Sascha Dublin

Elective induction of labor at term compared with expectant management: maternal and neonatal outcomes.

OBJECTIVE: To test the association of elective induction of labor at term compared with expectant management and maternal and neonatal outcomes. METHODS: This was a retrospective cohort study of all deliveries without prior cesarean delivery in California in 2006 using linked hospital discharge and vital statistics data. We compared elective induction at each term gestational age (37–40 weeks) as defined by The Joint Commission with expectant management in vertex, nonanomalous, singleton deliveries. We used multivariable logistic regression to test the association of elective induction and cesarean delivery, operative vaginal delivery, maternal third- or fourth-degree lacerations, perinatal death, neonatal intensive care unit admission, respiratory distress, shoulder dystocia, hyperbilirubinemia, and macrosomia (birth weight greater than 4,000 g) at each gestational week, stratified by parity. RESULTS: The cesarean delivery rate was 16%, perinatal mortality was 0.2%, and neonatal intensive care unit admission was 6.2% (N=362,154). The odds of cesarean delivery were lower among women with elective induction compared with expectant management across all gestational ages and parity (37 weeks [odds ratio (OR) 0.44, 95% confidence interval (CI) 0.34–0.57], 38 weeks [OR 0.43, 95% CI 0.38–0.50], 39 weeks [OR 0.46, 95% CI 0.41–0.52], 40 weeks [OR 0.57, CI 0.50–0.65]). Elective induction was not associated with increased odds of severe lacerations, operative vaginal delivery, perinatal death, neonatal intensive care unit admission, respiratory distress, shoulder dystocia, or macrosomia at any term gestational age. Elective induction was associated with increased odds of hyperbilirubinemia at 37 and 38 weeks of gestation and shoulder dystocia at 39 weeks of gestation. CONCLUSION: Elective induction of labor is associated with decreased odds of cesarean delivery when compared with expectant management. LEVEL OF EVIDENCE: II

Proton Pump Inhibitor Use and Dementia Risk: Prospective Population‐Based Study

To determine whether higher cumulative proton pump inhibitor (PPI) exposure is associated with greater dementia risk.

Use of Analgesics (Opioids and Nonsteroidal Anti-Inflammatory Drugs) and Dementia-Related Neuropathology in a Community-Based Autopsy Cohort

BACKGROUND Opioids may influence the development of Alzheimers disease (AD). Some studies have observed AD pathology in the brains of opioid abusers. No study has examined the association between prescription opioid use and dementia-related neuropathologic changes. OBJECTIVE To examine the relationship between prescription opioid or NSAID use and dementia-related neuropathologic changes. METHODS Within a community-based autopsy cohort (N = 420), we ascertained opioid and nonsteroidal anti-inflammatory drug (NSAID) use over a 10-year period from automated pharmacy data and calculated total standardized daily doses (TSDDs). A neuropathologist assessed outcomes including neuritic plaques, neurofibrillary tangles, and macroscopic infarcts. Outcome measures were dichotomized using established cutpoints. We used modified Poisson regression to calculate adjusted relative risks (RR) and 95% confidence intervals (CI), accounting for participant characteristics and using weighting to account for possible selection bias related to selection into the autopsy sample. RESULTS Heavier opioid exposure was not associated with greater neuropathologic changes. For neuritic plaques, the adjusted RR [95% CI] was 0.99 [0.64-1.47] for 91+ TSDDs of opioids versus little to no use, and for neurofibrillary tangles, 0.97 [0.49-1.78]. People with heavy NSAID use had higher risk of neuritic plaques (RR 1.39 [1.01-1.89]) than those with little to no use, as we have previously reported. Neither opioid nor NSAID use was associated with higher risk of macroscopic infarcts or with Lewy body disease. CONCLUSION Prescription opioid use is not associated with dementia-related neuropathologic changes, but heavy NSAID use may be. More research is needed examining chronic pain, its pharmacologic treatments, and neuropathologic changes.

