Is It Time to Be Dis-ENCHANTED with Low Dose Alteplase in Acute Ischemic Stroke?

Posted by • June 15th, 2016

2016-06-13_13-00-21Ms. M, is hustled in to your emergency room, a septuagenarian with a history of hypertension. She was last noted to be well and playing with her grandchildren 1 hour ago, when her family noticed she began to slur her words, her face drooped to the left and she felt a heaviness & inability to lift her left arm. You activate the stroke team and in minutes a stat head CT rules out a cerebral hemorrhage. With evidence of an acute ischemic stroke a decision for thrombolysis with intravenous alteplase is made. However, with her co-morbidities, and the risk of hemorrhage, one pauses to consider low-dose alteplase as a therapeutic avenue: Would a lower dose 0.6mg/kg intravenous alteplase be more beneficial compared to the standard 0.9mg/kg dose? How would it impact her immediate and eventual risk for death and disability?

Despite the lack of high quality evidence, many Asian centers have adopted low-dose alteplase as a therapeutic alternative to limit the risks of intracranial hemorrhage. The Enhanced Control of Hypertension and Thrombolysis Stroke (ENCHANTED) takes on this complex problem and through a well-designed trial endeavors to fulfill this gap.

The study, published in this week’s NEJM, was designed as a non-inferiority trial, with the goal to prove that the low-dose alternative was no worse than the standard regimen. It recruited 3310 eligible stroke patients from 111 clinical centers in 13 countries. Patients were randomly assigned to receive either the standard regimen or the low-dose alteplase, within 4.5 hours of suffering from stroke. The primary outcome was to determine death or disability at 90 days based on the modified Rankin scale (scores 2-6). Secondary outcomes included any intracranial hemorrhage, a shift (‘improvement’) in function across mRS scores, separately on death and disability, early neurological deterioration, health-related quality of life, length of hospital stay, need for permanent residential care, and serious adverse events.

The study failed to show non-inferiority of the low-dose strategy as the primary outcome was observed in 53.2% of the low-dose recipients, and 51.1% of those who received the standard dose regimen (odds ratio [OR], 1.09; 95% confidence interval [CI], 0.95 – 1.25). The non-inferiority margin was set at  1.14; and the P value for non-inferiority was 0.51). This outcome was consistent across all sub-group analyses, thus this study did not establish that low-dose is non-inferior to standard dose and perhaps suggests that it is not the time to make seismic shifts in treatment guidelines in favor of the low-dose strategy.

The authors note possible limitations of their study to be interobserver variability for the administration of the modified Rankin scale via telephone, the high percentage of Asian participants and a concurrent intensive blood pressure control arm precluding generalizability. Additionally, compared to other stroke trials, patients in this trial included those with mild neurological impairment who were treated at a later time point than symptom onset compared to other stroke trials, thus, leading to an element of selection bias.

However, the study did have some interesting findings, which may affect clinical decision-making. Patients in the low-dose group suffered from significantly fewer major, symptomatic intracranial hemorrhages, at 1% with low-dose vs. 2.1% with standard dose (OR 0.48, 95% CI 0.27-0.86, p= 0.01). Although in an accompanying editorial, it is noted the rates of hemorrhage in both arms were low. This trial does however provide some evidence in support of the low-dose strategy to treat patients of acute ischemic stroke who may have elevated risk of suffering from intracranial hemorrhage.

As this trial failed to demonstrate non-inferiority based on the authors’ pre-specified criterion, the results of ENCHANTED are unlikely to change current clinical practice. However, it does open the debate about considering a lower dose regimen in certain risk groups but future research would be necessary to determine whether low-dose alteplase is preferable in some patients.

Apply to Be an NEJM Editorial Fellow

Posted by • June 14th, 2016

The NEJM invites applications for three one-year, full-time, paid editorial fellowships beginning in July 2017 from medical professionals at any career stage. Applications are due by August 15, 2016.

The editorial fellows review and edit Images in Clinical Medicine submissions, organize the Clinical Decisions series, and write the Quick Takes under the supervision of senior editors. The fellows also moderate commenting at NEJM.org, review topic tagging for the NEJM website, write Insights posts for the Now@NEJM blog, and contribute to other Journal work according to their skills and inclinations. We would like one fellow with an interest in medical education to take the lead on managing NEJM Resident 360, a new website and discussion platform for residents — keeping the Rotation Prep current, facilitating discussions, and working with an editorial team to generate new ideas and content as needed. The fellows also participate in the day-to-day editorial activities of the Journal, including attending the editorial meetings.

