RESUMO
OBJECTIVE: High tidal volume ventilation is associated with ventilator-induced lung injury. Early introduction of lung protective ventilation improves patient outcomes. This study describes ventilator management during critical care transport and the association between transport ventilator settings and ventilator settings in the intensive care unit (ICU). METHODS: This was a retrospective review of mechanically ventilated adult patients transported to an academic medical center via a critical care transport program between January 2018 and April 2019. Ventilator settings during transport were compared with the initial and 6- and 12-hour postadmission ventilator settings. RESULTS: Three hundred eighty patients were identified; 114 (30%) received tidal volumes > 8 mL/kg predicted body weight at the time of transfer. The transport handoff tidal volume strongly correlated with the ICU tidal volume (Pearson r = 0.7). Patients receiving high tidal volumes during transport were more likely to receive high tidal volumes initially upon transfer (relative risk [RR] = 4.6; 95% confidence interval [CI], 3.3-6.5) and at 6 and 12 hours after admission (RR = 2.6; 95% CI, 1.8-3.8 and RR = 2.7; 95% CI, 1.7-4.3, respectively). CONCLUSION: Exposure to high tidal volumes during transport is associated with high tidal volume ventilation in the ICU, even up to 12 hours after admission. This study identifies opportunities for improving patient care through the application of lung protective ventilation strategies during transport.
Assuntos
Síndrome do Desconforto Respiratório , Adulto , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva , Respiração Artificial , Volume de Ventilação Pulmonar , Ventiladores MecânicosRESUMO
Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental and neuropsychiatric disorders characterized by deficits in verbal communication, impairment of social interaction, and restricted and repetitive patterns of interests and behaviour. To identify common genetic risk factors underlying ASDs, here we present the results of genome-wide association studies on a cohort of 780 families (3,101 subjects) with affected children, and a second cohort of 1,204 affected subjects and 6,491 control subjects, all of whom were of European ancestry. Six single nucleotide polymorphisms between cadherin 10 (CDH10) and cadherin 9 (CDH9)-two genes encoding neuronal cell-adhesion molecules-revealed strong association signals, with the most significant SNP being rs4307059 (P = 3.4 x 10(-8), odds ratio = 1.19). These signals were replicated in two independent cohorts, with combined P values ranging from 7.4 x 10(-8) to 2.1 x 10(-10). Our results implicate neuronal cell-adhesion molecules in the pathogenesis of ASDs, and represent, to our knowledge, the first demonstration of genome-wide significant association of common variants with susceptibility to ASDs.
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Transtorno Autístico/genética , Cromossomos Humanos Par 5/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Encéfalo/metabolismo , Caderinas/genética , Estudos de Casos e Controles , Adesão Celular/genética , Moléculas de Adesão Celular Neuronais/genética , Estudos de Coortes , Marcadores Genéticos/genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos TestesRESUMO
Autism spectrum disorders (ASDs) are childhood neurodevelopmental disorders with complex genetic origins. Previous studies focusing on candidate genes or genomic regions have identified several copy number variations (CNVs) that are associated with an increased risk of ASDs. Here we present the results from a whole-genome CNV study on a cohort of 859 ASD cases and 1,409 healthy children of European ancestry who were genotyped with approximately 550,000 single nucleotide polymorphism markers, in an attempt to comprehensively identify CNVs conferring susceptibility to ASDs. Positive findings were evaluated in an independent cohort of 1,336 ASD cases and 1,110 controls of European ancestry. Besides previously reported ASD candidate genes, such as NRXN1 (ref. 10) and CNTN4 (refs 11, 12), several new susceptibility genes encoding neuronal cell-adhesion molecules, including NLGN1 and ASTN2, were enriched with CNVs in ASD cases compared to controls (P = 9.5 x 10(-3)). Furthermore, CNVs within or surrounding genes involved in the ubiquitin pathways, including UBE3A, PARK2, RFWD2 and FBXO40, were affected by CNVs not observed in controls (P = 3.3 x 10(-3)). We also identified duplications 55 kilobases upstream of complementary DNA AK123120 (P = 3.6 x 10(-6)). Although these variants may be individually rare, they target genes involved in neuronal cell-adhesion or ubiquitin degradation, indicating that these two important gene networks expressed within the central nervous system may contribute to the genetic susceptibility of ASD.
