Q) A good friend was diagnosed with chronic kidney disease (CKD) and is presently undergoing workup for a transplant. He is 60 and otherwise healthy; his glomerular filtration rate (GFR) is 14, and he has no uremic symptoms. If I volunteer to give him a kidney, are there any long-term risks for me? 

Kidney failure, dialysis, and kidney transplant are terms that can invoke stress and uncertainty in patients with end-stage renal disease (ESRD) and among their family members and friends. In addition to adjusting to the changes wrought by ESRD, patients may also be burdened by the prospect of a family member or friend donating a kidney to them and the concern that the donation will lead to complications for their donor. Family members or friends who volunteer may also experience stress, uncertain of their own risk for ESRD in the future. 

Past research improperly compared relative risk for ESRD in donors with that in the general population (without accounting for higher propensity for complications in donors with preexisting conditions). In an effort to correct this misperception, a study recently published in JAMA compared the risk for ESRD in donors with that in a healthy group of nondonors.¹ The nondonor pool was taken from the National Health and Nutrition Examination Survey (NHANES III), which assesses the health and nutritional status of adults and children in the United States. 

The JAMA study included a cohort of 96,217 kidney donors in the US in a 17-year period and a cohort of 20,024 participants in a six-year period of the NHANES III trial. This data was then compared to Centers for Medicare & Medicaid Services (CMS) data to determine the development of ESRD in kidney donors. ESRD was defined by CMS as the initiation of dialysis, placement on the kidney transplant waiting list, or receipt of a living or deceased donor kidney transplant.

In addition to comparing risk for ESRD in kidney donors with that of a healthy population of nondonors, the researchers also stratified their results demographically. Thus, the lifetime rate of kidney failure in donors is 90 per 10,000, compared with 326 per 10,000 in the general population of nondonors. In healthy nondonors, the risk for kidney failure was 14 per 10,000. After 15 years, the risk for kidney failure associated with donating a kidney was 51 per 10,000 in African-American donors and 23 per 10,000 in white donors. So while the study did reveal an increased risk associated with kidney donation, the degree of risk is considered small. 

These findings demonstrate the importance of understanding the facts surrounding inherent risk for ESRD in kidney donation. Overall, a donor’s lifetime risk is considered minuscule. So, to answer the question, yes, there is a slight increase in risk for kidney failure if you donate to your friend. That said, the risk is 0.014 x a standardized risk of 1. This increases at 15 years to 0.51 for African-American and 0.23 for white donors. With such tiny increases, you can safely feel good about donating a kidney to your friend.

Donna Reesman, MSN, CNP
VP Clinical & Quality Management
St Clair Specialty Physicians Detroit

REFERENCES
1. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA. 2014;311(6):579-586.

2. CDC. HIV in the United States: at a glance (2013). www.cdc.gov/hiv/statistics/basics/ataglance.html. Accessed June 16, 2014.

3. Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009;5(10):582-589.

4. Malani PN. New law allows organ transplants from deceased HIV-infected donors to HIV-infected recipients. JAMA. 2013;310(23): 2492-2493.

5. Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362(24):2336-2337.

6. Mariani LH, Berns JS. Viral nephropathies. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Elsevier; 2014:253-261.

Q) A good friend was diagnosed with chronic kidney disease (CKD) and is presently undergoing workup for a transplant. He is 60 and otherwise healthy; his glomerular filtration rate (GFR) is 14, and he has no uremic symptoms. If I volunteer to give him a kidney, are there any long-term risks for me? 

Kidney failure, dialysis, and kidney transplant are terms that can invoke stress and uncertainty in patients with end-stage renal disease (ESRD) and among their family members and friends. In addition to adjusting to the changes wrought by ESRD, patients may also be burdened by the prospect of a family member or friend donating a kidney to them and the concern that the donation will lead to complications for their donor. Family members or friends who volunteer may also experience stress, uncertain of their own risk for ESRD in the future. 

Past research improperly compared relative risk for ESRD in donors with that in the general population (without accounting for higher propensity for complications in donors with preexisting conditions). In an effort to correct this misperception, a study recently published in JAMA compared the risk for ESRD in donors with that in a healthy group of nondonors.¹ The nondonor pool was taken from the National Health and Nutrition Examination Survey (NHANES III), which assesses the health and nutritional status of adults and children in the United States. 

The JAMA study included a cohort of 96,217 kidney donors in the US in a 17-year period and a cohort of 20,024 participants in a six-year period of the NHANES III trial. This data was then compared to Centers for Medicare & Medicaid Services (CMS) data to determine the development of ESRD in kidney donors. ESRD was defined by CMS as the initiation of dialysis, placement on the kidney transplant waiting list, or receipt of a living or deceased donor kidney transplant.

In addition to comparing risk for ESRD in kidney donors with that of a healthy population of nondonors, the researchers also stratified their results demographically. Thus, the lifetime rate of kidney failure in donors is 90 per 10,000, compared with 326 per 10,000 in the general population of nondonors. In healthy nondonors, the risk for kidney failure was 14 per 10,000. After 15 years, the risk for kidney failure associated with donating a kidney was 51 per 10,000 in African-American donors and 23 per 10,000 in white donors. So while the study did reveal an increased risk associated with kidney donation, the degree of risk is considered small. 

These findings demonstrate the importance of understanding the facts surrounding inherent risk for ESRD in kidney donation. Overall, a donor’s lifetime risk is considered minuscule. So, to answer the question, yes, there is a slight increase in risk for kidney failure if you donate to your friend. That said, the risk is 0.014 x a standardized risk of 1. This increases at 15 years to 0.51 for African-American and 0.23 for white donors. With such tiny increases, you can safely feel good about donating a kidney to your friend.

Donna Reesman, MSN, CNP
VP Clinical & Quality Management
St Clair Specialty Physicians Detroit

REFERENCES
1. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA. 2014;311(6):579-586.

2. CDC. HIV in the United States: at a glance (2013). www.cdc.gov/hiv/statistics/basics/ataglance.html. Accessed June 16, 2014.

3. Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009;5(10):582-589.

4. Malani PN. New law allows organ transplants from deceased HIV-infected donors to HIV-infected recipients. JAMA. 2013;310(23): 2492-2493.

5. Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362(24):2336-2337.

6. Mariani LH, Berns JS. Viral nephropathies. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Elsevier; 2014:253-261.

Q) A good friend was diagnosed with chronic kidney disease (CKD) and is presently undergoing workup for a transplant. He is 60 and otherwise healthy; his glomerular filtration rate (GFR) is 14, and he has no uremic symptoms. If I volunteer to give him a kidney, are there any long-term risks for me? 

Kidney failure, dialysis, and kidney transplant are terms that can invoke stress and uncertainty in patients with end-stage renal disease (ESRD) and among their family members and friends. In addition to adjusting to the changes wrought by ESRD, patients may also be burdened by the prospect of a family member or friend donating a kidney to them and the concern that the donation will lead to complications for their donor. Family members or friends who volunteer may also experience stress, uncertain of their own risk for ESRD in the future. 

Past research improperly compared relative risk for ESRD in donors with that in the general population (without accounting for higher propensity for complications in donors with preexisting conditions). In an effort to correct this misperception, a study recently published in JAMA compared the risk for ESRD in donors with that in a healthy group of nondonors.¹ The nondonor pool was taken from the National Health and Nutrition Examination Survey (NHANES III), which assesses the health and nutritional status of adults and children in the United States. 

The JAMA study included a cohort of 96,217 kidney donors in the US in a 17-year period and a cohort of 20,024 participants in a six-year period of the NHANES III trial. This data was then compared to Centers for Medicare & Medicaid Services (CMS) data to determine the development of ESRD in kidney donors. ESRD was defined by CMS as the initiation of dialysis, placement on the kidney transplant waiting list, or receipt of a living or deceased donor kidney transplant.

In addition to comparing risk for ESRD in kidney donors with that of a healthy population of nondonors, the researchers also stratified their results demographically. Thus, the lifetime rate of kidney failure in donors is 90 per 10,000, compared with 326 per 10,000 in the general population of nondonors. In healthy nondonors, the risk for kidney failure was 14 per 10,000. After 15 years, the risk for kidney failure associated with donating a kidney was 51 per 10,000 in African-American donors and 23 per 10,000 in white donors. So while the study did reveal an increased risk associated with kidney donation, the degree of risk is considered small. 

These findings demonstrate the importance of understanding the facts surrounding inherent risk for ESRD in kidney donation. Overall, a donor’s lifetime risk is considered minuscule. So, to answer the question, yes, there is a slight increase in risk for kidney failure if you donate to your friend. That said, the risk is 0.014 x a standardized risk of 1. This increases at 15 years to 0.51 for African-American and 0.23 for white donors. With such tiny increases, you can safely feel good about donating a kidney to your friend.

Donna Reesman, MSN, CNP
VP Clinical & Quality Management
St Clair Specialty Physicians Detroit

REFERENCES
1. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA. 2014;311(6):579-586.

2. CDC. HIV in the United States: at a glance (2013). www.cdc.gov/hiv/statistics/basics/ataglance.html. Accessed June 16, 2014.

3. Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009;5(10):582-589.

4. Malani PN. New law allows organ transplants from deceased HIV-infected donors to HIV-infected recipients. JAMA. 2013;310(23): 2492-2493.

5. Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362(24):2336-2337.

6. Mariani LH, Berns JS. Viral nephropathies. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Elsevier; 2014:253-261.

Q) Now that patients are living with HIV/AIDS, can they donate kidneys or receive a kidney transplant?

Kidney disease often has multiple causes, including hypertension, diabetes, inherited conditions, and viral illnesses. The latter include primarily HIV, hepatitis C, and hepatitis B. With advances in the treatment of viral illnesses, the question of whether patients with these viruses can donate or receive a kidney transplant is being discussed not only in the United States but also worldwide.

The most recent CDC figures estimate that more than 1.1 million people in the US are living with HIV, of whom one in six (or nearly 16%) are undiagnosed. There are approximately 50,000 new infections reported annually.²

The Organ Transplant Amendments Act of 1988 banned HIV-positive people from donating organs. However, with the introduction of highly active antiretroviral therapy (HAART, now often referred to as active antiretroviral therapy) and the effective prophylaxis and management of opportunistic infections, mortality has been reduced. HIV/AIDS is often seen as a chronic disease and not the death sentence it once was.³ Since the development of HAART, there have been successful transplants to HIV-positive recipients from non–HIV-infected donors.

