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1.
Am J Gastroenterol ; 119(5): 930-936, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38131626

RESUMO

INTRODUCTION: High rates of screen failure for the minimum Simple Endoscopic Score for Crohn's Disease (SES-CD) plague Crohn's disease (CD) clinical trials. We aimed to determine the accuracy of segmental intestinal ultrasound (IUS) parameters and scores to detect segmental SES-CD activity. METHODS: A single-center, blinded, cross-sectional cohort study of children and young adult patients with CD undergoing IUS and ileocolonoscopy, comparing segmental IUS bowel wall thickness (BWT), hyperemia (modified Limberg score [MLS]), and scores to detect segmental SES-CD activity: (i) SES-CD ≤2, (ii) SES-CD ≥6, and (iii) SES-CD ≥4 in the terminal ileum (TI) only. Primary outcome was accuracy of BWT, MLS, and IUS scores to detect SES-CD ≤2 and SES-CD ≥6. Secondary outcomes were accuracy of TI BWT, MLS, and IUS scores to detect SES-CD ≥4 and correlation with the SES-CD. RESULTS: Eighty-two patients (median [interquartile range] age 16.5 [12.9-20.0] years) underwent IUS and ileocolonoscopy of 323 bowel segments. Segmental BWT ≤3.1 mm had a similar high accuracy to detect SES-CD ≤2 as IUS scores (area under the receiver operating curve [AUROC] 0.833 [95% confidence interval 0.76-0.91], 94% sensitivity, and 73% specificity). Segmental BWT ≥3.6 mm and ≥4.3 mm had similar high accuracy to detect SES-CD ≥6 (AUROC 0.950 [95% confidence interval 0.92-0.98], 89% sensitivity, 93% specificity) in the colon and an SES-CD ≥4 in the TI (AUROC 0.874 [0.79-0.96], 80% sensitivity, and 91% specificity) as IUS scores. Segmental IUS scores strongly correlated with the SES-CD. DISCUSSION: Segmental IUS BWT is highly accurate to detect moderate-to-severe endoscopic inflammation. IUS may be the ideal prescreening tool to reduce unnecessary trial screen failures.


Assuntos
Colonoscopia , Doença de Crohn , Ultrassonografia , Humanos , Doença de Crohn/diagnóstico por imagem , Feminino , Masculino , Estudos Transversais , Adolescente , Ultrassonografia/métodos , Adulto Jovem , Criança , Índice de Gravidade de Doença , Íleo/diagnóstico por imagem , Íleo/patologia , Sensibilidade e Especificidade , Ensaios Clínicos como Assunto , Curva ROC
2.
Dig Dis Sci ; 69(5): 1826-1833, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521850

RESUMO

BACKGROUND: Data are limited on the safety and efficacy of combining advanced therapies for refractory patients with IBD. AIM: To evaluate the real-world efficacy and safety of dual advanced therapy (DAT), combining 2 biologics or a biologic with a small molecule, in children and young adults with refractory IBD. METHODS: Primary outcome of this single IBD center cohort was DAT remission (clinical and biomarker remission) at first assessment (T1). Secondary outcomes included remission at T2, if DAT de-intensification (De-I) occurred and T3, if T2 DAT re-intensification (Re-I) occurred. Efficacy and safety outcomes were described. RESULTS: Of the 30 patients [43% female, 30% CD, median age of 18.3 [15.1-19.8] years], all 11 UST + TOFA achieved T1 remission; 6/10 De-I failed at T2; and 4/4 Re-I achieved T3 remission. Of 9 VDZ + TOFA, 6 achieved T1 remission; 5/6 De-I failed at T2; and 1/1 failed T3 Re-I. Of 4 UST + VDZ, 3 achieved T1 remission; 2/3 De-I failed at T2; and 0 had Re-I. Of 5 UST + UPA, 4 achieved T1 remission; 1/5 De-I failed at T2 but recaptured T3 remission post-Re-I. One VDZ + OZA achieved T1 remission and maintained T2 remission post-De-I to OZA monotherapy. At last follow-up, 43% were on original DAT, 17% on one of original DAT, and 40% neither. One UST + TOFA patient developed mild leukopenia and another developed septic arthritis and venous thromboembolism on VDZ + TOFA and prednisone. CONCLUSION: Most children and young adults treated with DAT achieved remission with minimal safety events; however, de-intensification had limited success.


