ORLANDO – The investigational protease inhibitor simeprevir was associated with high levels of sustained virologic response in patients with both treatment-naive and relapsed hepatitis C viral infections, reported investigators at the annual Digestive Disease Week.

In the QUEST-2 phase III trial, 81.3% of previously untreated patients with hepatitis C (HCV) genotype 1 infections randomized to simeprevir (TMC435) and pegylated interferon-alfa (pegIFN/RBV) had a sustained virologic response following 12 weeks of therapy (SVR12, the primary endpoint), compared with 50% of those assigned to pegIFN/RBV and placebo (P less than .001), reported Dr. Fred Poordad from the University of Texas Health Science Center in San Antonio.

In the phase III PROMISE trial, 79.2% of patients with HCV genotype 1 infections who had a relapse following prior therapy with an interferon-based regimen had an SVR12 when treated with simeprevir, compared with 36.8% of patients treated with pegIFN/RBV and placebo (P less than .001), said Dr. Eric Lawitz, also from the University of Texas in San Antonio.

"Safety and tolerability appear to be comparable to placebo, and patient-reported outcomes support both the efficacy and the safety profiles of simeprevir," Dr. Poordad said.

QUEST-2

Simeprevir is a once-daily oral inhibitor of the HCV NS3/4A protease with demonstrated antiviral activity against HCV genotypes 1, 2, 4, 5, and 6.

In QUEST-2, 391 patients were randomized on a 2:1 basis to receive either simeprevir 150 mg daily plus pegIFN/RBV or placebo plus pegIFN/RBV for 12 weeks, followed by an additional 12 or 36 weeks of pegIFN/RBV depending on response-guided therapy criteria. If patients had HCV RNA less than 25 IU/mL at week 4 and undetectable at week 12, they received an additional 12 weeks of pegIFN/RBV. Patients outside of the response-guided criteria received a total of 36 additional weeks of pegIFN/RBV. In both treatment arms, patients were followed for an additional 24 months, for a total of 72 months.

A total of 235 of the 257 patients assigned to simeprevir (91.4%) met the response-guided criteria by week 24, completed therapy, and were then followed until study end. Of this group, 86% (202 patients) achieved SVR12.

Simeprevir was statistically significantly superior to placebo regardless of IL28B polymorphism genotype or METAVIR (fibrosis and inflammation) scores.

On-treatment failures, defined as a confirmed detectable HCV RNA level at the actual end of treatment, occurred in 7% of patients on simeprevir and 32.1% of controls. Relapses, defined as detectable HCV RNA on one or more follow-up visits following undetectable end-of-treatment levels, occurred in 12.7% and 23.9%, respectively (P values not shown).

Of the simeprevir-treated patients who did not achieve an SVR, 97.6% had emerging mutations in the NS3 protease domain at the time of treatment failure, Dr. Poordad said.

PROMISE

In the PROMISE trial, 393 patients who had experienced a relapse following interferon-based therapy were randomized to response guided therapy as described in the QUEST-2 study.

As noted before, 79.2% of patients assigned to simeprevir/pegIFN/RBV met the primary endpoint of SVR12, compared with 36.8% of patients assigned to placebo/pegIFN/RBV (P less than .001).

In this trial, simeprevir was significantly better than placebo in patients with both HCV genotypes 1a and 1b, and as in QUEST-2 was superior to placebo regardless of IL28B genotype or METAVIR score.

On-treatment failures occurred in 3.1% of simeprevir-treated patients and 27.1% of those on placebo and pegIFN/RBV. The respective relapse rates were 18.5% and 48.4%. As in QUEST-2, the large majority (92.3%) of simeprevir-treated patients who did not have an SVR had emerging mutations in the NS3 protease domain.

Safety

In QUEST-2, patients on simeprevir had more cases of rash, 27% vs. 20%, and photosensitivity, 4% vs. 1%. Anemia occurred in 13.6% and 15.7%, respectively. The incidences of other adverse events were similar between the groups.

In PROMISE, the most common adverse events were fatigue, influenzalike illness, pruritus, and headache. Anemia occurred in 17% of patients on the active drug plus pegIFN/RBV, compared with 20% for those on placebo/pegIFN/RBV. Neutropenia occurred in 18% and 22%, respectively. Rates of pruritus and rash were comparable between simeprevir and placebo.

The Food and Drug Administration has granted priority review status to simeprevir for the treatment of chronic HCV genotype 1.

The studies were funded by Janssen. Dr. Poordad and Dr. Lawitz have received grants and/or research support from the company, and several of their coauthors are employees of Janssen or its parent company Johnson & Johnson.

ORLANDO – The investigational protease inhibitor simeprevir was associated with high levels of sustained virologic response in patients with both treatment-naive and relapsed hepatitis C viral infections, reported investigators at the annual Digestive Disease Week.

In the QUEST-2 phase III trial, 81.3% of previously untreated patients with hepatitis C (HCV) genotype 1 infections randomized to simeprevir (TMC435) and pegylated interferon-alfa (pegIFN/RBV) had a sustained virologic response following 12 weeks of therapy (SVR12, the primary endpoint), compared with 50% of those assigned to pegIFN/RBV and placebo (P less than .001), reported Dr. Fred Poordad from the University of Texas Health Science Center in San Antonio.

In the phase III PROMISE trial, 79.2% of patients with HCV genotype 1 infections who had a relapse following prior therapy with an interferon-based regimen had an SVR12 when treated with simeprevir, compared with 36.8% of patients treated with pegIFN/RBV and placebo (P less than .001), said Dr. Eric Lawitz, also from the University of Texas in San Antonio.

"Safety and tolerability appear to be comparable to placebo, and patient-reported outcomes support both the efficacy and the safety profiles of simeprevir," Dr. Poordad said.

QUEST-2

Simeprevir is a once-daily oral inhibitor of the HCV NS3/4A protease with demonstrated antiviral activity against HCV genotypes 1, 2, 4, 5, and 6.

In QUEST-2, 391 patients were randomized on a 2:1 basis to receive either simeprevir 150 mg daily plus pegIFN/RBV or placebo plus pegIFN/RBV for 12 weeks, followed by an additional 12 or 36 weeks of pegIFN/RBV depending on response-guided therapy criteria. If patients had HCV RNA less than 25 IU/mL at week 4 and undetectable at week 12, they received an additional 12 weeks of pegIFN/RBV. Patients outside of the response-guided criteria received a total of 36 additional weeks of pegIFN/RBV. In both treatment arms, patients were followed for an additional 24 months, for a total of 72 months.

A total of 235 of the 257 patients assigned to simeprevir (91.4%) met the response-guided criteria by week 24, completed therapy, and were then followed until study end. Of this group, 86% (202 patients) achieved SVR12.

Simeprevir was statistically significantly superior to placebo regardless of IL28B polymorphism genotype or METAVIR (fibrosis and inflammation) scores.

On-treatment failures, defined as a confirmed detectable HCV RNA level at the actual end of treatment, occurred in 7% of patients on simeprevir and 32.1% of controls. Relapses, defined as detectable HCV RNA on one or more follow-up visits following undetectable end-of-treatment levels, occurred in 12.7% and 23.9%, respectively (P values not shown).

Of the simeprevir-treated patients who did not achieve an SVR, 97.6% had emerging mutations in the NS3 protease domain at the time of treatment failure, Dr. Poordad said.

PROMISE

In the PROMISE trial, 393 patients who had experienced a relapse following interferon-based therapy were randomized to response guided therapy as described in the QUEST-2 study.

As noted before, 79.2% of patients assigned to simeprevir/pegIFN/RBV met the primary endpoint of SVR12, compared with 36.8% of patients assigned to placebo/pegIFN/RBV (P less than .001).

In this trial, simeprevir was significantly better than placebo in patients with both HCV genotypes 1a and 1b, and as in QUEST-2 was superior to placebo regardless of IL28B genotype or METAVIR score.

On-treatment failures occurred in 3.1% of simeprevir-treated patients and 27.1% of those on placebo and pegIFN/RBV. The respective relapse rates were 18.5% and 48.4%. As in QUEST-2, the large majority (92.3%) of simeprevir-treated patients who did not have an SVR had emerging mutations in the NS3 protease domain.

Safety

In QUEST-2, patients on simeprevir had more cases of rash, 27% vs. 20%, and photosensitivity, 4% vs. 1%. Anemia occurred in 13.6% and 15.7%, respectively. The incidences of other adverse events were similar between the groups.

