Impact of 30-day prescribed opioid dose trajectory on fatal overdose risk: A population-based, statewide cohort study.

BACKGROUND: Both increases and decreases in patients' prescribed daily opioid dose have been linked to increased overdose risk, but associations between 30-day dose trajectories and subsequent overdose risk have not been systematically examined. OBJECTIVE: To examine the associations between 30-day prescribed opioid dose trajectories and fatal opioid overdose risk during the subsequent 15 days. DESIGN: Statewide cohort study using linked prescription drug monitoring program and death certificate data. We constructed a multivariable Cox proportional hazards model that accounted for time-varying prescription-, prescriber-, and pharmacy-level factors. PARTICIPANTS: All patients prescribed an opioid analgesic in California from March to December, 2013 (5,326,392 patients). MAIN MEASURES: Dependent variable: fatal drug overdose involving opioids. Primary independent variable: a 16-level variable denoting all possible opioid dose trajectories using the following categories for current and 30-day previously prescribed daily dose: 0-29, 30-59, 60-89, or ≥90 milligram morphine equivalents (MME). KEY RESULTS: Relative to patients prescribed a stable daily dose of 0-29 MME, large (≥2 categories) dose increases and having a previous or current dose ≥60 MME per day were associated with significantly greater 15-day overdose risk. Patients whose dose decreased from ≥90 to 0-29 MME per day had significantly greater overdose risk compared to both patients prescribed a stable daily dose of ≥90 MME (aHR 3.56, 95%CI 2.24-5.67) and to patients prescribed a stable daily dose of 0-29 MME (aHR 7.87, 95%CI 5.49-11.28). Patients prescribed benzodiazepines also had significantly greater overdose risk; being prescribed Z-drugs, carisoprodol, or psychostimulants was not associated with overdose risk. CONCLUSIONS: Large (≥2 categories) 30-day dose increases and decreases were both associated with increased risk of fatal opioid overdose, particularly for patients taking ≥90 MME whose opioids were abruptly stopped. Results align with 2022 CDC guidelines that urge caution when reducing opioid doses for patients taking long-term opioid for chronic pain.

Longitudinal Care Patterns and Utilization Among Patients With New-Onset Neck Pain by Initial Provider Specialty.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare utilization patterns for patients with new-onset neck pain by initial provider specialty. SUMMARY OF BACKGROUND DATA: Initial provider specialty has been associated with distinct care patterns among patients with acute back pain; little is known about care patterns among patients with acute neck pain. METHODS: De-identified administrative claims and electronic health record data were derived from the Optum Labs Data Warehouse, which contains longitudinal health information on over 200M enrollees and patients representing a mixture of ages and geographical regions across the United States. Patients had outpatient visits for new-onset neck pain from October 1, 2016 to September 30, 2019, classified by initial provider specialty. Utilization was assessed during a 180-day follow-up period, including subsequent neck pain visits, diagnostic imaging, and therapeutic interventions. RESULTS: The cohort included 770,326 patients with new-onset neck pain visits. The most common initial provider specialty was chiropractor (45.2%), followed by primary care (33.4%). Initial provider specialty was strongly associated with the receipt of subsequent neck pain visits with the same provider specialty. Rates and types of diagnostic imaging and therapeutic interventions during follow-up also varied widely by initial provider specialty. While uncommon after initial visits with chiropractors (≤2%), CT, or MRI scans occurred in over 30% of patients with initial visits with emergency physicians, orthopedists, or neurologists. Similarly, 6.8% and 3.4% of patients initially seen by orthopedists received therapeutic injections and major surgery, respectively, compared with 0.4% and 0.1% of patients initially seen by a chiropractor. CONCLUSION: Within a large national cohort, chiropractors were the initial provider for a plurality of patients with new-onset neck pain. Compared with patients initially seen by physician providers, patients treated initially by chiropractors or therapists received fewer and less costly imaging services and were less likely to receive invasive therapeutic interventions during follow-up. LEVEL OF EVIDENCE: 3.

Gender differences in the risk of depressive disorders following the loss of a young child: a nationwide population-based longitudinal study.

