Association Between Gestational Diabetes Mellitus and Hypertension: A Systematic Review and Meta-Analysis of Cohort Studies With a Quantitative Bias Analysis of Uncontrolled Confounding.

BACKGROUND: Whether individuals with gestational diabetes (GDM) had an increased risk of hypertension remains unclear. We conducted a systematic literature review and meta-analysis to examine the association between GDM and hypertension and performed a quantitative bias analysis to quantify the impact of uncontrolled confounding due to antenatal psychological stress. METHODS: We searched databases (PUBMED, EMBASE, and Web of Science) through 2022/11. Eligible studies were cohort studies that reported the association of GDM with hypertension. We assessed the risk of bias using the Newcastle-Ottawa Scale for cohort studies. We pooled adjusted risk ratios with 95% CIs using a random effects model. We performed the quantitative bias analysis using the bias formula. RESULTS: We included 15 cohort studies, with a total of 3 959 520 (GDM, 175 378; non-GDM, 3 784 142) individuals. During the follow-up of 2 to 20 years, 106 560 cases of hypertension were reported. We found that GDM was associated with a higher risk of hypertension (pooled risk ratio, 1.78 [95% CI, 1.47, 2.17]). The risk ratio was lower among cohorts assessing incident (1.58 [95% CI, 1.29, 1.95]) than prevalent hypertension (2.60 [95% CI, 2.40, 2.83]). However, other subgroup analyses showed no differences. The quantitative bias analysis revealed that if the uncontrolled confounder of antenatal psychological stress was additionally adjusted, the positive association between GDM and hypertension would attenuate slightly (≤18%) but remains positive. CONCLUSIONS: Limitations of this study included residual confounding and discrepancies in GDM and hypertension ascertainments. Our findings indicate that GDM is positively associated with hypertension after the index pregnancy.

Prevalence of maternal hyperglycemic subtypes by race/ethnicity and associations between these subtypes with adverse pregnancy outcomes: Findings from a large retrospective multi-ethnic cohort in the United States.

AIMS: With the two-step gestational diabetes mellitus (GDM) screening approach, hyperglycemic subtypes can be identified. We aimed to investigate racial/ethnic differences in the prevalence of hyperglycemic subtypes and to examine the associations between these subtypes and adverse pregnancy outcomes. METHODS: In this retrospective cohort, 11,405 pregnancies were screened using the two-step approach. Hyperglycemic subtypes included: pregnancy-impaired glucose intolerance-I (PIGT-I), PIGT-II, GDM-I (abnormal post-load glucose only), and GDM-II (abnormal fasting & post-load glucose). Modified Poisson regressions with robust error variance were used to estimate age-adjusted prevalence ratios (PR) of hyperglycemic subtypes and multivariable-adjusted risk ratios (RR) of adverse pregnancy outcomes. RESULTS: The prevalence of hyperglycemic subtypes was higher in Asians (PIGT-I: 1.51 [95% confidence interval 1.35-1.69]; PIGT-II: 2.18 [1.78-2.68]; GDM-I: 2.55 [2.10-3.10]; GDM-II: 1.55 [1.08-2.21]) and Hispanics (PIGT-I: 1.32 [1.16-1.50]; PIGT-II: 2.07 [1.67-2.57]; GDM-I: 1.69 [1.35-2.13]; GDM-II: 2.68 [1.93-3.71]) than non-Hispanic Whites (NHW). Despite low GDM prevalence, Japanese and Koreans had higher PIGT prevalence than NHW. PIGT-II was positively associated with hypertensive disorders of pregnancy (1.19 [1.02-1.38]), large-for-gestational age (1.73 [1.37-2.18]), and preterm birth (PB, 1.33 [1.05-1.68]). PIGT-I (1.23 [1.04-1.45]) and GDM-I (1.56 [0.87-1.71]) were positively related to PB. CONCLUSIONS: The prevalence of hyperglycemic subtypes varies by race/ethnicity and they have distinct health implications.

