Clinically recognized sleep disorders in people living with HIV.

OBJECTIVE: Despite recognition that people with HIV (PWH) are more vulnerable to sleep issues, there is limited understanding of clinically recognized sleep disorders in this population. Our objective was to evaluate the full spectrum of sleep disorder types diagnosed among PWH in care. METHODS: We conducted a retrospective cohort study of PWH, and a comparator group of people without HIV (PWoH), in a large healthcare system. The incidence of clinically diagnosed sleep disorders was calculated using Poisson regression for three outcomes: any type of sleep disorder, insomnia, and sleep apnea. Incidence was compared between PWH and PWoH by computing the adjusted incidence rate ratio (aIRR), accounting for sleep disorder risk factors. Comparisons to PWoH were made for all PWH combined, then with PWH stratified by HIV management status (well-managed HIV defined as being on antiretroviral therapy, HIV RNA <200 copies/mL, and CD4 count ≥500 cells/µL). RESULTS: The study included 9076 PWH and 205 178 PWoH (mean age 46 years, 90% men). Compared with PWoH, sleep disorder incidence was greater among PWH overall [aIRR = 1.19, 95% confidence interval (CI): 1.12-1.26], particularly for insomnia (aIRR = 1.56, 95% CI: 1.45-1.67). Sleep apnea incidence was lower among PWH (aIRR = 0.90, 95% CI: 0.84-0.97). In HIV management subgroups, PWH without well-managed HIV had lower sleep apnea incidence (vs. PWoH: aIRR = 0.79, 95% CI: 0.70-0.89) but PWH with well-managed HIV did not (vs. PWoH: aIRR = 0.97, 95% CI: 0.89-1.06). CONCLUSIONS: PWH have high sleep disorder incidence, and insomnia is the most common clinical diagnosis. Lower sleep apnea incidence among PWH may reflect underdiagnosis in those with sub-optimally treated HIV and will be important to investigate further.

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.

Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems.

BACKGROUND: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. OBJECTIVE: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). DESIGN: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of  ≥ 50 during six consecutive months. PATIENTS: We identified 60,040 non-cancer patients with  ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). MAIN MEASURES: Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. KEY RESULTS: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality. CONCLUSIONS: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.

COVID-19 pandemic-related changes in utilization of telehealth and treatment overall for alcohol use problems.

BACKGROUND: During the COVID-19 pandemic, specialty alcohol treatment transitioned rapidly to telehealth, which may have created barriers for some patients but increased access for others. This study evaluated the impact of the COVID-19 pandemic on alcohol treatment utilization and potential disparities. METHODS: We analyzed electronic health record and claims data from Kaiser Permanente Northern California for adults with alcohol use problems (alcohol use disorder or unhealthy alcohol use diagnoses) during pre-COVID-19 (March to December 2019, n = 32,806) and COVID-19 onset (March to December 2020, n = 26,763). Generalized estimating equation models were fit to examine pre-COVID-19 to COVID-19 onset changes in alcohol treatment initiation, engagement, and retention (days in treatment). Heterogeneity in pre-COVID-19 to COVID-19 onset changes in treatment utilization by age, race, and ethnicity; neighborhood deprivation index (NDI); and comorbid medical and psychiatric disorders were also examined. RESULTS: Treatment initiation increased during the COVID-19 onset period (adjusted odds ratio [aOR] = 1.46; 95% CI = 1.41-1.52). The increases in odds of treatment initiation during the COVID-19 onset period compared with the pre-COVID period were largest among patients aged 18-34 years (aOR = 1.59; 95% CI = 1.48-1.71), those without medical conditions (aOR = 1.56; 95% CI = 1.49-1.65), and those without psychiatric disorders (aOR = 1.60; 95% CI = 1.51-1.69). Patients aged 18-34 years (aOR = 5.21; 95% CI = 4.67-5.81), those with the second highest NDIs (aOR = 4.63; 95% CI = 4.12-5.19), and those without medical (aOR = 4.34; 95% CI = 4.06-4.65) or psychiatric comorbidities (aOR = 4.48; 95% CI = 4.11-4.89) had the greatest increases in telehealth treatment initiation from pre-COVID-19 to COVID-19 onset. Treatment engagement and retention also increased during COVID-19 onset, with the greatest increase among patients aged 35-49 years who initiated treatment via telehealth (engagement: aOR = 2.33; 95% CI = 1.91-2.83; retention: adjusted mean difference [aMD] = 3.3 days; 95% CI = 2.6-4.1). We found no significant variation of changes in treatment utilization by race and ethnicity. CONCLUSIONS: The transition to telehealth in this healthcare system may have attracted subgroups of individuals who have historically underutilized care for alcohol use problems, particularly younger and healthier adults, without exacerbating pre-pandemic racial and ethnic disparities in treatment utilization.

