Associations of hyperglycemic emergency and severe hypoglycemia incidences with seasonality and ambient temperature among pregnant women with diabetes: a nested case-control study in Taiwan.

BACKGROUND: Associations of acute glycemic complications with season and ambient temperature have been reported in general population with diabetes. However, little is known about the risks of acute glycemic complications in relation to season and ambient temperature in pregnant women, who are likely to be even more vulnerable. This work aimed to investigate the associations of season and ambient temperature with pregnancies complicated with hyperglycemia emergency or severe hypoglycemia. METHODS: Two separate case-control studies were nested within 150,153 pregnancies by women with type 1, type 2, or gestational diabetes between 2009 and 2014 in Taiwan. Hyperglycemia emergency (mainly diabetic ketoacidosis and hyperosmolar hyperglycemic state) and severe hypoglycemia occurred in 77 and 153 diabetic pregnancies (cases), respectively. Ten control pregnancies were randomly selected for each case by matching each case pregnancy on type of diabetes (i.e., T1DM, T2DM, or GDM), maternal age on the date of acute glycemic complication occurrence (i.e., index date), and "length of gestation at risk" (i.e., period between conception and index date). Meteorological parameters were retrieved from 542 meteorological monitoring stations across Taiwan during 2008-2014. Conditional logistic regression analysis with generalized estimation equation was separately performed to estimate the covariate adjusted odds ratios (ORs) of each of the two acute glycemic complications in association with season and ambient temperature within 30 days prior to the index date. RESULTS: Compared to summer, winter season was associated with a significantly elevated risk of severe hypoglycemia with an OR of 1.74 (95% confidence interval (CI) 1.08-2.79). The OR of hyperglycemic emergency was also elevated in winter season at OR of 1.88, but the significance is only marginal (95% CI 0.97-3.64, p = 0.0598). Subgroup analyses further noted that such seasonal variation was also observed in pregnancies with pre-pregnancy type 1 diabetes and gestational diabetes. On the other hand, ambient temperature was not significantly associated with the two acute glycemic complications. CONCLUSIONS: A moderately but significantly elevated risk of severe hypoglycemia was found in pregnant women with diabetes during winter season, and such increased risk was more evident in pregnancies with T1DM.

AMACR overexpression acts as a negative prognostic factor in oral squamous cell carcinoma.

Background: Alpha-methylacyl-CoA racemase (AMACR) is a key enzyme responsible for the metabolism of branched-chain fatty acids. It has been found to be an important prognostic factor in numerous types of cancers. This study was aimed to investigate the expression of AMACR and its prognostic significance in patients with oral squamous cell carcinoma (SCC). Methods: Analysis of publicly available microarray data of oral SCC revealed that AMACR was significantly upregulated in tumor tissue compared with normal mucosa. We further assessed the protein expression of AMACR in 164 patients with oral SCC by immunohistochemistry. The prognostic impact of AMACR expression and its association with various clinicopathological parameters were statistically analyzed. Results: AMACR overexpression was significantly associated with advanced tumor status (P=0.001), advanced nodal status (P=0.036), increased vascular invasion (P=0.026) and increased perineural invasion (P=0.004). Patients with high expression level of AMACR had significantly worse disease-specific survival (DSS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS) (all P<0.0001). In multivariate analysis, AMACR overexpression was also an independent negative prognostic factor for DSS (hazard ratio [HR]: 4.410, 95% confidence interval [CI]: 2.285-8.511, P<0.001), DMFS (HR: 5.157, 95% CI: 2.756-9.651, P<0.001) and LRFS (HR: 4.462, 95% CI: 2.429-8.198, P<0.001). Conclusions: High expression of AMACR was not only a key adverse prognostic factor but also a potential therapeutic target in oral SCC.

Mobile phone use and health symptoms in children.

