Introduction

Although opioid use disorder (OUD) is common in patients with cirrhosis, it is unclear how medication treatment for OUD (MOUD) is used in this population. We aimed to assess the factors associated with MOUD and mortality in a cohort of Veterans with cirrhosis and OUD.

Methods

Within the Veterans Health Administration Corporate Data Warehouse, we developed a cohort of Veterans with cirrhosis and active OUD, using 2 outpatient or 1 inpatient International Classification of Diseases, ninth revision codes from 2011 to 2015 to define each condition. We assessed MOUD initiation with methadone or buprenorphine over the 180 days following the first OUD International Classification of Diseases, ninth revision code in the study period. We fit multivariable regression models to assess the association of sociodemographic and clinical factors with receiving MOUD and the associations between MOUD and subsequent clinical outcomes, including new hepatic decompensation and mortality.

Results

Among 5,600 Veterans meeting criteria for active OUD and cirrhosis, 722 (13%) were prescribed MOUD over 180 days of follow-up. In multivariable modeling, MOUD was significantly, positively associated with age (adjusted odds ratio [AOR] per year: 1.04, 95% confidence interval (CI): 1.01-1.07), hepatitis C virus (AOR = 2.15, 95% CI = 1.37-3.35), and other substance use disorders (AOR = 1.47, 95% CI = 1.05-2.04) negatively associated with alcohol use disorder (AOR = 0.70, 95% CI = 0.52-0.95), opioid prescription (AOR = 0.51, 95% CI = 0.38-0.70), and schizophrenia (AOR = 0.59, 95% CI = 0.37-0.95). MOUD was not significantly associated with mortality (adjusted hazards ratio = 1.20, 95% CI = 0.95-1.52) or new hepatic decompensation (OR = 0.57, CI = 0.30-1.09).

Discussion

Few Veterans with active OUD and cirrhosis received MOUD, and those with alcohol use disorder, schizophrenia, and previous prescriptions for opioids were least likely to receive these effective therapies.

Background and aims

Despite the significant medical and economic consequences of coexisting alcohol use disorder (AUD) in patients with cirrhosis, little is known about AUD treatment patterns and their impact on clinical outcomes in this population. We aimed to characterize the use of and outcomes associated with AUD treatment in patients with cirrhosis.

Approach and results

This retrospective cohort study included Veterans with cirrhosis who received Veterans Health Administration care and had an index diagnosis of AUD between 2011 and 2015. We assessed the baseline factors associated with AUD treatment (pharmacotherapy or behavioral therapy) and clinical outcomes for 180 days following the first AUD diagnosis code within the study time frame. Among 93,612 Veterans with cirrhosis, we identified 35,682 with AUD, after excluding 2,671 who had prior diagnoses of AUD and recent treatment. Over 180 days following the index diagnosis of AUD, 5,088 (14%) received AUD treatment, including 4,461 (12%) who received behavioral therapy alone, 159 (0.4%) who received pharmacotherapy alone, and 468 (1%) who received both behavioral therapy and pharmacotherapy. In adjusted analyses, behavioral and/or pharmacotherapy-based AUD treatment was associated with a significant reduction in incident hepatic decompensation (6.5% vs. 11.6%, adjusted odds ratio [AOR], 0.63; 95% confidence interval [CI], 0.52, 0.76), a nonsignificant decrease in short-term all-cause mortality (2.6% vs. 3.9%, AOR, 0.79; 95% CI, 0.57, 1.08), and a significant decrease in long-term all-cause mortality (51% vs. 58%, AOR, 0.87; 95% CI, 0.80, 0.96).

Conclusions

Most Veterans with cirrhosis and coexisting AUD did not receive behavioral therapy or pharmacotherapy treatment for AUD over a 6-month follow-up. The reductions in hepatic decompensation and mortality suggest that future studies should focus on delivering evidence-based AUD treatments to patients with coexisting AUD and cirrhosis.

Background

All Department of Veterans Affairs Medical Centers (VAMCs) operate under a single national drug formulary, yet substantial variation in prescribing and spending exists across facilities. Local management of the national formulary may differ across VAMCs and may be one cause of this variation.

Objective

To characterize variation in the management of nonformulary medication requests and pharmacy and therapeutics (P&T) committee member perceptions of the formulary environment at VAMCs nationwide.

