B cell subset alteration and the expression of tissue homing molecules in dengue infected patients.

BACKGROUND: B cells play an essential role during dengue viral infection. While a major expansion of antibody secreting cells (ASCs) was observed, the importance of these increased frequencies of ASCs remains unclear. The alteration of B cell subsets may result from the expression of tissue specific homing molecules leading to their mobilization and distribution to different target organs during acute dengue viral infection. METHODS: In this study, whole blood samples were obtained from thirty pediatric dengue-infected patients and ten healthy children and then stained with fluorochrome-conjugated monoclonal antibodies against CD3, CD14, CD19, CD20, CD21, CD27, CD38, CD45, CD138 and homing molecules of interest before analyzed by polychromatic flow cytometry. B cell subsets were characterized throughout acute infection period. RESULTS: Data shows that there were no detectable differences in frequencies of resting, activated and tissue memory cells, whereas the frequency of ASCs was significantly increased and associated with the lower frequency of naïve cells. These results were found from patients with both dengue fever and dengue hemorrhagic fever, suggesting that such change or alteration of B cells was not associated with disease severity. Moreover, several homing molecules (e.g., CXCR3 and CCR2) were found in ASCs, indicating that ASCs may distribute to inflamed tissues and various organs. CONCLUSIONS: Findings from this study provide insight into B cell subset distribution. Furthermore, organ mobilization according to homing molecule expression on different B cell subsets during the course of dengue viral infection also suggests they are distributed to inflamed tissues and various organs.

The danish regions pediatric triage model has a limited ability to detect both critically ill children as well as children to be sent home without treatment - a study of diagnostic accuracy.

BACKGROUND: The Danish Regions Pediatric Triage model (DRPT) was introduced in 2012 and subsequent implemented in most Danish acute pediatric departments. The aim was to evaluate the validity of DRPT as a screening tool to detect both the most serious acute conditions and the non-serious conditions in the acute referred patients in a pediatric department. METHOD: The study was prospective observational, with follow-up on all children with acute referral to pediatric department from October to December 2015. The DRPT was evaluated by comparison to a predefined reference standard and to the actual clinical outcomes: critically ill children and children returned to home without any treatment. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and likelihood for positive and negative test were calculated. RESULTS: Five hundred fifty children were included. The DRPT categorized 7% very urgent, 28% urgent, 29% standard and 36% non-urgent. The DRPT was equal to the reference standard in 31% of the children (CI: 27-35%). DRPT undertriaged 55% of the children (CI: 51-59%) and overtriaged 14% of the children (CI: 11-17%). For the most urgent patients the sensitivity of DRPT was 31% (CI: 20-48%) compared to the reference standard and 20% (CI: 7-41) for critically ill. For children with non-urgent conditions the specificity of DRPT was 66% (CI: 62-71%) compared to the reference standard and 68% (CI: 62-75%) for the children who went home with no treatment. In none of the analyses, the likelihood ratio of the negative test was less than 0.7 and the positive likelihood ratio only reached more than 5 in one of the analyses. DISCUSSION: This study is the first to evaluate the DRPT triage system. From the very limited validity studies of other well-established triage systems, it is difficult to judge whether the DRPT performs better or worse than the alternatives. The DRPT errs to the undertriage side. If the sensitivity is low, a number of the sickest children are undetected and this is a matter of concern. CONCLUSION: The DRPT is a triage tool with limited ability to detect the critically ill children as well as the children who can be returned to home without any treatment. TRIAL REGISTRATION: Not relevant.

Discovery of temporal and disease association patterns in condition-specific hospital utilization rates.

Identifying temporal variation in hospitalization rates may provide insights about disease patterns and thereby inform research, policy, and clinical care. However, the majority of medical conditions have not been studied for their potential seasonal variation. The objective of this study was to apply a data-driven approach to characterize temporal variation in condition-specific hospitalizations. Using a dataset of 34 million inpatient discharges gathered from hospitals in New York State from 2008-2011, we grouped all discharges into 263 clinical conditions based on the principal discharge diagnosis using Clinical Classification Software in order to mitigate the limitation that administrative claims data reflect clinical conditions to varying specificity. After applying Seasonal-Trend Decomposition by LOESS, we estimated the periodicity of the seasonal component using spectral analysis and applied harmonic regression to calculate the amplitude and phase of the condition's seasonal utilization pattern. We also introduced four new indices of temporal variation: mean oscillation width, seasonal coefficient, trend coefficient, and linearity of the trend. Finally, K-means clustering was used to group conditions across these four indices to identify common temporal variation patterns. Of all 263 clinical conditions considered, 164 demonstrated statistically significant seasonality. Notably, we identified conditions for which seasonal variation has not been previously described such as ovarian cancer, tuberculosis, and schizophrenia. Clustering analysis yielded three distinct groups of conditions based on multiple measures of seasonal variation. Our study was limited to New York State and results may not directly apply to other regions with distinct climates and health burden. A substantial proportion of medical conditions, larger than previously described, exhibit seasonal variation in hospital utilization. Moreover, the application of clustering tools yields groups of clinically heterogeneous conditions with similar seasonal phenotypes. Further investigation is necessary to uncover common etiologies underlying these shared seasonal phenotypes.

