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Background Carpal tunnel syndrome is the most common upper-extremity nerve compression syndrome. Over 500,000 carpal tunnel release (CTR) procedures are performed in the U.S. yearly. We estimated the cost-effectiveness of endoscopic CTR (ECTR) versus open CTR (OCTR) using data from published meta-analyses comparing outcomes for ECTR and OCTR. Methods We developed a Markov model to examine the cost-effectiveness of OCTR versus ECTR for patients undergoing unilateral CTR in an office setting under local anesthesia and in an operating-room (OR) setting under monitored anesthesia care. The main outcomes were costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). We modeled societal (modeled with a 50-year-old patient) and Medicare payer (modeled with a 65-year-old patient) perspectives, adopting a lifetime time horizon. We performed deterministic and probabilistic sensitivity analyses (PSAs). Results ECTR resulted in 0.00141 additional QALY compared with OCTR. From a societal perspective, assuming 8.21 fewer days of work missed after ECTR than after OCTR, ECTR cost less across all procedure settings. The results are sensitive to the number of days of work missed following surgery. From a payer perspective, ECTR in the OR (ECTROR) cost $1,872 more than OCTR in the office (OCTRoffice), for an ICER of approximately $1,332,000/QALY. The ECTROR cost $654 more than the OCTROR, for an ICER of $464,000/QALY. The ECTRoffice cost $107 more than the OCTRoffice, for an ICER of $76,000/QALY. From a payer perspective, for a willingness-to-pay threshold of $100,000/QALY, OCTRoffice was preferred over ECTROR in 77% of the PSA iterations. From a societal perspective, ECTROR was preferred over OCTRoffice in 61% of the PSA iterations. Conclusions From a societal perspective, ECTR is associated with lower costs as a result of an earlier return to work and leads to higher QALYs. Additional research on return to work is needed to confirm these findings on the basis of contemporary return-to-work practices. From a payer perspective, ECTR is more expensive and is cost-effective only if performed in an office setting under local anesthesia. Level of evidence Economic and Decision Analysis Level I. See Instructions for Authors for a complete description of levels of evidence.

Background: The Controlled Study of Lanreotide Antiproliferative Response in Neuroendocrine Tumors (CLARINET) trial showed prolonged progression-free survival in patients initially treated with lanreotide versus placebo. We evaluated the cost-effectiveness of upfront lanreotide versus active surveillance with lanreotide administered after progression in patients with metastatic enteropancreatic neuroendocrine tumors (NETs), both of which are treatment options recommended in NCCN Clinical Practice Guidelines in Oncology for Neuroendocrine and Adrenal Tumors. Methods: We developed a Markov model calibrated to the CLARINET trial and its extension. We based the active surveillance strategy on the CLARINET placebo arm. We calculated incremental cost-effectiveness ratios (ICERs) in dollars per quality-adjusted life-year (QALY). We modeled lanreotide’s cost at $7,638 per 120 mg (average sales price plus 6%), used published utilities (stable disease, 0.77; progressed disease, 0.61), adopted a healthcare sector perspective and lifetime time horizon, and discounted costs and benefits at 3% annually. We examined sensitivity to survival extrapolation and modeled octreotide long-acting release (LAR) ($6,183 per 30 mg). We conducted one-way, multiway, and probabilistic sensitivity analyses. Results: Upfront lanreotide led to 5.21 QALYs and a cost of $804,600. Active surveillance followed by lanreotide after progression led to 4.84 QALYs and a cost of $590,200, giving an ICER of $578,500/QALY gained. Reducing lanreotide’s price by 95% (to $370) or 85% (to $1,128) per 120 mg would allow upfront lanreotide to reach ICERs of $100,000/QALY or $150,000/QALY. Across a range of survival curve extrapolation scenarios, pricing lanreotide at $370 to $4,000 or $1,130 to $5,600 per 120 mg would reach ICERs of $100,000/QALY or $150,000/QALY, respectively. Our findings were robust to extensive sensitivity analyses. The ICER modeling octreotide LAR is $482,700/QALY gained. Conclusions: At its current price, lanreotide is not cost-effective as initial therapy for patients with metastatic enteropancreatic NETs and should be reserved for postprogression treatment. To be cost-effective as initial therapy, the price of lanreotide would need to be lowered by 48% to 95% or 27% to 86% to reach ICERs of $100,000/QALY or $150,00/QALY, respectively.

