Amy Duff

Effect of anaemia and cardiovascular disease on surgical mortality and morbidity.

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.

Risk of bacterial infection associated with allogeneic blood transfusion among patients undergoing hip fracture repair.

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.

A pilot randomized trial comparing symptomatic vs. hemoglobin-level- driven red blood cell transfusions following hip fracture

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.

The effect of anesthetic technique on postoperative outcomes in hip fracture repair.

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.

Acute Liver Disease Associated with Erythromycins, Sulfonamides, and Tetracyclines

Recognizing reversible forms of disease is an important task for every clinician when evaluating a patient with acute hepatitis. Specific treatment is not available for most common forms of infectious hepatitis; however, if an offending drug is identified and discontinued, then the hepatitis related to that drug is likely to resolve. Many drugs have been implicated as causes of hepatitis, although nearly all the supportive data are from case reports or case series [1]. Case reports and case series suffer from the absence of a control group, making any causal relations difficult to determine [2, 3]. In addition, it is impossible to calculate from case reports the incidence rate of liver disease [4]. We describe the results of the first casecontrol study to examine the relation between acute hepatitis and commonly prescribed antibiotics. Our data suggest that three of the most commonly used antibiotics are associated with acute hepatitis. Methods Data Sources Data for this study were derived from the Computerized On-Line Medicaid Pharmaceutical Analysis and Surveillance System (COMPASS). The COMPASS derives its data as a by-product of the Medicaid Management Information System, which is a computed claims processing and management information system for this large health care system. The Food and Drug Administration has funded the development of COMPASS as a potential data resource for conducting postmarketing drug surveillance studies. Software has been created to store, retrieve, and abstract that fraction of each patients record that is useful for research. At the time of this study, billing data for each patient included age, sex, state, race (except in Florida), inpatient and outpatient diagnoses recorded by International Classification of Diseases 9th Revision Clinical Modification codes (ICD-9-CM) [5], and outpatient drugs dispensed. Use of over-the-counter drugs was recorded only if the drugs had been prescribed. This system has been described more fully elsewhere [6]. Selection of Cases and Controls A casecontrol study was done using COMPASS data from Michigan and Florida. Potential cases were defined as patients 20 years or older who received an inpatient diagnosis consistent with acute liver disease between 1980 and 1987. To identify the acute liver disease ICD-9-CM codes most suitable for this study, we reviewed medical records from 10 patients in a local hospital with each of the ICD-9-CM codes consistent with acute liver disease. The results of this review suggested that the inpatient codes for acute necrosis and for unspecified hepatitis (ICD-9-CM codes 570 and 573.3, respectively) were used exclusively for patients with acute hepatitis without a known cause (such as infections). Therefore, these codes were used to identify potential cases. Potential cases were excluded if a patient had an alcohol-related diagnosis any time before the study diagnosis. An alcohol-related diagnosis was defined as the presence of an ICD-9-CM code specific for heavy alcohol use, such as alcoholic hepatitis, Laennec cirrhosis, alcoholic pancreatitis, alcoholic cardiomyopathy, delirium tremens, and so forth. Patients with a history of chronic liver disease were also excluded. To assure that study patients were eligible for Medicaid benefits throughout the study period, a claim for medical service was required both before and after the study period. After application of the exclusion criteria and admissibility screen, 779 potential cases of acute liver disease remained. For each case, four controls who had passed the eligibility screen and who had no recorded history of liver disease were selected from the same state. Controls were also matched to the cases for sex and age (within 10-year age ranges). Medical Record Review To both validate the diagnosis of acute liver disease and to exclude cases with identifiable nondrug causes, we requested the medical records of all the potential cases. To acquire the medical records, the state Medicaid agency translated the anonymized COMPASS patient and provider identification numbers into Medicaid identification numbers. After receiving permission, a nurse visited the hospital with a portable copying machine and copied the relevant parts of the medical record. All identifying information was then blocked out, and the records were mailed to the investigators for review. We received 408 of the 779 medical records requested. The medical record review process and results have been previously described in detail [7]. Briefly, these records were abstracted into a computed database by two physician reviewers. We excluded any