RESUMO
BACKGROUND & AIMS: Tumor necrosis factor inhibitors, including infliximab and adalimumab, are a mainstay of pediatric Crohn's disease therapy; however, nonresponse and loss of response are common. As combination therapy with methotrexate may improve response, we performed a multicenter, randomized, double-blind, placebo-controlled pragmatic trial to compare tumor necrosis factor inhibitors with oral methotrexate to tumor necrosis factor inhibitor monotherapy. METHODS: Patients with pediatric Crohn's disease initiating infliximab or adalimumab were randomized in 1:1 allocation to methotrexate or placebo and followed for 12-36 months. The primary outcome was a composite indicator of treatment failure. Secondary outcomes included anti-drug antibodies and patient-reported outcomes of pain interference and fatigue. Adverse events (AEs) and serious AEs (SAEs) were collected. RESULTS: Of 297 participants (mean age, 13.9 years, 35% were female), 156 were assigned to methotrexate (110 infliximab initiators and 46 adalimumab initiators) and 141 to placebo (102 infliximab initiators and 39 adalimumab initiators). In the overall population, time to treatment failure did not differ by study arm (hazard ratio, 0.69; 95% CI, 0.45-1.05). Among infliximab initiators, there were no differences between combination and monotherapy (hazard ratio, 0.93; 95% CI, 0.55-1.56). Among adalimumab initiators, combination therapy was associated with longer time to treatment failure (hazard ratio, 0.40; 95% CI, 0.19-0.81). A trend toward lower anti-drug antibody development in the combination therapy arm was not significant (infliximab: odds ratio, 0.72; 95% CI, 0.49-1.07; adalimumab: odds ratio, 0.71; 95% CI, 0.24-2.07). No differences in patient-reported outcomes were observed. Combination therapy resulted in more AEs but fewer SAEs. CONCLUSIONS: Among adalimumab but not infliximab initiators, patients with pediatric Crohn's disease treated with methotrexate combination therapy experienced a 2-fold reduction in treatment failure with a tolerable safety profile. CLINICALTRIALS: gov, Number: NCT02772965.
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Metotrexato , Inibidores do Fator de Necrose Tumoral , Criança , Humanos , Feminino , Adolescente , Masculino , Metotrexato/efeitos adversos , Adalimumab/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Infliximab/efeitos adversos , Fator de Necrose Tumoral alfa , Resultado do TratamentoRESUMO
INTRODUCTION: Obesity is common among patients with pediatric Crohn's disease (PCD). Some adult studies suggest obese patients respond less well to anti-tumor necrosis factor (TNF) treatment. This study sought compares anti-TNF response and anti-TNF levels between pediatric patients with normal and high body mass index (BMI). METHODS: The COMBINE trial compared anti-TNF monotherapy with combination therapy with methotrexate in patients with PCD. In this secondary analysis, a comparison of time-to-treatment failure among patients with normal BMI vs BMI Z -score >1, adjusting for prescribed anti-TNF (infliximab [IFX] or adalimumab [ADA]), trial treatment assignment (combination vs monotherapy), and relevant covariates. Median anti-TNF levels across BMI category was also examined. RESULTS: Of 224 participants (162 IFX initiators and 62 ADA initiators), 111 (81%) had a normal BMI and 43 (19%) had a high BMI. High BMI was associated with treatment failure among ADA initiators (7/10 [70%] vs 12/52 [23%], hazard ratio 0.29, P = 0.007) but not IFX initiators. In addition, ADA-treated patients with a high BMI had lower ADA levels compared with those with normal BMI (median 5.8 vs 12.8 µg/mL, P = 0.02). IFX trough levels did not differ between BMI groups. DISCUSSION: Overweight and obese patients with PCD are more likely to experience ADA treatment failure than those with normal BMI. Higher BMI was associated with lower drug trough levels. Standard ADA dosing may be insufficient for overweight children with PCD. Among IFX initiators, there was no observed difference in clinical outcomes or drug levels, perhaps due to weight-based dosing and/or greater use of proactive drug monitoring.
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Adalimumab , Índice de Massa Corporal , Doença de Crohn , Quimioterapia Combinada , Infliximab , Metotrexato , Fator de Necrose Tumoral alfa , Humanos , Doença de Crohn/tratamento farmacológico , Masculino , Feminino , Infliximab/uso terapêutico , Adalimumab/uso terapêutico , Criança , Adolescente , Metotrexato/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Falha de Tratamento , Fármacos Gastrointestinais/uso terapêutico , Obesidade Infantil/complicações , Obesidade Infantil/tratamento farmacológicoRESUMO
OBJECTIVE: We aimed to determine whether mepolizumab, an anti-IL-5 antibody, was more effective than placebo for improving dysphagia symptoms and decreasing oesophageal eosinophil counts in eosinophilic oesophagitis (EoE). METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled, trial. In the first part, patients aged 16-75 with EoE and dysphagia symptoms (per EoE Symptom Activity Index (EEsAI)) were randomised 1:1 to 3 months of mepolizumab 300 mg monthly or placebo. Primary outcome was change in EEsAI from baseline to month 3 (M3). Secondary outcomes included histological, endoscopic and safety metrics. In part 2, patients initially randomised to mepolizumab continued 300 mg monthly for 3 additional months (mepo/mepo), placebo patients started mepolizumab 100 mg monthly (pbo/mepo), and outcomes were reassessed at month 6 (M6). RESULTS: Of 66 patients randomised, 64 completed M3, and 56 completed M6. At M3, EEsAI decreased 15.4±18.1 with mepolizumab and 8.3±18.0 with placebo (p=0.14). Peak eosinophil counts decreased more with mepolizumab (113±77 to 36±43) than placebo (146±94 to 160±133) (p<0.001). With mepolizumab, 42% and 34% achieved histological responses of <15 and ≤6 eos/hpf compared with 3% and 3% with placebo (p<0.001 and 0.02). The change in EoE Endoscopic Reference Score at M3 was also larger with mepolizumab. At M6, EEsAI decreased 18.3±18.1 points for mepo/mepo and 18.6±19.2 for pbo/mepo (p=0.85). The most common adverse events were injection-site reactions. CONCLUSIONS: Mepolizumab did not achieve the primary endpoint of improving dysphagia symptoms compared with placebo. While eosinophil counts and endoscopic severity improved with mepolizumab at 3 months, longer treatment did not yield additional improvement. TRIAL REGISTRATION NUMBER: NCT03656380.
