Avi Porath

Metformin use and mortality among patients with diabetes and atherothrombosis.

BACKGROUND Metformin is recommended in type 2 diabetes mellitus because it reduced mortality among overweight participants in the United Kingdom Prospective Diabetes Study when used mainly as a means of primary prevention. However, metformin is often not considered in patients with cardiovascular conditions because of concerns about its safety. METHODS We assessed whether metformin use was associated with a difference in mortality among patients with atherothrombosis. The study sample comprised 19 691 patients having diabetes with established atherothrombosis participating in the Reduction of Atherothrombosis for Continued Health (REACH) Registry between December 1, 2003, and December 31, 2004, treated with or without metformin. Multivariable adjustment and propensity score were used to account for baseline differences. The main outcome measure was 2-year mortality. RESULTS The mortality rates were 6.3% (95% confidence interval [CI], 5.2%-7.4%) with metformin and 9.8% 8.4%-11.2%) without metformin; the adjusted hazard ratio (HR) was 0.76 (0.65-0.89; P < .001). Association with lower mortality was consistent among subgroups, noticeably in patients with a history of congestive heart failure (HR, 0.69; 95% CI, 0.54-0.90; P = .006), patients older than 65 years (0.77; 0.62-0.95; P = .02), and patients with an estimated creatinine clearance of 30 to 60 mL/min/1.73 m(2) (0.64; 95% CI, 0.48-0.86; P = .003) (to convert creatinine clearance to mL/s/m(2), multiply by 0.0167). CONCLUSIONS Metformin use may decrease mortality among patients with diabetes when used as a means of secondary prevention, including subsets of patients in whom metformin use is not now recommended. Metformin use should be tested prospectively in this population to confirm its effect on survival.

Fertility drugs and the risk of breast and ovarian cancers: results of a long-term follow-up study

OBJECTIVE To investigate a possible linkage between the use of fertility drugs for infertility and the risk of breast and ovarian cancers. DESIGN Long-term, historic-prospective study. SETTING Fertility clinic in a university hospital. PATIENT(S) Files of 1,197 infertile women with a mean (+/- SD) follow-up of 17.9+/-5 years (21,407 person-years) were reviewed. Diagnoses, number of courses, and dosage of fertility drugs were extracted from the files. INTERVENTION(S) Cancers were identified by record linkage to the National Cancer Registry. Histopathologic reports and data on estrogen and progesterone receptors in breast cancer tissue were also reviewed. MAIN OUTCOME MEASURE(S) Standardized incidence ratio with 95% confidence interval (CI) were used for risk assessment. RESULT(S) Of 20 breast cancers (standardized incidence ratio, 1.40 [95% CI, 0.83-2.10]), 16 were detected among 780 women who had been exposed to 3,978 cycles of clomiphene citrate (CC) and/or hMG (standardized incidence ratio, 1.65 [95% CI, 0.94-2.68]). The standardized incidence ratio for this cancer was significantly increased only in patients with one or two CC treatments and a dose of < or =1,000 mg (2.6 [1.19-5.0] and 2.52 [1.21-4.64], respectively). Two cases of ovarian cancer (1 patient unexposed) were observed with no evidence of excessive risk. Six of the eight patients with data on estrogen and progesterone receptors were exposed to CC, and all tested positive for these receptors. CONCLUSION(S) An association between the use of fertility drugs and an increased risk of breast and ovarian cancers has not been confirmed.

Nosocomial multi-drug resistant Acinetobacter baumannii bloodstream infection: risk factors and outcome with ampicillin-sulbactam treatment

The emergence of multidrug-resistant (MDR) Acinetobacter baumannii poses a therapeutic problem. The aim of this study was to assess the risk factors for nosocomial MDR-A. baumannii bloodstream infection (BSI) and the efficacy of ampicillin-sulbactam (A/S) in its treatment. Of 94 nosocomial A. baumannii BSI during the year 2000, 54% involved MDR strains, 81% of which were genetically related. Various risk factors for MDR-A. baumannii were found, of which intensive-care unit admission and prior aminoglycoside therapy were independently associated with MDR-A. baumannii acquisition on multivariate analysis. Of MDR-A. baumannii BSI cases, 65% received A/S and 35% inadequate antibiotic therapy, whereas of 43 non-MDR cases, 86% were treated according to susceptibility and 14% inappropriately with antibiotics to which these organisms were resistant. Crude mortality was comparable in the adequately treated groups. Respective mortalities among patients treated adequately and inadequately were 41.4 and 91.7% (p<0.001). Among severely ill patients, A/S therapy significantly decreased the risk of death (P=0.02 OR=7.64). MDR-A. baumannii has become highly endemic in our institution. A/S appears to be one of the last effective and safe empirical resorts for treatment of MDR A. baumannii BSI.

