Evaluation of the accuracy of enzymatically determined carrier status for Krabbe disease by DNA-based testing.
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Biomedical subjects
Publications and source records attributed to A Duff.
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BACKGROUND: The impact of anesthetic choice on postoperative mortality and morbidity has not been determined with certainty. METHODS: The authors evaluated the effect of type of anesthesia on postoperative mortality and morbidity in a retrospective cohort study of consecutive hip fracture patients, aged 60 yr or older, who underwent surgical repair at 20 US hospitals between 1983 and 1993. The primary outcome was defined as death within 30 days of the operative procedure. The secondary outcomes were postoperative 7-day mortality, postoperative myocardial infarction, postoperative pneumonia, postoperative congestive heart failure, and postoperative change in mental status. Numerous comorbid conditions were controlled for individually and by several comorbidity indices using logistic regression. RESULTS: General anesthesia was used in 6,206 patients (65.8%) and regional anesthesia in 3,219 patients (3,078 spinal anesthesia and 141 epidural anesthesia). The 30-day mortality rate in the general anesthesia group was 4.4%, compared with 5.4% in the regional anesthesia group (unadjusted odds ratio = 0.80; 95% confidence interval = 0.66-0.97). However, the adjusted odds ratio for general anesthesia increased to 1.08 (0.84-1.38). The adjusted odds ratios for general anesthesia versus regional anesthesia for the 7-day mortality was 0.90 (0.59-1.39) and for postoperative morbidity outcomes were as follows: myocardial infarction: adjusted odds ratio = 1.17 (0.80-1.70); congestive heart failure: adjusted odds ratio = 1.04 (0.80-1.36); pneumonia: adjusted odds ratio = 1.21 (0.87-1.68); postoperative change in mental status: adjusted odds ratio = 1.08 (0.95-1.22). CONCLUSIONS: The authors were unable to demonstrate that regional anesthesia was associated with better outcome than was general anesthesia in this large observational study of elderly patients with hip fracture. These results suggest that the type of anesthesia used should depend on factors other than any associated risks of mortality or morbidity.
Placebo analgesia was produced by conditioning trials wherein heat induced experimental pain was surreptitiously reduced in order to test psychological factors of expectancy and desire for pain reduction as possible mediators of placebo analgesia. The magnitudes of placebo effects were assessed after these conditioning trials and during trials wherein stimulus intensities were reestablished to original baseline levels. In addition, analyses were made of the influence of these psychological factors on concurrently assessed pain and remembered pain intensities. Statistically reliable placebo effects on sensory and affective measures of pain were graded according to the extent of surreptitious lowering of stimulus strength during the manipulation trials, consistent with conditioning. However, all of these effects were strongly associated with expectancy but not desire for relief. These results show that although conditioning may be sufficient for placebo analgesia, it is likely to be mediated by expectancy. The results further demonstrated that placebo effects based on remembered pain were 3 to 4 times greater than those based on concurrently assessed placebo effects, primarily because baseline pain was remembered as being much more intense than it actually was. However, similar to concurrent placebo effects, remembered placebo effects were strongly associated with expected pain levels that occurred just after conditioning. Taken together, these results suggest that magnitudes of placebo effect are dependent on multiple factors, including conditioning, expectancy, and whether analgesia is assessed concurrently or retrospectively.
BACKGROUND: The relationship between allogeneic blood transfusion and bacterial infection remains uncertain. An increased risk of bacterial infection would represent the most important risk of allogeneic transfusion, because viral disease transmission has become so rare. STUDY DESIGN AND METHODS: A retrospective cohort study of 9598 consecutive hip fracture patients at least 60 years old who underwent surgical repair was performed. The primary outcome was serious bacterial infection, defined as bacteremia, pneumonia, deep wound infection, or septic arthritis or osteomyelitis. Secondary outcomes included two individual infections, pneumonia and urinary tract infection (UTI), and the cost of infection. Hospital cost of infection was assessed by linking the study population to Medicare data. RESULTS: Fifty-eight percent of patients received at least one transfusion. Serious bacterial infection occurred in 437 patients (4.6%); 28.8 percent of this group died during the hospital stay. Pneumonia occurred in 361 patients (3.8%) and UTI occurred in 1157 patients (12.1%). The adjusted risk of serious bacterial infection associated with transfusion was 1.35 (95% CI, 1.10-1.66). The adjusted risk for pneumonia was 1.52 (95% CI, 1.21-1.91), and that for UTI was 1.03 (95% CI, 0.91-1.17). A dose-response relationship was present for serious bacterial infection (p = 0.001) and pneumonia (p = 0.001). The cost of hospitalization was $14,000 greater for patients with serious infection than for patients without infection. CONCLUSION: Blood transfusion is associated with a 35-percent greater risk of serious bacterial infection and a 52-percent greater risk of pneumonia. Postoperative infections are costly. The risk of bacterial infection may be the most common life-threatening adverse effect of allogeneic blood transfusion.
