Use of conditional estimates of effect in cancer epidemiology: An application to lung cancer treatment.

BACKGROUND: In oncology clinical trials, there is the assumption that randomization sufficiently balances confounding covariates and therefore average treatment effects are usually reported. This paper explores the wider benefits provided by conditioning on covariates for reasons other than mitigation of confounding. METHODS: We reanalyzed the data from primary randomized controlled trials listed in two meta-analyses to explore the significance of conditioning on smoking status in terms of the effect magnitude of treatment on progression free survival in non-small cell lung cancer. RESULTS: The reanalysis revealed that conditioning on smoking status using sub-group analyses provided the closest empiric estimate of individual treatment effect based on smoking status and significantly reduced the heterogeneity of treatment effect observed across studies. In addition, smoking status was determined to be a modifier of the effect of treatment. CONCLUSION: Conditioning on prognostic covariates in randomized trials in oncology helps generate the closest empiric estimates of individual treatment benefit, addresses heterogeneity due to varying covariate distributions across trials and facilitates future decision making as well as evidence synthesis. Conditioning using sub-group analyses also allows examination for effect modification in meta-analysis.

Causes of death among international travellers in Peru, 2017 to 2021.

BACKGROUND: The wellbeing and safety of international tourists is a paramount concern for governments and stakeholders. Mortality among travellers and the causes of death serve as a significant metric of destination safety. We describe the epidemiology and causes of death among international travellers in Peru. METHODS: Data retrieved from the Peruvian government's deaths certificates registry included all non-residents who died between January 2017 and December 2021. We analysed the national incidence and causes of death among international travellers in Peru. Causes of death were classified into non-communicable diseases (NCD), communicable diseases and injuries. We classified fatalities according to the existence of preventive measures that could be provided during the travel medicine consultation to decrease the risk. RESULTS: We obtained records from 1514 deaths among international travellers (973 males, 64%). The incidence increased from 0.2 deaths per 10 000 travellers in 2017 to 9.9 in 2021. NCDs were the most common causes of death (n = 560, 37%), followed by communicable diseases (n = 487, 32%), and injuries (n = 321, 21%). Causes of death were unknown in 9.7% of the records. The leading causes of death in these categories were cancer, cardiovascular disease, COVID-19 and trauma. We found similar sex distribution of NCDs in travellers aged >50 years and higher rates of communicable diseases among males across all ages. Injury-associated deaths were significantly higher among males aged 18-29 years (P < 0.001) compared with other sex-age groups. We estimated that for 57.7% of deaths risk could have been decreased through pre-travel advice. CONCLUSION: Rates of deaths among travellers to Peru increased over time. Most deaths were due to NCDs, followed by communicable diseases and injuries. Pre-travel medical optimization and effective advice focused on age-sex and destination specific risks could reduce risk among travellers. Increased awareness among travel medicine practitioners and improvement of emergency medical response systems in Peru could decrease mortality.

Bloodstream Infection and Colorectal Cancer Risk in Queensland Australia, 2000-2019.

BACKGROUND: Bloodstream infections may occur as a complication of colorectal cancer or be a marker for its occult presence. The objectives of this study were to quantify the overall and etiology-specific risks for incident colorectal cancer-associated bloodstream infection. METHODS: Population-based surveillance for community-onset bloodstream infection was conducted among adults aged 20 years and older in Queensland, Australia between 2000 and 2019. Statewide databases were used to identify patients with incident colorectal cancer and collect clinical and outcome information. RESULTS: After exclusion of 1794 patients with prior colorectal cancer, a cohort of 84,754 patients was assembled, of which 1030 had colorectal cancer-associated bloodstream infection and 83,724 had no colorectal cancer. Bloodstream infection was associated with a 16-fold annualized increased risk for diagnosis of colorectal cancer (incidence rate ratio 16.1; 95% confidence interval [CI], 15.1-17.1) in the adult population. Patients who had colorectal cancer-associated bloodstream infection were more likely to be older and male, have hospital-onset and polymicrobial infections, and have fewer non-cancer-related comorbidities. The organisms associated with highest risk for colorectal cancer included Clostridium species (relative risk [RR] 6.1; 95% CI, 4.7-7.9); especially C. septicum (RR 25.0; 95% CI, 16.9-35.7), Bacteroides species (RR 4.7; 95% CI, 3.8-5.8); especially B. ovatus (RR 11.8; 95% CI, 2.4-34.5), Gemella species (RR 6.5; 95% CI, 3.0-12.5), Streptococcus bovis group (RR 4.4; 95% CI, 2.7-6.8); especially S. infantarius subsp. coli (RR 10.6; 95% CI, 2.9-27.3), Streptococcus anginosus group (RR 1.9; 95% CI, 1.3-2.7), and Enterococcus species (RR 1.4; 95% CI, 1.1-1.8). CONCLUSION: Although much attention has been afforded to S. bovis group over the past decades, there are many other isolates associated with higher risk for colorectal cancer-associated bloodstream infections.

