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Summary Background The quadrivalent human papillomavirus (HPV) vaccine was shown to prevent infections and lesions related to HPV6, 11, 16, and 18 in a randomised, placebo-controlled study in men aged 16–26 years. We assessed the incidences of external genital warts related to HPV6 or 11, and external genital lesions and anal dysplasia related to HPV6, 11, 16, or 18, over 10 years of follow-up. Methods The 3-year base study was an international, multicentre, double-blind, randomised, placebo-controlled trial done at 71 sites in 18 countries. Eligible participants were heterosexual men (aged 16–23 years) or men who have sex with men (MSM; aged 16–26 years). Men who had clinically detectable anogenital warts or genital lesions at screening that were suggestive of infection with non-HPV sexually transmitted diseases, or who had a history of such findings, were excluded. Eligible participants were randomly assigned (1:1) to receive three doses of either quadrivalent HPV vaccine or placebo on day 1, month 2, and month 6, administered as a 0·5-mL injection into the deltoid muscle. The 7-year, open-label, long-term follow-up extension study was done at 46 centres in 16 countries. Participants who received one or more doses of the quadrivalent HPV vaccine in the base study were eligible for enrolment into the long-term follow-up study (early vaccination group). Placebo recipients were offered the three-dose quadrivalent HPV vaccine at the end of the base study; those who received one or more quadrivalent HPV vaccine doses were eligible for enrolment into the long-term follow-up study (catch-up vaccination group). The primary efficacy endpoints were the incidence of external genital warts related to HPV6 or 11 and the incidence of external genital lesions related to HPV6, 11, 16, or 18 in all participants and the incidence of anal intraepithelial neoplasia (including anal warts and flat lesions) or anal cancer related to HPV6, 11, 16, or 18 in MSM only. The primary efficacy analysis was done in the per-protocol population for the early vaccination group, which included participants who received all three vaccine doses, were seronegative at day 1 and PCR-negative from day 1 through month 7 of the base study for the HPV type being analysed, had no protocol violations that could affect evaluation of vaccine efficacy, and had attended at least one visit during the long-term follow-up study. For the catch-up vaccination group, efficacy was assessed in the modified intention-to-treat population, which included participants who had received at least one vaccine dose, were seronegative and PCR-negative for HPV types analysed from day 1 of the base study to the final follow-up visit before receiving the quadrivalent HPV vaccine, and had at least one long-term follow-up visit. Safety was assessed in all randomised participants who received at least one vaccine dose. This study is registered with ClinicalTrials.gov , NCT00090285 . Findings Between Aug 10, 2010, and April 3, 2017, 1803 participants were enrolled in the long-term follow-up study, of whom 936 (827 heterosexual men and 109 MSM) were included in the early vaccination group and 867 (739 heterosexual men and 128 MSM) were included in the catch-up vaccination group. Participants in the early vaccination group were followed up for a median of 9·5 years (range 0·1–11·5) after receiving the third dose of the quadrivalent HPV vaccine, and participants in the catch-up vaccination group were followed up for a median of 4·7 years (0·0–6·6) after receiving the third dose. In early vaccine group participants during long-term follow-up compared with the placebo group in the base study, the incidence per 10 000 person-years of external genital warts related to HPV6 or 11 was 0·0 (95% CI 0·0–8·7) versus 137·3 (83·9–212·1), of external genital lesions related to HPV6, 11, 16, or 18 was 0·0 (0·0–7·7) versus 140·4 (89·0–210·7), and of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 in MSM only was 20·5 (0·5–114·4) versus 906·2 (553·5–1399·5). Compared with during the base study (ie, before quadrivalent HPV vaccine administration), during the long-term follow-up period, participants in the catch-up vaccination group had no new reported cases of external genital warts related to HPV6 or 11 (149·6 cases per 10 000 person-years [95% CI 101·6–212·3] vs 0 cases per 10 000 person-years [0·0–13·5]) or external genital lesions related to HPV6, 11, 16, or 18 (155·1 cases per 10 000 person-years [108·0–215·7] vs 0 cases per 10 000 person-years [0·0–10·2]), and a lower incidence of anal intraepithelial neoplasia or anal cancer related to HPV6, 11, 16, or 18 (886·0 cases per 10 000 person-years [583·9–1289·1] vs 101·3 cases per 10 000 person-years [32·9–236·3]). No vaccine-related serious adverse events were reported. Interpretation The quadrivalent HPV vaccine provides durable protection against anogenital disease related to HPV6, 11, 16, and 18. The results support quadrivalent HPV vaccination in men, including catch-up vaccination. Funding Merck Sharp & Dohme.