Assuntos
Transtorno Autístico/genética , Dosagem de Genes/genética , Variação Genética/genética , Genoma Humano/genética , Neurônios/metabolismo , Ubiquitina/metabolismo , Estudos de Casos e Controles , Moléculas de Adesão Celular Neuronais/genética , Estudos de Coortes , Europa (Continente)/etnologia , Redes Reguladoras de Genes/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único/genética , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Prescription opioid use and overdose deaths are increasing in the United States. Among disabled Medicare beneficiaries under the age of 65, the rise in musculoskeletal conditions as qualifying diagnoses suggests that opioid analgesic use may be common and increasing, raising safety concerns. METHODS: From a 40% random-sample Medicare denominator, we identified fee-for-service beneficiaries under the age of 65 and created annual enrollment cohorts from 2007 to 2011 (6.4 million person-years). We obtained adjusted, annual opioid use measures: any use, chronic use (≥ 6 prescriptions), intensity of use [daily morphine equivalent dose (MED)], and opioid prescribers per user. Geographic variation was studied across Hospital Referral Regions. RESULTS: Most measures peaked in 2010. The adjusted proportion with any opioid use was 43.9% in 2007, 44.7% in 2010, and 43.7% in 2011. The proportion with chronic use rose from 21.4% in 2007 to 23.1% in 2011. Among chronic users: mean MED peaked at 81.3 mg in 2010, declining to 77.4 mg in 2011; in 2011, 19.8% received ≥ 100 mg MED; 10.4% received ≥ 200 mg. In 2011, Hospital Referral Region-level measures varied broadly (5th-95th percentile): any use: 33.0%-58.6%, chronic use: 13.9%-36.6%; among chronic users, mean MED: 45 mg-125 mg; mean annual opioid prescribers: 2.4-3.7. CONCLUSIONS: Among these beneficiaries, opioid use was common. Although intensity stabilized, the population using opioids chronically grew. Variation shows a lack of a standardized approach and reveals regions with mean MED at levels associated with overdose risk. Future work should assess outcomes, chronic use predictors, and policies balancing pain control and safety.
Assuntos
Analgésicos Opioides/administração & dosagem , Pessoas com Deficiência/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Medicare/estatística & dados numéricos , Doenças Musculoesqueléticas/tratamento farmacológico , Adulto , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores Socioeconômicos , Estados UnidosRESUMO
Clinically significant sleep problems affect up to 86% of the autistic population in school-age. Sleep problems can have negative impacts on child cognition, behavior, and health. However, sex differences in the prevalence and types of sleep problems are not well understood in autism. To evaluate sex differences in sleep problems in the school-age autistic population, we obtained parent-report of sleep problems on the Children's Sleep Habits Questionnaire and conducted direct assessments to establish diagnosis and intellectual ability in 6-12-year-old children (autism n = 250; typical development [TD] n = 114). Almost 85% of autistic females demonstrated sleep problems compared to 65.8% of autistic males, 44.8% of TD females, and 42.4% of TD males; a statistically significant increase for autistic females. Autistic females demonstrated increased bedtime resistance, sleep anxiety, and sleepiness, and decreased sleep duration, but did not differ in sleep onset delay, night wakings, parasomnias, or disordered breathing compared with autistic males. Intellectual ability was not related to increased sleep problems. Higher anxiety scores were associated with more sleep problems for males but not females. In one of the first studies to evaluate sex differences in sleep in the school-age, autistic population, autistic females demonstrated increased sleep problems compared to autistic males, TD females, and TD males. Current autism assessment and intervention practices may benefit from increased attention to sleep problems in autistic school-age females and to anxiety in autistic males to enhance well-being and behavioral and health outcomes.