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1.
JAMA Netw Open ; 3(5): e205435, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32442291

RESUMO

Importance: Information to be included in advance informed consent forms for health care-associated pneumonia treatment trials remains to be determined. Objective: To identify and determine how to describe information to be included in an advance informed consent form for an early-enrollment noninferiority hospital-acquired and/or ventilator-associated bacterial pneumonia (HABP/VABP) clinical trial. Design, Setting, and Participants: A Delphi consensus process with stakeholders in HABP/VABP clinical trials was conducted using qualitative semistructured telephone interviews from June to August 2016, followed by 2 online surveys, the first from April to May 2017, and the second from September to October 2017. All stakeholders who participated in the interview were invited to participate in the first survey. Stakeholders who participated in the first survey were invited to participate in the second survey. Stakeholders were patients at risk of pneumonia, caregivers, representatives of institutional review boards, investigators, and study coordinators. Main Outcomes and Measures: Description and consensus of information to be included in advance informed consent forms for early enrollment in noninferiority HABP/VABP clinical trials. Results: Suggestions from 52 stakeholders about what key informed consent concepts to include and how to explain them were used to create 3 categories to be included in an advance consent form: (1) reassurances on patient health and treatment, (2) rationale for advance consent and early enrollment, and (3) an explanation of noninferiority. At the end of the Delphi process, at least 80% consensus was reached among the 40 stakeholders who participated in the second online survey on each of the statements to include in the proposed consent text. Throughout the process, however, describing and reaching consensus on statements about noninferiority was more problematic than the other categories. Conclusions and Relevance: The stakeholders endorsed consent language to be used in combination with a strategy for enrolling patients at highest risk for pneumonia before infection onset. Data-driven consent language may help potential participants make informed decisions about their involvement in clinical research and improve enrollment rates, which are necessary to evaluate new treatments and improve patient care. The proposed consent language may be adapted for other trials using an early enrollment strategy and for noninferiority trials.

2.
Value Health ; 23(2): 227-235, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32113628

RESUMO

OBJECTIVES: There are no approved vaccines for respiratory syncytial virus (RSV), and consensus on methods to assess RSV vaccine efficacy has not been established. In this study of an adjuvanted RSV vaccine, we evaluated an RSV disease endpoint using a patient-reported outcome instrument (the inFLUenza Patient-Reported Outcome instrument [FLU-PRO]) and molecular testing for virologic confirmation. METHODS: In a randomized, blinded efficacy study (NCT02508194), 1900 adult participants aged ≥60 years who had any respiratory symptom lasting ≥24 hours recorded symptoms in a FLU-PRO-based workbook for 21 days, self-collected nasal swabs on illness days 2 to 4, and had a site-collected swab obtained on (approximately) day 4. The endpoint, acute RSV-associated respiratory illness (ARA-RI), required specific symptoms with virologic confirmation. RESULTS: The FLU-PRO demonstrated reliability, ability to detect change, and validity and had high participant adherence and acceptable patient burden in the setting of an RSV prevention trial. The ARA-RI endpoint definition captured all 33 virologically confirmed RSV illnesses for which symptom data were provided, and in 32 of these, at least 1 lower respiratory symptom was reported. Sensitivity analysis with an endpoint requiring ≥2 lower respiratory symptoms captured greater symptom severity but fewer cases. Results of self- and site-collected swabs were highly correlated. Self-swabbing detected 9 additional cases that would have been missed by site swabbing only. CONCLUSIONS: These results demonstrated the reliability and validity of the ARA-RI definition and of the FLU-PRO for use in RSV studies. Self-swabbing improved RSV detection.

