المؤلفون: Li, Jingyao, Song, Yanhua, Wang, Fangke, Zhang, Xiaozhen, Zhu, Haiyuan, Zou, Haifeng

المصدر: Inorganic Chemistry Frontiers; 8/7/2023, Vol. 10 Issue 15, p4456-4470, 15p

المؤلفون: Xie, Fengyang, Zhen, Xiaoyue, Zhu, Haiyuan, Kou, Yan, Li, Changle, Guo, Ling, Shi, Li, Han, Jie, Zhou, Xuanchen

المصدر: ENT: Ear, Nose & Throat Journal; Jul2023, Vol. 102 Issue 7, pNP327-NP336, 10p

مصطلحات موضوعية: HEARING, STATISTICS, RESEARCH evaluation, CONFIDENCE intervals, CONVALESCENCE, MULTIPLE regression analysis, RETROSPECTIVE studies, ACQUISITION of data, COMPARATIVE studies, TYMPANOPLASTY, POSTOPERATIVE period, THEORY, MEDICAL records, DESCRIPTIVE statistics, RESEARCH funding, PREDICTION models, ODDS ratio, SENSITIVITY & specificity (Statistics), OTITIS media, LONGITUDINAL method, EVALUATION

مستخلص: Objective: To explore the factors affecting postoperative hearing recovery in chronic otitis media (COM) patients, establish a clinical prediction model for hearing recovery, and verify the accuracy of the model. Methods: Data of patients with COM who were admitted to our hospital between January 1, 2012 and September 30, 2020 were retrospectively analyzed. We collected data on relevant clinicopathological characteristics of patients. The patients were randomly divided into the development cohort and validation cohorts. A postoperative air-bone gap (ABG) ≤20 dB was defined as successful hearing recovery. Univariate and multivariable logistic regression analyses were used to investigate the association of several prognostic factors with hearing recovery. These factors were then used to establish a nomogram. The model was subjected to bootstrap internal validation and performance evaluation in terms of discrimination, calibration, and clinical validity. Results: This study included 2146 patients with COM: the development cohort comprised 1610 patients (mean [standard deviation; SD] age, 44.1 [14.7] years; 733 men [45.5%]) and the validation cohort included 536 patients (mean [SD] age, 42.9 [14.4] years; 234 men [43.7%]). Multivariable logistic regression analysis showed that age, duration of onset, styles of surgery (tympanoplasty, canal wall up-CWU, or canal wall down-CWD), ossicular prosthesis, granulation or calcified blocks around the ossicular chain, ossicular chain integrity, duration of drilling, eustachian tube dysfunction, mixed hearing loss, semicircular canal fistula, and second surgery were associated with hearing recovery. A nomogram based on these variables was constructed. The area under the curve was 0.797 (95% confidence interval [CI], 0.778–0.812) in the development cohort and 0.798 (95% CI, 0.7605–0.8355) in the validation cohort. Conclusions: This study demonstrated the various clinical factors correlated with hearing recovery in patients with COM. The nomogram developed with these data could provide personalized risk estimates of hearing recovery to enhance preoperative counseling and help to set realistic expectations in patients. [ABSTRACT FROM AUTHOR]

: Copyright of ENT: Ear, Nose & Throat Journal is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Feng, Lingsong, Ding, Guodong, Zhou, Yang, Zhu, Haiyuan, Jiang, Huiming

المصدر: Pharmacogenomics & Personalized Medicine; Oct2022, Vol. 15, p857-866, 10p

المؤلفون: Wigal, Sharon, Tsai, Joyce, Bates, John A., Sarma, Kaushik, Tortorich, Deidre, Zhu, Haiyuan, Goldman, Robert

المصدر: Journal of Attention Disorders; Aug2022, Vol. 26 Issue 10, p1357-1368, 12p

مصطلحات موضوعية: ATTENTION-deficit hyperactivity disorder, CLASSROOMS, LEAST squares