Assuntos
Indução de Remissão , Humanos , Feminino , Masculino , Adolescente , Adulto Jovem , Resultado do Tratamento , Quimioterapia Combinada , Fármacos Gastrointestinais/uso terapêutico , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Doença de Crohn/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/diagnóstico , Estudos Retrospectivos , Doenças Inflamatórias Intestinais/tratamento farmacológico
3.
Int J Lang Commun Disord ; 59(2): 608-622, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-36918757

RESUMO

BACKGROUND: Spoken discourse impairments post-traumatic brain injury (TBI) are well-documented and heterogeneous in nature. These impairments have chronic implications for adults in terms of employment, socializing and community involvement. Intervention delivered by a speech-language pathologist (SLP) is recommended for adults with discourse impairments post-TBI, with an emphasis on context-sensitive treatment. The developing evidence base indicates a wide array of treatment components for SLPs to evaluate and implement within their clinical practice. However, there is limited insight into how SLPs are currently treating discourse impairments and the rationales informing clinical practice. AIMS: To explore the under-researched area of clinical practice for spoken discourse interventions with adults post-TBI, including treatment components and clinician rationales, and to contribute towards a shared knowledge base. METHODS & PROCEDURES: Participants were recruited via purposeful sampling strategies. Six SLPs participated from Australia, the United Kingdom (UK) and the United States (US). Semi-structured interviews were conducted via Zoom. Interviews were manually transcribed, coded and analysed via a qualitative content analysis approach. OUTCOMES & RESULTS: Participants described discourse treatment practices across various settings and TBI recovery stages. Results indicated that SLPs used numerous treatment activities, resources and outcome measures. Intervention approaches primarily targeted social communication skills, strategy development/utilization and insight-building. Clinical practice conformed to available guidelines where possible, reflected best practice and incorporated components of the research literature. Participants reported using individualized treatment activities aimed at addressing client-specific factors and rationales prioritized tailored, context-sensitive and goal-directed treatment. CONCLUSIONS & IMPLICATIONS: This study provided insight into a previously under-researched area. It highlighted a wide range of treatment activities and factors informing current SLPs' treatment of spoken discourse impairment post-TBI. Overall, clinical practice and rationales discussed in this study were aligned with best practice and emphasized a contextualized, individualized approach to discourse treatment across service settings and stages of recovery. Participants identified areas requiring further support, including access to training, resources and research, and the challenge of finding suitable outcome measures. Further investigation into discourse management post-TBI, from initial assessment to outcome measurement, may help inform clinical decision-making and the transfer of research to practice. WHAT THIS PAPER ADDS: What is already known on the subject Spoken discourse impairments occur in dialogic and monologic productions post-TBI. Interventions targeting both genres are detailed within the research literature; however, studies exploring clinical practice and decision-making for discourse interventions post-TBI are limited. What this paper adds to existing knowledge This study provides new insight into the current treatment targets, activities, resources and outcome measures employed by clinicians supporting adults with discourse impairment post-TBI. It details the factors that influence clinical decision-making for this caseload and identifies an emphasis on client priorities and the value of clinician experience. What are the potential or actual clinical implications of this work? This study identifies the broad and complex considerations required to deliver context-sensitive discourse intervention post-TBI. It indicates the need for an in-depth review from assessment to treatment outcomes to better understand and support this area of practice and to direct future research. This study also highlighted the role of clinician experience in discourse intervention and the value of sharing clinical knowledge and resources within and across the profession to support all levels of clinician experience.


Assuntos
Lesões Encefálicas Traumáticas , Transtornos da Comunicação , Patologia da Fala e Linguagem , Adulto , Humanos , Patologistas , Fala , Transtornos da Comunicação/etiologia , Transtornos da Comunicação/terapia , Comunicação , Patologia da Fala e Linguagem/educação , Lesões Encefálicas Traumáticas/complicações
4.
Dig Dis Sci ; 68(4): 1121-1124, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36064828

