276 research outputs found
Tales from the EMR: Does a 21st-Century Data Warehouse Facilitate Clinical Research for Pancreatic Cancer?
Background: The importance of an electronic medical record has been highlighted for both clinical care and research. In the current era, data warehouses and repositories have been established to serve the dual function of patient care and investigation.
Purpose: The aim of this study was to compare a newly developed institutional clinical data warehouse, linked with the hospital information system (HIS), to a prospectively-maintained departmental database.
Methods: A novel HIS-linked institutional clinical data warehouse was queried for 9 primary and secondary ICD-9-CM discharge diagnosis codes for pancreatic cancer. The database captured inpatient and outpatient clinical and billing information from a pool of over 2 million patients evaluated at an academic medical institution and its affiliates since 1995. A cohort was identified; following Institutional Review Board approval, demographic and clinical data was obtained. This data was compared to a manually-entered and prospectively-maintained surgical oncology database of the same institution, tracking 394 patients since 1999. Duplicated patients, and those unique to either dataset, were flagged. Patients with diagnosis dates prior to 1999 were excluded to allow comparison over the same time period. For validation purposes, a 10% random sample of remaining patients unique to each dataset underwent manual review of medical records including clinic notes, admission/discharge notes, diagnostic imaging, and pathology reports.
Results: 1107 patients were identified from the HIS-linked dataset with pancreatic neoplasm-associated diagnosis codes dating from 1999 to 2009. Of these, 254 (22.9%) were captured in both datasets, while 853 (77.1%) were only in the HIS-linked dataset. Manual review of the 10% subset of the HIS-only group demonstrated that 55.6% of patients were without identifiable pancreatic pathology, suggesting miscoding, while 31.7% had diagnoses consistent with pancreatic neoplasm, and 12.7% had pseudocyst or pancreatitis. Of the 394 patients tracked by surgical oncology, 254 (64.5%) were captured in both datasets, while 140 (35.5%) had not been captured in the HIS-linked dataset. Manual review of the 10% subset of the non-captured patients demonstrated 93.3% with pancreatic neoplasm and 6.7% with pseudocyst or pancreatitis. Lastly, a review of the 10% subset of the 254 patient overlap demonstrated that 87.5% of patients were with pancreatic neoplasm, 8.3% with pseudocyst or pancreatitis, and 4.2% without pancreatic pathology.
Conclusions: While technological advances provide a powerful means to automate institutional-level cohort identification and data collection, a high degree of misclassification may be present if queries are based solely on ICD-9-CM discharge codes. For that reason, careful validation and data cleaning are critical steps prior to research use. These results also suggest cautious interpretation of national-level administrative data utilizing ICD-9-CM diagnosis codes. Our findings suggest that the current state-of-the-art data warehouses continue to require clinical correlation and validation through traditional retrospective mechanisms
Foregut Surgery in the Modern Era: A National Survey
Background: Foregut surgery is technically complex. In recent years, increasing attention has been paid to high-stakes surgery outcomes, including mortality and complications. In addition, the use of advanced technology including minimally invasive approaches has been introduced. The current study aims to determine national trends in utilization and outcomes of potentially curative cancer resections of the foregut, including esophagus, stomach, liver, and pancreas.
Methods: The Nationwide Inpatient Sample was queried to identify all esophageal, gastric, liver and pancreas resections performed for cancer during 1998-2009. Annual incidence, major in-hospital postoperative complications, length of stay and in-hospital mortality were evaluated. Univariate and multivariate analysis performed by chi square and logistic regression. For all comparisons, p-values
Results: 298,871 patients (nationally-weighted) underwent cancer directed foregut surgery 1998-2009. Of those 19,002 (6%) were esophagectomies, 123,198 (41%) were gastrectomies, 62,313 (21%) were hepatectomies and 94,358 (32%) were pancreatectomies. From early years (1998-2000) to late years (2007-2009) use of laparoscopy in foregut surgery increased from 3% to 5%. Laparoscopy in esophagectomy increased the most from 1% to 5%, while its use in hepatectomy remained unchanged at 4%. Gastrectomy and pancreatectomy involving minimally invasive techniques increased from 2% to 5% and 5% to 6%, respectively. For all four foregut surgery types, patient comorbidities increased over time; patients with ≥2 major comorbidities increased from 53% to 64%. Conversely, patient mortality and length of stay (LOS) decreased over time. However, we observed an increase in complications for all sites combined from 22.8% to 24.4%. Laparoscopy was not significantly associated with decreased complications, but was associated with lower mortality when compared to open resection alone 3.1% vs. 5%. Independent predictors of increased complications included older age, gender, higher comorbidity, hospital volume. Older age, male sex, higher comorbidity, low volume center and non-use of laparoscopy were independent predictors of in-hospital mortality.
