• Benefit-risk analysis of buprenorphine for pain management

      Hale, M.; Garofoli, M.; Raffa, R.B.; University of Arizona College of Pharmacy (Dove Medical Press Ltd, 2021)
      Health care providers in the United States are facing challenges in selecting appropriate medication for patients with acute and chronic pain in the midst of the current opioid crisis and COVID-19 pandemic. When compared with conventional opioids, the partial µ-opioid receptor agonist buprenorphine has unique pharmacologic properties that may be more desirable for pain management. The formulations of buprenorphine approved by the US Food and Drug Administration for pain management include intravenous injection, transdermal patch, and buccal film. A comparison of efficacy and safety data from studies of buprenorphine and conventional opioids suggests that buprenorphine may be a better-tolerated treatment option for many patients that provides similar or superior analgesia. Our benefit-risk assessment in this narrative review suggests that health care providers should consider that buprenorphine may be an appropriate alternative for pain management over other opioids. © 2021 Hale et al.
    • General theory of inflammation: patient self-administration of hydrocortisone safely achieves superior control of hydrocortisone-responding disorders by matching dosage with symptom intensity

      Irwin, John B.; Baldwin, A. L.; Stenberg, Virgil, I; Univ Arizona, Sch Med, Dept Physiol (Dove Medical Press Ltd, 2019-06)
      Objective: To determine if patient self-administration of hydrocortisone will safely achieve superior symptom control for all hydrocortisone-responding disorders as it does for Addison's disease and rheumatoid arthritis. Methods: Two thousand four hundred and twenty-eight participants with hydrocortisone-responding disorders were brought to a minimum symptom state using daily administered hydrocortisone tablets in a 24-week, open study. Thereafter, participants used 5-day, low-dose hydrocortisone regimens to quench subsequent disorder exacerbations (flares) to maintain the minimum symptom state. Stressors such as emotional traumas, infections, allergies, and injuries were minimized to reduce disorder intensity, hydrocortisone consumption, and participant discomfort. Results: Two thousand fifteen participants, 601 with fibromyalgia, 579 with osteoarthritis, 246 with rheumatoid arthritis, 226 with undifferentiated arthritis, 75 with back pain, 51 with Parkinson's disease, 44 with polymyalgia rheumatica, 25 with neuropathy, 25 with chronic fatigue syndrome, 25 with dementia, 21 with migraine headache, 19 with multiple sclerosis, and 78 with other disorders completed the 24-week study to achieve a composite average symptom improvement of 76% with equal response rates. The participants averaged ingesting 12 mg of hydrocortisone per day. No significant adverse reactions were observed. Conclusions: Patient self-administration of hydrocortisone safely achieves superior symptom control for 38 hydrocortisone-responding disorders at equal rates and symptom improvements to confirm and amplify an earlier double-blind study finding on rheumatoid arthritis. These results are consistent with the body having an inflammation control system and chronic inflammation being a disorder unto itself with differing symptoms sets dependent on its location.
    • Identification of gender differences in ultrasound milestone assessments during emergency medicine residency training: A pilot study

      Acuña, J.; Situ-Lacasse, E.H.; Patanwala, A.E.; Stolz, L.A.; Amini, R.; Friedman, L.; Adhikari, S.; Department of Emergency Medicine, University of Arizona (Dove Medical Press Ltd, 2019)
      Objectives: Prior literature suggests that incongruities between male and female resident’s procedural competency may be explained by gender bias during the evaluation process. There are no known studies investigating gender differences in the assessment of ultrasound-based procedural skills among emergency medicine (EM) residents. The purpose of this study was to evaluate for gender differences in ultrasound milestone assessments among EM residents. Methods: This is a retrospective study including EM residents. Milestone assessment data were collected from a total of 3 Accreditation Council for Graduate Medical Education (ACGME) EM residency programs representing a 3-year period The outcome measures included mean milestone levels, milestone levels at baseline and graduation and differences in milestone achievement between female and male EM residents. An unpaired Student’s t-test was used to compare milestone scores between female and male residents. Results: A total of 456 ultrasound milestone evaluations were collected from 91 EM residents (34 females [37%] and 57 males [63%]). No significant differences were noted in the overall mean milestone level between females (2.3±0.6) and males (2.2±0.6) (P=0.387). There were no significant differences noted in the ultrasound milestone level between females (0.8±0.6) and males (0.7±0.7) at baseline (P=0.754). Although it did not reach statistical significance (P=0.197), the increase in the mean ultrasound milestone level from baseline to graduation was greater in males (3.4±0.7) compared to females (3.1±0.7). Conclusion: Overall, there were no statistically significant differences in the mean ultrasound milestone levels between females and males. The rate of ultrasound milestone level achievement during EM residency training at our institution had a slight tendency to be higher for males than females in the observed residency programs; however, this also did not reach statistical significance. Possible gender bias while evaluating ultrasound milestone levels needs to be further studied on a larger scale. © 2019 Acuña et al.
    • Influence of comorbidities on healthcare expenditures and perceived physical and mental health status among adults with multiple sclerosis: A propensity score-matched us national-level study

