American Heart Association's Cardiology Patient Page takes an uncritical view of chelation

The article opens:

Don’t cringe when you hear the term chelation (key-LAY-shun) therapy. If you have heard about it at all, you may have heard that it is alternative medicine, quackery, expensive, and even dangerous. New research funded by the National Institutes of Health is suggesting that this old treatment has some real life in it and that it may particularly benefit patients with diabetes mellitus and prior heart attacks.

The article goes on with more of the same credulity along with this little tidbit:

There are reasons to think that chelation to remove metals might treat or prevent heart disease.1 Some complications of diabetes mellitus may be caused by chemical reactions that happen to the excess sugar in the blood. These reactions are catalyzed, or facilitated, by metals. The environment is polluted with metals that are toxic to our systems. Lead (gasoline, plumbing), arsenic (well water, rice, apple juice), mercury (many fish), and cadmium (from rechargeable batteries) are among the top 10 most toxic substances listed by the US government. EDTA chelates lead and cadmium.

So now we're adding environmental toxins to the list of risk factors for cardiovascular disease.  I've been following this field closely for a long time and this is new to me.  Like mercury and autism I guess.    It is only the latest in a growing list of purported mechanisms by which chelation might “work.”  None of them have strong biologic plausibility.  It's interesting to me how the proponents have jumped from one to another over the years.

This is all based, of course, on TACT and its diabetes substudy.  For my own take on these two studies see here and here.  Suffice it to say for this post that, at least among highly publicized clinical trials, TACT is the most conflicted and flawed study I have been aware of in my career as a physician.  (It's too bad the article didn't cite this paper).

The article, though an AHA publication, departs from the AHA's official post-TACT position on chelation, which gives it only a IIb recommendation.   And now it appears that TACT 2, a follow up trial, is in the works.  I'm not sure what to think about this.  I guess that since TACT has changed the status of chelation, in the perception of the medical community, from that of “quackery” to “controversial treatment” another trial may have to be done.  But if its funding and conflicts are like those of TACT 1 I am not optimistic.

The obesity-asthma link

From a recent review:

Recent findings: Clinical and epidemiological studies indicate that obese patients with asthma may represent a unique phenotype, which is more difficult to control, less responsive to asthma medications and by that may have higher healthcare utilization. A number of common comorbidities have been linked to both obesity and asthma, and may, therefore, contribute to the obese–asthma phenotype. Furthermore, recently published studies indicate that even a modest weight reduction can improve clinical manifestations and outcome of asthma.

Summary: Compared with normal-weight patients, obese and overweight patients with asthma have poorer asthma control and respond less to corticosteroid therapy. Future studies focusing on the mechanism underlying both obesity and asthma including the obese–asthma phenotype are required to better characterize the link between the conditions and target the management of this patient group.

Of particular interest, the review suggests weight loss as a treatment modality.

The emerging link between obesity and kidney disease

From a recent review:

It is well established that excessive caloric intake contributes to organ injury. The associated increased adiposity initiates a cascade of cellular events that leads to progressive obesity-associated diseases such as kidney disease. Recent evidence has indicated that adipose tissue produces bioactive substances that contribute to obesity-related kidney disease, altering the renal function and structure. In parallel, proinflammatory processes within the adipose tissue can also lead to pathophysiological changes in the kidney during the obese state.

The asthma-COPD overlap syndrome (ACOS)

From a recent update:

Purpose of review: Some individuals share characteristics of asthma and chronic obstructive pulmonary disease (COPD). The asthma–COPD overlap syndrome (ACOS) has been defined as symptoms of increased variability of airflow in association with an incompletely reversible airflow obstruction. In this review, we present the latest findings in the diagnosis, characterization and management of ACOS.

Recent findings: Around 15–20% of COPD patients may have an ACOS. Patients with ACOS are characterized by increased reversibility of airflow obstruction, eosinophilic bronchial and systemic inflammation, and increased response to inhaled corticosteroids, compared with the remaining patients with COPD. Patients with ACOS have more frequent exacerbations, more wheezing and dyspnoea, but similar cough and sputum production compared with COPD.

Summary: The relevance of the ACOS is to identify patients with COPD who may have underlying eosinophilic inflammation that responds to inhaled corticosteroids. So far, the previous diagnosis of asthma in a patient with COPD is the more reliable criterion for ACOS. Ongoing studies will clarify if concentrations of blood eosinophils may be useful to identify this subgroup of patients with COPD. If this is the case, the interest of ACOS may shift to that of eosinophilic COPD, which is easier to diagnose and has clear therapeutic implications.