Methods

We performed an online survey of the chief of pharmacy and an additional staff pharmacist and physician on the P&T committee at all VAMCs. Respondents were asked questions regarding criteria for use for nonformulary medications, specific procedures for ordering nonformulary medications in general and specific lipid-lowering and diabetes agents, the appeals process, and the formulary environment at their VAMCs. We compared responses across facilities and between chiefs of pharmacy, pharmacists, and physicians.

Results

A total of 212 chief pharmacists (n = 80), staff pharmacists (n = 78), and physicians (n = 54) responded, for an overall response rate of 49%. In total, 107/143 (75%) different VAMCs were represented. The majority of VAMCs reported adhering to national criteria for use, with 38 (36%) being very adherent and 69 (65%) being mostly adherent. There was substantial variation between VAMCs regarding how nonformulary drugs were ordered, evaluated, and appealed. The nonformulary lipid-lowering drugs ezetimibe, rosuvastatin, and atorvastatin were viewable to providers in the order entry screen at 67 (63%), 67 (63%), and 64 (60%) VAMCs, respectively. The nonformulary diabetes medication pioglitazone was only viewable at 58 (55%) VAMCs. In the remaining VAMCs, providers could not order these nonformulary drugs through the normal order-entry process. For questions about the formulary environment, physician respondent perceptions differed from those of staff pharmacists and chief pharmacists. Compared with pharmacy chiefs and staff pharmacists, physicians were less likely to agree that providers at their VAMC prescribed too many nonformulary medications (47% and 44% vs. 12%, P < 0.001), more likely to agree that providers must jump through too many hoops to prescribe nonformulary medication (5% and 3% vs. 25%, P < 0.001), and more likely to agree that providers make an effort to convert new patients from nonformulary to formulary lipid-lowering (65% and 73% vs. 94%, P <0.02) and diabetic medications (49% and 50% vs. 88%, P < 0.001).

Conclusions

Although the Department of Veterans Affairs (VA) operates under a single national formulary, we found significant differences among VAMCs regarding their management of nonformulary medication requests. We also found differences among formulary leaders regarding their perception of the environment in which their VAMC's formulary is managed. These findings have important implications not just for VA, but for any organization that develops, implements, and manages drug formularies across multiple facilities.

Background

The Procalcitonin Antibiotic Consensus Trial (ProACT) found provision of a procalcitonin antibiotic prescribing guideline to hospital-based clinicians did not reduce antibiotic use. Possible reasons include clinician reluctance to follow the guideline, with an observed 64.8% adherence rate. In this study we sought to determine the threshold adherence rate for reduction in antibiotic use, and to explore opportunities to increase adherence.

Methods

This study is a retrospective analysis of ProACT data. ProACT randomized 1656 patients presenting to 14 U.S. hospitals with suspected lower respiratory tract infection to usual care or provision of procalcitonin assay results and an antibiotic prescribing guideline to the treating clinicians. We simulated varying adherence to guideline recommendations for low procalcitonin levels and determined which threshold adherence rate could have resulted in rejection of the null hypothesis of no difference between groups at alpha = 0.05. We also performed sensitivity analyses within specific clinical settings and grouped patients initially prescribed antibiotics despite low procalcitonin into low, medium, and high risk of illness severity or bacterial infection.

Results

Our primary outcome was number of antibiotic-days by day 30 using an intention-to-treat approach and a null hypothesis of no difference in antibiotic use. We determined that an 84% adherence rate in the hospital setting (emergency department and inpatient) for low procalcitonin could have allowed rejection of the null hypothesis (3.7 vs 4.3 antibiotic-days, p = 0.048). The threshold adherence rate was 76% for continued guideline adherence after discharge. Even 100% adherence in the emergency department alone failed to reduce antibiotic-days. Of the 218 patients prescribed antibiotics in the emergency department despite low procalcitonin, 153 (70.2%) were categorized as low or medium risk.

Conclusions

High adherence in the hospital setting to a procalcitonin antibiotic prescribing guideline is necessary to reduce antibiotic use in suspected lower respiratory tract infection. Continued guideline adherence after discharge and withholding of antibiotics in low and medium risk patients with low procalcitonin may offer impactful potential opportunities for antibiotic reduction. Trial registration Procalcitonin Antibiotic Consensus Trial (ProACT), ClinicalTrials.gov Identifier: NCT02130986. First posted May 6, 2014.

