Neuroimmunological effects of omega-3 fatty acids on migraine: a review.

Migraine is a highly prevalent disease worldwide, imposing enormous clinical and economic burdens on individuals and societies. Current treatments exhibit limited efficacy and acceptability, highlighting the need for more effective and safety prophylactic approaches, including the use of nutraceuticals for migraine treatment. Migraine involves interactions within the central and peripheral nervous systems, with significant activation and sensitization of the trigeminovascular system (TVS) in pain generation and transmission. The condition is influenced by genetic predispositions and environmental factors, leading to altered sensory processing. The neuroinflammatory response is increasingly recognized as a key event underpinning the pathophysiology of migraine, involving a complex neuro-glio-vascular interplay. This interplay is partially mediated by neuropeptides such as calcitonin gene receptor peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP) and/or cortical spreading depression (CSD) and involves oxidative stress, mitochondrial dysfunction, nucleotide-binding domain-like receptor family pyrin domain containing-3 (NLRP3) inflammasome formation, activated microglia, and reactive astrocytes. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), crucial for the nervous system, mediate various physiological functions. Omega-3 PUFAs offer cardiovascular, neurological, and psychiatric benefits due to their potent anti-inflammatory, anti-nociceptive, antioxidant, and neuromodulatory properties, which modulate neuroinflammation, neurogenic inflammation, pain transmission, enhance mitochondrial stability, and mood regulation. Moreover, specialized pro-resolving mediators (SPMs), a class of PUFA-derived lipid mediators, regulate pro-inflammatory and resolution pathways, playing significant anti-inflammatory and neurological roles, which in turn may be beneficial in alleviating the symptomatology of migraine. Omega-3 PUFAs impact various neurobiological pathways and have demonstrated a lack of major adverse events, underscoring their multifaceted approach and safety in migraine management. Although not all omega-3 PUFAs trials have shown beneficial in reducing the symptomatology of migraine, further research is needed to fully establish their clinical efficacy and understand the precise molecular mechanisms underlying the effects of omega-3 PUFAs and PUFA-derived lipid mediators, SPMs on migraine pathophysiology and progression. This review highlights their potential in modulating brain functions, such as neuroimmunological effects, and suggests their promise as candidates for effective migraine prophylaxis.

A 12-week randomized double-blind clinical trial of eicosapentaenoic acid intervention in episodic migraine.

Omega-3 polyunsaturated fatty acids (PUFAs) may benefit migraine improvement, though prior studies are inconclusive. This study evaluated the effect of eicosapentaenoic acid (EPA) on episodic migraine (EM) prevention. Seventy individuals with EM participated in a 12-week randomized, double-blind, placebo-controlled trial from March 2020 and May 2022. They were randomly assigned to either the EPA (N = 35, 2 g fish oil with 1.8 g of EPA as a stand-alone treatment daily), or the placebo group (N = 35, 2 g soybean oil daily). Migraine frequency and headache severity were assessed using the monthly migraine days, visual analog scale (VAS), Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), and Pittsburgh Sleep Quality Index (PSQI) in comparison to baseline measurements. The EPA group significantly outperformed the placebo in reducing monthly migraine days (-4.4 ± 5.1 days vs. - 0.6 ± 3.5 days, p = 0.001), days using acute headache medication (-1.3 ± 3.0 days vs. 0.1 ± 2.3 days, p = 0.035), improving scores for headache severity (ΔVAS score: -1.3 ± 2.4 vs. 0.0 ± 2.2, p = 0.030), disability (ΔMIDAS score: -13.1 ± 16.2 vs. 2.6 ± 20.2, p = 0.001), anxiety and depression (ΔHADS score: -3.9 ± 9.4 vs. 1.1 ± 9.1, p = 0.025), and quality of life (ΔMSQ score: -11.4 ± 19.0 vs. 3.1 ± 24.6, p = 0.007). Notably, female particularly benefited from EPA, underscoring its potential in migraine management. In conclusion, high-dose EPA has significantly reduced migraine frequency and severity, improved psychological symptoms and quality of life in EM patients, and shown no major adverse events, suggesting its potential as a prophylactic for EM.

Update on gepants for the treatment of chronic migraine.

