Regional variation in cause of death in patients with type 2 diabetes: Insights from EXSCEL.

AIMS: Type 2 diabetes (T2D) is a risk factor for cardiovascular and non-cardiovascular mortality. However, global distribution of cause-specific deaths in T2D is poorly understood. We characterized cause-specific deaths by geographic region among individuals with T2D at risk for cardiovascular disease (CVD). METHODS AND RESULTS: The international EXSCEL trial included 14,752 participants with T2D (73% with established CVD). We identified the proportion of deaths over 5-year follow-up attributed to cardiovascular and non-cardiovascular causes, and associated risk factors. During median 3.2-year follow-up, 1,091 (7.4%) participants died. Adjudicated causes of death were 723 cardiovascular (66.3% of deaths), including 252 unknown, and 368 non-cardiovascular (33.7%). Most deaths occurred in North America (N = 356/9.6% across region) and Eastern Europe (N = 326/8.1%), with fewest in Asia/Pacific (N = 68/4.4%). The highest proportional cause-specific deaths by region were sudden cardiac in Asia/Pacific (23/34% of regional deaths) and North America (86/24%); unknown in Eastern Europe (90/28%) and Western Europe (39/21%); and non-malignant non-cardiovascular in Latin America (48/31%). Cox proportional hazards model for adjudicated causes of death showed prognostic risk factors (hazard ratio [95% CI]) for cardiovascular and non-cardiovascular deaths, respectively: heart failure 2.04 (1.72-2.42) and 1.86 (1.46-2.39); peripheral artery disease 1.83 (1.54-2.18) and 1.78 (1.40-2.26); and current smoking status 1.61 (1.29-2.01) and 1.77 (1.31-2.40). CONCLUSIONS: In a contemporary T2D trial population, with and without established CVD, leading causes of death varied by geographic region. Underlying mechanisms leading to variability in cause of death across geographic regions and its impact on clinical trial endpoints warrant future research.

Comparison of patient background between a real-world North American cohort and the Göteborg-2 trial.

OBJECTIVES: To analyze the generalizability of the Göteborg-2 findings to a North American cohort. METHODS: We replicated the Göteborg-2 inclusion criteria in our Henry Ford Health (HFH) cohort, by identifying all patients 50-60 years old who had a PSA test from 2013 to 2018. The first PSA within the study period was considered PSA at entry, and included in the analysis. Chi-square test was used to compare categorical variables between the Göteborg-2 and HFH cohort, with a particular focus on Black men, who were also analyzed separately. RESULTS: The HFH patients included in the cohort were 49 456, of which 8562 were Black. In patients within the entire HFH cohort, HFH Black cohort, Göteborg Reference cohort, and Göteborg Experimental cohort, the rate of PSA ≥3 ng/mL was, respectively, 6.8%, 10.2%, 6.8%, and 6.6%. The rate of biopsy performed was, respectively, 1.8%, 4.1%, 5.8%, and 2.5%. PCa was found in, respectively, 1.4%, 3.0%, 2.3%, and 1.5%; Gleason score 3 + 3 in, respectively, 0.5%, 0.8%, 1.2%, and 0.6%; Gleason score > 3 + 3 in, respectively, 0.9%, 2.2%, 1.1%, and 0.9%. CONCLUSIONS: Our cohort had a lower biopsy rate and a lower incidence of non-csPCa diagnosis than both Göteborg cohorts, while still maintaining the same incidence of csPCa. This implies that the benefits of reducing non-csPCa diagnosis, as observed in the Experimental Göteborg cohort, are not necessarily replicable in U.S. "real-world practice" patients. Also noteworthy, we had a significantly higher percentage of Black men, who showed more aggressive disease.

Safety of Same-Day Discharge after Bariatric Surgery: Retrospective 6-Year North American Analysis.