Substance use disorders among primary care patients screening positive for unhealthy alcohol use.

BACKGROUND: Despite high prevalence of polysubstance use, recent data on concurrent alcohol use in patients with specific substance use disorders (SUDs) are lacking. OBJECTIVE: To examine associations between specific SUDs and alcohol consumption levels. METHODS: Using electronic health record data, we conducted a cross-sectional study of 2,720,231 primary care adults screened for alcohol use between 2014 and 2017 at Kaiser Permanente Northern California. Alcohol consumption levels were categorized as no reported use, low-risk use, and unhealthy use (exceeding daily, weekly, or both recommended drinking limits). Using multinomial logistic regression, and adjusting for sociodemographic and health characteristics, we examined the odds of reporting each alcohol consumption level in patients with a prior-year SUD diagnosis (alcohol, cannabis, cocaine, inhalant, opioid, sedative/anxiolytic, stimulant, other drug, nicotine, any SUD except nicotine) compared to those without. RESULTS: The sample was 52.9% female, 48.1% White; the mean age was 46 years (SD = 18). Patients with SUDs were less likely to report low-risk alcohol use relative to no use compared with patients without SUDs. Patients with alcohol or nicotine use disorder had higher odds of reporting unhealthy alcohol use relative to no use; however, patients with all other SUDs (except cocaine) had lower odds. Among patients who reported any alcohol use (n = 861,427), patients with SUDs (except opioid) had higher odds of exceeding recommended limits than those without. CONCLUSION: The associations of unhealthy alcohol use and SUDs suggest that screening for both alcohol and drug use in primary care presents a crucial opportunity to prevent and treat SUDs early.

Patient and provider factors associated with receipt and delivery of brief interventions for unhealthy alcohol use in primary care.

BACKGROUND: Unhealthy alcohol use is a serious and costly public health problem. Alcohol screening and brief interventions are effective in reducing unhealthy alcohol consumption. However, rates of receipt and delivery of brief interventions vary significantly across healthcare settings, and relatively little is known about the associated patient and provider factors. METHODS: This study examines patient and provider factors associated with the receipt of brief interventions for unhealthy alcohol use in an integrated healthcare system, based on documented brief interventions in the electronic health record. Using multilevel logistic regression models, we retrospectively analyzed 287,551 adult primary care patients (and their 2952 providers) who screened positive for unhealthy drinking between 2014 and 2017. RESULTS: We found lower odds of receiving a brief intervention among patients exceeding daily or weekly drinking limits (vs. exceeding both limits), females, older age groups, those with higher medical complexity, and those already diagnosed with alcohol use disorders. Patients with other unhealthy lifestyle activities (e.g., smoking, no/insufficient exercise) were more likely to receive a brief intervention. We also found that female providers and those with longer tenure in the health system were more likely to deliver brief interventions. CONCLUSIONS: These findings point to characteristics that can be targeted to improve universal receipt of brief intervention.

Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users.

In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse.

The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin ß and ADAM10.

The in vivo roles of meprin metalloproteases in pathophysiological conditions remain elusive. Substrates define protease roles. Therefore, to identify natural substrates for human meprin α and ß we employed TAILS (terminal amine isotopic labeling of substrates), a proteomics approach that enriches for N-terminal peptides of proteins and cleavage fragments. Of the 151 new extracellular substrates we identified, it was notable that ADAM10 (a disintegrin and metalloprotease domain-containing protein 10)-the constitutive α-secretase-is activated by meprin ß through cleavage of the propeptide. To validate this cleavage event, we expressed recombinant proADAM10 and after preincubation with meprin ß, this resulted in significantly elevated ADAM10 activity. Cellular expression in murine primary fibroblasts confirmed activation. Other novel substrates including extracellular matrix proteins, growth factors and inhibitors were validated by western analyses and enzyme activity assays with Edman sequencing confirming the exact cleavage sites identified by TAILS. Cleavages in vivo were confirmed by comparing wild-type and meprin(-/-) mice. Our finding of cystatin C, elafin and fetuin-A as substrates and natural inhibitors for meprins reveal new mechanisms in the regulation of protease activity important for understanding pathophysiological processes.