Risk of Alzheimer's disease or dementia following a cancer diagnosis

Objective We evaluated dementia and Alzheimer’s disease (AD) risks after a cancer diagnosis in a population-based prospective cohort, the Adult Changes in Thought (ACT) study. Methods We followed community-dwelling people aged ≥65 years without dementia at study entry for incident dementia and AD from 1994–2015. We linked study data with cancer registry data and categorized cancer diagnoses as prevalent (diagnosed before ACT study enrollment) or incident (diagnosed during follow-up). We used Cox regression to estimate cause-specific hazard ratios (HRs) with 95% confidence intervals (CIs) for dementia or AD risk comparing people with a cancer diagnosis to people without cancer. We conducted sensitivity analyses restricted to people surviving beyond age 80, and stratified by cancer stage, type, and whether the cancer was smoking-related. Results Among 4,357 people, 756 (17.4%) had prevalent cancer; 583 (13.4%) developed incident cancer, 1,091 (25.0%) developed dementia, and 877 (20.1%) developed AD over a median 6.4 years (34,482 total person-years) of follow-up. Among complete cases (no missing covariates) with at least one follow-up assessment, adjusted HRs for dementia following prevalent and incident cancer diagnoses were 0.92 (95%CI: 0.76, 1.11) and 0.87 (95%CI: 0.64, 1.04), compared to no cancer history. HRs for AD were 0.95 (95%CI: 0.77, 1.17) for prevalent cancer and 0.73 (95%CI: 0.55, 0.96) for incident cancer. In sensitivity analyses, prevalent late-stage cancers were associated with reduced risks of dementia (HR = 0.51, 95%CI: 0.30, 0.89) and AD (HR = 0.50, 95%CI: 0.27, 0.94). When limited to people who survived beyond age 80, incident cancers were still associated with reduced AD risk (HR = 0.69, 95%CI: 0.51, 0.92). Conclusions Our results do not support an inverse association between prevalent cancer diagnoses, which were primarily early-stage, less aggressive cancers, and risk of dementia or AD. A reduced risk of AD following an incident cancer diagnosis is biologically plausible but may reflect selective mortality.

Prevalence of prescription opioid use disorder among chronic opioid therapy patients after health plan opioid dose and risk reduction initiatives

BACKGROUND No studies have assessed the comparative effectiveness of guideline-recommended interventions to reduce risk of prescription opioid use disorder among chronic opioid therapy (COT) patients. We compared the prevalence of prescription opioid use disorder among COT patients from intervention clinics that had implemented opioid dose and risk reduction initiatives for more than 4 years relative to control clinics that had not. METHODS After a healthcare system in Washington State implemented interventions to reduce opioid dose and risks, we surveyed 1588 adult primary care COT patients to compare the prevalence of prescription opioid use disorder among COT patients from the intervention and control clinics. Intervention clinics managed COT patients at lower COT doses and with more consistent use of risk reduction practices. Control clinics cared for similar COT patients but prescribed higher opioid doses and used COT risk reduction practices inconsistently. Prescription opioid use disorder was assessed with the Psychiatric Research Interview for Substance and Mental Disorders. RESULTS The prevalence of prescription opioid use disorder was 21.5% (95% CI=18.9% to 24.4%) among COT patients in the intervention clinics and 23.9% (95% CI=20.5% to 27.6%) among COT patients in the control clinics. The adjusted relative risk of prescription opioid use disorder was 1.08 (95% CI=0.89, 1.32) among the control clinic patients relative to the intervention clinic patients. CONCLUSIONS Long-term implementation of opioid dose and risk reduction initiatives was not associated with lower rates of prescription opioid use disorder among prevalent COT patients. Extreme caution should be exercised by clinicians considering COT for patients with chronic non-cancer pain until benefits of this treatment and attendant risks are clarified.

