Sunday, December 30, 2018
Saturday, December 29, 2018
Background A few studies have recently reported clockwise and counterclockwise rotations of QRS transition zone as predictors of mortality. However, their prospective correlates and associations with individual cardiovascular disease (CVD) outcomes are yet to be investigated.
Methods and Results Among 13 567 ARIC (Atherosclerosis Risk in Communities) study participants aged 45 to 64 years, we studied key correlates of changes in the status of clockwise and counterclockwise rotation over time as well as the association of rotation status with incidence of coronary heart disease (2408 events), heart failure (2196 events), stroke (991 events), composite CVD (4124 events), 898 CVD deaths, and 3469 non‐CVD deaths over 23 years of follow‐up. At baseline, counterclockwise rotation was most prevalent (52.9%), followed by no (40.5%) and clockwise (6.6%) rotation. Of patients with no rotation, 57.9% experienced counterclockwise or clockwise rotation during follow‐up, with diabetes mellitus and black race significantly predicting clockwise and counterclockwise conversion, respectively. Clockwise rotation was significantly associated with higher risk of heart failure (hazard ratio, 1.20; 95% confidence interval [CI], 1.02–1.41) and non‐CVD death (hazard ratio, 1.28; 95% CI, 1.12–1.46) after adjusting for potential confounders including other ECG parameters. On the contrary, counterclockwise rotation was significantly related to lower risk of composite CVD (hazard ratio, 0.93; 95% CI, 0.87–0.99]), CVD mortality (hazard ratio, 0.76; 95% CI, 0.65–0.88), and non‐CVD deaths (hazard ratio, 0.92; 95% CI, 0.85–0.99 [borderline significance with heart failure]).
Conclusions Counterclockwise rotation, the most prevalent QRS transition zone pattern, demonstrated the lowest risk of CVD and mortality, whereas clockwise rotation was associated with the highest risk of heart failure and non‐CVD mortality. These results have implications on how to interpret QRS transition zone rotation when ECG was recorded.
This makes perfect sense. Clockwise rotation is another term for poor R wave progression (PRWP). The differential diagnosis for PRWP, aside from the occasional normal variant, includes such things as LVH, anterior infarction, left anterior fascicle block, COPD and dilated cardiomyopathy, all bad things to one degree or another.
Background and Purpose—Primary angiitis of the central nervous system remains challenging. To report an overview and pictorial review of brain magnetic resonance imaging findings in adult primary angiitis of the central nervous system and to determine the distribution of parenchymal, meningeal, and vascular lesions in a large multicentric cohort.
Methods—Adult patients from the French COVAC cohort (Cohort of Patients With Primary Vasculitis of the Central Nervous System), with biopsy or angiographically proven primary angiitis of the central nervous system and brain magnetic resonance imaging available at the time of diagnosis were included. A systematic imaging review was performed blinded to clinical data.
Results—Sixty patients met inclusion criteria. Mean age was 45 years (±12.9). Patients initially presented focal deficit(s) (83%), headaches (53%), cognitive disorder (40%), and seizures (38.3%). The most common magnetic resonance imaging finding observed in 42% of patients was multiterritorial, bilateral, distal acute stroke lesions after small to medium artery distribution, with a predominant carotid circulation distribution. Hemorrhagic infarctions and parenchymal hemorrhages were also frequently found in the cohort (55%). Acute convexity subarachnoid hemorrhage was found in 26% of patients and 42% demonstrated pre-eminent leptomeningeal enhancement, which is found to be significantly more prevalent in biopsy-proven patients (60% versus 28%; P=0.04). Seven patients had tumor-like presentations. Seventy-seven percent of magnetic resonance angiographic studies were abnormal, revealing proximal/distal stenoses in 57% and 61% of patients, respectively.
Conclusions—Adult primary angiitis of the central nervous system is a heterogenous disease, with multiterritorial, distal, and bilateral acute stroke being the most common pattern of parenchymal lesions found on magnetic resonance imaging. Our findings suggest a higher than previously thought prevalence of hemorrhagic transformation and other hemorrhagic manifestations.