Chronic migraine (CM) is a profoundly debilitating condition that has detrimental clinical and social outcomes. Over the past two decades, novel small-molecule calcitonin gene-related peptide (CGRP) receptor antagonists, known as gepants, and CGRP monoclonal antibodies (mAbs) have been developed, ushering in a new era of migraine-specific treatment. In this review, we discuss the literature investigating the role of gepants for the treatment of CM. Numerous completed and ongoing clinical studies have conclusively demonstrated the safety, tolerability, and efficacy of several gepants for the acute treatment of migraine. However, preventive trials involving gepants have focused on patients with episodic migraine, with atogepant being the only gepant approved for CM prevention by the US Food and Drug Administration at the time of writing. Although some preliminary positive results have been reported, further research is still required to achieve additional advancements in the future. In summary, the effectiveness of gepants for treating individuals with CM are highly expected. This review highlights the development and current progress of gepants for the treatment of CM, focusing both on their role as acute abortive agents and preventive measures and on their concomitant use with other antimigraine medications, such as CGRP mAbs or triptans.

Prescription characteristics of Xue-Fu-Zhu-Yu-Tang in pain management: a population-based study using the National Health Insurance Research Database in Taiwan.

Objective: To explore the prevalence and distinctive features of Xue-Fu-Zhu-Yu-Tang (XFZYT) prescriptions by analyzing the National Health Insurance Research Database (NHIRD) to identify the specific medical problems for which XFZYT is prescribed. Methods: This nationwide, population-based, cross-sectional study included 109,073 XFZYT users and 532,848 XFZYT non-users among Chinese herbal product (CHP) users in NHIRD. Chi-squared tests were used to analyze disparities between the XFZYT user and XFZYT non-user cohorts, and the mean age was evaluated using the Wilcoxon rank-sum test. Logistic regression was used to compute the odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: XFZYT was frequently used to treat pain. The top five conditions for which the Taiwanese traditional Chinese medicine (TCM) practitioners would prescribe XFZYT were chest pain; headache; myalgia and myositis; lumbago; and neuralgia, neuritis, and radiculitis. Conclusion: This study represents an inaugural comprehensive survey conducted on the utilization of XFZYT prescriptions among patients with diverse diseases. XFZYT is mostly used to treat pain conditions in Taiwan. Combined with the combination use of other CHPs, XFZYT is used to treat symptoms of the chest and respiratory system, soft tissue conditions, menstruation disorders, and joint and back discomfort. These results suggest that further clinical trials are warranted to verify the effects of XFZYT in pain management.

Neuroimmunological Effect of Vitamin D on Neuropsychiatric Long COVID Syndrome: A Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). COVID-19 is now recognized as a multiorgan disease with a broad spectrum of manifestations. A substantial proportion of individuals who have recovered from COVID-19 are experiencing persistent, prolonged, and often incapacitating sequelae, collectively referred to as long COVID. To date, definitive diagnostic criteria for long COVID diagnosis remain elusive. An emerging public health threat is neuropsychiatric long COVID, encompassing a broad range of manifestations, such as sleep disturbance, anxiety, depression, brain fog, and fatigue. Although the precise mechanisms underlying the neuropsychiatric complications of long COVID are presently not fully elucidated, neural cytolytic effects, neuroinflammation, cerebral microvascular compromise, breakdown of the blood-brain barrier (BBB), thrombosis, hypoxia, neurotransmitter dysregulation, and provoked neurodegeneration are pathophysiologically linked to long-term neuropsychiatric consequences, in addition to systemic hyperinflammation and maladaptation of the renin-angiotensin-aldosterone system. Vitamin D, a fat-soluble secosteroid, is a potent immunomodulatory hormone with potential beneficial effects on anti-inflammatory responses, neuroprotection, monoamine neurotransmission, BBB integrity, vasculometabolic functions, gut microbiota, and telomere stability in different phases of SARS-CoV-2 infection, acting through both genomic and nongenomic pathways. Here, we provide an up-to-date review of the potential mechanisms and pathophysiology of neuropsychiatric long COVID syndrome and the plausible neurological contributions of vitamin D in mitigating the effects of long COVID.

Risks after Gestational Diabetes Mellitus in Taiwanese Women: A Nationwide Retrospective Cohort Study.

