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1.
Ann Allergy Asthma Immunol ; 130(1): 60-66, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35569802

RESUMO

BACKGROUND: The current characterization of patients with refractory or unexplained chronic cough (RCC and UCC, respectively) primarily stems from relatively small clinical studies. OBJECTIVE: To report the baseline medical history and clinical characteristics of individuals with RCC or UCC who were enrolled in COUGH-1 and COUGH-2, 2 large, global, phase 3 trials of gefapixant, a P2 × 3-receptor antagonist. METHODS: Adults with a chronic cough lasting for more than 1 year, diagnosis of RCC or UCC, and score greater than 40 mm on a 100-mm cough severity visual analog scale at both screening and baseline were eligible for enrollment. Demographics, medical history, and cough characteristics were collected at baseline. Cough-related measures included objective cough frequency, cough severity visual analog scale, Leicester Cough Questionnaire, and Hull Airway Reflux Questionnaire. The data were summarized using descriptive statistics. RESULTS: Of 2044 participants, 75% were women; mean age was 58 years, and mean cough duration was approximately 11 years. Among all participants, 73% were previously diagnosed with asthma, gastroesophageal reflux disease, or upper airway cough syndrome. The mean Leicester Cough Questionnaire total score was 10.4, with domain scores reflecting impaired cough-specific quality of life across physical, psychological, and social domains. The mean Hull Airway Reflux Questionnaire score was 39.6, with some of the most burdensome reported items being consistent with features of cough-reflex hypersensitivity. Participant characteristics and cough burden were comparable across geographic regions. CONCLUSION: Participants with RCC or UCC had characteristics consistent with published demographics associated with chronic cough. These data reflect a global population with burdensome cough of long duration and substantial impairment to quality of life. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: COUGH-1, NCT03449134 (https://www. CLINICALTRIALS: gov/ct2/show/NCT03449134); COUGH-2, NCT03449147 (https://clinicaltrials.gov/ct2/show/NCT03449147).


Assuntos
Tosse , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Renais/complicações , Doença Crônica , Tosse/tratamento farmacológico , Tosse/epidemiologia , Refluxo Gastroesofágico , Neoplasias Renais/complicações , Qualidade de Vida , Ensaios Clínicos Fase III como Assunto
2.
Lung ; 201(2): 111-118, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36879087

RESUMO

PURPOSE: We evaluated gefapixant, a P2X3 receptor antagonist, in participants with recent-onset (≤ 12 months) refractory chronic cough (RCC) or unexplained chronic cough (UCC). METHODS: Participants (≥ 18 years of age; ≥ 40 mm on a 100-mm cough severity visual analog scale [VAS] at screening and randomization) with chronic cough for < 12 months were enrolled in this phase 3b, double-blind, placebo-controlled, parallel group, multicenter study (NCT04193202). Participants were randomized 1:1 to gefapixant 45 mg BID or placebo for 12 weeks with a 2-week follow-up. The primary efficacy endpoint was change from baseline at Week 12 in Leicester Cough Questionnaire (LCQ) total score. Adverse events were monitored and evaluated. RESULTS: There were 415 participants randomized and treated (mean age 52.5 years; median [range] duration 7.5 [1-12] months): 209 received placebo and 206 received gefapixant 45 mg BID. A statistically significant treatment difference of 0.75 (95% CI: 0.06, 1.44; p = 0.034) for gefapixant vs. placebo was observed for change from baseline in LCQ total score at Week 12. The most common AE was dysgeusia (32% gefapixant vs. 3% placebo participants); serious AEs were rare (1.5% gefapixant vs. 1.9% placebo participants). CONCLUSION: Gefapixant 45 mg BID demonstrated significantly greater improvement in cough-specific health status from baseline compared to placebo, in participants with recent-onset chronic cough. The most common AEs were related to taste and serious AEs were rare.


