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Background and aims Design Setting Participants Intervention and comparator Measurement Findings Conclusion A 12‐week placebo‐controlled, sequential parallel Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder (ADAPT‐2) trial evaluated the effects of extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN) on methamphetamine (MA) use over two stages. This study reports on the previously unpublished stage 2 MA use in participants randomized at stage 1 to receive NTX + BUPN through both stages compared with those assigned to placebo.This is a secondary analysis of the US National Institute on Drug Abuse (NIDA) ADAPT‐2 network trial.The parent ADAPT‐2 trial was carried out across multiple NIDA Clinical Trials Network (CTN) sites in the United States.This analysis includes 403 people with MA use disorder who participated in the ADAPT‐2 CTN trial.NTX + BUPN was compared with placebo over the course of the trial.MA use was measured by urine drug screens conducted twice weekly for 12 weeks, then once in week 13 and once in week 16 post‐treatment follow‐up.Participants on NTX + BUPN in stage 1 showed an additional 9.2% increase [95% confidence interval (CI), 0.09%–17.9%, P = 0.038] during stage 2 in their probability of testing negative for MA, with a total increase of 27.1% (95% CI, 13.2%–41.1%, P < 0.001) over the full 12 weeks of treatment. In contrast, participants on placebo in both stages increased in probability of testing MA‐negative by a total of 11.4% (95% CI, 4.1%–18.6%, P = 0.002) over all 12 weeks. The 12‐week increase among participants on NTX + BUPN was significantly greater—by 15.8% (95% CI, 4.5%–27.0%, P = 0.006)—than the increase among those on placebo.For people with methamphetamine (MA) use disorder receiving treatment with extended‐release injectable naltrexone plus extended‐release oral bupropion (NTX + BUPN), continued treatment with NTX + BUPN after 6 weeks is associated with additional reductions in MA use up to 12 weeks. [ABSTRACT FROM AUTHOR]

The evolution of submarine canyons is primarily controlled by turbidity currents, which erode and fill them over time; however, many other hydrodynamic currents operate within canyons. Bottom currents from these other hydrodynamic processes, including internal tides, can be dominant processes, but their deposits are seldom recognized in sediment cores or the rock record. This study combines autonomous underwater vehicle swath bathymetry imagery and sub‐bottom profiles, high‐resolution sediment core analyses (X‐ray imagery and thin sections), and previously collected seabed video and flow measurements within Logan Canyon head (eastern Canada) to provide a detailed, modern record of facies associated with hydrodynamic processes in a canyon head. These results suggest that bottom currents are responsible for maintaining gullies on canyon sidewalls and an axial channel on the canyon floor. Thin sections of sediment cores reveal that muddy sand in the canyon head consists of mud aggregates and silt and fine‐grained sand, both behaving similarly in terms of flow dynamics. Three facies are present at macro‐scale and micro‐scale: laminated, partially laminated and bioturbated sandy mud. Sedimentary structures include rhythmic sand and mud aggregate couplets, planar to wavy laminations, current ripple cross‐laminations and fining‐upward successions, which are attributed to bottom currents induced by internal tides. Bioturbated facies, characterized by discrete biogenic structures and cross‐cutting relationships, predominate and overprint a mottled background. A mottled bioturbation fabric also alternates with or locally disrupts layering within the partially laminated facies. Internal tide currents, capable of bedload transport and forming ripples, were measured during a monitoring period in the canyon head, followed by rapid re‐establishment of benthos and associated biogenic structures, supporting the core interpretations. Preservation of sedimentary facies associated with these internal tides occurs when the sedimentation rate outpaces the rate of bioturbation, likely during stormier conditions on the shelf. These results represent observations of sedimentary facies associated with modern bottom currents and internal tides, and can be used to interpret similar occurrences within the rock record. [ABSTRACT FROM AUTHOR]

Summary: Background: Immune checkpoint inhibitors (ICIs) are effective oncologic agents which frequently cause immune‐related adverse events (irAEs) which can impact multiple organ systems. Onco‐Gastroenterology is a novel and emerging subspecialty within gastroenterology focused on cancer treatment‐related complications. Gastroenterologists must be prepared to identify and manage diverse immune‐mediated toxicities including enterocolitis, hepatitis, pancreatitis and other ICI‐induced toxicities. Aim: To provide a narrative review of the epidemiology, diagnostic evaluation and management of checkpoint inhibitor‐induced gastrointestinal and hepatic toxicities. Methods: We searched Cochrane and PubMed databases for articles published through August 2023. Results: Gastrointestinal and hepatic irAEs include most commonly enterocolitis and hepatitis, but also pancreatitis, oesophagitis, gastritis, motility disorders (gastroparesis) and other rarer toxicities. Guidelines from the National Comprehensive Cancer Network, American Society of Clinical Oncology and European Society for Medical Oncology, in combination with emerging cohort and clinical trial data, offer strategies for management of ICI toxicities. Evaluation of irAEs severity by formal classification and clinical stability, and a thorough workup for alternative etiologies which may clinically mimic irAEs underlie initial management. Treatments include corticosteroids, biologics and other immunosuppressive agents plus supportive care; decisions on dosing, timing and choice of steroid adjuncts and potential for subsequent checkpoint inhibitor dosing are nuanced and toxicity‐specific. Conclusions: Expanding clinical trial and cohort data have clarified the epidemiology and clinical characteristics of gastrointestinal, pancreatic and hepatic toxicities of ICIs. Guidelines, though valuable, remain based principally on retrospective cohort data. Quality prospective, controlled studies may refine algorithms for treatment and potential immunotherapy rechallenge. [ABSTRACT FROM AUTHOR]

