Search PubMed⌕ Search

Biomedical subjects

E J Thomas

Publications and source records attributed to E J Thomas.

At least 37 records · Page 2Linked to original sources
PubMed2000

Incidence and types of adverse events and negligent care in Utah and Colorado.

BACKGROUND: The ongoing debate on the incidence and types of iatrogenic injuries in American hospitals has been informed primarily by the Harvard Medical Practice Study, which analyzed hospitalizations in New York in 1984. The generalizability of these findings is unknown and has been questioned by other studies. OBJECTIVE: We used methods similar to the Harvard Medical Practice Study to estimate the incidence and types of adverse events and negligent adverse events in Utah and Colorado in 1992. DESIGN AND SUBJECTS: We selected a representative sample of hospitals from Utah and Colorado and then randomly sampled 15,000 nonpsychiatric 1992 discharges. Each record was screened by a trained nurse-reviewer for 1 of 18 criteria associated with adverse events. If > or =1 criteria were present, the record was reviewed by a trained physician to determine whether an adverse event or negligent adverse event occurred and to classify the type of adverse event. MEASURES: The measures were adverse events and negligent adverse events. RESULTS: Adverse events occurred in 2.9+/-0.2% (mean+/-SD) of hospitalizations in each state. In Utah, 32.6+/-4% of adverse events were due to negligence; in Colorado, 27.4+/-2.4%. Death occurred in 6.6+/-1.2% of adverse events and 8.8+/-2.5% of negligent adverse events. Operative adverse events comprised 44.9% of all adverse events; 16.9% were negligent, and 16.6% resulted in permanent disability. Adverse drug events were the leading cause of nonoperative adverse events (19.3% of all adverse events; 35.1% were negligent, and 9.7% caused permanent disability). Most adverse events were attributed to surgeons (46.1%, 22.3% negligent) and internists (23.2%, 44.9% negligent). CONCLUSIONS: The incidence and types of adverse events in Utah and Colorado in 1992 were similar to those in New York State in 1984. Iatrogenic injury continues to be a significant public health problem. Improving systems of surgical care and drug delivery could substantially reduce the burden of iatrogenic injury.

Adolescent↗
PubMed2000

Hospital ownership and preventable adverse events.

OBJECTIVE: To determine if type of hospital ownership is associated with preventable adverse events. DESIGN: Medical record review of a random sample of 15,000 nonpsychiatric, non-Veterans Administration hospital discharges in Utah and Colorado in 1992. MEASUREMENTS AND MAIN RESULTS: A two-stage record review process using nurse and physician reviewers was used to detect adverse events. Preventability was then judged by 2 study investigators who were blinded to hospital characteristics. The association among preventable adverse events and hospital ownership was evaluated using logistic regression with nonprofit hospitals as the reference group while controlling for other patient and hospital characteristics. We analyzed 4 hospital ownership categories: nonprofit, for-profit, major teaching government (e.g., county or state ownership), and minor or nonteaching government. RESULTS: When compared with patients in nonprofit hospitals, multivariate analyses adjusting for other patient and hospital characteristics found that patients in minor or nonteaching government hospitals were more likely to suffer a preventable adverse event of any type (odds ratio [OR] 2.46; 95% confidence interval [CI], 1.45 to 4.20); preventable operative adverse events (OR, 4.85; 95% CI, 2.44 to 9.62); and preventable adverse events due to delayed diagnoses and therapies (OR, 4.27; 95% CI, 1.48 to 12.31). Patients in for-profit hospitals were also more likely to suffer preventable adverse events of any type (OR, 1.57; 95% CI, 1.03 to 2.38); preventable operative adverse events (OR, 2.63; 95% CI, 1.42 to 4.87); and preventable adverse events due to delayed diagnoses and therapies (OR, 4.15; 95% CI, 1. 84 to 9.34). Patients in major teaching government hospitals were less likely to suffer preventable adverse drug events (OR, 0.38; 95% CI, 0.16 to 0.89). CONCLUSIONS: Patients in for-profit and minor teaching or nonteaching government-owned hospitals were more likely to suffer several types of preventable adverse events. Further research is needed to determine how these events could be prevented.

Colorado↗
PubMed2000

Expression of nucleotide-regulated Cl(-) currents in CF and normal mouse tracheal epithelial cell lines.