OBJECTIVE: An increasing trend in the prevalence of gestational diabetes mellitus (GDM) has been reported in Taiwan. GDM has been linked to various adverse maternal outcomes over a long period, including cardiovascular disease (CVD) and chronic kidney disease (CKD). However, evidence implies that the effects of GDM on the mid-term surrogate risk factors for these diseases are limited. Furthermore, data from nationwide cohort studies are limited. The primary aim of this study was to investigate the risk of developing type 2 diabetes mellitus (T2DM), arterial hypertension (aHTN), and hyperlipidemia (HL) through a 5-year follow-up post-delivery of women with GDM in a nationwide cohort study in Taiwan. The second objective was to investigate the risk of developing insulin resistance syndrome (IRS)-related diseases, including CVD, acute myocardial infarction (AMI), peripheral artery occlusive disease (PAOD), non-alcoholic fatty liver diseases (NAFLD), and CKD. METHODS: This was a retrospective, population-based nationwide cohort study. The data source comprises a merge of the Birth Certificate Application Database (BCA) and the National Health Insurance Research Database in Taiwan. Women aged between 15 and 45 years who gave birth in Taiwan between 2004 and 2011 were included. Women who were enrolled and had a GDM diagnosis were assigned to the exposure group. Women who were enrolled without a GDM diagnosis were assigned to the comparison group. The relative risk of developing T2DM, aHTN, HL, and IRS-related diseases, including CVD, AMI, PAOD, NAFLD, and CKD, were analyzed and presented as hazard ratio (HR) through Cox regression and log-rank regression analyses. RESULTS: A total of 1,180,477 women were identified through the BCA database between 2004 and 2011. Of those, 71,611 GDM-diagnosed women and 286,444 women without GDM were included in the final analysis. After adjusting for age, pre-existing cancer, and parity, developing T2DM, aHTN, and HL were still significantly increased in the GDM group (HR and interquartile range (IQR): 2.83 (2.59, 3.08), 1.09 (1.01, 1.06), and 1.29 (1.20, 1.38), accordingly). CVD, NAFLD, and CKD had a very low incidence and showed insignificant results. CONCLUSION: Our findings provide nationwide cohort data showing that GDM increased the risk of developing T2DM, aHTN, and HL 5 years after delivery within the same group. The GDM complications and risk of CVD, AMI, PAOD, NAFLD, and CKD need further investigation.

The immediate effects of lavender-based essential oil inhalation on subsequent polysomnography in people with poor sleep quality.

BACKGROUND: Although aromatherapy is considered an adjuvant therapy to promote sleep quality, few objective sleep testing instruments can confirm the effects of aromatherapy on sleep physiology. The purpose of this study was to confirm and compare the immediate effects of a single lavender essential oil (SLEO) group to a complex lavender essential oil (CLEO) group by objective polysomnography (PSG) recordings. METHODS: Participants were randomly divided into the SLEO group and CLEO group in this single-blind trial to explore the sleep effect of essential oil aroma. All the participants completed the sleep-related questionnaires and underwent two consecutive nights of PSG recordings, who had one night without aromatherapy and one night with one of the two aromas randomly assigned to them. RESULTS: Total of 53 participants were recruited for this study, 25 participants were in the SLEO group, and 28 were in the CLEO group. Baseline characteristics and sleep-related questionnaires were similar in both groups. Both SLEO and CLEO extended the total sleep time (TST) (Δ = 43.42 and 23.75 minutes, respectively) and sleep period time (SPT) (Δ = 38.86 and 24.07 minutes, respectively). The SLEO group further improved sleep efficiency and increased the amounts of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep and decreased spontaneous arousals. However, there was no significant difference in PSG parameters between the SLEO and CLEO groups. CONCLUSION: Both SLEO and CLEO extended TST and SPT, with no significant differences between these two groups. These results warrant practical applications and merit future studies (Clinical trial registration: ClinicalTrials.gov : NCT03933553).

Reduced mortality in patients with extended duration of methadone maintenance treatment: a five-year retrospective nationwide study.