RESUMO

INTRODUCTION: Dupilumab blocks IL4/IL13 and is used in atopic disease. There are concerns that blockade may lead to inflammatory bowel disease (IBD) inception or activity. Limited data exist on the use of this therapy in patients with IBD; we aimed to describe our experience using dupilumab in IBD to treat concomitant atopic dermatitis (AD) or anti-TNF-induced dermatitis. METHODS: We analyzed the electronic medical records (2018-2022) in a single, tertiary care center to identify patients with IBD on dupilumab. Clinical and demographic data were gathered, including disease location/behavior, personal/family history of atopy, indication for and response to dupilumab, IBD medication history, and adverse events. RESULTS: Seventeen patients (65% Crohn's) were identified with IBD on dupilumab for dermatitis; 9 for severe AD and 8 for a worsened dermatitis, either AD or psoriasiform dermatitis (PD), induced by anti-TNF. They were treated for a median 1.2 [IQR 0.6-2.3] years. All patients had a dermatologic response to dupilumab and remained on dupilumab at last follow-up. No adverse events were identified, including no increase in IBD activity. In those with dermatitis worsened or induced by anti-TNF, all started dupilumab in combination with another biologic: 3 with anti-TNF, 4 with ustekinumab, and 1 with vedolizumab. Seven of the eight had a response to the initial combination of biologics; however, one patient using dupilumab-anti-TNF ultimately changed to combination dupilumab-ustekinumab to achieve resolution of the dermatitis. CONCLUSION: Dupilumab is safe and effective for dermatitis in patients with IBD, both primary atopic dermatitis and dermatitis induced or worsened by anti-TNF.


Assuntos
Dermatite Atópica , Doenças Inflamatórias Intestinais , Humanos , Dermatite Atópica/diagnóstico , Dermatite Atópica/tratamento farmacológico , Ustekinumab/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Resultado do Tratamento , Índice de Gravidade de Doença
5.
J Neurosci ; 41(8): 1816-1829, 2021 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-33468567

RESUMO

Childhood epilepsy with centrotemporal spikes (CECTS) is the most common focal epilepsy syndrome, yet the cause of this disease remains unknown. Now recognized as a mild epileptic encephalopathy, children exhibit sleep-activated focal epileptiform discharges and cognitive difficulties during the active phase of the disease. The association between the abnormal electrophysiology and sleep suggests disruption to thalamocortical circuits. Thalamocortical circuit dysfunction resulting in pathologic epileptiform activity could hinder the production of sleep spindles, a brain rhythm essential for memory processes. Despite this pathophysiologic connection, the relationship between spindles and cognitive symptoms in epileptic encephalopathies has not been previously evaluated. A significant challenge limiting such work has been the poor performance of available automated spindle detection methods in the setting of sharp activities, such as epileptic spikes. Here, we validate a robust new method to accurately measure sleep spindles in patients with epilepsy. We then apply this detector to a prospective cohort of male and female children with CECTS with combined high-density EEGs during sleep and cognitive testing at varying time points of disease. We show that: (1) children have a transient, focal deficit in spindles during the symptomatic phase of disease; (2) spindle rate anticorrelates with spike rate; and (3) spindle rate, but not spike rate, predicts performance on cognitive tasks. These findings demonstrate focal thalamocortical circuit dysfunction and provide a pathophysiological explanation for the shared seizures and cognitive symptoms in CECTS. Further, this work identifies sleep spindles as a potential treatment target of cognitive dysfunction in this common epileptic encephalopathy.SIGNIFICANCE STATEMENT Childhood epilepsy with centrotemporal spikes is the most common idiopathic focal epilepsy syndrome, characterized by self-limited focal seizures and cognitive symptoms. Here, we provide the first evidence that focal thalamocortical circuit dysfunction underlies the shared seizures and cognitive dysfunction observed. In doing so, we identify sleep spindles as a mechanistic biomarker, and potential treatment target, of cognitive dysfunction in this common developmental epilepsy and provide a novel method to reliably quantify spindles in brain recordings from patients with epilepsy.


Assuntos
Córtex Cerebral/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Epilepsias Parciais/fisiopatologia , Sono/fisiologia , Tálamo/fisiopatologia , Adolescente , Criança , Pré-Escolar , Disfunção Cognitiva/etiologia , Eletroencefalografia , Epilepsias Parciais/complicações , Feminino , Humanos , Masculino , Vias Neurais/fisiopatologia
6.
Gastroenterology ; 161(1): 47-65, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33940007

RESUMO

Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, are chronic, progressive, immune-mediated diseases of adults and children that have no cure. IBD can cause significant morbidity and lead to complications such as strictures, fistulas, infections, and cancer. In children, IBD can also result in growth impairment and pubertal delays. IBD is highly heterogenous, with severity ranging from mild to severe and symptoms ranging from mild to debilitating. Delay in IBD diagnosis, especially in Crohn's disease, is common and associated with adverse outcomes. Early diagnosis and prompt institution of treatment are the cornerstones for improving outcomes and maximizing health. Early diagnosis requires a low threshold of suspicion and red flags to guide early specialist referral at the primary provider level. Although the armamentarium of IBD medications is growing, many patients will not respond to treatment, and the selection of first-line therapy is critical. Risk stratification of disease severity, based on clinical, demographic, and serologic markers, can help guide selection of first-line therapy. Clinical decision support tools, genomics, and other biomarkers of response to therapy and risk of adverse events are the future of personalized medicine. After starting appropriate therapy, it is important to confirm remission using objective end points (treat to target) with continued control of inflammation with adjustment of therapy using surrogate biomarkers (tight control). Lastly, IBD therapy extends far beyond medications, and other aspects of the overall health and wellbeing of the patient are critical. These include preventive health, nutrition, and psychobehavioral support addressing patients' concerns around complementary therapy and medication adherence, prevention of disability, and ensuring open communication.


