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1.
Artigo em Inglês | MEDLINE | ID: mdl-31676360

RESUMO

In the last decade, several new therapies with different mechanisms of action have been approved for the management of moderate to severe Crohn's disease (CD). However, there is limited guidance on optimal positioning of agents as first- or second-line therapies due to the absence of head-to-head trials. Furthermore, given the lack of comparative studies, treatment guidelines provide limited insight. In this review, we will discuss data on key treatment attributes, comparative efficacy and safety, factors predictive of response to each agent and propose an algorithm for positioning therapies for the management of patients with low-risk and high-risk CD.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31678602

RESUMO

BACKGROUND & AIMS: Patients with solid tumors who undergo chemotherapy have an increased risk of hepatitis B virus (HBV) reactivation, but a low proportion of these patients are screened for HBV infection and guidelines make conflicting recommendations. Further, the cost-effectiveness of newer treatments for HBV prophylaxis has not been examined for this population. We aimed to analyze the cost-effectiveness of HBV screening before chemotherapy for patients with solid tumors. METHODS: We compared 3 HBV screening strategies (screen all, screen only high-risk patients, or screen none) using a Markov model of a population of adults in the United States who initiated chemotherapy for a solid tumor. We modeled use of entecavir prophylaxis for HB surface antigen (HBsAg)-positive patients and surveillance for HBsAg-negative patients who are positive for HBV core antibody. The Markov cycle length was 1 year, with model simulation for up to 5 years. RESULTS: The screen all strategy was the most cost effective, with an incremental cost-effectiveness ratio of $42,761 compared to screening only high-risk patients. The screen none strategy was less effective and less costly than screening all patients or only high-risk patients. The screen-all strategy was the most cost effective for all estimates of prevalence of HBsAg-positive patients and estimates of HBV reactivation in HBsAg-positive patients. Screening only high-risk patients was the most cost-effective strategy when more than 25% of high-risk patients were screened for HBV infection. CONCLUSIONS: In a Markov model analysis, we found screening all patients with solid tumors for HBV infection before chemotherapy to be the most cost-effective strategy. Guidelines should consider recommending HBV tests for patients initiating chemotherapy.

3.
Gastroenterology ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711925

RESUMO

BACKGROUND & AIMS: Non-invasive tests to measure endoscopic activity in patients with Crohn's disease (CD) have limitations. We aimed to develop a test to identify patients in remission, based on endoscopic analysis, and monitor CD activity based on serum levels of proteins. METHODS: We developed a test to measure 13 proteins in blood (ANG1, ANG2, CRP, SAA1, IL7, EMMPRIN, MMP1, MMP2, MMP3, MMP9, TGFA, CEACAM1, and VCAM1), called the endoscopic healing index [EHI] using samples from 278 patients with CD from multi-national training cohort. We validated the test using 2 independent cohorts of patients with CD: 116 biologic-naïve patients with early-stage CD (validation cohort 1) and 195 biologic-exposed patients with chronic CD (validation cohort 2). The ability of the test to identify patients with active disease vs patients in remission (defined as a simple endoscopic score for CD of ≤ 2 and ≤ 1 in each segment, or a total CD endoscopic index of severity score < 3) was assessed using area under receiver operating characteristic curve (AUROC) analysis. The diagnostic accuracy of the test was compared with that of measurement of serum CRP and fecal calprotectin (FC). RESULTS: The EHI scores range from 0 to 100 units; higher scores indicate more severe CD activity, based on endoscopy findings. The EHI identified patients in remission with an AUROC of 0.962 in validation cohort 1 (95% CI, 0.942-0.982) and an AUROC of 0.693 in validation cohort 2 (95% CI, 0.619-0.767), regardless of CD location or phenotype. A cut-off value of 20 points identified patients in remission with the highest level of sensitivity (97.1% in validation cohort 1 and 83.2% in validation cohort 2), with specificity values of 69.0% and 36.6%, respectively. A cut-off value of 50 points identified patients in remission with the highest level of specificity (100% in validation cohort 1 and 87.8% in validation cohort 2), with sensitivity values of 37.3% and 30.0%, respectively. The EHI identified patients in remission with a significantly higher AUROC value than the test for CRP (0.876, P<.001 in validation cohort 1 and 0.624, P=.109 in validation cohort 2). In analysis of patients with available FC measurements, the AUROC value for the EHI did not differ significantly from that of measurement of FC (AUROC, 0.950 for EHI vs AUROC, 0.923 for FC, P=.147 in validation cohort 1 and AUROC, 0.803 for EHI vs AUROC, 0.854 for FC, P=.298 in validation cohort 2). CONCLUSIONS: We developed an index to identify patients with CD in endoscopic remission based on blood levels of 13 proteins, called the EHI. The EHI identified patients with resolution of endoscopic disease activity, with good overall accuracy, although with variation between the 2 cohorts assessed. The EHI AUROC values were comparable to measurement of FC and higher than measurement of serum CRP. The test might be used in practice for assessing endoscopic activity in patients with CD.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31712084