In November 2013, President Obama signed the HIV Organ Policy Equity (HOPE) Act, which lifted the ban on using organs from HIV-infected donors. The legislation directs the Department of Health and Human Services and the Organ Procurement and Transplantation Network to develop standards to make these transplants possible.⁴

Although there have not been any documented cases of transplants from HIV-infected donors to HIV-infected recipients in this country, such transplants have been very successful in South Africa.⁵ There, to qualify for kidney transplant, all recipients must have proven adherence, virologic suppression, and immune constitution. Donor suitability is defined as HIV infection (confirmed with the use of enzyme-linked immunosorbent assay), absence of proteinuria, and a normal kidney as assessed with post hoc renal biopsy.⁵

One of the chief concerns has been the effect of further immunosuppression on the recipients and the possibility of disease progression. Although the sample size is limited (four transplants), data from the available cases indicate no evidence of organ rejection at 12 months post-transplantation. In addition, the recipients’ CD4 counts remained lower than baseline due to immunosuppressive therapy. All four patients maintained a viral load of less than 50 copies, which suggested that any virus transplanted along with the kidney had not affected control of HIV infection.⁵ However, it should be noted that many of the agents used for posttransplant maintenance immunosuppression (mycophenolate mofetil, cyclosporine, tacrolimus, and sirolimus) have antiretroviral properties.³

HIV patients in the US must meet the following criteria to be listed for a transplant: 

• Diagnosis of ESRD with at least a five-year life-expectancy

• CD4 count of > 200 cells/ μL for at least six months

• Undetectable HIV viremia (< 50 HIV-1 RNA copies/mL)

• Demonstrated adherence to stable antiviral regimen for at least six months

• Absence of AIDS-defining illness following successful immune reconstitution⁶

A prospective trial of 150 patients in 19 US transplant centers who met the above criteria demonstrated patient survival and graft survival rates comparable to those in patients ages 65 and older.⁶

While awaiting the donation, HIV patients can continue hemodialysis and peritoneal dialysis. With the improved antiviral drugs, HIV patients have a survival rate similar to the non–HIV-infected population.

Transplantation is the goal and certainly the hope of many advanced-stage kidney patients, but in reality, the need far exceeds the resources. The HOPE Act opens the door for many patients who were previously excluded from the possibility of a life without dialysis. Taking care of these patients will be a team effort, encompassing HIV and infectious disease specialists, pharmacists, nephrologists, transplant surgeons and coordinators, and primary care providers—­including, of course, advanced practitioners.

Shelly Levinstein, MSN, CRNP
Nephrology Associates of York
York, PA

REFERENCES
1. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA. 2014;311(6):579-586.

2. CDC. HIV in the United States: at a glance (2013). www.cdc.gov/hiv/statistics/basics/ataglance.html. Accessed June 16, 2014.

3. Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009;5(10):582-589.

4. Malani PN. New law allows organ transplants from deceased HIV-infected donors to HIV-infected recipients. JAMA. 2013;310(23): 2492-2493.

5. Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362(24):2336-2337.

6. Mariani LH, Berns JS. Viral nephropathies. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Elsevier; 2014:253-261.

Q) Now that patients are living with HIV/AIDS, can they donate kidneys or receive a kidney transplant?

Kidney disease often has multiple causes, including hypertension, diabetes, inherited conditions, and viral illnesses. The latter include primarily HIV, hepatitis C, and hepatitis B. With advances in the treatment of viral illnesses, the question of whether patients with these viruses can donate or receive a kidney transplant is being discussed not only in the United States but also worldwide.

The most recent CDC figures estimate that more than 1.1 million people in the US are living with HIV, of whom one in six (or nearly 16%) are undiagnosed. There are approximately 50,000 new infections reported annually.²

The Organ Transplant Amendments Act of 1988 banned HIV-positive people from donating organs. However, with the introduction of highly active antiretroviral therapy (HAART, now often referred to as active antiretroviral therapy) and the effective prophylaxis and management of opportunistic infections, mortality has been reduced. HIV/AIDS is often seen as a chronic disease and not the death sentence it once was.³ Since the development of HAART, there have been successful transplants to HIV-positive recipients from non–HIV-infected donors.

In November 2013, President Obama signed the HIV Organ Policy Equity (HOPE) Act, which lifted the ban on using organs from HIV-infected donors. The legislation directs the Department of Health and Human Services and the Organ Procurement and Transplantation Network to develop standards to make these transplants possible.⁴

Although there have not been any documented cases of transplants from HIV-infected donors to HIV-infected recipients in this country, such transplants have been very successful in South Africa.⁵ There, to qualify for kidney transplant, all recipients must have proven adherence, virologic suppression, and immune constitution. Donor suitability is defined as HIV infection (confirmed with the use of enzyme-linked immunosorbent assay), absence of proteinuria, and a normal kidney as assessed with post hoc renal biopsy.⁵

One of the chief concerns has been the effect of further immunosuppression on the recipients and the possibility of disease progression. Although the sample size is limited (four transplants), data from the available cases indicate no evidence of organ rejection at 12 months post-transplantation. In addition, the recipients’ CD4 counts remained lower than baseline due to immunosuppressive therapy. All four patients maintained a viral load of less than 50 copies, which suggested that any virus transplanted along with the kidney had not affected control of HIV infection.⁵ However, it should be noted that many of the agents used for posttransplant maintenance immunosuppression (mycophenolate mofetil, cyclosporine, tacrolimus, and sirolimus) have antiretroviral properties.³

HIV patients in the US must meet the following criteria to be listed for a transplant: 

• Diagnosis of ESRD with at least a five-year life-expectancy

• CD4 count of > 200 cells/ μL for at least six months

• Undetectable HIV viremia (< 50 HIV-1 RNA copies/mL)

• Demonstrated adherence to stable antiviral regimen for at least six months

• Absence of AIDS-defining illness following successful immune reconstitution⁶

A prospective trial of 150 patients in 19 US transplant centers who met the above criteria demonstrated patient survival and graft survival rates comparable to those in patients ages 65 and older.⁶

While awaiting the donation, HIV patients can continue hemodialysis and peritoneal dialysis. With the improved antiviral drugs, HIV patients have a survival rate similar to the non–HIV-infected population.

Transplantation is the goal and certainly the hope of many advanced-stage kidney patients, but in reality, the need far exceeds the resources. The HOPE Act opens the door for many patients who were previously excluded from the possibility of a life without dialysis. Taking care of these patients will be a team effort, encompassing HIV and infectious disease specialists, pharmacists, nephrologists, transplant surgeons and coordinators, and primary care providers—­including, of course, advanced practitioners.

Shelly Levinstein, MSN, CRNP
Nephrology Associates of York
York, PA

REFERENCES
1. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA. 2014;311(6):579-586.

2. CDC. HIV in the United States: at a glance (2013). www.cdc.gov/hiv/statistics/basics/ataglance.html. Accessed June 16, 2014.

3. Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009;5(10):582-589.

4. Malani PN. New law allows organ transplants from deceased HIV-infected donors to HIV-infected recipients. JAMA. 2013;310(23): 2492-2493.

5. Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362(24):2336-2337.

6. Mariani LH, Berns JS. Viral nephropathies. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Elsevier; 2014:253-261.

Q) Now that patients are living with HIV/AIDS, can they donate kidneys or receive a kidney transplant?

Kidney disease often has multiple causes, including hypertension, diabetes, inherited conditions, and viral illnesses. The latter include primarily HIV, hepatitis C, and hepatitis B. With advances in the treatment of viral illnesses, the question of whether patients with these viruses can donate or receive a kidney transplant is being discussed not only in the United States but also worldwide.

The most recent CDC figures estimate that more than 1.1 million people in the US are living with HIV, of whom one in six (or nearly 16%) are undiagnosed. There are approximately 50,000 new infections reported annually.²

The Organ Transplant Amendments Act of 1988 banned HIV-positive people from donating organs. However, with the introduction of highly active antiretroviral therapy (HAART, now often referred to as active antiretroviral therapy) and the effective prophylaxis and management of opportunistic infections, mortality has been reduced. HIV/AIDS is often seen as a chronic disease and not the death sentence it once was.³ Since the development of HAART, there have been successful transplants to HIV-positive recipients from non–HIV-infected donors.

In November 2013, President Obama signed the HIV Organ Policy Equity (HOPE) Act, which lifted the ban on using organs from HIV-infected donors. The legislation directs the Department of Health and Human Services and the Organ Procurement and Transplantation Network to develop standards to make these transplants possible.⁴

Although there have not been any documented cases of transplants from HIV-infected donors to HIV-infected recipients in this country, such transplants have been very successful in South Africa.⁵ There, to qualify for kidney transplant, all recipients must have proven adherence, virologic suppression, and immune constitution. Donor suitability is defined as HIV infection (confirmed with the use of enzyme-linked immunosorbent assay), absence of proteinuria, and a normal kidney as assessed with post hoc renal biopsy.⁵

One of the chief concerns has been the effect of further immunosuppression on the recipients and the possibility of disease progression. Although the sample size is limited (four transplants), data from the available cases indicate no evidence of organ rejection at 12 months post-transplantation. In addition, the recipients’ CD4 counts remained lower than baseline due to immunosuppressive therapy. All four patients maintained a viral load of less than 50 copies, which suggested that any virus transplanted along with the kidney had not affected control of HIV infection.⁵ However, it should be noted that many of the agents used for posttransplant maintenance immunosuppression (mycophenolate mofetil, cyclosporine, tacrolimus, and sirolimus) have antiretroviral properties.³

HIV patients in the US must meet the following criteria to be listed for a transplant: 

• Diagnosis of ESRD with at least a five-year life-expectancy

• CD4 count of > 200 cells/ μL for at least six months

• Undetectable HIV viremia (< 50 HIV-1 RNA copies/mL)

• Demonstrated adherence to stable antiviral regimen for at least six months

• Absence of AIDS-defining illness following successful immune reconstitution⁶

A prospective trial of 150 patients in 19 US transplant centers who met the above criteria demonstrated patient survival and graft survival rates comparable to those in patients ages 65 and older.⁶

While awaiting the donation, HIV patients can continue hemodialysis and peritoneal dialysis. With the improved antiviral drugs, HIV patients have a survival rate similar to the non–HIV-infected population.

Transplantation is the goal and certainly the hope of many advanced-stage kidney patients, but in reality, the need far exceeds the resources. The HOPE Act opens the door for many patients who were previously excluded from the possibility of a life without dialysis. Taking care of these patients will be a team effort, encompassing HIV and infectious disease specialists, pharmacists, nephrologists, transplant surgeons and coordinators, and primary care providers—­including, of course, advanced practitioners.

Shelly Levinstein, MSN, CRNP
Nephrology Associates of York
York, PA

REFERENCES
1. Muzaale AD, Massie AB, Wang MC, et al. Risk of end-stage renal disease following live kidney donation. JAMA. 2014;311(6):579-586.

2. CDC. HIV in the United States: at a glance (2013). www.cdc.gov/hiv/statistics/basics/ataglance.html. Accessed June 16, 2014.

3. Frassetto LA, Tan-Tam C, Stock PG. Renal transplantation in patients with HIV. Nat Rev Nephrol. 2009;5(10):582-589.

4. Malani PN. New law allows organ transplants from deceased HIV-infected donors to HIV-infected recipients. JAMA. 2013;310(23): 2492-2493.