BACKGROUND/PURPOSE: To investigate the mobile phone (MP) use for talking in relation to health symptoms among 2042 children aged 11-15 years in Taiwan. METHODS: A nationwide, cross-sectional study, using the computer assisted telephone interview (CATI) technique, was conducted in 2009 to collect information on children's utilization of MPs and the perceived health symptoms reported by their parents. RESULTS: The overall prevalence of MP use in the past month was estimated at 63.2% [95% confidence interval (CI) = 61.1-65.3%]. MP use was associated with a significantly increased adjusted odds ratio (AOR) for headaches and migraine (1.42, 95% CI = 1.12-1.81) and skin itches (1.84, 95% CI = 1.47-2.29). Children who regularly used MPs were also considered to have a health status worse than it was 1 year ago (ß = 0.27, 95% CI = 0.17-0.37). CONCLUSION: Although the cross-sectional design precludes the causal inference for the observed association, our study tended to suggest a need for more cautious use of MPs in children, because children are expected to experience a longer lifetime exposure to radiofrequency electromagnetic fields (RF-EMF) from MPs.

Profiles of pregnant women encountering motor vehicle crashes in Taiwan, 2008-2017.

BACKGROUND: Understanding demographic profiles is essential to the assessment of health burden imposed by motor vehicle crashes (MVCs) on pregnant women. However, Asian studies that have examined it are lacking. The study aimed to describe the demographic characteristics and prevalence of MVCs involving pregnant women in Taiwan. METHODS: A cross-sectional study conducted by the Taiwan Birth Notification dataset from 2008 to 2017 was linked with the police-reported traffic collision registry to identify pregnant women involved in MVCs. The pregnant women were categorized according to their gestational age, age at delivery, the role of road user (driver, passenger, or pedestrian), and vehicle types (car, two-wheeled motor vehicle, or others). A chi-square test was performed for the significance test. RESULTS: A total of 22,134 (1.13%) pregnant women were involved in MVCs in the study period. Two-wheeled motor vehicle (47.9%) and driver (81.4%) were the mainly reported vehicle type and road user at the crash scenes, respectively. The majority of MVCs occurred in pregnant women aged 28-34 years. The number of MVCs rapidly declined after 37 weeks of gestation, especially two-wheeled motor vehicle or car crashes. However, the number of pedestrian victims climbed up during the third trimester. CONCLUSION: Pregnant women are susceptible to MVCs regardless of their gestational age, role of a road user, or type of vehicle. The findings of this study emphasize the need for increased awareness of traffic collision prevention among pregnant women aged 28-34. In addition, improving pedestrian safety is essential for the reduction of pregnant victims.

Candida invasion and influences in smoking patients with multiple oral leucoplakias--a retrospective study.

Treating patients with multiple oral leucoplakias (MOLs) who smoke is more difficult and complicated than treating those with single oral leucoplakia (SOL). Removing the aetiological factors causing MOL can effectively prevent its recurrence. The aim was to study the infection by and influences of Candida in smoking patients with MOLs. A retrospective study was conducted on 136 smoking patients who had clinicopathological OLs. Among these patients, 73 lesions in 31 patients were MOLs, while 105 patients had SOLs. All patients were treated by complete resection. All specimens were tested for epithelial dysplasia, and stained with periodic acid-Schiff reagent. The rate of MOL concurrence with candidal infection was higher than that of SOLs. The incidence of Candida associated with MOLs was higher for recurrent than for non-recurrent lesions. The disease-free time was shorter in MOL patients with candidal infection. Moreover, MOLs with candidal infection were more likely to have an increasing ratio to combine with epithelial dysplasia. Candida is an important risk factor in smoking patients with MOLs. Microscopic and fungal examinations of those lesions should permit a detailed diagnosis in such patients and for long-term predictive assessments.

Population-Based Study on the All-Cause and Cause-Specific Risks of Mortality among Long-Term Opioid Analgesics Users without Cancer in Taiwan.