The dominant route for Cl(-) secretion in mouse tracheal epithelium is via Cl(-) channels different from the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), the channel that is defective in CF. It has been proposed that the use of purinergic agonists to activate these alternative channels in human airways may be beneficial in CF. In the present study, two conditionally immortal epithelial cell lines were established from the tracheae of mice possessing the tsA58 T antigen gene, one of which [MTE18-(-/-)] was homozygous for a knockout of CFTR and the other [MTE7b-(+/-)] heterozygous for CFTR expression. In Ussing chamber studies, amiloride (10(-4) M) and a cocktail of cAMP-activating agents (forskolin, IBMX, and dibutyryl cAMP) resulted in small changes in the short-circuit current (I(sc)) and resistance of both cell lines, with larger increases in I(sc) being elicited by ionomycin (10(-6) M). Both cell lines expressed P(2)Y(2) receptors and responded to the purinergic agonists ATP, UTP, and 5'-adenylylimidodiphosphate (10(-4) M) with an increase in I(sc). This response could be inhibited by DIDS and was abolished in the presence of Cl(-)-free Ringer solution. Reducing the mucosal Cl(-) concentration increased the response to UTP of both cell lines, with a significantly greater increase in MTE18-(-/-) cells. Pretreatment of these cells with thapsigargin caused a direct increase in I(sc) and inhibited the response to UTP. These data suggest that both cell lines express purinergic-regulated Cl(-) currents and may prove valuable tools in studying the properties of this pathway.

Amiloride↗
PubMed2000

Evidence that endometriosis behaves in a malignant manner.

It is well known that certain aspects of endometriosis are similar to those of malignant disease. For example, like cancer, endometriosis can be both locally and distantly metastatic; it attaches to other tissues, invades, and damages them. Endometriosis is a common disease that does not create a cachectic or catabolic state, and is rarely fatal. There are, however, numerous reported cases of malignancy arising from endometriotic deposits and substantial histologic evidence that endometriosis is associated with endometrioid carcinoma and clear cell carcinoma of the ovary. A large review article by Mostoufizadeh and Scully investigated the association between endometriosis and endometrioid carcinoma, noting that women who had both diseases tended to be younger [1]. They found no association between endometriosis and serous or mucinous carcinoma of the ovary, and reported that malignant transformation of endometriosis was rare and associated with the use of exogenous estrogens. An epidemiological study of Swedish women reported a higher incidence of breast and ovarian cancer and non-Hodgkin's lymphoma in women with endometriosis compared with controls [2]. Vercellini and colleagues also reported a higher incidence of endometrioid and clear cell carcinoma in women with endometriosis compared with controls [3]. Mutations in genes associated with galactose metabolism have been identified as one possible mechanism for this association. These mutations are more common in ovarian cancer and have been reported to be more common in women with endometriosis. We compared 78 women with endometriosis with 248 controls and were unable to demonstrate an increased frequency of these mutations in any of these groups.

Animals↗
PubMed2000

Molecular genetic defects in endometriosis.

In a series of studies, we have hypothesised that endometriotic proliferation is, in part, precipitated by mutations in oncogenes or deletions in tumor suppressor genes that have been shown to be important steps in the transformation from a benign to a malignant epithelium. We reported previously that we could find no mutations in the TP53 and RASK genes in cases of endometriosis. However, having shown that endometriotic deposits were monoclonal, we showed loss of heterozygosity on chromosomes 9p (18%), 11q (18%), and 22q (15%) - in total 28% of endometriotic lesions showed loss of heterozygosity at one or more sites [1]. We could not demonstrate any loss of heterozygosity in normal endometrium. We examined adjacent endometriosis, atypical endometriosis, and endometrioid carcinoma of the ovary and showed common genetic alterations that are consistent with a common lineage. These common alterations were not seen in lesions that were distant from each other [2]. In endometrioid tumors, we reported an increased frequency of mutations in the PTEN/MMAC tumor suppressor genes that was not seen in clear cell or serous carcinoma, suggesting distinct developmental pathways for these tumors [3].

Carcinoma, Endometrioid↗
PubMed2000

Hospital ownership and preventable adverse events.

To determine whether hospital ownership was associated with preventable adverse events, the authors reviewed the medical records of a random sample of 15,000 hospitalizations in Utah and Colorado in 1992. Hospitals were categorized as nonprofit, for-profit, major teaching government (e.g., county, state ownership), and minor or nonteaching government. Multivariate analyses adjusting for other patient and hospital characteristics found that, when compared with patients in nonprofit hospitals, patients in minor or nonteaching government hospitals were more likely to suffer a preventable adverse event of any type (odds ratio (OR), 2.46; 95 percent confidence interval (95% CI), 1.45 to 4.20); preventable operative adverse events (OR, 4.85; 95% CI, 2.44 to 9.62); and preventable adverse events due to delayed diagnoses and therapies (OR, 4.27; 95% CI, 1.48 to 12.31). Patients in for-profit hospitals were also more likely to suffer preventable adverse events of any type (OR, 1.57; 95% CI, 1.03 to 2.38); preventable operative adverse events (OR, 2.63; 95% CI, 1.42 to 4.87); and preventable adverse events due to delayed diagnoses and therapies (OR, 4.15; 95% CI, 1.84 to 9.34). Patients in major teaching government hospitals were less likely to suffer preventable adverse drug events (OR, 0.38; 95% CI, 0.16 to 0.89).