Assuntos
Tosse , Pirimidinas , Humanos , Pessoa de Meia-Idade , Tosse/tratamento farmacológico , Doença Crônica , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Método Duplo-Cego , Resultado do Tratamento
3.
BMC Bioinformatics ; 23(Suppl 3): 140, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35439945

RESUMO

BACKGROUND: Chronic cough affects approximately 10% of adults. The lack of ICD codes for chronic cough makes it challenging to apply supervised learning methods to predict the characteristics of chronic cough patients, thereby requiring the identification of chronic cough patients by other mechanisms. We developed a deep clustering algorithm with auto-encoder embedding (DCAE) to identify clusters of chronic cough patients based on data from a large cohort of 264,146 patients from the Electronic Medical Records (EMR) system. We constructed features using the diagnosis within the EMR, then built a clustering-oriented loss function directly on embedded features of the deep autoencoder to jointly perform feature refinement and cluster assignment. Lastly, we performed statistical analysis on the identified clusters to characterize the chronic cough patients compared to the non-chronic cough patients. RESULTS: The experimental results show that the DCAE model generated three chronic cough clusters and one non-chronic cough patient cluster. We found various diagnoses, medications, and lab tests highly associated with chronic cough patients by comparing the chronic cough cluster with the non-chronic cough cluster. Comparison of chronic cough clusters demonstrated that certain combinations of medications and diagnoses characterize some chronic cough clusters. CONCLUSIONS: To the best of our knowledge, this study is the first to test the potential of unsupervised deep learning methods for chronic cough investigation, which also shows a great advantage over existing algorithms for patient data clustering.


Assuntos
Aprendizado Profundo , Adulto , Algoritmos , Análise por Conglomerados , Tosse , Humanos
4.
Lung ; 200(6): 717-724, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36348054

RESUMO

PURPOSE: Objective cough frequency is used to assess efficacy of chronic cough (CC) treatments. The objective of this study was to explore the relationship between objective cough frequency and cough-specific patient-reported outcomes (PROs) and estimate a clinically meaningful change threshold (MCT) for objective cough frequency. METHODS: Data collected in a phase 2b study in participants with refractory or unexplained CC were used to investigate the relationship between 24-h cough frequency (measured using an ambulatory cough monitor) and cough-specific PROs (i.e., cough severity visual analog scale, cough severity diary, Leicester Cough Questionnaire). Convergent validity was assessed using Spearman ρ. An MCT for 24-h cough frequency was estimated using the patient global impression of change (PGIC) scale as an anchor. RESULTS: Correlations between 24-h cough frequency and cough-specific PROs at baseline, Week 4, and Week 12 were significant (P < 0.0001) but low to moderate in strength (ρ = 0.30-0.58). Participants categorized as very much improved/much improved (i.e., PGIC of 1 or 2) or minimally improved (i.e., PGIC of 3) had mean 24-h cough frequency reductions of 55% and 30%, respectively. Receiver operating characteristic curve analysis suggested that a 24-h cough frequency reduction of 38% optimizes sensitivity and specificity for predicting a PGIC score of 1-3. CONCLUSION: Objective 24-h cough frequency is significantly associated with cough-specific PROs, but cough frequency and PROs most likely capture distinct aspects of CC. A ≥ 30% reduction in 24-h cough frequency is a reasonable MCT to define treatment response in CC clinical trials.


Assuntos
Tosse , Procedimentos de Cirurgia Plástica , Humanos , Tosse/diagnóstico , Medição da Dor , Medidas de Resultados Relatados pelo Paciente , Curva ROC
5.
Lung ; 200(4): 423-429, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35895098

RESUMO

INTRODUCTION: In phase 3 trials (COUGH-1/COUGH-2), gefapixant 45 mg twice daily significantly reduced 24-h cough frequency vs placebo in refractory or unexplained chronic cough (RCC or UCC). METHODS: Here, the efficacy of gefapixant 45 mg vs placebo was evaluated across COUGH-1/COUGH-2 in predefined subgroups based on sex, region, age, cough duration, cough severity, cough frequency, and diagnosis (RCC, UCC). Awake cough frequency reductions at Week 12 and LCQ response rates (i.e., ≥ 1.3-point improvement) at Week 24 were assessed. RESULTS: Among 1360 participants analyzed, gefapixant 45 mg resulted in consistent awake cough frequency reductions overall and across predefined subgroups at Week 12. Gefapixant also resulted in improved LCQ scores across subgroups at Week 24; ≥ 70% of participants in each subgroup treated with gefapixant 45 mg had an LCQ response. CONCLUSION: These data suggest gefapixant 45 mg provides consistent objective and subjective efficacy across subgroups of individuals with RCC or UCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Doença Crônica , Tosse/diagnóstico , Humanos , Pirimidinas , Sulfonamidas/uso terapêutico
6.
Allergol Int ; 71(4): 498-504, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35752582