(1) Background: The prevalence of opioid use in Taiwan increased by 41% between 2002 and 2014. However, little is known regarding the risk of mortality among long-term opioid analgesics users who do not have cancer. This study investigated this mortality risk with an emphasis on the calendar year and patients' age and sex. (2) Methods: This retrospective cohort study included 12,990 adult individuals without cancer who were long-term users of opioid analgesics and were randomly selected from the data set of Taiwan's National Health Insurance program from 2000 to 2012. They were then followed up through 2013. Information on the underlying causes of death was retrieved from the Taiwan Death Registry. Age, sex, and calendar year-standardized mortality ratios (SMRs) of all-cause and cause-specific mortality were calculated with reference to those of the general population. (3) Results: With up to 14 years of follow-up, 558 individuals had all-cause mortality in 48,020 person-years (cumulative mortality: 4.3%, mortality rate: 11.62 per 1000 person-years). Compared with the general population, the all-cause SMR of 4.30 (95% confidence interval (95% CI): 3.95-4.66) was significantly higher: it was higher in men than in women, declined with calendar year and age, and was significantly higher for both natural (4.15, 95% CI: 3.78-4.53) and unnatural (5.04, 95% CI: 3.88-6.45) causes. (4) Conclusions: Long-term opioid analgesics use among individuals without cancer in Taiwan was associated with a significantly increased risk of mortality. The notably increased mortality in younger adults warrants attention. Strategies to reduce long-term opioid analgesics use, especially their overuse or misuse, are in an urgent need.

Resolution of oral bisphosphonate and steroid-related osteonecrosis of the jaw--a serial case analysis.

PURPOSE: To offer recommendations of risk factors, prevention, and treatment of oral bisphosphonate and steroid-related osteonecrosis of the jaw (BSRONJ) in Taiwan. MATERIALS AND METHODS: Twelve patients were clinicopathologically proved to have bisphosphonate-related osteonecrosis of the jaw (BRONJ). All of the patients were taking oral bisphosphonates and were concurrently administered long-term steroids. Of the 12 patients, 3 patients were assigned to the first stage of BRONJ; 5 patients were assigned to the second stage, and 4 patients were assigned to the third stage. The patients' symptoms, localization of necrosis, presence of a fistula, and association with possible triggering factors for onset of the lesion were recorded. RESULTS: The radiologic investigations revealed osteolytic areas and scintigraphy demonstrated increased bone metabolism. Microbiologic analysis showed pathogenic actinomycosis organisms in a majority of patients (91.6%). Antibiotic therapy, minor debridement surgery, and combined hyperbaric oxygen therapy were useful in obtaining short-term symptomatic relief. CONCLUSIONS: Comorbidities of steroid use along with bisphosphonates may cause osteonecrosis of the jaw to occur sooner, be more severe, and respond more slowly to a drug discontinuation. The clinical disease of BSRONJ is more severe and more unpredictable to treat than BRONJ. From the data gained from other published studies of BRONJ and our clinical experience with the series of cases of BSRONJ, we offer recommendations of risk factors, prevention, and treatment of BSRONJ in southern Taiwan.

Mechanistic and compositional studies of the autophagy-inducing areca nut ingredient.

BACKGROUND/PURPOSE: We previously found that the partially purified 30-100 kDa fraction of areca-nut-extract (ANE 30-100K) induces autophagy in different types of cells including oral carcinoma OECM-1 cells. This study was to analyze the composition and possible mechanisms of ANE 30-100K-induced autophagy (AIA). MATERIALS AND METHODS: Phenol-sulfuric acid method and high performance anion exchange chromatography were utilized to analyze the composition of ANE 30-100K. OECM-1 and esophageal CE81T/VGH cells were taken as the experimental models. Microscope and transmission electron microscope were used to observe morphological changes. Cell viability and specific proteins were respectively measured by XTT and Western bot assay. shRNA and chemical inhibitors were applied to assess the involvement of Atg5, caveolin, and proteasome in AIA. RESULTS: ANE 30-100K contains ∼67% carbohydrate, which is composed of fucose (5.938%), arabinose (24.631%), glucosamine (8.066%), galactose (26.820%), glucose (21.388%), and mannose (13.157%). After ANE 30-100K stimulation, CE81T/VGH cells showed intracellular vacuoles, acidic vesicles, double-membrane vacuoles, and elevated LC3-II level. ANE 30-100K-induced cytotoxicity and LC3-II accumulation were significantly inhibited by Atg5 knockdown. Furthermore, the endocytosis inhibitor (methyl-ß-cyclodextrin) and two caveolin shRNAs, as well as two proteasome inhibitors (lactacystin and epoxomicin), were shown to significantly attenuate ANE 30-100K-induced cytotoxicity and LC3-II accumulation in both OECM-1 and CE81T/VGH cells. CONCLUSION: The major components of ANE 30-100K are carbohydrates. CE81T/VGH also exhibited autophagic responses to ANE 30-100K. Caveolin-mediated endocytosis and proteasome are involved in AIA. This study may have provided new knowledges of the action mechanisms and compositions of ANE 30-100K.