Background. Whole pancreas transplantation (Tx) is a successful treatment for type 1 diabetes resulting in independence from antidiabetic therapies. Transplant-related factors contributing to pancreatic islet failure are largely unknown; both recurring insulitis and pancreatitis have been implicated. The aim was to determine if cellular changes in islets and exocrine tissue are evident early in Tx, which could contribute to eventual graft failure using well-preserved tissue of grafts explanted from largely normoglycemic recipients. Methods. Histological specimens of explants (n = 31), Tx duration 1 day–8 years (median 29 d), cold ischemia time 7.2–17.3 hours (median 11.1 h), donor age 13–54 years (median 38 y) were examined; sections were labeled for inflammation, islet amyloidosis, and tissue fibrosis, and morphometry performed on immunolabeled insulin and glucagon positive islet cells. Data were related to clinical details of donor, recipient, and features of Tx. Results. Islet inflammation consistent with recurrent insulitis was not seen in any sample. Insulin-labeled islet cell proportion decreased with donor age (P Conclusions. Explant histological changes after short-term Tx are similar to those seen in type 2 diabetes and occur in the absence of immunologic rejection without causing hyperglycemia. This suggests that factors associated with Tx affect islet stability; persistent deterioration of islet integrity and exocrine tissue fibrosis could impact on sustainability of islet function.

This study aims to explore the biopsychosocial factors linked with the well-being of students and educators during the Coronavirus Disease 2019 (COVID-19) pandemic, and how these factors affect feelings, thoughts, behavior, family relationships, and work environment. We developed a questionnaire comprising three domains: biological, psychological, and social. These three domains covered some of the symptoms that occurred in people during the COVID-19 pandemic. The sample included educators and students who were randomly selected from two countries: the United Arab Emirates (UAE) and Jordan. The sample consisted of 56 academic staff, 6 administrative staff, and 232 students at the tertiary level. The main findings showed that the most commonly reported biopsychosocial factors linked with educators’ and students’ well-being were the effect on family, depression, negative effect of media, headache, increased eating and sleep, physical comfort, and positive effect on goal achievement. In addition, the results showed that the demographic variables, gender and academic levels, had no statistically significant effect on the participants’ responses, but there was a significant effect of social status. In addition, the study highlighted the common coping strategies used by educators and students, such as doing physical exercise, finding a hobby, sleeping, and eating more meals.

Disability hate crime is under-reported in the UK with perceived lim-ited support given to the victims. The use of online communication resulted in cyber-disability hate cases, recognised by the Police with the addition of an ‘online-flag’ in the documentation. However, the cases remain under-reported, with potential individual, societal and organisational barriers to reporting espe-cially during a pandemic. This paper aims to contextualise the reporting of cyber-disability hate cases, identify potential barriers, and provide recommendations to improve support to victims by the Police.The retrospective examination was car-ried out on disability-related cyber incidentsdocumented by a police force in the UK for 19 months. Among 3,349 cyber-crimes, 23 cases were included. The anal-ysis covereddescriptive statistics and qualitative document analysis (QDA). Only 0.7% of cyber incidentsor 6.7% of cyber-hate incidentswere disability re-lated. The age of victims ranged between 15 and61 years, with a mean of 25.8 years. Most of the victims (78%) were from White ethnic background, and the majority were females (61.5%). Three overarching themes emerged from the qualitative dataas influencers of reporting or documentation, these were: psy-chological impact, fear for safety, and the type of disability.Cyber-offences re-sulted in a serious impact on wellbeing, however, cases that included people with visible disabilitieswere more documented. Further awareness-raising targeting the police and public is needed to understand the impact of cyber-offences and recognise the different types of disabilities, which might encourage both report-ing and documentation

This report describes the clinical signs, diagnostic findings and treatment of a female spayed Domestic Shorthair with exocrine pancreatic insufficiency (EPI) who presented in shock due to severe gastrointestinal haemorrhage secondary to coagulopathy caused by vitamin K-dependent clotting factor deficiency. Diagnostics revealed a prolonged prothrombin time, activated partial thromboplastin time, low trypsin-like immunoreactvity and gross evidence of pancreatic atrophy. Gastrointestinal haemorrhage resolved quickly with transfusion of fresh frozen plasma and vitamin K supplementation. Following treatment with oral pancreatic enzyme supplementation, the cat was found to have resolution of gastrointestinal signs, improved body condition and normalisation of clotting times. Fat-soluble vitamin levels were below the expected range and improved following treatment. This is the second report of coagulopathy in a cat with EPI and the first to describe fat-soluble vitamin deficiency that improved with pancreatic enzyme supplementation.