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Transtornos de Deglutição , Esofagite Eosinofílica , Adulto , Humanos , Adolescente , Esofagite Eosinofílica/tratamento farmacológico , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/etiologia , Resultado do Tratamento , Anticorpos Monoclonais Humanizados , Eosinófilos/patologia , Método Duplo-CegoRESUMO
Acute pouchitis is the most common complication after a restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for ulcerative colitis, affecting 40% of patients within the first year after surgery.1 Although up to 80% of patients can develop pouchitis symptoms,2,3 substantial gaps remain in our understanding of the epidemiology and burden of pouchitis. Administrative claims have been used to advance the knowledge of other areas of inflammatory bowel disease4-6; however, a prerequisite to conducting such studies in pouchitis is a valid, reliable case-finding algorithm. Given concerns that the International Classification of Diseases (ICD) code for pouchitis may not be reliably used by clinicians (resulting in a low sensitivity), the objectives of the study were to (1) develop a series of case-finding definitions for acute pouchitis and (2) compare the performance of these case-finding definitions to that of a single ICD code for pouchitis.
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Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Pouchite , Proctocolectomia Restauradora , Colite Ulcerativa/cirurgia , Humanos , Pouchite/diagnóstico , Pouchite/epidemiologia , Proctocolectomia Restauradora/efeitos adversosRESUMO
Macrophages (MΦs) are heterogeneous and metabolically flexible, with metabolism strongly affecting immune activation. A classic response to proinflammatory activation is increased flux through glycolysis with a downregulation of oxidative metabolism, whereas alternative activation is primarily oxidative, which begs the question of whether targeting glucose metabolism is a viable approach to control MΦ activation. We created a murine model of myeloid-specific glucose transporter GLUT1 (Slc2a1) deletion. Bone marrow-derived MΦs (BMDM) from Slc2a1M-/- mice failed to uptake glucose and demonstrated reduced glycolysis and pentose phosphate pathway activity. Activated BMDMs displayed elevated metabolism of oleate and glutamine, yet maximal respiratory capacity was blunted in MΦ lacking GLUT1, demonstrating an incomplete metabolic reprogramming. Slc2a1M-/- BMDMs displayed a mixed inflammatory phenotype with reductions of the classically activated pro- and anti-inflammatory markers, yet less oxidative stress. Slc2a1M-/- BMDMs had reduced proinflammatory metabolites, whereas metabolites indicative of alternative activation-such as ornithine and polyamines-were greatly elevated in the absence of GLUT1. Adipose tissue MΦs of lean Slc2a1M-/- mice had increased alternative M2-like activation marker mannose receptor CD206, yet lack of GLUT1 was not a critical mediator in the development of obesity-associated metabolic dysregulation. However, Ldlr-/- mice lacking myeloid GLUT1 developed unstable atherosclerotic lesions. Defective phagocytic capacity in Slc2a1M-/- BMDMs may have contributed to unstable atheroma formation. Together, our findings suggest that although lack of GLUT1 blunted glycolysis and the pentose phosphate pathway, MΦ were metabolically flexible enough that inflammatory cytokine release was not dramatically regulated, yet phagocytic defects hindered MΦ function in chronic diseases.
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Modelos Animais de Doenças , Transportador de Glucose Tipo 1/metabolismo , Macrófagos/metabolismo , Animais , Transportador de Glucose Tipo 1/deficiência , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , FenótipoRESUMO
OBJECTIVES: Obese habitus can lead to adverse outcomes for colorectal surgeries due to technical challenges and pro-inflammatory immune mediators associated with excess adipose tissue. Surgical planning, pre-operative risk stratification, and patient counseling of pediatric Crohn disease (CD) patients are limited by the scarcity of data on this topic. We sought to determine the association between obesity and hospital readmission in children with CD undergoing intestinal resection. METHODS: We used the National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database to identify pediatric CD patients undergoing intestinal resection between 2012 and 2018. We calculated age- and sex-adjusted body mass index (BMI) z scores using CDC population statistics. We used logistic regression to evaluate the association between obesity and readmission compared to average-BMI patients adjusting for age, race, sex, steroid exposure, disease activity, and surgery type. RESULTS: We evaluated 1258 pediatric CD intestinal resections occurring between 2012 and 2018. Patients were predominantly adolescent (91%), white (84%), and male (56%). Those with average BMI comprised 50% of the cohort, 31% were underweight, 11% overweight, and 8% obese. The overall 30-day hospital readmission rate was 8.8%. Compared to those with average BMI, obese children had a 2-fold (adjusted odds ratio 1.9, 95% confidence interval 1.0-3.8) increase in risk of hospital readmission. CONCLUSIONS: Obese patients undergoing intestinal resection face a higher risk of 30-day hospital readmission compared to average-BMI patients. These results can inform pre-surgical risk counseling and underscore the need for long-term weight management strategies to aid in risk reduction for obese children with CD at risk of future surgery.