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CONTEXT: The risks of blood transfusion have been studied extensively but the benefits and the hemoglobin concentration at which patients should receive a transfusion have not. OBJECTIVE: To determine the effect of perioperative transfusion on 30- and 90-day postoperative mortality. DESIGN: Retrospective cohort study. SETTING: A total of 20 US hospitals between 1983 and 1993. PARTICIPANTS: A total of 8787 consecutive hip fracture patients, aged 60 years or older, who underwent surgical repair. MAIN OUTCOME MEASURES: Primary outcome was 30-day postoperative mortality; secondary outcome was 90-day postoperative mortality. The "trigger" hemoglobin level was defined as the lowest hemoglobin level prior to the first transfusion during the time period or, for patients in the nontranfused group, as the lowest hemoglobin level during the time period. RESULTS: Overall 30-day mortality was 4.6% (n=402; 95% confidence interval [CI], 4.1%-5.0%); overall 90-day mortality was 9.0% (n=788; 95% CI, 8.4%-9.6%). A total of 42% of patients (n=3699) received a postoperative transfusion. Among patients with trigger hemoglobin levels between 80 and 100 g/L (8.0 and 10.0 g/dL), 55.6% received a transfusion, while 90.5% of patients with hemoglobin levels less than 80 g/L (8.0 g/dL) received postoperative transfusions. Postoperative transfusion did not influence 30- or 90-day mortality after adjusting for trigger hemoglobin level, cardiovascular disease, and other risk factors for death: for 30-day mortality, the adjusted odds ratio (OR) was 0.96 (95% CI, 0.74-1.26); for 90-day mortality, the adjusted hazard ratio was 1.08 (95% CI, 0.90-1.29). Similarly, 30-day mortality after surgery did not differ between those who received a preoperative transfusion and those who did not (adjusted OR, 1.23; 95% CI, 0.81-1.89). CONCLUSIONS: Perioperative transfusion in patients with hemoglobin levels 80 g/L (8.0 g/dL) or higher did not appear to influence the risk of 30- or 90-day mortality in this elderly population. At hemoglobin concentrations of less than 80 g/L (8.0 g/dL), 90.5% of patients received a transfusion, precluding further analysis of the association of transfusion and mortality.
PURPOSE: Utilization report cards are commonly used to assess hospitals. However, in practice, they rarely account for differences in patient populations among hospitals. Our study questions were: (1) How does transfusion utilization for hip fracture patients vary among hospitals? (2) What patient characteristics are associated with transfusion and how do those characteristics vary among hospitals? (3) Is the apparent pattern of variation of utilization among hospitals altered by controlling for these patient characteristics? SUBJECTS AND METHODS: We included consecutive hip fracture patients aged 60 years or older who underwent surgical repair between 1982 and 1993 in 19 hospitals from four states, excluding those who refused blood transfusion, had multiple trauma, metastatic cancer, multiple myeloma, an above the knee amputation, or were paraplegic or quadriplegic. The outcome of interest was postoperative blood transfusion. "Trigger hemoglobin" was the lowest hemoglobin recorded before transfusion or recorded at any time during the week before or after surgery for patients who were not transfused. RESULTS: There was considerable variation in transfusion among hospitals postoperatively (range 31.2% to 54.0%, P = 0.001). Trigger hemoglobin also varied considerably among hospitals. In unadjusted analyses, four of nine teaching and two of nine nonteaching hospitals had postoperative transfusion rates significantly higher than the reference (teaching) hospital, while one nonteaching hospital had a lower rate. In an analysis controlling for trigger hemoglobin and multiple clinical variables, one of nine teaching and four of nine nonteaching hospitals had rates higher than the reference hospital, while four teaching hospitals and one nonteaching hospital had lower rates. CONCLUSIONS: The apparent pattern of variation of transfusion among hospitals varies according to how one adjusts for relevant patient characteristics. Utilization report cards that fail to adjust for these characteristics may be misleading.