3.
Clin Infect Dis ; 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32107536

RESUMO

BACKGROUND: Ceftazidime-avibactam has in vitro activity against some carbapenem-resistant gram-negative infections (GNIs), and therefore may be a useful alternative to more toxic antibiotics such as colistin. Understanding ceftazidime-avibactam uptake and usage patterns would inform hospital formularies, stewardship, and antibiotic development. METHODS: A retrospective cohort study assessed inpatient encounters in the Vizient database. Ceftazidime-avibactam and colistin administrations were categorized into presumed empiric (3 consecutive days of therapy or less with qualifying exclusions) versus targeted therapy (≥4 consecutive days of therapy) for presumed carbapenem-resistant GNIs. Quarterly percentage change (QPC) using modified Poisson regression and relative change in frequency of targeted ceftazidime-avibactam to colistin encounters was calculated. Factors associated with preferentially receiving targeted ceftazidime-avibactam versus colistin were identified using generalized estimating equations. RESULTS: Between 2015 quarter (q) 1 and 2017q4, ceftazidime-avibactam was administered 21 215 times across 1901 encounters. Inpatient prescriptions for ceftazidime-avibactam increased from 0.44/10 000 hospitalizations in 2015q1 to 7.7/10 000 in 2017q4 (QPC, +11%; 95% CI, 10-13%; P < .01), while conversely colistin prescriptions decreased quarterly by 5% (95% CI, 4-6%; P < .01). Ceftazidime-avibactam therapy was categorized as empiric 25% of the time, targeted 65% of the time, and indeterminate 10% of the time. Patients with chronic kidney disease were twice as likely to receive targeted ceftazidime-avibactam versus colistin (RR, 2.02; 95% CI, 1.82-2.25), whereas those on dialysis were less likely to receive ceftazidime-avibactam than colistin (RR, 0.71; 95% CI, .61-.83). CONCLUSIONS: Since approval in 2015, ceftazidime-avibactam use has grown for presumed carbapenem-resistant GNIs, while colistin has correspondingly declined. Renal function drove the choice between ceftazidime-avibactam and colistin as targeted therapy.

5.
Open Forum Infect Dis ; 6(11): ofz424, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31696140

RESUMO

Background: Molecular detection methods allow for the simultaneous detection of several infectious agents. This study assesses whether co-infection with 2 viruses as compared with 1 is associated with increased hospitalization in those with acute respiratory infections. Methods: We prospectively enrolled a cohort of pediatric and adult participants with influenza-like illness during 2010-2014 in Mexico. Clinical information and respiratory samples were collected at enrollment. Respiratory viruses were detected with multiplex polymerase chain reaction (PCR) and influenza-specific reverse transcription PCR assays. Participants were followed for 14 and 28 days after inclusion. Severity of disease, as measured by hospitalization with acute respiratory infections, was compared between single and dual viral infections. Results: Among 5662 participants in the study, either 1 (n = 3285) or 2 (n = 641) viruses were detected in 3926 participants. Rhinovirus (n = 1433), influenza (n = 888), and coronaviruses (n = 703) were the most frequently detected viruses (either alone or in co-infection). Bocavirus, respiratory syncytial virus (RSV), metapneumovirus, and rhinovirus cases were hospitalized more often than other viruses. Bocavirus+rhinovirus cases were hospitalized more often than those with rhinovirus alone (but not bocavirus alone). RSV cases were more likely to be hospitalized than cases with co-infections of RSV and parainfluenza virus or coronavirus. Metapneumovirus cases were hospitalized more often than those co-infected with metapneumovirus+coronavirus. Conclusions: In this study, detection of 2 viruses did not significantly increase hospitalizations compared with single virus infections. Larger studies will allow for distinguishing between sequential and simultaneous infection and for a better understanding of the role of each virus during the evolution of acute respiratory episodes.

6.
Orphanet J Rare Dis ; 14(1): 243, 2019 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-31699126

RESUMO

BACKGROUND: Barth syndrome (BTHS, OMIM 302060) is a rare, life-threatening, x-linked genetic disorder that occurs almost exclusively in males and is characterized by cardiomyopathy, neutropenia, skeletal muscle myopathy primarily affecting larger muscles, and shorter stature in youth. A greater number of individuals with BTHS are now surviving into adulthood due to advancements in diagnosis and disease management. Given these improvements in life expectancy, understanding the disease experience over time has become increasingly important to individuals with the condition, treatment developers, and regulatory agencies. A study was conducted to explore the experience of BTHS from the perspective of adult males at least 35 years of age with the condition via in-depth qualitative interviews. RESULTS: Findings showed that adults with BTHS experienced a variety of signs/symptoms with variable onset and severity throughout their lives, the most frequently reported being the symptoms of tiredness, muscle weakness, and a fast and/or irregular heart rate, and the sign of short stature in youth. These signs/symptoms negatively impacted individuals' emotional, physical, social, and role functioning. Tiredness and weakness impacted some individuals' physical functioning from an early age and into adulthood. These symptoms generally worsened over time, increasingly interfering with individuals' ability to fully participate in paid and unpaid labor and to partake in family and leisure activities. CONCLUSIONS: This research complements recent studies characterizing the potentially degenerative and progressive nature of BTHS and can encourage future research into the natural history and progression of BTHS in untreated individuals. Participants' interview responses revealed a range of symptoms and the potential for multiple impacts on individuals' physical, social, emotional, and role functioning as a result of BTHS symptoms, yet also revealed variability in severity of experience as well as the possibility of resilience and adaptation to the condition.

