A 32-Year-Old Woman with Recurrent Episodes of Altered Consciousness

Posted by Sara Fazio • June 14th, 2013

In the latest Case Record of the Massachusetts General Hospital, a 32-year-old woman was seen in the neurology clinic because of episodes of altered consciousness — staring, aphasia, and occasional sudden loss of postural tone and collapse. EEG revealed left-temporal-lobe seizures; brain imaging revealed a left-temporal-lobe mass.

The relationship between seizures and cardiac dysrhythmia may take several demonstrated or hypothetical forms. For example, dysrhythmia can cause seizure (convulsive syncope), seizure can cause dysrhythmia (arrhythmogenic epilepsy), treatment can cause dysrhythmia, or seizure and dysrhythmia can occur as epiphenomena caused by a shared underlying mechanism.

Clinical Pearls

•  How common are cardiac dysrhythmias in epilepsy?        

Cardiac dysrhythmias in epilepsy are not uncommon and have been hypothesized to underlie sudden unexplained death in epilepsy (sometimes referred to as SUDEP), which affects 0.5 to 1.0% of patients with epilepsy each year and is the leading cause of death associated with epilepsy. Both bradyarrythmias and tachyarrhythmias have been described. Ictal tachycardia is most common, although in one study, 7 of 20 patients had ictal bradycardia in at least one seizure, and 3 of those patients had asystolic events. Only a minority of events recorded from any given patient show bradyarrhythmia, indicating that this phenomenon can be intermittent.

• How might seizures cause dysrhythmia?           

It is possible that catecholamine release, acidosis, or hyperkalemia resulting from prolonged convulsive activity could induce arrhythmia. Alternatively, seizure activity may involve cerebral structures that are important in the regulation of cardiac rhythm, including the amygdala, insula, or hypothalamus. Studies of cortical stimulation in humans indicate that direct electrical stimulation or transcranial direct-current stimulation of the left hemisphere, particularly the insula, may activate parasympathetic descending pathways, leading to bradycardia. Similarly, the infusion of amobarbital into the left carotid artery anesthetizes the left hemisphere and produces tachycardia, whereas infusion into the right carotid artery produces the opposite result. Case reports of ictal asystole suggest that the onset of seizures occurs predominantly on the left side, but clear cases of onset on the right side have been documented.

Morning Report Questions

Q: What is the relationship between long-QT syndrome and epilepsy? 

A: The loci for long-QT syndrome include more than 17 genes encoding ion channels, connexins, and transcription factors. Mutations in these genes produce paroxysmal bradycardia and syncope; electrocardiographic features include long and short QT intervals, torsades de pointes, and asystole. Most of these genes show dual expression in the heart and brain, and perhaps additional expression in the autonomic nerves, defining a singular mechanism linking epilepsy, cardiac arrhythmia, and sudden death. Patients with the long-QT syndrome have a high incidence of seizures; furthermore, seizures, the long-QT syndrome, and sudden cardiac death occur in transgenic mice carrying human genes with mutations in the most common gene for the long-QT syndrome.

Q: What are the indications for surgical treatment of epilepsy? 

A: Indications for surgical treatment of epilepsy include medical intractability, disabling seizures, and a reasonable likelihood that the situation can be improved at an acceptable level of risk. Additional indications are seizures that are immediately life-threatening and a diagnosis of underlying lesions, usually tumors.

Tags: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Posted in Physicians-In-Training | Permalink | No Comments

Racemic Adrenaline in Acute Bronchiolitis

Posted by Sara Fazio • June 14th, 2013

In this study of infants with bronchiolitis, there was no difference in the length of hospital stay between those treated with inhaled adrenaline and those treated with inhaled saline. Infants treated on demand had a shorter length of stay than those treated on a fixed schedule.

Acute bronchiolitis in infants frequently results in hospitalization, but there is no established consensus on inhalation therapy – either the type of medication or the frequency of administration.

Clinical Pearls

• What is the usual etiology and clinical manifestations of acute bronchiolitis in infants?

Acute bronchiolitis in infants, which frequently leads to hospitalization and sometimes requires ventilatory support, is occasionally fatal; it is usually viral in origin, with respiratory syncytial virus being the most common cause. The clinical disease is characterized by nasal flaring, tachypnea, dyspnea, chest recessions, crepitations, and wheezing.

• How is bronchiolitis in infants typically managed?

Bronchodilators are not recommended but are often used in the treatment of bronchiolitis, as are saline inhalations. Adrenaline reduces mucosal swelling, giving it an edge over the (beta)2-adrenergic agonists, and has led to the frequent use of inhaled adrenaline, which has improved symptoms and reduced the need for hospitalization in outpatients with acute bronchiolitis. Among inpatients, however, inhaled adrenaline has not been found to reduce the length of the hospital stay. Glucocorticoids are not recommended.