We retrospectively reviewed the medical records of 604 meningitis patients from the emergency department (ED) of our tertiary care, university-affiliated hospital over a five-year period. We analyzed the ability of blood PCT levels on admission to predict the outcome at discharge (defined as Glasgow Outcome Scale scores of 1–4). Of 71 patients with acute bacterial meningitis, 28 (39 %) experienced an unfavorable outcome at discharge (overall mortality: 5 %). The serum PCT level at admission was a predictive indicator of an unfavorable outcome [adjusted odds ratio: 1.04, 95 % confidence interval (CI) 1.01–1.09, p = 0.05]. As assessed using receiver operating characteristic curves for an unfavorable outcome, the area under the PCT curve was 0.708 (95 % CI 0.58–0.84, p less than 0.01). When the PCT cutoff value was greater than or equal to 1.10 ng/mL, the sensitivity, specificity, positive predictive value and negative predictive value for an unfavorable outcome were 75, 70, 62, and 81 %, respectively. An association between the serum PCT level and an unfavorable outcome is observed.
Friday, December 28, 2018
Objectives: To prospectively validate that the inability to decrease procalcitonin levels by more than 80% between baseline and day 4 is associated with increased 28-day all-cause mortality in a large sepsis patient population recruited across the United States.
Design: Blinded, prospective multicenter observational clinical trial following an Food and Drug Administration-approved protocol.
Setting: Thirteen U.S.-based emergency departments and ICUs.
Patients: Consecutive patients meeting criteria for severe sepsis or septic shock who were admitted to the ICU from the emergency department, other wards, or directly from out of hospital were included.
Interventions: Procalcitonin was measured daily over the first 5 days.
Measurements and Main Results: The primary analysis of interest was the relationship between a procalcitonin decrease of more than 80% from baseline to day 4 and 28-day mortality using Cox proportional hazards regression. Among 858 enrolled patients, 646 patients were alive and in the hospital on day 4 and included in the main intention-to-diagnose analysis. The 28-day all-cause mortality was two-fold higher when procalcitonin did not show a decrease of more than 80% from baseline to day 4 (20% vs 10%; p = 0.001). This was confirmed as an independent predictor in Cox regression analysis (hazard ratio, 1.97 [95% CI, 1.18–3.30; p less than 0.009]) after adjusting for demographics, Acute Physiology and Chronic Health Evaluation II, ICU residence on day 4, sepsis syndrome severity, antibiotic administration time, and other relevant confounders.
Conclusions: Results of this large, prospective multicenter U.S. study indicate that inability to decrease procalcitonin by more than 80% is a significant independent predictor of mortality and may aid in sepsis care.
Despite dramatic changes in the legal landscape and rates of cannabis use, the evidence base regarding its potential health and therapeutic effects remains surprisingly scant…
Thursday, December 27, 2018
Clinical PerspectiveWhat Is New?
In a longitudinal, population‐based sample of 13 168 residents from 4 US communities followed for a median of 23.6 years, participants with the metabolic syndrome had a 4.1% incidence of sudden cardiac death compared with 2.3% among participants without it.
The metabolic syndrome was independently associated with sudden cardiac death irrespective of sex or race.
Sudden cardiac death risk was proportional to the number of metabolic syndrome components.
What Are the Clinical Implications?
Sudden cardiac death risk associated with the metabolic syndrome may be reduced by treatment of high blood pressure, impaired glucose tolerance, and lipid levels.
Sunday, December 23, 2018
Here is a free full text review on the associations.
From the review:
Parathyroid hormone (PTH) acts on G-protein coupled receptors in the heart to exert changes in cardiac myocyte contractility, proliferation, and hypertrophy.
In the vasculature, PTH alters the endothelium.
Excess PTH (as seen in primary and secondary hyperparathyroidism) is associated with a higher incidence of hypertension, left ventricular hypertrophy, heart failure, cardiac arrhythmias, and valvular calcific disease, which may contribute to higher cardiac morbidity and mortality.
Low PTH states (as seen in congenital and acquired disorders of the parathyroid glands) are associated with cardiac arrhythmias and dilated cardiomyopathy.
Early medical and/or surgical treatment of parathyroid disorders can reverse detrimental structural and functional changes in the cardiovascular system such as left ventricular mass, conduction abnormalities, atherosclerotic disease, and valvular calcifications. This may result in reduced cardiac morbidity and mortality.
