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Noncardiac chest pain is associated with poor quality of life and high care expenditure. The majority of noncardiac chest pain is either gastresophageal reflux disease related or due to esophageal motility disorders, and the rest are considered functional chest pain (FCP) due to central and peripheral hypersensitivity. Current treatment of FCP improves 40-50% of patients. Cannabinoid receptors 1 (CB1) and 2 (CB2) modulate release of neurotransmitters; CB1 is located in the esophageal epithelium and reduces excitatory enteric transmission and potentially could reduce esophageal hypersensitivity. We performed a prospective study to evaluate its effects on pain threshold, frequency, and intensity in FCP. Subjects with FCP received dronabinol (5 mg, twice daily; n = 7; average age, 44 years; mean body mass index, 26.7) or placebo (n = 6; average age, 42 years; mean body mass index, 25.9) for 28 days (4 weeks). Chest pain, general health, and anxiety/depression questionnaires were assessed at baseline and at 4 weeks. Subjects underwent an esophageal balloon distention test prior to treatment and on last day of the study. Dronabinol increased pain thresholds significantly (3.0 vs. 1.0; P = 0.03) and reduced pain intensity and odynophagia compared to placebo (0.18 vs. 0.01 and 0.12 vs. 0.01, respectively, P = 0.04). Depression and anxiety scores did not differ between the groups at baseline or after treatment. No significant adverse effects were observed. In this novel study, dronabinol increased pain threshold and reduced frequency and intensity of pain in FCP. Further, large scale studies are needed to substantiate these findings. [ABSTRACT FROM AUTHOR]

Abstract Background There is growing concern certain not-for-profit hospitals are not providing enough uncompensated care to justify their tax exempt status. Our objective was to compare the amount of uncompensated care provided by not-for-profit (NFP), for-profit (FP) and government owned hospitals. Methods We used 2005 state inpatient data (SID) for 10 states to identify patients hospitalized for three common conditions: acute myocardial infarction (AMI), coronary artery bypass grafting (CABG), or childbirth. Uncompensated care was measured as the proportion of each hospital's total admissions for each condition that were classified as being uninsured. Hospitals were categorized as NFP, FP, or government owned based upon data obtained from the American Hospital Association. We used bivariate methods to compare the proportion of uninsured patients admitted to NFP, FP and government hospitals for each diagnosis. We then used generalized linear mixed models to compare the percentage of uninsured in each category of hospital after adjusting for the socioeconomic status of the markets each hospital served. Results Our cohort consisted of 188,117 patients (1,054 hospitals) hospitalized for AMI, 82,261 patients (245 hospitals) for CABG, and 1,091,220 patients for childbirth (793 hospitals). The percentage of admissions classified as uninsured was lower in NFP hospitals than in FP or government hospitals for AMI (4.6% NFP; 6.0% FP; 9.5% government; P < .001), CABG (2.6% NFP; 3.3% FP; 7.0% government; P < .001), and childbirth (3.1% NFP; 4.2% FP; 11.8% government; P < .001). In adjusted analyses, the mean percentage of AMI patients classified as uninsured was similar in NFP and FP hospitals (4.4% vs. 4.3%; P = 0.71), and higher for government hospitals (6.0%; P < .001 for NFP vs. government). Likewise, results demonstrated similar proportions of uninsured patients in NFP and FP hospitals and higher levels of uninsured in government hospitals for both CABG and childbirth. Conclusions For the three conditions studied NFP and FP hospitals appear to provide a similar amount of uncompensated care while government hospitals provide significantly more. Concerns about the amount of uncompensated care provided by NFP hospitals appear warranted.