Conclusion: Foregut surgery in the modern era is being increasingly deployed on sicker patients. While decreased in-hospital mortality and LOS are commendable, complication rates remain substantial and nondecreasing. Minimally invasive techniques have minor but increasing penetrance in foregut surgery. Our results suggest comparable advances and potential pitfalls among major types of foregut surgery in the current era
Endemic Gallbladder Cancer: Is There a Role for Prophylactic Cholecystectomy?
Background: Gallbladder cancer (GBC) is an often lethal malignancy with variable distribution. Incidence in the United States is low. However, in areas of Central/South America, Central Europe, Japan, and the Indian subcontinent, GBC is a major cause of cancer death. Cholecystectomy is safe and commonly performed worldwide. Thus, prophylactic cholecystectomy (PCCY) has been proposed in regions with endemic GBC. We developed a simple decision model to assist caregivers in determining the optimal strategy for managing GBC based on local incidence and technological capabilities.
Methods: Rates of disease and outcomes were derived from a review of the literature. Using TreeAge-Pro software, a decision model was created to simulate expected health outcomes for populations with high GBC incidence, following 3 treatment strategies: no early intervention, one-time screening ultrasound (US), or PCCY. Lifetime cancer-specific survival was the outcome of interest. Sensitivity analyses were performed to determine threshold values.
Results: Based on our model, populations where lifetime risk of GBC exceeds 0.4% may benefit from early intervention by US or PCCY. Two-way sensitivity analysis shows that over a relatively narrow range of disease incidence, US may be favored if sensitivity exceeds 50%. In many cases where lifetime risk exceeds 1%, PCCY may improve survival.
Conclusions: GBC varies in incidence, but affects many individuals in some populations in the Americas. The lethality of GBC may justify aggressive public health intervention including screening or prophylactic cholecystectomy. Decision analysis models using best-available evidence may help determine the optimal treatment of individuals at risk for GBC
Is pancreatic cancer palliatable? A national study
Background: Pancreatic cancer is frequently diagnosed at advanced stages where potentially curative resection is no longer possible. Palliative procedures can be performed; however, results on a national level are unknown. This study examines pancreatic cancer patients who underwent potentially palliative procedures including gastric bypass, biliary bypass surgery, celiac block, biliary stent, gastrostomy or jejunostomy, and examines post-intervention complications and 30-day mortality.
Methods: SEER-Medicare 1991-2005 was used to identify patients with Stage 3-4 pancreatic cancer. Complication rates were calculated including post-op infection, myocardial infarction, aspiration pneumonia, DVT/PE, pulmonary compromise, gastric bleed, acute renal failure, and reoperation. Kaplan-Meier survival analysis was performed. Finally, Cox proportional hazards modeling was used to control for the effects of age, sex, race, stage, and resection.
Results: Of 22,314 pancreatic cancer patients, 858 (3.9%) patients were Stage 3, and 11,149 (50.0%) stage 4. Post-procedure median survival for all patients is approximately two months, with longest survival for biliary bypass patients (3.2mo, 95% CI(2.9-3.7), and lowest survival for jejunostomy 1.3 mo (1.2-1.5) and gastrostomy 1.5 mo (1.4-1.8). Post-procedure 30-day mortality was highest for gastrostomy patients at 41.5%; followed by jejunostomy (39.1%), celiac plexus block (30.0%), gastric bypass (23.8%), biliary bypass (17.8%), and biliary stent (21.2%). The rate of complications averaged 40%, with highest rate for gastrostomy (47.4%) and gastric bypass (45.3%) and lowest for celiac plexus block (29.3%). Stage 4 disease was an independent predictor of death for patients undergoing five out of six procedures.