Morning Report Questions

Q: What were the study results comparing the use of inhaled racemic adrenaline versus inhaled saline?

A: There was no significant difference in length of hospital stay between children treated with inhaled racemic adrenaline and those treated with inhaled saline (P=0.43). There were also no significant between-group differences in the use of nasogastric-tube feeding, supplementary oxygen, or ventilatory support; clinical scores before and after the first inhalation of the study medication; or the number of children in whom the study medication was discontinued.

Table 2. Length of Stay and Use of Supportive Therapy According to Medication and Inhalation Strategy.

Q: What did the analysis of on-demand versus fixed-schedule dosing of racemic adrenaline demonstrate?

A: The mean length of the hospital stay was significantly shorter for children in the group receiving treatment on demand than in the group receiving treatment on a fixed schedule (P=0.01). Children in the on-demand group received a mean of 5.0 (30%) fewer inhalations than those in the fixed-schedule group (P<0.001). Children receiving inhalations on demand also had a lower probability of being treated with ventilatory support (P=0.01) or supplementary oxygen (P=0.04), and inhalations given on demand were not associated with nasogastric-tube feeding or treatment discontinuation.

Table 2. Length of Stay and Use of Supportive Therapy According to Medication and Inhalation Strategy.

 

Tags: , , , , , , , , , , , , , , , , , , , , , ,
Posted in Physicians-In-Training | Permalink | No Comments

Global Health Author Q&A: London School of Hygiene and Tropical Medicine’s Peter Piot

Posted by Jennifer Zeis • June 13th, 2013

In a feature for Now@NEJM, we ask the authors of the new Global Health review article series — all with different backgrounds, experiences, and perspectives — the same set of questions.

Answers from Peter Piot, M.D., Ph.D., of the London School of Hygiene and Tropical Medicine, London, UK.

Dr. Piot is a co-author of the June 6 article, “The AIDS Pandemic —A Global Health Model.”

What do you regard as the most significant triumph in global health within the past decade?

In general there has been more progress in terms of life expectancy, under five mortality, and several of the health related millennium development goals than ever before.

It is the global AIDS response that basically generated the current global health movement (even the term “global health” appeared only around the millennium).  AIDS also put global health at the highest political agendas, where it had never been – a necessary condition for major policy and financial commitments.

Thanks to an unprecedented international mobilization of financial and human resources, HIV incidence and mortality have declined significantly in most countries, and for the first time significant resources are available against tuberculosis and malaria.

In the coming decade, which arena of global health do you feel warrants increased attention and awareness?

First of all, we should not neglect the major unfinished agenda of infectious diseases, maternal, neonatal and child mortality and under nutrition.

At the same time there is a growing pandemic of obesity and chronic diseases emerging, together with high levels of the most neglected of all health issues- mental health. In addition, climate change and environmental degradation may affect health in a major way in low and middle income countries, many of which are highly vulnerable in terms of environmental resilience. Finally, inequalities in health and access to health services must be addressed.

Chronic diseases and environmental health require very different approaches than infectious diseases, as key upstream interventions are largely based outside the health sector – from anti-smoking laws to dietary and exercise interventions. This implies that we must work much more with other sectors to ensure that they contribute to good health, instead to ill health as is often the case now.

How can we best harness the revolution in IT to improve health outcomes in the developing world?

The penetration of mobile phones in even the poorest countries is a true game changer for many aspects of life, including poverty alleviation and health promotion and access to health services. It will have an impact on everything we do in health, from disease surveillance and information systems, to point of care diagnosis and training of health workers. They are an invaluable tool to make task shifting a reality with good quality standards.

Above all, mobile technologies are a major tool for empowerment of poor and marginalized people by giving them access to bank accounts, money transfer, prices of commodities, and even an identity. Commercial companies are already offering a growing range of IT applications, and it seems most effective to team up with them to accelerate their wide spread us and affordability in low and middle income countries.

What are other ways for physicians to contribute to global health?

As a start, we should remind ourselves that global health is not just about health far away, but starts at home, where significant health inequalities continue to exist, and where increasingly people from all over the world are living. Therefore we can all contribute wherever we live and work.

In addition, we can engage in research relevant for the developing world, and ensure that both the substance and application of our research are mindful of low and middle income countries’ issues. Encouraging  young colleagues to gain on the ground experience in global health, and valuing that experience for their career advancement, are important incentives for main streaming global health in medicine and public health in high income countries. Supporting funding for global health is always useful.

