The Use of Rifaximin in the Prevention of Overt Hepatic Encephalopathy After Transjugular Intrahepatic Portosystemic Shunt: A Randomized Controlled Trial: Annals of Internal Medicine: Vol 174, No 5

Background: The efficacy of rifaximin in the secondary prevention of overt hepatic encephalopathy (HE) is well documented, but its effectiveness in preventing a first episode in patients after transjugular intrahepatic portosystemic shunt (TIPS) has not been established. Objective: To determine whether rifaximin prevents overt HE after TIPS compared with placebo. Design: Randomized, double-blind, multicenter, placebo-controlled trial. (ClinicalTrials.gov: NCT02016196) Participants: 197 patients with cirrhosis undergoing TIPS for intractable ascites or prevention of variceal rebleeding. Intervention: Patients were randomly assigned to receive rifaximin (600 mg twice daily) or placebo, beginning 14 days before TIPS and continuing for 168 days after the procedure. Measurements: The primary efficacy end point was incidence of overt HE within 168 days after the TIPS procedure. Results: An episode of overt HE occurred in 34% (95% CI, 25% to 44%) of patients in the rifaximin group (n = 93) and 53% (CI, 43% to 63%) in the placebo group (n = 93) during the postprocedure period (odds ratio, 0.48 [CI, 0.27 to 0.87]). Neither the incidence of adverse events nor transplant-free survival was significantly different between the 2 groups. Limitations: The study's conclusion applies mainly to patients with alcoholic cirrhosis, who made up the study population. The potential benefit of rifaximin 6 months after TIPS and beyond remains to be investigated. Conclusion: In patients with cirrhosis treated with TIPS, rifaximin was well tolerated and reduced the risk for overt HE. Rifaximin should therefore be considered for prophylaxis of post-TIPS HE. Primary Funding Source: French Public Health Ministry.

Addressing Patient Bias Toward Health Care Workers: Recommendations for Medical Centers

Some patients engage in behavior or use language that demeans clinicians on the basis of their social identity traits, such as race, ethnicity, sex, disability, gender presentation, and sexual orientation, and some patients even request reassignment of involved clinicians. Despite the importance and prevalence of this problem, many medical centers lack an organizational approach for addressing patient conduct. Policy development can be daunting because organizations may encounter various barriers, including reluctance of staff to have difficult conversations about race or other identity traits; uncertainty about what constitutes an appropriate response to the spectrum of demeaning behaviors and who should make this determination; what, if any, support should be offered to targeted clinicians; whether these incidents should be reported and to whom; and whether the medical center's response should differ depending on whether nurses, trainees, or other clinicians are involved. These determinations have important implications for patients' informed consent rights, clinicians' employment rights, and medical centers' obligations to protect patients' health while adhering to workplace antidiscrimination laws and institutional commitments to diversity, equality, and inclusion. This article addresses these considerations and offers guidance to organizations on devising effective policies that meet the needs of medical centers, patients, and health care workers across services and roles, including physicians, nurses, and trainees.

Maternal Influenza A(H1N1) Immunization During Pregnancy and Risk for Autism Spectrum Disorder in Offspring: A Cohort Study: Annals of Internal Medicine: Vol 173, No 8