Immunogenicity of a single fractional intradermal dose of Japanese encephalitis live attenuated chimeric vaccine.

BACKGROUND: Japanese encephalitis (JE) is endemic in Asia and the western Pacific. Vaccination is recommended for travellers to endemic regions, but the high cost of the vaccine is a major barrier to uptake. METHODS: A quasi-experimental, pre-post intervention clinical trial without a control group was conducted to assess the immunogenicity and safety of intradermal (ID) JE vaccine. Healthy adults (18-45 years) received one dose of 0.1 mL (20% of standard dose) ID Imojev® (JE live attenuated chimeric vaccine, Sanofi-Aventis). Adverse events following immunization (AEFIs) were recorded 10 days post-vaccination. Blood samples were collected at baseline, 4 and 8 weeks post-vaccination. Neutralizing antibodies were measured using 50% plaque reduction neutralization test (PRNT50). Seroconversion was defined as PRNT50 titre ≥10. An in vitro study was also conducted to quantify the rate of decay of vaccine potency after reconstitution. RESULTS: In total, 51 participants (72.6% females, median age 31 years), all non-reactive to JE virus at baseline were enrolled. Mild and moderate AEFIs were reported by 19.6% of participants; none required medical attention or interfered with normal daily activities. All participants seroconverted at 4 weeks (GMT 249.3; 95%CI:192.8-322.5) and remained seropositive at 8 weeks (GMT 135.5; 95%CI:104.5-175.6). Vaccine potency declined at a rate of 0.14 log plaque-forming units/0.5 mL per hour. CONCLUSIONS: In healthy adults, a single 0.1 mL ID dose of Imojev was safe and immunogenic, at least in the short term. Reconstituted vials of Imojev vaccine may not retain their potency after 6 hours. Fractional JE ID vaccination could be a cheaper yet effective alternative for short-term travellers. Further studies need to investigate the immune response in a wider age range of individuals and the long-term immunogenicity of fractional JE ID vaccines. CLINICAL TRIALS REGISTRATION: ACTRN12621000024842.

Does the Sex of the Firstborn Child Affect the Breast Cancer Risk and Survival: A Systematic Review and Meta-analysis of Over 1 Million Cases

Background: Reports on the risk and prognosis of breast cancer in relation to the sex of a child have been conflicting. Since medical sciences play an important role in informing sociocultural understandings of health and illness, evidence-based studies have the potential to foster or counter stigma and shape social attitudes toward a newborn's sex. Aims: To pool all available evidence to provide the highest level of evidence on the association between the sex of the first child and breast cancer risk or prognosis. Study Design: Systematic review and meta-analyses. Methods: A comprehensive search using three databases was conducted from inception until May 2020. Titles and abstracts of all papers identified were independently screened by two authors. Data extraction and quality assessment were also performed independently by two researchers. The breast cancer risk was quantified using the odds ratio, and the prognosis (i.e., mortality) was measured using the risk ratio. Results: In the meta-analysis, 11 studies with more than 1 million participants were included. The pooled estimate from the five studies on risk and the six studies on prognosis were odds ratio 0.99 (95% confidence interval, 0.95-1.03) and risk ratio 1.00 (95% confidence interval, 0.80-1.26), respectively. Conclusion: When we pooled all available evidence, the sex of the firstborn child was neither associated with risk nor prognosis in breast cancer. Clinically, our findings are reassuring and important, especially in light of previous studies that recommended differential treatment and counseling based on the sex of the first child. Socially, our findings challenge conventional social stereotypes that regard male children as biologically superior to female children.

Determinants of Atrial Fibrillation Development among Patients undergoing Ibrutinib Therapy.

