Tuesday, August 06, 2019

The cholesterol hypothesis is alive again!



Key Points

Question Is consuming dietary cholesterol or eggs associated with incident cardiovascular disease (CVD) and all-cause mortality?

Findings Among 29 615 adults pooled from 6 prospective cohort studies in the United States with a median follow-up of 17.5 years, each additional 300 mg of dietary cholesterol consumed per day was significantly associated with higher risk of incident CVD (adjusted hazard ratio [HR], 1.17; adjusted absolute risk difference [ARD], 3.24%) and all-cause mortality (adjusted HR, 1.18; adjusted ARD, 4.43%), and each additional half an egg consumed per day was significantly associated with higher risk of incident CVD (adjusted HR, 1.06; adjusted ARD, 1.11%) and all-cause mortality (adjusted HR, 1.08; adjusted ARD, 1.93%).

Meaning Among US adults, higher consumption of dietary cholesterol or eggs was significantly associated with higher risk of incident CVD and all-cause mortality in a dose-response manner.

This paper has been wildly overhyped. It’s new data but concludes nothing we didn’t already know: cholesterol matters. The real problem is, so do a lot of other things. Those who would hype this finding lack an appreciation of the concept of population attributable risk.


Sunday, August 04, 2019

Check point inhibitor induced colitis


Saturday, August 03, 2019

Which patients post cardiac arrest need to go straight to the cath lab?



CAD is a common substrate, and its severity is a potential trigger for OHCA, especially in the case of shockable rhythms. Patients with VF/pVT OHCA should be considered at the highest severity of a continuum of acute coronary syndromes. Patients with VF/pVT have a significant burden of CAD: acute, chronic, or acute on chronic (Figure 8)…

Current guidelines recommend early CAG and reperfusion for postarrest patients manifesting ST-segment elevation after ROSC is achieved. However, because of a lack of conclusive randomized data and ongoing perceived clinical equipoise, there is no consensus guideline on the use of CAG and coronary revascularization in patients without ST-segment elevation on ECG. Multiple randomized trials addressing this question are underway. Until their completion, there is a significant body of observational studies that address the role of the CCL in this population.

The current evidence suggests that early access to the CCL in patients resuscitated from VF/pVT cardiac arrest is associated with 2- to 3-fold higher functionally favorable survival rates than more conservative approaches of late or no access to the CCL. This body of evidence, with potential for unmeasured selection bias, suggests that patients resuscitated from OHCA, especially those with presenting shockable rhythms, should be considered for early CAG, identification of reversible causes, and revascularization when indicated.

This is in line with the current ACLS guidelines, which say that if there’s ST elevation post ROSC an immediate trip to the cath lab carries a class I recommendation. For patients without STE, the guidelines give a IIa recommendation to go straight to the cath lab if the arrest is of suspected cardiac origin on clinical grounds.

Friday, August 02, 2019

Cardiorenal syndrome


The AHA scientific statement is available as free full text here.

Thursday, August 01, 2019

Rates of cardiac testing prior to hip fracture surgery



Hip fracture is a common reason for urgent inpatient surgery. In the past few years, several professional societies have identified preoperative echocardiography and stress testing for noncardiac surgeries as low-value diagnostics. We utilized data on hospitalizations with a primary diagnosis of hip fracture surgery between 2011 and 2015 from the State Inpatient Databases (SID) of Maryland, New Jersey, and Washington, combined with data on hospital characteristics from the American Hospital Association (AHA). We found that the rate of preoperative ischemic testing is surprisingly but encouragingly low (stress tests 1.1% and cardiac catheterizations 0.5%), which is consistent with studies evaluating the outpatient utilization of these tests for low- and intermediate-risk surgeries. The rate of echocardiograms was 12.6%, which was higher than other published reports. Our findings emphasize the importance of ensuring that quality improvement efforts are directed toward areas where quality improvement is, in fact, needed.

Wednesday, July 31, 2019

Blood stream infections: how long to treat? When is PO sufficient?


This review in the Journal of Hospital Medicine is an excellent resource.

Tuesday, July 30, 2019

Non invasive ventilation for acute hypoxemic respiratory failure: what’s the latest?