Conclusion: We found that morbidity and mortality of palliative procedures in unresectable pancreatic cancer is high, especially in stage 4 patients. Further studies need to be conducted to identify patients who will have sufficient expected post-procedure survival to benefit from these palliative interventions
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Pathological Margin Clearance and Survival After Pancreaticoduodenectomy in a US and European Pancreatic Center
Background: The optimal definition of a margin-negative resection and its exact prognostic significance on survival in resected pancreatic adenocarcinoma remains unknown. This study was designed to assess the relationship between pathological margin clearance, margin type, and survival. Methods: Patients who underwent pancreaticoduodenectomy with curative intent at two academic institutions, in Amsterdam, the Netherlands, and Boston, Massachusetts, between 2000 and 2014 were retrospectively evaluated. Overall survival, recurrence rates, and progression-free survival (PFS) were assessed by Kaplan–Meier estimates and multivariate Cox proportional hazards analysis, according to pathological margin clearance and type of margin involved. Results: Of 531 patients identified, the median PFS was 12.9, 15.4, and 24.1 months, and the median overall survival was 17.4, 22.9, and 27.7 months for margin clearances of 0, < 1, and ≥1 mm, respectively (all log-rank p < 0.001). On multivariate analysis, patients with a margin clearance of ≥1 mm demonstrated a survival advantage relative to those with 0 mm clearance [hazard ratio (HR) 0.71, p < 0.01], whereas survival was comparable for patients with a margin clearance of < 1 mm versus 0 mm (HR: 0.93, p = 0.60). Patients with involvement (0 or < 1 mm margin clearance) of the SMV/PV margin demonstrated prolonged median overall survival (25.7 months) relative to those with SMA involvement (17.5 months). Conclusions: In patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma, a margin clearance of ≥1 mm correlates with improved survival relative to < 1 mm clearance and may be a more accurate predictor of a complete margin-negative resection in pancreatic cancer. The type of margin involved also appears to impact survival. Electronic supplementary material The online version of this article (10.1245/s10434-018-6467-9) contains supplementary material, which is available to authorized users
Staphylococcus aureus Panton-Valentine Leukocidin Contributes to Inflammation and Muscle Tissue Injury
Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) threatens public health worldwide, and epidemiologic data suggest that the Panton-Valentine Leukocidin (PVL) expressed by most CA-MRSA strains could contribute to severe human infections, particularly in young and immunocompetent hosts. PVL is proposed to induce cytolysis or apoptosis of phagocytes. However, recent comparisons of isogenic CA-MRSA strains with or without PVL have revealed no differences in human PMN cytolytic activity. Furthermore, many of the mouse studies performed to date have failed to demonstrate a virulence role for PVL, thereby provoking the question: does PVL have a mechanistic role in human infection? In this report, we evaluated the contribution of PVL to severe skin and soft tissue infection. We generated PVL mutants in CA-MRSA strains isolated from patients with necrotizing fasciitis and used these tools to evaluate the pathogenic role of PVL in vivo. In a model of necrotizing soft tissue infection, we found PVL caused significant damage of muscle but not the skin. Muscle injury was linked to induction of pro-inflammatory chemokines KC, MIP-2, and RANTES, and recruitment of neutrophils. Tissue damage was most prominent in young mice and in those strains of mice that more effectively cleared S. aureus, and was not significant in older mice and mouse strains that had a more limited immune response to the pathogen. PVL mediated injury could be blocked by pretreatment with anti-PVL antibodies. Our data provide new insights into CA-MRSA pathogenesis, epidemiology and therapeutics. PVL could contribute to the increased incidence of myositis in CA-MRSA infection, and the toxin could mediate tissue injury by mechanisms other than direct killing of phagocytes
The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations
Insect bite hypersensitivity (IBH) is a chronic allergic dermatitis common in horses. Affected horses mainly react against antigens present in the saliva from the biting midges, Culicoides ssp, and occasionally black flies, Simulium ssp. Because of this insect dependency, the disease is clearly seasonal and prevalence varies between geographical locations. For two distinct horse breeds, we genotyped four microsatellite markers positioned within the MHC class II region and sequenced the highly polymorphic exons two from DRA and DRB3, respectively. Initially, 94 IBH-affected and 93 unaffected Swedish born Icelandic horses were tested for genetic association. These horses had previously been genotyped on the Illumina Equine SNP50 BeadChip, which made it possible to ensure that our study did not suffer from the effects of stratification. The second population consisted of 106 unaffected and 80 IBH-affected Exmoor ponies. We show that variants in the MHC class II region are associated with disease susceptibility (praw = 2.34 × 10−5), with the same allele (COR112:274) associated in two separate populations. In addition, we combined microsatellite and sequencing data in order to investigate the pattern of homozygosity and show that homozygosity across the entire MHC class II region is associated with a higher risk of developing IBH (p = 0.0013). To our knowledge this is the first time in any atopic dermatitis suffering species, including man, where the same risk allele has been identified in two distinct populations