Chronic Stimulation of the Autophagy-inducing Ingredient of Areca Nut Promotes Tumor Growth In Vivo Through Up-regulation of Tumoral Autophagy.

BACKGROUND/AIM: Autophagy can be either tumor promotive or suppressive. We previously identified an autophagy-inducing activity in the 30-100 kDa fraction of areca-nut-extract (ANE 30-100K) and showed that several tumor cells subjected to chronic ANE 30-100K stimulation (CAS) exhibited higher resistance against stressed environments including serum-free (SF) conditions in vitro. Herein, we aimed to assess whether CAS can also provide growth advantages for tumor cells in vivo and the therapeutic effect of autophagy inhibition on CAS-treated tumors. MATERIALS AND METHODS: Esophageal CE81T/VGH cells and nude mice were used as experimental models. Autophagy inhibitors 3-methyladenine (3-MA) and chloroquine (CQ), as well as another anticancer drug cisplatin (DDP), were chosen to challenge CAS-treated CE81T/VGH cells in vitro and in vivo. RESULTS: CAS-treated CE81T/VGH cells expressed higher levels of microtubule-associated protein 1 light chain 3A/B-II (LC3-II) and beclin 1 proteins, and showed stronger resistance to SF and hypoxia conditions, that were mitigated by CQ or 3-MA in vitro. Furthermore, CAS-treated CE81T/VGH cells induced significantly larger tumors in mice, which were also attenuated by single 3-MA or CQ treatment. Finally, the combined treatment of 3-MA or CQ with DDP further up-regulated DDP-induced caspase-3 activity in vitro and exhibited synergistic anti-tumor effects on mice. CONCLUSION: CAS may up-regulate tumoral autophagy and provide growth advantage for tumors both in vitro and in vivo. Furthermore, autophagy inhibition alone or in combination with DDP may achieve positive therapy for tumors encountered with CAS.

A cohort study of age and sex specific risk of pyogenic liver abscess incidence in patients with type 2 diabetes mellitus.

To investigate the age-sex-specific incidence and relative risk of pyogenic liver abscess (PLA) in patients with type 2 diabetes mellitus (T2DM), and to assess the joint effects of T2DM and other clinical risk factors for PLA on PLA incidence. We used a population-based cohort design with Taiwan's National Health Insurance claim data. Study subjects included 613,921 T2DM patients and 614,613 controls identified in 2000 and were followed to the end of 2010. Cox regression model was employed to calculate the hazard ratio (HR) and 95% confidence interval (CI) of PLA in relation to T2DM. Over an 11-year follow-up, 5336 T2DM and 1850 controls were admitted for PLA, representing a cumulative incidence of 0.87% and 0.30%, respectively. T2DM was significantly associated with increased hazard of PLA (HR, 2.88; 95% CI, 2.73-3.04). We also found that age and gender may significantly modify the relationship between T2DM and PLA, with a higher HR noted in males patients and those aged <45 years. Biliary tract diseases (HR, 8.60; 95% CI, 7.87-9.40) and liver cirrhosis (HR, 7.52; 95% CI, 6.58-8.59) may add substantially additional risk to the incidence of PLA in T2DM patients. The increased risk of PLA in T2DM was greater in male and younger patients. Careful management of biliary tract diseases and liver cirrhosis may also help reduce the incidence of PLA in T2DM patients.

Upregulation of matrix metalloproteinase-1 (MMP-1) expression in oral carcinomas of betel quid (BQ) users: roles of BQ ingredients in the acceleration of tumour cell motility through MMP-1.