From a review:
Purpose of review
As Streptococcus pneumoniae was considered the etiological agent of nearly all the cases of pneumonia at the beginning of the 20th century, and today is identified in fewer than 10–15% of cases, we analyze the possible causes of such a decline.
Extensive use of early empiric antimicrobial therapy, discovery of previously unrecognized pathogens, availability to newer diagnostic methods for the recognition of the pneumonia pathogens (PCR, urinary antigens, monoclonal antibodies etc.) and of improved preventive measures, including vaccines, are some of possible explanations of the declining role of S. pneumoniae in the cause of pneumonia.
The 14-valent and the 23-valent capsular polysaccharide pneumococcal vaccines were licensed in 1977 and 1983, respectively. The seven-valent protein-conjugated capsular polysaccharide vaccine, approved for routine use in children starting at 2 months of age, was highly effective in preventing invasive pneumococcal disease in children but also in adults because of the herd effect. In 2010, the 13-valent protein-conjugated capsular polysaccharide vaccine replaced seven-valent protein-conjugated capsular polysaccharide vaccine. With the use of conjugated vaccines, a decrease of the vaccine-type invasive pneumococcal disease for all age groups was observed. Both the direct effect of the vaccine and the so-called herd immunity are considered responsible for much of the decline.
Saturday, December 22, 2018
It’s actually a gem of an article.
Recent review here.
It can mimic other pulmonary conditions, eg pneumonia, neoplasm.
Textbook reading plays a foundational role in a resident’s knowledge base. Many residency programs place residents on identical reading schedules, regardless of the clinical work or rotation the resident is doing. We sought to develop a reading curriculum that takes into account the clinical work a resident is doing so their reading curriculum corresponds with their clinical work. Preliminary data suggests an increased amount of resident reading and an increased interest in reading as a result of this change to their reading curriculum.
Long live the textbook. After evidence based medicine “became a thing” there were some who went so far as to recommend against reading textbooks. The idea was that there should be a singular focus on looking up answers to focused clinical questions at the point of care, a process known as “foreground reading.” Textbook reading is considered background reading. I contend both are important and dealt with the question in more detail here.
Friday, December 21, 2018
Question What is the association of thiazolidinedione therapy with advanced liver fibrosis in nonalcoholic steatohepatitis?
Findings In this meta-analysis of 8 randomized clinical trials enrolling 516 patients with biopsy-proven nonalcoholic steatohepatitis, thiazolidinedione therapy was associated with reversed advanced fibrosis, improved overall fibrosis stages, and resolution of nonalcoholic steatohepatitis. Pioglitazone hydrochloride use accounted for all of the effects of thiazolidinedione therapy in nonalcoholic steatohepatitis, and these benefits were observed in patients without diabetes as well.
Meaning Pioglitazone use improves advanced fibrosis in nonalcoholic steatohepatitis, even in patients without diabetes, and may thus halt disease progression to end-stage liver disease in this patient population.
Thursday, December 20, 2018
Orac thinks it might be. I think it’s just become so common in the mainstream that it’s losing its allure.
Vancomycin may be inferior to β-lactams for the empiric treatment of methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We compared empiric β-lactams to vancomycin to assess clinical outcomes in patients with MSSA bacteremia.
We conducted a retrospective cohort study of adult inpatients with their first episode of MSSA bacteremia at two tertiary care hospitals in Vancouver, Canada, between 2007 and 2014. Exposure was either empiric β-lactam with or without vancomycin or vancomycin monotherapy. All patients received definitive treatment with cloxacillin or cefazolin. The primary outcome was 28-day mortality. Secondary outcomes were 90-day mortality, duration of bacteremia, and hospital length-of-stay. Outcomes were adjusted using multivariable logistic regression.
Of 669 patients identified, 255 met inclusion criteria (β-lactam = 131, vancomycin = 124). Overall 28-day mortality was 7.06 % (n = 18). There were more cases of infective endocarditis in the β-lactam than in the vancomycin group [24 (18.3 %) vs 12 (9.7 %), p = 0.05]. Adjusted mortality at 28 days was similar between the two groups (OR 0.85; 95 % CI 0.27–2.67). The duration of bacteremia was longer in the vancomycin group (97.1 vs 70.7 h, p = 0.007). Transition to cloxacillin or cefazolin occurred within a median of 68.3 h in the vancomycin group.