5. Muller E, Kahn D, Mendelson M. Renal transplantation between HIV-positive donors and recipients. N Engl J Med. 2010;362(24):2336-2337.

6. Mariani LH, Berns JS. Viral nephropathies. In: Gilbert SJ, Weiner DE, eds. National Kidney Foundation’s Primer on Kidney Diseases. 6th ed. Elsevier; 2014:253-261.

PRACTICE CHANGER
Stop ordering nebulizers to deliver β-agonists to patients older than 2 who have mild or moderate asthma exacerbations. A metered-dose inhaler (MDI) with a spacer produces the same benefits with fewer adverse effects.¹

STRENGTH OF RECOMMENDATION
A: Based on an updated Cochrane meta-analysis of 39 randomized controlled trials (RCTs). ¹

ILLUSTRATIVE CASE
A 6-year-old girl with a history of reactive airway disease comes to your office complaining of cough and wheezing. On exam, she has mild retractions, a respiratory rate of 35 breaths/min, and an O₂ saturation of 96% on room air. Her lung fields are diffusely wheezy. Her parents would like to keep her out of the hospital. How should you order her albuterol to decrease her wheezing and minimize adverse effects?

Asthma affects nearly 19 million adults and 7 million children in the United States.² Asthma exacerbations are the third most common reason for hospitalization in children.^2,3 Treatment usually requires multiple agents, including inhaled β-agonists. These are most effective when delivered to the peripheral airways, which is a challenge during an asthma exacerbation because of airway swelling and rapid breathing. Two devices have been developed to effectively deliver medication to the peripheral airways: nebulizers and MDIs with a holding chamber (spacer).¹ 

Several studies have demonstrated that for mild to moderate asthma exacerbations, administering a β-agonist via an MDI with a spacer is as effective as using a nebulizer.^4,5 Asthma treatment guidelines also state that spacers are either comparable or preferable to nebulizers for β-agonist administration in children and adults.^6,7 However, based on our experience, clinicians still frequently order nebulizer treatments for patients with asthma exacerbations, despite several advantages of MDIs with spacers. Notably, they cost less and don’t require maintenance or a power source. Clinicians administered nebulizer therapy at more than 3.6 million emergency department (ED) visits in 2006.⁸

In this latest Cochrane review, Cates et al¹ added four new studies to those included in their earlier Cochrane meta-analysis and evaluated what, if any, effect these studies had on our understanding of nebulizers versus MDIs with spacers.

STUDY SUMMARY
Outcomes with nebulizers are no better than those with spacers
This systematic review and meta-analysis pooled the results of RCTs comparing spacers to nebulizers for administering β-agonists during acute, non–life-threatening asthma exacerbations.¹ The authors reviewed studies conducted in EDs, hospitals, and outpatient settings that included children and adults. The primary outcomes were hospital admission rates and duration of hospital stay. Secondary outcomes included time spent in the ED, change in pulse rate, and incidence of tremor.

Cates et al¹ analyzed 39 trials that included 1,897 children and 729 adults and were conducted primarily in an ED or outpatient setting. The four new studies added 295 children and 58 adults to the researchers’ earlier meta-analysis. Studies involving adults and children were pooled separately. Most patients received multiple treatments with β-­agonists titrated to the individual’s response.

No differences in hospitalizations. Rates of hospital admissions did not differ between patients receiving β-agonists via a spacer compared to a nebulizer in both adults (relative risk [RR] = 0.94) and children (RR = 0.71). Duration of hospital stay did not differ between the two delivery methods in adults (mean difference [MD] = –0.60 d) and children (MD = 0.33 d).

For kids, spacers meant less time in the ED. Duration in the ED was approximately half an hour shorter for children using spacers (MD = –33.48 min). There was no difference observed in adults (MD = 1.75 min). The rate of tremor was lower in children using spacers (RR = 0.64) and was similar in adults (RR = 1.12). The rise in pulse rate was lower in children using spacers
(MD = –5.41% change from baseline) and was similar in adults (MD = –1.23%).

On the next page: What's new and challenges to implementation >>

WHAT’S NEW
Additional evidence that spacers are as effective as nebulizers
This meta-analysis, which included four new studies, should finally dispel the myth that nebulizers deliver β-agonists more effectively than MDIs with spacers. Additionally, in children, spacers are associated with lower rates of adverse effects, including tremor and elevated pulse rate.

CAVEATS
Most studies involving children were open label
Although most of the adult trials in this meta-analysis involved a double-dummy design, which allows for effective participant blinding, most of the studies involving children were open label. This open-label design might have been a source of reporting bias for symptom-related outcomes but should not have affected hospital admission rates or duration of hospital stay.

In the double-dummy studies, adults received both a nebulizer and a spacer, which likely explains the similar time spent in the ED by the treatment and control groups.

CHALLENGES TO IMPLEMENTATION
Old habits are hard to break
Clinicians may think that patients view nebulizers as more potent or more effective than spacers and thus be more likely to order them. Some patients may prefer nebulizers because of convenience or other factors.

REFERENCES
1. Cates CJ, Welsh EJ, Rowe BH. Holding ­chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9: CD000052.

2. Barrett ML, Wier LM, Washington R. Trends in pediatric and adult hospital stays for asthma, 2000-2010. HCUP Statistical Brief #169. www.hcup-us.ahrq.gov/reports/stat briefs/sb169-Asthma-Trends-Hospital-Stays.pdf. Accessed June 16, 2014.

3. Pfuntner A, Wier LM, Stocks C. Most frequent conditions in US hospitals, 2011. HCUP Statistical Brief #162. www.hcup-us.ahrq.gov/reports/statbriefs/sb162.pdf.  Accessed June 16, 2014.

4. Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006;(2): CD000052.

5. Turner MO, Patel A, Ginsburg S, et al. Bronchodilator delivery in acute airflow obstruction: a meta-analysis. Arch Intern Med. 1997;157:1736-1744.

6. National Heart, Lung, and Blood Institute Expert Panel Report 3 (EPR3): Guidelines for the diagnosis and management of asthma. www.nhlbi.nih.gov/guidelines/asthma/asth gdln.htm. Accessed June 16, 2014.

7. British Thoracic Society. British guideline of the management of asthma: a national clinical guideline. www.brit-thoracic.org.uk/document-library/clinical-information/asth ma/btssign-guideline-on-the-management-of-asthma/. Accessed June 16, 2014.

8. Pitts SR, Niska RW, Xu J, et al. National Hospital Ambulatory Medical Care Survey: 2006 emergency department summary. www.cdc.gov/nchs/data/nhsr/nhsr007.pdf.  Accessed June 16, 2014.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(6):321-322, 346.

PRACTICE CHANGER
Stop ordering nebulizers to deliver β-agonists to patients older than 2 who have mild or moderate asthma exacerbations. A metered-dose inhaler (MDI) with a spacer produces the same benefits with fewer adverse effects.¹

STRENGTH OF RECOMMENDATION
A: Based on an updated Cochrane meta-analysis of 39 randomized controlled trials (RCTs). ¹

ILLUSTRATIVE CASE
A 6-year-old girl with a history of reactive airway disease comes to your office complaining of cough and wheezing. On exam, she has mild retractions, a respiratory rate of 35 breaths/min, and an O₂ saturation of 96% on room air. Her lung fields are diffusely wheezy. Her parents would like to keep her out of the hospital. How should you order her albuterol to decrease her wheezing and minimize adverse effects?

Asthma affects nearly 19 million adults and 7 million children in the United States.² Asthma exacerbations are the third most common reason for hospitalization in children.^2,3 Treatment usually requires multiple agents, including inhaled β-agonists. These are most effective when delivered to the peripheral airways, which is a challenge during an asthma exacerbation because of airway swelling and rapid breathing. Two devices have been developed to effectively deliver medication to the peripheral airways: nebulizers and MDIs with a holding chamber (spacer).¹ 

Several studies have demonstrated that for mild to moderate asthma exacerbations, administering a β-agonist via an MDI with a spacer is as effective as using a nebulizer.^4,5 Asthma treatment guidelines also state that spacers are either comparable or preferable to nebulizers for β-agonist administration in children and adults.^6,7 However, based on our experience, clinicians still frequently order nebulizer treatments for patients with asthma exacerbations, despite several advantages of MDIs with spacers. Notably, they cost less and don’t require maintenance or a power source. Clinicians administered nebulizer therapy at more than 3.6 million emergency department (ED) visits in 2006.⁸

In this latest Cochrane review, Cates et al¹ added four new studies to those included in their earlier Cochrane meta-analysis and evaluated what, if any, effect these studies had on our understanding of nebulizers versus MDIs with spacers.

STUDY SUMMARY
Outcomes with nebulizers are no better than those with spacers
This systematic review and meta-analysis pooled the results of RCTs comparing spacers to nebulizers for administering β-agonists during acute, non–life-threatening asthma exacerbations.¹ The authors reviewed studies conducted in EDs, hospitals, and outpatient settings that included children and adults. The primary outcomes were hospital admission rates and duration of hospital stay. Secondary outcomes included time spent in the ED, change in pulse rate, and incidence of tremor.

Cates et al¹ analyzed 39 trials that included 1,897 children and 729 adults and were conducted primarily in an ED or outpatient setting. The four new studies added 295 children and 58 adults to the researchers’ earlier meta-analysis. Studies involving adults and children were pooled separately. Most patients received multiple treatments with β-­agonists titrated to the individual’s response.

No differences in hospitalizations. Rates of hospital admissions did not differ between patients receiving β-agonists via a spacer compared to a nebulizer in both adults (relative risk [RR] = 0.94) and children (RR = 0.71). Duration of hospital stay did not differ between the two delivery methods in adults (mean difference [MD] = –0.60 d) and children (MD = 0.33 d).

For kids, spacers meant less time in the ED. Duration in the ED was approximately half an hour shorter for children using spacers (MD = –33.48 min). There was no difference observed in adults (MD = 1.75 min). The rate of tremor was lower in children using spacers (RR = 0.64) and was similar in adults (RR = 1.12). The rise in pulse rate was lower in children using spacers
(MD = –5.41% change from baseline) and was similar in adults (MD = –1.23%).

On the next page: What's new and challenges to implementation >>

WHAT’S NEW
Additional evidence that spacers are as effective as nebulizers
This meta-analysis, which included four new studies, should finally dispel the myth that nebulizers deliver β-agonists more effectively than MDIs with spacers. Additionally, in children, spacers are associated with lower rates of adverse effects, including tremor and elevated pulse rate.

CAVEATS
Most studies involving children were open label
Although most of the adult trials in this meta-analysis involved a double-dummy design, which allows for effective participant blinding, most of the studies involving children were open label. This open-label design might have been a source of reporting bias for symptom-related outcomes but should not have affected hospital admission rates or duration of hospital stay.

