Health care decision-maker perceptions and trends in the utilization of preapproval information for formulary decision-making.

BACKGROUND: Preapproval information exchange (PIE) has increased between biopharma companies and health care decision-makers (HCDMs) over the last several years. However, there still exists a gap in what HCDMs need and what biopharma companies are providing. OBJECTIVE: To assess trends in the utilization of preapproval information by HCDMs and identify resources that may best support organizations in evaluating product information for formulary coverage prior to US Food and Drug Administration approval. METHODS: A double-blinded, web-based survey was fielded to a research panel of HCDMs from FormularyDecisions from May 16, 2022, to May 23, 2022. RESULTS: A total of 30 advisors were invited to take the survey and 17 responded to the survey, with representation largely from health plans (41%), pharmacy benefit managers (24%), and integrated delivery networks (12%) across commercial, Medicare, and Medicaid lines of business. Of the respondents, 47% noted that the availability of preapproval information has shortened the time to make a formulary decision. Almost all respondents (90%) ranked the availability of clinical and economic information in a timely manner to evaluate budget impact as a top benefit for PIE. Respondents noted that Academy of Managed Care Pharmacy (AMCP) preapproval dossiers (88%), AMCP PIE webinars (76%), preapproval presentations/videos (65%), and posters and abstracts of clinical trials results (59%) were the main resources used to facilitate PIE. CONCLUSIONS: The availability of preapproval information for HCDMs (particularly content related to anticipated place in therapy and product pricing) has an impact on shortening formulary decision-making timelines.

Triage of V-V ECMO referrals for COVID-19 respiratory failure.

BACKGROUND: As the pandemic progressed, the use of extracorporeal membrane oxygenation (ECMO) for COVID-19-related acute respiratory distress syndrome increased, and patient triage and transfer to ECMO centers became important to optimize patient outcomes. Our objectives are to identify predictors of patient transfer for veno-venous extracorporeal membrane oxygenation (V-V ECMO) evaluation as well as to describe the outcomes of accepted patients. METHODS: This is a single-center, retrospective analysis of V-V ECMO transfer requests for adult patients with known or suspected COVID-19 and respiratory failure from March 2020 until March 2021. Data were collected prospectively during the triage process for transfer requests as part of clinical patient care at our institution. RESULTS: Of 341 referred patients, 112 (33%) were accepted for transfer to our facility, whereas 229 (67%) patients were declined for transfer. The Classification and Regression Tree analysis showed that patients' high pressure during airway pressure release ventilation (APRV) and age were the variables most significantly associated with the decision to accept or decline patients for transfer. CONCLUSIONS: Our triage process enabled one-third of referred patients to be transferred for evaluation, with nearly 70% of those patients ultimately receiving ECMO support. High ventilator settings on APRV and young age were associated with acceptance for transfer. Accepted patients also had a higher incidence of adjunctive therapies (proning and paralysis) prior to transfer request, less cardiac or renal dysfunction, and a shorter duration of mechanical ventilation. Further research is warranted to investigate the outcomes of nontransferred patients.

Clinical characteristics and outcomes of obstetric patients transferred directly to intensive care units.

BACKGROUND: Medical complications in peripartum patients are uncommon. Often, these patients are transferred to tertiary care centers, but their conditions and outcomes are not well understood. Our study examined peripartum patients transferred to an intensive care unit (ICU) at an academic quaternary center. METHODS: We reviewed charts of adult, non-trauma, interhospital transfer (IHT) peripartum patients sent to an academic quaternary ICU between January 2017 and December 2021. We conducted a descriptive analysis and used multivariable ordinal regression to examine associations of demographic and clinical factors with ICU length of stay (LOS) and hospital length of stay (HLOS). RESULTS: Of 1,794 IHT peripartum patients, 60 (3.2%) were directly transferred to an ICU. The average was 32 years, with a median Sequential Organ Failure Assessment (SOFA) score of 3 (1-4.25) and Acute Physiology and Chronic Health Evaluation (APACHE) II score of 8 (7-12). Respiratory failure was most common (32%), followed by postpartum hemorrhage (15%) and sepsis (14%). Intubation was required for 24 (41%), and 4 (7%) needed extracorporeal membrane oxygenation. Only 1 (1.7%) died, while 45 (76.3%) were discharged. Median ICU LOS and HLOS were 5 days (212) and 8 days (5-17). High SOFA score was linked to longer HLOS, as was APACHE II. CONCLUSIONS: Transfers of critically ill peripartum patients between hospitals were rare but involved severe medical conditions. Despite this, their outcomes were generally positive. Larger studies are needed to confirm our findings.