Empiric β-lactams was associated with earlier clearance of bacteremia by a median of 1 day compared to vancomycin. Future prospective studies are needed to confirm our findings.
Objectives: Delayed initiation of appropriate antimicrobials is linked to higher sepsis mortality. We investigated interphysician variation in septic patients’ door-to-antimicrobial time.
Design: Retrospective cohort study.
Setting: Emergency department of an academic medical center.
Subjects: Adult patients treated with antimicrobials in the emergency department between 2009 and 2015 for fluid-refractory severe sepsis or septic shock. Patients who were transferred, received antimicrobials prior to emergency department arrival, or were treated by an attending physician who cared for less than five study patients were excluded.
Measurements and Main Results: We employed multivariable linear regression to evaluate the association between treating attending physician and door-to-antimicrobial time after adjustment for illness severity (Acute Physiology and Chronic Health Evaluation II score), patient age, prehospital or arrival hypotension, admission from a long-term care facility, mode of arrival, weekend or nighttime admission, source of infection, and trainee involvement in care. Among 421 eligible patients, 74% received antimicrobials within 3 hours of emergency department arrival. After covariate adjustment, attending physicians’ (n = 40) median door-to-antimicrobial times varied significantly, ranging from 71 to 359 minutes (p = 0.002). The percentage of each physician’s patients whose antimicrobials began within 3 hours of emergency department arrival ranged from 0% to 100%. Overall, 12% of variability in antimicrobial timing was explained by the attending physician compared with 4% attributable to illness severity as measured by the Acute Physiology and Chronic Health Evaluation II score (p less than 0.001). Some but not all physicians started antimicrobials later for patients who were normotensive on presentation (p = 0.017) or who had a source of infection other than pneumonia (p = 0.006). The adjusted odds of in-hospital mortality increased by 20% for each 1 hour increase in door-to-antimicrobial time (p = 0.046).
Conclusions: Among patients with severe sepsis or septic shock receiving antimicrobials in the emergency department, door-to-antimicrobial times varied five-fold among treating physicians. Given the association between antimicrobial delay and mortality, interventions to reduce physician variation in antimicrobial initiation are likely indicated.
From the green journal:
Long-term predictors and causes of death are understudied in elderly patients with acute venous thromboembolism.
We prospectively followed up 991 patients aged ≥65 years with acute venous thromboembolism in a multicenter Swiss cohort study. The primary outcome was overall mortality. We explored the association between patient baseline characteristics and mortality, adjusting for other baseline variables and periods of anticoagulation as a time-varying covariate. Causes of death over time were adjudicated by a blinded, independent committee.
The median age was 75 years. During a median follow-up period of 30 months, 206 patients (21%) died. Independent predictors of overall mortality were age (hazard ratio [HR], 1.32; 95% confidence interval [CI], 1.05-1.65, per decade), active cancer (HR, 5.80; 95% CI, 4.22-7.97), systolic blood pressure less than 100 mm Hg (HR, 2.77; 95% CI, 1.56-4.92), diabetes mellitus (HR, 1.50; 95% CI, 1.02-2.22), low physical activity level (HR, 1.92; 95% CI, 1.38-2.66), polypharmacy (HR, 1.41; 95% CI, 1.01-1.96), anemia (HR, 1.48; 95% CI, 1.07-2.05), high-sensitivity C-reactive protein greater than 40 mg/L (HR, 1.88; 95% CI, 1.36-2.60), ultra-sensitive troponin greater than 14 pg/mL (HR, 1.54; 95% CI, 1.06-2.25), and D-dimer greater than 3000 ng/mL (HR, 1.45; 95% CI, 1.04-2.01). Cancer (34%), pulmonary embolism (18%), infection (17%), and bleeding (6%) were the most common causes of death.
Elderly patients with acute venous thromboembolism have a substantial long-term mortality, and several factors, including polypharmacy and a low physical activity level, are associated with long-term mortality. Cancer, pulmonary embolism, infections, and bleeding are the most common causes of death in the elderly with venous thromboembolism.
Wednesday, December 19, 2018
Background and Purpose—Pioglitazone reduced major vascular events after ischemic stroke in a recent randomized controlled trial. The purpose of this study was to conduct a meta-analysis of randomized controlled trials to evaluate the effect of pioglitazone therapy in reducing the risk of recurrent stroke in stroke patients.
