Same-day discharge after appendectomy for uncomplicated appendicitis in children: Potential barriers to increased utilization.

BACKGROUND: Utilization of same-day discharge (SDD) after appendectomy for uncomplicated appendicitis (UA) was closely examined to explore potential barriers to greater use of SDD. METHODS: Children (≤18 years) who underwent appendectomy for UA between 2015 and 2019 at a tertiary care children's hospital were reviewed. Associations with SDD were evaluated using multivariable regression models. RESULTS: Among 973 children, SDD was less frequently utilized after appendectomy performed between 12pm and 5pm (aOR 0.14, p < 0.001) and after 5pm (aOR 0.01, p < 0.001) compared to before 12pm. SDD utilization was also less frequent in those from lower resource neighborhoods (adjusted odds ratio [aOR] 0.90 per decile increase in Area Deprivation Index, p = 0.04), females (aOR 0.53, p = 0.005), and patients residing 30-60 min away (aOR 0.56, p = 0.04) compared to <30 min away. CONCLUSIONS: SDD utilization was primarily impacted by operative timing and socioeconomic and travel factors, focuses for quality improvement efforts to further increase utilization of SDD.

Association of Neighborhood Socioeconomic Disadvantage With Complicated Appendicitis in Children.

BACKGROUND: Lower socioeconomic status (SES) is linked to poorer outcomes for a variety of health conditions in children, potentially through delay in accessing care. The objective of this study was to measure the association between SES and delay in surgical care as marked by presentation with complicated appendicitis (CA). METHODS: Children treated for acute appendicitis between 2015-2019 at a large academic children's hospital were reviewed. Patient home addresses were used to calculate travel time to the children's hospital and to determine Area Deprivation Index (ADI), a neighborhood-level SES marker. Multivariable logistic regression models were used to compare the likelihood of CA across ADI while adjusting for confounders. RESULTS: Of 1,697 children with acute appendicitis, 38.8% had CA. Compared to those with uncomplicated disease, children with CA were younger, lived farther from the children's hospital, and were more likely to have Medicaid insurance and have ED visits in the 30 days preceding diagnosis. Children with CA disproportionately came from disadvantaged neighborhoods (P < 0.007), with 32% from the two most disadvantaged ADI deciles. The odds of CA rose 5% per ADI decile-increase (adjusted odds ratio [aOR] 1.05, 95%CI 1.01-1.09, P = 0.02). Younger age and >60-min travel time were also associated with CA. Association between ADI and CA remained among younger (<10 y) children (aOR 1.07, 95%CI 1.00-1.15, P = 0.048) and those living closer (<30 min) to the hospital (aOR 1.06, 95%CI 1.01-1.11, p=0.02). CONCLUSIONS: ADI is associated with CA among children, suggesting ADI may be a valuable marker of difficulty accessing surgical care among disadvantaged children.

Role of Conserved Histidine and Serine in the HCXXXXXRS Motif of Human Dual-Specificity Phosphatase 5.

BACKGROUND: The mitogen-activated protein kinase (MAPK) pathway is functionally generic and critical in maintaining physiological homeostasis and normal tissue development. This pathway is under tight regulation, which is in part mediated by dual-specific phosphatases (DUSPs), which dephosphorylate serine, threonine, and tyrosine residues of the ERK family of proteins. DUSP5 is of high clinical interest because of mutations we identified in this protein in patients with vascular anomalies. Unlike other DUSPs, DUSP5 has unique specificity toward substrate pERK1/2. Using molecular docking and simulation strategies, we previously showed that DUSP5 has two pockets, which are utilized in a specific fashion to facilitate specificity toward catalysis of its substrate pERK1/2. Remarkably, most DUSPs share high similarity in their catalytic sites. Studying the catalytic domain of DUSP5 and identifying amino acid residues that are important for dephosphorylating pERK1/2 could be critical in developing small molecules for therapies targeting DUSP5. RESULTS: In this study, we utilized computational modeling to identify and predict the importance of two conserved amino acid residues, H262 and S270, in the DUSP5 catalytic site. Modeling studies predicted that catalytic activity of DUSP5 would be altered if these critical conserved residues were mutated. We next generated independent Glutathione-S-Transferase (GST)-tagged full-length DUSP5 mutant proteins carrying specific mutations H262F and S270A in the phosphatase domain. Biochemical analysis was performed on these purified proteins, and consistent with our computational prediction, we observed altered enzyme activity kinetic profiles for both mutants with a synthetic small molecule substrate (pNPP) and the physiological relevant substrate (pERK) when compared to wild type GST-DUSP5 protein. CONCLUSION: Our molecular modeling and biochemical studies combined demonstrate that enzymatic activity of phosphatases can be manipulated by mutating specific conserved amino acid residues in the catalytic site (phosphatase domain). This strategy could facilitate generation of small molecules that will serve as agonists/antagonists of DUSP5 activity.

