Extended Right-Sided Colon Resection Does Not Reduce the Risk of Colon Cancer Local-Regional Recurrence: Nationwide Population-Based Study From Danish Colorectal Cancer Group Database.

BACKGROUND: It is controversial whether extensive resection of right-sided colon cancer confers oncological benefits. OBJECTIVE: The aim of this study was to evaluate short- and long-term outcomes of extended surgical removal of the mesocolon compared to the conventional approach. DESIGN: This was a retrospective population-based study. SETTING: Study is based on a prospectively maintained Danish Colorectal Cancer Group database. MAIN OUTCOME MEASURES: Primary outcome measures included local-regional recurrence in patients who underwent curative resection for right-sided colon cancer and 30-day postoperative complications. Distant metastasis, unplanned intraoperative adverse events, and 30- and 90-day postoperative mortality were also investigated. Patients who had palliative or compromised resection, emergency surgery, or neoadjuvant chemotherapy were excluded. RESULTS: Of the 12,855 patients with resection of right-sided colon cancer retrieved, 1151 underwent extended right hemicolectomy. Patients who had extended right hemicolectomy were younger males with lower ASA scores, were operated on by colorectal surgeons using a laparoscopic approach, and had a significantly higher number of harvested lymph nodes. The rate of local-regional recurrence was 1.1% (136/12,855), with no difference between conventional right hemicolectomy and extended right hemicolectomy (OR, 1.7; 95% CI, 0.63-2.18). Postoperative medical complications were significantly higher in extended right hemicolectomy even after adjusting for age, comorbidity, access to the abdomen, and other covariates (OR, 1.26; 95% CI, 1.01-1.58). No significant difference was noticed between conventional right hemicolectomy and extended right hemicolectomy in the rates of distant metastasis, unplanned intraoperative adverse events, and mortality. LIMITATIONS: Because it is a register-based study, underreporting cannot be excluded. Extended right hemicolectomy, as defined in this study, does not reflect the extent of lymphatic dissection performed during the surgery. CONCLUSIONS: This large population-based register study showed no difference in local-regional recurrence of right-sided colon cancer between conventional and extended right hemicolectomy with mesenteric resection and ligation of the middle colic vessels. Extended resection was associated with higher rates of postoperative complications. See Video Abstract at http://links.lww.com/DCR/B907 . LA RESECCIN AMPLIADA DEL COLON DERECHO NO REDUCE EL RIESGO DE RECURRENCIA LOCALREGIONAL DEL CNCER DE COLON ESTUDIO POBLACIONAL A NIVEL NACIONAL DE LA BASE DE DATOS DEL GRUPO DANS DE CNCER COLORRECTAL: ANTECEDENTES:Es aun un tema controversial si la resección ampliada del cáncer de colon del lado derecho confiere beneficios oncológicos.OBJETIVOS:El objetivo de este estudio fue examinar los resultados a corto y largo plazo de la resección quirúrgica ampliada del mesocolon en comparación con el enfoque convencional.DISEÑO:Este fue un estudio poblacional de tipo retrospectivo basado en una base de datos del Grupo Danés de Cáncer Colorrectal mantenida de manera prospectiva.AJUSTES:La medida de resultado primaria fue la recurrencia local-regional en pacientes sometidos a resección curativa por cáncer de colon del lado derecho y las medidas de resultado secundarias fueron las complicaciones posoperatorias a los 30 días. También fueron investigadas las metástasis a distancia, los eventos adversos intraoperatorios no planificados y la mortalidad posoperatoria a los 30 y 90 días. Se excluyeron los pacientes sometidos a resección paliativa o comprometida, cirugía de urgencia y quimioterapia neoadyuvante.RESULTADOS:De los 12.855 pacientes recuperados y sometidos a resección de cáncer de colon del lado derecho, 1151 fueron sometidos a hemicolectomía derecha ampliada. Los pacientes sometidos a hemicolectomía derecha ampliada fueron varones más jóvenes con puntuaciones ASA más bajas, operados por cirujanos colorrectales, utilizando la vía laparoscópica, y tuvieron un número significativamente mayor de ganglios linfáticos extraídos. La tasa de recidiva local-regional fue del 1,1% (136 / 12.855) sin diferencia entre la hemicolectomía derecha convencional y la hemicolectomía derecha ampliada (OR 1,7 IC 95% 0,63-2,18). Las complicaciones médicas post operatorias fueron significativamente mayores en la hemicolectomía derecha ampliada incluso después del ajuste por edad, comorbilidad, acceso al abdomen y otras covariables (OR 1,26; IC 95% 1,01-1,58). No se observaron diferencias significativas entre la hemicolectomía derecha convencional y la hemicolectomía derecha ampliada con respecto a las tasas de metástasis a distancia, eventos adversos intraoperatorios no planificados y mortalidad.LIMITACIONES:Es un estudio basado en registros, por lo tanto, no se puede excluir la sub notificación. La hemicolectomía derecha ampliada como se define en este estudio no refleja la extensión de la disección linfática realizada durante la cirugía.CONCLUSIONES:Este gran estudio basado en el registro poblacional no mostró diferencias en la recurrencia local-regional del cáncer de colon del lado derecho entre la hemicolectomía derecha convencional y ampliada con resección mesentérica y ligadura de los vasos cólicos medios. La resección ampliada se asoció con tasas más altas de complicaciones posoperatorias. Consulte Video Resumen en http://links.lww.com/DCR/B907 . (Traducción-Dr. Osvaldo Gauto ).