Objective: To determine long-term outcomes for islet-alone and islet-after-kidney transplantation in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia., Research Design and Methods: This was a prospective interventional and observational cohort study of islet-alone (n = 48) and islet-after-kidney (n = 24) transplant recipients followed for up to 8 years after intraportal infusion of one or more purified human pancreatic islet products under standardized immunosuppression. Outcomes included duration of islet graft survival (stimulated C-peptide ≥0.3 ng/mL), on-target glycemic control (HbA1c <7.0%), freedom from severe hypoglycemia, and insulin independence., Results: Of the 48 islet-alone and 24 islet-after-kidney transplantation recipients, 26 and 8 completed long-term follow-up with islet graft function, 15 and 7 withdrew from follow-up with islet graft function, and 7 and 9 experienced islet graft failure, respectively. Actuarial islet graft survival at median and final follow-up was 84% and 56% for islet-alone and 69% and 49% for islet-after-kidney (P = 0.007) with 77% and 49% of islet-alone and 57% and 35% of islet-after-kidney transplantation recipients maintaining posttransplant HbA1c <7.0% (P = 0.0017); freedom from severe hypoglycemia was maintained at >90% in both cohorts. Insulin independence was achieved by 74% of islet-alone and islet-after-kidney transplantation recipients, with more than one-half maintaining insulin independence during long-term follow-up. Kidney function remained stable during long-term follow-up in both cohorts, and rates of sensitization against HLA were low. Severe adverse events occurred at 0.31 per patient-year for islet-alone and 0.43 per patient-year for islet-after-kidney transplantation., Conclusions: Islet transplantation results in durable islet graft survival permitting achievement of glycemic targets in the absence of severe hypoglycemia for most appropriately indicated recipients having impaired awareness of hypoglycemia, with acceptable safety of added immunosuppression for both islet-alone and islet-after-kidney transplantation., (© 2022 by the American Diabetes Association.)

Purpose: To evaluate the safety and efficacy of N-acetylmannosamine (ManNAc) in GNE myopathy, a genetic muscle disease caused by deficiency of the rate-limiting enzyme in N-acetylneuraminic acid (Neu5Ac) biosynthesis., Methods: We conducted an open-label, phase 2, single-center (NIH, USA) study to evaluate oral ManNAc in 12 patients with GNE myopathy (ClinicalTrials.gov NCT02346461). Primary endpoints were safety and biochemical efficacy as determined by change in plasma Neu5Ac and sarcolemmal sialylation. Clinical efficacy was evaluated using secondary outcome measures as part of study extensions, and a disease progression model (GNE-DPM) was tested as an efficacy analysis method., Results: Most drug-related adverse events were gastrointestinal, and there were no serious adverse events. Increased plasma Neu5Ac (+2,159 nmol/L, p < 0.0001) and sarcolemmal sialylation (p = 0.0090) were observed at day 90 compared to baseline. A slower rate of decline was observed for upper extremity strength (p = 0.0139), lower extremity strength (p = 0.0006), and the Adult Myopathy Assessment Tool (p = 0.0453), compared to natural history. Decreased disease progression was estimated at 12 (γ = 0.61 [95% CI: 0.09, 1.27]) and 18 months (γ = 0.55 [95% CI: 0.12, 1.02]) using the GNE-DPM., Conclusion: ManNAc showed long-term safety, biochemical efficacy consistent with the intended mechanism of action, and preliminary evidence clinical efficacy in patients with GNE myopathy., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