Artificial pancreas (AP) device development for ambulatory subjects with type 1 diabetes, has focused on using continuous subcutaneous (SC) insulin infusion (CSII) and glucose measurement. The substantial insulin absorption time-lag associated with CSII makes successful automatic glucose regulation extremely difficult. This work considers using an alternative approach, namely continuous intra-peritoneum (IP) insulin infusion (CIPII) which simplifies the control problem by reducing the insulin absorption time-lag. This could lead to improved glucose regulation and as a consequence improve subject safety with a corresponding reduction in time spent in both hypo- and hyper-glycaemic zones. An in silico performance comparison, between a CSII-based AP, that uses Model Predictive Control, and a CIPII-based AP, that uses Proportional, Integral and Derivative Control is carried out where the virtual subject has a heavy daily meal intake. AP performance both with and without a mealtime prandial bolus is examined as well as the robust performance of a single tuned controller, based on an average subject, on a cohort of simulated type 1 diabetes mellitus subjects.

Background Complex regional pain syndrome (CRPS) occurs in 2 to 8% of patients that receive open or endoscopic carpal tunnel release (CTR). Because CRPS is difficult to treat after onset, identifying risk factors can inform prevention. We determined the incidence of CRPS following open and endoscopic CTR using a national claims database. We also examined whether psychosocial conditions were associated with CRPS after CTR. Methods We accessed insurance claims using diagnostic and procedural codes. We calculated the incidence of CRPS following open carpal tunnel release and endoscopic carpal tunnel release within 1 year. The response variable was the presence of CRPS after CTR. Explanatory variables included procedure type, age, gender, and preoperative diagnosis of anxiety or depression. Results The number of open CTRs (85% of total) outweighs the number of endoscopic procedures. In younger patients, the percentage of endoscopic CTRs is increasing. Rates of CRPS are nearly identical between surgery types for both privately insured (0.3%) and Medicare patients (0.1%). Middle aged (range: 40–64 years) and female patients had significantly higher rates of CRPS than did the general population. Preoperative psychosocial conditions did not correlate with the presence of CRPS in surgical patients. Clinical Relevance The decision between endoscopic and open CTR should not be made out of concern for development of CRPS postsurgery, as rates are low and similar for both procedures. Rates of CRPS found in this study are much lower than rates found in previous studies, indicating inconsistency in diagnosis and reporting or generalizability of prior work. Preoperative psychosocial disorders and CRPS are unrelated.

Ibrutinib is a novel oral therapy that has shown significant efficacy as initial treatment of chronic lymphocytic leukemia (CLL). It is a high-cost continuous therapy differing from other regimens that are given for much shorter courses. Our objective was to evaluate the cost-effectiveness of ibrutinib for first-line treatment of CLL in patients older than age 65 years without a 17p deletion. We developed a semi-Markov model to analyze the cost-effectiveness of ibrutinib vs a comparator therapy from a US Medicare perspective. No direct comparison between ibrutinib and the best available treatment alternative, obinutuzumab plus chlorambucil (chemoimmunotherapy), exists. Therefore, we compared ibrutinib to a theoretical treatment alternative, which was modeled to confer the effectiveness of an inferior treatment (chlorambucil alone) and the costs and adverse events of chemoimmunotherapy, which would provide ibrutinib with the best chance of being cost-effective. Even so, the incremental cost-effectiveness ratio of ibrutinib vs the modeled comparator was $189 000 per quality-adjusted life-year (QALY) gained. To reach a willingness-to-pay threshold (WTP) of $150 000 per QALY, the monthly cost of ibrutinib would have to be at most $6800, $1700 less than the modeled cost of $8500 per month (a reduction of $20 400 per year). When the comparator efficacy is increased to more closely match that seen in trials evaluating chemoimmunotherapy, ibrutinib costs more than $262 000 per QALY gained, and the monthly cost of ibrutinib would need to be lowered to less than $5000 per month to be cost-effective. Ibrutinib is not cost-effective as initial therapy at a WTP threshold of $150 000 per QALY gained.