ECCO Guidelines on Therapeutics in Ulcerative Colitis: Surgical Treatment.

This is the second of a series of two articles reporting the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of adult patients with ulcerative colitis [UC]. The first article is focused on medical management, and the present article addresses medical treatment of acute severe ulcerative colitis [ASUC] and surgical management of medically refractory UC patients, including preoperative optimisation, surgical strategies, and technical issues. The article provides advice for a variety of common clinical and surgical conditions. Together, the articles represent an update of the evidence-based recommendations of the ECCO for UC.

Active case finding of pulmonary TB in a European refugee camp: lessons learnt from Oinofyta hosting site in Greece.

OBJECTIVES: To report on an active case finding (ACF) intervention that took place in the migrant camp of Oinofyta, Greece, upon suspicion of active TB transmission. METHODS: Upon diagnosis of 3 TB cases among camp residents, an ACF intervention among contacts was implemented. All camp residents were offered two-step screening, that is tuberculin skin testing (TST) followed by chest X-ray in case of positive TST (defined as ≥5 mm). RESULTS: 336 of 379 (89%) camp residents underwent TST testing, of whom 110 (33%) exhibited a positive skin reaction. The rate of positive TST results was particularly high in the elderly and significantly higher in adults than in children. Differences by sex or nationality were not observed. Of the 110 cases with positive TST, only 75 underwent chest X-ray, resulting in the detection of one pulmonary TB case in an adult woman. CONCLUSIONS: In the given intervention context, two-step ACF proved to be operationally cumbersome, with many residents lost to follow-up and a high Number Needed to Screen. Simpler ACF designs should be pilot-tested in similar settings in the future, and blanket screening of all camp residents should be reconsidered. Conclusions drawn by these exercises should pave the way for adopting a comprehensive, context-specific and evidence-based national strategy on TB in migrants.

The coexistence of asthma and COPD: risk factors, clinical history and lung function trajectories.

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV1/FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood.

Cumulative Occupational Exposures and Lung-Function Decline in Two Large General-Population Cohorts.

Rationale: Few longitudinal studies have assessed the relationship between occupational exposures and lung-function decline in the general population with a sufficiently long follow-up.Objectives: To examine the potential association in two large cohorts: the ECRHS (European Community Respiratory Health Survey) and the SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults).Methods: General-population samples of individuals aged 18 to 62 were randomly selected in 1991-1993 and followed up approximately 10 and 20 years later. Spirometry (without bronchodilation) was performed at each visit. Coded complete job histories during follow-up visits were linked to a job-exposure matrix, generating cumulative exposure estimates for 12 occupational exposures. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were jointly modeled in linear mixed-effects models, fitted in a Bayesian framework, taking into account age and smoking.Results: A total of 40,024 lung-function measurements from 17,833 study participants were analyzed. We found accelerated declines in FEV1 and the FEV1/FVC ratio for exposure to biological dust, mineral dust, and metals (FEV1 = -15.1 ml, -14.4 ml, and -18.7 ml, respectively; and FEV1/FVC ratio = -0.52%, -0.43%, and -0.36%, respectively; per 25 intensity-years of exposure). These declines were comparable in magnitude with those associated with long-term smoking. No effect modification by sex or smoking status was identified. Findings were similar between the ECRHS and the SAPALDIA cohorts.Conclusions: Our results greatly strengthen the evidence base implicating occupation, independent of smoking, as a risk factor for lung-function decline. This highlights the need to prevent or control these exposures in the workplace.