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Doença de Crohn , Obesidade Infantil , Adolescente , Índice de Massa Corporal , Criança , Doença de Crohn/complicações , Doença de Crohn/cirurgia , Humanos , Masculino , Readmissão do Paciente , Obesidade Infantil/complicações , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Despite decreasing prevalence over the last several decades, cigarette smoking remains the leading cause of preventable death and disease, underscoring the need for innovative, effective solutions. Pivot is a novel, inclusive smoking cessation program designed for smokers along the entire spectrum of readiness to quit. Pivot leverages proven methods and technological advancements, including a personal portable breath carbon monoxide sensor, smartphone app, and in-app text-based coaching. We previously reported outcomes from the end of active Pivot program participation in 319 adult smokers. Herein, we report longer-term follow up in this cohort. OBJECTIVE: The aim of this study was to assess and report participant outcomes 3 months after completion of Pivot, including smoking behavior, quit rates, continuous abstinence rates and durability, and predictors of abstinence. METHODS: This prospective remote cohort study included US-based cigarette smokers aged 18 to 65 years who smoked ≥5 cigarettes per day (CPD). Three months after completion of active participation in Pivot, final follow-up data were collected via an online questionnaire. Outcomes included smoking behavior (CPD and quit attempts), self-reported quit rates (7- and 30-day point prevalence abstinence [PPA]), and continuous abstinence rates (proportion who achieved uninterrupted abstinence) and duration. Exploratory regression analyses were performed to identify baseline characteristics associated with achievement of 7-day PPA, 30-day PPA, and continuous abstinence. RESULTS: A total of 319 participants completed onboarding (intention-to-treat [ITT]); 288/319 participants (90.3%) completed follow up (completers) at a mean of 7.2 (SD 1.2) months after onboarding. At final follow up, CPD were reduced by 52.6% (SE 2.1; P<.001) among all 319 participants, and most completers (152/288, 52.8%) reduced their CPD by at least 50%. Overall, most completers (232/288, 80.6%) made at least one quit attempt. Quit rates increased after the end of Pivot; using ITT analyses, 35.4% (113/319) achieved 7-day PPA and 31.3% (100/319) achieved 30-day PPA at final follow up compared with 32.0% (102/319) and 27.6% (88/319), respectively, at the end of the Pivot program. Continuous abstinence was achieved in about a quarter of those who onboarded (76/319, 23.8%) and in most who reported 30-day PPA at the end of Pivot (76/88, 86.4%), with a mean abstinence duration of 5.8 (SD 0.6) months. In exploratory regression analyses, lower baseline CPD, more positive baseline attitudes reflecting higher self-efficacy (higher confidence to quit and lower perceived difficulty of quitting), and higher education were associated with achieving abstinence. CONCLUSIONS: This study provides the first longer-term outcomes of the Pivot smoking cessation program. At final follow up, quit rates increased and continuous abstinence was favorable; the majority who achieved abstinence at the end of Pivot sustained abstinence throughout follow up. Decreases in CPD persisted and most participants made a quit attempt. Overall, final follow-up outcomes were stable or improved when compared to previous outcomes from the end of the program. These findings validate earlier results, and suggest that Pivot is an effective and durable solution for smoking cessation. TRIAL REGISTRATION: ClinicalTrials.gov NCT03295643; https://clinicaltrials.gov/ct2/show/NCT03295643.
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Testes Respiratórios/métodos , Tutoria/métodos , Aplicativos Móveis/tendências , Abandono do Hábito de Fumar/métodos , Fumar/tendências , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Autorrelato , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND & AIMS: The prevalence of diverticulosis differs with demographic features of patients, but evidence is limited. Well-defined demographic studies are necessary to understand diverticulosis biology. We estimated the prevalence of diverticulosis among patients of different ages, sexes, and races and ethnicities and calculated odds ratios. DESIGN: Using data from an endoscopic database, we identified 271,181 colonoscopy procedures performed from 2000 through 2012 at 107 sites in the United States. Our analysis included individuals 40 years and older who underwent colonoscopy examination for average-risk screening. The outcome was any reported diverticulosis on colonoscopy. Multivariate analyses were performed using logistic regression to estimate odds ratios (ORs) and 95% CI values, adjusting for confounding variables. RESULTS: The prevalence of diverticulosis increased with age in men and women of all races and ethnicities. Women 40-49 years old had significantly lower odds of any diverticulosis (OR, 0.71; 95% CI, 0.63-0.80) compared with men 40-49 years old, after adjustment. The strength of this association decreased with age. Compared with non-Hispanic white individuals, non-Hispanic black individuals (OR, 0.80; 95% CI, 0.77-0.83) and Asian/Pacific Islanders (OR, 0.38; 95% CI, 0.35-0.41) had lower odds of any diverticulosis. However, non-Hispanic black individuals (OR, 1.53, 95% CI, 1.44-1.62) had increased odds of any proximal diverticulosis, whereas Asian/Pacific Islanders (OR, 3.12; 95% CI, 2.67-3.66) had increased odds of only proximal diverticulosis. CONCLUSIONS: In an analysis of data from 271,181 colonoscopy procedures, diverticulosis was less prevalent in women compared with men in the same age groups, indicating that sex hormones might affect pathogenesis. Differences in the odds of diverticulosis by race and ethnicity indicate a genetic contribution to risk.
