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1.
J Food Drug Anal ; 30(1): 150-162, 2022 03 15.
Article in English | MEDLINE | ID: mdl-35647726

ABSTRACT

Drug substances are at risk of contamination with N-nitrosamines (NAs), well-known carcinogenic agents, during synthesis processes and/or long-term storage. Therefore, in this study, we developed an efficient data-based screening approach to systemically assess marketed products and investigated its scalability for benefiting both regulatory agencies and pharmaceutical industries. A substructure-based screening method employing DataWarrior, an open-source software, was established to evaluate the risks of NA impurities in drug substances. Eight NA substructures containing susceptible amino sources for N-nitrosation have been identified as screening targets: dimethylamine (DMA), diethylamine, isopropylethylamine, diisopropylamine, N-methyl-2-pyrrolidone, dibutylamine, methylphenylamine, and tetrazoles. Our method detected 192 drug substances with a theoretical possibility of NA impurity, 141 of which had not been reported previously. In addition, the DMA moiety was significantly dominant among the eight NA substructures. The results were validated using data from the literature, and a high detection sensitivity of 0.944 was demonstrated. Furthermore, our approach has the advantage of scalability, owing to which 31 additional drugs with suspected NA-contaminated substructures were identified using the substructures of 1-methyl-4-piperazine in rifampin and 1-cyclopentyl-4-piperazine in rifapentine. In conclusion, the reported substructure-based approach provides an effective and scalable method for the screening and investigation of NA impurities in various pharmaceuticals and might be used as an ancillary technique in the field of pharmaceutical quality control for risk assessments of potential NA impurities.


Subject(s)
Drug Contamination , Nitrosamines , Piperazines , Quality Control , Risk Assessment
2.
Arch Med Sci ; 16(3): 627-634, 2020.
Article in English | MEDLINE | ID: mdl-32399112

ABSTRACT

INTRODUCTION: Chronic pain may cause many comorbidities in the elderly; however, nationwide data about this issue remain insufficient. We conducted this study to address the data gap. MATERIAL AND METHODS: We identified geriatric participants (≥ 65 years) with chronic pain between 2000 and 2013 from the Taiwan National Health Insurance Research Database. The causes of chronic pain and use of analgesics between two sexes and among three age subgroups were compared. RESULTS: A total of 21,018 participants were identified with the mean age (standard deviation) of 72.7 years (5.6) and the female percentage of 50.8%. The prevalence of chronic pain in the elderly was 21.5%, and it was higher in the females than males. The proportions of each age subgroup were 65-74 (66.8%), 75-84 (29.4%), and ≥ 85 years (3.8%). Common causes of chronic pain were osteoarthritis (21.9%), spinal disorders (19.0%), peripheral vascular diseases (12.4%), and osteoporosis (11.4%). Non-steroidal anti-inflammatory drugs were the most common medication, followed by acetaminophen and opioids. The most commonly used opioid was morphine. The use of opioids increased with age. CONCLUSIONS: This study delineated the causes of chronic pain and use of analgesics in a geriatric population, which may help further studies about this issue in the future.

3.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Article in English | MEDLINE | ID: mdl-31974550

ABSTRACT

CONTEXT: Chronic pancreatitis (CP), is a long-term inflammation of the pancreatic parenchyma, and might increase risk of a hyperglycemia crisis or hypoglycemia in patients with diabetes mellitus (DM); however, the relationship has not been previously investigated. OBJECTIVE: To investigate the risk of diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), hypoglycemia, and long-term outcomes in DM patients with CP. DESIGN: A population-based cohort study. SETTING AND PARTICIPANTS: Tapping Taiwan's National Health Insurance Research Database, we identified 506 DM patients with newly diagnosed CP from 1999 to 2010 and created a control cohort consisting of 5060 age- and sex-matched DM patients without CP from the same time period. We followed those 2 cohorts from the index date to occurrence of outcomes, the date of death or 31 December 2012. MAIN OUTCOME MEASURES: DKA, HHS, hypoglycemia and mortality. RESULTS: DM patients with CP, who were predominantly male (88%) and younger (60% < 45 years old), had a 9.5-, 5.0-, and 3.0-fold higher risk for DKA (95% confidence interval [CI]: 6.51-13.91), HHS (95% CI: 2.85-8.62), and hypoglycemia (95% CI: 2.23-4.08), respectively. They also had lower 1-, 5-, and 10-year cumulative survival rates (98.4% vs 99.0%, 87.7% vs 96.6%, and 78.7% vs 93.6%, respectively) (log-rank test: P < .001), and a 2.43-fold higher risk for death (HR: 2.43, 95% CI: 1.82-3.27). CONCLUSIONS: In Taiwan, DM patients with CP have a higher incidence of DKA, HHS, hypoglycemia, and mortality. More attention is needed for preventing hyperglycemia crisis and hypoglycemia prevention in this population.


