Predicting adverse drug effects: A heterogeneous graph convolution network with a multi-layer perceptron approach.

We apply a heterogeneous graph convolution network (GCN) combined with a multi-layer perceptron (MLP) denoted by GCNMLP to explore the potential side effects of drugs. Here the SIDER, OFFSIDERS, and FAERS are used as the datasets. We integrate the drug information with similar characteristics from the datasets of known drugs and side effect networks. The heterogeneous graph networks explore the potential side effects of drugs by inferring the relationship between similar drugs and related side effects. This novel in silico method will shorten the time spent in uncovering the unseen side effects within routine drug prescriptions while highlighting the relevance of exploring drug mechanisms from well-documented drugs. In our experiments, we inquire about the drugs Vancomycin, Amlodipine, Cisplatin, and Glimepiride from a trained model, where the parameters are acquired from the dataset SIDER after training. Our results show that the performance of the GCNMLP on these three datasets is superior to the non-negative matrix factorization method (NMF) and some well-known machine learning methods with respect to various evaluation scales. Moreover, new side effects of drugs can be obtained using the GCNMLP.

Pre-existing Symptoms and Healthcare Utilization Prior to Diagnosis of Neuroendocrine Tumors: A SEER-Medicare Database Study.

The incidence and prevalence of neuroendocrine tumors (NETs) are continually increasing. While it is known that NET symptoms often predate diagnosis, their prevalence and impact on resource utilization and costs are largely unknown. We identified 9,319 elderly patients diagnosed with NETs between 1/2003 and 12/2011 from the Surveillance, Epidemiology and End Results (SEER)-Medicare. We examined the patients' conditions potentially associated with NET, resource utilization and costs during the year before diagnosis. We found that NET patients were more likely to have diagnoses of hypertension (63.8% vs. 53.3%), abdominal pain (22.2% vs. 7.6%), heart failure (11.7% vs. 8.0%), diarrhea (5.8% vs. 1.8%), peripheral edema (5.4% vs. 3.8%) and irritable bowel syndrome (1.2% vs. 0.5%) compared to the non-cancer control group. They also had much higher resource utilization including number of outpatient visits (mean: 22.1 vs. 17.2), percentage with ER visits (20.9% vs. 11.6%), and hospitalizations (28.4% vs. 17.0%). Similarly, NET patients incurred significantly higher total (mean: $14602 vs. $9464), outpatient (mean: $5987 vs. $4253), and inpatient costs (mean: $8615 vs. $5211). This first population-based study on the pre-diagnosis symptoms and healthcare utilization found that NET patients were more likely to have certain conditions and incur higher resource utilizations and costs.

Clinical, pathological, and demographic factors associated with development of recurrences after surgical resection in elderly patients with neuroendocrine tumors.

BACKGROUND: Incidence of locoregional neuroendocrine tumors (NETs) is rising. However, after curative resection, the patterns and risk factors associated with recurrence remain unknown. Consensus guidelines recommend surveillance every 6-12 months for up to 10 years after surgery for resected, well-differentiated NETs irrespective of patient demographics, site, grade or stage of tumor with few exceptions. PATIENTS AND METHODS: From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified localized and regional stage NET patients who underwent surgical resection between January 2002 and December 2011. Development of recurrence was identified by capturing at least two claims indicative of metastatic disease until 31 December 2013. RESULTS: Of the 2366 identified patients (median age 73 years), 369 (16%) developed metastatic disease within 5 years and only an additional 1% developed metastases between years 5 and 10 with the majority dying due to unrelated causes. The 5-year risk of developing metastases (hazard ratio, HR) varied significantly (log-rank P < 0.001) by grade: 9.9% versus 25.9% (2.2) versus 48.1% (4.4) for grades 1, 2, and ≥ 3, respectively; stage: 10.3% versus 31.1% (2.8) for localized versus regional; primary tumor size: 7.6% versus 15% (1.3) versus 26.6% (1.5) for <1, 1-2, and > 2 cm, respectively; and site: ranging from 11.3% for colon to 23.9% for pancreas. CONCLUSIONS: Contrary to current guidelines, our study suggests that surveillance recommendations should be tailored according to patient and tumor characteristics. Surveillance past 5 years may be avoided in elderly patients with competing morbidities or low risk of recurrence. Pancreatic, lung, higher grade, and regional NETs have a higher risk of recurrence and may be considered for future adjuvant trials.