7.
JAMA Intern Med ; 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31710344

RESUMO

Importance: Regulatory and scientific guidelines stipulate that indirect, surrogate measures of patient benefit, such as a change in microbial culture status, should be used as primary end points only in pivotal trials of chronic conditions that are serious or life threatening and when the experimental therapy is expected to offer substantial benefit compared with available therapy. However, many recent US Food and Drug Administration (FDA) anti-infective drug approvals for acute and/or non-life-threatening diseases have been based on pivotal trials using surrogate measures as primary end points rather than clinical outcomes, such as symptom resolution or survival. Objectives: To review FDA recommendations for primary end points in pivotal trials of new anti-infective drugs and assess the concordance of those recommendations with the regulatory and scientific conditions for the appropriate use of surrogate measures as primary trial outcomes. Evidence Review: All guidance documents for antimicrobial drug development hosted on the FDA website were searched in November 2017; the search was updated in June 2018. For each document, 2 reviewers independently extracted data on the recommended primary end points for a pivotal or phase 3 trial. Findings: Twenty-two FDA guidance documents met the inclusion criteria, which included recommendations for primary end points in pivotal clinical trials in 27 infectious disease indications. Twenty-one of 27 indications recommended surrogate outcomes as either the sole primary end point or as components of composite end points. None of the recommendations for the use of surrogate measures matched the regulatory and scientific conditions favoring indirect outcomes in place of clinical outcomes. Conclusions and Relevance: The FDA guidance documents for developing new anti-infective agents frequently recommend indirect measures of patient benefit, rather than direct measures of patient benefit, as sole primary end points or components of primary end points. Existing guidance documents should be updated and revised to recommend appropriate clinical outcomes consistent with general scientific and regulatory parameters.

8.
Contemp Clin Trials Commun ; 15: 100401, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31312748

RESUMO

Background/aims: The Food and Drug Administration recommends research into developing well-defined and reliable endpoints to evaluate treatments for severe influenza requiring hospitalization. A novel 6-category ordinal endpoint of patient health status after 7 days that ranges from death to hospital discharge with resumption of normal activities is being used in a randomized placebo-controlled trial of intravenous immunoglobulin (IVIG) for severe influenza (FLU-IVIG). We compare the power of the ordinal endpoint under a proportional odds model to other types of endpoints as a function of various trial parameters. Methods: We used closed-form analysis and empirical simulation to compare the power of the ordinal endpoint to time-to-event, longitudinal, and binary endpoints. In the simulation setting, we varied the treatment effect and the distribution of the placebo group across the follow-up period with consideration of adjustment for baseline health status. Results: In the analytic setting, ordinal endpoints of high granularity provided greater power than time-to-event endpoints when most patients in the placebo group had either naturally progressed to the category of hospital discharge by day 7 or were far from hospital discharge on day 7. In the simulation setting, adjustment for baseline health status universally raised power for the proportional odds model. Across different placebo group distributions of the ordinal endpoint regardless of adjustment for baseline health status, only time-to-event endpoints yielded higher power than the ordinal endpoint for certain treatment effects. Conclusions: In this case study, the FLU-IVIG ordinal endpoint provided greater power than time-to-event, binary, and longitudinal endpoints for most scenarios of the treatment effect and placebo group distribution, including the target population studied for FLU-IVIG. The ordinal endpoint was only surpassed by the time-to-event endpoint when many patients in the placebo group were on the cusp of hospital discharge on day 7 and the follow-up period for the time-to-event endpoint was extended to allow for additional events. Our general approach for evaluating the power of several potential endpoints for an influenza trial can be used for designing other influenza trials with different target populations and for other trials in other disease areas.

9.
Open Forum Infect Dis ; 6(4): ofz110, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31240236

RESUMO

Difficult-to-treat resistance (DTR; ie, co-resistance to all first-line antibiotics) in gram-negative bloodstream infection (GNBSI) is associated with decreased survival in administrative data models. We externally validated DTR prevalence and associated mortality risk in GNBSI using detailed clinical data from electronic health records to adjust for baseline differences in acute illness severity.

