REMAP Periop: a randomised, embedded, multifactorial adaptive platform trial protocol for perioperative medicine to determine the optimal enhanced recovery pathway components in complex abdominal surgery patients within a US healthcare system.

INTRODUCTION: Implementation of enhanced recovery pathways (ERPs) has resulted in improved patient-centred outcomes and decreased costs. However, there is a lack of high-level evidence for many ERP elements. We have designed a randomised, embedded, multifactorial, adaptive platform perioperative medicine (REMAP Periop) trial to evaluate the effectiveness of several perioperative therapies for patients undergoing complex abdominal surgery as part of an ERP. This trial will begin with two domains: postoperative nausea/vomiting (PONV) prophylaxis and regional/neuraxial analgesia. Patients enrolled in the trial will be randomised to arms within both domains, with the possibility of adding additional domains in the future. METHODS AND ANALYSIS: In the PONV domain, patients are randomised to optimal versus supraoptimal prophylactic regimens. In the regional/neuraxial domain, patients are randomised to one of five different single-injection techniques/combination of techniques. The primary study endpoint is hospital-free days at 30 days, with additional domain-specific secondary endpoints of PONV incidence and postoperative opioid consumption. The efficacy of an intervention arm within a given domain will be evaluated at regular interim analyses using Bayesian statistical analysis. At the beginning of the trial, participants will have an equal probability of being allocated to any given intervention within a domain (ie, simple 1:1 randomisation), with response adaptive randomisation guiding changes to allocation ratios after interim analyses when applicable based on prespecified statistical triggers. Triggers met at interim analysis may also result in intervention dropping. ETHICS AND DISSEMINATION: The core protocol and domain-specific appendices were approved by the University of Pittsburgh Institutional Review Board. A waiver of informed consent was obtained for this trial. Trial results will be announced to the public and healthcare providers once prespecified statistical triggers of interest are reached as described in the core protocol, and the most favourable interventions will then be implemented as a standardised institutional protocol. TRIAL REGISTRATION NUMBER: NCT04606264.

Personality, gender, and family history in the prediction of college gambling.

The present study examined the degree to which gambling behaviors and gambling-relevant cognitive distortions could be predicted by personality factors, gender, and familial history of substance use and gambling problems in a large sample of college students (N = 581). Results indicate that parental gambling problems and, especially for males, a propensity to experience negative emotions predicted time spent gambling and gambling problems. Negative emotionality, along with parental substance use problems, impulsivity, and being male predicted gambling-related cognitive distortions. The differing pattern for impulsivity with respect to behaviors and beliefs might be explained by the low accessibility of gambling venues for the student population. We compare the present findings with past studies examining gambling behaviors in adult populations.

Muir-Torre syndrome.

In this case report of Muir-Torre syndrome (MTS), we describe a 47-year-old man with a personal and family history of colon cancer and a personal history of keratoacanthoma who presented with a sebaceous carcinoma and, subsequently, had a cystic sebaceous tumor. Immunohistochemical examination of the patient's colonic tumor, located proximal to the splenic flexure, revealed absence of MutL homolog (MLH)-1 protein. MTS is a rare genodermatosis defined clinically by the occurrence of a sebaceous neoplasm and an internal malignancy in the absence of other predisposing factors. Most patients present with sebaceous adenomas, but cystic sebaceous neoplasms have been reported as specific markers of MTS. Gastrointestinal and genitourinary cancers are the most common internal malignancies, with colorectal cancers often occurring at or proximal to the splenic flexure, contrary to most sporadic colorectal cancers. MTS is most frequently found as a variant of the autosomal dominant disorder hereditary non-polyposis colorectal cancer (HNPCC), with tumors demonstrating microsatellite instability and germline mutations in the DNA mismatch repair genes MutS homolog (MSH)-2 and MLH1. However, the distribution of gene mutations of patients with MTS is slightly different from that seen in all HNPCC families, and some cases of MTS arise spontaneously. Physicians should consider MTS in patients presenting with a sebaceous neoplasm, and immunohistochemical examination of tumors for MSH2 and MLH1 protein can be used as a screening test to identify patients with MTS. While the sebaceous and internal neoplasms of MTS are thought to follow a more indolent course than sporadic malignancies, patients with this disorder should be treated with standard therapies and carefully followed. Evidence indicates that for individuals with or at risk of MTS or HNPCC, colonoscopy every 1-2 years beginning at age 20-25 or 10 years younger than the youngest age at diagnosis in the family can be strongly recommended. Additionally, most experts believe that an annual history and physical examination, including a complete skin examination and urinalysis, as well as periodic endometrial sampling and/or transvaginal ultrasound for women, are worthwhile screening tests for these high-risk patients.