RESUMO

The epidemiology of inflammatory bowel disease (IBD) is progressively evolving impacting the type of patients with IBD we will see in clinical practice. In this review, we discuss specific challenges and solutions in the management of (a) obese, (b) older and (c) obstetric (pregnant) patients with IBD. With the global obesity epidemic, almost one in three patients with IBD are obese. Obesity is associated with greater difficulty in achieving remission, higher risk of disease relapse and higher burden and costs of hospitalization in patients with IBD. Obese patients also have inferior response to biologic therapy related to altered pharmacokinetics and obesity-mediated chronic inflammation. Surgical management of obese patients with IBD is also challenging. Similar to obesity, the prevalence of IBD in older patients is rising and it is anticipated that almost one-third of patients with IBD will be older than 60 years within the next decade. Older patients present unique diagnostic and therapeutic dilemmas, and management of these individuals warrants careful consideration of the risks of disease-related vs. treatment-related complications, non-IBD-related extra-intestinal complications (e.g. cardiovascular disease, malignancy), in the context of individual values, preferences, functional status and comorbidities. With evolving therapeutics, medical management of IBD surrounding pregnancy continues to be challenging. Overall, the management of pregnant patients requires a pro-active, multidisciplinary approach, with an emphasis on optimal disease control not just during, but prior to pregnancy. This often involves continuation of highly effective therapies, of which the vast majority are safe during pregnancy and breastfeeding, resulting in a reduction of risk of adverse maternal fetal outcomes.

5.
Inflamm Bowel Dis ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31748806

RESUMO

BACKGROUND: Longer disease duration is associated with inferior response to biologic therapy in Crohn's disease. However, the effect of disease duration on response to biologic therapy in ulcerative colitis (UC) has not been well studied. METHODS: In a single-center retrospective cohort study of outpatients with UC starting a biologic agent, we evaluated treatment response by disease duration. The primary outcome was treatment failure (composite outcome of inflammatory bowel disease [IBD]-related surgery/hospitalization or treatment modification including dose escalation, treatment discontinuation, or addition of corticosteroids); secondary outcomes were risk of IBD-related surgery/hospitalization and endoscopic remission. We conducted multivariate Cox proportional hazard analyses to evaluate the independent impact of disease duration on clinical outcomes. RESULTS: We included 160 biologic-treated UC patients (73% biologic-naïve) with a median age (interquartile range) of 36 (26-52) years and disease duration (range) of 4.5 (1-9) years. After adjusting for immunosuppressive medications, albumin, and body mass index, each 1-year increase in disease duration was associated with a 5% lower risk of treatment failure (adjusted hazard ratio, 0.95; 95% confidence interval [CI], 0.91-0.99) and a 9% higher risk of achieving endoscopic remission (adjusted odds ratio, 1.09; 95% CI, 1.01-1.18). This association of short disease duration with treatment failure was observed only in biologic-naïve patients, but not biologic-experienced patients. No significant association was seen between disease duration and risk of surgery or hospitalization. CONCLUSION: Shorter disease duration is independently associated with increased risk of treatment failure in biologic-treated patients with UC. Requirement of biologic therapy early in the course of disease may be a negative prognostic marker in patients with UC.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31755121