Key Points Question Among patients with newly diagnosed diabetes, are preexisting mental health (MH) or substance use (SU) disorders and primary care utilization before a new diabetes diagnosis associated with the long-term severity of diabetes complications? Findings In this cohort study of 122 992 patients in the US Department of Veterans Affairs health system, more than 90% of patients with MH or SU disorders had primary care visits before diabetes was newly diagnosed, compared with approximately 58% of patients without MH or SU disorders. Patients with MH or SU disorders experienced significantly lower severity of diabetes complications for 7 years thereafter, compared with patients without preexisting MH or SU disorders, even after controlling for sociodemographic characteristics and medical comorbidities. Meaning Among patients with MH or SU disorders, receiving more medical and mental health care from an integrated health care system before the onset of diabetes is associated with modest, albeit impermanent, health benefits after the onset of diabetes., This cohort study uses data from the US Veterans Affairs health care systems to examine whether preexisting mental health or substance use disorders and primary care utilization before a new diabetes diagnosis are associated with the long-term severity of diabetes complications., Importance Among people with diabetes, co-occurring mental health (MH) or substance use (SU) disorders increase the risk of medical complications. Identifying how to effectively promote long-term medical benefits for at-risk populations, such as people with MH or SU disorders, is essential. Knowing more about how health care accessed before the onset of diabetes is associated with health benefits after the onset of diabetes could inform treatment planning and population health management. Objective To analyze how preexisting MH or SU disorders and primary care utilization before a new diabetes diagnosis are associated with the long-term severity of diabetes complications. Design, Setting, and Participants This cohort study analyzed medical record data from US Department of Veterans Affairs health care systems nationwide and used mixed-effects regressions to test associations between prediabetes patient or health care factors and longitudinal progression of diabetes complication severity from 2006 to 2015. Participants included patients who received a new diabetes diagnosis in 2008 and who were aged 18 to 85 years at the time of their diagnosis. Data analysis was conducted from March to August 2017. Exposures Patients were assigned to groups on the basis of a 2-year look-back period for MH or SU disorders status (MH disorder only, SU disorder only, MH and SU disorder, or no MH or SU disorder diagnoses) and on the basis of the amount of primary care utilization before diabetes was diagnosed. Main Outcomes and Measures Nine-year trajectories of Diabetes Complication Severity Index (DCSI) scores. Results Among 122 992 patients with newly diagnosed diabetes, the mean (SD) age was 62.3 (11.1) years, 118 810 (96.6%) were male, and 28 633 (23.3%) had preexisting MH or SU disorders diagnoses. From the onset of diabetes to 7 years later, patients’ mean estimated DCSI scores increased from 0.84 (95% CI, 0.82-0.87) to 1.42 (95% CI, 1.36-1.47). Controlling for sociodemographic characteristics and medical comorbidities, SU disorders only (decrease in DCSI score, −0.09; 95% CI, −0.13 to −0.04; P

Maltreated children with reactive attachment disorder (RAD) have severe problems with social relationships and affect regulation. An association between early maltreatment and changes in the daily rhythm of cortisol secretion has already been reported for maltreated toddlers. We sought to find out whether such changes were apparent in school-age children with symptoms of RAD, who had experienced early maltreatment but were currently adopted in well-functioning families. We recruited 66 children: 34 adopted children, aged 5–12 years, with an early history of maltreatment and with social difficulties such as indiscriminate friendliness; and 32 age- and sex-matched comparison children with no history of maltreatment or social difficulties. Daily rhythms of cortisol production were determined from saliva samples collected over 2 days. The adopted group had significantly lower absolute levels of cortisol compared to the control group, but a typical profile of cortisol secretion. There was no association between cortisol secretion and symptom scores for psychopathology.

Purpose of review Abdominal wall transplantation is a technique used to achieve abdominal closure after intestinal and multivisceral transplantation. This review focuses on whether there are additional benefits for the skin component as an immune-monitoring tool. Recent findings The largest series of abdominal wall transplants has recently been published. Alongside the physiological advantage gained in abdominal closure, the authors describe the immunological insight that the skin component can provide and how this contributes to the management of patients. The skin appears to develop a rash with early rejection, which facilitates early systemic treatment before significant visceral rejection occurs. It can also help in cases in which there is diagnostic doubt regarding the cause of bowel dysfunction such as in instances of intestinal infection. Despite the additional immunological burden of donor tissue, there appears to be no requirement for increased immunosuppressive therapy. Summary The technical and immunological feasibility of abdominal wall transplantation has now been demonstrated by several centres. Skin transplanted as part of the abdominal wall or as a separate vascularized sentinel skin flap may aid in the diagnosis of rejection. This has the potential to improve graft survival and reduce immunosuppressive morbidity.