Highlights



Noninvasive ventilation reduces the risk of intubation in subgroups of acute hypoxemic patients.


Immunosuppressed, acute pulmonary edema and pneumonia patients may benefit most from NIV.


Well designed randomized clinical trials are required to address the benefit in other populations.

Abstract

Purpose

Evaluate current recommendation for the use of noninvasive ventilation (Bi-level positive airway pressure- BiPAP modality) in hypoxemic acute respiratory failure, excluding chronic obstructive pulmonary disease.

Methods

Electronic searches in MEDLINE, Web of Science, Clinical Trials, and The Cochrane Central Register of Controlled Clinical Trials. We searched for randomized controlled trials comparing BiPAP to a control group in patients with hypoxemic acute respiratory failure. Endotracheal intubation and death were the assessed outcomes.

Results

Of the 563 studies found, nine met the inclusion criteria for this systematic review. The pooled RR (95% CI) for intubation in patients with acute pulmonary edema (APE)/community acquired pneumonia (CAP) and in immunosuppressed patients (cancer and transplants) were 0.61 (0.39–0.84) and 0.77 (0.60–0.93), respectively. For Intensive Care Units (ICU) mortality, the RR (95% CI) in patients with APE/CAP was 0.51 (0.22–0.79). The heterogeneity was low in all comparisons.

Conclusions

NIV showed a significant protective effect for intubation in immunosuppressed patients (cancer and transplants) and in patients with APE/CAP. However, the benefits of NIV for other etiologies are not clear and more trials are needed to prove these effects.

Monday, July 29, 2019

Biomarkers in midlife may predict physical decline years later



Clinical Perspective

What Is New?

Lower levels of NT-proBNP (N-terminal pro-B-type natriuretic peptide) and interleukin-6 in middle-aged adults were independently associated with better physical capability (a key component of healthy aging) up to 9 years later.

Such associations were meaningfully stronger than those observed for conventional risk markers including lipids, blood pressure, and glycemia and were not explained by the onset of cardiovascular and kidney disease or diabetes mellitus.

What Are the Clinical Implications?

Elevated NT-proBNP and interleukin-6 in midlife could help identify (and thereby target) individuals set to have poor physical capability as they age.

Such findings may relate in part to such biomarkers capturing early end-organ damage, or cumulative stressor pathways that lead to physical decline.

Future trials targeting improvements in physical capability should include middle-aged as well as older adults and use measurements of cardio-renal biomarkers as intermediate outcomes.


Sunday, July 28, 2019

Adverse drug reactions in the elderly: a clinical vignette and a reminder of the Beers list


The free full text article is here. The newly revised Beers list can be accessed here.

Saturday, July 27, 2019

Antiplatelet therapy reduces mortality in sepsis



Highlights



Antiplatelet drugs can reduce the mortality rate in patients with sepsis.


Aspirin can effectively reduce mortality in patients with sepsis.


Antiplatelet drugs reduce mortality regardless of the timing of administration.

Abstract

Purpose

Abnormal platelet activation plays an important role in the development of sepsis. The effect of antiplatelet drugs on the outcome of patients with sepsis remains unclear. This meta-analysis aimed to determine the effect of antiplatelet drugs on the prognosis of patients with sepsis.

Materials and methods

PubMed, Cochrane Library, CBM, and Embase were searched for all related articles published from inception to April 2018. The primary end point was mortality. Adjusted data were used and statistically analysed.

Results

Ten cohort studies were included. The total number of patients with sepsis was 689,897. Data showed that the use of antiplatelet drugs could effectively reduce the mortality of patients with sepsis (odds ratio (OR) = 0.82, 95% CI: 0.81–0.83, p less than 0.05). Seven studies used aspirin for antiplatelet therapy, and subgroup analysis showed that aspirin effectively reduced ICU or hospital mortality in patients with sepsis (OR = 0.60, 95% CI: 0.53–0.68, p less than 0.05). A subgroup analysis on the timing of anti-platelet drug administration showed that antiplatelet drugs can reduce mortality when administered either before (OR = 0.78, 95% CI: 0.77–0.80) or after sepsis (OR = 0.59, 95% CI: 0.52–0.67).

