The impact of preoperative benzodiazepine use on postoperative opioid use in total shoulder arthroplasty.

BACKGROUND: As the rate of total shoulder arthroplasty (TSA) and preoperative benzodiazepine use rise, there is an increased need to understand the impact of preoperative benzodiazepine use on postoperative opioid consumption following TSA, especially amid the current opioid epidemic. The relationship between preoperative benzodiazepine use and chronic opioid use postoperatively has been well described following other orthopedic procedures; however, the impact on patients undergoing TSA remains unclear. This study aims to identify the impact of preoperative benzodiazepine use on opioid use following TSA. METHODS: A retrospective chart review of 4488 patients undergoing primary TSA (Current Procedural Terminology code 23472) at a single institution from 2014 to 2022 was performed. Patient demographics, surgical variables, comorbidities, Distressed Communities Index (DCI), and clinical outcomes, including readmission and revision, were collected. The Charlson Comorbidity Index (CCI) was used to assess preoperative health status. Opioid use in morphine milligram equivalents (MMEs) and benzodiazepine use were also recorded using the Prescription Drug Monitoring Program Database. Opioid use was collected at 30-, 60-, and 90-day intervals both before and after each patient's date of surgery. Statistical analysis included stepwise logistic regression to identify variables independently affecting benzodiazepine use pre- and postoperatively. RESULTS: Overall, 16% of patients used benzodiazepines within 90 days before their date of surgery. Of those patients, 46.4% were also using preoperative opioids, compared with just 30.0% of patients who were benzodiazepine-naïve (P < .001). Preoperative benzodiazepine use was also associated with increased pre- and postoperative total opioid use in MMEs and the number of opioid prescriptions across all time points when compared to benzodiazepine-naïve patients (P < .001). Furthermore, 37.4% of preoperative benzodiazepine users went on to prolonged opioid use (filled prescriptions >30 days after surgery) compared to 19.0% of those who were benzodiazepine-naïve (P < .001). CONCLUSION: This study demonstrates a significant association between preoperative benzodiazepine use and increased and prolonged opioid use following TSA. Further exploration of risk factors contributing to preoperative benzodiazepine use may help to reduce overall opioid use in patients undergoing TSA.

Racial Inequality in Receipt of Medications for Opioid Use Disorder.

BACKGROUND: Since 2010, Black persons in the United States have had a greater increase in opioid overdose-related mortality than other groups, but national-level evidence characterizing racial and ethnic disparities in the use of medications for opioid use disorder (OUD) is limited. METHODS: We used Medicare claims data from the 2016-2019 period for a random 40% sample of fee-for-service beneficiaries who were Black, Hispanic, or White; were eligible for Medicare owing to disability; and had an index event related to OUD (nonfatal overdose treated in an emergency department or inpatient setting, hospitalization with injection drug use-related infection, or inpatient or residential rehabilitation or detoxification care). We measured the receipt of medications to treat OUD (buprenorphine, naltrexone, and naloxone), the receipt of high-risk medications (opioid analgesics and benzodiazepines), and health care utilization, all in the 180 days after the index event. We estimated differences in outcomes according to race and ethnic group with adjustment for beneficiary age, sex, index event, count of chronic coexisting conditions, and state of residence. RESULTS: We identified 25,904 OUD-related index events among 23,370 beneficiaries, with 3937 events (15.2%) occurring among Black patients, 2105 (8.1%) among Hispanic patients, and 19,862 (76.7%) among White patients. In the 180 days after the index event, patients received buprenorphine after 12.7% of events among Black patients, after 18.7% of those among Hispanic patients, and after 23.3% of those among White patients; patients received naloxone after 14.4%, 20.7%, and 22.9%, respectively; and patients received benzodiazepines after 23.4%, 29.6%, and 37.1%, respectively. Racial differences in the receipt of medications to treat OUD did not change appreciably from 2016 to 2019 (buprenorphine receipt: after 9.1% of index events among Black patients vs. 21.6% of those among White patients in 2016, and after 14.1% vs. 25.5% in 2019). In all study groups, patients had multiple ambulatory visits in the 180 days after the index event (mean number of visits, 6.6 after events among Black patients, 6.7 after events among Hispanic patients, and 7.6 after events among White patients). CONCLUSIONS: Racial and ethnic differences in the receipt of medications to treat OUD after an index event related to this disorder among patients with disability were substantial and did not change over time. The high incidence of ambulatory visits in all groups showed that disparities persisted despite frequent health care contact. (Funded by the National Institute on Drug Abuse and the National Institute on Aging.).

Trends and variation in benzodiazepine use in nursing homes in the USA.