Methods—Pubmed, EMBASE, Medline, and Cochrane Central Register of Controlled Trials from 1966 to March 2016 were searched to identify relevant studies. We included randomized controlled trials that included comparison of pioglitazone versus control and trials in which quantitative estimates of the hazard ratio and 95% confidence interval for recurrent stroke associated with pioglitazone therapy among stroke patients were reported. Hazard ratios with 95% confidence intervals were used as a measure of the association between use of pioglitazone and risks of recurrent stroke (ischemic and hemorrhagic) and major vascular events (nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death) after pooling data across trials. Between-study heterogeneity was assessed using the I2 statistic.
Results—Three randomized controlled trials with 4980 participants were identified. Use of pioglitazone in stroke patients with insulin resistance, prediabetes, and diabetes mellitus was associated with lower risk of recurrent stroke (hazard ratio 0.68; 95% confidence interval, 0.50–0.92; P=0.01) and future major vascular events (hazard ratio 0.75; 95% confidence interval, 0.64–0.87; P=0.0001). There was no heterogeneity across trials. There was no evidence of an effect on all-cause mortality and heart failure.
Conclusions—Pioglitazone reduces recurrent stroke and major vascular events in ischemic stroke patients with insulin resistance, prediabetes, and diabetes mellitus.
Tuesday, December 18, 2018
It may not be what you think. Most did not have the triad in this report.
From the article:
Of the 92 cases included 64% had presented as an incidentaloma, 32% as a suspected pheochromocytoma and 4% had been screened because of previously diagnosed MEN2A. Those screened were youngest while those with incidentalomas were oldest. The females were more common in the incidentaloma and the screening groups, and males in the suspected pheochromocytoma group. Measurements of noradrenaline/normetanephrine levels were highest in the suspected pheocromocytoma group and lowest in the screening group. Hypertension was present in 63% of the incidentalomas, 79% of suspected pheochromocytomas and in none of the screening group. Paroxysmal symptoms were present in almost all with suspected pheochromocytoma while only in half of the other groups. The suspected pheocromocytoma group had most symptoms and the screening group least. The classic triad was present in 14% of the incidentalomas, in 28% of the suspected and in none of the screening group, while no symptoms at all was present in 12%, 0% and 25%, respectively. Pheochromocytoma crisis occurred in 5%. There was a positive correlation between tumor size vs hormone levels, and catecholamine levels vs blood pressure…
This large modern study confirms the wide spectrum of presentations of pheochromocytomas but also that hypertension and typical symptoms may not be present at all. The predominant presentation was serendipitously in the workup of an incidentaloma. Even though the patients with incidentalomas had not sought medical attention for pheochromocytoma-related symptoms, in hindsight, 88% had symptoms, which could be related to this disorder. Those screened had very few symptoms while those found in the workup of suspected pheochromocytoma had most symptoms. The classic triad, i.e., headaches, sweating and palpitation, was only present in a minority of patients.
Monday, December 17, 2018
Patients with pulmonary embolism (PE) are commonly admitted to hospital for their initial treatment. We aimed to assess the association of length of hospital stay with commonly available clinical variables and their combinations.
A retrospective multicenter cohort study was conducted on consecutive PE patients admitted to eight Italian centers. Logistic regression analysis was performed to evaluate the association between the length of hospital stay and the Pulmonary Embolism Severity Index (PESI) parameters, National Early Warning Score (NEWS) and other possible determinants.
We enrolled 391 patients, with a median hospital stay of 10 days (IQR 7–14). Among PESI parameters, only oxygen saturation less than 90% was significantly associated with length of hospital stay at univariable analysis (OR 1.99; 95% CI 1.3–3.2). At multivariable analysis, NEWS greater than or equal to 5 was associated with prolonged hospitalization (OR 3.14; 95% CI 1.2–8.3). A difference of median hospital stay was found between simplified PESI high and low risk groups (10 and 9 days, respectively, p = 0.027).
The median duration of hospital stay was generally long and not influenced by single parameters of PESI or common prognostic factors. The difference of one day between the low- and high-risk groups according to simplified PESI was not clinically significant.