Objective: Within the last decade, the use of ibrutinib, a first-generation, non-selective, irreversible Burton's tyrosine kinase inhibitor for the treatment of hematological malignancies has proven highly effective in improving patient outcomes.Background: Ibrutinib has been associated with an increase in atrial fibrillation (AF). The predisposing factors are thought to be pre-existing cardiovascular risk factors, but these have not been directly evaluated.Methods: We conducted a nested case-control study, recruiting consecutive ibrutinib treated subjects to evaluate cardiovascular risk factors associated with the development of AF in patients diagnosed with hematological B-cell malignancies.Results: Of the 189 patients treated with ibrutinib and without AF at baseline, 54 (29%) developed AF. Cardiovascular risk factors associated with AF development were, older age, prior hypertension (HTN), history of heart failure (HF) and congenital heart disease. A patient with HF at baseline had a 1, 2, 6, and 12 month cumulative hazard of AF of 40%, 48%, 64%, and 71%, respectively. Patients with prior HTN without HF at baseline had a 1, 2, 6, and 12 month cumulative hazard of AF of 5%, 10%, 23%, and 31%, respectively while on ibrutinib therapy.Conclusions: The relationship between ibrutinib, cardiovascular comorbidities, and AF is through pre-existing cardiovascular disease. An individualized, multidisciplinary approach involving cardiologists should be considered when initiating ibrutinib, particularly when there is a history of HTN, HF or congenital heart disease. In such patients, there should be close cardiovascular monitoring and prompt intervention when AF develops to improve patient outcomes.

Evaluation of Gender Inequity in Thyroid Cancer Diagnosis: Differences by Sex in US Thyroid Cancer Incidence Compared With a Meta-analysis of Subclinical Thyroid Cancer Rates at Autopsy.

Importance: Thyroid cancer is more common in women than in men, but the associated causes of these differences are not fully understood. Objective: To compare sex-specific thyroid cancer rates in the US to the prevalence of subclinical thyroid cancer at autopsy. Data Sources: Data on thyroid cancer incidence and mortality by sex among US adults (≥18 years) were extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER) data for 1975 to 2017. Embase, PubMed, and Web of Science databases were searched for studies on the prevalence of subclinical thyroid cancer at autopsy of men and women, from inception to May 31, 2021. Study Selection: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used to perform a systematic search for articles reporting the prevalence of subclinical thyroid cancer in autopsy results of both women and men. Of 101 studies identified, 8 studies containing 12 data sets met inclusion criteria; ie, they examined the whole thyroid gland, stated the number of thyroids examined, and reported results by sex. Excluded studies reported thyroid cancer in Japan after the atomic bombs or Chernobyl after the nuclear disaster; did not examine the whole thyroid gland or had incomplete information on thyroid examination methods; or did not report rates by sex. Data Extraction and Synthesis: Thyroid cancer incidence and mortality data by sex, histologic type, and tumor size were extracted from SEER. The inverse variance heterogeneity model was used to meta-analyze the prevalence and the odds ratio of subclinical thyroid cancer by sex from 8 studies (12 data sets) on thyroid cancer prevalence in autopsy results. Main Outcomes and Measures: Incidence and mortality of thyroid cancer, by histologic type and tumor size; prevalence of thyroid cancer in autopsy results. Results: In 2017, 90% of thyroid cancers diagnosed were papillary thyroid cancer (PTC) and in 2013 to 2017, the women to men incidence ratio for small (≤2 cm) PTC was 4.39:1. The incidence ratio approached 1:1 as cancer type lethality increased. The ratio of thyroid cancer mortality by gender was 1.02:1 and remained stable from 1992 to 2017. Results of the meta-analysis showed that the pooled autopsy prevalence of subclinical PTC was 14% in women (95% CI, 8%-20%) and 11% in men (95% CI, 5%-18%). The pooled odds ratio of subclinical PTC in women compared with men was 1.07 (95% CI, 0.80-1.42). Conclusions and Relevance: This cohort study and meta-analysis found that the belief that women get thyroid cancer more often than men is an oversimplification. The gender disparity is mostly confined to the detection of small subclinical PTCs, which are equally common in both sexes at autopsy but identified during life much more often in women than men. As the lethality of the cancer type increases, the ratio of detection by gender approaches 1:1. This phenomenon may be associated with gender differences in health care utilization and patterns of clinical thinking and can harm both women, who are subject to overdetection, and men, who may be at risk of underdetection.

Efficacy of one-dose intramuscular rabies vaccine as pre-exposure prophylaxis in travellers.