In PROMISE, the most common adverse events were fatigue, influenzalike illness, pruritus, and headache. Anemia occurred in 17% of patients on the active drug plus pegIFN/RBV, compared with 20% for those on placebo/pegIFN/RBV. Neutropenia occurred in 18% and 22%, respectively. Rates of pruritus and rash were comparable between simeprevir and placebo.

The Food and Drug Administration has granted priority review status to simeprevir for the treatment of chronic HCV genotype 1.

The studies were funded by Janssen. Dr. Poordad and Dr. Lawitz have received grants and/or research support from the company, and several of their coauthors are employees of Janssen or its parent company Johnson & Johnson.

ORLANDO – The investigational protease inhibitor simeprevir was associated with high levels of sustained virologic response in patients with both treatment-naive and relapsed hepatitis C viral infections, reported investigators at the annual Digestive Disease Week.

In the QUEST-2 phase III trial, 81.3% of previously untreated patients with hepatitis C (HCV) genotype 1 infections randomized to simeprevir (TMC435) and pegylated interferon-alfa (pegIFN/RBV) had a sustained virologic response following 12 weeks of therapy (SVR12, the primary endpoint), compared with 50% of those assigned to pegIFN/RBV and placebo (P less than .001), reported Dr. Fred Poordad from the University of Texas Health Science Center in San Antonio.

In the phase III PROMISE trial, 79.2% of patients with HCV genotype 1 infections who had a relapse following prior therapy with an interferon-based regimen had an SVR12 when treated with simeprevir, compared with 36.8% of patients treated with pegIFN/RBV and placebo (P less than .001), said Dr. Eric Lawitz, also from the University of Texas in San Antonio.

"Safety and tolerability appear to be comparable to placebo, and patient-reported outcomes support both the efficacy and the safety profiles of simeprevir," Dr. Poordad said.

QUEST-2

Simeprevir is a once-daily oral inhibitor of the HCV NS3/4A protease with demonstrated antiviral activity against HCV genotypes 1, 2, 4, 5, and 6.

In QUEST-2, 391 patients were randomized on a 2:1 basis to receive either simeprevir 150 mg daily plus pegIFN/RBV or placebo plus pegIFN/RBV for 12 weeks, followed by an additional 12 or 36 weeks of pegIFN/RBV depending on response-guided therapy criteria. If patients had HCV RNA less than 25 IU/mL at week 4 and undetectable at week 12, they received an additional 12 weeks of pegIFN/RBV. Patients outside of the response-guided criteria received a total of 36 additional weeks of pegIFN/RBV. In both treatment arms, patients were followed for an additional 24 months, for a total of 72 months.

A total of 235 of the 257 patients assigned to simeprevir (91.4%) met the response-guided criteria by week 24, completed therapy, and were then followed until study end. Of this group, 86% (202 patients) achieved SVR12.

Simeprevir was statistically significantly superior to placebo regardless of IL28B polymorphism genotype or METAVIR (fibrosis and inflammation) scores.

On-treatment failures, defined as a confirmed detectable HCV RNA level at the actual end of treatment, occurred in 7% of patients on simeprevir and 32.1% of controls. Relapses, defined as detectable HCV RNA on one or more follow-up visits following undetectable end-of-treatment levels, occurred in 12.7% and 23.9%, respectively (P values not shown).

Of the simeprevir-treated patients who did not achieve an SVR, 97.6% had emerging mutations in the NS3 protease domain at the time of treatment failure, Dr. Poordad said.

PROMISE

In the PROMISE trial, 393 patients who had experienced a relapse following interferon-based therapy were randomized to response guided therapy as described in the QUEST-2 study.

As noted before, 79.2% of patients assigned to simeprevir/pegIFN/RBV met the primary endpoint of SVR12, compared with 36.8% of patients assigned to placebo/pegIFN/RBV (P less than .001).

In this trial, simeprevir was significantly better than placebo in patients with both HCV genotypes 1a and 1b, and as in QUEST-2 was superior to placebo regardless of IL28B genotype or METAVIR score.

On-treatment failures occurred in 3.1% of simeprevir-treated patients and 27.1% of those on placebo and pegIFN/RBV. The respective relapse rates were 18.5% and 48.4%. As in QUEST-2, the large majority (92.3%) of simeprevir-treated patients who did not have an SVR had emerging mutations in the NS3 protease domain.

Safety

In QUEST-2, patients on simeprevir had more cases of rash, 27% vs. 20%, and photosensitivity, 4% vs. 1%. Anemia occurred in 13.6% and 15.7%, respectively. The incidences of other adverse events were similar between the groups.

In PROMISE, the most common adverse events were fatigue, influenzalike illness, pruritus, and headache. Anemia occurred in 17% of patients on the active drug plus pegIFN/RBV, compared with 20% for those on placebo/pegIFN/RBV. Neutropenia occurred in 18% and 22%, respectively. Rates of pruritus and rash were comparable between simeprevir and placebo.

The Food and Drug Administration has granted priority review status to simeprevir for the treatment of chronic HCV genotype 1.

The studies were funded by Janssen. Dr. Poordad and Dr. Lawitz have received grants and/or research support from the company, and several of their coauthors are employees of Janssen or its parent company Johnson & Johnson.

Many of your patients will head for international destinations this summer, where they may be exposed to infectious diseases and other health risks they normally do not encounter in the United States.

For the majority of patients, these exposures will be brief; however, several may be extended due to study abroad or parental job relocation. More and more adolescents also are traveling to resource-limited areas doing volunteer work or adventure travel, and many are residing with host families. Children with chronic diseases pose concerns directly related to their underlying conditions, susceptibility, and availability of medical care in the host country. While most international travel plans are made at least 3 months in advance, health precautions such as immunizations and preventive medication often are not considered as travel plans are being finalized. If you are lucky, your patients will have mentioned their plans to you prior to finalizing their trips. You may receive a call at the last minute for assistance in helping to prepare them for a safe and healthy journey.

The U.S. Office of Travel & Tourism reports that slightly more than 60 million Americans traveled outside of the United States in 2012, with 28.5 million of the final destinations being overseas. Children accounted for approximately 2.4 million travelers. While tourism was the most common reason for travel, children were more likely to be visiting friends and relatives (VFR). Studies have revealed significantly increased health risks among VFR travelers, who often stay in private homes and in less-developed areas, compared with vacationers or business travelers who are more likely to be staying in hotels and in urban areas (Pediatrics 2010;125:e1072-80).

Is it really necessary to seek pretravel advice? Some travelers are not convinced. To facilitate this discussion, I thought I would share a recent call.

You are informed via voicemail that a 3-year-old is traveling with his family to Madras, India, for 8 weeks. He is visiting relatives, and the family may visit rural areas. The accommodations are air conditioned and the family is departing in 5 days! They would like to schedule an appointment immediately. What can you do?

Vital information has already been provided. The destination, type of accommodations, activities, duration of stay, and that the patient is a VFR are all important details when making vaccine and other recommendations. First, determine if the child’s routine immunizations are up to date. Next, determine the potential exposures for this patient, and identify vaccine-preventable and nonpreventable diseases. If there is a travel medicine specialist in your area who also sees children, you can refer the patient. If one is not readily available or you prefer to manage the patient, a great resource is the Centers for Disease Control and Prevention Traveler's Health site.

Vaccine preventable diseases include hepatitis A, hepatitis B, Japanese encephalitis, polio, rabies, typhoid, and influenza. Nonvaccine preventable diseases include chikungunya and dengue fevers. Avian influenza, malaria, tuberculosis, and traveler’s diarrhea are also cause for concern.

If you determine the routine immunizations are up to date, remember that measles is still a concern in many countries, and current U.S. recommendations state that all children at least 12 months of age should have two doses prior to leaving the United States. Although routinely administered at 4 years of age, the second dose of MMR can be administered as early as 4 weeks after the first dose. Those aged 6-11 months should have one dose prior to leaving the country. The remaining two doses should be administered at the usual time. Therefore, a total of three doses will be required to complete the series. Since the immunizations are up to date, this patient will also be protected against hepatitis A and B in addition to polio. Hepatitis A is the most common vaccine preventable disease acquired by travelers.