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Transtornos do Sono-Vigília , Criança , Humanos , Masculino , Feminino , Transtorno Autístico/diagnóstico , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/epidemiologia , Caracteres Sexuais , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/diagnóstico , Sono , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND OBJECTIVES: The severity of autism spectrum disorder (ASD) varies widely and is associated with intellectual disability (ID) and brain dysmorphology. We tested the hypothesis that the heterogeneity of ASD can be accounted for, in part, by altered associative learning measured by eye-blink conditioning (EBC) paradigms, used to test for forebrain and cerebellar dysfunction across the full range of ASD severity and intellectual ability. METHODS: Children in this cohort study were diagnosed with ASD or typical development (TD); most children were recruited from a 10-year longitudinal study. Outcome measures were the percentage and timing of conditioned eye-blink responses (CRs) acquired to a tone, recorded photometrically and related to measures of ASD severity, IQ, and age 2 brain morphometry by MRI. A sequence of trace and delay EBC was used. Analysis of variance, t test, and logistic regression (LR) were used. RESULTS: Sixty-two children were studied at school age. Nine children with ASD with ID since age 2 (ASD + ID; IQ = 49 ± 6; 11.9 ± 0.2 years old [±SD]) learned more slowly than 30 children with TD (IQ = 120 ± 16; 10.5 ± 1.5 years old [±SD]) during trace EBC and showed atypically early-onset CRs (1.4 SD pre-TD) related to hypoplasia of the cerebellum at age 2 but not of the amygdala, hippocampus, or cerebral cortex. Conversely, 16 children with ASD with robust intellectual development since age 2 (IQ = 100 ± 3; 12.0 ± 0.4 years old [±SD]) learned typically but showed early-onset CRs only during long-delay EBC (0.8 SD pre-TD) unrelated to hypoplasia of any measured brain area. Using 16 EBC measures, binary LR classified ASD and TD with 80% accuracy (95% CI = 72-88%), 81% sensitivity (95% CI = 69-92%), and 79% specificity (95% CI = 68-91%); multinomial LR more accurately classified children based on ID (94% accuracy, 95% CI = 89-100%) than ASD severity (85% accuracy, 95% CI = 77-93%). Separate analyses of 39 children with MRI (2.1 ± 0.3 years old [±SD]) indicated that cerebellar hypoplasia did not predict ASD + ID over ages 2-4 (Cohen d = 0.3) compared with early-onset CRs during age 11 trace EBC (Cohen d = -1.3). DISCUSSION: Trace EBC reveals the relationship between cerebellar hypoplasia and ASD + ID likely by engaging cerebrocerebellar circuits involved in intellectual ability and implicit timing. Follow-up prospective studies using associative learning can determine whether ID can be predicted in children with early ASD diagnoses.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Deficiência Intelectual , Humanos , Criança , Pré-Escolar , Lactente , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/diagnóstico por imagem , Estudos de Coortes , Deficiência Intelectual/complicações , Estudos Longitudinais , Estudos Prospectivos , Cerebelo/diagnóstico por imagem , ProsencéfaloRESUMO
PURPOSE: Proton pump inhibitors (PPIs) and corticosteroids are commonly prescribed drugs; however, each has been associated with fracture and community-acquired pneumonia. How physicians select patients for co-therapy may have implications for potential additive or synergistic toxicities. METHODS: We conducted a retrospective cohort study of 13 749 incident corticosteroid users with no prior PPI exposure using the HealthCore Integrated Research Database(SM) . We used logistic regression to evaluate the association between PPI initiation in the first 30 days of steroid therapy and corticosteroid dose, clinical risk factors including comorbid diseases, and medication use including prescription nonsteroidal anti-inflammatory drugs (NSAIDs). RESULTS: A new PPI prescription within 30 days of starting corticosteroids was filled by 1050 patients (7.6%). PPI use was associated with the number of baseline comorbid conditions (OR = 1.21 for each additional condition, 95%CI = 1.13-1.28), recent hospitalization (OR = 4.71, 95%CI = 4.02-5.52), prednisone dose higher than 40 mg/day (OR = 1.87, 95%CI = 1.45-2.41), history of gastroesophageal reflux or gastric ulcer disease (OR = 1.54, 95%CI = 1.24-1.91), renal insufficiency (OR = 2.06, 95%CI = 1.73-2.46), and liver disease (OR = 1.82, 95%CI = 1.45-2.28). The concomitant use of prescription NSAIDs was also associated with PPI use (OR = 1.89, 95%CI = 1.32-2.70); however, the total use of PPIs in this group was low (6.3%, 95%CI = 4.4-8.2%). CONCLUSIONS: Overall, PPI therapy among corticosteroid users was uncommon, even among those with risk factors for gastrointestinal toxicity. PPI use was significantly more common among patients who had recently been hospitalized, had a greater burden of comorbid illness, or were receiving high daily doses of corticosteroids.