No academic health sciences center should be considered complete without a global health component!

Tags: , ,
Posted in What's New | Permalink | No Comments

A randomized trial of MRSA-control strategies in the ICU

Posted by Jamie Colbert • June 12th, 2013

As healthcare workers we have become accustomed to seeing that yellow sign on the door indicating that a patient is on “Contact Precautions” to prevent the spread of healthcare-associated methicillin-resistant Staph aureus (MRSA) infection. So we dutifully wash our hands and put on gown and gloves prior to entering the room to examine the patient. In the ICU where I trained as a medical resident, all patients underwent nasal swab testing for the presence of MRSA. Patients who tested negative for MRSA could come off of precautions. Those who tested positive would stay on precautions for the duration of their hospital stay.

This week’s issue of NEJM presents the results of a three-armed randomized trial aimed at reducing MRSA colonization and bloodstream infections. MRSA control strategies are now standard at many ICUs across the United States, yet there is much debate as to how best to reduce hospital-acquired infections. The argument for targeted testing for MRSA is that this pathogen is particularly nasty: it is multi-drug resistant, highly virulent, and its prevalence in both the community and healthcare settings has been increasing with time. In 2011, NEJM published the results of a large Veteran’s Affairs MRSA screening initiative which was able to reduce health-care associated MRSA infections. Yet, an independent analysis of the data suggested that the reduction in infections may have been due to other factors besides the MRSA screening and isolation of those colonized. A separate randomized trial of MRSA screening and infection control measures that was also published in NEJM in 2011 found no reduction in MRSA infections as a result of the intervention. Furthermore, this study found that compliance with the infection control measures was poor: hand hygiene was used only 2/3 of the time and gowns were worn only ¾ of the time.

An unintended consequence of targeted screening for MRSA is that patients who test positive are not only isolated from other patients in the hospital – they become isolated from caregivers as well. A recent study from Maryland found that hospitalized patients on contact precautions received 36% fewer visits from healthcare workers and 24% fewer visits from family and friends as compared to their non-precaution peers. Given the questionable benefit of MRSA screening and isolation strategies for preventing healthcare-associated infections as well as the fact that such isolation can result in social isolation of patients, many in the infection control community have begun to explore other strategies for reducing the transmission of healthcare-associated infections.

Instead of simply placing MRSA-positive patients on contact precautions, another option exists: dropping the bacterial load with intra-nasal mupirocin and chlorhexidine bathing. The study published in this week’s NEJM compares standard MRSA screening and isolation with two other approaches to infection control. Arm 1 of the study underwent usual care with MRSA screening and contact precautions for those testing positive. Arm 2 also underwent screening for MRSA and standard contact precautions, but those testing positive underwent decolonization with mupirocin and chlorhexidine. Patients in the third arm of the study did not have MRSA screening, but instead they received universal decolonization with mupirocin and chlorhexidine. Because the patients in the third arm did not undergo MRSA screening, they were not placed on contact precautions unless they had a prior history of MRSA or their clinical cultures grew a pathogen requiring precautions.

This was a large study with more than 40 participating hospitals and over 70,000 patients. The results showed that those in the universal decolonization group had a greater reduction in MRSA-positive clinical cultures as well as a greater reduction in all-pathogen bloodstream infections as compared with targeted decolonization or standard screening and isolation strategies.  The study also examined rates of MRSA bloodstream infection and did not find any statistical difference between the groups.

In an accompanying editorial, Dr. Michael Edmond and Dr. Richard Wenzel write that the results of this study cast doubt on the benefits of MRSA screening and isolation strategies and “should prompt hospitals to discontinue [this] practice for control of endemic MRSA.” Furthermore, they note “A benefit will be a reduced proportion of patients in contact precautions, which is a patient unfriendly practice that interferes with care.”

While these data are compelling, the stakes are high – as many hospital-acquired infections are no longer reimbursed by some insurers. Further studies are needed to corroborate these findings as well as to examine whether a strategy of universal decolonization with mupirocin and chlorhexidine could lead to greater microbacterial resistance. A cost-benefit analysis would also be useful, given that MRSA screening and isolation programs can exact both a direct financial cost as well as the labor cost of nursing and support staff who must implement such programs. But more important than the potential for cost savings is the possibility that moving towards a strategy of universal decolonization could reduce the number of patients on contact precautions and remove an unfortunate barrier to visitation by health workers, family, and friends.

Connect with Dr. Colbert on Twitter: @jcolbertMD

Tags: , , , , , , , , ,
Posted in Insights | Permalink | No Comments

The AIDS Pandemic

Posted by Sara Fazio • June 7th, 2013

The HIV–AIDS pandemic is now in its fourth decade. The latest article in our new Global Health series describes how HIV–AIDS has been transformed from a death sentence into a manageable illness and outlines the need for continued and coordinated international efforts.