PURPOSE: Because of toxicities, benzodiazepines are not usually recommended in older adults. We therefore sought to describe the trends in benzodiazepine use in long-term care and examine the variation in benzodiazepine use among nursing homes. METHODS: In this retrospective repeated cross-sectional analysis of Medicare Parts A, B, and D claims data linked to the Minimum Data Set from 2013 to 2018, we included long-term residents who stayed in a nursing home for at least one entire quarter of a calendar year in 2013-2018. The outcome was whether residents were prescribed a benzodiazepine drug for at least 30 days during each quarter stay. We use mixed effects logistic regression models to assess the variation in benzodiazepine use among nursing homes, adjusting for patient and nursing home characteristics. RESULTS: The cohort for the time trend analysis included 270,566 unique residents and 1,843,580 quarter stays for 2013-2018. Prescribing rates for short-acting benzodiazepines were stable over 2013-2016, then declined from 12.1% in 2016 to 10.6% in 2018. The rate of long-acting benzodiazepine use remained relatively steady at around 4% over 2013-2018. During 2017-2018, the variation among nursing homes in benzodiazepine use was 7.2% for short-acting vs. 9.3% for long-acting benzodiazepines, after controlling for resident characteristics. CONCLUSION: Prescribing for short-acting benzodiazepines in long-term care declined after 2016, while long-acting benzodiazepine use did not change. The variation in benzodiazepine use among nursing homes is substantial. Identifying factors that explain this variation may help in developing strategies for deprescribing benzodiazepines in nursing home residents.

Mortality and concurrent use of opioids and hypnotics in older patients: A retrospective cohort study.

BACKGROUND: Benzodiazepine hypnotics and the related nonbenzodiazepine hypnotics (z-drugs) are among the most frequently prescribed medications for older adults. Both can depress respiration, which could have fatal cardiorespiratory effects, particularly among patients with concurrent opioid use. Trazodone, frequently prescribed in low doses for insomnia, has minimal respiratory effects, and, consequently, may be a safer hypnotic for older patients. Thus, for patients beginning treatment with benzodiazepine hypnotics or z-drugs, we compared deaths during periods of current hypnotic use, without or with concurrent opioids, to those for comparable patients receiving trazodone in doses up to 100 mg. METHODS AND FINDINGS: The retrospective cohort study in the United States included 400,924 Medicare beneficiaries 65 years of age or older without severe illness or evidence of substance use disorder initiating study hypnotic therapy from January 2014 through September 2015. Study endpoints were out-of-hospital (primary) and total mortality. Hazard ratios (HRs) were adjusted for demographic characteristics, psychiatric and neurologic disorders, cardiovascular and renal conditions, respiratory diseases, pain-related diagnoses and medications, measures of frailty, and medical care utilization in a time-dependent propensity score-stratified analysis. Patients without concurrent opioids had 32,388 person-years of current use, 260 (8.0/1,000 person-years) out-of-hospital and 418 (12.9/1,000) total deaths for benzodiazepines; 26,497 person-years,150 (5.7/1,000) out-of-hospital and 227 (8.6/1,000) total deaths for z-drugs; and 16,177 person-years,156 (9.6/1,000) out-of-hospital and 256 (15.8/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (respective HRs: 0.99 [95% confidence interval, 0.81 to 1.22, p = 0.954] and 0.95 [0.82 to 1.14, p = 0.513] and z-drugs (HRs: 0.96 [0.76 to 1.23], p = 0.767 and 0.87 [0.72 to 1.05], p = 0.153) did not differ significantly from that for trazodone. Patients with concurrent opioids had 4,278 person-years of current use, 90 (21.0/1,000) out-of-hospital and 127 (29.7/1,000) total deaths for benzodiazepines; 3,541 person-years, 40 (11.3/1,000) out-of-hospital and 64 (18.1/1,000) total deaths for z-drugs; and 2,347 person-years, 19 (8.1/1,000) out-of-hospital and 36 (15.3/1,000) total deaths for trazodone. Out-of-hospital and total mortality for benzodiazepines (HRs: 3.02 [1.83 to 4.97], p < 0.001 and 2.21 [1.52 to 3.20], p < 0.001) and z-drugs (HRs: 1.98 [1.14 to 3.44], p = 0.015 and 1.65 [1.09 to 2.49], p = 0.018) were significantly increased relative to trazodone; findings were similar with exclusion of overdose deaths or restriction to those with cardiovascular causes. Limitations included composition of the study cohort and potential confounding by unmeasured variables. CONCLUSIONS: In US Medicare beneficiaries 65 years of age or older without concurrent opioids who initiated treatment with benzodiazepine hypnotics, z-drugs, or low-dose trazodone, study hypnotics were not associated with mortality. With concurrent opioids, benzodiazepines and z-drugs were associated with increased out-of-hospital and total mortality. These findings indicate that the dangers of benzodiazepine-opioid coadministration go beyond the documented association with overdose death and suggest that in combination with opioids, the z-drugs may be more hazardous than previously thought.