Quality of Care Standards in Inflammatory Bowel Diseases: a European Crohn's and Colitis Organisation [ECCO] Position Paper.

The management of inflammatory bowel disease [IBD] is complex, and requires tight control of disease activity, close monitoring to avoid treatment side effects, health care professionals with expertise in IBD, and an interdisciplinary, holistic approach. Despite various efforts to standardise structures, processes, and outcomes,1-8 and due to the high variability at the local, national, and international levels, there are still no clear definitions or outcome measures available to establish quality of care standards for IBD patients which are applicable in all contexts and all countries. For this reason, the European Crohn's and Colitis Organisation [ECCO] supported the construction of a list of criteria summarising current standards of care in IBD. The list comprises 111 quality standard points grouped into three main domains [structure n = 31, process n = 42, outcomes n = 38] and is based on scientific evidence, interdisciplinary expert consensus, and patient-oriented perspectives. The list of proposed criteria is intended to represent the position of ECCO regarding the optimum quality of care that should be available to patients. Since health care systems and regulations vary considerably between countries, this list may require adaptation at local and national levels. It is recognised that not all these criteria that have been identified as optimal will be available in every unit. However, ECCO will continue its efforts to develop and coordinate projects and initiatives that will help to guarantee optimal quality of care for all IBD patients.

Antibody Response Following Pre-Exposure Immunization Against Rabies in High-Risk Professionals.

Vaccination against rabies and routine antibody testing of subjects participating in programs for the surveillance and control of rabies in animals is strongly recommended. The scope of this study is to describe the antibody level as measured by a commercial enzyme-linked immunosorbent assay (ELISA) after primary and booster intramuscular vaccination with a purified vero-cell rabies vaccine (PVRV) in high-risk professionals and to determine the influence of an array of factors on antibody level, that is, time elapsed since primary immunization series and booster dose, sex, age, pathologic conditions, high-risk occupation, and peak antibody level after initial scheme and booster dose. A primary series of three doses of PVRV was administered and a commercial ELISA was recommended 14 days postimmunization with continuous repetition at 6 months and yearly intervals for the laboratory personnel and the rest of the professionals, respectively. The protective antibody titer was defined as a minimum of 0.5 equivalent units/mL (EU/mL) (seroconvertion) and a booster dose was applied if the titer was determined nonprotective. The seroconversion rate (SCR) after primary vaccination was 100%, with a geometric mean titer (GMT) of 2.90 EU/mL (interquartile range [IQR]: 1.85-3.45). After booster vaccination due to nonprotective titer, the SCR was 100% and the GMT increased by 678% (95% confidence interval [CI]: 514-887) reaching 4.25 EU/mL (IQR: 4.00-4.60), 2.5 times higher than the GMT elicited by the primary vaccine scheme in the respective recipients. The titer dropped by 1.20% per month (95% CI: 0.52-1.89) regardless of booster administration or any other factor. Women had 51% higher titer compared with men (95% CI: 6-116). High-risk professionals should be verified for adequate antibody titers, but routine administration of a single booster dose of PVRV 1 year after the primary series could be considered; more evidence is needed to support the benefit in terms of immunity and logistics.

ECCO Guidelines on Therapeutics in Crohn's Disease: Surgical Treatment.

This article is the second in a series of two publications relating to the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of previous guidelines.

Environmental Risk Factors for Inflammatory Bowel Diseases: An Umbrella Review of Meta-analyses.