It was not until the third decade of the epidemic that the world’s public health officials, community leaders, and politicians united to combat AIDS. In 2001, the United Nations General Assembly endorsed a historic Declaration of Commitment on HIV/AIDS and renewed this commitment in 2011. These actions resulted in the formation of the Global Fund to Fight AIDS, Tuberculosis, and Malaria to finance anti-AIDS activities in developing countries. In 2003, President George W. Bush announced the President’s Emergency Plan for AIDS Relief (PEPFAR), which allocated billions of dollars to countries hardest hit by AIDS.

Clinical Pearls

• How many people were estimated to be living with HIV in 2011?           

UNAIDS (United Nations Program on HIV/AIDS) estimates that in 2011, 34.2 million people were living with HIV, as compared to 29.1 million in 2001; 2.5 million had become newly infected, a 22% decline as compared to 2001, and 1.7 million died, a decline of 26% from 2005. Similarly, new infections among neonates and infants have decreased from a peak of 570,000 in 2003 to 330,000 in 2011 as a result of interventions to prevent mother-to-child transmission.

• What regions of the world are most affected by HIV, and in what regions has the spread of HIV begun to decline and where has it increased?         

According to the authors, sub-Saharan Africa continues to be the most affected continent, followed by Eastern Europe and the Caribbean. A special case is southern Africa, where HIV has become hyperendemic, with adult HIV prevalence rates as high as 31% in Swaziland, 25% in Botswana, and 17% in South Africa, reaching an astonishing 54% among women between the ages of 30 and 34 years in Swaziland. Even within a country, differences in HIV prevalence can vary widely by region and risk group. Thus, in 2010 within South Africa, provincial antenatal  HIV prevalence ranged from 18.4% in the Northern Cape to 39.5% in KwaZulu Natal. Men who have sex with men, female sex workers, users of injection drugs, truck drivers, fishermen, and military personnel are disproportionately affected around the world. There is also heterogeneity in epidemiologic trends. Whereas HIV spread is slowing in most regions, HIV incidence continues to increase in Eastern Europe and several Asian countries. There is also a resurgence of HIV infection due to increased risk behavior among men who have sex with men in several European cities, such as a 68% increase in sexual risk behavior among such men in Amsterdam — in spite of high rates of HIV testing and access to antiretroviral therapy (ART). At the same time,  HIV is spreading to previously unaffected populations, such as injection drug users in parts of Africa and men who have sex with men across Asia and Africa, where widespread homophobia drives these men underground.

Figure 1. World Map of Prevalence of HIV Infection.

Morning Report Questions

Q: What are current recommendations regarding the initiation of treatment of HIV/AIDS?

A: With the life expectancy of an HIV-infected person under treatment approaching that of an uninfected person, there has been an increased emphasis on starting ART therapy much earlier in the course of infection. The revised 2012 U.S. Department of Health and Human Services guidelines recommend ART for all HIV-infected individuals. These recommendations are based on evidence of ongoing HIV replication on disease progression. Additionally, because ART use prevents transmission of HIV in discordant couples, the guidelines recommend that ART be offered to all HIV-infected individuals to reduce the risk for their sexual partners. In contrast to the U.S. and European guidelines, the World Health Organization guidelines continue to recommend treating all persons with CD4 counts less than or equal to 350, recognizing the limitations of cost and availability in many countries. However, all guidelines strongly recommend ART for persons, regardless of CD4 count, who are pregnant or who have a history of an AIDS-defining illness, tuberculosis, or coinfection with HIV and hepatitis B, and, more recently, the guidelines were updated to recommend ART for HIV-discordant couples.

Table 1. Guidelines for the Initiation of Antiretroviral Drugs in Adults with HIV Infection.

Q: What are the principles of preexposure prophylaxis (PrEP)? 

A: Use of ARTs prior to sex is referred to as preexposure prophylaxis. Precoital use of 1% tenofovir gel reduced HIV acquisition by 39% in women and daily oral tenofovir and emtricitabine among men who have sex with men reduced HIV acquisition by 44%, with greater efficacy observed among individuals who achieved high levels of adherence in both trials. Daily tenofovir or tenofovir plus emtricitabine reduced HIV acquisition by 66% and 73%, respectively, among uninfected partners in HIV serodiscordant partnerships, and in young heterosexuals in Botswana. While these studies are encouraging, two studies produced conflicting results, finding no efficacy with either oral or gel Tenofovir. The explanation for these discrepant studies may be due to low adherence to the drug regimens or differences in mucosal penetration. Recently, the Food and Drug Administration approved daily oral Truvada (emtricitabine and tenofovir disoproxil fumarate) for PrEP in combination with safer sex practices to reduce the risk of sexually acquired HIV infection in adults at high risk.