Characteristics and quality of life of opioid-dependent pregnant women in Austria.

This study investigated pregnant opioid-dependent women undergoing maintenance therapy, applying a multidisciplinary, case-management approach at the Addiction Clinic of the Medical University of Vienna, Austria. It aimed at characterizing the patients' basic demographic and clinical parameters and evaluating their overall quality of life (QoL) prepartum and postpartum. Three hundred ninety women were treated between 1994 and 2009 with buprenorphine (n = 77), methadone (n = 184), or slow-release oral morphine (SROM) (n = 129) on an outpatient basis throughout their pregnancy and postpartum period. All patients were subject to standardized prepartum and postpartum medical and psychiatric assessments, including QoL assessments using a German adaptation of the Lancashire QoL Profile (Berliner Lebensqualitaetsprofil), and regular supervised urine toxicologies. No medication group differences were revealed regarding basic demographic or clinical data. Mean maintenance doses (SD) at time of delivery were as follows: 64 mg (36 mg) methadone, 10 mg (6 mg) buprenorphine, 455 mg (207 mg) SROM. However, buprenorphine-medicated women showed significantly less concomitant benzodiazepine consumption than methadone- or SROM-maintained women (p = 0.005), and significantly less concomitant opioid consumption than methadone-maintained women (p = 0.033) during the last trimester. Overall QoL was good prepartum and postpartum in all measured domains except "finances" and "prospect of staying in the same housing situation," and no differences were observed in QoL among the three medication groups (p = 0.177). QoL improved significantly after delivery in most of the domains (p < 0.001). Although opioid-dependent pregnant women face high-risk pregnancies and show variability in addiction severity, they report good QoL independent of the medication administered. These results show that individually tailored treatment interventions are effective for this patient population and suggest a QoL improvement after delivery.

Substance abuse/dependence treatment: a European perspective.

During the past decade, substantial progress has been made in the field of addiction medicine in Europe, particularly regarding the development of new treatment interventions, resulting in a wide range of therapeutic options for patients with substance use disorders. However, not all interventions are evidence based. Patients with cannabis and cocaine/amphetamine use disorders and special patient populations especially lack evidence-based treatment recommendations. Many patients undergo treatment that has not been scientifically evaluated for quality and efficacy. Moreover, there are large disparities regarding availability and treatment access across Europe, with the new member states of the European Union (EU) reporting long waiting lists and low treatment coverage. Even in Austria, which ranks among the countries with relatively high treatment coverage and good diversification of treatment in opioid maintenance therapy due to the availability of methadone, buprenorphine, and slow-release oral morphine (SROM), a considerable population of untreated or inadequately treated patients exists. Treatment for substance use disorders in Europe still has scope for improvement in terms of treatment availability and access, which is ideally provided by further development and implementation of evidence-based interventions.

Addiction Medicine Treatment Utilization by Race/Ethnicity Among Adolescents With Substance Use Problems Before Versus During the COVID-19 Pandemic.

PURPOSE: To examine changes in addiction medicine treatment utilization during the COVID-19 pandemic among adolescents (aged 13-17 years) and differences by race/ethnicity. METHODS: We compared treatment initiation (overall and telehealth), engagement, and 12-week retention between insured adolescents with substance use problems during pre-COVID-19 (March to December 2019, n = 1,770) and COVID-19 (March to December 2020, n = 1,177) using electronic health record data from Kaiser Permanente Northern California. RESULTS: Compared to pre-COVID-19, odds of treatment initiation, overall (adjusted odds ratio [95% confidence interval] = 1.42 [1.21-1.67]), and telehealth (5.98 [4.59-7.80]) were higher during COVID-19, but odds of engagement and retention did not significantly change. Depending on the outcome, Asian/Pacific Islander, Black, and Latino/Hispanic (vs. White) adolescents had lower treatment utilization across both periods. Changes in utilization over time did not differ by race/ethnicity. DISCUSSION: Addiction medicine treatment initiation increased among insured adolescents during the pandemic, especially via telehealth. Although racial/ethnic disparities in treatment utilization persisted, they did not worsen.

Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

Overall and Telehealth Addiction Treatment Utilization by Age, Race, Ethnicity, and Socioeconomic Status in California After COVID-19 Policy Changes.

Importance: Addiction treatment rapidly transitioned to a primarily telehealth modality (telephone and video) during the COVID-19 pandemic, raising concerns about disparities in utilization. Objective: To examine whether there were differences in overall and telehealth addiction treatment utilization after telehealth policy changes during the COVID-19 pandemic by age, race, ethnicity, and socioeconomic status. Design, Setting, and Participants: This cohort study examined electronic health record and claims data from Kaiser Permanente Northern California for adults (age ≥18 years) with drug use problems before the COVID-19 pandemic (from March 1, 2019, to December 31, 2019) and during the early phase of the COVID-19 pandemic (March 1, 2020, to December 31, 2020; hereafter referred to as COVID-19 onset). Analyses were conducted between March 2021 and March 2023. Exposure: The expansion of telehealth services during COVID-19 onset. Main Outcomes and Measures: Generalized estimating equation models were fit to compare addiction treatment utilization during COVID-19 onset with that before the COVID-19 pandemic. Utilization measures included the Healthcare Effectiveness Data and Information Set of treatment initiation and engagement (including inpatient, outpatient, and telehealth encounters or receipt of medication for opioid use disorder [OUD]), 12-week retention (days in treatment), and OUD pharmacotherapy retention. Telehealth treatment initiation and engagement were also examined. Differences in changes in utilization by age group, race, ethnicity, and socioeconomic status (SES) were examined. Results: Among the 19 648 participants in the pre-COVID-19 cohort (58.5% male; mean [SD] age, 41.0 [17.5] years), 1.6% were American Indian or Alaska Native; 7.5%, Asian or Pacific Islander; 14.3%, Black; 20.8%, Latino or Hispanic; 53.4%, White; and 2.5%, unknown race. Among the 16 959 participants in the COVID-19 onset cohort (56.5% male; mean [SD] age, 38.9 [16.3] years), 1.6% were American Indian or Alaska Native; 7.4%, Asian or Pacific Islander; 14.6%, Black; 22.2%, Latino or Hispanic; 51.0%, White; and 3.2%, unknown race. Odds of overall treatment initiation increased from before the COVID-19 pandemic to COVID-19 onset for all age, race, ethnicity, and SES subgroups except for patients aged 50 years or older; patients aged 18 to 34 years had the greatest increases (adjusted odds ratio [aOR], 1.31; 95% CI, 1.22-1.40). Odds of telehealth treatment initiation increased for all patient subgroups without variation by race, ethnicity, or SES, although increases were greater for patients aged 18 to 34 years (aOR, 7.17; 95% CI, 6.24-8.24). Odds of overall treatment engagement increased (aOR, 1.13; 95% CI, 1.03-1.24) without variation by patient subgroups. Retention increased by 1.4 days (95% CI, 0.6-2.2 days), and OUD pharmacotherapy retention did not change (adjusted mean difference, -5.2 days; 95% CI, -12.7 to 2.4 days). Conclusions: In this cohort study of insured adults with drug use problems, there were increases in overall and telehealth addiction treatment utilization after telehealth policies changed during the COVID-19 pandemic. There was no evidence that disparities were exacerbated, and younger adults may have particularly benefited from the transition to telehealth.

Disparities in the receipt of alcohol brief intervention: The intersectionality of sex, age, and race/ethnicity.