Background It is unknown whether the place of birth would affect colon cancer survival. Methods An observational study of colon cancer patient data using the SEER database from 1973 to 2010 was performed. Patients with more than one primary cancer in their lifetime or patients who were under age 18 were excluded. The primary outcome was cancer-specific survival. Cox proportional hazards analyses were performed, adjusting for patient demographics and oncological characteristics. Results A total of 262,618 colon cancer patients were analyzed, with the majority (86.0%) born in the US. The overall 5-year cancer-specific survival rate was 51.4% and was significantly lower for US-born than non-US born patients (50.4% vs 58.1%). This difference persisted in local/regional disease and in cases with distant metastasis, and across racial groups. On adjusted analysis, US-born patients had worse disease-specific survivals (HR 1.28, 95% CI 1.24-1.33), and this effect persisted in all racial groups except in Asians. Conclusion US-born patients have worse survivals than non-US born patients. This is paradoxical given known disparities in quality of care delivered to immigrant populations. It may be useful to consider including geographical histories in patient interviews.

In response to the rapidly deteriorating pandemic situation, a national lockdown was imposed in March 2020 which had profound effects for students across the UK higher education sector. Given their...

Psychosocial, evidence-based interventions (EBI) may support personal recovery from psychosis; however, little is known about their implementation.: This paper describes the adaptation, implement...

Aim In colorectal cancer (CRC), surgery of the primary site is commonly curative. Our aim was to determine estimates of 'no surgery' for primary CRC while identifying common reasons for no surgery. Method We identified all patients with a diagnosis of colorectal adenocarcinoma from the National Cancer Database between January 2004 and December 2016. Then, we identified patients who did not undergo surgery on the primary tumour and their demographic, tumour and institutional characteristics. Kaplan-Meier and logistic regression analyses were used to evaluate specific factors associated with overall survival as related to no surgery and recommendations against operative management. Results A total of 1,208,878 patients with CRC were identified, 14.5% of whom had no surgery of the primary cancer. No surgery was more common in rectal cancer than in colon cancer. Despite a steady incidence of CRC diagnoses, the likelihood of no surgery grew by 170% over the study period. Metastatic disease was noted in 53.7% of the no surgery cohort. Nine per cent of the no surgery patient cohort received a recommendation against surgery despite the absence of metastatic disease, 7.5% refused surgery and only 2% underwent palliative surgery. On multivariable analysis, patients who were not recommended to have surgery were more likely to be older, uninsured, comorbid and receive care at a single hospital. The no surgery patients had significantly lower overall survival. Conclusion A substantial proportion of patients with CRC do not have surgery. Interventions aimed at expanding access and promoting second opinions at other cancer hospitals might reduce the growing rate of no surgery in CRC.

Background In men, the incidence of human papillomavirus (HPV)–related cancer is rising, but data regarding male HPV infection and seroprevalence are available from only a few countries. Methods This analysis of a global HPV vaccine trial evaluated baseline data from 1399 human immunodeficiency virus–negative heterosexual men (HM) and men who have sex with men (MSM). Key objectives included assessment of HPV prevalence and risk factors for seropositivity to 9-valent HPV (9vHPV) vaccine types (6, 11, 16, 18, 31, 33, 45, 52, and 58), and concordance between seropositivity and prevalent HPV type. Results Overall, 455 of 3463 HM (13.1%) and 228 of 602 MSM (37.9%) were HPV DNA positive for any 9vHPV vaccine type at baseline. Infection prevalence and seroprevalence (≥1 9vHPV vaccine type) were 13.2% and 8.1%, respectively, among 333 HM from Europe, and 37.9% and 29.9%, respectively, among 335 MSM from Europe or North America. Among men with baseline infection, MSM had higher seroprevalence for concordant HPV types (39.5% vs 10.8% in HM). The seropositivity risk (irrespective of baseline infection status) was higher among MSM versus HM (age-adjusted odds ratio, 3.0 [95% confidence interval, 2.4–6.4]). Among MSM, statistically significant seropositivity risk factors included younger age at sexual debut, higher number of receptive anal sex partners, and less frequent condom use. No factors assessed were associated with seropositivity in HM. Conclusions Higher proportions of MSM than HM were HPV DNA positive and seropositive, and concordance between HPV DNA positivity and seropositivity, a potential marker of true infection versus carriage, was higher in MSM. Most MSM and HM were seronegative for all 9vHPV vaccine types, suggesting the potential benefit of catch-up vaccination after sexual debut. Clinical Trials Registration. NCT00090285.

