Entries from May 2008
Comparison of angiotensin-converting enzyme inhibitor alone and in combination with irbesartan for the treatment of heart failure.
Int J Cardiol. 2008 Mar 28;125(1):16-21
Authors: Kum LC, Yip GW, Lee PW, Lam YY, Wu EB, Chan AK, Fung JW, Chan JY, Zhang Q, Kong SL, Yu CM
OBJECTIVE: Angiotensin-converting enzyme inhibitor (ACEI) is beneficial in patients with congestive heart failure (CHF). Some, but not all, angiotensin receptor blocker (ARB) was demonstrated to be effective as "add-on" therapy. We investigated whether irbesartan is useful as an add-on therapy in CHF. DESIGN: Randomized control trial. SETTING: Single center. PATIENTS: 50 CHF patients on stable doses of ACEI. INTERVENTIONS: Add-on therapy with irbesartan (300 mg/day) or continuation of conventional therapy (control group) for 1 year. MAIN OUTCOME MEASURES: Serial clinical and echocardiographic assessment were performed as baseline, 3 months and 1 year after therapy. RESULTS: There was no difference in clinical characteristics between 2 groups. Patients in the add-on therapy group had significant increase in 6-Minute Hall-Walk distance (351+/-89 to 392+/-84 m, P<0.01), achieved higher METs exercise time on treadmill test (3.9+/-1.1 to 4.6+/-1.3 METs, P=0.01), reduction of NYHA Class (2.4+/-0.5 to 2.0+/-0.8, P<0.005) and improvement of QOL score (28+/-19 to 17+/-18, P<0.05). These parameters were not improved in the control group and a worsening of exercise capacity was observed (P<0.05). A reduction of left ventricular end-systolic diameter (4.94+/-0.85 vs 4.30+/-1.17 cm, P<0.05) was observed in the add-on group. At the end of 1 year, more patients have normal or abnormal relaxation pattern in the add-on group than the control group (82% vs 53% chi(2)=7.1, P=0.02). Blood pressure and renal function were unchanged in both groups. CONCLUSION: The addition of irbesartan to conventional ACEI therapy in CHF further improves symptoms, exercise capacity and quality of life without adverse effects on hemodynamics and renal function.
PMID: 17433840 [PubMed - indexed for MEDLINE]
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Tags: Int J Cardiol
Efficacy and safety of renal tubule cell therapy for acute renal failure.
J Am Soc Nephrol. 2008 May;19(5):1034-40
Authors: Tumlin J, Wali R, Williams W, Murray P, Tolwani AJ, Vinnikova AK, Szerlip HM, Ye J, Paganini EP, Dworkin L, Finkel KW, Kraus MA, Humes HD
The mortality rate for patients with acute renal failure (ARF) remains unacceptably high. Although dialysis removes waste products and corrects fluid imbalance, it does not perform the absorptive, metabolic, endocrine, and immunologic functions of normal renal tubule cells. The renal tubule assist device (RAD) is composed of a conventional hemofilter lined by monolayers of renal cells. For testing whether short-term (up to 72 h) treatment with the RAD would improve survival in patients with ARF compared with conventional continuous renal replacement therapy (CRRT), a Phase II, multicenter, randomized, controlled, open-label trial involving 58 patients who had ARF and required CRRT was performed. Forty patients received continuous venovenous hemofiltration + RAD, and 18 received CRRT alone. The primary efficacy end point was all-cause mortality at 28 d; additional end points included all-cause mortality at 90 and 180 d, time to recovery of renal function, time to intensive care unit and hospital discharge, and safety. At day 28, the mortality rate was 33% in the RAD group and 61% in the CRRT group. Kaplan-Meier analysis revealed that survival through day 180 was significantly improved in the RAD group, and Cox proportional hazards models suggested that the risk for death was approximately 50% of that observed in the CRRT-alone group. RAD therapy was also associated with more rapid recovery of kidney function, was well tolerated, and had the expected adverse event profile for critically ill patients with ARF.