Cannula associated deep vein thromboses in COVID-19 patients supported with VV ECMO.

BACKGROUND: VV ECMO is increasingly used as a rescue strategy for hypercarbic and hypoxic respiratory failure refractory to conventional management, and more than 14,000 patients with COVID-19 related respiratory failure have been supported with VV ECMO to date. One of the known complications of VV ECMO support is the development of cannula-associated deep vein thromboses (CaDVT). The purpose of this study was to identify the incidence of CaDVT in COVID-19 patients supported with VV ECMO as compared to non-COVID-19 patients. We hypothesized that due to the hypercoagulable state and longer duration of VV ECMO support required for patients with COVID-19, a higher incidence of CaDVT would be observed in these patients. METHODS: This is a single center, retrospective observational study. About 291 non-trauma adult patients who were cannulated for VV ECMO and managed at our institution from January 1, 2014 to January 10, 2022 were included. The primary outcome was the presence of CaDVT 24 h after decannulation in COVID-19 versus non-COVID-19 patients. Our secondary outcome was continued presence of DVT on follow up imaging. CaDVT were defined as venous thrombi detected at prior cannulation sites. RESULTS: Both groups had a high incidence of CaDVT. There was no significant difference in the incidence of CaDVT in COVID-19 patients compared to non-COVID-19 patients (95% vs 88%, p = 0.13). Patients with COVID-19 had an increased incidence of persistent CaDVT on repeat imaging (78% vs 56%, p = 0.03). CONCLUSION: Given the high number of post-decannulation CaDVT in both groups, routine screening should be a part of post ECMO care in both populations. Repeat venous duplex ultrasound should be performed to assess for the need for ongoing treatment given the high incidence of CaDVT that persisted on repeat duplex scans.

Body mass index does not impact survival in COVID-19 patients requiring veno-venous extracorporeal membrane oxygenation.

INTRODUCTION: With the increased demand for veno-venous extracorporeal membrane oxygenation (VV ECMO) during the COVID-19 pandemic, guidelines for patient candidacy have often limited this modality for patients with a body mass index (BMI) less than 40 kg/m2. We hypothesize that COVID-19 VV ECMO patients with at least class III obesity (BMI ≥ 40) have decreased in-hospital mortality when compared to non-COVID-19 and non-class III obese COVID-19 VV ECMO populations. METHODS: This is a single-center retrospective study of COVID-19 VV ECMO patients from January 1, 2014, to November 30, 2021. Our institution used BMI ≥ 40 as part of a multi-disciplinary VV ECMO candidate screening process in COVID-19 patients. BMI criteria were not considered for exclusion criteria in non-COVID-19 patients. Univariate and multivariable analyses were performed to assess in-hospital mortality differences. RESULTS: A total of 380 patients were included in our analysis: The COVID-19 group had a lower survival rate that was not statistically significant (65.7% vs.74.9%, p = .07). The median BMI between BMI ≥ 40 COVID-19 and non-COVID-19 patients was not different (44.5 vs 45.5, p = .2). There was no difference in survival between the groups (73.3% vs. 78.5%, p = .58), nor was there a difference in survival between the COVID-19 BMI ≥ 40 and BMI < 40 patients (73.3, 62.7, p= .29). Multivariable logistic regression with the outcome of in-hospital mortality was performed and BMI was not found to be significant (OR 0.99, 95% CI 0.89, 1.01; p = .92). CONCLUSION: BMI ≥ 40 was not an independent risk factor for decreased in-hospital survival in this cohort of VV ECMO patients at a high-volume center. BMI should not be the sole factor when deciding VV ECMO candidacy in patients with COVID-19.