Rabies is prevalent in India, and all animal bites should be taken seriously. Because the patient is in a major urban area, access to both rabies vaccine and immunoglobulin should not be a concern. Japanese encephalitis will be circulating (May-October), but is usually found in rural agricultural areas. Mosquito precautions utilizing DEET (30%) on exposed areas or Permethrine-containing sprays on clothes to repel mosquitoes and ticks should be emphasized if travel to rural areas occurs. Vaccines for rabies and Japanese encephalitis would not be recommended for this patient. If the itinerary were different, they may be considered. Ixiaro, an inactivated Japanese encephalitis (JE) vaccine was approved for use in children as young as 2 months of age in May 2013. Previously, it was approved for use only in those at least 17 years of age in the United States. Both rabies and JE require a minimum of 21 and 28 days, respectively, to complete, and JE should be completed at least 1 week prior to exposure.

Typhoid fever (enteric fever) occurs worldwide, with an estimated 22 million cases annually. In 2012, 343 cases were reported in the United States, most of which were in recent travelers. The risk for typhoid fever is highest for travelers to southern Asia (6-30 times higher) than for all other destinations (Centers for Disease Control and Prevention. CDC Health Information for International Travel 2012. New York: Oxford University Press; 2012). Two types of vaccine are available: an oral, live attenuated vaccine for those at least 6 years of age and an injectable polysaccharide vaccine for those at least 2 years of age. In this case there is only one option, the injectable vaccine. Ideally, it should be administered at least 2 weeks prior to travel. Although this patient will not have optimal benefit of vaccine for at least 2 weeks, he will be there an additional 6 weeks, staying with friends and relatives, and is traveling to a high-risk country. Vaccine administration is recommended, and the parent should be fully informed when maximum benefit will occur. Food and water precautions are essential, especially during the first 2 weeks.

Precautions such as consumption of only boiled or bottled water, avoidance of undercooked or raw meat and seafood, and avoidance of raw fruit and vegetables to minimize acquisition of traveler’s diarrhea should be discussed. Antimicrobials also can be provided.

Options for malaria prophylaxis are limited due to the ensuing departure date and the child’s age. Atovaquone-Proguanil can be prescribed because it can be initiated 1-2 days prior to departure. It is taken daily while in India and for 1 week after return. He is too young for doxycycline. Mefloquine, administered weekly, should begin at least 2 weeks prior to exposure, so it is not an option. There is no role for chloroquine because chloroquine-resistant malaria is present in this country. In contrast to malaria, where mosquitoes usually feed dusk to dawn, chikungunya and dengue fever are transmitted by mosquitoes during the daytime.

No specific prevention for tuberculosis is available. Avoidance of persons with chronic cough or known disease is recommended.

It can be challenging for a busy practitioner to stay abreast of the latest developments in non–routinely administered vaccines, disease outbreaks, or country-specific entry requirements. Many vaccines, such as those against typhoid or rabies, are not routinely available in the patient’s medical home.

Ideally, patients planning international travel should be referred to a travel medicine clinic 1 month prior to travel. Some vaccines take up to 2 weeks to become effective, while others – such as yellow fever – should be administered at least 10 days prior to travel. However, interventions are still available for the last-minute patient, as in this case. Counseling for a variety of issues is provided. It’s not just about the vaccines.

International travel among children and adolescents will continue to rise. It behooves every primary care practitioner to develop a system to determine the summertime plans/needs of their patients. Not all travel medicine clinics provide services to children. It’s a good idea to find out which ones do in your area. You can always locate a clinic through the International Society of Travel Medicine and the Centers for Disease Control and Prevention.

While this call is not the norm, it occurs frequently. In contrast, another call for a 2-month photography trip to Uganda was received the same day. Departure was 6 weeks later!

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at [email protected].

Many of your patients will head for international destinations this summer, where they may be exposed to infectious diseases and other health risks they normally do not encounter in the United States.

For the majority of patients, these exposures will be brief; however, several may be extended due to study abroad or parental job relocation. More and more adolescents also are traveling to resource-limited areas doing volunteer work or adventure travel, and many are residing with host families. Children with chronic diseases pose concerns directly related to their underlying conditions, susceptibility, and availability of medical care in the host country. While most international travel plans are made at least 3 months in advance, health precautions such as immunizations and preventive medication often are not considered as travel plans are being finalized. If you are lucky, your patients will have mentioned their plans to you prior to finalizing their trips. You may receive a call at the last minute for assistance in helping to prepare them for a safe and healthy journey.

The U.S. Office of Travel & Tourism reports that slightly more than 60 million Americans traveled outside of the United States in 2012, with 28.5 million of the final destinations being overseas. Children accounted for approximately 2.4 million travelers. While tourism was the most common reason for travel, children were more likely to be visiting friends and relatives (VFR). Studies have revealed significantly increased health risks among VFR travelers, who often stay in private homes and in less-developed areas, compared with vacationers or business travelers who are more likely to be staying in hotels and in urban areas (Pediatrics 2010;125:e1072-80).

Is it really necessary to seek pretravel advice? Some travelers are not convinced. To facilitate this discussion, I thought I would share a recent call.

You are informed via voicemail that a 3-year-old is traveling with his family to Madras, India, for 8 weeks. He is visiting relatives, and the family may visit rural areas. The accommodations are air conditioned and the family is departing in 5 days! They would like to schedule an appointment immediately. What can you do?

Vital information has already been provided. The destination, type of accommodations, activities, duration of stay, and that the patient is a VFR are all important details when making vaccine and other recommendations. First, determine if the child’s routine immunizations are up to date. Next, determine the potential exposures for this patient, and identify vaccine-preventable and nonpreventable diseases. If there is a travel medicine specialist in your area who also sees children, you can refer the patient. If one is not readily available or you prefer to manage the patient, a great resource is the Centers for Disease Control and Prevention Traveler's Health site.

Vaccine preventable diseases include hepatitis A, hepatitis B, Japanese encephalitis, polio, rabies, typhoid, and influenza. Nonvaccine preventable diseases include chikungunya and dengue fevers. Avian influenza, malaria, tuberculosis, and traveler’s diarrhea are also cause for concern.

If you determine the routine immunizations are up to date, remember that measles is still a concern in many countries, and current U.S. recommendations state that all children at least 12 months of age should have two doses prior to leaving the United States. Although routinely administered at 4 years of age, the second dose of MMR can be administered as early as 4 weeks after the first dose. Those aged 6-11 months should have one dose prior to leaving the country. The remaining two doses should be administered at the usual time. Therefore, a total of three doses will be required to complete the series. Since the immunizations are up to date, this patient will also be protected against hepatitis A and B in addition to polio. Hepatitis A is the most common vaccine preventable disease acquired by travelers.

Rabies is prevalent in India, and all animal bites should be taken seriously. Because the patient is in a major urban area, access to both rabies vaccine and immunoglobulin should not be a concern. Japanese encephalitis will be circulating (May-October), but is usually found in rural agricultural areas. Mosquito precautions utilizing DEET (30%) on exposed areas or Permethrine-containing sprays on clothes to repel mosquitoes and ticks should be emphasized if travel to rural areas occurs. Vaccines for rabies and Japanese encephalitis would not be recommended for this patient. If the itinerary were different, they may be considered. Ixiaro, an inactivated Japanese encephalitis (JE) vaccine was approved for use in children as young as 2 months of age in May 2013. Previously, it was approved for use only in those at least 17 years of age in the United States. Both rabies and JE require a minimum of 21 and 28 days, respectively, to complete, and JE should be completed at least 1 week prior to exposure.

Typhoid fever (enteric fever) occurs worldwide, with an estimated 22 million cases annually. In 2012, 343 cases were reported in the United States, most of which were in recent travelers. The risk for typhoid fever is highest for travelers to southern Asia (6-30 times higher) than for all other destinations (Centers for Disease Control and Prevention. CDC Health Information for International Travel 2012. New York: Oxford University Press; 2012). Two types of vaccine are available: an oral, live attenuated vaccine for those at least 6 years of age and an injectable polysaccharide vaccine for those at least 2 years of age. In this case there is only one option, the injectable vaccine. Ideally, it should be administered at least 2 weeks prior to travel. Although this patient will not have optimal benefit of vaccine for at least 2 weeks, he will be there an additional 6 weeks, staying with friends and relatives, and is traveling to a high-risk country. Vaccine administration is recommended, and the parent should be fully informed when maximum benefit will occur. Food and water precautions are essential, especially during the first 2 weeks.

Precautions such as consumption of only boiled or bottled water, avoidance of undercooked or raw meat and seafood, and avoidance of raw fruit and vegetables to minimize acquisition of traveler’s diarrhea should be discussed. Antimicrobials also can be provided.

