Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems.

OBJECTIVE: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. METHODS: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription. RESULTS: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply). CONCLUSIONS: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.

Mouse organoids as an in vitro tool to study the in vivo intestinal response to cytotoxicants.

Cross-species comparison of drug responses at the organoid level could help to determine the human relevance of findings from animal studies. To this end, we first need to evaluate the in vitro to in vivo translatability of preclinical organoids. Here, we used 5-fluorouracil (5-FU) as an exemplar drug to test whether the in vivo gut response to this cytotoxicant was preserved in murine intestinal organoids. Mice treated with 5-FU at 20 or 50 mg/kg IV (low and high dose, respectively) displayed diarrhea at clinically relevant exposures. 5-FU also induced intestinal lesions, increased epithelial apoptosis, and decreased proliferation in a dose-dependent manner. To enable comparison between the in vitro and in vivo response, top nominal in vitro drug concentrations that caused significant cytotoxicity were chosen (dose range 1-1000 µM). The inferred intracellular concentration in organoids at 1000 µM was within the tissue exposure range related to intestinal toxicity in vivo. 5-FU at ≥ 100 µM decreased ATP levels and increased Caspase-3 activity in intestinal organoids. In keeping with the in vivo findings, 5-FU increased the percentage of Caspase-3-positive cells and reduced Ki67 staining. At the transcriptome level, there was an overlap in the activity of pathways related to 5-FU's mode of action, lipid and cholesterol metabolism and integrin signaling across in vivo gut and organoids. The predicted activity state of upstream regulators was generally well preserved between setups. Collectively, our results suggest that despite their inherent limitations, organoids represent an adequate tool to explore the intestinal response to cytotoxicants.

Eosinophil-derived TGFß1 controls the new bone formation in chronic rhinosinusitis with nasal polyps

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by chronic eosinophilic inflammation and new bone formation (NBF). These processes may be associated with each other in the pathogenesis and influence the severity and prognosis of the disease. However, it is still unclear how eosinophilic inflammation is involved in the NBF. METHODOLOGY: Sinus bone cells were isolated from ethmoid bone tissues of patients with CRSwNP and controls. Transforming growth factor beta 1 (TGFß1) and alkaline phosphatase (ALP) expression in sinus bone cells was determined using quantitative RT-PCR, immunoblotting, and immunohistochemistry. The co-localization of TGFß1 with eosinophils was assessed by immunofluorescence staining. Sinus bone cells were co-cultured with eosinophils (Eol-1 cell line), which were differentiated with butyrate, to measure the osteoblast differentiation activity of sinus bone cells. RESULTS: TGFß1 expression was increased in sinus bone tissues and correlated with CT scores in CRSwNP. TGFß1 was also increased in the submucosa of CRSwNP and co-localized predominantly with eosinophils compared with neutrophils Differentiated Eol-1 cells-derived TGFß1 increased ALP expression in sinus bone cells. Treatment with a TGFß inhibitor attenuated TGFß1-induced ALP expression and staining in sinus bone cells of CRSwNP, leading to loss of bone formation. CONCLUSIONS: Eosinophil-derived TGFß1 was enriched in the submucosa of CRSwNP, which induced ALP expression in sinus bone cells and NBF. Therefore, eosinophil-derived TGFß1 may mediate aberrant bone remodeling in CRSwNP.

Increased microchimerism in peripheral blood of women with systemic lupus erythematosus: relation with pregnancy.

OBJECTIVES: We aimed to determine the presence, amount and origin of microchimerism in peripheral blood of pregnant and non-pregnant parous women with systemic lupus erythematosus (SLE) as compared to control subjects. METHODS: We performed a comparative study in which peripheral blood was drawn from eleven female non-pregnant SLE-patients and 22 control subjects, and from six pregnant SLE-patients and eleven control subjects during gestation and up to six months postpartum. Quantitative PCR for insertion-deletion polymorphisms and null alleles was used to detect microchimerism in peripheral blood mononuclear cells and granulocytes. RESULTS: Microchimerism was detected more often in non-pregnant SLE-patients than control subjects (54.4% vs. 13.6%, respectively; p=0.03). When present, the median total number of foetal chimeric cells was 5 gEq/106 in patients and 2.5gEq/106 in control subjects (p=0.048). Microchimerism was mostly foetal in origin; maternal microchimerism was detected in one patient and one control subject. In control subjects, microchimerism was always derived from only one source whereas in 50% of patients it originated from multiple sources. The pregnant patients had a significantly higher median number of foetal chimeric cells in the granulocyte fraction just after delivery than control subjects (7.5 gEq/106 vs. 0 gEq/106, respectively; p=0.02). CONCLUSIONS: Just after delivery, SLE-patients had more microchimerism than control subjects. Three months post-partum, microchimerism was no longer detectable, only to reappear many years after the last pregnancy, more often and at higher levels in SLE-patients than in control subjects. This suggests that these chimeric cells may originate from non-circulating foetal chimeric stem cells.