BACKGROUND AND AIMS: The increasing trend in alcohol consumption among women, exacerbated by the COVID-19 pandemic, is of growing concern. Screening, brief intervention, and referral to treatment in primary care is an efficacious and cost-effective treatment approach for unhealthy alcohol use. However, disparities exist in delivery of brief interventions by sex, age and race/ethnicity. This study measures brief intervention rates among eligible patients by sex, age and race/ethnicity and their intersectionality, in the context of a program of systematic alcohol screening and brief intervention program in adult primary care in a large, integrated health-care delivery system. DESIGN, SETTING AND PARTICIPANTS: This was a population-based observational study among primary care clinics in an integrated health-care delivery system in Northern California, USA. The participants comprised adult (18+) patients (n = 287 551) screening positive for unhealthy alcohol use between January 2014 and December 2017. MEASUREMENTS: Receipt of brief intervention, patient and provider characteristics from electronic health records. FINDINGS: Multi-level logistic regression showed that women had lower odds of receiving brief intervention than men among all age, racial/ethnic groups and drinking levels. Sex differences were greater among those aged 35-49 years [odds ratio (OR) = 0.67, 95% confidence interval (CI) = 0.64, 0.69]) and 50-65 years (OR = 0.69, 95% CI =0.66, 0.72) than among other age groups. Sex differences in odds of receiving brief intervention were greater for the Latino/Hispanic group for women versus men (OR = 0.69, 95% CI = 0.66, 0.72) and smaller for the Asian/Pacific Islander group (OR = 0.76, 95% CI = 0.72, 0.81). CONCLUSION: In the United States, compared with men, women appear to have lower odds of receiving brief intervention for unhealthy alcohol use across all age groups, particularly during middle age. Black women and Latina/Hispanic women appear to be less likely to receive brief intervention than women in other race/ethnicity groups. Receipt of brief intervention does not appear to differ by drinking levels between men and women.

Associations between alcohol brief intervention in primary care and drinking and health outcomes in adults with hypertension and type 2 diabetes: a population-based observational study.

OBJECTIVES: To evaluate associations between alcohol brief intervention (BI) in primary care and 12-month drinking outcomes and 18-month health outcomes among adults with hypertension and type 2 diabetes (T2D). DESIGN: A population-based observational study using electronic health records data. SETTING: An integrated healthcare system that implemented system-wide alcohol screening, BI and referral to treatment in adult primary care. PARTICIPANTS: Adult primary care patients with hypertension (N=72 979) or T2D (N=19 642) who screened positive for unhealthy alcohol use between 2014 and 2017. MAIN OUTCOME MEASURES: We examined four drinking outcomes: changes in heavy drinking days/past 3 months, drinking days/week, drinks/drinking day and drinks/week from baseline to 12-month follow-up, based on results of alcohol screens conducted in routine care. Health outcome measures were changes in measured systolic and diastolic blood pressure (BP) and BP reduction ≥3 mm Hg at 18-month follow-up. For patients with T2D, we also examined change in glycohaemoglobin (HbA1c) level and 'controlled HbA1c' (HbA1c<8%) at 18-month follow-up. RESULTS: For patients with hypertension, those who received BI had a modest but significant additional -0.06 reduction in drinks/drinking day (95% CI -0.11 to -0.01) and additional -0.30 reduction in drinks/week (95% CI -0.59 to -0.01) at 12 months, compared with those who did not. Patients with hypertension who received BI also had higher odds for having clinically meaningful reduction of diastolic BP at 18 months (OR 1.05, 95% CI 1.00 to 1.09). Among patients with T2D, no significant associations were found between BI and drinking or health outcomes examined. CONCLUSIONS: Alcohol BI holds promise for reducing drinking and helping to improve health outcomes among patients with hypertension who screened positive for unhealthy drinking. However, similar associations were not observed among patients with T2D. More research is needed to understand the heterogeneity across diverse subpopulations and to study BI's long-term public health impact.

Influence of site differences between urban and rural American and Central European opioid-dependent pregnant women and neonatal outcome characteristics.

BACKGROUND: Multi-center trials enable the recruitment of larger study samples, although results might be influenced by site-specific factors. METHODS: Site differences of a multi-center prospective double-blind, double-dummy randomized controlled trial (7 centers: Central Europe (Vienna)/USA (3 urban/3 rural centers)) comparing safety and efficacy of methadone and buprenorphine in pregnant opioid-dependent women and their neonates. RESULTS: Urban US women had the highest rate of concomitant opioid (p = 0.050) and cocaine consumption (p = 0.003), the highest dropout rate (p = 0.001), and received the lowest voucher sums (p = 0.001). Viennese neonates had significantly higher Apgar scores 1 min (p = 0.001) and 5 min after birth (p < 0.001) and were more often born by cesarean section (p = 0.024). Rural US newborns had a significantly shorter neonatal abstinence syndrome treatment duration compared to Viennese and urban US sites (p = 0.006), in addition to other site-specific differences, suggesting a more severely affected group of women in the urban US sites. CONCLUSION: This clinical trial represents a role model for pharmacological treatment in this unique sample of pregnant women and demonstrates the clinical importance of considering site-specific factors in research and clinical practice.