In the era of free flap reconstruction, mandibular defects are routinely reconstructed with osseous free flaps, and non‐free flap bony reconstruction options are limited. A patient with T4N0 mandibular squamous cell carcinoma underwent resection with fibula free flap reconstruction of a parasymphyseal to angle defect. After free flap failure due to venous congestion, the flap was explanted. He declined additional free flap reconstruction and elected to proceed with pedicled osteomyocutaneous pectoralis major with rib. In this case presentation, we discuss the technical details of harvest of this flap using the 6th rib. The pedicled osteomyocutaneous pectoralis major flap with osseous rib harvest, which is infrequently described in the literature, remains a viable option for bony reconstruction, particularly in the salvage setting. [ABSTRACT FROM AUTHOR]

The 2022 mpox outbreak predominantly impacted gay, bisexual, and other men who have sex with men (gbMSM). Two models were developed to support situational awareness and management decisions in Canada. A compartmental model characterized epidemic drivers at national/provincial levels, while an agent‐based model (ABM) assessed municipal‐level impacts of vaccination. The models were parameterized and calibrated using empirical case and vaccination data between 2022 and 2023. The compartmental model explored: (1) the epidemic trajectory through community transmission, (2) the potential for transmission among non‐gbMSM, and (3) impacts of vaccination and the proportion of gbMSM contributing to disease transmission. The ABM incorporated sexual‐contact data and modeled: (1) effects of vaccine uptake on disease dynamics, and (2) impacts of case importation on outbreak resurgence. The calibrated, compartmental model followed the trajectory of the epidemic, which peaked in July 2022, and died out in December 2022. Most cases occurred among gbMSM, and epidemic trajectories were not consistent with sustained transmission among non‐gbMSM. The ABM suggested that unprioritized vaccination strategies could increase the outbreak size by 47%, and that consistent importation (≥5 cases per 10 000) is necessary for outbreak resurgence. These models can inform time‐sensitive situational awareness and policy decisions for similar future outbreaks. [ABSTRACT FROM AUTHOR]

Background and Objective: Racial disparities have been documented in care of many respiratory diseases but little is known about the impact of race on the treatment of interstitial lung diseases. The purpose of this study was to determine how race and ethnicity influence treatment of idiopathic pulmonary fibrosis. Methods: Adults with idiopathic pulmonary fibrosis (>18 years) were identified using TriNetX database and paired‐wised comparisons were performed for antifibrotic treatment among White, Black, Hispanic and Asian patients. Mortality of treated and untreated IPF patients was compared after propensity score matching for age, sex, nicotine dependence, oxygen dependence and predicted FVC. Additional comparisons were performed in subgroups of IPF patients older than 65 years of age and with lower lung function. Results: Of 47,184 IPF patients identified, the majority were White (35,082), followed by Hispanic (6079), Black (5245) and Asian (1221). When subgroups were submitted to matched cohort pair‐wise comparisons, anti‐fibrotic usage was lower among Black patients compared to White (6.2% vs. 11.4%, p‐value <0.0001), Hispanic (10.8% vs. 20.2%, p‐value <0.0001) and Asian patients (9.6% vs. 14.7%, p‐value = 0.0006). Similar treatment differences were noted in Black individuals older than 65 years and those with lower lung function. Mortality among White patients, but not Hispanic, Black, or Asian patients, was lower in patients on antifibrotic therapy versus not on therapy. Conclusion: This study demonstrated that Black IPF patients had lower antifibrotic use compared to White, Hispanic and Asian patients. Our findings suggest that urgent action is needed to understand the reason why racial disparities exist in the treatment of IPF. We uncovered racial and ethnic disparities in the treatment of IPF. Black patients had lower antifibrotic use compared to White, Hispanic and Asian patients, even among older patients and those with lower lung function. White IPF patients on antifibrotics had a lower mortality, while treated and untreated Hispanic, Asian and Black IPF patients had similar mortality risk. See relatededitorial [ABSTRACT FROM AUTHOR]

Background: Sinonasal malignancy (SNM) is a heterogeneous group of diseases for which induction chemotherapy (IC) may reduce tumor burden. The purpose of this study was to characterize the response to IC in SNM as a prognostic factor through its effect on survival. Methods: Retrospective cohort of patients undergoing IC for SNM between 2010 and 2019 at our quaternary referral center. Results: Forty‐two patients with advanced SNM were included in the analysis. Patients with a favorable response to IC had higher survival rates than those who had an unfavorable response (5‐year OS: 66.8% vs. 9.7%; p < 0.001; PFS: 56.8% vs. 0%; p < 0.001). Conclusions: Response to IC in our patient cohort was a prognostic indicator of overall response to treatment. Further elucidation of predictors of response is needed for appropriate patient selection. [ABSTRACT FROM AUTHOR]

Humans can learn complex functional relationships between variables from small amounts of data. In doing so, they draw on prior expectations about the form of these relationships. In three experiments, we show that people learn to adjust these expectations through experience, learning about the likely forms of the functions they will encounter. Previous work has used Gaussian processes—a statistical framework that extends Bayesian nonparametric approaches to regression—to model human function learning. We build on this work, modeling the process of learning to learn functions as a form of hierarchical Bayesian inference about the Gaussian process hyperparameters. [ABSTRACT FROM AUTHOR]

It is estimated that a majority of people who use psychostimulants, particularly methamphetamine (MA) and cocaine, experience withdrawal upon abstinence from sustained use. This review of clinical research reports the evidence regarding biomedical and behavioral treatments for psychostimulant withdrawal symptoms. It provides a framework for clinicians and scientists to increase impact on attenuating MA and cocaine withdrawal during initial and sustained abstinence. Articles reviewed included reports of controlled clinical trials (randomized or non‐randomized) reporting at least one withdrawal symptom among the outcomes or specifically studying patients in withdrawal. Potential efficacy for MA withdrawal is noted for a few medications (mirtazapine, naltrexone, bupropion) and repetitive transcranial magnetic stimulation during acute (first week), early protracted (weeks 2–4) and late protracted (> 4 weeks) withdrawal phases. Topiramate shows mixed evidence of efficacy for cocaine withdrawal. In general, there is inconsistent signal for biomedical and behavioral treatments on MA and cocaine withdrawal. [ABSTRACT FROM AUTHOR]