BACKGROUND: With increasing implementation of Enhanced Recovery After Surgery protocols and rising demand for inpatient hospital beds accentuated by COVID-19, there has been interest in same-day discharge (SDD) for bariatric surgery. The aim of this study was to determine the national trends, safety profile, and risk factors for complications of SDD for minimally invasive bariatric surgery. STUDY DESIGN: We analyzed the MBSAQIP database from 2016 to 2021 to characterize trends in SDD for minimally invasive bariatric operation. Multivariate logistic regression was performed on preoperative patient characteristics predictive of increased complications associated with SDD. A comparative analysis of postoperative outcomes within 30 days was performed for SDD and admission after 1:1 nearest neighbor propensity score matching for patient demographics and preoperative comorbidities. RESULTS: SDD increased from 2.4% in 2016 to 7.4% in 2021. Major preoperative factors associated with increased complications for SDD included Black race, history of MI, renal insufficiency, deep vein thrombosis, and smoking. SDD for Roux-en-Y gastric bypass had 72% increased risk of postoperative complications compared with sleeve gastrectomy. The overall major complications were lower in SDD cohort vs admission cohort (odds ratio [OR] 0.62, p < 0.01). However, there was a significant increase in deaths within 30 days (OR 2.11, p = 0.01), cardiac arrest (OR 2.73; p < 0.01), and dehydration requiring treatment (OR 1.33; p < 0.01) in SDD cohort compared with admission cohort. CONCLUSIONS: Nationally, there has been a rise in SDD for bariatric operation from 2016 to 2021. Matched analysis demonstrates that SDD is associated with a significantly higher mortality rate. Additionally, the risk of complications with SDD is higher for RYGB compared with sleeve gastrectomy. Therefore, further studies are required to appropriately select patients for whom bariatric surgery can be safely performed as an outpatient.

Longitudinal trends in causes of death among adults with HIV on antiretroviral therapy in Europe and North America from 1996 to 2020: a collaboration of cohort studies.

BACKGROUND: Mortality rates among people with HIV have fallen since 1996 following the widespread availability of effective antiretroviral therapy (ART). Patterns of cause-specific mortality are evolving as the population with HIV ages. We aimed to investigate longitudinal trends in cause-specific mortality among people with HIV starting ART in Europe and North America. METHODS: In this collaborative observational cohort study, we used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. We included data for people with HIV who started ART between 1996 and 2020 at the age of 16 years or older. Causes of death were classified into a single cause by both a clinician and an algorithm if International Classification of Diseases, Ninth Revision or Tenth Revision data were available, or independently by two clinicians. Disagreements were resolved through panel discussion. We used Poisson models to compare cause-specific mortality rates during the calendar periods 1996-99, 2000-03, 2004-07, 2008-11, 2012-15, and 2016-20, adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period. FINDINGS: Among 189 301 people with HIV included in this study, 16 832 (8·9%) deaths were recorded during 1 519 200 person-years of follow-up. 13 180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996-99 to 16% during 2016-20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4-18·4) during 1996-99 to 7·9 deaths (7·6-8·2) during 2016-20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84-0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79-0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79-0·87), liver-related (0·88, 0·84-0·93), non-AIDS infection-related (0·91, 0·86-0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90-0·97), and suicide or accident-related mortality (0·89, 0·82-0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00-1·14) and decreased slightly in men (0·96, 0·93-0·99). INTERPRETATION: Reductions of most major causes of death, particularly AIDS-related deaths among people with HIV on ART, were not seen for all subgroups. Interventions targeted at high-risk groups, substance use, and comorbidities might further increase life expectancy in people with HIV towards that in the general population. FUNDING: US National Institute on Alcohol Abuse and Alcoholism.

Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Late mortality among 5-year survivors of childhood cancer: A systematic review and meta-analysis.

BACKGROUND: Childhood cancer survivors are at increased risk of late mortality (death ≥5 years after diagnosis) from cancer recurrence and treatment-related late effects. The authors conducted a systematic review and meta-analysis to provide comprehensive estimates of late mortality risk among survivors internationally and to investigate differences in risk across world regions. METHODS: Health sciences databases were searched for cohort studies comprised of 5-year childhood cancer survivors in which the risk of mortality was evaluated across multiple cancer types. Eligible studies assessed all-cause mortality risk in survivors relative to the general population using the standardized mortality ratio (SMR). The absolute excess risk (AER) was assessed as a secondary measure to examine excess deaths. Cause-specific mortality risk was also assessed, if reported. SMRs from nonoverlapping cohorts were combined in subgroup meta-analysis, and the effect of world region was tested in univariate meta-regression. RESULTS: Nineteen studies were included, and cohort sizes ranged from 314 to 77,423 survivors. Throughout survivorship, SMRs for all-cause mortality generally declined, whereas AERs increased after 15-20 years from diagnosis in several cohorts. All-cause SMRs were significantly lower overall in North American studies than in European studies (relative SMR, 0.63; 95% confidence interval, 0.49-0.80). SMRs for subsequent malignant neoplasms and for cardiovascular, respiratory, and external causes did not vary significantly between world regions. CONCLUSIONS: The current findings suggest that late mortality risk may differ significantly between world regions, but these conclusions are based on a limited number of studies with considerable heterogeneity. Reasons for regional differences remain unclear but may be better elucidated through future analyses of individual-level data.