We are looking for candidates who have good medical judgment, can communicate that judgment in good written English, and can work independently. Applicants are not required to be U.S. citizens, but successful candidates must reside in the Boston area for the duration of the fellowship. To apply, please send curriculum vitae and a letter of interest to Pam Miller, 10 Shattuck St., Boston, MA 02115 or editorial@nejm.org by August 15, 2016.

For more insight on the NEJM fellowship experience, see the article by Dr. Terry Schraeder, a former NEJM fellow, “NEJM Fellowship: The Ultimate Journal Club,” in Science Editor. Although written 10 years ago, it remains applicable to today’s fellowship.

A Woman with Dyspnea

Posted by • June 10th, 2016

2016-06-03_12-11-02Bronchiolitis is a disease of the small airways, which are defined as airways less than 2 mm in diameter and without cartilage. The bronchioles are especially vulnerable to infectious or inhalational insults because of their narrow diameter.
A 60-year-old woman was seen in a pulmonary clinic because of increasing dyspnea. Chest imaging revealed bronchiectasis and mild, diffuse bronchial-wall thickening. A diagnostic procedure was performed. A new Case Record of the Massachusetts General Hospital summarizes.

Clinical Pearl

• What are some of the general characteristics of bronchiolitis?

The primary symptoms of bronchiolitis are cough and dyspnea. Pulmonary-function testing reveals a nonreversible obstructive ventilatory defect and hyperinflation and often reveals diffusion impairment. Bronchiolitis may occur as a distinct clinical entity, such as acute bronchiolitis or obliterative bronchiolitis, or as part of an interstitial lung disease with bronchiolar involvement, such as respiratory bronchiolitis–associated interstitial lung disease. High-resolution computed tomography (CT) of the chest is the imaging study of choice, and characteristic findings include areas of gas trapping, bronchial-wall thickening, and centrilobular nodules.

Clinical Pearl

• What is obliterative bronchiolitis?

Obliterative bronchiolitis, the histopathological equivalent of constrictive bronchiolitis, is a condition in which the airway lumen of the bronchioles becomes narrowed. Patients present with cough, dyspnea, and nonreversible airway obstruction. Obliterative bronchiolitis is progressive and can result in respiratory failure, because the bronchioles may ultimately become obliterated. As this disease advances, both bronchiectasis and diffusion abnormalities may develop. High-resolution CT reveals mosaic attenuation (i.e., areas of differing attenuation) and gas trapping.

Figure 1. Axial CT Scans of the Chest.

Figure 2. Lung-Biopsy Specimen.

Morning Report Questions

Q: What diseases or exposures are associated with obliterative bronchiolitis?

A: Obliterative bronchiolitis is rarely postinfectious. It has been described in conjunction with exposure to certain medications, including penicillamine and gold, and exposure to certain toxins, such as sulfur dioxide, sulfur mustard, nitrogen oxides, and the food flavoring diacetyl. The bronchiolitis obliterans syndrome refers to obliterative bronchiolitis that occurs during the post-transplantation period, specifically after allogeneic hematopoietic stem-cell transplantation and lung transplantation. Like many of the other types of bronchiolitis, obliterative bronchiolitis can be seen in patients with inflammatory bowel diseases and connective-tissue diseases; on rare occasions, it is idiopathic. Rheumatoid arthritis is the connective-tissue disease most frequently associated with bronchiolitis. It is important to note that, in some patients, the development of connective-tissue disease–associated lung disease can precede the development of the connective-tissue disease itself.

Q: What are some of the other types of bronchiolitis?

A: Acute bronchiolitis is infectious in origin and often caused by respiratory syncytial virus, although it can be seen with influenza, parainfluenza, adenovirus, and mycoplasma. Acute bronchiolitis primarily occurs in children but can occur in adults and is most often self-limiting. Diffuse panbronchiolitis primarily affects middle-aged Japanese men, causing a progressive disease that leads to bronchiectasis, to recurrent infections, and often sinusitis. Respiratory bronchiolitis is primarily seen in smokers and most often detected as an incidental finding on pathological examination of the lungs. Follicular bronchiolitis is also characterized by centrilobular nodules and ground-glass opacities on imaging studies of the chest and is associated with connective-tissue diseases (e.g., rheumatoid arthritis and Sjögren’s syndrome) and immunodeficiency syndromes (e.g., HIV and common variable immunodeficiency). Granulomatous bronchiolitis is a condition that can be seen with inflammatory bowel diseases with pulmonary involvement, interstitial lung diseases (e.g., hypersensitivity pneumonitis, sarcoidosis, and granulomatous–lymphocytic interstitial lung disease), and infectious causes (e.g., tuberculous and nontuberculous mycobacteria).

