Characterization of three new intra- I region recombinant mouse strains, B10.ASR7 ( H-2 as3 ), B10.BAR4 ( H-2 h6 ), and B10.BASR1 ( H-2 as4 )

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46741/1/251_2004_Article_BF00387862.pd

Evaluation of Cough Medication Use Patterns in Ambulatory Care Settings in the United States: 2003–2018

Using 2003–2018 National Ambulatory Medical Care Survey data for office-based visits and 2003–2018 National Hospital Ambulatory Medical Care Survey data for emergency department (ED) visits, we conducted cross-sectional analyses to examine cough medication (CM) use trends in the United States (US) ambulatory care settings. We included adult (≥18 years) patient visits with respiratory-infection-related or non-infection-related cough as reason-for-visit or diagnosis without malignant cancer or benign respiratory tumor diagnoses. Using multivariable logistic regressions, we examined opioid antitussive, benzonatate, dextromethorphan-containing antitussive, and gabapentinoid use trends. From 2003–2005 to 2015–2018, opioid antitussive use decreased in office-based visits (8.8% to 6.4%, Ptrend = 0.03) but remained stable in ED visits (6.3% to 5.9%, Ptrend = 0.99). In both settings, hydrocodone-containing antitussive use declined over 50%. Benzonatate use more than tripled (office-based:1.6% to 4.8%; ED:1.5% to 8.0%; both Ptrend < 0.001). Dextromethorphan-containing antitussive use increased in ED visits (1.8% to 2.6%, Ptrend = 0.003) but stayed unchanged in office-based visits (3.8% to 2.7%; Ptrend = 0.60). Gabapentinoid use doubled in office-based visits (1.1% in 2006–2008 to 2.4% in 2015–2018, Ptrend < 0.001) but was negligible in ED visits. In US office-based and ED ambulatory care settings, hydrocodone-containing antitussive use substantially declined from 2003 to 2018, while benzonatate use more than tripled, and dextromethorphan-containing antitussive and gabapentinoid use remained low (<3%)

Patterns of Cough Medication Prescribing among Patients with Chronic Cough in Florida: 2012–2021

Among patients with chronic cough (CC) in the 2012–2021 statewide OneFlorida Clinical Research Consortium database, we examined trends in cough medication (CM) prescribing prevalence over time in repeated cross-sectional analyses and identified distinct CM utilization trajectories using group-based trajectory modeling (GBTM) in a retrospective cohort study. Among eligible adults (≥18 years) without cancer/benign respiratory tumor diagnoses, we identified CC patients and non-CC patients with any cough-related diagnosis. In the GBTM analysis, we calculated the number of monthly prescriptions for any CMs (excluding gabapentinoids) during the 12 months from the first qualifying cough event to identify distinct utilization trajectories. From 2012 to 2021, benzonatate (9.6% to 26.1%), dextromethorphan (5.2% to 8.6%), and gabapentinoid (5.3% to 14.4%) use increased among CC patients, while opioid antitussive use increased from 2012 to 2015 and decreased thereafter (8.4% in 2012, 14.7% in 2015, 6.7% in 2021; all p < 0.001). Of 15,566 CC patients and 655,250 non-CC patients identified in the GBTM analysis, CC patients had substantial burdens of respiratory/non-respiratory comorbidities and healthcare service and concomitant medication use compared to non-CC patients. Among CC patients, GBTM identified three distinct CM utilization trajectories: (1) no CM use (n = 11,222; 72.1%); (2) declining CM use (n = 4105; 26.4%); and (3) chronic CM use (n = 239; 1.5%). CC patients in Florida had limited CM use with increasing trends in use of benzonatate, dextromethorphan, and gabapentinoids and a decreasing trend in opioid antitussive use. CC patients, particularly with chronic prescription CM use, experienced substantial disease burden

Patient-reported experiences with refractory or unexplained chronic cough: a qualitative analysis