The purpose of this review is to broadly identify technological advances in supports and evaluation for individuals on the autism spectrum. Literature review with commentary on the evolving technologies supporting and/or evaluating social‐emotional, behavioral, academic, and cognitive domains. There has been an increasing synthesis of technology within the education domain. A growing body of research has investigated the potentiality and efficacy of technological interventions, specifically in the area of support for individuals on the autism spectrum. This growth must also factor in sustainability and feasibility to be practical within the school setting. Continued research is also necessary to ensure the equity of technology supporting individuals on the autism spectrum. Practitioner Points: Researchers have been investigating the utility of various modern technologies for autism assessment and intervention for over 50 years.Advances in technology have allowed researchers to develop new interventions and assessment techniques that are responsive to the needs of individuals on the autism spectrum.Applications of artificial intelligence (AI) to the assessment and treatment of autism spectrum disorder is an emerging area of research with tremendous potential for facilitating early identification and the implementation of adaptable interventions. [ABSTRACT FROM AUTHOR]

Suppose a fraction HT ht (the I ascertainment ratio i ) of these cases is reported (i.e., HT ht is the ratio of reported cases to the true incidence; for simplicity, we assume here that HT ht is constant over time). The upper bound[[1], [3]] also involves HT ht . Cases identified at time HT ht are claimed to be representative of the number of cases counted twice: why?. [Extracted from the article]

International Statistical Classification of Disease and Related Health Problems, 10th Revision codes (ICD‐10) are used to characterize cohort comorbidities. Recent literature does not demonstrate standardized extraction methods. Objective: Compare COVID‐19 cohort manual‐chart‐review and ICD‐10‐based comorbidity data; characterize the accuracy of different methods of extracting ICD‐10‐code‐based comorbidity, including the temporal accuracy with respect to critical time points such as day of admission. Design: Retrospective cross‐sectional study. Measurements: ICD‐10‐based‐data performance characteristics relative to manual‐chart‐review. Results: Discharge billing diagnoses had a sensitivity of 0.82 (95% confidence interval [CI]: 0.79–0.85; comorbidity range: 0.35–0.96). The past medical history table had a sensitivity of 0.72 (95% CI: 0.69–0.76; range: 0.44–0.87). The active problem list had a sensitivity of 0.67 (95% CI: 0.63–0.71; range: 0.47–0.71). On day of admission, the active problem list had a sensitivity of 0.58 (95% CI: 0.54–0.63; range: 0.30–0.68)and past medical history table had a sensitivity of 0.48 (95% CI: 0.43–0.53; range: 0.30–0.56). Conclusions and Relevance: ICD‐10‐based comorbidity data performance varies depending on comorbidity, data source, and time of retrieval; there are notable opportunities for improvement. Future researchers should clearly outline comorbidity data source and validate against manual‐chart‐review. [ABSTRACT FROM AUTHOR]

The outbreak of COVID‐19 led to a record‐breaking race to develop a vaccine. However, the limited vaccine capacity creates another massive challenge: how to distribute vaccines to mitigate the near‐end impact of the pandemic? In the United States in particular, the new Biden administration is launching mass vaccination sites across the country, raising the obvious question of where to locate these clinics to maximize the effectiveness of the vaccination campaign. This paper tackles this question with a novel data‐driven approach to optimize COVID‐19 vaccine distribution. We first augment a state‐of‐the‐art epidemiological model, called DELPHI, to capture the effects of vaccinations and the variability in mortality rates across age groups. We then integrate this predictive model into a prescriptive model to optimize the location of vaccination sites and subsequent vaccine allocation. The model is formulated as a bilinear, nonconvex optimization model. To solve it, we propose a coordinate descent algorithm that iterates between optimizing vaccine distribution and simulating the dynamics of the pandemic. As compared to benchmarks based on demographic and epidemiological information, the proposed optimization approach increases the effectiveness of the vaccination campaign by an estimated 20%, saving an extra 4000 extra lives in the United States over a 3‐month period. The proposed solution achieves critical fairness objectives—by reducing the death toll of the pandemic in several states without hurting others—and is highly robust to uncertainties and forecast errors—by achieving similar benefits under a vast range of perturbations. [ABSTRACT FROM AUTHOR]

Objective: To illustrate the efficacy and safety profile of double‐balloon enteroscopy (DBE)‐assisted endoscopic retrograde cholangiopancreatography (ERCP) using a short enteroscope in patients with surgically altered anatomy. Methods: A retrospective study was performed to review the endoscopic outcomes of patients undergoing DBE‐assisted ERCP for biliary diseases in Tuen Mun and Pok Oi hospitals in Hong Kong SAR, China from December 2015 to December 2020. Results: Altogether 46 DBE‐assisted ERCP procedures were performed in 37 patients. The enteroscopic success rate, defined as reaching the papilla or bilioenteric anastomosis, was 95.7% (95% confidence interval [CI] 85.2%‐99.5%), which was significantly lower in patients with intact stomach than in those who had a previous gastrectomy (67% vs 100%, P = 0.014). The diagnostic ERCP success rate, defined as performance in an informative cholangiogram, was 84.1% (95% CI 69.9%‐93.4%) in cases where it was attempted. Intended biliary therapeutic interventions were successfully performed in 76.1% (95% CI 61.2%‐87.4%) of all procedures. Adverse events were reported in six (13.0%) procedures (95% CI 4.9%‐26.3%), including the micro‐perforation of the intestine in two (4.3%) patients with prior Roux‐en‐Y gastrectomy, three (6.5%) of acute cholangitis and one (2.2%) of acute pancreatitis. All adverse events were managed successfully using conservative methods except in one case of micro‐perforation, which required a laparotomy. Conclusions: DBE‐assisted ERCP using a short enteroscope is a promising technique for managing biliary diseases in patients with surgically altered anatomy. It must be performed to avoid perforation, particularly in patients with a Roux‐en‐Y reconstruction. [ABSTRACT FROM AUTHOR]