BACKGROUND & AIMS: Multiple environmental factors have been associated with the development of inflammatory bowel diseases (IBDs). We performed an umbrella review of meta-analyses to summarize available epidemiologic evidence and assess its credibility. METHODS: We systematically identified and appraised meta-analyses of observational studies examining environmental factors and risk of IBD (Crohn's disease [CD] or ulcerative colitis [UC]). For each meta-analysis, we considered the random effects estimate, its 95% confidence interval, the estimates of heterogeneity, and small-study effects, and we graded the evidence according to prespecified criteria. Methodologic quality was assessed with AMSTAR (ie, A Measurement Tool to Assess Systematic Reviews) 2. RESULTS: We examined 183 estimates in 53 meta-analyses of 71 environmental factors related to lifestyles and hygiene, surgeries, drug exposures, diet, microorganisms, and vaccinations. We identified 9 factors that increase risk of IBD: smoking (CD), urban living (CD and IBD), appendectomy (CD), tonsillectomy (CD), antibiotic exposure (IBD), oral contraceptive use (IBD), consumption of soft drinks (UC), vitamin D deficiency (IBD), and non-Helicobacter pylori-like enterohepatic Helicobacter species (IBD). We identified 7 factors that reduce risk of IBD: physical activity (CD), breastfeeding (IBD), bed sharing (CD), tea consumption (UC), high levels of folate (IBD), high levels of vitamin D (CD), and H pylori infection (CD, UC, and IBD). Epidemiologic evidence for all of these associations was of high to moderate strength; we identified another 11 factors associated with increased risk and 16 factors associated with reduced risk with weak credibility. Methodologic quality varied considerably among meta-analyses. Several associations were based on findings from retrospective studies, so it is not possible to determine if these are effects of IBD or the results of recall bias. CONCLUSIONS: In an umbrella review of meta-analyses, we found varying levels of evidence for associations of different environmental factors with risk of IBD. High-quality prospective studies with analyses of samples from patients with recent diagnoses of IBD are needed to determine whether these factors cause or are results of IBD and their pathogenic mechanisms.

Occupational exposures and incidence of chronic bronchitis and related symptoms over two decades: the European Community Respiratory Health Survey.

OBJECTIVES: Chronic bronchitis (CB) is an important chronic obstructive pulmonary disease (COPD)-related phenotype, with distinct clinical features and prognostic implications. Occupational exposures have been previously associated with increased risk of CB but few studies have examined this association prospectively using objective exposure assessment. We examined the effect of occupational exposures on CB incidence in the European Community Respiratory Health Survey. METHODS: Population samples aged 20-44 were randomly selected in 1991-1993, and followed up twice over 20 years. Participants without chronic cough or phlegm at baseline were analysed. Coded job histories during follow-up were linked to the ALOHA Job Exposure Matrix, generating occupational exposure estimates to 12 categories of chemical agents. Their association with CB incidence over both follow-ups was examined with Poisson models using generalised estimating equations. RESULTS: 8794 participants fulfilled the inclusion criteria, contributing 13 185 observations. Only participants exposed to metals had a higher incidence of CB (relative risk (RR) 1.70, 95% CI 1.16 to 2.50) compared with non-exposed to metals. Mineral dust exposure increased the incidence of chronic phlegm (RR 1.72, 95% CI 1.43 to 2.06). Incidence of chronic phlegm was increased in men exposed to gases/fumes and to solvents and in women exposed to pesticides. CONCLUSIONS: Occupational exposures are associated with chronic phlegm and CB, and the evidence is strongest for metals and mineral dust exposure. The observed differences between men and women warrant further investigation.