Comparison of two generalized transfer functions for measuring central systolic blood pressure by an oscillometric blood pressure monitor.

Central aortic systolic blood pressure (SBP-C) can be estimated from a cuff oscillometric waveform derived during the pulse volume plethysmography (PVP) by applying a device-specific aortic pressure-to-PVP waveform-generalized transfer function (A2P(GTF)). The present study compared the performance of an aortic-to-brachial pressure waveforms generalized transfer function (A2B(GTF)), which is independent of any PVP devices, with an A2P(GTF). Generalized transfer function of aortic-to-brachial (A2B(GTF)) and aortic-to-PVP (A2P(GTF)) were generated from the simultaneously obtained central aortic and brachial pressure waveforms recorded by a high-fidelity dual pressure sensor catheter, and the PVP waveform recorded by a customized noninvasive blood pressure monitor during cardiac catheterization in 40 patients, and were then applied in another 100 patients with simultaneously recorded invasive aortic pressure and noninvasively calibrated (using cuff SBP and diastolic blood pressures) PVP waveforms. The mean difference±s.d. between the noninvasively estimated and invasively recorded SBP-C was -2.1±7.7 mm Hg for A2B(GTF), which was not greater than that of -3.0±7.7 mm Hg for A2P(GTF) (P<0.01). In conclusion, SBP-C can be measured reliably using a noninvasive blood pressure monitor by applying either an A2P(GTF) or A2B(GTF) to a noninvasively calibrated PVP waveform. The performance of an A2B(GTF) is not inferior to that of an A2P(GTF).

Cigarette smoking and proteinuria in Taiwanese men with Type 2 diabetes mellitus.

AIMS: Cigarette smoking is a well-known risk factor associated with diabetic nephropathy. The objective of this study was to further investigate the dose-response effect of tobacco exposure on proteinuria in males with Type 2 diabetes. METHODS: Five hundred and nine males with Type 2 diabetes were selected from a cohort participating in a glucose control study in Taiwan. Pack-years of cigarette smoking were calculated to define tobacco exposure. Proteinuria was identified if albumin-to-creatinine ratio was > or = 30 mg/g in at least two of three consecutive urine tests. Logistic regression and trend tests were used to delineate the association between smoking status and proteinuria. RESULTS: Compared with non-smokers, those who had smoked 15-30 or more than 30 pack-years were respectively 2.78 (95% CI 1.34-5.76, P < 0.01) and 3.20 (95% CI 1.74-5.86, P < 0.001) times more likely to develop proteinuria. The dose-response effect of tobacco exposure on the development of proteinuria is highly significant in all subjects (P = 0.001) and in subgroups with relatively short duration of diabetes mellitus (P < 0.001), good blood pressure control (P = 0.001) and those of young age (P = 0.007). CONCLUSIONS: The current study shows a clear dose-response effect of cigarette smoking on development of proteinuria in male Type 2 diabetic patients. These findings reinforce the urgent need to encourage diabetic patients to stop smoking regardless of age, duration of diabetes mellitus or status of blood pressure control.

White matter damage in carbon monoxide intoxication assessed in vivo using diffusion tensor MR imaging.

BACKGROUND AND PURPOSE: White matter (WM) injury in carbon monoxide (CO) intoxication is thought to be related to delayed cognitive sequelae. To determine if microstructural changes in WM are responsible for the delayed onset of cognitive symptoms, we performed diffusion tensor imaging (DTI) in patients with CO intoxication. MATERIALS AND METHODS: DTI was performed in 14 patients with delayed sequelae after CO intoxication and in 16 sex- and age-matched healthy volunteers. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) of several WM regions were measured. We also determined the correlation between FA of the selected WM and neuropsychological rating scores for the CO intoxication group. RESULTS: FA of patients with CO intoxication decreased in the corpus callosum, orbitofrontal WM, high frontal WM, parietal WM, and temporal lobes in comparison with the corresponding regions of healthy controls. FA of the WM in the occipital lobe and internal capsule of patients was not significantly different from that in controls. ADCs of all measured WM increased significantly in patients exposed to CO. High correlations were found between the FA of all selected WM and the Mini-Mental State Examination score (gamma = 0.631, P = .016) and the digit span backward task (gamma = 0.759, P = .001). CONCLUSIONS: CO intoxication may cause FA decline in associated cortical areas. This observation indicates microstructural WM pathology in CO intoxication, which is related to delayed cognitive encephalopathy.

