The hemochromatosis C282Y allele: a risk factor for hepatic veno-occlusive disease after hematopoietic stem cell transplantation.

Hepatic veno-occlusive disease (HVOD) is a serious complication of hematopoietic stem cell transplantation (HSCT). Since the liver is a major site of iron deposition in HFE-associated hemochromatosis, and iron has oxidative toxicity, we hypothesized that HFE genotype might influence the risk of HVOD after myeloablative HSCT. We determined HFE genotypes in 166 HSCT recipients who were evaluated prospectively for HVOD. We also tested whether a common variant of the rate-limiting urea cycle enzyme, carbamyl-phosphate synthetase (CPS), previously observed to protect against HVOD in this cohort, modified the effect of HFE genotype. Risk of HVOD was significantly higher in carriers of at least one C282Y allele (RR=3.7, 95% CI 1.2-12.1) and increased progressively with C282Y allelic dose (RR=1.7, 95% CI 0.4-6.8 in heterozygotes; RR=8.6, 95% CI 1.5-48.5 in homozygotes). The CPS A allele, which encodes a more efficient urea cycle enzyme, reduced the risk of HVOD associated with HFE C282Y. We conclude that HFE C282Y is a risk factor for HVOD and that CPS polymorphisms may counteract its adverse effects. Knowledge of these genotypes and monitoring of iron stores may facilitate risk-stratification and testing of strategies to prevent HVOD, such as iron chelation and pharmacologic support of the urea cycle.

Cost perspectives of laparoscopic and open appendectomy.

BACKGROUND: Despite multiple studies comparing laparoscopic and open appendectomies, the clinically and economically superior procedure still is in question. A cost analysis was performed using both institutional and societal perspectives. METHODS: A decision analytic model was developed to evaluate laparoscopic and open appendectomies. The institutional perspective addressed direct health care costs, whereas the societal perspective addressed direct and indirect health care costs. Baseline values and ranges were taken from randomized controlled trials, meta-analyses, and Medicare databases. RESULTS: From the institutional perspective, open appendectomy is the least expensive strategy, with an expected cost of $5,171, as compared with $6,118 for laparoscopic appendectomy. The laparoscopic approach is less expensive if open appendectomy wound infection rates exceed 23%. From the societal perspective, laparoscopic appendectomy is the least expensive strategy, with an expected cost of $10,400, as compared with $12,055 for open appendectomy. CONCLUSIONS: The decision analysis demonstrated an economic advantage to the hospital of open appendectomy. In contrast, laparoscopic appendectomy represents a better economic choice for the patient.

Improving compliance with breast cancer screening in older women. Results of a randomized controlled trial.

BACKGROUND: To compare three approaches for improving compliance with breast cancer screening in older women. METHODS: Randomized controlled trial using three parallel group practices at a public hospital. Subjects included women aged 65 years and older (n = 803) who were seen by residents (n = 66) attending the ambulatory clinic from October 1, 1989, through March 31, 1990. All provider groups received intensive education in breast cancer screening. The control group received no further intervention. Staff in the second group offered education to patients at their visit. In addition, flowsheets were used in the "Prevention Team" group and staff had their tasks redefined to facilitate compliance. RESULTS: Medical records were reviewed to determine documented offering/receipt of clinical breast examination and mammography. A subgroup of women without previous clinical breast examination (n = 540) and without previous mammography (n = 471) were analyzed to determine the effect of the intervention. During the intervention period, women without a previous clinical breast examination were offered an examination significantly more often in the Prevention Team group than in the control group, adjusting for age, race, and comorbidity and for physicians' gender and training level. The patients in the Prevention Team group were offered clinical breast examination (31.5%) more frequently than those in the patient education or control groups, but this was not significant after adjusting for the above covariates. Likewise, mammography was offered more frequently to patients in the Prevention Team and in the patient education group than to patients in the control group, after adjusting for the factors above using logistic regression. CONCLUSIONS: The results provide support for patient education and organizational changes that involve nonphysician personnel to enhance breast cancer screening among older women, particularly those without previous screening.