مستخلص: Objective: To evaluate the efficacy of dasotraline 2 mg/day for treatment of ADHD in children weighing ≤30 kg. Method: Children (ages 6–12) with ADHD were randomized to 14 days of once-daily evening doses of dasotraline 2 mg (n = 47) or placebo (n = 48). Efficacy was assessed at Baseline and day-15 in seven, 30-minutes classroom sessions on each day (8:00 a.m. to 8:00 p.m.; 12–24 hours post-dose). The primary endpoint was change from Baseline at Day-15 in the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) combined score averaged over the seven, serial timepoints. Results: Treatment with dasotraline was associated with significant improvement versus placebo in the primary SKAMP-combined score (least squares mean [ SE ] change from Baseline at Day-15: −3.67 [0.775] vs. +1.57 [0.773]; p <.001; effect size, 1.04). Conclusion: Dasotraline 2 mg/day was found to be efficacious and generally well tolerated in this placebo-controlled, laboratory classroom study of children ages 6 to 12 years with ADHD. Clinicaltrials.gov identifier: NCT03231800. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Attention Disorders is the property of Sage Publications Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Zhu, Haiyuan¹ (AUTHOR)

المصدر: Statistics in Biopharmaceutical Research. Jan-Mar2017, Vol. 9 Issue 1, p107-115. 9p.

مصطلحات موضوعية: *CLINICAL trials, *MEDICAL research

مستخلص: Poisson and negative binomial models are frequently used to analyze count data in clinical trials. While several sample size calculation methods have recently been developed for superiority tests for these two models, similar methods for noninferiority and equivalence tests are not available. When a noninferiority or equivalence trial is designed to compare Poisson or negative binomial rates, an appropriate method is needed to estimate the sample size to ensure the trial is properly powered. In this article, several sample size calculation methods for noninferiority and equivalence tests have been derived based on Poisson and negative binomial models. All of these methods accounted for potential over-dispersion that commonly exists in count data obtained from clinical trials. The precision of these methods was evaluated using simulations. Supplementary materials for this article are available online. [ABSTRACT FROM PUBLISHER]

المؤلفون: Zhu, Haiyuan¹, Wu, Xiao¹

المصدر: Pharmaceutical Statistics. Nov2014, Vol. 13 Issue 6, p403-409. 7p.

مصطلحات موضوعية: *CONFIDENCE intervals, *DISEASE exacerbation, *POISSON processes, *CLINICAL trials, *REGRESSION analysis

مستخلص: The number of patient-years needed to treat (NPYNT), also called the event-based number needed to treat, to avoid one additional exacerbation has been reported in recently published respiratory trials, but the confidence intervals are not routinely reported. The challenge of constructing confidence intervals for NPYNT is due to the fact that exacerbation data or count data in general are usually analyzed using Poisson-based models such as Poisson or negative binomial regression and the rate ratio is the natural metric for between-treatment comparison, while NPYNT is based on rate difference, which is not usually calculated for those models. Therefore, the variance estimates from these analysis models are directly related to the rate ratio rather than the rate difference. In this paper, we propose several methods to construct confidence intervals for the NPYNT, assuming that the event rates are estimated using Poisson or negative binomial regression models. The coverage property of the confidence intervals constructed with these methods is assessed by simulations. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

المؤلفون: Zhu, Haiyuan¹, Lakkis, Hassan¹

المصدر: Statistics in Medicine. Feb2014, Vol. 33 Issue 3, p376-387. 12p.