Background: In the current study, the authors assessed the risks and outcomes of immune checkpoint inhibitor (ICI) rechallenge in patients with resolved grade 3 to 4 ICI hepatitis because current guidelines recommend permanent ICI discontinuation in these patients. Methods: The authors performed a retrospective cohort study from 2010 through 2019 of patients with melanoma who were treated with ≥1 ICIs and who recovered from grade 3 to 4 ICI hepatitis. The primary outcome was hepatitis recurrence and the secondary outcome was the development of any immune‐related adverse event (irAE) requiring the discontinuation of ICI rechallenge. Best overall response and time to all‐cause death were compared between the patients who did and those who did not undergo ICI rechallenge. Grading was performed using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). Results: Of the 102 patients with melanoma who developed high‐grade ICI hepatitis, 31 underwent ICI rechallenge. Although 15 of 31 patients (48%) developed an irAE of any grade, only 6 patients (19%) required ICI discontinuation due to irAE severity (4 of 29 patients [14%] rechallenged with anti–PD‐1 or anti‐PD‐L1 and 2 of 2 patients [100%] rechallenged with ipilimumab). Recurrent hepatitis accounted for 4 of these 6 cases. Rechallenged patients who did not require ICI discontinuation were found to be significantly less likely to receive ipilimumab rather than anti–PD‐1 or anti‐PD‐L1 monotherapy (0% vs 33%; relative risk (RR), 0.1 [95% CI, 0.1‐0.3; P =.032]) and significantly less likely to be rechallenged with their original ICI (8% vs 50%; RR, 0.2 [95% CI, 0.1‐0.7; P =.038]). There was no difference noted with regard to best overall response or time to death between rechallenged and non‐rechallenged patients. Conclusions: ICI therapy can be resumed in patients with melanoma who have recovered from grade 3 to 4 ICI hepatitis with a modest risk of serious irAEs. It remains unclear whether ICI retreatment improves clinical outcomes. After resolution of high‐grade immune‐mediated hepatitis, the majority of patients who are rechallenged with immune checkpoint inhibitors can remain on treatment without developing serious immune‐related adverse events. It remains unclear whether immune checkpoint inhibitor retreatment improves clinical outcomes. [ABSTRACT FROM AUTHOR]

This study examines the influence of the strength of Atlantic Meridional Overturning Circulation (AMOC) on storminess at different latitudes in the North Atlantic, based on a new 6.5‐Kyr record of large storms from the Scotian Shelf (Eastern Canada) that provides the first >3.5‐ka record from middle latitudes. Comparison with a compilation of other paleostorm records shows that peaks in storminess are at times synchronous (4.5–2.5 and since 0.5 ka) between low and middle latitudes but in the intervening period (2.5–0.5 ka) were latitudinally asynchronous. Synchronous (asynchronous) behavior correlates with sustained increase (decrease) of AMOC. Regime shifts in storm activity between low and middle latitudes were more frequent since 2.5 ka, related to increased frequency of abrupt climate changes. These findings indicate a latitudinal response of storm activity due to abrupt climate change, which is critical to correctly assess future storm risks along the North Atlantic coastline. Plain Language Summary: The Atlantic Meridional Overturning Circulation (AMOC) is one of the well‐established tipping elements of the Earth's climate system, redistributing heat and thus influencing storm activity. Yet critical questions remain unanswered regarding the latitudinal response of storm activity to AMOC‐related abrupt climate change. Here, we present a storminess record north of 34°N that goes back to >3.5 ka, namely, a 6.5‐Kyr record from the Scotian Shelf (Eastern Canada). We describe for the first time the impact of abrupt climate change on storminess at different latitudes in the North Atlantic in response to changes in AMOC strength. This is based on a comparison of our study with a compilation of other paleostorm records. Synchronous (asynchronous) behavior correlates with sustained increase (decrease) of AMOC. Such information is fundamental to correctly assess future storm risks along the North Atlantic coastline, especially in densely populated coastal areas. Key Points: We provide the first reconstruction of >3.5‐ka record of large storms north of 34° N in the North AtlanticPeaks in storminess in the past 4.5 Kyr are for some periods synchronous at low and middle latitudes; during other periods this is not soSustained increase of AMOC results in latitudinal synchroneity of storm activity; asynchronous activity results from decreasing AMOC [ABSTRACT FROM AUTHOR]

While tissue engineering holds significant potential to address current limitations in reconstructive surgery of the head and neck, few constructs have made their way into routine clinical use. In this review, we aim to appraise the state of head and neck tissue engineering over the past five years, with a specific focus on otologic, nasal, craniofacial bone, and laryngotracheal applications. A comprehensive scoping search of the PubMed database was performed and over 2000 article hits were returned with 290 articles included in the final review. These publications have addressed the hallmark characteristics of tissue engineering (cellular source, scaffold, and growth signaling) for head and neck anatomical sites. While there have been promising reports of effective tissue engineered interventions in small groups of human patients, the majority of research remains constrained to in vitro and in vivo studies aimed at furthering the understanding of the biological processes involved in tissue engineering. Further, differences in functional and cosmetic properties of the ear, nose, airway, and craniofacial bone affect the emphasis of investigation at each site. While otolaryngologists currently play a role in tissue engineering translational research, continued multidisciplinary efforts will likely be required to push the state of translation towards tissue‐engineered constructs available for routine clinical use. Level of Evidence: NA. [ABSTRACT FROM AUTHOR]