Nativity and the risk of opioid use disorder among Hispanic/Latinx women in primary care in Los Angeles, CA.

BACKGROUND: While rates of opioid use disorder (OUD) are lower among women compared to men, nativity may have disproportionate impacts on OUD risk among Hispanic/Latinx women but remain understudied. OBJECTIVE: To assess the association between country of birth and reported OUD risk among low-income Hispanic/Latinx women in primary care in Los Angeles, CA. METHODS: This was a cross-sectional study of 1189 non-pregnant, Hispanic/Latinx women attending two federally qualified health centers in Los Angeles between March and July 2013. OUD risk was assessed using the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST), and moderate-to-high risk was defined as ASSIST score ≥ 4. RESULTS: Overall, 4.2% of women (n = 49) were at moderate-to-high risk for OUD. Risk for OUD was higher among US-born women compared to foreign-born women (6.7 vs. 1.7%; p < .01), those who reported 2+ chronic medical conditions (p < .01), and those who were at moderate-to-high risk for other substance use disorders (p < .01). In multivariable logistic regression analyses, being U.S.-born was independently associated with being at moderate-to-high risk for OUD among Hispanic/Latinx women as compared to those who were foreign-born (AOR = 2.8; 95% CI 1.2-6.8). CONCLUSION: Among low-income Hispanic/Latinx women presenting to primary care, one in twenty patients is at-risk for OUD. The odds of moderate-high risk of OUD were three times as high in US-born compared to foreign-born women, and higher among those with chronic medical conditions and those at risk of other substance use disorders. Gender-specific and culturally-tailored screening for OUD may inform overdose prevention interventions for US-born Hispanic/Latinx women.

Gestational diabetes mellitus and risk of neurodevelopmental disorders in young offspring: does the risk differ by race and ethnicity?

BACKGROUND: Previous studies examined the associations of gestational diabetes mellitus with autism spectrum disorder and attention deficit hyperactivity disorder. However, the associations between gestational diabetes mellitus and other neurodevelopmental disorders, such as the common speech/language disorder and developmental coordination disorder, are rarely studied, and whether the associations vary by race/ethnicity remains unknown. OBJECTIVE: This study aimed to examine the associations of gestational diabetes mellitus with individual neurodevelopmental disorders in young offspring, and to investigate whether the associations vary by race/ethnicity. STUDY DESIGN: This retrospective cohort study (Glucose in Relation to Women and Babies' Health [GrownB]) included 14,480 mother-offspring pairs in a large medical center in the United States from March 1, 2013 to August 31, 2021. We ascertained gestational diabetes mellitus using the validated ICD (International Classification of Diseases) codes (ICD-9: 648.8x; ICD-10: O24.4x), and identified neurodevelopmental disorders (speech/language disorder, developmental coordination disorder, autism spectrum disorder, and other neurodevelopmental disorders [attention deficit hyperactivity disorder, behavioral disorder, intellectual disability, and learning difficulty]) and their combinations using validated algorithms. We compared the hazard of neurodevelopmental disorders during the entire follow-up period between offspring born to mothers with and without gestational diabetes mellitus using multivariable Cox regression models. RESULTS: Among all mothers, 19.9% were Asian, 21.8% were Hispanic, 41.0% were non-Hispanic White, and 17.3% were of other/unknown race/ethnicity. During the median follow-up of 3.5 years (range, 1.0-6.3 years) after birth, 8.7% of offspring developed at least 1 neurodevelopmental disorder. Gestational diabetes mellitus was associated with a higher risk of speech/language disorder (adjusted hazard ratio, 1.59 [95% confidence interval, 1.07-2.35]), developmental coordination disorder (2.36 [1.37-4.04]), autism spectrum disorder (3.16 [1.36-7.37]), other neurodevelopmental disorders (3.12 [1.51-6.47]), any neurodevelopmental disorder (1.86 [1.36-2.53]), the combination of speech/language disorder and autism spectrum disorder (3.79 [1.35-10.61]), and the combination of speech/language disorder and developmental coordination disorder (4.22 [1.69-10.51]) among offspring born to non-Hispanic White mothers. No associations between gestational diabetes mellitus and any neurodevelopmental disorders or their combinations were observed among offspring born to mothers of other racial/ethnic groups. CONCLUSION: We observed an elevated risk of neurodevelopmental disorders among young offspring born to non-Hispanic White mothers with gestational diabetes mellitus, but not among other racial/ethnic groups.