In the double-dummy studies, adults received both a nebulizer and a spacer, which likely explains the similar time spent in the ED by the treatment and control groups.

CHALLENGES TO IMPLEMENTATION
Old habits are hard to break
Clinicians may think that patients view nebulizers as more potent or more effective than spacers and thus be more likely to order them. Some patients may prefer nebulizers because of convenience or other factors.

REFERENCES
1. Cates CJ, Welsh EJ, Rowe BH. Holding ­chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9: CD000052.

2. Barrett ML, Wier LM, Washington R. Trends in pediatric and adult hospital stays for asthma, 2000-2010. HCUP Statistical Brief #169. www.hcup-us.ahrq.gov/reports/stat briefs/sb169-Asthma-Trends-Hospital-Stays.pdf. Accessed June 16, 2014.

3. Pfuntner A, Wier LM, Stocks C. Most frequent conditions in US hospitals, 2011. HCUP Statistical Brief #162. www.hcup-us.ahrq.gov/reports/statbriefs/sb162.pdf.  Accessed June 16, 2014.

4. Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006;(2): CD000052.

5. Turner MO, Patel A, Ginsburg S, et al. Bronchodilator delivery in acute airflow obstruction: a meta-analysis. Arch Intern Med. 1997;157:1736-1744.

6. National Heart, Lung, and Blood Institute Expert Panel Report 3 (EPR3): Guidelines for the diagnosis and management of asthma. www.nhlbi.nih.gov/guidelines/asthma/asth gdln.htm. Accessed June 16, 2014.

7. British Thoracic Society. British guideline of the management of asthma: a national clinical guideline. www.brit-thoracic.org.uk/document-library/clinical-information/asth ma/btssign-guideline-on-the-management-of-asthma/. Accessed June 16, 2014.

8. Pitts SR, Niska RW, Xu J, et al. National Hospital Ambulatory Medical Care Survey: 2006 emergency department summary. www.cdc.gov/nchs/data/nhsr/nhsr007.pdf.  Accessed June 16, 2014.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(6):321-322, 346.

PRACTICE CHANGER
Stop ordering nebulizers to deliver β-agonists to patients older than 2 who have mild or moderate asthma exacerbations. A metered-dose inhaler (MDI) with a spacer produces the same benefits with fewer adverse effects.¹

STRENGTH OF RECOMMENDATION
A: Based on an updated Cochrane meta-analysis of 39 randomized controlled trials (RCTs). ¹

ILLUSTRATIVE CASE
A 6-year-old girl with a history of reactive airway disease comes to your office complaining of cough and wheezing. On exam, she has mild retractions, a respiratory rate of 35 breaths/min, and an O₂ saturation of 96% on room air. Her lung fields are diffusely wheezy. Her parents would like to keep her out of the hospital. How should you order her albuterol to decrease her wheezing and minimize adverse effects?

Asthma affects nearly 19 million adults and 7 million children in the United States.² Asthma exacerbations are the third most common reason for hospitalization in children.^2,3 Treatment usually requires multiple agents, including inhaled β-agonists. These are most effective when delivered to the peripheral airways, which is a challenge during an asthma exacerbation because of airway swelling and rapid breathing. Two devices have been developed to effectively deliver medication to the peripheral airways: nebulizers and MDIs with a holding chamber (spacer).¹ 

Several studies have demonstrated that for mild to moderate asthma exacerbations, administering a β-agonist via an MDI with a spacer is as effective as using a nebulizer.^4,5 Asthma treatment guidelines also state that spacers are either comparable or preferable to nebulizers for β-agonist administration in children and adults.^6,7 However, based on our experience, clinicians still frequently order nebulizer treatments for patients with asthma exacerbations, despite several advantages of MDIs with spacers. Notably, they cost less and don’t require maintenance or a power source. Clinicians administered nebulizer therapy at more than 3.6 million emergency department (ED) visits in 2006.⁸

In this latest Cochrane review, Cates et al¹ added four new studies to those included in their earlier Cochrane meta-analysis and evaluated what, if any, effect these studies had on our understanding of nebulizers versus MDIs with spacers.

STUDY SUMMARY
Outcomes with nebulizers are no better than those with spacers
This systematic review and meta-analysis pooled the results of RCTs comparing spacers to nebulizers for administering β-agonists during acute, non–life-threatening asthma exacerbations.¹ The authors reviewed studies conducted in EDs, hospitals, and outpatient settings that included children and adults. The primary outcomes were hospital admission rates and duration of hospital stay. Secondary outcomes included time spent in the ED, change in pulse rate, and incidence of tremor.

Cates et al¹ analyzed 39 trials that included 1,897 children and 729 adults and were conducted primarily in an ED or outpatient setting. The four new studies added 295 children and 58 adults to the researchers’ earlier meta-analysis. Studies involving adults and children were pooled separately. Most patients received multiple treatments with β-­agonists titrated to the individual’s response.

No differences in hospitalizations. Rates of hospital admissions did not differ between patients receiving β-agonists via a spacer compared to a nebulizer in both adults (relative risk [RR] = 0.94) and children (RR = 0.71). Duration of hospital stay did not differ between the two delivery methods in adults (mean difference [MD] = –0.60 d) and children (MD = 0.33 d).

For kids, spacers meant less time in the ED. Duration in the ED was approximately half an hour shorter for children using spacers (MD = –33.48 min). There was no difference observed in adults (MD = 1.75 min). The rate of tremor was lower in children using spacers (RR = 0.64) and was similar in adults (RR = 1.12). The rise in pulse rate was lower in children using spacers
(MD = –5.41% change from baseline) and was similar in adults (MD = –1.23%).

On the next page: What's new and challenges to implementation >>

WHAT’S NEW
Additional evidence that spacers are as effective as nebulizers
This meta-analysis, which included four new studies, should finally dispel the myth that nebulizers deliver β-agonists more effectively than MDIs with spacers. Additionally, in children, spacers are associated with lower rates of adverse effects, including tremor and elevated pulse rate.

CAVEATS
Most studies involving children were open label
Although most of the adult trials in this meta-analysis involved a double-dummy design, which allows for effective participant blinding, most of the studies involving children were open label. This open-label design might have been a source of reporting bias for symptom-related outcomes but should not have affected hospital admission rates or duration of hospital stay.

In the double-dummy studies, adults received both a nebulizer and a spacer, which likely explains the similar time spent in the ED by the treatment and control groups.

CHALLENGES TO IMPLEMENTATION
Old habits are hard to break
Clinicians may think that patients view nebulizers as more potent or more effective than spacers and thus be more likely to order them. Some patients may prefer nebulizers because of convenience or other factors.

REFERENCES
1. Cates CJ, Welsh EJ, Rowe BH. Holding ­chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9: CD000052.

2. Barrett ML, Wier LM, Washington R. Trends in pediatric and adult hospital stays for asthma, 2000-2010. HCUP Statistical Brief #169. www.hcup-us.ahrq.gov/reports/stat briefs/sb169-Asthma-Trends-Hospital-Stays.pdf. Accessed June 16, 2014.

3. Pfuntner A, Wier LM, Stocks C. Most frequent conditions in US hospitals, 2011. HCUP Statistical Brief #162. www.hcup-us.ahrq.gov/reports/statbriefs/sb162.pdf.  Accessed June 16, 2014.

4. Cates CJ, Crilly JA, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2006;(2): CD000052.

5. Turner MO, Patel A, Ginsburg S, et al. Bronchodilator delivery in acute airflow obstruction: a meta-analysis. Arch Intern Med. 1997;157:1736-1744.

6. National Heart, Lung, and Blood Institute Expert Panel Report 3 (EPR3): Guidelines for the diagnosis and management of asthma. www.nhlbi.nih.gov/guidelines/asthma/asth gdln.htm. Accessed June 16, 2014.

7. British Thoracic Society. British guideline of the management of asthma: a national clinical guideline. www.brit-thoracic.org.uk/document-library/clinical-information/asth ma/btssign-guideline-on-the-management-of-asthma/. Accessed June 16, 2014.

8. Pitts SR, Niska RW, Xu J, et al. National Hospital Ambulatory Medical Care Survey: 2006 emergency department summary. www.cdc.gov/nchs/data/nhsr/nhsr007.pdf.  Accessed June 16, 2014.

ACKNOWLEDGEMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center for Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health.

Copyright © 2014. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice. 2014;63(6):321-322, 346.

ANSWER
Several findings are evident from this radiograph. First, the quality is slightly diminished due to the patient’s size and artifact from the backboard. The patient’s mediastinum is somewhat widened, which is concerning for possible occult chest/vascular injury. There is some haziness within the left apical region suggestive of a hemothorax; no definite pneumothorax is seen. The left clavicle is fractured and displaced, and the left scapula is fractured as well.

ANSWER
Several findings are evident from this radiograph. First, the quality is slightly diminished due to the patient’s size and artifact from the backboard. The patient’s mediastinum is somewhat widened, which is concerning for possible occult chest/vascular injury. There is some haziness within the left apical region suggestive of a hemothorax; no definite pneumothorax is seen. The left clavicle is fractured and displaced, and the left scapula is fractured as well.

ANSWER
Several findings are evident from this radiograph. First, the quality is slightly diminished due to the patient’s size and artifact from the backboard. The patient’s mediastinum is somewhat widened, which is concerning for possible occult chest/vascular injury. There is some haziness within the left apical region suggestive of a hemothorax; no definite pneumothorax is seen. The left clavicle is fractured and displaced, and the left scapula is fractured as well.

ANSWER
The correct answer is tuberous sclerosis (choice “d”), a genetic disorder affecting cellular differentiation and proliferation. As a result, hamartomas commonly form in organs such as the brain.

Von Recklinghausen disease (choice “a”; also known as neurofibromatosis type 1) presents with hyperpigmented macules and patches called café au lait macules. These and other findings differentiate it considerably from tuberous sclerosis.

“No unifying explanation” (choice “b”) is incorrect, because, as stated above, there is a unifying explanation for these findings!

Vitiligo (choice “c”) involves hypopigmented macules and patches. However, it does not present with some of the other findings seen in this case.

DISCUSSION
Tuberous sclerosis was first described in 1862 by von Recklinghausen, who noted the collection of findings we now term tuberous sclerosis complex (TSC) due to the wide variation in presentation.

In the United States, TSC occurs in an estimated one in 6,000 to one in 30,000 newborns. Usually, it manifests when the child is between ages 2 and 6, but genetic penetrance is highly variable—a major reason for the shift to the use of the term complex with this condition. (This case, with its late presentation, illustrates this variability.)

In about 60% of cases, TSC is transmitted in autosomal dominant mode, although at least 20% of cases may be due to spontaneous mutations. It has not shown any racial or gender predilections. Up to 90% of TSC patients will present with seizures, and 60% to 70% of those affected will demonstrate some developmental disability.