Background: Chronic cough, defined as a cough lasting 8 or more weeks, affects up to 10% of adults. Refractory chronic cough (RCC) is a cough that is uncontrolled despite comprehensive investigation and treatment of comorbid conditions while unexplained chronic cough (UCC) is a cough with no identifiable cause despite extensive evaluation of comorbid conditions. RCC and UCC are often poorly controlled. Understanding individuals’ lived experience of the symptoms and impacts of these conditions may guide therapeutic strategies. Objectives: The primary objectives of this study were to assess respondents’ perceptions of the key symptoms of RCC and UCC and the impacts of RCC and UCC and their symptoms on well-being, health-related quality of life, work productivity, and social relationships. Design: Qualitative study. Methods: This study enrolled 30 adults with physician-diagnosed RCC or UCC. Two trained qualitative researchers conducted individual, in-depth telephone interviews using a semi-structured interview guide. Interviews were audio-recorded, transcribed, coded, and systematically analyzed to identify content themes. Results: A total of 15 respondents with RCC and 15 with UCC were included in the study. Many respondents had RCC or UCC for a long duration (median 9 years, range: 0–24). Half of the respondents reported having a coughing episode at least once daily. Only 40% of respondents reported that medication had improved their symptoms. In over half of the respondents, RCC or UCC hindered communication, caused embarrassment, frustration, and worry, and lowered quality of life. Perceptions of meaningful treatment benefits in RCC or UCC varied widely across respondents. Conclusion: RCC and UCC remained poorly managed in many individuals and were associated with a wide range of symptoms and cough triggers that hindered daily activities and reduced emotional well-being. Understanding individuals’ lived experiences may inform the development of RCC and UCC therapeutic strategies

Photovoltaic restoration of high visual acuity in rats with retinal degeneration

Patients with retinal degeneration lose sight due to gradual demise of photoreceptors. Electrical stimulation of the surviving retinal neurons provides an alternative route for delivery of visual information. We developed subretinal photovoltaic arrays to convert pulsed light into bi-phasic pulses of current to stimulate the nearby inner retinal neurons. Bright pulsed illumination is provided by image projection from video goggles and avoids photophobic effects by using near-infrared (NIR, 880-915nm) light. Experiments in-vitro and in-vivo demonstrate that the network-mediated retinal stimulation preserves many features of natural vision, such as flicker fusion, adaptation to static images, and most importantly, high spatial resolution. Our implants with 70μm pixels restored visual acuity to half of the normal level in rats with retinal degeneration. Ease of implantation and tiling of these wireless arrays to cover a large visual field, combined with their high resolution opens the door to highly functional restoration of sight

Characterization of Patients With Refractory or Unexplained Chronic Cough Participating in a Phase 2 Clinical Trial of the P2X3-Receptor Antagonist Gefapixant

Purpose: This analysis assesses clinical characteristics of patients with refractory chronic cough (RCC) or unexplained chronic cough (UCC) enrolled in a phase 2 study to better understand this patient population. Methods: Patients with RCC/UCC lasting for ≥ 1year and cough severity visual analog scale (VAS) score of > 40mm at screening were eligible. Demographics, clinical characteristics, and medical history were collected at baseline. Cough-related measures included cough severity VAS, Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), and a structured cough-trigger questionnaire. Medication history included all medications 30days before screening and chronic cough treatments within 1year before screening. Data were summarized using descriptive statistics. Results: Patients (N = 253; female, 76%; mean age, 60years) had severe (mean cough severity VAS, 57.5mm) and long-lasting (median duration, 11years) cough. The most burdensome self-reported aspects included psychological and social factors (LCQ) and cough frequency and intensity (CSD). Patient-reported triggers were consistent with cough hypersensitivity (e.g., 95% to 96% reported irritation or tickle in throat). Common reported comorbidities included gastroesophageal reflux disease (GERD; 56%), allergic rhinitis (47%), and asthma (30%); 12% of patients had been diagnosed with all 3 conditions. The most common prior medications included inhaled or oral steroids (21%), antihistamines (15%), and antacids (15%). Conclusion: Patients with RCC/UCC had severe, long-lasting, and burdensome cough with clinical features of cough hypersensitivity. Many patients had been diagnosed with GERD, allergic rhinitis, and asthma but had a persistent cough despite treatment of these conditions. Trial registration: ClinicalTrials.gov, NCT02612610; registered November 20, 201