The impact of maternal pertussis vaccination recommendation on infant pertussis incidence and mortality in the USA: an interrupted time series analysis.

BACKGROUND: Pertussis is a contagious respiratory disease. Maternal tetanus-diphtheria-acellular pertussis vaccination during pregnancy has been recommended by the United States Centres for Disease Control (US CDC) Advisory Committee on Immunization Practices (ACIP) for unvaccinated pregnant women since October 2011 to prevent infection among infants; in 2012, ACIP extended this recommendation to every pregnancy, regardless of previous vaccination status. The population-level effect of these recommendations on infant pertussis is unknown. This study aimed to examine the impact of the 2011/2012 ACIP pertussis recommendation on pertussis incidence and mortality among US infants. METHODS: We used monthly data on pertussis deaths among infants aged <1 year between January 2005 and December 2017 in the CDC Death Data and yearly infant pertussis incidence data from the CDC National Notifiable Disease Surveillance System to perform an interrupted time series analysis, accounting for the passage of the Affordable Care Act. RESULTS: This study included 156 months of data. A potential decline in trend in infant pertussis incidence was noted during the post-recommendations period. No appreciable differences in trend were found in population-level infant pertussis mortality after the guideline changes in both adjusted and unadjusted models. Results were similar for all mortality sensitivity analyses. CONCLUSIONS: The 2011/2012 ACIP maternal pertussis vaccination recommendations were not associated with a population-level change in the trend in mortality, but were potentially associated with a decrease in incidence in the USA between 2005 and 2017.

Association of current substance use treatment with future reduced methamphetamine use in an observational cohort of men who have sex with men in Los Angeles.

INTRODUCTION: Methamphetamine use is highly prevalent among men who have sex with men (MSM), but knowledge of the long-term dynamics, and how they are affected by substance use treatment, is limited. This study aimed to describe trajectories of methamphetamine use among MSM, and to evaluate the impact of treatment for any kind of substance use on frequency of methamphetamine use. METHODS: This analysis used data from a cohort of MSM in Los Angeles, CA, who participated in semi-annual study visits from 2014 to 2022. The study characterized trajectories of methamphetamine use using a continuous time multistate Markov model with three states. States were defined using self-reported frequency of methamphetamine use in the past six months: frequent (daily), occasional (weekly or less), and never. The model estimated the association between receiving treatment for any kind of substance use and changes in state of frequency of methamphetamine use. RESULTS: This analysis included 2348 study visits among 285 individuals who were followed-up for an average of 4.4 years. Among participants who were in the frequent use state, 65 % (n = 26) of those who were receiving any kind of substance use treatment at a study visit had reduced their methamphetamine use at their next visit, compared to 33 % (n = 95) of those who were not receiving treatment. Controlling for age, race/ethnicity, and HIV-status, those who reported receiving current treatment for substance use were more likely to transition from occasional to no use (HR: 1.63, 95 % CI: 1.10-2.42) and frequent to occasional use (HR: 4.25, 95 % CI: 2.11-8.59) in comparison to those who did not report receiving current treatment for substance use. CONCLUSIONS: Findings from this dynamic modeling study provide a new method for assessing longitudinal methamphetamine use outcomes and add important evidence outside of clinical trials that substance use treatment may reduce methamphetamine use.

Drug overdose mortality rates by educational attainment and sex for adults aged 25-64 in the United States before and during the COVID-19 pandemic, 2015-2021.