BACKGROUND: Losing a child to death is one of the most stressful life events experienced in adulthood. The aim of the current study is to investigate parental risk of seeking treatment for major depression disorders (MDD) after a child's death and to explore whether such connection may operate differentially by parents' prior medical condition. METHODS: We studied a retrospective cohort of 7245 parents (2987 mothers and 4258 fathers) identified in the National Health Insurance Research Database of Taiwan (NHIRD) who had lost a child with age between 1 and 12 years. For comparison, the parents of 1:4 birth year- and gender-matched non-deceased children were retrieved (16,512 mothers and 17,753 fathers). Gender-specific Cox regression analyses were performed to estimate risk. RESULTS: Nearly 5.0% and 2.4% of bereaved mothers and fathers sought treatment for MDD within three years after a child's death, significantly higher than 0.8% and 0.5% in the non-bereaved parents. With covariate adjustment, the hazard ratio (HR) for maternal and paternal seeking treatment for MDD was estimated 4.71 (95% confidence interval [CI]: 3.35-6.64) and 1.93 (95% CI: 1.27-2.95), respectively. The increased risk of MDD varied by prior disease history; specifically, the increased risk of seeking treatment for MDD was especially prominent for those without chronic physical condition (CPC) (e.g., mothers with CPC: aHR = 2.38, 95% CI: 1.56-3.65 vs. no CPC: aHR = 9.55, 95% CI: 6.17-14.79). CONCLUSIONS: After the death of a child, parental elevated risk of MDD was especially prominent for the women and those without prior medical condition. Effective strategies addressing bereavement may require family-based, integrated physical and mental healthcare and even extended counseling service.

Inadequate prenatal care utilization among women with and without methadone-treated opioid use disorders in Taiwan.

AIMS: The present study aims to investigate the utilization pattern of prenatal care and correlates for women with opioid use disorders (OUD) in Taiwan. METHOD: Using the data linkage between the Methadone Maintenance Treatment (MMT) register with national health insurance, national birth notification system, and birth registration system, we identified 1712 pregnancies with 20 or more gestational weeks from women enrolled in the MMT (heroin-exposed: receiving no methadone treatment during pregnancy, n = 1053 by 882 women; methadone-treated: receiving methadone for at least one day during pregnancy, n = 659 by 574 women) and their 1:10 matched pregnancies from 17,060 women without substance use disorder in the period of 2004-2013. The generalized linear mixed models with negative binomial and logit distributions were performed to evaluate the relationship between individual sociodemographic, health, and addiction treatment characteristics with the number of prenatal visits and receiving prenatal care in the first trimester (i.e., early entry). FINDINGS: Eighteen percent of pregnancies by women with OUD received no prenatal services and 21% had started prenatal care in the first trimester as compared with 1% and 46% in pregnancies by women without substance use disorders. For pregnancies by women with OUD, methadone treatment was not linked associated with prenatal care visits (adjusted relative risk [aRR] = 1.02; 95% = 0.92, 1.12). For methadone-treated pregnancies, treatment enrollment before pregnancy and spousal methadone treatment elevated prenatal visits by 8% and 18% (0.48 and 1.08 visits, respectively). Additionally, HIV infection (adjusted odds ratio [aOR] = 0.30, 95% CI = 0.10, 0.83) and prior delivery (aOR = 0.05, 95% CI = 0.01, 0.19) significantly reduced the odds of early entry into prenatal care. CONCLUSION: Integrating addiction treatment programs with prenatal care is urgently needed to increase adequate prenatal care for pregnant women with OUD, especially the multiparous ones.

Seasonal variation of refractive error change among young schoolchildren in a population-based cohort study in Taipei.