11.
Chest ; 155(6): 1109-1118, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30772386

RESUMO

BACKGROUND: Procalcitonin (PCT)-guided antibiotic discontinuation appears to decrease antibiotic use in critically ill patients, but its impact on survival remains less certain. METHODS: We searched PubMed, Embase, Scopus, Web of Science, and CENTRAL for randomized controlled trials (RCTs) of PCT-guided antibiotic discontinuation in critically ill adults reporting survival or antibiotic duration. Searches were conducted without language restrictions from inception to July 23, 2018. Two reviewers independently conducted all review stages; another adjudicated differences. Data were pooled using random-effects meta-analysis. Study quality was assessed with the Cochrane risk of bias tool, and evidence was graded using GRADEpro. RESULTS: Among critically ill adults (5,158 randomized; 5,000 analyzed), PCT-guided antibiotic discontinuation was associated with decreased mortality (16 RCTs; risk ratio [RR], 0.89; 95% CI, 0.83-0.97; I2 = 0%; low certainty). Death was the primary outcome in only one study and a survival benefit was not observed in the subset specified as sepsis (10 RCTs; RR, 0.94; 95% CI, 0.85-1.03; I2 = 0%), those without industry sponsorship (nine RCTs; RR, 0.98; 95% CI, 0.87-1.10; I2 = 0%), high PCT-guided algorithm adherence (five RCTs; RR, 0.93; 95% CI, 0.71-1.22; I2 = 0%), and PCT-guided algorithms without C-reactive protein (eight RCTs; RR, 0.96; 95% CI, 0.87-1.06; I2 = 0%). PCT-guided antibiotic discontinuation decreased antibiotic duration (mean difference, 1.31 days; 95% CI, -2.27 to -0.35; I2 = 93%) (low certainty). CONCLUSIONS: Our findings of increased survival and decreased antibiotic utilization associated with PCT-guided antibiotic discontinuation represent low-certainty evidence with a high risk of bias. This relationship was primarily observed in studies without high protocol adherence and in studies with algorithms combining PCT and C-reactive protein. Properly designed studies with mortality as the primary outcome are needed to address this question. TRIAL REGISTRY: International Prospective Register of Systematic Reviews (PROSPERO); No.: CRD42016049715; URL: http://www.crd.york.ac.uk/PROSPERO_REBRANDING/display_record.asp?ID=CRD42016049715.

12.
J Infect Dis ; 219(10): 1536-1544, 2019 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-30649434

RESUMO

BACKGROUND: The US Food and Drug Administration solicited evidence-based recommendations to improve guidance for studies of hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP). METHODS: We analyzed 7 HABP/VABP datasets to explore novel noninferiority study endpoints and designs, focusing on alternatives to all-cause mortality (ACM). RESULTS: ACM at day 28 differed for ventilated HABP (27.8%), VABP (18.0%), and nonventilated HABP (14.5%). A "mortality-plus" (ACM+) composite endpoint was constructed by combining ACM with patient-relevant, infection-related adverse events from the Medical Dictionary for Regulatory Activities toxic/septic shock standardized query. The ACM+ rate was 3-10 percentage points above that of ACM across the studies and treatment groups. Predictors of higher ACM/ACM+ rates included older age and elevated acute physiology and chronic health evaluation (APACHE) II score. Only patients in the nonventilated HABP group were able to report pneumonia symptom changes. CONCLUSIONS: If disease groups and patient characteristics in future studies produce an ACM rate so low (<10%-15%) that a fixed noninferiority margin of 10% cannot be justified (requiring an odds ratio analysis), an ACM+ endpoint could lower sample size. Enrichment of studies with patients with a higher severity of illness would increase ACM. Data on symptom resolution in nonventilated HABP support development of a patient-reported outcome instrument.