Skin is affected in at least 70% of TSC cases. This patient typifies the common dermatologic findings: dart-shaped hypopigmented macules (known as mountain ash leaf spots) and fleshy facial papules in the nasolabial region (originally called adenoma sebaceum and now called angiofibromas). Periungal fibromas are also common. Other major diagnostic criteria for TSC include cortical tubers seen on imaging and retinal hamartomas. Minor diagnostic criteria include pits in dental enamel and gingival fibromas.

Definitive diagnosis depends on identification of either two major manifestations or one major and two minor findings. There are no blood tests to confirm the diagnosis. In terms of treatment, the various elements that comprise TSC can be dealt with (eg, control of seizures and destruction or modification of skin lesions).

This patient received a diagnosis of TSC. She was returned to her primary care provider, who referred her for additional imaging of her lungs and heart and for ophthalmologic evaluation of her retinas. Genetic counseling was also arranged. With her seizures under control, she was able to continue matriculation through high school.

ANSWER
The correct answer is tuberous sclerosis (choice “d”), a genetic disorder affecting cellular differentiation and proliferation. As a result, hamartomas commonly form in organs such as the brain.

Von Recklinghausen disease (choice “a”; also known as neurofibromatosis type 1) presents with hyperpigmented macules and patches called café au lait macules. These and other findings differentiate it considerably from tuberous sclerosis.

“No unifying explanation” (choice “b”) is incorrect, because, as stated above, there is a unifying explanation for these findings!

Vitiligo (choice “c”) involves hypopigmented macules and patches. However, it does not present with some of the other findings seen in this case.

DISCUSSION
Tuberous sclerosis was first described in 1862 by von Recklinghausen, who noted the collection of findings we now term tuberous sclerosis complex (TSC) due to the wide variation in presentation.

In the United States, TSC occurs in an estimated one in 6,000 to one in 30,000 newborns. Usually, it manifests when the child is between ages 2 and 6, but genetic penetrance is highly variable—a major reason for the shift to the use of the term complex with this condition. (This case, with its late presentation, illustrates this variability.)

In about 60% of cases, TSC is transmitted in autosomal dominant mode, although at least 20% of cases may be due to spontaneous mutations. It has not shown any racial or gender predilections. Up to 90% of TSC patients will present with seizures, and 60% to 70% of those affected will demonstrate some developmental disability.

Skin is affected in at least 70% of TSC cases. This patient typifies the common dermatologic findings: dart-shaped hypopigmented macules (known as mountain ash leaf spots) and fleshy facial papules in the nasolabial region (originally called adenoma sebaceum and now called angiofibromas). Periungal fibromas are also common. Other major diagnostic criteria for TSC include cortical tubers seen on imaging and retinal hamartomas. Minor diagnostic criteria include pits in dental enamel and gingival fibromas.

Definitive diagnosis depends on identification of either two major manifestations or one major and two minor findings. There are no blood tests to confirm the diagnosis. In terms of treatment, the various elements that comprise TSC can be dealt with (eg, control of seizures and destruction or modification of skin lesions).

This patient received a diagnosis of TSC. She was returned to her primary care provider, who referred her for additional imaging of her lungs and heart and for ophthalmologic evaluation of her retinas. Genetic counseling was also arranged. With her seizures under control, she was able to continue matriculation through high school.

ANSWER
The correct answer is tuberous sclerosis (choice “d”), a genetic disorder affecting cellular differentiation and proliferation. As a result, hamartomas commonly form in organs such as the brain.

Von Recklinghausen disease (choice “a”; also known as neurofibromatosis type 1) presents with hyperpigmented macules and patches called café au lait macules. These and other findings differentiate it considerably from tuberous sclerosis.

“No unifying explanation” (choice “b”) is incorrect, because, as stated above, there is a unifying explanation for these findings!

Vitiligo (choice “c”) involves hypopigmented macules and patches. However, it does not present with some of the other findings seen in this case.

DISCUSSION
Tuberous sclerosis was first described in 1862 by von Recklinghausen, who noted the collection of findings we now term tuberous sclerosis complex (TSC) due to the wide variation in presentation.

In the United States, TSC occurs in an estimated one in 6,000 to one in 30,000 newborns. Usually, it manifests when the child is between ages 2 and 6, but genetic penetrance is highly variable—a major reason for the shift to the use of the term complex with this condition. (This case, with its late presentation, illustrates this variability.)

In about 60% of cases, TSC is transmitted in autosomal dominant mode, although at least 20% of cases may be due to spontaneous mutations. It has not shown any racial or gender predilections. Up to 90% of TSC patients will present with seizures, and 60% to 70% of those affected will demonstrate some developmental disability.

Skin is affected in at least 70% of TSC cases. This patient typifies the common dermatologic findings: dart-shaped hypopigmented macules (known as mountain ash leaf spots) and fleshy facial papules in the nasolabial region (originally called adenoma sebaceum and now called angiofibromas). Periungal fibromas are also common. Other major diagnostic criteria for TSC include cortical tubers seen on imaging and retinal hamartomas. Minor diagnostic criteria include pits in dental enamel and gingival fibromas.

Definitive diagnosis depends on identification of either two major manifestations or one major and two minor findings. There are no blood tests to confirm the diagnosis. In terms of treatment, the various elements that comprise TSC can be dealt with (eg, control of seizures and destruction or modification of skin lesions).

This patient received a diagnosis of TSC. She was returned to her primary care provider, who referred her for additional imaging of her lungs and heart and for ophthalmologic evaluation of her retinas. Genetic counseling was also arranged. With her seizures under control, she was able to continue matriculation through high school.

ANSWER
The ECG reveals sinus bradycardia with second-degree atrioventricular (AV) block (Mobitz I), also known as Wenckebach block.

Mobitz I heart block often occurs with reversible reasons of conduction block at the level of the AV node. While the P-P intervals remain constant, conduction fatigue within the AV node results in the P-R interval becoming progressively longer, until the AV node completely blocks conduction from the atria to the ventricles. The process then repeats itself in a pattern of P to QRS groups.

In this case, there are three P waves for every two QRS complexes, resulting in a 3:2 pattern. The PR interval is longest prior to the blocked QRS and shortest immediately after it. The diagnosis of sinus bradycardia results from a constant P-P interval of 58 beats/min.

Further questioning of the patient revealed that he had inadvertently doubled his dose of metoprolol. Correcting this resulted in the return of normal sinus rhythm. 

ANSWER
The ECG reveals sinus bradycardia with second-degree atrioventricular (AV) block (Mobitz I), also known as Wenckebach block.

Mobitz I heart block often occurs with reversible reasons of conduction block at the level of the AV node. While the P-P intervals remain constant, conduction fatigue within the AV node results in the P-R interval becoming progressively longer, until the AV node completely blocks conduction from the atria to the ventricles. The process then repeats itself in a pattern of P to QRS groups.

In this case, there are three P waves for every two QRS complexes, resulting in a 3:2 pattern. The PR interval is longest prior to the blocked QRS and shortest immediately after it. The diagnosis of sinus bradycardia results from a constant P-P interval of 58 beats/min.

Further questioning of the patient revealed that he had inadvertently doubled his dose of metoprolol. Correcting this resulted in the return of normal sinus rhythm. 

ANSWER
The ECG reveals sinus bradycardia with second-degree atrioventricular (AV) block (Mobitz I), also known as Wenckebach block.

Mobitz I heart block often occurs with reversible reasons of conduction block at the level of the AV node. While the P-P intervals remain constant, conduction fatigue within the AV node results in the P-R interval becoming progressively longer, until the AV node completely blocks conduction from the atria to the ventricles. The process then repeats itself in a pattern of P to QRS groups.

In this case, there are three P waves for every two QRS complexes, resulting in a 3:2 pattern. The PR interval is longest prior to the blocked QRS and shortest immediately after it. The diagnosis of sinus bradycardia results from a constant P-P interval of 58 beats/min.

Further questioning of the patient revealed that he had inadvertently doubled his dose of metoprolol. Correcting this resulted in the return of normal sinus rhythm. 

New practice guidelines on skin and soft tissue infections from the Infectious Diseases Society of America stress careful clinical attention to the type of infection, the epidemiological setting in which the infection occurred, the health status of the patient, and the selection and dosage of the most appropriate treatment agents.

The guidelines, published online June 18 in Clinical Infectious Diseases (doi:10.1093/cid/ciu296), update those issued by IDSA in 2005 and cover everything from preventing infections caused by animal bites in healthy hosts to life-threatening infections in immunocompromised patients. They also emphasize accurate identification of pathogens, stressing that clinical presentations can be very similar.

"This is not one of those guidelines that boils complex issues down to a choice between a couple of different drugs or combinations of drugs," said Dr. Dennis Stevens of the Department of Veterans Affairs in Boise, Idaho, the guidelines’ lead author. "Skin and soft tissue infections [SSTIs] have multiple causes and different presentations, depending upon the immune status of the host. Here it’s much more complicated and really requires an astute physician to consider a number of things."

The guidelines, drafted by a 10-member panel, offer a novel algorithm for management of nonpurulent and purulent infections that aims to define a pathway for mild, moderate, and severe infections in each category. For example, no antibiotic is recommended for a purulent infection – only incision and drainage – if the patient has no signs of systemic involvement.

For moderate cases of purulent infection with some systemic involvement, incision and drainage should be followed by culture and sensitivity testing, the guidelines say, listing two antibiotics, trimethoprim-sulfamethoxazole and doxycycline, as appropriate for empiric treatment, while trimethoprim-sulfamethoxazole is recommended if the pathogen is found to be methicillin-resistant Staphylococcus aureus (MRSA) and dicloxacillin or cephalexin if it is methicillin-susceptible S. aureus (MSSA).

The purpose of the algorithm, expressed in the guidelines in chart form, "is to make the physician think," Dr. Stevens said in an interview. "There is a huge move to try and monitor antibiotic stewardship to prevent resistance, and we’re just trying to get the clinician to think of tier 1, tier 2, and tier 3 approaches, depending not only on the bug, but on how sick the patient is. Instead of a knee-jerk approach treating everybody with highly expensive IV antibiotics, [the algorithm] provides a clear pathway to treat appropriately."

In people with an abscess who have failed antibiotic treatment, are immunocompromised, or have fever and elevated white blood cell counts or other evidence of severe infection, "we’re not going to gamble," Dr. Stevens said, adding that the guidelines recommend prompt treatment using "an antibiotic that gets all of these organisms, including resistant ones." Newly approved agents dalbavancin and tedizolid are effective in treating SSTIs caused by MRSA, the guidelines note.

The guidelines are intended for use by clinicians in emergency departments, family practice, internal medicine, general surgery, orthopedics, gynecology, dermatology, infectious disease, and oncology.