Assuntos
Glucocorticoides/uso terapêutico , Seleção de Pacientes , Padrões de Prática Médica/estatística & dados numéricos , Inibidores da Bomba de Prótons/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos de Coortes , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Feminino , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/etiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Hospitalização/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To compare the relative hazard of muscle toxicity, renal dysfunction, and hepatic dysfunction associated with the drug interaction between statins and concomitant medications that inhibit the CYP3A4 isoenzyme. BACKGROUND: Although statins provide important clinical benefits related to mitigating the risk of cardiovascular events, this class of medications also has the potential for severe adverse reactions. The risk for adverse events may be potentiated by concomitant use of medications that interfere with statin metabolism. METHODS: Data from The Health Improvement Network (THIN) from 1990 to 2008 were used to conduct a retrospective cohort study. Cohorts were created to evaluate each outcome (muscle toxicity, renal dysfunction, and hepatic dysfunction) independently. Each cohort included new statin initiators and compared the relative hazard of the outcome. The interaction ratio (I*R) was the primary contrast of interest. The I*R represents the relative effect of each statin type (statin 3A4 substrate vs. statin non-3A4 substrate) with a CYP3A4 inhibitor, independent of the effect of the statin type without a CYP3A4 inhibitor. We adjusted for confounding variables using the multinomial propensity score. RESULTS: The median follow-up time per cohort was 1.5 years. There were 7889 muscle toxicity events among 362,809 patients and 792,665 person-years. The adjusted muscle toxicity I*R was 1.22 (95% confidence interval [CI] = 0.90-1.66). There were 1449 renal dysfunction events among 272,099 patients and 574,584 person-years. The adjusted renal dysfunction I*R was 0.91 (95%CI = 0.58-1.44). There were 1434 hepatic dysfunction events among 367,612 patients and 815,945 person-years. The adjusted hepatic dysfunction I*R was 0.78 (95%CI = 0.45-1.31). CONCLUSIONS: Overall, this study found no difference in the relative hazard of muscle toxicity, renal dysfunction, or hepatic dysfunction for patients prescribed a statin 3A4 substrate versus a statin non-3A4 substrate with CYP3A4 inhibitor concomitancy.
Assuntos
Inibidores do Citocromo P-450 CYP3A , Inibidores Enzimáticos/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Idoso , Estudos de Coortes , Bases de Dados Factuais , Interações Medicamentosas , Inibidores Enzimáticos/farmacologia , Feminino , Seguimentos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacocinética , Nefropatias/epidemiologia , Nefropatias/etiologia , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Doenças Musculares/epidemiologia , Doenças Musculares/etiologia , Estudos Retrospectivos , Reino UnidoRESUMO
RATIONALE: Bilateral lung transplantation (BLT) improves survival compared with single lung transplantation (SLT) for some individuals with chronic obstructive pulmonary disease (COPD). However, it is unclear which strategy optimally uses this scarce societal resource. OBJECTIVES: To compare the effect of SLT versus BLT strategies for COPD on waitlist outcomes among the broader population of patients listed for lung transplantation. METHODS: We developed a Markov model to simulate the transplant waitlist using transplant registry data to define waitlist size, donor frequency, the risk of death awaiting transplant, and disease- and procedure-specific post-transplant survival. We then applied this model to 1,000 simulated patients and compared the number of patients under each strategy who received a transplant, the number who died before transplantation, and total post-transplant survival. MEASUREMENTS AND MAIN RESULTS: Under baseline assumptions, the SLT strategy resulted in more patients transplanted (809 vs. 758) and fewer waitlist deaths (157 vs. 199). The strategies produced similar total post-transplant survival (SLT = 4,586 yr vs. BLT = 4,577 yr). In sensitivity analyses, SLT always maximized the number of patients transplanted. The strategy that maximized post-transplant survival depended on the relative survival benefit of BLT versus SLT among patients with COPD, donor interval, and waitlist size. CONCLUSIONS: In most circumstances, a policy of SLT for COPD improves access to organs for other potential recipients without significant reductions in total post-transplant survival. However, there may be substantial geographic variations in the effect of such a policy on the balance between these outcomes.