Tags: , , , , , , , , , , , , , ,
Posted in Physicians-In-Training | Permalink | No Comments

Waiting for the Other Foot to Drop

Posted by Sara Fazio • June 7th, 2013

In the latest article in our Clinical Practice series, a  65-year-old man presented with a 4-month history of fevers, sweats, fatigue, and weakness. He also reported that pain in his feet and calves was sufficiently distracting that he could not enjoy reading.

Mononeuropathy multiplex is typically is manifested by findings in several focal, noncontiguous nerve distributions. The differential diagnosis for mixed motor and sensory multiple mononeuropathy includes hereditary neuropathy with a propensity for pressure palsies, diabetic neuropathy, vasculitides (systemic and nonsystemic), sarcoidosis, infectious processes (e.g., leprosy, Lyme disease, syphilis, cytomegalovirus infection, human immunodeficiency virus [HIV] infection), amyloidosis, and neoplastic infiltration (most commonly lymphomatous).

Clinical Pearls

• What is polyarteritis nodosa?  

Classically, polyarteritis nodosa is a necrotizing vasculitis affecting medium-size or small arteries; in 50 to 75% of patients, the peripheral nervous system is involved. The incidence of polyarteritis nodosa is estimated at 5 to 77 cases per million persons per year, of which about one third of cases are attributable to HBV, although this fraction varies with local HBV burden. Clinical features overlap with those of microscopic polyangiitis, which targets arterioles, venules, and capillaries.

• How is hepatitis B transmitted, and how should serologies be interpreted?     

HBV is a DNA virus transmitted through percutaneous, sexual, and perinatal routes. Nosocomial transmission is well documented. Subclinical infection can persist without detection for long periods, making it difficult to pinpoint the timing of viral acquisition.  Laboratory studies performed to distinguish acute infection from chronic disease flares are imperfect. The IgM antibody against hepatitis B core (HBc), classically considered an indicator of acute infection, can be present in reactivation and flares of chronic infection. Higher titers of IgM antibody against HBc (positive at >1:10,000) and relatively low HBV DNA levels (<0.5 pg per milliliter or <10[5] copies per milliliter) suggest acute infection in patients with symptomatic hepatitis.

Morning Report Questions

Q: How should patients with polyarteritis nodosa caused by HBV infection be treated?       

A: Polyarteritis nodosa caused by HBV infection generally requires both immunosuppressive and antiviral therapy, since the disease appears to be driven by viral replication and immune-complex formation and deposition. Although there is a paucity of data from clinical trials, observational data from patients treated with antiviral therapy in combination with immunosuppression suggest improved event-free survival relative to historical controls treated only with immunosuppression. Managing coincident HBV infection and polyarteritis nodosa is challenging. Immune suppression is warranted to arrest tissue damage caused by vasculitic inflammation but may promote uncontrolled viral replication and fulminant hepatitis. To balance these concerns, treatment strategies generally involve simultaneous immune suppression, targeted antiviral therapy, and plasma exchange to eliminate immune complexes.

Q: What is the duration of therapy in patients with concomitant polyarteritis nodosa and HBV, and how well do neurologic symptoms respond to treatment?

A: The duration of antiviral therapy is guided in part by seroconversion (i.e., negative antigen and positive antibody titers); after stopping treatment, HBV DNA levels are monitored to confirm eradication. Patients with neuropathic symptoms often have delayed responses to treatment, with clinically significant changes reported months to years after the initiation of therapy in many cases; improvements in motor deficits are often greater than improvements in sensory deficits.

Tags: , , , , , , , , , , , , , , , , , , , , , , , ,
Posted in Physicians-In-Training | Permalink | No Comments

The Truth Behind the Lie: Prone Positioning in Severe Acute Respiratory Distress Syndrome

Posted by John Staples • June 5th, 2013

Physicians have long realized that a little change in position can go a long way. Is Mr. X’s peripheral arterial disease causing him ischemic rest pain? Keep those legs dependant. Is Mrs. Y getting orthopnea from uncontrolled heat failure? Sit her up and she might get some relief. Is the sight of blood making your medical student a little lightheaded? Perhaps he’d better lie down.

In patients with the acute respiratory distress syndrome (ARDS), the positional solution is more complicated. Mechanically ventilating ARDS patients in the prone position improves ventilation-perfusion matching but risks accidental extubation and complicates daily medical care. Clinicians could flip a coin to decide what to do with their patients (“Heads up … face up?”), but both doctors and patients would greatly prefer an evidence-based solution.