Stratification of children by medical complexity.

OBJECTIVE: To stratify children using available software, Clinical Risk Groups (CRGs), in a tertiary children's hospital, Seattle Children's Hospital (SCH), and a state's Medicaid claims data, Washington State (WSM), into 3 condition groups: complex chronic disease (C-CD); noncomplex chronic disease (NC-CD), and nonchronic disease (NC). METHODS: A panel of pediatricians developed consensus definitions for children with C-CD, NC-CD, and NC. Using electronic medical record review and expert consensus, a gold standard population of 700 children was identified and placed into 1 the 3 groups: 350 C-CD, 100 NC-CD, and 250 NC. CRGs v1.9 stratified the 700 children into the condition groups using 3 years of WSM and SCH encounter data (2008-2010). WSM data included encounters/claims for all sites of care. SCH data included only inpatient, emergency department, and day surgery claims. RESULTS: A total of 678 of 700 children identified in SCH data were matched in WSM data. CRGs demonstrated good to excellent specificity in correctly classifying all 3 groups in SCH and WSM data; C-CD in SCH (94.3%) and in WSM (91.1%); NC-CD in SCH (88.2%) and in WSM (83.7%); and NC in SCH (84.9%) and in WSM (94.6%). There was good to excellent sensitivity for C-CD in SCH (75.4%) and in WSM (82.1%) and for NC in SCH (98.4%) and in WSM (81.1%). CRGs demonstrated poor sensitivity for NC-CD in SCH (31.0%) and WSM (58.0%). Reasons for poor sensitivity in NC-CD are explored. CONCLUSIONS: CRGs can be used to stratify children receiving care at a tertiary care hospital according to complexity in both hospital and Medicaid administrative data. This method will enhance reporting of health-related outcome data.

The PIRO (predisposition, insult, response, organ dysfunction) model: toward a staging system for acute illness.

Multimodal therapy for diseases like cancer has only become practicable following the development of staging systems like the TNM (tumor, nodes, metastases) system. Staging enables the identification of subgroups of patients with a disease who not only have a differing prognosis, but who are also more likely to benefit from a specific therapeutic modality. Critically ill patients represent a highly heterogeneous population for whom multiple therapeutic options are potentially available, each carrying not only the potential for differential benefit, but also the potential for differential harm. The PIRO system (predisposition, insult, response, organ dysfunction) is a template proposal for a staging system for acute illness that incorporates assessment of pre-morbid baseline susceptibility (predisposition), the specific disorder responsible for acute illness (insult), the response of the host to that insult, and the resulting degree of organ dysfunction. However the creation of a valid, robust, and clinically useful system presents significant challenges arising from the complexity of the disease state, the lack of a clear phenotype, the confounding influence of the effects of therapy and of cultural and socio-economic factors, and the relatively low profile of acute illness with clinicians and the general public. This review summarizes the rationale for such a model of illness stratification and the results of preliminary cohort studies testing the concept. It further proposes two strategies for building a staging system, recognizing that this will be a demanding undertaking that will require decades of work.

Reliability of acute pancreatitis diagnosis coding in a National Patient Register: a validation study in Sweden.