RESUMO

BACKGROUND: Treatment targets for ulcerative colitis are evolving towards achievement of endoscopic improvement and remission in addition to symptom resolution. It remains to be accurately quantified what proportion of patients with symptom resolution have residual endoscopic activity that might warrant treatment modification. AIM: To quantify the prevalence of endoscopic improvement and remission amongst ulcerative colitis patients with various permutations of patient-reported outcomes. METHODS: Individual participant data from active intervention and placebo arms of clinical trials of infliximab, golimumab, vedolizumab and tofacitinib were pooled to estimate the prevalence of endoscopic improvement (Mayo endoscopic sub-score [MES] 0 or 1) and remission (MES 0) scores with various permutations of the rectal bleeding sub-score (RBS) and stool frequency sub-score (SFS) of the Mayo score, following induction (6-8 weeks) and maintenance (30-54 weeks) therapy. Subgroup analyses were performed by year of publication and centrally read endoscopy scoring. RESULTS: Data from 2586 trial participants were analysed. Using locally scored endoscopy, the prevalence of endoscopic improvement and remission was highest among participants with a RBS 0 + SFS 0 post-induction (MES 0/1:81%, [95% CI 78-84]; MES 0:29% [26-33]) and during maintenance (MES 0/1:91% [87-93]; MES 0:57% [52-62]). Prevalence estimates were lower for more recently performed trials (P < .01). In comparison to locally scored endoscopy, when using central endoscopy scoring, the prevalence of endoscopic improvement and remission was lower post-induction (MES 0/1 57% [50-64], P < .001; MES 0 15% [11-21], P = .09) and during maintenance (MES 0/1 74% [67-81], P = .001; MES 0 31% [24-38], P = .001) for participants achieving a RBS 0 + SFS 0. CONCLUSIONS: Approximately 8 of 10 patients with normalisation of rectal bleeding and stool frequency have improvement in endoscopic disease activity, whereas approximately only half of these patients have endoscopic remission.

7.
Parasite Immunol ; 41(11): e12669, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31494954

RESUMO

CD8+ T-cell function is compromised in chronic diseases such as visceral leishmaniasis (VL). However, little is known about the changes in gene expression that cause CD8+ T-cell dysfunction during VL. We used targeted transcriptional profiling of peripheral blood CD8+ T cells from VL patients pre- and post-anti-parasitic drug treatment, and compared them with the same cell population from healthy endemic controls to assess their activation, differentiation and functional status during disease. We found a predominance of downregulated immune genes in CD8+ T cells from VL patients. However, genes encoding several notable immune checkpoint molecules, including LAG-3, TIM-3 and CTLA-4, cytolytic molecules, such as granzymes A, B and H and perforin, as well as SOCS3, STAT1, JAK2 and JAK3 cytokine signalling genes were found to be increasingly expressed by VL patient CD8+ T cells. Additional studies confirmed increased expression of the inhibitory receptors LAG3 and TIM3 on VL patient CD8+ T cells, thereby identifying these molecules as potential targets to improve antigen-specific CD8+ T-cell responses during disease.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31546056