Ablation for Paroxysmal Atrial Fibrillation

Posted by • June 10th, 2016

2016-06-03_12-16-42According to a 2012 expert consensus statement, catheter ablation of drug-refractory paroxysmal atrial fibrillation is a class I level A indication, and pulmonary-vein isolation is the standard approach. Kuck et al. conducted a randomized trial to compare the performance of the rather complex yet well-established approach of radiofrequency ablation with that of the apparently simpler approach of cryoballoon ablation in a larger population of patients with paroxysmal atrial fibrillation.
Over 700 patients with drug-refractory paroxysmal atrial fibrillation were randomly assigned to cryoballoon or radiofrequency ablation. Cryoballoon ablation was noninferior to radiofrequency for the composite of recurrent atrial arrhythmia, use of antiarrhythmic drugs, or repeat ablation. A new Original Article summarizes.

Clinical Pearl

• How do the two commonly used ablation techniques differ?

The two most frequently used ablation technologies for pulmonary-vein isolation differ in the energy source and mode of application. The most common method is the use of radiofrequency current applied in a point-by-point mode, which leads to cellular necrosis by tissue heating; the other method is the use of cryogenic energy applied with a balloon in a single-step mode, which leads to necrosis by freezing.

Figure 1. Catheter Ablation Methods.

Clinical Pearl

• What are the relative advantages of each of these two ablation techniques?

Radiofrequency ablation for atrial fibrillation requires only limited use of fluoroscopy, because catheter guidance is achieved with the use of an electroanatomical mapping system, but the approach demands extensive training. The complexity of radiofrequency ablation technology has restricted ablation therapy for atrial fibrillation to a few specialized centers and has limited the availability of ablation therapy. Cryoablation for atrial fibrillation requires more extensive fluoroscopic guidance to position the balloon catheter at the pulmonary veins. The cryoballoon was developed to create a circular lesion around each pulmonary vein in a relatively simple manner.

Morning Report Questions

Q: Is cryoballoon ablation as effective as radiofrequency ablation for the treatment of paroxysmal atrial fibrillation?

A: In the study by Kuck et al., cryoballoon ablation was found to be noninferior to radiofrequency ablation with regard to the primary efficacy end point, and superiority was not achieved in either group. The primary efficacy end point in a time-to-event analysis was the first documented clinical failure (recurrence of atrial fibrillation, occurrence of atrial flutter or atrial tachycardia, use of antiarrythmic drugs, or repeat ablation,) following a 90 day period after the index ablation. In the modified intention-to-treat analysis, after the 90-day blanking period, the primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 patients in the radiofrequency group (1-year Kaplan–Meier event-rate estimates, 34.6% and 35.9%, respectively; hazard ratio, 0.96; 95% confidence interval [CI], 0.76 to 1.22; P<0.001 for noninferiority). In the per-protocol analysis, the primary efficacy end point occurred in 118 patients in the cryoballoon group and in 131 patients in the radiofrequency group (1-year Kaplan–Meier event-rate estimates, 31.9% and 35.0%, respectively; hazard ratio, 0.91; 95% CI, 0.71 to 1.17; P<0.001 for noninferiority). A prespecified superiority test performed for the primary efficacy end point did not indicate a significant difference between the treatment groups (P=0.74).

Table 2. Efficacy End Points.

Figure 2. Event-free Survival for the Primary Efficacy and Safety End Points in the Modified Intention-to-Treat Cohort.

Q: In the study by Kuck et al. what was the most common safety event in each of the two study groups?

A: Phrenic-nerve injury was the most common safety event in the cryoballoon group, although the 2.7% rate in the trial was substantially lower than the 13.5% rate reported in the Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) trial. The most common safety events in the radiofrequency group were groin-site complications, which were unusually frequent in this trial (4.3%). Serious treatment-related adverse events of atrial arrhythmia occurred in 2.7% of the patients in the radiofrequency group and in 0.8% of the patients in the cryoballoon group (P=0.09). There was no significant difference in the primary safety end point (a composite of death from any cause, stroke or transient ischemic attack from any cause, and serious adverse events) between the radiofrequency group and the cryoballoon group.

Table 3. Safety End Points.

A New Combination Therapy to Help Prevent COPD Exacerbations?