Assuntos
Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Associada à Ventilação Mecânica/tratamento farmacológico , Projetos de Pesquisa , Resultado do Tratamento , APACHE , Fatores Etários , Antibacterianos/uso terapêutico , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Mortalidade
13.
BMC Infect Dis ; 18(1): 353, 2018 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-30055573

RESUMO

BACKGROUND: In clinical studies involving a healthy volunteer human challenge model, a valid and reliable measure to assess the evolution of patient-reported symptom type and severity following viral exposure is necessary. This study examines the use of the InFLUenza Patient-Reported Outcome (FLU-PRO) diary as a standardized measure of symptom severity in a healthy volunteer human challenge model. METHODS: Healthy adults admitted to the NIH Clinical Center (Day - 1) underwent a 9-day inpatient quarantine after intranasal challenge with a wild-type influenza A/H1N1pdm virus (Day 0). Participants completed the 32-item FLU-PRO diary twice daily for 14 days to assess presence, severity, and duration of symptoms across six body systems. Secondary analyses included descriptive statistics to examine FLU-PRO scores over the course of illness and analysis of variance to compare scores on Day 3 post-challenge by presence of viral shedding, and pre-challenge hemagglutinin and neuraminidase inhibition (HAI and NAI) titers. RESULTS: All but one subject (99%), who was lost to follow-up, completed twice daily FLU-PRO diaries on all study assessment days. FLU-PRO demonstrated that 61 of 65 subjects reported symptoms (Days: Median 5, Mean 6 ± 7), of whom 37 (61%) had viral shedding. Pre-challenge, 39 (64%) and 10 (16%) subjects had low (< 1:40) HAI and NAI titers, respectively. Nose, throat, body, and gastrointestinal (GI) symptoms reached peak intensity at Day 3, followed by chest/respiratory and eye symptoms at Day 4. Subjects with viral shedding had higher mean FLU-PRO scores compared to those without, except for Eye and GI domains (p <0.05). Mean FLU-PRO scores were significantly higher for subjects with low NAI titer (p <0.05) across all domains. No significant differences were observed between HAI titer groups. FLU-PRO scores of the low HAI-low NAI group (n = 10) were significantly higher (more severe) than the other two groups (p < 0.05) (high HAI-high NAI (n = 22), low HAI-high NAI (n = 29)). CONCLUSIONS: The FLU-PRO had high adherence and low respondent burden. It can be used to track symptom onset, intensity, duration, and recovery from influenza infection in clinical research. In this human challenge study, scores were responsive to change and distinguished known clinical subgroups. TRIAL REGISTRATION: NCT01971255 First Registered October 2, 2013.


Assuntos
Voluntários Saudáveis , Influenza Humana , Registros Médicos , Modelos Biológicos , Medidas de Resultados Relatados pelo Paciente , Adolescente , Adulto , Feminino , Experimentação Humana , Humanos , Vírus da Influenza A/fisiologia , Influenza Humana/diagnóstico , Influenza Humana/patologia , Influenza Humana/virologia , Masculino , Orthomyxoviridae/fisiologia , Inquéritos e Questionários , Eliminação de Partículas Virais , Adulto Jovem
14.
Clin Infect Dis ; 67(12): 1803-1814, 2018 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-30052813

RESUMO

Background: Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for ≥1 active first-line antibiotic. Methods: The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ß-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to ≥1 first-line agent, and graded loss of active categories. Results: Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0. Conclusion: Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/epidemiologia , Farmacorresistência Bacteriana Múltipla , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/mortalidade , Adolescente , Adulto , Idoso , Bacteriemia/tratamento farmacológico , Carbapenêmicos/uso terapêutico , Bases de Dados Factuais , Feminino , Fluoroquinolonas/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Hospitais , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
15.
Open Forum Infect Dis ; 5(3): ofy038, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29564363

RESUMO

We present a case of acute epiglottitis in a 16-year-old with severe aplastic anemia. He was admitted with a history suggestive of a severe upper airway infection and an absolute neutrophil count of 0 per cubic millimeter. Despite his immunocompromised state, he presented with the classical signs and symptoms of epiglottitis. We review here the presentation and comorbidities of immunocompromised patients with epiglottitis. In addition, the appropriate choice of empirical antibiotic therapy is important for the management of epiglottitis in immunocompromised patients, especially in the post-Haemophilus influenza type B vaccination era. In our patient, Enterobacter cloacae was isolated from endoscopically directed throat cultures, and treatment was successful without the need for intubation. The current literature suggests that in immunocompromised patients, particularly those who are neutropenic, there is a potentially wide range of organisms, both bacterial and fungal, that may play a role in the pathology of acute epiglottitis.