Background Transcatheter edge-to-edge (TEER) mitral repair may be complicated by residual or recurrent mitral regurgitation. An increasing need for surgical reintervention has been reported, but operative outcomes are ill defined. Objectives This study evaluated national outcomes of mitral surgery after TEER. Methods The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database was used to identify 524 adults who underwent mitral surgery after TEER between July 2014 and June 2020. Emergencies (5.0%; n = 26), previous mitral surgery (5.3%; n = 28), or open implantation of transcatheter prostheses (1.5%; n = 8) were excluded. The primary outcome was 30-day or in-hospital mortality. Results In the study cohort of 463 patients, the median age was 76 years (interquartile range [IQR]: 67 to 81 years), median left ventricular ejection fraction was 57% (IQR: 48% to 62%), and 177 (38.2%) patients had degenerative disease. Major concomitant cardiac surgery was performed in 137 (29.4%) patients: in patients undergoing isolated mitral surgery, the median STS-predicted mortality was 6.5% (IQR: 3.9% to 10.5%), the observed mortality was 10.2% (n = 23 of 225), and the ratio of observed to expected mortality was 1.2 (95% confidence interval [CI]: 0.8 to 1.9). Predictors of mortality included urgent surgery (odds ratio [OR]: 2.4; 95% CI: 1.3 to 4.6), nondegenerative/unknown etiology (OR: 2.2; 95% CI: 1.1 to 4.5), creatinine of >2.0 mg/dl (OR: 3.8; 95% CI: 1.9 to 7.9) and age of >80 years (OR: 2.1; 95% CI: 1.1 to 4.4). In a volume outcomes analysis in an expanded cohort of 591 patients at 227 hospitals, operative mortality was 2.6% (n = 2 of 76) in 4 centers that performed >10 cases versus 12.4% (n = 64 of 515) in centers performing fewer (p = 0.01). The surgical repair rate after failed TEER was 4.8% (n = 22) and was 6.8% (n = 12) in degenerative disease. Conclusions This study indicates that mitral repair is infrequently achieved after failed TEER, which may have implications for treatment choice in lower-risk and younger patients with degenerative disease. These findings should inform patient consent for TEER, clinical trial design, and clinical performance measures.

Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1− B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome data, 29.5% with favorable outcomes (5-year OS 65% to 80%) were deemed standard risk (DUX4-rearranged [9.2%], ETV6-RUNX1/-like [2.3%], TCF3-PBX1 [6.9%], PAX5 P80R [4.1%], high-hyperdiploid [6.9%]); 50.2% had high-risk genotypes with 5-year OS of 0% to 27% (Ph-like [21.2%], KMT2A-AFF1 [12%], low-hypodiploid/near-haploid [14.3%], BCL2/MYC-rearranged [2.8%]); 20.3% had intermediate-risk genotypes with 5-year OS of 33% to 45% (PAX5alt [12.4%], ZNF384/-like [5.1%], MEF2D-rearranged [2.8%]). IKZF1 alterations occurred in 86% of Ph-like, and TP53 mutations in patients who were low-hypodiploid (54%) and BCL2/MYC-rearranged (33%) but were not independently associated with outcome. Of patients considered high risk based on presenting age and white blood cell count, 40% harbored subtype-defining genetic alterations associated with standard- or intermediate-risk outcomes. We identified distinct immunophenotypic features for DUX4-rearranged, PAX5 P80R, ZNF384-R/-like, and Ph-like genotypes. These data in a large adult B-ALL cohort treated with a non–risk-adapted approach on a single trial show the prognostic importance of genomic analyses, which may translate into future therapeutic benefits.

Patients with diverticular disease complicated by abscess and/or perforation represent the most severely afflicted with the highest mortality and poorest outcomes. This study investigated patient and operative factors associated with poor outcomes from diverticulitis complicated by abscess or perforation. We analyzed the National Inpatient Sample to identify inpatient discharges for colonic diverticulitis in the United States from 1/1988 to 9/2015. We identified patients with perforation and/or intestinal abscess based on ICD-9 codes. The primary outcome was inpatient mortality. During the study period, a total of 993,220 patients were discharged with diverticulitis from sampled U.S. hospitals. From this group, 10.7% had an abscess and 1.0% had a perforation associated with diverticular disease. Inpatient mortality of diverticulitis patients with a perforation was 5.4% compared to 1.5% in those without a perforation (p

We report the 12-year follow-up of the prospective randomized EBMT LYM1 trial to determine whether the benefit of brief duration rituximab maintenance (RM) on progression-free survival (PFS) in patients with relapsed follicular lymphoma (FL) receiving an autologous stem cell transplant (ASCT) is sustained. One hundred and thirty-eight patients received RM with or without purging. The median follow-up after random assignment is 12 years (range 10-13) for the whole series. The 10-year PFS after ASCT is 47% (95% CI 40-54) with only 4 patients relapsing after 7.5 years. RM continues to significantly improve 10-year PFS after ASCT in comparison with NM [P = 0.002; HR 0.548 (95% CI 0.38-0.80)]. Ten-year non-relapse mortality (NRM) was not significantly different between treatment groups (7% overall). 10-year overall survival (OS) after ASCT was 75% (69-81) for the whole series, with no significant differences according to treatment sub-groups. 10-year OS for patients who progressed within 24 months (POD24T) was 60%, in comparison with 85% for patients without progression. Thus the benefit of rituximab maintenance after ASCT on relapse prevention is sustained at 12 years, suggesting that RM adds to ASCT-mediated disease eradication and may enhance the curative potential of ASCT.