      Bhattacharjee, S.; Yegezu, Z.; Kollecas, K.; Duhrkopf, K.; Hashemi, L.; Greene, N.; Department of Pharmacy Practice and Science, College of Pharmacy, The University of Arizona (Dove Medical Press Ltd, 2021)
      Objective: To evaluate the effect of comorbidities on healthcare expenditures and perceived physical and mental health status among adults with multiple sclerosis (MS) compared to propensity score-matched non-MS controls. Methods: A retrospective, cross-sectional, matched cohort study was conducted using Medical Expenditure Panel Survey (2005–2015) data. The base study sample consisted of adults (age ≥18 years) who were alive and had positive total healthcare expenditures during the survey calendar year. Adults with MS were propensity-matched (1:1) to non-MS controls based on age, gender, and race/ethnicity using greedy matching algorithm. Healthcare expenditures consisted of total and subtypes of expenditures. Health status consisted of perceived physical and mental health status. Comorbidities were identified using ICD-9-CM and Clinical Classification System codes. Ordinary least squares regression and multinomial logistic regression were used to analyze the healthcare expenditures and health status variables, respectively. Results: Final study sample consisted of 541 adults in each MS and non-MS control groups after propensity score matching. After adjusting for potential confounders, individuals with MS had greater total and subtypes of expenditures compared to non-MS controls, and several comorbidities (eg, depression, hypertension) were significantly associated with increased healthcare expenditures. Yearly average total expenditures (expressed in 2018 US$) were significantly (p<0.001) higher for adults with MS ($29,396) than propensity score-matched non-MS adults ($7875). Moreover, after adjusting for all individual-level factors, adults with MS experienced 363% (p<0.001) higher total expenditures compared to propensity score-matched non-MS controls. Individuals with MS were more likely to report poorer physical and good mental health status compared to propensity score-matched non-MS controls, and several comorbidities (eg, anxiety, depression) were significant independent predictors of poorer health status. For example, adults with MS were four times more likely (OR: 4.10, 95% CI: 2.42–6.96) to report fair/poor physical health status compared to excellent/very good physical health status compared with non-MS controls. Adults with MS were 42% (OR: 1.42, 95% CI: 1.01–1.99) more likely than propensity score-matched non-MS controls to report good rather than very good or excellent mental health status. However, there was no difference between adults with MS and propensity score-matched non-MS controls in terms of reporting fair or poor than very good or excellent mental health status. Conclusion: Findings from this study indicate substantial economic and health status burdens among adults with MS at the US national-level that are significantly influenced by comorbidities. © 2021 Bhattacharjee et al.
    • Longitudinal imaging-based clusters in former smokers of the copd cohort associate with clinical characteristics: The subpopulations and intermediate outcome measures in copd study (spiromics)

      Zou, C.; Li, F.; Choi, J.; Haghighi, B.; Choi, S.; Rajaraman, P.K.; Comellas, A.P.; Newell, J.D.; Jnr; Lee, C.H.; et al. (Dove Medical Press Ltd, 2021)
      Purpose: Quantitative computed tomography (qCT) imaging-based cluster analysis identified clinically meaningful COPD former-smoker subgroups (clusters) based on cross-sectional data. We aimed to identify progression clusters for former smokers using longitudinal data. Patients and Methods: We selected 472 former smokers from SPIROMICS with a baseline visit and a one-year follow-up visit. A total of 150 qCT imaging-based variables, comprising 75 variables at baseline and their corresponding progression rates, were derived from the respective inspiration and expiration scans of the two visits. The COPD progression clusters identified were then associated with subject demography, clinical variables and biomarkers. Results: COPD severities at baseline increased with increasing cluster number. Cluster 1 patients were an obese subgroup with rapid progression of functional small airway disease percentage (fSAD%) and emphysema percentage (Emph%). Cluster 2 exhibited a decrease of fSAD% and Emph%, an increase of tissue fraction at total lung capacity and airway narrowing over one year. Cluster 3 showed rapid expansion of Emph% and an attenuation of fSAD%. Cluster 4 demonstrated severe emphysema and fSAD and significant structural alterations at baseline with rapid progression of fSAD% over one year. Subjects with different progression patterns in the same cross-sectional cluster were identified by longitudinal clustering. Conclusion: qCT imaging-based metrics at two visits for former smokers allow for the derivation of four statistically stable clusters associated with unique progression patterns and clinical characteristics. Use of baseline variables and their progression rates enables identification of longitudinal clusters, resulting in a refinement of cross-sectional clusters. © 2021 Zou et al.
    • Outcomes of conductive keratoplasty combined with corneal crosslinking in advanced ectatic corneal disease