BACKGROUND: Current guidelines for rabies pre-exposure prophylaxis (PrEP) recommend multiple vaccine doses. Travellers sometimes present for pre-travel consultation with insufficient time to complete standard PrEP schedules. We investigated the efficacy of one-dose intramuscular (IM) vaccine in priming the immune system (as PrEP) by measuring antibody response to simulated post-exposure prophylaxis (PEP). METHODS: A quasi-experimental pre-post intervention clinical trial was conducted at a specialist travel clinic in Australia. Adults (≥18 years) without a history of rabies vaccination were included. At Visit 1, seronegative status was confirmed and one dose of 0.5 ml IM rabies vaccine (Verorab®) administered. At Visit 2 (≥60 days after Visit 1), serology was repeated and a simulated PEP dose (0.5 ml IM) given on this day and again 3 days later (Visit 3). Serology was repeated at Visit 4 (7 days after Visit 2). RESULTS: A total of 94 antibody-negative participants were included (<50 years [n = 50]; ≥50 years [n = 44]). At Visit 2, 38.0 and 31.8% of participants aged <50 and ≥50 years were antibody-positive (≥0.5 EU/ml). At Visit 4, all participants were antibody-positive; 82.0 and 47.7% of participants aged <50 and ≥50 years had antibody levels >4 EU/ml, respectively. CONCLUSIONS: One-dose IM vaccine was effective as PrEP for priming the immune system in both age groups, resulting in rapid development of antibodies 7 days after commencing simulated PEP. If there is insufficient time to complete a standard PrEP schedule, one-dose IM could be considered as an alternative schedule for short trips, rather than not offering travellers any doses at all.Clinical trials registration: ACTRN12619000946112.

Intradermal rabies pre-exposure vaccination schedules in older travellers: comparison of immunogenicity post-primary course and post-booster.

BACKGROUND: Intradermal (ID) rabies vaccination for pre-exposure prophylaxis (PrEP) has become increasingly popular; however, there is limited evidence about the effectiveness of different ID PrEP schedules in travellers aged > 50 years or their response to ID boosters. This study aimed to compare across different ID vaccine schedules and age groups the proportion of travellers who were seropositive after (i) primary course of ID PrEP and (ii) a booster. METHODS: Travellers who received ID PrEP at a travel medicine clinic in South Australia from 2000 to 2016 were included. Three schedules were examined: 1IDx3 (1 × 0.1 ml on days 0, 7, 21-28), 2IDx2 (2 × 0.1 ml on days 0, 7) and 4IDx1 (4x0.1 ml on day 0). The 4IDx1 is a non-standard schedule that has been previously explored in research settings, but not endorsed by WHO for PrEP. Antibody titres of ≥0.5 IU/ml were considered seropositive. The proportion seropositive after a primary course or post-booster was estimated for each schedule and age category. Predictors of seronegative status after a primary course were examined using multivariable logistic regression models. RESULTS: Overall, 835 travellers (median age 37.5 years; 37.1% > 50 years) were included in the analyses of seropositivity after a primary course. Another group of 771 travellers (median age 45.9 years; 43.5% > 50 years) was included in the analyses of seropositivity post-booster. The proportion seropositive after primary course was 92.5% (95%CI: 90.5-94.1%) and highest with the 1IDx3 schedule (93.4%; 95%CI: 91.4-95.0%). After adjusting for age and timing of the serology, the odds of seronegative status were four times higher (OR 4.17; 95%CI: 1.43-12.18) with the 4IDx1 schedule compared to 1IDx3. Overall, 98.7% (95%CI: 97.6-99.3%) were seropositive post-booster. Of 46 travellers who received a booster ≥3 years after PrEP, all were seropositive post-booster. CONCLUSIONS: In older travellers, the 1IDx3 schedule was the most effective, and a high proportion were seropositive post-booster even many years after a primary course.

P value-driven methods were underpowered to detect publication bias: analysis of Cochrane review meta-analyses.