Options for malaria prophylaxis are limited due to the ensuing departure date and the child’s age. Atovaquone-Proguanil can be prescribed because it can be initiated 1-2 days prior to departure. It is taken daily while in India and for 1 week after return. He is too young for doxycycline. Mefloquine, administered weekly, should begin at least 2 weeks prior to exposure, so it is not an option. There is no role for chloroquine because chloroquine-resistant malaria is present in this country. In contrast to malaria, where mosquitoes usually feed dusk to dawn, chikungunya and dengue fever are transmitted by mosquitoes during the daytime.

No specific prevention for tuberculosis is available. Avoidance of persons with chronic cough or known disease is recommended.

It can be challenging for a busy practitioner to stay abreast of the latest developments in non–routinely administered vaccines, disease outbreaks, or country-specific entry requirements. Many vaccines, such as those against typhoid or rabies, are not routinely available in the patient’s medical home.

Ideally, patients planning international travel should be referred to a travel medicine clinic 1 month prior to travel. Some vaccines take up to 2 weeks to become effective, while others – such as yellow fever – should be administered at least 10 days prior to travel. However, interventions are still available for the last-minute patient, as in this case. Counseling for a variety of issues is provided. It’s not just about the vaccines.

International travel among children and adolescents will continue to rise. It behooves every primary care practitioner to develop a system to determine the summertime plans/needs of their patients. Not all travel medicine clinics provide services to children. It’s a good idea to find out which ones do in your area. You can always locate a clinic through the International Society of Travel Medicine and the Centers for Disease Control and Prevention.

While this call is not the norm, it occurs frequently. In contrast, another call for a 2-month photography trip to Uganda was received the same day. Departure was 6 weeks later!

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at [email protected].

Many of your patients will head for international destinations this summer, where they may be exposed to infectious diseases and other health risks they normally do not encounter in the United States.

For the majority of patients, these exposures will be brief; however, several may be extended due to study abroad or parental job relocation. More and more adolescents also are traveling to resource-limited areas doing volunteer work or adventure travel, and many are residing with host families. Children with chronic diseases pose concerns directly related to their underlying conditions, susceptibility, and availability of medical care in the host country. While most international travel plans are made at least 3 months in advance, health precautions such as immunizations and preventive medication often are not considered as travel plans are being finalized. If you are lucky, your patients will have mentioned their plans to you prior to finalizing their trips. You may receive a call at the last minute for assistance in helping to prepare them for a safe and healthy journey.

The U.S. Office of Travel & Tourism reports that slightly more than 60 million Americans traveled outside of the United States in 2012, with 28.5 million of the final destinations being overseas. Children accounted for approximately 2.4 million travelers. While tourism was the most common reason for travel, children were more likely to be visiting friends and relatives (VFR). Studies have revealed significantly increased health risks among VFR travelers, who often stay in private homes and in less-developed areas, compared with vacationers or business travelers who are more likely to be staying in hotels and in urban areas (Pediatrics 2010;125:e1072-80).

Is it really necessary to seek pretravel advice? Some travelers are not convinced. To facilitate this discussion, I thought I would share a recent call.

You are informed via voicemail that a 3-year-old is traveling with his family to Madras, India, for 8 weeks. He is visiting relatives, and the family may visit rural areas. The accommodations are air conditioned and the family is departing in 5 days! They would like to schedule an appointment immediately. What can you do?

Vital information has already been provided. The destination, type of accommodations, activities, duration of stay, and that the patient is a VFR are all important details when making vaccine and other recommendations. First, determine if the child’s routine immunizations are up to date. Next, determine the potential exposures for this patient, and identify vaccine-preventable and nonpreventable diseases. If there is a travel medicine specialist in your area who also sees children, you can refer the patient. If one is not readily available or you prefer to manage the patient, a great resource is the Centers for Disease Control and Prevention Traveler's Health site.

Vaccine preventable diseases include hepatitis A, hepatitis B, Japanese encephalitis, polio, rabies, typhoid, and influenza. Nonvaccine preventable diseases include chikungunya and dengue fevers. Avian influenza, malaria, tuberculosis, and traveler’s diarrhea are also cause for concern.

If you determine the routine immunizations are up to date, remember that measles is still a concern in many countries, and current U.S. recommendations state that all children at least 12 months of age should have two doses prior to leaving the United States. Although routinely administered at 4 years of age, the second dose of MMR can be administered as early as 4 weeks after the first dose. Those aged 6-11 months should have one dose prior to leaving the country. The remaining two doses should be administered at the usual time. Therefore, a total of three doses will be required to complete the series. Since the immunizations are up to date, this patient will also be protected against hepatitis A and B in addition to polio. Hepatitis A is the most common vaccine preventable disease acquired by travelers.

Rabies is prevalent in India, and all animal bites should be taken seriously. Because the patient is in a major urban area, access to both rabies vaccine and immunoglobulin should not be a concern. Japanese encephalitis will be circulating (May-October), but is usually found in rural agricultural areas. Mosquito precautions utilizing DEET (30%) on exposed areas or Permethrine-containing sprays on clothes to repel mosquitoes and ticks should be emphasized if travel to rural areas occurs. Vaccines for rabies and Japanese encephalitis would not be recommended for this patient. If the itinerary were different, they may be considered. Ixiaro, an inactivated Japanese encephalitis (JE) vaccine was approved for use in children as young as 2 months of age in May 2013. Previously, it was approved for use only in those at least 17 years of age in the United States. Both rabies and JE require a minimum of 21 and 28 days, respectively, to complete, and JE should be completed at least 1 week prior to exposure.

Typhoid fever (enteric fever) occurs worldwide, with an estimated 22 million cases annually. In 2012, 343 cases were reported in the United States, most of which were in recent travelers. The risk for typhoid fever is highest for travelers to southern Asia (6-30 times higher) than for all other destinations (Centers for Disease Control and Prevention. CDC Health Information for International Travel 2012. New York: Oxford University Press; 2012). Two types of vaccine are available: an oral, live attenuated vaccine for those at least 6 years of age and an injectable polysaccharide vaccine for those at least 2 years of age. In this case there is only one option, the injectable vaccine. Ideally, it should be administered at least 2 weeks prior to travel. Although this patient will not have optimal benefit of vaccine for at least 2 weeks, he will be there an additional 6 weeks, staying with friends and relatives, and is traveling to a high-risk country. Vaccine administration is recommended, and the parent should be fully informed when maximum benefit will occur. Food and water precautions are essential, especially during the first 2 weeks.

Precautions such as consumption of only boiled or bottled water, avoidance of undercooked or raw meat and seafood, and avoidance of raw fruit and vegetables to minimize acquisition of traveler’s diarrhea should be discussed. Antimicrobials also can be provided.

Options for malaria prophylaxis are limited due to the ensuing departure date and the child’s age. Atovaquone-Proguanil can be prescribed because it can be initiated 1-2 days prior to departure. It is taken daily while in India and for 1 week after return. He is too young for doxycycline. Mefloquine, administered weekly, should begin at least 2 weeks prior to exposure, so it is not an option. There is no role for chloroquine because chloroquine-resistant malaria is present in this country. In contrast to malaria, where mosquitoes usually feed dusk to dawn, chikungunya and dengue fever are transmitted by mosquitoes during the daytime.

No specific prevention for tuberculosis is available. Avoidance of persons with chronic cough or known disease is recommended.

It can be challenging for a busy practitioner to stay abreast of the latest developments in non–routinely administered vaccines, disease outbreaks, or country-specific entry requirements. Many vaccines, such as those against typhoid or rabies, are not routinely available in the patient’s medical home.

Ideally, patients planning international travel should be referred to a travel medicine clinic 1 month prior to travel. Some vaccines take up to 2 weeks to become effective, while others – such as yellow fever – should be administered at least 10 days prior to travel. However, interventions are still available for the last-minute patient, as in this case. Counseling for a variety of issues is provided. It’s not just about the vaccines.

International travel among children and adolescents will continue to rise. It behooves every primary care practitioner to develop a system to determine the summertime plans/needs of their patients. Not all travel medicine clinics provide services to children. It’s a good idea to find out which ones do in your area. You can always locate a clinic through the International Society of Travel Medicine and the Centers for Disease Control and Prevention.

While this call is not the norm, it occurs frequently. In contrast, another call for a 2-month photography trip to Uganda was received the same day. Departure was 6 weeks later!

Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Write to Dr. Word at [email protected].