PURPOSE: To investigate the relationship between seasonal variation of daylight length and spherical equivalent (SE) progression among the schoolchildren participating in the Myopia Investigation Study in Taipei. METHODS: We used the first-year data from grade 2 schoolchildren who completed all the baseline and two follow-up examinations (n=6790). There were two 6-month intervals between visits over winter and summer, respectively. For each interval, we calculated average daily daylight length using data from Taiwan's Central Weather Bureau and measured 6-month SE progression rate based on right eye cycloplegic autorefraction data. The midpoint month was defined as the month midway between two consecutive visits. RESULTS: By the midpoint month, average daily daylight length was the shortest in December (671±7 min/day) and the longest (785±7 min/day) in June, and SE progression rate was the fastest (-0.23±0.48 D) in December and the slowest (-0.17±0.51 D) in June. Significant variation of SE progression rate with season can be observed only among the schoolchildren (n=1905) whose midpoint months for the winter and summer intervals were December and June (winter rate, -0.25±0.47 D; summer rate, -0.17±0.49 D; p<0.001). Of those, the summer progression rate was approximately 80%, 65% and 61.5% of that measured in winter for myopic (p=0.252), emmetropic (p=0.012) and hyperopic (p=0.012) schoolchildren, respectively. CONCLUSION: Our data demonstrate a seasonal variation of minus shift in refractive error among Taipei schoolchildren who had significant daytime fluctuation during the 1-year follow-up. Of those, non-myopic children had significant and more pronounced variation of SE progression than myopic children.

Excess mortality in children born to opioid-addicted parents: A national register study in Taiwan.

BACKGROUND: Young offspring of individuals with opioid use disorders have great exposure to a wide array of social disadvantages and stressors. This study aimed to investigate excess mortality before the age of six and predictors of premature death in children born to opioid-involved parents. METHODS: A total of 3210 children born between 2004 and 2009 to parents with opioid use disorders (roughly a quarter of whom were born after parental methadone treatment enrollment) were identified in Taiwan. Information concerning sociodemographic characteristics, history of medical condition, and survival status was obtained through data linkage with the National Health Insurance Database and death registration. The age-, birth year-, and sex-adjusted standardized mortality ratios (SMRs) and survival analyses were used to assess risk estimates and evaluate predictors. RESULTS: The overall SMR for children with opioid-involved parents was 2.31 (95% confidence interval [CI] = 1.68-3.10), with the estimate reaching 4.23 (95% CI = 2.37-6.97) when the causes of death were unnatural (e.g., injury and accident). The most salient predictors of premature death were low birth weight and paternal opioid problem severity, which increased risk of premature death 2.5--5.2-fold (all P < 0.05). Being born after parents enrolled in methadone treatment was slightly associated with a reduced risk of death in those mothered by opioid users (adjusted hazard ratio = 0.30). CONCLUSION: The elevated risk of premature death in the offspring of opioid-addicted parents suggests the need to prioritize resource allocation to safeguard this marginalized and vulnerable segment of the pediatric population.

Prevalence and association of refractive anisometropia with near work habits among young schoolchildren: The evidence from a population-based study.

BACKGROUND: Lifestyle behaviour may play a role in refractive error among children, but the association between near work habits and refractive anisometropia remains unclear. METHODS: We estimated the prevalence of refractive anisometropia and examined its association with near work activities among 23,114 children in the Myopia Investigation Study in Taipei who were grade 2 elementary school students at baseline in 2013 and 2014. Baseline data on demographics, medical history, parental history and near work habits were collected by parent-administered questionnaire survey. Refractive status was determined by cycloplegic autorefraction. Refractive anisometropia was defined as the spherical equivalent difference ≥ 1.0 diopter between eyes. RESULTS: The prevalence of refractive anisometropia was 5.3% (95% confidence interval [CI], 5.0% to 5.6%). The prevalence and severity of refractive anisometropia increased with both myopic and hyperopic refractive error. Multivariate logistic regression analysis revealed that refractive anisometropia was significantly associated with myopia (odds ratio [OR], 2.98; 95% CI, 2.53-3.51), hyperopia (OR, 2.37; 95% CI, 1.98-2.83), degree of astigmatism (OR, 1.005; 95% CI, 1.005-1.006), amblyopia (OR, 2.54; 95% CI, 2.06-3.12), male gender (OR, 0.88; 95% CI, 0.78-0.99) and senior high school level of maternal education (OR, 0.69; 95% CI, 0.52-0.92). Though anisometropic children were more likely to spend more time on near work (crude OR, 1.15; 95% CI, 1.02-1.29) and to have less eye-to-object distance in doing near work (crude OR, 1.15; 95% CI, 1.01-1.30), these associations became insignificant after additional adjustment for ocular, demographic and parental factors. CONCLUSIONS: The present study provides large-scale, population-based evidence showing no independent association between refractive anisometropia and near work habits, though myopia is associated with refractive anisometropia.