Strategies for reduction in hospital readmissions---what does the evidence say?

From a recent review (free full text):

PRACTICE RECOMMENDATIONS

› Use risk stratification methods such as the Probability of Repeated Admission (Pra) or the LACE index to identify patients at high risk for readmission. B

› Take steps to ensure that follow-up appointments are made within the first one to 2 weeks of discharge, depending on the patient’s risk of readmission. C

› Reconcile preadmission and postdischarge medications to identify discrepancies and possible interactions. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence

B Inconsistent or limited-quality patient-oriented evidence

C Consensus, usual practice, opinion, disease-oriented evidence, case series

Via Hospital Medicine Virtual Journal Club.

Proton pump inhibitors and esophageal varices

From a systematic review:

Data Synthesis: Of 1156 studies, 20 were included after assessment. There was wide methodological heterogeneity and moderately high risk of bias among studies. Level I evidence suggests that PPIs reduce esophageal ulcer size post–elective esophageal ligation; the clinical importance of such findings is not known given the self-limiting nature of esophageal ulcer. Available evidence does not support a role of PPIs for long-term prophylaxis of portal hypertension–related bleeding and high-dose infusion for acute management of GEV hemorrhage. Retrospective data demonstrate a potential increase in the incidence of spontaneous bacterial peritonitis in patients with cirrhosis receiving PPIs. Conclusions: The best available evidence supports the use of short-course (10 days) PPI post–endoscopic variceal ligation to reduce ulcer size if ulcer healing is a concern. Practices such as high-dose infusion and prolonged use should be discouraged until evidence of benefit becomes available.

Pneumonia as a cardiovascular risk factor

Pneumonia increased short and long term risk for cardiovascular events in two databases, published here.

This is not the first such report. See here.

Microvascular angina

I can remember when decades ago this was often referred to, due to its mysterious nature, as syndrome X. That term is now less commonly used due to the confusing association of “syndrome X” with another entity which is now known as the metabolic syndrome. Moreover with improvement in our understanding it's not so mysterious anymore.

Here is a nice review in American Journal of Cardiovascular Drugs. (Medscape free full text here).

Microvascular angina may be primary (no associated defined cardiac disease) or secondary (defined underlying cardiac disease present).

MSSA bacteremia: cefazolin versus cloxacillin

From a recent study:

RESULTS:

Of 354 patients included in the study, 105 (30%) received cefazolin and 249 (70%) received cloxacillin as the definitive antibiotic therapy. In 90 days, 96 (27%) patients died: 21/105 (20%) in the cefazolin group and 75/249 (30%) in the cloxacillin group. Within 90 days, 10 patients (3%) had a relapse of S. aureus infection: 6/105 (6%) in the cefazolin group and 4/249 (2%) in the cloxacillin group. All relapses in the cefazolin group were related to a deep-seated infection. Based on the estimated propensity score, 90 patients in the cefazolin group were matched with 90 patients in the cloxacillin group. In the propensity score-matched groups, cefazolin had an HR of 0.58 (95% CI 0.31-1.08, P = 0.0846) for 90 day mortality.

CONCLUSIONS:

There was no significant clinical difference between cefazolin and cloxacillin in the treatment of MSSA bacteraemia with respect to mortality. Cefazolin was associated with non-significantly more relapses compared with cloxacillin, especially in deep-seated S. aureus infections.

Accidental over correction of hyponatremia during volume resuscitation

You have a patient in the ER in septic shock. You are about to administer resuscitation fluid but notice that the patient is severely hyponatremic. You don't want to correct too rapidly and risk osmotic myelinolysis. What do you do? I've seen this situation many times. This problem is addressed in a post at Academic Life in Emergency Medicine and some references provided.

One thing you could do, says the author, is use lactated ringers which is hypotonic to normal saline (though it may still be hypertonic to a patient with severe hyponatremia). After all, there's been a shift toward lactated ringers in sepsis resuscitation for entirely different reasons anyway so why not?