Lymphatic and hematopoietic cancers among benzene-exposed workers.

OBJECTIVE: High benzene exposure is related to acute nonlymphocytic leukemia. Recently, myelodysplastic syndrome has been observed at low benzene exposure levels. METHODS: We updated a mortality study of workers with benzene exposure examining acute nonlymphocytic leukemia and myelodysplastic syndrome. We calculated standardized mortality ratios with 95% confidence intervals and examined latency and trends for cumulative exposure levels. RESULTS: All leukemias (standardized mortality ratio = 1.21; 95% confidence interval = 0.74 to 1.97) and acute non-lymphocytic leukemia (standardized mortality ratio = 1.04; 95% confidence interval = 0.34 to 2.44) were at expected levels. We observed one death from myelodysplastic syndrome (standardized mortality ratio = 6.48; 95% confidence interval = 0.17 to 38.15). We observed no trend for cumulative exposure levels. CONCLUSIONS: Our results for all leukemias are consistent with a small increase in risk observed in the lower-exposed subgroups of the Pliofilm study; however, our results are also consistent with no increased risk especially for acute nonlymphocytic leukemia.

Surveillance for angiosarcoma of the liver among vinyl chloride workers.

OBJECTIVE: We report the results of our angiosarcoma of the liver (ASL) registry to assess the occurrence, the impact of exposures to vinyl chloride, and to quantify latency. METHODS: We examined more than 73,000 death certificates of North American workers employed between 1940 and 2008. RESULTS: We found 13 deaths of ASL among workers with vinyl chloride exposure. All 13 occurred at single plant among workers with high vinyl chloride exposure. The mean latency after first exposure was 36.5 years ranging from 24 to 56 years. No ASL deaths occurred among workers with vinyl chloride exposures after 1974, when exposures were reduced. CONCLUSIONS: We may have seen the last case of ASL among workers exposed to vinyl chloride. Nevertheless, given the long latency of this cancer, continued surveillance seems prudent.

Mindfulness goes to work: impact of an online workplace intervention.

OBJECTIVE: The objective of this study was to determine whether a mindfulness program, created for the workplace, was both practical and efficacious in decreasing employee stress while enhancing resiliency and well-being. METHODS: Participants (89) recruited from The Dow Chemical Company were selected and randomly assigned to an online mindfulness intervention (n = 44) or wait-list control (n = 45). Participants completed the Perceived Stress Scale, the Five Facets of Mindfulness Questionnaire, the Connor-Davidson Resiliency Scale, and the Shirom Vigor Scale at pre- and postintervention and 6-month follow-up. RESULTS: The results indicated that the mindfulness intervention group had significant decreases in perceived stress as well as increased mindfulness, resiliency, and vigor. CONCLUSIONS: This online mindfulness intervention seems to be both practical and effective in decreasing employee stress, while improving resiliency, vigor, and work engagement, thereby enhancing overall employee well-being.

Elimination rates of dioxin congeners in former chlorophenol workers from Midland, Michigan.

BACKGROUND: Exposure reconstructions and risk assessments for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and other dioxins rely on estimates of elimination rates. Limited data are available on elimination rates for congeners other than TCDD. OBJECTIVES: We estimated apparent elimination rates using a simple first-order one-compartment model for selected dioxin congeners based on repeated blood sampling in a previously studied population. METHODS: Blood samples collected from 56 former chlorophenol workers in 2004-2005 and again in 2010 were analyzed for dioxin congeners. We calculated the apparent elimination half-life in each individual for each dioxin congener and examined factors potentially influencing elimination rates and the impact of estimated ongoing background exposures on rate estimates. RESULTS: Mean concentrations of all dioxin congeners in the sampled participants declined between sampling times. Median apparent half-lives of elimination based on changes in estimated mass in the body were generally consistent with previous estimates and ranged from 6.8 years (1,2,3,7,8,9-hexachlorodibenzo-p-dioxin) to 11.6 years (pentachlorodibenzo-p-dioxin), with a composite half-life of 9.3 years for TCDD toxic equivalents. None of the factors examined, including age, smoking status, body mass index or change in body mass index, initial measured concentration, or chloracne diagnosis, was consistently associated with the estimated elimination rates in this population. Inclusion of plausible estimates of ongoing background exposures decreased apparent half-lives by approximately 10%. Available concentration-dependent toxicokinetic models for TCDD underpredicted observed elimination rates for concentrations < 100 ppt. CONCLUSIONS: The estimated elimination rates from this relatively large serial sampling study can inform occupational and environmental exposure and serum evaluations for dioxin compounds.

Mortality rates among workers exposed to dioxins in the manufacture of pentachlorophenol.