Clinical implementation of suicide risk prediction models in healthcare: a qualitative study.

BACKGROUND: Suicide risk prediction models derived from electronic health records (EHR) are a novel innovation in suicide prevention but there is little evidence to guide their implementation. METHODS: In this qualitative study, 30 clinicians and 10 health care administrators were interviewed from one health system anticipating implementation of an automated EHR-derived suicide risk prediction model and two health systems piloting different implementation approaches. Site-tailored interview guides focused on respondents' expectations for and experiences with suicide risk prediction models in clinical practice, and suggestions for improving implementation. Interview prompts and content analysis were guided by Consolidated Framework for Implementation Research (CFIR) constructs. RESULTS: Administrators and clinicians found use of the suicide risk prediction model and the two implementation approaches acceptable. Clinicians desired opportunities for early buy-in, implementation decision-making, and feedback. They wanted to better understand how this manner of risk identification enhanced existing suicide prevention efforts. They also wanted additional training to understand how the model determined risk, particularly after patients they expected to see identified by the model were not flagged at-risk and patients they did not expect to see identified were. Clinicians were concerned about having enough suicide prevention resources for potentially increased demand and about their personal liability; they wanted clear procedures for situations when they could not reach patients or when patients remained at-risk over a sustained period. Suggestions for making risk model workflows more efficient and less burdensome included consolidating suicide risk information in a dedicated module in the EHR and populating risk assessment scores and text in clinical notes. CONCLUSION: Health systems considering suicide risk model implementation should engage clinicians early in the process to ensure they understand how risk models estimate risk and add value to existing workflows, clarify clinician role expectations, and summarize risk information in a convenient place in the EHR to support high-quality patient care.

Patient expectations of and experiences with a suicide risk identification algorithm in clinical practice.

BACKGROUND: Suicide risk prediction models derived from electronic health records (EHR) and insurance claims are a novel innovation in suicide prevention but patient perspectives on their use have been understudied. METHODS: In this qualitative study, between March and November 2020, 62 patients were interviewed from three health systems: one anticipating implementation of an EHR-derived suicide risk prediction model and two others piloting different implementation approaches. Site-tailored interview guides focused on patients' perceptions of this technology, concerns, and preferences for and experiences with suicide risk prediction model implementation in clinical practice. A constant comparative analytic approach was used to derive themes. RESULTS: Interview participants were generally supportive of suicide risk prediction models derived from EHR data. Concerns included apprehension about inducing anxiety and suicidal thoughts, or triggering coercive treatment, particularly among those who reported prior negative experiences seeking mental health care. Participants who were engaged in mental health care or case management expected to be asked about their suicide risk and largely appreciated suicide risk conversations, particularly by clinicians comfortable discussing suicidality. CONCLUSION: Most patients approved of suicide risk models that use EHR data to identify patients at-risk for suicide. As health systems proceed to implement such models, patient-centered care would involve dialogue initiated by clinicians experienced with assessing suicide risk during virtual or in person care encounters. Health systems should proactively monitor for negative consequences that result from risk model implementation to protect patient trust.

Prevalence and Medication Treatment of Opioid Use Disorder Among Primary Care Patients with Hepatitis C and HIV.

BACKGROUND: Hepatitis C and HIV are associated with opioid use disorders (OUD) and injection drug use. Medications for OUD can prevent the spread of HCV and HIV. OBJECTIVE: To describe the prevalence of documented OUD, as well as receipt of office-based medication treatment, among primary care patients with HCV or HIV. DESIGN: Retrospective observational cohort study using electronic health record and insurance data. PARTICIPANTS: Adults ≥ 18 years with ≥ 2 visits to primary care during the study (2014-2016) at 6 healthcare systems across five states (CO, CA, OR, WA, and MN). MAIN MEASURES: The primary outcome was the diagnosis of OUD; the secondary outcome was OUD treatment with buprenorphine or oral/injectable naltrexone. Prevalence of OUD and OUD treatment was calculated across four groups: HCV only; HIV only; HCV and HIV; and neither HCV nor HIV. In addition, adjusted odds ratios (AOR) of OUD treatment associated with HCV and HIV (separately) were estimated, adjusting for age, gender, race/ethnicity, and site. KEY RESULTS: The sample included 1,368,604 persons, of whom 10,042 had HCV, 5821 HIV, and 422 both. The prevalence of diagnosed OUD varied across groups: 11.9% (95% CI: 11.3%, 12.5%) for those with HCV; 1.6% (1.3%, 2.0%) for those with HIV; 8.8% (6.2%, 11.9%) for those with both; and 0.92% (0.91%, 0.94%) among those with neither. Among those with diagnosed OUD, the prevalence of OUD medication treatment was 20.9%, 16.0%, 10.8%, and 22.3%, for those with HCV, HIV, both, and neither, respectively. HCV was not associated with OUD treatment (AOR = 1.03; 0.88, 1.21), whereas patients with HIV had a lower probability of OUD treatment (AOR = 0.43; 0.26, 0.72). CONCLUSIONS: Among patients receiving primary care, those diagnosed with HCV and HIV were more likely to have documented OUD than those without. Patients with HIV were less likely to have documented medication treatment for OUD.