16.
PLoS One ; 13(3): e0194180, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29566007

RESUMO

BACKGROUND: The inFLUenza Patient Reported Outcome (FLU-PRO) measure is a daily diary assessing signs/symptoms of influenza across six body systems: Nose, Throat, Eyes, Chest/Respiratory, Gastrointestinal, Body/Systemic, developed and tested in adults with influenza. OBJECTIVES: This study tested the reliability, validity, and responsiveness of FLU-PRO scores in adults with influenza-like illness (ILI). METHODS: Data from the prospective, observational study used to develop and test the FLU-PRO in influenza virus positive patients were analyzed. Adults (≥18 years) presenting with influenza symptoms in outpatient settings in the US, UK, Mexico, and South America were enrolled, tested for influenza virus, and asked to complete the 37-item draft FLU-PRO daily for up to 14-days. Analyses were performed on data from patients testing negative. Reliability of the final, 32-item FLU-PRO was estimated using Cronbach's alpha (α; Day 1) and intraclass correlation coefficients (ICC; 2-day reproducibility). Convergent and known-groups validity were assessed using patient global assessments of influenza severity (PGA). Patient report of return to usual health was used to assess responsiveness (Day 1-7). RESULTS: The analytical sample included 220 ILI patients (mean age = 39.3, 64.1% female, 88.6% white). Sixty-one (28%) were hospitalized at some point in their illness. Internal consistency reliability (α) of FLU-PRO Total score was 0.90 and ranged from 0.72-0.86 for domain scores. Reproducibility (Day 1-2) was 0.64 for Total, ranging from 0.46-0.78 for domain scores. Day 1 FLU-PRO scores correlated (≥0.30) with the PGA (except Gastrointestinal) and were significantly different across PGA severity groups (Total: F = 81.7, p<0.001; subscales: F = 6.9-62.2; p<0.01). Mean score improvements Day 1-7 were significantly greater in patients reporting return to usual health compared with those who did not (p<0.05, Total and subscales, except Gastrointestinal and Eyes). CONCLUSIONS: Results suggest FLU-PRO scores are reliable, valid, and responsive in adults with influenza-like illness.


Assuntos
Influenza Humana/patologia , Influenza Humana/fisiopatologia , Registros Médicos , Autorrelato , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
17.
Value Health ; 21(2): 210-218, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29477403

RESUMO

OBJECTIVES: To assess the reliability, validity, and responsiveness of InFLUenza Patient-Reported Outcome (FLU-PRO©) scores for quantifying the presence and severity of influenza symptoms. METHODS: An observational prospective cohort study of adults (≥18 years) with influenza-like illness in the United States, the United Kingdom, Mexico, and South America was conducted. Participants completed the 37-item draft FLU-PRO daily for up to 14 days. Item-level and factor analyses were used to remove items and determine factor structure. Reliability of the final tool was estimated using Cronbach α and intraclass correlation coefficients (2-day reliability). Convergent and known-groups validity and responsiveness were assessed using global assessments of influenza severity and return to usual health. RESULTS: Of the 536 patients enrolled, 221 influenza-positive subjects comprised the analytical sample. The mean age of the patients was 40.7 years, 60.2% were women, and 59.7% were white. The final 32-item measure has six factors/domains (nose, throat, eyes, chest/respiratory, gastrointestinal, and body/systemic), with a higher order factor representing symptom severity overall (comparative fit index = 0.92; root mean square error of approximation = 0.06). Cronbach α was high (total = 0.92; domain range = 0.71-0.87); test-retest reliability (intraclass correlation coefficient, day 1-day 2) was 0.83 for total scores and 0.57 to 0.79 for domains. Day 1 FLU-PRO domain and total scores were moderately to highly correlated (≥0.30) with Patient Global Rating of Flu Severity (except nose and throat). Consistent with known-groups validity, scores differentiated severity groups on the basis of global rating (total: F = 57.2, P < 0.001; domains: F = 8.9-67.5, P < 0.001). Subjects reporting return to usual health showed significantly greater (P < 0.05) FLU-PRO score improvement by day 7 than did those who did not, suggesting score responsiveness. CONCLUSIONS: Results suggest that FLU-PRO scores are reliable, valid, and responsive to change in influenza-positive adults.


Assuntos
Influenza Humana/fisiopatologia , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , Adulto , Análise Fatorial , Feminino , Humanos , Influenza Humana/epidemiologia , Masculino , Estudos Prospectivos , Psicometria , Reprodutibilidade dos Testes , Estados Unidos/epidemiologia
20.
N Engl J Med ; 378(3): 304, 2018 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-29345881
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