Background: Two-generational trauma-informed assessment (TIA) helps providers conduct holistic family well-being assessment (FWbA). This tool makes it possible to use families' trauma history in the case-finding process., Objective: This study compares the documentation and frequency of adverse childhood experiences (ACEs) and service referral rates for index children and their caretakers in two groups of families evaluated in a child abuse clinic (CAC)., Participants and Setting: The sample consisted of 364 children stratified into two groups: Group 1 - children seen in the CAC after implementation of FWbA in years 2014, 2015, 2016 and Group 2 - children seen in the CAC prior to implementation of FWbA in years 2011, 2012, 2013., Methods: Researchers utilized retrospective chart review method and analyzed data regarding ACEs and service referrals for patients and their caregivers., Results: Documentation of ACEs was higher in Group 1 for children (77.7 % vs 26.6 %,p <  0.0001) and caretakers (60.7 % vs 7.3 % p <  0.0001). Caretakers in Group 1 had a higher rate of four or more ACEs (47.0 % vs 5.1 % p <  0.001) while the increase for children was not statistically significant (61.4 % vs 51.1 %, p =  0.110). Both children and caretakers were referred to more services in Group 1 (2.7 + 1.5 vs 1.5 + 1.3, and 3.0 + 1.9 vs 1.2 + 1.2, respectively, p <  0.0001)., Conclusions: In families evaluated for child abuse and neglect, conducting TIA in addition to conventional psychosocial evaluation increased documentation regarding trauma history, which led to increased referral rates., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: When transplanted human pancreatic islets are exposed to blood during intraportal infusion, an innate immune response is triggered. This instant blood-mediated inflammatory reaction (IBMIR) activates the coagulation and complement cascades and leads to the destruction of 25% of all transplanted islets within minutes, contributing to the need, in most patients, for islets from more than 1 donor. Low molecular dextran sulfate (LMW-DS) has been shown in experimental settings to inhibit IBMIR., Methods: The Clinical Islet Transplantation consortium 01 study was a phase II, multicenter, open label, active control, randomized study. Twenty-four subjects were randomized to peritransplant intraportal and systemic treatment with either LMW-DS or heparin, targeting an activated partial thromboplastin time of 150 ± 10 seconds and 50 ± 5 seconds, respectively. C-peptide response was measured with a mixed meal tolerance test at 75 and 365 days after transplant., Results: Low molecular dextran sulfate was safe and well tolerated with similar observed adverse events (mostly attributed to immunosuppression) as in the heparin arm. There was no difference in the primary endpoint (stimulated C-peptide 75 ± 5 days after the first transplant) between the 2 arms (1.33 ± 1.10 versus 1.56 ± 1.36 ng/mL, P = 0.66). Insulin requirement, metabolic parameters, Clarke and HYPO score, quality of life, and safety were similar between the 2 treatments groups., Conclusions: Even with low dosing, LMW-DS showed similar efficacy in preventing IBMIR to promote islet engraftment when compared to "state-of-the art" treatment with heparin. Furthermore, no substantial differences in the efficacy and safety endpoints were detected, providing important information for future studies with more optimal dosing of LMW-DS for the prevention of IBMIR in islet transplantation.

The standardization of patient evaluation and monitoring methods has a special importance in evaluating the effectiveness of therapeutic methods using drugs or rehabilitative techniques in stroke rehabilitation. The aim of this study was to investigate the relationships between clinical instruments and transcranial magnetic stimulation (TMS)-evoked neurophysiological parameters in stroke patients. This study included 22 chronic post-stroke patients who were clinically assessed using the Motricity Index (MI), finger-tapping test (FTT), Motor Activity Log (MAL) 28, Brunnstrom motor staging and Ashworth Scale (ASH). Motor-evoked potential (MEP) latency and amplitude, resting motor threshold (rMT) and central motor conduction time (CMCT) were measured with TMS. Shorter MEP-latency, shorter CMCT, higher motor-evoked potential amplitude, and diminished rMT exhibited significant correlations with clinical measures evaluating motor stage, dexterity, and daily life functionality. rMT exhibited a negative correlation with hand and lower extremity Brunnstrom stages (r = -0.64, r = -0.51, respectively), MI score (r = -0.48), FTT score (r = -0.69), and also with amount of use scale and quality of movement scale of MAL 28 scores (r = -0.61, r = -0.62, respectively). Higher MEP amplitude and diminished rMT showed positive correlations with reduced ASH score (r = -0.65, r = 0.44, respectively). The TMS-evoked neurophysiologic parameters including MEP latency, amplitude, rMT and CMCT generally have positive correlation with clinical measures which evaluate motor stage, dexterity and daily life functionality. Additionally, spasticity has also remarkable relationships with MEP amplitude and rMT. These results suggest that TMS-evoked neurophysiological parameters were useful measures for monitoring post-stroke patients.