Assuntos
Doenças Inflamatórias Intestinais , Adulto , Fatores Etários , Biomarcadores/sangue , Criança , Progressão da Doença , Gastroenterologia , Humanos , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Prognóstico , Medição de Risco
7.
Artigo em Inglês | MEDLINE | ID: mdl-36117377

RESUMO

BACKGROUND: Spoken discourse is commonly affected after traumatic brain injury (TBI). Although guidelines recommend prioritizing discourse-level skills in cognitive communication management, previous literature has highlighted challenges in managing discourse clinically. Little is known about how speech-language pathologists (SLPs) assess and treat discourse after TBI. AIMS: To investigate current SLP practice to determine the alignment of clinical practice with research evidence and recommendations. METHODS & PROCEDURES: This online survey consisted of 30 questions on SLPs' practice with discourse assessment, analysis and treatment processes, including the materials and methods used and rationales for decision-making. Participants were recruited through national and international SLP professional bodies, TBI-specific or SLP special-interest groups and social media. Survey responses were analysed using descriptive statistics, with free text included to support individual responses. OUTCOMES & RESULTS: There were 70 participants, from Australia, the United States, UK and New Zealand. Nearly half the participants had over 11 years of experience working with adults with TBI and a quarter had over 20 years of experience. Participants reported that they regularly evaluated the discourse ability of people with TBI, most commonly during spontaneous conversation or with a personal narrative task. Discourse intervention approaches mostly targeted client self-monitoring ability, social skills or conversational interactions. Practice varied dependent on setting, with more SLPs in community or outpatient services undertaking discourse assessment and treatment than in hospital settings. CONCLUSIONS & IMPLICATIONS: Overall, survey respondents' management of spoken discourse aligned with recommendations in the research literature, incorporating an individualized, goal-based approach. Factors affecting the use of discourse in practice included client-specific factors and needs, availability of time for transcription and analysis, and SLPs' knowledge level and confidence with discourse. Increased knowledge of discourse methods and treatment approaches could help inform decision-making for SLPs working in TBI. WHAT THIS PAPER ADDS: What is already known on this subject Spoken discourse is one of the most affected areas of communication for people with TBI. Although recent research has provided guidance on assessment and treatment options for TBI discourse, it is unknown how SLPs manage spoken discourse clinically. What this paper adds to existing knowledge This research adds to the limited research on how SLPs across clinical settings and regions manage discourse assessment and treatment. Respondents' practice was generally aligned with recommendations, featuring individualized, goal-based practice. Potential barriers to discourse implementation included client factors and SLP knowledge, training, and service delivery factors. What are the potential or actual clinical implications of this work? This survey provides evidence that clinical translation is starting to occur in this field, but there remains a need for increased knowledge of assessment and treatment methods, training, and TBI-specific resources to better support SLP practice, particularly relating to transcription. Core reporting outcomes in research on TBI discourse management would assist with translation of the findings to practice.

8.
J Pediatr Gastroenterol Nutr ; 73(6): 710-716, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34292216

RESUMO

OBJECTIVES: Current clinical algorithms position surgery as the last option in pediatric Crohn disease (CD). Studies suggest improved outcomes with earlier surgery, but pediatric postoperative outcomes data in the biologic era are limited. We aimed to describe the preoperative management and postoperative outcomes in a pediatric CD cohort who underwent ileocolic resection (ICR) at a tertiary care inflammatory bowel disease center over the last decade. METHODS: Single-center, retrospective study of pediatric (<18 years) CD patients who underwent ICR between 2008 and 2019 with primary outcome of rate of endoscopic recurrence (Rutgeerts' >i2) at 2 years post-ICR. Key secondary outcomes included endoscopic remission (Rutgeerts' i0), frequency of 30-day postoperative complications, anthropometric changes, and histologic recurrence. Uni- and multivariable analyses examined associations of clinical/laboratory characteristics with endoscopic recurrence. Factors predictive of 30-day complications were also analyzed. RESULTS: Seventy-eight children underwent ICR a median of 17.8 months (interquartile range [IQR] 2.6-53.9) from diagnosis. Median age at diagnosis and surgery was 13.8 (11.1-16.7) and 16.8 years (15.1-17.8), respectively. In the 41 patients with >1 post-operative endoscopy, the rate of endoscopic recurrence was 46% at 2 years (median time to recurrence: 10 [7-20] months). Histologic recurrence was present in 44% in endoscopic remission (κ = 0.11, P = 0.53). Endoscopic recurrence was associated with younger age at diagnosis and longer disease duration. 30-day complications occurred at a rate of 18%; only 1% experienced severe complications. All anthropometric measures significantly improved after surgery. CONCLUSIONS: Given the inherent risk of postoperative recurrence associated with age and disease duration, children would benefit from postoperative surveillance and effective prophylaxis.