      Sinjab, M.M.; Rubinfeld, R.S.; Wagner, K.; Parsons, Jnr, E.C.; Cummings, A.B.; Belin, M.W.; Department of Ophthalmology, University of Arizona (Dove Medical Press Ltd, 2021)
      Purpose: To assess the effectiveness of a novel treatment for patients with advanced corneal ectasia and loss of visual acuity (VA). Conductive keratoplasty (CK) is performed to improve VA followed by epithelium-on (epi-on) corneal crosslinking (CXL) to stabilize the cornea after CK. Methods: Retrospective, exploratory cohort study. Patients with keratoconus or postsurgical ectasia and best spectacle-corrected distance VA (CDVA) ≤ 20/40 were included. Conductive keratoplasty was performed (ViewPoint CK System, Refractec, Inc., Bloomington, MN); followed a day later by epi-on CXL (CXLUSA/CXLO, Bethesda, MD/CXLO Encinitas, CA). Measures included uncorrected distance visual acuity (UDVA) and CDVA, as well as refractive and tomographic measures and tomographic indices. Results: Data from 50 eyes of 45 patients were analyzed. Mean follow-up was 15.1 ± 12.2 months (range: 2 to 51). Overall, UDVA and CDVA improved postoperatively. Subjective refraction and tomographic metrics did not show consistent changes, but changes in tomographic indices were associated with treatment follow-up time. At the 1-year visit, mean UDVA significantly improved over baseline (P = 0.009) by approximately 3 lines; mean CDVA improved significantly (P = 10−5) by approximately 2 lines. No eye lost lines of CDVA. Change in the Index of Surface Variance (ISV) was associated with treatment, and the D-Index trended over follow-up time. Conclusion: Conductive keratoplasty with a proprietary epi-on CXL treatment improved vision in patients with advanced ectasia This CK/epi-on CXL treatment offers the possibility of improved VA for patients with compromised vision due to ectasia. © 2021 Sinjab et al.
    • Real-world outcomes in patients with diabetic macular edema treated long term with ranibizumab (Vision study)

      Van, Aken, E.; Favreau, M.; Ramboer, E.; Denhaerynck, K.; Macdonald, K.; Abraham, I.; Brié, H.; Center for Health Outcomes and Pharmacoeconomic Research, University of Arizona; Department of Pharmacy Practice and Science, College of Pharmacy, University of Arizona; Department of Family and Community Medicine, College of Medicine - Tucson, University of Arizona (Dove Medical Press Ltd, 2020)
      Aim: Evaluate long-term real-world treatment patterns and associated effectiveness and safety outcomes in patients with diabetic macular edema (DME) treated ≥36 months with 0.5mg ranibizumab. Methods: Open-label observational effectiveness study in 9 Belgian clinics. Included were primary treated eyes of 55 DME patients between August 2014 and March 2015 and followed for 3.5±1.8 years. Eyes were 21.8% treatment (TX)-naïve, 9.1% non-naïve with exclusive prior anti-VEGF treatment (PRIOR-anti-VEGF), and 63.6% non-naïve with other prior treatments (PRIOR-other). Intravitreal injections with ranibizumab were administered per ophthalmologists’ best clinical judgment. Trend testing of changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) over time occurred using mixed regression analysis. Results: The mean±SD number of treatments in the first year was 5.1±3.0 (TX-naïve), 4.5 ±2.7 (PRIOR-anti-VEGF) and 5.6±3.1 (PRIOR-other). At 12 months, BCVA increased by 8.9±16.4 letters from 59.7±9.3 at baseline in TX-naïve (p<0.0001), by 11.8±9.9 from 61.6 ±8.5 in PRIOR-anti-VEGF (p=0.03), and by 4.2±10.6 from 58.2±14.6 in PRIOR-other groups (p=0.0002). BCVA remained stable for the remainder of follow-up in all groups. CRT decreased over the first 2 months by monthly rates of −43.8µm in TX-naïve (p=0.04), −75.7µm in PRIOR-anti-VEGF (p=0.02), and −65.8µm in PRIOR-other eyes (p=0.0003), showing stability afterwards. No unknown adverse events were recorded; a painful eye following injection was registered with a possible relationship to the treatment. Conclusion: This real-world study confirms the effectiveness of ranibizumab in preventing a decline in BCVA and demonstrated initial improvement and subsequent retention of BCVA in DME patients ≥36 months. Ranibizumab initially reduced and then maintained CRT. However, these data reveal that treatment intensity and BCVA and CRT outcomes are lower than those found in early efficacy trials. Under-treatment likely accounts for this efficacy-effectiveness gap. Yet, intravitreal ranibizumab is an effective and safe long-term treatment for DME under conditions of significant heterogeneity in patients and treatment patterns. © 2020 Van Aken et al.
    • The use of point-of-care ultrasound for arthrocentesis among emergency medicine residents