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Alocação de Recursos para a Atenção à Saúde/métodos , Transplante de Pulmão/métodos , Doença Pulmonar Obstrutiva Crônica/cirurgia , Listas de Espera , Técnicas de Apoio para a Decisão , Humanos , Cadeias de Markov , Sistema de Registros , Análise de SobrevidaRESUMO
INTRODUCTION: Pneumococcal vaccination recommendations are constantly evolving. Recent pneumococcal vaccination guidelines have been updated to recommend pneumococcal conjugate vaccines in older adults. However, the clinical benefits of protein conjugate vaccine (PCV 13), pneumococcal polysaccharide vaccine (PPSV 23) and dual vaccination when compared to each other remain unclear. METHODS: A retrospective cohort study conducted between 2014 and 2016 conducted at the Veterans Health administration (VHA) (N = 1,277,575). Primary outcomes were pneumococcal pneumonia and pneumococcal meningitis. Secondary outcomes were "other" pneumonia and "other" meningitis. "Other" referred to episodes of pneumonia and meningitis without an identified etiological agent. RESULTS: PCV 13 was associated with decreased risk of pneumococcal pneumonia (Adjusted HR 0.69; 95 % CI 0.51 to 0.93) and "other" pneumonia (Adjusted HR 0.74; 95 % CI 0.64 to 0.86) when compared to PPSV 23. No significant difference was found between PCV 13 and PPSV 23 in terms of pneumococcal meningitis (Adjusted HR 3.98; 95 % CI 0.74 to 21.32; P = 0.12) and "other" meningitis (Adjusted HR 0.81; 95 % CI 0.33 to 2.03; P = 0.66). Dual vaccination was also associated with a decrease in the rate of pneumococcal pneumonia (Adjusted HR 0.88; 95 % CI 0.77 to 0.99; P = 0.03) and "other" pneumonia (Adjusted HR 0.90; 95 % CI 0.85 to 0.95; P < 0.01) in comparison to PPSV 23. CONCLUSIONS: PCV 13 was associated with a 31% decrease in the rate of pneumococcal pneumonia in comparison to PPSV 23 in older adult Veterans. Our results demonstrating clinical benefit with PCV 13 vaccination are in alignment with the latest pneumococcal vaccination guidelines that recommend routine vaccination with pneumococcal conjugate vaccines in all older adults.
Assuntos
Meningite Pneumocócica , Infecções Pneumocócicas , Pneumonia Pneumocócica , Veteranos , Idoso , Humanos , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/uso terapêutico , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/prevenção & controle , Estudos Retrospectivos , Estados Unidos/epidemiologia , Vacinação , Vacinas Conjugadas/uso terapêuticoRESUMO
In addition to being a hallmark symptom of schizophrenia-spectrum disorders, auditory verbal hallucinations (AVH) are present in a range of psychiatric disorders as well as among individuals who are otherwise healthy. People who experience AVH are heterogeneous, and research has aimed to better understand what characteristics distinguish, among those who experience AVH, those who experience significant disruption and distress from those who do not. The cognitive model of AVH suggests that appraisals of voices determine the extent to which voices cause distress and social dysfunction. Previous work has relied largely on comparisons of "clinical" and "non-clinical" voice hearers, and few studies have been able to provide insight into the moment-to-moment relationships between appraisals and outcomes. The current study examines longitudinal data provided through ecological momentary assessment and passive sensors of 465 individuals who experience cross-diagnostic AVH. Results demonstrated associations of AVH appraisals to negative affect and social functioning. Above and beyond within-individual averages, when a participant reported increased appraisals of their voices as powerful and difficult to control, they were more likely to feel increased negative affect and reduced feelings of safety. AVH power appraisals were also associated with next-day number and duration of phone calls placed, and AVH controllability appraisals were associated with increased time near speech and reduced next-day time away from primary location. These results suggest that appraisals are state-like characteristics linked with day-to-day and moment-to-moment changes in impactful affective and behavioral outcomes; intervention approaches should aim to address these domains in real-time.