A population pharmacodynamic Markov mixed-effects model for determining remimazolam-induced sedation when co-administered with fentanyl in procedural sedation.

The clinical effects of remimazolam (an investigational, ultra-short acting benzodiazepine being studied in procedural sedation) were measured using the Modified Observer's Assessment of Awareness/Sedation Scale (MOAA/S). The objective of this analysis was to develop a population pharmacokinetic/pharmacodynamic model to describe remimazolam-induced sedation with fentanyl over time in procedural sedation. MOAA/S from 10 clinical phase I-III trials were pooled for analysis, where data were collected after administration of placebo or remimazolam with or without concomitant fentanyl. A Markov model described transition states for 35,356 MOAA/S-time observations from 1071 subjects. Effect-compartment models of remimazolam and fentanyl linked plasma concentrations to the Markov model, and drug effects were described using a synergistic maximum effect (Emax ) model. Simulations were performed to identify the optimal remimazolam-fentanyl combination doses in procedural sedation. Fentanyl showed synergistic effects with remimazolam in sedation. Increasing age was related to longer recovery from sedation. Patients with body mass index greater than 25 kg/m2 had ~30% higher rates of distribution from plasma to the effect site (keo), indicating a slightly faster onset of sedation. Simulations showed that remimazolam 5 mg was more appropriate than 4 or 6 mg when administered with fentanyl 50 µg. The model and simulations support that a combination of remimazolam 5 mg with fentanyl 50 µg is an appropriate dosing regimen and the dose of remimazolam does not need to be changed in elderly patients, but some elderly patients may have a longer duration of sedation.

Assessment of benzodiazepine dosing strategies for the management of status epilepticus in the emergency department.

PURPOSE: Although guidelines recommend specific benzodiazepine doses for the treatment of generalized convulsive status epilepticus (GCSE), underdosing appears to be common. The purpose of this investigation was to assess benzodiazepine dosing strategies for the initial management of GCSE in patients presenting to the Emergency Department (ED). METHODS: This was a retrospective review of adult patients who received benzodiazepines in the ED for treatment of GCSE. Characteristics of those achieving seizure cessation following initial benzodiazepine therapy were assessed. RESULTS: 222 patients presented to the ED and received 403 doses of benzodiazepines, of which 1.5% conformed with recommendations. First-line therapy was successful in 86.8% of patients with an average dose of 1.6 mg (0.02 mg/kg). No difference in dosing was noted between those experiencing early cessation and those that did not (p = 0.132). Patients experiencing early cessation were significantly less likely to receive further doses, be intubated, or be admitted to the intensive care unit (ICU) or hospital (p < 0.05 for all comparisons). Those that received early antiepileptic drug therapy were significantly less likely to receive additional benzodiazepine doses, be intubated, or be admitted to the ICU or hospital (p < 0.05 for all comparisons). CONCLUSIONS: According to guideline recommendations, there was consistent underdosing of benzodiazepines noted in both prehospital and ED settings. Early seizure cessation and the early receipt of an antiepileptic drug were found to be associated with multiple significant clinical outcomes. Future investigations should explore optimal dosing strategies for benzodiazepines as well as the impact of early antiepileptic drug administration.

New Persistent Opioid and Benzodiazepine Use After Curative-Intent Treatment in Patients With Breast Cancer.