Posted by • June 8th, 2016

2016-06-01_14-11-44You walk into your office to see, once again, Mr. Jones, at 64-year-old male who suffers from chronic obstructive pulmonary disorder (COPD). Mr. Jones is recovering from a recent visit to the ED due to his third COPD exacerbation event this year. He’s frustrated with his recurrent COPD exacerbations, and wants to know if his current treatment plan really is the best way to prevent them.

Treatment guidelines for prevention of COPD exacerbations recommend either inhaled corticosteroids (ICS) with long-acting β2-agonists (LABA) or an inhaled long-acting muscarinic antagonist (LAMA). However, the dual bronchodilator regimen of LABA/LAMA has yet to be tested in comparison to the ICS/LABA combination. To address the efficacy of this treatment plan, Wedzicha et al report the results of the FLAME trial in this week’s issue of NEJM. The authors enrolled over 3000 patients across 43 countries in this multicenter, randomized, double-blind, non-inferiority study. In terms of their primary endpoint, the LABA/LAMA regimen, indacaterol/glycopyrronium or IND/GLY, reached non-inferiority in comparison to the ICS/LABA regimen, salmaterol/fluticasone or SFC. In addition, IND/GLY showed superiority in reducing the annual rate of exacerbations in comparison to SFC, and prolonged time to first moderate or severe exacerbation. Although high blood eosinophil count had previously been suggested to be a biomarker that indicates better response to ICS/LABA treatment, blood eosinophilia, above or below 2%, did not impact the outcome of this trial. There was no detectable increase in adverse events with IND/GLY vs. SFC in fact there were fewer episodes of pneumonia, 3.2% in the IND/GLY group vs. 4.8% in the SFC group, P,0.02.

From these outcomes, the authors conclude that IND/GLY appears more effective at reducing exacerbations in comparison to SFC. In an accompanying editorial, however, James Donohue, MD, cautions against immediately switching your patients, like Mr. Jones, to this treatment regimen. He warns that more trials, especially those of longer duration and with patients with more severe co-morbidities are needed.

Knife and Gun Club: The Rez Edition

Posted by • June 7th, 2016

2016-06-03_14-09-26In 1989, Eugene Richards published the visual chronicle of scenes from the Denver Country Hospital Emergency Department.  Anyone who has worked in an emergency department (ED) would recognize the grainy photos that put on display the gruesome injuries that people incur as a result of senseless violence.

Let’s face it — in addition to unscheduled primary care and geriatric medicine, much of what we manage in the ED is trauma.  My wife has pointed out that when an emergency doctor is having an interesting, productive, and intellectually engaging day at work, it means someone else is having an extremely bad day.  And over these past months on the reservation, I have noticed a stunning amount of trauma as a result of violence, many of which involve family members and a majority that are complicated by drugs, alcohol, or both. These experiences have left me questioning what might be causing such a stunning disregard for human life in our tiny part of the world.

For example, in one recent week during three separate night shifts, our ED cared for a limb-threatening gunshot wound, a bowel-eviscerating stab wound, five assault and batteries, and a homicide victim who died after a gunshot wound to the chest.  At the same scene where the last patient was found and brought into the ED, another person was killed as a result of a gunshot wound to the head.  In addition, I evaluated a sexual assault victim of intimate partner violence and a victim of elder abuse that absolutely broke my heart.

The Navajo Nation covers a land area of roughly 27,000 square miles, about the same size of West Virginia, with a population of about 180,000. An FBI report in 2013 found that the homicide rate per capita on the rez outpaced that of places like Boston and Seattle, major metropolitan areas that have significantly higher population density.  The per capita homicide rate here is four times the national average.  And even more concerning is that it seems to be affecting native children and adolescents to a much high degree, as reports show that American Indian and Alaska Native (AIAN) children suffer disproportionately from abuse and violence that result in rates of post-traumatic stress disorder that are similar to those seen in service members returning from war.  Here kids are twice as likely to die before the age of 24 when compared to all other races in the U.S.  Tucked back amidst the red rocks, spiritual mesas, and sacred peaks is one of the most dangerous places to grow up in America.

The causes of such trauma and violence are difficult to pin down, but likely result from a confluence of factors including systemic issues arising from complex and contrived jurisdictional tribal laws, an underfunded and understaffed law enforcement force, severe poverty and unemployment, undertreated and undiagnosed mental health conditions, the proliferation of illegal drug-use and alcohol abuse, and the proliferations of gang activity and broken families, due to many of the same issues above

It seems there is a desperation and loneliness which seems to have led to a staggering disregard for the traditional values of Native people — those of community, family, love, generosity, and harmony.