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Colonoscopia , Divertículo , Adulto , Etnicidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND & AIMS: Obesity has been associated with an increased risk of colonic diverticulosis. Evidence for this association is limited. We assessed whether anthropometric measures of obesity were associated with colonic diverticulosis. METHODS: We analyzed data from a prospective study of 623 patients undergoing screening colonoscopies from 2013 through 2015; colonoscopies included examinations for diverticulosis. Body measurements were made the day of the procedure. Multivariate analyses were performed using modified Poisson regression to estimate prevalence ratios (PRs) and 95% CIs while adjusting for confounding variables. All analyses were stratified by sex. RESULTS: Among men, there was no association between any measure of obesity and diverticulosis. After adjustment, women with an obese body mass index (BMI ≥ 30) had an increased risk of any diverticulosis (PR, 1.48; 95% CI, 1.08-2.04) compared with women with a normal body mass index (BMI 18.5-24.9). The strength of this association was greater for more than 5 diverticula (PR, 2.05; 95% CI, 1.23-3.40). There was no significant association between measures of central obesity and diverticulosis in women. Stratified by sex, colonic diverticulosis was significantly less prevalent in women compared with men before the age of 51 years (29% vs 45%, P = .06). The prevalence of diverticulosis did not differ by sex in older age groups. CONCLUSIONS: In an analysis of data from 623 patients undergoing screening colonoscopies, we found that obesity (BMI ≥30) significantly increased the risk of colonic diverticulosis in women but not men. Colonic diverticulosis was less prevalent in premenopausal-age women compared with similar-age men. These findings suggest that sex hormones may influence the development of diverticulosis.
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Diverticulose Cólica/diagnóstico , Obesidade/complicações , Adulto , Antropometria , Índice de Massa Corporal , Tamanho Corporal , Colonoscopia/métodos , Diverticulose Cólica/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Estudos Prospectivos , Fatores de Risco , Fatores SexuaisRESUMO
BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is chronic and recurs if treatment is discontinued. We aimed to determine rates of recurrence, and whether initial treatment with oral viscous budesonide (OVB) resulted in less recurrence than fluticasone from a multidose inhaler (MDI). METHODS: This was the observation phase of a randomized, double-blind, double-dummy trial comparing OVB with MDI for initial EoE treatment. Subjects with a histologic response (<15 eosinophils/high-power field) in the trial entered an observation phase in which treatment was discontinued and symptoms were monitored. Patients underwent an endoscopy or a biopsy when symptoms recurred or at 1 year. We analyzed time to symptom recurrence and assessed endoscopic severity and histologic relapse (≥15 eosinophils/high-power field) at follow-up endoscopy. RESULTS: Thirty-three of the 58 subjects (57%) had symptom recurrence before 1 year. The overall median time to symptom recurrence was 244 days. There was no difference in the rate of symptom recurrence for subjects treated with OVB vs MDI (hazard ratio, 1.04; 95% CI, 0.52-2.08). At symptom recurrence, 78% of patients had histologic relapse. The patients had significant increases in mean Dysphagia Symptom Questionnaire score (3.8 vs 8.7; P < .001), and the EoE Endoscopic Reference Score (1.3 vs 4.6; P < .001) compared with end of treatment. CONCLUSIONS: EoE disease activity recurred rapidly after initial histologic response to topical steroids (either OVB or MDI). Because most subjects had recurrent endoscopic and histologic signs not reliably detected by symptoms, maintenance therapy should be recommended in EoE patients achieving histologic response to topical steroids. Clinicaltrials.gov no: NCT02019758.
Assuntos
Esofagite Eosinofílica , Anti-Inflamatórios/uso terapêutico , Esofagite Eosinofílica/tratamento farmacológico , Esofagoscopia , Humanos , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Topical steroid treatments for eosinophilic esophagitis (EoE) include swallowed fluticasone from a multi-dose inhaler (MDI) or oral viscous budesonide (OVB) slurry, but the 2 have never been compared. We assessed whether OVB was more effective than MDI for initial treatment of patients with EoE. METHODS: In a double-blind, double-dummy trial, patients with a new diagnosis of EoE were randomly assigned to groups given 8 weeks of either OVB (1 mg/4 mL) twice daily plus a placebo inhaler (n = 56) or fluticasone MDI (880 µg) twice daily plus a placebo slurry (n = 55). Primary outcomes were post-treatment maximum eosinophil counts per high-power field (eos/hpf) and a validated dysphagia score (dysphagia symptom questionnaire [DSQ]) at week 8. Secondary outcomes included endoscopic severity (validated EoE endoscopic reference score), histologic response (<15 eos/hpf), and safety. RESULTS: In a modified intention-to-treat analysis, the subjects had baseline peak eosinophil counts of 73 and 77 eos/hpf in the OVB and MDI groups, respectively, and DSQ scores of 11 and 8. Post-treatment eosinophil counts were 15 and 21 in the OVB and MDI groups, respectively (P = .31), with 71% and 64% achieving histologic response (P = .38). DSQ scores were 5 and 4 in the OVB and MDI groups (P = .70). Similar trends were noted for post-treatment total EoE endoscopic reference scores (2 vs 3; P = .06). Esophageal candidiasis developed in 12% of patients receiving OVB and 16% receiving MDI; oral thrush was observed in 3% and 2%, respectively. CONCLUSIONS: In a randomized clinical trial, initial treatment of EoE with either OVB or fluticasone MDI produced a significant decrease in esophageal eosinophil counts and improved dysphagia and endoscopic features. However, OVB was not superior to MDI, so either is an acceptable treatment for EoE. ClinicalTrials.gov ID NCT02019758.