BACKGROUND: The indications for transfusion have never been evaluated in an adequately sized clinical trial. A pilot study was conducted to plan larger clinical trials. STUDY DESIGN AND METHODS: Hip fracture patients undergoing surgical repair who had postoperative hemoglobin levels less than 10 g per dL were randomly assigned to receive 1) symptomatic transfusion: that is, transfusion for symptoms of anemia or for a hemoglobin level that dropped below 8 g per dL or 2) threshold transfusion: that is, patients receive 1 unit of packed RBCs at the time of random assignment and as much blood as necessary to keep the hemoglobin level above 10 g per dL. Outcomes were 60-day mortality, morbidity, functional status, and place of residence. RESULTS: Among 84 eligible patients enrolled, mean (+/- SD) prerandomization hemoglobin was 9.1 (+/- 0.6) g/ dL. The median number of units transfused in the threshold transfusion group was 2 (interquartile range, = 1-2), and that in the symptomatic transfusion group was 0 (6; interquartile range, = 0-2) (p < 0.001). Mean hemoglobin levels were approximately 1 g per dL higher in the threshold group than in the symptomatic group: for example, on Day 2, 10.3 (+/- 0.9) g per dL versus 9.3 (+/- 1.2) g per dL, respectively (p < 0.001). At 60 days, death or inability to walk across the room without assistance occurred in 16 (39.0%) of the symptomatic transfusion group and 19 (45.2%) of the threshold transfusion group. Death occurred by 60 days in 5 (11.9%) of the symptomatic transfusion group and 2 (4.8%) in the threshold transfusion group (relative risk = 2.5; 95% CI, 0.5-12.2). Other outcomes were similar for the two groups. CONCLUSIONS: Symptomatic transfusion may be an effective blood-sparing protocol associated with the transfusion of appreciably fewer units of RBCs and lower mean hemoglobin levels than are associated with the threshold transfusion policy. However, it is unknown whether these two clinical strategies have comparable mortality, morbidity, or functional status. A definitive trial is needed.
BACKGROUND: Guidelines have been offered on haemoglobin thresholds for blood transfusion in surgical patients. However, good evidence is lacking on the haemoglobin concentrations at which the risk of death or serious morbidity begins to rise and at which transfusion is indicated. METHODS: A retrospective cohort study was performed in 1958 patients, 18 years and older, who underwent surgery and declined blood transfusion for religious reasons. The primary outcome was 30-day mortality and the secondary outcome was 30-day mortality or in-hospital 30-day morbidity. Cardiovascular disease was defined as a history of angina, myocardial infarction, congestive heart failure, or peripheral vascular disease. FINDINGS: The 30-day mortality was 3.2% (95% CI 2.4-4.0). The mortality was 1.3% (0.8-2.0) in patients with preoperative haemoglobin 12 g/dL or greater and 33.3% (18.6-51.0) in patients with preoperative haemoglobin less than 6 g/dL. The increase in risk of death associated with low preoperative haemoglobin was more pronounced in patients with cardiovascular disease than in patients without (interaction p < 0.03). The effect of blood loss on mortality was larger in patients with low preoperative haemoglobin than in those with a higher preoperative haemoglobin (interaction p < 0.001). The results were similar in analyses of postoperative haemoglobin and 30-day mortality or in-hospital morbidity. INTERPRETATION: A low preoperative haemoglobin or a substantial operative blood loss increases the risk of death or serious morbidity more in patients with cardiovascular disease than in those without. Decisions about transfusion should take account of cardiovascular status and operative blood loss as well as the haemoglobin concentration.