Laparoscopic cholecystectomy is commonly performed, and several factors increase the risk of open conversion, prolonging operating time and hospital stay. Preoperative stratification would improve consent, scheduling and identify appropriate training cases. The aim of this study was to develop a validated risk score for conversion for use in clinical practice.Preoperative patient and disease-related variables were identified from a prospective cholecystectomy database (CholeS) of 8820 patients, divided into main and validation sets. Preoperative predictors of conversion were identified by multivariable binary logistic regression. A risk score was developed and validated using a forward stepwise approach.Some 297 procedures (3.4%) were converted. The risk score was derived from six significant predictors: age (p = 0.005), sex (p 0.001), indication for surgery (p 0.001), ASA (p 0.001), thick-walled gallbladder (p = 0.040) and CBD diameter (p = 0.004). Testing the score on the validation set yielded an AUROC = 0.766 (p 0.001), and a score6 identified patients at high risk of conversion (7.1% vs. 1.2%).This validated risk score allows preoperative identification of patients at six-fold increased risk of conversion to open cholecystectomy.

Hypothyroidism in pregnancy can lead to adverse maternal and fetal outcomes. Although screening of high-risk women is advocated, universal screening remains controversial.The objective of the study was to compare the cost-effectiveness of universal screening of pregnant women for autoimmune thyroid disease (AITD) with screening only high-risk women and with no screening.A decision-analytic model compared the incremental cost per quality-adjusted life-year (QALY) gained among the following: 1) universal screening, 2) high-risk screening, and 3) no screening. Screening consisted of a first-trimester thyroid-stimulating hormone level and antithyroid peroxidase antibodies. Women with abnormal results underwent further testing and, when indicated, levothyroxine therapy. Randomized controlled trials provided probabilities for adverse obstetrical outcomes. The model accounted for the development of postpartum thyroiditis and overt hypothyroidism. Additional scenarios in which therapy prevented cases of decreased child intelligence quotient were explored.Medical consequences of AITD in pregnancy, QALY, and costs were measured.Risk-based screening and universal screening were both cost-effective relative to no screening, with incremental cost-effectiveness ratios (ICERs) of $6,753/QALY and $7,138/QALY, respectively. Universal screening was cost-effective compared with risk-based screening, with an ICER of $7,258/QALY. Screening remained cost-effective in various clinical scenarios, including when only overt hypothyroidism was assumed to have adverse obstetrical outcomes. Universal screening was cost-saving in the scenario of untreated maternal hypothyroidism resulting in decreased child intelligence, with levothyroxine therapy being preventive.Universal screening of pregnant women in the first trimester for AITD is cost-effective, not only compared with no screening but also compared with screening of high-risk women.

The significant increase in the detection and treatment of ductal carcinoma in situ (DCIS) since the introduction of screening mammography has not been accompanied by the anticipated reduction in invasive breast cancer (IBC) incidence. The prevalence of DCIS requires a reexamination of the population level effects of detecting and treating DCIS. To further our understanding of the possible impact of DCIS diagnosis and treatment on IBC incidence in the U.S., we simulated breast cancer incidence over 25 years under various assumptions regarding the baseline incidence of IBC and the progression of DCIS to IBC. The simulations demonstrate a tradeoff between the expected increased incidence of IBC absent any DCIS detection and treatment and the rate of progression of DCIS to IBC. Our analyses indicate that a high progression of DCIS to IBC implies a significant increase in incidence of IBC over what is observed had we not detected and treated DCIS. Conversely, if we assume that there would not have been a significant increase over and above the observed incidence evident in SEER, then our model indicates that the rate of DCIS progression to clinically significant IBC is low. Given the tradeoff illustrated by our model, we must reevaluate the assumption that DCIS is a short-term obligate precursor of invasive cancer and instead focus on further exploration of the true natural history of DCIS.

Venomous snakebites may be difficult to manage because of the varied clinical presentations that may lead to uncertainty regarding the most appropriate medical and surgical management. Frequently, snakebite victims are referred from smaller rural hospitals to larger tertiary centers offering more specialized services and care. A retrospective chart review was performed using medical records from both adult and pediatric hospitals in a rural state over a 7-year period (January 2004 to January 2011) to investigate the utility of intensive care and specialized medical services offered at tertiary referral centers. The results demonstrated that presentation of venomous snakebites is the same in adults and children as well as the management. The results also demonstrated that the use of supportive care and antivenin alone was successful in the management of the vast majority of snakebites. Most snakebite victims recovered with nonsurgical care; thus surgical intervention is rarely warranted. These findings demonstrate that snakebite victims may not need referral to a tertiary center, if the primary local hospital has supportive care capacity and familiarity with antivenin usage.