Heeding this call for evidence, Dr. Claude Guérin (Hôpital de la Croix-Rousse, Lyon, France) and colleagues report the results of the PROSEVA trial in this week’s NEJM. This multicenter study randomized 466 mechanically-ventilated patients with severe ARDS to undergo prone-positioning or to be left supine. Patients in the prone group were turned by an experienced team (see video at nejm.org) and were prone for 73% of eligible patient-hours, a higher intensity of prone positioning than applied in previous trials.

At the completion of the trial, the 28-day all-cause mortality observed in the prone group was about half that observed in the supine group (16% vs 33%; HR 0.39, 95%CI 0.25-0.63). The prone group also required less aggressive ventilator settings and had fewer cardiac arrests. Other adverse effects were not significantly different between the two groups.

In an accompanying editorial, Dr Guy W Soo Hoo (Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA) notes that a treatment effect of this size is “virtually unprecedented in modern medicine.” He notes that the results of PROSEVA are compelling but reminds readers that the trial enrolled a highly select group of patients with severe ARDS, took place in centers with substantial experience in prone-positioning, and ensured that patients were prone for a substantial proportion of time.

Proper body position can optimize ventilation (just ask any yogi, soprano, or expectant mother) and can provide hydrostatic benefits (as your presyncopal medical student can attest). Thanks to the PROSEVA trial, intensivists can be more confident that these principles result in substantial practical benefits when prone-positioning patients with severe ARDS.

Tags: , , , , , , , , ,
Posted in Insights | Permalink | No Comments

Poorly Controlled Diabetes Mellitus and Fatigue

Posted by Sara Fazio • May 31st, 2013

In the latest Case Record from the Massachusetts General Hospital, a 56-year-old woman with diabetes mellitus was admitted to the hospital because of hyperglycemia and chest pain. Approximately 4 years earlier, a chest radiograph showed a solitary pulmonary nodule in the right upper lobe.

The differential diagnosis for uncontrolled diabetes includes undertreatment or misdiagnosis of the type of diabetes, a progressive course due to weight gain or advancing beta-cell failure, or a superimposed pathological process (e.g., pancreatitis, pancreatic cancer, hemochromatosis, cystic fibrosis, acromegaly, lipodystrophy, medication use, or high levels of endogenous or exogenous glucocorticoids).

Clinical Pearls

• What characteristics of solitary pulmonary nodules are suggestive of benign conditions as opposed to cancer?   

Benign nodules typically are less than 5 mm in the greatest dimension, have smooth borders, and appear dense or solid, with a concentric, central, or homogeneous pattern of calcification. Benign nodules tend to double in size either very rapidly (in <1 month) or very slowly (in >1 year). Features of nodules that are worrisome for cancer include a size greater than 10 mm, the presence of irregular or spiculated borders, a nonsolid ground-glass appearance, the absence of calcifications or the presence of eccentric  calcifications, and a doubling time between 1 month and 1 year.  Additional clinical factors incorporated into treatment algorithms include smoking history, age, and a personal cancer history.

• What are the clinical features of Cushing’s syndrome?

Many of the clinical features of Cushing’s syndrome (e.g., obesity,  hypertension, hyperglycemia, edema, hypokalemia, fatigue, mood disorders, and insomnia) are common but nonspecific; others (e.g. easy bruising, purple striae, facial plethora, and proximal-muscle weakness) are more specific and particularly helpful in reaching a clinical diagnosis.

Morning Report Questions

Q: According to the authors, what nonpathological forms of hypercortisolism should be considered when patients present with features that are suggestive of Cushing’s syndrome?     

A: Patients with nonpathological forms of hypercortisolism (e.g.,  pregnancy, depression, alcohol abuse, morbid obesity) can present  with similar features, and these diagnoses should keep these in mind as potential causes of abnormal laboratory values during evaluation.

Q: What diagnostic assays are available for Cushing’s syndrome?

