• Comparative Effectiveness of Carbidopa–Levodopa Enteral Suspension and Deep Brain Stimulation on Parkinson’s Disease-Related Pill Burden Reduction in Advanced Parkinson’s Disease: A Retrospective Real-World Cohort Study

      Soileau, M.J.; Pagan, F.; Fasano, A.; Rodriguez-Cruz, R.; Wang, L.; Kandukuri, P.L.; Yan, C.H.; Alobaidi, A.; Bao, Y.; Kukreja, P.; et al. (Adis, 2022)
      Introduction: In advanced Parkinson’s disease (PD), a high pill burden is associated with poor compliance, reduced control of symptoms, and decreased quality of life. We assessed the impact of carbidopa–levodopa enteral suspension (CLES) and deep brain stimulation (DBS) on PD-related pill burden. Methods: A retrospective cohort analysis was conducted in the IBM MarketScan and Medicare Supplemental databases. Patients with advanced PD, taking only PD medications, and initiating CLES or DBS between 9 January 2015 and 31 July 2019 were identified. CLES patients were matched to DBS patients in a 1:3 ratio based on a propensity score to balance patient characteristics. Pill burden was measured as a 30-day average number of PD-related pills per day and was captured monthly. Pill-free status was evaluated as the percentage of patients receiving CLES or DBS monotherapy. Descriptive statistics were used to compare pill counts and assess the proportion of patients on monotherapy at 6 and 12 months after initiating CLES or DBS. Results: The cohorts included 34 CLES patients matched to 97 DBS patients. A significant reduction in PD-related pill burden was observed at 6 months after initiation of CLES or DBS (∆CLES: −5.62, p < 0.0001; ∆DBS: −1.48, p = 0.0022). PD-related pill burden reduction in CLES patients was significantly greater than in matched DBS patients at 6 months (∆: −4.14, p < 0.0001), which was sustained at 12 months after initiation. At 12 months, nearly three times more CLES patients were pill free than DBS patients (29.41% and 10.31%, respectively, p = 0.0123). Conclusions: Device-aided therapies such as CLES and DBS are effective in significantly reducing PD-related pill burden. Patients treated with CLES were more likely to achieve pill-free status than patients receiving DBS. © 2022, The Author(s).
    • Cost-Effectiveness of PD-L1 Testing in Non-Small Cell Lung Cancer (NSCLC) Using In Vitro Diagnostic (IVD) Versus Laboratory-Developed Test (LDT)

      Hurwitz, J.T.; Vaffis, S.; Grizzle, A.J.; Nielsen, S.; Dodson, A.; Parry, S.; Center for Health Outcomes and PharmacoEconomic Research, College of Pharmacy, University of Arizona (Adis, 2022)
      Introduction: Accurate PD-L1 testing for non-small cell lung cancer (NSCLC) maximizes the benefits of immune checkpoint inhibitor (ICI) drugs like pembrolizumab. False negative test results deny ICI treatments to eligible patients, worsening clinical and economic outcomes, while false positives increase costs by using ICI treatments without their benefits. This study evaluates the cost-effectiveness of PD-L1 testing with an in vitro diagnostic (IVD) compared to a laboratory-developed test (LDT) for allocating patients with NSCLC to treatment with either pembrolizumab or chemotherapy using the German healthcare system as a model. Methods: We developed a decision analytical model to evaluate the cost-effectiveness of PD-L1 testing with a regulatory body approved IVD compared to an LDT from the national German healthcare payer (statutory health insurance system) perspective. Accuracy of PD-L1 testing was based on data from two independent proficiency testing programs. The 1-year model was based on outcomes data from the KEYNOTE-024 clinical trial and treatment patterns reflecting current German practices. Results: IVDs produced accurate PD-L1 testing results in 93% (752/811) of tested cases compared to 73% (492/672) with LDTs. Most misclassifications concerned false negatives, occurring in 21% of LDTs vs 7% of IVDs. Total costs of the IVD group (48,878 €) were 196 € higher than the LDT group (48,682 €). These costs incorporate testing, first- and second-line therapy, managing treatment-related grade 3+ adverse events (AEs), and end-of-life costs for those who died within the year. Total effectiveness (percentage of patients successfully diagnosed and prescribed the correct therapy per German treatment guidelines) was 19 percentage points higher for the IVD group (88%) compared to the LDT group (69%). These differences in costs and effects lead to an incremental cost-effectiveness ratio (ICER) of 1057 €. Conclusion: Compared to LDT technology, on-label IVD use for PD-L1 testing is only slightly more costly and substantially more effective for aligning patients with PD-L1-positive NSCLC with ICI therapy according to German practice guidelines. Given these findings, changes to testing and reimbursement policies may be considered to maximize patient outcomes in NSCLC. © 2022, The Author(s).
    • Influences of Gender on Intravenous Nalbuphine Actions After Major Abdominal Surgery: A Multicenter Study

