Opioid therapy trajectories of patients with chronic non-cancer pain over 1 year of follow-up after initiation of short-acting opioid formulations.

OBJECTIVE: This study compared opioid utilization trajectories of persons initiating tramadol, short-acting hydrocodone, or short-acting oxycodone, and it characterized opioid dose trajectories and type of opioid in persistent opioid therapy subsamples. METHODS: A retrospective cohort study of adults with chronic non-cancer pain who were initiating opioid therapy was conducted with the IQVIA PharMetrics® Plus for Academics data (2008-2018). Continuous enrollment was required for 6 months before ("baseline") and 12 months after ("follow-up") the first opioid prescription ("index date"). Opioid therapy measures were assessed every 7 days over follow-up. Group-based trajectory modeling (GBTM) was used to identify trajectories for any opioid and total morphine milligram equivalent measures, and longitudinal latent class analysis was used for opioid therapy type. RESULTS: A total of 40 276 tramadol, 141 023 hydrocodone, and 45 221 oxycodone initiators were included. GBTM on any opioid therapy identified 3 latent trajectories: early discontinuers (tramadol 39.0%, hydrocodone 54.1%, oxycodone 61.4%), late discontinuers (tramadol 37.9%, hydrocodone 39.4%, oxycodone 33.3%), and persistent therapy (tramadol 6.7%, hydrocodone 6.5%, oxycodone 5.3%). An additional fourth trajectory, intermittent therapy (tramadol 16.4%), was identified for tramadol initiators. Of those on persistent therapy, 2687 individuals were on persistent therapy with tramadol, 9169 with hydrocodone, and 2377 with oxycodone. GBTM on opioid dose resulted in 6 similar trajectory groups in each persistent therapy group. Longitudinal latent class analysis on opioid therapy type identified 6 latent classes for tramadol and oxycodone and 7 classes for hydrocodone. CONCLUSION: Opioid therapy patterns meaningfully differed by the initial opioid prescribed, notably the presence of intermittent therapy among tramadol initiators and higher morphine milligram equivalents and prescribing of long-acting opioids among oxycodone initiators.

Human PD-1 agonist treatment alleviates neutrophilic asthma by reprogramming T cells.

BACKGROUND: Neutrophilic asthma is associated with disease severity and corticosteroid insensitivity. Novel therapies are required to manage this life-threatening asthma phenotype. Programmed cell death protein-1 (PD-1) is a key homeostatic modulator of the immune response for T-cell effector functions. OBJECTIVE: We sought to investigate the role of PD-1 in the regulation of acute neutrophilic inflammation in a murine model of airway hyperreactivity (AHR). METHODS: House dust mite was used to induce and compare neutrophilic AHR in wild-type and PD-1 knockout mice. Then, the therapeutic potential of a human PD-1 agonist was tested in a humanized mouse model in which the PD-1 extracellular domain is entirely humanized. Single-cell RNA sequencing and flow cytometry were mainly used to investigate molecular and cellular mechanisms. RESULTS: PD-1 was highly induced on pulmonary T cells in our inflammatory model. PD-1 deficiency was associated with an increased neutrophilic AHR and high recruitment of inflammatory cells to the lungs. Consistently, PD-1 agonist treatment dampened AHR, decreased neutrophil recruitment, and modulated cytokine production in a humanized PD-1 mouse model. Mechanistically, we demonstrated at the transcriptional and protein levels that the inhibitory effect of PD-1 agonist is associated with the reprogramming of pulmonary effector T cells that showed decreased number and activation. CONCLUSIONS: PD-1 agonist treatment is efficient in dampening neutrophilic AHR and lung inflammation in a preclinical humanized mouse model.

Cannabinoid receptor 2 engagement promotes group 2 innate lymphoid cell expansion and enhances airway hyperreactivity.