RESUMO

BACKGROUND & AIMS: Little is known about the association between rectal bleeding and increased stool frequency with endoscopic findings in patients with mild to moderate ulcerative colitis (UC). We evaluated the associations between rectal bleeding or stool frequency and endoscopic remission in this population. METHODS: We performed a post-hoc analysis of data from a phase 3 non-inferiority trial of 817 adults with mild to moderate UC who received treatment with mesalazine. We obtained information on rectal bleeding, stool frequency, and Mayo endoscopic subscores (MESs) at weeks 0, 8, and 38. The sensitivity, specificity, and positive and negative predictive values with which rectal bleeding and stool frequency identified patients with MESs of 0 and/or 1 were calculated at weeks 8 and 38 of treatment. The associations between change in rectal bleeding and stool frequency and change in MES after treatment were quantified using the Spearman's rank correlation coefficient. RESULTS: Among patients with a MES of 0, 7/82 patients (9%) had a rectal bleeding score of 1 or more and 40/82 patients (49%) had a stool frequency score of 1 or more at week 8; at week 38, 6/167 patients (4%) had a rectal bleeding score of 1 or more and 63/167 patients (38%) had a stool frequency score of 1 or more. Among patients with MESs of 0 or 1, 50/310 patients (16%) had a rectal bleeding score of 1 or more and 162/310 patients (52%) had had a stool frequency score of 1 or more at week 8; at week 38, 18/363 patients (5%) had a rectal bleeding score of 1 or more and 141/363 patients (39%) had a stool frequency score of 1 or more. The Spearman rank correlation coefficients for change in rectal bleeding and stool frequency with change in MES at week 8 were 0.39 (95% CI, 0.32-0.45) and 0.34 (95% CI, 0.27-0.40), respectively. In patients with reduced MESs at week 8, 39/389 patients (10%) had unchanged or worsening rectal bleeding and 81/389 patients (21%) had unchanged or increasing stool frequencies. CONCLUSIONS: In a post-hoc analysis of data from a phase 3 trial of adults with mild to moderate UC treated with mesalazine, we found absence of rectal bleeding to identify patients in endoscopic remission. However, many patients in remission still have increased stool frequency, indicating that it may not be a sensitive marker of disease activity in patients with mild to moderate UC.

9.
Aliment Pharmacol Ther ; 50(8): 848-857, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31483522

RESUMO

BACKGROUND: There has been limited evaluation of the association between vedolizumab trough concentration and clinical outcomes in patients with inflammatory bowel diseases (IBD). AIM: To perform a systematic review and meta-analysis to evaluate the potential role of therapeutic drug monitoring (TDM) for vedolizumab. METHODS: Through a systematic literature search through 28 February 2019, we identified five cohort studies (558 patients, 42% with ulcerative colitis) reporting the association between vedolizumab trough concentration and clinical outcomes in patients with IBD. We calculated mean difference (MD) in vedolizumab trough concentration in patients achieving vs not achieving clinical outcomes, and qualitatively synthesized thresholds associated with favourable outcomes. RESULTS: In patients with UC, median vedolizumab trough concentrations were consistently higher in patients achieving clinical remission (median, 14.3 µg/mL vs 10.5 µg/mL; MD, 5.1 µg/mL, 95% CI, 2.8-7.4) or endoscopic remission (median, 13.0 µg/mL vs 9.7; MD, 5.1 µg/mL, 95% CI, 2.2-7.9). In patients with CD, there was no significant difference in median vedolizumab trough concentrations in patients achieving vs not achieving clinical remission (MD, 2.0 µg/mL; 95% CI, -0.5 to 4.5) or endoscopic remission (MD, 3.6 µg/mL; 95% CI, -1.4 to 8.6). In patients with UC, week 6 vedolizumab trough concentrations ≥18.5-20.8 µg/mL, and maintenance trough concentrations ≥9.0-12.6 µg/mL were associated with favourable clinical outcomes. Antibodies to vedolizumab were reported in 1.7%-3.0% patients on maintenance therapy. CONCLUSION: Based on meta-analysis, patients with UC who achieve endoscopic and clinical remission have significantly higher vedolizumab trough concentration during maintenance therapy. Vedolizumab trough concentration >20 µg/mL at week 6, and >12 µg/mL during maintenance may be associated with better outcomes, though cause-effect relationship remains unclear. Prospective studies on reactive and proactive therapeutic drug monitoring of vedolizumab (vs empiric dose escalation) are warranted.