Adolescent↗
PubMed1999

Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery.

BACKGROUND: Cardiac complications are important causes of morbidity after noncardiac surgery. The purpose of this prospective cohort study was to develop and validate an index for risk of cardiac complications. METHODS AND RESULTS: We studied 4315 patients aged > or = 50 years undergoing elective major noncardiac procedures in a tertiary-care teaching hospital. The main outcome measures were major cardiac complications. Major cardiac complications occurred in 56 (2%) of 2893 patients assigned to the derivation cohort. Six independent predictors of complications were identified and included in a Revised Cardiac Risk Index: high-risk type of surgery, history of ischemic heart disease, history of congestive heart failure, history of cerebrovascular disease, preoperative treatment with insulin, and preoperative serum creatinine >2.0 mg/dL. Rates of major cardiac complication with 0, 1, 2, or > or = 3 of these factors were 0.5%, 1.3%, 4%, and 9%, respectively, in the derivation cohort and 0.4%, 0.9%, 7%, and 11%, respectively, among 1422 patients in the validation cohort. Receiver operating characteristic curve analysis in the validation cohort indicated that the diagnostic performance of the Revised Cardiac Risk Index was superior to other published risk-prediction indexes. CONCLUSIONS: In stable patients undergoing nonurgent major noncardiac surgery, this index can identify patients at higher risk for complications. This index may be useful for identification of candidates for further risk stratification with noninvasive technologies or other management strategies, as well as low-risk patients in whom additional evaluation is unlikely to be helpful.

Aged↗
PubMed1999

The clinician's view of endometriosis.

Clinicians have a number of unmet needs regarding the diagnosis and management of endometriosis. The fulfilment of these would result in better advice for patients.

Endometriosis↗
PubMed1999

The incidence and nature of surgical adverse events in Colorado and Utah in 1992.

BACKGROUND: Despite more than three decades of research on iatrogenesis, surgical adverse events have not been subjected to detailed study to identify their characteristics. This information could be invaluable, however, for guiding quality assurance and research efforts aimed at reducing the occurrence of surgical adverse events. Thus we conducted a retrospective chart review of 15,000 randomly selected admissions to Colorado and Utah hospitals during 1992 to identify and analyze these events. METHODS: We selected a representative sample of hospitals from Utah and Colorado and then randomly sampled 15,000 nonpsychiatric discharges from 1992. With use of a 2-stage record-review process modeled on previous adverse event studies, we estimated the incidence, morbidity, and preventability of surgical adverse events that caused death, disability at the time of discharge, or prolonged hospital stay. We characterized their distribution by type of injury and by physician specialty and determined incidence rates by procedure. RESULTS: Adverse events were no more likely in surgical care than in nonsurgical care. Nonetheless, 66% of all adverse events were surgical, and the annual incidence among hospitalized patients who underwent an operation or child delivery was 3.0% (confidence interval 2.7% to 3.4%). Among surgical adverse events 54% (confidence interval 48.9% to 58.9%) were preventable. We identified 12 common operations with significantly elevated adverse event incidence rates that ranged from 4.4% for hysterectomy (confidence interval 2.9% to 6.8%) to 18.9% for abdominal aortic aneurysm repair (confidence interval 8.3% to 37.5%). Eight operations also carried a significantly higher risk of a preventable adverse event: lower extremity bypass graft (11.0%), abdominal aortic aneurysm repair (8.1%), colon resection (5.9%), coronary artery bypass graft/cardiac valve surgery (4.7%), transurethral resection of the prostate or of a bladder tumor (3.9%), cholecystectomy (3.0%), hysterectomy (2.8%), and appendectomy (1.5%). Among all surgical adverse events, 5.6% (confidence interval 3.7% to 8.3%) resulted in death, accounting for 12.2% (confidence interval 6.9% to 21.4%) of all hospital deaths in Utah and Colorado. Technique-related complications, wound infections, and postoperative bleeding produced nearly half of all surgical adverse events. CONCLUSION: These findings provide direction for research to identify the causes of surgical adverse events and for targeted quality improvement efforts.

Adult↗
PubMed1999

Costs of medical injuries in Utah and Colorado.

Patient injuries are thought to have a substantial financial impact on the health care system, but recent studies have been limited to estimating the costs of adverse drug events in teaching hospitals. This analysis estimated the costs of all types of patient injuries from a representative sample of hospitals in Utah and Colorado. We detected 459 adverse events (of which 265 were preventable) by reviewing the medical records of 14,732 randomly selected 1992 discharges from 28 hospitals. The total costs (all results are discounted 1996 dollars) were $661,889,000 for adverse events, and $308,382,000 for preventable adverse events. Health care costs totaled $348,081,000 for all adverse events and $159,245,000 for the preventable adverse events. Fifty-seven percent of the adverse event health care costs, and 46% of the preventable adverse event costs were attributed to outpatient medical care. Surgical complications, adverse drug events, and delayed or incorrect diagnoses and therapies were the most expensive types of adverse events. The costs of adverse events were similar to the national costs of caring for people with HIV/AIDS, and totaled 4.8% of per capita health care expenditures in these states.