Background: In microvascular reconstruction of ablative oncologic defects, coupler devices have traditionally been used for venous anastomosis, whereas the arterial anastomosis is hand‐sewn. In the setting of repeated intraoperative arterial anastomotic thrombosis, a coupler device may be of use in reducing the risk of rethrombosis. Methods: Two patients were seen with advanced stage head and neck cancer and underwent oncologic resection. During microvascular reconstruction, a clot at the arterial anastomosis was encountered in both cases. Results: After starting therapeutic anticoagulation and attempting unsuccessful suture reanastomosis, coupler devices were used for arterial anastomosis, resulting in viable free‐tissue transfer. Conclusions: Although traditionally used for venous anastomosis, coupler devices may serve a purpose in the salvage setting when facing repeated intraoperative arterial thrombosis. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)-mediated oropharyngeal cancer (OPC) is associated with dramatically improved survival in comparison with HPV-negative OPC and can be successfully treated with surgical and nonsurgical approaches. National treatment trends for OPC were investigated with the National Cancer Data Base (NCDB).Methods: The NCDB was reviewed for primary HPV-mediated OPC in 2010-2014. Multivariable regression was used to identify predictors of both nonsurgical therapy and receipt of adjuvant chemoradiation (CRT).Results: There were 13,363 patients identified with a median age at diagnosis of 58 years. The incidence of triple-modality treatment (surgery with adjuvant chemotherapy) decreased from 23.7% in 2010 to 16.9% in 2014 (R2  = 0.96), whereas the incidence of nonsurgical treatment increased from 63.9% to 68.7% (R2  = 0.89). Hospitals in the top treatment volume quartile (quartile 1 [Q1]; n = 29) had a lower rate of positive margins (16.3%) than bottom-quartile centers (n = 741; rate of positive margins, 36.4%; P < .001); Q1 hospitals used surgical therapy significantly more. Independent predictors of nonsurgical therapy included older age, advanced disease, lower hospital volume, and living closer to the hospital or outside the Pacific United States. In surgically treated patients, younger age, lower hospital volume, nodal disease, positive surgical margins, and extranodal extension (ENE) also predicted more adjuvant CRT use.Conclusions: The use of upfront surgical treatment decreased from 2010 to 2014. Hospital volume shows a strong, inverse correlation with the rate of positive surgical margins. The upfront treatment strategy is predicted not only by staging but also by patient-, geographic-, and hospital-specific factors. Lower hospital volume remains independently associated with increased triple-modality therapy after adjustments for positive margins, ENE, and pathologic staging. [ABSTRACT FROM AUTHOR]

Introduction: Laparoscopic colorectal resection is becoming the gold standard for treating colorectal cancers because it offers superior short‐term and comparable long‐time outcomes compared to open surgery. Intraoperative colonoscopy (IOC) is increasingly performed for tumor localization and mucosal assessment. The aim of this report was to review the safety and efficacy of IOC in laparoscopic colorectal surgery. Method: A MEDLINE search of studies of IOC in laparoscopic colorectal surgery was performed. We focused on three aspects of IOC use: (i) IOC for intraoperative tumor localization; (ii) colonic irrigation and IOC for obstructive left‐sided colorectal cancers; and (iii) IOC for assessing colorectal anastomosis. Results: During laparoscopic colorectal surgery, IOC enables accurate localization of early mucosal tumors, detection of lesions in the proximal unexamined colon for obstructive left‐sided cancer, and visual assessment of anastomosis. Additionally, IOC allows for proper surgical resection, management of concomitant lesions, immediate maintenance of hemostasis, suture repair of leaks, and the creation of a protective stoma as necessary. Conclusions: Intraoperative colonoscopy is beneficial in laparoscopic colorectal surgery. Experienced surgical endoscopists should be trained to safely perform IOC. [ABSTRACT FROM AUTHOR]

Summary: Background: Little is known of the outcome of patients with perianal Crohn's disease after stopping anti‐tumour necrosis factor (TNF) therapy. Aim: To evaluate the rate of relapse in perianal Crohn's disease (CD) after stopping anti‐TNF therapy. Methods: Consecutive perianal CD patients treated with anti‐TNF therapy with subsequent discontinuation were retrieved from prospective inflammatory bowel disease database of institutes in Hong Kong, Shanghai, Taiwan, Malaysia, Thailand and Singapore from 1997 to June 2019. Cumulative probability of perianal CD relapse was estimated using Kaplan‐Meier method. Results: After a median follow‐up of 89 months (interquartile range [IQR]: 65‐173 months), 44 of the 78 perianal CD patients (56.4%) relapsed after stopping anti‐TNF, defined as increased fistula drainage or recurrence of previously healed fistula, after stopping anti‐TNF therapy. Cumulative probabilities of perianal CD relapse were 50.8%, 72.6% and 78.0% at 12, 36 and 60 months, respectively. Younger age at diagnosis of CD [adjusted hazard ratio (HR): 1.04; 95% CI 1.01‐1.09; P = .04] was associated with a higher chance of perianal CD relapse. Among those with perianal CD relapse (n = 44), retreatment with anti‐TNF induced remission in 24 of 29 patients (82.8%). Twelve (27.3%) patients required defunctioning surgery and one (2.3%) required proctectomy. Maintenance with thiopurine was not associated with a reduced likelihood of relapse [HR = 1.10; 95% CI: 0.58‐2.12; P = .77]. Among the 17 patients who achieved radiological remission of perianal CD, five (35.3%) developed relapse after stopping anti‐TNF therapy after a median of 6 months. Conclusions: More than half of the perianal CD patients developed relapse after stopping anti‐TNF therapy. Most regained response after resuming anti‐TNF. However, more than one‐fourth of the perianal CD patients with relapse required defunctioning surgery. Radiological assessment before stopping anti‐TNF is crucial in perianal CD. [ABSTRACT FROM AUTHOR]

