Tuesday, April 09, 2019
Tuesday, April 02, 2019
Extended infusion protocols for piperacillin-tazobactam (PTZ): do they mitigate nephrotoxicity?
Not in this study. From the paper:
Our findings suggest a similar rate of nephrotoxicity between patients who received vancomycin in combination with PTZ EI versus PTZ SI. These results need to be further validated in a prospective randomized controlled study.
A little background on thalidomide
Thalidomide is a drug with interesting therapeutic properties but also with severe side effects which require a careful and monitored use. Potential immunomodulatory, antiinflammatory, anti-angiogenic and sedative properties make thalidomide a good candidate for the treatment of several diseases such as multiple myeloma. Through an increase in the degradation of TNFα-mRNA, thalidomide reduces the production of TNFα by monocytes and macrophages stimulated by lipopolysaccharide or by T lymphocytes induced by mitogenic stimuli. The decreased level of TNFα alters the mechanisms of intracellular transduction by preventing the activation of NF-kB and by decreasing the synthesis of proteins, in particular IL-6, involved in cell proliferation, inflammation, angiogenesis and protection from apoptosis. Furthermore, thalidomide affects VEGF levels by down-regulating its expression. Nowadays, new safer and less toxic drugs, analogs of thalidomide, are emerging as beneficial for a more targeted treatment of multiple myeloma and several other diseases such as Crohn';s disease, rheumatoid arthritis, sarcoidosis, erythema nodosum leprosum, graft-versus-host disease.
Syncope guidelines
Unbelievably long
for what should be a simple topic, but everything you’re likely to
want or need to know is here.
Monday, April 01, 2019
Saturday, March 30, 2019
Friday, March 29, 2019
Low vitamin D levels associated with increased mortality
Objective
To determine the relationship between 25-hydroxyvitamin D (25[OH]D) values and all-cause and cause-specific mortality.
Patients and Methods
We identified all serum 25(OH)D measurements in adults residing in Olmsted County, Minnesota, between January 1, 2005, and December 31, 2011, through the Rochester Epidemiology Project. All-cause mortality was the primary outcome. Patients were followed up until their last clinical visit as an Olmsted County resident, December 31, 2014, or death. Multivariate analyses were adjusted for age, sex, race/ethnicity, month of measurement, and Charlson comorbidity index score.
Results
A total of 11,022 individuals had a 25(OH)D measurement between January 1, 2005, and December 31, 2011, with a mean ± SD value of 30.0±12.9 ng/mL. Mean age was 54.3±17.2 years, and most were female (77.1%) and white (87.6%). There were 723 deaths after a median follow-up of 4.8 years (interquartile range, 3.4-6.2 years). Unadjusted all-cause mortality hazard ratios (HRs) and 95% CIs for 25(OH)D values of less than 12, 12 to 19, and more than 50 ng/mL were 2.6 (95% CI, 2.0-3.2), 1.3 (95% CI, 1.0-1.6), and 1.0 (95% CI, 0.72-1.5), respectively, compared with the reference value of 20 to 50 ng/mL. In a multivariate model, the interaction between the effect of 25(OH)D and race/ethnicity on mortality was significant (P<.001). In white patients, adjusted HRs for 25(OH)D values of less than 12, 12 to 19, 20 to 50, and greater than 50 ng/mL were 2.5 (95% CI, 2.2-2.9), 1.4 (95% CI, 1.2-1.6), 1.0 (referent), and 1.0 (95% CI, 0.81-1.3), respectively. In patients of other race/ethnicity, adjusted HRs were 1.9 (95% CI, 1.5-2.3), 1.7 (95% CI, 1.1-2.6), 1.5 (95% CI, 1.0-2.0), and 2.1 (95% CI, 0.77-5.5).
Conclusion
White patients with 25(OH)D values of less than 20 ng/mL had greater all-cause mortality than those with values of 20 to 50 ng/mL, and white patients had greater mortality associated with low 25(OH)D values than patients of other race/ethnicity. Values of 25(OH)D greater than 50 ng/mL were not associated with all-cause mortality.
Troponin elevation in stroke may point to a cardioembolic etiology
Abstract
Background Our aim was to determine whether patients with embolic strokes of undetermined source (ESUS) have higher rates of elevated troponin than patients with noncardioembolic strokes.
Methods and Results CAESAR (The Cornell Acute Stroke Academic Registry) prospectively enrolled all adults with acute stroke from 2011 to 2014. Two neurologists used standard definitions to retrospectively ascertain the etiology of stroke, with a third resolving disagreements. In this analysis we included patients with ESUS and, as controls, patients with small‐ and large‐artery strokes; only patients with a troponin measured within 24 hours of stroke onset were included. A troponin elevation was defined as a value exceeding our laboratory's upper limit (0.04 ng/mL) without a clinically recognized acute ST‐segment elevation myocardial infarction. Multiple logistic regression was used to evaluate the association between troponin elevation and ESUS after adjustment for demographics, stroke severity, insular infarction, and vascular risk factors. In a sensitivity analysis we excluded patients diagnosed with atrial fibrillation after discharge. Among 512 patients, 243 (47.5%) had ESUS, and 269 (52.5%) had small‐ or large‐artery stroke. In multivariable analysis an elevated troponin was independently associated with ESUS (odds ratio 3.3; 95% confidence interval 1.2, 8.8). This result was unchanged after excluding patients diagnosed with atrial fibrillation after discharge (odds ratio 3.4; 95% confidence interval 1.3, 9.1), and the association remained significant when troponin was considered a continuous variable (odds ratio for log[troponin], 1.4; 95% confidence interval 1.1, 1.7).
Conclusions Elevations in cardiac troponin are more common in patients with ESUS than in those with noncardioembolic strokes.