A phase 2, randomized, double-blind, placebo-controlled trial of AMG 301, a pituitary adenylate cyclase-activating polypeptide PAC1 receptor monoclonal antibody for migraine prevention.

OBJECTIVE: To assess the safety and efficacy of AMG 301, an inhibitor of the pituitary adenylate cyclase-activating polypeptide (PACAP)-1 (PAC1) receptor, for prevention of migraine. METHODS: In a double-blind trial, patients were randomized 4:3:3 to placebo, AMG 301 210 mg every 4 weeks, or AMG 301 420 mg every 2 weeks for 12 weeks. Effect on monthly migraine days and other secondary measures were assessed over weeks 9-12. Safety and tolerability were assessed. RESULTS: Of 343 randomized patients (mean age, 41.8-42.5 years), the majority were women (85.4-90.4%), white (94.1-96.2%), and had episodic migraine (62.5-67.9%). A total of 305 patients completed treatment (placebo, n = 124; AMG 301 210 mg, n = 94; AMG 301 420 mg, n = 87). Least squares mean reduction at week 12 in monthly migraine days from baseline was -2.5 (0.4) days for placebo and -2.2 (0.5) days for both AMG 301 treatment groups. No difference between AMG 301 and placebo on any measure of efficacy was observed; mean (95% confidence interval) treatment difference versus placebo for monthly migraine days for AMG 301 210 mg, 0.3 (-0.9 to 1.4); AMG 301 420 mg, 0.3 (-0.9 to 1.4). The incidence of adverse events was similar across groups. CONCLUSION: AMG 301 offered no benefit over placebo for migraine prevention; further studies may be necessary to fully understand the role of PACAP isoforms and its receptors in migraine pathophysiology. STUDY REGISTRATION: ClinicalTrials.gov: NCT03238781.

Reduction in acute migraine-specific and non-specific medication use in patients treated with erenumab: post-hoc analyses of episodic and chronic migraine clinical trials.

BACKGROUND: In patients with migraine, overuse of acute medication, including migraine-specific medication (MSM) such as triptans and ergots, can lead to adverse health outcomes, including development of medication overuse headache. Here, we examined the effect of erenumab on reducing acute medication use, in particular MSM, in patients with episodic migraine (EM) and chronic migraine (CM). METHODS: The current post-hoc analyses were based on data from the double-blind treatment phase (DBTP) of two erenumab studies, a pivotal EM (N = 955) and a pivotal CM (N = 667) trial, and their respective extensions. Patients were administered subcutaneous placebo or erenumab (70 or 140 mg) once monthly. Daily acute headache medication use (including MSM and non-MSM) was recorded using an electronic diary during a 4-week pretreatment baseline period until the end of the treatment period. Outcome measures included change in monthly acute headache medication days (HMD) in acute headache medication users at baseline, and changes in monthly MSM days (MSMD) in MSM users at baseline and non-MSMD in non-MSM users at baseline. RESULTS: In total, 60 and 78 % of patients (all acute headache medication users) with EM and CM used MSM at baseline, respectively. For acute headache medication users, the change in mean monthly acute HMD over Months 4, 5 and 6 compared with the pre-DBTP was 1.5, 2.5, and 3.0 for placebo, erenumab 70 mg and 140 mg, respectively for the EM study. The respective change in monthly MSMD in MSM users was 0.5, 2.1 and 2.8, and in monthly non-MSMD in non-MSM users was 2.3, 2.6, and 2.7. In the acute headache medication users at baseline, the change in monthly acute HMD at Month 3 compared with pre-DBTP was 3.4, 5.5, and 6.5 for placebo, erenumab 70 mg and 140 mg, respectively for the CM study. The respective change in monthly MSMD in MSM users was 2.1, 4.5, and 5.4, and in monthly non-MSMD in non-MSM users was 5.9, 6.4, and 6.6. Reductions in MSMD versus placebo were sustained in the extension periods of both studies. Erenumab was also associated with a higher proportion of MSM users achieving ≥ 50 %, ≥ 75 and 100 % reduction from baseline in monthly MSMD versus placebo in both EM and CM. CONCLUSIONS: In both EM and CM, treatment with erenumab is associated with a significant and sustained reduction in the use of acute headache medication, in particular MSM. TRIAL REGISTRATIONS: NCT02456740; NCT02066415; NCT02174861.

A Controlled Trial of Erenumab for Episodic Migraine.