Efforts to improve compliance with the National Cholesterol Education Program guidelines. Results of a randomized controlled trial.

STUDY OBJECTIVE: We compared three approaches for improving compliance with the practice guidelines of the National Cholesterol Education Program (NCEP). DESIGN: A randomized controlled trial. SETTING: Academic group practices of a major urban teaching hospital. PARTICIPANTS: Study physicians were three equivalent groups of PG-2 and PG-3 residents (N = 33) seeing patients in equivalent outpatient clinics. Continuity patients of these residents were included (N = 240) if they were younger than 66 years, saw their primary physician during the intervention period, were not pregnant, and had no serious life-shortening noncardiac illnesses. INTERVENTIONS: Three interventions were implemented over a 5-week period. Control group physicians (group 1) were offered only a standard lecture provided through the Physician Cholesterol Education Program (PCEP). Group 2 physicians were offered the PCEP lecture and also received generic chart reminders of the NCEP guidelines on each eligible patient's chart. Group 3 physicians were offered the PCEP lecture and also received timely patient-specific feedback, including acknowledgement of recent lipid values and management, and explicit recommendations for further action. Knowledge of lipid disorders was tested before and after the PCEP lecture, and physicians' attitudes were surveyed following the intervention period. MEASUREMENTS AND MAIN RESULTS: The three groups were similar in baseline (preintervention) compliance with NCEP recommendations (average, 39%) and physicians' knowledge. Patients were similar across groups in number of coronary artery disease risk factors and cholesterol values. Significant within-group improvements in compliance were noted for groups 2 and 3 (7.6% and 10.6%, respectively), but not for group 1 (4.5%). Importantly, there were no differences observed in improvements across groups. In exploratory analyses, however, there was a significant correlation between improved compliance and the number of patients seen by each provider in group 3 that was not observed in groups 1 or 2. Notably, changes in compliance were unrelated to PCEP lecture attendance (8.6% vs 8.1% for attenders vs nonattenders, respectively), level of postgraduate training, baseline or later tests of knowledge, or patient factors. The postintervention survey revealed marked overestimation by physicians of their personal compliance with NCEP guidelines, although there was strong support for clinic efforts that would screen patients for lipid disorders independent of physician initiative. CONCLUSIONS: This study raises questions about the effectiveness of education alone for improving compliance with NCEP guidelines. The effectiveness and efficiency of timely, individualized feedback should be explored in studies over a longer period. Innovative alternative approaches are suggested by the responses to our survey and other research in preventive practices.

Variation in the use of do-not-resuscitate orders in patients with stroke.

OBJECTIVES: To identify sociodemographic and clinical characteristics associated with the use of do-not-resuscitate (DNR) orders in hospitalized patients with stroke. To examine whether the use of DNR orders varies across hospitals. METHODS: This observational cohort study used data collected for 13337 consecutive eligible patients with a primary diagnosis of stroke. These patients were discharged in 1991 through 1994 from 30 hospitals in a large metropolitan area. Study data were abstracted from patients' hospital records using standard forms. Admission severity of illness was measured using a validated multivariable model. Sociodemographic and clinical factors independently associated with the use of DNR orders were identified using stepwise logistic regression. RESULTS: Do-not-resuscitate orders were written for 2898 patients (22%). Patient characteristics independently (P < .01) associated with increased use of DNR orders included increasing age (odds ratio [OR], 1.06 per year); admission from a skilled nursing facility (OR, 2.44) or through the emergency department (OR, 1.49); cancer (OR, 2.73), intracerebral hemorrhage (OR, 2.12), coma (OR, 7.47), or lethargy or stupor on admission neurological assessment (OR, 3.38); and increasing admission severity (OR; 1.29 per decile). In contrast, African American race was associated with lower use of DNR orders (OR, 0.54). Although substantial variation in the use of DNR orders was observed across hospitals, with rates ranging from 12% to 32%, adjusting for the above patient characteristics eliminated much of this variation, including differences between major teaching and other hospitals and between hospitals with and without religious affiliations. CONCLUSIONS: In our community-based analysis of patients with stroke, the use of DNR orders was common and was strongly related to several patient characteristics. These factors explained much of the variation across hospitals. While our analysis did not account for differences in patient preferences for treatment, the differences we observed in the use of DNR orders across sociodemographic groups are suggestive of variations in care and may have important implications for the cost and quality of hospital care.