As an emergency department physician who sees the traumatic aftermath but who has individual patient encounters that are episodic and transactional, I was left wondering what is my profession’s role in injury and trauma prevention.  It is vital and should be incorporated into every setting where we care for acutely injured patients.  As emergency physicians on the front lines, we should be at the vanguard of trauma and injury prevention, and control and educate ourselves of the science and evidence-based practices of trauma and injury prevention.

But where to start?

The Center for Disease Control and Prevention is a good resource, and have outlined a systems-based approach to injury prevention. And we, as emergency medicine physicians, can recognize and flag important signals of homicide or suicide clusters, in addition to being effective screeners for intimate partner violence, child and elder abuse, and unsafe social environments for our patients.  Once high-risk individuals are identified, a community-wide agency network is needed to provide needed support.  Perhaps we could partner with national organizations or trauma centers to engage in population and public health research that could help determine which interventions are the most effective and sustainable.

As a profession, our duty to our patients is to always keep them safe and show them how much we care.  Much more than dispensers of medical knowledge and remedies we are advocates, protectors, and promoters of wellness.

What do you think could strengthen our Native communities and help keep them safe from violence?  Please share and thank you for your efforts!

The Hidden Lesion

Posted by • June 3rd, 2016

112The repeated occurrences of clots involving the veins in the proximal left leg raise suspicion for the May–Thurner syndrome (compression of the left iliac vein by the overlying right iliac artery).

A 24-year-old woman presented to the ED with pain in the left leg. She had been training for a 5-km race when, 2 days before presentation, she had crampy pain in her left leg, extending to the left lower abdomen and buttock, plus leg swelling and exertional dyspnea. A new Clinical Problem-Solving summarizes.

Clinical Pearl

• What subset of patients with iliofemoral deep-vein thrombosis may benefit from thrombolysis or thrombectomy?

Selected patients with extensive, acute iliofemoral deep-vein thrombosis who have good functional capacity, favorable life expectancy, and a low risk of bleeding may benefit from early thrombus removal in the form of thrombolysis or thrombectomy. These interventions are invasive and carry procedural risks, including hemorrhage, but they also preserve venous valve function. Thus, they may prevent the onset of the post-thrombotic syndrome, a debilitating long-term complication of deep-vein thrombosis that is characterized by leg swelling, claudication, and ulceration due to valvular incompetence and venous outflow obstruction.

Clinical Pearl

• Is thrombophilia testing indicated in patients who present with a first provoked episode of venous thromboembolism?

Thrombophilia testing is not indicated in patients who present with a first, provoked episode of venous thromboembolism, because the risk of recurrent thrombosis is not greatly affected by the presence of a heritable thrombophilia. The American Society of Hematology recommends against routine thrombophilia testing in patients with provoked venous thromboembolism if the thrombotic event can be readily attributed to a transient, major risk factor. For unprovoked venous thromboembolism, guidelines from consensus groups are less clear and often differ.

Morning Report Questions

Q: What are some clinical features of the May–Thurner syndrome?  

A: The May–Thurner syndrome, or the iliac vein compression syndrome, is the most frequently recognized anatomical abnormality that confers a predisposition to deep-vein thrombosis of the proximal left leg. Patients typically present in their third, fourth, or fifth decade, and there is a strong female preponderance, with a 2:1 ratio of affected women to men. Although the left common iliac vein is classically affected, compression of the left external iliac vein, and even compression of the right iliac vein have also been described.

Q: Is the MayThurner syndrome easy to diagnose and how successful are available therapies? 

A: Making the diagnosis of the May–Thurner syndrome requires a high index of suspicion. Intravascular ultrasonography is more sensitive than traditional angiography in detecting venous obstruction and stenosis. Magnetic resonance imaging can be useful, but the degree of stenosis may be difficult to assess once thrombosis and inflammation have occurred. Case series have shown excellent long-term outcomes after combination therapy with catheter-directed thrombolysis, iliac vein stenting, and anticoagulation; recurrent ipsilateral deep-vein thrombosis owing to stent occlusion has been reported to occur in fewer than 15% of adults treated with this approach and can be managed with repeat thrombolysis and stent placement. Anticoagulation therapy is usually continued for 6 months to a year after stenting, to allow for full endothelialization of the stent. Patients in whom the post-thrombotic syndrome develops may be given extended anticoagulation therapy owing to venous stasis.

Figure 3. Pelvic Venograms.

Figure 4. Intravascular Ultrasonography.