Background We aimed to identify factors associated with refusal of surgery among patients with colon cancer. Methods This 2004–2016 NCDB retrospective study identified AJCC stage I-III colon cancer patients who were recommended surgery. Multivariable logistic regression defined adjusted odds ratios of refusing treatment, with sociodemographic and clinical covariates. Treatment propensity-adjusted Cox proportional hazard ratios defined differential survival stratified by clinical stage, controlling for potential confounders. Results Of 170,594 patients recommended surgery, 1116 refused. Increased rates of surgery refusal were associated with older age, African American race, CDCC>3, and female sex. Decreased rates of surgery refusal were associated with higher income and private insurance. Stratifying by stage, refusal rates among African Americans remained disparately high. Refusal of surgery was associated with worse overall survival. Conclusions Disparate rates of refusal of surgery for resectable colon cancer by race and other sociodemographic factors highlight potential treatment adherence reinforcement beneficiaries, necessitating further study of shared decision-making.

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Tumor border configuration (TBC) is a prognostic factor in colorectal adenocarcinoma; however, the significance of TBC is not well-documented in colon adenocarcinoma alone. Our aim was to study the effect of TBC on overall and disease-free survival in stage II and III colon adenocarcinoma. We included patients with stage II and III colon adenocarcinoma who were surgically treated at a tertiary medical center between 2004 and 2015, to ensure long-term follow-up. Patients were stratified into four groups based on stage and TBC. A Cox regression was used to model the relationship of groups while accounting for relevant confounders. The cohort consisted of 700 patients (371 stage II and 329 stage III). Infiltrating TBC was statistically significantly associated with stage (p

Extramural vascular invasion (EMVI) is a poor prognostic factor in colon cancer. However, the benefit of adjuvant chemotherapy in patients with EMVI is not well defined. The objective of this study is to determine if there is a survival benefit for using adjuvant chemotherapy in patients with EMVI-positive colon cancers. We performed a retrospective review of all patients with stages II and III colon adenocarcinoma who underwent surgical resection between 2004 and 2015. Cox regression was used to determine the effect of chemotherapy on EMVI-positive patients while adjusting for the extent of invasion, regional lymph node metastasis, histologic grade, age, site of tumor, and ASA score. A total of 750 patients were included in this study. Extramural vascular invasion was present in 93 out of 387 stage II patients (24%) and 187 out of 363 stage III patients (52%). The Cox regression model showed that in patients with EMVI, those who did not receive adjuvant chemotherapy had a 1.6-fold (1.1–2.3) increase in the hazard of death compared with those who received chemotherapy. Patients who were EMVI-negative fared better than those who were EMVI-positive. In patients who were EMVI-positive, adjuvant chemotherapy improved overall survival.

Background Recurrence-free patients after esophageal cancer surgery face long-term nutritional consequences, occurring in the context of an exaggerated postprandial gut hormone response. Acute gut hormone suppression influences brain reward signaling and eating behavior. This study aimed to suppress gut hormone secretion and characterize reward responses and eating behavior among postesophagectomy patients with unintentional weight loss. Methods This pilot study prospectively studied postoperative patients with 10% or greater body weight loss (BWL) beyond 1 year who were candidates for clinical treatment with long-acting octreotide (LAR). Before and after 4 weeks of treatment, gut hormone secretion, food cue reactivity (functional magnetic resonance imaging), eating motivation (progressive ratio task), ad libitum food intake, body composition, and symptom burden were assessed. Results Eight patients (7 male, age: mean ± SD 62.8 ± 9.4 years, postoperative BWL: 15.5 ± 5.8%) participated. Octreotide LAR did not significantly suppress total postprandial plasma glucagon-like peptide-1 response at 4 weeks (P = .08). Postprandial symptom burden improved after treatment (Sigstad score median [range]: 12 [2-28] vs 8 [3-18], P = .04) but weight remained stable (pre: 68.6 ± 12.8 kg vs post: 69.2 ± 13.4 kg, P = .13). There was no significant change in brain reward system responses, during evaluation of high-energy or low-energy food pictures, nor their appeal rating. Moreover, treatment did not alter motivation to eat (P = .41) nor ad libitum food intake(P = .46). Conclusion The protocol used made it feasible to characterize the gut-brain axis and eating behavior in this cohort. Inadequate suppression of gut hormone responses 4 weeks after octreotide LAR administration may explain the lack of gut-brain pathway alterations. A higher dose or shorter interdose interval may be required to optimize the intervention.