Alcohol Use Among Young Adults in Northern California During the COVID-19 Pandemic-An Electronic Health Records-Based Study.

Background: Individuals globally were affected by the COVID-19 pandemic in myriad of ways, including social isolation and economic hardship, resulting in negative impacts on mental health and substance use. Young adults have been subjected to extraordinary challenges such as job loss, virtual school, or childcare issues, but have received limited attention from research so far. Methods: Using electronic health record data from a large integrated healthcare system in Northern California, this longitudinal observational study examined changes in the prevalence of unhealthy alcohol use (identified via systematic alcohol screening in adult primary care) from pre- (3/1/2019-12/31/2019) to post-COVID onset (3/1/2020-12/31/2020) among young adults (18-34 years). Among the 663,111 and 627,095 young adults who utilized primary care in the pre- and post-COVID onset periods, 342,889 (51.9%) and 186,711 (29.8%) received alcohol screening, respectively. We fit generalized estimating equation Poisson models to estimate the change in prevalence of unhealthy alcohol use from pre- to post-COVID onset among those who were screened, while using inverse probability weighting to account for potential selection bias of receiving alcohol screening. Heterogeneity in the change of prevalence by patient characteristics was also examined. Results: Overall, the unadjusted prevalence of unhealthy alcohol use slightly decreased from 9.2% pre-COVID to 9.0% post-COVID onset. After adjusting for patient covariates, the prevalence of unhealthy alcohol use decreased by about 2% [adjusted prevalence ratio (aPR) = 0.98, 95% CI = 0.96, 1.00]. The prevalence of unhealthy alcohol use increased among women by 8% (aPR = 1.08, 95% CI = 1.06, 1.11), patients 18-20 years by 7% (aPR = 1.07, 95% CI = 1.00, 1.15), and Latino/Hispanic patients by 7% (aPR = 1.07, 95% CI = 1.03, 1.11). While the prevalence of unhealthy alcohol use decreased among men by 12% (aPR = 0.88, 95% CI = 0.86, 0.90), patients 21-34 years by 2% (aPR = 0.98, 95% CI = 0.96, 0.99), White patients by 3% (95% CI = 0.95, 1.00), and patients living in neighborhoods with the lowest deprivation indices by 9% (aPR = 0.91, 95% CI = 0.88, 0.94), their unadjusted prevalence remained higher than their counterparts post-COVID onset. There was no variation in the change of prevalence by comorbid mental health conditions or drug use disorders. Conclusions: While changes in unhealthy alcohol use prevalence among young adults were small, findings raise concerns over increased drinking among women, those younger than the U.S. legal drinking age, and Latino/Hispanic patients.

Effectiveness of a pharmacist-delivered primary care telemedicine intervention to increase access to pharmacotherapy and specialty treatment for alcohol use problems: Protocol for the alcohol telemedicine consult cluster-randomized pragmatic trial.

BACKGROUND: Alcohol use problems are associated with serious medical, mental health and socio-economic consequences. Yet even when patients are identified in healthcare settings, most do not receive treatment, and use of pharmacotherapy is rare. This study will test the effectiveness of the Alcohol Telemedicine Consult (ATC) Service, a novel, personalized telehealth intervention approach for primary care patients with alcohol use problems. METHODS: This cluster-randomized pragmatic trial, supplemented by qualitative interviews, will include adults with a primary care visit between 9/10/21-3/10/23 from 16 primary care clinics at two large urban medical centers within Kaiser Permanente Northern California, a large, integrated healthcare system. Clinics are randomized to the ATC Service (intervention), including alcohol pharmacotherapy and SBIRT (screening, MI (Motivational Interviewing)-based brief intervention and referral to addiction treatment) delivered by clinical pharmacists, or the Usual Care (UC) arm that provides systematic alcohol SBIRT. Primary outcomes include a comparison of the ATC and UC arms on 1) implementation outcomes (alcohol pharmacotherapy prescription rates, specialty addiction treatment referrals); and 2) patient outcomes (medication fills, addiction treatment initiation, alcohol use, healthcare services utilization) over 1.5 years. A general modeling approach will consider clustering of patients/providers, and a random effects model will account for intra-class correlations across patients within providers and across clinics. Qualitative interviews with providers will examine barriers and facilitators to implementation. DISCUSSION: The ATC study examines the effectiveness of a pharmacist-provided telehealth intervention that combines pharmacotherapy and MI-based consultation. If effective, the ATC study could affect treatment models across the spectrum of alcohol use problems. CLINICAL TRIALS REGISTRATION: This study has been registered on ClinicalTrials.gov (NCT05252221).