Reported in this paper is a single-case experimental design study on the behaviour of a 32-year-old schizophrenic female inpatient, presenting with maladaptive behaviours necessitating care in a medium secure environment. A baseline of her observed behaviour on the unit was taken. The information gathered was used to assist in deciding the differential effects of psychosis vs. behavioural manipulation on her presentation and to assist in planning her immediate and future management/treatment. Situational factors portrayed as likely indicators of maladaptive behaviours proved difficult to influence, owing to the nature of the subject's environment. Cognitions and learnt behaviours were targeted. Recent research indicates that for some schizophrenics cognitive-behavioural treatment of hallucinations/delusions using a focusing strategy is effective in reducing the symptoms' frequency. Frequency of the behaviours was recorded whilst this cognitive approach to symptom reduction was used. A marked decrease in her maladaptive behaviours was noted.
BACKGROUND: Previous studies suggest that most patients with pulmonary embolism die of their underlying diseases and pulmonary embolism is itself responsible for a minority of deaths. It has not been determined whether pulmonary embolism is associated with increased mortality among patients with different specific diseases. METHODS: We assessed the mortality in 1,487 patients who had lung scans to pursue the diagnosis of pulmonary embolism. An outcome classification committee prospectively reviewed deaths occurring up to 1 year after each patient's entry into the study. RESULTS: Ninety-five (23.8%) patients with pulmonary embolism and 189 (18.9%) without pulmonary embolism died within 1 year of study entry (estimated relative risk, 1.34; 95% confidence interval, 1.01 to 1.79). Mortality according to pulmonary embolism status was different among patients with COPD from mortality among patients who did not have COPD (interaction p = 0.03). Of 45 patients with COPD and pulmonary embolism, 24 (53.3%; 95% confidence interval, 38.8 to 67.9%) died within 1 year. After adjustment for patient characteristics, the estimated risk of dying within 1 year was 1.94 times (95% confidence interval, 1.17 to 3.24) for patients with COPD and pulmonary embolism compared with those without pulmonary embolism, and 1.14 (95% confidence interval, 0.85 to 1.54) for patients without COPD (interaction p = 0.08). CONCLUSIONS: Patients with COPD and pulmonary embolism have an increased 1-year mortality. Further study is needed to clarify the reason(s) for the increase in mortality.
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We have investigated further the anomalously high concentration of brain extracellular uric acid detected with in vivo sampling probes reported recently. The contribution by uric acid and 5-hydroxyindoleacetic acid (5-HIAA) to peak 2 recorded in rat striatum with chronically implanted carbon paste electrodes (CPEs) of different sizes was estimated by comparing peak current densities and the effect of the monoamine oxidase inhibitor pargyline. The concentration of uric acid in the extracellular fluid was some 50 times greater for 320-microns-diameter CPEs than for 160-microns-diameter electrodes, where the urate level was estimated at approximately 1 microM. The concentration of 5-HIAA was similar for 320-, 260-, and 160-microns-diameter CPEs. These data provide an explanation for the previously observed differences in 5-HIAA/urate ratios recorded with 320-microns-diameter CPEs and smaller carbon fibre electrodes. The results also indicate that chronically implanted sampling probes of diameter > 160 microns perturb the surrounding tissue, which produces uric acid by a mechanism yet unknown, although preliminary histological data suggest that glial cells may be involved.