Efficacy and Safety of Eliapixant in Refractory Chronic Cough: The Randomized, Placebo-Controlled Phase 2b PAGANINI Study

Introduction: The PAGANINI study evaluated the efficacy and safety of the selective P2X3 antagonist eliapixant in patients with refractory chronic cough (RCC). Methods: PAGANINI was a randomized, double-blind, parallel-group, placebo-controlled, multicenter, dose-finding, phase 2b study. Adults with RCC lasting ≥ 12 months and cough severity ≥ 40 mm on a visual analog scale at screening were enrolled. Participants were randomized 1:1:1:1 to twice-daily 25 mg, 75 mg, or 150 mg oral eliapixant or placebo for 12 weeks. The primary endpoint was change from baseline in 24-h cough count after 12 weeks of intervention. Results: Overall, 310 participants were randomized to twice-daily eliapixant 25 mg (n = 75), 75 mg (n = 78), 150 mg (n = 80), or placebo (n = 77). A statistically significant dose–response signal with eliapixant was detected for the primary endpoint (all dose–response models, adjusted p < 0.1; one-sided). Adverse events (AEs) were reported in 39 (51%) participants with placebo and 43–51 (57–65%) participants receiving eliapixant. The most common AE was dysgeusia, occurring in 1% (n = 1) of the placebo group and 1–16% (n = 1–13) of the eliapixant groups in a dose-related manner. One case of a moderate drug-induced liver injury occurred in a participant receiving 150 mg twice-daily eliapixant. Conclusion: Eliapixant demonstrated efficacy and a favorable taste tolerability profile in RCC. However, a drug-induced liver injury contributed to intensified liver monitoring in clinical trials with eliapixant and discontinuation of the entire development program in all indications by Bayer AG. Trial Registration: ClinicalTrials.gov identifier NCT04562155; registered September 18, 2020

Photovoltaic retinal prosthesis : implant fabrication and performance

The objective of this work is to develop and test a photovoltaic retinal prosthesis for restoring sight to patients blinded by degenerative retinal diseases. A silicon photodiode array for subretinal stimulation has been fabricated by a silicon-integrated-circuit/MEMS process. Each pixel in the two-dimensional array contains three series-connected photodiodes, which photovoltaically convert pulsed near-infrared light into bi-phasic current to stimulate nearby retinal neurons without wired power connections. The device thickness is chosen to be 30 µm to absorb a significant portion of light while still being thin enough for subretinal implantation. Active and return electrodes confine current near each pixel and are sputter coated with iridium oxide to enhance charge injection levels and provide a stable neural interface. Pixels are separated by 5 µm wide trenches to electrically isolate them and to allow nutrient diffusion through the device. Three sizes of pixels (280, 140 and 70 µm) with active electrodes of 80, 40 and 20 µm diameter were fabricated. The turn-on voltages of the one-diode, two-series-connected diode and three-series-connected diode structures are approximately 0.6, 1.2 and 1.8 V, respectively. The measured photo-responsivity per diode at 880 nm wavelength is ~0.36 A W−1, at zero voltage bias and scales with the exposed silicon area. For all three pixel sizes, the reverse-bias dark current is sufficiently low (<100 pA) for our application. Pixels of all three sizes reliably elicit retinal responses at safe near-infrared light irradiances, with good acceptance of the photodiode array in the subretinal space. The fabricated device delivers efficient retinal stimulation at safe near-infrared light irradiances without any wired power connections, which greatly simplifies the implantation procedure. Presence of the return electrodes in each pixel helps to localize the current, and thereby improves resolution