Improving compliance with immunization in the older adult: results of a randomized cohort study.

OBJECTIVE: To compare three approaches for improving compliance with influenza and pneumococcal vaccination of elderly patients. DESIGN: Randomized controlled trial using three parallel group practices at a public urban teaching hospital. SETTING: Public teaching hospital. SUBJECTS: All patients 65 years of age and older (n = 1202) seen by resident physicians (n = 66) attending three ambulatory medical practices from October 1, 1989 to March 31, 1990. INTERVENTIONS: All three provider groups received intensive education in immunization standards. The control group received no further intervention. Staff in the second group offered education to patients at their visits. In the third group, the prevention team, a flowsheet was used, patient education offered, and staff had their tasks redefined to facilitate compliance; for vaccinations, eg, nurses could vaccinate independent of MD initiative. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed for the 1202 patients seen, including 756 patients seen during both the 1988-89 and 1989-90 influenza seasons, to determine documented offering and receipt of vaccinations. During the intervention period (1989-90), influenza vaccinations were offered significantly more frequently to prevention team patients (68.3%) than to patients in either the patient education (50.4%) or control (47.6%) groups (P = 0.006), even after adjusting for the patients' prior vaccination status, age, gender, race, and high-risk co-morbidity and for physicians' level of training. Likewise, pneumococcal vaccinations were offered more frequently to previously unvaccinated prevention team patients (28.3%) than to patient education (6.5%) or control (5.4%) group patients (P = 0.001), even after adjusting for the factors using multivariate analysis. Compliance rates did not differ between patient education and control subjects for either vaccine. Pre-intervention physician surveys documented higher perceived than actual compliance for both vaccines, with 89.0% and 52.8% of physicians believing that they complied with influenza and pneumococcal vaccination guidelines, respectively. CONCLUSIONS: The results of this trial provide strong support for organizational changes that involve non-physician personnel to enhance vaccination rates among older adults.

Risk factors for postthyroidectomy hypocalcemia.

BACKGROUND: Hypocalcemia is a common sequela of thyroidectomy; however, its causative factors have not been completely delineated. METHODS: A prospective study of 60 patients who underwent unilateral (n = 15) or bilateral (n = 45) thyroidectomy between 1990 and 1993 was completed to determine the incidence and risk factors for hypocalcemia. Free thyroxine, thyrotropin, and alkaline phosphatase levels were obtained before operation in all patients, together with preoperative and postoperative ionized calcium, parathyroid hormone (PTH), calcitonin, and 1,25-dihydroxyvitamin D3 levels. All patients were examined for age, gender, extent of thyroidectomy, initial versus reoperative neck surgery, weight and pathologic characteristics of resected thyroid tissue, substernal thyroid extension, and parathyroid resection and autotransplantation. RESULTS: Hypocalcemia, defined by an ionized calcium level less than 4.5 mg/dl, occurred in 28 patients (47%), including nine (15%) symptomatic patients who required vitamin D and/or calcium for 2 to 6 weeks. In no patient did permanent hypoparathyroidism develop. With a multivariate logistic regression analysis, factors that were predictive of postoperative hypocalcemia included an elevated free thyroxine level (p = 0.003), cancer (p = 0.010), and substernal extension (p = 0.046). CONCLUSIONS: Postoperative decline in parathyroid hormone was not an independent risk factor for hypocalcemia, indicating that other factors besides parathyroid injury, ischemia, or removal are involved in the pathogenesis of postthyroidectomy hypocalcemia. An elevated free thyroxine level, substernal thyroid disease, and carcinoma are risk factors for postthyroidectomy hypocalcemia, and their presence should warrant routine postoperative calcium measurement. In the absence of these risk factors, routine postoperative measurement of serum calcium is unnecessary.