BACKGROUND: Cannabinoids modulate the activation of immune cells and physiologic processes in the lungs. Group 2 innate lymphoid cells (ILC2s) are central players in type 2 asthma, but how cannabinoids modulate ILC2 activation remains to be elucidated. OBJECTIVE: Our goal was to investigate the effects of cannabinoids on ILC2s and their role in asthma. METHODS: A combination of cannabinoid receptor (CB)2 knockout (KO) mice, CB2 antagonist and agonist were used in the mouse models of IL-33, IL-25, and Alternaria alternata ILC2-dependent airway inflammation. RNA sequencing was performed to assess transcriptomic changes in ILC2s, and humanized mice were used to assess the role of CB2 signaling in human ILC2s. RESULTS: We provide evidence that CB2 signaling in ILC2s is important for the development of ILC2-driven airway inflammation in both mice and human. We showed that both naive and activated murine pulmonary ILC2s express CB2. CB2 signaling did not affect ILC2 homeostasis at steady state, but strikingly it stimulated ILC2 proliferation and function upon activation. As a result, ILC2s lacking CB2 induced lower lung inflammation, as we made similar observations using a CB2 antagonist. Conversely, CB2 agonism remarkably exacerbated ILC2-driven airway hyperreactivity and lung inflammation. Mechanistically, transcriptomic and protein analysis revealed that CB2 signaling induced cyclic adenosine monophosphate-response element binding protein (CREB) phosphorylation in ILC2s. Human ILC2s expressed CB2, as CB2 antagonism and agonism showed opposing effects on ILC2 effector function and development of airway hyperreactivity in humanized mice. CONCLUSION: Collectively, our results define CB2 signaling in ILC2s as an important modulator of airway inflammation.

LAIR-1 acts as an immune checkpoint on activated ILC2s and regulates the induction of airway hyperreactivity.

BACKGROUND: Type 2 innate lymphoid cells (ILC2s) are relevant players in type 2 asthma. They initiate eosinophil infiltration and airway hyperreactivity (AHR) through cytokine secretion. Leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) is an inhibitory receptor considered to be an immune checkpoint in different inflammatory diseases. OBJECTIVE: Our aim here was to investigate the expression of LAIR-1 and assess its role in human and murine ILC2s. METHODS: Wild-type and LAIR-1 knockout mice were intranasally challenged with IL-33, and pulmonary ILC2s were sorted to perform an ex vivo comparative study based on RNA sequencing and flow cytometry. We next studied the impact of LAIR-1 deficiency on AHR and lung inflammation by using knockout mice and adoptive transfer experiments in Rag2-/-Il2rg-/- mice. Knockdown antisense strategies and humanized mice were used to assess the role of LAIR-1 in human ILC2s. RESULTS: We have demonstrated that LAIR-1 is inducible on activated ILC2s and downregulates cytokine secretion and effector function. LAIR-1 signaling in ILC2s was mediated via inhibitory pathways, including SHP1/PI3K/AKT, and LAIR-1 deficiency led to exacerbated ILC2-dependent AHR in IL-33 and Alternaria alternata models. In adoptive transfer experiments, we confirmed the LAIR-1-mediated regulation of ILC2s in vivo. Interestingly, LAIR-1 was expressed and inducible in human ILC2s, and knockdown approaches of Lair1 resulted in higher cytokine production. Finally, engagement of LAIR-1 by physiologic ligand C1q significantly reduced ILC2-dependent AHR in a humanized ILC2 murine model. CONCLUSION: Our results unravel a novel regulatory axis in ILC2s with the capacity to reduce allergic AHR and lung inflammation.

IL-10 production by ILC2s requires Blimp-1 and cMaf, modulates cellular metabolism, and ameliorates airway hyperreactivity.