Matrix metalloproteinases (MMPs) are commonly expressed in carcinomas including oral squamous cell carcinomas (OSCCs). On the other hand, some evidences suggested that ingredients of betel quid (BQ) inhibit the activity and/or expression of some MMPs thought to be the pathogenesis of oral submucous fibrosis. This study was to analyse whether MMP-1 expression is inhibited in OSCC specimens from BQ users and in cell lines survived from the challenge of BQ ingredients. We found that MMP-1 mRNA was expressed in all the tested 27 OSCC. Levels of MMP-1 mRNA and protein were significantly elevated in the tested five OSCC specimens than in their adjacent tissues (P<0.001 and 0.05, respectively). Esophageal carcinoma (CE81T/VGH) and OSCC (OECM-1) cell lines survived from the cytotoxic BQ extract (BQE) and arecoline selection process were found to express higher MMP-1 mRNA and protein levels, or to exhibit a significant acceleration of two-dimensional (2D) motility than their non-selected parental cells. The enhanced motility was further demonstrated to be specifically and significantly inhibited by the MMP-1 neutralizing antibody and/or by the transfection of an MMP-1 specific antisense oligodeoxynucleotide. These results suggest that in some carcinomas of the upper aerodigestive tract, BQ usage may upregulate MMP-1 expression in the survived tumour cells, and increase their mobility in an MMP-1-dependent manner.

Maternal Exposure to Air Pollutants and Risk of Gestational Diabetes Mellitus in Taiwan.

Mounting evidence has shown an increased risk of gestational diabetes mellitus (GDM) in association with elevated exposure to air pollution. However, limited evidence is available concerning the effect of specific air pollutant(s) on GDM incidence. We conducted this case-control study on 6717 mothers with GDM diagnosed in 2006-2013 and 6717 age- and year of delivery-matched controls to further address the risk of GDM in relation to specific air pollutant. Both cases and controls were selected from a cohort of 1-million beneficiaries of Taiwan's National Health Insurance program registered in 2005. Maternal exposures to mean daily air pollutant concentration, derived from 76 fixed air quality monitoring stations within the 12-week period prior to pregnancy and during the 1st and 2nd trimesters, were assessed by the spatial analyst method (i.e., ordinary kriging) with the ArcGIS software. After controlling for potential confounders and other air pollutants, an increase in pre-pregnancy exposure of 1 inter-quartile range (IQR) for PM2.5 and SO2 was found to associate with a significantly elevated odds ratio (OR) of GDM at 1.10 (95% confidence interval (CI) 1.03-1.18 and 1.37 (95% CI 1.30-1.45), respectively. Exposures to PM2.5 and SO2 during the 1st and 2nd trimesters were also associated with significantly increased ORs, which were 1.09 (95% CI 1.02-1.17) and 1.07 (95% CI 1.01-1.14) for PM2.5, and 1.37 (95% CI 1.30-1.45) and 1.38 (95% CI 1.31-1.46) for SO2. It was concluded that higher pre- and post-pregnancy exposures to PM2.5 and SO2 for mothers were associated with a significantly but modestly elevated risk of GDM.

Medical claims-based case-control study of temporal relationship between clinical visits for hand syndromes and subsequent diabetes diagnosis: implications for identifying patients with undiagnosed type 2 diabetes mellitus.