RESUMO

BACKGROUND: In two phase 3, global clinical trials (COUGH-1 and COUGH-2), the P2X3-receptor antagonist gefapixant significantly reduced objective 24-h cough frequency in participants with refractory or unexplained chronic cough (RCC or UCC) at a dosage of 45 mg twice daily (BID), with an acceptable safety profile. The primary objective of this phase 3, randomized, double-blind, parallel-group study was to assess the safety and tolerability of gefapixant in Japanese participants with RCC or UCC (ClinicalTrials.gov, NCT03696108; JAPIC-CTI, 184154). METHODS: Participants aged ≥20 years with chronic cough lasting ≥4 months and a diagnosis of RCC or UCC despite treatment in accordance with Japanese Respiratory Society guidelines were randomized 1:1 to receive gefapixant 15 or 45 mg BID for 52 weeks. The primary objective was to evaluate the safety and tolerability of gefapixant, including adverse events (AEs) and discontinuations due to AEs. Cough-specific quality of life was assessed using the Leicester Cough Questionnaire as a secondary objective. RESULTS: Of 169 randomized and treated participants, 63% were female and mean age was 58 years. Adverse events were reported by 79 (94%) and 82 (96%) participants in the 15- and 45-mg BID groups, respectively. Most treatment-related AEs were taste related. Discontinuations due to AEs occurred in 6 (7%) and 17 (20%) participants receiving gefapixant 15 or 45 mg BID, respectively. There were no serious treatment-related AEs or deaths. Leicester Cough Questionnaire total scores improved from baseline through Week 52. CONCLUSIONS: Gefapixant had an acceptable safety profile, with no serious treatment-related AEs in Japanese participants.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Adulto , Doença Crônica , Tosse/tratamento farmacológico , Método Duplo-Cego , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Pirimidinas , Qualidade de Vida , Sulfonamidas
8.
Lancet ; 390(10091): 276-288, 2017 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-28596043

RESUMO

BACKGROUND: Tildrakizumab is a high-affinity, humanised, IgG1 κ antibody targeting interleukin 23 p19 that represents an evolving treatment strategy in chronic plaque psoriasis. Previous research suggested clinical improvement with inhibition of interleukin 23 p19. We did two phase 3 trials to investigate whether tildrakizumab is superior to placebo and etanercept in the treatment of chronic plaque psoriasis. METHODS: We did two three-part, parallel group, double-blind, randomised controlled studies, reSURFACE 1 (at 118 sites in Australia, Canada, Japan, the UK, and the USA) and reSURFACE 2 (at 132 sites in Europe, Israel, and the USA). Participants aged 18 years or older with moderate-to-severe chronic plaque psoriasis (body surface area involvement ≥10%, Physician's Global Assessment [PGA] score ≥3, and Psoriasis Area and Severity Index [PASI] score ≥12) were randomised (via interactive voice and web response system) to tildrakizumab 200 mg, tildrakizumab 100 mg, or placebo in reSURFACE 1 (2:2:1), or to tildrakizumab 200 mg, tildrakizumab 100 mg, placebo, or etanercept 50 mg (2:2:1:2). Randomisation was done by region and stratified for bodyweight (≤90 kg or >90 kg) and previous exposure to biologics therapy for psoriasis. Investigators, participants, and study personnel were blinded to group allocation and remained blinded until completion of the studies. Assigned medication was identical in appearance and packaging. Tildrakizumab was administered subcutaneously at weeks 0 and 4 during part 1 and at week 16 during part 2 (weeks 12 and 16 for participants re-randomised from placebo to tildrakizumab; etanercept was given twice weekly in part 1 of reSURFACE 2 and once weekly during part 2). The co-primary endpoints were the proportion of patients achieving PASI 75 and PGA response (score of 0 or 1 with ≥2 grade score reduction from baseline) at week 12. Safety was assessed in the all-participants-as-treated population, and efficacy in the full-analysis set. These trials are registered with ClinicalTrials.gov, numbers NCT01722331 (reSURFACE 1) and NCT01729754 (reSURFACE 2). These studies are completed, but extension studies are ongoing. FINDINGS: reSURFACE 1 ran from Dec 10, 2012, to Oct 28, 2015. reSURFACE 2 ran from Feb 12, 2013, to Sept 28, 2015. In reSURFACE 1, 772 patients were randomly assigned, 308 to tildrakizumab 200 mg, 309 to tildrakizumab 100 mg, and 155 to placebo. At week 12, 192 patients (62%) in the 200 mg group and 197 patients (64%) in the 100 mg group achieved PASI 75, compared with 9 patients (6%) in the placebo group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo). 182 patients (59%) in the 200 mg group and 179 patients (58%) in the 100 mg group achieved PGA responses, compared with 11 patients (7%) in the placebo group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo). In reSURFACE 2, 1090 patients were randomly assigned, 314 to tildrakizumab 200 mg, 307 to tildrakizumab 100 mg, 156 to placebo, and 313 to etanercept. At week 12, 206 patients (66%) in the 200 mg group, and 188 patients (61%) in the 100 mg group achieved PASI 75, compared with 9 patients (6%) in the placebo group and 151 patients (48%) in the etanercept group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo; p<0·0001 for 200 mg vs etanercept and p=0·0010 for 100 mg vs etanercept). 186 patients (59%) in the 200 mg group, and 168 patients (59%) [corrected] in the 100 mg group achieved a PGA response, compared with 7 patients (4%) in the placebo group and 149 patients (48%) in the etanercept group (p<0·0001 for comparisons of both tildrakizumab groups vs placebo; p=0·0031 for 200 mg vs etanercept and p=0·0663 for 100 mg vs etanercept). Serious adverse events were similar and low in all groups in both trials. One patient died in reSURFACE 2, in the tildrakizumab 100 mg group; the patient had alcoholic cardiomyopathy and steatohepatitis, and adjudication was unable to determine the cause of death. INTERPRETATION: In two phase 3 trials, tildrakizumab 200 mg and 100 mg were efficacious compared with placebo and etanercept and were well tolerated in the treatment of patients with moderate-to-severe chronic plaque psoriasis. FUNDING: Merck & Co.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Etanercepte/administração & dosagem , Psoríase/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Doença Crônica , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
9.
Lancet Respir Med ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39222649

