Availability bias in the management of myocardial infarction.
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Delivery of Health Care↗
Biomedical subjects
M Brezis
Publications and source records attributed to M Brezis.
Attitudes of medical practitioners towards "Do Not Resuscitate" orders.
When the desires of a patient are unknown or cannot be ascertained, cardio-pulmonary resuscitation (CPR) is the default procedure. Explicit, Do Not Resuscitate (DNR), orders are required to prevent implementation of CPR. We studied the response of general medical internists in specific clinical situations demanding consideration of DNR orders and respect for patient preferences; their current practice regarding slow codes and participation in CPR attempts considered futile provide information as to how often they discuss DNR issues with patients or families. Eighty-five internists attending the monthly meeting of the Internal Medicine Forum participated in the study. The physicians demonstrated their consent to participate by accepting a remote transmitter that elicited a response 2-3 minutes following the presentation of case vignettes or practice-related questions. The survey showed that 73% of the physicians agreed to assign a DNR order for a terminally ill patient unable to express her preferences. Only 55% agreed to do the same for a competent patient who specifically requested that CPR be withheld in the event of a cardiopulmonary arrest (p<0.05). 77% reported to have performed CPR, at least three times, in situations where they expected no benefit. 59% affirmed that their team had performed a partial CPR (slow code) at least once. Only 28% discussed the subject of DNR with patients or family more than 5 times a year. Paternalism, disregard for patients' preferences and poor communication skills influence normative behaviour in end-of-life decision-making.
Case Reports↗
Prevention of perioperative venous thromboembolism and coronary events: differential responsiveness to an intervention program to improve guidelines adherence.
INTRODUCTION: Prevention of venous thromboembolism and coronary events (with beta-blockers) during and after surgery is at the top of a list of safety practices for hospitalized patients, recommended by the Agency for Health Care Research and Quality (AHRQ). We wished to determine and improve adherence to clinical guidelines for these topics in our institution. PATIENTS, MATERIAL, AND METHODS: A prospective survey was conducted over several weeks on operated patients in a 1200-beds medical center (a teaching, community and referral hospital in Jerusalem, Israel). Eligibility for and actual administration of prophylactic treatment with anticoagulant and beta-blockers were determined. Following an intervention program, which included staff meetings, development of local protocols, and academic detailing by a nurse, the survey was repeated. RESULTS: In general, adherence to recommended anticoagulation prophylaxis was low, found in only 29% [95% confidence interval (CI) = 23-36] of eligible patients. After the intervention, adequate anticoagulation increased to 50% (95% CI = 40-59) of eligible patients (P < 0.001). Initiation of beta-blockers in preventing perioperative cardiac events was very low (0%, 95% CI = 0-5%) and did not increase after intervention. CONCLUSIONS: Adherence to guidelines for prevention of surgical complications was found to be low in our institution. A multifaceted intervention significantly increased use of prophylaxis for venous thromboembolism but not for coronary events. This differential response suggests that the success of a quality improvement project strongly depends on topic content and its phase of acceptance.
Adrenergic beta-Antagonists↗
Cyclosporine A for induction of remission in severe ulcerative colitis.