BACKGROUND: We tested erenumab, a fully human monoclonal antibody that inhibits the calcitonin gene-related peptide receptor, for the prevention of episodic migraine. METHODS: We randomly assigned patients to receive a subcutaneous injection of either erenumab, at a dose of 70 mg or 140 mg, or placebo monthly for 6 months. The primary end point was the change from baseline to months 4 through 6 in the mean number of migraine days per month. Secondary end points were a 50% or greater reduction in mean migraine days per month, change in the number of days of use of acute migraine-specific medication, and change in scores on the physical-impairment and everyday-activities domains of the Migraine Physical Function Impact Diary (scale transformed to 0 to 100, with higher scores representing greater migraine burden on functioning). RESULTS: A total of 955 patients underwent randomization: 317 were assigned to the 70-mg erenumab group, 319 to the 140-mg erenumab group, and 319 to the placebo group. The mean number of migraine days per month at baseline was 8.3 in the overall population; by months 4 through 6, the number of days was reduced by 3.2 in the 70-mg erenumab group and by 3.7 in the 140-mg erenumab group, as compared with 1.8 days in the placebo group (P<0.001 for each dose vs. placebo). A 50% or greater reduction in the mean number of migraine days per month was achieved for 43.3% of patients in the 70-mg erenumab group and 50.0% of patients in the 140-mg erenumab group, as compared with 26.6% in the placebo group (P<0.001 for each dose vs. placebo), and the number of days of use of acute migraine-specific medication was reduced by 1.1 days in the 70-mg erenumab group and by 1.6 days in the 140-mg erenumab group, as compared with 0.2 days in the placebo group (P<0.001 for each dose vs. placebo). Physical-impairment scores improved by 4.2 and 4.8 points in the 70-mg and 140-mg erenumab groups, respectively, as compared with 2.4 points in the placebo group (P<0.001 for each dose vs. placebo), and everyday-activities scores improved by 5.5 and 5.9 points in the 70-mg and 140-mg erenumab groups, respectively, as compared with 3.3 points in the placebo group (P<0.001 for each dose vs. placebo). The rates of adverse events were similar between erenumab and placebo. CONCLUSIONS: Erenumab administered subcutaneously at a monthly dose of 70 mg or 140 mg significantly reduced migraine frequency, the effects of migraines on daily activities, and the use of acute migraine-specific medication over a period of 6 months. The long-term safety and durability of the effect of erenumab require further study. (Funded by Amgen and Novartis; STRIVE ClinicalTrials.gov number, NCT02456740 .).

The Spectrum of Response to Erenumab in Patients With Episodic Migraine and Subgroup Analysis of Patients Achieving ≥50%, ≥75%, and 100% Response.

OBJECTIVE: To assess the efficacy of erenumab at the ≥50%, ≥75%, and 100% reduction in monthly migraine days (MMD) response thresholds, using data from the 6-month double-blind treatment phase (DBTP) of the Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention (STRIVE) pivotal clinical trial. METHODS: Enrolled patients with episodic migraine (EM; ≥4 MMD and <15 monthly headache days) were randomized (1:1:1) to erenumab 70 mg (n = 312), erenumab 140 mg (n = 318), or placebo (n = 316) once monthly. We determined the proportions of patients with ≥50%, ≥75% and 100% reduction in MMD over the last 3 months of the STRIVE DBTP (months 4 through 6) and conducted post hoc analyses to contextualize the treatment benefit in patient subgroups achieving, and not achieving, these response thresholds. Outcome measures included changes in MMD, acute migraine-specific medication days (MSMD), and patient-reported outcomes. RESULTS: The proportions of patients with a reduction in MMD from baseline were greater for erenumab than for placebo at all response thresholds. As previously reported for the ≥50% response threshold, 135/312 (43.3%) of patients on erenumab 70 mg and 159/318 (50.0%) on erenumab 140 mg responded, vs 84/316 (26.6%) for placebo. At months 4 through 6, 65/312 (20.8%) and 70/318 (22.0%) of those on erenumab 70 mg and erenumab 140 mg, respectively, achieved ≥75% reductions vs 25/316 (7.9%) on placebo. A reduction of 100% response, which required no migraine days over 3 consecutive months based on observed data, was achieved by 10/312 (3.2%) of patients treated with erenumab 70 mg and 16/318 (5.0%) for erenumab 140 mg, vs 9/316 (2.8%) for placebo. At all response thresholds, responders achieved numerically greater reductions in mean MMD and MSMD, and greater improvements in disability than did the overall population; importantly, these remarkable responses were noted early. Meanwhile, 60/312 (19.2%) and 53/318 (16.7%) patients on erenumab 70 and 140 mg, respectively, had no reduction in MMD from baseline in months 4 through 6, compared with 104/316 (32.9%) patients on placebo. CONCLUSIONS: The responses at the ≥50%, ≥75%, and 100% thresholds provide context for establishing realistic patient and physician expectations regarding the magnitude of treatment benefit that may be achieved by patients with EM responding to erenumab (STRIVE, NCT02456740).