PMID: 18272842 [PubMed - indexed for MEDLINE]
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Tags: J Am Soc Nephrol
Zoledronic acid and survival in patients with metastatic bone disease from lung cancer and elevated markers of osteoclast activity.
J Thorac Oncol. 2008 Mar;3(3):228-36
Authors: Hirsh V, Major PP, Lipton A, Cook RJ, Langer CJ, Smith MR, Brown JE, Coleman RE
INTRODUCTION: Bone metastases from non-small cell lung cancer (NSCLC) are associated with skeletal-related events (SREs) and elevated levels of N-telopeptide of type I collagen (NTX) in some patients. Zoledronic acid (ZOL) reduces SRE risk and NTX levels. METHODS: To assess effects of baseline variables, including NTX levels (normal = NTX < 64 nmol/mmol creatinine; high = NTX > or = 64 nmol/mmol creatinine), on treatment effects in NSCLC patients, a retrospective analysis was performed in NSCLC patients with bone metastases (N = 382) treated with ZOL or placebo every 3 weeks in a 21-month randomized clinical trial in patients with NSCLC or other solid tumors. Cox proportional hazards models assessed relative risks (RRs) of SREs, bone lesion progression, and death. Multivariate models analyzed covariate effects on survival. RESULTS: For both placebo- and ZOL-treated patients, high baseline NTX correlated with increased SRE risk (p = 0.068 and 0.012, respectively). Although high versus normal baseline NTX correlated with more than twofold increased risks of bone lesion progression and death in the placebo group (p = 0.039 and 0.001, respectively), correlations were weaker in the ZOL group (RR = 1.38; p = 0.0186 and RR = 1.27; p = 0.142, respectively), suggesting an interaction effect of ZOL and baseline NTX. Among patients with high baseline NTX, ZOL significantly reduced the RR of death by 35% versus placebo (p = 0.024). Per multivariate analysis, ZOL treatment (p = 0.005), higher lymphocyte count (p = 0.011), performance status 0 to 1 (p = 0.012), and absence of narcotic use (p = 0.016) correlated with improved survival. CONCLUSIONS: This retrospective analysis revealed statistically significant correlations between ZOL and increased survival versus placebo in NSCLC patients and high baseline NTX levels.
PMID: 18317064 [PubMed - indexed for MEDLINE]
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Tags: J Thorac Oncol
A Markov model to evaluate hospital readmission.
BMC Med Res Methodol. 2008;8:23
Authors: Bartolomeo N, Trerotoli P, Moretti A, Serio G
BACKGROUND: The analysis of non-fatal recurring events is frequently found in studies on chronic-degenerative diseases. The aim of this paper is to estimate the probability of readmission of patients with Chronic Obstructive Pulmonary Disease (COPD) or with Respiratory Failure (RF). METHODS: The Repeated hospital admissions of a patient are considered as a Markov Chain. The transitions between the states are estimated using the Nelson-Aalen estimator. The analysis was carried out using the Puglia Region hospital patient discharge database for the years 1998-2005. Patients were selected on the basis of first admission between 01/01/2001 and 31/12/2005 with ICD-9-CM code of COPD or RF as principal and/or secondary diagnosis. For those selected two possible transitions were considered in the case they had the second and third admission with an ICD-9-CM code of COPD or RF as principal diagnosis. RESULTS: The probability of readmission is increased in patients with a diagnosis of RF (OR = 1.618 in the first transition and 1.279 in the second) and also in those with a diagnosis of COPD or RF as the principal diagnosis at first admission (OR = 1.615 in the first transition and 1.193 in the second). The clinical gravity and the ward from which they were discharged did not significantly influence the probability of readmission. CONCLUSION: The time to readmission depends on the gravity of the pathology at onset. In patients with a grave clinical picture, either COPD or Respiratory Failure, when treated and controlled after the first admission, they become minor problems and they are indicated among secondary diagnoses in any further admission.
PMID: 18430214 [PubMed - indexed for MEDLINE]
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Tags: BMC Med Res Methodol
Can inhaled corticosteroids influence the natural history of asthma?