Conclusions

Antiplatelet drugs, particularly aspirin, could be used to effectively reduce mortality in patients with sepsis.

Antithrombotic therapy for sepsis is not a new concept. The coagulation system is activated and accounts for some of the injury in sepsis. Activated protein C was found beneficial in selected septic patients and was approved as an adjunct in the treatment of sepsis with organ dysfunction in 2001. The company withdrew the product from the market in 2011.

Monday, May 06, 2019

Management of acute kidney injury


From a review in the Journal of Hospital Medicine:

Acute kidney injury (AKI) is a common complication in hospitalized patients and is associated with mortality, prolonged hospital length of stay, and increased healthcare costs. This paper reviews several areas of controversy in the identification and management of AKI. Serum creatinine and urine output are used to identify and stage AKI by severity. Although standardized definitions of AKI are used in research settings, these definitions do not account for individual patient factors or clinical context which are necessary components in the assessment of AKI. After treatment of reversible causes of AKI, patients with AKI should receive adequate volume resuscitation with crystalloid solutions. Balanced crystalloid solutions generally prevent severe hyperchloremia and could potentially reduce the risk of AKI, but additional studies are needed to demonstrate a clinical benefit. Intravenous albumin may be beneficial in patients with chronic liver disease either to prevent or attenuate the severity of AKI; otherwise, the use of albumin or other colloids (eg, hydroxyethyl starch) is not recommended. Diuretics should be used to treat volume overload, but they do not facilitate AKI recovery or reduce mortality. Nutrition consultation may be helpful to ensure that patients receive adequate, but not excessive, dietary protein intake, as the latter can lead to azotemia and electrolyte disturbances disproportionate to the patient’s kidney failure. The optimal timing of dialysis initiation in AKI remains controversial, with conflicting results from two randomized controlled trials.

Friday, May 03, 2019

A fib ablation vs antiarrhythmic medication


From a recent study published in JAMA, the CAPTAF trial:

Key Points

Question Is pulmonary vein isolation more effective than optimized antiarrhythmic drug therapy for improving general health in patients with symptomatic atrial fibrillation?

Findings In this randomized clinical trial that included 155 patients with paroxysmal or persistent symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months for those treated with catheter ablation compared with antiarrhythmic medication was 11.9 vs 3.1 points on the 0- to 100-point 36-Item Short-Form Health Survey questionnaire, a difference that was statistically and clinically significant.

Meaning In patients with either paroxysmal or persistent symptomatic atrial fibrillation despite medication, catheter ablation may help improve quality of life.

Abstract

Importance Quality of life is not a standard primary outcome in ablation trials, even though symptoms drive the indication.

Objective To assess quality of life with catheter ablation vs antiarrhythmic medication at 12 months in patients with atrial fibrillation.

Design, Setting, and Participants Randomized clinical trial at 4 university hospitals in Sweden and 1 in Finland of 155 patients aged 30-70 years with more than 6 months of atrial fibrillation and treatment failure with 1 antiarrhythmic drug or β-blocker, with 4-year follow-up. Study dates were July 2008–September 2017. Major exclusions were ejection fraction less than 35%, left atrial diameter greater than 60 mm, ventricular pacing dependency, and previous ablation.

Interventions Pulmonary vein isolation ablation (n = 79) or previously untested antiarrhythmic drugs (n = 76).

Main Outcomes and Measures Primary outcome was the General Health subscale score (Medical Outcomes Study 36-Item Short-Form Health Survey) at baseline and 12 months, assessed unblinded (range, 0 [worst] to 100 [best]). There were 26 secondary outcomes, including atrial fibrillation burden (% of time) from baseline to 12 months, measured by implantable cardiac monitors. The first 3 months were excluded from rhythm analysis.