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Esquizofrenia , Voz , Humanos , Interação Social , Alucinações , Esquizofrenia/complicações , Esquizofrenia/diagnóstico , FalaRESUMO
LAY ABSTRACT: This is a study of the secondary effects of interventions for young children with autism on their parents. Specifically, we were interested in the impact on parent's sense of efficacy, or how confident and competent a parent feels about themselves as a parent. We tested three ideas: (1) that the style of the intervention, whether it was more or less structured and whether the parent had a more or less formal role, would impact a parent's sense of efficacy; (2) that the intensity of the intervention, how many hours per week the intervention was delivered, would impact parental efficacy; and (3) that the parent's level of stress prior to intervention would impact how intensity and style effected efficacy. We randomly assigned 87 children with autism, age 13-30 months, into one of four conditions: 15 versus 25 intervention hours crossed with two different styles of intervention. We used statistical tests to examine these ideas. We found that parental efficacy was related to intervention intensity but not style. Parents with higher stress at the beginning of a 1-year, home-based, comprehensive intervention program had a higher sense of parenting efficacy if their child received lower intensity intervention; parents with lower stress at baseline had a higher sense of efficacy if their child received higher intensity intervention. If a parent can emerge from the process of diagnosis and early intervention with an increased sense that they can make a difference in their child's life (i.e. increased sense of efficacy), it may set the stage for meeting the long-term demands of parenting a child with autism.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Transtorno Autístico/terapia , Pré-Escolar , Intervenção Educacional Precoce , Humanos , Lactente , Poder Familiar , PaisRESUMO
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease with no known aetiology and no proven treatment. Despite the absence of efficacy data, many physicians treat IPF with corticosteroids either as monotherapy or in combination with a cytotoxic agent. Specialty society guidelines published in 1999 and 2000 recognize that treatment may not be appropriate for all patients with IPF, but recommend that if treatment is to be initiated, a combination of corticosteroids with a cytotoxic agent is preferred over corticosteroids alone. It is not known how the use of corticosteroids and cytotoxic agents in the treatment of IPF has changed over time and whether published guidelines have altered prescribing practices. WHAT THIS STUDY ADDS: The results of this study demonstrate a modest but statistically significant reduction in the overall use of corticosteroids since the publication of treatment guidelines. At the same time, there was a more pronounced increase in the combined use of corticosteroids and cytotoxic agents consistent with recommendations. Even with the increase in the use of combination therapy, corticosteroid monotherapy remained the most commonly prescribed regimen among treated patients. Given the lack of established benefit and the risks associated with corticosteroid therapy, the reasons for the continued use of corticosteroid monotherapy in the majority of treated patients warrant further investigation. AIMS: To assess the impact of specialty society guidelines on the use of corticosteroids and cytotoxic agents in the initial management of patients with idiopathic pulmonary fibrosis. METHODS: A retrospective cohort study of 941 patients with an incident diagnosis of IPF was conducted using a large medical records database. The primary outcome was a new prescription for corticosteroids with or without a cytotoxic agent within 30 days of diagnosis. The primary exposure was whether diagnosis occurred before or after the publication of treatment guidelines. Logistic regression was used to control for changes in population demographics and disease characteristics across time. RESULTS: In total, 187 patients (19.9%) received a new corticosteroid prescription within 30 days of diagnosis. Fewer patients received corticosteroids after the publication of guidelines (22.2% vs. 17.7%; adjusted OR for steroid use after the publication of guidelines 0.65, 95% confidence interval 0.46, 0.92, P = 0.014). Among the 187 patients treated with corticosteroids, 22 (11.8%) also received a cytotoxic agent. The use of cytotoxic agents among users of corticosteroids increased significantly after the publication of guidelines (5.1% vs. 19.3%) with a fully adjusted OR = 4.71 (95% CI 1.56, 14.21, P = 0.006). CONCLUSIONS: Since the publication of treatment guidelines, there has been a small reduction in the overall use of corticosteroids. Consistent with these guidelines, the use of cytotoxic agents among those prescribed corticosteroids has increased significantly; however, the use of these agents remains uncommon.