Breathing Life Back Into the Kidney-Continuous Renal Replacement Therapy and Veno-Venous Extracorporeal Membrane Oxygenation.

The purpose of this study was to evaluate the incidence of continuous renal replacement therapy (CRRT) in patients supported with veno-venous extracorporeal membrane oxygenation (VV ECMO). Secondary outcomes included mortality and the need for hemodialysis on hospital discharge. We performed a retrospective cohort study of all patients admitted to a specialty unit on VV ECMO between August 2014 and August 2018. Trauma and bridge to lung transplant patients were excluded. Demographics, comorbidities, pre-ECMO, ECMO, and renal replacement therapy outcome data were collected and analyzed with parametric and nonparametric statistics as appropriate. One hundred eighty-seven patients were enrolled. Median age was 45 (32, 55) years; precannulation pH, 7.21 (7.12, 7.30); PaO2/FiO2 ratio, 69 (56, 86); respiratory ECMO survival prediction score, 3 (0, 5); sequential organ failure assessment score, 12 (10, 14); and creatinine, 1.45 (0.93, 2.35) mg/dL. Overall survival to hospital discharge was 74.6%. Ninety-four (50.3%) patients had CRRT while on VV ECMO. Median time on CRRT was 14 (7, 21) days with 59 (61.4%) of these patients surviving to hospital discharge. Four (6.8%) patients, none with documented preexisting renal disease, required hemodialysis on discharge. CRRT patients had a statistically higher precannulation sequential organ failure assessment score, creatinine, total bilirubin and lower precannulation pH, respiratory ECMO survival prediction score, and platelet count compared with non-CRRT patients. Survival was 61.4% vs. 88.1% (p < 0.001). More than half of our patients received CRRT while on VV ECMO. CRRT was used in a more critically ill patient population and was associated with higher in-hospital mortality. However, for patients who survived to hospital discharge, the majority have full renal recovery.

Review of outcomes associated with restricted access to atypical antipsychotics.

OBJECTIVES: Cost containment policies, such as prior authorization (PA), have increasingly been used by formulary decision makers to manage drug spending of the atypical antipsychotic (AAP) drug class. However, these drug cost containment policies may result in cost shifting rather than cost savings. Given the interest in coordination of care, the objective of this study was to evaluate the impact of restricted access to AAPs on healthcare costs and health outcomes in individuals with schizophrenia or bipolar disorder. STUDY DESIGN: Narrative literature review. METHODS: A literature search was conducted using MEDLINE (via PubMed) for studies published between January 1993 and December 2013. RESULTS: A total of 15 published studies were identified that evaluated restricted access to AAPs in regard to healthcare costs or health outcomes: 11 studies assessed PAs, 2 studies assessed carve-outs, 1 study assessed a payment limit (cap), and 1 study assessed Medicare Part D cost sharing. Among 8 studies evaluating changes in pharmacy costs and clinical outcomes, 5 studies reported that formulary restrictions were associated with pharmacy cost savings and increases in healthcare utilization or treatment discontinuation. Of the 4 studies that measured overall cost changes, 3 studies reported increases in overall cost burden and 1 study showed modest cost savings associated with formulary restrictions. CONCLUSIONS: Study findings revealed there exists a gap in the literature as to whether restricted access to AAPs results in overall cost savings or, rather, shifts the cost burden from pharmacy spending to other parts of the healthcare system, such as service utilization.