Results Among 155 randomized patients (mean age, 56.1 years; 22.6% women), 97% completed the trial. Of 79 patients randomized to receive ablation, 75 underwent ablation, including 2 who crossed over to medication and 14 who underwent repeated ablation procedures. Of 76 patients randomized to receive antiarrhythmic medication, 74 received it, including 8 who crossed over to ablation and 43 for whom the first drug used failed. General Health score increased from 61.8 to 73.9 points in the ablation group vs 62.7 to 65.4 points in the medication group (between-group difference, 8.9 points; 95% CI, 3.1-14.7; P = .003). Of 26 secondary end points, 5 were analyzed; 2 were null and 2 were statistically significant, including decrease in atrial fibrillation burden (from 24.9% to 5.5% in the ablation group vs 23.3% to 11.5% in the medication group; difference –6.8% [95% CI, –12.9% to –0.7%]; P = .03). Of the Health Survey subscales, 5 of 7 improved significantly. Most common adverse events were urosepsis (5.1%) in the ablation group and atrial tachycardia (3.9%) in the medication group.

Conclusions and Relevance Among patients with symptomatic atrial fibrillation despite use of antiarrhythmic medication, the improvement in quality of life at 12 months was greater for those treated with catheter ablation compared with antiarrhythmic medication. Although the study was limited by absence of blinding, catheter ablation may offer an advantage for quality of life.


Tuesday, April 23, 2019

Should you get immunoglobulin levels on patients admitted with community acquired pneumonia?



BACKGROUND: Immunodeficiency is an underrecognized risk factor for infections, such as community-acquired pneumonia (CAP).

OBJECTIVE: We evaluated patients admitted with CAP for humoral immunodeficiency.

DESIGN: Prospective cohort study.

SETTING: Inpatients

PATIENTS, INTERVENTION, AND MEASUREMENTS: We enrolled 100 consecutive patients admitted with a diagnosis of CAP from February 2017 to April 2017. Serum IgG, IgM, IgA, and IgE levels were obtained within the first 24 hours of admission. CURB-65 score and length of hospital stay were calculated. The Wilcoxon rank-sum test, Kruskal-Wallis test, and simple linear regression analysis were used in data analysis.

RESULTS: The prevalence of hypogammaglobinemia in patients with CAP was 38% (95% CI: 28.47% to 48.25%). Twenty-seven of 100 patients had IgG hypogammaglobinemia (median: 598 mg/dL, IQ range: 459-654), 23 of 100 had IgM hypogammaglobinemia (median: 38 mg/dL, IQ range: 25-43), and 6 of 100 had IgA hypogammaglobinemia (median: 36 mg/dL, IQ range: 18-50). The median hospital length of stay for patients with IgG hypogammaglobinemia was significantly higher when compared to patients with normal IgG levels (five days, IQ range [3-10] vs three days, IQ range [2-5], P = .0085). Fourteen patients underwent further immune evaluation, resulting in one diagnosis of multiple myeloma, three patients diagnosed with specific antibody deficiency, and one patient diagnosed with selective IgA deficiency.

CONCLUSION: There is a high prevalence of hypogammaglobinemia in patients hospitalized with CAP, with IgG and IgM being the most commonly affected classes. IgG hypogammaglobinemia was associated with an increased length of hospitalization. Screening immunoglobulin levels in CAP patients may also uncover underlying humoral immunodeficiency or immuno-proliferative disorders.

Should docusate be removed from your hospital’s formulary?


According to this article it should.

Saturday, April 20, 2019

Prealbumin testing is not useful in the assessment for malnutrition


Prealbumin (aka transthyretin) is, like albumin, an acute phase reactant. It is, also like albumin, a negative acute phase reactant because it goes down during illness. It was originally proposed as better nutritional marker than albumin because of its shorter half life, giving more of a “right now” nutritional assessment. Nowadays, neither test is considered useful for nutritional assessment. Instead one should use a clinical instrument based on a nutrition focused H&P.

From the Journal of Hospital Medicine’s Things We Do for No Reason series.

What’s the value in diagnosing malnutrition in the first place? Well, it identifies you and your hospital as having a population of patients with a markedly higher mortality. That’s good for reimbursement and severity adjustment, as the linked article points out. Does it help patients? The evidence that it leads to interventions that improve outcome is scant to none as far as I know.  What I am prompted to do, at least, is give thiamine.