      Ayad, A.E.; Salman, O.H.; Ibrahim, A.M.F.; Al-Taher, W.A.M.; Mishriky, A.M.; Pergolizzi, J.V.; Viswanath, O.; Urits, I.; Rekatsina, M.; Peppin, J.F.; et al. (Adis, 2021)
      Introduction: Nalbuphine, a synthetic kappa-opioid receptor (KOR) agonist and a partial µ-opioid receptor (MOR) antagonist, has been used for years as an effective analgesic. It has been shown to have a better safety profile than morphine. Considering the long history of use of this drug, it is interesting that only a limited amount of information exists on how gender differences influence nalbuphine responses. In this randomized double-blind comparative trial after major abdominal surgery, the analgesic effects of two doses of continuous intravenous infusion of nalbuphine were evaluated based on gender. Methods: Enrolled patients were divided into four groups (two females and two males with 32 patients in each group). Two of them (groups A1 and A2), one male and one female, received postoperative continuous intravenous infusions of nalbuphine at 2 mg/h via patient-controlled analgesia (PCA). Each patient had the potential of receiving a rescue bolus of 1 mg of nalbuphine with a lock out time of 15 min. The other two groups (groups B1 and B2) received half the infusion dose, 1 mg/h, and half the nalbuphine rescue dose with the PCA pump, 0.5 mg maximum every 15 min as needed. Patients' vital signs, numerical pain rating scores, rescue nalbuphine, and incidence of side effects were assessed immediately after the operation, and every 3 h during the first 12 h. Results: Nalbuphine 2 mg/h dosing led to significantly lower pain scores amongst females compared to males at 6, 9, and 12 h; while the 1 mg/h infusion pain scores were only lower at the 9-h time period. Females receiving the nalbuphine 2 mg dose at 6 h, and the 1 mg dose at 6, 9, and 12-h measurements needed significantly lower doses of rescue nalbuphine. Females on the 1 mg dose experienced significantly more nausea, vomiting, and sedation at the 6-, 9-, and 12-h measurement times. In the multivariate analysis, female gender was a negative predictor at all measurement times. Conclusions: The current study supports the hypothesis that although nalbuphine was found to be an effective and well-tolerated analgesic after major abdominal surgery, females were statistically more responsive than males. Trial Registration: The study was registered at the Pan African Clinical trials Registry PACTR201304000486309, and approved for the Ethical aspects. © 2021, The Author(s).
    • Respiratory Symptoms among US Adults: a Cross-Sectional Health Survey Study

      Pleasants, R.A.; Heidari, K.; Ohar, J.; Donohue, J.F.; Lugogo, N.L.; Kanotra, S.M.; Kraft, M.; Mannino, D.M.; Strange, C.B.; Department of Internal Medicine, University of Arizona (Adis, 2022)
      Introduction: Data collected through ongoing, state-based, cross-sectional health surveys could be used to better understand the contribution of respiratory symptoms to impaired health among the US adult population. Methods: We used the 2015 Behavioral Risk Factor Surveillance System telephone health survey in four states (Kentucky, Florida, South Carolina, Texas) to describe the relationship between symptoms, associated factors such as tobacco smoking, and health impairments. Self-reported productive cough, shortness of breath (SOB), and dyspnea on exertion (DOE) were categorized as minimal, moderate, or severe. Data were analyzed using multiple logistic regression models with age as a covariate to assess relationships of symptoms with other factors. Results: Among adults ≥ 18 years, respiratory impairment [current asthma, chronic obstructive pulmonary disease (COPD), or a current moderate or severe symptom] occurred in 39.1% of the population. More than half of adults reporting moderate or severe symptoms had not been diagnosed with asthma or COPD, particularly with DOE and productive cough. Subjects were at greater risk of moderate and severe SOB or productive cough with increasing age, prolonged smoking duration (≥ 20 years), being an ever-smoker, or if reporting COPD, current asthma, or any other comorbidity except cancer. Morbid obesity [body mass index (BMI) &gt; 35 kg/m2] was associated with severe DOE at a rate similar to current asthma or COPD (25.6%, 95% CI 20.9–30.3%; 20.8%, 95% CI 16.4–25.1%; 21.3%, 95% CI 17.5–25.1%, respectively); it was the most common cause of DOE. SOB was associated with worse general health impairment and limited ambulation compared with other symptoms. Tobacco smoking prevalence and race varied among states, affecting symptom prevalence. Conclusion: In the largest US survey in decades, we provide a current perspective of respiratory symptoms among adults of all ages. While known risk factors were apparent, low-risk persons also frequently reported symptoms and impairments. © 2022, The Author(s).