Correlates of Benzodiazepine Use and Adverse Outcomes Among Patients with Chronic Pain Prescribed Long-term Opioid Therapy.

OBJECTIVE: To examine the correlates and odds of receiving overlapping benzodiazepine and opioid prescriptions and whether co-prescription was associated with greater odds of falling or visiting the emergency department. DESIGN: Cross-sectional study. SETTING: A large private integrated health system and a Veterans Health Administration integrated health system. SUBJECTS: Five hundred seventeen adults with musculoskeletal pain and current prescriptions for long-term opioid therapy. METHODS: A multivariate logistic regression model examined correlates of having overlapping benzodiazepine and opioid prescriptions in the year before enrollment in the cross-sectional study. Negative binomial models analyzed the number of falls in the past three months and past-year emergency department visits. In addition to propensity score adjustment, models controlled for demographic characteristics, psychiatric diagnoses, medications, overall comorbidity score, and opioid morphine equivalent dose. RESULTS: Twenty-five percent (N = 127) of participants had co-occurring benzodiazepine and opioid prescriptions in the prior year. Odds of receiving a benzodiazepine prescription were significantly higher among patients with the following psychiatric diagnoses: anxiety disorder (adjusted odds ratio [AOR] = 4.71, 95% confidence interval [CI] = 2.67-8.32, P < 0.001), post-traumatic stress disorder (AOR = 2.24, 95% CI = 1.14-4.38, P = 0.019), and bipolar disorder (AOR = 3.82, 95% CI = 1.49-9.81, P = 0.005). Past-year overlapping benzodiazepine and opioid prescriptions were associated with adverse outcomes, including a greater number of falls (risk ratio [RR] = 3.27, 95% CI = 1.77-6.02, P = 0.001) and emergency department visits (RR = 1.66, 95% CI = 1.08-2.53, P = 0.0194). CONCLUSIONS: Among patients with chronic pain prescribed long-term opioid therapy, one-quarter of patients had co-occurring prescriptions for benzodiazepines, and dual use was associated with increased odds of falls and emergency department visits.

Healthcare Effectiveness Data and Information Set (HEDIS) measures of alcohol and drug treatment initiation and engagement among people living with the human immunodeficiency virus (HIV) and patients without an HIV diagnosis.

Background: Problematic use of alcohol and other drugs (AOD) is highly prevalent among people living with the human immunodeficiency virus (PLWH), and untreated AOD use disorders have particularly detrimental effects on human immunodeficiency virus (HIV) outcomes. The Healthcare Effectiveness Data and Information Set (HEDIS) measures of treatment initiation and engagement are important benchmarks for access to AOD use disorder treatment. To inform improved patient care, we compared HEDIS measures of AOD use disorder treatment initiation and engagement and health care utilization among PLWH and patients without an HIV diagnosis. Methods: Patients with a new AOD use disorder diagnosis documented between October 1, 2014, and August 15, 2015, were identified using electronic health records (EHR) and insurance claims data from 7 health care systems in the United States. Demographic characteristics, clinical diagnoses, and health care utilization data were also obtained. AOD use disorder treatment initiation and engagement rates were calculated using HEDIS measure criteria. Factors associated with treatment initiation and engagement were examined using multivariable logistic regression models. Results: There were 469 PLWH (93% male) and 86,096 patients without an HIV diagnosis (60% male) in the study cohort. AOD use disorder treatment initiation was similar in PLWH and patients without an HIV diagnosis (10% vs. 11%, respectively). Among those who initiated treatment, few engaged in treatment in both groups (9% PLWH vs. 12% patients without an HIV diagnosis). In multivariable analysis, HIV status was not significantly associated with either AOD use disorder treatment initiation or engagement. Conclusions: AOD use disorder treatment initiation and engagement rates were low in both PLWH and patients without an HIV diagnosis. Future studies need to focus on developing strategies to efficiently integrate AOD use disorder treatment with medical care for HIV.

The prevalence of Healthcare Effectiveness Data and Information Set (HEDIS) initiation and engagement in treatment among patients with cannabis use disorders in 7 US health systems.