OBJECTIVE: To determine whether erythromycins, sulfonamides, and tetracyclines are associated with an increased risk for acute hepatitis. DESIGN: Case-control study. SETTING: Medicaid billing data from Michigan and Florida between 1980 and 1987. PATIENTS: The 107 cases included patients hospitalized with acute symptomatic hepatitis without an identifiable cause of liver disease noted in the medical record. Four controls per case were randomly selected and were matched for age, sex, and state. RESULTS: Five cases (4.7%) and four controls (0.9%) were exposed to erythromycins, yielding an odds ratio of 5.2 (95% Cl, 1.1 to 26.6). No case or control was exposed to erythromycin estolate. Eight cases (7.5%) and three controls (0.7%) were exposed to oral sulfonamides, yielding an odds ratio of 11.4 (Cl, 2.7 to 67.8). All (except one control) had received trimethoprimsulfamethoxazole. Five cases (4.7%) and four controls (0.9%) were exposed to tetracyclines, yielding an odds ratio of 5.2 (Cl, 1.4 to 19.7). The results did not change substantively for erythromycin or sulfonamides after adjustment using multiple logistic regression for age, sex, state, and use of other hepatotoxic drugs. With tetracyclines, however, the odds ratio decreased to 3.6 (Cl, 0.9 to 14.3). Associations were also seen with isoniazid (P = 0.008) and rifampicin (P = 0.04). The number of patients developing acute symptomatic liver disease resulting in hospitalization for each million patients treated with a 10-day course of erythromycin was 2.28 cases; for sulfonamides, this figure was 4.8 cases; and for tetracycline, the figure was 1.56 cases. CONCLUSION: Erythromycin, sulfonamides, and tetracyclines are associated with acute symptomatic hepatitis resulting in hospitalization. Given the widespread use of these drugs, they will be among the more common drugs associated with hepatitis.
OBJECTIVE: To examine the magnitude of the risk of acute hepatitis associated with the use of nonsteroidal antiinflammatory drugs. METHODS: We calculated the annual incidence rate of hepatitis resulting in hospitalization and then performed a case-control study using 1980 to 1987 Medicaid billing data from Michigan and Florida. The 107 cases included patients with symptomatic acute hepatitis without an identifiable cause of liver disease. Four controls per case were randomly selected and were matched for age, sex, and state. Antecedent drug exposure was assessed 30 days prior to the onset of the disease in the cases and during the same period in the controls. RESULTS: The annual incidence rate (95% confidence interval) of acute idiopathic symptomatic hepatitis resulting in hospitalization was 2.2 (2.0 to 2.4) per 100,000 persons per year. Nine cases (8.4%) and 26 controls (6.1%) were exposed to nonsteroidal anti-inflammatory drugs, yielding an odds ratio of 1.4 (0.6 to 3.1). After adjustment for potential confounding variables, the odds ratio was 1.2 (0.5 to 2.8). CONCLUSIONS: Acute symptomatic idiopathic liver disease severe enough to result in hospitalization is uncommon, and no association was evident between nonsteroidal anti-inflammatory drugs and acute hepatitis. This study was large enough to exclude a relative risk of 2.8. These data suggest that acute symptomatic liver disease from nonsteroidal anti-inflammatory drugs is not a frequent clinical problem.
BACKGROUND: Pulmonary embolism is a potentially fatal disorder. Information about the outcome of clinically recognized pulmonary embolism is sparse, particularly given that new treatments for more seriously ill patients are now available. METHODS: We prospectively followed 399 patients with pulmonary embolism diagnosed by lung scanning and pulmonary angiography, who were enrolled in a multicenter diagnostic trial. We reviewed all hospitalizations, all new investigations of pulmonary embolism, and all deaths among the patients within one year of diagnosis. RESULTS: Of the 399 patients, 375 (94 percent) received treatment for pulmonary embolism, usually conventional anticoagulation. Only 10 patients (2.5 percent) died of pulmonary embolism; 9 of them had clinically suspected recurrent pulmonary embolism. Clinically apparent pulmonary embolism recurred in 33 patients (8.3 percent), of whom 45 percent died during follow-up. Ninety-five patients with pulmonary embolism (23.8 percent) died within one year. The conditions associated with these deaths were cancer (relative risk, 3.8; 95 percent confidence interval, 2.3 to 6.4), left-sided congestive heart failure (relative risk, 2.7; 95 percent confidence interval, 1.5 to 4.6), and chronic lung disease (relative risk, 2.2; 95 percent confidence interval, 1.2 to 4.0). The most frequent causes of death in patients with pulmonary embolism were cancer (in 34.7 percent), infection (22.1 percent), and cardiac disease (16.8 percent). CONCLUSIONS: When properly diagnosed and treated, clinically apparent pulmonary embolism was an uncommon cause of death, and it recurred in only a small minority of patients. Most deaths were due to underlying diseases. Patients with pulmonary embolism who had cancer, congestive heart failure, or chronic lung disease had a higher risk of dying within one year than did other patients with pulmonary embolism.