Catheter-Associated Urinary Tract Infection

Posted by • June 3rd, 2016

2016-05-31_11-31-21Catheter-associated urinary tract infection (UTI) is a common device-associated infection in the United States and one of the most common health care–associated infections worldwide. Preventing health care–associated infection in general, and catheter-associated UTI in particular, has emerged as a priority in the United States, with government agencies taking a lead role. The Agency for Healthcare Research and Quality, along with the Health Research and Educational Trust (the research and education affiliate of the American Hospital Association) and its partners, launched a nationwide effort to implement the Comprehensive Unit-based Safety Program (CUSP) to reduce catheter-associated UTIs in U.S. hospitals. Saint et al. report the results from the first four of nine cohorts of hospital units in the June 2, 2016, issue of the New England Journal of Medicine.

In this study of an educational program to prevent catheter-associated urinary tract infection, implemented in more than 10% of U.S. acute care hospitals, both catheter use and catheter-associated UTI rates were significantly decreased in the non-ICU setting. A new Original Article summarizes.

Clinical Pearl

• To what extent is catheter-associated urinary tract infection preventable?

Up to 69% of catheter-associated UTIs are considered to be avoidable, provided that recommended infection-prevention practices are implemented.

Clinical Pearl

• How much success have efforts beginning in 2009 had in reducing the rate of catheter-associated UTI in acute care hospitals?

Catheter-associated UTI was the first hospital-acquired complication chosen by the Centers for Medicare and Medicaid Services in 2008 as the basis for denial of additional payment to hospitals. In 2009, the Department of Health and Human Services released the “National Action Plan to Prevent Health Care–Associated Infections: Road Map to Elimination,” which provided strategic guidance for preventing infections in acute care hospitals. The goal was to reduce the rates of catheter-associated UTI by 25% by 2013. Despite these efforts, national data indicate that the incidence of catheter-associated UTI increased by 6% from 2009 to 2013.

Morning Report Questions

Q: What kinds of interventions might contribute to a decrease in catheter-associated UTI in acute care hospitals? 

A: In the Comprehensive Unit-based Safety Program, key interventions were as follows: conducting a daily assessment of the presence and necessity of an indwelling urinary catheter; avoiding the use of an indwelling urinary catheter by considering alternative urine collection methods, such as intermittent straight catheterization; and emphasizing the importance of aseptic technique during insertion of a catheter and proper maintenance after insertion. Additional recommended interventions were as follows: providing feedback to the units’ nurses and physicians on catheter use and catheter-associated UTI rates and providing training to address any identified gaps in knowledge about urinary management processes (i.e., proper insertion and maintenance of indwelling urinary catheters, use of alternative urine collection methods, and prevention of infectious and noninfectious consequences of urinary catheter use). Education on the prevention of catheter-associated UTI was provided to participating units through in-person meetings, coaching calls, and webinars. In addition, monthly national content calls were conducted, during which experts provided education on both technical and socioadaptive aspects of catheter-associated UTI prevention. The leaders also led monthly coaching calls with the participating units in the leader’s state to review data trends, discuss unit-specific issues, and share best practices in the prevention of catheter-associated UTI.

Table 1. Program Recommendations and Examples of Interventions.

Figure 1. Study Timeline.

Q: Did the interventions in the Comprehensive Unit-based Safety Program reduce rates of catheter-associated UTI?

A: Saint et al. found that a collaborative effort focusing on both technical and socioadaptive interventions can reduce catheter-associated UTI rates in the non-intensive care unit (ICU) setting. Data on catheter use and catheter-associated UTI rates were collected during three phases: baseline (3 months), implementation (2 months), and sustainability (12 months). In an adjusted analysis, the rates decreased from 2.40 to 2.05 infections per 1000 catheter-days (incidence rate ratio, 0.86; 95% confidence interval [CI], 0.76 to 0.96; P=0.009). Reductions occurred mainly in non-ICUs, where catheter-associated UTI rates decreased from 2.28 to 1.54 infections per 1000 catheter-days (incidence rate ratio, 0.68; 95% CI, 0.56 to 0.82; P<0.001). The rates did not change significantly in the ICUs.

Table 3. Multivariable-Regression Estimates of Changes in Catheter-Associated UTI Rates, According to Unit Type.