OBJECTIVES: The aim of the study was to investigate the effect of number of studies in a meta-analysis on the detection of publication bias using P value-driven methods. METHODS: The proportion of meta-analyses detected by Egger's, Harbord's, Peters', and Begg's tests to have asymmetry suggestive of publication bias were examined in 5,014 meta-analyses from Cochrane reviews. P values were also assessed in meta-analyses with varying number of studies, whereas symmetry was held constant. A simulation study was conducted to investigate if the above tests underestimate or overestimate the presence of publication bias. RESULTS: The proportion of meta-analyses detected as asymmetrical via Egger's, Harbord's, Peters', and Begg's tests decreased by 42.6%, 41.1%, 29.3%, and 28.3%, respectively, when the median number of studies in the meta-analysis decreased from 87 to 14. P values decreased as the number of studies increased in the meta-analysis, despite the level of symmetry remaining constant. The simulation study confirmed that when publication bias is present, P value tests underestimate the presence of publication bias, particularly when study numbers are small. CONCLUSION: P value-based tests used for the detection of publication bias-related asymmetry in meta-analysis require careful examination, as they underestimate asymmetry. Alternative methods not dependent on the number of studies are preferable.

Is there truly an increase in risk of cardiovascular and hematological adverse events with vascular endothelial growth factor receptor tyrosine kinase inhibitors?

Objectives: Recent studies have shown an increase risk of cardiovascular and hematological adverse events associated with vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs). The authors hypothesize that the original studies may have produced exaggerated results because of the small baseline risks involved.Methods: A meta-analysis that included 71 trials, 8 different VEGFR-TKIs, and 11 adverse events were re-analyzed. The outcome of interest was re-defined as the complementary outcome (i.e. remaining free of an adverse event). The inverse variance heterogeneity model was used to pool the effect size.Results: VEGFR-TKIs decreased the risk of remaining free of hypertension by 7% (RR 0.93; 95%CI:0.88-0.97). Specific VEGFR-TKIs; pazopanib, regorafenib, and nintedanib were associated with a decrease risk of remaining free of an arterial thrombotic event (RR 0.96; 95%CI:0.93-0.99), thrombocytopenia (RR 0.91; 95%CI:0.89-0.93), and bleeding (RR 0.96; 95%CI:0.93-0.99) respectively. VEGFR-TKIs were not associated with the thrombotic event, myocardial infarction, stroke, venous thrombotic event, pulmonary embolism, left ventricular dysfunction, or QTc interval prolongation.Conclusion: VEGFR-TKIs are associated with a small increase in the risk of patients developing hypertension, arterial thrombotic events, thrombocytopenia, and bleeding. Previous studies overestimated the actual risk associated with VEGFR-TKIs by analyzing the outcome with the lower baseline risk.

2019 update of the WSES guidelines for management of Clostridioides (Clostridium) difficile infection in surgical patients.

In the last three decades, Clostridium difficile infection (CDI) has increased in incidence and severity in many countries worldwide. The increase in CDI incidence has been particularly apparent among surgical patients. Therefore, prevention of CDI and optimization of management in the surgical patient are paramount. An international multidisciplinary panel of experts from the World Society of Emergency Surgery (WSES) updated its guidelines for management of CDI in surgical patients according to the most recent available literature. The update includes recent changes introduced in the management of this infection.

Drug-free Holidays: Compliance, Tolerability, and Acceptability of a 3-Day Atovaquone/Proguanil Schedule for Pretravel Malaria Chemoprophylaxis in Australian Travelers.

BACKGROUND: Poor compliance with chemoprophylaxis is a major contributing factor to the risk of malaria in travelers. Pre-travel chemoprophylaxis may improve compliance by enabling "drug-free holidays." The standard treatment dose of atovaquone/proguanil (250 mg/100 mg, 4 tablets/day for 3 days) provides protection against malaria for at least 4 weeks, and could therefore potentially be used for pre-travel chemoprophylaxis. In this study, we assessed the compliance, tolerability, and acceptability of the 3-day atovaquone/proguanil schedule for malarial chemoprophylaxis. METHODS: Two hundred thirty-three participants were recruited from 4 specialized travel medicine clinics in Australia. Adults traveling to malaria-endemic areas with low/medium risk for ≤4 weeks were enrolled and prescribed the 3-day schedule of atovaquone/proguanil, completed at least 1 day before departure. Questionnaires were used to collect data on demographics, travel destination, medication compliance, side effects, and reasons for choosing the 3-day schedule. RESULTS: Overall, 97.7% of participants complied with the 3-day schedule. Although side effects were reported in 43.3% of the participants, these were well tolerated, and mainly occurred during the first and second days. None of the participants developed malaria. The main reasons for choosing the 3-day schedule over standard chemoprophylaxis options were that it was easier to remember (72.1%), required taking fewer tablets (54.0%), and to help scientific research (54.0%). CONCLUSIONS: The 3-day atovaquone/proguanil schedule had an impressively high compliance rate, and was well tolerated and accepted by travelers. Further studies are required to assess the effectiveness of this schedule for chemoprophylaxis in travelers. CLINICAL TRIALS REGISTRATION: ACTRN12616000640404.