RESUMO

BACKGROUND: Approximately two-thirds of women with chronic cough have cough-induced stress urinary incontinence (CSUI). We aimed to evaluate the efficacy and safety of gefapixant in reducing CSUI episodes in women with refractory or unexplained chronic cough. METHODS: This phase 3b, double-blind, randomised, placebo-controlled trial done at 90 sites in 12 countries enrolled women aged 18 years or older who had chronic cough for at least 1 year, a diagnosis of refractory or unexplained chronic cough, a cough severity visual analogue scale score of 40 mm or more (100 mm maximum), and CSUI for 3 months or more. Participants were randomised 1:1 to oral gefapixant or placebo for 12 weeks. The primary outcome was percentage change from baseline in daily CSUI episodes (7-day average) at week 12. This study is registered with ClinicalTrials.gov (NCT04193176). FINDINGS: From May 10, 2020, to Sept 2, 2022, 375 participants were randomised to and treated with gefapixant 45 mg twice daily (n=185) or placebo (n=190). Mean age was 56·4 years (SD 11·4), with mean chronic cough duration of 5·2 years (SD 6·6) and SUI duration of 4·0 years (SD 5·9). Least-squares mean percentage change from baseline in daily CSUI episodes was -52·8% (95% CI -58·4 to -47·1%) for gefapixant and -41·1% (-46·7 to -35·4%) for placebo (estimated treatment difference: -11·7% [95% CI -19·7 to -3·7]; p=0·004). 129 (70%) of 185 participants who received gefapixant and 71 (37%) of 190 participants who received placebo had at least one adverse event. Safety and tolerability were consistent with previous trials of gefapixant; the most frequent adverse events were taste related. INTERPRETATION: Gefapixant 45 mg twice daily is the first treatment to show efficacy versus placebo in reducing CSUI episodes in participants with refractory or unexplained chronic cough. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