OBJECTIVE: We sought to determine if workers exposed to dioxins in pentachlorophenol (PCP) manufacturing were at increased risk of death from specific causes. METHODS: We examined death rates among 773 workers exposed to chlorinated dioxins during PCP manufacturing from 1937 to 1980 using serum dioxin evaluations to estimate exposures to five dioxins. RESULTS: Deaths from all causes combined, all cancers combined, lung cancer, diabetes, and ischemic heart disease were near expected levels. There were eight deaths from non-Hodgkin lymphoma (standardized mortality ratios = 2.4, 95% CI = 1.0 to 4.8). We observed no trend of increasing risk for any cause of death with increasing dioxin exposure. However, the highest rates of non-Hodgkin lymphoma were found in the highest exposure group (standardized mortality ratios = 4.5, 95% CI = 1.2 to 11.5). CONCLUSIONS: Other than possibly an increased risk of non-Hodgkin lymphoma, we find no other cause of death related to the mixture of the dioxin contaminants found in PCP.

Mortality rates among trichlorophenol workers with exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The authors examined 1,615 workers exposed to dioxins in trichlorophenol production in Midland, Michigan, to determine if there were increased mortality rates from exposure. Historical dioxin levels were estimated by a serum survey of workers. Vital status was followed from 1942 to 2003, and cause-specific death rates and trends with exposure were evaluated. All cancers combined (standardized mortality ratio (SMR) = 1.0, 95% confidence interval (CI): 0.8, 1.1), lung cancers (SMR = 0.7, 95% CI: 0.5, 0.9), and nonmalignant respiratory disease (SMR = 0.8, 95% CI: 0.6, 1.0) were at or below expected levels. Observed deaths for leukemia (SMR = 1.9, 95% CI: 1.0, 3.2), non-Hodgkin lymphoma (SMR = 1.3, 95% CI: 0.6, 2.5), diabetes (SMR = 1.1, 95% CI: 0.6, 1.8), and ischemic heart disease (SMR = 1.1, 95% CI: 0.9, 1.2) were slightly greater than expected. No trend was observed with exposure for these causes of death. However, for 4 deaths of soft tissue sarcoma (SMR = 4.1, 95% CI: 1.1, 10.5), the mortality rates increased with exposure. The small number of deaths and the uncertainty in both diagnosis and nosology coding make interpretation of this finding tenuous. With the exception of soft tissue sarcoma, the authors found little evidence of increased disease risk from exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Mortality study update of ethylene oxide workers in chemical manufacturing: a 15 year update.

OBJECTIVE: To investigate the long-term mortality patterns of workers with past exposure to ethylene oxide (EO). METHODS: We redefined and updated a cohort of male workers employed in industrial facilities where EO was produced or used. All 2063 men were employed between 1940 and the end of 1988 and were observed for mortality through 2003. Cause specific Standardized Mortality Ratios were calculated. Internal analyses were made by applying Cox proportional hazards models to the data. RESULTS: No indications were found for excess cancer risks from EO exposures, including the lymphohematopoietic malignancies. There were 11 leukemia deaths and 11.8 expected and 12 non-Hodgkin lymphoma deaths and 11.5 expected. Proportional hazards modeling for all cause, leukemia and lymphoid malignancies mortality revealed no trends or associations with cumulative exposure. CONCLUSION: Despite the relatively high EO exposures in the past and extensive mortality follow-up, the cause specific mortality rates are comparable with those of the general US population. The Standardized Mortality Ratio analyses and the proportional hazards modeling for all cause mortality, leukemia and lymphoid malignancies mortality do not indicate exposure related effects in this cohort.

Respiratory cancer risks among workers with glutaraldehyde exposure.

OBJECTIVE: Glutaraldehyde is a substance that represents a substantial portion of the human exposure to aldehydes in medicine and industry. Other aldehydes such as formaldehyde have been associated with increased cancer rates of the upper respiratory tract and leukemia. Our study is the only one, to our knowledge, to examine cancer rates among exposed glutaraldehyde workers. METHODS: In an extended follow up using death certificates, we calculated standardized mortality ratios (SMRs) and 95% confidence intervals (CIs) for three cumulative exposure categories of glutaraldehyde. There were 99,730 person-years of observation among unexposed workers, 2934 person-years in the lower exposure category, < 0-100.0 parts per billion (ppb)-years, and 2805 person-years in the higher exposure category of 100.0+ ppb-years. RESULTS: For all respiratory cancers for these exposure categories, the SMRs were 0.9 (95% CI = 0.7-1.1), 1.0 (95% CI = 0.2-3.0), and 0.3 (95% CI = 0.0-1.5). No increasing trend of SMR with increasing exposure is observed for any cause of death examined. We observed no cancers of the nasal cavity and sinus (0.03 expected), nasopharynx (0.02 expected), or leukemia (0.6 expected) among all glutaraldehyde-exposed workers. CONCLUSIONS: Although our study findings should be tempered by the small size and the potentially low prevalence of smoking among glutaraldehyde workers, we found no increased rates of respiratory tract cancer or leukemia related to glutaraldehyde exposure.