Background: Cannabis use disorders (CUDs) have increased with more individuals using cannabis, yet few receive treatment. Health systems have adopted the Healthcare Effectiveness Data and Information Set (HEDIS) quality measures of initiation and engagement in alcohol and other drug (AOD) dependence treatment, but little is known about the performance of these among patients with CUDs. Methods: This cohort study utilized electronic health records and claims data from 7 health care systems to identify patients with documentation of a new index CUD diagnosis (no AOD diagnosis ≤60 days prior) from International Classification of Diseases, Ninth revision, codes (October 1, 2014, to August 31, 2015). The adjusted prevalence of each outcome (initiation, engagement, and a composite of both) was estimated from generalized linear regression models, across index identification settings (inpatient, emergency department, primary care, addiction treatment, and mental health/psychiatry), AOD comorbidity (patients with CUD only and CUD plus other AOD diagnoses), and patient characteristics. Results: Among 15,202 patients with an index CUD diagnosis, 30.0% (95% confidence interval [CI]: 29.2-30.7%) initiated, 6.9% (95% CI: 6.2-7.7%) engaged among initiated, and 2.1% (95% CI: 1.9-2.3%) overall both initiated and engaged in treatment. The adjusted prevalence of outcomes varied across index identification settings and was highest among patients diagnosed in addiction treatment, with 25.0% (95% CI: 22.5-27.6%) initiated, 40.9% (95% CI: 34.8-47.0%) engaged, and 12.5% (95% CI: 10.0-15.1%) initiated and engaged. The adjusted prevalence of each outcome was generally highest among patients with CUD plus other AOD diagnosis at index diagnosis compared with those with CUD only, overall and across index identification settings, and was lowest among uninsured and older patients. Conclusion: Among patients with a new CUD diagnosis, the proportion meeting HEDIS criteria for initiation and/or engagement in AOD treatment was low and demonstrated variation across index diagnosis settings, AOD comorbidity, and patient characteristics, pointing to opportunities for improvement.

The association between medical comorbidity and Healthcare Effectiveness Data and Information Set (HEDIS) measures of treatment initiation and engagement for alcohol and other drug use disorders.

Background: Medical comorbidity may influence treatment initiation and engagement for alcohol and other drug (AOD) use disorders. We examined the association between medical comorbidity and Healthcare Effectiveness Data and Information Set (HEDIS) treatment initiation and engagement measures.Methods: We used electronic health record and insurance claims data from 7 US health care systems to identify patients with AOD use disorders between October 1, 2014, and August 15, 2015 (N = 86,565). Among patients identified with AOD use disorders in outpatient and emergency department (ED) settings, we examined how Charlson/Deyo comorbidity index scores and medical complications of AOD use were associated with treatment initiation. Among those who initiated treatment in inpatient and outpatient/ED settings, we also examined how comorbidity and AOD use-related medical complications were associated with treatment engagement. Analyses were conducted using generalized estimating equation logistic regression modeling.Results: Among patients identified as having an AOD diagnosis in outpatient and ED settings (n = 69,965), Charlson/Deyo comorbidity index scores of 2 or more were independently associated with reduced likelihood of initiation (risk ratio [RR] = 0.80, 95% confidence interval [CI] = 0.74, 0.86; reference score = 0), whereas prior-year diagnoses of cirrhosis (RR = 1.25, 95% CI = 1.12, 1.35) and pancreatic disease (RR = 1.34, 95% CI = 1.15, 1.56) were associated with greater likelihood of initiation. Among those who were identified in outpatient/ED settings and initiated, higher comorbidity scores were associated with lower likelihood of engagement (score 1: RR = 0.85, 95% CI = 0.76, 0.94; score 2+: RR = 0.61, 95% CI = 0.53, 0.71).Conclusion: Medical comorbidity was associated with lower likelihood of initiating or engaging in AOD treatment, but cirrhosis and pancreatic disease were associated with greater likelihood of initiation. Interventions to improve AOD treatment initiation and engagement for patients with comorbidities are needed, such as integrating medical and AOD treatment.

Factors associated with Healthcare Effectiveness Data and Information Set (HEDIS) alcohol and other drug measure performance in 2014-2015.

Background: Only 10% of patients with alcohol and other drug (AOD) disorders receive treatment. The AOD Initiation and Engagement in Treatment (AOD-IET) measure was added to the national Healthcare Effectiveness Data and Information Set (HEDIS) to improve access to care. This study identifies factors related to improving AOD-IET rates. Methods: We include data from 7 health systems with differing geographic, patient demographic, and organizational characteristics; all used a common Virtual Data Warehouse containing electronic health records and insurance claims data. Multilevel logistic regression models examined AOD-IET among adults (18+). Results: A total of 86,565 patients had an AOD diagnosis qualifying for the HEDIS denominator. The overall initiation rate was 27.9% with wide variation; the overall engagement rate was 11.5% and varied from 4.5% to 17.9%. Women versus men (odds ratio [OR] = 0.81, 95% confidence interval [CI] = 0.76-0.86); Hispanics (OR = 0.85, 95% CI = 0.79-0.91), black/African Americans (OR = 0.82, 95% CI = 0.75-0.90), and Asian Americans (OR = 0.83, 95% CI = 0.72-0.95) versus whites; and patients aged 65+ versus 18-29 (OR = 0.82, 95% CI = 0.74-0.90) had lower odds of initiation. Patients aged 30-49 versus 18-29 (OR = 1.11, 95% CI = 1.04-1.19) and those with prior psychiatric (OR = 1.26, 95% CI = 1.18-1.35) and medical (OR = 1.18, 95% CI = 1.10-1.26) conditions had higher odds of initiation. Identification in primary care versus other departments was related to lower odds of initiation (emergency department [ED]: OR = 1.55, 95% CI = 1.45-1.66; psychiatry/AOD treatment: OR = 3.58, 95% CI = 3.33-3.84; other outpatient: OR = 1.19, 95% CI = 1.06-1.32). Patients aged 30-49 versus 18-29 had higher odds of engagement (OR = 1.26, 95% CI = 1.10-1.43). Patients aged 65+ versus 18-29 (OR = 0.51, 95% CI = 0.43-0.62) and black/African Americans versus whites (OR = 0.64, 95% CI = 0.53-0.77) had lower odds. Those initiating treatment in psychiatry/AOD treatment versus primary care (OR = 7.02, 95% CI = 5.93-8.31) had higher odds of engagement; those in inpatient (OR = 0.40, 95% CI = 0.32-0.50) or other outpatient (OR = 0.73, 95% CI = 0.59-0.91) settings had lower odds. Discussion: Rates of initiation and engagement varied but were low. Findings identified age, race/ethnicity, co-occurring conditions, and department of identification as key factors associated with AOD-IET. Focusing on these could help programs develop interventions that facilitate AOD-IET for those less likely to receive care.