Catheter-Associated Urinary Tract Infections

Posted by • June 2nd, 2016

118In your role as Unit Medical Director, you regularly meet with nursing leadership for 6-West.  Today, they bring to your attention several cases from the last month: a 67-year old female admitted for severe pneumonia who initially rapidly improved on antibiotics, but then developed a new fever and was found to have a urinary tract infection; an 83-year old male admitted for elective hip replacement who became obtunded and hypotensive on hospital day 3, and was found to have a urinary tract infection; and a 77-year old male with heart failure on a furosemide drip who this morning was found to have a new leukocytosis that was preliminarily being attributed to a urinary tract infection.  All of them had urinary catheters in place prior to and at the time of their diagnoses.  One nurse states, “I think we could have prevented these events.  How can we work together to decrease the risk of CAUTI for all our patients?”  

Catheter associated urinary tract infection (CAUTI) affects about 2 million patients per year.  Its mechanism of infection is understood, the technical means to prevent it are known, and it remains a high-profile topic of national concern.  Despite this, recent data from the Centers for Disease Control and Prevention indicate that between 2009 and 2012 the US national CAUTI rate actually rose by 3%.  This week’s NEJM contains a study that informs our efforts to minimize CAUTI.

Saint et al. report on a partnership between The Agency for Healthcare Research and Quality and the American Hospital Association known as Comprehensive Unit-based Safety Program (CUSP) to Reduce CAUTI.  This effort was launched nationally with the goal of implementing best practices to prevent CAUTI at United States Hospitals.  Since 2011, nine cohorts of hospital units have been recruited.  Participating units agreed to form local teams focused on CAUTI prevention, collect and share relevant data, and participate in ongoing interventions.  Interventions included technical/educational (e.g. appropriate use, aseptic insertion, proper maintenance, and timely removal of catheters) as well as “socio-adaptive”, a term the authors use to describe aspects related to the challenges of improvement implementation.  Beyond this, local teams were empowered to tailor CAUTI prevention initiatives to meet their unique situations and needs.  Ongoing mentorship was provided by project leadership.

Saint et al. now present data on the CAUTI rate and the proportion of patients with indwelling catheters collected from CUSP to Reduce CAUTI’s first 4 cohorts between March 2011 and November 2013.  In the 926 analyzed hospital units, study authors found that adjusted CAUTI rates significantly decreased from 2.4 to 2.05 per 1,000 urinary catheter-days.  During this time, catheter utilization rate also significantly decreased from 20.1% to 18.8%.  On subgroup analysis, authors found that these effects were predominantly driven by non-ICU units.  In fact, in the subset of ICU units, there was neither a significant change in the rate of catheter utilization nor in the CAUTI rate.

At this point, you may be asking yourself, So what? We’ve known for a long time that appropriate use, aseptic insertion, proper maintenance, and timely removal of catheters can help prevent CAUTI.  How is this news?  The significance of CUSP to Reduce CAUTI relates to its focus on teams, communication, problem solving, and implementation mentoring to achieve change in clinical practice.  As patient safety expert Dr. Lucien Leape commented in NEJM in 2014, “The key is recognizing that changing practice is not a technical problem… but a social problem of human behavior and interaction.” CUSP to Reduce CAUTI succeeds by addressing both the technical as well as the social.

While providing us with hope for attainable change in preventing CAUTI in the non-ICU setting, Saint et al. do leave us wondering about the future of CAUTI prevention efforts in the ICU.  In an accompanying editorial, Dr. Susan Huang of UC Irvine School of Medicine draws attention to several factors, both patient-specific and general, that may have complicated CAUTI reduction efforts for critically ill patients in this study.  Among them, ICU patients may require longer use of catheters (and a resulting increased risk for CAUTI) as a direct result of their critical illness.  There may also be an inappropriate perceived need for longer use of catheters in this population, a potential social barrier to catheter discontinuation.  Lastly, successive changes to the definition of CAUTI may have resulted in increased rates of CAUTI beginning in 2012, and decreased rates beginning in 2015.  For the data presented by Saint et al. (collected between 2011 and 2013) this may have underestimated the benefits of CUSP to Reduce CAUTI.

Recognizing the importance of CAUTI prevention, you organize a team of interested nurses, patient care technicians, resident and attending physicians, and administrators.  You engage hospital leadership and contact other units in your hospital who have lower CAUTI rates than yours.  While several members of the group are developing a nursing-driven catheter discontinuation protocol, you begin to think about what social barriers to change might exist to this intervention.  

Have you participated in a CAUTI prevention project on your unit?  What barriers to change did you face?