Curr Opin Allergy Clin Immunol. 2008 Feb;8(1):77-81
Authors: Murray CS
PURPOSE OF REVIEW: Asthma is characterised by variable airflow obstruction, airway inflammation and hyper-responsiveness. Persistent inflammation is thought to lead to ‘remodelling’ of the airway, which in turn leads to the progressive loss of lung function seen in asthmatics. It would appear logical that anti-inflammatory drugs such as inhaled corticosteroids (ICS) would influence the natural history of asthma by reducing inflammation, subsequent remodelling, and thus preventing the decline in lung function. This review will summarise the effects of ICS on the secondary prevention of asthma, lung function and remodelling. RECENT FINDINGS: Many published studies show a reduction in airway inflammation, improvement in clinical symptoms and prebronchodilator lung function whilst taking ICS. Few studies, however, examine their effect on the natural history of asthma. Several recent studies have targeted very young children with asthma using ICS, and despite their differing target populations and treatment strategies, have failed to show any difference in lung function. Studies in adults with mild persistent asthma show similar findings. ICS appear to reverse some of the processes involved in airway remodelling, but not all. SUMMARY: Although ICS are effective in controlling symptoms they do not appear to alter the natural history of asthma.
PMID: 18188022 [PubMed - indexed for MEDLINE]
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Tags: Curr Opin Allergy Clin Immunol
A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to glucose-lowering drugs in insulin-naive people with type 2 diabetes.
Diabetologia. 2008 Mar;51(3):408-16
Authors: Rosenstock J, Davies M, Home PD, Larsen J, Koenen C, Schernthaner G
AIMS/HYPOTHESIS: This 52-week multinational, randomised, open-label, parallel-group, non-inferiority trial compared clinical outcomes following supplementation of oral glucose-lowering drugs with basal insulin analogues detemir and glargine in type 2 diabetic patients. METHODS: Insulin-naive adults (n=582, HbA(1c) 7.5-10.0%, BMI <or= 40.0 kg/m(2)) were randomised 1:1 to receive insulin detemir or glargine once daily (evening) actively titrated to target fasting plasma glucose (FPG) <or= 6.0 mmol/l. An additional morning insulin detemir dose was permitted if pre-dinner plasma glucose (PG) was >7.0 mmol/l after achieving FPG <7.0 mmol/l. Due to labelling restrictions, no second glargine dose was allowed. RESULTS: Baseline HbA(1c) decreased from 8.6 to 7.2 and 7.1% (NS) with detemir and glargine, respectively. FPG improved from 10.8 to 7.1 and 7.0 mmol/l (NS), respectively. With detemir, 45% of participants completed the study on once daily dosing and 55% on twice daily dosing, with no difference in HbA(1c). Overall, 52% of participants achieved HbA(1c) <or= 7.0%: 33% (detemir) and 35% (glargine) without hypoglycaemia. Within-participant variability for self-monitored FPG and pre-dinner PG did not differ by insulin treatment, nor did the relative risk of overall or nocturnal hypoglycaemia. Modest reductions in weight gain were seen with detemir vs glargine in completers (3.0 vs 3.9 kg, p=0.01) and in the intention-to-treat population (2.7 vs 3.5 kg, p=0.03), primarily related to completers on once-daily detemir. Mean daily detemir dose was higher (0.78 U/kg [0.52 with once daily dosing, 1.00 U/kg with twice daily dosing]) than glargine (0.44 IU/kg). Injection site reactions were more frequent with detemir (4.5 vs 1.4%). CONCLUSIONS/INTERPRETATION: Supplementation of oral agents with detemir or glargine achieves clinically important improvements in glycaemic control with low risk of hypoglycaemia. Non-inferiority was demonstrated for detemir using higher insulin doses (mainly patients on twice daily dosing); weight gain was somewhat reduced with once daily insulin detemir.
PMID: 18204830 [PubMed - indexed for MEDLINE]
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Tags: Diabetologia
The effect of 1 month of therapy with midodrine, octreotide-LAR and albumin in refractory ascites: a pilot study.