AIM: National patient registers are powerful tools in epidemiological research and healthcare administration. As the level of reliability of diagnoses that are partly based on clinical signs, such as acute pancreatitis, may be low, the reliability of discharge diagnoses in these registers needs to be validated. The main aim of this study was to validate the diagnosis coding for acute pancreatitis in the Swedish National Patient Register. METHOD: We randomly sampled 650 admissions of all patients registered in the Swedish National Patient Register with acute pancreatitis or other nonmalignant pancreatic disorders as the main diagnosis in 2007 and 1998, and as the secondary diagnosis in 2007. The medical records for these admissions were reviewed. We analyzed the concordance between the coding of acute pancreatitis in the Swedish National Patient Register and criteria based on internationally accepted diagnostic standards. RESULTS: We received 603 medical records for manual review. Among the 530 patients with a diagnosis of acute pancreatitis in the Swedish National Patient Register, 442 (83%) were, after review, defined as definitive acute pancreatitis, 80 (15%) as probable acute pancreatitis, and 8 (2%) as no acute pancreatitis. There were no significant differences in the reliability of the diagnosis with regard to sex, age, time period or whether the patient had been treated at a county or university hospital. Among the 73 patients registered with a non-malignant pancreatic disorder other than acute pancreatitis, the number of false-negative cases of acute pancreatitis was 23 (32%). They were mainly found among patients registered with a diagnosis of chronic pancreatitis. CONCLUSION: The Swedish National Patient Register is highly reliable as regards correct coding of acute pancreatitis. However, there seems to be a non-negligible share of false-negative cases of acute pancreatitis among patients registered with a diagnosis of chronic pancreatitis.

Acute health effects associated with exposure to volcanic air pollution (vog) from increased activity at Kilauea Volcano in 2008.

In 2008, the Kilauea Volcano on the island of Hawai'i increased eruption activity and emissions of sulfurous volcanic air pollution called vog. The purpose of this study was to promptly assess for a relative increase in cases of medically diagnosed acute illnesses in an exposed Hawaiian community. Using a within-clinic retrospective cohort design, comparisons were made for visits of acute illnesses during the 14 wk prior to the increased volcanic emissions (low exposure) to 14 wk of high vog exposure when ambient sulfur dioxide was threefold higher and averaged 75 parts per billion volume per day. Logistic regression analysis estimated effect measures between the low- and high-exposure cohorts for age, gender, race, and smoking status. There were statistically significant positive associations between high vog exposure and visits for medically diagnosed cough, headache, acute pharyngitis, and acute airway problems. More than a sixfold increase in odds was estimated for visits with acute airway problems, primarily experienced by young Pacific Islanders. These findings suggest that the elevated volcanic emissions in 2008 were associated with increased morbidity of acute illnesses in age and racial subgroups of the general Hawaiian population. Continued investigation is crucial to fully assess the health impact of this natural source of sulfurous air pollution. Culturally appropriate primary- and secondary-level health prevention initiatives are recommended for populations in Hawai'i and volcanically active areas worldwide.

The successful management of severe protamine-induced pulmonary hypertension using inhaled prostacyclin.

Acute pulmonary hypertension is a severe and life-threatening reaction that rarely occurs secondary to protamine administration. Management of systemic hypotension combined with severe pulmonary hypertension causing right ventricular failure is challenging. We describe a case of acute pulmonary hypertension induced by protamine during elective coronary artery bypass surgery refractory to multiple systemic inotropic and vasopressor therapies. After inhaled prostacyclin administration, our patient's pulmonary artery pressures decreased from 70/37 to 45/23 mm Hg within 10 min. The case highlights a role for inhaled nebulized prostacyclin as a selective pulmonary vasodilator with minimal systemic hypotensive effects.

Early-onset lichenoid graft-vs.-host disease: a unique variant of acute graft-vs.-host disease occurring in peripheral blood stem cell transplant recipients.

BACKGROUND: A complication of stem cell transplantation is chronic graft-vs.-host disease (GvHD), developing months to years after transplant; the two commonest manifestations are lichenoid GvHD and scleroderma. The purpose of this study was to characterize early-onset lichenoid GvHD. METHODS: A retrospective study identified patients diagnosed with early-onset lichenoid GvHD. This diagnosis was correlated with type of transplant and concurrent or prior episodes of acute GvHD. RESULTS: Patients in whom a sex mismatch was present between donor and recipient were included, representing a study population of 17. All received an allogeneic peripheral blood stem cell transplant (PBSCT). All patients had biopsy proven lichenoid GvHD within 60 days or less following transplantation. All had concurrent gastrointestinal symptoms which was biopsy proven GvHD in thirteen of the cases. FISH XY studies revealed that the infiltrating lymphocytes were of donor origin in 12 of the cases, mixed in three and of host origin in two cases. CONCLUSIONS: Early-onset lichenoid GvHD is exclusive to the PBSCT setting and appears to be mediated by donor lymphocytes, reflecting the higher numbers of donor T cells encountered in PBSCT. We consider this reaction pattern a distinctive subtype of acute GvHD.

Acute health problems related to the operation mounted to clean the Hebei Spirit oil spill in Taean, Korea.