The continued emergence and spread of antimicrobial resistance (AMR), particularly multidrug resistant (MDR) bacteria, are increasing threats driving the search for additional and alternative antimicrobial agents. The World Health Organization (WHO) has categorized bacterial risk levels and includes Escherichia coli among the highest priority, making this both a convenient model bacterium and a clinically highly relevant species on which to base investigations of antimicrobials. Among many compounds examined for use as antimicrobials, Ga(III) complexes have shown promise. Nonetheless, the spectrum of activities, susceptibility of bacterial species, mechanisms of antimicrobial action, and bacterial characteristics influencing antibacterial actions are far from being completely understood; these are important considerations for any implementation of an effective antibacterial agent. In this investigation, we show that an alteration in growth conditions to physiologically relevant lowered oxygen (anaerobic) conditions substantially increases the minimum inhibitory concentrations (MICs) of Ga(III) required to inhibit growth for 46 wild-type E. coli strains. Several studies have implicated a Trojan horse hypothesis wherein bacterial Fe uptake systems have been linked to the promotion of Ga(III) uptake and result in enhanced antibacterial activity. Our studies show that, conversely, the carriage of accessory Fe uptake systems (Fe_acc) significantly increased the concentrations of Ga(III) required for antibacterial action. Similarly, it is shown that MDR strains are more resistant to Ga(III). The increased tolerance of Fe_acc/MDR strains was apparent under anaerobic conditions. This phenomenon of heightened tolerance has not previously been shown although the mechanisms remain to be defined. Nonetheless, this further highlights the significant contributions of bacterial metabolism, fitness, and AMR characteristics and their implications in evaluating novel antimicrobials.

OBJECTIVE To review the racial composition of the study populations that the current USPSTF screening guidelines for lung, breast, and colorectal cancer are based on, and the effects of their application across non-white individuals. SUMMARY OF BACKGROUND DATA USPSTF guidelines commonly become the basis for establishing standards of care, yet providers are often unaware of the racial composition of the study populations they are based on. METHODS We accessed the USPSTF screening guidelines for lung, breast, and colorectal cancer via their website, and reviewed all referenced publications for randomized controlled trials (RCTs), focusing on the racial composition of their study populations. We then used PubMed to identify publications addressing the generalizability of such guidelines across non-white individuals. Lastly, we reviewed all guidelines published by non-USPSTF organizations to identify the availability of race-specific recommendations. RESULTS Most RCTs used as basis for the current USPSTF guidelines either did not report race, or enrolled cohorts that were not representative of the U.S. POPULATION Several studies were identified demonstrating the broad application of such guidelines across non-white individuals can lead to underdiagnosis and higher levels of advanced disease. Nearly all guideline-issuing bodies fail to provide race-specific recommendations, despite often acknowledging increased disease burden among non-whites. CONCLUSION Concerted efforts to overcome limitations in the generalizability of RCTs are required to provide screening guidelines that are truly applicable to non-white populations. Broader policy changes to improve the pipeline for minority populations into science and medicine are needed to address the ongoing lack of diversity in these fields.

Summary Late relapse [>3 years from complete remission (CR)] in acute lymphoblastic leukaemia (ALL), is unusual. Data from the MRC UKALLXII/ECOG E2993 trial are presented to evaluate the incidence and characteristics of late relapse in adult ALL. Of 1,909 patients, 1,752 (92%) achieved CR and among these 757 (43·2%) relapsed; 691 (91·3%) within three years and 66 (8·7%) beyond. Among these 66 patients, median time to relapse was 47 (37–144) months. Relapse beyond three years occurred in 3·8% of all who achieved CR. The cumulative risk of relapse was 40%, 43% and 45% at three, five and ten years respectively. Out of the 1 752 patients who achieved CR, 11·7% underwent autologous and 40·6% allogeneic transplant, while in CR1. Of the autologous patients, 43·2% relapsed early and 3·4% relapsed late. However, among the allogeneic patients, 13·2% relapsed early and only 1·3% late. The five‐year overall survival from relapse was 5·8% and 20% in the early and late relapse patients respectively. In conclusion, late relapse in adults with ALL is not uncommon, and is associated with better outcome after relapse compared to early relapse.

Objective: We aimed to describe patterns of substance use among patients admitted to an emergency psychiatric unit for non-fatal suicidal behaviour (NFSB) or another psychiatric reason and establis...

Patients with cancer have higher COVID-19 morbidity and mortality. Here we present the prospective CAPTURE study, integrating longitudinal immune profiling with clinical annotation. Of 357 patients with cancer, 118 were SARS-CoV-2 positive, 94 were symptomatic and 2 died of COVID-19. In this cohort, 83% patients had S1-reactive antibodies and 82% had neutralizing antibodies against wild type SARS-CoV-2, whereas neutralizing antibody titers against the Alpha, Beta and Delta variants were substantially reduced. S1-reactive antibody levels decreased in 13% of patients, whereas neutralizing antibody titers remained stable for up to 329 days. Patients also had detectable SARS-CoV-2-specific T cells and CD4+ responses correlating with S1-reactive antibody levels, although patients with hematological malignancies had impaired immune responses that were disease and treatment specific, but presented compensatory cellular responses, further supported by clinical recovery in all but one patient. Overall, these findings advance the understanding of the nature and duration of the immune response to SARS-CoV-2 in patients with cancer.