Achieving Balance with the AMCP Format for Formulary Submissions, Version 4.0: A Dossier Producer's Perspective.

DISCLOSURES: Both authors are employed by Xcenda and develop AMCP Format dossiers.

Treatment Patterns and Outcomes in Patients with Varicose Veins.

BACKGROUND: Approximately 24% of adults in the United States have visible varicose veins, and an estimated 6% have evidence of advanced chronic venous disease. The majority of individuals with varicose veins seek treatment because of symptoms, such as aching, throbbing, fatigue, pruritus, ankle swelling, and tenderness, rather than cosmetic reasons. Furthermore, varicose veins are a manifestation of chronic venous insufficiency, which can progress to leg pain, leg edema, chronic skin changes, and nonhealing ulcers. OBJECTIVE: To assess varicose vein treatment patterns and their corresponding outcomes, including additional treatment rates, disease progression to new ulcers, and associated costs from a US perspective. METHODS: We conducted a retrospective claims database study using data from the Truven Health MarketScan database. Adults who were newly diagnosed with varicose veins between January 1, 2008, and June 30, 2010, and met the study inclusion criteria were eligible to participate and were divided into 6 cohorts based on the type of first or initial therapy they received after the index diagnosis date, including surveillance and compression therapy, surgery, laser ablation, radiofrequency ablation, sclerotherapy, or multiple therapies. The patients were followed for 2 years after the index diagnosis date to assess their treatment patterns and outcomes. RESULTS: A total of 144,098 patients met the study criteria. Of these patients, 100,072 (69.5%) were under surveillance for disease progression and/or received compression therapy; 14,007 (9.7%) received laser ablation; 9125 (6.3%) received radiofrequency ablation; 4778 (3.3%) received sclerotherapy; 4851 (3.4%) had surgery; and 11,265 (7.8%) received multiple therapies. During the 2-year follow-up period, among patients receiving interventional treatment, 54.7% of patients received additional interventional treatment (either with the same mode or a different mode from the initial treatment); 30.1% had >1 postintervention claim for symptomatic varicose veins (not including additional procedures) at 8 weeks; and 44.2% had >1 postintervention claim for symptomatic varicose veins at 1 year after the initial interventional therapy. CONCLUSIONS: A majority of the patients in the study received conservative management. For patients receiving interventional therapy, the outcomes varied based on the treatment cohort. The surgery cohort was associated with the most favorable outcome regarding the need for additional treatment and evidence of postintervention claims for symptomatic varicose veins, followed by the multiple therapies cohort. A better understanding of these treatment outcomes in the real-world setting may affect new strategies to improve the management of patients with varicose veins.

Intraosseous infusion rates under high pressure: a cadaveric comparison of anatomic sites.

BACKGROUND: When traditional vascular access methods fail, emergency access through the intraosseous (IO) route can be lifesaving. Fluids, medications, and blood components have all been delivered through these devices. We sought to compare the performance of IO devices placed in the sternum, humeral head, and proximal tibia using a fresh human cadaver model. METHODS: Commercially available IO infusion devices were placed into fresh human cadavers: sternum (FAST-1), humeral head (EZ-IO), and proximal tibia (EZ-IO). Sequentially, the volume of 0.9% saline infused into each site under 300 mm Hg pressure over 5 minutes was measured. Rates of successful initial IO device placement and subjective observations related to the devices were also recorded. RESULTS: For 16 cadavers over a 5-minute bolus infusion, the total volume of fluid infused at the three IO access sites was 469 (190) mL for the sternum, 286 (218) mL for the humerus, and 154 (94) mL for the tibia. Thus, the mean (SD) flow rate infused at each site was as follows: (1) sternum, 93.7 (37.9) mL/min; (2) humerus, 57.1 (43.5) mL/min; and (3) tibia, 30.7 (18.7) mL/min. The tibial site had the greatest number of insertion difficulties. CONCLUSION: This is the first study comparing the rate of flow at the three most clinically used adult IO infusion sites in an adult human cadaver model. Our results showed that the sternal site for IO access provided the most consistent and highest flow rate compared with the humeral and tibial insertion sites. The average flow rate in the sternum was 1.6 times greater than in the humerus and 3.1 times greater than in the tibia.