Objective

Evaluate self-reported electronic screening (eScreening) in a VA Transition Care Management Program (TCM) to improve the accuracy and completeness of administrative ethnicity and race data.

Materials and methods

We compared missing, declined, and complete (neither missing nor declined) rates between (1) TCM-eScreening (ethnicity and race entered into electronic tablet directly by patient using eScreening), (2) TCM-EHR (Veteran-completed paper form plus interview, data entered by staff), and (3) Standard-EHR (multiple processes, data entered by staff). The TCM-eScreening (n = 7113) and TCM-EHR groups (n = 7113) included post-9/11 Veterans. Standard-EHR Veterans included all non-TCM Gulf War and post-9/11 Veterans at VA San Diego (n = 92 921).

Results

Ethnicity: TCM-eScreening had lower rates of missingness than TCM-EHR and Standard-EHR (3.0% vs 5.3% and 8.6%, respectively, P < .05), but higher rates of "decline to answer" (7% vs 0.5% and 1.2%, P < .05). TCM-EHR had higher data completeness than TCM-eScreening and Standard-EHR (94.2% vs 90% and 90.2%, respectively, P < .05). Race: No differences between TCM-eScreening and TCM-EHR for missingness (3.5% vs 3.4%, P > .05) or data completeness (89.9% vs 91%, P > .05). Both had better data completeness than Standard-EHR (P < .05), which despite the lowest rate of "decline to answer" (3%) had the highest missingness (10.3%) and lowest overall completeness (86.6%). There was strong agreement between TCM-eScreening and TCM-EHR for ethnicity (Kappa = .92) and for Asian, Black, and White Veteran race (Kappas = .87 to .97), but lower agreement for American Indian/Alaska Native (Kappa = .59) and Native Hawaiian/Other Pacific Islander (Kappa = .50) Veterans.

Conculsions

eScreening is a promising method for improving ethnicity and race data accuracy and completeness in VA.

Background & aims

Despite increased risks for adverse effects in patients with cirrhosis, little is known about opioid prescriptions for this population. We aimed to assess time trends in opioid prescribing and factors associated with receiving opioids among patients with cirrhosis.

Methods

Among Veterans with cirrhosis, identified using national Veterans Health Administration data (2005-2014), we assessed characteristics of patients and their prescriptions for opioids. We calculated the annual proportion of patients receiving any opioid prescription. Among opioid recipients, we assessed prescriptions that were long-term (>90 days' supply), for high doses (>100 MME/day), or involved combinations of opioids and acetaminophen or benzodiazepine. We evaluated patient characteristics independently associated with long-term and any opioid prescriptions using mixed-effects regression models.

Results

Among 127,239 Veterans with cirrhosis, 97,974 (77.0%) received a prescription for an opioid. Annual opioid prescriptions increased from 36% in 2005 to 47% in 2014 (P < .01). Among recipients of opioids, the proportions of those receiving long-term prescriptions increased from 47% in 2005 to 54% in 2014 (P < .01), and19%-21% received prescriptions for high-dose opioids. Prescriptions for combinations of opioids and acetaminophen decreased from 68% in 2005 to 50% in 2014 (P < .01) and for combinations of opioids and benzodiazepines decreased from 24% to 19% over this time (P < .01). Greater probability of long-term opioid prescriptions was independently associated with younger age, female sex, white race, hepatitis C, prior hepatic decompensation, hepatocellular carcinoma, mental health disorders, nicotine use disorders, medical comorbidities, surgery, and pain-related conditions.

Conclusion

Among Veterans with cirrhosis, 36%-47% were prescribed opioids in each year. Mental health disorders and hepatic decompensation were independently associated with long-term opioid prescriptions.

Background

Overuse of antibiotics is a major public health problem, contributing to growing antibiotic resistance. Procalcitonin has been reported to be commonly elevated in bacterial, but not viral infection. Multiple European trials found procalcitonin-guided care reduced antibiotic use in lower respiratory tract infection, with no apparent harm. However, applicability to US practice is limited due to trial design features impractical in the US, between-country differences, and residual safety concerns.

Methods

The Procalcitonin Antibiotic Consensus Trial (ProACT) is a multicenter randomized trial to determine the impact of a procalcitonin antibiotic prescribing guideline, implemented with basic reproducible strategies, in US patients with lower respiratory tract infection.

Discussion

We describe the trial methods using the Consolidated Standards of Reporting Trials (CONSORT) framework, and the rationale for key design decisions, including choice of eligibility criteria, choice of control arm, and approach to guideline implementation.