BACKGROUND: Group 2 innate lymphoid cells (ILC2s) are the dominant innate lymphoid cell population in the lungs at steady state, and their release of type 2 cytokines is a central driver in responding eosinophil infiltration and increased airway hyperreactivity. Our laboratory has identified a unique subset of ILC2s in the lungs that actively produce IL-10 (ILC210s). OBJECTIVE: Our aim was to characterize the effector functions of ILC210s in the development and pathology of allergic asthma. METHODS: IL-4-stimulated ILC210s were isolated to evaluate cytokine secretion, transcription factor signaling, metabolic dependence, and effector functions in vitro. ILC210s were also adoptively transferred into Rag2-/-γc-/- mice, which were then challenged with IL-33 and assessed for airway hyperreactivity and lung inflammation. RESULTS: We have determined that the transcription factors cMaf and Blimp-1 regulate IL-10 expression in ILC210s. Strikingly, our results demonstrate that ILC210s can utilize both autocrine and paracrine signaling to suppress proinflammatory ILC2 effector functions in vitro. Further, this subset dampens airway hyperreactivity and significantly reduces lung inflammation in vivo. Interestingly, ILC210s demonstrated a metabolic dependency on the glycolytic pathway for IL-10 production, shifting from the fatty acid oxidation pathway conventionally utilized for proinflammatory effector functions. CONCLUSION: These findings provide an important and previously unrecognized role of ILC210s in diseases associated with ILC2s such as allergic lung inflammation and asthma. They also provide new insights into the metabolism dependency of proinflammatory and anti-inflammatory ILC2 phenotypes.

Clinical Impact of Accelerate Pheno Rapid Blood Culture Detection System in Bacteremic Patients.

BACKGROUND: Accelerate Pheno blood culture detection system (AXDX) provides rapid identification and antimicrobial susceptibility testing results. Limited data exist regarding its clinical impact. Other rapid platforms coupled with antimicrobial stewardship program (ASP) real-time notification (RTN) have shown improved length of stay (LOS) in bacteremia. METHODS: A single-center, quasi-experimental study of bacteremic inpatients before and after AXDX implementation was conducted comparing clinical outcomes from 1 historical and 2 intervention cohorts (AXDX and AXDX + RTN). RESULTS: Of 830 bacteremic episodes, 188 of 245 (77%) historical and 308 (155 AXDX, 153 AXDX + RTN) of 585 (65%) intervention episodes were included. Median LOS was shorter with AXDX (6.3 days) and AXDX + RTN (6.7 days) compared to historical (8.1 days) (P = .001). In the AXDX and AXDX + RTN cohorts, achievement of optimal therapy (AOT) was more frequent (93.6% and 95.4%, respectively) and median time to optimal therapy (TTOT) was faster (1.3 days and 1.4 days, respectively) compared to historical (84.6%, P ≤ .001 and 2.4 days, P ≤ .001, respectively). Median antimicrobial days of therapy (DOT) was shorter in both intervention arms compared to historical (6 days each vs 7 days; P = .011). Median LOS benefit during intervention was most pronounced in coagulase-negative Staphylococcus bacteremia (P = .003). CONCLUSIONS: LOS, AOT, TTOT, and total DOT significantly improved after AXDX implementation. Addition of RTN did not show further improvement over AXDX and an already active ASP. These results suggest that AXDX can be integrated into healthcare systems with an active ASP even without the resources to include RTN.

Whole Health Options and Pain Education (wHOPE): A Pragmatic Trial Comparing Whole Health Team vs Primary Care Group Education to Promote Nonpharmacological Strategies to Improve Pain, Functioning, and Quality of Life in Veterans-Rationale, Methods, and Implementation.

BACKGROUND: The Whole Health model of the U.S. Department of Veterans Affairs (VA) emphasizes holistic self-care and multimodal approaches to improve pain, functioning, and quality of life. wHOPE (Whole Health Options and Pain Education) seeks to be the first multisite pragmatic trial to establish evidence for the VA Whole Health model for chronic pain care. DESIGN: wHOPE is a pragmatic randomized controlled trial comparing a Whole Health Team (WHT) approach to Primary Care Group Education (PC-GE); both will be compared to Usual VA Primary Care (UPC). The WHT consists of a medical provider, a complementary and integrative health (CIH) provider, and a Whole Health coach, who collaborate with VA patients to create a Personalized Health Plan emphasizing CIH approaches to chronic pain management. The active comparator, PC-GE, is adapted group cognitive behavioral therapy for chronic pain. The first aim is to test whether the WHT approach is superior to PC-GE and whether both are superior to UPC in decreasing pain interference in functioning in 750 veterans with moderate to severe chronic pain (primary outcome). Secondary outcomes include changes in pain severity, quality of life, mental health symptoms, and use of nonpharmacological and pharmacological therapies for pain. Outcomes will be collected from the VA electronic health record and patient-reported data over 12 months of follow-up. Aim 2 consists of an implementation-focused process evaluation and budget impact analysis. SUMMARY: This trial is part of the Pain Management Collaboratory, which seeks to create national-level infrastructure to support evidence-based nonpharmacological pain management approaches for veterans and military service personnel.