INTRODUCTION: Dramatic increases in U.S. drug overdose deaths involving synthetic opioids, especially fentanyl, beginning around 2014 have driven a marked progression in overall drug overdose deaths in the U.S., which sharply rose to unprecedented levels amid the COVID-19 pandemic. Disparities in drug overdose deaths by educational attainment (EA) during the fentanyl era of the drug overdose epidemic and its intersection with the COVID-19 pandemic have not been widely scrutinized. METHODS: Utilizing restricted-use mortality data from the National Vital Statistics System and population estimates from the American Community Survey, we estimated annual national age-adjusted mortality rates (AAMRs) from drug overdoses jointly stratified by EA and sex for adults aged 25-64 from 2015 to 2021. State-level AAMRs in 2015 and 2021 were also estimated to examine the geographic variation in the cumulative evolution of EA-related disparities over the course of the analysis period. RESULTS: Nationally, AAMRs rose fastest among persons with at most a high school-level education, whereas little to no change was observed for bachelor's degree holders, widening pre-existing disparities. During the analysis period, the difference in national AAMRs between persons with at most a high school-level education and bachelor's degree holders increased from less than 8-fold (2015) to approximately 13-fold (2021). The national widening of EA-related disparities accelerated amid the COVID-19 pandemic, and they widened in nearly every state. Among non-bachelor's degree holders, national AAMRs increased markedly faster for males. CONCLUSIONS: The widening disparities in drug overdose deaths by EA are a likely indicator of a rapidly increasing socioeconomic divide in drug overdose mortality more broadly. Policy strategies should address upstream socioeconomic drivers of drug use and overdose, particularly among males.

Moderate-to-vigorous intensity physical activity among U.S. adolescents before and during the COVID-19 pandemic: Findings from the Adolescent Brain Cognitive Development Study.

Only 16.1% percent of U.S. adolescents meet the recommendation of at least 60 minutes of moderate-to-vigorous intensity physical activity (MVPA) per day. Studies report declined levels of adolescent MVPA in early stages of the pandemic, but gaps remain in understanding changes beyond the initial three months of the pandemic. This study aims to describe and compare self-reported adolescent MVPA levels at multiple timepoints before and during the COVID-19 pandemic among 11,865 9-11-year-old U.S. adolescents from the Adolescent Brain Cognitive Development (ABCD) Study, including pre-pandemic (September 2016-October 2018), early (May, June, and August 2020), and later (October and December 2020, March 2021) stages of the pandemic. Poisson regression models with robust error variance were used to estimate crude and adjusted prevalence ratios (APRs) of the proportion of adolescents meeting national MVPA guidelines during early and later stages of the pandemic compared to pre-pandemic. The proportion of adolescents meeting MVPA guidelines decreased from pre (16.4%), early (11.0%), and later (4.7%) COVID-19 pandemic timepoints. Adolescent MVPA guideline adherence at early- and later-pandemic stages was 24% lower (APR 0.76, 95% CI 0.62, 0.93) and 68% lower (APR 0.32, 95% CI 0.24, 0.43) than pre-pandemic adherence, respectively. Weekly MVPA duration decreased throughout May 2020 to March 2021 (χ2 = 488.9, p < 0.0001). Study findings build upon existing evidence that the low achievement of national MVPA guidelines before the pandemic became even lower during the pandemic, demonstrating the need to support and improve access to adolescent MVPA opportunities during COVID-19 pandemic recovery efforts and in future pandemics.

Breaking Research Silos and Stimulating "Innovation at the Edges" in Epidemiology.

Epidemiological training often requires specialization in a subdiscipline (e.g., pharmacoepidemiology, genetic epidemiology, social epidemiology, or infectious disease epidemiology). While specialization is necessary and beneficial, it comes at the cost of decreased awareness of scientific developments in other subdisciplines of epidemiology. In this commentary, we argue for the importance of promoting an exchange of ideas across seemingly disparate epidemiologic subdisciplines. Such an exchange can lead to invaluable opportunities to learn from and merge knowledge across subdisciplines. It can promote "innovation at the edges," a process of borrowing and transforming methods from one subdiscipline in order to develop something new and advance another subdiscipline. Further, we outline specific actionable steps at the researcher, institution, and professional society level that can promote such innovation.