Outcomes of SADI and OAGB Compared to RYGB from the Metabolic and Bariatric Surgery Quality Improvement Program: The North American Experience.

BACKGROUND: Rapid adoption of sleeve gastrectomy (SG) in the last decade aptly reflects the desire of patients and surgeons for alternatives to RYGB and DS. While SG provides good outcomes, other options that address specific patient needs are warranted. Recently approved by ASMBS, SADI, and OAGB have garnered increasing interest due to their single anastomosis technique. METHODS: Using the Metabolic and Bariatric Surgery Quality Improvement Program database, we examined laparoscopic and robotic cases from 2018 to 2021 to understand the percentage of primary bariatric surgery cases that are SADI and OAGB. We used coarsened exact matching to match patients who underwent SADI or OAGB to patients who underwent Roux-en-Y gastric bypass (RYGB). We examined outcomes of matched patients using logistic regression. RESULTS: Of the 667,979 patients that underwent bariatric-metabolic surgery, 1326 (0.2%) underwent SADI, and 2541 (0.4%) underwent OAGB. SADI was not identified in the database until 2020. In 2020, there were 487 SADI procedures compared to 839 in 2021. From 2018 to 2021, OAGBs went from 149 to 940. Compared with RYGB, SADI was associated with higher rates of anastomotic or staple line leak (OR 2.21 (95% CI 1.08-4.53)) and sepsis (OR 3.62 (95% CI 1.62-8.12)). Compared with RYGB, OAGB was associated with lower rates of gastrointestinal bleeding (OR 0.29 (95% CI 0.12-0.71)) and bowel obstruction (OR 0.10 (95% CI 0.02-0.39)). Of note, there were no differences between these procedures and RYGB for 30-day mortality. CONCLUSION: More SADIs and OAGBs are being performed. However, there were higher complication rates associated with the SADI procedure. Further studies will be needed to better understand the key drivers for these outcomes.

Frequency of colorectal surveillance colonoscopies for adenomatous polyps: systematic review and meta-analysis.

BACKGROUND AND AIM: The purpose of this study was to assess evidence on the frequency of polyp surveillance colonoscopies performed earlier than the recommended follow-up intervals in clinical practice guidelines. METHODS: A systematic review was performed based on electronic searches in PubMed and Embase. Research articles, letters to the editors, and review articles, published before April 2022, were included. Studies that focused on the intervals of polyp surveillance in adult populations were selected. The Risk Of Bias In Non-randomized Studies of Exposure (ROBINS-E) was used to assess the risk of bias. A meta-analysis was performed with Forest plots to illustrate the results. RESULTS: In total, 16 studies, comprising 11 172 patients from Australia, Europe, and North America, were included for analysis. The quality of the studies was moderate. Overall, 38% (95% CI: 30-47%) of colonoscopies were undertaken earlier than their respective national clinical guidelines. In risk-stratified surveillance, 10 studies contained data relating to low-risk polyp surveillance intervals and 30% (95% CI: 29-31%) of colonoscopies were performed earlier than recommended. Eight studies contained data relating to intermediate-risk polyp surveillance and 15% (95% CI: 14-17%) of colonoscopies were performed earlier than recommended. One study showed that 6% (95% CI: 4-10%) of colonoscopies performed for high-risk polyp surveillance were performed earlier than recommended. CONCLUSIONS: A significant proportion of polyp surveillance was performed earlier than the guidelines suggested. This provides evidence of the potential overuse of healthcare resources and the opportunity to improve hospital efficiency.

A clinical overview of adolescent e-cigarette use (vaping).