Trial registration

ClinicalTrials.gov NCT02130986 . Registered May 1, 2014.

Background

Pulmonary infections remain more common in HIV-infected (HIV+) compared with uninfected individuals. The increase in chronic lung diseases among aging HIV+ individuals may contribute to this persistent risk. We sought to determine whether chronic obstructive pulmonary disease (COPD) is an independent risk factor for different pulmonary infections requiring hospitalization among HIV+ patients.

Methods

We analyzed data from 41,993 HIV+ Veterans in the nationwide Veterans Aging Cohort Study Virtual Cohort from 1996 to 2009. Using International Classification of Diseases, Ninth Revision codes, we identified baseline comorbid conditions, including COPD, and incident community-acquired pneumonia (CAP), pulmonary tuberculosis (TB), and Pneumocystis jirovecii pneumonia (PCP) requiring hospitalization within 2 years after baseline. We used multivariable Poisson regression to determine incidence rate ratios (IRRs) associated with COPD for each type of pulmonary infection, adjusting for comorbidities, CD4 cell count, HIV viral load, smoking status, substance use, vaccinations, and calendar year at baseline.

Results

Unadjusted incidence rates of CAP, TB, and PCP requiring hospitalization were significantly higher among persons with COPD compared to those without COPD (CAP: 53.9 vs. 19.4 per 1000 person-years; TB: 8.7 vs. 2.8; PCP: 15.5 vs. 9.2; P ≤ 0.001). In multivariable Poisson regression models, COPD was independently associated with increased risk of CAP, TB, and PCP (IRR: 1.94, 95% confidence interval [CI]: 1.64 to 2.30; IRR: 2.60, 95% CI: 1.70 to 3.97; and IRR: 1.48, 95% CI: 1.10 to 2.01, respectively).

Conclusions

COPD is an independent risk factor for CAP, TB, and PCP requiring hospitalization among HIV+ individuals. As the HIV+ population ages, the growing burden of COPD may confer substantial risk for pulmonary infections.

Background

The effect of procalcitonin-guided use of antibiotics on treatment for suspected lower respiratory tract infection is unclear.

Methods

In 14 U.S. hospitals with high adherence to quality measures for the treatment of pneumonia, we provided guidance for clinicians about national clinical practice recommendations for the treatment of lower respiratory tract infections and the interpretation of procalcitonin assays. We then randomly assigned patients who presented to the emergency department with a suspected lower respiratory tract infection and for whom the treating physician was uncertain whether antibiotic therapy was indicated to one of two groups: the procalcitonin group, in which the treating clinicians were provided with real-time initial (and serial, if the patient was hospitalized) procalcitonin assay results and an antibiotic use guideline with graded recommendations based on four tiers of procalcitonin levels, or the usual-care group. We hypothesized that within 30 days after enrollment the total antibiotic-days would be lower - and the percentage of patients with adverse outcomes would not be more than 4.5 percentage points higher - in the procalcitonin group than in the usual-care group.

Results

A total of 1656 patients were included in the final analysis cohort (826 randomly assigned to the procalcitonin group and 830 to the usual-care group), of whom 782 (47.2%) were hospitalized and 984 (59.4%) received antibiotics within 30 days. The treating clinician received procalcitonin assay results for 792 of 826 patients (95.9%) in the procalcitonin group (median time from sample collection to assay result, 77 minutes) and for 18 of 830 patients (2.2%) in the usual-care group. In both groups, the procalcitonin-level tier was associated with the decision to prescribe antibiotics in the emergency department. There was no significant difference between the procalcitonin group and the usual-care group in antibiotic-days (mean, 4.2 and 4.3 days, respectively; difference, -0.05 day; 95% confidence interval [CI], -0.6 to 0.5; P=0.87) or the proportion of patients with adverse outcomes (11.7% [96 patients] and 13.1% [109 patients]; difference, -1.5 percentage points; 95% CI, -4.6 to 1.7; P<0.001 for noninferiority) within 30 days.

Conclusions

The provision of procalcitonin assay results, along with instructions on their interpretation, to emergency department and hospital-based clinicians did not result in less use of antibiotics than did usual care among patients with suspected lower respiratory tract infection. (Funded by the National Institute of General Medical Sciences; ProACT ClinicalTrials.gov number, NCT02130986 .).