Facile whole mitochondrial genome resequencing from nipple aspirate fluid using MitoChip v2.0
<p>Abstract</p> <p>Background</p> <p>Mutations in the mitochondrial genome (mtgenome) have been associated with many disorders, including breast cancer. Nipple aspirate fluid (NAF) from symptomatic women could potentially serve as a minimally invasive sample for breast cancer screening by detecting somatic mutations in this biofluid. This study is aimed at 1) demonstrating the feasibility of NAF recovery from symptomatic women, 2) examining the feasibility of sequencing the entire mitochondrial genome from NAF samples, 3) cross validation of the Human mitochondrial resequencing array 2.0 (MCv2), and 4) assessing the somatic mtDNA mutation rate in benign breast diseases as a potential tool for monitoring early somatic mutations associated with breast cancer.</p> <p>Methods</p> <p>NAF and blood were obtained from women with symptomatic benign breast conditions, and we successfully assessed the mutation load in the entire mitochondrial genome of 19 of these women. DNA extracts from NAF were sequenced using the mitochondrial resequencing array MCv2 and by capillary electrophoresis (CE) methods as a quality comparison. Sequencing was performed independently at two institutions and the results compared. The germline mtDNA sequence determined using DNA isolated from the patient's blood (control) was compared to the mutations present in cellular mtDNA recovered from patient's NAF.</p> <p>Results</p> <p>From the cohort of 28 women recruited for this study, NAF was successfully recovered from 23 participants (82%). Twenty two (96%) of the women produced fluids from both breasts. Twenty NAF samples and corresponding blood were chosen for this study. Except for one NAF sample, the whole mtgenome was successfully amplified using a single primer pair, or three pairs of overlapping primers. Comparison of MCv2 data from the two institutions demonstrates 99.200% concordance. Moreover, MCv2 data was 99.999% identical to CE sequencing, indicating that MCv2 is a reliable method to rapidly sequence the entire mtgenome. Four NAF samples contained somatic mutations.</p> <p>Conclusion</p> <p>We have demonstrated that NAF is a suitable material for mtDNA sequence analysis using the rapid and reliable MCv2. Somatic mtDNA mutations present in NAF of women with benign breast diseases could potentially be used as risk factors for progression to breast cancer, but this will require a much larger study with clinical follow up.</p
Development of a core set of outcome measures for OAB treatment
© 2017, The Author(s). Introduction and hypothesis: Standardized measures enable the comparison of outcomes across providers and treatments giving valuable information for improving care quality and efficacy. The aim of this project was to define a minimum standard set of outcome measures and case-mix factors for evaluating the care of patients with overactive bladder (OAB). Methods: The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group (WG) of leading clinicians and patients to engage in a structured method for developing a core outcome set. Consensus was determined by a modified Delphi process, and discussions were supported by both literature review and patient input. Results: The standard set measures outcomes of care for adults seeking treatment for OAB, excluding residents of long-term care facilities. The WG focused on treatment outcomes identified as most important key outcome domains to patients: symptom burden and bother, physical functioning, emotional health, impact of symptoms and treatment on quality of life, and success of treatment. Demographic information and case-mix factors that may affect these outcomes were also included. Conclusions: The standardized outcome set for evaluating clinical care is appropriate for use by all health providers caring for patients with OAB, regardless of specialty or geographic location, and provides key data for quality improvement activities and research
sodC-Based Real-Time PCR for Detection of Neisseria meningitidis
Real-time PCR (rt-PCR) is a widely used molecular method for detection of
Neisseria meningitidis (Nm). Several rt-PCR assays for Nm
target the capsule transport gene, ctrA. However, over
16% of meningococcal carriage isolates lack ctrA,
rendering this target gene ineffective at identification of this sub-population
of meningococcal isolates. The Cu-Zn superoxide dismutase gene,
sodC, is found in Nm but not in other
Neisseria species. To better identify Nm, regardless of
capsule genotype or expression status, a sodC-based TaqMan
rt-PCR assay was developed and validated. Standard curves revealed an average
lower limit of detection of 73 genomes per reaction at cycle threshold
(Ct) value of 35, with 100% average reaction efficiency
and an average R2 of 0.9925. 99.7% (624/626) of Nm isolates
tested were sodC-positive, with a range of average
Ct values from 13.0 to 29.5. The mean sodC
Ct value of these Nm isolates was 17.6±2.2 (±SD).
Of the 626 Nm tested, 178 were nongroupable (NG) ctrA-negative
Nm isolates, and 98.9% (176/178) of these were detected by
sodC rt-PCR. The assay was 100% specific, with all
244 non-Nm isolates testing negative. Of 157 clinical specimens tested,
sodC detected 25/157 Nm or 4 additional specimens compared
to ctrA and 24 more than culture. Among 582 carriage specimens,
sodC detected Nm in 1 more than ctrA and
in 4 more than culture. This sodC rt-PCR assay is a highly
sensitive and specific method for detection of Nm, especially in carriage
studies where many meningococcal isolates lack capsule genes
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