Liver Int. 2008 May 19;
Authors: Tandon P, Tsuyuki RT, Mitchell L, Hoskinson M, Ma MM, Wong WW, Mason AL, Gutfreund K, Bain VG
Background: The pathogenesis of refractory ascites (RA) is linked to splanchnic vasodilation. We hypothesized that a combination of midodrine, octreotide long-acting release (LAR) and albumin would result in increased natriuresis, better control of ascites and an improvement in renal function in patients with RA+/-Type 2 hepatorenal syndrome. Methods: A prospective pilot study in patients with RA as defined by the International Ascites Club. Consecutive patients received an intramuscular injection of octreotide-LAR, 50 g of albumin three times per week and midodrine titrated to increase the systolic blood pressure for 1 month. Results: Ten patients with RA were enrolled and eight with complete data to 1 month post-treatment were included in the analysis. There was no change in renal function but there was a trend towards a reduction in the volume of ascites removed by paracentesis (P=0.08) and a significant reduction in the plasma renin (P=0.01) and aldosterone concentrations (P=0.01). Interestingly, there was a transient worsening in the model for end-stage liver disease (MELD) score (P=0.01). The deterioration in MELD was completely reversible after discontinuation of therapy. Conclusions: To our knowledge, this is the first study of prolonged midodrine, octreotide and albumin therapy in RA. We observed a significant reduction in the plasma renin and aldosterone concentrations and a trend towards a reduction in the volume of ascites removed by paracentesis without an effect on renal function. The beneficial effects are at the expense of a reversible deterioration in the MELD score. Large controlled trials are needed before this therapy can be routinely recommended.
PMID: 18492024 [PubMed - as supplied by publisher]
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Tags: Liver Int
Preparing medical students for clerkships: a descriptive analysis of transition courses.
Acad Med. 2008 May;83(5):444-51
Authors: Poncelet A, O’Brien B
Students have reported several challenging aspects of the transition to clerkships, such as applying clinical knowledge, learning experientially, using clinical skills, adjusting to clinical settings, and understanding roles. In an effort to address some of these challenges, a number of medical schools have added transition courses to their curricula, but little information about these courses has been published. The authors draw on findings from a study of the design and content of 30 transition courses offered in U.S. medical schools, to examine various approaches and provide a framework to guide the design of transition courses.Most courses (83%) were between one day and one week long. The authors identified three primary course themes: presentation of new information and skills, review and application of content covered in the preclerkship curriculum, and student well-being. All courses presented new information and skills, and more than half of the courses (53%) addressed all three themes. The most common curricular topics were technical/procedural skills, safety precautions, orientation to clinical settings, review of clinical skills, and stress management. Hands-on experience was the most frequently used instructional approach. Few courses had explicit goals and objectives, and evaluation of students was rare.Transition courses can address some of the needs and challenges associated with early clerkship experiences. These courses should explicitly target areas of need that are described in the literature as well as those identified within one’s own institution. They should include clear objectives, learning activities tailored to the areas of need and objectives, and student and course evaluations.
PMID: 18448897 [PubMed - indexed for MEDLINE]
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Tags: Acad Med
What makes a good clinical teacher in medicine? A review of the literature.
Acad Med. 2008 May;83(5):452-66
Authors: Sutkin G, Wagner E, Harris I, Schiffer R
PURPOSE: The authors perform a review of the literature pertinent to the question, “What makes a good clinical teacher in medicine?” METHOD: After framing the question, based on discussions of their own experiences with clinical teachers, the authors performed a search of the literature pertinent to the question, “What are the qualities of a good clinical teacher in medicine?” Between July and December, 2006, they reviewed titles from Index Medicus (1909-1966), PubMed (1966 to the present), PubMed Related Articles, and referenced articles. The initial selections were chosen by scanning pre-1966 Index Medicus title lists and post-1966 abstracts. Chosen articles were then read in their entirety, and those which described specific characteristics of clinical teachers were selected for inclusion. Qualitative analysis was used to identify themes. RESULTS: From 4,914 titles, 68 articles were selected for analysis-26 published before 1966, and 42 published after 1966. Four hundred eighty descriptors were identified and grouped into 49 themes, which were clustered into three main categories: physician, teacher, and human characteristics. Echoing the authors’ intuitive descriptions, noncognitive characteristics dominated the descriptions and themes. CONCLUSIONS: Excellent clinical teaching, although multifactorial, transcends ordinary teaching and is characterized by inspiring, supporting, actively involving, and communicating with students. Faculty development programs and future research should focus on development of the noncognitive attributes of clinical teachers, as well as the knowledge and skills associated with effective teaching.