Background The demand for kidney retransplantation following graft failure is rising. Repeat transplantation is often associated with poorer outcomes due to both immunological and surgical challenges. The aim of this study was to compare surgical and functional outcomes of kidney retransplantation in recipients that had previously had at least 2 kidney transplants with a focus on those with antibody incompatibility. Methods We analysed 66 patients who underwent renal transplantation at a single centre between 2003 and 2011. Consecutive patients receiving their 3rd or 4th kidney were case-matched with an equal number of 1st and 2nd transplants. Results Twenty-two 3rd and 4th kidney transplants were matched with 22 first and 22 second transplants. Operative times and length of stay were equivalent between the subgroups. Surgical complication rates were similar in all groups (22.7% in 1st and 2nd transplants, and 27.2% in 3rd/4th transplants). There was no significant difference in patient or graft survival over 5 years. Graft function was similar between transplant groups at 1, 3 and 5 years. Conclusions Third and fourth kidney transplants can be performed safely with similar outcomes to 1st and 2nd transplants. Kidney retransplantation from antibody incompatible donors may be appropriate for highly sensitised patients. This article is protected by copyright. All rights reserved.

We aimed to explore the extent of neurodevelopmental difficulties in severely maltreated adopted children. We recruited 34 adopted children, referred with symptoms of indiscriminate friendliness and a history of severe maltreatment in their early childhood and 32 typically developing comparison children without such a history, living in biological families. All 66 children, aged 5-12 years, underwent a detailed neuropsychiatric assessment. The overwhelming majority of the adopted/indiscriminately friendly group had a range of psychiatric diagnoses, including Attention Deficit Hyperactivity Disorder (ADHD), Post-Traumatic Stress Disorder (PTSD) and Reactive Attachment Disorder (RAD) and one third exhibited the disorganised pattern of attachment. The mean IQ was 15 points lower than the comparison group and the majority of the adopted group had suspected language disorder and/or delay. Our findings show that school-aged adopted children with a history of severe maltreatment can have very complex and sometimes disabling neuropsychiatric problems.

OBJECTIVE To evaluate the safety and feasibility of exhaled breath condensate (EBC) collection in children recovering from status asthmaticus (SA) in a pediatric intensive care unit (PICU); and to investigate whether 8-isoprostane (8-Iso) could be detected in the EBC of these children and to compare its concentration with that in the EBC collected from healthy children. DESIGN Prospective study. SETTING Multidisciplinary PICU in a teaching hospital. PATIENTS Sixteen consecutive patients (7-18 yrs of age) with SA and 16 age- and sex-matched controls. INTERVENTIONS The Wood clinical asthma score and the pulmonary index were used to assess the clinical severity of patients with SA upon admission to the PICU. EBC samples were collected within 24 hrs of admission to the PICU and were analyzed for the concentration of 8-Iso. MEASUREMENTS AND MAIN RESULTS Data are presented as mean ± sd values. There were no differences in age (12 ± 3.3 yrs vs.12 ± 2 yrs, p > .05) or sex (n = 10 males and n = 6 females in each group), between SA patients and controls. All patients with SA and the controls completed the EBC collection without complications. There was no statistically significant difference in the pulmonary index (3.2 ± 2.7 vs. 3.1 ± 2.8, p 0.9) post collection of EBC compared with the baseline values. There was a statistically significant correlation between Wood score and pulmonary index at the time of admission to the PICU in children with SA (r = .7, p < .01). The concentration of 8-Iso was significantly higher in the EBC of children with SA compared with controls (14.3 ± 1.8 pg/mL vs. 5.2 ± 0.7 pg/mL, p < .001). The correlation between the concentration 8-Iso and either the pulmonary index or Wood score at the time admission to the PICU was not statistically significant. CONCLUSIONS EBC collection is well tolerated by children aged 7-18 yrs who are recovering from SA in a PICU. 8-Iso is elevated in the EBC from children with SA and may provide insight into the biochemical changes of oxidative stress in children in this clinical setting.

A ring fixator was used in the treatment of five patients (ages 11 to 16 years) with proximal tibial growth arrest after trauma. The mean corrections were 14.2 degrees (maximum 28 degrees , minimum 0 degrees ) in the saggital plane and 14 degrees (maximum 38 degrees , minimum 2 degrees ) in the coronal plane. Leg length discrepancy was also corrected (max 1 cm). The average time in frame was 17.8 weeks, with an average correction time of 29.8 days. Knee Society Clinical Rating System scores post operatively ranged from 95-100. All patients returned to full activity, and would accept the same treatment if offered again. The circular fixator is an effective, minimally invasive method for treating the complex deformities arising from this rare injury. Patients remain active during treatment, encouraging a rapid return to school/work activities.