The impact of delirium in the intensive care unit on hospital length of stay.

STUDY OBJECTIVE: To determine the relationship between delirium in the intensive care unit (ICU) and outcomes including length of stay in the hospital. DESIGN: A prospective cohort study. SETTING: The adult medical ICU of a tertiary care, university-based medical center. PARTICIPANTS: The study population consisted of 48 patients admitted to the ICU, 24 of whom received mechanical ventilation. MEASUREMENTS: All patients were evaluated for the development and persistence of delirium on a daily basis by a geriatric or psychiatric specialist with expertise in delirium assessment using the Diagnostic Statistical Manual IV (DSM-IV) criteria of the American Psychiatric Association, the reference standard for delirium ratings. Primary outcomes measured were length of stay in the ICU and hospital. RESULTS: The mean onset of delirium was 2.6 days (S.D.+/-1.7), and the mean duration was 3.4+/-1.9 days. Of the 48 patients, 39 (81.3%) developed delirium, and of these 29 (60.4%) developed the complication while still in the ICU. The duration of delirium was associated with length of stay in the ICU ( r=0.65, P=0.0001) and in the hospital ( r=0.68, P<0.0001). Using multivariate analysis, delirium was the strongest predictor of length of stay in the hospital ( P=0.006) even after adjusting for severity of illness, age, gender, race, and days of benzodiazepine and narcotic drug administration. CONCLUSIONS: In this patient cohort, the majority of patients developed delirium in the ICU, and delirium was the strongest independent determinant of length of stay in the hospital. Further study and monitoring of delirium in the ICU and the risk factors for its development are warranted.

Altered urinary beta 2-microglobulin excretion as an index of nephrotoxicity.

The experimental and clinical evidence indicate that beta 2-microglobulin (beta 2m) is actively reabsorbed from the glomerular filtrate by receptors on the brush border located in the proximal third of the proximal tubule. Increased beta 2m excretion in the absence of increased filtered load of beta 2m is indicative of nephrotoxicity. The data presented show that urine beta 2m increases and creatinine concentrations decrease within four hours of administration of diatrizoate megalumine (DMG). In 9 of the 20 patients, the urinary excretion of beta 2m (U beta 2m) increased to clearly abnormal values. In 12 of the 20 patients, the beta 2m excretion expressed as mg per g creatinine (Cr), increased from normal (less than 0.30) to an abnormal beta 2m excretion rate. The increased beta 2m excretion per g Cr occurring immediately after DMG administration lead us to conclude that this effect occurs when the nephrotoxic agent is present in the kidney. Based on these data we believe that the onset of abnormal urinary beta 2m excretion coincides with the presence of the causative agent. This criterion therefore, should prove to be useful in determining the time to conduct studies designed to search for the causative agent(s) in Balkan endemic nephropathy.

Lens model analysis of hemodynamic status in the critically ill.

The lens model recently has been extended to consider multiple outcomes and sequential use of clinical information. The authors have used this extended model 1) to describe the relationship between clinical information and physicians' assessments of hemodynamic status, 2) to describe the empirical relationship between clinical information and physiologic measures of hemodynamic status, and 3) to compare physicians' use of information with its empirical utility. Physicians prospectively provided estimates of cardiac index and pulmonary capillary wedge pressure for 440 intensive care unit patients prior to right heart catheterization. The correlation between physicians' estimates and measured hemodynamic status was lower than that between clinical information and hemodynamic status (0.42 versus 0.67). Only 7% of physicians' judgement was related to subsequent ancillary testing. Empirically, subsequent ancillary testing contributed 30% to the explanation of hemodynamic status. The lens model describes limitations of physician judgement in estimating left ventricular function and helps explain how patient features relate to measured hemodynamic status.