BACKGROUND: Ulcerative colitis (UC) is characterized by a life-long chronic course with remissions and exacerbations. Approximately 15% of patients have a severe attack requiring hospitalization at some time during their illness. These patients are traditionally treated with intravenous corticosteroids, with a response rate of approximately 60%. The patients who do not respond to steroid treatment usually require surgical removal of the large bowel (proctocolectomy or colectomy with an anal pouch). This surgical procedure essentially cures the patient from the disease but is associated with complications such as pouchitis. Few alternative treatments exist for severe ulcerative colitis: immunosuppressive medications (such as azathioprine) have a slow onset of action and are therefore usually ineffective. Antibiotics are not proven to be effective and biological treatments such as infliximab are still under investigation. The introduction of cyclosporine-A (CsA) for use in patients with severe ulcerative colitis (UC) has provided an alternative to patients previously facing only surgical options. Cyclosporine acts mainly by inhibiting T lymphocyte function, which is essential for the propagation of inflammation. Unlike most other immunosuppressive agents, CsA does not suppress the activity of other hematopoietic cells, does not cause bone marrow suppression and has a rapid onset of action. This reviews aims to systematically assess the effectiveness and safety of CsA for severe UC. OBJECTIVES: This review aimed to evaluate the effectiveness of cyclosporine A for patients with severe ulcerative colitis. SEARCH STRATEGY: Electronic searches of The Cochrane Library (Issue 1, 2004), EMBASE (1980-2004), and MEDLINE (1966-2004); hand searching the references of all identified studies; contacting the first author of each included trial. SELECTION CRITERIA: Randomised clinical trials comparing cyclosporine A with placebo or no intervention to obtain and maintain remission of idiopathic ulcerative colitis. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted the data from the included trials. Relative risks (RR) with 95% confidence intervals (CI) were estimated. The reviewers assumed an intention to treat analysis for the outcome measures. MAIN RESULTS: Only two randomized controlled trials were identified that satisfied the inclusion criteria. These two trials could not be pooled for analysis because of major differences in design and patient populations. In the first trial, 11 patients received intravenous cyclosporine (4 mg/kg) and 9 received placebo. Two of 11 in the treatment group failed to respond to therapy compared with nine of nine in the placebo group (RR 0.18, 95% CI 0.05 - 0.64). However, 3/11 and 4/9 eventually underwent colectomy in the treatment and placebo groups respectively and follow-up was less than a month. In the second trial 15 patients were treated with intravenous cyclosporine and 15 with intravenous methylprednisolone. Five of 15 patients in the cyclosporine group failed to respond to therapy as compared to 7/15 in the methylprednisolone group (RR 0.71, 95% CI 0.29 - 1.75). After 1 year 7/9 responders in the cyclosporine group were still in remission compared with 4/8 in the steroid group (p > 0.05) and the colectomy rate was similar in both groups. The mean time to response in the cyclosporine group in the 2 trials was short (7 days and 5.2 days). These results should be interpreted with caution given the small numbers of trials and patients evaluated for comparison, and limited follow-up (few weeks in one trial to a year in the other). The precise assessment of the occurrence of adverse events was difficult because the trials described different adverse reactions, which reversed after discontinuation of cyclosporine. There was no evidence in the trials reviewed that cyclosporine was more effective than standard treatment for preventing colectomy but this effect cannot be excluded due to the small sample size and rarity of this outcome. Additional limitations of current research include lack of data on quality of life, costs and long-term results of cyclosporine therapy. AUTHORS' CONCLUSIONS: There is limited evidence that cyclosporine is more effective than standard treatment alone for severe ulcerative colitis. The relatively quick response makes the short-term use of cyclosporine potentially attractive, but the long-term benefit is unclear, when adverse events such as cyclosporine-induced nephrotoxicity may become more obvious. There is a need for additional research on quality of life, costs and long-term results from cyclosporine therapy in severe ulcerative colitis.
Colitis, Ulcerative↗
Discordant public and professional perceptions on transparency in healthcare.
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Attitude of Health Personnel↗
Interactive learning in medicine: socrates in electronic clothes.
Traditional lectures have limited ability to maintain attention and to promote changes in behaviour. Active learning, which stimulates the audience to think and participate, may be more effective. We describe our experience with an interactive polling system in lectures to physicians and students. Audience's answers to questions are displayed, providing instant feedback to both lecturer and audience, and promoting the use of case discussions and problem-solving exercises. In our experience, this modality improves the quality of clinical learning and deserves further evaluation.
Bayes Theorem↗
Antibiotic prophylaxis of bacterial infections in cirrhotic inpatients: a meta-analysis of randomized controlled trials.
