% confidence interval (CI) = 0.38-0.77) in patients with stage I-III GC and DM. In subgroup analysis, metformin users with stage III GC and DM had significantly prolonged CSS compared to non-metformin users (HR = 0.45, 95% CI = 0.30-0.68), with an insignificant difference in patients with stage I-II GC. Adjusted HRs for RFS and CSS were significantly lower in patients with stage I-III GC and DM than those in patients without DM (0.67 (95% CI = 0.54-0.92) and 0.62 (95% CI = 0.50-0.77), respectively), with an insignificant difference in patients with stage I GC. Metformin significantly reduces tumour recurrence risk and improves CSS in patients with stage III GC and DM post-gastrectomy. Further prospective studies may confirm the efficacy of metformin as an adjunctive treatment for advanced GC postoperatively.

Adverse birth outcomes in adolescent and young adult female cancer survivors: a nationwide population-based study.

BACKGROUND: For female adolescent and young adult (AYA), cancer with treatments may affect their children's health. Our aim was to determine reliable risk estimates of adverse birth outcomes in AYA cancer survivors and the differential effects of treatments. METHODS: The study population of 4547 births in the AYA cancer survivor group and 45,463 in the comparison group were identified from two national databases between 2004 and 2014. Detailed maternal health conditions, such as maternal comorbidities, medication use during pregnancy and lifestyles, were adjusted in the statistical analyses. The outcomes included low birth weight, preterm labour, stillbirth, small or large for gestational age, a 5-min Apgar score <7, congenital malformation and foetal distress. RESULTS: The AYA cancer survivor group had a 9% higher risk of overall adverse birth outcomes (adjusted odds ratio, 1.09; 95% confidence interval, 1.02-1.16), especially low birth weight and preterm labour than the comparison group. The radiotherapy-only group additionally had a higher risk of foetal distress, and a 5-min Apgar score <7. CONCLUSION: AYA cancer survivors, especially those who have received radiotherapy, still have higher risks of adverse birth outcomes after adjusting for detailed maternal health conditions. Preconception counselling and additional surveillance may be warranted in this population.

Incidence and Time Course of Symptomatic Paroxysmal Supraventricular Tachycardia During Pregnancy: A Nation-Wide Database Study.

BACKGROUND: Paroxysmal supraventricular tachycardia (PSVT) is a common arrhythmia. However, its incidence and time course in pregnant women are unclear. This study was conducted to determine the incidence of PSVT in pregnant women by trimester. METHODS: From 2001 to 2012, all pregnant women in Taiwan were monitored for PSVT events. Women who visited the emergency department or were admitted for symptomatic PSVT were enrolled in this study, and those with congenital heart diseases were excluded. RESULTS: A total of 2,387,588 pregnancies (1,623,596 mothers) were analyzed. For the women with no previous history of a PSVT event, the incidence rates of symptomatic PSVT were 15, 33, and 60 per 100,000 pregnancies during the first, second, and third trimester, respectively. For the women with a previous history of PSVT, the incidence rates were 5625, 9525, and 11526 per 100,000 pregnancies, respectively. Most PSVT events occurred during the third trimester. CONCLUSIONS: In this Taiwanese cohort of pregnant women there was a stepwise increase in the incidence of symptomatic PSVT, which peaked during the third trimester. A past history of PSVT was associated with a higher risk of recurrence during pregnancy. We suggest that clinicians should be aware of this trend. Prompt management of PSVT events may prevent maternal and fetal complications.

Impact of urate-lowering drugs on the progression and recovery from chronic kidney disease among gout patients.

BACKGROUND: This study investigates the association between exposure to urate-lowering drugs (ULDs) and progression and recovery from chronic kidney disease (CKD). METHODS: We identified 5860 incident gout patients at Chang Gung Memorial Hospital from 2012 to 2015. Propensity score (PS)-weighted Cox proportional hazards model was used to estimate hazard ratios (HRs) for CKD progression and improvement. A separate analysis was conducted to assess the HR for CKD progression and CKD recovery among those with worsening CKD. RESULTS: The incidence of CKD progression among allopurinol, febuxostat and uricosuric agent users were 1.98, 1.88 and 1.64 per 1000 person-days. Compared with allopurinol users, the PS-weighted HR (95% confidence intervals [CIs]) was 1.77 (0.85-1.76) for febuxostat users and 1.37 (0.71-1.37) for uricosuric agent users for CKD progression and 1.43 (1.26-1.62) for febuxostat users and 1.00 (0.88-1.14) for uricosuric agent users for CKD improvement. Compared to allopurinol users, the HRs for CKD progression were 1.14 (0.80-1.66) for febuxostat users and 0.92 (0.67-1.31) for uricosuric agent users. Among 741 patients who had CKD progression, the incidence of CKD recovery was 1.33, 6.21 and 3.53 per 1000 person-days for allopurinol, febuxostat and uricosuric agent users. The HRs (95% CIs) for recovery in febuxostat and uricosuric agent users were 2.17 (1.40-3.47) and 1.80 (1.20-2.83) compared to allopurinol users. CONCLUSIONS: CKD progression and recovery are common in gout patients using ULDs. Febuxostat and benzbromarone were associated with a similar risk of CKD progression with allopurinol, which has a poorer recovery compared with other ULDs.