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Budesonida/uso terapêutico , Esofagite Eosinofílica/tratamento farmacológico , Fluticasona/uso terapêutico , Glucocorticoides/uso terapêutico , Administração Oral , Administração Tópica , Adolescente , Adulto , Esofagite Eosinofílica/patologia , Esofagoscopia , Feminino , Humanos , Masculino , Inaladores Dosimetrados , Pessoa de Meia-Idade , Resultado do Tratamento , Anel Vascular , Adulto JovemRESUMO
BACKGROUND: Tobacco use is the leading cause of preventable morbidity and mortality. Existing evidence-based treatments are underutilized and have seen little recent innovation. The success of personal biofeedback interventions in other disease states portends a similar opportunity in smoking cessation. The Pivot Breath Sensor is a personal interactive FDA-cleared (over-the-counter) device that measures carbon monoxide (CO) in exhaled breath, enabling users to link their smoking behavior and CO values, and track their progress in reducing or quitting smoking. OBJECTIVE: The objective of this study is to assess the Pivot Breath Sensor in people who smoke cigarettes, evaluating changes in attitudes toward quitting smoking, changes in smoking behavior, and use experience. METHODS: US adults (18-80 years of age, ≥10 cigarettes per day [CPD]) were recruited online for this remote 12-week study. Participants completed a screening call, informed consent, and baseline questionnaire, and then were mailed their sensor. Participants were asked to submit 4 or more breath samples per day and complete questionnaires at 1-4, 8, and 12 weeks. Outcomes included attitudes toward quitting smoking (Stage of Change, success to quit, and perceived difficulty of quitting), smoking behavior (quit attempts, CPD reduction, and 7-, 30-day point prevalence abstinence [PPA]), and use experience (impact and learning). RESULTS: Participants comprised 234 smokers, mean age 39.9 (SD 11.3) years, 52.6% (123/234) female, mean CPD 20.3 (SD 8.0). The 4- and 12-week questionnaires were completed by 92.3% (216/234) and 91.9% (215/234) of participants, respectively. Concerning attitude outcomes, at baseline, 15.4% (36/234) were seriously thinking of quitting in the next 30 days, increasing to 38.9% (84/216) at 4 weeks and 47.9% (103/215) at 12 weeks (both P<.001). At 12 weeks, motivation to quit was increased in 39.1% (84/215), unchanged in 54.9% (118/215), and decreased in 6.0% (13/215; P<.001). Additional attitudes toward quitting improved from baseline to 12 weeks: success to quit 3.3 versus 5.0 (P<.001) and difficulty of quitting 2.8 versus 4.3 (P<.001). Regarding smoking behavior, at 4 weeks, 28.2% (66/234) had made 1 or more quit attempts (≥1 day of abstinence), increasing to 48.3% (113/234) at 12 weeks. At 4 weeks, 23.1% (54/234) had reduced CPD by 50% or more, increasing to 38.5% (90/234) at 12 weeks. At 12 weeks, CPD decreased by 41.1% from baseline (P<.001), and 7- and 30-day PPA were 12.0% (28/234) and 6.0% (14/234), respectively. Concerning use experience, 75.3% (171/227) reported the sensor increased their motivation to quit. More than 90% (>196/214) indicated the sensor taught them about their CO levels and smoking behavior, and 73.1% (166/227) reported that seeing their CO values made them want to quit smoking. CONCLUSIONS: Use of the Pivot Breath Sensor resulted in a significant increase in motivation to quit, a reduction in CPD, and favorable quit attempt rates. These outcomes confer increased likelihood of quitting smoking. Accordingly, the results support a role for biofeedback via personal CO breath sampling in smoking cessation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04133064; https://clinicaltrials.gov/ct2/show/NCT04133064.