Effect of cannabis on opioid use in patients with cancer receiving palliative care.

OBJECTIVE: Opioids are the primary therapy for cancer-related pain in patients receiving palliative care. More states are legalizing medical cannabis, which may provide a pain management alternative for some of these patients. This study aimed to estimate the effect of cannabis on opioid use in patients with cancer receiving palliative care. METHODS: This was a retrospective cohort study of patients with cancer at an academic medical center palliative care clinic. The primary outcome was change in morphine equivalent daily dose (MEDD) from baseline to 84-day follow-up in the cannabis plus opioid group compared to that in the opioid-only group. RESULTS: A total of 83 patients were included: 61 in the opioid monotherapy group and 22 in the cannabis plus opioid group. An increase in MEDD from the baseline to 84 days was seen in both the opioid monotherapy and opioid plus cannabis group (28.8 vs. 10.8); however, the study lacked power to detect a statistical difference. CONCLUSION: A possibly meaningful difference in MEDD increase was seen when comparing the opioid monotherapy group with the opioid plus cannabis group. However, the study was not powered to test this hypothesis; the findings suggest that further research is warranted to determine the impact of cannabis use on opioid dosing in patients receiving palliative care for cancer.

The risk of varenicline-induced seizure among those who have attempted to quit smoking using pharmacotherapy.

OBJECTIVE: Varenicline is an effective smoking cessation agent; however, its use is limited because of black box warnings issued by regulatory agencies in the U.S. and Australia. The U.S. Food and Drug Administration updated the label for varenicline in 2015 to warn about the risk of varenicline-induced seizures. The objective of this study was to examine the risk of seizure associated with varenicline use. METHODS: A nested case-control study was performed using IMS LifeLink PharMetrics Plus administrative claims data (2009-2015). The outcome was presumptive seizures. All smokers making an attempt to quit smoking and having no recent seizure events were included in the nest. Cases and controls were matched (1:4) on age (±5 years), sex, index date (±30 days), event date, and duration of enrollment. An exposure period of 90 days preceding the event date was used. Chi-square tests were used to compare the characteristics of cases and controls. Conditional logistic regression was conducted to determine if an association between presumptive seizures and varenicline use exists. RESULTS: Our final sample was comprised of 1342 cases and 5368 controls. The adjusted analysis showed that odds of a seizure for patients with a varenicline prescription were 1.09 (confidence interval [CI] = 0.88-1.36) times those of patients with no varenicline exposure. CONCLUSIONS: This study did not find a significant association between varenicline and increased risk of presumptive seizures. These findings raise questions regarding the necessity for a warning label for increased risk of seizures associated with varenicline.

Efficacy and Safety of the Early Addition of Vasopressin to Norepinephrine in Septic Shock.

BACKGROUND: Delays in achievement of target mean arterial pressure (MAP) have been associated with increased mortality in patients with septic shock. Vasopressin may be added to norepinephrine to raise MAP or decrease norepinephrine dosage. The purpose of this study was to determine whether early initiation of vasopressin to norepinephrine resulted in a reduced time to target MAP compared to norepinephrine monotherapy. METHODS: This retrospective cohort study compared early addition of vasopressin within 4 hours of septic shock onset to norepinephrine versus initial norepinephrine monotherapy in medically, critically ill patients with septic shock admitted from May 2014 to October 2015. Time to goal MAP was compared using Student t test and examined with Kaplan-Meier curves. Changes in Sequential Organ Failure Assessment (SOFA) scores were evaluated with Wilcoxon rank sum test. RESULTS: Each group contained 48 patients. Mean arterial pressure (61.5 vs 58.6 mm Hg) and intravenous fluid volume received at vasopressor initiation (14.3 vs 25.2 hours, P = .014) were similar. Patients started on early vasopressin achieved and maintained goal MAP sooner (6.2 vs 9.9 hours, P = .023), experienced greater reductions in SOFA scores at 72 hours (-4 vs -1, P = .012), and had shorter hospital durations (343 vs 604 hours, P = .014). Not initiating early vasopressin trended toward an association with increased time to goal MAP (P = .067). CONCLUSION: Early initiation of vasopressin in patients with septic shock may achieve and maintain goal MAP sooner and resolve organ dysfunction at 72 hours more effectively than later or no initiation.