The effect of statin therapy on infection-related mortality in patients with atherosclerotic diseases*

Objective:Statins have pleiotropic effects that are independent of their lipid-lowering ability. We have previously shown that prior statin therapy is associated with a decreased risk of severe sepsis in patients admitted with acute bacterial infection. The aim of this study was to determine whether statin therapy is associated with a decreased risk of infection-related mortality. Design:A prospective, observational, population-based study. Setting:Tertiary university medical center. Patients:Using a computerized database, 11,490 patients with atherosclerotic diseases were identified and followed for up to 3 yrs. Two groups of patients were compared: those receiving statins in the final month before follow-up termination and those who were not. Interventions:None. Measurements and Main Results:The primary outcome was infection-related mortality. Of the 11,362 patients included in the final analysis, 5,698 (50.1%) belonged to the statin group. Median follow-up was 19.8 months (interquartile range, 14.3–33.3). The risk of infection-related mortality was significantly lower in the statin compared with the no-statin group (0.9% vs. 4.1%), reflecting a relative risk of 0.22 (95% confidence interval, 0.17–0.28). Stepwise Cox proportional hazard survival analysis including a propensity score for receiving statins revealed that the protective effect of statins adjusted for all known potential confounders remained highly significant (hazard ratio, 0.37; 95% confidence interval, 0.27–0.52). Conclusions:Therapy with statins may be associated with a reduced risk of infection-related mortality. This protective effect is independent of all known comorbidities and dissipates when the medication is discontinued. If this finding is supported by prospective controlled trials, statins may play an important role in the primary prevention of infection-related mortality.

A simple bedside test of 1-minute heart rate variability during deep breathing as a prognostic index after myocardial infarction☆☆☆

BACKGROUND We evaluate a simple, bedside test that measures 1-minute heart rate variability in deep breathing as a predictor of death after myocardial infarction. METHODS Bedside heart rate variability was assessed in 185 consecutive patients 5.1 +/- 2.5 days after a first myocardial infarction. Patients were instructed to take 6 deep respirations in 1 minute while changes in heart rate were measured and calculated by an electrocardiographic recorder. An abnormal test result was defined as a difference of less than 10 beats/min between the shortest and longest heart rate interval. RESULTS Heart rate variability <10 beats/min was found in 65 patients (35%) and was significantly lower (P <.05) in women, patients >60 years of age, patients with diabetes, patients with congestive heart failure, and patients taking angiotensin-converting enzyme inhibitors. Mean follow-up period was 16 months. Ten patients died during follow-up: 9 of cardiac causes and 1 of stroke. Nine of these 10 patients had heart rate variability <10 beats/min (P =.004). The sensitivity and specificity of this test for cardiovascular mortality is 90.0% and 68.0%, respectively. The negative predictive value is 99.2% and the relative risk is 16.6. Heart rate variability <10 beats/min remained a significant predictor of death after adjusting for clinical, demographic, and left ventricular function with an odds ratio of 1.38 (95% confidence interval, 1.13-1.63). CONCLUSIONS This simple, brief bedside deep breathing test of heart rate variability in patients after myocardial infarction appears to be a good predictor for all-cause mortality and sudden death. It may be used as a clinical test for risk stratification after myocardial infarction.

Dibromochloropropane (dbcp): A 17-year Reassessment of Testicular Function and Reproductive Performance

The current study summarizes a 17-year revaluation of testicular function and reproductive performance of 15 production workers with dibromochloropropane (DBCP)-induced testicular dysfunction. Sperm count recovery was evident within 36 to 45 months in three of the nine azoospermic and in three of the six oligozoospermic men with no improvement thereafter. A significant increase in plasma folliclestimulating hormone (FSH) and luteinizing hormone (LH) and a nonsignificant decrease in testosterone level were detected in the severely affected individuals. There was no increase in the rate of spontaneous abortions and congenital malformations among pregnancies conceived during or after exposure. A low prevalence of male infants conceived during paternal exposure was found as compared with the preexposure period (16.6% versus 52.9%; P<.025). Restoration of fertility was followed by a gradual increase of this value to 41.4%.

Persistence with Statins and Onset of Rheumatoid Arthritis: A Population-Based Cohort Study

In a retrospective cohort study, Gabriel Chodick and colleagues find a significant association between persistence with statin therapy and reduced risk of developing rheumatoid arthritis, but only a modest decrease in risk of osteoarthritis.

