Monday, July 31, 2017

Timing of anticoagulant initiation for atrial fibrillation in patients with intracerebral hemorrhage



Background and Purpose—This study aims to provide observational data on the relationship between the timing of antithrombotic treatment and the competing risks of severe thrombotic and hemorrhagic events in a cohort of Swedish patients with atrial fibrillation and intracerebral hemorrhage (ICH).

Methods—Patients with atrial fibrillation and a first-ever ICH were identified in the Swedish Stroke Register, Riksstroke, 2005 to 2012. Riksstroke was linked with other national registers to find information on treatment, comorbidity, and outcome. The optimal timing of treatment in patients with low and high thromboembolic risk was described through cumulative incidence functions separately for thrombotic and hemorrhagic events and for the combined end point vascular death or nonfatal stroke.

Results—The study included 2619 ICH survivors with atrial fibrillation with 5759 person-years of follow-up. Anticoagulant treatment was associated with a reduced risk of vascular death and nonfatal stroke in high-risk patients with no significantly increased risk of severe hemorrhage. The benefit seemed to be greatest when treatment was started 7 to 8 weeks after ICH. For high-risk women, the total risk of vascular death or stroke recurrence within 3 years was 17.0% when anticoagulant treatment was initiated 8 weeks after ICH and 28.6% without any antithrombotic treatment (95% confidence interval for difference, 1.4%–21.8%). For high-risk men, the corresponding risks were 14.3% versus 23.6% (95% confidence interval for difference, 0.4%–18.2%).

Conclusions—This nationwide observational study suggests that anticoagulant treatment may be initiated 7 to 8 weeks after ICH in patients with atrial fibrillation to optimize the benefit from treatment and minimize risk.

Sunday, July 30, 2017

Carbapenem-resistant Enterobacteriaceae (CRE): what can be done?



Abstract:

Purpose of review: Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide challenge and associated with a high mortality rate in critically ill patients. This review focused on rapid diagnosis, optimization of antimicrobial therapy, and implication of effective infection control precautions to reduce impact of CRE on vulnerable patients.

Recent findings: Several new diagnostic assays have recently been described for the early diagnosis of CRE. Retrospective studies are supportive for colistin plus meropenem combination for the treatment of CRE infections; however, solid evidence is still lacking. Ceftazidime–avibactam may be an effective therapeutic agent for infections caused by carbapenem-hydrolyzing oxacillinase-48 and Klebsiella pneumoniae carbapenamase-producing Enterobacteriaceae, but not for New Delhi metallo-β-lactamase producers. Gastrointestinal screening may permit early identification of patients with CRE infections. There is not enough evidence to recommend selective digestive decontamination for CRE carriers.

Summary: The information for rapid diagnosis of CRE is accumulating. There are new agents with high in-vitro activity against CRE, but clinical experience is limited to case reports. Active surveillance with a high rate of compliance to basic infection control precautions seems to be the best approach to reduce the impact of CRE on vulnerable patients.


Saturday, July 29, 2017

Computerized physician order entry: a negative factor in physician productivity and morale



Abstract:

Objectives: To examine the impact of clerical support personnel for physician order entry on physician satisfaction, productivity, timeliness with electronic health record (EHR) documentation, and physician attitudes.

Methods: All seven part-time physicians at an academic general internal medicine practice were included in this quasi-experimental (single group, pre- and postintervention) mixed-methods study. One full-time clerical support staff member was trained and hired to enter physician orders in the EHR and conduct previsit planning. Physician satisfaction, productivity, timeliness with EHR documentation, and physician attitudes toward the intervention were measured.

Results: Four months after the intervention, physicians reported improvements in overall quality of life (good quality, 71%–100%), personal balance (43%–71%), and burnout (weekly, 43%–14%; callousness, 14%–0%). Matched for quarter, productivity increased: work relative value unit (wRVU) per session increased by 20.5% (before, April–June 2014; after, April–June 2015; range −9.2% to 27.5%). Physicians reported feeling more supported, more focused on patient care, and less stressed and fatigued after the intervention.

Conclusions: This study supports the use of physician order entry clerical personnel as a simple, cost-effective intervention to improve the work lives of primary care physicians.

This would represent going back to what we had before meaningful use, not a new intervention.