Loss of Response to Vedolizumab and Ability of Dose Intensification to Restore Response in Patients With Crohn's Disease or Ulcerative Colitis: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Vedolizumab is effective and safe for the treatment of Crohn's disease (CD) and ulcerative colitis (UC). Little is known about the incidence rate of loss of response to vedolizumab maintenance therapy or whether dose intensification restores response to this drug. METHODS: We searched PubMed, Scopus and conference abstracts (Digestive Disease Week, European Crohn's and Colitis Organization, and United European Gastroenterology Week), through December 2017, for experimental or observational cohort studies of vedolizumab use in adult patients with CD or UC; we identified studies that provided sufficient data to determine the incidence rate of loss of response among initial responders and the ability of dose intensification to restore response. Two reviewers independently abstracted study data and outcomes and rated each study's risk of bias. The studies were evaluated for heterogeneity and publication bias. Summary estimates were calculated using random effects models. RESULTS: We analyzed data from 10 eligible cohorts; most patients had received prior treatment with a tumor necrosis factor antagonist. The pooled incidence rates of loss of response were 47.9 per 100 person-years of follow up (95% CI, 26.3‒87.0; I2 = 74%) among patients with CD and 39.8 per 100 person-years of follow up (95% CI, 35.0‒45.3; I2 = 0%) among patients with UC. Dose intensification restored response to the drug in 53.8% of secondary non-responders (95% CI, 21.8%‒82.9%; I2 = 77%). CONCLUSIONS: In a systematic review and meta-analysis, we found high proportions of patients with CD or UC to lose responsiveness to vedolizumab maintenance therapy. Dose intensification restores responsiveness to more than half of these patients. Additional studies are warranted to inform clinical decision making.

Update of an occupational asthma-specific job exposure matrix to assess exposure to 30 specific agents.

OBJECTIVES: We aimed to update an asthmagen job exposure matrix (JEM) developed in the late 1990s. Main reasons were: the number of suspected and recognised asthmagens has since tripled; understanding of the aetiological role of irritants in asthma and methodological insights in application of JEMs have emerged in the period. METHODS: For each agent of the new occupational asthma-specific JEM (OAsJEM), a working group of three experts out of eight evaluated exposure for each International Standard Classification of Occupations, 1988 (ISCO-88) job code into three categories: 'high' (high probability of exposure and moderate-to-high intensity), 'medium' (low-to-moderate probability or low intensity) and 'unexposed'. Within a working group, experts evaluated exposures independently from each other. If expert assessments were inconsistent the final decision was taken by consensus. Specificity was favoured over sensitivity, that is, jobs were classified with high exposure only if the probability of exposure was high and the intensity moderate-to-high. In the final review, all experts checked assigned exposures and proposed/improved recommendations for expert re-evaluation after default application of the JEM. RESULTS: The OAsJEM covers exposures to 30 sensitisers/irritants, including 12 newly recognised, classified into seven broad groups. Initial agreement between the three experts was mostly fair to moderate (κ values 0.2-0.5). Out of 506 ISCO-88 codes, the majority was classified as unexposed (from 82.6% (organic solvents) to 99.8% (persulfates)) and a minority as 'high-exposed' (0.2% (persulfates) to 2.6% (organic solvents)). CONCLUSIONS: The OAsJEM developed to improve occupational exposure assessment may improve evaluations of associations with asthma in epidemiological studies and contribute to assessment of the burden of work-related asthma.

Risk of malignancies using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis.

INTRODUCTION: Malignancies have been reported in patients with rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, treated with anti-tumour necrosis factor (anti-TNF) agents. Areas covered: We conducted a systematic review of randomized controlled trials (RCTs) to determine the effect of anti-TNF agents on the occurrence of cancer (any type). Literature databases were searched up to May 2014 to identify relevant studies that evaluated adalimumab, certolizumab, etanercept, golimumab, or infliximab, compared with placebo or no treatment. Data on cancer occurrence were extracted at the maximum follow-up time reported. Expert opinion: Fifty-five RCTs with 20,631 patients met the eligibility criteria. Of these, 32 trials with 15,539 patients reported at least one case of cancer, for a total of 112 malignancies. The degree of variability between studies was consistent with what would be expected to occur by chance alone. There was no evidence of an association between anti-TNF agents and cancer risk (fixed-effects model (OR: 1.31, 95% CI: 0.89, 1.95); a random-effects model (OR: 1.16, 95% CI: 0.75, 1.81)). We found evidence of selective outcome reporting or publication bias suggesting that the pooled effect estimate for cancer may have been overestimated. The evidence is imprecise, and the risk of bias was high or unclear across primary studies.

Risk of infections using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: a systematic review and meta-analysis.