Effect of Etomidate on Pneumonia Development in Critically Ill, Nontrauma Patients.

PURPOSE:: To determine whether etomidate use before intubation increased development of hospital-acquired pneumonia (HAP) in critically ill, nontrauma patients. MATERIALS AND METHODS:: A single-center, retrospective, cohort study of critically ill, nontrauma patients admitted to the medical intensive care unit (ICU) from 2012 to 2015 and intubated with or without etomidate was conducted. Demographics, comorbidities, primary diagnosis, critical illness scores, concomitant medications, and outcomes were obtained from medical records. Student t, chi-square, and Fisher exact tests were performed as appropriate. Relevant characteristics were modeled using logistic regression techniques to determine whether any predicted HAP independently. RESULTS:: Of the 174 patients, 94 (54%) received etomidate and 80 (46%) did not. There was no difference in HAP between etomidate and no etomidate groups (13.8% vs 23.7%, P = .092). Duration of mechanical ventilation (4.4 vs 4.6 days, P = .845), ICU length of stay (7.4 vs 6.9 days, P = .547), ICU mortality (14.9% vs 12.5%, P = .648), and hospital mortality (17% vs 16.2%, P = .892) were similar between the groups. For each 1-day increase in mechanical ventilation duration, the likelihood of HAP development increased by 21%. Patients who received etomidate but no neuromuscular-blocking drug were 80% less likely to develop HAP than those who did not receive etomidate or a neuromuscular-blocking drug (odds ratio: 0.202, 95% confidence interval: 0.045-0.908). CONCLUSION:: Etomidate use was not associated with a difference in HAP development in critically ill, nontrauma patients.

Discontinuation of Vasopressin Before Norepinephrine in the Recovery Phase of Septic Shock.

BACKGROUND: Guidance for the discontinuation of vasopressors in the recovery phase of septic shock is limited. Norepinephrine is more easily titrated; however, septic shock is a vasopressin deficient state, which exogenous vasopressin endeavors to resolve. Discontinuation of vasopressin before norepinephrine may result in clinically significant hypotension. METHODS: This retrospective, cohort study compared discontinuation of norepinephrine and vasopressin in medically, critically ill patients in the recovery phase of septic shock from May 2014 to June 2016. Difference in clinically significant hypotension after norepinephrine or vasopressin discontinuation was evaluated with χ2 test. Linear regression was performed, examining the effect of agent discontinuation on clinically significant hypotension. Baseline variables were examined for a bivariate relationship with clinically significant hypotension; those with P < .2 were included in the model. RESULTS: Vasopressin was discontinued first or last in 62 and 92 patients, respectively. Sequential Organ Failure Assessment scores at 72 hours (7.9 vs 7.6, P = .679) were similar. In unadjusted analysis, when vasopressin was discontinued first, more clinically significant hypotension developed (10.9% vs 67.8%, P < .001). There was no difference in intensive care unit (174 vs 216 hours, P = .178) or hospital duration (470 vs 473 hours, P = .977). In adjusted analyses, discontinuing vasopressin first was associated with increased clinically significant hypotension (odds ratio [OR]: 13.837, 95% confidence interval [CI]: 3.403-56.250, P < .001) but not in-hospital (OR: 0.659, 95% CI: 0.204-2.137, P = .488) or 28-day mortality (OR: 0.215, 95% CI: 0.037-1.246, P = .086). CONCLUSION: Adult patients receiving norepinephrine and vasopressin in the resolving phase of septic shock may be less likely to develop clinically significant hypotension if vasopressin is the final vasopressor discontinued.