Thursday, July 27, 2017

A recent review of the latest Surviving Sepsis guidelines suggests that we go back to early goal directed therapy


Low value systems update: CPOE based insulin order sets didn’t help with glycemic control


Systematic review of non invasive positive pressure ventilation (NIPPV) in acute exacerbation of COPD with hypercapnic respiratory failure



Main results

We included in the review 17 randomised controlled trials involving 1264 participants. Available data indicate that mean age at recruitment was 66.8 years (range 57.7 to 70.5 years) and that most participants (65%) were male. Most studies (12/17) were at risk of performance bias, and for most (14/17), the risk of detection bias was uncertain. These risks may have affected subjective patient-reported outcome measures (e.g. dyspnoea) and secondary review outcomes, respectively.

Use of NIV decreased the risk of mortality by 46% (risk ratio (RR) 0.54, 95% confidence interval (CI) 0.38 to 0.76; N = 12 studies; number needed to treat for an additional beneficial outcome (NNTB) 12, 95% CI 9 to 23) and decreased the risk of needing endotracheal intubation by 65% (RR 0.36, 95% CI 0.28 to 0.46; N = 17 studies; NNTB 5, 95% CI 5 to 6). We graded both outcomes as 'moderate' quality owing to uncertainty regarding risk of bias for several studies. Inspection of the funnel plot related to need for endotracheal intubation raised the possibility of some publication bias pertaining to this outcome. NIV use was also associated with reduced length of hospital stay (mean difference (MD) -3.39 days, 95% CI -5.93 to -0.85; N = 10 studies), reduced incidence of complications (unrelated to NIV) (RR 0.26, 95% CI 0.13 to 0.53; N = 2 studies), and improvement in pH (MD 0.05, 95% CI 0.02 to 0.07; N = 8 studies) and in partial pressure of oxygen (PaO2) (MD 7.47 mmHg, 95% CI 0.78 to 14.16 mmHg; N = 8 studies) at one hour. A trend towards improvement in PaCO2 was observed, but this finding was not statistically significant (MD -4.62 mmHg, 95% CI -11.05 to 1.80 mmHg; N = 8 studies). Post hoc analysis revealed that this lack of benefit was due to the fact that data from two studies at high risk of bias showed baseline imbalance for this outcome (worse in the NIV group than in the usual care group). Sensitivity analysis revealed that exclusion of these two studies resulted in a statistically significant positive effect of NIV on PaCO2. Treatment intolerance was significantly greater in the NIV group than in the usual care group (risk difference (RD) 0.11, 95% CI 0.04 to 0.17; N = 6 studies). Results of analysis showed a non-significant trend towards reduction in dyspnoea with NIV compared with usual care (standardised mean difference (SMD) -0.16, 95% CI -0.34 to 0.02; N = 4 studies). Subgroup analyses revealed no significant between-group differences.

Authors' conclusions

Data from good quality randomised controlled trials show that NIV is beneficial as a first-line intervention in conjunction with usual care for reducing the likelihood of mortality and endotracheal intubation in patients admitted with acute hypercapnic respiratory failure secondary to an acute exacerbation of chronic obstructive pulmonary disease (COPD). The magnitude of benefit for these outcomes appears similar for patients with acidosis of a mild (pH 7.30 to 7.35) versus a more severe nature (pH less than 7.30), and when NIV is applied within the intensive care unit (ICU) or ward setting.


Wednesday, July 26, 2017

Normalization of testosterone levels following replacement therapy associated with a decreased incidence of atrial fibrillation


Abnormal p wave axis is a risk factor for stroke



Conclusions—aPWA is independently associated with ischemic stroke. This association seems to be stronger for cardioembolic strokes. Collectively, our findings suggest that alterations in atrial electric activation may predispose to cardiac thromboembolism independent of atrial fibrillation.

Tuesday, July 25, 2017

Disclosing conflicts of interest to patients


Here is another article from JAMA’s theme issue on COI.

Negative cost incentives as COIs have received relative little attention in the past but are dealt with in this piece:

Physicians and hospitals can also participate in financial agreements in which they generate more revenue if less health care or less expensive medications or devices are used…

..considerable evidence suggests that these financial relationships may exert unconscious influences on physician behavior, particularly when the cost of care, rather than patient clinical outcomes, is involved.

That is a real concern and should present a huge problem to those among our leadership who advocate for the “new professionalism” under which the doctor is to simultaneously advocate for the patient and the population. That puts the individual clinician right in the middle of the conflict which, when disclosed (and disclose we must in this age of transparency) has the potential to undermine trust.