Determination of risk factors for burn mortality based on a regional population study in Taiwan.

BACKGROUND: Burns are not only major personal catastrophic events but also constitute a national health problem due to its associated morbidity, rehabilitation, mortality and high cost medical services. Advances in care and treatment have increased survival from major burn injury. However, information on the epidemiology and risk factors of burn mortality in Taiwan is limited. The study aim was to determine the nationwide epidemiological characteristics, trends, and mortality risk factors of burn inpatients in Taiwan. METHODS: This nationwide population-based study evaluated data retrieved from the Taiwan National Health Insurance database. Patients hospitalized for burns (ICD-9-CM codes 940-949) between 2003 and 2013 were identified from hospitalization records. RESULTS: A total of 73,774 patients were included. The data showed increases in age, revised Baux score, and Charlson Comorbidity Index during the study period, but it was also accompanied by a continuing decrease in burn incidence and a significant shortening of the length of hospital stay. The average in-hospital mortality was 17.5/1000 in 2003 and 12.2/1000 in 2013 but did not showed significant change. Male gender, older age, higher Charlson Comorbidity Index, presence of inhalation injury, large total burn surface area (TBSA), and higher revised Baux score were significant predictors of mortality. CONCLUSION: Population-based burn epidemiology data demonstrated ongoing improvement in hospital care during the past decade. Male gender, older age, higher Charlson Comorbidity Index, presence of inhalation injury, large TBSA, and higher revised Baux score were significant predictors of mortality.

Prostate-selective α antagonists increase fracture risk in prostate cancer patients with and without a history of androgen deprivation therapy: a nationwide population-based study.

INTRODUCTIONS: Prostate-selective α antagonists are recommended for relief of lower urinary tract symptoms in prostate cancer patients despite uncertainty of fracture risk as an addition to androgen deprivation therapy (ADT). The purpose of this study is to estimate fracture risk associated with these medications in prostate cancer patients who did and did not receive ADT. METHODS: The Taiwan National Health Insurance database was used to identify prostate cancer patients. We identified all 90-day person-quarters exposed to and not exposed to prostate-selective α antagonists. A generalized estimating equation model was used to estimated adjusted odd ratios (ORs) and 95% confidence intervals (CIs) for fracture associated with prostate-selective α antagonists with consideration for confounding by indication bias using propensity score. RESULTS: During 1997-2008, 16,601 persons received a diagnosis of prostate cancer, among whom 13,694 received ADT. Among prostate cancer patients receiving ADT, fracture was significantly more common in person-quarters with prostate-selective α antagonist use than in quarters without such treatment (OR, 1.08; 95% CI, 1.00-1.18). Prostate-selective α antagonist use was most strongly associated with femur fracture (OR, 1.22; 95% CI, 1.09-1.38), followed by skull fracture (OR, 1.29; 95% CIs: 0.93-1.80). Among patients who did not receive ADT, fracture was more common in person-quarters with prostate-selective α antagonist use than in those without medication use (OR, 1.19; 95% CI, 0.91-1.55). CONCLUSIONS: Prostate-selective α antagonist is associated with an increased fracture risk, particular for fractures in skull and femur. Patients should be well-informed on this potential risk before taking prostate-selective α antagonists.

Validity of cancer diagnosis in the National Health Insurance database compared with the linked National Cancer Registry in Taiwan.