10.
Ther Adv Respir Dis ; 18: 17534666241274261, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39235438

RESUMO

BACKGROUND: Chronic cough, a cough lasting >8 weeks, includes refractory chronic cough (RCC) and unexplained chronic cough (UCC). Patient-reported outcome (PRO) measures are needed to better understand chronic cough impacts that matter most to patients. The 19-item Leicester Cough Questionnaire (LCQ), an existing PRO measure of chronic cough, assesses impacts of cough across physical, psychological, and social domains. However, the content validity of the LCQ evaluating these concepts in patients with RCC/UCC had not been established. OBJECTIVES: To evaluate the content validity of the LCQ in patients with RCC/UCC. DESIGN: A cross-sectional, qualitative interview study. METHODS: First, previously completed qualitative interview results in adults with RCC/UCC (N = 30) were evaluated and mapped to LCQ concepts. Next, a clinical cough expert reviewed each LCQ item and assessed the salience of its concepts for patients with RCC/UCC. Finally, semistructured interviews-including both concept elicitation and cognitive debriefing-were conducted in adults with RCC/UCC (N = 20) to elicit a comprehensive set of participant experiences and to assess the appropriateness of using the LCQ in this population. RESULTS: Concepts reported in the past and present qualitative interviews were included across all LCQ items, and most impacts reported to be the "most bothersome" were assessed in the LCQ. In the current study, all participants indicated that reduced cough frequency would be an important treatment target. During cognitive debriefing, each LCQ item was endorsed by ⩾70% of participants. Additionally, participants were generally able to understand, recall, and select a response for each LCQ item. All participants and the clinical expert indicated that the LCQ was appropriate and assessed the impacts most relevant to patients with RCC/UCC. CONCLUSION: Our findings support the content validity of the LCQ and demonstrate that this measure is fit-for-purpose and includes important cough impacts in adults with RCC/UCC.


Assuntos
Tosse , Entrevistas como Assunto , Medidas de Resultados Relatados pelo Paciente , Humanos , Tosse/diagnóstico , Tosse/fisiopatologia , Tosse/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Doença Crônica , Estudos Transversais , Adulto , Idoso , Reprodutibilidade dos Testes , Pesquisa Qualitativa , Inquéritos e Questionários , Qualidade de Vida , Valor Preditivo dos Testes , Tosse Crônica
11.
CPT Pharmacometrics Syst Pharmacol ; 12(8): 1107-1118, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37147897

RESUMO

Gefapixant, a P2X3-receptor antagonist, demonstrated objective and subjective efficacy in individuals with refractory or unexplained chronic cough. We report a population pharmacokinetic (PopPK) analysis that characterizes gefapixant pharmacokinetics (PKs), quantifies between- and within-participant variability, and evaluates the impact of intrinsic and extrinsic factors on gefapixant exposure. The PopPK model was initially developed using PK data from six phase I studies. Stepwise covariate method was utilized to identify covariates impacting PK parameters; the model was re-estimated and covariate effects were re-assessed after integrating PK data from three phase II and III studies. Simulations were conducted to evaluate the magnitude of covariate effects on gefapixant exposure. Of 1677 participants included in this data set, 1618 had evaluable PK records. Age, body weight, and sex had statistically significant, but not clinically relevant, effects on exposure. Degree of renal impairment (RI) had statistically significant and clinically relevant effects on exposure; exposure was 17% to 89% higher in those with versus without RI. Simulation results indicated that gefapixant 45 mg administered once daily to patients with severe RI has similar exposure to gefapixant 45 mg administered twice daily to patients with normal renal function. There were no significant effects of proton pump inhibitors or food. Of evaluated intrinsic and extrinsic factors, only RI had a clinically relevant effect on gefapixant exposure. Patients with mild or moderate RI do not require dosage adjustments; however, for patients with severe RI who are not on dialysis, gefapixant 45 mg once daily is recommended.


Assuntos
Tosse , Insuficiência Renal , Humanos , Tosse/induzido quimicamente , Sulfonamidas , Pirimidinas/efeitos adversos , Diálise Renal
12.
Ther Adv Respir Dis ; 16: 17534666221099737, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35614875