Assuntos
Testes Respiratórios/instrumentação , Monóxido de Carbono/química , Fumaça/análise , Fumar/patologia , Fumar Tabaco/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
BACKGROUND & AIMS: Adults with ulcerative colitis (UC) who undergo colectomy at high-volume centers have better outcomes and fewer complications than those at low-volume centers. We aimed to evaluate the hospital volume of total abdominal colectomy (TAC) for pediatric patients with UC and explore time trends in the proportion of colectomies performed at high-volume centers. We then evaluated the association between hospital colectomy volume and complications. METHODS: We performed a cross-sectional analysis of pediatric patients (age, ≤18 y) hospitalized for UC using the Kids' Inpatient Database, a nationally representative database of pediatric hospitalizations. We identified UC hospitalizations with a procedural code (International Classification of Diseases, 9th or 10th revision) for TAC from 1997 through 2016. We defined complications using diagnosis codes adapted from published algorithms. We defined high-volume as hospitals that performed 10 or more TACs annually. We used multivariate statistics to evaluate the association between hospital volume and in-hospital complications. RESULTS: A total of 1453 hospitalizations of children with UC included a TAC (2306 colectomies nationwide). A total of 766 hospitals performed 1 or more annual colectomies and only 36 (4.7%) were high-volume hospitals, accounting for 21% of colectomies. The proportion of colectomies at high-volume hospitals decreased over time. The absolute risk of complication was 16% at high-volume centers compared with 22% at low-volume centers (adjusted odds ratio, 0.7; 95% CI, 0.5-0.9). The effect of annual TAC volume on complication risk was not statistically significant for nonemergent admissions. CONCLUSIONS: Pediatric patients with UC who undergo colectomy at high-volume centers have fewer complications. However, only a small proportion of pediatric colectomies (<5%) are performed at high-volume centers.
Assuntos
Colectomia/estatística & dados numéricos , Colite Ulcerativa/cirurgia , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Negro ou Afro-Americano , Criança , Pré-Escolar , Colectomia/tendências , Estudos Transversais , Feminino , Hispânico ou Latino , Humanos , Íleus/epidemiologia , Seguro Saúde/estatística & dados numéricos , Modelos Logísticos , Masculino , Medicaid/estatística & dados numéricos , Análise Multivariada , Atelectasia Pulmonar/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia , Estados Unidos/epidemiologia , População BrancaRESUMO
BACKGROUND & AIMS: Colonic diverticulosis has been reported to be associated with low-grade mucosal inflammation, possibly leading to chronic gastrointestinal symptoms. However, there is poor evidence for this association. We aimed to determine mucosal inflammation and whether diverticula are associated with chronic gastrointestinal symptoms. We explored whether inflammation was present among symptomatic participants with and without diverticula. METHODS: We analyzed data from a prospective study of 619 patients undergoing a screening colonoscopy from 2013 through 2015 at the University of North Carolina Hospital in Chapel Hill, North Carolina. Among our participants, 255 (41%) had colonic diverticula. Colonic mucosal biopsy specimens were analyzed for levels of interleukin 6 (IL6), IL10, and tumor necrosis factor messenger RNAs by quantitative reverse-transcriptase polymerase chain reaction, and numbers of immune cells (CD4+, CD8+, CD57+, and mast cell tryptase) by immunohistochemistry. Gastrointestinal symptoms were assessed using Rome III criteria. Proportional odds models were used to estimate odds ratios (ORs) and 95% confidence interval (CIs). RESULTS: After adjustment for potential confounders, there was no association between diverticulosis and tumor necrosis factor (OR, 0.85; 95% CI, 0.63-1.16), and no association with CD4+ cells (OR, 1.18; 95% CI, 0.87-1.60), CD8+ cells (OR, 0.97; 95% CI, 0.71-1.32), or CD57+ cells (OR, 0.80; 95% CI, 0.59-1.09). Compared with controls without diverticulosis, biopsy specimens from individuals with diverticulosis were less likely to express the inflammatory cytokine IL6 (OR, 0.59; 95% CI, 0.36-0.96). There was no association between diverticulosis and irritable bowel syndrome (OR, 0.53; 95% CI, 0.26-1.05) or chronic abdominal pain (OR, 0.68; 95% CI, 0.38-1.23). There was no evidence for inflammation in patients with symptoms when patients with vs without diverticulosis were compared. CONCLUSIONS: We found no evidence that colonic diverticulosis is associated with mucosal inflammation or gastrointestinal symptoms. Among patients with symptoms and diverticula, we found no mucosal inflammation.
Assuntos
Colite/etiologia , Colite/patologia , Divertículo do Colo/complicações , Mucosite/etiologia , Mucosite/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Colonoscopia , Citocinas/análise , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , North Carolina , Estudos ProspectivosRESUMO
BACKGROUND AND AIMS: Despite evidence that most nonmalignant colorectal polyps can be managed endoscopically, a substantial proportion of patients with a nonmalignant colorectal polyp are still sent to surgery. Risks associated with this surgery are not well characterized. We describe 30-day postoperative morbidity and mortality and explore risk factors for adverse events in patients undergoing surgical resection for nonmalignant colorectal polyps. METHODS: We analyzed data collected prospectively as part of the National Surgical Quality Improvement Program. Our analysis included 12,732 patients who underwent elective surgery for a nonmalignant colorectal polyp from 2011 through 2014. We report adverse events within 30 days of the index surgery. Modified Poisson regression was used to estimate risk ratios and 95% confidence intervals. RESULTS: Thirty-day mortality was .7%. The risk of a major postoperative adverse event was 14%. Within 30 days of resection, 7.8% of patients were readmitted and 3.6% of patients had a second major surgery. The index surgery resulted in a colostomy in 1.8% and ileostomy in .4% of patients. Patients who had surgical resection of a nonmalignant polyp in the rectum or anal canal compared with the colon had a risk ratio of 1.58 (95% confidence interval, 1.09-2.28) for surgical site infection and 6.51 (95% confidence interval, 4.97-8.52) for ostomy. CONCLUSIONS: Surgery for a nonmalignant colorectal polyp is associated with significant morbidity and mortality. A better understanding of the risks and benefits associated with surgical management of nonmalignant colorectal polyps will better inform discussions regarding the relative merits of management strategies.