Comparing the performance of statistical methods that generalize effect estimates from randomized controlled trials to much larger target populations.

Policymakers use results from randomized controlled trials to inform decisions about whether to implement treatments in target populations. Various methods - including inverse probability weighting, outcome modeling, and Targeted Maximum Likelihood Estimation - that use baseline data available in both the trial and target population have been proposed to generalize the trial treatment effect estimate to the target population. Often the target population is significantly larger than the trial sample, which can cause estimation challenges. We conduct simulations to compare the performance of these methods in this setting. We vary the size of the target population, the proportion of the target population selected into the trial, and the complexity of the true selection and outcome models. All methods performed poorly when the trial size was only 2% of the target population size or the target population included only 1,000 units. When the target population or the proportion of units selected into the trial was larger, some methods, such as outcome modeling using Bayesian Additive Regression Trees, performed well. We caution against generalizing using these existing approaches when the target population is much larger than the trial sample and advocate future research strives to improve methods for generalizing to large target populations.

A Two-stage Approach for Rapid Assessment of the Proportion Achieving Viral Suppression Using Routine Clinical Data.

BACKGROUND: Improving viral suppression among people with HIV reduces morbidity, mortality, and transmission. Accordingly, monitoring the proportion of patients with a suppressed viral load is important to optimizing HIV care and treatment programs. But viral load data are often incomplete in clinical records. We illustrate a two-stage approach to estimate the proportion of treated people with HIV who have a suppressed viral load in the Dominican Republic. METHODS: Routinely collected data on viral load and patient characteristics were recorded in a national database, but 74% of patients on treatment at the time of the study did not have a recent viral load measurement. We recruited a subset of these patients for a rapid assessment that obtained additional viral load measurements. We combined results from the rapid assessment and main database using a two-stage weighting approach and compared results to estimates obtained using standard approaches to account for missing data. RESULTS: Of patients with recent routinely collected viral load data, 60% had a suppressed viral load. Results were similar after applying standard approaches to account for missing data. Using the two-stage approach, we estimated that 77% (95% confidence interval [CI] = 74, 80) of those on treatment had a suppressed viral load. CONCLUSIONS: When assessing the proportion of people on treatment with a suppressed viral load using routinely collected data, applying standard approaches to handle missing data may be inadequate. In these settings, augmenting routinely collected data with data collected through sampling-based approaches could allow more accurate and efficient monitoring of HIV treatment program effectiveness.

Prevalence of prescription and illicit drugs in suicides by non-poisoning means in the National Violent Death Reporting System 2003-2017.

Background: Prescription and illicit drugs are important social environmental variables in many suicides regardless of their role as an immediate cause of death. Objectives: To investigate the presence of prescription and illicit drugs, either through mention in the death record or toxicology reports, among suicides attributed to nonpoisonous causes to identify patterns of risk. Methods: Using the 2003-2017 National Violent Death Reporting System (NVDRS), we examined the presence of prescription and illicit drugs among 143,175 suicides (119,563 males 23,612 females) due to firearms and suffocation/hanging. The presence of drugs (opioids, stimulants, benzodiazepines, muscle relaxants, and cannabis) was determined from toxicology reports and text searches of coroner/medical examiner and law enforcement summaries. We fit multivariable logistic regression models to estimate associations between drug class and suicide method adjusting for decedent characteristics. Results: Overall prescription and illicit drugs were present in 22% of firearm deaths and 28% of suffocation deaths. Among victims with toxicology reports, over 20% tested positive for benzodiazepines. Benzodiazepines were mentioned in 4% of firearm and 5% of suffocation suicides without toxicology testing. Stimulants were more likely to occur in suffocation than firearm deaths among victims with toxicology testing (aOR = 1.44, 95% CI: 1.33-1.56) and without toxicology testing (aOR = 1.61, 95% CI: 1.31-1.98). Conclusions: Benzodiazepines were most frequently identified in both toxicology reports and narratives of suicides by firearms or suffocation. Better distinction of the presence of prescription and illicit drugs in the environment versus apparent ingestion among non-poisoning suicides are needed to inform prevention approaches.