The risk for atrial fibrillation increases with age and the presence of structural heart disease. AF exerts an enormous financial burden on the U.S. health care system. The overall prevalence of AF is 1%, and 70% of people with AF are 65 years of age or older. Inclusive of inpatient and outpatient expenditures, costs for the first episode of atrial fibrillation are estimated to be $15,000.

Perhaps we are all too familiar with the staggering resources consumed by patients who, despite adequate rate control, remain symptomatic. In these cases, an ounce of prevention could literally have been thousands of dollars of cure.

So, can we prevent A-fib?

Statins have been proposed as a way to do this. So, what’s the most recent evidence telling us about its efficacy?

Researchers in France conducted an updated systematic review of the literature to determine the benefit of statins for the prevention of AF (Curr. Opin. Cardiol. 2013;28:7-18). Studies were selected for inclusion if they were randomized, controlled clinical trials including a direct comparison between a statin and control condition or placebo.

Thirty-two studies were included, which enrolled a total of 71,005 patients. Statin use was significantly associated with a decreased risk of AF (odds ratio, 0.69; 95% CI: 0.57-0.83). The benefit of statin therapy was significant for the prevention of postoperative AF (OR, 0.37; 95% CI: 0.28-0.51) and secondary prevention of AF (OR, 0.57; 95% CI: 0.36-0.91). No clear benefit of statins for new-onset AF was identified, and no difference was observed between intensive and standard therapy.

The mechanism of action is hypothesized to be exerted through the anti-inflammatory and antioxidant effects of statins.

Some of these patients may already be on statins. But for those who are not and could tolerate them, the use of statins decreased the odds of postoperative and secondary AF by 40%-60%. This could result in enormous potential cost savings to the U.S. health care system.

The evidence is strong, so we need to ask ourselves, why are we not doing this already?

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

The risk for atrial fibrillation increases with age and the presence of structural heart disease. AF exerts an enormous financial burden on the U.S. health care system. The overall prevalence of AF is 1%, and 70% of people with AF are 65 years of age or older. Inclusive of inpatient and outpatient expenditures, costs for the first episode of atrial fibrillation are estimated to be $15,000.

Perhaps we are all too familiar with the staggering resources consumed by patients who, despite adequate rate control, remain symptomatic. In these cases, an ounce of prevention could literally have been thousands of dollars of cure.

So, can we prevent A-fib?

Statins have been proposed as a way to do this. So, what’s the most recent evidence telling us about its efficacy?

Researchers in France conducted an updated systematic review of the literature to determine the benefit of statins for the prevention of AF (Curr. Opin. Cardiol. 2013;28:7-18). Studies were selected for inclusion if they were randomized, controlled clinical trials including a direct comparison between a statin and control condition or placebo.

Thirty-two studies were included, which enrolled a total of 71,005 patients. Statin use was significantly associated with a decreased risk of AF (odds ratio, 0.69; 95% CI: 0.57-0.83). The benefit of statin therapy was significant for the prevention of postoperative AF (OR, 0.37; 95% CI: 0.28-0.51) and secondary prevention of AF (OR, 0.57; 95% CI: 0.36-0.91). No clear benefit of statins for new-onset AF was identified, and no difference was observed between intensive and standard therapy.

The mechanism of action is hypothesized to be exerted through the anti-inflammatory and antioxidant effects of statins.

Some of these patients may already be on statins. But for those who are not and could tolerate them, the use of statins decreased the odds of postoperative and secondary AF by 40%-60%. This could result in enormous potential cost savings to the U.S. health care system.

The evidence is strong, so we need to ask ourselves, why are we not doing this already?

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

The risk for atrial fibrillation increases with age and the presence of structural heart disease. AF exerts an enormous financial burden on the U.S. health care system. The overall prevalence of AF is 1%, and 70% of people with AF are 65 years of age or older. Inclusive of inpatient and outpatient expenditures, costs for the first episode of atrial fibrillation are estimated to be $15,000.

Perhaps we are all too familiar with the staggering resources consumed by patients who, despite adequate rate control, remain symptomatic. In these cases, an ounce of prevention could literally have been thousands of dollars of cure.

So, can we prevent A-fib?

Statins have been proposed as a way to do this. So, what’s the most recent evidence telling us about its efficacy?

Researchers in France conducted an updated systematic review of the literature to determine the benefit of statins for the prevention of AF (Curr. Opin. Cardiol. 2013;28:7-18). Studies were selected for inclusion if they were randomized, controlled clinical trials including a direct comparison between a statin and control condition or placebo.

Thirty-two studies were included, which enrolled a total of 71,005 patients. Statin use was significantly associated with a decreased risk of AF (odds ratio, 0.69; 95% CI: 0.57-0.83). The benefit of statin therapy was significant for the prevention of postoperative AF (OR, 0.37; 95% CI: 0.28-0.51) and secondary prevention of AF (OR, 0.57; 95% CI: 0.36-0.91). No clear benefit of statins for new-onset AF was identified, and no difference was observed between intensive and standard therapy.

The mechanism of action is hypothesized to be exerted through the anti-inflammatory and antioxidant effects of statins.

Some of these patients may already be on statins. But for those who are not and could tolerate them, the use of statins decreased the odds of postoperative and secondary AF by 40%-60%. This could result in enormous potential cost savings to the U.S. health care system.

The evidence is strong, so we need to ask ourselves, why are we not doing this already?

Dr. Ebbert is professor of medicine and a primary care clinician at the Mayo Clinic in Rochester, Minn. He reported having no relevant financial conflicts. The opinions expressed are those of the author.

The FDA recently widened the approved use of nanoparticle albumin bound (nab) paclitaxel (nab-paclitaxel) to include first-line treatment for non–small-cell lung cancer (NSCLC), in combination with carboplatin. This approval was based on results of a global, phase 3 randomized trial conducted by Socinski et al that compared the use of nab-paclitaxel and solventbased paclitaxel injection in combination with carboplatin as first-line treatment of advanced NSCLC.1 Taxanes are the most widely used chemotherapeutic agents in solid tumor oncology. Paclitaxel and docetaxel are effective in the treatment of NSCLC and are frequently used for adjuvant therapy after resection, in combination with radiation for locally advanced disease and for treatment of patients with advanced disease. They are usually used in combination with platinum agents or as single-agent therapy in the relapsed refractory setting. Paclitaxel and docetaxel require synthetic solvents for intravenous administration, which can cause life-threatening allergic reactions and significant toxicity. Nab-paclitaxel is a novel, solvent-free formulation of paclitaxel, which can be administered without the need for steroid and antihistamine premedication. Furthermore, nab-paclitaxel delivers high concentrations of the drug’s active ingredient into the cancer cell with a reduced incidence of side effects compared with the solvent-based formulation. As summarized in the Community Translations article on page 166, the administration of nab-paclitaxel as firstline therapy in combination with carboplatin was efficacious and resulted in a significantly improved overall response rate (ORR), compared with paclitaxel (33% vs 25%, respectively; response rate ratio [RRR], 1.313; 95% CI, 1.082-1.593; P .005), and it achieved the study’s primary end point. Of note, ORR was significantly greater with nab-paclitaxel in patients with squamous cell histology (41% vs 24%; RRR, 1.680; P .001), with no difference between treatments being observed in patients with nonsquamous histology (ORR, 26% vs 25%) or adenocarcinoma (ORR, 26% vs 27%). There was no difference in PFS or survival between the 2 arms.

The FDA recently widened the approved use of nanoparticle albumin bound (nab) paclitaxel (nab-paclitaxel) to include first-line treatment for non–small-cell lung cancer (NSCLC), in combination with carboplatin. This approval was based on results of a global, phase 3 randomized trial conducted by Socinski et al that compared the use of nab-paclitaxel and solventbased paclitaxel injection in combination with carboplatin as first-line treatment of advanced NSCLC.1 Taxanes are the most widely used chemotherapeutic agents in solid tumor oncology. Paclitaxel and docetaxel are effective in the treatment of NSCLC and are frequently used for adjuvant therapy after resection, in combination with radiation for locally advanced disease and for treatment of patients with advanced disease. They are usually used in combination with platinum agents or as single-agent therapy in the relapsed refractory setting. Paclitaxel and docetaxel require synthetic solvents for intravenous administration, which can cause life-threatening allergic reactions and significant toxicity. Nab-paclitaxel is a novel, solvent-free formulation of paclitaxel, which can be administered without the need for steroid and antihistamine premedication. Furthermore, nab-paclitaxel delivers high concentrations of the drug’s active ingredient into the cancer cell with a reduced incidence of side effects compared with the solvent-based formulation. As summarized in the Community Translations article on page 166, the administration of nab-paclitaxel as firstline therapy in combination with carboplatin was efficacious and resulted in a significantly improved overall response rate (ORR), compared with paclitaxel (33% vs 25%, respectively; response rate ratio [RRR], 1.313; 95% CI, 1.082-1.593; P .005), and it achieved the study’s primary end point. Of note, ORR was significantly greater with nab-paclitaxel in patients with squamous cell histology (41% vs 24%; RRR, 1.680; P .001), with no difference between treatments being observed in patients with nonsquamous histology (ORR, 26% vs 25%) or adenocarcinoma (ORR, 26% vs 27%). There was no difference in PFS or survival between the 2 arms.