There is growing evidence that cardiac dysfunction in patients with chronic epilepsy could play a pathogenic role in sudden unexpected death in epilepsy (SUDEP). Recent animal studies have revealed that epilepsy secondarily alters the expression of cardiac ion channels alongside abnormal cardiac electrophysiology and remodeling. These molecular findings represent novel evidence for an acquired cardiac channelopathy in epilepsy, distinct from inherited ion channels mutations associated with cardiocerebral phenotypes. Specifically, seizure activity has been shown to alter the messenger RNA (mRNA) and protein expression of voltage‐gated sodium channels (Nav1.1, Nav1.5), voltage‐gated potassium channels (Kv4.2, Kv4.3), sodium‐calcium exchangers (NCX1), and nonspecific cation‐conducting channels (HCN2, HCN4). The pathophysiology may involve autonomic dysfunction and structural cardiac disease, as both are independently associated with epilepsy and ion channel dysregulation. Indeed, in vivo and in vitro studies of cardiac pathology reveal a complex network of signaling pathways and transcription factors regulating ion channel expression in the setting of sympathetic overactivity, cardiac failure, and hypertrophy. Other mechanisms such as circulating inflammatory mediators or exogenous effects of antiepileptic medications lack evidence. Moreover, an acquired cardiac channelopathy may underlie the electrophysiologic cardiac abnormalities seen in chronic epilepsy, potentially contributing to the increased risk of malignant arrhythmias and sudden death. Therefore, further investigation is necessary to establish whether cardiac ion channel dysregulation similarly occurs in patients with epilepsy, and to characterize any pathogenic relationship with SUDEP. [ABSTRACT FROM AUTHOR]

Summary: Nucleos(t)ide analogues (NA) are effective in suppressing hepatitis B virus (HBV) replication, but most patients require long‐term treatment. This study aimed to investigate switching to peginterferon as a strategy to stop NA. Hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B patients who developed HBeAg seroconversion during NA treatment were studied. All patients received open‐label peginterferon alfa‐2a 180 μg/wk for 48 weeks, and NA was stopped at week 4 of peginterferon treatment. The primary endpoint was sustained response, which was defined as negative HBeAg, positive anti‐HBe and HBV DNA <2000 IU/mL at week 72. Other secondary endpoints including HBsAg loss at week 72 were also studied. Forty‐one patients treated with entecavir for 56 ± 23 months were recruited. Sustained response was achieved in 30 patients (73%, 95% confidence interval 58%‐84%). At week 72, 31 (76%) patients had HBeAg seroconversion, 56 (23%) patients had undetectable HBV DNA, 31 (76%) patients had normal ALT, and 6 patients (15%) had HBsAg loss. Baseline HBsAg level was the best predictor for both sustained response and HBsAg loss; the best HBsAg cut‐off for sustained response was <1500 IU/mL and that for HBsAg loss was <500 IU/mL by receiver operating characteristic curve analysis. Twenty‐two of 25 (88%) patients with baseline HBsAg <1500 IU/mL had sustained response. Five of 10 (50%) patients with baseline HBsAg <500 IU/mL developed HBsAg loss. Switching to peginterferon can be considered as a treatment option in NA‐treated patients with HBeAg seroconversion, particularly among those with lower HBsAg levels. [ABSTRACT FROM AUTHOR]

Objective To determine the incidence of posttracheostomy tracheal stenosis and to investigate variables related to the patient, hospitalization, or operation that may affect stenosis rates. Study Design A combined retrospective cohort and case-control study. Setting Tertiary care academic medical center. Subjects and Methods A total of 1656 patients who underwent tracheostomy at a tertiary care medical center from January 2011 to November 2016 were reviewed for evidence of subsequent tracheal stenosis on airway endoscopy or computed tomography. Forty-three confirmed cases of posttracheostomy tracheal stenosis (PTTS) were compared with a subgroup of 319 controls. Factors including medical comorbidity, type and setting of tracheostomy, and hospitalization details were analyzed. Results Five-year incidence of PTTS was 2.6%. Obesity was the sole demographic factor associated with stenosis. Hospitalization-related variables associated with stenosis included tracheostomy after 10 days of orotracheal intubation and endotracheal tube cuff pressure ≥30 mm H2O. The surgical variables associated with higher rates of stenosis included percutaneous technique and insertion of an initial tracheostomy tube size >6. Bjork flap creation was negatively associated with stenosis. In multivariable analysis, obesity and insertion of tracheostomy tube size >6 were identified as risk factors. Conclusion Greater than 10 days of orotracheal intubation prior to tracheostomy and endotracheal tube cuff pressure ≥30 mm H2O were associated with greater rates of subsequent tracheal stenosis. The only patient-related factor associated with tracheal stenosis was obesity. Surgical variables associated with increased rates of subsequent stenosis included placement of a tracheostomy tube size >6, use of percutaneous technique, and failure to create a Bjork flap. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Tension‐free mesh repair is currently the gold standard treatment for inguinal hernia. Recent evidence has shown that both open and laparoscopic approaches to inguinal hernia repair can achieve good results. Lots of meshes with different properties are available on the market, but direct comparisons between them are scare. We conducted a prospective randomized controlled trial comparing a partially absorbable lightweight mesh (ULTRAPRO™) and a multifilament polyester anatomical mesh (Parietex™) in laparoscopic total extraperitoneal inguinal hernia repair. Methods: This study was a single‐center, prospective randomized controlled trial to compare the surgical handling and clinical outcomes between two different types of meshes. All operations were performed using a standardized operative protocol. This study was approved by the Institutional Review Board of the Hong Kong East Cluster Health Service in 2009 (reference number: 2009‐087). The study was registered in the Australian New Zealand Clinical Trial Registry (ACTRN12610000031066). Results: From October 2009 to August 2011, 85 laparoscopic total extraperitoneal inguinal hernia repairs were performed. The mean mesh handling time was 152 s for the ULTRAPRO group and 206 s for the Parietex group (P = 0.001). There were three cases of seroma formation in the ULTRAPRO group and nine in the Parietex group (P = 0.02). The overall recurrence rate was 2.5%. Conclusion: It took less time to manipulate the flat mesh (ULTRAPRO) than the anatomical mesh (Parietex) in laparoscopic total extraperitoneal inguinal hernia repair, but the time difference was small. Lightweight mesh and heavyweight mesh offered similar clinical outcomes in terms of discomfort sensation and foreign body sensation during long‐term follow‐up. [ABSTRACT FROM AUTHOR]