Predictors of Healthcare Effectiveness Data and Information Set (HEDIS) treatment initiation and engagement among patients with opioid use disorder across 7 health systems.

Background: The prevalence of opioid use disorder (OUD) has increased rapidly in the United States and improving treatment access is critical. Among patients with OUD, we examined factors associated with the Healthcare Effectiveness Data and Information Set (HEDIS) performance measures of alcohol and other drug (AOD) treatment initiation and engagement. Methods: Electronic health record and claims data between October 1, 2014, and August 15, 2015, from 7 health systems were used to identify patients (n = 11,490) with a new index OUD diagnosis (no AOD diagnosis prior <60 days) based on International Classification of Diseases (ICD)-9 codes. Multivariable generalized linear models with a logit link clustered on health system were used to examine the associations of patient demographic and clinical characteristics, and department of index diagnosis, with HEDIS measures of treatment initiation and engagement. Results: The prevalence of OUD among all AOD diagnoses varied across health systems, as did rates of AOD initiation (5.7%-21.6%) and engagement (7.6%-24.6%). Those diagnosed in the emergency department (adjusted odds ratio [aOR] = 1.58, 95% confidence interval [CI] = 1.27,1.97) or psychiatry/AOD treatment (aOR = 2.92, 95% CI = 2.47,3.46) were more likely to initiate treatment compared with primary care. Older patients were less likely to initiate (age 50-64 vs. age 18-29: aOR = 0.42, 95% CI = 0.35, 0.51; age 65+ vs. age 18-29: aOR = 0.34, 95% CI = 0.26, 0.43), as were women (aOR = 0.72, 95% CI = 0.62, 0.85). Patients diagnosed in psychiatry/AOD treatment (aOR = 2.67, 95% CI = 1.98, 3.60) compared with primary care were more likely to engage in treatment. Those identified in an inpatient setting (aOR = 0.19, 95% CI = 0.14, 0.27 vs. primary care), those with medical comorbidity (aOR = 0.70, 95% CI = 0.52, 0.95), and older patients (age 50-64 vs. 18-29: aOR = 0.64, 95% CI = 0.46, 0.88; age 65+ vs. 18-29: aOR = 0.36, 95% CI = 0.22, 0.57) were less likely to engage in treatment. Conclusions: Rates of initiation and engagement for OUD patients vary widely with noticeable room for improvement, particularly in this critical time of the opioid crisis. Targeting patient and system factors may improve health system performance, which is key to improving patient outcomes.

Psychiatric comorbidity and Healthcare Effectiveness Data and Information Set (HEDIS) measures of alcohol and other drug treatment initiation and engagement across 7 health care systems.

Background: Psychiatric comorbidity is common among patients with alcohol and other drug (AOD) use disorders. To better understand how psychiatric comorbidity influences AOD treatment access in health care systems, the present study examined treatment initiation and engagement among a large, diverse sample of patients with comorbid psychiatric and AOD use disorders. Methods: This study utilized data from a multisite observational study examining Healthcare Effectiveness Data and Information Set (HEDIS) measures of initiation and engagement in treatment (IET) among patients with AOD use disorders from 7 health care systems. Participants were aged 18 or older with at least 1 AOD index diagnosis between October 1, 2014, and August 15, 2015. Data elements extracted from electronic health records and insurance claims data included patient demographic characteristics, ICD-9 (International Classification of Diseases, Ninth Revision) diagnostic codes, and procedure codes. Descriptive analyses and multivariate logistic regression models were used to examine the relationship between patient-level factors and IET measures. Results: Across health care systems, out of a total of 86,565 patients who had at least 1 AOD index diagnosis during the study period, 66.2% (n = 57,335) patients also had a comorbid psychiatric disorder. Among patients with a comorbid psychiatric disorder, 34.9% (n = 19,998) initiated AOD treatment, and of those, 10.3% (n = 2,060) engaged in treatment. After adjusting for age, sex, and race/ethnicity, patients with comorbid psychiatric disorders were more likely to initiate (odds ratio [OR] = 3.20, 95% confidence interval [CI] = 3.08, 3.32) but no more likely to engage (OR = 0.56, 95% CI = 0.51, 0.61) in AOD treatment, compared with those without a comorbid psychiatric disorder. Conclusions: Findings suggest that identification of comorbid psychiatric disorders may increase initiation in AOD treatment. However, innovative efforts are needed to enhance treatment engagement both generally and especially for individuals without diagnosed psychiatric conditions.

