Studying the Long-term Impact of COVID-19 in Kids (SLICK). Healthcare use and costs in children and young people following community-acquired SARS-CoV-2 infection: protocol for an observational study using linked primary and secondary routinely collected healthcare data from England, Scotland and Wales.

INTRODUCTION: SARS-CoV-2 infection rarely causes hospitalisation in children and young people (CYP), but mild or asymptomatic infections are common. Persistent symptoms following infection have been reported in CYP but subsequent healthcare use is unclear. We aim to describe healthcare use in CYP following community-acquired SARS-CoV-2 infection and identify those at risk of ongoing healthcare needs. METHODS AND ANALYSIS: We will use anonymised individual-level, population-scale national data linking demographics, comorbidities, primary and secondary care use and mortality between 1 January 2019 and 1 May 2022. SARS-CoV-2 test data will be linked from 1 January 2020 to 1 May 2022. Analyses will use Trusted Research Environments: OpenSAFELY in England, Secure Anonymised Information Linkage (SAIL) Databank in Wales and Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 in Scotland (EAVE-II). CYP aged ≥4 and <18 years who underwent SARS-CoV-2 reverse transcription PCR (RT-PCR) testing between 1 January 2020 and 1 May 2021 and those untested CYP will be examined.The primary outcome measure is cumulative healthcare cost over 12 months following SARS-CoV-2 testing, stratified into primary or secondary care, and physical or mental healthcare. We will estimate the burden of healthcare use attributable to SARS-CoV-2 infections in the 12 months after testing using a matched cohort study of RT-PCR positive, negative or untested CYP matched on testing date, with adjustment for confounders. We will identify factors associated with higher healthcare needs in the 12 months following SARS-CoV-2 infection using an unmatched cohort of RT-PCR positive CYP. Multivariable logistic regression and machine learning approaches will identify risk factors for high healthcare use and characterise patterns of healthcare use post infection. ETHICS AND DISSEMINATION: This study was approved by the South-Central Oxford C Health Research Authority Ethics Committee (13/SC/0149). Findings will be preprinted and published in peer-reviewed journals. Analysis code and code lists will be available through public GitHub repositories and OpenCodelists with meta-data via HDR-UK Innovation Gateway.

Prevalence, Diagnosis and Management of Pancreatic Cystic Neoplasms: Current Status and Future Directions.

Cystic neoplasms of the pancreas are found with increasing prevalence, especially in elderly asymptomatic individuals. Although the overall risk of malignancy is very low, the presence of these pancreatic cysts is associated with a large degree of anxiety and further medical investigation due to concerns about malignancy. This review discusses the different cystic neoplasms of the pancreas and reports diagnostic strategies based on clinical features and imaging data. Surgical and nonsurgical management of the most common cystic neoplasms, based on the recently revised Sendai guidelines, is also discussed, with special reference to intraductal papillary mucinous neoplasm (IPMN; particularly the branch duct variant), which is the lesion most frequently identified incidentally. IPMN pathology, its risk for development into pancreatic ductal adenocarcinoma, the pros and cons of current guidelines for management, and the potential role of endoscopic ultrasound in determining cancer risk are discussed. Finally, surgical treatment, strategies for surveillance of pancreatic cysts, and possible future directions are discussed.

Asymptomatic pancreatic cystic neoplasms: maximizing survival and quality of life using Markov-based clinical nomograms.

BACKGROUND & AIMS: The natural history and management of pancreatic cysts, especially for branch duct intraductal papillary mucinous neoplasms (BD-IPMNs), remain uncertain. We developed evidence-based nomograms to assist with clinical decision making. METHODS: We used decision analysis with Markov modeling to compare competing management strategies in a patient with a pancreatic head cyst radiographically suggestive of BD-IPMN, including the following: (1) initial pancreaticoduodenectomy (PD), (2) yearly noninvasive radiographic surveillance, (3) yearly invasive surveillance with endoscopic ultrasound, and (4) "do nothing." We derived probability estimates from a systematic literature review. The primary outcomes were overall and quality-adjusted survival. We depicted the results in a series of nomograms accounting for age, comorbidities, and cyst size. RESULTS: Initial PD was the dominant strategy to maximize overall survival for any cyst greater than 2 cm, regardless of age or comorbidities. In contrast, surveillance was the dominant strategy for any lesion less than 1 cm. However, when measuring quality-adjusted survival, the do-nothing approach maximized quality of life for all cysts less than 3 cm in patients younger than age 75. Once age exceeded 85 years, noninvasive surveillance dominated. Initial PD did not maximize quality of life in any age group or cyst size. CONCLUSIONS: Management of pancreatic cysts can be guided using novel Markov-based clinical nomograms, and depends on age, cyst size, comorbidities, and whether patients value overall survival vs quality-adjusted survival. For patients focused on overall survival, regardless of quality of life, surgery is optimal for lesions greater than 2 cm. For patients focused on quality-adjusted survival, a 3-cm threshold is more appropriate for surgery except for the extreme elderly.

Colonic stent vs. emergency surgery for management of acute left-sided malignant colonic obstruction: a decision analysis.