Assuntos
Colectomia , Pólipos do Colo/cirurgia , Neoplasias Colorretais/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Colostomia/estatística & dados numéricos , Bases de Dados Factuais , Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Ileostomia/estatística & dados numéricos , Pólipos Intestinais/cirurgia , Masculino , Pessoa de Meia-Idade , Morbidade , Complicações Pós-Operatórias/mortalidade , Reto/cirurgia , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
BACKGROUND & AIMS: Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown. METHODS: We investigated the association between renal failure at the time of LT and patient outcome in patients with alcoholic liver disease (ALD) (n = 6920), non-alcoholic steatohepatitis (NASH) (n = 2956) and hepatitis C (HCV) (n = 14 922) using the United Network for Organ Sharing (UNOS) database between February 2002 and December 2013. A total of 24 798 transplant recipients were included. RESULTS: The presence of renal failure was more frequently seen in patients with ALD (23.95%) and NASH (23.27%) compared to patients with HCV (19.38%) (P < 0.001). In multivariate analysis, renal failure was an independent predictor of poor survival. Renal failure showed detrimental effect on patient survival in the overall series (HR = 1.466, P < 0.0001). Importantly, the impact of renal failure was less marked in patients with ALD (HR = 1.31, P < 0.0001) than in patients with NASH (HR = 1.73, P < 0.0001) or HCV (HR = 1.52, P < 0.0001). Despite a higher model for end-stage liver disease (MELD) score at the time of LT, ALD patients with renal failure had better long-term prognosis than non-ALD patients. CONCLUSIONS: Renal failure at the time of LT conferred a lower patient and graft survival post-LT. However, renal failure has less impact on the outcome of patients with ALD than that of patients with non-alcoholic liver disease after LT.
Assuntos
Hepatite C/complicações , Hepatopatias Alcoólicas/complicações , Transplante de Fígado , Hepatopatia Gordurosa não Alcoólica/complicações , Insuficiência Renal/epidemiologia , Bases de Dados Factuais , Feminino , Sobrevivência de Enxerto , Hepatite C/cirurgia , Humanos , Hepatopatias Alcoólicas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Fatores de Risco , Estados UnidosRESUMO
Arsenic (+3 oxidation state) methyltransferase (As3mt) is the key enzyme in the pathway for methylation of inorganic arsenic (iAs). Altered As3mt expression and AS3MT polymorphism have been linked to changes in iAs metabolism and in susceptibility to iAs toxicity in laboratory models and in humans. As3mt-knockout mice have been used to study the association between iAs metabolism and adverse effects of iAs exposure. However, little is known about systemic changes in metabolism of these mice and how these changes lead to their increased susceptibility to iAs toxicity. Here, we compared plasma and urinary metabolomes of male and female wild-type (WT) and As3mt-KO (KO) C57BL/6 mice and examined metabolomic shifts associated with iAs exposure in drinking water. Surprisingly, exposure to 1 ppm As elicited only small changes in the metabolite profiles of either WT or KO mice. In contrast, comparisons of KO mice with WT mice revealed significant differences in plasma and urinary metabolites associated with lipid (phosphatidylcholines, cytidine, acyl-carnitine), amino acid (hippuric acid, acetylglycine, urea), and carbohydrate (L-sorbose, galactonic acid, gluconic acid) metabolism. Notably, most of these differences were sex specific. Sex-specific differences were also found between WT and KO mice in plasma triglyceride and lipoprotein cholesterol levels. Some of the differentially changed metabolites (phosphatidylcholines, carnosine, and sarcosine) are substrates or products of reactions catalyzed by other methyltransferases. These results suggest that As3mt KO alters major metabolic pathways in a sex-specific manner, independent of iAs treatment, and that As3mt may be involved in other cellular processes beyond iAs methylation.
Assuntos
Intoxicação por Arsênico/enzimologia , Arsênio/toxicidade , Metabolismo Energético/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Metiltransferases/metabolismo , Poluentes Químicos da Água/toxicidade , Aminoácidos/metabolismo , Animais , Arsênio/sangue , Arsênio/metabolismo , Arsênio/urina , Intoxicação por Arsênico/sangue , Intoxicação por Arsênico/metabolismo , Intoxicação por Arsênico/urina , Arsenicais/sangue , Arsenicais/metabolismo , Arsenicais/urina , Biomarcadores/sangue , Biomarcadores/urina , Biotransformação , Metabolismo dos Carboidratos/efeitos dos fármacos , Resistência a Medicamentos , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metilação , Metiltransferases/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Caracteres Sexuais , Toxicocinética , Poluentes Químicos da Água/sangue , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/urinaRESUMO
BACKGROUND & AIMS: Looping is a common problem during colonoscopy that prolongs procedure time. We aimed to determine the efficacy and safety of ColoWrap, an external abdominal compression device, with respect to insertion time and other procedural outcomes. METHODS: We performed a prospective study of outpatients undergoing elective colonoscopy (40-80 years old; mean age, 60.5 years) at endoscopy facilities in the University of North Carolina Hospitals from April 2013 through March 2014. Subjects were randomly assigned to groups that received either ColoWrap (n = 175) or a sham device (control, n = 175) during colonoscopy. Colonoscopists and staff were blinded to the application. The primary outcome was cecal intubation time (CIT). Secondary outcomes included use of manual pressure and position change. RESULTS: The mean CIT was similar for the control and ColoWrap groups (6.69 vs 6.67 minutes; P = .98). There were no statistical differences in the frequency of manual pressure (45% for controls vs 37% for ColoWrap group, P = .13) or position changes (4% for controls vs 2% for ColoWrap group, P = .36). Among patients with body mass index between 30 and 40 kg/m(2) (n = 78), CIT was significantly lower for patients in the ColoWrap group (4.69 minutes) than controls (6.10 minutes) (P = .03). Adverse events were similar between groups. CONCLUSIONS: In patients undergoing elective colonoscopy, application of an external abdominal compression device did not improve CIT or affect the frequency of ancillary maneuvers. A possible benefit was observed in patients with body mass index between 30 and 40 kg/m(2), but further studies are needed. ClinicalTrials.gov number: NCT02025504.