Hemodynamic assessment in managing the critically ill: is physician confidence warranted?

Prior to right-heart catheterization of 846 patients, 198 study physicians estimated values of pulmonary capillary wedge pressure (WP), cardiac index (Cl), and systemic vascular resistance index (VRI). The physicians also expressed their confidence in these estimates. Actual values of WP, Cl, and VRI as determined by catheterization enabled the authors to evaluate the quality of the physicians' judgments. The discrimination of the judgments was modest; areas under the ROC curves for WP, Cl, and VRI were 0.724, 0.681, and 0.656, respectively. Calculated using clinically relevant cutoff values, sensitivities were 64%, 50%, and 64%, and specificities were 71%, 75%, and 63%, respectively. Calibration of the estimates of WP, Cl, and VRI was also modest; physicians tended to overestimate low values and underestimate high values. Physicians were generally confident of their estimates, but there was no relation between confidence and accuracy. Experienced physicians were no more accurate than less experienced ones, although they were significantly more confident. The authors conclude that physicians should not use their levels of confidence in their subjective estimates of cardiac function in deciding whether to base therapy on these estimates.

The covariance decomposition of the probability score and its use in evaluating prognostic estimates. SUPPORT Investigators.

The probability score (PS) or Brier score has been used in a large number of studies in which physician judgment performance was assessed. However, the covariance decomposition of the PS has not previously been used to evaluate medical judgment. The authors introduce the technique and demonstrate it by analyzing prognostic estimates of three groups: physicians, their patients, and the patients' decision-making surrogates. The major components of the covariance decomposition--bias, slope, and scatter--are displayed in covariance graphs for each of the three groups. The decomposition reveals that whereas the physicians have the best overall estimation performance, their bias and their scatter are not always superior to those of the other two groups. This is primarily due to two factors. First, the physicians' prognostic estimates are pessimistic. Second, the patients place the large majority of their estimates in the most optimistic category, thereby achieving low scatter. The authors suggest that the calculational simplicity of this decomposition, its informativeness, and the intuitive nature of its components make it a useful tool with which to analyze medical judgment.

Participation of nurses in decision making for seriously ill adults.

The purpose of this study is to describe the involvement of nurses in the decision-making process of seriously ill hospitalized adults. Nurses (696) completed interviews with 1,427 patients. Patient, surrogate, and physician interviews were also completed. Patients and surrogates perceive the nurse as more influential in decision making than does the nurse or physician. Many nurses reported having no (31%) or little (36%) knowledge of their patients' preferences, and 53% of the nurses did not advocate for their patients' preferences. Only 50% of the nurses reported educating their patients about the treatment plan chosen or discussing treatment options with their patients, and few (17%) discuss prognosis. This study indicates nurses are not actively involved in the decision-making process of their patients, especially older or more experienced nurses and those working in intensive care units.

Health-related quality of life before and after solid organ transplantation. Measurement consideration, reported outcomes, and future directions.

The initial focus in organ transplantation clinical research was demonstrating acceptable technical and survival outcomes. Both patient and graft survival have reached well-documented, laudable levels, and solid organ (liver, heart, kidney, lung) transplantation procedures are now relatively common. As with any complex medical procedure that entails relatively high risk, financial costs, and life-long follow-up care, reliable and valid assessments of the "quality" of the extended life years are of interest to patients, their families, policy makers, and payers. This review focuses on health-related quality of life (HRQOL) and functional performance in adults following solid organ transplantation, with an emphasis on: 1) instruments and methods; 2) outcomes in liver, heart, kidney, and lung transplant recipients; and 3) future research directions. Practical considerations for developing longitudinal HRQOL assessment strategies are reviewed. The current emphasis on modeling demographic and clinical factors that promote or limit optimal HRQOL is illustrated. These lines of research will help identify potential interventions designed to promote better HRQOL in organ transplant recipients.