The FDA recently widened the approved use of nanoparticle albumin bound (nab) paclitaxel (nab-paclitaxel) to include first-line treatment for non–small-cell lung cancer (NSCLC), in combination with carboplatin. This approval was based on results of a global, phase 3 randomized trial conducted by Socinski et al that compared the use of nab-paclitaxel and solventbased paclitaxel injection in combination with carboplatin as first-line treatment of advanced NSCLC.1 Taxanes are the most widely used chemotherapeutic agents in solid tumor oncology. Paclitaxel and docetaxel are effective in the treatment of NSCLC and are frequently used for adjuvant therapy after resection, in combination with radiation for locally advanced disease and for treatment of patients with advanced disease. They are usually used in combination with platinum agents or as single-agent therapy in the relapsed refractory setting. Paclitaxel and docetaxel require synthetic solvents for intravenous administration, which can cause life-threatening allergic reactions and significant toxicity. Nab-paclitaxel is a novel, solvent-free formulation of paclitaxel, which can be administered without the need for steroid and antihistamine premedication. Furthermore, nab-paclitaxel delivers high concentrations of the drug’s active ingredient into the cancer cell with a reduced incidence of side effects compared with the solvent-based formulation. As summarized in the Community Translations article on page 166, the administration of nab-paclitaxel as firstline therapy in combination with carboplatin was efficacious and resulted in a significantly improved overall response rate (ORR), compared with paclitaxel (33% vs 25%, respectively; response rate ratio [RRR], 1.313; 95% CI, 1.082-1.593; P .005), and it achieved the study’s primary end point. Of note, ORR was significantly greater with nab-paclitaxel in patients with squamous cell histology (41% vs 24%; RRR, 1.680; P .001), with no difference between treatments being observed in patients with nonsquamous histology (ORR, 26% vs 25%) or adenocarcinoma (ORR, 26% vs 27%). There was no difference in PFS or survival between the 2 arms.

The Food and Drug Administration has approved lenalidomide for the treatment of patients whose mantle cell lymphoma has relapsed or progressed after two prior therapies, one of which included bortezomib.

Lenalidomide, a thalidomide analogue, is already approved for use in combination with dexamethasone for multiple myeloma in patients who have received at least one prior therapy. Lenalidomide also is approved for transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities.

"There remains a tremendous unmet need for [therapies for] patients with previously treated mantle cell lymphoma," said Dr. Andre Goy, chairman and director, and chief of the division of lymphoma at the John Theurer Cancer Center at Hackensack (N.J.) University Medical Center, in a statement issued by lenalidomide maker Celgene. "The approval of lenalidomide delivers a new option and the first oral therapy in this area of lymphoma."

Mantle cell lymphoma is fairly rare, accounting for about 6% of the 66,360 new cases of non-Hodgkin’s lymphoma diagnosed in the United States each year, according to the Leukemia and Lymphoma Society.

The Food and Drug Administration (FDA) said it based its approval on a single-arm, multicenter study with 134 patients who had relapsed after or were refractory to bortezomib or a bortezomib-containing regimen. In the 133 patients who were evaluable for efficacy, the overall lenalidomide response rate was 26%. Nine patients (7%) had a complete response or unconfirmed complete response, and 25 (19%) had a partial response. In the 34 responders, the median duration of response was 16.6 months.

Due to adverse events, a little more than half of the patients had to interrupt therapy; 38% had a dose reduction and 19% discontinued therapy. The most common reactions included neutropenia, thrombocytopenia, fatigue, anemia, diarrhea, nausea, cough, pyrexia, rash, dyspnea, pruritus, constipation, peripheral edema, and leukopenia, according to the FDA.

In May 2012, the agency also determined that patients taking the drug for newly diagnosed multiple myeloma are at increased risk for secondary cancers.

Lenalidomide was approved at a recommended dose and schedule of 25 mg orally once daily on days 1-21 of repeated 28-day cycles. Celgene also received approval for a new 20-mg strength of lenalidomide.

[email protected]

On Twitter @aliciaault

The Food and Drug Administration has approved lenalidomide for the treatment of patients whose mantle cell lymphoma has relapsed or progressed after two prior therapies, one of which included bortezomib.

Lenalidomide, a thalidomide analogue, is already approved for use in combination with dexamethasone for multiple myeloma in patients who have received at least one prior therapy. Lenalidomide also is approved for transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities.

"There remains a tremendous unmet need for [therapies for] patients with previously treated mantle cell lymphoma," said Dr. Andre Goy, chairman and director, and chief of the division of lymphoma at the John Theurer Cancer Center at Hackensack (N.J.) University Medical Center, in a statement issued by lenalidomide maker Celgene. "The approval of lenalidomide delivers a new option and the first oral therapy in this area of lymphoma."

Mantle cell lymphoma is fairly rare, accounting for about 6% of the 66,360 new cases of non-Hodgkin’s lymphoma diagnosed in the United States each year, according to the Leukemia and Lymphoma Society.

The Food and Drug Administration (FDA) said it based its approval on a single-arm, multicenter study with 134 patients who had relapsed after or were refractory to bortezomib or a bortezomib-containing regimen. In the 133 patients who were evaluable for efficacy, the overall lenalidomide response rate was 26%. Nine patients (7%) had a complete response or unconfirmed complete response, and 25 (19%) had a partial response. In the 34 responders, the median duration of response was 16.6 months.

Due to adverse events, a little more than half of the patients had to interrupt therapy; 38% had a dose reduction and 19% discontinued therapy. The most common reactions included neutropenia, thrombocytopenia, fatigue, anemia, diarrhea, nausea, cough, pyrexia, rash, dyspnea, pruritus, constipation, peripheral edema, and leukopenia, according to the FDA.

In May 2012, the agency also determined that patients taking the drug for newly diagnosed multiple myeloma are at increased risk for secondary cancers.

Lenalidomide was approved at a recommended dose and schedule of 25 mg orally once daily on days 1-21 of repeated 28-day cycles. Celgene also received approval for a new 20-mg strength of lenalidomide.

[email protected]

On Twitter @aliciaault

The Food and Drug Administration has approved lenalidomide for the treatment of patients whose mantle cell lymphoma has relapsed or progressed after two prior therapies, one of which included bortezomib.

Lenalidomide, a thalidomide analogue, is already approved for use in combination with dexamethasone for multiple myeloma in patients who have received at least one prior therapy. Lenalidomide also is approved for transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities.

"There remains a tremendous unmet need for [therapies for] patients with previously treated mantle cell lymphoma," said Dr. Andre Goy, chairman and director, and chief of the division of lymphoma at the John Theurer Cancer Center at Hackensack (N.J.) University Medical Center, in a statement issued by lenalidomide maker Celgene. "The approval of lenalidomide delivers a new option and the first oral therapy in this area of lymphoma."

Mantle cell lymphoma is fairly rare, accounting for about 6% of the 66,360 new cases of non-Hodgkin’s lymphoma diagnosed in the United States each year, according to the Leukemia and Lymphoma Society.

The Food and Drug Administration (FDA) said it based its approval on a single-arm, multicenter study with 134 patients who had relapsed after or were refractory to bortezomib or a bortezomib-containing regimen. In the 133 patients who were evaluable for efficacy, the overall lenalidomide response rate was 26%. Nine patients (7%) had a complete response or unconfirmed complete response, and 25 (19%) had a partial response. In the 34 responders, the median duration of response was 16.6 months.