Assuntos
Neoplasias do Colo/diagnóstico , Colonoscopia/métodos , Equipamentos e Provisões , Pressão Hidrostática , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , North Carolina , Fatores de TempoRESUMO
BACKGROUND & AIMS: Colonic diverticula are the most common finding from colonoscopy examinations. Little is known about the distribution of colonic diverticula, which are responsible for symptomatic and costly diverticular disease. We aimed to assess the number, location, and characteristics of colonic diverticula in a large US screening population. METHODS: We analyzed data from a prospective study of 624 patients (mean age, 54 years) undergoing screening colonoscopy at the University of North Carolina Hospital from 2013 through 2015. The examination included a detailed assessment of colonic diverticula. To assess the association between participant characteristics and diverticula, we used logistic regression to estimate odds ratios and 95% confidence intervals. RESULTS: Of our population, 260 patients (42%) had 1 or more diverticula (mean number, 14; range, 1-158). Participants with diverticula were more likely to be older, male, and have a higher body mass index than those without diverticula. The distribution of diverticula differed significantly by race. Among white persons, 75% of diverticula were in the sigmoid colon, 11% in the descending splenic flexure, 6% in the transverse colon, and 8% were in the ascending colon or hepatic flexure. In black persons 64% of diverticula were in the sigmoid colon, 8% in the descending colon or splenic flexure, 7% in the transverse colon, and 20% in the ascending colon or hepatic flexure (P = .0008). The proportion of patients with diverticula increased with age: 35% were 50 years or younger, 40% were 51-60 years, and 58% were older than 60 years. The proportion of patients with more than 10 diverticula increased with age: 8% were 50 years or younger, 15% were 51-60 years, and 30% were older than 60 years. CONCLUSIONS: Older individuals not only have a higher prevalence of diverticula than younger individuals, but also a greater density, indicating that this is a progressive disease. Black persons have a greater percentage of their diverticula in the proximal colon and fewer in the distal colon compared with white persons. Understanding the distribution and determinants of diverticula is the first step in preventing diverticulosis and its complications.
Assuntos
Divertículo do Colo/epidemiologia , Divertículo do Colo/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colonoscopia , Demografia , Detecção Precoce de Câncer , Etnicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Prevalência , Estudos ProspectivosRESUMO
BACKGROUND: Obesity is associated with an aggressive subtype of breast cancer called basal-like breast cancer (BBC). BBC has no targeted therapies, making the need for mechanistic insight urgent. Reducing adiposity in adulthood can lower incidence of BBC in humans. Thus, this study investigated whether a dietary intervention to reduce adiposity prior to tumor onset would reverse HFD-induced BBC. METHODS: Adult C3(1)-Tag mice were fed a low or high fat diet (LFD, HFD), and an obese group initially exposed to HFD was then switched to LFD to induce weight loss. A subset of mice was sacrificed prior to average tumor latency to examine unaffected mammary gland. Latency, tumor burden and progression was evaluated for effect of diet exposure. Physiologic, histology and proteomic analysis was undertaken to determine mechanisms regulating obesity and weight loss in BBC risk. Statistical analysis included Kaplan-Meier and log rank analysis to investigate latency. Student's t tests or ANOVA compared variables. RESULTS: Mice that lost weight displayed significantly delayed latency compared to mice fed HFD, with latency matching those on LFD. Plasma leptin concentrations significantly increased with adiposity, were reduced to control levels with weight loss, and negatively correlated with tumor latency. HFD increased atypical ductal hyperplasia and ductal carcinoma in situ in mammary gland isolated prior to mean latency-a phenomenon that was lost in mice induced to lose weight. Importantly, kinome analysis revealed that weight loss reversed HFD-upregulated activity of PKC-α, PKD1, PKA, and MEK3 and increased AMPKα activity in unaffected mammary glands isolated prior to tumor latency. CONCLUSIONS: Weight loss prior to tumor onset protected against the effects of HFD on latency and pre-neoplastic lesions including atypical ductal hyperplasia and DCIS. Using innovative kinomics, multiple kinases upstream of MAPK/P38α were demonstrated to be activated by HFD-induced weight gain and reversed with weight loss, providing novel targets in obesity-associated BBC. Thus, the HFD-exposed microenvironment that promoted early tumor onset was reprogrammed by weight loss and the restoration of a lean phenotype. Our work contributes to an understanding of underlying mechanisms associated with tumor and normal mammary changes that occur with weight loss.