The pathogenesis of eosinophilic chronic rhinosinusitis (ECRS) is still unclear. Paranasal mucosa inflammation is thought to be related to eosinophilic infiltration. This infiltration seems to induce changes in the expression of cell adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1). The E-cadherin-beta-catenin complex maintains the integrity of the epithelium. Downregulation of beta-catenin and E-cadherin is a pivotal factor for progressive cell growth. This study aimed to assess which cytokines regulate the expression of the adhesion molecule E-cadherin and the multi-functional protein beta-catenin, which plays a key role in cadherin-mediated anchoring in ECRS. Cultured ECRS specimens were incubated with human VCAM-1. After a period of up to 72 h, expression of E-cadherin and beta-catenin was determined using cytokine immunoassay and immunohistochemistry. In ECRS, significant increases in E-cadherin expression were found in fibroblast cell cultures. Stimulation with VCAM-1 did not produce a significant alteration in the expression of the adherens junction protein beta-catenin. In addition, VCAM-1 did not decrease the levels of membrane staining for adherens junction proteins. The selective increase in E-cadherin expression in eosinophilic fibroblast cultures might be explained by a higher concentration of the Th2-type cytokines in these cultures. The tissue remodelling observed during chronic eosinophilic inflammation offers new insight into the pathogenesis of ECRS.

ObjectiveAbnormal wound healing processes can result in hypertrophic scars and keloids. TGF-β1 and HGF/SF are biphasic growth factor cytokines in physiological and pathophysiological conditions. TGF-β1 has been found to be pivotal in the formation of keloid tissue and therefore neutralising antibodies may allow wound healing without keloid formation. TGF-β1 has been reported to be antagonised by HGF/SF. Some authors have reported that exogenous administration of HGF/SF prevented scar formation. Hence in this study, we targeted TGF-β1 and determined the levels of HGF/SF in fibroblast cell culture.MethodsKeloid tissue was taken from 7 patients while another 7 patients with mature non-hypertrophic scar served as controls. All tissues were cultured and fibroblast cultures were used for further experiments. TGF-β1 antisense was administered at 3 and 6 μmol/ml and HGF/SF levels were determined after 16, 24 and 48 hours of incubation.ResultsThe levels of HGF/SF showed significant differences after incubation wit...

Many of the factors in the pathogenesis and experimental production of acute pancreatitis are conflicting and controversial. It is generally conceded that interstitially extravasated, active trypsin in the pancreas plays a dominant role. 1,2 Evidence further indicates that if, in addition, ductal obstruction or ischemia supervenes, necrotic or hemorrhagic pancreatitis is likely to ensue. 1-4 The pivotal issues seem to be (1) the mechanism by which trypsin or trypsinogen is extravasated, (2) whether trypsinogen itself can cause pancreatitis, and (3) the manner in which trypsinogen is activated. The majority of investigators have utilized ductal perfusion of bile or pancreatic juice. 1,3 Stein and co-workers have produced hemorrhagic pancreatitis by injection of trypsin into the dog's pancreaticoduodenal artery and ligation of the pancreatic ducts. Hosie and Ziffren 5 have implicated collagenase, normally contained in pancreatic juice, as the initiator of pancreatitis. Since much of the experimental evidence indicating active trypsin as

Objectives: To assess the quality of care given to elderly people and compare the care given to residents in nursing homes with those living in their own homes. Design: Controlled observational study. Setting: Primary care, Bristol. Subjects: Elderly individuals (aged 65 years) registered with three general practices, of whom 172 were residents in nursing homes (cases) and 526 lived at home (matched controls). Main outcome measures: The quality of clinical care given to patients was measured against explicit standards. Quality indicators were derived from national sources and agreed with participating general practitioners. Results: The overall standard of care was inadequate when judged against the quality indicators, irrespective of where patients lived. The overall prescribing of beneficial drugs for some conditions was deficient—for example, only 38% (11/29) (95% confidence interval 20% to 58%) of patients were prescribed β blockers after myocardial infarction. The proportion of patients with heart disease or diabetes who had had their blood pressure measured in the past two years (heart disease) or past year (diabetes) was lower among those living in nursing homes: for heart disease, 74% (17/23) v 96% (122/127) (adjusted odds ratio 0.18, 0.04 to 0.75); for diabetes, 62% (8/13) v 96% (50/52) (adjusted odds ratio 0.05, 0.01 to 0.38). In terms of potentially harmful prescribing, significantly more patients in nursing homes were prescribed neuroleptic medication (28% (49/172) v 11% (56/526) (3.82, 2.37 to 6.17)) and laxatives (39% (67/172) v 16% (85/526) (2.79, 1.79 to 4.36)). Nursing home residents were less likely to have the appropriate diagnostic Read code linked to their prescribed neuroleptic drug (0.22, 0.07 to 0.71). Conclusions: The quality of medical care that elderly patients receive in one UK city, particularly those in nursing homes, is inadequate. We suggest that better coordinated care for these patients would avoid the problems of overuse of unnecessary or harmful drugs, underuse of beneficial drugs, and poor monitoring of chronic disease. What is already known on this topic Doctors too often prescribe harmful drugs and too seldom prescribe beneficial drugs for elderly people The quality of medical care for those living in nursing and residential homes has also been questioned What this study adds Elderly people in one UK city receive inadequate care when judged against explicit quality indicators Those living in nursing homes receive poorer care than those living at home in terms of underuse of beneficial drugs, poor monitoring of chronic disease, and overuse of inappropriate or unnecessary drugs