Purpose: Dronabinol (synthetic Δ(9)- tetrahydrocannabinol) is used in patients with nausea and vomiting from chemotherapy and in AIDS patients for appetite stimulation. Recently, dronabinol was used to successfully treat visceral hypersensitivity causing noncardiac chest pain. With widening uses of this medication, we aim to explore its effects on metabolic parameters in long-term dosing and hypothesize that it will not affect major metabolic parameters., Methods: A double-blind, placebo-controlled, 28-day trial was performed with patients 18 to 75 years old without cardiac disease. Patients had at least 2 weekly episodes of chest pain for the last 3 months and evidence of esophageal hypersensitivity after balloon distention testing. Prior use of pain medication, psychiatric diagnosis, or significant medical comorbidities precluded inclusion in the study. Patients were randomized to receive 5 mg dronabinol or placebo twice daily with metabolic parameters examined before and after the use of medication., Findings: Thirteen patients completed the study (7 with dronabinol [6 women and 1 man] and 6 with placebo [5 women and 1 man]). None of the measured values, including body mass index, HDL, triglycerides, calculated LDL, high-sensitivity C-reactive protein, glucose, insulin, leptin, aspartate aminotransferase, alanine aminotransferase, LDH, or non-HDL, differed significantly in either group before or after treatment. In general, treatment with dronabinol coincided with favorable trends in some parameters, although these trends were not statistically significant., Implications: Dronabinol administration does not significantly affect basic metabolic components after a period of 28 days. The implications of these findings are important because dronabinol may be able to be used in patients with metabolic disorders. The favorable trends observed here warrant further exploration into its long-term effects. ClinicalTrials.gov identifier: NCT01598207., (Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.)

Objective: This project explored the impact of staff training on the rates of perinatal maternal and neonatal illicit drug testing., Methods: Controlled, retrospective chart review on 1186 newborn and mother dyads from 2006 (pre-training control group) and on 1861 dyads from 2009 (post-training study group) was completed. Differences between rates of infant and mother drug testing were compared., Results: Increased drug testing rates for the mothers and infants led to increased case finding that tripled both for the mothers (13-3.7%, p < 0.001) and for the infants (0.9-2.9%, p < 0.001). Missed opportunities for newborn testing was reduced by 35 times (20.9-0.6%, p < 0.001)., Conclusion: This retrospective study led to an increase in the number of documented drug-exposed newborns. This research emphasizes the importance of and encourages other hospitals to analyze the efficacy of their current protocol and staff training practices in place to ensure the best child protection services.

Background: Eosinophilic oesophagitis (EoO) has been associated with allergic disorders as well as aeroallergens. The current literature has shown a possible association between seasonal variation, mainly in the spring, and the incidence of EoO. However, this data was based on small population studies that did not exclude proton-pump inhibitor (PPI)-responsive oesophageal eosinophilia (PPI-ROE) in their cohort., Aim: The aim of this study was to determine if there is a seasonal variation associated with the diagnosis of EoO in patients that had been treated with high-dose PPI prior to diagnosis., Methods: Oesophageal biopsies were obtained from a cohort of patients who presented with symptoms of dysphagia, odynophagia, and heartburn during a 10-year period. Symptomatic patients who had biopsies from the mid and distal oesophagus with ≥20 eosinophils per high-power field (hpf) while on high-dose PPI treatment for at least 5 weeks were diagnosed as having EoO. The monthly and seasonal incidences were determined (winter, January-March; spring, April-June; summer, July-September; Autumn, October-December)., Results: A total of 20,718 patients were identified and their records evaluated. From this cohort, 193 (0.93%) symptomatic patients had biopsy-proven oesophageal eosinophilia (≥20 eosinophils/hpf) and no seasonal variation was seen in this group. However, only 57 (0.28%) had been adequately treated with PPI prior to diagnosis (i.e. non-PPI-ROE biopsy-proven EoO; ≥20 eosinophils/hpf: 39 males, 18 females; age 29.5 years). The most common medical history components included asthma (12.3%) and food allergies (3.5%), and the most common presenting symptoms included dysphagia (50.9%) and heartburn (26.3%). The monthly and seasonal incidences in our cohort were with no apparent trend (p = 0.713 and 0.703, respectively)., Conclusions: The incidence of EoO was consistent across all 12 months as well as during the four seasons. Our data does not support a seasonal variation in relation to the incidence of EoO in the US midwestern non-PPI-ROE population.