BACKGROUND: Acute colonic obstruction because of malignancy is often a surgical emergency. Surgical decompression with colostomy with or without resection and eventual re-anastomosis is the traditional treatment of choice. Endoscopic colonic stent insertion effectively decompresses the obstructed colon, allowing for surgery to be performed electively. This study sought to determine the cost-effectiveness of colonic stent vs. surgery for emergent management of acute malignant colonic obstruction. METHODS: Decision analysis was used to calculate the cost-effectiveness of two competing strategies in a hypothetical patient presenting with acute, complete, malignant colonic obstruction: (1) emergent colonic stent followed by elective surgical resection and re-anastomosis; (2) emergent surgical resection followed by diversion (Hartmann's procedure) or primary anastomosis. Cost estimates were obtained from a third-party payer perspective. Primary outcome measures were mortality, stoma requirement, and total number of operative procedures. RESULTS: Colonic stent resulted in 23% fewer operative procedures per patient (1.01 vs. 1.32 operations per patient), an 83% reduction in stoma requirement (7% vs. 43%), and lower procedure-related mortality (5% vs. 11%). Colonic stent was associated with a lower mean cost per patient ($45,709 vs. $49,941). CONCLUSIONS: Colonic stent insertion followed by elective surgery appears more effective and less costly than emergency surgery under base-case conditions. This finding remains robust over a wide range of assumptions for clinical inputs in sensitivity analysis. Our findings suggest that colonic stent insertion should be offered, whenever feasible, as a bridge to elective surgery in patients presenting with malignant colonic obstruction.

Examination of hydrophobic contaminant adsorption in mineral micropores with grand canonical Monte Carlo simulations.

A molecular level understanding of the interactions between hydrophobic organic contaminants (HOCs) and sediments is needed in order to assess contaminant fate in the environment. Grand canonical Monte Carlo simulations were performed to investigate water and trichloroethylene (TCE) adsorption in slit micropores confined by charged and uncharged silica surfaces. Gas-phase single-sorbate simulations with water or TCE were performed as well as mixture simulations of bulk water containing TCE at 1% of its saturation concentration. Gas-phase isosteric heats for water adsorption in the uncharged pores ranged from -40 to -52 kJ/mol, and the densities of the adsorbed water phases were always less than that for bulk water. Gas-phase isosteric heats for water adsorption in the charged pores ranged from -79 to -170 kJ/mol, and the densities of the adsorbed water phases were close to that for bulk water. The isosteric heats and water densities indicated that the uncharged pores were mildly hydrophobic, and the charged pores were very hydrophilic. In mixture simulations of adsorption from solution, the presence of water promoted TCE adsorption in uncharged pores with widths between 14 and 20 A. The isosteric heats for TCE adsorption from solution ranged from -14 to -27 kJ/mol in the uncharged pores and from -9.3 to -50 kJ/mol in the charged pores. Strong attractions to the pore surfaces were significantly diminished after adsorption of the first two monolayers of either adsorbate. Aqueous-phase TCE at a concentration equal to 1% of its saturation concentration was able to completely displace adsorbed water in uncharged pores. Even in highly hydrophilic pores, TCE at this concentration was able to displace up to 50% of the adsorbed water. Apparent differential enthalpies of adsorption determined from the temperature dependence of TCE adsorption isotherms underestimated the magnitude of the true isosteric heats of adsorption by up to 30 kJ/mol. This shows that HOC adsorption enthalpies determined from the temperature dependence of their adsorption isotherms underestimate the true strength of HOC-adsorbent interactions.

Experimental and molecular mechanics and ab initio investigation of activated adsorption and desorption of trichloroethylene in mineral micropores.

This research investigated activated adsorption of a hydrophobic organic contaminant(HOC) in mineral micropores using experimental and molecular modeling techniques. Adsorption of trichloroethylene (TCE) on a silica gel adsorbent was measured using a frontal analysis chromatography technique at atmospheric and elevated fluid pressures. Increasing the fluid pressure yielded increased TCE uptake that was not released upon lowering the pressure back to atmospheric conditions. This showed that the increase in pressure was able to rapidly induce the formation of a desorption-resistant fraction that previous investigations have shown requires months to develop at atmospheric pressure. Grand Canonical Monte Carlo (GCMC) modeling was then used to elucidate the nature of water and TCE behavior within silica micropores. The GCMC modeling showed that molecular scale packing restrictions resulted in pore fluid densities that ranged from 0.28 to 0.78 of those in the bulk solution. The modeling also showed that TCE was able to displace water from hydrophilic mineral pores due to molecular scale packing restrictions. Exothermic isosteric heats for TCE adsorption up to -27 kJ/mol were observed and were greatest in pores of 7 and 8 A. This indicated that TCE adsorption was energetically most favorable in pores that were minimally large enough to accommodate a TCE molecule. The pressure-induced uptake appeared to result primarily from an increase in the packing density in the smallest pores. Ab initio calculations showed that small distortions of a TCE molecule from its low energy conformation require high activation energies. Results from this study indicate that activated adsorption requiring bond angle distortions in the adsorbate may be responsible forthe slow attainment of adsorptive equilibrium of HOCs on microporous solids. Likewise, activated desorption from molecular-sized adsorption sites may contribute to the slow release of HOCs from aquifer sediments.