Accounting for lack of representation in dementia research: Generalizing KHANDLE study findings on the prevalence of cognitive impairment to the California older population.

INTRODUCTION: Most dementia studies are not population-representative; statistical tools can be applied to samples to obtain critically-needed population-representative estimates, but are not yet widely used. METHODS: We pooled data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study and the California Behavioral Risk Factor Surveillance System (CA-BRFSS), a population-representative study. Using weights accounting for sociodemographic/health differences between KHANDLE and CA-BRFSS, we estimated cognitive impairment prevalence and age- and sex-adjusted racial/ethnic inequalities in California adults 65+ without prior dementia diagnosis. RESULTS: After weighting KHANDLE, the estimated cognitive impairment prevalence in California was 20.3% (95% confidence interval 17.8-23.0); unweighted prevalence was 24.8% (23.1%-26.6%). Inequalities (larger prevalences) were observed among Black and Asian groups versus whites. DISCUSSION: We used a novel statistical approach to estimate population-representative cognitive impairment prevalence and inequalities. Such statistical tools can help obtain population-representative estimates from existing studies and inform efforts to reduce racial/ethnic disparities.

Mental Health Conservatorship Among Homeless People With Serious Mental Illness.

OBJECTIVE: The purpose of this study was to examine associations between homelessness and length of psychiatric hospitalization and to explore the role of mental health conservatorship in determining discharge location for patients who are homeless and have a grave disability from serious mental illness. METHODS: This observational study used administrative data from a safety-net psychiatric hospital in Los Angeles. The sample included 795 adults (≥18 years) who were hospitalized on an involuntary psychiatric hold between 2016 and 2018. The outcome variables were length of stay (days) and discharge location (home, locked psychiatric facility, unlocked psychiatric facility, unhoused). The predictor variables were homelessness status and whether a mental health conservatorship was initiated during hospitalization. Multiple regression models were used to estimate associations between variables. RESULTS: Homelessness status was associated with 27.5 additional days (SE=3.5 days) of hospitalization in adjusted models. Homeless patients for whom conservatorship was initiated comprised 6% of the sample but 41% of total inpatient days. Among people who were homeless, initiation of a conservatorship was associated with significantly longer length of inpatient stay (mean=154.8 days versus 25.6 days for the whole sample) but also with lower odds of being unhoused at the time of discharge (risk ratio=0.19, 95% confidence interval=0.09-0.34). CONCLUSIONS: A mental health conservatorship can be a mechanism for helping homeless people with a grave disability from mental illness to transition from the streets to residential psychiatric treatment, but it requires substantial resources from facilities that initiate such conservatorships and does not guarantee resolution of long-term supportive housing needs.

Effort-Reward Imbalance at Work and Drug Misuse: Evidence from a National Survey in the U.S.

With the rise of drug misuse among workers in recent years, preliminary research on potential risk factors in the workplace of single-type of drug misuse has been reported. This is the first study to examine cross-sectional associations of work stress, in terms of effort-reward imbalance, with multiple drug misuse (including any drug misuse, opioid misuse, sedatives misuse, cannabis misuse, and other drug misuse) during the past 12 months in a national sample of U.S. workers. Data of 2211 workers were derived from the nationally representative and population-based Midlife in the United States (MIDUS) study. Internal consistency reliability and factorial validity of a 17-item effort-reward imbalance measure were robust and satisfactory. After adjustment for relevant covariates, logistic regression analyses showed that workers experiencing effort-reward imbalance at work had significantly higher odds of any drug misuse (OR and 95% CI = 1.18 (1.03, 1.37)), especially opioid misuse (OR and 95% CI = 1.35 (1.07, 1.69)) and other drug misuse (OR and 95% CI = 1.36 (1.01, 1.83)). The findings suggest that a stressful work environment may act as a determinant of drug misuse, and further prospective evidence is needed.