A recent history of opioid use in the US: Three decades of change.

BACKGROUND: The opioid epidemic in the United States is a problem that has developed over decades. While clinical, regulatory, and legislative changes have been implemented to combat this issue, changes will not be immediate. Moreover, the changes that have been carried out may have unintended negative consequences such as increased use of illicit opioids (e.g., heroin and synthetics) and challenges in effective and appropriate pain management. OBJECTIVES: This review focuses on the last three decades and presents key changes the United States has seen in the use of opioids. Conclusions/Importance: There have been numerous policy changes and programs aimed at decreasing opioid use and abuse in the United States; however, it will take a major shift in the mindset of clinicians, the general public, and policy makers to alleviate this epidemic.

Association of the "CDC Guideline for Prescribing Opioids for Chronic Pain" With Emergency Department Opioid Prescribing.

BACKGROUND: The number of unintentional deaths due to prescription drug overdose has risen in recent years due to the increased utilization of opioid analgesics. Pain is one of the most common reasons for patients to visit an emergency department (ED) and is often treated with opioid analgesics. In 2016, the Centers for Disease Control and Prevention (CDC) released guidelines for primary care providers on prescribing opioids for chronic pain. OBJECTIVES: The objective of this study was to determine if release of the 2016 CDC guidelines for prescribing opioids for chronic pain was associated with changes in prescribing habits in the ED of an academic medical center. METHODS: The data were extracted from patient electronic health records between January 2015 and June 2017. The primary endpoint of the study was average morphine equivalent daily dose (MEDD) for the pre- and postguideline cohorts. RESULTS: A total of 8652 patients were included in the analysis (4389 in the preguideline cohort and 4263 in the postguideline cohort). The average MEDD decreased significantly from 30.6 ± 20.2 MEDD in the preguideline cohort to 29.8 ± 19.5 MEDD in the postguideline cohort (p = 0.0460). There was also a significant decrease in the rate of concomitant opioid and benzodiazepine prescribing as well as average days' supply per prescription in the postguideline cohort, as compared with the preguideline cohort. CONCLUSIONS: The average MEDD prescribed in the ED of an academic medical center decreased after the release of the CDC guidelines on opioid prescribing for chronic pain.

Factors Associated with Opioid Initiation in OEF/OIF/OND Veterans with Traumatic Brain Injury.

Objective: These analyses examined opioid initiation and chronic use among Iraq (OIF) and Afghanistan (OEF/OND) veterans with a new diagnosis of traumatic brain injury (TBI) in the Veterans Health Administration (VHA). Methods: Data were obtained from national VHA data repositories. Analyses included OEF/OIF/OND veterans with a new TBI diagnosis in 2010-2012 who used the VHA at least twice, had not received a VHA opioid prescription in the 365 days before diagnosis, and had at least 365 days of data available after TBI diagnosis. Results: Analyses included 35,621 veterans. Twenty-one percent initiated opioids; among new initiators, 23% used chronically. The mean dose was 24.0 mg morphine equivalent dose (MED) daily (SD = 24.26); mean days supplied was 60.52 (SD = 74.69). Initiation was significantly associated with age 36-45 years (odds ratio [OR] = 1.09, 95% CI = 1.01-1.17, P = 0.04), female gender (OR = 1.22, P < 0.001), having back pain (OR = 1.38, P < 0.0001), arthritis/joint pain (OR = 1.24, P < 0.0001), or neuropathic pain (OR = 1.415, P < 0.02). In veterans age 36-45 years, those living in small rural areas had higher odds of chronic opioid use (OR = 1.31, P < 0.0001, and OR = 1.33, P = 0.006, respectively) and back pain (OR = 1.36, P = 0.003). Headache/migraine pain was associated with decreased odds of chronic opioid use (OR = 0.639, P = 0.003). Conclusions: Prevalence of opioid use is relatively low among OEF/OIF/OND veterans with newly diagnosed TBI who are using VHA. Among those who initiated opioids, about 25% use them chronically. Prescribing was mostly limited to moderate doses, with most veterans using opioids for approximately two months of the 12-month study period.