Objective: To determine staff compliance with the hospital perinatal illicit drug screening-intervention and the prevalence of dyads that are not tested who present with risk factors indicating the need for testing., Methods: This is a retrospective, controlled chart review of mother/newborn dyads presenting to a university hospital for delivery services in 2002 and 2003. Group 1 included all dyads, in which the newborns were tested for illegal drugs after delivery (n = 121). Group 2 included every 25th delivery that did not qualify for Group 1 (n = 107). The documentation rate of demographic characteristics and risk factors were compared., Results: Multiple risk factors were documented in 95.9% of the Group 1 dyads and 32.7% of the Group 2 dyads (p < 0.0001). However, 50 mothers in Group 2 with risk factors, eligible for urine drug testing were not tested. In Group 2, 35.5% of newborns were eligible for drug testing, but were not tested. Twelve infants were not tested when their mothers were tested and two infants were not tested when their mothers tested positive during the study period., Conclusion: The data in the present study revealed the necessity of a staff-training program and the revision of the hospital perinatal illicit drug screening practices- intervention.

Objective: To estimate the incremental costs associated with sepsis as a complication of general surgery, controlling for patient risk factors that may affect costs (eg, surgical complexity and comorbidity) and hospital-level variation in costs., Design: Database analysis., Setting: One hundred eighteen Veterans Health Affairs hospitals., Patients: A total of 13 878 patients undergoing general surgery during fiscal year 2006 (October 1, 2005, through September 30, 2006)., Main Outcome Measures: Incremental costs associated with sepsis as a complication of general surgery (controlling for patient risk factors and hospital-level variation of costs), as well as the increase in costs associated with complications that co-occur with sepsis. Costs were estimated using the Veterans Health Affairs Decision Support System, and patient risk factors and postoperative complications were identified in the Veterans Affairs Surgical Quality Improvement Program database., Results: Overall, 564 of 13 878 patients undergoing general surgery developed postoperative sepsis, for a rate of 4.1%. The average unadjusted cost for patients with no sepsis was $24 923, whereas the average cost for patients with sepsis was 3.6 times higher at $88 747. In risk-adjusted analyses, the relative costs were 2.28 times greater for patients with sepsis relative to patients without sepsis (95% confidence interval, 2.19-2.38), with the difference in risk-adjusted costs estimated at $26 972 (ie, $21 045 vs $48 017). Sepsis often co-occurred with other types of complications, most frequently with failure to wean the patient from mechanical ventilation after 48 hours (36%), postoperative pneumonia (31%), and reintubation for respiratory or cardiac failure (29%). Costs were highest when sepsis occurred with pneumonia or failure to wean the patient from mechanical ventilation after 48 hours., Conclusion: Given the high cost of treating sepsis, a business case can be made for quality improvement initiatives that reduce the likelihood of postoperative sepsis.

Background: Surgical complications contribute substantially to costs. Most important, surgical complications contribute to morbidity and mortality, and some may be preventable. This study estimates costs of specific surgical complications for patients undergoing general surgery in VA hospitals using merged data from the VA Surgical Quality Improvement Program and VA Decision Support System., Methods: Costs associated with 19 potentially preventable complications within 6 broader categories were estimated using generalized, linear mixed regression models to control for patient-level determinants of costs (eg, type of operation, demographics, comorbidity, severity) and hospital-level variation in costs. Costs included costs of the index hospitalization and subsequent 30-day readmissions., Results: In 14,639 patients undergoing general surgical procedures from 10/2005 through 9/2006, 20% of patients developed postoperative surgical complications. The presence of any complication significantly increased unadjusted costs nearly 3-fold ($61,083 vs $22,000), with the largest cost differential attributed to respiratory complications. Patients who developed complications had several markers for greater preoperative severity, including increased age and a lesser presurgery functional health status. After controlling for differences in patient severity, costs for patients with any complication were 1.89 times greater compared to costs for patients with no complications (P < .0001). Within major complication categories, adjusted costs were significantly greater for patients with respiratory, cardiac, central nervous system, urinary, wound, or other complications., Conclusion: Surgical complications contribute markedly to costs of inpatient operations. Investment in quality improvement that decreases the incidence of surgical complications could decrease costs., (Copyright © 2011 Mosby, Inc. All rights reserved.)