Another algorithm charted in the guidelines covers wound infections following surgeries, which can involve multiple pathogens. The algorithm provides simple clinical clues as to which require antibiotics, a simple opening of the suture line, "or a full-court press for the kind of devastating infections that occur within the first 48 hours," Dr. Stevens said. Additional recommendations address infections that can occur in individuals receiving treatment for cancer or receiving immunosuppressant medications, or those who have had an organ transplant or who have HIV/AIDS.

Immunocompromised patients, Dr. Stevens said, are among the most challenging to treat because they may have a history of extensive antibiotic exposure, are likely to have infections with resistant bacteria, and often see involvement with fungal and parasitic agents that might be considered innocuous in normal individuals. "This is the first time physicians will have some decent guidelines about how to approach the problem of skin and soft tissue infections in these kinds of patients," he noted.

The guidelines’ development was funded by the IDSA. Dr. Stevens reported no conflicts of interest. Panel member Alan L. Bisno disclosed receiving honoraria from UpToDate, while five other members – Dr. Henry F. Chambers, Dr. E. Patchen Dellinger, Dr. Ellie J. C. Goldstein, Dr. Sherwood L. Gorbach, and Dr. Sheldon L. Kaplan – disclosed financial relationships with pharmaceutical manufacturers.

New practice guidelines on skin and soft tissue infections from the Infectious Diseases Society of America stress careful clinical attention to the type of infection, the epidemiological setting in which the infection occurred, the health status of the patient, and the selection and dosage of the most appropriate treatment agents.

The guidelines, published online June 18 in Clinical Infectious Diseases (doi:10.1093/cid/ciu296), update those issued by IDSA in 2005 and cover everything from preventing infections caused by animal bites in healthy hosts to life-threatening infections in immunocompromised patients. They also emphasize accurate identification of pathogens, stressing that clinical presentations can be very similar.

"This is not one of those guidelines that boils complex issues down to a choice between a couple of different drugs or combinations of drugs," said Dr. Dennis Stevens of the Department of Veterans Affairs in Boise, Idaho, the guidelines’ lead author. "Skin and soft tissue infections [SSTIs] have multiple causes and different presentations, depending upon the immune status of the host. Here it’s much more complicated and really requires an astute physician to consider a number of things."

The guidelines, drafted by a 10-member panel, offer a novel algorithm for management of nonpurulent and purulent infections that aims to define a pathway for mild, moderate, and severe infections in each category. For example, no antibiotic is recommended for a purulent infection – only incision and drainage – if the patient has no signs of systemic involvement.

For moderate cases of purulent infection with some systemic involvement, incision and drainage should be followed by culture and sensitivity testing, the guidelines say, listing two antibiotics, trimethoprim-sulfamethoxazole and doxycycline, as appropriate for empiric treatment, while trimethoprim-sulfamethoxazole is recommended if the pathogen is found to be methicillin-resistant Staphylococcus aureus (MRSA) and dicloxacillin or cephalexin if it is methicillin-susceptible S. aureus (MSSA).

The purpose of the algorithm, expressed in the guidelines in chart form, "is to make the physician think," Dr. Stevens said in an interview. "There is a huge move to try and monitor antibiotic stewardship to prevent resistance, and we’re just trying to get the clinician to think of tier 1, tier 2, and tier 3 approaches, depending not only on the bug, but on how sick the patient is. Instead of a knee-jerk approach treating everybody with highly expensive IV antibiotics, [the algorithm] provides a clear pathway to treat appropriately."

In people with an abscess who have failed antibiotic treatment, are immunocompromised, or have fever and elevated white blood cell counts or other evidence of severe infection, "we’re not going to gamble," Dr. Stevens said, adding that the guidelines recommend prompt treatment using "an antibiotic that gets all of these organisms, including resistant ones." Newly approved agents dalbavancin and tedizolid are effective in treating SSTIs caused by MRSA, the guidelines note.

The guidelines are intended for use by clinicians in emergency departments, family practice, internal medicine, general surgery, orthopedics, gynecology, dermatology, infectious disease, and oncology.

Another algorithm charted in the guidelines covers wound infections following surgeries, which can involve multiple pathogens. The algorithm provides simple clinical clues as to which require antibiotics, a simple opening of the suture line, "or a full-court press for the kind of devastating infections that occur within the first 48 hours," Dr. Stevens said. Additional recommendations address infections that can occur in individuals receiving treatment for cancer or receiving immunosuppressant medications, or those who have had an organ transplant or who have HIV/AIDS.

Immunocompromised patients, Dr. Stevens said, are among the most challenging to treat because they may have a history of extensive antibiotic exposure, are likely to have infections with resistant bacteria, and often see involvement with fungal and parasitic agents that might be considered innocuous in normal individuals. "This is the first time physicians will have some decent guidelines about how to approach the problem of skin and soft tissue infections in these kinds of patients," he noted.

The guidelines’ development was funded by the IDSA. Dr. Stevens reported no conflicts of interest. Panel member Alan L. Bisno disclosed receiving honoraria from UpToDate, while five other members – Dr. Henry F. Chambers, Dr. E. Patchen Dellinger, Dr. Ellie J. C. Goldstein, Dr. Sherwood L. Gorbach, and Dr. Sheldon L. Kaplan – disclosed financial relationships with pharmaceutical manufacturers.

New practice guidelines on skin and soft tissue infections from the Infectious Diseases Society of America stress careful clinical attention to the type of infection, the epidemiological setting in which the infection occurred, the health status of the patient, and the selection and dosage of the most appropriate treatment agents.

The guidelines, published online June 18 in Clinical Infectious Diseases (doi:10.1093/cid/ciu296), update those issued by IDSA in 2005 and cover everything from preventing infections caused by animal bites in healthy hosts to life-threatening infections in immunocompromised patients. They also emphasize accurate identification of pathogens, stressing that clinical presentations can be very similar.

"This is not one of those guidelines that boils complex issues down to a choice between a couple of different drugs or combinations of drugs," said Dr. Dennis Stevens of the Department of Veterans Affairs in Boise, Idaho, the guidelines’ lead author. "Skin and soft tissue infections [SSTIs] have multiple causes and different presentations, depending upon the immune status of the host. Here it’s much more complicated and really requires an astute physician to consider a number of things."

The guidelines, drafted by a 10-member panel, offer a novel algorithm for management of nonpurulent and purulent infections that aims to define a pathway for mild, moderate, and severe infections in each category. For example, no antibiotic is recommended for a purulent infection – only incision and drainage – if the patient has no signs of systemic involvement.

For moderate cases of purulent infection with some systemic involvement, incision and drainage should be followed by culture and sensitivity testing, the guidelines say, listing two antibiotics, trimethoprim-sulfamethoxazole and doxycycline, as appropriate for empiric treatment, while trimethoprim-sulfamethoxazole is recommended if the pathogen is found to be methicillin-resistant Staphylococcus aureus (MRSA) and dicloxacillin or cephalexin if it is methicillin-susceptible S. aureus (MSSA).

The purpose of the algorithm, expressed in the guidelines in chart form, "is to make the physician think," Dr. Stevens said in an interview. "There is a huge move to try and monitor antibiotic stewardship to prevent resistance, and we’re just trying to get the clinician to think of tier 1, tier 2, and tier 3 approaches, depending not only on the bug, but on how sick the patient is. Instead of a knee-jerk approach treating everybody with highly expensive IV antibiotics, [the algorithm] provides a clear pathway to treat appropriately."

In people with an abscess who have failed antibiotic treatment, are immunocompromised, or have fever and elevated white blood cell counts or other evidence of severe infection, "we’re not going to gamble," Dr. Stevens said, adding that the guidelines recommend prompt treatment using "an antibiotic that gets all of these organisms, including resistant ones." Newly approved agents dalbavancin and tedizolid are effective in treating SSTIs caused by MRSA, the guidelines note.

The guidelines are intended for use by clinicians in emergency departments, family practice, internal medicine, general surgery, orthopedics, gynecology, dermatology, infectious disease, and oncology.

Another algorithm charted in the guidelines covers wound infections following surgeries, which can involve multiple pathogens. The algorithm provides simple clinical clues as to which require antibiotics, a simple opening of the suture line, "or a full-court press for the kind of devastating infections that occur within the first 48 hours," Dr. Stevens said. Additional recommendations address infections that can occur in individuals receiving treatment for cancer or receiving immunosuppressant medications, or those who have had an organ transplant or who have HIV/AIDS.

Immunocompromised patients, Dr. Stevens said, are among the most challenging to treat because they may have a history of extensive antibiotic exposure, are likely to have infections with resistant bacteria, and often see involvement with fungal and parasitic agents that might be considered innocuous in normal individuals. "This is the first time physicians will have some decent guidelines about how to approach the problem of skin and soft tissue infections in these kinds of patients," he noted.

The guidelines’ development was funded by the IDSA. Dr. Stevens reported no conflicts of interest. Panel member Alan L. Bisno disclosed receiving honoraria from UpToDate, while five other members – Dr. Henry F. Chambers, Dr. E. Patchen Dellinger, Dr. Ellie J. C. Goldstein, Dr. Sherwood L. Gorbach, and Dr. Sheldon L. Kaplan – disclosed financial relationships with pharmaceutical manufacturers.

MILAN—Results of a phase 2 trial suggest thalidomide can elicit solid—though not necessarily durable—responses among patients with hereditary hemorrhagic telangiectasia (HHT) suffering from severe, recurrent epistaxis.

All 29 evaluable patients responded to thalidomide, with 4 achieving a complete response.

Unfortunately, 11 patients relapsed at a median of 43 weeks. But re-treatment was possible for a few patients and did prompt additional responses.

“Our results strongly support the hypothesis that low-dose thalidomide is safe and very effective for the treatment of severe epistaxis in HHT patients who did not benefit from other available modalities of treatment,” said Rosangela Invernizzi, MD, of the University of Pavia in Italy.

“However, the effect of thalidomide is not permanent, and maintenance therapy may be required.”

Dr Invernizzi presented these discoveries at the 19th Congress of the European Hematology Association (EHA) as abstract S692.

She and her colleagues enrolled 31 HHT patients on this phase 2 study. The patients had a median age of 64 years (range, 44-84). Nine had grade 2 epistaxis, and 22 had grade 3.

Previous treatments included argon plasma coagulation (n=19), electrocautery (n=12), embolization (n=7), laser coagulation (n=2), septodermoplasty (n=2), and arterial ligation (n=1). Eighteen patients had received less than 10 units of red blood cells, and 13 had received 10 or more units.

For this study, patients received thalidomide at 50 mg a day for 4 weeks. Complete responders received 8 additional weeks of treatment at the same dosage. Partial responders received 16 additional weeks of treatment at the same dosage.

For non-responders, the dose was increased by 50 mg per day every 4 weeks until they attained a complete or partial response (with a maximum dose of 200 mg). If patients did not respond, they received 24 additional weeks of treatment. Thalidomide courses could be repeated 3 times at the most.

Response and relapse

The median follow-up was 67 weeks (range, 3-130 weeks). All of the 29 evaluable patients achieved a response, with 4 complete responses (14%) and 25 partial responses (86%).