Background: There are concerns that influenza vaccine exposure during pregnancy may be associated with increased risk for autism spectrum disorder (ASD). Objective: To examine the risk for ASD in offspring of mothers who were vaccinated against influenza A(H1N1)pdm09 (“swine flu”) during pregnancy. Design: Population-based cohort study using nationwide registers. Setting: Seven health care regions in Sweden. Participants: Live births between October 2009 and September 2010, with follow-up through December 2016. In total, 39 726 infants were prenatally exposed to H1N1 vaccine (13 845 during the first trimester) and 29 293 infants were unexposed. Measurements: Cox regression was used to estimate hazard ratios (HRs) for the primary outcome, ASD, before and after adjustment for potential confounders. The secondary outcome was autistic disorder (AD). Results: Mean follow-up was 6.7 years in both unexposed and exposed children. During follow-up, 394 (1.0%) vaccine-exposed and 330 (1.1%) unexposed children had a diagnosis of ASD. In adjusted analyses, prenatal exposure to H1N1 vaccination was not associated with a later diagnosis of ASD (adjusted HR [aHR], 0.95 [95% CI, 0.81 to 1.12]) or AD (aHR, 0.96 [CI, 0.80 to 1.16]). The 6-year standardized cumulative incidence difference between the unexposed and exposed children was 0.04% (CI, −0.09% to 0.17%) for ASD and 0.02% (CI, −0.09% to 0.14%) for AD. Restricting the analysis to vaccination in the first trimester of pregnancy did not influence risk estimates (aHR, 0.92 [CI, 0.74 to 1.16] for ASD and 0.91 [CI, 0.70 to 1.18] for AD). Limitation: Data on H1N1 influenza infection are lacking. Conclusion: This large cohort study found no association between maternal H1N1 vaccination during pregnancy and risk for ASD in the offspring. Primary Funding Source: Swedish Research Council.

Contributions of Adenocarcinoma and Carcinoid Tumors to Early-Onset Colorectal Cancer Incidence Rates in the United States

Background: Early-onset colorectal cancer (EOCRC) incidence rates (IRs) are rising, according to previous cancer registry analyses. However, analysis of histologic subtypes, including adenocarcinoma (the focus of CRC screening and diagnostic testing) and carcinoid tumors (which are classified as “colorectal cancer” in SEER [Surveillance, Epidemiology, and End Results] databases but have a distinct pathogenesis and are managed differently from adenocarcinoma), has not been reported. Objective: To assess EOCRC IRs and changes in IRs over time, stratified by histology. Design: Retrospective analysis. Setting: Yearly IRs according to SEER 18 data from 2000 to 2016 on age-specific colon-only, rectal-only, and combined-site CRC cases, stratified by histology (“overall” CRC [all histologic subtypes], adenocarcinoma, and carcinoid tumors) and age. Patients: 119 624 patients with CRC. Measurements: IRs per 100 000 population, changes in 3-year average annual IRs (pooled IRs from 2000 to 2002 vs. those from 2014 to 2016), and annual percentage change (APC) in persons aged 20 to 29, 30 to 39, 40 to 49, and 50 to 54 years. Results: The steepest changes in adenocarcinoma 3-year average annual IRs were for rectal-only cases in persons aged 20 to 29 years (+39% [0.33 to 0.46 per 100 000]; P < 0.050) and 30 to 39 years (+39% [1.92 to 2.66 per 100 000]; P < 0.050) and colon-only cases in those aged 30 to 39 years (+20% [3.30 to 3.97 per 100 000]; P < 0.050). Corresponding APCs were 1.6% (P < 0.050), 2.2% (P < 0.050), and 1.2% (P < 0.050), respectively. In persons aged 40 to 49 years, 3-year average annual IRs increased in both colon-only (+13% [12.21 to 13.85 per 100 000]; P < 0.050) and rectal-only (+16% [7.50 to 8.72 per 100 000]; P < 0.050) subsites. Carcinoid tumors were common, representing approximately 4% to 20% of all colorectal and 8% to 34% of all rectal cancer cases, depending on age group and calendar year. Colon-only carcinoid tumors were rare. Colorectal carcinoid tumor IRs increased more steeply than adenocarcinoma in all age groups, thus affecting the contribution of carcinoid tumors to overall cancer cases over time. These changes were driven by rectal subsites and were most pronounced in persons aged 50 to 54 years, in whom rectal carcinoid tumors increased by 159% (2.36 to 6.10 per 100 000) between 2000 to 2002 and 2014 to 2016, compared with 10% for adenocarcinoma (18.07 to 19.84 per 100 000), ultimately accounting for 22.6% of all rectal cancer cases. Limitation: Population-based data. Conclusion: These findings underscore the importance of assessing histologic CRC subtypes independently. Doing so may lead to a better understanding of the drivers of temporal changes in overall CRC incidence and a more accurate measurement of outcomes from efforts to reduce adenocarcinoma risk, and can guide future research. Primary Funding Source: None.