Assuntos
Produtos Biológicos , Doença de Crohn , Produtos Biológicos/uso terapêutico , Criança , Colo/patologia , Colo/cirurgia , Colonoscopia , Doença de Crohn/tratamento farmacológico , Humanos , Íleo/patologia , Íleo/cirurgia , Recidiva , Estudos Retrospectivos
9.
Bull Math Biol ; 83(3): 22, 2021 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-33452943

RESUMO

Between Fall 2011 and Fall 2012 students at Utah State University played several rounds of Humans versus Zombies (HvZ), a role-playing variant of tag popular on college campuses. The goal of the game is for the zombies to tag humans, converting them into more zombies. Based on portrayals of 'zombieism' in popular culture, one might treat HvZ as a disease system. However, a traditional SIR model with mass-action dynamics does a poor job of modeling HvZ, leading to the natural question: What mechanisms drive the dynamics of the HvZ system? We use model competition, with Bayesian Information Criterion as arbiter, to answer this question. First, we develop a suite of models with a variety of transmission mechanisms and fit to data from fall 2011. We use model competition to determine which model(s) have the most support from the data, thereby offering insight into driving mechanisms for HvZ. Bootstrapping is used to both assess the significance of individual mechanisms and to determine confidence in the performance of our models. Finally, we test predictions of the best models with data from fall 2012. Results indicate that through both years of the game humans tend to cluster defensively, zombies tend to hunt in groups, some zombies are more proficient hunters, and some humans leave the game.


Assuntos
Conceitos Matemáticos , Modelos Biológicos , Teorema de Bayes , Jogos Recreativos , Humanos , Estudantes , Universidades , Utah
10.
Health Commun ; 36(8): 927-939, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32019346

RESUMO

Despite the importance of cost-of-care conversations between physicians and patients, such discussions are not well understood. We used multiple goals theory to examine the specific goals that are salient in these discussions and how physicians pursue these goals. We used qualitative descriptive coding to analyze the verbatim transcripts from in-depth interviews with 36 primary care physicians. Our analysis identified a number of goals that are commonly salient in cost conversations, including task goals (reducing the cost of care, making treatment decisions, and promoting patient adherence), identity goals (reinforcing their professional identity as a "good doctor," acting as a steward of medical resources, being an advocate for patients, and preventing patient embarrassment), and relational goals (strengthening the physician-patient relationship and mitigating damage to the physician-patient relationship). In addition, participants articulated a number of ways in which these goals compete with each other, making cost conversations challenging. We found that physicians use a common repertoire of rhetorical strategies to manage these goals, including directly addressing cost, avoiding discussion of cost, and falsely reassuring patients about cost concerns. Our analysis revealed that the meaning of the cost conversation explains the connection between physicians' goals and strategies. Specifically, we found that physicians invoke polysemic meanings of cost conversations to achieve their multiple goals using seemingly contradictory strategies. The results of our analysis have implications for building theory and improving practice.


Assuntos
Médicos de Atenção Primária , Comunicação , Objetivos , Humanos , Cooperação do Paciente , Relações Médico-Paciente
11.
Exp Eye Res ; 189: 107836, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31626797