INTRODUCTION: Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection). We searched Medline, Embase, and the Cochrane Library up to May 2014 to identify eligible studies in adult patients with rheumatoid arthritis, psoriatic arthritis, or ankylosing spondylitis that evaluated anti-TNF drugs compared with placebo or no treatment. Expert opinion: Our study encompassed data from 71 randomized controlled trials involving 22,760 participants (range of follow-up: 1-36 months) and seven open label extension studies with 2,236 participants (range of follow-up: 6-48 months). Quantitative synthesis of the available data found statistically significant increases in the occurrence of any infections (20%), serious infections (40%), and tuberculosis (250%) associated with anti-TNF drug use, while the data for opportunistic infections were scarce. The quality of synthesized evidence was judged as moderate. Further evidence from registries and long-term epidemiological studies are needed to better define the relationship between anti-TNF agents and infection complications.

Calcium supplementation for the prevention of colorectal adenomas: A systematic review and meta-analysis of randomized controlled trials.

AIM: To determine the efficacy of calcium supplementation in reducing the recurrence of colorectal adenomas. METHODS: We conducted a systematic review and meta-analysis of published studies. We searched PubMed, Scopus, the Cochrane Library, the WHO International Clinical Trials Registry Platform, and the ClinicalTrials.gov website, through December 2015. Randomized, placebo-controlled trials assessing supplemental calcium intake for the prevention of recurrence of adenomas were eligible for inclusion. Two reviewers independently selected studies based on predefined criteria, extracted data and outcomes (recurrence of colorectal adenomas, and advanced or "high-risk" adenomas), and rated each trial's risk-of-bias. Between-study heterogeneity was assessed, and pooled risk ratio (RR) estimates with their 95% confidence intervals (95%CI) were calculated using fixed- and random-effects models. To express the treatment effect in clinical terms, we calculated the number needed to treat (NNT) to prevent one adenoma recurrence. We also assessed the quality of evidence using GRADE. RESULTS: Four randomized, placebo-controlled trials met the eligibility criteria and were included. Daily doses of elemental calcium ranged from 1200 to 2000 mg, while the duration of treatment and follow-up of participants ranged from 36 to 60 mo. Synthesis of intention-to-treat data, for participants who had undergone follow-up colonoscopies, indicated a modest protective effect of calcium in prevention of adenomas (fixed-effects, RR = 0.89, 95%CI: 0.82-0.96; random-effects, RR = 0.87, 95%CI: 0.77-0.98; high quality of evidence). The NNT was 20 (95%CI: 12-61) to prevent one colorectal adenoma recurrence within a period of 3 to 5 years. On the other hand, the association between calcium treatment and advanced adenomas did not reach statistical significance (fixed-effects, RR = 0.92, 95%CI: 0.75-1.13; random-effects, RR = 0.92, 95%CI: 0.71-1.18; moderate quality of evidence). CONCLUSION: Our results suggest a modest chemopreventive effect of calcium supplements against recurrent colorectal adenomas over a period of 36 to 60 mo. Further research is warranted.

Biologic Therapies and Risk of Infection and Malignancy in Patients With Inflammatory Bowel Disease: A Systematic Review and Network Meta-analysis.

BACKGROUND & AIMS: Safety issues are a major concern for patients considering treatments for inflammatory bowel disease (IBD). We performed a systematic review and meta-analysis to determine whether biologic agents affect the risk of infection or malignancy in adults with IBD. METHODS: We searched PubMed, Embase, Scopus, Cochrane IBD Group Specialized Trials Register, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov through March 2016 for randomized placebo-controlled or head-to-head trials of biologic agents approved for treatment of adults with IBD (ie, adalimumab, certolizumab, golimumab, infliximab, natalizumab, or vedolizumab). Two reviewers independently extracted study data and outcomes (serious infections, opportunistic infections, tuberculosis, any infection, and malignancies) and rated each trial's risk of bias. We used conventional meta-analysis to synthesize direct evidence and a network meta-analysis for adjusted indirect treatment comparisons. RESULTS: We identified 49 randomized placebo-controlled studies comprising 14,590 participants. Synthesis of the evidence indicated that patients treated with biologics had a moderate increase in risk of any infection (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.10-1.29) and a significant increase in risk of opportunistic infections (OR, 1.90; 95% CI, 1.21-3.01). Risk of serious infections was not increased in patients treated with biologics (OR, 0.89; 95% CI, 0.71-1.12). On the contrary, biologics appeared to significantly reduce risk of serious infections in studies with low risk of bias (OR, 0.56; 95% CI, 0.35-0.90). We did not find an increased risk of malignancy with use of biologic agents (OR, 0.90; 95% CI, 0.54-1.50), but data were insufficient in terms of exposure and follow-up times. None of the indirect comparisons, either among the individual agents or between the anti-tumor necrosis factor and anti-integrin classes, reached significance for any of the outcomes analyzed. CONCLUSIONS: On the basis of a systematic review and meta-analysis, biologic agents increase the risk of opportunistic infections in patients with IBD, but not the risk of serious infections. It is necessary to continue to monitor the comparative and long-term safety profiles of these drugs.