Comparing Pain and Depressive Symptoms of Chronic Opioid Therapy Patients Receiving Dose Reduction and Risk Mitigation Initiatives With Usual Care

Dose reduction and risk mitigation initiatives have been recommended to reduce opioid-related risks among patients receiving chronic opioid therapy (COT), but questions remain over whether these initiatives worsen pain control and quality of life. In 2014 to 2015, we interviewed 1,588 adult COT patients within a health care system in Washington State and compared those who received dose reduction and risk mitigation initiatives in primary care clinics (intervention) with patients in comparable health care settings without initiatives (control). The primary outcomes were pain assessed using the pain, enjoyment, and general activity (PEG) scale, a 3-item scale to assess global pain intensity and interference, with secondary measures including depression (Patient Health Questionnaire-8 scale). Generalized estimating equations for linear regression models were used to estimate differences in mean scores between intervention and control sites. Estimated differences, adjusted for patient characteristics and weighted for nonresponse, between patients at intervention and control clinics were not clinically significant for the PEG (-.03, 95% confidence interval = -.25 to .19) or Patient Health Questionnaire-8 (-.64, 95% confidence interval = -1.19 to -.08). We found no evidence that COT patients in clinics with dose reduction and risk mitigation initiatives had clinically meaningful differences in pain intensity, interference with activities and enjoyment of life, or depressive symptoms compared with control health care settings. PERSPECTIVE This article evaluates the effect of dose reduction and risk mitigation initiatives, such as those recently recommended by the Centers for Disease Control and Prevention, to reduce risks associated with COT on global pain and interference, depressive symptoms, and perceived pain relief and bothersomeness of side effects.

Associations between Use of Specific Analgesics and Concentrations of Amyloid-β 42 or Phospho-Tau in Regions of Human Cerebral Cortex

Analgesics are commonly used by older adults, raising the question of whether their use might contribute to dementia risk and neuropathologic changes of Alzheimers disease (AD). The Adult Changes in Thought (ACT) study is a population-based study of brain aging and incident dementia among people 65 years or older who are community dwelling and not demented at entry. Amyloid-β (Aβ)42 and phospho-tau were quantified using Histelide in regions of cerebral cortex from 420 brain autopsies. Total standard daily doses of prescription opioid and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) exposure during a defined 10-year exposure window were identified using automated pharmacy dispensing data and used to classify people as having no/low, intermediate, or high exposure. People with high NSAID exposure had significantly greater Aβ42 concentration in middle frontal gyrus and superior and middle temporal gyri, but not inferior parietal lobule; no Aβ42 regional concentration was associated with prescription opioid usage. People with high opioid usage had significantly greater concentration of phospho-tau in middle frontal gyrus than people with little-to-no opioid usage. Consistent with our previous studies, findings suggest that high levels of NSAID use in older individuals may promote Aβ42 accumulation in cerebral cortex.

Impact of Chronic Opioid Therapy Risk Reduction Initiatives on Opioid Overdose

We assessed the effects of opioid dose and risk reduction initiatives on opioid overdose rates among patients on chronic opioid therapy (COT). Using an interrupted time series design, we compared trends in overdose rates. We compared patients on COT in settings that implemented a COT dose reduction initiative and then a COT risk stratification/monitoring initiative to similar patients on COT from control settings. From 2006 to 2014, 31,142 patients on COT (22,673 intervention, 8,469 control) experienced 311 fatal or nonfatal opioid overdoses. In primary analyses, changes in opioid overdose rates among patients on COT did not differ significantly between intervention and control settings with the implementation of either dose reduction or risk stratification/monitoring. In planned secondary analyses, overdose rates decreased significantly (17% per year) during the dose reduction initiative among patients on COT in intervention settings (relative annual change, 0.83; 95% confidence interval, 0.70-0.99), but not in control settings (0.98. 95% confidence interval, 0.70-1.39). We conclude that overdose rates among patients on COT were not decreased by risk stratification and monitoring initiatives. Results were inconsistent for COT dose reduction, with no significant difference between intervention and control settings (primary hypothesis test), but a significant decrease in overdose rates within the intervention setting during dose reduction (secondary hypothesis test). PERSPECTIVE: Risk stratification/monitoring interventions among patients on COT did not decrease opioid overdose rates. The effects of COT dose reduction on opioid overdose rates were inconsistent. Greater decreases in COT dose, a larger control group, or both may have been needed to identify conclusive reductions in opioid overdose rates.

Proton pump inhibitor use and the risk of fractures among an older adult cohort

The purpose of the study is to determine if the use of a proton pump inhibitor (PPI) is associated with an increased fracture risk, as some prior studies have suggested.