BACKGROUND: Opioid and benzodiazepine use and abuse is a national healthcare crisis to which patients with cancer are particularly vulnerable. Long-term use and risk factors for opioid and benzodiazepine use in patients with breast cancer is poorly characterized. METHODS: We conducted a retrospective population-based study of patients with breast cancer diagnosed between 2008 and 2015 undergoing curative-intent treatment identified through the SEER-Medicare linked database. Primary outcomes were new persistent opioid use and new persistent benzodiazepine use. Factors associated with new opioid and benzodiazepine use were investigated by univariate and multivariable logistic regression. RESULTS: Among opioid-naïve patients, new opioid use was observed in 22,418 (67.4%). Of this group, 611 (2.7%) developed persistent opioid use at 3 months and 157 (0.7%) at 6 months after treatment. Risk factors for persistent use at 3 and 6 months included stage III disease (odds ratio [OR], 2.16; 95% CI, 1.49-3.12, and OR, 3.48; 95% CI, 1.58-7.67), surgery plus chemotherapy (OR, 1.44; 95% CI, 1.10-1.88, and OR, 2.28; 95% CI, 1.40-3.71), surgery plus chemoradiation therapy (OR, 1.47; 95% CI, 1.10-1.96, and OR, 2.34; 95% CI, 1.38-3.96), and initial tramadol use (OR, 2.66; 95% CI, 2.05-3.46, and OR, 3.12; 95% CI, 1.93-5.04). Among benzodiazepine-naïve patients, new benzodiazepine use was observed in 955 (10.3%), and 111 (11.6%) developed new persistent use at 3 months. Tamoxifen use was statistically significantly associated with new persistent benzodiazepine use at 3 months. CONCLUSIONS: A large percentage of patients receiving curative-intent treatment of breast cancer were prescribed new opioids; however, only a small number developed new persistent opioid use. In contrast, a smaller proportion of patients received a new benzodiazepine prescription; however, new persistent use after completion of treatment was more likely and particularly related to concurrent treatment with tamoxifen.

Larger Initial Opioid Prescriptions Following Total Joint Arthroplasty Are Associated with Greater Risk of Prolonged Use.

BACKGROUND: The ongoing U.S. opioid epidemic threatens quality of life and poses substantial economic and safety burdens to opioid abusers and their communities, physicians, and health-care systems. Public health experts have argued that prescription opioids are implicated in this epidemic; however, opioid dosing following surgical procedures remains controversial. The purpose of this study was to evaluate the relationship between initial opioid prescribing following total hip arthroplasty (THA) and total knee arthroplasty (TKA) and the risk and quantity of long-term opioid use. METHODS: Patients undergoing THA or TKA from January 1, 2016, to June 30, 2016, were identified. Preoperative 30-day opioid and benzodiazepine exposures were evaluated using the Rhode Island Prescription Drug Monitoring Program. Cumulative morphine milligram equivalents (MMEs) in the postoperative inpatient stay, initial outpatient opioid prescription, and prescriptions filled from 31 to 90 days (prolonged use) and 91 to 150 days (chronic use) following the surgical procedure were calculated. Regression analyses evaluated the association between the initial postoperative opioid dosing and prolonged or chronic use, controlling for demographic characteristics, procedure, preoperative opioid and benzodiazepine exposures, anesthesia type, and use of a peripheral nerve block. RESULTS: A total of 507 patients (198 who underwent a THA and 309 who underwent a TKA) were identified. Increased inpatient opioid dosing (odds ratio [OR], 1.49 per 1 standard deviation increase in inpatient opioid MMEs; p = 0.001) and increased dosing in the first outpatient prescription (OR, 1.26 per 1 standard deviation increase in initial outpatient prescription MMEs; p = 0.049) were each independently associated with an increased risk of prolonged opioid use. Additionally, increased inpatient dosing postoperatively was strongly associated with a greater risk of chronic use (OR, 1.77 per 1 standard deviation increase in inpatient MMEs; p < 0.001). Among the 30% (151 of 507) of patients requiring prolonged postoperative opioids, each 1-MME increase in the initial outpatient prescription dose was associated with a 0.997-MME increase in quantity filled during the prolonged period (p < 0.001). Among the 14% (73 of 507) of patients requiring chronic opioids, every 1-MME increase in the initial outpatient dose was associated with a 1.678-MME increase in chronic opioid dosing (p = 0.008). CONCLUSIONS: Increased opioid dosing in the early postoperative period following total joint arthroplasty (TJA) is associated with an increased risk of extended opioid use. A dose-dependent relationship between initial outpatient dosing and greater future quantities consumed by those with prolonged usage and those with chronic usage was noted. This study suggests that providers should attempt to minimize inpatient and early outpatient opioid utilization following TJA. Multimodal pain management strategies may be employed to assist in achieving adequate pain control while minimizing opioid utilization. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Impact of COVID-19 related policy changes on filling of opioid and benzodiazepine medications.