A unique case of recurrent brain abscess as the primary manifestation of pulmonary arteriovenous fistula is presented. In the absence of hematologic abnormalities and characteristic physical findings, the diagnosis of pulmonary arteriovenous fistula is particularly elusive. Patients with brain abscess must be carefully evaluated for the presence of pulmonary arteriovenous fistula or hereditary hemorrhagic telangiectasia.

The value of postoperative prophylactic antibiotics in general surgery has long been debated. At the time this study was undertaken, sufficient evidence to condemn or justify such use of antibiotics had not been presented. In a complete review of the literature, several studies concerning this problem were found. McKittrick and, more recently, Sanchez-Ubeda published work suggesting that prophylactic postoperative antibiotics do not diminish the incidence of postoperative infections in general surgical patients. Appleton and Wisebrun in urology and Tachdjian and Compere in orthopedics reached similar conclusions. The present investigation studied the effect of routinely administered antibiotics on the postoperative course of general surgical patients. To assure the validity of the findings, it was necessary to meet two criteria. The first was that the number of patients be significantly large. The second was that the study be adequately controlled. Materials and Methods All major operative cases of the general surgical service

Introduction: Delayed graft function (DGF) remains a significant and detrimental postoperative phenomenon following living-related renal allograft transplantation, with a published incidence of up to 15%. Early therapeutic vasodilatory interventions have been shown to improve DGF, and modifications to immunosuppressive regimens may subsequently lessen its impact. This pilot study assesses the potential applicability of perioperative non-invasive cardiac output monitoring (NICOM), transit-time flow monitoring (TTFM) of the transplant renal artery and pre-/perioperative thromboelastography (TEG) in the early prediction of DGF and perioperative complications.\ud \ud Methods: Ten consecutive living-related renal allograft recipients were studied. Non-invasive cardiac output monitoring commenced immediately following induction of anaesthesia and was maintained throughout the perioperative period. Doppler-based TTFM was performed during natural haemostatic pauses in the transplant surgery: immediately following graft reperfusion and following ureteric implantation. Central venous blood sampling for TEG was performed following induction of anaesthesia and during abdominal closure.\ud \ud Results: A single incidence of DGF was seen within the studied cohort and one intra-operative (thrombotic) complication noted. NICOM confirmed a predictable trend of increased cardiac index (CI) following allograft reperfusion (mean CI - clamped: 3.17 ± 0.29 L/min/m2, post-reperfusion: 3.50 ± 0.35 L/min/m2; P < 0.05) mediated by a significant reduction in total peripheral resistance. Reduced TTFM at the point of allograft reperfusion (227 ml/min c.f. mean; 411 ml/min (95% CI: 358 to 465)) was identified in a subject who experienced intra-operative transplant renal artery thrombosis. TEG data exhibited significant reductions in clot lysis (LY30 (%): pre-op: 1.0 (0.29 to 1.71), post reperfusion 0.33 (0.15 to 0.80); P = 0.02) and a trend towards increased clot initiation following allograft reperfusion.\ud \ud Conclusions: Reduced renal arterial blood flow (falling without the 95% CI of the mean), was able to accurately predict anastomotic complications within this pilot study. TEG data suggest the emergence of a prothrombotic state, of uncertain clinical significance, following allograft reperfusion. Abrogation of characteristic haemodynamic trends, as determined by NICOM, following allograft reperfusion may permit prediction of individuals at risk of DGF. The findings of this pilot study mandate a larger definitive trial to determine the clinical applications and predictive value of these technologies.