If you do the math (a link to a calculator is provided) you find that, all other things being equal, lactated ringers raises sodium in a severely hyponatremic patient a lot less than saline. And, using the calculator, you can reliably predict how fast the sodium will rise with a given rate of fluid resuscitation, right? Wrong. Because all other things are not equal. You can bet that patient is pouring out vasopressin, driven by non-osmotic stimuli (volume receptor mediated).  When you replete the patient's volume you will turn off that signal and a water diuresis may ensue. That is a variable that cannot be anticipated in the calculation. The only way I know to deal with that situation is to recheck the patient's chemistries frequently, pay attention to the urine output and urine osm in order to catch any trend toward overcorrection early, then deal with it however your sound clinical judgement may dictate.

That is not to take away from the point that lactated ringers may be preferable.

Interventions for mild cognitive impairment

From a recent JAMA paper:

Evidence Acquisition We searched PubMed for English-language articles in peer-reviewed journals and the Cochrane Library database from inception through July 2014. Relevant references from retrieved articles were also evaluated.

Findings The prevalence of MCI in adults aged 65 years and older is 10% to 20%; risk increases with age and men appear to be at higher risk than women. In older patients with MCI, clinicians should consider depression, polypharmacy, and uncontrolled cardiovascular risk factors, all of which may increase risk for cognitive impairment and other negative outcomes. Currently, no medications have proven effective for MCI; treatments and interventions should be aimed at reducing cardiovascular risk factors and prevention of stroke. Aerobic exercise, mental activity, and social engagement may help decrease risk of further cognitive decline. Although patients with MCI are at greater risk for developing dementia compared with the general population, there is currently substantial variation in risk estimates (from less than 5% to 20% annual conversion rates), depending on the population studied...

Conclusions and Relevance Cognitive decline and MCI have important implications for patients and their families and will require that primary care clinicians be skilled in identifying and managing this common disorder as the number of older adults increases in coming decades. Current evidence supports aerobic exercise, mental activity, and cardiovascular risk factor control in patients with MCI.

Shrinking contraindications to metformin

From a study in JAMA:

Objective To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function.

Evidence Acquisition In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial.

Results Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus—use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use.

Conclusions and Relevance Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.

What is excessive ST segment discordance in LBBB?

There is a law of proportionality that applies. Via Dr. Smith's ECG blog.

Isolated cardiac sarcoidosis

This entitity is being increasingly recognized. Diagnostic difficulties are discussed in this review.

Via Hospital Medicine Virtual Journal Club.

Hypothyroid myopathy

This case reportand brief review focuses on the rare variant Hoffmann syndrome.

Humanities versus science in premed education: Does it matter?

From a recent systematic review:

Results: A total of 1,548 citations were identified with 20 papers included in the review. SSH premedical education is predominately an American experience. For medical students with SSH background, equivalent academic, clinical, and research performance compared with medical students with a premedical science background is reported, yet different patterns of competencies exist. Post-medical-school equivalent or improved clinical performance is associated with an SSH background. Medical students with SSH backgrounds were more likely to select primary care or psychiatry careers. SSH major/course concentration, not SSH course counts, is important for admission decision making. The impact of today’s admission milieu decreases the value of an SSH premedical education.

High sensitivity troponin T as a marker for diuretic response in acute decompensated heart failure

Elevations are seen in a large number of acutely decompensated patients. The biomarker was analogous to proBNP in this study.

Hashimoto’s encephalopathy

This is an entity you may not think of.

Via Hospital Medicine Virtual Journal Club.

Gila monster envenomation

From a poison control database:

Results. A total of 319 calls regarding Gila monsters were identified in the NPDS. Of these, 105 (33%) were human exposures; most (79%) occurred in males. A total of 71 (68%) of these 105 cases were referred to a health care facility (HCF); 30 (29%) were managed on-site. Of the 71 HCF referrals, 36 (51%) were discharged home and 17 (24%) were admitted. Most (65%) admissions were to an intensive care unit (ICU). Arizona's PCCs received 70 unique reports of Gila monster bite. Most (77%) of the bites in Arizona involved an upper extremity. Eight (11%) involved patients under the age of 18 years. Eleven (16%) Arizona cases were work-related. Twenty-eight (40%) of the 70 bites in Arizona were evaluated in a HCF, but not admitted. Eleven (16%) were admitted, of which five were to an ICU. Six patients had edema of airway structures; three required emergent airway management, one by cricothyrotomy. There were no deaths. Conclusion. Gila monster bites are uncommon. Many cases did not require hospitalization. Edema of airway structures is an infrequent, but life-threatening complication.