E-cigarette use (also known as "vaping") has become increasingly popular among adolescents over the past decade and grown into a significant public health concern in North America, the United Kingdom, and other countries. Concerns about this new trend have generated numerous new research studies. This aim of this study was to summarize recent scientific findings, with a focus on their relevance to clinicians working with adolescents. The first half covers epidemiology, risk factors for e-cigarette use, characteristics of e-cigarette use, youth perceptions of e-cigarettes, physical health risks of e-cigarettes, evidence for "gateway effects" of e-cigarette exposure on subsequent substance use, and the relationship between e-cigarette use and mental health. The review concludes with a clinical focus on assessment of youth who vape, psychoeducation for youth and families, clinical management of vaping, and regulatory considerations.

Awareness of human papillomavirus infection among Indigenous males in North America and Oceania: a Scoping Review.

PURPOSE: Human papillomavirus (HPV) is the most commonly transmitted sexually transmitted infection. HPV infections have been on the rise among males, especially in the form of oropharyngeal cancer. Despite this, there is a gap in healthcare guidelines to increase HPV vaccine administration among males. In this study, we focus on the Indigenous population of North America and Oceania to determine existing barriers resulting in low HPV vaccination rates among the population. METHOD: We surveyed peer-reviewed literature on the awareness of HPV infection among Indigenous males in North America and Oceania. Using keywords HPV plus male, men or boy, and ethnical filters such as Indigenous, Aboriginal or First Nations, we retrieved 54 articles based on titles, of which 15 were included after reading the abstracts. RESULTS: Reported HPV awareness was generally low in Indigenous males in North America, with no peer-reviewed data from Oceania. The lower understanding by males compared to females was largely attributable to misconceptions about HPV-related diseases, their transmission, and prevention. Lack of awareness and concern toward the risk of contracting HPV infection in Indigenous males suggests an impediment in disseminating health information about this cancer-causing virus. CONCLUSION: Culturally sensitive education, with emphasis on Indigenous males, is needed to improve this group's HPV knowledge. Researchers should also engage meaningfully with Indigenous communities by building rapport to achieve a positive change in attitude.

Disparities in outcomes between Black and White patients in North America with thoracic malignancies and COVID-19 infection (TERAVOLT).

BACKGROUND: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied. METHODS: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities. Patients with missing race data or races and ethnicities with fewer than 50 patients were excluded from analysis. Multivariable analyses for endpoints of hospitalization and death were performed on these 471 patients. RESULTS: Of the 471 patients, 73% were White and 27% were Black. The majority (90%) were non-Hispanic ethnicity, 5% were Hispanic, and 4% were missing ethnicity data. Black patients were more likely to have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 2 (p-value = 0.04). On multivariable analysis, Black patients were more likely than White patients to require hospitalization (Odds Ratio (OR): 1.69, 95% CI: 1.01-2.83, p-value = 0.044). These differences remained across different waves of the pandemic. However, no statistically significant difference in mortality was found between Black and White patients (OR 1.29, 95% CI: 0.69-2.40, p-value = 0.408). CONCLUSIONS: Black patients with thoracic malignancies who acquire COVID-19 infection are at a significantly higher risk of hospitalization compared to White patients, but there is no significant difference in mortality. The underlying drivers of racial disparity among patients with thoracic malignancies and COVID-19 infection require ongoing investigation.

Burden of prostate cancer in the Middle East: A comparative analysis based on global cancer observatory data.

BACKGROUND: Prostate cancer represents a significant global health issue, yet our understanding of its impact in the Middle East remains limited. This study aimed to assess the incidence and mortality of prostate cancer in the Middle East, and compare these rates to those in Europe and North America. MATERIALS AND METHODS: We utilized the 2020 Global Cancer Observatory data, compiling incidence and mortality rates of prostate cancer in 20 Middle Eastern countries. We calculated mortality-to-incidence ratios (MIR) and compared the age-standardized incidence rate (ASIR) and MIR between the Middle East and the combined regions of North America and Europe. The countries were further stratified based on the Human Development Index (HDI) and income level for additional analysis. RESULTS: In 2020, the Middle East documented an estimated 51,649 new prostate cancer diagnoses, accounting for 3.7% of global cases. Despite a significantly lower ASIR in the Middle East compared with Europe and North America (10.50 vs. 21.50, p = 0.0087), the region had a higher MIR (12.35 vs. 3.00, p = 0.0476). When stratified based on HDI or income levels, there was no significant difference in MIRs; however, a significant trend of increasing MIR with decreasing HDI (p = 0.028) and income levels (p = 0.016) was observed. CONCLUSIONS: Despite a lower incidence, our analysis showed a significantly higher MIR for prostate cancer in the Middle East compared with Europe and North America. These findings underscore the unique challenges posed by prostate cancer in the Middle East and emphasize the necessity of tailored strategies to address this pressing public health issue.