BACKGROUND: The retention of patients under methadone maintenance treatment (MMT) is an indication for the effectiveness of the therapy. We aimed to explore the relation between mortality and the cumulative MMT duration. METHODS: A retrospective cohort analysis was performed using Taiwan Illicit Drug Issue Database (TIDID) and National Health Insurance Research Database (NHIRD) during 2012-2016. We included 9149 and 11 112 MMT patients as the short and long groups according to the length of their cumulative MMT duration, 1-364 and ⩾365 days, respectively. The risk of mortality was calculated by Cox proportional hazards regression model with time-dependent exposure to MMT, and the survival probability was plotted with the Kaplan-Meier curve. RESULTS: The mortality rates were 2.51 and 1.51 per 100 person-years in the short and long cumulative MMT duration groups, respectively. After adjusting for on or off MMT, age, sex, marital status, education level, maximum methadone dose, and comorbidities (human immunodeficiency virus, depression, hepatitis C virus, hepatitis B virus, alcoholic liver disease, and cardiovascular disease), the long group had a lower risk of death (hazard ratio = 0.67; 95% confidence interval 0.60-0.75) than the short group. Increased risk was observed in patients with advanced age, being male, unmarried, infected by HIV, HCV, and HBV, and diagnosed with depression, ALD, and CVD. Causes of death were frequently related to drug and injury. CONCLUSIONS: Longer cumulative MMT duration is associated with lower all-cause and drug-related mortality rate.

Long-term exposure to particulate matter was associated with increased dementia risk using both traditional approaches and novel machine learning methods.

Air pollution exposure has been linked to various diseases, including dementia. However, a novel method for investigating the associations between air pollution exposure and disease is lacking. The objective of this study was to investigate whether long-term exposure to ambient particulate air pollution increases dementia risk using both the traditional Cox model approach and a novel machine learning (ML) with random forest (RF) method. We used health data from a national population-based cohort in Taiwan from 2000 to 2017. We collected the following ambient air pollution data from the Taiwan Environmental Protection Administration (EPA): fine particulate matter (PM2.5) and gaseous pollutants, including sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), nitrogen oxide (NOx), nitric oxide (NO), and nitrogen dioxide (NO2). Spatiotemporal-estimated air quality data calculated based on a geostatistical approach, namely, the Bayesian maximum entropy method, were collected. Each subject's residential county and township were reviewed monthly and linked to air quality data based on the corresponding township and month of the year for each subject. The Cox model approach and the ML with RF method were used. Increasing the concentration of PM2.5 by one interquartile range (IQR) increased the risk of dementia by approximately 5% (HR = 1.05 with 95% CI = 1.04-1.05). The comparison of the performance of the extended Cox model approach with the RF method showed that the prediction accuracy was approximately 0.7 by the RF method, but the AUC was lower than that of the Cox model approach. This national cohort study over an 18-year period provides supporting evidence that long-term particulate air pollution exposure is associated with increased dementia risk in Taiwan. The ML with RF method appears to be an acceptable approach for exploring associations between air pollutant exposure and disease.

Risk of psychosis in illicit amphetamine users: a 10 year retrospective cohort study.

QUESTION: Amphetamine use is a risk factor for psychosis, which imposes a substantial burden on society. We aimed to investigate the incidence of psychosis associated with illicit amphetamine use and whether rehabilitation treatments could influence the psychosis risk. STUDY SELECTION AND ANALYSIS: A retrospective cohort study was conducted using the population based Taiwan Illicit Drug Issue Database (TIDID) and the National Health Insurance Research Database (NHIRD), from 2007 to 2016. We identified 74 601 illicit amphetamine users as the amphetamine cohort and 2 98 404 subjects as the non-amphetamine cohort. The incidence rate of newly diagnosed psychosis was the main outcome. Cox proportional hazards models were applied to assess the effects of amphetamine, and the Kaplan-Meier method was used to estimate the cumulative psychosis incidence curves. FINDINGS: Illicit amphetamine users were 5.28 times more likely to experience psychosis than those without illicit drug use records. The risk was higher for subjects with multiple arrests for amphetamine use. A greater hazard ratio (HR) magnitude was observed in female patients. We also observed a significant decrease in the risk of psychosis in patients receiving rehabilitation treatments during deferred prosecution (adjusted HR 0.74, 95% CI 0.61 to 0.89). CONCLUSIONS: Illicit amphetamine use was associated with an increased incidence of psychosis. The risk was identified across all age groups, particularly in women and in those arrested multiple times, and was inversely correlated with rehabilitation treatments for amphetamine misuse.

