Browsing by Subject "Treatment outcomes"

Now showing 1 - 3 of 3
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    Developing Effective Alzheimer's Disease Therapies: Clinical Experience and Future Directions
    (IOS Press, 2019) Elmaleh, David R.; Farlow, Martin R.; Conti, Peter S.; Tompkins, Ronald G.; Kundakovic, Ljiljana; Tanzi, Rudolph E.; Neurology, School of Medicine
    Alzheimer's disease (AD) clinical trials, focused on disease modifying drugs and conducted in patients with mild to moderate AD, as well as prodromal (early) AD, have failed to reach efficacy endpoints in improving cognitive function in most cases to date or have been terminated due to adverse events. Drugs that have reached clinical stage were reviewed using web resources (such as clinicaltrials.gov, alzforum.org, company press releases, and peer reviewed literature) to identify late stage (Phase II and Phase III) efficacy clinical trials and summarize reasons for their failure. For each drug, only the latest clinical trials and ongoing trials that aimed at improving cognitive function were included in the analysis. Here we highlight the potential reasons that have hindered clinical success, including clinical trial design and choice of outcome measures, heterogeneity of patient populations, difficulties in diagnosing and staging the disease, drug design, mechanism of action, and toxicity related to the long-term use. We review and suggest approaches for AD clinical trial design aimed at improving our ability to identify novel therapies for this devastating disease.
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    Stripping versus ligation of vas deferens in microscopic denervation of spermatic cord in men with chronic orchialgia: A multicenter study
    (Wiley, 2025) El-Achkar, Adnan; Hammad, Muhammed; Barham, David; Service, Chad A.; Patel, Darshan; Hsieh, Tung Chin; Mills, Jesse; Kianian, Reza; Eleswarapu, Sriram; Ziegelmann, Matthew; Smith, Ryan; Bryk, Darren; Bernie, Helen L.; Egert, Melissa; Raheem, Omer; Fendereski, Kiarad; Gross, Kelli; Pastuszak, Alex; Hotaling, James; Yafi, Faysal; Urology, School of Medicine
    Background: Microdenervation of the spermatic cord (MSCD) is an effective treatment modality for men with intractable scrotal content pain. For patients not interested in preserving fertility, some centers advocate ligation of the vas during denervation, while others prefer stripping of the vas deferens to preserve the vasal artery, hence preserving vasculature to the testis and possibly decreasing post-operative congestion pain. Objective: To compare outcomes of patients with chronic orchialgia, who underwent MSCD by either stripping or ligating the vas deferens. Materials and methods: A retrospective chart review of 85 patients who underwent MSCD from 2017-2023 was performed. Patients' demographics including history of prior surgical procedures were recorded. Response to surgery was evaluated as either complete resolution of pain, partial resolution of pain, or no improvement in pain. Results: Eighty-five patients underwent MSCD with a median (interquartile range, IQR) age of 36 (25.5-46.5) years and median duration of pain of 16 (6-31) months. Thirty-seven patients underwent stripping of vas, while 48 underwent ligation of vas during MSCD. Median follow up was 12 months. Twenty-one (43.5%) patients had prior inguinal scrotal surgery in the ligation group compared to 5 (13.5%) in the stripping group, p = 0.003. The etiology of pain was similar between the groups. The response to MSCD between the two groups was similar, 67.6% of patients who underwent stripping had complete resolution of pain versus 66.7% of those who had ligation (p = 0.968), with similar rates of post-operative complications (p-value = 0.132). Conclusions: In men with intractable chronic scrotal content pain with no interest in preserving fertility, ligation, or stripping of the vas deferens yields similar outcomes with regard to pain resolution. Both techniques are safe with no reports of any testicular atrophy.
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    Variation in Early Anakinra Use and Short-Term Outcomes in Multisystem Inflammatory Syndrome in Children
    (Wiley, 2023) Chang, Joyce C.; Young, Cameron C.; Muscal, Eyal; Sexson Tejtel, Sara K.; Newhams, Margaret M.; Kucukak, Suden; Crandall, Hillary; Maddux, Aline B.; Rowan, Courtney M.; Halasa, Natasha B.; Harvey, Helen A.; Hobbs, Charlotte V.; Hall, Mark W.; Kong, Michele; Aguiar, Cassyanne L.; Schuster, Jennifer E.; Fitzgerald, Julie C.; Singh, Aalok R.; Wellnitz, Kari; Nofziger, Ryan A.; Cvijanovich, Natalie Z.; Mack, Elizabeth H.; Schwarz, Adam J.; Heidemann, Sabrina; Newburger, Jane W.; Zambrano, Laura D.; Campbell, Angela P.; Patel, Manish M.; Randolph, Adrienne G.; Son, Mary Beth F.; Overcoming COVID Investigators; Pediatrics, School of Medicine
    Objective: Evidence regarding effectiveness of interleukin-1 receptor antagonism in Multisystem Inflammatory Syndrome in Children (MIS-C) is lacking. We characterized variation in initial treatment with anakinra and evaluated cardiovascular outcomes associated with adding anakinra to standard initial therapy. Methods: We conducted a retrospective cohort study of MIS-C cases in a U.S. surveillance registry November 2020-December 2021. Day 0 was the first calendar day of immunomodulatory treatment. Factors associated with initial anakinra use (days 0–1) were identified. We compared cases ages 2–20 years receiving intravenous immunoglobulin (IVIG) and glucocorticoids vs. anakinra plus IVIG and/or glucocorticoids (days 0–1), using inverse probability weighting to balance severity. Primary outcomes were vasopressor requirement (day 3) and impaired left ventricular ejection fraction (days 3–4). The secondary outcome was 50% reduction in C-reactive protein (day 3). Results: Among 1516 MIS-C cases (44 sites), 193 (13%) received anakinra alone or with other immunomodulators as initial treatment (range 0–74% by site). Site accounted for 59% of residual variance in anakinra use. After balancing severity, initial treatment with anakinra plus IVIG and/or glucocorticoids (N=121) vs. IVIG and glucocorticoids (N=389) was not associated with significant differences in vasopressor requirement (25.6% vs. 20.1%; RR 1.27, 95% CI [0.88–1.84]), ventricular dysfunction (33.7% vs. 25.7%; RR 1.31, 95% CI [0.98–1.75]), or C-reactive protein reduction. Conclusions: We identified substantial variation in initial anakinra use in a real-world population of children with MIS-C, but no average short-term improvement in cardiovascular outcomes associated with early addition of anakinra to IVIG and/or glucocorticoids compared to IVIG and glucocorticoids alone.