Assuntos
Corticosteroides/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/tendências , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Farmacoepidemiologia , Guias de Prática Clínica como Assunto/normas , Estudos RetrospectivosRESUMO
PURPOSE: Idiopathic pulmonary fibrosis (IPF) has not been shown to respond to corticosteroid therapy; however, many patients receive these drugs at the time of diagnosis. The factors that are associated with the decision to prescribe corticosteroids have not been examined. METHODS: We conducted a retrospective cohort study of 1126 patients with a new diagnosis of IPF using The Health Improvement Network (THIN) database from the United Kingdom. We used generalized estimating equation (GEE) regression models to test the association of patient characteristics, co-morbid diseases, and disease characteristics with the use of corticosteroids within 30 days of IPF diagnosis. RESULTS: Bivariable analyses demonstrated an association between female sex, the presence of dyspnea, the need for oxygen, past steroid use, and the use of corticosteroids immediately prior to diagnosis with the use of corticosteroids at the time of diagnosis. After adjustment with multivariable GEE regression, only the use of oxygen at the time of diagnosis (OR 1.69, CI 1.14-2.49), the past use of corticosteroids (OR 1.50, CI 1.04-2.15), and use of corticosteroids immediately prior to diagnosis (OR 5.72, CI 3.80-8.60) remained significantly associated with the use of corticosteroids immediately following diagnosis. No association was found between prior diabetes, osteoporosis, glaucoma, hypertension, congestive heart failure, obesity, or peptic ulcer disease and use of corticosteroids at diagnosis. CONCLUSIONS: The decision to prescribe corticosteroids is associated with oxygen use and past corticosteroid use but is not influenced by factors such as age, gender, or common co-morbid conditions that may pre-dispose patients to adverse events of therapy.
Assuntos
Glucocorticoides/uso terapêutico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Oxigenoterapia/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Reino UnidoRESUMO
Sleep problems are prevalent in children with neurodevelopmental disabilities and are associated with the expression of restricted and repetitive behaviors (RRBs). Children (n = 57) with autism spectrum disorder (ASD, n = 38) or developmental delay (DD, n = 19) participated in multiple assessments of intellectual ability, ASD symptoms, and RRBs (3 timepoints for ASD, 2 for DD). Sleep problems assessed at age 4 via parent report were associated with trajectories of higher-order RRBs (sameness/ritualistic/compulsive behaviors) from age 2-6 in the ASD group, and from age 2-4 in the DD group, even after controlling for intellectual ability, social-affective symptoms, and anxiety. Trajectories of stereotyped/restricted behaviors were unrelated to sleep problems. Sleep problems were associated with trajectories of higher-order (but not lower-order) RRBs in a transdiagnostic sample.
Assuntos
Transtornos do Neurodesenvolvimento/psicologia , Pais/psicologia , Transtornos do Sono-Vigília/psicologia , Transtorno de Movimento Estereotipado/psicologia , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/psicologia , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Transtornos do Neurodesenvolvimento/diagnóstico , Transtornos do Neurodesenvolvimento/epidemiologia , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/epidemiologia , Transtorno de Movimento Estereotipado/diagnóstico , Transtorno de Movimento Estereotipado/epidemiologiaRESUMO
Abnormalities in olfactory function have been identified in a number of neurological and psychiatric disorders, including Parkinson's disease and schizophrenia. However, little is known about olfactory function in autism spectrum disorder (ASD). The present study aims to assess the olfactory profiles of children with ASD, compared to an age- and sex-matched comparison group of typically developing children and a second clinical control group consisting of non-ASD children with sensory processing dysfunction (SPD). Participants completed a battery of sensory and behavioral assessments including olfactory tasks (Sniffin' Sticks Threshold Test and self-reported valence ratings for two target odorants (phenylethyl alcohol and vanillin) and the University of Pennsylvania Smell Identification Test), and an autism evaluation (Autism Diagnostic Observation Schedule-2). Children with ASD showed intact odor detection with reduced odor identification ability. Poor odor identification was significantly correlated with autism symptom severity. Children with SPD demonstrated reduced odor detection and identification ability. These findings provide evidence for differential patterns of smell processing among ASD and non-ASD neurodevelopmental disorders. Future studies are needed to determine whether the association of impaired olfaction and increased autism symptoms is due to shared etiology.