Intravenous Versus Oral Iron for the Treatment of Anemia in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Anemia is the most prevalent extraintestinal complication of inflammatory bowel disease (IBD). Our aim was to evaluate the comparative efficacy and harm of intravenous (IV) versus oral iron supplementation for correcting anemia in adult IBD patients.We conducted a systematic review and meta-analysis to integrate evidence from randomized controlled trials having enrolled adults with IBD, and comparing IV versus oral iron (head-to-head) for correcting iron-deficiency anemia. Medline, Embase, Scopus, and the Web of Science database were searched through July 2015. The Cochrane Central Register of Controlled Trials, the WHO International Clinical Trials Registry Platform, the ClinicalTrials.gov, and international conference proceedings were also investigated. Two reviewers independently abstracted study data and outcomes, and rated each trial's risk-of-bias. Pooled odds ratio (OR) estimates with their 95% CIs were calculated using fixed- and random-effects models.Five eligible studies, including 694 IBD patients, were identified. In meta-analysis, IV iron demonstrated a higher efficacy in achieving a hemoglobin rise of ≥2.0 g/dL as compared to oral iron (OR: 1.57, 95% CI: 1.13, 2.18). Treatment discontinuation rates, due to adverse events or intolerance, were lower in the IV iron groups (OR: 0.27, 95% CI: 0.13, 0.59). Similarly, the occurrence of gastrointestinal adverse events was consistently lower in the IV iron groups. On the contrary, serious adverse events (SAEs) were more frequently reported among patients receiving IV iron preparations (OR: 4.57, 95% CI: 1.11, 18.8); however, the majority of the reported SAEs were judged as unrelated or unlikely to be related to the study medication. We found no evidence of publication bias, or between-study heterogeneity, across all analyses. Risk of bias was high across primary studies, because patients and personnel were not blinded to the intervention.IV iron appears to be more effective and better tolerated than oral iron for the treatment of IBD-associated anemia.

Statins and the risk of colorectal cancer: an updated systematic review and meta-analysis of 40 studies.

AIM: To investigate the association between statin use and colorectal cancer risk, we conducted an updated meta-analysis of published studies. METHODS: We performed a comprehensive search for studies published up to July 2013. Eligible studies for this meta-analysis were either randomized controlled trials (RCTs) or observational studies (case-control or cohort) evaluating any exposure to statins and the risk of colorectal cancer. Two reviewers selected studies based on predefined inclusion criteria, and abstracted the data. Pooled relative risk (RR) estimates with their 95%CI were calculated using fixed- and random-effects models. Then, we assessed the potential presence of publication bias and between-studies heterogeneity. To evaluate the results, we also performed a "leave-one-out" sensitivity analysis. RESULTS: A total of 40 studies, involving more than eight million subjects, contributed to the analysis. They were grouped on the basis of study design and, consequently, three separate meta-analyses were conducted. A similar modest reduction in the risk of colorectal cancer with statin use was observed, which was not statistically significant among RCTs (RR = 0.89, 95%CI: 0.74-1.07; n = 8), but reached statistical significance among cohort studies (RR = 0.91, 95%CI: 0.83-1.00; n = 13) and case-control studies (RR = 0.92, 95%CI: 0.87-0.98; n = 19). While we did not find significant evidence of selective outcome reporting or publication bias, substantial heterogeneity was detected, mainly among the observational studies. The sensitivity analysis confirmed the stability of our results. CONCLUSION: A modest reduction in risk of colorectal cancer among statin users cannot be disproved. Further targeted research is warranted.