Predicting severe alcohol use disorders in primary care using number of heavy drinking days.

BACKGROUND AND AIMS: Although screening for unhealthy alcohol use is becoming more common, severe alcohol use disorders (AUDs) associated with the most severe medical and socio-economic sequelae still often go unidentified in primary care. To improve identification of severe AUDs and aid clinical decision-making, we aimed to identify a threshold of heavy drinking days (HDDs) associated with severe AUDs. DESIGN, SETTING AND CASES: This cohort study analyzed electronic health record data of 138 765 adults who reported ≥ 1 HDD (4+ drinks/occasion for women and men aged ≥ 65 years, 5+ for men aged 18-64 years) during a 3-month period at a routine alcohol screening in primary care in a large Northern California, USA health-care system from 2014 to 2017. Our sample was 66.5% male, 59.7% white, 11.0% Asian/Pacific Islander, 5.0% black, 17.4% Latino/Hispanic and 7.0% other/unknown race/ethnicity; the mean age was 40.6 years (standard deviation = 15.2). MEASUREMENTS: We compared sensitivity and specificity of different thresholds of the reported number of HDDs during a 3-month period for predicting severe AUD diagnoses in the following year, in the full sample and by sex and age. FINDINGS: The prevalence of severe AUD diagnoses in the year after the screening was 0.6%. The optimal threshold predicting future severe AUD diagnoses in the full sample was ≥ 5 HDDs during a 3-month period [sensitivity = 68.9%, 95% confidence interval (CI) = 65.9, 72.0; specificity = 63.2%, 95% CI = 62.9, 63.4], but varied by sex and age. Women had a lower threshold than men (4 versus 6 HDDs), which decreased as women aged (from 5 HDDs among 18-24 years to 4 HDDs ≥ 25 years), but increased as men aged (from 5 HDDs among 18-24 years to 6 HDDs among 25-64 years, to 7 HDDs ≥ 65 years). CONCLUSIONS: Five or more heavy drinking days in a 3-month period may indicate heightened risk of future severe alcohol use disorder in an adult primary care population. The optimal thresholds are lower for women than for men, and thresholds decrease as women age but increase as men age.

Young Adult Substance Use and Healthcare Use Associated With Screening, Brief Intervention and Referral to Treatment in Pediatric Primary Care.

PURPOSE: Screening, brief intervention, and referral to treatment (SBIRT) may impact future comorbidity and healthcare utilization among adolescents screening positive for substance use or mood problems. METHODS: In a randomized trial sample, we compared an SBIRT group to usual care for substance use, mental health, medical diagnoses, and healthcare utilization over 7 years postscreening. RESULTS: In logistic regression models adjusting for patient characteristics, the SBIRT group had lower odds of any substance (Odds Ratio[OR] = 0.80, 95% Confidence Interval [CI] = 0.66-.98), alcohol (OR = 0.69, 95% CI = 0.51-0.94), any drug (OR = 0.73, 95% CI = 0.54-0.98), marijuana (OR = 0.70, 95% CI = 0.50-0.98), and tobacco (OR = 0.83, 95% CI = 0.69-1.00) diagnoses, and lower odds of any inpatient hospitalizations (OR = 0.59, 95% CI = 0.41-0.85) compared with usual care. Negative binomial models examining number of visits among adolescents with at least one visit of that type found that those in the SBIRT group had fewer primary care (incidence rate ratio[iRR] = 0.90, p < .05) and psychiatry (iRR = 0.64, p < .01) and more addiction medicine (iRR = 1.52, p < .01) visits over 7 years compared with usual care. In posthoc analyses, we found that among Hispanic patients, those in the SBIRT group had lower odds of any substance, any drug and marijuana use disorder diagnoses compared with usual care, and among Black/African American patients, those in the SBIRT group had lower odds of alcohol use disorder diagnoses compared with usual care. DISCUSSION: Beneficial effects of adolescent SBIRT on substance use and healthcare utilization may persist into young adulthood.