Sunday, July 23, 2017

Capillary leak syndrome


From a recent review:

In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment.

Background here.

Saturday, July 22, 2017

Heavy cannabis use: bad for bone health




The effects of cannabinoids on bone mass and bone turnover in humans are unknown.

Using a cross-sectional study design we found that heavy cannabis use is associated with low body mass index, high bone turnover, low bone density, and an increased risk of fracture.

Heavy cannabis use has a detrimental effect on bone health by a direct effect on the skeleton and an indirect effect mediated by low body mass index.

Friday, July 21, 2017

Babesiosis at Stony Brook University Hospital





Background

Babesiosis is a potentially life-threatening, tick-borne infection endemic in New York. The purpose of this study was to review recent trends in babesiosis management and outcomes focusing on patients, who were treated with combination of azithromycin and atovaquone.

Methods

A retrospective chart review of patients seen at Stony Brook University Hospital between 2008 and 2014 with peripheral blood smears positive for Babesia was performed. Clinical and epidemiological information was recorded and analyzed.
Results

62 patients had confirmed babesiosis (presence of parasitemia). Forty six patients (74%) were treated exclusively with combination of azithromycin and atovaquone; 40 (87%) of these patients were hospitalized, 11 (28%) were admitted to Intensive Care Unit (ICU), 1 (2%) died. Majority of patients presented febrile with median temperature 38.5 °C. Median peak parasitemia among all patients was 1.3%, and median parasitemia among patients admitted to ICU was 5.0%. Six patients (15%) required exchange transfusion. Majority of patients (98%) improved and were discharged from hospital or clinic.

Conclusion

Symptomatic babesiosis is still rare even in endemic regions. Recommended treatment regimen is well tolerated and effective. Compared to historical controls we observed a lower overall mortality.




Saturday, July 15, 2017

Management of atrial fibrillation in the elderly


The elderly are under represented in clinical trials. This review summarizes the available evidence for the management of AF in the elderly. The conclusions of this evidence synthesis are in line with current AF recommendations in general:

Stroke prophylaxis


Elderly adults with AF are at greater risk than those without AF of stroke without anticoagulation and greater risk of bleeding with anticoagulation, posing a therapeutic challenge

Studies assessing the net clinical benefit of anticoagulation (which weighs the risk of ischemic stroke against the risk of major bleeding) demonstrate a significant benefit of anticoagulation in most elderly adults

Recently available direct oral anticoagulants may tip the balance further in favor of anticoagulation by reducing the rate of major bleeding, in particular intracranial hemorrhage

Evidence to support antiplatelet therapy for AF stroke prophylaxis is relatively weak, and in general, antiplatelet agents should have a limited role

In elderly adults who are unable to undergo long-term anticoagulation, percutaneous left atrial appendage occlusion devices may provide a reasonable alternative, although data are still emerging in this area


Symptom management


As a routine strategy, there is no benefit of rhythm control (using anti-arrhythmic drugs, cardioversion, or both) over rate control with AV nodal blocking agents

In individuals treated using rate control, a lenient strategy (target resting heart rate less than 110 bpm) is as effective for symptom control as strict rate control (target resting heart rate less than 80)

Individuals who cannot tolerate rate-slowing agents or those with tachycardia–bradycardia syndrome may benefit from pacemaker implantation plus AV nodal blocking drugs or ablation of the AV node

AF catheter ablation may be beneficial in appropriately selected elderly adults with inadequately controlled symptoms on medical therapy, although data on outcomes of ablation in elderly adults are limited


Wednesday, July 12, 2017

Homocysteine, B12 levels, folic acid levels and various categories of CAD


Elevated homocysteine, low B12 and low folate levels are risk factors for CAD. It remains to be seen whether treatment with these vitamins reduces cardiovascular events in patients identified with abnormal levels.

Tuesday, July 11, 2017

Monday, July 10, 2017

What’s the best BP target in non-diabetic patients with CKD to reduce progression?


Best practice advisories in the EMR


Asthma COPD overlap syndrome: clarifying the confusion


Here are key points from a recent article on this subject:

1) A patient with asthma may develop non-fully reversible airflow obstruction but this is not COPD, not even ACO; it is obstructive asthma.