Patient characteristics associated with treatment initiation and engagement among individuals diagnosed with alcohol and other drug use disorders in emergency department and primary care settings.

Background: Treatment initiation and engagement rates for alcohol and other drug (AOD) use disorders differ depending on where the AOD use disorder was identified. Emergency department (ED) and primary care (PC) are 2 common settings where patients are identified; however, it is unknown whether characteristics of patients who initiate and engage in treatment differ between these settings. Methods: Patients identified with an AOD disorder in ED or PC settings were drawn from a larger study that examined Healthcare Effectiveness Data and Information Set (HEDIS) AOD treatment initiation and engagement measures across 7 health systems using electronic health record data (n = 54,321). Multivariable generalized linear models, with a logit link, clustered on health system, were used to model patient factors associated with initiation and engagement in treatment, between and within each setting. Results: Patients identified in the ED had higher odds of initiating treatment than those identified in PC (adjusted odds ratio [aOR] = 1.89, 95% confidence interval [CI] = 1.73-2.07), with no difference in engagement between the settings. Among those identified in the ED, compared with patients aged 18-29, older patients had higher odds of treatment initiation (age 30-49: aOR = 1.25, 95% CI = 1.12-1.40; age 50-64: aOR = 1.42, 95% CI = 1.26-1.60; age 65+: aOR = 1.27, 95% CI = 1.08-1.49). However, among those identified in PC, compared with patients aged 18-29, older patients were less likely to initiate (age 30-49: aOR = 0.81, 95% CI = 0.71-0.94; age 50-64: aOR = 0.68, 95% CI = 0.58-0.78; age 65+: aOR = 0.47, 95% CI = 0.40-0.56). Women identified in ED had lower odds of initiating treatment (aOR = 0.80, 95% CI = 0.72-0.88), whereas sex was not associated with treatment initiation in PC. In both settings, patients aged 65+ had lower odds of engaging compared with patients aged 18-29 (ED: aOR = 0.61, 95% CI = 0.38-0.98; PC: aOR = 0.42, 95% CI = 0.26-0.68). Conclusion: Initiation and engagement in treatment differed by sex and age depending on identification setting. This information could inform tailoring of future AOD interventions.

Remote electrical neuromodulation (REN) in the acute treatment of migraine: a comparison with usual care and acute migraine medications.

BACKGROUND: There is a significant unmet need for new, effective and well tolerated acute migraine treatments. A recent study has demonstrated that a novel remote electrical neuromodulation (REN) treatment provides superior clinically meaningful pain relief with a low rate of device-related adverse events. The results reported herein compare the efficacy of REN with current standard of care in the acute treatments of migraine. METHODS: We performed a post-hoc analysis on a subgroup of participants with migraine from a randomized, double-blind, parallel-group, sham-controlled, multicenter study on acute care. The original study included a 2-4 weeks run-in phase, in which migraine attacks were treated according to patient preference (i.e., usual care) and reported in an electronic diary; next, participants entered a double-blind treatment phase in which they treated the attacks with an active or sham device. The efficacy of REN was compared to the efficacy of usual care or pharmacological treatments in the run-in phase in a within-subject design that included participants who treated at least one attack with the active REN device and reported pain intensity at 2 h post-treatment. RESULTS: Of the 252 patients randomized, there were 99 participants available for analysis. At 2 h post-treatment, pain relief was achieved in 66.7% of the participants using REN versus 52.5% participants with usual care (p < 0.05). Pain relief at 2 h in at least one of two attacks was achieved by 84.4% of participants versus 68.9% in usual care (p < 0.05). REN and usual care were similarly effective for pain-free status at 2 h. The results also demonstrate the non-inferiority of REN compared with acute pharmacological treatments and its non-dependency on preventive medication use. CONCLUSION: REN is an effective acute treatment for migraine with non-inferior efficacy compared to current acute migraine therapies. Together with a very favorable safety profile, these findings suggest that REN may offer a promising alternative for the acute treatment of migraine and could be considered first line treatment in some patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03361423 . Registered 18 November 2017.