Risk factors for myopia progression in second-grade primary school children in Taipei: a population-based cohort study.

PURPOSE: To evaluate the 1-year progression of myopia and associated risk factors in second-grade primary school children. METHODS: The myopia investigation study in Taipei provided semiannual visual acuity testing and cycloplegic refraction for all second-grade primary school children (mean age: 7.49 years) in Taipei who provided parental consent. A questionnaire was distributed to the participants' parents before the first and third examinations. We evaluated 1-year follow-up data for children noted to have myopia on the first examination. Multinomial logistic regression models were applied to assess risk factors associated with myopia progression. Myopia progression was categorised, based on the change in spherical equivalent (ΔSE) over 1 year, as slow (ΔSE>-0.5 dioptres (D)), moderate (-1.0 D<ΔSE≤-0.5 D) or fast (ΔSE≤-1.0 D). Of the 4214 myopic children, data were analysed for 3256 (77.3%) who completed the 1-year follow-up evaluation. RESULTS: The baseline SE was -1.43±1.1 D. The average ΔSE was -0.42±0.85 D, with 46.96%, 28.50% and 24.54% of the study subjects showing slow, moderate and fast myopia progression, respectively. When compared with slow myopia progression, fast myopia progression was associated with a greater myopic SE at baseline (OR: 0.67, 95% CI: 0.61 to 0.72) and a shorter eye-object distance when doing near work (OR: 1.45, 95% CI: 1.18 to 1.78). More outdoor activity time and self-reported cycloplegic treatment were not associated with slow myopia progression. CONCLUSIONS: Children with fast annual myopia progression were more myopic at baseline and had a shorter reading distance. Our study results highlight the importance of having children keep a proper reading distance.

Myopia Development Among Young Schoolchildren: The Myopia Investigation Study in Taipei.

Purpose: To investigate the annual incidence of myopia and associated factors among young schoolchildren in Taipei City. Methods: The Myopia Investigation Study in Taipei was a citywide, population-based cohort study. During the fall 2013 semester (baseline), a total of 11,590 grade 2 schoolchildren completed ocular examination and were included for further analysis. A parent-completed questionnaire was administered to collect data on risk factors for myopia development. Follow-up visits were arranged biannually over 3 years. The first-year results are reported here. Schoolchildren who were emmetropic/hyperopic at baseline and had myopia (spherical equivalent ≤ -0.5 diopters) in either eye at follow-up were identified as having incident myopia. Results: Among 7376 baseline nonmyopic participants, 6794 (92.1%) were examined during the first-year follow-up, and 1856 (25.2%) with incident myopia were identified. The incidence density of myopia was 31.7 (95% confidence interval [CI]: 30.6-32.8) per 100 person-years. Cox hazard proportional regression analysis revealed that participants who were emmetropic at baseline (hazards ratio [HR]: 19.37; 95% CI: 4.84-77.57), who had two myopic parents (HR: 1.21; 95% CI: 1.04-1.42), and who spent ≥5 hours every week on after-school tutoring programs (HR: 1.12; 95% CI: 1.02-1.22) had greater risk for incident myopia. By contrast, protective factors included suburban area of residence (HR: 0.91; 95% CI: 0.83-1.00) and spending ≥30 minutes outdoors after school every weekday (HR: 0.90; 95% CI: 0.82-0.99). Conclusions: This study provides population-based data on the annual incidence of myopia among Taiwanese schoolchildren, and found that baseline refractive status, parental myopia, area of residence, time outdoors after school on weekdays, and time spent on after-school tutoring programs are associated with risk of new-onset myopia.

Health insurance coverage and healthcare utilization among infants of mothers in the national methadone maintenance treatment program in Taiwan.