PMID: 18448899 [PubMed - indexed for MEDLINE]
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Tags: Acad Med
Strategies for residency programs that improve medicine departments and teaching hospitals.
Am J Med. 2008 May;121(5):450-5
Authors: Rahim A, Anderson RA
PMID: 18456042 [PubMed - indexed for MEDLINE]
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Tags: Am J Med
The impact of increasing medical school class size on clinical clerkships: a national survey of internal medicine clerkship directors.
Acad Med. 2008 May;83(5):432-7
Authors: Hemmer PA, Ibrahim T, Durning SJ
PURPOSE: To determine the impact of increasing medical school class size on the internal medicine clerkship. METHOD: In 2006, the Clerkship Directors in Internal Medicine surveyed its 110 institutional members to discover whether their medical school class size had increased (or would increase) and the impact of increasing class size on number of students per teaching site, number of clerkship sites needed, and resources needed. Respondents rated their agreement or disagreement with statements about increasing class size, and they provided free-text responses. Analyses included descriptive statistics and qualitative analysis. RESULTS: Response rate was 76% (83/110). In the three years preceding the survey, one medical school decreased class size; 43% increased by a mean of 14 students per year (10%). Most respondents (51%) expected class size to increase by a mean of 17 students per year (12%) through 2009; none expected class size to decrease.Increasing class size by 15% would mean adding 3.7 (standard deviation = 2.2) students per inpatient site, 2.9 (2.9) new inpatient sites, 3.0 (2.2) students per ambulatory site, and 4.9 (5.5) ambulatory sites.Respondents disagreed with the questionnaire statements that they would have more resources, teachers, and protected time; they agreed with statements that recruiting teachers would be harder as class size increases. Free-text responses to the challenges of increasing class size revealed two themes: strain on resources (space, time, faculty), and the impact on the educational experience. CONCLUSIONS: Internal medicine clerkship directors believe increasing medical school class size will dramatically increase resources needed during clerkships and may adversely impact education.
PMID: 18448895 [PubMed - indexed for MEDLINE]
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Tags: Acad Med
Perspective: the unintended consequences of training residents in dysfunctional outpatient settings.
Acad Med. 2008 May;83(5):498-502
Authors: Keirns CC, Bosk CL
In the past 25 years, academic leaders and accreditation bodies in internal medicine and pediatrics have made multiple efforts to increase residents’ exposure to ambulatory primary care medicine, to bring hospital-based residency training more in line with the career paths of graduates. Current proposals continue the trend of increasing ambulatory exposure through providing more clinical hours in the outpatient setting as a pedagogic strategy to improve residents’ practical skills in providing quality care in outpatient settings. Resident clinics, however, are often understaffed and dysfunctional. Under these circumstances, the work environment encourages some residents to learn only that providing high-quality primary care is a frustrating and unrewarding form of labor. Leaders in medicine have used innovative organizational strategies to improve residents’ outpatient experiences. Model primary care residency programs and clinics have been created. The diffusion of model primary care clinical practices and structures is, however, limited by the strain of generating sufficient clinical revenue to run an academic medical center efficiently and reliably in the current environment. Increased outpatient exposure, without attention to the quality of practice settings, is potentially counterproductive, generating an unintended consequence that is the opposite of the goals of policy: it may reinforce residents’ interest in subspecialty practice.
PMID: 18448907 [PubMed - indexed for MEDLINE]
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Tags: Acad Med
Why internists need to be able to manage patients with myocardial infarction.