BACKGROUND: Healthcare access has changed drastically during the COVID-19 pandemic. Elective medical procedures, including routine office visits, were restricted raising concerns regarding opioid and benzodiazepine provider and prescription availability. OBJECTIVE: To examine how the cancelation of elective medical procedures due to COVID-19 impacted the dispensing of opioid and benzodiazepine prescriptions in Texas. METHODS: Interrupted time series analyses were preformed to examine changes in prescription trends for opioids and benzodiazepines before and after the restriction on elective medical procedures. Samples of patients who filled an opioid or benzodiazepine prescription from January 5, 2020 to May 12, 2020 were identified from the Texas Prescription Monitoring Program. Elective medical procedures were restricted starting March 23, 2020 indicating the beginning of the intervention period. RESULTS: Restricting elective procedures was associated with a significant decrease in the number of patients (ß = -6029, 95%CI = -8810.40, -3246.72) and prescribers (ß = -2784, 95%CI = -3671.09, -1896.19) filling and writing opioid prescriptions, respectively. Also, the number of patients filling benzodiazepine prescriptions decreased significantly (ß = -1982, 95%CI = -3712.43, -252.14) as did the number of prescribers (ß = -708.62, 95%CI = -1190.54, -226.71). CONCLUSION: Restricting elective procedures resulted in a large care gap for patients taking opioid or benzodiazepine prescriptions.

Harm reduction in the time of COVID-19: Case study of homelessness and drug use in Dublin, Ireland.

Dublin appears to have performed very well as compared to various scenarios for COVID-19 mortality amongst homeless and drug using populations. The experience, if borne out by further research, provides important lessons for policy discussions on the pandemic, as well as broader lessons about pragmatic responses to these key client groups irrespective of COVID-19. The overarching lesson seems that when government policy is well coordinated and underpinned by a science-driven and fundamentally pragmatic approach, morbidity and mortality can be reduced. Within this, the importance of strategic clarity and delivery, housing, lowered thresholds to methadone provision, Benzodiazepine (BZD) provision and Naloxone availability were key determinants of policy success. Further, this paper argues that the rapid collapse in policy barriers to these interventions that COVID-19 produced should be secured and protected while further research is conducted.

[Need for Prescription Suggestions for Long-term Inpatients in the Psychiatric Ward].

Additional fees for ward pharmacists' services have been valued for hospitals in Japan. However, the calculation period for services provided to inpatients in the psychiatric ward is limited to 8 weeks. This study aimed to reveal the need for the services of pharmacists in the hospital ward for inpatients hospitalized for >8 weeks in the psychiatric ward. Patients who were hospitalized in the psychiatric ward from September 2016 to February 2017 were analyzed retrospectively. The pharmacists suggested prescriptions for inpatients admitted for >8 weeks, similar to those admitted for <9 weeks, and this supported pharmacotherapy without exacerbating patient outcomes. Moreover, significant decreases in benzodiazepine doses were found between the prior and post prescription suggestions of the pharmacist for inpatients >8 weeks of admission. Healthcare expenditures were also reduced. These results suggest that the prescriptions suggested by pharmacists for inpatients admitted for >8 weeks in the psychiatric ward were useful. In conclusion, our findings show that ward pharmacists' services were necessary not only for the inpatients hospitalized for <9 weeks, but also for those hospitalized for >8 weeks.

Medical, Political, and Economic Considerations for the Use of MAC for Endoscopic Sedation: Big Price, Little Justification?

The last few decades of gastrointestinal (GI) endoscopy have seen phenomenal growth. In many aspects, GI endoscopy has led the field of nonsurgical interventional medicine. In many aspects, this growth is facilitated by advancements in sedation-both drugs and techniques. Unfortunately, the topic of GI endoscopy sedation is also mired in many controversies, mainly emanating from the cost of anesthesia providers. While no one debates their role in the majority of advanced endoscopic procedures, the practice of universal propofol sedation in the USA, delivered by anesthesia providers, needs a closer look. In this review, medical, political, and economic considerations of this important topic are discussed in a very frank and honest way. While such ubiquitous propofol use has increased satisfaction of both patients and gastroenterologists, there is little justification. More importantly, going by the evidence, there is even less justification for the mandated anesthesia providers use for such delivery. Unfortunately, the FDA could not be convinced otherwise. The new drug fospropofol met the same fate. Approval of SEDASYS®, the first computer-assisted personalized sedation system, was a step in the right direction, nevertheless an insufficient step that failed to takeoff. As a result, in spite of years of research and efforts of many august societies, the logjam of balancing cost and justification of propofol sedation has continued. We hope that recent approval of remimazolam, a novel benzodiazepine, and potential approval of oliceridine, a novel short-acting opioid, might be able to contain the cost without compromising the quality of sedation.

Pattern evolution of antidepressants and benzodiazepines use in a cohort.