The effect of bright light therapy in migraine patients with sleep disturbance: A prospective, observational cohort study protocol.

Background: Migraine is a common disabling disorder, and its substantial burden is associated with a considerable negative impact on the patients' quality of life. Moreover, aging patients with migraine have more cognitive complaints. Additionally, the elderly are more likely to have sleep disturbances, which may also predict the risk of incident dementia. Migraines are reported to be closely associated with sleep and circadian rhythms. Sleep disturbance is a well-known trigger for migraine episodes; moreover, shift work or jet lag reportedly triggers some migraines. The hypothalamus is thought to be the migraine generator; sleep and circadian activity rhythm are also controlled by the hypothalamus. Evidence suggests an influence of both sleep and circadian system on migraine. Previously, light therapy has been show to stabilize sleep architecture and further improve insomnia related to circadian rhythm disorders. However, the beneficial effect of light therapy on migraine with sleep disturbance has not yet been determined. We aim to explore the effects of light therapy for migraine combined with sleep disturbance. Methods and analysis: This project is a 2-year, randomized, double-blind, placebo-controlled clinical trial. The study design includes a 4-week monitoring period (baseline and pretest), a 4-week treatment period, and a posttest. The study participants will undergo assessments on headache frequency and severity and subjective and objective (wrist actigraphy and polysomnography) sleep disturbances, and quality of life and a series of blood tests for serum biomarkers. Discussion: This study will establish evidence-based alternative medicine for the preventive effect of bright light therapy in migraine patients with sleep disturbances. Moreover, our data will be useful to comprehend the biochemical mechanism of light therapy in migraine prevention.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04890691.

High Risk for Attention-Deficit Hyperactive Disorder in Children with Strabismus: A Nationwide Cohort Study from the National Health Insurance Research Database.

Strabismus is associated with amblyopia and a lower quality of life. Attention-deficit hyperactivity disorder (ADHD) is common among children and adolescents, and influences their academic, vocational, and social life. Previous studies have suggested an association between strabismus and ADHD. Using data from the Taiwan National Health Insurance Research Database between 2000 and 2010, we performed a large-scale cohort study comparing the incidence, risk factors, and severity of ADHD in children with and without strabismus. A total of 2049 patients <18 years old with newly diagnosed strabismus (esotropia: 404; exotropia: 1645) were identified, and 8196 age- and sex-matched controls without strabismus were also included. After an average of 6.5 ± 2.9 years of follow-up, the incidence of ADHD per 1000 person-years was 5.39 in the strabismus group (esotropia: 9.93; exotropia: 4.11) and 3.23 in the control group. The cumulative incidence of ADHD was significantly greater in the esotropia (hazard ratio [HR]: 2.04; 95% confidence interval [CI]:1.36-3.06; p = 0.0007) and exotropia groups (HR: 1.44; 95% CI: 1.03-2.03; p = 0.038) than in the controls. Patients with strabismus had more comorbidities than those without (p < 0.05). In summary, this large-scale study found a higher cumulative incidence of ADHD in patients with strabismus, especially in those with esotropia.

Lipid-Free Parenteral Nutrition Is Associated with an Increased Risk of Hepatic Dysfunction in Surgical Critically Ill Patients: A Retrospective Observational Study.