Don’t miss the NEJM Quick Take video summary on this study:

Cryptogenic Stroke

Posted by • May 27th, 2016

2016-05-23_14-38-46Cryptogenic ischemic strokes are symptomatic cerebral infarcts for which no probable cause is identified after adequate diagnostic evaluation. In general, the percentage of ischemic strokes that are classified as cryptogenic has declined over time as diagnostic testing has advanced. However, stroke that is cryptogenic after a standard diagnostic evaluation remains a common clinical challenge, accounting for 20 to 30% of all ischemic strokes and therefore occurring in 120,000 to 180,000 patients each year in the United States. As compared with strokes of determined origin, cryptogenic ischemic strokes typically result in less severe presenting neurologic deficits, less final disability, and lower mortality.

One quarter of ischemic strokes are cryptogenic (no obvious cause). Additional investigation involves assessment for arteriopathies, cardiac sources of embolism (in particular, occult low-burden atrial fibrillation), and disturbances of coagulation. A new Clinical Practice summarizes.

Clinical Pearl

• What are some of the causes of cryptogenic stroke that may be discovered after more specialized testing?

In patients with ischemic stroke that is considered to be cryptogenic after standard evaluation, causes that are most often found after more specialized testing include occult atherosclerosis, including nonstenosing but unstable plaques at intracranial and cervical sites or stenosing plaques at the thoracic origins of the common carotid and thoracic vertebral arteries; nonatherosclerotic arteriopathies, such as dissection or vasculitis; hypercoagulable states; cardioembolism from medium-grade sources, such as low-burden paroxysmal atrial fibrillation or dilated cardiomyopathy of moderate degree; and paradoxical embolism.

Clinical Pearl

• What is the most common cause of cryptogenic stroke in young adults?

The age of the patient influences the likelihood of various causes. In young adults 18 to 30 years of age, dissection is most common, but thrombophilias and congenital cardiac disease are also noteworthy causes. In persons 31 to 60 years of age, early-onset atherosclerosis and acquired structural cardiac disease are increasingly common. In patients older than 60 years of age, occult atrial fibrillation becomes more frequent.

Morning Report Questions

Q: What patient characteristics increase the likelihood that protracted cardiac monitoring will reveal occult atrial fibrillation? 

A: Technology to detect infrequent paroxysmal atrial fibrillation has dramatically improved over the past decade, with the development of mobile cardiac telemetry systems that may be worn externally for 2 to 4 weeks, subcutaneous loop recorders with battery lives enabling detection for 1 to 3 years, and in patients needing therapeutic internal pacemakers or defibrillators, implantable therapeutic devices with the capability to detect atrial fibrillation for 3 years or more. Among patients whose ischemic strokes are cryptogenic after conventional inpatient evaluation, prolonged outpatient cardiac monitoring detects low-burden atrial fibrillation in 15%. Patients with low-burden paroxysmal atrial fibrillation have a lower risk of stroke than patients with chronic or high-burden paroxysmal atrial fibrillation. However, their risk of stroke is higher than that among persons without atrial fibrillation. As little as a single 1-hour episode of atrial fibrillation during 2 years of monitoring has been associated with a doubling in the risk of ischemic stroke. The characteristics of patients that increase the likelihood that protracted monitoring will uncover low-burden atrial fibrillation include older age and higher CHA2DS2-VASc score (on which scores range from 0 to 9, with higher scores indicating greater risk), cerebral infarct topographic features (such as multiple vascular territories and cortical location), and indexes of left atrial cardiopathy, including left atrial dilatation, strain, and reduced emptying fraction, left atrial appendage size and single-lobe morphologic features, p-wave dispersion on ECG [electrocardiogram], frequent atrial premature beats, and elevated N-terminal pro–brain natriuretic peptide serum levels.

Q: When a patent foramen ovale is found during the work up of cryptogenic stroke, how is one to know if it is causally related?

A: A patent foramen ovale is present in approximately one quarter of the general patient population but in one half of patients with cryptogenic stroke. A Bayesian attributable risk analysis of pooled data from 12 studies suggested that among patients with cryptogenic stroke who had a patent foramen ovale, the patent foramen ovale is probably causally related to the stroke in approximately half. Features that increase the likelihood of a causal relationship include younger age; Valsalva maneuver at the onset of stroke; extended plane or car travel preceding the stroke; concomitant venous thrombosis in the leg or pelvis; coexisting venous hypercoagulable state; coexisting atrial septal aneurysm; history of migraine with aura; cortical location, multiplicity, and large size of cerebral infarcts; and absence of hypertension, diabetes, and smoking.

Figure 1. Algorithm for the Identification and Diagnostic Evaluation of Patients with Cryptogenic Ischemic Stroke or Transient Ischemic Attack (TIA).

Table 1. Suggestive Findings on History and Physical Examination in Patients with Cryptogenic Stroke.