Organisational culture: variation across hospitals and connection to patient safety climate.

CONTEXT: Bureaucratic organisational culture is less favourable to quality improvement, whereas organisations with group (teamwork) culture are better aligned for quality improvement. OBJECTIVE: To determine if an organisational group culture shows better alignment with patient safety climate. DESIGN: Cross-sectional administration of questionnaires. Setting 40 Hospital Corporation of America hospitals. PARTICIPANTS: 1406 nurses, ancillary staff, allied staff and physicians. MAIN OUTCOME MEASURES: Competing Values Measure of Organisational Culture, Safety Attitudes Questionnaire (SAQ), Safety Climate Survey (SCSc) and Information and Analysis (IA). RESULTS: The Cronbach alpha was 0.81 for the group culture scale and 0.72 for the hierarchical culture scale. Group culture was positively correlated with SAQ and its subscales (from correlation coefficient r = 0.44 to 0.55, except situational recognition), ScSc (r = 0.47) and IA (r = 0.33). Hierarchical culture was negatively correlated with the SAQ scales, SCSc and IA. Among the 40 hospitals, 37.5% had a hierarchical dominant culture, 37.5% a dominant group culture and 25% a balanced culture. Group culture hospitals had significantly higher safety climate scores than hierarchical culture hospitals. The magnitude of these relationships was not affected after adjusting for provider job type and hospital characteristics. CONCLUSIONS: Hospitals vary in organisational culture, and the type of culture relates to the safety climate within the hospital. In combination with prior studies, these results suggest that a healthcare organisation's culture is a critical factor in the development of its patient safety climate and in the successful implementation of quality improvement initiatives.

The SQUIRE (Standards for QUality Improvement Reporting Excellence) guidelines for quality improvement reporting: explanation and elaboration.

As the science of quality improvement in health care advances, the importance of sharing its accomplishments through the published literature increases. Current reporting of improvement work in health care varies widely in both content and quality. It is against this backdrop that a group of stakeholders from a variety of disciplines has created the Standards for QUality Improvement Reporting Excellence, which we refer to as the SQUIRE publication guidelines or SQUIRE statement. The SQUIRE statement consists of a checklist of 19 items that authors need to consider when writing articles that describe formal studies of quality improvement. Most of the items in the checklist are common to all scientific reporting, but virtually all of them have been modified to reflect the unique nature of medical improvement work. This "Explanation and Elaboration" document (E & E) is a companion to the SQUIRE statement. For each item in the SQUIRE guidelines the E & E document provides one or two examples from the published improvement literature, followed by an analysis of the ways in which the example expresses the intent of the guideline item. As with the E & E documents created to accompany other biomedical publication guidelines, the purpose of the SQUIRE E & E document is to assist authors along the path from completion of a quality improvement project to its publication. The SQUIRE statement itself, this E & E document, and additional information about reporting improvement work can be found at http://www.squire-statement.org.

Relationship between patient complaints and surgical complications.

BACKGROUND: Patient complaints are associated with increased malpractice risk but it is unclear if complaints might be associated with medical complications. The purpose of this study was to determine whether an association exists between patient complaints and surgical complications. METHODS: A retrospective analysis of 16,713 surgical admissions was conducted over a 54 month period at a single academic medical center. Surgical complications were identified using administrative data. The primary outcome measure was unsolicited patient complaints. RESULTS: During the study period 0.9% of surgical admissions were associated with a patient complaint. 19% of admissions associated with a patient complaint included a postoperative complication compared with 12.5% of admissions without a patient complaint (p = 0.01). After adjusting for surgical specialty, co-morbid illnesses and length of stay, admissions with complications had an odds ratio of 1.74 (95% confidence interval 1.01 to 2.98) of being associated with a complaint compared with admissions without complications. CONCLUSIONS: Admissions with surgical complications are more likely to be associated with a complaint than surgical admissions without complications. Further research is necessary to determine if patient complaints might serve as markers for poor clinical outcomes.