case without medical records and any case meeting the following criteria: 1) no diagnosis of liver disease [n = 26]; 2) an admission date different from that requested [n = 1]; 3) a diagnosis of or evidence for chronic liver disease [n = 13]; 4) a diagnosis consistent with a nondrug origin (for example, acute hepatitis A or B or choledocholithiasis) [n = 112]; or 5) a previous exposure consistent with a nondrug cause, including a history of alcohol abuse (n = 39), intravenous drug use (n = 33), or a transfusion within 180 days of the diagnosis (n = 10). A total of 239 (59%) patients met these exclusion criteria. To avoid ascertainment bias, we also excluded patients whose liver disease was mild (n = 25) or whose liver disease was diagnosed incidentally during the hospitalization (n = 44). Mild liver disease was defined as the absence of liver enzyme test values (aspartate aminotransferase [AST], alanine aminotransferase [ALT], bilirubin, or alkaline phosphatase) exceeding two times the control value. Liver disease diagnosed incidentally during hospitalization included patients hospitalized for reasons other than symptoms from liver disease (for example, surgery). After completion of the medical record review, 107 cases of acute idiopathic symptomatic liver disease and their 428 matched controls remained for analysis. Study Variables Exposure was defined as the presence in the computed data of a pharmacy bill for dispensing an antibiotic within 30 days before the index date. The index date for cases was defined as the hospitalization date for acute liver disease. The index date for controls was identical to that of their respective matched cases. The probable indication for the antibiotic was determined by review of the computer profile of exposed cases and controls. The computer profile included all billing diagnoses near the time that the antibiotic was dispensed. The diagnoses considered to be the probable indication for the antibiotic included infections or other diseases (for example, acne) for which these drugs are commonly used. We evaluated the common antibiotics that have been implicated by case reports in the literature as causes of hepatitis. These included the erythromycins, nitrofurantoin, isoniazid, rifampicin, the sulfonamides, and the tetracyclines. For purposes of comparison, we also evaluated other antibiotics that might be used for similar indications including ampicillin, amoxicillin, and cephalosporins. In addition to the antibiotics of interest, information on other potential confounding variables was also obtained. Specifically, we collected information on 46 drugs and 36 conditions thought to be associated with liver disease based on a review of the literature. These included use of drugs such as -methyldopa, estrogens, nonsteroidal anti-inflammatory drugs, phenytoin, phenothiazines, and quinidine, and diseases such as Epstein-Barr infection, inflammatory arthritis, biliary tract disease, and congestive heart failure. Most of these conditions were exceedingly rare in our study samples, in part because the primary record review excluded patients with an identifiable nondrug cause of their liver disease, and, in part, because many of these conditions are very rare in the general population (for example, Q Fever and Wilson disease). The drug codes and ICD-9-CM codes used for each study variable and potential confounder are available from the authors. Data Analysis We first described the demographics of the patient population and then the casecontrol distribution of antibiotic exposure and potential confounding variables. Odds ratios with 95% confidence intervals (CIs) were calculated using the method of Woolf [8] for calculating the CIs. If any cell in the table had an expected value of less than five, then exact CIs were calculated. An unmatched analysis was done because of the broad nature of the matching variables (age, sex, and state). We then used stratified analysis to evaluate the association between liver disease and antibiotic exposure, controlling for each potential confounding variable, and calculated summary statistics using the Mantel-Haenszel procedure [9]. Evidence for interaction between antibiotic exposure and each potential confounding variable was examined. Multiple logistic regression was then used to evaluate the relation between each antibiotic and acute liver disease, controlling for the simultaneous effects of all confounding variables. The independent variables in the model included state, age, and sex, in addition to other interactions or potential confounders identified in the univariate analysis or thought to be clinically plausible. Because the database did not contain information on drug use during hospitalization, we conducted a subanalysis that excluded all patients hospitalized in the 30 days before the index date. We also examined the frequency of hepatitis after re-exposure to the antibiotics among the cases. The excess risk for liver disease from each of the drugs was calculated by 1) multiplying the adjusted odds ratio for each drug times the baseline incidence rate per 10 days of acute symptomatic liver disease resulting in hospitalization [assuming a 10-day course of antibiotics]; and 2) subtracting the baseline incidence rate of acute symptomatic liver disease resulting in hospitalization. The incidence rate