PURPOSE: We aimed to evaluate the validity of cancer diagnosis in the National Health Insurance (NHI) database, which has routinely collected the health information of almost the entire Taiwanese population since 1995, compared with the Taiwan National Cancer Registry (NCR). METHODS: There were 26,542,445 active participants registered in the NHI database between 2001 and 2012. National Cancer Registry and NHI database records were compared for cancer diagnosis; date of cancer diagnosis; and 1, 2, and 5 year survival. In addition, the 10 leading causes of cancer deaths in Taiwan were analyzed. RESULTS: There were 908,986 cancer diagnoses in NCR and NHI database and 782,775 (86.1%) in both, with 53,192 (5.9%) in the NHI database only and 73,019 (8.0%) in the NCR only. The positive predictive value of the NHI database cancer diagnoses was 94% for all cancers; the positive predictive value of the 10 specific cancers ranged from 95% (lung cancer) to 82% (cervical cancer). The date of diagnosis in the NHI database was generally delayed by a median of 15 days (interquartile range 8-18) compared with the NCR. The 1, 2, and 5 year survival rates were 71.21%, 60.85%, and 47.44% using the NHI database and were 71.18%, 60.17%, and 46.09% using NCR data. CONCLUSIONS: Recording of cancer diagnoses and survival estimates based on these diagnosis codes in the NHI database are generally consistent with the NCR. Studies using NHI database data must pay careful attention to eligibility and record linkage; use of both sources is recommended.

Maternal and fetal outcomes of pregnant women with type 1 diabetes, a national population study.

Pregnancy in women with type 1 diabetes is associated with poor maternal and neonatal outcomes. However, the risk of these outcomes has never been evaluated in an Asian national population. In this work, we report the maternal and fetal outcomes of pregnant women with type 1 diabetes in Taiwan. A total of 2,350,339 pregnancy records created between 2001 and 2012 were obtained from the National Health Insurance database and analyzed. Here, 630 pregnancy records were identified in women having type 1 diabetes. Compared with pregnant women without type 1 diabetes, pregnant women with the disease showed increased risk of multiple adverse outcomes, including preeclampsia, eclampsia, cesarean delivery, adult respiratory distress syndrome, pulmonary edema, sepsis, chorioamnionitis, pregnancy-related hypertension, puerperal cerebrovascular disorders, acute renal failure, and shock. Fetuses of type 1 diabetic mothers were at increased risk of stillbirth, premature birth, large for gestational age, low birth weight, and low Apgar score. Of the studied endpoints, only preeclampsia showed an improvement in the late period (2011-2012) when compared with the early period (2001-2010). These findings reveal that pregnant women with type 1 diabetes are at significantly increased risk of developing many adverse maternal and fetal outcomes. Therefore, pregnancy outcomes in women with type 1 diabetes should be improved.

Imatinib dose escalation versus sunitinib as a second-line treatment against advanced gastrointestinal stromal tumors: A nationwide population-based cohort study.

BACKGROUND: Although treatment with imatinib in advanced gastrointestinal stromal tumor (GIST) patients has led to significant clinical benefits, the disease will eventually progress due to imatinib resistance. Treatment options after failure of first-line imatinib include imatinib dose escalation or shifting to sunitinib. However, there is no large-scale study to compare the efficacy difference between these two treatment strategies or the role of surgery. RESULTS: This study recruited 521 advanced GIST patients including 246, 125, and 150 placed in groups 1, 2, and 3, respectively. Groups 1 and 2 had significantly longer overall survival (OS) as compared with the group 3 (median 37.5 months versus 16.0 months; p < 0.0001). After adjusting for confounding variables, groups 1 and 2 had longer OS than group 3. A favorable survival trend was seen with surgery, although this benefit disappeared after adjusting for confounding factors. MATERIALS AND METHODS: We conducted a nationwide population-based cohort study using data from the Taiwan National Health Insurance Research Database from July 2004 to December 2010. Advanced GIST patients who no longer responded to first-line imatinib were stratified into three groups: imatinib dose escalation (group 1); imatinib dose escalation and a shift to sunitinib (group 2); a direct shift to sunitinib (group 3). The therapeutic success of the three treatment regimens and the effect of surgery were evaluated by overall survival. CONCLUSIONS: For advanced GIST patients who failed first-line imatinib treatment, imatinib dose escalation confers significantly longer OS compared to a direct switch to sunitinib. Surgery does not provide survival benefits.

Association Between Use of Non-Vitamin K Oral Anticoagulants With and Without Concurrent Medications and Risk of Major Bleeding in Nonvalvular Atrial Fibrillation.