Friday, April 19, 2019

Very low utilization of advance care planning (ACP) CPT codes among hospitalists


From a recent study:

We analyzed advance care planning (ACP) billing for adults aged 65 years or above and who were managed by a large national physician practice that employs acute care providers in hospital medicine, emergency medicine and critical care between January 1, 2017 and March 31, 2017. Prompting hospitalists to answer the validated “surprise question” (SQ; “Would you be surprised if the patient died in the next year?”) for inpatient admissions served to prime hospitalists and triggered an icon next to the patient’s name. Among 113,621 hospital-based encounters, only 6,146 (5.4%) involved a billed ACP conversation: 8.3% among SQ-prompted who answered “no” and 4.1% SQ-prompted who answered “yes” (for non-SQ prompted cases, the fraction was 3.5%; P less than .0001). ACP conversations were associated with a comfort-focused care trajectory. Low ACP rates among even those with high hospitalist-predicted mortality risk underscore the need for quality improvement interventions to increase hospital-based ACP.

The last sentence is a non sequitur. The codes are an unreliable measure because many, I would wager most, ACP discussions are not billed with these particular codes. Many hospitalists don’t even know they exist. The codes, 99497 and 99498, were not even included in the fee schedule until 2016 so they were brand new at the time of the study.

Ten years ago similar codes were proposed under the Affordable Care Act but spurred fierce debate around “death panel” fears. Those provisions were dropped before final passage of the law. What’s interesting is how these provisions were slipped in out of most people’s awareness, with no public debate to speak of, seven years later. Political winds change and people are easily distracted.

Only the American Association of Physicians and Surgeons, (AAPS), a relatively minor player in the larger physician community, seemed to mind. They argued that the codes, which pay more than ordinary CPT codes, would incentivize doctors to talk patients out of life prolonging treatments. That’s an oversimplification, of course, because some ACP conversations produce decisions for more care, not lessThat said, the intent of the measure is to reward doctors for giving less care toward the end of life.  It creates the perception of a conflict of interest though based on the data above the measure has had minimal impact.

The public debate about the proposal in 2009 was confused. The idea of the “death panel” (merely an inflammatory term for an advance care discussion) was nothing new. We had been having those discussions for decades. Moreover, the pre-existing ordinary CPT codes already rewarded doctors for long discussions through the provision that a higher level of service could be coded if greater than half the encounter time was spent in counseling or care coordination. Nobody on either side of the debate seemed aware of those facts.

Thursday, April 18, 2019

Survey data on the state of research in hospital medicine


From a recent paper in the Journal of Hospital Medicine:

BACKGROUND: Little is known about the state of research in academic hospital medicine (HM) despite the substantial growth of this specialty.
METHODS: We used the Society of Hospital Medicine (SHM) membership database to identify research programs and their leadership. In addition, the members of the SHM Research Committee identified individuals who lead research programs in HM. A convenience sample of programs and individuals was thus created. A survey instrument containing questions regarding institutional information, research activities, training opportunities, and funding sources was pilot tested and refined for electronic dissemination. Data were summarized using descriptive statistics.
RESULTS: A total of 100 eligible programs and corresponding individuals were identified. Among these programs, 28 completed the survey in its entirety (response rate 28%). Among the 1,586 faculty members represented in the 28 programs, 192 (12%) were identified as engaging in or having obtained extramural funding for research, and 656 (41%) were identified as engaging in quality improvement efforts. Most programs (61%) indicated that they received $500,000 or less in research funding, whereas 29% indicated that they received greater than $1 million in funding. Major sources of grant support included the Agency for Healthcare Research and Quality, National Institutes of Health, and the Veterans Health Administration. Only five programs indicated that they currently have a research fellowship program in HM. These programs cited lack of funding as a major barrier to establishing fellowships. Almost half of respondents (48%) indicated that their faculty published between 11-50 peer-reviewed manuscripts each year.
CONCLUSION: This survey provides the first national summary of research activities in HM. Future waves of the survey can help determine whether the research footprint of the field is growing.

Are residents getting enough training in managing crashing patients in the hospital?