Colorado↗
PubMed1998

Absorptive apical amiloride-sensitive Na+ conductance in human endometrial epithelium.

1. Human endometrial epithelial cells cultured on porous tissue culture supports formed tight, polarized epithelial monolayers with features characteristic of tight epithelia. Endometrial epithelial layers generated significant transepithelial electrical resistance (750 Omega cm2) and potential difference (15.3 mV), with an inward short-circuit current (Isc; 20.5 microA cm-2). 2. The Isc was linearly proportional to the external Na+ concentration and was abolished in the absence of Na+. The Isc was sensitive to apical amiloride. Net 22Na+ flux was in the absorptive apical to basolateral direction and fully accounted for the inward Isc. In addition, apical to basolateral and net 22Na+ transport were reduced in the presence of amiloride. 3. The Isc was also sensitive to addition of ouabain and Ba2+ to the basal solution, consistent with a role for basolateral Na+-K+-ATPase and K+ channels in generation of the current. 4. These data demonstrate that human endometrial epithelial cells in primary culture produce tight, functional monolayers on permeable supports. We provide the first evidence that human endometrial epithelial cells have an inward Isc accounted for by an amiloride-sensitive Na+ conductance. The Na+-absorptive function of the endometrium may provide an appropriate environment for sperm function and embryo growth.

Absorption↗
PubMed1998

Mutation of galactose-1-phosphate uridyl transferase and its association with ovarian cancer and endometriosis.

Impaired galactose metabolism has been proposed as a risk factor for ovarian cancer and endometriosis, which is a putative precursor of endometrioid and clear cell histological sub-types of ovarian cancer. The prevalence of the most common galactose-I-phosphate uridyl transferase gene mutations, Q188R and N314D, was assessed in 206 women with ovarian cancer, 78 women with endometriosis and 248 controls. No Q188R mutations were found in any of the groups. A statistically significant increase in the frequency of N314D mutations was observed in women with serous and undifferentiated histological sub-types of ovarian cancer, but not mucinous, endometrioid or clear cell sub-types. There were no significant differences observed in the N314D mutation frequency between women with endometriosis (18%) and controls (17%). Our results support previous reports of an association of impaired galactose metabolism with serous and undifferentiated ovarian cancers but contradict previous findings of increased N314D mutation frequencies among women with endometriosis and endometrioid and clear cell sub-types ovarian cancer.

Adult↗
PubMed1998

Frequent PTEN/MMAC mutations in endometrioid but not serous or mucinous epithelial ovarian tumors.

Epithelial ovarian cancer comprises three major histological subtypes (serous, mucinous, and endometrioid), and it is becoming clear that the developmental pathways for these subtypes are fundamentally different. In particular, endometrioid ovarian cancers probably arise by the malignant transformation of ectopic endometrial implants called endometriosis and not the ovarian surface epithelium. The PTEN/MMAC gene on chromosome 10q23 is a tumor suppressor implicated in the pathogenesis of a wide variety of malignancies, but to date, somatic mutations in PTEN have not been identified in studies of predominantly serous ovarian cancers. In endometrial cancers, PTEN mutations are very common in tumors of the endometrioid type but have rarely been found in serous types, and we hypothesized that a similar histological subtype bias might be occurring in ovarian cancer. We have analyzed 81 ovarian tumors, including 34 endometrioid, 29 serous, 10 mucinous, and 8 clear cell tumors, for loss of heterozygosity (LOH) on 10q23 and for mutations in all 9 coding exons of PTEN. LOH was common among the endometrioid (43%) and serous (28%) tumors but was infrequent among the other histological subtypes. Somatic PTEN mutations were detected in seven (21%) of the endometrioid tumors, and in all informative cases, the mutation was accompanied by loss of the wild-type allele. One mucinous tumor without 10q23 LOH was shown to harbor two somatic PTEN mutations. In this tumor, the histological appearance of the mucinous areas was atypical, and the mucinous areas contained foci of endometrioid differentiation. The majority of tumors with PTEN mutations were grade 1 and/or stage 1, suggesting that inactivation of PTEN is an early event in ovarian tumorigenesis. No PTEN mutations were found among the serous or clear cell tumors. The identification of frequent somatic PTEN mutations in endometrioid ovarian tumors indicates that it plays a significant role in the etiology of this subtype. The absence of mutations in other histological subtypes is consistent with the hypothesis that epithelial ovarian cancers arise through distinct developmental pathways.

Adenocarcinoma, Clear Cell↗