Due to adverse events, a little more than half of the patients had to interrupt therapy; 38% had a dose reduction and 19% discontinued therapy. The most common reactions included neutropenia, thrombocytopenia, fatigue, anemia, diarrhea, nausea, cough, pyrexia, rash, dyspnea, pruritus, constipation, peripheral edema, and leukopenia, according to the FDA.

In May 2012, the agency also determined that patients taking the drug for newly diagnosed multiple myeloma are at increased risk for secondary cancers.

Lenalidomide was approved at a recommended dose and schedule of 25 mg orally once daily on days 1-21 of repeated 28-day cycles. Celgene also received approval for a new 20-mg strength of lenalidomide.

[email protected]

On Twitter @aliciaault

Many hospitalists are anxious about looming changes to the American Board of Medicine’s (ABIM) Maintenance of Certification (MOC) process, but hospital medicine leaders say the effect will be positive.

In January, ABIM and the American Board of Medical Specialties (ABMS) will begin reporting on whether hospitalists and other physicians are meeting MOC requirements. To do so, physicians need to complete 20 ABIM MOC points by December 2015, and every two years after that. Physicians also need to earn 100 ABIM MOC points by December 2018, and every five years after that.

Previously, physicians had to amass a total of 100 points every 10 years between secure exams. The new rules are aimed at keeping “pace with the changes in the science of medicine and assessment,” ABIM says on its website.

“I think the anxiety is coming out of it being misunderstood,” says Jeff Wiese, MD, MHM, professor of medicine and associate dean for graduate medical education at Tulane University Health Sciences Center in New Orleans. “It’s not that big of a deal when you put it in the context of what you do for CME now.”

Dr. Wiese emphasizes the secure exam will still be taken every 10 years, but increasing the frequency of learning via practice-improvement modules (PIMs) and other vehicles should serve to improve hospitalists’ efficiency and care delivery.

Ethan Cumbler, MD, FACP, of the University of Colorado at Denver, an annual faculty member for the ABIM’s MOC pre-course at SHM’s annual meetings, says that codifying additional learning is a good thing for the specialty. “If the point of this is to actually improve how we’re practicing as doctors, then we do want to be practicing this in an ongoing fashion,” Dr. Cumbler says.

Visit our website for more information on CME.

Many hospitalists are anxious about looming changes to the American Board of Medicine’s (ABIM) Maintenance of Certification (MOC) process, but hospital medicine leaders say the effect will be positive.

In January, ABIM and the American Board of Medical Specialties (ABMS) will begin reporting on whether hospitalists and other physicians are meeting MOC requirements. To do so, physicians need to complete 20 ABIM MOC points by December 2015, and every two years after that. Physicians also need to earn 100 ABIM MOC points by December 2018, and every five years after that.

Previously, physicians had to amass a total of 100 points every 10 years between secure exams. The new rules are aimed at keeping “pace with the changes in the science of medicine and assessment,” ABIM says on its website.

“I think the anxiety is coming out of it being misunderstood,” says Jeff Wiese, MD, MHM, professor of medicine and associate dean for graduate medical education at Tulane University Health Sciences Center in New Orleans. “It’s not that big of a deal when you put it in the context of what you do for CME now.”

Dr. Wiese emphasizes the secure exam will still be taken every 10 years, but increasing the frequency of learning via practice-improvement modules (PIMs) and other vehicles should serve to improve hospitalists’ efficiency and care delivery.

Ethan Cumbler, MD, FACP, of the University of Colorado at Denver, an annual faculty member for the ABIM’s MOC pre-course at SHM’s annual meetings, says that codifying additional learning is a good thing for the specialty. “If the point of this is to actually improve how we’re practicing as doctors, then we do want to be practicing this in an ongoing fashion,” Dr. Cumbler says.

Visit our website for more information on CME.

Many hospitalists are anxious about looming changes to the American Board of Medicine’s (ABIM) Maintenance of Certification (MOC) process, but hospital medicine leaders say the effect will be positive.

In January, ABIM and the American Board of Medical Specialties (ABMS) will begin reporting on whether hospitalists and other physicians are meeting MOC requirements. To do so, physicians need to complete 20 ABIM MOC points by December 2015, and every two years after that. Physicians also need to earn 100 ABIM MOC points by December 2018, and every five years after that.

Previously, physicians had to amass a total of 100 points every 10 years between secure exams. The new rules are aimed at keeping “pace with the changes in the science of medicine and assessment,” ABIM says on its website.

“I think the anxiety is coming out of it being misunderstood,” says Jeff Wiese, MD, MHM, professor of medicine and associate dean for graduate medical education at Tulane University Health Sciences Center in New Orleans. “It’s not that big of a deal when you put it in the context of what you do for CME now.”

Dr. Wiese emphasizes the secure exam will still be taken every 10 years, but increasing the frequency of learning via practice-improvement modules (PIMs) and other vehicles should serve to improve hospitalists’ efficiency and care delivery.

Ethan Cumbler, MD, FACP, of the University of Colorado at Denver, an annual faculty member for the ABIM’s MOC pre-course at SHM’s annual meetings, says that codifying additional learning is a good thing for the specialty. “If the point of this is to actually improve how we’re practicing as doctors, then we do want to be practicing this in an ongoing fashion,” Dr. Cumbler says.

Visit our website for more information on CME.

After a monstrous tornado roared through Moore, Okla., chewing up and spitting out everything in its path, hospitalist Joe R. Womble, MD, who was off that day, wondered what had become of his colleagues, his patients, and his hospital, Moore Medical Center.

The initial news was encouraging: Everyone who had been inside the hospital—roughly 200 to 300 people, including a few dozen patients—had survived. He thought that boded well for the hospital as well.

“When I was getting information back from people who were there and I was hearing that everyone was fine, all the patients and staff, and no one got injured, I was thinking that either the hospital was missed by the storm, or that it must not have really damaged it very significantly,” says Dr. Womble. “And then they started showing aerial shots [on TV] and I was just shocked. My jaw was just dropped. The main entrance that I would go in every day was literally stacked three or four cars deep with … about 30 cars.” Likewise, the storm ripped through patient rooms on the second floor, obliterating some and reducing others to their steel innards.

About a week after the storm, word came back that Moore Medical Center will have to be demolished.

“Nobody knows what will happen next, but a lot of us speculate that they will not rebuild an inpatient facility,” says Dr. Womble. “It’s the only hospital in that city of Moore, and it’s just me and my partner to take care of virtually everyone that comes in with any kind of medical problem.

“And so I definitely feel a tie to the community. … Now that it’s gone, it’s just hard to put into words,” he says. “I would just say devastating, I guess.”

After a monstrous tornado roared through Moore, Okla., chewing up and spitting out everything in its path, hospitalist Joe R. Womble, MD, who was off that day, wondered what had become of his colleagues, his patients, and his hospital, Moore Medical Center.

The initial news was encouraging: Everyone who had been inside the hospital—roughly 200 to 300 people, including a few dozen patients—had survived. He thought that boded well for the hospital as well.

“When I was getting information back from people who were there and I was hearing that everyone was fine, all the patients and staff, and no one got injured, I was thinking that either the hospital was missed by the storm, or that it must not have really damaged it very significantly,” says Dr. Womble. “And then they started showing aerial shots [on TV] and I was just shocked. My jaw was just dropped. The main entrance that I would go in every day was literally stacked three or four cars deep with … about 30 cars.” Likewise, the storm ripped through patient rooms on the second floor, obliterating some and reducing others to their steel innards.

About a week after the storm, word came back that Moore Medical Center will have to be demolished.

“Nobody knows what will happen next, but a lot of us speculate that they will not rebuild an inpatient facility,” says Dr. Womble. “It’s the only hospital in that city of Moore, and it’s just me and my partner to take care of virtually everyone that comes in with any kind of medical problem.

“And so I definitely feel a tie to the community. … Now that it’s gone, it’s just hard to put into words,” he says. “I would just say devastating, I guess.”

After a monstrous tornado roared through Moore, Okla., chewing up and spitting out everything in its path, hospitalist Joe R. Womble, MD, who was off that day, wondered what had become of his colleagues, his patients, and his hospital, Moore Medical Center.

The initial news was encouraging: Everyone who had been inside the hospital—roughly 200 to 300 people, including a few dozen patients—had survived. He thought that boded well for the hospital as well.

“When I was getting information back from people who were there and I was hearing that everyone was fine, all the patients and staff, and no one got injured, I was thinking that either the hospital was missed by the storm, or that it must not have really damaged it very significantly,” says Dr. Womble. “And then they started showing aerial shots [on TV] and I was just shocked. My jaw was just dropped. The main entrance that I would go in every day was literally stacked three or four cars deep with … about 30 cars.” Likewise, the storm ripped through patient rooms on the second floor, obliterating some and reducing others to their steel innards.