A: The most sensitive test is the measurement of the 24-hour urinary free cortisol level, which is recommended in the setting of a high clinical suspicion of Cushing’s syndrome. However, there are a number of considerations: the urine volume must be adequate (if the volume is too high, it can lead to a false positive result, and, if too low, to a false negative result), the patient must not be taking exogenous glucocorticoids that might interfere with the test, and the creatinine level should be normal. If the level of urinary free cortisol is higher than three times the upper limit of the normal range, it is diagnostic for Cushing’s syndrome. For the 1 mg overnight dexamethasone suppression test, the patient needs to take 1 mg of dexamethasone between 11 p.m. and midnight the night before the test. Then, the serum cortisol level should be measured at precisely 8 a.m. A level greater than 5 micrograms per deciliter (138 nmol per liter) is suggestive of Cushing’s syndrome. To increase the sensitivity of the test, some advocate lowering the cut-off point to 1.8 micrograms per deciliter (50 nmol per liter). The 1-mg dexamethasone suppression test has a very good negative predictive value — a cortisol level less than 1.8 micrograms per deciliter effectively rules out Cushing’s syndrome. A high-dose dexamethasone suppression test is used to screen for Cushing’s disease, since a low dose test does not typically cause suppression, but a high dose of dexamethasone will. A measurement of the salivary cortisol level is a test that can beperformed at home. The patient chews on a cotton swab and deposits the saliva in a vial that can be sent back to the laboratory. Saliva is collected between 11 p.m. and midnight.

 

Tags: , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
Posted in Physicians-In-Training | Permalink | No Comments

Antithrombotic Therapy in Invasive Procedures

Posted by Sara Fazio • May 31st, 2013

In this trial, patients receiving oral anticoagulation therapy who required pacemaker or defibrillator surgery were assigned to heparin bridging or continuation of warfarin. Patients receiving warfarin had a markedly lower risk of clinically significant device-pocket hematoma.  This latest review article in our Current Concepts series comes from Dr. Patrick Kamath, Dr. Todd Baron, and Dr. Robert McBane at Mayo Clinic.

The question of whether antithrombotic therapy should be suspended in a patient who will be undergoing an invasive procedure involves balancing the risk of postprocedural bleeding with continued treatment against the thrombotic risk with suspension of treatment and use of bridging anticoagulation therapy. In general, a patient undergoing a procedure that is associated with a low risk of bleeding (low-risk procedure) can safely continue antithrombotic therapy and should do so, particularly if the patient is at high risk for a thromboembolic event (high-risk patient). Conversely, a patient undergoing a high-risk procedure can temporarily discontinue antithrombotic agents safely if the patient is at low risk for a thromboembolic event (low-risk patient).

Clinical Pearls

• What is the CHADS2-VASc score?

For patients with nonvalvular atrial fibrillation, important determinants of the risk of stroke include the CHADS2 score and, more recently, the CHA2DS2-VASc score, which includes cardiovascular atherosclerotic disease and female sex as additional risk factors. Scores on the CHADS2 range from 0 to 6, with higher scores indicating a greater risk of stroke; congestive heart failure, hypertension, diabetes, and an age of 75 years or older are each assigned 1 point, and prior stroke or transient ischemic attack is assigned 2 points. The CHA2DS2-VASc score reflects the risk of stroke among patients with atrial fibrillation who are not receiving anticoagulation therapy; values range from 0 to 9, with higher scores indicating greater risk.

• How does the risk of coronary stent thrombosis differ between bare-metal stents and drug-eluting stents? 

The risk of stent thrombosis differs between bare-metal stents and drug-eluting stents. The risk of thrombosis is highest within 6 weeks after the placement of a bare-metal stent and within 3 to 6 months after the placement of a drug-eluting stent; antiplatelet therapy is required for at least 1 month after placement of a bare-metal stent and for 1 year after placement of a drug-eluting stent. After acute coronary syndromes, continuation of dual antiplatelet therapy is recommended for up to 12 months in patients with bare-metal stents and for at least 12 months in patients with drug-eluting stents, unless the risk of bleeding is excessive.

Morning Report Questions

Q: What are the recommendations for elective procedures in patients with coronary-artery stents?   

A: Most patients receiving dual antiplatelet therapy have coronary-artery stents. For these patients, an elective procedure associated with a high risk of bleeding should be postponed, if possible, for at least 6 weeks after the placement of a bare-metal stent and for at least 6 months after the placement of a drug-eluting stent. Ideally, a high-risk procedure should be delayed until completion of dual antiplatelet therapy (at least 12 months after the placement of either a bare-metal or drug-eluting stent). If an elective high-risk procedure must be performed (Table S2 in the Supplementary Appendix) within 6 weeks after the placement of a bare-metal stent or within 6 months after the placement of a drug-eluting stent, dual antiplatelet therapy should be continued, if possible. Aspirin therapy should never be discontinued. For patients with coronary-artery stents who are undergoing a high-risk procedure more than 6 weeks after the placement of a bare-metal stent or more than 6 months after the placement of a drug-eluting stent, aspirin should be continued, with thienopyridine therapy temporarily discontinued at an appropriate interval before the procedure.

Q: When should antithrombotic therapy be initiated after an invasive procedure?   