Generalizability of Subgroup Effects.

Generalizability methods are increasingly used to make inferences about the effect of interventions in target populations using a study sample. Most existing methods to generalize effects from sample to population rely on the assumption that subgroup-specific effects generalize directly. However, researchers may be concerned that in fact subgroup-specific effects differ between sample and population. In this brief report, we explore the generalizability of subgroup effects. First, we derive the bias in the sample average treatment effect estimator as an estimate of the population average treatment effect when subgroup effects in the sample do not directly generalize. Next, we present a Monte Carlo simulation to explore bias due to unmeasured heterogeneity of subgroup effects across sample and population. Finally, we examine the potential for bias in an illustrative data example. Understanding the generalizability of subgroup effects may lead to increased use of these methods for making externally valid inferences of treatment effects using a study sample.

Geographical and socioeconomic disparities in opioid access in Mexico, 2015-19: a retrospective analysis of surveillance data.

BACKGROUND: In 2015, Mexico implemented regulatory changes and an electronic system to improve access to prescription opioids. We aimed to investigate trends in opioid dispensing after the implementation of these changes and assess how opioid dispensing varied geographically and by socioeconomic status. METHODS: In this retrospective analysis of prescription medication surveillance data, we analysed dispensing data for group 1 medications (all opioids, including morphine, methadone, hydromorphone, oxycodone, tapentadol, fentanyl, sufentanil, and remifentanil) obtained from the Federal Commission for the Protection against Sanitary Risk database for 32 states and six large metropolitan areas in Mexico. We calculated crude annual opioid prescriptions per 10 000 people at the national, state, and municipal levels. Adapting methods from the report of the Lancet Commission on Palliative Care and Pain Relief, we calculated the need for palliative opioids by state, and then assessed the observed opioid dispensing rates as a percentage of expected need by geographical socioeconomic status. Within the six major metropolitan areas, we mapped the geocoded location of opioid prescriptions and assessed the association between opioid dispensing and socioeconomic status as well as the association between opioid dispensing and time to US border crossing for areas on the US-Mexico border. FINDINGS: Between June 25, 2015, and Oct 7, 2019, opioid dispensing rates increased by an average of 13% (95% CI 6·8-19·6) per quarter (3 months). The overall national opioid dispensing rate during the study period was 26·3 prescriptions per 10 000 inhabitants. States with a higher socioeconomic status had higher opioid dispensing rates than states with lower socioeconomic status (rate ratio [RR] 1·88, 95% CI 1·33-2·58, p=0·00016) after controlling for the estimated opioid requirement per state, the presence of methadone clinics, and the presence of tertiary hospitals and cancer centres. The same association between opioid dispensing and socioeconomic status was observed in the metropolitan areas, and in those metropolitan areas on the US-Mexico border a 20% decrease (RR 0·80, 95% CI 0·75-0·86) in opioid dispensation was observed per each SD increase (SD 17·1 min) in travel time to the border. INTERPRETATION: Measures introduced by the Mexican federal Government to increase opioid access for patients with palliative care needs were only marginally successful in raising opioid prescription rates. Opioid access should be improved for patients with palliative care needs who live in geographical areas of lower socioeconomic status. FUNDING: US National Institutes of Health.

Adverse childhood experiences (ACEs) and transitions in stages of alcohol involvement among US adults: Progression and regression.