RESUMO

INTRODUCTION: The Leicester Cough Questionnaire (LCQ), a cough-specific quality-of-life measure, evaluates the impact of cough across physical, psychological, and social domains in patients with chronic cough (CC). This study assessed the psychometric properties of the LCQ. METHODS: Data from a phase IIb, randomized controlled trial of the P2X3-receptor antagonist gefapixant were analyzed (NCT02612610). Subjective [Cough Severity Diary, cough severity visual analogue scale, and patient global impression of change (PGIC)] and objective (awake and 24-h cough frequency) data were used to validate the LCQ for use in patients with refractory or unexplained CC (RCC and UCC, respectively). Psychometric analyses included confirmatory factor analyses, internal consistency and test-retest reliability, validity, responsiveness, and estimated within-patient thresholds for clinically meaningful change. RESULTS: Model-fit values for the proposed three-factor LCQ domains and most individual items were acceptable. Analyses suggest that a mean improvement ranging from 1.3 to 2.3 points for the LCQ total and ⩾0.8, ⩾0.9, and ⩾0.8 points for physical, psychological, and social domain scores, respectively, had the best sensitivity and/or specificity for predicting patient ratings of improvement on the PGIC. CONCLUSIONS: The LCQ is a valid and reliable measure to evaluate cough-specific quality of life and is a fit-for-purpose measure for use in patients with RCC or UCC. Although a single threshold for defining clinically meaningful change depends on the context of use, the results can help guide both treatment decisions and drug development. Therefore, clinicians may consider a ⩾1.3-point increase in the LCQ total score as clinically meaningful.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Doença Crônica , Tosse/diagnóstico , Tosse/tratamento farmacológico , Humanos , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários
13.
Comput Methods Programs Biomed ; 210: 106395, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34525412

RESUMO

BACKGROUND AND OBJECTIVE: Chronic cough (CC) affects approximately 10% of adults. Many disease states are associated with chronic cough, such as asthma, upper airway cough syndrome, bronchitis, and gastroesophageal reflux disease. The lack of an ICD code specific for chronic cough makes it challenging to identify such patients from electronic health records (EHRs). For clinical and research purposes, computational methods using EHR data are urgently needed to identify chronic cough cases. This research aims to investigate the data representations and deep learning algorithms for chronic cough prediction. METHODS: Utilizing real-world EHR data from a large academic healthcare system from October 2005 to September 2015, we investigated Natural Language Representation of the EHR data and systematically evaluated deep learning and traditional machine learning models to predict chronic cough patients. We built these machine learning models using structured data (medication and diagnosis) and unstructured data (clinical notes). RESULTS: The sensitivity and specificity of a transformer-based deep learning algorithm, specifically BERT with attention model, was 0.856 and 0.866, respectively, using structured data (medication and diagnosis). Sensitivity and specificity improved to 0.952 and 0.930 when we combined structured data with symptoms extracted from clinical notes. We further found that the attention mechanism of deep learning models can be used to extract important features that drive the prediction decisions. Compared with our previously published rule-based algorithm, the deep learning algorithm can identify more chronic cough patients with structured data. CONCLUSIONS: By applying deep learning models, chronic cough patients can be reliably identified for prospective or retrospective research through medication and diagnosis data, widely available in EHR and electronic claims data, thus improving the generalizability of the patient identification algorithm. Deep learning models can identify chronic cough patients with even higher sensitivity and specificity when structured and unstructured EHR data are utilized. We anticipate language-based data representation and deep learning models developed in this research could also be productively used for other disease prediction and case identification.


Assuntos
Aprendizado Profundo , Adulto , Algoritmos , Tosse/diagnóstico , Registros Eletrônicos de Saúde , Humanos , Aprendizado de Máquina , Estudos Prospectivos , Estudos Retrospectivos
14.
ERJ Open Res ; 6(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33263037

RESUMO

BACKGROUND: We present study designs, dose selection and preliminary patient characteristics from two phase 3 clinical trials of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough (RCC) or unexplained chronic cough (UCC). METHODS: COUGH-1 (NCT03449134) and COUGH-2 (NCT03449147) are randomised, placebo-controlled, double-blind, parallel-group trials in subjects with RCC or UCC (age ≥18 years; cough duration ≥1 year; Cough Severity Visual Analogue Scale score ≥40 mm). The primary efficacy study periods are 12 weeks (40-week extension; COUGH-1) and 24 weeks (28-week extension; COUGH-2). Interventions include placebo, gefapixant 15 mg and gefapixant 45 mg (1:1:1 ratio). The primary efficacy endpoints are average 24-h cough frequency at Week 12 (COUGH-1) and Week 24 (COUGH-2). Awake cough frequency, patient-reported outcomes and responder analyses are secondary endpoints. RESULTS: The doses of 45 mg (to provide maximal efficacy and acceptable tolerability) and 15 mg (to provide acceptable efficacy and improved tolerability) were selected based on phase 1 and 2 studies. In COUGH-1, 730 participants have been randomised and treated; 74% are female with mean age of 59 years (39% over 65 years), and mean baseline duration of cough of 11.5 years. In COUGH-2, 1314 participants have been randomised and treated; 75% are female with mean age of 58 years (33% over 65 years), and mean baseline duration of cough of 11.1 years. CONCLUSIONS: These global studies include participants with baseline characteristics consistent with previous RCC and UCC studies and will inform the efficacy and safety profile of gefapixant in the treatment of patients with RCC and UCC.