Twenty-four patients responded within 4 weeks of treatment initiation, and 5 responded within 8 weeks. The minimum dose of thalidomide was 50 mg, and the maximum was 100 mg.

“A significant decrease of all epistaxis parameters—frequency [P=0.001], intensity [P<0.0001], and duration [P=0.0001]—was recorded,” Dr Invernizzi noted.

“As a consequence, thalidomide treatment significantly increased hemoglobin levels [P=0.02] and abolished or greatly decreased transfusion need [P=0.0003] and improved the quality of life.”

However, 11 patients relapsed at a median of 43 weeks. Patients who relapsed within 52 weeks of ending thalidomide could be treated again for 8 weeks at the same maximum dose employed during induction.

Four patients received re-treatment and achieved partial responses. One of these patients relapsed again at 13 weeks. But, for the other 3 patients, clinical improvement persisted at more than 17 weeks, more than 26 weeks, and more than 27 weeks.

Safety and tolerability

Dr Invernizzi said there were no noticeable side effects associated with re-treatment of relapsed patients.

The most common adverse events among all patients were gastrointestinal symptoms, such as constipation, vomiting, and dry mouth (n=15); drowsiness (n=9); and constitutional symptoms, such as asthenia, malaise, and peripheral edema (n=7).

There were 2 patients with psychiatric symptoms (confusion, depression) and 2 patients with thyroid dysfunction.

There was 1 cardiovascular event, (bradycardia, heart failure), 1 patient with low hematologic counts, 1 patient with neurologic symptoms (peripheral neuropathy, dizziness, tremor), 1 dermatologic event (toxic cutaneous rashes, skin dryness), and 1 infection.

MILAN—Results of a phase 2 trial suggest thalidomide can elicit solid—though not necessarily durable—responses among patients with hereditary hemorrhagic telangiectasia (HHT) suffering from severe, recurrent epistaxis.

All 29 evaluable patients responded to thalidomide, with 4 achieving a complete response.

Unfortunately, 11 patients relapsed at a median of 43 weeks. But re-treatment was possible for a few patients and did prompt additional responses.

“Our results strongly support the hypothesis that low-dose thalidomide is safe and very effective for the treatment of severe epistaxis in HHT patients who did not benefit from other available modalities of treatment,” said Rosangela Invernizzi, MD, of the University of Pavia in Italy.

“However, the effect of thalidomide is not permanent, and maintenance therapy may be required.”

Dr Invernizzi presented these discoveries at the 19th Congress of the European Hematology Association (EHA) as abstract S692.

She and her colleagues enrolled 31 HHT patients on this phase 2 study. The patients had a median age of 64 years (range, 44-84). Nine had grade 2 epistaxis, and 22 had grade 3.

Previous treatments included argon plasma coagulation (n=19), electrocautery (n=12), embolization (n=7), laser coagulation (n=2), septodermoplasty (n=2), and arterial ligation (n=1). Eighteen patients had received less than 10 units of red blood cells, and 13 had received 10 or more units.

For this study, patients received thalidomide at 50 mg a day for 4 weeks. Complete responders received 8 additional weeks of treatment at the same dosage. Partial responders received 16 additional weeks of treatment at the same dosage.

For non-responders, the dose was increased by 50 mg per day every 4 weeks until they attained a complete or partial response (with a maximum dose of 200 mg). If patients did not respond, they received 24 additional weeks of treatment. Thalidomide courses could be repeated 3 times at the most.

Response and relapse

The median follow-up was 67 weeks (range, 3-130 weeks). All of the 29 evaluable patients achieved a response, with 4 complete responses (14%) and 25 partial responses (86%).

Twenty-four patients responded within 4 weeks of treatment initiation, and 5 responded within 8 weeks. The minimum dose of thalidomide was 50 mg, and the maximum was 100 mg.

“A significant decrease of all epistaxis parameters—frequency [P=0.001], intensity [P<0.0001], and duration [P=0.0001]—was recorded,” Dr Invernizzi noted.

“As a consequence, thalidomide treatment significantly increased hemoglobin levels [P=0.02] and abolished or greatly decreased transfusion need [P=0.0003] and improved the quality of life.”

However, 11 patients relapsed at a median of 43 weeks. Patients who relapsed within 52 weeks of ending thalidomide could be treated again for 8 weeks at the same maximum dose employed during induction.

Four patients received re-treatment and achieved partial responses. One of these patients relapsed again at 13 weeks. But, for the other 3 patients, clinical improvement persisted at more than 17 weeks, more than 26 weeks, and more than 27 weeks.

Safety and tolerability

Dr Invernizzi said there were no noticeable side effects associated with re-treatment of relapsed patients.

The most common adverse events among all patients were gastrointestinal symptoms, such as constipation, vomiting, and dry mouth (n=15); drowsiness (n=9); and constitutional symptoms, such as asthenia, malaise, and peripheral edema (n=7).

There were 2 patients with psychiatric symptoms (confusion, depression) and 2 patients with thyroid dysfunction.

There was 1 cardiovascular event, (bradycardia, heart failure), 1 patient with low hematologic counts, 1 patient with neurologic symptoms (peripheral neuropathy, dizziness, tremor), 1 dermatologic event (toxic cutaneous rashes, skin dryness), and 1 infection.

MILAN—Results of a phase 2 trial suggest thalidomide can elicit solid—though not necessarily durable—responses among patients with hereditary hemorrhagic telangiectasia (HHT) suffering from severe, recurrent epistaxis.

All 29 evaluable patients responded to thalidomide, with 4 achieving a complete response.

Unfortunately, 11 patients relapsed at a median of 43 weeks. But re-treatment was possible for a few patients and did prompt additional responses.

“Our results strongly support the hypothesis that low-dose thalidomide is safe and very effective for the treatment of severe epistaxis in HHT patients who did not benefit from other available modalities of treatment,” said Rosangela Invernizzi, MD, of the University of Pavia in Italy.

“However, the effect of thalidomide is not permanent, and maintenance therapy may be required.”

Dr Invernizzi presented these discoveries at the 19th Congress of the European Hematology Association (EHA) as abstract S692.

She and her colleagues enrolled 31 HHT patients on this phase 2 study. The patients had a median age of 64 years (range, 44-84). Nine had grade 2 epistaxis, and 22 had grade 3.

Previous treatments included argon plasma coagulation (n=19), electrocautery (n=12), embolization (n=7), laser coagulation (n=2), septodermoplasty (n=2), and arterial ligation (n=1). Eighteen patients had received less than 10 units of red blood cells, and 13 had received 10 or more units.

For this study, patients received thalidomide at 50 mg a day for 4 weeks. Complete responders received 8 additional weeks of treatment at the same dosage. Partial responders received 16 additional weeks of treatment at the same dosage.

For non-responders, the dose was increased by 50 mg per day every 4 weeks until they attained a complete or partial response (with a maximum dose of 200 mg). If patients did not respond, they received 24 additional weeks of treatment. Thalidomide courses could be repeated 3 times at the most.

Response and relapse

The median follow-up was 67 weeks (range, 3-130 weeks). All of the 29 evaluable patients achieved a response, with 4 complete responses (14%) and 25 partial responses (86%).

Twenty-four patients responded within 4 weeks of treatment initiation, and 5 responded within 8 weeks. The minimum dose of thalidomide was 50 mg, and the maximum was 100 mg.

“A significant decrease of all epistaxis parameters—frequency [P=0.001], intensity [P<0.0001], and duration [P=0.0001]—was recorded,” Dr Invernizzi noted.

“As a consequence, thalidomide treatment significantly increased hemoglobin levels [P=0.02] and abolished or greatly decreased transfusion need [P=0.0003] and improved the quality of life.”

However, 11 patients relapsed at a median of 43 weeks. Patients who relapsed within 52 weeks of ending thalidomide could be treated again for 8 weeks at the same maximum dose employed during induction.

Four patients received re-treatment and achieved partial responses. One of these patients relapsed again at 13 weeks. But, for the other 3 patients, clinical improvement persisted at more than 17 weeks, more than 26 weeks, and more than 27 weeks.

Safety and tolerability

Dr Invernizzi said there were no noticeable side effects associated with re-treatment of relapsed patients.

The most common adverse events among all patients were gastrointestinal symptoms, such as constipation, vomiting, and dry mouth (n=15); drowsiness (n=9); and constitutional symptoms, such as asthenia, malaise, and peripheral edema (n=7).

There were 2 patients with psychiatric symptoms (confusion, depression) and 2 patients with thyroid dysfunction.

There was 1 cardiovascular event, (bradycardia, heart failure), 1 patient with low hematologic counts, 1 patient with neurologic symptoms (peripheral neuropathy, dizziness, tremor), 1 dermatologic event (toxic cutaneous rashes, skin dryness), and 1 infection.

As obesity continues to ravage the health of the United States, bariatric surgery offers an effective strategy for individual patients suffering from medical complications.

When performed in adults with a body mass index of at least 30 kg/m², bariatric surgery is associated with a mean weight loss of 20%-35% of baseline weight at 2-3 years. Bariatric surgery is associated with greater reductions in obesity comorbidities, compared with lifestyle intervention and supervised weight loss. Contemporary bariatric surgeries include Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, biliopancreatic diversion with duodenal switch, sleeve gastrectomy, and mini–gastric bypass.

Bariatric surgical procedures affect weight loss through two mechanisms: malabsorption and restriction. Such alterations in human physiology can change the absorption of common drugs of addiction, such as alcohol. This can increase the risk for problem drinking behaviors.

Wendy C. King, Ph.D., of the department of epidemiology at the University of Pittsburgh and her colleagues conducted an analysis of data from 1,945 patients in a cohort who underwent bariatric surgery in 10 U.S. hospitals. Symptoms of alcohol use disorder (AUD) were assessed pre- and postoperatively (JAMA 2012;307:2516-25).

The prevalence of AUD was significantly higher at 2 years postoperatively (9.6%), compared with the preoperative period (7.6%; P less than .01). Factors associated with a higher risk of postoperative AUD included male gender, younger age, smoking, regular alcohol consumption, a history of AUD, recreational drug use, low social support, and receiving Roux-en-Y gastric bypass.

AUD can disqualify patients from bariatric surgery – but 7.6% of patients in this survey (taken independently of clinical care) reported it. The authors noted that a 2% increase in AUD associated with bariatric surgery translates into 2,000 additional people with AUD each year.

This is particularly problematic for this population, because a large number of calories are associated with alcohol intake, and alcohol intake can lower inhibitions for other types of eating behaviors – all of which can lead to weight regain.

So, what do we do?

I think it may be helpful to take alcohol use histories in the patients we are seeing in bariatric surgery follow-up, especially those who appear to be regaining weight. Some patients may not be aware of this connection. For the patients who I have told about this relationship, they recognize it, which may be the first step toward dealing with it.