Risk factors for overweight and obesity after childhood acute lymphoblastic leukemia in North America and Switzerland: A comparison of two cohort studies.

BACKGROUND: After childhood acute lymphoblastic leukemia (ALL), sequelae include overweight and obesity, yet with conflicting evidence. We compared the prevalence of overweight and obesity between ≥5-year ALL survivors from the North American Childhood Cancer Survivor Study (CCSS) and the Swiss Childhood Cancer Survivor Study (SCCSS) and described risk factors. METHODS: We included adult childhood ALL survivors diagnosed between 1976 and 1999. We matched CCSS participants (3:1) to SCCSS participants by sex and attained age. We calculated body mass index (BMI) from self-reported height and weight for 1287 CCSS and 429 SCCSS participants; we then compared those with siblings (2034) in North America and Switzerland (678) siblings. We assessed risk factors for overweight (BMI 25-29.9 kg/m2 ) and obesity (≥30 kg/m2 ) using multinomial regression. RESULTS: We found overweight and obesity significantly more common among survivors in North America when compared with survivors in Switzerland [overweight: 30%, 95% confidence interval (CI): 27-32 vs. 24%, 21-29; obesity: 29%, 27-32 vs. 7%, 5-10] and siblings (overweight: 30%, 27-32 vs. 25%, 22-29; obesity: 24%, 22-26 vs. 6%, 4-8). Survivors in North America [odds ratio (OR) = 1.24, 1.01-1.53] and Switzerland (1.27, 0.74-2.21) were slightly more often obese than siblings. Among survivors, risk factors for obesity included residency in North America (5.8, 3.7-9.0); male (1.7, 1.3-2.3); attained age (≥45 years: 5.1, 2.4-10.8); Non-Hispanic Black (3.4, 1.6-7.0); low household income (2.3, 1.4-3.5); young age at diagnosis (1.6, 1.1-2.2). Cranial radiotherapy ≥18 Gray was only a risk factor for overweight (1.4, 1.0-1.8); steroids were not associated with overweight or obesity. Interaction tests found no evidence of difference in risk factors between cohorts. CONCLUSIONS: Although treatment-related risk for overweight and obesity were similar between regions, higher prevalence among survivors in North America identifies important sociodemographic drivers for informing health policy and targeted intervention trials.

Performance evaluation of a North American center using the established global benchmark for laparoscopic liver resections: A retrospective study.

BACKGROUND: The global benchmark cut-offs were set for laparoscopic liver resection procedures: left lateral sectionectomy, left hepatectomy, and right hepatectomy. We aimed to compare the performance of our North American center with the established global benchmarks. METHODS: This is a single-center study of adults who underwent laparoscopic liver resection between 2010 to 2022 at the Toronto General Hospital. Fourteen benchmarking outcomes were assessed: operation time, intraoperative blood transfusion, estimated blood loss, blood loss ≥500 mL, blood loss ≥1000mL, open-conversion, postoperative length of stay, return to operation, postoperative morbidity, postoperative major-morbidity, 30-day mortality, 90-day mortality, R1 resection, and failure to rescue. Low-risk benchmark cases were defined as follows: patients aged 18 to 70 years, American Society of Anesthesiologist score ≤ 2, tumor size <10 cm, and Child-Pugh score ≤A. Cases involving bilio-enteric anastomosis, hilar dissection, or concomitant major procedures were excluded from the low-risk category. Cases that did not meet the criteria for low-risk selection were considered high-risk cases. RESULTS: A total of 178 laparoscopic liver resection cases were analyzed (109 left lateral sectionectomies, 45 left hepatectomies, 24 right hepatectomies). Forty-four (25%) cases qualified as low-risk cases (23 left lateral sectionectomies, 16 left hepatectomies, 5 right hepatectomies). The postoperative major morbidity and 90-day mortality after left lateral sectionectomy, left hepatectomy, and right hepatectomy for the low-risk cases were 0%, 0%, and 0%, and 0%, 0%, and 0%, respectively. For the high-risk cases post-2017, the outcomes in the same order were 0%, 0%, and 12%; 0%, 0%, and 0%, respectively. For the high-risk cases operated pre2017, the outcomes in the same order were 9%∗, 16%∗, and 18%; 2%∗, 0%, and 9%∗ (asterisks indicate not meeting the global cut-off), respectively. CONCLUSION: A North American center was able to achieve outcomes comparable to the established global benchmark for laparoscopic liver resection.