مستخلص: Negative binomial model has been increasingly used to model the count data in recent clinical trials. It is frequently chosen over Poisson model in cases of overdispersed count data that are commonly seen in clinical trials. One of the challenges of applying negative binomial model in clinical trial design is the sample size estimation. In practice, simulation methods have been frequently used for sample size estimation. In this paper, an explicit formula is developed to calculate sample size based on the negative binomial model. Depending on different approaches to estimate the variance under null hypothesis, three variations of the sample size formula are proposed and discussed. Important characteristics of the formula include its accuracy and its ability to explicitly incorporate dispersion parameter and exposure time. The performance of the formula with each variation is assessed using simulations. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

المؤلفون: Frenkl, Tara L., Zhu, Haiyuan, Reiss, Theodore, Seltzer, Olga, Rosenberg, Elizabeth, Green, Stuart

المصدر: Journal of Urology; Aug2010, Vol. 184 Issue 2, p616-622, 7p

مصطلحات موضوعية: OVERACTIVE bladder, TACHYKININS, ANTIEMETICS, TOLTERODINE, URINATION disorders, PLACEBOS, RANDOMIZED controlled trials, BLADDER disease treatment

مستخلص: Purpose: Neurokinin-1 receptor dependent mechanisms may regulate urinary frequency and urgency. We conducted this study to assess the efficacy and tolerability of the neurokinin-1 receptor antagonist serlopitant vs placebo or tolterodine in patients with overactive bladder. Materials and Methods: This randomized, double-blind, 69-center trial enrolled adults with overactive bladder (8 or more average daily micturitions and 1 or more daily urge incontinence episodes). After a 1-week placebo run-in the patients were randomized to 8 weeks of daily 0.25, 1 or 4 mg serlopitant, 4 mg tolterodine extended release or placebo. Patients kept 7-day voiding diaries. The primary end point was change from baseline in micturitions per day. Secondary end points included urgency, total incontinence, urge incontinence episodes and incidence of dry mouth. Results: Of 557 patients randomized 476 completed the trial and had valid efficacy data for analysis. Mean change from baseline in daily micturitions was significantly greater for 0.25 (–1.1) and 4 mg (–1.1) serlopitant, and for tolterodine (–1.5) than for placebo (–0.5), but not for 1 mg serlopitant (–0.8). No serlopitant dose response was demonstrated. Tolterodine was numerically superior to all doses of serlopitant in mean micturitions per day and secondary end points. The incidence of dry mouth on serlopitant (3.3%) was comparable to placebo (4.6%) and lower than tolterodine (8.8%). Serlopitant was generally well tolerated. Conclusions: Serlopitant (0.25 and 4 mg) significantly decreased the primary end point of daily micturitions but not the secondary end points compared with placebo. Serlopitant was generally well tolerated. Thus, NK-1 receptor antagonists may have a role in the treatment of overactive bladder but this compound does not offer advantages in efficacy compared to tolterodine. [Copyright &y& Elsevier]

: Copyright of Journal of Urology is the property of Wolters Kluwer UK and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Hedayat, A. S., Zhu, Haiyuan

المصدر: Journal of Combinatorial Designs; 2003, Vol. 11 Issue 1, p51-77, 27p

المؤلفون: Kaul, Inder¹ (AUTHOR), Sawchak, Sharon¹ (AUTHOR), Correll, Christoph U^2,3,4 (AUTHOR), Kakar, Rishi⁵ (AUTHOR), Breier, Alan⁶ (AUTHOR), Zhu, Haiyuan¹ (AUTHOR), Miller, Andrew C¹ (AUTHOR), Paul, Steven M¹ (AUTHOR) spaul@karunatx.com, Brannan, Stephen K¹ (AUTHOR)

المصدر: Lancet. Jan2024, Vol. 403 Issue 10422, p160-170. 11p.

مصطلحات موضوعية: *MUSCARINIC receptors, *CLINICAL trials, *MUSCARINIC agonists, *GASTROPARESIS, *PEOPLE with schizophrenia, *DOPAMINE receptors