Betel nut chewing and other risk factors associated with obesity among Taiwanese male adults.

OBJECTIVE: The research aimed at examining betel nut chewing and other risk factors associated with obesity among Taiwanese male adults. DESIGN: The research analyzed the data obtained by the 2001 National Health Interview Survey in Taiwan that covered all the administrative divisions in Taiwan. Multistage stratified systematic sampling design was adopted for survey. All members of a sampled household received the interview. SUBJECTS: The research analyzed questionnaires answered by nonaboriginal male respondents aged between 20 and 59 years old, and the total number of samples analyzed read 6126. Since very few female subjects chewed betel nut, they were excluded from the analysis. MEASUREMENTS: Criteria of obesity was defined as body mass index > or = 27 kg/m2. The variables incorporated for analysis included the respondents' status of betel nut chewing, age, educational background, presence of hypertension and diabetes mellitus, drinking and smoking status, exercise status, and demand for physical strength at job. Generalized estimating equations model was employed to estimate the odd ratios (with 95% CI) of obesity of each independent variable. RESULTS: Approximately 16.2% of respondents were obese. The distribution of betel nut chewing was current chewers 15.9%, ex-chewers 4.3%, and nonchewers 79.8%. After controlling above-mentioned independent variables, hypertension, diabetes mellitus, betel nut chewing, never exercising, and sedentary jobs were closely associated with obesity. CONCLUSION: The research found that betel nut chewing closely associated with obesity. The increased appetite of betel nut chewers is speculated as the underlying cause. The prospective study is needed to clarify this issue. In addition to increasing the risk of developing oral cancer, betel nut chewing seemed to be related with another health hazard: obesity.

Disaster epidemiology and medical response in the Chi-Chi earthquake in Taiwan.

STUDY OBJECTIVE: We examine the mortality and morbidity associated with earthquakes in the Chi-Chi earthquake in Taiwan in 1999. METHODS: Crude casualty data were collected from the reports of the government, local health bureaus, and 97 hospitals. The demographic data from the annual report of the Department of Interior were also employed for data analysis. Cross tables showing incidence of deaths and injuries by age, sex, time, and geographic distribution were generated to compare the mortality among different subgroups. Multiple regression models were established to explore the risk factors related to the mortality caused by earthquakes. RESULTS: The following results were found: the mortality rate increased with proximity to the epicenter, mortality was higher among the elderly than among young people, 30% of the victims died from head injuries caused by the collapse of dwellings, and the peak of medical demand was 12 hours after the earthquake and significantly increased demand for care lasted as long as 3 days. Furthermore, the regression model indicated that 78.5% of the variation of locality-age-sex-specific mortality was explained by the intensity of the earthquake, age, population density, distance to epicenter, medical beds per 10,000 people, and physicians per 10,000 people. CONCLUSION: The results implied that fragile minorities, specifically the elderly and children, require special consideration and attention in regard to disaster rescue and emergency medical care allocation. Epidemiologic analysis can guide disaster response and preparation.

Clinical analysis of a dysentery outbreak in Taichung.

In September 1993, we collected 207 patients due to dysentery, who visited the Department of Pediatrics at China Medical College Hospital. In our report, 67.6% of these patients were amebic dysentery, 19.3% were combined infection with amebic and Shigella sonnei dysentery, and 13.1% were Shigella sonnei dysentery. Therefore, amebic dysentery was the predominant cause during this outbreak. The clinical features of this outbreak were, in descending order, watery stool, fever, abdominal pain, mucinous stool and bloody stool. No concurrent liver abscess was discerned. Because there had not been such a clustering of dysentery in Taichung for so many years, we thought that travel to endemic areas might have been the underlying predisposing cause. Most of the school water supplying system was ground water, which might have been contaminated by a few patients returning from endemic areas. We thought that fecal-oral route by contaminated water might have been the primary transmission route.