Assessment of thrombotic adverse events and treatment patterns associated with varicose vein treatment.

OBJECTIVE: This retrospective study assessed varicose vein treatment patterns and associated thrombotic complications in a real-world setting. METHODS: A retrospective study was conducted with health care claims data from Truven Health, covering more than 40 million insured lives per year and representing all U.S. census regions. The study sample included subjects aged ≥ 18 years with a new diagnosis of varicose veins who had received at least one invasive treatment (eg, surgery, endovenous thermal ablation [radiofrequency or laser], or sclerotherapy [liquid or foam]). The adverse events of interest included a coded diagnosis of deep venous thrombosis (DVT) or pulmonary embolism within 30 days of a claim for invasive treatment. Patients treated between January 1, 2008, and June 30, 2012, were observed for up to 2 years after diagnosis. RESULTS: There were 985,632 unique subjects diagnosed with varicose veins; of them, a total of 131,887 subjects met all of the study criteria: 63,033 (47.8%) having multiple therapies; 22,980 (17.4%) having laser ablation; 21,637 (16.4%) having radiofrequency ablation; 12,708 (9.6%) having sclerotherapy; and 11,529 (8.7%) having surgery. The mean age of the sample was 52.8 years, ranging from 51.5 years (surgery cohort) to 54.5 years (radiofrequency ablation cohort); 77% of the sample was female, ranging from 71% (radiofrequency ablation cohort) to 92% (sclerotherapy cohort). The mean time to treatment after diagnosis was 105 days, ranging from 75 days (sclerotherapy cohort) to 116 days (radiofrequency ablation cohort). The diagnosed prevalence (percentage of subjects within each treatment cohort) of DVT was as follows: radiofrequency ablation, 4.4%; multiple therapies--same day, 3.4%; laser ablation, 3.1%; multiple therapies--deferred, 2.6%; surgery, 2.4%; and sclerotherapy, 0.8%. For pulmonary embolism, the diagnosed prevalence was as follows: radiofrequency ablation, surgery, and laser ablation, 0.3% each; and multiple therapies--same day, multiple therapies--deferred, and sclerotherapy, 0.2% each. CONCLUSIONS: Thrombotic complications associated with invasive varicose vein treatments in the real-world setting may be higher than what has been reported in clinical trials, particularly in regard to DVT after endovenous thermal ablation therapy. A better understanding of these patterns of adverse events may have an impact on new strategies to safely and effectively manage patients with varicose veins.

Assessment and treatment of the trauma patient in shock.

High-volume crystalloid resuscitation is associated with increased length of stay, ICU and ventilator days, and organ failure and infection rates. Rapid evaluation of a hemodynamically unstable trauma patient is vital to diagnosis and treatment of the cause of shock. CT scanning should be used liberally in trauma patients to effect decreased mortality. Nonoperative management and catheter-based interventions are becoming the standard of care in appropriately selected patients with solid organ injuries.

Disease burden and treatment outcomes in second-line therapy of patients with estrogen receptor-positive (ER+) advanced breast cancer: a review of the literature.