To evaluate the effects of lipid-free parenteral nutrition (PN) and various intravenous fat emulsions (IVFEs) on hepatic function in surgical critically ill trauma/acute care surgery patients. We retrospectively reviewed trauma/acute care surgery patients without admission hepatic disorder that received PN. The PN groups include lipid-free, soybean oil/medium-chain triglyceride, olive oil-based, and fish-oil contained PN. We excluded patients with (1) age <18 years, (2) without surgery, (3) preexisting liver injury/diseases, (4) hyperbilirubinemia at admission, (5) received more than one type of PN, and (6) repeated ICU episodes in the same hospitalization. Hepatic dysfunction was considered as serum total-bilirubin >6.0 mg/dL. The demographics, severity score, comorbidities, blood stream infection, and mortality were collected for analyses. The major outcome is hepatic function. We also performed analyses stratified by separated lipid doses (g/kg/day). A total of 249 patients were enrolled. There were no demographic differences among groups. The lipid-free PN group had a higher incidence of hepatic dysfunction and mortality. Compared to the lipid-free group, the other three IVFEs had significantly lower risks of hepatic dysfunction, while the olive oil-based group had a significantly lower risk of 30 and 90-day mortality. After being stratified by separating lipid doses, the soybean oils showed a decreasing trend of hepatic dysfunction and mortality with increased dosage. Fish oil >0.05 g/kg/day was associated with lower hepatic dysfunction incidences. Our findings suggest that, when compared to IVFEs, surgical critically ill patients with trauma/acute care surgery that received lipid-free PN are associated with an increased risk of hepatic dysfunction. In addition, the olive oil-based group had a significantly lower risk of mortality, while fish oil >0.05 g/kg/day was associated with lower incidences of hepatic dysfunction; however, further studies are warranted.

The Morphological and Dynamic Changes of Ultrasound in the Evaluation of Effects of Oral Steroids Treatment for Patients with Carpal Tunnel Syndrome.

The role of oral steroids in carpal tunnel syndrome (CTS) remains elusive. This study aims to depict the ultrasound findings and conceivable mechanisms in relation to the efficacy of oral steroids for patients with CTS by measuring the morphological and motion changes in the median nerve. In this study, CTS patients were randomized to the oral steroid group (14 participants and 22 wrists) or nicergoline group (22 participants and 35 wrists) for 4 weeks. Both treatment arms were given global symptom score (GSS) measurements and completed an ultra-sound at baseline and at 2- and 4-weeks post-treatment. In the nerve conduction study (NCS), distal motor latency (DML) was used to assess the treatment response at baseline and 4 weeks post-treatment. The cross-sectional area (CSA) and amplitude (AMP) evaluated by the maximum lateral sliding displacement represented the morphological and dynamic changes in the median nerve, respectively. The results showed that AMP, CSA, GSS, and DML were significantly im-proved in the steroid group, as compared to the nicergoline group at weeks 2 and 4 (p < 0.05). The mean improvement in ultrasound parameters CSA (15.03% reduction) and AMP (466.09% increase) was better than the DML (7.88% reduction) parameter of NCS, and ultrasound changes were detectable as early as 2 weeks after oral steroid administration. Ultrasounds can serve as a tool for the quantitative measurement of treatment effects and can potentially elucidate the pathogenesis of CTS in a non-invasive and more effective manner.

Diabetes mellitus risk after hysterectomy: A population-based retrospective cohort study.

ABSTRACT: We explored whether hysterectomy with or without bilateral oophorectomy was associated with the increasing incidence of diabetes mellitus (DM) in an East Asian population. This was a retrospective population-based cohort study that analyzed DM risk in Taiwanese women, using a health insurance research database of 1998 to 2013 containing nearly 1 million people. We identified 7088 women aged 30 to 49 years who had undergone hysterectomy with or without oophorectomy. The comparison group included 27,845 women without a hysterectomy who were randomly selected from the population and matched to women in the hysterectomy group by age (exact year) and year of the surgery. DM comorbidities were identified. The incidence and hazard ratios for DM were calculated with Cox proportional hazard regression models. The median ages of patients in the hysterectomy and comparison groups were both approximately 44 years. After a median 7.1 years of follow-up, the incidence of DM was 40% higher in the hysterectomized women as compared with the comparisons (9.12 vs 6.78/1000 person-years, P < .001), with an adjusted hazard ratio (aHR) of 1.37 (95% confidence interval [CI] = 1.23 -1.52). However, the DM risk was not increased in the women with hysterectomy plus oophorectomy (aHR=1.28, 95% CI = 0.93-1.76). Furthermore, among women aged 30 to 39 years, 40 to 49 years, the risk in hysterectomized women was higher than the comparisons (aHR = 1.75, 95% CI = 1.27-2.41; aHR = 1.33, 95% CI = 1.19-1.49, respectively). Our study provides essential and novel evidence for the association between hysterectomy and DM risk in women aged 30 to 49 years, which is relevant to these women and their physicians. Physicians should be aware of the increased DM risk associated with hysterectomy and take this into consideration when evaluating a patient for a hysterectomy. The current results might help gynecologists prevent DM and encourage diagnostic and preventive interventions in appropriate patients.