The authors investigated acute health problems in people engaged in the operation mounted to clear the Hebei Spirit oil spill which occurred in December 2007 in Taean County, South Korea, and identified the risk factors associated with the development of symptoms. Eight hundred forty-six people engaged in the clean up operation for periods between 7 and 14 days were examined. Demographic information and risk factors were obtained using a questionnaire. Symptoms were classified into six categories: back pain, skin lesions, headache, and eye, neurovestibular, and respiratory symptoms. Residents and volunteers engaged in the Hebei Spirit oil spill clean up operation experienced acute health problems. Risk analyses revealed that more frequent and greater exposure was strongly associated with a higher occurrence of symptoms.

Pathology of graft-versus-host disease in the gastrointestinal tract.

Graft-versus-host disease (GVHD), a common complication of hematopoietic stem cell transplantation, is a clinical syndrome that requires synthesis of clinical, laboratory, and histopathologic findings for diagnosis. The gastrointestinal (GI) tract is commonly affected, and pathologists must recognize subtle morphologic alterations in GI mucosal biopsies to make the diagnosis and to rule out other causes of GI dysfunction such as cytomegalovirus infection and drug effects. This review summarizes the histopathologic features of GVHD in the GI tract and outlines recent recommendations for reporting of GI biopsies with suspected GVHD.

Derivation and internal validation of a rule to predict hospital admission in prehospital patients.

OBJECTIVE: To derive and internally validate a simple prediction rule, using routinely collected prehospital patient data, that discriminates between hospital admission and emergency department (ED) discharge for adult patients who arrive by ambulance. METHODS: We performed a retrospective cohort study of consecutive adult nontrauma patients transported to two separate EDs over two months by a city-run emergency medical services (EMS) system. We tested whether specific prehospital variables could predict hospital admission using chi-square tests, logistic regression, and receiver-operating characteristic curves. We created a rule to predict the probabilities of hospital admission for individual patients. RESULTS: Of 401 patients, the mean age was 47 years; 60% were black and 32% were white; 51% were female; and 33% were admitted to an inpatient service after evaluation in the ED. Independent predictors of admission were dyspnea (adjusted odds ratio [OR] 6.8; awarded 3 points), chest pain (OR 5.2; 3 points), and dizziness, weakness, or syncope (OR 3.5; 2 points). Also predictive were age>or=60 years (OR 5.5; 3 points) and the prehospital identification of a history of diabetes (OR 1.9; 1 point) or cancer (OR 3.9; 2 points). Patients who had a score of 5 or higher had a greater than 69% chance of being admitted to an inpatient unit. CONCLUSION: Routinely collected EMS patient information can help predict hospital admission for certain ED patients.

Impaired expression of peripheral blood apoptotic-related gene transcripts in acute multiple sclerosis relapse.

Differential expression of apoptotic genes may influence the susceptibility of activated lymphocytes to expand and induce acute relapse and persistent inflammation in patients with relapsing-remitting multiple sclerosis (RRMS). The exact relationship between alterations in apoptotic-related gene expression and clinical disease activity has not been broadly evaluated. In this study we studied peripheral blood mononuclear cells (PBMCs) expression of pro- and antiapoptotic genes in RRMS patients during acute relapse in comparison to patients in remission. Using cDNA Affymetrix microarrays platform (U133A2 microarrays) we analyzed the gene expression profile of PBMC derived from 22 RRMS patients in acute relapse (15 females, mean age 34.6 +/- 1.8 years, disease duration 5.6 +/- 0.8 years) in comparison to 20 sex- and age-matched RRMS patients in remission. One thousand five hundred seventy-eight gene transcripts significantly differentiated acute multiple sclerosis (MS) relapse from remission. This characteristic gene expression signature was enriched by an apoptotic-related pathway. The 1578 gene transcripts that significantly differentiated acute relapse from remission were enriched by 55 apoptotic-related genes in that reflected different operating pathways during the acute phase of the disease. These genes mainly involved the caspase-dependent pathway and included overexpression of the negative regulator of FAS-induced apoptosis (TOSO) and the BCL2 antiapoptotic family members (BCL2, BCL2 AA) as well as downexpression of proapoptotic genes like BAX, apoptotic protease-activating factor 1 (APAF1) and caspases 1, 2, 8, 9. and 10. An additional group of antiapoptotic genes related to T cell receptor-mediated apoptosis was also found to be overexpressed in acute relapse and included TCR-binding CD3E antigen, antiapoptotic serine threonin kinase (AKT), and NF kappa B-associated genes like reticuloendotheliosis viral oncogene homolog A (RELA) and human T cell leukemia virus type I-binding protein (Tax1BP) known to inhibit tumor necrosis factor (TNF)-induced apoptosis. Our findings demonstrate impaired apoptotic mechanisms in peripheral lymphocytes from RRMS patients during acute relapse. This suggests that the inflammatory process in active disease is targeted by inhibition of proapoptotic and repression of antiapoptotic genes that allow prolonged abnormal immune responses.