Differentiated thyroid cancer: millions spent with no tangible gain?

The incidence of differentiated thyroid cancer (DTC) has rapidly increased worldwide over the last decades. It is unknown if the increase in diagnosis has been mirrored by an increase in thyroidectomy rates with the concomitant economic impact that this would have on the health care system. DTC and thyroidectomy incidence as well as DTC-specific mortality were modeled using Poisson regression in New South Wales (NSW), Australia per year and by sex. The incidence of 2002 was the point from which the increase in rates was assessed cumulatively over the subsequent decade. The economic burden of potentially avoidable thyroidectomies due to the increase in diagnosis was estimated as the product of the additional thyroidectomy procedures during a decade attributable to rates beyond those reported for 2002 and the national average hospital cost of an uncomplicated thyroidectomy in Australia. The following results were obtained. The incidence of both DTC and thyroidectomy doubled in NSW between 2003 and 2012, while the DTC-specific mortality rate remained unchanged over the same period. Based on the 2002 incidence, the projected increase over 10 years (2003-2012) in thyroidectomy procedures was 2196. This translates to an extra cost burden of over AUD$ 18,600,000 in surgery-related health care expenditure over one decade in NSW. Our findings suggest that, if this rise is solely attributable to overdetection, then the rising expenditure serves no additional purpose. Reducing unnecessary detection and a conservative approach to managing DTC are sensible and would lead to millions of dollars in savings and reduced harms to patients.

Geographical outcome disparities in infection occurrence after colorectal surgery: An analysis of 58,096 colorectal surgical procedures.

BACKGROUND: Despite improved surgical practices and in-hospital surveillance systems, surgical site infections remain a major public health problem worldwide and often require readmission to hospital. The aim was to apply an advance and innovative spatial analysis approach to identify spatial pattern and clustering (hotspots) of surgical site infection rate (CSIR), and quantifying disparities across communities. METHODS: We used the Admitted Patient Data Collection for patients aged 18 years and over who underwent colorectal surgery in a public hospital between 2002 and 2013 in the Australian State of New South Wales (NSW). The colorectal surgical infection rate (CSIR) was computed. We assessed geographical variation and clustering in CSIR patterning to demonstrate spatial pattern and clustering across communities in NSW, Australia. RESULTS: There were 58,096 colorectal surgical procedures conducted in NSW from 2002 to 2013. The overall occurrence of CSIR was 9.64% (95%CI 9.40-9.88%). We found significant clusters of both high and low CSIR in outer regional and remote areas of NSW. CONCLUSION: Use of advanced spatial analyses allows identification of hotspots/clusters of adverse events that can help policy makers and clinicians better understand national patterns and initiate research to address disparities/geographical variation, and clustering of adverse events after surgery.

Clostridium difficile Infection and Risk of Colectomy in Patients with Inflammatory Bowel Disease: A Bias-adjusted Meta-analysis.

BACKGROUND: Clostridium difficile infection (CDI) is a common complication of inflammatory bowel diseases (IBDs) and is associated with worse outcome. Variable rates of colectomy have been reported among IBD complicated by CDI. We conducted a systematic review and meta-analysis of studies to assess the association between CDI and colectomy among patients with IBD. METHODS: The literature was systematically searched using PubMed from inception through April 2016. Studies were limited to cohort, case-control, and cross-sectional studies reporting colectomy risk stratified by CDI in patients with IBD. We estimated summary ORs and 95% CIs using the quality-effects model. Study quality was assessed using an adaptation of the Newcastle-Ottawa scale. RESULTS: Six studies were included in the meta-analysis, comprising 8 data sets. Results from meta-analysis showed that CDI was a significant risk factor for colectomy among patients with IBD, mainly patients with ulcerative colitis, almost doubling the odds (OR 1.90; 95% CI, 1.23-2.93). There was significant heterogeneity across studies (Q = 22.02, P < 0.001; I = 68%). Funnel plots were grossly asymmetrical. Results of sensitivity analysis restricting studies to those reporting ulcerative colitis only and studies using laboratory tests to confirm CDI were consistent with the result from the main analysis. CONCLUSIONS: CDI is a significant risk factor for colectomy in patients with IBD. Further research is needed to investigate the attributable risks of surgery due to CDI among patients with Crohn's disease.