Am J Med. 2008 May;121(5):357
Authors: Alpert JS
PMID: 18456024 [PubMed - indexed for MEDLINE]
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Tags: Am J Med
Catheter ablation vs antiarrhythmic drug therapy for atrial fibrillation: a systematic review.
Arch Intern Med. 2008 Mar 24;168(6):581-6
Authors: Noheria A, Kumar A, Wylie JV, Josephson ME
BACKGROUND: Circumferential pulmonary vein ablation (CPVA) has become common therapy for atrial fibrillation (AF), but results of large randomized controlled trials comparing this procedure with antiarrhythmic drug therapy (ADT) have not been published to date. We conducted a systematic literature review to assess whether CPVA is superior to ADT for the management of AF. METHODS: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials for relevant randomized controlled trials. Data were abstracted to construct a 2 x 2 table for each trial. Recurrence of any atrial tachyarrhythmia (AT) was considered the primary end point of the trials. The estimate and confidence interval for the pooled risk ratio of AT recurrence-free survival in the CPVA group vs the ADT group were obtained using the random-effects model. RESULTS: Four trials qualified for the meta-analysis. In total, 162 of 214 patients (75.7%) in the CPVA group had AT recurrence-free survival vs 41 of 218 patients (18.8%) in the ADT group. The random-effects pooled risk ratio for AT recurrence-free survival was 3.73 (95% confidence interval, 2.47-5.63). In addition, fewer adverse events were reported in the CPVA group compared with that in the ADT group. CONCLUSIONS: We observed statistically significantly better AT recurrence-free survival with CPVA than with ADT. These results highlight the need for larger trials to determine the appropriate role for CPVA in the management of AF. Ongoing clinical trials may provide further guidance on these treatment options for AF.
PMID: 18362249 [PubMed - indexed for MEDLINE]
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Tags: Arch Intern Med
Efficacy of oral beta-lactam versus non-beta-lactam treatment of uncomplicated cellulitis.
Am J Med. 2008 May;121(5):419-25
Authors: Madaras-Kelly KJ, Remington RE, Oliphant CM, Sloan KL, Bearden DT
BACKGROUND: Preferred therapy for purulent skin and soft tissue infections is incision and drainage, but many infections cannot be drained. Empiric therapies for these infections are ill-defined in the era of community-acquired methicillin-resistant Staphylococcus aureus. METHODS: A multicenter retrospective cohort study of outpatients treated for cellulitis was conducted to compare clinical failure rates of oral beta-lactam and non-beta-lactam treatments. Exclusion criteria included purulent infection requiring incision and drainage, complicated skin and soft tissue infection, chronic ulceration, and intravenous antibiotics. Failure rates were compared using logistic regression to adjust for both covariates associated with failure and a propensity score for beta-lactam treatment. RESULTS: Of 2977 patients, 861 met inclusion criteria and were classified by treatment: beta-lactam (n = 631) or non-beta-lactam therapy (n = 230). Failure rates were 14.7% versus 17.0% (odds ratio [OR] 0.85, 95% confidence interval [CI], 0.56-1.31) for beta-lactam and non-beta-lactam therapy, respectively. Failure was associated with: age (P = .02), acute symptom severity (P = .03), animal bites (P = .03), Charlson score > 3 (P = .02), and histamine-2 receptor antagonist use (P = .09). Relative efficacy of beta-lactam therapy was greater after adjustment for factors associated with failure but remained statistically insignificant (adjusted OR 0.81, 95% CI, 0.53-1.24); adjusted including propensity score covariate (OR 0.71, 95% CI, 0.45-1.13). Discontinuation due to adverse effects differed between beta-lactam (0.5%) and non-beta-lactam (2.2%) therapies (P = .04). CONCLUSION: There was no significant difference in clinical failure between beta-lactam and non-beta-lactam antibiotics for the treatment of uncomplicated cellulitis. Increased discontinuation due to adverse events with non-beta-lactam therapy was observed.
PMID: 18456038 [PubMed - indexed for MEDLINE]
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Tags: Am J Med