مستخلص: New treatments with new mechanisms are urgently needed for people with schizophrenia. Xanomeline is a dual M 1 and M 4 -preferring muscarinic receptor agonist that does not block D 2 dopamine receptors, unlike all currently approved treatments for schizophrenia. Xanomeline–trospium (KarXT) combines xanomeline with the peripherally restricted muscarinic receptor antagonist trospium chloride with the goal of ameliorating xanomeline-related adverse events associated with peripheral muscarinic receptors. The EMERGENT-2 trial aimed to assess the efficacy and safety of KarXT in people with schizophrenia experiencing acute psychosis. EMERGENT-2 was a randomised, double-blind, placebo-controlled, flexible-dose, 5-week, inpatient, phase 3 trial in people with schizophrenia. Participants were adults aged 18–65 years with a diagnosis of schizophrenia who had a recent worsening of psychosis warranting hospital admission, a Positive and Negative Syndrome Scale (PANSS) score of 80 or higher, and a Clinical Global Impression-Severity score of 4 or higher. The participants were recruited from 22 inpatient sites in the USA, and were randomly assigned (1:1) to KarXT or placebo twice per day. Participants randomly assigned to KarXT received 50 mg xanomeline and 20 mg trospium twice per day for the first 2 days and then 100 mg xanomeline and 20 mg trospium twice per day for days 3–7. Beginning on day 8, KarXT dosing was flexible with an optional increase to 125 mg xanomeline and 30 mg trospium twice per day and the option to return to 100 mg xanomeline and 20 mg trospium based on tolerability. The primary endpoint was change from baseline to week 5 in PANSS total score. Efficacy analyses used the modified intention-to-treat population (all randomly assigned participants who received at least one trial medication dose and had at least one post-baseline PANSS assessment). Least squares mean change from baseline, SE, and least squares mean difference between the KarXT and placebo groups at week 5, along with the 95% CI and two-sided p values were calculated for the primary and secondary continuous efficacy endpoints. Safety analyses included all participants receiving at least one trial medication dose and used descriptive statistics. This trial is registered with ClinicalTrials.gov (NCT04659161). From Dec 16, 2020, to April 13, 2022, of 407 people who were screened, 252 participants meeting enrolment criteria were randomly assigned to the KarXT (n=126) or placebo (n=126). Baseline PANSS total scores were 98·3 (KarXT; n=126) and 97·9 (placebo; n=125). The trial met the primary endpoint with a mean change from baseline to week 5 in PANSS total score that favoured KarXT (–21·2 points, SE 1·7) versus placebo (–11·6 points, 1·6; least squares mean difference –9·6; 95% CI –13·9 to –5·2; p<0·0001, Cohen's d effect size=0·61). All secondary endpoints were also met, and favoured KarXT versus placebo (p<0·05). The most common adverse events with KarXT versus placebo were constipation (27 [21%] vs 13 [10%]), dyspepsia (24 [19%] vs 10 [8%]), headache (17 [14%] vs 15 [12%]), nausea (24 [19%] vs seven [6%]), vomiting (18 [14%] vs one [1%]), hypertension (12 [10%] vs one [1%]), dizziness (11 [9%] vs four [3%]), gastro-oesophageal reflux disease (eight [6%] vs zero [0%]), and diarrhoea (seven [6%] vs four [3%]). Treatment-emergent adverse event rates of extrapyramidal motor symptoms (KarXT, zero [0%] vs placebo, zero [0%]), akathisia (one [1%] vs one [1%]), weight gain (zero [0%] vs one [1%]), and somnolence (six [5%] vs five [4%]) were similar between the KarXT and placebo groups, as were adverse event-related discontinuation rates (nine [7%] vs seven [6%]). In the EMERGENT-2 trial, KarXT was effective in reducing positive and negative symptoms and was generally well tolerated. These results support the potential for KarXT to represent a new class of effective and well tolerated antipsychotic medicines based on activating muscarinic receptors, not the D 2 dopamine receptor-blocking mechanism of all current antipsychotic medications. Results from additional trials, including the identical EMERGENT-3 trial and the 52-week, open-label EMERGENT-4 and EMERGENT-5 trials, will provide additional information on the efficacy and safety of KarXT in people with schizophrenia. Karuna Therapeutics. [ABSTRACT FROM AUTHOR]