15.
J Food Prot ; 72(10): 2217-20, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19833050

RESUMO

A microbiological study of saffron spice was undertaken in the context of a European research project (Methodologies for Implementing International Standards for Saffron Purity and Quality, the acronym for which is SAFFIC), analyzing 79 samples obtained from the main producer countries, namely Greece, Iran, Italy, Morocco, and Spain. Current microbiological quality criteria are the same as for other spices, but saffron is added in minute quantities during the cooking process, so the health risk associated with microbial contamination might be lower. We did not detect Salmonella either by culture or by PCR methods in any sample, and Escherichia coli was only found in five samples. Enterobacteriaceae were frequently found (70.9% of the samples), but most of them belonged to species of probable environmental origin. Aerobic sporulated bacteria were also common, but only three samples contained Bacillus cereus at low levels (<200 CFU g(-1)). Clostridium perfringens counts were also very low, with only one sample reaching >100 CFU g(-1), an acceptable value. Overall, microbial contamination in saffron was markedly lower than it was in other spices.


Assuntos
Qualidade de Produtos para o Consumidor , Crocus/microbiologia , Contaminação de Alimentos/análise , Controle de Qualidade , Clostridium perfringens/isolamento & purificação , Contagem de Colônia Microbiana , Enterobacteriaceae/isolamento & purificação , Escherichia coli/isolamento & purificação , Manipulação de Alimentos/métodos , Humanos , Salmonella/isolamento & purificação
16.
Span J Psychol ; 20: E3, 2017 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-28102117

RESUMO

In the current socioeconomic situation, the need to improve employability of potential workers is especially relevant. The aim of this study was to evaluate the efficacy of an intervention program focusing on improving employability of university students. To do this, a two-group study was designed: one group undertook the intervention program and the other group were used for comparison. Two measurements were taken at different times (pre-intervention and post-intervention). The sample consisted of 271 university students. The results show that the group that underwent the intervention program improved their perceived employability F(1, 269) = 17.49, p < .001; η2 = .06, openness to learning F(1, 269) = 4.24, p < .05; η2 = .02, self-efficacy for labor market insertion F(1, 269) = 75.70, p < .001; η2 = .22 and for teamwork F(1, 269) = 39.43, p < .001; η2 = .13, and their knowledge of employment resources F(1, 269) = 512.89, p < .001; η2 = .66 compared to the group that did not. Furthermore, there was a high level of satisfaction of participants with the intervention program.


Assuntos
Comportamento Cooperativo , Emprego/psicologia , Aprendizagem , Autoeficácia , Estudantes/psicologia , Adulto , Feminino , Humanos , Masculino , Avaliação de Programas e Projetos de Saúde , Universidades , Adulto Jovem
17.
Medisan ; 25(2)mar.-abr. 2021. tab
Artigo em Espanhol | LILACS, CUMED | ID: biblio-1250339

RESUMO

Introducción: La discromía dental es una afectación estética, de causa multifactorial, caracterizada por el cambio de coloración de uno o varios dientes. Objetivo: Evaluar la efectividad de la terapia láser como fuente de luz y calor en pacientes con discromías dentales. Método: Se realizó un estudio cuasi experimental, de intervención terapéutica, en 24 pacientes con discromías dentales atendidos en la Clínica Estomatológica Provincial DocenteMártires del Moncada de Santiago de Cuba, desde julio de 2017 hasta julio de 2018. Los integrantes del estudio se asignaron de forma aleatoria a 2 grupos de tratamiento:a los pares (grupo de estudio) se les aplicó láser combinado con la técnica convencional de peróxido de hidrógeno;a los impares (grupo control), tratamiento convencional solamente.Se utilizaron las frecuencias absoluta y relativa como medidas de resumen, así como la prueba de X 2 de homogeneidad para la validación estadística, con un nivel de significación de 0,05. Resultados: Para los pacientes del grupo de estudio, la segunda y tercera sesiones fueron más efectivas. Al culminar el tratamiento, ambos resultaron efectivos, pero los que recibieron láser evolucionaron más rápidamente que los tratados solo con peróxido de hidrógeno. Conclusiones: El uso de la terapia láser y peróxido de hidrógeno fue efectivo en pacientes con discromías dentales y demostró que no provoca efectos adversos en los dientes tratados.