MUSKRATS (ONDATRA ZIBETHICUS) ARE COMPETENT INTERMEDIATE HOSTS OF ECHINOCOCCUS MULTILOCULARIS IN NORTH AMERICA.

The tapeworm Echinococcus multilocularis is an emerging pathogen of significance to human and animal health in Canada, yet little is known about key rodent intermediate hosts in local urban ecosystems. In Europe, invasive muskrats (Ondatra zibethicus) are an important indicator intermediate host species; however, the role of this semiaquatic rodent in the ecology of E. multilocularis is undetermined in the North American context. We examined 93 muskrats that were livetrapped in the spring of 2017 within Calgary, Alberta, Canada, for the presence of E. multilocularis infection. The objectives of this study were to 1) diagnose alveolar echinococcosis using macroscopic assessment, histopathology, and molecular analyses; 2) quantify infection severity; and 3) assess host demographic risk factors for infection. Macroscopic cysts consistent with alveolar echinococcosis were present in 24% of muskrats (22/93). Most individuals had hepatic cysts; however, cysts were also occasionally detected in the mesentery, reproductive organs, omentum, peritoneum, spleen, diaphragm, lung, or kidney. The mean number of cysts per liver was 2.1 (range, 1-4). We examined hepatic cysts from 18 individuals using histology; all had lesions compatible with alveolar echinococcosis. Protoscoleces, indicative of patent infections, were present in 14/18 (78%). No demographic risk factors (sex, body condition, body mass) were significantly associated with infection. Muskrats in the North American context are competent intermediate hosts with high infection prevalence and may play an important role in the ecology of this emerging parasite.

Low Anterior Resection Syndrome in a Reference North American Sample: Prevalence and Associated Factors.

BACKGROUND: Low anterior resection syndrome (LARS) is a well-described consequence of rectal cancer treatment. Studying the degree to which bowel dysfunction exists in the general population may help to better interpret to what extent LARS is related to disease and/or cancer treatment. Currently, North American LARS normative data are lacking. The aim of this study was to describe the prevalence of bowel dysfunction, as measured by the LARS score, and quality of life (QoL) in a reference North American sample. Quality of life was measured and associations between participant characteristics and LARS were identified. STUDY DESIGN: This was a single-institution cross-sectional study of asymptomatic adults who underwent screening and surveillance colonoscopies from 2018 to 2021 with no/benign endoscopic findings. Survey was conducted on select comorbidities, sociodemographic factors, LARS, and QoL. Outcomes were LARS and QoL. Multivariable linear regression accounting for a priori clinical factors associated with bowel dysfunction was performed. RESULTS: Of 1,004 subjects approached, 502 (50.0%) participated, and 135 (26.9%) participants had major/minor LARS. On multiple linear regression, female sex (ß = 2.15, 95% CI 0.30 to 4.00), younger age (ß = -0.10, 95% CI -0.18 to -0.03), White ethnicity (ß = 2.45, 95% CI 0.15 to 4.74), and the presence of at least one of the following factors: diabetes, depression, neurologic disorder, or cholecystectomy (ß = 3.54, 95% CI 1.57 to 5.51) were independently associated with a higher LARS score. Individuals with LARS had lower global QoL, functional subscales, and various symptom subscale scores. CONCLUSIONS: Our study identified the baseline prevalence of LARS in asymptomatic adults who have not undergone a low anterior resection. These normative data will allow for more accurate interpretation of ongoing studies on LARS in North American rectal cancer patients.