OBJECTIVE: In recent decades there has been an increase in the use of antidepressants (AD) and a decrease in the use of benzodiazepines (BDZ). Prevalence, cumulative incidence, and factors associated with the incidence of AD and BDZ use in a Brazilian population were estimated in this article. METHODS: Data were collected with a self-administered questionnaire in a cohort of employees from a university in Rio de Janeiro. The prevalence of the use of AD and BDZ was calculated for 1999 (4,030), 2001 (3,574), 2006-07 (3,058), and 2012 (2,933). The cumulative incidences of the use of AD and BDZ between 1999 and 2007 were estimated by the Poisson models with robust variance estimates. RESULTS: In 1999, the prevalence of the use of AD and BDZ were 1.4% (95%CI: 1.1-1.8) and 4.7% (95%CI: 4.1-5.4), respectively; in 2012, they were 5.4% (95%CI: 5.5-6.2) and 6.8% (95%CI: 6.0-7.8). The incidence of use, between 1999 and 2007, was 4.9% (95%CI: 4.2-5.7) for AD and 8.3% (95%CI: 7.3-9.3) for BDZ. The incidences of AD and BDZ use were higher among women and participants with a positive General Health Questionnaire. CONCLUSION: In this population, the increase in the use of AD was not accompanied by a decrease in the use of BDZ, showing the prescriptions for psychotropic medication do not follow the currently recommended guidelines for treatment of common mental health disorders.

Risk Factors and Outcomes of Opioid Users with and Without Concurrent Benzodiazepine Use in the North Carolina Medicaid Population.

BACKGROUND: Concurrent use of opioids and benzodiazepines is associated with increased risk of opioid overdose and death. Clinical guidelines recommend against this practice and quality measures incentivize plans to minimize concurrent use. OBJECTIVE: To compare comorbidities, risky opioid-related behaviors such as high daily doses or multiple prescribers or pharmacies, and outcomes of users of opioids with and without benzodiazepine in the 2017-2018 North Carolina Medicaid population. METHODS: This was a retrospective claims analysis that used 2017-2018 North Carolina Medicaid enrollment and administrative claims data to describe 3 populations: (1) opioid users who concurrently used benzodiazepine for at least 30 days, (2) opioid users who used some benzodiazepine for 0 to less than 30 overlapping days, and (3) opioid users who did not use benzodiazepines. RESULTS: From 2017 to 2018, 6% of opioid users concurrently used opioids and benzodiazepines for at least 30 days, and 14% used some benzodiazepine for less than 30 overlapping days. Persons filling prescriptions for opioids and benzodiazepines were more likely to have mood disorders and more likely to have depression than opioid users who did not use benzodiazepines. Compared with those not using benzodiazepines, opioid users using benzodiazepine were also more likely to have higher daily opioid doses (at least 90 morphine milligram equivalents), at least 3 prescribers, and at least 3 pharmacies for opioid prescriptions. Although enrollees with at least 30 days of overlapping benzodiazepines and opioids had a higher percentage diagnosed with opioid use disorder compared with those with less than 30 days (30% vs. 13%), a similar percentage received medication-assisted treatment continuously for 90 days (2.6% vs. 2.7%) during 2017-2018. Users of opioids and benzodiazepines, whether for at least 30 overlapping days or less, had higher 1-year cumulative incidences of all-cause outpatient emergency department visits (64% and 65% vs. 52%) and all-cause hospitalizations (25% and 21% vs. 14%) compared with opioid users without benzodiazepine use. CONCLUSIONS: Despite guidelines and quality measures, patients continue to use opioids and benzodiazepines concurrently. Addressing underlying mood disorders and depression, curbing risky opioid-related behaviors, and increasing access to medication-assisted treatment may benefit this population. DISCLOSURES: This project was supported by Arnold Ventures (formerly Arnold Foundation). Hung reports personal fees from CVS Health and Blue Cross Blue Shield Association, unrelated to this work. Maciejewski reports Amgen stock ownership due to spouse employment, unrelated to this work. McKethan reports personal fees from North Carolina Department of Health and Human Services. All other authors have nothing to disclose. Part of this content was presented as a poster at AMCP Nexus 2019; October 29-November 1, 2019; National Harbor, MD.

Changes in Concurrent Opioid and Benzodiazepine Use Following a Low-Touch Prescriber Fax Intervention.