Summary: Objectives: To review clinical evidence on the antiepileptic effects of deep brain stimulation (DBS) for drug‐resistant epilepsy, its safety, and the factors influencing individual outcomes. Methods: A comprehensive search of the medical literature (PubMed, Medline) was conducted to identify relevant articles investigating DBS therapy for drug‐resistant epilepsy. Reference lists of these articles were used to source further articles. Results: Stimulation of the anterior nucleus of the thalamus (ANT) and hippocampus (HC) has been shown to decrease the frequency of refractory seizures. Half of all patients from clinical studies experienced a 46%‐90% seizure reduction with ANT‐DBS, and a 48%‐95% seizure reduction with HC‐DBS. The efficacy of stimulating other targets remains inconclusive due to lack of evidence. Approximately three‐fourths of patients receiving ANT, HC, or centromedian nucleus of the thalamus (CMT) stimulation are responders—experiencing a seizure reduction of at least 50%. The time course of clinical benefit varies dramatically, with both an initial lesional effect and ongoing stimulation effect at play. Improved quality of life and changes to cognition or mood may also occur. Side effects are similar in nature to those reported from DBS therapy for movement disorders. Several factors are potentially associated with stimulation efficacy, including an absence of structural abnormality on imaging for ANT and HC stimulation, and electrode position relative to the target. Certain seizure types or syndromes may respond more favorably to specific targets, including ANT stimulation for deep temporal or limbic seizures, and CMT stimulation for generalized seizures and Lennox‐Gastaut syndrome. Significance: We have identified several patient, disease, and stimulation factors that potentially predict seizure outcome following DBS. More large‐scale clinical trials are needed to explore different stimulation parameters, reevaluate the indications for DBS, and identify robust predictors of patient response. [ABSTRACT FROM AUTHOR]

Background and Aim There are scanty data on the health-care utilization from Asia where the incidence of inflammatory bowel disease (IBD) is rising rapidly. We aim to determine the direct health-care costs in the first 2 years of diagnosis in an IBD cohort from Hong Kong and the factors associated with high cost outliers. Methods This is a retrospective cohort study that included patients newly diagnosed with IBD in a territory-wide IBD registry. Patients' clinical information, hospitalization records, investigations, and IBD treatments were retrieved for up to 2 years following diagnosis of IBD. Results Four hundred and thirty-five newly diagnosed IBD patients were included: 198 with Crohn's disease and 237 with ulcerative colitis. Total direct medical expenditure for this cohort 2 years after the IBD diagnosis was $7 072 710: hospitalizations (33%), 5-aminosalicylic acid (23%), imaging and endoscopy (17%), outpatient visits (10%), surgery (8%), and biologics (6%). Mean direct medical costs per patient-year were significantly higher for Crohn's disease ($9918) than ulcerative colitis ($6634; P, 0.001). The total direct health-care cost decreased significantly after transition to the second year ( P < 0.01). High cost (> 90th percentile) outliers were associated with surgery (OR 7.1, 95% CI 2.9-17.2) and low hemoglobin on presentation (OR 0.83, 95% CI 0.70-0.96). Conclusions Hospitalization and 5-aminosalicylic acid usage accounted for 56% of total direct medical costs in the first 2 years of our newly diagnosed IBD patients. Direct health-care costs were higher in the first year compared with the second year of diagnosis. Surgery and low hemoglobin on presentation were associated with high cost outliers. [ABSTRACT FROM AUTHOR]