Purpose of review: Monitoring of mental status and peripheral circulatory changes can be accomplished noninvasively in patients in the ICU. Emphasis on physical examination in conditions such as sepsis have gained increased attention as these evaluations can often serve as a surrogate marker for short-term treatment efficacy of therapeutic interventions. Sepsis associated encephalopathy and mental status changes correlate with worse prognosis in patients. Evaluation of peripheral circulation has been shown to be a convenient, easily accessible, and accurate marker for prognosis in patients with septic shock. The purpose of this article is to emphasize the main findings according to recent literature into the monitoring of physical examination changes in patients with sepsis.
Recent findings: Several recent studies have expanded our knowledge about the pathophysiology of mental status changes and the clinical assessment of peripheral circulation in patients with sepsis. Sepsis-associated encephalopathy is associated with an increased rate of morbidity and mortality in an intensive care setting. Increased capillary refill time (CRT) and persistent skin mottling are strongly predictive of mortality, whereas temperature gradients can reveal vasoconstriction and more severe organ dysfunction.
Summary: Monitoring of physical examination changes is a significant and critical intervention in patients with sepsis. Utilizing repeated neurologic evaluations, and assessing CRT, mottling score, and skin temperature gradients should be emphasized as important noninvasive diagnostic tools. The significance of these methods can be incorporated during the utilization of therapeutic strategies in resuscitation protocols in patients with sepsis.
Sunday, December 16, 2018
From the article:
•Pulmonary embolism (PE) is simultaneously one of the most overtested yet underdiagnosed diseases.•Even with reasonable and prudent care, some cases of PE will be missed.•Clinicians must use gestalt and intuition to decide whether to start testing for PE.•Clinicians should use the D-dimer more often.•Know the image quality of computed tomography when ruling out PE with a high pretest probability.
Failure to test for pulmonary embolism (PE) can be a lethal mistake, but PE and produces symptoms similar to many other diseases. Overtesting for PE has negative consequences.
Use published evidence to create a rationale and safe diagnostic approach for ambulatory and emergency patients with suspected PE in 2017.
Pulmonary embolism need not be pursued in patients with no symptoms of PE in the present or recent history (dyspnea, chest pain, cough or syncope), and always normal vital signs. When clinicians have a low clinical suspicion for PE or a Wells score less than 2, they can reasonably exclude PE with the Pulmonary Embolism Rule out Criteria (PERC rule). For patients with a “PE-unlikely” pretest probability (Wells or simplified revised Geneva score less than 5), PE can be ruled out with a normal or age-adjusted D-dimer concentrations. Other patients should undergo pulmonary vascular imaging, and the choices are discussed, including computerized tomographic pulmonary angiography, planar and single-photon emission computed tomography (SPECT).
A thoughtful algorithm for PE exclusion and diagnosis requires pretest probability assessment in all patients, followed by selective use of clinical criteria, the quantitative D-dimer, and pulmonary vascular imaging.
Appropriate periprocedural management of the chronically anticoagulated patient with an inherited or acquired thrombophilia is uncertain. The objective of this study was to test “thrombophilia” as a potential predictor of the 3-month cumulative incidence of thromboembolism and major bleeding among chronically anticoagulated patients undergoing an invasive procedure.
In a prospective cohort study, consecutive chronically anticoagulated patients referred to the Mayo Thrombophilia Center for standardized periprocedural anticoagulation management who had venous thromboembolism and complete thrombophilia testing were categorized as “severe,” “non-severe,” or “no identifiable” thrombophilia. The 3-month cumulative incidence rates of thromboembolism, bleeding, and death were estimated using the Kaplan-Meier product limit method.
Among 362 patients with complete thrombophilia testing, 165 (46%) had a defined thrombophilia; 76 patients had severe thrombophilia, mainly due to antiphospholipid syndrome (66%). Half of the patients in each of the 3 groups received pre- and postprocedure heparin. During follow-up, there were no thromboembolic events, rare major bleeding events (1% for each group), and 4 deaths. Due to the very low event rates for each of these outcomes, Cox proportional hazard modeling could not be performed.
Periprocedural event rates were low irrespective of thrombophilia status. Inherited or acquired thrombophilia was not a predictor of thromboembolism, major bleeding, or mortality after temporary interruption of chronic anticoagulation for an invasive procedure.