This study examines trends in the diffusion of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) during 1993-2004 for patients with acute myocardial infarction in markets with and without Certificate of Need (CON) regulations for open-heart surgery or cardiac catheterization and in markets that repealed CON for either of these procedures. In contrast to prior studies, this study accounts for regional hospital markets that cross state boundaries-often with different CON activities in each state. The overall use of CABG increased modestly throughout the 1990s and subsequently decreased, corresponding to a dramatic increase in PCI. There was a greater rise in the number of CABG programs in markets with significant reduction in CON regulations during 1993-2004 compared with other markets, but CON reduction was not related to growth of PCI programs. Reimbursement, ease of use, clinician endorsement, and technological advances in PCI may outweigh effects of CON.

Objective: Compare characteristics and outcomes of patients hospitalized in specialty cardiac and general hospitals for acute myocardial infarction (AMI) and coronary artery bypass grafting (CABG)., Data: 2000-2005 all-payor administrative data from Arizona, California, Texas, and Wisconsin., Study Design: We identified patients admitted to specialty and competing general hospitals with AMI or CABG and compared patient demographics, comorbidity, and risk-standardized mortality in specialty and general hospitals., Principal Findings: Specialty hospitals admitted a lower proportion of women and blacks and treated patients with less comorbid illness than general hospitals. Unadjusted in-hospital AMI mortality for Medicare enrollees in specialty and general hospitals was 6.1 and 10.1 percent (p<.0001) and for non-Medicare enrollees was 2.8 and 4.0 percent (p<.04). Unadjusted in-hospital CABG mortality for Medicare enrollees in specialty and general hospitals was 3.2 and 4.7 percent (p<.01) and for non-Medicare enrollees was 1.1 and 1.8 percent (p=.02). After adjusting for patient characteristics and hospital volume, risk-standardized in-hospital mortality for all AMI patients was 2.7 percent for specialty hospitals and 4.1 percent for general hospitals (p<.001) and for CABG was 1.5 percent for specialty hospitals and 2.0 percent for general hospitals (p=.07)., Conclusions: In-hospital mortality in specialty hospitals was lower than in general hospitals for AMI but similar for CABG. Our results suggest that specialty hospitals may offer significantly better outcomes for AMI but not CABG.

Background: Racial disparities in coronary revascularization--percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG)--have been extensively documented. However, it is unclear whether disparities are consistent among patients with similar health insurance coverage. Our objective was to assess racial disparities in coronary revascularization among white, black, and Hispanic patients with similar insurance coverage hospitalized with acute myocardial infarction (AMI)., Methods: We used 2000-2005 state inpatient data for 9 states to identify white, black, and Hispanic patients hospitalized with AMI. Patients were grouped into 3 health insurance cohorts: (1) Medicare, (2) private insurance, and (3) Medicaid/uninsured. We examined use of revascularization (PCI or CABG) among blacks and Hispanics as compared to whites in each of the 3 insurance cohorts., Results: The 418 study hospitals admitted 430509 AMI patients with Medicare, 238956 with private insurance, and 74926 patients who were uninsured/Medicaid. In unadjusted analyses, black and Hispanic patients were significantly less likely to receive in-hospital revascularization among the Medicare cohort (38.9% vs 44.9% vs 47.3%, P < .001), privately insured cohort (62.9% vs 69.7% vs 74.2%, P < .001), and uninsured/Medicaid cohort (55.2% vs 61.0% vs 68.4%, P <.001). In Cox models adjusting for patient demographics, comorbidity, and clustering of patients within hospitals, blacks were approximately 25% less likely and Hispanics 5% less likely to receive revascularization as compared to whites with similar insurance., Conclusions: Blacks hospitalized with AMI are significantly less likely to receive revascularization when compared to whites and Hispanics with similar health insurance. Our data suggest that patients' ability to pay for costly procedures is unlikely to explain racial disparities.