Recommended Adult Immunization Schedule, United States, 2020*

Pricing Patients Out of Primary Care

Association Between Bariatric Surgery and All-Cause Mortality: A Population-Based Matched Cohort Study in a Universal Health Care System

Background: Mortality after bariatric surgery has been previously studied, but cohort selection bias, completeness of follow-up, and collection of confounders have limited the inference of results. Objective: To determine the association between bariatric surgery and all-cause mortality. Design: Population-based matched cohort study. Setting: Ontario, Canada. Participants: 13 679 patients who underwent bariatric surgery from January 2010 to December 2016 and 13 679 matched nonsurgical patients. Intervention: Bariatric surgery. Measurements: The primary outcome was all-cause mortality, with cause-specific mortality as the secondary outcome. Patients were matched according to age, sex, body mass index, and diabetes duration. Results: 13 679 patients who underwent bariatric surgery were matched to 13 679 nonsurgical patients. After a median follow-up of 4.9 years, the overall mortality rate was 1.4% (n = 197) in the surgery group and 2.5% (n = 340) in the nonsurgery group, with a lower adjusted hazard ratio (HR) of overall all-cause mortality (HR, 0.68 [95% CI, 0.57 to 0.81]). Patients aged 55 years or older had an absolute risk reduction of 3.3% (CI, 2.3% to 4.3%), with a lower HR of mortality in the surgery group (HR, 0.53 [CI, 0.41 to 0.69]). Observed relative effects were similar across sex; however, the observed association in absolute terms was greater in men. Surgery also was associated with lower cardiovascular mortality (HR, 0.53 [CI, 0.34 to 0.84]) and lower cancer mortality (HR, 0.54 [CI, 0.36 to 0.80]). Limitation: The observational design limits causal inference. Conclusion: Bariatric surgery was associated with substantially lower all-cause, cardiovascular, and cancer mortality. The lowered observed mortality of surgery was significant across most subgroups. The largest absolute effects were for men and patients aged 55 years or older. Primary Funding Source: Ontario Bariatric Network.

Disparities in Preventive Health Services: Targeting Minorities and Majorities

Health Is More Than Health Care

Caring for the Transgender Patient: Grand Rounds Discussion From Beth Israel Deaconess Medical Center: Annals of Internal Medicine: Vol 172, No 3

The term transgender refers to persons whose gender identity is different from that recorded at birth. Similar to other marginalized populations, transgender patients commonly experience discrimination in the health care setting, and they may not have access to medical professionals who can provide competent care. In addition to primary medical and preventive health care, transgender patients need access to gender-affirming interventions, including hormone therapy and surgeries. In 2017, the Endocrine Society updated its clinical practice guideline for the care of transgender persons on the basis of the best available evidence from systematic reviews and individual studies. Among its general requirements for adolescents and recommendations for adults were the following: Involvement of a mental health professional who is knowledgeable about the diagnostic criteria for gender dysphoria and criteria for gender-affirming treatment, has training and experience in assessing psychopathology, and is willing to participate in ongoing care. Hormone therapy should be offered to transgender adult patients, with levels maintained within the normal range for gender identity and treatment appropriately monitored. Clinicians involved in the care of transgender adult patients should be knowledgeable about diagnostic criteria for gender dysphoria/gender incongruence, the use of medical and surgical gender-affirming interventions, and appropriate monitoring for reproductive organ cancer risk. Here, 2 clinicians with expertise in this area debate whether psychological evaluation is warranted in a transgender patient requesting gender-affirming hormones or surgery, the potential risks and benefits of estrogen therapy, and the role of the primary care practitioner in the care of transgender persons.