We evaluated the performance of Fitbit Charge 3™ (FC3), a multi-sensor commercial sleep-tracker, for measuring sleep in adolescents against gold-standard laboratory polysomnography (PSG). Single-night PSG and FC3 sleep outcomes were compared in thirty-nine adolescents (22 girls; 16–19years), 12 of whom presented with clinical/subclinical DSM-5 insomnia symptoms (7 girls). Discrepancy analysis, Bland–Altman plots, and epoch-by-epoch analyses were used to evaluate FC3 performance. The influence of several factors potentially affecting FC3 performance (e.g., sex, age, body mass index, firmware version, and magnitude of heart rate changes between consecutive PSG epochs) was also tested. In the sample of healthy adolescents, FC3 systematically underestimated PSG total sleep time by about 11min and sleep efficiency by 2.5%, and overestimated wake after sleep onset by 9min. Proportional biases were detected for “light” and “deep” sleep duration, resulting in significant underestimation of these parameters for those participants having longer PSG N1+N2 and N3 durations, respectively. No significant systematic bias was detected for sleep efficiency and sleep onset latency. Epoch-by-epoch analysis showed sleep-stage sensitivity (average proportion of PSG epochs correctly classified by the device for a given sleep stage) of 68% for wake, 78% for “light” sleep, 59% for “deep” sleep, and 69% for rapid eye movement (REM) sleep in healthy sleepers. Similar results were found in the sample of adolescents with insomnia symptoms. Body mass index was positively associated with FC3-PSG discrepancies in wake after sleep onset (R2=.16, p =.048). The magnitude of the heart rate acceleration/deceleration between consecutive PSG epochs was an important factor affecting FC3 classifications of sleep stages. Our results are in line with a general trend in the literature, suggesting better performance for the recently introduced multi-sensor devices compared to motion-only devices, although further developments are needed to improve accuracy in sleep stage classification and wake detection. Further insight is needed to determine factors potentially affecting device performance, such as accuracy and reliability (consistency of performance over time), in different samples and conditions.

International audience; Prader-Willi syndrome (PWS) is a rare neuroendocrine genetic syndrome. Characteristics of PWS include hyperphagia, hypotonia, and intellectual disability. Pituitary hormone deficiencies, caused by hypothalamic dysfunction, are common and hypogonadism is the most prevalent. Untreated hypogonadism can cause osteoporosis, which is already an important issue in PWS. Therefore, timely detection and treatment of hypogonadism is crucial. To increase understanding and prevent undertreatment, we (1) performed a cohort study in the Dutch PWS population, (2) thoroughly reviewed the literature on female hypogonadism in PWS and (3) provide clinical recommendations on behalf of an international expert panel. For the cohort study, we retrospectively collected results of a systematic health screening in 64 female adults with PWS, which included a medical questionnaire, medical file search, medical interview, physical examination and biochemical measurements. Our data show that hypogonadism is frequent in females with PWS (94%), but is often undiagnosed and untreated. This could be related to unfamiliarity with the syndrome, fear of behavioral changes, hygienic concerns, or drug interactions. To prevent underdiagnosis and undertreatment, we provide practical recommendations for the screening and treatment of hypogonadism in females with PWS.