RESUMO

TAK-639 is a topical, 9-amino acid, synthetic, C-type natriuretic peptide analog in development for the treatment of primary open-angle glaucoma and ocular hypertension. This study investigated the impact of TAK-639 on intraocular pressure (IOP), the levels of TAK-639 in aqueous humor, and the pharmacokinetic/pharmacodynamic relationship of TAK-639 following topical ocular administration to normotensive female Dutch belted rabbits, beagle dogs, and cynomolgus monkeys. In the IOP studies, rabbits (n = 6/group) and dogs (n = 8/group) received a single topical ocular dose of TAK-639 0.03%, 0.1%, 0.3%, or 0.6% in the right eye and vehicle in the left eye; monkeys (n = 8/group) received TAK-639 0.1%, 0.3%, 0.6%, 0.9%, or 1.2% in the right eye only. IOP was measured pre dose and at various time points from 0.5 to 24 h post dose for rabbits, and 1-48 h post dose for dogs and monkeys. To assess exposure in aqueous humor, another set of animals received a single ocular dose of TAK-639 0.03%, 0.1%, 0.3%, or 0.6% (rabbits, n = 20/group; dogs, n = 14/group) or TAK-639 0.3%, 0.6%, or 1.2% (monkeys, n = 10/group) in both eyes. Aqueous humor and plasma were collected at the same post dose time points at which IOP was measured. Aqueous humor and plasma TAK-639 concentrations were measured by liquid chromatography-mass spectrometry, and pharmacokinetic parameters were estimated with non-compartmental analysis. Topical ocular administration of TAK-639 resulted in a dose-dependent decrease in IOP, with maximum mean decreases in IOP ranging from -8.90% to -34.4% in the rabbit, from -16.5% to -26.4% in the dog, and from -3.43% to -13.5% in the monkey. The duration of the IOP-lowering effect was 12 h in the rabbit and monkey and 48 h in the dog. TAK-639 exposure in aqueous humor (both maximum concentration and area under the curve) was also dose dependent, with maximum concentration ranging from 0.152 to 93.6 ng/mL (0.03% and 0.6% doses, respectively) in rabbits, 0.490-13.8 ng/mL (0.03% and 0.3% doses, respectively) in dogs, and 1.16-18.1 ng/mL (0.3% and 1.2% doses, respectively) in monkeys. The pharmacokinetic/pharmacodynamic profile, when fitted to an inhibitory sigmoidal model, demonstrated that TAK-639 exposure in aqueous humor correlated well with IOP reduction in these species. The TAK-639 exposure in aqueous humor at half maximal IOP reduction (EC50) was lower in monkey and dog than in rabbit (0.2 and 0.4 vs. 2.0 ng/mL, respectively). In plasma, quantifiable concentrations of TAK-639 were low and detectable predominantly at early time points. In conclusion, in rabbit, dog, and monkey, a single topical ocular drop of TAK-639 had a significant IOP-lowering effect that correlated well with increases in TAK-639 levels in aqueous humor and resulted in minimal systemic exposure of TAK-639.


Assuntos
Anti-Hipertensivos/farmacocinética , Humor Aquoso/metabolismo , Glaucoma de Ângulo Aberto/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Peptídeo Natriurético Tipo C/análogos & derivados , Administração Tópica , Animais , Anti-Hipertensivos/administração & dosagem , Cromatografia Líquida , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Feminino , Glaucoma de Ângulo Aberto/metabolismo , Macaca fascicularis , Coelhos
12.
J Pediatr Gastroenterol Nutr ; 68(3): 343-347, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30320666

RESUMO

OBJECTIVES: Recurrent Clostridium difficile infection (RCDI) increases morbidity and mortality in patients with inflammatory bowel disease (IBD). Fecal microbiota transplant (FMT) is known to be very effective for RCDI in non-IBD patients with cure rates up to 91%. The same success rates of FMT have not been reported in patients with IBD with RCDI, and the data in pediatrics are limited. We aimed to determine the effectiveness of FMT for RCDI in established pediatric patients with IBD. METHODS: We performed a retrospective chart review of pediatric patients with IBD and RCDI (≥3 episodes) who underwent FMT via colonoscopy at a tertiary care IBD center. The primary outcome was the rate of RCDI within 60 days post-FMT. The secondary outcomes were recurrence rate by 6 months, rate of colectomy, and time to recurrence. RESULTS: Of the 8 eligible patients, 6 had ulcerative colitis, 1 had IBD-unspecified, and 1 had Crohn disease. Median (interquartile range) age was 13 (11-14) years. All patients were on vancomycin at FMT. Two patients (25%) had RCDI by 60 days post-FMT and another 3 patients had RCDI between 60 days and 6 months. The median time to recurrence was 101 (40-139) days. Two patients (25%) who developed recurrence went to colectomy after FMT. CONCLUSIONS: With a cure rate of 75% at 60 days, FMT administered for the treatment of RCDI may be an effective treatment option in pediatric IBD. However, there appears to be a significant rate of late recurrence of C difficile infection after 60 days in these patients.