Nonpharmacist Health Care Providers' Knowledge of and Opinions Regarding Medication Costs in Critically Ill Patients.

Purpose: Medication cost is frequently overlooked when treating critically ill patients. Stewardship of health care resources in high-utilization settings is imperative. This study was conducted to determine nonpharmacist health care providers' knowledge and perceptions of medication costs in a medical intensive care unit (MICU). Methods: Nonpharmacist health care providers in a MICU completed a 27-item survey. The survey queried perceptions regarding medication cost, cost-limiting strategies, and most/least expensive medications in 8 classes, medication price ranges, and intravenous-to-oral comparisons for commonly prescribed medications. Responses were analyzed using descriptive statistics and compared between providers using Fisher exact tests. Results: Among 98 health care providers (76 medical trainees, 5 attending physicians, 17 nurses), when ordering a medication, 49% consider its cost. Few (15%) providers considered themselves knowledgeable regarding medication costs with no difference between providers (P = .174). Attending physicians were more aware of the most/least expensive medications than residents (correct out of 16: 9.6 vs 8.5, P = .044). The correct price ranges for select medications (11%-36%, P = .373) and intravenous-to-oral relative costs (3%-49%, P = .596) were similarly low. Most (59%) believed pharmacists limit expensive medication use, particularly senior physicians (58% resident vs 100% attending, P = .007). Conclusion: In spite of a goal of cost consideration, most nonpharmacist health care providers are unaware of medication costs and fail to include them in decision making. These knowledge gaps and perceptions should inform future efforts to improve knowledge and attitudes regarding medication costs.

HIV patient and provider feedback on a telehealth collaborative care for depression intervention.

In the HIV Translating Initiatives for Depression into Effective Solutions project, we conducted a randomized controlled effectiveness and implementation trial comparing depression collaborative care with enhanced usual care in Veterans Health Administration HIV clinics in the US. An offsite HIV depression care team including a psychiatrist, a depression care manager (DCM), and a clinical pharmacist provided collaborative care using a stepped-care model of treatment and made recommendations to providers through the electronic health record system. The DCM delivered care management to HIV patients through phone calls, performing routine assessments and providing counseling in self-management and problem-solving. The DCM documented all calls in each patient's electronic medical record. In this paper we present results from interviews conducted with patients and clinical staff in a multi-stage formative evaluation (FE). We conducted semi-structured FE interviews with 26 HIV patients and 30 clinical staff at the three participating sites during and after the trial period to gather their experiences and perspectives concerning the intervention components. Interviews were transcribed verbatim and analyzed using rapid content analysis techniques. Patients reported high satisfaction with the depression care manager (DCM) phone calls. Both HIV and mental health providers reported that the DCM's chart notes in the electronic health record were very helpful, and most felt that a dedicated DCM for HIV patients is ideal to meet patient needs. Sites encountered barriers to achieving and maintaining universal depression screening, but had greater success when such screening was incorporated into routine intake processes. FE results demonstrated that depression care management via telehealth from an offsite team is acceptable and helpful to both HIV patients and their providers. Given that a centralized offsite depression care team can deliver effective, cost-effective, cost-saving services for multiple HIV clinics in different locations with high patient and provider satisfaction, broad implementation should be considered.

Comparative Effectiveness of Intra-Articular Hyaluronic Acid and Corticosteroid Injections on the Time to Surgical Knee Procedures.