Unfortunately the
test characteristics for determining cardioembolic stroke are poor.
Most patients with cardioembolic stroke do not have elevated
troponins and some with other types of stroke have elevations.
Thursday, March 28, 2019
Appropriateness of troponin ordering in the hospital
Troponin assays are integral to the diagnosis of acute myocardial infarction (AMI), but there is concern that testing is over utilized and may not conform to published guidelines. We reviewed all testing performed at 14 hospitals over 12 months and associated troponin values with the primary and secondary diagnoses for each visit. Troponin was determined to be negative, indeterminate or elevated based on reference ranges. The majority of troponin measurements were single, not serial (64%). The rate of AMI was low, with only 3.5% of tested patients having a primary or secondary diagnosis of AMI. Sensitivity, specificity and negative predictive value were excellent, exceeding 90%. However, positive predictive value was low, suggesting testing of populations with diseases known to be associated with elevated troponin levels in the absence of AMI. The majority (79%) of elevated troponin values were associated with primary diagnoses other than AMI. Only 28% of elevated troponins were associated with a primary or secondary diagnosis of AMI. These data suggest possible overuse of troponin testing in our healthcare system. Journal of Hospital Medicine 2017;12:329-331. © 2017 Society of Hospital Medicine
This conclusion is
premised on the idea that the only reason to order a troponin is to
diagnose or exclude MI.
Triple antibiotic therapy against carbapenemase producing bacteria
Here is a review
on the topic. These regimens have been our go-to for a while now and
are effective although the crude mortality for these infections
remains high, in the 30+% range. Newer antibiotics either approved
or in the pipeline have brightened the outlook. From the article:
A few emerging treatment options for CPKP infections appear promising. The most prominent new agent is ceftazidime–avibactam, a cephalosporin combined with a novel β-lactamase inhibitor approved by the US Food and Drug Administration (FDA) in February 2015 [60]. Ceftazidime–avibactam has shown potent in vitro activity against CRE isolates [61–63]. and there have also been reports that ceftazidime–avibactam is effective for CPKP infections after other combination regimens have failed [19, 64, 65]. Other β-lactam/β-lactamase inhibitor combinations are also being investigated including ceftolozane–tazobactam and aztreonam–avibactam [12, 66]. Plazomicin, a novel aminoglycoside that has shown in vitro activity against CRE, is currently undergoing a Phase 3 clinical trial (NCT01970371) as part of a combination therapy [67]. Another agent showing potential is eravacycline, a tetracycline derivative, which has shown in vitro efficacy against CRE as well as for complicated intra-abdominal infections and complicated urinary tract infections in clinical trials [68, 69].
Targeted temperature management post arrest: how long?
Question Does targeted temperature management at 33°C for 48 hours result in better neurologic outcome compared with standard 24-hour targeted temperature management in unconscious patients with out-of-hospital cardiac arrest?
Findings In this randomized clinical trial enrolling 355 adults with out-of-hospital cardiac arrest, there was no significant difference in favorable neurologic outcome at 6 months for those treated for 48 hours (69%) vs 24 hours (64%) (difference, 5%).
Meaning Prolonged targeted temperature management at 33°C did not result in better neurologic outcome; however, the study may have had limited power to detect clinically important differences, and further research may be warranted.
Wednesday, March 27, 2019
Hospitalization rates and lengths of stay for VTE in Alberta Canada
Background
Acute venous thromboembolism leads to significant morbidity and mortality. Advances in pharmacotherapy facilitate outpatient care in low-risk acute venous thromboembolism. The proportion of hospitalized acute venous thromboembolism cases and the average length of stay are not known. We sought to identify predictors of hospitalization, changes in hospitalization rates and length of stay of acute venous thromboembolism over a decade in Alberta, Canada.
Methods
Using linked administrative health databases, we identified adult patients diagnosed primarily with acute venous thromboembolism between April 2002 and March 2012. We measured trends using Poisson regression, adjusted length of stay using analysis of covariance. We identified predictors of hospitalization using multivariate logistic regression.
Results
8198 out of 31,656 acute venous thromboembolism cases were hospitalized. The overall venous thromboembolism admission rates ranged between 23.7% and 27.8% with no evident temporal trend (P = 0.10). The average admission rate was 51.9% for pulmonary embolism and 16.1% for deep vein thrombosis. The mean length of stay for deep vein thrombosis and pulmonary embolism remained unchanged with an adjusted mean for venous thromboembolism of 6.9 ± 1.0 days. Higher Charlson index, older age, male gender, pulmonary embolism at presentation and multiple comorbidities were associated with hospitalization. Hospitalization was associated with 30-day mortality (odds ratio:2.8, 95% CI: 2.2–3.5) whereas the length of stay was not (odds ratio:1.0, 95% CI: 0.99–1.0).
Conclusion
Hospitalization rates and mean length of stay for acute venous thromboembolism did not change significantly between 2002 and 2012. Advances in pharmacotherapy have not yet reduced hospitalization rates or length of stay for venous thromboembolism.
Tuesday, March 26, 2019
Hepatic encephalopathy update
Hepatic encephalopathy is a state of brain dysfunction resulting from decompensation of cirrhosis. The mortality and morbidity associated with the overt form of hepatic encephalopathy are high, and even the covert form associates with poor outcomes and poor quality of life. We know that the dysfunction is not just an acute insult to the brain but rather results in long-standing cognitive issues that get worse with each episode of HE. Hence, there is an urgency to accurately diagnose these conditions, start appropriate therapy, and to maintain remission. Currently, we have two mainstay pharmacological treatment options (lactulose and rifaximin), but the narrative is evolving with new therapies under trial. Microbiome manipulation resulting in a favorable change to the gut microbiota seems to be a promising new area of therapy.
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