Assuntos
Infecções por Clostridium/complicações , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal , Doenças Inflamatórias Intestinais/complicações , Adolescente , Antibacterianos/administração & dosagem , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Recidiva , Estudos Retrospectivos , Índice de Gravidade de Doença , Vancomicina/administração & dosagem
13.
J Pediatr Gastroenterol Nutr ; 69(4): 455-460, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31136563

RESUMO

BACKGROUND: Approximately 10% of children with ulcerative colitis (UC) undergo colectomy with ileal pouch-anal anastomosis (IPAA). We aimed to describe the postoperative outcomes, with an emphasis on chronic pouch inflammation including de novo Crohn disease (CD) at a tertiary care inflammatory bowel disease center. METHODS: Electronic medical records of all children who underwent colectomy ≤18 years between 2008 and 2017 were reviewed. Clinical and laboratory data were recorded. Primary outcome was frequency of chronic pouch inflammation including de novo CD. Secondary outcomes included early (≤30 days from index surgery) and late postoperative complications. Descriptive statistics (median and interquartile range) summarized the data and univariate analysis tested associations with outcomes. RESULTS: Fifty-eight children underwent colectomy and 56 completed IPAA. Median age at diagnosis was 14 years (12-16.2) and at colectomy 16.2 years (14.2-17.7) with median follow-up of 13 months (5-43). Sixty-six percent underwent 3-stage IPAA and 78% were biologic exposed. Eleven had chronic pouchitis, 73% antibiotic refractory and 25% met criteria for de novo CD by median of 19 months (9-41). A total of 21% and 50% experienced early and late surgical complications, most commonly ileus and recurrent IPAA stricture. The pouch failure rate was 3.6%. Chronic pouch inflammation was associated with a later diagnosis of de novo CD (P = 0.0025). CONCLUSIONS: In pediatric UC, CD is not uncommon after IPAA. Chronic pouch inflammation often precedes a diagnosis of de novo CD. Families should be informed of the short- and long-term outcomes in children before UC surgery.


Assuntos
Colite Ulcerativa/cirurgia , Doença de Crohn/epidemiologia , Pouchite/epidemiologia , Proctocolectomia Restauradora/efeitos adversos , Adolescente , Criança , Doença de Crohn/etiologia , Feminino , Humanos , Masculino , Prontuários Médicos , Cidade de Nova Iorque/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pouchite/etiologia , Estudos Retrospectivos
14.
BMC Geriatr ; 19(1): 190, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315578

RESUMO

BACKGROUND: The value of biomarkers for diagnosing bacterial infections in older outpatients is uncertain and limited official guidance exists for clinicians in this area. The aim of this review is to critically appraise and evaluate biomarkers for diagnosing bacterial infections in older adults (aged 65 years and above). METHODS: We searched Medline, Embase, Web of Science and the Cochrane Library, from inception to January 2018. We included studies assessing the diagnostic accuracy of blood, urinary, and salivary biomarkers in diagnosing bacterial infections in older adults. The QUADAS-2 tool was used to assess study quality. RESULTS: We identified 11 eligible studies of moderate quality (11,034 participants) including 51 biomarkers at varying thresholds for diagnosing bacterial infections. An elevated Procalcitonin (≥ 0.2 ng/mL) may help diagnose bacteraemia in older adults [+ve LR range 1.50 to 2.60]. A CRP ≥ 50 mg/L only raises the probability of bacteraemia by 5%. A positive urine dipstick aids diagnosis of UTI (+ve LR range 1.23 to 54.90), and absence helps rule out UTI (-ve LR range 0.06 to 0.46). An elevated white blood cell count is unhelpful in diagnosing intra-abdominal infections (+ve LR range 0.75 to 2.62), but may aid differentiation of bacterial infection from other acute illness (+ve LR range 2.14 to 7.12). CONCLUSIONS: The limited available evidence suggests that many diagnostic tests useful in younger patients, do not help to diagnose bacterial infections in older adults. Further evidence from high quality studies is urgently needed to guide clinical practice. Until then, symptoms and signs remain the mainstay of diagnosis in community based populations.