RESUMO
OBJECTIVE: Auditory verbal hallucinations (AVH) are common in multiple clinical populations but also occur in individuals who are otherwise considered healthy. Adopting the National Institute of Mental Health's Research Domain Criteria (RDoC) framework, the aim of the current study was to integrate a variety of measures to evaluate whether AVH experience varies across clinical and nonclinical individuals. METHODS: A total of 384 people with AVH from 41 US states participated in the study; 295 participants (77%) who received inpatient, outpatient, or combination treatments for AVH and 89 participants (23%) who never received care. Participants used a multi-modal smartphone data collection system to report on their AVH experiences and co-occurring psychological states multiple times daily, over 30 days. In parallel, smartphone sensors recorded their physical activity, geolocation, and calling and texting behavior continuously. RESULTS: The clinical sample experienced AVH more frequently than the nonclinical group and rated their AVH as significantly louder and more powerful. They experienced more co-occurring negative affect and were more socially withdrawn, spending significantly more time at home and significantly less time near other people. Participants with a history of inpatient care also rated their AVH as infused with significantly more negative content. The groups did not differ in their physical activity or use of their smartphones for digital communication. CONCLUSION: Smartphone-assisted remote data collection revealed real-time/real-place phenomenological, affective, and behavioral differences between clinical and nonclinical samples of people who experience AVH. The study provided strong support for the application of RDoC-informed approaches in psychosis research.
Assuntos
Amilases/economia , Aprovação de Drogas/legislação & jurisprudência , Lipase/economia , Peptídeo Hidrolases/economia , Honorários por Prescrição de Medicamentos/tendências , United States Food and Drug Administration/legislação & jurisprudência , Aprovação de Drogas/economia , Combinação de Medicamentos , Acessibilidade aos Serviços de Saúde/economia , Honorários por Prescrição de Medicamentos/estatística & dados numéricos , Estados UnidosRESUMO
Parents of children with developmental disabilities, particularly autism spectrum disorders (ASDs), are at risk for high levels of distress. The factors contributing to this are unclear. This study investigated how child characteristics influence maternal parenting stress and psychological distress. Participants consisted of mothers and developmental-age matched preschool-aged children with ASD (N = 51) and developmental delay without autism (DD) ( N = 22). Evidence for higher levels of parenting stress and psychological distress was found in mothers in the ASD group compared to the DD group. Children's problem behavior was associated with increased parenting stress and psychological distress in mothers in the ASD and DD groups. This relationship was stronger in the DD group. Daily living skills were not related to parenting stress or psychological distress. Results suggest clinical services aiming to support parents should include a focus on reducing problem behaviors in children with developmental disabilities.
Assuntos
Transtorno Autístico/diagnóstico , Transtornos do Comportamento Infantil/prevenção & controle , Deficiências do Desenvolvimento/diagnóstico , Mães/psicologia , Poder Familiar/psicologia , Estresse Psicológico/diagnóstico , Atividades Cotidianas/psicologia , Adaptação Psicológica , Adulto , Transtorno Autístico/epidemiologia , Transtorno Autístico/psicologia , Transtornos do Comportamento Infantil/psicologia , Pré-Escolar , Comorbidade , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/psicologia , Feminino , Humanos , Masculino , Relações Pais-Filho , Inventário de Personalidade , Estresse Psicológico/psicologia , Inquéritos e QuestionáriosRESUMO
Little is known about outcomes of early intervention for children with autism spectrum disorder reared in bilingual homes. There are concerns that social communication deficits among children with autism spectrum disorder may reduce the developmental benefits of early intervention for children with autism spectrum disorder raised in bilingual environments. We conducted an exploratory analysis of cross-sectional and longitudinal data from a larger study to explore associations between home language environment and language ability and social skills in response to early autism spectrum disorder intervention. Participants, aged 12-26 months when recruited, were a subset of a larger 2-year, randomized intervention trial (ClinicalTrials.gov identifier: NCT00698997). Children from bilingual homes ( n = 13) began intervention with lower gesture use but otherwise demonstrated equal baseline language and social abilities as compared with age and nonverbal IQ-matched children from monolingual homes ( n = 24). Significant language growth was exhibited by children from both language groups and there was no moderating effect of home language environment. The bilingual home group demonstrated increased gesture use over the course of intervention as compared with the monolingual home group. Preliminary data revealed no basis for concerns regarding negative impact of a bilingual home environment on language or social development in young children with autism spectrum disorder.