BACKGROUND: Antibiotic prophylaxis has been reported to decrease bacterial infections and fatality rates in inpatients with cirrhosis. We performed a systematic review to evaluate the efficacy of antibiotic prophylaxis in inpatients with cirrhosis, regardless of the underlying risk factors that led to hospital admission. METHODS: A comprehensive literature search strategy was performed including the Cochrane Library, Embase, Medline, a manual search of bibliographic references, and contacting the authors of each included trial. We included any randomized clinical trial comparing different types of antibiotic prophylaxis with placebo or no intervention in inpatients with cirrhosis. Two reviewers independently applied the selection criteria to all identified references, appraised the methodological quality of each trial and extracted the relevant data. Relative risks and 95% confidence intervals were estimated using the fixed effect model. A test of heterogeneity and a funnel plot were performed and an intention-to-treat approach was used for the outcome measures. RESULTS: Nineteen randomized trials were identified, 13 of which were included in the review. A significant beneficial effect on mortality (RR: 0.70; 95% CI: 0.56, 0.89) and prevention of bacterial infections (RR: 0.39; 95% CI: 0.32, 0.48) was observed, regardless of the underlying risk factors. Few adverse events were reported and there was no heterogeneity between studies. We identified a funnel plot asymmetry for the included trials. CONCLUSIONS: Antibiotic prophylaxis for inpatients with cirrhosis is efficacious in reducing the number of deaths and bacterial infections regardless of the underlying risk factors.
Antibiotic Prophylaxis↗
Do patients recall and understand communicated information upon discharge from the emergency department?
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Emergency Service, Hospital↗
Evidence based case report. Antibiotic treatment for spontaneous bacterial peritonitis.
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Acute Disease↗
Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding.
BACKGROUND: Bacterial infections are a frequent complication in patients with cirrhosis and gastrointestinal bleeding. Antibiotic prophylaxis seems to decrease the incidence of bacterial infections. Oral antibiotics, active against enteric bacteria, have been most often used as antibiotic prophylaxis in cirrhotic patients with gastrointestinal bleeding. OBJECTIVES: This review aims to evaluate the effects of antibiotic prophylaxis in the prevention of bacterial infections in cirrhotic patients with gastrointestinal bleeding. SEARCH STRATEGY: Electronic searches on The Cochrane Hepato-Biliary Group Controlled Trials Register (May 2001), The Cochrane Library (Issue 2, 2001), EMBASE (1980-2001), and MEDLINE (1966-2001); handsearching the references of all identified studies; contacting the first author of each included trial. SELECTION CRITERIA: Randomised clinical trials comparing different types of antibiotic prophylaxis with placebo, no intervention, or another antibiotic to prevent bacterial infections in cirrhotic patients with gastrointestinal bleeding. DATA COLLECTION AND ANALYSIS: Two reviewers independently appraised the quality of each trial and extracted the data from the included trials. Relative risks (RR) or average differences, with their 95% confidence intervals (CI) were estimated. The reviewers assumed an intention to treat basis for the outcome measures. MAIN RESULTS: Eight trials evaluated the effects of antibiotic prophylaxis compared with placebo or no antibiotic prophylaxis in 864 patients. A significant beneficial effect on decreasing mortality (RR 0.73, 95% CI 0.55 to 0.95) and the incidence of bacterial infections (RR 0.40, 95% CI 0.32 to 0.51) was observed. No serious adverse events were reported. The trials showed no significant heterogeneity. Three additional trials evaluated the effects of antibiotics compared with a different regimen of antibiotics in 503 patients. Data could not be combined as each trial used different interventions. None of the examined antibiotic regimens was superior to the control regimen regarding mortality or the incidence of bacterial infections. REVIEWER'S CONCLUSIONS: Antibiotic prophylaxis for cirrhotic inpatients with gastrointestinal bleeding is efficacious in reducing the number of deaths and bacterial infections, are well tolerated, and should be advocated.
Antibiotic Prophylaxis↗
Antibiotics for spontaneous bacterial peritonitis in cirrhotics.