Importance: Non-vitamin K oral anticoagulants (NOACs) are commonly prescribed with other medications that share metabolic pathways that may increase major bleeding risk. Objective: To assess the association between use of NOACs with and without concurrent medications and risk of major bleeding in patients with nonvalvular atrial fibrillation. Design, Setting, and Participants: Retrospective cohort study using data from the Taiwan National Health Insurance database and including 91 330 patients with nonvalvular atrial fibrillation who received at least 1 NOAC prescription of dabigatran, rivaroxaban, or apixaban from January 1, 2012, through December 31, 2016, with final follow-up on December 31, 2016. Exposures: NOAC with or without concurrent use of atorvastatin; digoxin; verapamil; diltiazem; amiodarone; fluconazole; ketoconazole, itraconazole, voriconazole, or posaconazole; cyclosporine; erythromycin or clarithromycin; dronedarone; rifampin; or phenytoin. Main Outcomes and Measures: Major bleeding, defined as hospitalization or emergency department visit with a primary diagnosis of intracranial hemorrhage or gastrointestinal, urogenital, or other bleeding. Adjusted incidence rate differences between person-quarters (exposure time for each person during each quarter of the calendar year) of NOAC with or without concurrent medications were estimated using Poisson regression and inverse probability of treatment weighting using the propensity score. Results: Among 91 330 patients with nonvalvular atrial fibrillation (mean age, 74.7 years [SD, 10.8]; men, 55.8%; NOAC exposure: dabigatran, 45 347 patients; rivaroxaban, 54 006 patients; and apixaban, 12 886 patients), 4770 major bleeding events occurred during 447 037 person-quarters with NOAC prescriptions. The most common medications co-prescribed with NOACs over all person-quarters were atorvastatin (27.6%), diltiazem (22.7%), digoxin (22.5%), and amiodarone (21.1%). Concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs had a significant increase in adjusted incidence rates per 1000 person-years of major bleeding than NOACs alone: 38.09 for NOAC use alone vs 52.04 for amiodarone (difference, 13.94 [99% CI, 9.76-18.13]); 102.77 for NOAC use alone vs 241.92 for fluconazole (difference, 138.46 [99% CI, 80.96-195.97]); 65.66 for NOAC use alone vs 103.14 for rifampin (difference, 36.90 [99% CI, 1.59-72.22); and 56.07 for NOAC use alone vs 108.52 for phenytoin (difference, 52.31 [99% CI, 32.18-72.44]; P < .01 for all comparisons). Compared with NOAC use alone, the adjusted incidence rate for major bleeding was significantly lower for concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin and was not significantly different for concurrent use of verapamil; diltiazem; cyclosporine; ketoconazole, itraconazole, voriconazole, or posaconazole; and dronedarone. Conclusions and Relevance: Among patients taking NOACs for nonvalvular atrial fibrillation, concurrent use of amiodarone, fluconazole, rifampin, and phenytoin compared with the use of NOACs alone, was associated with increased risk of major bleeding. Physicians prescribing NOAC medications should consider the potential risks associated with concomitant use of other drugs.

Trends in the incidence of primary malignant brain tumors in Taiwan and correlation with comorbidities: A population-based study.

OBJECTIVE: Primary malignant brain tumors are relatively uncommon, and their incidence and survival rates have seldom been reported. PATIENTS AND METHODS: We identified all patients with malignant brain tumors in Taiwan between 1997 and 2012 using the National Health Insurance database. We estimated the stratified incidence of malignant brain tumors by age and sex. We estimated the median 1-, 2-, and 5-year survival, taking comorbidities into account. Trends for incidence and survival were analyzed using Joinpoint regression. The incidence in different geographic areas was also evaluated. RESULTS: A total of 7746 men and 5846 women were identified. The incidence of malignant brain tumor was 3.34 (95% CI, 3.09-3.59) per 100,000 person-years in 1997 and 3.82 (95% CI, 3.56-4.08) per 100,000 person-years in 2012. The average annual percentage change (APC) of the standardized incidence over this period was 0.1 (95% CI, -1.9 to 2.2), suggesting a relatively stable incidence. However, the incidence significantly decreased between 1999 and 2012, with an APC of -1.8 [95% CI, -2.5 to -1.0]. One- and 5-year survival was 53.8% (50.0%-57.5%) and 27.5% (24.1%-30.9%) in 1997 and 67.6% (64.3%-70.7%) and 32.8% (29.6%-35.9%) in 2012. The average APC was 1.1 (95% CI, 0.7-1.5) for 1-year survival and 0.2 (95% CI, -1.0-1.4) for 5-year survival. The trend of improvement in the survival rate was seen for short-term but not long-term survival, especially in the group with more comorbidities. CONCLUSIONS: A slightly decreased trend in incidence of primary malignant brain tumors was observed in Taiwanese general population since 1999. Over the past 15 years, the short-term survival of malignant brain tumors has improved, especially in adults.