BACKGROUND: Adverse childhood experiences (ACEs) are associated with a number of medical comorbidities. However, there is a paucity of data on the role ACEs play in transitions in stages of alcohol involvement. OBJECTIVE: To examine the association between ACEs and transitions in alcohol problems progression and regression between No Problems, Moderate Problems and Severe Problems stages. PARTICIPANTS AND SETTING: Data from 14,363 male and 19,774 female participants in Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). METHODS: We used latent transition analysis (LTA) with propensity score adjustment to estimate the odds of transitioning across stages of alcohol involvement, between waves, based on the number of types of ACEs experienced. We hypothesized that ACEs would be associated with increased risk of progression and decreased risk of regression. RESULTS: ACEs were associated with progression to higher alcohol involvement stages, with greatest likelihood of progression from No Problems to Severe Problems for those reporting ≥3 ACEs (males: aOR = 4.78 [CI (1.84-12.44)]; females: aOR = 3.81 [CI (1.69-8.57)]). ACEs were also associated with decreased odds of regression to less problematic alcohol involvement stages, with some distinctive patterns of associations in males and in females. CONCLUSIONS: This study suggests that ACEs impact transitions in alcohol involvement in both males and females, affecting both progression and regression. The association is magnified for those with multiple types of ACE exposures. These results highlight the need for prevention, early identification and intervention to mitigate the risks associated with childhood maltreatment.

Comparative Effectiveness of High-Dose Versus Standard-Dose Influenza Vaccine Among Patients Receiving Maintenance Hemodialysis.

RATIONALE & OBJECTIVE: Studies of patients on maintenance dialysis therapy suggest that standard-dose influenza vaccine (SDV) may not prevent influenza-related outcomes. Little is known about the comparative effectiveness of SDV versus high-dose influenza vaccine (HDV) in this population. STUDY DESIGN: Cohort study using data from the US Renal Data System. SETTING & PARTICIPANTS: 507,552 adults undergoing in-center maintenance hemodialysis between the 2010 to 2011 and 2014 to 2015 influenza seasons. EXPOSURES: SDV and HDV. OUTCOMES: All-cause mortality, hospitalization due to influenza or pneumonia, and influenza-like illness during the influenza season. ANALYTIC APPROACH: Patients were eligible for inclusion in multiple yearly cohorts; thus, our unit of analysis was the influenza patient-season. To examine the relationship between vaccine dose and effectiveness outcomes, we estimated risk differences and risk ratios using propensity score weighting of Kaplan-Meier functions, accounting for a wide range of patient- and facility-level characteristics. For nonmortality outcomes, we used competing-risk methods to account for the high mortality rate in the dialysis population. RESULTS: Within 225,215 influenza patient-seasons among adults 65 years and older, 97.4% received SDV and 2.6% received HDV. We observed similar risk estimates for HDV and SDV recipients for mortality (risk difference, -0.08%; 95% CI, -0.85% to 0.80%), hospitalization due to influenza or pneumonia (risk difference, 0.15%; 95% CI, -0.69% to 0.93%), and influenza-like illness (risk difference, 0.00%; 95% CI, -1.50% to 1.08%). Our findings were similar among adults younger than 65 years, as well as within other subgroups defined by influenza season, age group, dialysis vintage, month of influenza vaccination, and vaccine valence. LIMITATIONS: Residual confounding and outcome misclassification. CONCLUSIONS: The HDV does not appear to provide additional protection beyond the SDV against all-cause mortality or influenza-related outcomes for adults undergoing hemodialysis. The additional cost and side effects associated with HDV should be considered when offering this vaccine. Future studies of HDV and other influenza vaccine strategies are warranted.

Association between US Pharmacopeia (USP) monograph standards, generic entry and prescription drug costs.

Despite the importance of pharmacopeial standards, little is known regarding their effect on drug competition. Such information is of particular relevance given the rising costs of prescription drugs and the focus of policy-makers and other stakeholders on addressing these costs. We examined 982 prescription drugs approved by U.S Food and Drug Administration since 1982 to examine the association between U.S. Pharmacopeia (USP) standards, generic entry and prescription costs. The presence of a USP drug product monograph was not associated with the time to the third generic entrant or with the likelihood of having a generic competitor. However, on average, drugs with USP drug product monographs had approximately fifty percent more generic manufacturers in the U.S. than their counterparts after accounting for factors such as market volume, age, route of administration and vintage. This greater competition was associated with an approximate savings of $6.22 billion in 2016, suggesting that USP drug product monographs may play an important role in promoting pharmaceutical competition and reducing prescription drug costs.