Dr. Ebbert is a professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no disclosures.

As obesity continues to ravage the health of the United States, bariatric surgery offers an effective strategy for individual patients suffering from medical complications.

When performed in adults with a body mass index of at least 30 kg/m², bariatric surgery is associated with a mean weight loss of 20%-35% of baseline weight at 2-3 years. Bariatric surgery is associated with greater reductions in obesity comorbidities, compared with lifestyle intervention and supervised weight loss. Contemporary bariatric surgeries include Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, biliopancreatic diversion with duodenal switch, sleeve gastrectomy, and mini–gastric bypass.

Bariatric surgical procedures affect weight loss through two mechanisms: malabsorption and restriction. Such alterations in human physiology can change the absorption of common drugs of addiction, such as alcohol. This can increase the risk for problem drinking behaviors.

Wendy C. King, Ph.D., of the department of epidemiology at the University of Pittsburgh and her colleagues conducted an analysis of data from 1,945 patients in a cohort who underwent bariatric surgery in 10 U.S. hospitals. Symptoms of alcohol use disorder (AUD) were assessed pre- and postoperatively (JAMA 2012;307:2516-25).

The prevalence of AUD was significantly higher at 2 years postoperatively (9.6%), compared with the preoperative period (7.6%; P less than .01). Factors associated with a higher risk of postoperative AUD included male gender, younger age, smoking, regular alcohol consumption, a history of AUD, recreational drug use, low social support, and receiving Roux-en-Y gastric bypass.

AUD can disqualify patients from bariatric surgery – but 7.6% of patients in this survey (taken independently of clinical care) reported it. The authors noted that a 2% increase in AUD associated with bariatric surgery translates into 2,000 additional people with AUD each year.

This is particularly problematic for this population, because a large number of calories are associated with alcohol intake, and alcohol intake can lower inhibitions for other types of eating behaviors – all of which can lead to weight regain.

So, what do we do?

I think it may be helpful to take alcohol use histories in the patients we are seeing in bariatric surgery follow-up, especially those who appear to be regaining weight. Some patients may not be aware of this connection. For the patients who I have told about this relationship, they recognize it, which may be the first step toward dealing with it.

Dr. Ebbert is a professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no disclosures.

As obesity continues to ravage the health of the United States, bariatric surgery offers an effective strategy for individual patients suffering from medical complications.

When performed in adults with a body mass index of at least 30 kg/m², bariatric surgery is associated with a mean weight loss of 20%-35% of baseline weight at 2-3 years. Bariatric surgery is associated with greater reductions in obesity comorbidities, compared with lifestyle intervention and supervised weight loss. Contemporary bariatric surgeries include Roux-en-Y gastric bypass, laparoscopic adjustable gastric banding, biliopancreatic diversion with duodenal switch, sleeve gastrectomy, and mini–gastric bypass.

Bariatric surgical procedures affect weight loss through two mechanisms: malabsorption and restriction. Such alterations in human physiology can change the absorption of common drugs of addiction, such as alcohol. This can increase the risk for problem drinking behaviors.

Wendy C. King, Ph.D., of the department of epidemiology at the University of Pittsburgh and her colleagues conducted an analysis of data from 1,945 patients in a cohort who underwent bariatric surgery in 10 U.S. hospitals. Symptoms of alcohol use disorder (AUD) were assessed pre- and postoperatively (JAMA 2012;307:2516-25).

The prevalence of AUD was significantly higher at 2 years postoperatively (9.6%), compared with the preoperative period (7.6%; P less than .01). Factors associated with a higher risk of postoperative AUD included male gender, younger age, smoking, regular alcohol consumption, a history of AUD, recreational drug use, low social support, and receiving Roux-en-Y gastric bypass.

AUD can disqualify patients from bariatric surgery – but 7.6% of patients in this survey (taken independently of clinical care) reported it. The authors noted that a 2% increase in AUD associated with bariatric surgery translates into 2,000 additional people with AUD each year.

This is particularly problematic for this population, because a large number of calories are associated with alcohol intake, and alcohol intake can lower inhibitions for other types of eating behaviors – all of which can lead to weight regain.

So, what do we do?

I think it may be helpful to take alcohol use histories in the patients we are seeing in bariatric surgery follow-up, especially those who appear to be regaining weight. Some patients may not be aware of this connection. For the patients who I have told about this relationship, they recognize it, which may be the first step toward dealing with it.

Dr. Ebbert is a professor of medicine and a general internist at the Mayo Clinic in Rochester, Minn., and a diplomate of the American Board of Addiction Medicine. The opinions expressed are those of the author. He reports no disclosures.

Leukemia patient

Credit: Bill Branson

Children recently diagnosed with standard-risk acute lymphoblastic leukemia (ALL) are likely to have few long-term complications into adulthood, investigators have reported in The Lancet Oncology.

The team said this is because current therapies are less harsh than their predecessors.

Newer protocols have eliminated radiation and restricted the use of chemotherapeutics that may cause subsequent malignancies and other chronic health conditions.

Previous research had only assessed the very long-term outcomes of children treated with older protocols, leaving physicians to piece together information from this outdated data and anecdotal evidence.

“This is one of the first studies to show that, in addition to their excellent probability of survival, long-term survivors of standard-risk childhood ALL are at low risk for complications of their therapy once they enter adulthood,” said study author Paul Nathan, MD, of The Hospital for Sick Children in Toronto, Canada.

He and his colleagues used longitudinal data from the Childhood Cancer Survivor Study, a North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986.

The team analyzed 556 patients from this study who were older than 1 year of age and younger than 10 at the time of diagnosis and who had received treatment consistent with current therapies for standard-risk ALL.

Patients were followed from 5 years following diagnosis to a median of 18 years. The survivor group was compared with a group of their siblings who had not had cancer, as well as the general population.

Twenty-eight patients in the survivor group died. Sixteen of these deaths were from causes other than relapse.

Survivors were at a slightly increased risk of death due to non-relapse causes, when compared to controls. However, no individual cause was increased.

Six survivors developed another malignancy. The risk for most chronic health disorders did not differ between survivors and siblings. But survivors appeared to have a moderately increased risk for osteoporosis or osteopenia, short stature, and cataracts.

Survivors and their siblings had similar socioeconomic outcomes, including education, rates of marriage, independent living, and household income.

While these results suggest the prognosis is favorable, Dr Nathan noted that ALL survivors should receive ongoing care from a knowledgeable primary-care practitioner.

“Among kids with standard-risk ALL, we expect most to survive,” Dr Nathan said. “Now we can say with more certainty that they will probably do well in the long-term as well. This information will be very useful for oncologists counselling newly diagnosed patients and their families and will be quite reassuring to parents.”

Leukemia patient

Credit: Bill Branson

Children recently diagnosed with standard-risk acute lymphoblastic leukemia (ALL) are likely to have few long-term complications into adulthood, investigators have reported in The Lancet Oncology.

The team said this is because current therapies are less harsh than their predecessors.

Newer protocols have eliminated radiation and restricted the use of chemotherapeutics that may cause subsequent malignancies and other chronic health conditions.

Previous research had only assessed the very long-term outcomes of children treated with older protocols, leaving physicians to piece together information from this outdated data and anecdotal evidence.

“This is one of the first studies to show that, in addition to their excellent probability of survival, long-term survivors of standard-risk childhood ALL are at low risk for complications of their therapy once they enter adulthood,” said study author Paul Nathan, MD, of The Hospital for Sick Children in Toronto, Canada.

He and his colleagues used longitudinal data from the Childhood Cancer Survivor Study, a North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986.

The team analyzed 556 patients from this study who were older than 1 year of age and younger than 10 at the time of diagnosis and who had received treatment consistent with current therapies for standard-risk ALL.

Patients were followed from 5 years following diagnosis to a median of 18 years. The survivor group was compared with a group of their siblings who had not had cancer, as well as the general population.

Twenty-eight patients in the survivor group died. Sixteen of these deaths were from causes other than relapse.

Survivors were at a slightly increased risk of death due to non-relapse causes, when compared to controls. However, no individual cause was increased.

Six survivors developed another malignancy. The risk for most chronic health disorders did not differ between survivors and siblings. But survivors appeared to have a moderately increased risk for osteoporosis or osteopenia, short stature, and cataracts.

Survivors and their siblings had similar socioeconomic outcomes, including education, rates of marriage, independent living, and household income.

While these results suggest the prognosis is favorable, Dr Nathan noted that ALL survivors should receive ongoing care from a knowledgeable primary-care practitioner.

“Among kids with standard-risk ALL, we expect most to survive,” Dr Nathan said. “Now we can say with more certainty that they will probably do well in the long-term as well. This information will be very useful for oncologists counselling newly diagnosed patients and their families and will be quite reassuring to parents.”

Leukemia patient

Credit: Bill Branson

Children recently diagnosed with standard-risk acute lymphoblastic leukemia (ALL) are likely to have few long-term complications into adulthood, investigators have reported in The Lancet Oncology.

The team said this is because current therapies are less harsh than their predecessors.

Newer protocols have eliminated radiation and restricted the use of chemotherapeutics that may cause subsequent malignancies and other chronic health conditions.

Previous research had only assessed the very long-term outcomes of children treated with older protocols, leaving physicians to piece together information from this outdated data and anecdotal evidence.

“This is one of the first studies to show that, in addition to their excellent probability of survival, long-term survivors of standard-risk childhood ALL are at low risk for complications of their therapy once they enter adulthood,” said study author Paul Nathan, MD, of The Hospital for Sick Children in Toronto, Canada.

He and his colleagues used longitudinal data from the Childhood Cancer Survivor Study, a North American study of 5-year survivors of childhood cancer diagnosed between 1970 and 1986.

The team analyzed 556 patients from this study who were older than 1 year of age and younger than 10 at the time of diagnosis and who had received treatment consistent with current therapies for standard-risk ALL.

Patients were followed from 5 years following diagnosis to a median of 18 years. The survivor group was compared with a group of their siblings who had not had cancer, as well as the general population.

Twenty-eight patients in the survivor group died. Sixteen of these deaths were from causes other than relapse.

Survivors were at a slightly increased risk of death due to non-relapse causes, when compared to controls. However, no individual cause was increased.

Six survivors developed another malignancy. The risk for most chronic health disorders did not differ between survivors and siblings. But survivors appeared to have a moderately increased risk for osteoporosis or osteopenia, short stature, and cataracts.

Survivors and their siblings had similar socioeconomic outcomes, including education, rates of marriage, independent living, and household income.

While these results suggest the prognosis is favorable, Dr Nathan noted that ALL survivors should receive ongoing care from a knowledgeable primary-care practitioner.

“Among kids with standard-risk ALL, we expect most to survive,” Dr Nathan said. “Now we can say with more certainty that they will probably do well in the long-term as well. This information will be very useful for oncologists counselling newly diagnosed patients and their families and will be quite reassuring to parents.”