Objective The present paper describes our experience of developing and piloting a best practice model of medical clinical handover. Secondary aims were to improve reliability of communication, identify negative effects on patient care and assess staff adherence and acceptance of the process. Methods We described existing handover practice. We designed and implemented a process incorporating bedside handover, the Identification, Situation, Background, Assessment, Requirements and Requests ( ISBAR) tool and handover documentation. We audited the process and surveyed doctors before and after the intervention regarding their practice and preferences. Results Existing handover practice was remote from the patient, neither standardised nor documented. The new process resulted in a median 87% (95% CI 70.4-92.1) of handovers in the presence of the patient. ISBAR elements were consistently communicated, median 100% (95% CI 91.8-100). Risk events were directly identified in a median 8.3% (95% CI 0.0-13.8) of bedside handovers. Handover documentation did not improve. FACEM and registrar perception that bedside handover improves patient care fell from 71%, 80% to 56%, 58%, respectively. Preference for bedside handover fell from 79% and 80%, respectively, to being evenly divided between bedside and centralised models; 80.9% of respondents reported that ISBAR improved communication. Conclusion Bedside handover using ISBAR resulted in improved patient involvement, communication and a non-significant trend to improved patient safety. Despite a majority of doctors acknowledging these findings, preference remained for a centralised handover using ISBAR. Gaining staff acceptance of a process change is essential to its success. A barrier to acceptance could be that staff are time-poor. We suggest handover processes can be strengthened by adequate staffing and small, incremental improvements to existing models combined with auditing of outcomes. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this paper was to determine individual and shared levels of psychosocial, behavioral, and symptomological health characteristics among Hispanics with recent history of cancer and their primary social support person (PSSP) in the years following diagnosis.Patients and Methods: Recruited from a population-based cohort study were 409 Hispanic patients with a previous diagnosis of colorectal cancer. Forty-seven patients identified a PSSP, who assists with medical decision-making and health-related matters, who also participated in the study. Current behavioral (smoking, alcohol use, physical activity, and complementary and alternative medicine use), psychosocial (stress and mindfulness), and physical symptom (fatigue) data were obtained using validated instruments. Analyses tested the individual and shared (between patients and PSSPs) variance in these health measures.Results: The sample was diagnosed on average 3.1 years (standard deviation = 1.7) prior to assessment. PSSPs were mainly spouses/partners (63%) or children (28%) of patients. Among patients, stress was positively associated with being a current smoker (p < 0.01) and with fatigue (r = 0.45, p < 0.001); stress was negatively correlated with mindfulness (r = -0.41, p < 0.001); mindfulness was negatively associated with smoking (odds ratio (OR) = 0.72, p < 0.01) and alcohol consumption (OR = 0.83, p < 0.05); the inverse relationship between mindfulness and fatigue was partially mediated through lower levels of stress (β = -0.17, p < 0.001). Similar patterns were observed among PSSPs. Patient mindfulness was negatively correlated with PSSP stress (r = -0.45, p < 0.01). Complementary and alternative medicine use showed interdependence between patients and PSSPs for use of herbal remedies (OR = 6.2; p < 0.01) and bodywork (OR = 8.3, p < 0.05).Conclusion: Hispanic colorectal cancer patients and their PSSP share a common health milieu in the years following a cancer diagnosis, offering opportunities for advancing interpersonal intervention approaches in cancer care. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective With the rapid increase in the incidence of inflammatory bowel disease (IBD) in Asia, the natural course of the early phase of disease in these patients remains poorly defined. This study aimed to determined the incidence and characteristics of infection-related hospitalization in the first year in patients newly diagnosed with IBD in Hong Kong SAR, China. Methods Patients newly diagnosed with IBD and enrolled in the territory-wide Hong Kong IBD Registry were identified. Details of their hospitalization within the first 12 months after diagnosis were retrieved and analyzed. Results Altogether 433 newly diagnosed IBD patients were enrolled, including 188 with Crohn's disease (CD), 230 with ulcerative colitis (UC) and 15 with IBD-unclassified (IBD-U). Among them, 110 (25.4%) had at least one unscheduled hospitalization in the first year and 34 (7.9%) had infection-related hospitalization, leading to 43 (23.4%) of total hospitalizations. Gastrointestinal tract (30.2%), respiratory tract (34.9%) and skin and soft tissues (11.6%) were the most common sites of infection. Bacterial and viral infections accounted for 46.7% and 20.8% of hospitalizations for infection, respectively. Common identified pathogens included Clostridium difficile (16.3%) and Cytomegalovirus (11.6%). Multivariate analysis found that patient's age (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.06) and the presence of comorbidity (OR 2.32, 95% CI 1.05-5.13) were significantly associated with hospitalization from infection in IBD patients. Conclusions Infection-related hospitalizations were found in 7.9% of newly diagnosed IBD patients within the first year after diagnosis in Hong Kong, which accounted for about one-quarter of all unscheduled hospitalizations. Elder patients with concurrent illnesses were at higher risk. [ABSTRACT FROM AUTHOR]

Introduction Lack of depth perception and spatial orientation are drawbacks of laparoscopic surgery. The advent of the 3- D camera system enables surgeons to regain binocular vision. The aim of this study was to gain subjective and objective data to determine whether 3- D systems are superior to 2- D systems. Materials and Methods Our study consisted of two parts: a laparoscopic training model and an actual operation assessment. In the first part, we compared two groups of surgeon (specialists and trainees) performing a laparoscopic task using a 2- D and a 3- D camera system. In the second part, surgeons were assessed on their performance of standard laparoscopic cholecystectomies using the two different camera systems. At the end of each assessment, participants were required to complete a questionnaire on their impressions of the comparative ease of operation tasks under 2- D and 3- D vision. Result In the laboratory training model, trainees' performance time was shorter with the 3- D camera system than with the 2- D camera, but no difference was observed in the specialists group. In the surgical (cholecystectomy) assessment, no significant difference was observed between the 2- D and 3- D camera systems in terms of operative time and precision. The questionnaire indicated that all participants did not significantly favor the 3- D system. Conclusion We believe that the 3- D camera system can allow young surgeons to perform standard laparoscopic tasks safely and quickly, so as to accelerate the learning curve. However, new-generation 3- D systems will be essential to overcome surgeons' discomfort. [ABSTRACT FROM AUTHOR]

Catalytic processes have been one of the main pillars of the chemical industry in recent years. Protocols that make use of homogeneous and heterogeneous catalysts have been extensively implemented for the production of fine chemicals, fuels, materials, and relevant products. Importantly, the need for benign by design processes and technologies became recently a major driver in both research and industry for a more sustainable future. This contribution has been aimed to discuss and highlight key examples on room temperature catalytic processes as one of the most relevant research avenues for future developments in catalysis. WIREs Energy Environ 2015, 4:316-338. doi: 10.1002/wene.141 For further resources related to this article, please visit the . Conflict of interest: The authors have declared no conflicts of interest for this article. [ABSTRACT FROM AUTHOR]

Groin hernias are very common, and surgical treatment is usually recommended. In fact, hernia repair is the most common surgical procedure performed worldwide. In countries such as the USA, China, and India, there may easily be over 1 million repairs every year. The need for this surgery has become an important socioeconomic problem and may affect health-care providers, especially in aging societies. Surgical repair using mesh is recommended and widely employed in Western countries, but in many developing countries, tissue-to-tissue repair is still the preferred surgical procedure due to economic constraints. For these reason, the development and implementation of guidelines, consensus, or recommendations may aim to clarify issues related to best practices in inguinal hernia repair in Asia. A group of Asian experts in hernia repair gathered together to debate inguinal hernia treatments in Asia in an attempt to reach some consensus or develop recommendations on best practices in the region. The need for recommendations or guidelines was unanimously confirmed to help overcome the discrepancy in clinical practice between countries; the experts decided to focus mainly on the technical aspects of open repair, which is the most common surgery for hernia in our region. After the identification of 12 main topics for discussion (indication, age, and sex; symptomatic and asymptomatic hernia: type of hernia; type of treatment; hospital admission; preoperative care; anesthesia; surgical technique; perioperative care; postoperative care; early complications; and long-term complications), a search of the literature was carried out according to the five levels of the Oxford Classification of Evidence and the four grades of recommendation. [ABSTRACT FROM AUTHOR]