Overactive bladder: special considerations in the geriatric population.

Overactive bladder (OAB) is a highly prevalent condition among older patients, and its presence is associated with the use of substantial healthcare resources and economic costs. Within the next 30 years, it is expected that the demand for services related to OAB will increase dramatically. Treatment of OAB is challenging and depends on several factors, including the age of the patient, cognitive functioning, and the degree of mobility. Pharmacotherapy, such as the use of tolterodine and oxybutynin, is a viable option for the treatment of OAB, and muscarinic antagonists are commonly used. The efficacy of an agent may differ in older patients compared with younger ones. In addition, certain side effects can be particularly troublesome in the geriatric population. A retrospective analysis of a large managed care database showed an age-related increase in the number of women seeking care for OAB. Caring for incontinent patients in the long-term care setting was shown to result in substantial additional costs, which were higher in those with more frequent incontinent episodes. Prompted voiding may be effective in reducing the number of incontinent episodes for those in institutionalized care; however, this practice is labor intensive and generally is only effective in 40% of cases. Moreover, assistance with prompted voiding must be maintained continuously. Future research should focus on defining the most cost-effective methods of treating OAB in the long-term care setting.

Immunogenicity and safety of standard-titer AIK-C measles vaccine in nine-month-old infants.

Because of the interference by maternal antibody before 1 year of age, the Schwarz strain of measles vaccine, which has been routinely used in Taiwan, must be given at 9 months and 15 months of age to ensure an optimal immune response. The AIK-C strain of measles vaccine has been reported to be highly immunogenic. This study evaluated the immunogenicity and safety of the AIK-C vaccine in 9-month-old Taiwanese infants. A total of 135 infants were recruited and were randomly assigned to receive either Schwarz vaccine (68 cases) or AIK-C vaccine (67 cases). Measles antibodies were assayed before and 1 month after the vaccination. Sixty-five (97%) infants who received the AIK-C vaccine seroconverted after the vaccination, whereas the seroconversion rate in those receiving the Schwarz vaccine was 77% (P = 0.001). The incidences of adverse reactions were comparable between the two groups. We conclude that even in 1990s, the failure rate of Schwarz vaccine in 9-month-old infants is still high. The AIK-C vaccine is more immunogenic in infants and its long-term immunogenicity and safety deserve further evaluation.

Detection of congenital cytomegalovirus infection in Chinese newborn infants using polymerase chain reaction.

Polymerase chain reaction (PCR) amplification was used to detect cytomegalovirus (CMV) in 1000 urine specimens from Chinese newborns for defining the incidence of congenital CMV infection in the Chinese population. The major immediate-early and the late antigen genes of CMV were amplified and detected by gel electrophoresis. There were 18 congenitally infected infants found when tests were performed with one or both primer pairs. Comparing with tissue culture, PCR of both primer sets provided a sensitivity of 94%, a specificity of 100% and a predictive value of positive result of 100%.

Human immunodeficiency virus infection in Taiwan, 1984 to 1994.

From 1984 to September 1994, a total of 9,099,734 serum samples from six population groups were tested for the antibody to human immunodeficiency virus type 1 (HIV). Mandatory testing was carried out for blood donors, military recruits, immigrants and prisoners; other population groups were tested anonymously with consent. A total of 695 samples were seropositive and, of these HIV carriers, 142 developed acquired immunodeficiency syndrome (AIDS). Although the prevalence of HIV infection and AIDS has remained low, there has been a rapid increase since 1991. Of the 142 AIDS cases, 68 were in homosexuals/bisexuals, 6 were in hemophiliacs, 7 were in prisoners/intravenous drug users, 49 were in heterosexuals and for 12 cases, the risk factors were unknown. Before 1987, 69 (90.8%) of the 76 HIV-infected persons were homosexuals or hemophiliacs. Thereafter, the risk groups diversified, with the main group shifting from hemophiliacs to intravenous drug users, and the number of heterosexuals surpassing that of homosexuals. Among the 142 cases of AIDS, 135 were males and only 7 were females. Despite the short period of follow-up, 114 have died (including 3 suicides).