BACKGROUND: Concurrent use of opioids and benzodiazepines (COB) can lead to additive respiratory and central nervous system effects, putting patients at increased risk of fatal overdose. In 2016, the Centers for Disease Control and Prevention released an opioid-prescribing guideline recommending against COB, and the Pharmacy Quality Alliance (PQA) endorsed a COB measure in its core opioid set. From May 1, 2017, to December 4, 2017, a California Medicaid plan launched a COB-focused prescriber outreach intervention for members receiving recent opioid and benzodiazepine claims with the intent of decreasing concurrent use. OBJECTIVE: To assess the effect of a prescriber fax intervention by a Medicaid plan on COB. METHODS: Two retrospective analyses were conducted using administrative pharmacy claims data: a comparison of the PQA COB rate among selected California Medicaid plans for 2016 and 2017 and a cohort utilization analysis of members identified for the fax intervention compared with controls. Intervention and control members were matched based on 12 pre-index utilization characteristics. Outcomes assessed included proportion of members with resolution of COB in the post-index period, change in mean number of COB days before and after the index date, and proportion of members with decreased benzodiazepine daily dose after the index date. Analyses were also performed for the subgroups of members with < 30 days of COB and ≥ 30 days of COB in the pre-index period. RESULTS: All California Medicaid plans in the study saw an improvement in the PQA COB rate between 2016 and 2017. In the utilization analysis, 4,182 intervention members were eligible according to study criteria and matched to similar control members. Many differences in medication use existed between the subgroups with < 30 days and ≥ 30 days of COB in the pre-index period, with the latter group consisting of much more chronic, complex users. The intervention cohort had a statistically significant higher proportion of members with complete resolution of COB compared with the control cohort (43.8% vs. 40.0%; P < 0.01), which was also statistically significant for the 2 subgroups. The intervention cohort had a decrease in the mean number of COB days from pre- to post-index periods, but this was only statistically significant for the subgroup with < 30 COB days (-2.5 vs. -1.5; P = 0.0217). No statistically significant differences were detected between cohorts in proportion of members with decreased benzodiazepine dose. CONCLUSIONS: Our analyses demonstrated that this low-touch prescriber fax intervention produced statistically significant improvements in COB outcomes, despite the overall trend of declining COB among the other California Medicaid plans. Low-touch, targeted prescriber outreach can be an inexpensive yet effective tool to affect prescriber behavior, particularly before COB becomes chronic. DISCLOSURES: No outside funding was used to support this study. The authors do not have any financial relationships or potential conflicts of interest relevant to this article to disclose. At the time of conducting this research, all authors were employees of MedImpact Healthcare Systems. The results of this study were presented at the AMCP Managed Care & Specialty Pharmacy Annual Meeting 2019; March 25-28, 2019; San Diego, CA.

Evidence-based clinical practice guidelines for the management of sedoanalgesia and delirium in critically ill adult patients. / Guías de práctica clínica basadas en la evidencia para el manejo de la sedoanalgesia y delirium en el paciente adulto críticamente enfermo.

Given the importance of the management of sedation, analgesia and delirium in Intensive Care Units, and in order to update the previously published guidelines, a new clinical practice guide is presented, addressing the most relevant management and intervention aspects based on the recent literature. A group of 24 intensivists from 9 countries of the Pan-American and Iberian Federation of Societies of Critical Medicine and Intensive Therapy met to develop the guidelines. Assessment of evidence quality and recommendations was made according to the Grading of Recommendations Assessment, Development and Evaluation Working Group. A systematic search of the literature was carried out using MEDLINE, Cochrane Library databases such as the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects, the National Health Service Economic Evaluation Database and the database of Latin American and Caribbean Literature in Health Sciences (LILACS). A total of 438 references were selected. After consensus, 47 strong recommendations with high and moderate quality evidence, 14 conditional recommendations with moderate quality evidence, and 65 conditional recommendations with low quality evidence were established. Finally, the importance of initial and multimodal pain management was underscored. Emphasis was placed on decreasing sedation levels and the use of deep sedation only in specific cases. The evidence and recommendations for the use of drugs such as dexmedetomidine, remifentanil, ketamine and others were incremented.

Pattern evolution of antidepressants and benzodiazepines use in a cohort

ABSTRACT OBJECTIVE In recent decades there has been an increase in the use of antidepressants (AD) and a decrease in the use of benzodiazepines (BDZ). Prevalence, cumulative incidence, and factors associated with the incidence of AD and BDZ use in a Brazilian population were estimated in this article. METHODS Data were collected with a self-administered questionnaire in a cohort of employees from a university in Rio de Janeiro. The prevalence of the use of AD and BDZ was calculated for 1999 (4,030), 2001 (3,574), 2006-07 (3,058), and 2012 (2,933). The cumulative incidences of the use of AD and BDZ between 1999 and 2007 were estimated by the Poisson models with robust variance estimates. RESULTS In 1999, the prevalence of the use of AD and BDZ were 1.4% (95%CI: 1.1-1.8) and 4.7% (95%CI: 4.1-5.4), respectively; in 2012, they were 5.4% (95%CI: 5.5-6.2) and 6.8% (95%CI: 6.0-7.8). The incidence of use, between 1999 and 2007, was 4.9% (95%CI: 4.2-5.7) for AD and 8.3% (95%CI: 7.3-9.3) for BDZ. The incidences of AD and BDZ use were higher among women and participants with a positive General Health Questionnaire. CONCLUSION In this population, the increase in the use of AD was not accompanied by a decrease in the use of BDZ, showing the prescriptions for psychotropic medication do not follow the currently recommended guidelines for treatment of common mental health disorders.