A: In patients receiving bridging therapy, heparin at a therapeutic dose should be withheld for 48 hours after the procedure. If the risk of postprocedural bleeding is deemed acceptably low, full-dose anticoagulation therapy may be initiated after a shorter interval. Because achieving full anticoagulation after the reinstitution of warfarin therapy takes several days, it can be reinstituted the evening of the procedure unless there is a substantial risk of delayed bleeding or unless reoperation is anticipated. The authors recommend delaying the reinitiation of treatment with dabigatran, rivaroxaban, or apixaban for at least 48 hours after high-risk procedures because the full anticoagulatory effect occurs shortly after administration and there are no reliable reversal agents for these medications. Clopidogrel administered at maintenance doses has a delayed onset of action, and treatment can therefore be reinitiated within 24 hours after the procedure. Treatment with other antiplatelet agents, including aspirin, can be reinitiated within 24 hours. The authors recommend caution when reinitiating treatment with prasugrel or ticagrelor because of their rapid onset of action, potent antiplatelet inhibition, and the lack of agents to reverse their effects.

Table 4. Overview of Traditional and Newer Antithrombotic Agents.

Tags: , , , , ,
Posted in Physicians-In-Training | Permalink | No Comments

Medicine in the Air – A Report on In-Flight Emergencies

Posted by Sushrut Jangi • May 29th, 2013

On a recent flight back to Boston, the woman sitting next to me began to have a panic attack about half an hour before we landed. “Can’t deal with turbulence,” she whimpered, grasping my arm.   She closed her eyes and began to mumble a prayer. “It’ll be okay,” I said, trying to talk her down, asking her to take deep, slow breaths. With my free hand, I tried to palpate her racing pulse.

About 2.75 billion people travel on commercial airlines each year.  Some of these people are bound to get sick, ranging from something as simple as a cold or a stomach bug to something as emergent as a heart attack. Medical personnel are frequently called upon to assist flight crews with managing such occasions, but the nature of air travel can turn a simple medical problem into a tense situation.

This week’s NEJM investigates medicine in the air, presenting one of the largest and most detailed reports on in-flight medical emergencies and their outcomes. When a medical emergency occurs on a plane, airline personnel will usually contact a partnered call center staffed by emergency room physicians who will provide consultation over radio and satellite. After gathering records from one of these centers, the authors of this week’s study reviewed communications among five domestic and international airlines between January 2008 and October 2010, representing 10% of the global flight volume over that time period.

When emergencies occurred, the authors found that in almost half of all cases, physicians were the primary responders (48%), followed by nurses (20%), then EMS providers (4%).  Most frequently, responders addressed syncope (37.5%) followed by respiratory symptoms, then nausea or vomiting. Planes carried numerous medical supplies in a Federal Aviation Administration mandated emergency kit, but responders reached most frequently for oxygen, normal saline, or aspirin.  Drugs such as morphine, epinephrine, and dextrose were almost never used.

While treating run-of-the-mill symptoms on a plane can prove to be difficult, dealing with an extenuating circumstance such as a heart attack or stroke may require the provider to potentially ask the pilot to ground the plane before it has reached its original destination.  However, such medical conditions presented rarely – cardiac arrest was only witnessed in 0.3% of all emergencies.   Still, planes landed early in almost 7% of emergencies.

While flight crews rarely diverted a plane (4%) physicians were most likely to ask the pilot to ground the aircraft early (10%) reflecting the challenge of providing care in unfamiliar settings with limited resources.  However, the report suggests that most conditions on planes can be managed simply, through the use of intravenous fluids, supplemental oxygen, and aspirin, with flight diversion reserved for rare cardiac arrests, strokes, or obstetrical emergencies.

Although I knew none of these statistics as we landed in Boston during my recent flight, a differential had run through my mind as I watched the woman with the labored breaths, sweats, and racing heart who sat beside me. She kept her eyes closed, even after we had touched down on the runway. “I’m so sorry,” she apologized later, after the plane had stopped moving.  Even if it wasn’t a physician sitting beside her, anyone might have offered her the same comfort that I did. Under the 1998 Aviation Medical Assistance Act, passengers are protected from liability while offering medical assistance.  But as medical providers, this week’s report equips us to take the initiative and make informed decisions while delivering clinical care – even under unusual circumstances.

Check out the NEJM Quick Take on in-flight medical emergencies. It’s a lively, animated overview of the study, narrated by NEJM Editor-in-Chief Jeffrey Drazen, and offers some recommendations on how to handle the situation. 

Tags: , , , , , , , , , , , , , , , , , , , ,
Posted in Insights | Permalink | No Comments