2) A patient with asthma who smokes may also develop non-fully reversible airflow obstruction, which differs from obstructive asthma and from “pure” COPD. This is the most frequent type of patient with ACO.

3) Some patients who smoke and develop COPD may have a genetic Th2 background (even in the absence of a previous history of asthma) and can be identified by high eosinophil counts in peripheral blood. These individuals could be included under the umbrella term of ACO.

4) A patient with COPD and a positive bronchodilator test (greater than 200 mL and >12% FEV1 change) has reversible COPD but is not an asthmatic, or even ACO.

5) A patient with COPD and a very positive bronchodilator test (greater than 400 mL FEV1 change) is more likely to have some features of asthma and could also be classified as ACO.

Sunday, July 09, 2017

Comparative effectiveness research in action: enoxaparin versus fondaparinux for acute coronary syndrome




Results

Seven studies with a total number of 9618 patients (mainly composed of non-ST elevated myocardial infarction/NSTEMI) were included. This analysis showed mortality to be similarly observed between enoxaparin and fondaparinux with OR: 1.05, 95% CI: 0.67–1.63; P = 0.84. Myocardial infarction (MI) and stroke were also not significantly different throughout different follow up periods. However, minor, major and total bleeding were significantly lower with fondaparinux (OR: 0.40, 95% CI: 0.27–0.58; P = 0.00001), (OR: 0.46, 95% CI: 0.32–0.66; P = 0.0001) and (OR: 0.47, 95% CI: 0.37–0.60; P = 0.00001) respectively during the 10-day follow up period. Even during a follow up period of 30 days or a midterm follow up, major and minor bleeding still significantly favored fondaparinux in comparison to enoxaparin.

Conclusion

In patients who were treated for ACS, fondaparinux might be a better choice when compared to enoxaparin in terms of short to midterm bleeding events. This result was mainly applicable to patients with NSTEMI. However, due to a limited number of patients analyzed, further larger randomized trials should be able to confirm this hypothesis.


The reduced bleeding risk likely has to do with dosing, as I once explained here:

It would appear that the improved outcome was driven by a reduction in bleeding with fondaparinux. I think this relates to the fact that for acute coronary syndrome fondaparinux is administered in the same dose as is used for VTE prophylaxis rather than in a full therapeutic anticoagulation dose.

And, depending on the patient’s body weight, that ACS dose could amount to half, one third or even a quarter the VTE treatment dose. This usage for ACS, while validated in clinical trials, remains off label in the US. This indication based difference in dosing for fondaparinux is similar to that with unfractionated heparin where the ACS dose is lower than the VTE treatment dose. Though enoxaparin is used in the same dose for VTE and ACS treatment, for all we know it might be effective for ACS at a lower dose but as far as I know it has not been studied in that manner.

Saturday, July 08, 2017

Babesiosis review


Post marketing withdrawal of weight loss drugs




Background

We identified anti-obesity medications withdrawn since 1950 because of adverse drug reactions after regulatory approval, and examined the evidence used to support such withdrawals, investigated the mechanisms of the adverse reactions, and explored the trends over time.

Methods

We conducted searches in PubMed, the World Health Organization database of drugs, the websites of drug regulatory authorities, and selected full texts, and we hand searched references in retrieved documents. We included anti-obesity medications that were withdrawn between 1950 and December 2015 and assessed the levels of evidence used for making withdrawal decisions using the Oxford Centre for Evidence-Based Medicine criteria.

Results

We identified 25 anti-obesity medications withdrawn between 1964 and 2009; 23 of these were centrally acting, via monoamine neurotransmitters. Case reports were cited as evidence for withdrawal in 80% of instances. Psychiatric disturbances, cardiotoxicity (mainly attributable to re-uptake inhibitors), and drug abuse or dependence (mainly attributable to neurotransmitter releasing agents) together accounted for 83% of withdrawals. Deaths were reportedly associated with seven products (28%). In almost half of the cases, the withdrawals occurred within 2 years of the first report of an adverse reaction.

Conclusions

Most of the drugs that affect monoamine neurotransmitters licensed for the treatment of obesity over the past 65 years have been withdrawn because of adverse reactions. The reasons for withdrawal raise concerns about the wisdom of using pharmacological agents that target monoamine neurotransmitters in managing obesity. Greater transparency in the assessment of harms from anti-obesity medications is therefore warranted.