Epidemiology, treatment patterns, and disease burden of cytomegalovirus in hematopoietic cell transplant recipients in selected countries outside of Europe and North America: A systematic review.

BACKGROUND: Cytomegalovirus (CMV) disease impacts morbidity and mortality in hematopoietic cell transplant (HCT) recipients. This systematic review summarized data on the epidemiology, management, and burden of CMV post-HCT outside of Europe and North America. METHODS: The MEDLINE, Embase, and Cochrane databases were searched for observational studies and treatment guidelines in HCT recipients across 15 selected countries from Asia-Pacific, Latin America, and Middle East (search period: 1 January 2011-17 September 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatments, refractory, resistant CMV, and burden. RESULTS: Of 2708 references identified, 68 were eligible (67 studies and one guideline; 45/67 studies specific to adult allogeneic HCT recipients). The rates of CMV infection and disease within 1 year of allogeneic HCT were 24.9%-61.2% (23 studies) and 2.9%-15.7% (10 studies), respectively. Recurrence occurred in 19.8%-37.9% of cases (11 studies). Up to 10% of HCT recipients died of CMV-related causes. In all countries, first-line treatment for CMV infection/disease involved intravenous ganciclovir or valganciclovir. Conventional treatments were associated with serious adverse events such as myelosuppression (10.0%) or neutropenia only (30.0%, 39.8%) and nephrotoxicity (11.0%) (three studies), frequently leading to treatment discontinuation (up to 13.6%). Refractory CMV was reported in 2.9%, 13.0%, and 28.9% of treated patients (three studies) with resistant CMV diagnosed in 0%-10% of recipients (five studies). Patient-reported outcomes and economic data were scarce. CONCLUSION: The incidence of CMV infection and disease post-HCT is high outside of North America and Europe. CMV resistance and toxicity highlight a major unmet need with current conventional treatments.

Socioeconomic indices guided linear mixed-effects and meta-regression modelling of the temporal, global and regional prevalence of Helicobacter pylori in environmental waters: A class I carcinogen.

Environmental waters (EW) substantially lend to the transmission of Helicobacter pylori (Hp). But the increase in Hp infections and antimicrobial resistance is often attributed to socioeconomic status. The connection between socioeconomic status and Hp prevalence in EW is however yet to be investigated. This study aimed to assess the impacts of socioeconomic indices (SI: continent, world bank region (WBR), world bank income (WBI), WHO region, Socio-demographic Index (SDI quintile), Sustainable Development Index (SuDI), and Human Development Index (HDI)) on the prevalence of Hp in EW. Hp-EW data were fitted to a generalized linear mixed-effects model and SI-guided meta-regression models with a 1000-resampling test. The worldwide prevalence of Hp in EW was 21.76% [95% confidence interval [CI]: 10.29-40.29], which declined significantly from 59.52% [43.28-74.37] in 1990-99 to 19.36% [3.99-58.09] in 2010-19 and with increasing trend in 2020-22 (33.33%, 22.66-45.43). Hp prevalence in EW was highest in North America (45.12%, 17.07-76.66), then Europe (22.38%, 5.96-56.74), South America (22.09%, 13.76-33.49), Asia (2.98%, 0.02-85.17), and Africa (2.56%, 0.00-99.99). It was negligibly different among sampling settings, WBI, and WHO regions demonstrating highest prevalence in rural location [42.62%, 3.07-94.56], HIEs [32.82%, 13.19-61.10], and AMR [39.43%, 19.92-63.01], respectively. However, HDI, sample size, and microbiological method robustly predict Hp prevalence in EW justifying 26.08%, 21.15%, and 16.44% of the true difference, respectively. In conclusion, Hp is highly prevalence in EW across regional/socioeconomic strata and thus challenged the uses of socioeconomic status as surrogate for hygienic/sanitary practices in estimating Hp infection prevalence.

Epidemiology, management, and burden of cytomegalovirus in solid organ transplant recipients in selected countries outside of Europe and North America: A systematic review.