Assuntos
Assistência Ambulatorial/tendências , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Assistência Ambulatorial/métodos , Biomarcadores/metabolismo , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/tendências , Humanos , Estudos Observacionais como Assunto/métodos
15.
Gastroenterology ; 163(4): 1124-1125, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35809614
18.
Augment Altern Commun ; 34(3): 242-253, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30231643

RESUMO

The aim of this review was to critically synthesize barriers and facilitators to the use of AAC systems by children with autism spectrum disorder (ASD) and their communication partners. Qualitative data related to barriers and facilitators were synthesized from 42 studies located using a systematic search. A diverse range of studies was examined in order to identify the span of barriers and facilitators reported in the literature. Included studies comprised quasi-experimental, non-experimental, and qualitative study designs. The full range of unaided, low-tech aided, and high-tech aided AAC systems were reported across the included studies. The critical synthesis identified 5 themes to which barriers and facilitators are related: (a) Intervention Services and Service Providers, (b) AAC Systems and Technologies (c), Communication Partners of Children with ASD, (d) Parents of Children with ASD, and (e) Children with ASD. The findings suggest that barriers and facilitators to the use of AAC vary across individuals, AAC modalities, and environments. By identifying barriers and facilitators to the use of AAC experienced by children with ASD and their communication partners, service providers might be better equipped to support these children and their communication partners. Clinical implications and future research directions are discussed.


Assuntos
Transtorno do Espectro Autista/reabilitação , Auxiliares de Comunicação para Pessoas com Deficiência , Transtornos da Comunicação/reabilitação , Pessoal de Saúde , Pais , Criança , Comunicação , Humanos , Relações Interpessoais , Competência Profissional , Pesquisa Qualitativa
19.
Brain Inj ; 31(13-14): 1889-1902, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28945465

RESUMO

BACKGROUND: There has been limited empirical speech-language pathology (SLP) study of language and cognitive communication during post-traumatic amnesia (PTA) and the early stages after TBI. The purpose of the current research was to explore the potential means and utility of assessing cognitive communication during PTA and the post-acute recovery period. METHOD: This research used a longitudinal mixed methods design to describe language and cognitive communication assessment and recovery profiles of three patients with TBI. Cognitive communication was assessed with repeated standardised and non-standardised methods during PTA (rated with Westmead PTA Scale) and at follow-up 3 months after PTA emergence. RESULTS: All participants demonstrated a profile of language and cognitive communication strengths and weaknesses during PTA and the post-acute period, also evident at follow-up. Improvement occurred gradually throughout PTA, although with individual fluctuation across test occasions. There was no marked change in communication function immediately before and after PTA emergence, indicating that cognitive communication ability and those functions measured on the Westmead PTA Scale (memory and orientation) did not recover at the same rate. CONCLUSION: It was feasible to assess language and cognitive communication throughout PTA and the post-acute period, and early assessment results were relevant to the patient's ongoing communicative function. It is suggested that early and repeated SLP assessment may contribute to the prediction of persisting cognitive communication issues.


Assuntos
Amnésia/complicações , Amnésia/etiologia , Lesões Encefálicas Traumáticas/complicações , Transtornos Cognitivos/etiologia , Transtornos da Comunicação/etiologia , Adulto , Feminino , Humanos , Testes de Linguagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Índices de Gravidade do Trauma
20.
Brain Inj ; 31(10): 1320-1330, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28657359

RESUMO

BACKGROUND: Social communication impairment is a persisting and debilitating consequence of traumatic brain injury (TBI). However, there has been little empirical speech-language pathology (SLP) study focusing on the early stage of recovery after TBI, including during post-traumatic amnesia (PTA). This research reports on social communication presentation and recovery during late PTA and the post-acute period, assessed with standardized measures. METHOD: Using mixed-methods case study research, four participants with severe TBI were assessed with social communication assessment measures over the later stages of PTA and/or at PTA emergence, and at follow-up three months later. Assessment tools included the Measure of Cognitive Linguistic Abilities Family Questionnaire, the La Trobe Communication Questionnaire and The Profile of Pragmatic Impairment in Communication and included patient and friend/family perspectives. RESULTS: It was possible to identify a profile of social communication disorder on SLP measures for participants during PTA that persisted at follow-up, but with decreased severity. Self and friend/family member ratings of social communication indicated an increased awareness of social difficulty at three months after PTA emergence. CONCLUSION: Findings provided information about presentation and course of recovery of social communication ability for participants in the early stage of rehabilitation after TBI. These findings have implications for timing and methods of SLP assessment during PTA.


Assuntos
Amnésia/psicologia , Lesões Encefálicas Traumáticas/psicologia , Transtornos da Comunicação/diagnóstico , Comunicação , Comportamento Social , Adulto , Amnésia/etiologia , Lesões Encefálicas Traumáticas/complicações , Cognição/fisiologia , Transtornos da Comunicação/etiologia , Transtornos da Comunicação/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Patologia da Fala e Linguagem , Inquéritos e Questionários
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