BACKGROUND: Spontaneous bacterial peritonitis is mainly a complication of cirrhotic ascites that occurs in the absence of any intra-abdominal, surgically treatable source of infection. Antibiotics have been recommended as the mainstay treatment for spontaneous bacterial peritonitis. However, this recommendation is not based on convincing evidence. It has been proposed that treatment should cover Gram-negative enteric bacteria and Gram-positive cocci, that are responsible for up to 90% of cases. OBJECTIVES: To evaluate the effectiveness and safety of different types and ways of antibiotic therapy for spontaneous bacterial peritonitis in cirrhotic patients. SEARCH STRATEGY: Electronic searches on the Cochrane Library (Issue 3, 2000), the Cochrane Hepato-Biliary Group Trials Register (March 2000), EMBASE (1980-2000), MEDLINE (1966-2000); scanning the references of all identified studies; contacting the first author of each included trial. SELECTION CRITERIA: Randomised trials comparing different types of antibiotics for spontaneous bacterial peritonitis in cirrhotic patients. DATA COLLECTION AND ANALYSIS: Data were independently extracted by two reviewers. Relative risks or weighted mean differences, with their 95% confidence intervals were estimated using 'intention-to-treat' analyses. MAIN RESULTS: Nine trials dealing with 684 patients diagnosed with spontaneous bacterial peritonitis were included. No placebo-controlled trial was found. Each of the included trials compared different antibiotics, and no meta-analysis could be performed. We were unable to establish the optimal dose or duration of antibiotic therapy and found no convincing evidence that cefotaxime is more effective than ampicillin-tobramycin or that oral quinolones should be recommended for patients with less severe manifestations of the disease. REVIEWER'S CONCLUSIONS: This review provides no clear evidence for the treatment of cirrhotic patients with spontaneous bacterial peritonitis. Until large, well-conducted, trials provide adequate evidence, treatment must be based on clinical experience.
Anti-Bacterial Agents↗
Transient urethral obstruction predisposes to ascending pyelonephritis and tubulo-interstitial disease: studies in rats.
Chronic tubulo-interstitial disease, an important cause of end-stage renal disease, often results from the combined effects of a disturbed urinary outflow tract and urinary tract infection. Acute unilateral ureteral obstruction in rats rapidly induces foci of medullary necrosis, confined to the region of the papilla and fornices. This injury may provide a nidus for bacterial invasion and may invoke reactive and regenerative changes, ultimately leading to chronic pyelonephritis and tubulo-interstitial nephropathy. To explore this possibility, adult rats underwent renal morphological evaluation 2-7 days following transient 24-h unilateral ureteral obstruction. In some experiments the bladder was inoculated with bacteria (10(8)-10(9) cfu/ml Escherichia coli in 0.5 ml) after release of ureteral obstruction, with subsequent cultures obtained from the pelvis of both kidneys and from the urinary bladder. Morphologic evaluation of perfusion-fixed kidneys, 2-7 days after the release of 24-h ureteral obstruction disclosed papillary necrosis, urothelial proliferation, marked inner-stripe interstitial expansion, and fibrosis and proximal tubular (S3) dilatation. The lateral (perihilar region) was predominantly affected, with lesions spreading from the fornices. There was some progression of interstitial fibrosis during the postobstructive time course or following more prolonged ureteral obstruction. By contrast, infection hardly contributed to the tubulointerstitial changes. In rats subjected to infection, cultures were positive in all 15 postobstructive kidneys, as opposed to five contralateral kidneys (P < 0.0001). Viable counts from the postobstructive kidney were also higher than those from the contralateral side (79,000 +/- 12,000 vs 2900 +/- 1600 cfu/ml, mean +/- SEM, P < 0.0001), and were comparable to those obtained from the bladder (77,000 +/- 13,000 cfu/ml). We conclude that transient ureteral obstruction predisposes to ascending pyelonephritis and to tubulointerstitial disease. This vulnerability may relate to altered urodynamics and medullary tissue destruction.
Animals↗
Compensated heart failure predisposes to outer medullary tubular injury: studies in rats.