Augmentation in Healthcare Utilization of Patients with Opioid Use Disorder After Methadone Maintenance Treatment: A Retrospective Nationwide Study.

INTRODUCTION: The health benefits of entering methadone maintenance treatment (MMT) for opioid-dependent persons may not be merely limited to therapy of opioid use disorder. We aimed to compare the healthcare utilization of MMT patients before and after MMT. METHODS: A retrospective analysis was performed using the Taiwan Illicit Drug Issue Database and the National Health Insurance Research Database (NHIRD) between 2014 and 2016. We included 1255 newly enrolled MMT patients in 2015 and randomly selected 5020 patients from NHIRD matched by age and gender as the comparison group. Changes in healthcare utilization 1 year before and 1 year after the date of the index date (MMT initiation) were compared within and between MMT and comparison groups. RESULTS: During the 1-year period following MMT, the hospitalization length was considerably decreased, while the number of outpatient visits, emergency department (ED) visits, and ED expenditure significantly increased in MMT patients. Multivariable linear regression with the difference-in-difference approach revealed that all the categories of healthcare utilization increased, except for a minor increase of outpatient expenditure and a slight decrease of hospitalization length for the MMT group relative to the comparison group. Increases in utilization of the departments of psychiatry and infectious diseases of the MMT patients were considerable. CONCLUSION: MMT is associated with increased healthcare utilization, and departments of psychiatry and infectious diseases play substantial roles. Policy-makers should warrant access for all who need healthcare by ensuring the availability of the treatment for drug dependence.

Factors Impacting Survival in Patients With Major Burn-Induced Acute Kidney Injury Postrenal Replacement Therapy: A Nationwide Study With 15 Years Follow-Up in Taiwan.

BACKGROUND: Major burn-induced acute kidney injury (AKI) causes extremely high mortality, even though renal replacement therapy (RRT) was thought of as the most efficient treatment. There was scanty research for investigating the characteristic of burn-AKI-RRT patients during intensive care. This study aims to investigate the factors impacting the survival outcomes in those burn-AKI-RRT cases. METHODS: Using the Taiwan National Health Insurance Research Database and its affiliated database, the Registry for Catastrophic Illness Patients, we defined a cohort composed of 171 patients encountering major burn-induced AKI and receiving RRT during burn care for a 15-year observation period. Demographic characteristic, comorbidities, total body surface area (TBSA), major procedures, and complications were analyzed to explore the factors affecting the survival outcomes during acute burn care and 1 year after discharge. RESULTS: Patients who underwent tracheostomy and skin grafting had higher survival rates during acute burn care (tracheostomy: mortality vs survival, 15.7% vs 30.2%; P = 0.0257; skin grafting: mortality vs survival, 57.4% vs 76.2%; P = 0.0134). Multivariate regression analysis showed that tracheostomy group significantly presented with lower mortality risk by 65% (odds ratio [OR], 0.35; P = 0.0372), and subgroup analysis of delaminating follow-up duration showed that patients with tracheostomy had higher overall survival by 22% (90-day postburn mortality: nontracheostomy vs tracheostomy, 58.3% vs 36.3%; adjusted hazards ratio, 0.39; 95% confidence interval, 0.22-0.69; P = 0.0011), especially during postburn first 30 days (adjusted hazards ratio, 0.15; 95% confidence interval, 0.05-0.49; P = 0.0016). Total body surface area did not significantly affect survival; however, mortality risk was significantly higher in those with a larger TBSA (TBSA, ≥80%; OR, 6.48; P = 0.0022; TBSA, 60-79%; OR, 3.12; P = 0.0518; TBSA, 40-59%; OR, 1.88; P = 0.2402; TBSA, 30-39% as reference). CONCLUSIONS: For patients with major burn-induced AKI receiving RRT, tracheostomy and skin grafting may improve survival in the cases living through acute burn stage.