Introduction: The dental dischromya is an esthetic disorder, of multifactorial cause, characterized by the change of coloration of one or several teeth. Objective: To evaluate the effectiveness of laser therapy as a source of light and heat in patients with dental dischromya. Method: A quasi-experiment, of therapeutic intervention study, was carried out in 24 patients with dental dischromya assisted in Mártires del Moncada Teaching Provincial Stomatological Clinic in Santiago de Cuba, from July, 2017 to March, 2018. The members of the study were assigned at random with 2 treatment groups: a study group (pairs) to whom laser combined with the conventional technique of peroxide of hydrogen was applied; to odd number patients (control group), conventional treatment only. The absolute and relative frequencies were used as summary measures, as well as the chi-square test of homogeneity for the statistical validation, with a level of significance of 0.05. Results: For the patients of the study group, the second and third sessions were more effective. When culminating the treatment, both were effective, but those that received laser evolved more quickly than those treated with peroxide of hydrogen. Conclusions: The use of the laser therapy and peroxide of hydrogen was effective in patients with dental dischromya and it was demonstrated that doesn't cause adverse effects in the treated teeth.


Assuntos
Descoloração de Dente/terapia , Terapia a Laser , Clareamento Dental/métodos , Peróxido de Hidrogênio/uso terapêutico
18.
Hum Mutat ; 22(2): 179-80, 2003 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12872266

RESUMO

In the present study the entire NF1 coding region was analyzed for mutations in 132 unrelated Italian NF1 patients. Using PTT, SSCP, and DNA sequencing, we found 8 novel mutations. Clinical diagnosis of NF1 was established according to the NIH consensus criteria. We detected 59 truncated fragments, and 46 of them were characterized by SSCP and direct sequencing. Eight mutations represent novel changes that contribute to the germline mutational spectrum of the NF1 gene. In two patients, premature termination was due to substitutions at nucleotide c.3982C>T (Q1298X) and c.7411C>T (Q2471X), respectively. Two other mutations were caused by the deletions (1756delA, 4699delA), and two by the insertions (c.5266_5267insT, c.7464_7465insTCCA) of a small number of nucleotides. Lastly, we found 2 splice-site mutations (c.2252-2A>C, c.2251+1G>A).


Assuntos
Genes da Neurofibromatose 1 , Mutação/genética , Neurofibromatose 1/genética , Análise Mutacional de DNA , Mutação da Fase de Leitura/genética , Humanos , Itália , Mutagênese Insercional/genética , Deleção de Sequência/genética
19.
Hum Mutat ; 20(1): 74-5, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12112660

RESUMO

The entire NF1 coding region was analyzed for mutations in a panel of 108 unrelated Italian NF1 patients. Using PTT, SSCP, and DNA sequencing, we found 10 mutations which have never been reported before. Clinical diagnosis of NF1 was established according to the NIH consensus criteria in 100 individuals, while 8 were young children with only multiple cafè-au-lait spots. We detected 46 truncated fragments, and 24 of them were fully characterized by SSCP and direct sequencing. Of the 24, 14 were known mutations (R304X, R681X, Q682X, R1306X, R1362X, R1513X, R1748X, Q1794X, R1947X, Y2264X, R2237X, 2674delA, 6789delTTAC, 2027insC). The other 10 mutations represent novel changes that contribute to the germline mutational spectrum of the NF1 gene (K810X, Q2595X, 6772delT, 7190delCT, 7331delA, 1021insTT, 3921insT, 4106insTA, 7149insC, 2033insCG / 2034delA). PTT in a large number of Italian NF1 patients supports the usefulness of this method for characterization of mutations in disorders where the responsible gene is very large and the disease-causing mutations often create a stop codon. In agreement with previous reports, no mutational hotspots within the NF1 gene were detected.


Assuntos
Neurofibromatose 1/genética , Neurofibromina 1/genética , Sequência de Bases , Análise Mutacional de DNA , DNA de Neoplasias/química , DNA de Neoplasias/genética , Humanos , Itália , Mutação , Neurofibromatose 1/patologia , Polimorfismo Conformacional de Fita Simples , Biossíntese de Proteínas , RNA Neoplásico/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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