BACKGROUND: Heart failure (HF) is considered a putative factor predisposing to acute renal failure (ARF). Since outer medullary hypoxic injury may play an important role in the pathogenesis of acute tubular necrosis, we explored the impact of experimental HF on the propensity to develop ARF with hypoxic medullary injury following the inhibition of prostaglandin and nitric oxide synthesis. METHODS: Compensated, high-output HF was induced in Sprague-Dawley rats by aorto-caval fistula. At the eighth to ninth postoperative day, the rats were injected with indomethacin and N(omega) nitro-L-arginine methyl ester (L-NAME; ARF protocol) and were sacrificed 24 hours later for morphologic evaluation. RESULTS: Kidney function comparably declined in HF-ARF rats and in control sham operated animals (CTR-ARF). Nevertheless, outer medullary hypoxic damage with medullary thick ascending limb (mTAL) necrosis occurred almost exclusively in the HF-ARF group (11 +/- 4% vs. 0.2 +/- 0.2% of tubules in CTR-ARF, P < 0.03). In a third group of HF animals subjected to vehicles only (HF-Nil), kidney function was preserved and renal morphology remained intact. Papillary-tip necrosis was consistently found in all animals subjected to indomethacin and L-NAME, irrespective of preconditioning. Morphometric evaluation disclosed that HF was not associated with mTAL hypertrophy. CONCLUSIONS: Incipient HF predisposes to hypoxic outer medullary injury, probably reflecting the impact of regional vasoconstrictive stimuli rather than tubular hypertrophy when protective local vasodilating mechanisms are hampered. The presence and extent of outer medullary hypoxic damage cannot be predicted from the functional derangement, which in the experimental settings may also represent prerenal azotemia or papillary damage.
Acute Kidney Injury↗
Renal effects of nabumetone, a COX-2 antagonist: impairment of function in isolated perfused rat kidneys contrasts with preserved renal function in vivo.
The constitutive cyclooxygenase (COX)-1 enzyme has been considered the physiologically important isoform for prostaglandin synthesis in the normal kidney. It has, therefore, been suggested that selective inhibitors of the 'inducible' isoform (COX-2) may be free from renal adverse effects. We studied the renal effects of the predominantly COX-2 antagonist nabumetone in isolated perfused kidneys. As compared with controls, kidneys removed after in vivo administration of oral nabumetone (15 mg/kg) disclosed altered renal function with reduced glomerular filtration rate, filtration fraction, and urine volume and enhanced hypoxic outer medullary tubular damage. By contrast, renal function and morphology were not affected in vivo by nabumetone or its active metabolite 6-methoxy-2-naphthylacetic acid. The latter agent (10-20 mg/kg i.v.) did not significantly alter renal microcirculation, as opposed to a selective substantial reduction in medullary blood flow noted with the nonselective COX inhibitor indomethacin (5 mg/kg i.v.). In a rat model of acute renal failure, induced by concomitant administration of radiocontrast, nitric oxide synthase, and COX inhibitors, the decline in kidney function and the extent of hypoxic medullary damage with oral nabumetone (80 mg/kg) were comparable to a control group, and significantly less than those induced by indomethacin. In rats subjected to daily oral nabumetone for 3 consecutive weeks, renal function and morphology were preserved as well. Both nabumetone and 6-methoxy-2-naphthylacetic acid reduced renal parenchymal prostaglandin E2 to the same extent as indomethacin. It is concluded that while nabumetone adversely affects renal function and may intensify hypoxic medullary damage ex vivo, rat kidneys are not affected by this agent in vivo, both in acute and chronic studies. COX selectivity may not explain the renal safety of nabumetone.
Acute Kidney Injury↗
Increased risk of exposure to hepatitis B infection among butchers sharing knives.
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Case-Control Studies↗
Pathophysiology of radiocontrast nephropathy: a role for medullary hypoxia.