OBJECTIVE: To determine the variable burden of disease of patients with advanced estrogen receptor-positive (ER+) breast cancer and assess the current treatment landscape after failure of first-line endocrine therapy. METHODS: A comprehensive literature review was performed (2000-2011) by searching Medline via PubMed, and Embase and Cochrane databases, to assess disease burden (i.e. societal, humanistic, and/or economic burden) and treatment landscape for second-line therapy of ER+ advanced breast cancer in postmenopausal women. RESULTS: Only 1 study was identified that evaluated burden of disease based on ER status (ER+, ER-negative, or ER-unknown); this study was a subgroup analysis assessing the impact of breast cancer recurrence over 10 years. The investigators reported that only minor differences in survival and medical costs were noted based on ER status in relapsing patients. Regardless of ER status, patients with breast cancer recurrence consumed more healthcare resources and were associated with more costly care than those without recurrence. A total of 7 studies were identified related to treatment outcomes of second-line therapy in ER+ patients. A combined international population totaled >3800 patients who had progressed on prior hormonal therapy, including tamoxifen and aromatase inhibitors. Three trials performed a comparative efficacy/safety assessment of an ER antagonist vs. aromatase inhibitor, 1 trial compared an aromatase inhibitor to megestrol acetate, and 1 trial compared 2 aromatase inhibitors. Among each of the studies evaluated, no significant differences were observed in the primary efficacy endpoint, and the safety profiles were similar. Two additional studies demonstrated a similar or better efficacy and safety profile based on different dosing evaluations. CONCLUSIONS: Currently, there is insufficient evidence on the economic and humanistic burden associated with ER status, and this gap warrants further research. With increasing drug resistance and greater economic burden associated with breast cancer recurrence, there is an unmet medical need for improved treatment in this patient population.

Evolving trends in insulin delivery in pursuit of improvements in diabetes management.

Diabetes mellitus affects 23.6 million Americans and its incidence is rapidly increasing, particularly in older, overweight patients. Large-scale studies conclusively show that elevated blood glucose levels are associated with an increased risk for microvascular complications, such as retinopathy and nephropathy. The high rates of morbidity and mortality associated with this disease, and the costs associated with it, underscore the importance of effective glycemic control. Conventional syringe/vial insulin delivery is associated with many barriers for patients with diabetes mellitus and for their healthcare providers. Substantial developments in insulin delivery show promise in overcoming these barriers. New technologies in insulin delivery focus on increasing patient convenience, reducing the frequency of daily injections, and improving glycemic control. This article outlines the challenges associated with conventional insulin delivery and describes recent developments that may help to overcome these barriers and, ultimately, could enhance glycemic control.

Adverse event profile of tramadol in recent clinical studies of chronic osteoarthritis pain.

OBJECTIVE: To review the safety profile of tramadol hydrochloride (tramadol) in the treatment of chronic osteoarthritis pain, with specific reference to the incidence of adverse events (AEs) reported in large clinical trials. METHODS: An extensive review of published clinical trials with tramadol was conducted, using literature searches in MEDLINE and EMBASE (since 1997) and the key search terms: tramadol, immediate-release (IR), extended-release (ER), sustained-release (SR), chronic pain, and osteoarthritis. Studies were included based on appropriate study design, appropriately reported safety data, and chronic osteoarthritis as a pain condition. Secondary analyses of previously published pain studies were excluded. RESULTS: Fifteen studies met the inclusion criteria. The most common AEs reported across all tramadol formulations were nausea, dizziness, constipation, vomiting, somnolence, and headache. Most AEs were mild to moderate in severity and occurred more commonly during initial treatment than during maintenance treatment. Differences in the rates of selected gastrointestinal and central nervous system AEs were seen between long-acting and immediate-release tramadol formulations, both within individual studies and across all studies. AEs appeared to be dose-dependent in fixed-dose studies. CONCLUSIONS: This review provides a robust base for descriptive assessment of AEs associated with long-acting tramadol formulations. Although the actions of different tramadol formulations are biologically similar, differences in pharmacokinetics, drug-release patterns, and availability may influence the incidence of AEs associated with tramadol. Because of the limitations of a qualitative safety analysis across studies with different populations and study designs, any observed differences should be interpreted with caution, but these differences may help educate healthcare providers about tramadol treatment in patients with chronic osteoarthritis pain and help them select the optimal dose for specific patients.