Prevalence of Differentiated Thyroid Cancer in Autopsy Studies Over Six Decades: A Meta-Analysis.

PURPOSE: Differentiated thyroid cancer (DTC) incidence has been reported to have increased three- to 15-fold in the past few decades. It is unclear whether this represents overdiagnosis or a true increase in incidence. Therefore, the current study aimed to estimate the prevalence of incidental DTC in published autopsy series and determine whether this prevalence has been increasing over time. MATERIALS AND METHODS: PubMed, Embase, and Web of Science were searched from inception to December 2015 for relevant studies. Two authors searched for all autopsy studies that had included patients with no known history of thyroid pathology and reported the prevalence of incidental DTC (iDTC). Two authors independently extracted the data, and discrepancies were resolved by another author. The pooled prevalence of iDTC was assessed using a fixed-effects meta-analysis model with robust error variance. The time effect was studied using an inverse-variance weighted logit-linear regression model with robust error variance and a time variable. RESULTS: Thirty-five studies, conducted between 1949 and 2007, met the inclusion criteria and contributed 42 data sets and 12,834 autopsies. The prevalence of iDTC among the partial and whole examination subgroups was 4.1% (95% CI, 3.0% to 5.4%) and 11.2% (95% CI, 6.7% to 16.1%), respectively. Once the intensiveness of thyroid examination was accounted for in the regression model, the prevalence odds ratio stabilized from 1970 onward, and no time effect was observed. CONCLUSION: The current study confirms that iDTC is common, but the observed increasing incidence is not mirrored by prevalence within autopsy studies and, therefore, is unlikely to reflect a true population-level increase in tumorigenesis. This strongly suggests that the current increasing incidence of iDTC most likely reflects diagnostic detection increasing over time.

The McGill Brisbane Symptom Score in relation to survival in pancreatic adenocarcinoma: a validation study.

PURPOSE: The McGill Brisbane Symptom Score (MBSS) is a clinical score for pancreatic cancer patients upon initial presentation that takes into account four variables (weight loss, abdominal pain, jaundice, and history of smoking) to stratify them into two MBSS intensity categories. Several studies have suggested that these categories are strongly associated with eventual survival in patients with resectable (rPCa) and unresectable (uPCa) pancreatic cancer. This study aimed to validate the MBSS in a cohort of patients with pancreatic cancer from a single institution. METHODS: Survival time by resection status and MBSS intensity category were analyzed among 633 patients from our institution between 2001 and 2010. Hazard ratios for death using Cox proportional hazards models, with age as the timescale, adjustment for sex and year of diagnosis, and stratified by adjuvant chemotherapy status were estimated. RESULTS: Median survival time was the longest in patients with low-intensity MBSS and rPCa (817 days), whereas the shortest survival time was found among patients with uPCa regardless of MBSS status (144-147 days). After consideration of age and chemotherapy status, high-intensity MBSS was associated with poorer survival for both rPCa (HR 1.64; 95 % CI 1.07-2.52) and uPCa (HR 1.35; 95 % CI 1.06-1.72). CONCLUSIONS: Preoperative MBSS intensity is a useful prognostic indicator of survival in resectable as well as unresectable pancreatic cancer.

Comorbidities, Exposure to Medications, and the Risk of Community-Acquired Clostridium difficile Infection: a systematic review and meta-analysis.