BACKGROUND: Use of intra-articular hyaluronic acid (HA) injections to manage knee osteoarthritis (OA) remains controversial because of weak and conflicting evidence. The objective was to evaluate the effectiveness of intra-articular HA injections for knee OA management. METHODS: A nested cohort of persons with knee OA seeing a specialist was created using a 10% random sample of LifeLink Plus claims (2010-2015) to compare the risk of composite (any) knee surgical interventions, total (TKA)/unicompartmental knee arthroplasty (UKA) and TKA only among HA users and 2 comparison groups: corticosteroid (CS) users and HA/CS nonusers. A high-dimensional propensity score (hdPS) was used to match HA users with CS users and with HA/CS nonusers on background covariates. The risk of surgical interventions among HA users relative to the comparison groups was assessed using Cox proportional hazard models. RESULTS: Among 13,849 patients, 797 were HA users, 5327 were CS users, and 7725 were HA/CS nonusers. After hdPS matching, the risk of composite surgical interventions did not differ between HA users and HA/CS nonusers (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.67-1.16) and CS users (HR, 0.89; 95% CI, 0.65-1.12). Seven of the 8 sensitivity analyses demonstrated no significant benefit among HA users compared to CS users and HA/CS nonusers. A sensitivity analysis that restricted the study cohort to those who ultimately have knee surgery showed a lower risk of surgery of HA (HR, 0.87; 95% CI, 0.79-0.95). CONCLUSION: There were no significant differences in the risk of surgical interventions among HA users compared to HA/CS nonusers and CS users after accounting for residual confounding using an hdPS.

Comparison of Low-, Moderate-, and High-Molecular-Weight Hyaluronic Acid Injections in Delaying Time to Knee Surgery.

BACKGROUND: We compared the effectiveness of low-molecular-weight (MW) hyaluronic acid (HA) injections (LMWHA), moderate-MW HA injections (MMWHA), and high-MW HA injections (HMWHA) for prevention or delay of knee surgery in patients with knee osteoarthritis. METHODS: An observational cohort study using LifeLink Plus claims (2006-2015) was used. The primary outcome measure of the study included all surgical interventions of the knee. The secondary outcome measures were the following: (1) unicompartmental knee arthroplasty or total knee arthroplasty and (2) total knee arthroplasty only. A high-dimensional propensity score (hdPS) using 1:1 matching was used to adjust for confounding. The likelihood of each outcome was assessed using Cox proportional hazard models. RESULTS: A cohort of 30,417 incident HA users with knee osteoarthritis met our inclusion-exclusion criteria. There was no difference in the likelihood of composite surgical events between LMWHA users (hazard ratio, 0.939; 95% confidence interval, 0.870-1.013) and MMWHA users (hazard ratio, 1.032; 95% confidence interval, 0.952-1.119) when compared with HMWHA users in a matched hdPS analysis. However, a significantly lower likelihood for all outcome measures was demonstrated in LMWHA and MMWHA users compared with HMWHA users when hdPS was not used. CONCLUSION: There was no significant difference in the likelihood of surgical interventions between LMWHA, MMWHA, and HMWHA users after accounting for empirically derived confounders.

Impact of Targeted Educational Interventions on Clostridium difficile Infection Treatment in Critically Ill Adults.

Background: Clostridium difficile infection (CDI) is a growing clinical and economic burden throughout the world. Pharmacists often are members of the primary care team in the intensive care unit (ICU) setting; however, the impact of pharmacists educating other health care providers on appropriateness of CDI treatment has not been previously examined. Objective: This study was performed to determine the impact of structured educational interventions on CDI treatment on appropriateness of CDI treatment and clinical outcomes. Methods: This was a single-center, retrospective, cohort study of patients with CDI in the medical ICU at an academic medical center between January and June 2014 (pre-period) and 2015 (post-period). All patients were evaluated for appropriate CDI treatment before and after implementing pharmacist-provided educational interventions on CDI treatment. Results: Patients in the post-period were prescribed appropriate CDI treatment more frequently than patients in the pre-period (91.7% vs 41.7%; p = .03) and received fewer inappropriate doses of a CDI treatment agent (14 doses vs 30 doses). Patients in the pre-period had a shorter ICU length of stay [1.5 days (range, 1-19) vs 3.5 days (range, 2-36); p = .01] and a similar hospital length of stay [9.5 days (range, 4-24) vs 11.5 days (range, 3-56); p = .30]. Total time spent providing interventions was 4 hours. Conclusion: Patients had appropriate CDI treatment initiated more frequently in the post-period. This low-cost intervention strategy should be easy to implement in institutions where pharmacists interact with physicians during clinical rounds and should be evaluated in institutions where interactions between pharmacists and physicians occur more frequently in non-rounding situations.