[Beta-thalassemia major complicated with Vibrio vulnificus septicemia: report of one case].

Vibrio vulnificus is a halophilic Vibrio that has been isolated repeatedly from sea-water and shellfish during the warm months of the year. It's a virulent pathogen for men and is frequently associated with overwhelming infections including sepsis, gangrene of extremities and high mortality rate. We encountered a 13-year-old boy who had a history of beta-thalassemia major with secondary hemochromatosis, suffering from vomiting, diarrhea, fever and hypotension. Physical examination revealed that ecchymosis, bullae and ulceration were noted over the left leg. Vibrio vulnificus was isolated from the blood. Initially, the patient did not respond to the appropriate antibiotics treatment, subsequently surgical debridement was performed. After that, the patient recovered gradually, and discharged home after 17 days of admission. In conclusion, when patients present with sepsis and/or characteristic skin lesion-hemorrhagic bullae, particularly those with thalassemia major, hemochromatosis or underlying liver disease and a history of marine exposure, clinicians should be alerted to this potentially fatal infection and should commence appropriate assessment and treatment immediately.

Ozone removal capability of a welding fume respirator containing activated charcoal.

Development of air purifying respirators for protection against ozone has been slowed by concerns about oxidation of charcoal and other available sorbents. The suitability of a charcoal sorbent for low concentrations of ozone was evaluated as a part of the development of a half-mask air purifying respirator designed for welding fumes and ozone. Testing of the respirator confirmed that charcoal can be a suitable sorbent for low levels of ozone. Where the respirator is properly selected, fit tested, and worn, respirator use against welding fumes and ozone at concentrations not exceeding 10 times the permissible exposure limit had been recommended.

Determination of trace metals as n-butyl-2-naphthylmethyldithiocarbamates by high-performance liquid chromatography with a fixed-wavelength absorbance detector.

The determination of traces of metals by high-performance liquid chromatography of their n-butyl-2-naphthylmethyldithiocarbamate complexes, with a fixed-wavelength absorbance detector, is described. Metal complexes of this ligand are thermodynamically stable and kinetically inert towards dissociation. Various metal complexes, including those of nickel(II), iron(III), mercury(II), thallium(III), platinum(II), palladium(II), copper(II), and cobalt(II) are readily determined. The practical aspects of their separation on various nonpolar stationary phase columns are discussed. The detection limits compare very favorably with those of atomic spectrometry and are about 0.1 ng or approximately 10nM.

A mass vaccination program in Taiwan against hepatitis B virus infection in infants of hepatitis B surface antigen-carrier mothers.

To combat hepatitis B virus (HBV) infection in Taiwan, a mass immunoprophylaxis program was launched on July 1, 1984, aiming first at prevention of chronic HBV carriage from perinatal mother-to-infant infection. In the first 15-month period, 352,721 (78%) of 450,585 pregnant women were screened for hepatitis B surface antigen (HBsAg); HBsAg was present in 62,359 (18%), with 50% of them categorized as highly infectious. Infants born to HBsAg-positive women were given 5 micrograms of a plasma-derived hepatitis B vaccine at ages 1, 5, and 9 weeks, with a booster at age 12 months. Infants of highly infectious carrier mothers received an additional 0.5 mL of hepatitis B immune globulin within 24 hours after birth. The coverage rate of the hepatitis B immune globulin was 77% in 27,375 infants born to highly infectious mothers, and that of the first, second, third, and the fourth doses of vaccine was 88%, 86%, 84%, and 71%, respectively, in infants of 55,620 carrier mothers. The reported untoward reactions to immunization were negligible. We conclude that a mass hepatitis B vaccination program is feasible in hyperendemic areas such as Taiwan; this should be a significant step toward the effective control of HBV infection in these areas.

Silmization of stainless-steel frits for use in trace metal analysis by high performance liquid chromatography.

A simple method has been developed to minimize the interferences related to the metal parts of an analytical system used for trace metal analysis by HPLC. This is accomplished by blocking the exposed metal surfaces with an organosilane. The effect of the silanized stainless steel frits has been demonstrated by injecting diethyldithiocarbamate into columns with and without high metal surface area components. The coating of the silane is quite stable for routine use.