The Bundled Payments for Care Improvement initiative links payments for Medicare beneficiaries during an episode of care (90 days from index surgery).This study aimed to determine whether major bowel participating Bundled Payments for Care Improvement organizations experience greater cost savings for colectomy while maintaining satisfactory quality outcomes compared to nonparticipating organizations.This is an Analysis of all Bundled Payments for Care Improvement participating hospitals for major bowel procedures (major bowel group) and propensity score-matched against Bundled Payments for Care Improvement organizations that do not include major bowel procedures (nonmajor bowel group) and those that do not participate in any Bundled Payments for Care Improvement program (non-Bundled Payments for Care Improvement group).Programs accepting Medicare and Medicaid in the United States.Patients included were major bowel cases in the Medicare Standard Analytic file within Medicare Severity Diagnosis-Related Groups 329-331 at participating facilities between January 1, 2011, and June 30, 2016.Main outcome measures included average total care expenditure and quality of care (length of stay, morbidity, and mortality) from 3 days preoperatively to 90 days postoperatively.We abstracted 7609 major bowel episodes from 23 major bowel group facilities, 21,872 episodes from nonmajor bowel-matched hospitals, and 19,383 episodes from non-Bundled Payments for Care Improvement-matched hospitals. From the baseline (January 2011 to June 2012) to final period (July 2015 to June 2016), we noted a $2955 average reduction in care expenditures. The largest decrease in average total episode expenditure occurred within the major bowel group (14% reduction) compared to the other groups (6% reduction for nonmajor bowel and 5% reduction for non-Bundled Payments for Care Improvement). Utilizing a generalized estimating equation to adjust for patient demographics, comorbidities, and hospital characteristics, the average total episode expenditure for the major bowel group decreased by $4885 (95% CI $4838-$4932; p0.001) compared to $2050 (95% CI $2038-$2061) for the non-Bundled Payments for Care Improvement group. All groups had similar reductions in length of stay, 30-day and 90-day complication rates, and readmission rates.Analyses were limited by the retrospective nature of the study.Bundled Payments for Care Improvement participation for major bowel procedures resulted in a greater decrease in average total cost per episode of care than in nonparticipating hospitals without compromise in quality of care. See Video Abstract at http://links.lww.com/DCR/B837.IMPACTO DE LA INICIATIVA BUNDLED PAYMENT AGRUPADOS PARA LA MEJORA DE LA ATENCIÓN DEL GASTO SANITARIO EN LOS PROCEDIMIENTOS INTESTINALES MAYORESANTECEDENTES:La iniciativa de Bundled Payment para la mejora de la atención vincula los pagos para los beneficiarios de Medicare durante un episodio de atención (90 días desde la cirugía índice).OBJETIVO:Determinar si las principales organizaciones de Bundled Payment para el mejoramiento de la atención relacionados a los procedimientos intestinales experimentan mayores ahorros en los costos para una colectomía manteniendo resultados satisfactorios de calidad en comparación con las organizaciones no participantes.DISEÑO:Análisis de todos los hospitales participantes del programa Bundled Payment para la mejora de la atención para procedimientos intestinales mayores (grupo que incluyen procedimientos intestinales mayores) y puntaje de propensión comparado con las organizaciones que no incluyen dichos procedimientos (grupo que no incluye procedimientos intestinales mayores) y aquellos que no participan en ningún programa de Bundled Payment para la mejora de la atención (grupo no BPCI).MARCO:Programas que aceptan Medicare y Medicaid en los Estados Unidos.PACIENTES:Casos intestinales mayores en el archivo analítico estándar de Medicare dentro de los grupos relacionados con el diagnóstico 329-331 en los centros participantes entre el 1/1/2011-30/6/2016.PRINCIPALES MEDIDAS DE RESULTADO:Gasto total promedio y calidad de la atención (duración de la estadía, morbilidad, mortalidad) desde los 3 días preoperatorio hasta los 90 días postoperatorio.RESULTADOS:Hemos extraído 7609 episodios intestinales mayores de 23 instalaciones del grupo que incluyen procedimientos intestinales mayores, 21.872 episodios de hospitales del grupo que no incluyen procedimientos intestinales mayores y 19.383 episodios de hospitales del grupo no BPCI. Desde la línea de base (1/2011 - 6/2012) hasta el período final (7/2015 - 6/2016), notamos una reducción promedio de $2955 en los gastos de atención. La mayor disminución en el gasto promedio total por episodios ocurrió dentro del grupo que incluyen intestinales mayores (14% de reducción) en comparación con los otros grupos (6% de reducción para el grupo que no incluyen procedimientos intestinales mayores, 5% de reducción para el no BPCI). Utilizando una ecuación de estimación generalizada para ajustar los datos demográficos del paciente, las comorbilidades y las características del hospital, el gasto total promedio por episodio para el grupo que incluyen procedimientos intestinales mayores disminuyó en $ 4885 (IC del 95%: $4838-4932; p0,001) en comparación con $2050 (IC del 95%: $2038-2061) para el grupo que no pertenece al programa BPCI. Todos los grupos tuvieron reducciones similares en la duración de la estancia, tasas de complicaciones de 30/90 días y de readmisión.LIMITACIONES:Análisis limitados por la naturaleza retrospectiva del estudio.CONCLUSIONES:La participación de Bundled Payment para la mejora de la atención en aquellos procedimientos intestinales mayores resultó en una disminución mayor en el costo total promedio por episodio de atención que en los hospitales no participantes, sin comprometer la calidad de la atención. Consulte Video Resumen en http://links.lww.com/DCR/B837. (Traducción-Dr Osvaldo Gauto).

Objective: The aim of this study was to examine the clinical efficacy and safety of the duodenal-jejunal bypass liner (DJBL) while in situ for 12 months and for 12 months after explantation.Summary of background data: This is the largest randomized controlled trial (RCT) of the DJBL, a medical device used for the treatment of people with type 2 diabetes mellitus (T2DM) and obesity. Endoscopic interventions have been developed as potential alternatives to those not eligible or fearful of the risks of metabolic surgery.Methods: In this multicenter open-label RCT, 170 adults with inadequately controlled T2DM and obesity were randomized to intensive medical care with or without the DJBL. Primary outcome was the percentage of participants achieving a glycated hemoglobin reduction of ≥20% at 12 months. Secondary outcomes included weight loss and cardiometabolic risk factors at 12 and 24 months.Results: There were no significant differences in the percentage of patients achieving the primary outcome between both groups at 12 months [DJBL 54.6% (n = 30) vs control 55.2% (n = 32); odds ratio (OR) 0.93, 95% confidence interval (CI): 0.44-2.0; P = 0.85]. Twenty-four percent (n = 16) patients achieved ≥15% weight loss in the DJBL group compared to 4% (n = 2) in the controls at 12 months (OR 8.3, 95% CI: 1.8-39; P = .007). The DJBL group experienced superior reductions in systolic blood pressure, serum cholesterol, and alanine transaminase at 12 months. There were more adverse events in the DJBL group.Conclusions: The addition of the DJBL to intensive medical care was associated with superior weight loss, improvements in cardiometabolic risk factors, and fatty liver disease markers, but not glycemia, only while the device was in situ. The benefits of the devices need to be balanced against the higher rate of adverse events when making clinical decisions.Trial registration: ISRCTN30845205. isrctn.org; Efficacy and Mechanism Evaluation Programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership reference 12/10/04.