A revised classification scheme for acute transfusion reactions.

BACKGROUND: Although the standard classification system for acute transfusion reactions adequately describes the general features associated with the various types of reactions, it was not designed to provide strict criteria for diagnosis and classification. Consequently, its use to classify individual reactions can result in significant inter- and intraobserver variability, which can complicate patient management and clinical research. STUDY DESIGN AND METHODS: A total of 595 transfusion reactions that occurred at a single institution between January 1, 1996, and December 31, 2003, were reviewed and were initially classified according to the established conventions of the AABB. Each reaction was then reclassified with a revised system that refines and clarifies reaction categories, adds severity grades in the format of the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), and includes terminology to indicate the attribution or likelihood that the adverse event is related to the transfusion. RESULTS: Comparison of the two approaches as applied to these 595 transfusion reactions showed clear advantages for the revised system. Of 128 reactions classified by AABB criteria as inconclusive, a mixture of reaction types, or otherwise qualified, all but 5 were accommodated by discrete categories within our revised scheme. In each case with a classifiable reaction, the severity of the reaction could be readily graded. CONCLUSION: The advantages of this revised classification scheme for acute transfusion reactions warrant prospective evaluation and ultimately consideration of its incorporation into clinical practice.

Association between health information, use of protective devices and occurrence of acute health problems in the Prestige oil spill clean-up in Asturias and Cantabria (Spain): a cross-sectional study.

BACKGROUND: This paper examines the association between use of protective devices, frequency of acute health problems and health-protection information received by participants engaged in the Prestige oil spill clean-up in Asturias and Cantabria, Spain. METHODS: We studied 133 seamen, 135 bird cleaners, 266 volunteers and 265 paid workers selected by random sampling, stratified by type of worker and number of working days. Information was collected by telephone interview conducted in June 2003. The association of interest was summarized, using odds ratios (OR) obtained from logistic regression. RESULTS: Health-protection briefing was associated with use of protective devices and clothing. Uninformed subjects registered a significant excess risk of itchy eyes (OR:2.89; 95%CI:1.21-6.90), nausea/vomiting/dizziness (OR:2.25; 95%CI:1.17-4.32) and throat and respiratory problems (OR:2.30; 95%CI:1.15-4.61). There was a noteworthy significant excess risk of headaches (OR:3.86: 95%CI:1.74-8.54) and respiratory problems (OR:2.43; 95%CI:1.02-5.79) among uninformed paid workers. Seamen, the group most exposed to the fuel-oil, were the worst informed and registered the highest frequency of toxicological problems. CONCLUSION: Proper health-protection briefing was associated with greater use of protective devices and lower frequency of health problems. Among seamen, however, the results indicate poorer dissemination of information and the need of specific guidelines for removing fuel-oil at sea.

Setting national priorities for quality assessment of health care services in Korea.

OBJECTIVE: To identify target services and determine national priorities among those services identified for a national quality assessment program of the Health Insurance Review Agency (HIRA) in Korea. DESIGN: Target services were identified from published sources addressing quality problems, various quality-monitoring programs in other countries, suggestions from 26 medical specialty associations in Korea, and frequently reported consumer claims. Three steps were involved in the prioritization decision: (i) development of a set of priority criteria; (ii) expert panel survey to evaluate the extent to which individual services satisfy each of the priority criteria and to calculate mean priority ratings for individual services; and (iii) formation of four levels of priority groups-top, high-middle, middle, and low-according to the allocated priority ratings. RESULTS: Five priority criteria were selected: "burden of the condition", "seriousness of the quality problem", "interest and demand of society", "acceptability", and "the feasibility of quality assessment". Among the 57 services identified as targets for the national quality assessment program, 10 were selected as having a top priority for quality assessment because of their high feasibility rating. These are: cardiac surgery; cataract surgery; tonsillectomy; appendectomy; tooth extraction; usage of albumin/globulin products; treatments for hypertension, pneumonia, and acute upper respiratory infection; and services provided by clinical laboratory centers. CONCLUSION: The priority services identified from the studies will assist the HIRA in selecting target services and implementing the national assessment program.