BACKGROUND: Children of heroin-using women have a higher risk of unfavorable health and developmental outcomes. Although methadone maintenance treatment (MMT) has been widely used to treat heroin-using pregnant women, potential effects on accessibility and utilization of healthcare service for their offspring are less explored. METHODS: We used four national registry and health insurance datasets in Taiwan from 2004 to 2009 to form a population-based matched retrospective cohort study. A total of 1056 neonates born to women in the MMT program (857 born before mother's enrollment in the MMT program [BM], 199 born after mother's enrollment in the MMT program [AM]) was established; 10547 matched non-drug [ND] exposed neonates were identified for comparison. Outcome variables included offspring's health insurance coverage and utilization of preventive, outpatient, and emergency room cares in the first year after birth. RESULTS: Infants born to mothers on MMT were more likely to have no or incomplete insurance coverage (BM: adjusted odds ratio [aOR]=1.29, 95% CI: 1.10-1.53; AM: aOR=1.56, 95% CI: 1.14-2.13) as compared with the socioeconomic status-matched ND group. The BM infants appeared to have fewer preventive care visits (adjusted relative risk [aRR]=0.85, 95% CI: 0.80-0.90), whereas the AM infants utilized outpatient and emergency room services more frequently (outpatient: aRR=1.11, 95% CI: 1.01-1.23; emergency: aRR=1.46, 95% CI: 1.11-1.90). CONCLUSIONS: Addiction treatment and harm reduction programs for women of childbearing ages should be delivered in the coordinated framework that ensures comprehensiveness and continuity in healthcare and social services.

Prenatal Infection and Autism Spectrum Disorders in Childhood: A Population-Based Case-Control Study in Taiwan.

BACKGROUND: Infection in pregnancy has long been linked with negative postnatal development and health. This study aims to assess the association between prenatal infections and autism spectrum disorders (ASDs) across three trimesters and to probe possible sex heterogeneity in such link. METHOD: A total of 4184 children with incident ASDs and 16,734 matched children were identified from the 2000-2007 National Health Insurance Research Database. For each child, information pertaining to the mother's infection during pregnancy, sociodemographics, and medical history was retrieved from healthcare records. Conditional logistic analyses were carried out to estimate the strength of associations with adjustment for multiple comparisons. RESULT: Pooled analyses demonstrated that having two or more outpatient visits for genital infection [adjusted odds ratio (aOR): 1.34; 95% confidence interval (95% CI) 1.12, 1.60; false discovery rate (FDR) < 0.01] and bacterial infection (aOR: 1.24; 95% CI 1.06, 1.43; FDR < 0.05) in the third trimester were slightly associated with increased risk of ASDs. No statistically significant sex differences were found. CONCLUSION: The present study contributes updated population-based evidence about the connection between prenatal infection and ASDs. Potential effect of bacterial and genital tract infections during the third trimester on risk of ASDs warrants further exploration.

Overlapping Prescriptions of Stimulants for Children and Adolescents With Attention-Deficit Hyperactivity Disorder.

OBJECTIVES: The study aimed to assess the occurrence of overlapping prescriptions for methylphenidate among children and adolescents with newly diagnosed attention-deficit hyperactivity disorder (ADHD) and to evaluate the extent to which physician-level and patient-level characteristics affected the risk of prescription overlap during a one-year treatment period. METHODS: The analytic sample comprised 3,081 incident cases of ADHD in 2002 involving children aged 17 years or younger from a retrospective cohort study in Taiwan. Medical and pharmacy claims data from 1999 to 2002 were retrieved from the National Health Insurance Program. All records of methylphenidate prescriptions within a year of treatment initiation were retrieved for each patient, and the number of overlapping days for any two successive prescriptions (new, renewal, or refill) was measured. Multilevel analyses were performed to identify predictors of methylphenidate prescription overlap. RESULTS: Within a year of treatment initiation, approximately 3% to 4% individuals with a new diagnosis of ADHD had experienced methylphenidate prescription overlap. Youngsters who resided in a rural region (adjusted odds ratio [AOR]=2.68) or who had ever changed prescribing doctors (AOR=3.04) were more likely to have visits with a methylphenidate prescription overlap. Receiving methylphenidate from physicians aged 46 or older was associated with 3.6-fold increased odds of prescription overlap. CONCLUSIONS: In an effort to improve the quality and safety of prescription of controlled substances in younger populations, interventions or policies should be devised to target both the service providers and the patients.