Introduction The ideal time interval between the completion of chemoradiotherapy and subsequent surgical resection of advanced stage rectal tumors is highly debated. Our aim is to study the effect of the time interval between the completion of chemoradiotherapy and surgical resection on postoperative and oncologic outcomes in rectal cancer. Methods Patients who underwent neoadjuvant chemoradiotherapy for resected locally advanced rectal tumors between 2004 and 2015 were included in this analysis. The time interval was calculated from the date of radiation completion to date of surgery. Patients were split into 2 groups based on the time interval (8 weeks). Postoperative outcomes (anastomotic leak, pathologic complete response (pCR), and readmission) and survival were assessed with multivariable logistic regression and Cox regression models while adjusting for relevant confounders. Results 200 patients (62% male) underwent resection with a median time interval of 8 weeks from completion of radiotherapy. On multivariable logistic regression, there was no significant increase in odds between time interval to surgery and anastomotic leak (aOR = .8 [.27-2.7], P = .8), pCR (aOR = 1.2[.58-2.6] P = .6), or readmission (aOR = 1.02, 95% CI:0.49-2.24, P = .9). Time interval to surgery was not an independent prognostic factor for overall (HR = 1.04 CI = .4-2.65, P = .9) and disease-free survival (HR = 1.2 CI = .5-2.9, P = .6). Conclusion The time interval between neoadjuvant radiotherapy completion and surgical resection does not affect anastomotic leak rate, achievement of pCR, or overall and disease-free survival in patients with rectal cancer. Extended periods of time to surgical resection are relatively safe.

Sleep-tracking devices, particularly within the consumer sleep technology (CST) space, are increasingly used in both research and clinical settings, providing new opportunities for large-scale data collection in highly ecological conditions. Due to the fast pace of the CST industry combined with the lack of a standardized framework to evaluate the performance of sleep trackers, their accuracy and reliability in measuring sleep remains largely unknown. Here, we provide a step-by-step analytical framework for evaluating the performance of sleep trackers (including standard actigraphy), as compared with gold-standard polysomnography (PSG) or other reference methods. The analytical guidelines are based on recent recommendations for evaluating and using CST from our group and others (de Zambotti and colleagues; Depner and colleagues), and include raw data organization as well as critical analytical procedures, including discrepancy analysis, Bland–Altman plots, and epoch-by-epoch analysis. Analytical steps are accompanied by open-source R functions (depicted at https://sri-human-sleep.github.io/sleep-trackers-performance/AnalyticalPipeline_v1.0.0.html). In addition, an empirical sample dataset is used to describe and discuss the main outcomes of the proposed pipeline. The guidelines and the accompanying functions are aimed at standardizing the testing of CSTs performance, to not only increase the replicability of validation studies, but also to provide ready-to-use tools to researchers and clinicians. All in all, this work can help to increase the efficiency, interpretation, and quality of validation studies, and to improve the informed adoption of CST in research and clinical settings.

Prader-Willi syndrome (PWS) is a complex genetic syndrome characterized by hyperphagia, intellectual disability, hypotonia and hypothalamic dysfunction. Adults with PWS often have hormone deficiencies, hypogonadism being the most common. Untreated male hypogonadism can aggravate PWS-related health issues including muscle weakness, obesity, osteoporosis, and fatigue. Therefore, timely diagnosis and treatment of male hypogonadism is important. In this article, we share our experience with hypogonadism and its treatment in adult males with PWS and present a review of the literature. In order to report the prevalence and type of hypogonadism, treatment regimen and behavioral issues, we retrospectively collected data on medical interviews, physical examinations, biochemical measurements and testosterone replacement therapy (TRT) in 57 Dutch men with PWS. Fifty-six (98%) of the patients had either primary, central or combined hypogonadism. Untreated hypogonadism was associated with higher body mass index and lower hemoglobin concentrations. TRT was complicated by behavioral challenges in one third of the patients. Undertreatment was common and normal serum testosterone levels were achieved in only 30% of the patients. Based on the Dutch cohort data, review of the literature and an international expert panel discussion, we provide a practical algorithm for TRT in adult males with PWS in order to prevent undertreatment and related adverse health outcomes.