BACKGROUND: Clostridium difficile infection (CDI) has been extensively described in healthcare settings; however, risk factors associated with community-acquired (CA) CDI remain uncertain. This study aimed to synthesize the current evidence for an association between commonly prescribed medications and comorbidities with CA-CDI. METHODS: A systematic search was conducted in 5 electronic databases for epidemiologic studies that examined the association between the presence of comorbidities and exposure to medications with the risk of CA-CDI. Pooled odds ratios were estimated using 3 meta-analytic methods. Subgroup analyses by location of studies and by life stages were conducted. RESULTS: Twelve publications (n=56,776 patients) met inclusion criteria. Antimicrobial (odds ratio, 6.18; 95% CI, 3.80-10.04) and corticosteroid (1.81; 1.15-2.84) exposure were associated with increased risk of CA-CDI. Among the comorbidities, inflammatory bowel disease (odds ratio, 3.72; 95% CI, 1.52-9.12), renal failure (2.64; 1.23-5.68), hematologic cancer (1.75; 1.02-5.68), and diabetes mellitus (1.15; 1.05-1.27) were associated with CA-CDI. By location, antimicrobial exposure was associated with a higher risk of CA-CDI in the United States, whereas proton-pump inhibitor exposure was associated with a higher risk in Europe. By life stages, the risk of CA-CDI associated with antimicrobial exposure greatly increased in adults older than 65 years. CONCLUSIONS: Antimicrobial exposure was the strongest risk factor associated with CA-CDI. Further studies are required to investigate the risk of CA-CDI associated with medications commonly prescribed in the community. Patients with diarrhea who have inflammatory bowel disease, renal failure, hematologic cancer, or diabetes are appropriate populations for interventional studies of screening.

Neoplasia escamosa de la superficie ocular en pacientes con pterigión en Perú / Squamous neoplasia of the ocular surface in patients with pterygium in Peru

Objetivos. Estimar la frecuencia de neoplasia escamosa de la superficie ocular (NESO) no sospechada en pterigión, la precisión del diagnóstico clínico y las características demográficas y clínicas asociadas. Materiales y métodos. Se examinaron los informes histopatológicos de los pacientes con diagnóstico clínico de pterigión y/o NESO que fueron quirúrgicamente tratados entre marzo de 2009 y diciembre de 2012 en el Instituto Nacional de Oftalmología en Lima, Perú. La precisión del diagnóstico clínico para identificar la NESO se evaluó mediante la sensibilidad, especificidad y los cocientes de probabilidad. Se realizaron modelos de regresión log-log negativos para identificar las características demográficas y clínicas asociadas con un aumento de las probabilidades de diagnosticar NESO. Resultados. Se examinaron 3021 informes de histopatología. La frecuencia de NESO no sospechada en pterigión fue de 0,65%. El diagnóstico clínico presentó una sensibilidad del 85%, una especificidad del 99%, un cociente de probabilidad positiva de 111,89 y un cociente probabilidad negativa de 0,15. Las características asociadas fueron el sexo masculino (OR 1,15; IC 95%:1,01-1,30), pacientes de 61 a 80 años (OR 1,54; IC 95%: 1,28-1,85), ≥ de 81 años (OR 3,10; IC 95%: 2,09-4,58), pacientes con lesiones recurrentes (OR 1,59; IC 95%: 1,03-2,46) y lesiones en el lado temporal (OR 3,57; IC 95%: 2,63-4,85) presentaron mayor probabilidad de NESO. Conclusiones. Se encontró una baja frecuencia de NESO no sospechada, sin embargo, es recomendable realizar el estudio histopatológico de forma rutinaria para evitar diagnósticos erróneos de NESO como pterigión.

Objectives. To estimate the frequency of unsuspected ocular surface squamous neoplasia (OSSN) in pterygium, the accuracy of clinical diagnosis, and associated demographic and clinical characteristics. Materials and methods. We reviewed histopathological reports of patients with a clinical diagnosis of pterygium and/or OSSN who were surgically treated between March 2009 and December 2012 at the National Eye Institute in Lima, Peru. The accuracy of the clinical diagnosis of OSSN was assessed by sensitivity, specificity, and likelihood ratios. Models of negative log-log regression were performed to identify demographic and clinical characteristics associated with increased odds of diagnosing OSSN. Results. 3,021 histopathological reports were reviewed. The frequency of unsuspected OSSN in pterygium was 0.65%. Clinical diagnosis had a sensitivity of 85%, a specificity of 99%, a positive likelihood ratio of 111.89, and a negative likelihood ratio of 0.15. Associated characteristics were male gender (OR =1.15; 95% CI: 1.01 to 1.30), age group of 61- 80 years (OR = 1.54, 95% CI: 1.28 to 1.85) ≥ 81 years (OR = 3.10; 95% CI: 2.09 to 4.58), presence of recurrent lesions (OR = 1.59; 95% CI: 1.03 to 2.46) and temporal location lesions (OR = 3.57; 95% CI: 2.63 to 4.85). These characteristics were associated with a greater likelihood of OSSN. Conclusions. A low frequency of unsuspected OSSN was found; however, it is recommended to routinely perform histopathology studies to avoid misdiagnosis of OSSN as pterygium.