Recent experimental data underlies the role of hypoxic tubular injury in the pathophysiology of radiocontrast nephropathy. Although systemic transient hypoxemia, increased blood viscosity, and a leftward shift of the oxygen-hemoglobin dissociation curve may all contribute to intrarenal hypoxia, imbalance between oxygen demand and supply plays a major role in radiocontrast-induced outer medullary hypoxic damage. Low oxygen tension normally exists in this renal region, reflecting the precarious regional oxygen supply and a high local metabolic rate and oxygen requirement, resulting from active salt reabsorption by medullary thick ascending limbs of Henle's loop. Radiologic contrast agents markedly aggravate outer medullary physiologic hypoxia. This results from enhanced metabolic activity and oxygen consumption (as a result of osmotic diuresis and increased salt delivery to the distal nephron) because the regional blood flow and the oxygen supply actually increase. The latter effect may result in part from the activation of various regulatory mediators of outer medullary blood flow to ensure maximal regional oxygen supply. Low-osmolar radiocontrast agents may be less nephrotoxic because of the smaller osmotic load and vasomotor alterations. Experimental radiocontrast-induced renal failure requires preconditioning of animals with various insults (for example, congestive heart failure, reduced renal mass, salt depletion, or inhibition of nitric oxide and prostaglandin synthesis). In all these perturbations, which resemble clinical conditions that predispose to contrast nephropathy, outer medullary hypoxic injury results from insufficiency or inactivation of mechanisms designed to preserve regional oxygen balance. This underlines the importance of identifying and ameliorating predisposing factors in the prevention of this iatrogenic disease.
Acute Kidney Injury↗
Tissue oxygenation modifies nitric oxide bioavailability.
OBJECTIVE: Because changes in blood oxygenation acutely alter vascular tone, we explored a possible modulation of nitric oxide-induced vasodilation (nitrovasodilation) by oxygen. METHODS: We studied the effects of manipulation of tissue oxygenation on renal parenchymal nitric oxide (NO) with a selective NO electrode placed in the well-oxygenated renal cortex or in the physiologically hypoxemic outer medulla. RESULTS: In the cortex, as expected, NO signals fell in response to the NO synthase (NOS) inhibitor L-NAME. By contrast, in the outer medulla, NO signals paradoxically rose following NOS inhibition, known to intensify local hypoxia. Other manipulations that intensify outer medullary hypoxia (such as indomethacin or radiologic contrast media) increased local NO readings, while measures known to ameliorate outer medullary hypoxia (furosemide, L-arginine, hypotension) reduced regional NO readings. CONCLUSIONS: Oxygen appears to modulate NO bioavailability, in particular, in tissues with low ambient pO2, perhaps through enhanced binding to oxygenated hemoglobin. It is proposed that this phenomenon may participate in physiological microvascular regulation, with hypoxemia enhancing NO concentration, while hyperoxemia resulting in accelerated NO removal.
Animals↗
Likelihood ratios: getting diagnostic testing into perspective.
In modern medicine, sophisticated laboratory tests and imaging studies are often emphasized at the expense of history and physical examination, rather than complementing clinical assessment. Ancillary testing often fails to advance the diagnostic process, and increases patient risk and the expense of medical care. The relative value of clinical evaluation and technological methods is rarely considered, and the power of the clinical evaluation is therefore underestimated. The likelihood ratio (LR) is a semiquantitative measure of the performance of diagnostic tests which indicates how much a diagnostic procedure modifies the probability of disease, and is calculated from the sensitivity and specificity of the test (or directly from the change in probability associated with the test result). We review the performance of frequently-used tests by their LRs, and compare them to the power of clinical assessment, with clinical cases to illustrate the application of LRs in the diagnostic process. The discriminative power of clinical assessment and ancillary tests is often similar, and the combination of the two greatly increases accuracy in the diagnostic process. Clinical assessment is indeed frequently more informative than current technical modalities. LRs assist in putting the value of testing in proper perspective. Practice in evaluating pre-test probabilities of disease and in the application of LRs should be enhanced in medical training.
Diagnostic Techniques and Procedures↗