OBJECTIVES: To investigate whether a temporal relationship is present between clinical visits for diabetes-related hand syndromes (DHSs) and subsequent type 2 diabetes mellitus (T2DM) diagnosis and, accordingly, whether DHSs can be used for identifying patients with undiagnosed T2DM. DESIGN: This study had a case-control design nested within a cohort of 1 million people from the general population, which was followed from 2005 to 2010. The odds of prior clinical visits for DHSs, namely carpal tunnel syndrome (CTS), flexor tenosynovitis, limited joint mobility and Dupuytren's disease, were estimated for cases and controls. We used a conditional logistic regression model to estimate the OR and 95% CI of T2DM in association with a history of DHSs. The validity and predictive value of using the history of DHSs in predicting T2DM diagnosis were calculated. SETTING: Taiwan National Health Insurance medical claims. PARTICIPANTS: We identified 33 571 patients receiving a new diagnosis of T2DM (cases) between 2005 and 2010. Each T2DM case was matched with 5 controls who had the same sex and birth year and were alive on the date of T2DM diagnosis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure was T2DM diagnosis. RESULTS: The OR of T2DM in association with prior clinical visits was significantly increased for overall DHS and CTS, being 1.15 (95% CI 1.10 to 1.20) and 1.22 (95% CI 1.16 to 1.29), respectively. Moreover, 11% of patients with T2DM made clinical visits for CTS within 3 months prior to T2DM diagnosis. The history of DHSs had low sensitivity (<0.1% to 5.2%) and a positive predictive value (9.9% to 11.7%) in predicting T2DM. CONCLUSIONS: Despite the unsatisfactory validity and performance of DHSs as a clinical tool for detecting patients with undiagnosed T2DM, this study provided evidence that clinical visits for DHSs, particularly for CTS, can be a sign of undiagnosed T2DM.

Outpatient visits by dentists: a nationwide cohort study in Taiwan.

We conducted a cohort study of 7,760 dentists in Taiwan between 2003 and 2007 to assess the risk of outpatient visit among dentists. Control groups included physicians and other health personnel. Over the 5-yr study period, the dentist cohort made a total of 270,712 outpatient visits, representing an incidence rate of 7,038 visits /10(3) person-years. Compared to physicians, dentists experienced a significantly reduced covariate adjusted rate ratio (ARR) for all-cause visits (ARR=0.59, 95%CI=0.58-0.59), as well as for nearly all other causes, except neoplasm (ARR=1.06, 95%CI=1.02-1.09). Compared to other health personnel, the dentists still experienced a significantly reduced ARR for all causes (ARR=0.70), but had a slightly but significantly increased risk for endocrine/metabolic/immunity (ARR=1.04, 95%CI=1.02-1.05) and mental (ARR=1.04, 95%CI=1.01-1.07) disorders. Although the dentists in Taiwan utilized lesser outpatient visits than did their medical colleagues, they tended to have slightly higher rates of outpatient visits for neoplasm, endocrine/metabolic/immunity disorders, and mental illnesses. Policy makers and hospital administrators must not overlook dentists' potentially unseen health problems. A mandatory periodical physical examination for dentists can seriously be considered.

Treatment effects of maxillary flat occlusal splints for painful clicking of the temporomandibular joint.

Existing therapies for symptoms related to painful clicking of the temporomandibular joint (TMJ) have rarely met with complete success and predicting prognosis remains difficult. Few studies have reported the efficacy of maxillary flat occlusal splints (MFOSs) for the treatment of painful clicking of the TMJ, and few studies have evaluated the predisposing factors that influence the clinical outcomes of MFOSs. The aim of this study was to investigate the treatment efficacy of MFOSs for painful clicking of the TMJ, and to determine the factors influencing TMJ therapy with MFOSs. We conducted a retrospective study of 109 patients suffering from unilateral clicking concurrent with preauricular area pain for at least 2 months between 2004 and 2008. Seventy-five patients were treated with an MFOS, while 34 patients did not receive MFOS therapy. Clicking score, pain-free maximal mouth opening, pain score, duration of the clicking sounds, age and bruxism were recorded during treatment and involved into the reviews. The degree of joint clicking was determined by a stethoscope placed in the anterolateral area of the external auditory canal and was divided into four grades. Data were analyzed using a Mann-Whitney U test, Fisher's exact test, and Student's t test. Results showed statistically significant differences in treatment outcomes between the MFOS-treated and control groups in clicking index, maximal mouth opening, pain and complete remission rates of symptoms within 1 year. Furthermore, for patients treated with MFOS, there were statistically significant differences in the clinical outcomes between those with a high clicking index and those with a low index before treatment. Factors significantly correlated with successful outcomes of MFOS included nocturnal bruxism, patient age and duration of clicking. MFOSs can be used to treat patients with painful clicking of the TMJ and related symptoms. The severity of clicking, bruxism, age and duration of clicking are all important factors influencing treatment outcomes with MFOSs.