10.
Inflamm Bowel Dis ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31504528

RESUMO

BACKGROUND: We summarized the protocol-specified corticosteroid tapering regimens in clinical trials of moderate-severe ulcerative colitis (UC) and Crohn's disease (CD) and calculated differences in rates of clinical remission vs corticosteroid-free clinical remission (CSF-CR). METHODS: Through a systematic literature review through February 28, 2019, we identified 16 randomized controlled trials (RCTs) of biologics or small molecules in patients with moderate-severe UC or CD who reported CSF-CR as an outcome. We estimated the relative risk and 95% confidence interval of achieving CSF-CR vs overall clinical remission in patients treated with active intervention or placebo through random-effects meta-analysis. RESULTS: Across trials of UC (11 trials) and CD (5 trials), a median of 53% and 49% of participants were on corticosteroids at the time of trial entry, respectively. Participants were allowed to enter trials at a median corticosteroid dose (range) of 35 (20-40) mg/d. Doses were kept stable for a median (range) of 8 (5-10) weeks during induction therapy, after which a mandatory and structured taper was implemented, albeit with the investigators' discretion depending on clinical status. Pooled rates of CSF-CR in patients with UC and CD treated with placebo were 9.7% and 19.1%, respectively. In UC and CD trials, the rate of CSF-CR was 24% and 18% lower than the rate of overall clinical remission, respectively. CONCLUSIONS: Protocol-specified corticosteroid tapering regimens vary across trials. These findings will help to inform the design and interpretation of future clinical trials and highlight the need for standardization.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31470176

RESUMO

BACKGROUND & AIMS: We investigated 30- and 90-day rates and causes of, risk factors for, and interventions to reduce hospital readmission in patients who received medical treatment for inflammatory bowel diseases (IBD). METHODS: We performed a systematic search of publications through July 1, 2018 for studies of rates of hospital readmission and associated causes and risk factors in patients who received medical treatments for IBD. Our final analysis included 17 cohort studies (6324 patients) of hospitalized adults with IBD who had received medical treatment, along with reported readmission rates with detailed chart review. We performed random effects meta-analysis to estimate 30- and 90-day rates of readmission and identified causes and risk factors associated with readmission. We also performed qualitative analyses of studies that focused on interventions to reduce readmission. RESULTS: Overall, the 30-day rate of readmission was 18.1% (95% CI, 14.4-22.4) and the 90-day rate was 26.0% (95% CI, 22.7-29.6). On meta-regression, studies with higher proportions of patients with ulcerative colitis than Crohn's disease reported higher risks for readmission. Most common reasons for readmission were IBD flare, infection, or complications from unplanned surgeries during hospitalizations. Consistent risk factors for 30-day readmission were admission for pain control (odds ratio [OR], 2.27; 95% CI, 1.69-3.03), need for total parenteral nutrition on discharge (OR, 2.13; 95% CI, 1.36-3.35), and prior or unplanned surgery during admission (OR, 3.11; 95% CI, 2.27-4.25). Only 1 study focused on interventions (specialized inpatient IBD service) to reduce risk of readmission. CONCLUSIONS: Overall 30- and 90-day rates of readmission for patients who received medical treatment for IBD are 18.1% and 26.0%, respectively. IBD flares and infections are common reasons for readmission, and inadequate pain control and need for parenteral nutrition were common risk factors. Interventional studies to reduce risk of readmission are needed.

12.
JACC Cardiovasc Interv ; 12(15): 1462-1464, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31395216
13.
J Biol Chem ; 294(38): 14081-14095, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31366730