Subject(s)
Diabetes Mellitus, Type 1/mortality , Diabetes Mellitus, Type 2/mortality , Diabetic Ketoacidosis/mortality , Hyperglycemia/mortality , Hypoglycemia/mortality , Pancreatitis, Chronic/physiopathology , Adolescent , Adult , Aged , Biomarkers/analysis , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Diabetic Ketoacidosis/etiology , Diabetic Ketoacidosis/pathology , Female , Follow-Up Studies , Humans , Hyperglycemia/etiology , Hyperglycemia/pathology , Hypoglycemia/etiology , Hypoglycemia/pathology , Longitudinal Studies , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate , Taiwan , Young Adult
4.
Eur Geriatr Med ; 10(5): 777-784, 2019 Oct.
Article in English | MEDLINE | ID: mdl-34652710

ABSTRACT

PURPOSE: This study was conducted to clarify the long-term mortality in the older population with chronic pain (CP), which is still unclear. METHODS: We identified 17,568 older participants (aged ≥ 65 years) with CP and an identical number of comparison cohort without CP matched 1:1 by age and sex between 1996 and 2000 from the Taiwan National Health Insurance Research Database. Causes of CP, underlying comorbidities, living areas, and mortality were collected for analyses. The long-term mortality and the causes of mortality were compared between the two cohorts through follow-up since 2000 until 2015. RESULTS: The mean age (± standard deviation) was 73.5 ± 5.7 years, and female participants comprised 55.1% in both cohorts. The most common causes of CP were osteoarthritis (24.2%), spinal disorders (22.4%), peripheral vascular diseases (14.0%), and osteoporosis (9.5%). Older participants with CP had an increased rate of long-term mortality compared to that among their counterparts without CP after adjusting for the underlying comorbidities and the causes of CP (adjusted hazard ratio [AHR]: 1.18; 95% confidence interval [CI] 1.14-1.21). The increased mortality rate was observed even after the follow-up of 6 years (AHR 1.15; 95% CI 1.10-1.20). No significant difference was observed in the causes of mortality between the two cohorts. The most common cause of mortality was malignancy, followed by cardiovascular and cerebrovascular diseases. CONCLUSIONS: Chronic pain was associated with an increased rate of long-term mortality in the older population. Early detection and intervention for treating CP are suggested for this population.

5.
Nephrol Dial Transplant ; 32(10): 1731-1736, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28088773

ABSTRACT

BACKGROUND: The objective of this study is to determine the incidence and severity of acute pancreatitis (AP) in patients with end-stage renal disease (ESRD) on dialysis and whether the dialysis modality [hemodialysis (HD) versus peritoneal dialysis (PD)] confers a higher risk for AP as well as complications or mortality related to AP. METHODS: We analyzed national health insurance claims data of 67 078 ESRD patients initiating dialysis between 1999 and 2007 in Taiwan. All patients were followed up from the start of their dialysis to first AP diagnosis, death, end of dialysis or 31 December 2008. Cox proportional hazards models were used to identify risk factors. RESULTS: The cumulative incidence rates of AP were 0.6, 1.7, 2.6, 3.4 and 4% at 1, 3, 5, 7 and 9 years, respectively. ESRD patients on HD and PD had an AP incidence of 5.11 and 5.86 per 1000 person-years, respectively. Independent risk factors for AP in this population were being elderly, being female, having biliary stones or liver disease, and being on PD. Severe AP occurred in 44.9% of the HD patients and in 36% of the PD patients. Patients with AP on HD had a higher incidence of upper gastrointestinal (UGI) bleeding than those on PD (P = 0.002). In contrast, those with AP on PD had a higher incidence of need for total parenteral nutrition (TPN) support than those on HD (P = 0.072). Overall in-hospital mortality was 8.1%. The risk factors for mortality after an AP attack were male gender, increased age, AP severity, and the presence of diabetes mellitus or liver disease. CONCLUSIONS: ESRD patients on PD were at higher risk for AP than those on HD. HD patients with AP attacks had a greater incidence of UGI bleeding and PD patients with AP attacks a more frequent need for TPN support.


Subject(s)
Kidney Failure, Chronic/complications , Pancreatitis/epidemiology , Pancreatitis/mortality , Renal Dialysis/adverse effects , Acute Disease , Adolescent , Adult , Aged , Female , Hospital Mortality , Humans , Incidence , Kidney Failure, Chronic/therapy , Longitudinal Studies , Male , Middle Aged , Pancreatitis/etiology , Risk Factors , Survival Rate , Taiwan/epidemiology , Time Factors , Young Adult
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