Overlapping prescriptions of opioids, benzodiazepines, and carisoprodol: "Holy Trinity" prescribing in the state of Florida.

BACKGROUND: High-risk combinations of controlled medications, such as those involving opioid analgesics, are under increased scrutiny because of their contribution to the opioid epidemic in the United States. Responsible prescribing guidelines indicate that the triple drug combination--opioids, benzodiazepines and skeletal muscle relaxants, especially carisoprodol--should not be concurrently prescribed. METHODS: This pharmacoepidemiologic study was designed to primarily examine the characteristics of patients receiving this triple combination compared to the group receiving only opioids and benzodiazepines. RESULTS: Results show that, while the number of exposed patients has declined since 2012, approximately 17,000 Floridians were prescribed this combination in 2017 alone. Demographically, recipients of these prescriptions were younger, more likely to be female, and geographically-localized. Furthermore, these patients were more frequently associated with a prescriber in the top 1% of opioid and/or benzodiazepine prescribing, have more multiple provider episodes ("doctor shopping"), and receive higher mean daily opioid dosages. CONCLUSIONS: These findings raise important questions as to how frequently prescribers are checking prescription drug monitoring programs, following US Centers for Disease Control and Prevention opioid prescribing guidelines, and/or handling the clinical challenges associated with pharmaceutical management of patients with complex, painful health conditions.

Association of Opioid, Anti-Depressant, and Benzodiazepines With Workers' Compensation Cost: A Cohort Study.

BACKGROUND: Antidepressants, benzodiazapines, and opioid medications are used to manage the pain, anxiety, or depression associated with workplace injuries. OBJECTIVE: To evaluate the impact of these medications on workers' compensation costs and time lost from work. METHODS: A cohort of 22,383 indemnity claims from 2008 to 2013 were evaluated for the association of prescribed medications on claim cost and delayed claim closure controlling for confounders. RESULTS: Claims with anti-depressant, opioid, or benzodiazepine prescriptions were 2.24 (95% CI: 2.00 to 2.51), 1.14 (95% CI: 1.02 to 1.27), and 1.38 (95% CI: 1.23 to 1.54) times more likely to remain open at the end of the study. CONCLUSION: The concurrent treatment of pain, depression or anxiety, and occupational injuries are associated with large increases in claim cost and delayed return to work.

Gender differences in prescribing of zolpidem in the Veterans Health Administration.

OBJECTIVES: Use of nonbenzodiazepine sedative hypnotics, especially zolpidem, has grown substantially, raising concerns about safety. Here, we evaluated prescribing patterns of zolpidem in the Veterans Health Administration. STUDY DESIGN: A cross-sectional study of veterans receiving zolpidem in the outpatient setting from October 1, 2011, to September 30, 2016. METHODS: The study population consisted of 500,332 zolpidem users (58,598 women and 441,734 men) and a random 10% sample (n = 631,449) of nonusers. We examined 2 outcomes related to inappropriate prescribing: high-dose zolpidem prescribing and overlap with benzodiazepines. We generated interrupted time series and logistic regression models to analyze these outcomes in men and women separately. RESULTS: In 2016, 29.7% of female veterans received an inappropriately high guideline-discordant dosage compared with 0.1% of male veterans (P <.001 for all reported comparisons). Furthermore, more women than men had overlapping benzodiazepine and zolpidem prescriptions (18.8% vs 14.3%). In fully adjusted models, inappropriately high doses were more commonly received by younger women (adjusted odds ratios [AORs]: 2.75 for 21-39 years and 2.97 for 40-49 years compared with ≥80 years) and women with substance use disorder (AOR, 1.48). In the second inappropriateness outcome models, women with anxiety (AOR, 2.28) or schizophrenia (AOR, 2.05) and men with cancer (AOR, 1.42), anxiety (AOR, 2.66), or schizophrenia (AOR, 2.46) were more likely to receive an overlapping prescription of zolpidem and benzodiazepines. CONCLUSIONS: We found evidence of inappropriate zolpidem prescribing among veterans, particularly women. Greater understanding of the drivers of this inappropriate prescribing is necessary to develop interventions to promote safer, more guideline-concordant prescribing.