RESUMO

TP53 is the most frequently mutated tumor suppressor gene in many cancers, yet biochemical characterization of several of its reported mutations with probable biological significance have not been accomplished enough. Specifically, missense mutations in TP53 can contribute to tumorigenesis through gain-of-function of biochemical and biological properties that stimulate tumor growth. Here, we identified a relatively rare mutation leading to a proline to leucine substitution (P152L) in TP53 at the very end of its DNA-binding domain (DBD) in a sample from an Indian oral cancer patient. Although the P152Lp53 DBD alone bound to DNA, the full-length protein completely lacked binding ability at its cognate DNA motifs. Interestingly, P152Lp53 could efficiently tetramerize, and the mutation had only a limited impact on the structure and stability of full-length p53. Significantly, when we expressed this variant in a TP53-null cell line, it induced cell motility, proliferation, and invasion compared with a vector-only control. Also, enhanced tumorigenic potential was observed when P152Lp53-expressing cells were xenografted into nude mice. Investigating the effects of P152Lp53 expression on cellular pathways, we found that it is associated with up-regulation of several pathways, including cell-cell and cell-extracellular matrix signaling, epidermal growth factor receptor signaling, and Rho-GTPase signaling, commonly active in tumorigenesis and metastasis. Taken together, our findings provide a detailed account of the biochemical and cellular alterations associated with the cancer-associated P152Lp53 variant and establish it as a gain-of-function TP53 variant.

15.
Expert Rev Clin Immunol ; 15(9): 969-979, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31322018

RESUMO

Introduction: Efficacy and safety are key aspects when choosing therapies for patients with inflammatory bowel diseases (IBD). While several randomized trials and indirect comparisons have informed the comparative efficacy of medications, there has been a limited synthesis of safety of different agents. Areas covered: We focus on the overall and comparative risk of serious and opportunistic infections and malignancy of biologic and immunosuppressive therapy in IBD, based on randomized trials, open-label extension and registry studies, and real-world comparative observational studies. Expert opinion: TNFα antagonists may be more immunosuppressive than non-TNF-targeted biologic agents and increase the risk of systemic infections. Most consistent risk factors for serious infections include use of combination therapy with immunosuppressive agents and/or corticosteroids, moderate to severe disease activity, and older age. TNFα antagonists may also be associated with an increased risk of lymphoma, especially when combined with thiopurines. Real-world comparative safety studies, especially with newer biologic agents, are warranted to inform decision-making. Comparative safety of pharmacotherapy for IBD should be viewed in conjunction with efficacy and in the context of treatment strategies/approach, rather than in the context of specific agents used.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31327401

RESUMO

With availability of several different classes of biologic agents with variable efficacy and safety profiles for moderate-severe Crohn's disease (CD), positioning of different agents in treatment course is an important question for clinicians. Though in an ideal world, positioning would be personalized and driven by likelihood of response to different agents based on biomarkers in individual patients, that is still far from reality, and decisions are empiric. In the absence of head-to-head trials of different medications, decisions on treatment choice and positioning are primarily based on clinician experience, opinion-based treatment algorithms, patient preference and insurance reimbursement. Understandably, in the absence of guidance, there is considerable practice variability on optimal choice of first- and second-line biologics in the treatment of patients with CD. In the absence of direct evidence from head-to-head trials, network meta-analysis can help assess comparative efficacy of several interventions and synthesize evidence across a network of randomized controlled trials. In this review, we discuss what network meta-analyses, what do they tell us about positioning different agents, and strengths and limitations of such an approach.


Assuntos
Produtos Biológicos/uso terapêutico , Doença de Crohn/tratamento farmacológico , Meta-Análise em Rede , Produtos Biológicos/farmacologia , Doença de Crohn/patologia , Humanos
17.
Artigo em Inglês | MEDLINE | ID: mdl-31301452

RESUMO

It is unclear whether ulcerative colitis (UC) is a progressive disease similar to Crohn's disease (CD). Patients with UC often are undertreated because of the possibility of curative colectomy and the perception that the disease burden is lower than that of CD. We discuss findings from studies that aimed to determine whether UC and CD have the same disease burden and should be treated in the same intensive way. We discuss the similarities between CD and UC, including effects on quality of life, long-term complications, strictures, increased risk of cancer, pseudopolyps, functional abnormalities, and anorectal dysfunction. Contrary to the generally accepted idea, surgery cannot cure UC. Postoperative complications, especially pouchitis and fecal incontinence, affect more than one third of patients. CD and UC each pose substantial economic burdens. Monitoring, treatments, and goals of therapy are similar for all inflammatory bowel diseases. Earlier initiation of disease-modifying drugs might reduce the progression of UC and reduce its burden after surgery, although UC might not cause the irreversible damage observed in patients with CD.