The epidemiology of community-acquired pneumonia among hospitalized adults

OBJECTIVE To identify and characterize the aetiological agents of community-acquired pneumonia (CAP) among hospitalized patients, as an aid in therapeutic decision-making. METHOD A prospective 1 year study of all patients hospitalized with CAP in the Negev region of Israel. The aetiology was determined by blood and pleural fluid cultures, and specific serological testing for pathogenic agents. Eighty-nine percent of the patients underwent follow-up for a month after discharge. RESULTS The study included 346 patients (53% males, mean age 49.3 +/- 19.5, range 17-94). A single aetiologic agent was identified in 146 patients (42.2%), multiple agents were found in 133 (38.4%), and no agent was identified in 67 (19.4%). Among the common pathogens were Pneumococcus sp. in 148 patients (42.8%). Mycoplasma pneumoniae (101, 29.2%), Chlamydia pneumoniae (62, 17.9%), Legionella sp. (56, 16.2%), viruses (35, 10.1%), Coxiella burnetti (20, 5.8%). Haemophilus influenzae (19, 5.5%), and other bacteria (21, 6.1%). Approximately 70% of the patients infected with M. pneumoniae and C. burnetti were younger than 45 years (P < 0.05). In contrast, about 50% of the patients with C. pneumoniae (TWAR) were over the age of 65 (P = 0.03). The presence of comorbidity was associated with a greater frequency of bacterial aetiologies (57% vs. 44%, P = 0.02), and fewer infections with M. pneumoniae (15% vs. 36%, P = 0.0004), or C. burnetii (2% vs. 8%, P = 0.02). Specific causative agents were associated with specific seasons: viruses between December and April (P = 0.03), and Legionella sp. from July to October (P = 0.003). In contrast, no seasonal variation was associated with pneumococcus, M. pneumoniae, or C. pneumoniae (TWAR). CONCLUSIONS Patients are hospitalized with CAP throughout the year. Since the pathogen is usually unknown at hospitalization, epidemiological data is important for choosing medication. The findings of this study point to the importance of macrolides alone or in combination with cephalosporins, as the treatment of choice for patients in our region.

Mycoplasma pneumoniae community-acquired pneumonia: a review of 101 hospitalized adult patients.

The features of community-acquired Mycoplasma pneumoniae pneumonia (MP-CAP) were assessed in a prospective study of 101 adults who were hospitalized over the course of 1 year, and were compared with 245 patients who were hospitalized during the same period of time with community-acquired pneumonia (CAP) not caused by M. pneumoniae (non-MP-CAP). MP was the second most common etiology (29.2%) in all CAP patients, and the most common etiological agent (43.2%) in the 17- to 44-year age group. In 65 patients (64.3%) at least one other pathogen was identified for CAP in addition to MP. Although the disease was most prevalent among younger patients, it also involved older and even elderly patients. Compared to non-MP-CAP patients, the severity of disease was significantly lower on average in the MP-CAP group and the length of hospitalization was significantly shorter. Radiologic findings were the same in the two groups. Twenty-two MP-CAP patients recovered without receiving the treatment which is recognized as effective in this disease. We concluded that (1) in most patients with MP-CAP a second CAP pathogen can be identified serologically, (2) MP-CAP cannot be differentiated from non-MP-CAP on the basis of clinical, radiologic, or routine laboratory tests, and (3) in some MP-CAP patients the disease is self-limited, and in these patients the usefulness of standard antibiotic therapy is doubtful.

Routine Laboratory Results and Thirty Day and One-Year Mortality Risk Following Hospitalization with Acute Decompensated Heart Failure

Introduction Several blood tests are performed uniformly in patients hospitalized with acute decompensated heart failure and are predictive of the outcomes: complete blood count, electrolytes, renal function, glucose, albumin and uric acid. We sought to evaluate the relationship between routine admission laboratory tests results, patient characteristics and 30-day and one-year mortality of patients admitted for decompensated heart failure and to construct a simple mortality prediction tool. Methods A retrospective population based study. Data from seven tertiary hospitals on all admissions with a principal diagnosis of heart failure during the years 2002–2005 throughout Israel were captured. Results 8,246 patients were included in the study cohort. Thirty day mortality rate was 8.5% (701 patients) and one-year mortality rate was 28.7% (2,365 patients). Addition of five routine laboratory tests results (albumin, sodium, blood urea, uric acid and WBC) to a set of clinical and demographic characteristics improved c-statistics from 0.76 to 0.81 for 30-days and from 0.72 to 0.76 for one-year mortality prediction (both p-values <0.0001). Three dichotomized abnormal laboratory results with highest odds ratio for one-year mortality (hypoalbuminaemia, hyponatremia and elevated blood urea) were used to construct a simple prediction score, capable of discriminating from 1.1% to 21.4% in 30-day and from 11.6% to 55.6% in one-year mortality rates between patients with a score of 0 (1,477 patients) vs. score of 3 (544 patients). Discussion A small set of abnormal routine laboratory results upon admission can risk-stratify and independently predict 30-day and one-year mortality in patients hospitalized with acute decompensated heart failure.