Gender differences in widowhood effects among community-dwelling elders by causes of death in Taiwan.

PURPOSE: We sought to determine whether widowhood-associated excess mortality differs by gender in terms of causes of death. METHODS: Data were collected from a five-wave interview of approximately 2500 community-dwelling elders in the Survey of Health and Living Status of the Nearly Elderly and Elderly. Baseline characteristics were used to derive the risk score (RS) to reflect individual's baseline pre-widowhood vulnerability. Time-dependent Cox regression analyses were used to estimate spousal loss-related mortality by causes. RESULTS: For males, the adjusted hazard ratios (aHRs) of widowhood for all-cause and some major causes of death (e.g., neoplasm) increased inversely with RS: the aHRs for all-cause death were 4.81 and 1.76 in the lowest and highest RS groups, respectively. In contrast, the corresponding aHRs were relatively homogeneous for women (1.52 and 1.70). CONCLUSIONS: Identifying gender heterogeneity in widowhood effects can guide further efforts to devise gender-tailored programs to enhance healthy aging.

Five-year trajectories of long-term benzodiazepine use by adolescents: patient, provider, and medication factors.

OBJECTIVES: This study sought to understand the stability of and change in benzodiazepine use among incident long-term benzodiazepine users over a five-year period and to investigate predictors of variation in use patterns from adolescence into adulthood. METHODS: Long-term use was defined as receipt of benzodiazepine prescriptions for 31 or more cumulative days in a calendar year. Data for 1999-2005 were obtained from the National Health Insurance Research Database in Taiwan. Two age groups of incident long-term users in 2000 were identified--1,758 aged 12-15 and 5,265 aged 16-19-and their benzodiazepine prescription records from 2001 to 2005 were retrieved. Group-based trajectory analyses and polytomous logistic regression were performed to evaluate differential risk of benzodiazepine use over time. RESULTS: From 3% to 5% of the incident benzodiazepine users were long-term users. Four distinct groups of users emerged from the five years of study data: occasional, decelerating, accelerating, and chronic users. Overall, one-quarter were accelerating or chronic users. A history of psychosis or epilepsy, prescription by providers from multiple specialties, and receipt of benzodiazepines with a long half-life or mixed indications significantly increased one's risk of becoming a chronic or accelerating user (range of adjusted odds ratios from 2 to 6). CONCLUSIONS: Patient characteristics and attributes of service providers and pharmacological agents played significant roles in benzodiazepine use patterns. Prescribers can reduce the risk of long-term use by assessing whether pediatric patients have received benzodiazepines from multiple doctors for various medical conditions.

Predictors of the incidence and discontinuation of long-term use of benzodiazepines: a population-based study.

Long-term use of benzodiazepines (BZDs) has been linked with an array of negative health consequences and increased medical costs and social burden. In this study, we sought to investigate the factors accounting for differential risks in the process from incident BZD use to long-term use and discontinuation in the general population. On the basis of a random sample of 187,413 people enrolled in Taiwan's National Health Insurance program on January 1, 2000, data of 2000-2002 healthcare and pharmacological services utilization were retrieved. Long-term use (LTU) was defined by having received BZD prescriptions for 180 or more days within any given calendar year. Multivariate logistic regression analyses were carried out to assess the strength of associations while adjusting for the effects of individual sociodemographics, service providers, and pharmacological agents simultaneously. Results indicated that males, elderly, and those with physical or mental disorders were more likely to become long-term users of BZDs. Having received BZD prescriptions in multiple pharmacological agents, short-acting or mixed-type agents, and hypnotic indication were associated with a roughly 2- to 5-fold increased risk of BZD LTU soon after prescription initiation. With respect to discontinuation, the effects of pharmacological characteristics seem more salient as compared to those of individual and service-provider factors. Future strategies targeting individual factors and modifying service-provider prescription behaviors may be considered to reduce possible negative consequences of BZD LTU.