From a recent study in the Journal of Hospital Medicine:

BACKGROUND: Internal Medicine (IM) residency graduates should be able to manage hospital emergencies, but the rare and critical nature of such events poses an educational challenge. IM residents’ exposure to inpatient acute clinical events is currently unknown.
OBJECTIVE: We developed an instrument to assess IM residents’ exposure to and confidence in managing hospital acute clinical events.
METHODS: We administered a survey to all IM residents at our institution assessing their exposure to and confidence in managing 50 inpatient acute clinical events. Exposures assessed included mannequin-based simulation or management of hospital-based events as a part of a team or independently in a leadership role. Confidence was rated on a five-point scale and dichotomized to “confident” versus “not confident.” Results were analyzed by multivariable logistic regression to assess the relationship between exposure and confidence accounting for year in training.
RESULTS: A total of 140 of 170 IM residents (82%) responded. Postgraduate year 1 (PGY-1) residents had managed 31.3% of acute events independently vs 71.7% of events for PGY-3/4 residents (P less than .0001). In multivariable analysis, residents’ confidence increased with level of training (PGY-1 residents were confident to manage 24.9% of events vs 72.5% of events for PGY-3/4 residents, P less than .0001) and level of exposure, independent of training year (P = .001). Events with the lowest levels of exposure and confidence for graduating residents were identified.
CONCLUSIONS: IM residents’ confidence in managing inpatient acute events correlated with level of training and clinical exposure. We identified events with low levels of resident exposure and confidence that can serve as targets for future curriculum development.

Wednesday, April 10, 2019

Atul Gawande on the electronic medical record


Atul Gawande has a piece in the New Yorker titled Why Doctors Hate their Computers. The title is deceptive. In the first place doctors don’t hate computers (I’ve never met one who did, have you?). In the body of the paper Gawande doesn’t even seem to attempt to make that case. He does point out how doctors hated the way in which they were forced to adopt health information technology and the culture that went alongside. But, though he talks around it (and he talks a lot around it) he fails to answer the question of why. Is there something wrong with computers themselves in the current state of development? Is it the way policymakers and administrators have forced the implementation? Or is it that docs just need an attitude adjustment? He implies a little of each. Overall the article is incoherent.

Gawande has thrown together a mishmash of anecdotes, unreferenced claims and quotes from supposed experts. And the qualifications of these experts? Well, consider this one:

Gregg Meyer sympathizes, but he isn’t sorry. As the chief clinical officer at Partners HealthCare, Meyer supervised the software upgrade. An internist in his fifties, he has the commanding air, upright posture, and crewcut one might expect from a man who spent half his career as a military officer.

Hmmm. A commanding air, an upright posture and a crewcut. I think I’m afraid of this guy. He seems to think doctors have too much autonomy and a bad attitude to boot. He says:

“But we think of this as a system for us and it’s not,” he said. “It is for the patients.” 

Emphasis his.

Meyer just gave himself away. He’s operating on the idea that the interests of doctors are opposed to the interests of patients. It’s an ethical question worth pondering but not a great starting premise. Gawande seems to accept it uncritically. A little further on Gawande says of Meyer, also uncritically:

Gregg Meyer is understandably delighted to have the electronic levers to influence the tens of thousands of clinicians under his purview. He had spent much of his career seeing his hospitals blighted by unsafe practices that, in the paper-based world, he could do little about.

Evidence based medicine, particularly its third pillar (the importance of the expertise of the individual clinician) opposes such a top down approach. Does Gawande see anything wrong with Meyer’s line of thinking? If he does he doesn’t say so.

It’s style over substance:

Jessica Jacobs, a longtime office assistant in my practice—mid-forties, dedicated, with a smoker’s raspy voice—

As if that’s supposed to be a convincer in some way. But what does it mean, exactly? That she’s got savvy? That her dedication to her work has taken its toll? It’s left to our imagination.

Gawande fails to even come close to making the case that doctors hate computers, let alone answer the question
of why, but he does point out some of the negative consequences of the EMR. Maybe this is progress, because it would have been nearly forbidden speech about a decade ago.


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

Visceral fat: an inflammatory engine driving worse outcomes in sepsis?


Recent study findings here.

Strength training improved cognition in older patients


What explains strokes in young people (ages 18-55)?


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.



Testosterone replacement associated with better cardiovascular outcomes


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.