The low risk of upper gastrointestinal bleeding in patients dispensed corticosteroids

PURPOSE To determine the incidence of upper gastrointestinal bleeding in patients treated with corticosteroids. PATIENTS AND METHODS The incidence of upper gastrointestinal tract bleeding was assessed in a cohort of 19,880 patients from the Michigan Medicaid billing database with dermatitis and/or asthma treated with corticosteroids during 1980 to 1984. The frequency of upper gastrointestinal bleeding was assessed within 60 days after each corticosteroid prescription. RESULTS The incidence of upper gastrointestinal bleeding in patients without a past history of upper gastrointestinal bleeding who were exposed to corticosteroids was only 2.8 cases per 10,000 person-months. The rate of upper gastrointestinal bleeding was notably higher in patients receiving anticoagulants and those with a prior history of upper gastrointestinal bleeding (23.0 and 15.9 cases per 10,000 person-months, respectively). CONCLUSION Because the incidence of upper gastrointestinal bleeding in ambulatory patients treated with corticosteroids is so low, prophylactic therapy should be restricted to high-risk patients, if it is to be used at all.

The risks of blood transfusion : the relative influence of acquired immunodeficiency syndrome and non-A, non-B hepatitis

Abstract purpose: The acquired immunodeficiency syndrome epidemic has greatly increased concern about the risk of blood transfusion. Many transfusions are now autologous, and when these are not available, both physicians and patients are more likely to question the advisability of transfusion. We evaluate the risk of preoperative blood transfusion and the contribution of human immunodeficiency virus (HIV) infection to that risk. methods: We used decision analysis to characterize the risk associated with HIV infection in days of life lost. The contributions to risk of acute transfusion reaction, hepatitis B, and nonA, non-B hepatitis are also estimated. Sensitivity analyses show the implications for transfusion risk of recent information about HIV infection in the blood supply and a new test for hepatitis C. results: The analysis shows that the contribution of HIV infection to the risk of death from transfusion, expressed in days of life expectancy lost, has become extremely small over the last several years. Currently, HIV infection accounts for less than 1% of the risk of death, while nonA, non-B hepatitis accounts for 97% to 98%. Further reductions in the risk of HIV infection, even to zero, will make relatively little difference in the safety of transfusion. The analysis also shows that the remaining risk from transfusion should decrease sharply, by more than two thirds, with the adoption of the test for hepatitis C. conclusions: Efforts to improve the safety of blood should focus on reducing the risk of non-A, non-B hepatitis. The remaining risk of HIV infection is very small.

The feasibility of studying drug‐induced acute hepatitis with use of Medicaid data

To determine the feasibility of the use of Medicaid data to study drug‐induced acute liver disease, we reviewed the medical records of 414 patients receiving Medicaid, age 20 or older, with an ICD‐9‐CM inpatient billing code consistent with acute hepatitis. Of the patients whose records were reviewed, 15.9% were alcoholics, 31.9% had acute hepatitis A or B, 13.5% were intravenous drug users, 8.2% had acute cholecystitis or choledocholithiasis, and 4.1% had received a blood transfusion within the previous 6 months. No diagnosis of liver disease was found in 10.6% of the patients, and 5.7% had chronic liver disease. Of the 169 patients with idiopathic acute liver disease identified, many had very mild liver disease and were hospitalized for reasons other than liver disease. We conclude that Medicaid billing data has high reliability and validity for the diagnosis of acute liver disease. However, primary medical records are essential for the study of drug‐induced hepatitis, to be able to exclude other causes of liver disease, and to obtain information not included in the computer data.

The Risks of Blood Transfusion: The Relative Influence of Acquired Immunodeficiency Syndrome and Non-A, Non-B Hepatitis

PURPOSE The acquired immunodeficiency syndrome epidemic has greatly increased concern about the risk of blood transfusion. Many transfusions are now autologous, and when these are not available, both physicians and patients are more likely to question the advisability of transfusion. We evaluate the risk of preoperative blood transfusion and the contribution of human immunodeficiency virus (HIV) infection to that risk. METHODS We used decision analysis to characterize the risk associated with HIV infection in days of life lost. The contributions to risk of acute transfusion reaction, hepatitis B, and non-A, non-B hepatitis are also estimated. Sensitivity analyses show the implications for transfusion risk of recent information about HIV infection in the blood supply and a new test for hepatitis C. RESULTS The analysis shows that the contribution of HIV infection to the risk of death from transfusion, expressed in days of life expectancy lost, has become extremely small over the last several years. Currently, HIV infection accounts for less than 1% of the risk of death, while non-A, non-B hepatitis accounts for 97% to 98%. Further reductions in the risk of HIV infection, even to zero, will make relatively little difference in the safety of transfusion. The analysis also shows that the remaining risk from transfusion should decrease sharply, by more than two thirds, with the adoption of the test for hepatitis C. CONCLUSIONS Efforts to improve the safety of blood should focus on reducing the risk of non-A, non-B hepatitis. The remaining risk of HIV infection is very small.