      Acuna, J.; Yarnish, A.; Situ-Lacasse, E.; Amini, R.; Adhikari, S.; Department of Emergency Medicine, University of Arizona (Dove Medical Press Ltd, 2021)
      Introduction: The objective of this study is to determine if EM resident physicians are able to successfully utilize POCUS to perform an arthrocentesis in the ED. This is a retrospective review of ED patients who received an ultrasound-guided or ultrasound-assisted arthrocent-esis performed in the ED over a 6-year period by an EM resident physician. Methods: This was a retrospective review of ED patients who received an ultrasound-guided or ultrasound-assisted arthrocentesis performed in the ED over a 6-year period by an EM resident physician. An ED POCUS database was reviewed for POCUS examinations where an arthrocentesis was performed. Electronic medical records were then reviewed for demographic characteristics, history, physical examination findings, ED course, additional imaging studies, and the impact of the POCUS study on patient care and disposition. Results: A total of 101 POCUS examinations of patients were included in the final analysis. The POCUS examinations and procedures were performed by 59 different EM residents at various levels of training. Overall, 92.1% (93/101) of the procedures were successful. When assessing for image quality, 98/101 (97%) had recognizable structures at minimum. The majority of the patients (84/101, 83.2%) received additional imaging of the affected joint. In the minority of cases (23/101, 22.8%), the ultrasound-assisted approach was utilized, while 78/100 (77.2%) utilized the ultrasound-guided approach. For the studies that utilized the ultrasound-guided approach, the quality of needle visualization was determined to be “good” 40/78 (51.3%). Conclusion: EM resident physicians are able to utilize POCUS to perform an arthrocentesis in the ED. Further research is encouraged to determine whether having residents utilize POCUS to perform an arthrocentesis has a significant impact on outcomes and patient care. © 2021 Acuna et al.
    • Vision Recovery Velocity, Momentum and Acceleration: Advanced Vitreoretinal Analytics as Measure of Treatment Efficacy for Neovascular Age-Related Macular Degeneration

      Almeida, David RP; Ruzicki, Jessica; Xu, Kunyong; Chin, Eric K; Department of Ophthalmology and Visual Sciences, University of Arizona (Dove Medical Press Ltd, 2021-01)
      Purpose: Currently, varying treatment paradigms and different clinical trial constructs preclude cross-trial comparison between different available vascular endothelial growth factor (VEGF) inhibitors. This study aimed to review the evidence and compare the efficacy of anti-VEGF therapies for neovascular age-related macular degeneration (nAMD), and to develop metrics as a means of facilitating standardized comparison between different anti-VEGF agents within the Advanced VitreoRetinal Analytics (AVRA) model. Methods: The study analyzed key outcomes in clinical trials of bevacizumab, ranibizumab, aflibercept, and brolucizumab, including best corrected visual acuity (BCVA), number of injections, and duration of follow-up (minimum follow-up of 48 weeks). Results: The AVRA model includes 1) vision recovery velocity (VRV; letters per unit time), which provides a metric of letters gained or lost over time (or the speed of improvement); 2) injection momentum (InjMom; number of injections multiplied by letters per unit time; units of injections•(letters/time)), which is defined as the number of injections multiplied by VRV and describes the quantity of treatment needed to achieve a vision outcome; and 3) vision recovery acceleration (VRA; letters per unit time squared; units of letters/time2), which denotes final VRV minus initial VRV, per unit time, and describes the rate of change in letters gained or lost over time. Conclusion: AVRA stipulates that the ideal VEGF inhibitor to treat nAMD would have a higher positive VRV (more letters gained per unit time), low InjMom (lower treatment burden requiring fewer interventions for a given visual acuity outcome), and VRA approx-imating zero (indicating stable vision over time). AVRA allows comparisons across different trials to determine the optimal anti-VEGF agent for the treatment of nAMD.