BACKGROUND: Cytomegalovirus (CMV) is a frequent infectious complication following solid organ transplantation (SOT). Considering significant differences in healthcare systems, a systematic review was conducted to describe the epidemiology, management, and burden of CMV post-SOT in selected countries outside of Europe and North America. METHODS: MEDLINE, Embase, and Cochrane databases were searched for observational studies in SOT recipients across 15 countries in the regions of Asia, Pacific, and Latin America (search period: January 1, 2011 to September 17, 2021). Outcomes included incidence of CMV infection/disease, recurrence, risk factors, CMV-related mortality, treatment patterns and guidelines, refractory and/or resistant CMV, patient-reported outcomes, and economic burden. RESULTS: Of 2708 studies identified, 49 were eligible (n = 43/49; 87.8% in adults; n = 34/49, 69.4% in kidney recipients). Across studies, selection of CMV preventive strategy was based on CMV serostatus. Overall, rates of CMV infection (within 1 year) and CMV disease post-SOT were respectively, 10.3%-63.2% (9 studies) and 0%-19.0% (17 studies). Recurrence occurred in 35.4%-41.0% cases (3 studies) and up to 5.3% recipients died of CMV-associated causes (11 studies). Conventional treatments for CMV infection/disease included ganciclovir (GCV) or valganciclovir. Up to 4.4% patients were resistant to treatment (3 studies); no studies reported on refractory CMV. Treatment-related adverse events with GCV included neutropenia (2%-29%), anemia (13%-48%), leukopenia (11%-37%), and thrombocytopenia (13%-24%). Data on economic burden were scarce. CONCLUSION: Outside of North America and Europe, rates of CMV infection/disease post-SOT are highly variable and CMV recurrence is frequent. CMV resistance and treatment-associated adverse events, including myelosuppression, highlight unmet needs with conventional therapy.

Racial Disparities in Treatment Initiation and Outcomes of Chronic Hepatitis B Virus Infection in North America.

Importance: Disparities in treatment initiation may affect outcomes, but data on racially diverse populations with chronic hepatitis B virus (HBV) infection are limited. Objective: To examine whether HBV treatment initiation and outcomes differ among racial groups. Design, Setting, and Participants: From January 14, 2011, to January 28, 2018, hepatitis B surface antigen-positive adults (age ≥18 years) not receiving anti-HBV therapy were enrolled and followed up at weeks 12, 24, and every 24 weeks thereafter in a multicenter longitudinal cohort study (Hepatitis B Research Network [HBRN] adult cohort study) conducted in North America. The last study visit and data collection were completed January 28, 2019. Data were analyzed from August 27, 2021, to August 25, 2022. All HBRN participants were included unless they had acute HBV, HIV, hepatitis C or D, less than 24-weeks of follow-up after enrollment, initiated treatment at or immediately after enrollment, or had unknown race. Exposures: Participants had clinical and laboratory assessments and could receive anti-HBV treatment after enrollment. Main Outcomes and Measures: Hepatitis B virus treatment initiation and major adverse liver outcomes (hepatic decompensation, hepatocellular carcinoma, liver transplant, and death). Results: Of 1550 participants, 193 (12%) were African American or Black, 1157 (75%) were Asian, 157 (10%) were White, and 43 (3%) were other races; 789 (51%) were women, and the median age was 41.2 (IQR, 32.9-51.6) years. Sociodemographic and virologic parameters differed between groups. During 5727 person-years of follow-up, 504 participants initiated treatment, with incidences of 4.8 per 100 person-years in African American or Black individuals, 9.9 per 100 person-years in Asian individuals, 6.6 per 100 person-years in White individuals, and 7.9 per 100 person-years in those of other races (P < .001). A lower proportion (14%) of African American or Black participants met treatment criteria compared with Asian (22%) and White (27%) individuals (P = .01). The cumulative probabilities of treatment initiation after meeting the criteria were not significantly different among racial groups (African American or Black, 0.45; Asian, 0.38; White, 0.40 at 48 weeks and African American or Black, 0.45; Asian, 0.51; White, 0.51 at 72 weeks; P = .68). The incidence of major adverse liver outcomes was 0.1 per 100 person-years and did not differ by race. Conclusions and Relevance: In this observational study of chronic HBV, African American or Black participants were less likely than individuals of other races to meet treatment criteria, but among those who did, HBV treatment receipt did not differ significantly by race or socioeconomic factors. Not all eligible participants initiated treatment, but adverse liver outcomes were rare. These findings may not be generalizable to patients with chronic HBV receiving care in other settings.