19.
Gastrointest Endosc ; 90(6): 893-903.e7, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31310744

RESUMO

BACKGROUND AND AIMS: Variable diagnostic performance of sampling techniques during EUS-guided tissue acquisition of solid pancreatic masses based on needle type (FNA versus fine-needle biopsy [FNB]) and gauge (19-gauge vs 22-gauge vs 25-gauge) has been reported. We performed a systematic review with network meta-analysis to compare the diagnostic accuracy of EUS-guided techniques for sampling solid pancreatic masses. METHODS: Through a systematic literature review to November 2018, we identified 27 randomized controlled trials (2711 patients) involving adults undergoing EUS-guided sampling of solid pancreatic masses that evaluated the diagnostic performance of FNA and FNB needles based on needle gauge. The primary outcome was diagnostic accuracy. Secondary outcomes were sample adequacy, histologic core procurement rate, and number of needle passes. We performed pairwise and network meta-analyses and appraised the quality of evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. RESULTS: In the network meta-analysis, no specific EUS-guided tissue sampling technique was superior, based on needle type (FNA vs FNB) or gauge (19-gauge vs 22-gauge vs 25-gauge) (low-quality evidence). Specifically, there was no difference between 25-gauge FNA versus 22-gauge FNA (relative risk [RR], 1.03; 95% confidence interval [CI], 0.91-1.17) and 22-gauge FNB versus 22-gauge FNA (RR, 1.03; 95% CI, 0.89-1.18) needles for diagnostic accuracy, sample adequacy, and histologic core procurement. Findings were confirmed in sensitivity analysis restricted to studies with no rapid on-site cytologic evaluation and no use of the fanning technique. CONCLUSION: In a network meta-analysis, no specific EUS-guided tissue sampling technique was superior with regard to diagnostic accuracy, sample adequacy, or histologic procurement rate for solid pancreatic masses, with low confidence in estimates.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31108227

RESUMO

BACKGROUND & AIMS: With several options available for patients with moderate-severe ulcerative colitis (UC), rapidity of symptom resolution could be an important differentiator. We compared the efficacy and speed of onset of action of infliximab vs golimumab induction therapy using patient-level data from phase 3 trials (ACT-1, ACT-2, and PURSUIT-SC). METHODS: We compared differences in proportions of patients who achieved the composite outcome of a rectal bleeding score=0 and stool frequency score ≤1 (patient-reported outcome 2 remission) at weeks 2 and 6 of treatment with standard-dose infliximab vs golimumab using logistic generalized estimating equation. Overall efficacy for inducing clinical remission (Mayo clinic score <3) was compared using logistic regression. Analyses were adjusted for sex, disease extent, baseline clinical and endoscopic severity, C-reactive protein, albumin, body weight and concomitant medications (immunomosuppressives, corticosteroids, and 5-aminsalicylates). RESULTS: Trial populations were similar and no differences were observed among the placebo groups in the studies. A significantly higher proportion patients treated with infliximab than golimumab achieved patient-reported outcome 2 remission at week 2 (35% vs 30%; adjusted odds ratio [OR], 1.71; 95% CI, 1.15-2.55) and at week 6 (50.0% vs 38.9%; adjusted OR, 2.0; 95% CI, 1.40-2.94). Infliximab-treated patients were also significantly more likely to achieve clinical remission than golimumab-treated patients (adjusted OR, 3.01; 95% CI, 1.95-4.70), with consistent findings in patients with moderate or severe UC. CONCLUSIONS: Based on a patient-level analysis of data from phase 3 trials, infliximab resolves symptoms more rapidly and has greater efficacy for inducing remission than golimumab in patients with moderate-severe UC.

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