About a week after the storm, word came back that Moore Medical Center will have to be demolished.

“Nobody knows what will happen next, but a lot of us speculate that they will not rebuild an inpatient facility,” says Dr. Womble. “It’s the only hospital in that city of Moore, and it’s just me and my partner to take care of virtually everyone that comes in with any kind of medical problem.

“And so I definitely feel a tie to the community. … Now that it’s gone, it’s just hard to put into words,” he says. “I would just say devastating, I guess.”

Maybe it’s because spring is here and the flowers are blooming. Or it may be because my wife and I are marrying off our daughter this summer. (Why, thank you.) Whatever the reason, I thought I would share some of the ways my married patients met each other. When I ask couples how they got together, they are usually happy to tell me. Even after many years, most of them have no trouble remembering the particular circumstances of their introduction. They smile, and tell me a tale they have probably told many times. (Remember that this is a selected group – these couples are still together!)

Some of the stories are conventional – a mutual friend or family member fixed them up, or they met in high school or college. Nowadays, more and more are technological, though sometimes with a twist. ("I had so many bad experiences on EBliss4Ever.com that I was ready to give up. But then I decided to give it one more try – and got Stanley!") Sometimes, however, people share tales that sound too cute to be true, ones that even Hollywood script committees – lovers of the "cute-meet" – would reject as too schmaltzy and improbable to work in a romantic comedy. And yet, out here in real life, they somehow did.

"I met Lars in a bar," says Bridget. "My friend Susie and I were having a beer, and I decided to stand up and move to another table. Lars is a large person, and he was walking by just when I got up. I turned to my left- – and hit him right in the chest with my glass. The beer splashed all over him and made a real mess. It took a long time to clean up."

"Oh come on. Did that really happen?"

"Absolutely! We were married a year ago."

Then there is Shane Walsh, who tells me not about himself but about his sister. "We’re a close-knit Irish family," he says. "Five boys and a girl. We were very protective of our sister and made sure that the guys she went out with were the right sort. Then she met the man who’s now her husband, and we all agree that he’s terrific. His name is also Walsh."

"In fact, that’s how they met," Shane says. "They were both at a party, when a guy across the room called out, ‘Hey, Walshie!’ "

"Both of them turned around at the same time and saw each other. The rest is history."

The luck of the Irish, I guess.

My last tale concerns an older pair, Gregory and Kate, married 39 years. They remember their first meeting very fondly.

"We both belonged to an apple-picking club," recalls Kate. "That fall weekend the whole group traveled by bus up to Maine. It was raining and miserable. When we got to the farm, the lady handing out the collecting baskets said, ‘You’re not from around here, are you?’ She meant that anybody local would have too much sense to pick apples in the driving rain."

"We were standing near each other under the same tree," said Gregory. "It was just like ..."

"Wait a minute," I interrupt, "you don’t mean ..."

"Yes indeed," says Greg, with a twinkle. "She handed me an apple." Kate laughs in agreement.

There you have it – life imitating Scripture. Although there’s nothing in the Good Book about Adam and Eve hiding under the Tree of Knowledge to keep from getting wet.

Here’s to happy endings, however they start out.

Dr. Rockoff practices dermatology in Brookline, Mass. To respond to this column, e-mail him at our editorial offices at [email protected]. 

Maybe it’s because spring is here and the flowers are blooming. Or it may be because my wife and I are marrying off our daughter this summer. (Why, thank you.) Whatever the reason, I thought I would share some of the ways my married patients met each other. When I ask couples how they got together, they are usually happy to tell me. Even after many years, most of them have no trouble remembering the particular circumstances of their introduction. They smile, and tell me a tale they have probably told many times. (Remember that this is a selected group – these couples are still together!)

Some of the stories are conventional – a mutual friend or family member fixed them up, or they met in high school or college. Nowadays, more and more are technological, though sometimes with a twist. ("I had so many bad experiences on EBliss4Ever.com that I was ready to give up. But then I decided to give it one more try – and got Stanley!") Sometimes, however, people share tales that sound too cute to be true, ones that even Hollywood script committees – lovers of the "cute-meet" – would reject as too schmaltzy and improbable to work in a romantic comedy. And yet, out here in real life, they somehow did.

"I met Lars in a bar," says Bridget. "My friend Susie and I were having a beer, and I decided to stand up and move to another table. Lars is a large person, and he was walking by just when I got up. I turned to my left- – and hit him right in the chest with my glass. The beer splashed all over him and made a real mess. It took a long time to clean up."

"Oh come on. Did that really happen?"

"Absolutely! We were married a year ago."

Then there is Shane Walsh, who tells me not about himself but about his sister. "We’re a close-knit Irish family," he says. "Five boys and a girl. We were very protective of our sister and made sure that the guys she went out with were the right sort. Then she met the man who’s now her husband, and we all agree that he’s terrific. His name is also Walsh."

"In fact, that’s how they met," Shane says. "They were both at a party, when a guy across the room called out, ‘Hey, Walshie!’ "

"Both of them turned around at the same time and saw each other. The rest is history."

The luck of the Irish, I guess.

My last tale concerns an older pair, Gregory and Kate, married 39 years. They remember their first meeting very fondly.

"We both belonged to an apple-picking club," recalls Kate. "That fall weekend the whole group traveled by bus up to Maine. It was raining and miserable. When we got to the farm, the lady handing out the collecting baskets said, ‘You’re not from around here, are you?’ She meant that anybody local would have too much sense to pick apples in the driving rain."

"We were standing near each other under the same tree," said Gregory. "It was just like ..."

"Wait a minute," I interrupt, "you don’t mean ..."

"Yes indeed," says Greg, with a twinkle. "She handed me an apple." Kate laughs in agreement.

There you have it – life imitating Scripture. Although there’s nothing in the Good Book about Adam and Eve hiding under the Tree of Knowledge to keep from getting wet.

Here’s to happy endings, however they start out.

Dr. Rockoff practices dermatology in Brookline, Mass. To respond to this column, e-mail him at our editorial offices at [email protected]. 

Maybe it’s because spring is here and the flowers are blooming. Or it may be because my wife and I are marrying off our daughter this summer. (Why, thank you.) Whatever the reason, I thought I would share some of the ways my married patients met each other. When I ask couples how they got together, they are usually happy to tell me. Even after many years, most of them have no trouble remembering the particular circumstances of their introduction. They smile, and tell me a tale they have probably told many times. (Remember that this is a selected group – these couples are still together!)

Some of the stories are conventional – a mutual friend or family member fixed them up, or they met in high school or college. Nowadays, more and more are technological, though sometimes with a twist. ("I had so many bad experiences on EBliss4Ever.com that I was ready to give up. But then I decided to give it one more try – and got Stanley!") Sometimes, however, people share tales that sound too cute to be true, ones that even Hollywood script committees – lovers of the "cute-meet" – would reject as too schmaltzy and improbable to work in a romantic comedy. And yet, out here in real life, they somehow did.

"I met Lars in a bar," says Bridget. "My friend Susie and I were having a beer, and I decided to stand up and move to another table. Lars is a large person, and he was walking by just when I got up. I turned to my left- – and hit him right in the chest with my glass. The beer splashed all over him and made a real mess. It took a long time to clean up."

"Oh come on. Did that really happen?"

"Absolutely! We were married a year ago."

Then there is Shane Walsh, who tells me not about himself but about his sister. "We’re a close-knit Irish family," he says. "Five boys and a girl. We were very protective of our sister and made sure that the guys she went out with were the right sort. Then she met the man who’s now her husband, and we all agree that he’s terrific. His name is also Walsh."

"In fact, that’s how they met," Shane says. "They were both at a party, when a guy across the room called out, ‘Hey, Walshie!’ "

"Both of them turned around at the same time and saw each other. The rest is history."

The luck of the Irish, I guess.

My last tale concerns an older pair, Gregory and Kate, married 39 years. They remember their first meeting very fondly.

"We both belonged to an apple-picking club," recalls Kate. "That fall weekend the whole group traveled by bus up to Maine. It was raining and miserable. When we got to the farm, the lady handing out the collecting baskets said, ‘You’re not from around here, are you?’ She meant that anybody local would have too much sense to pick apples in the driving rain."

"We were standing near each other under the same tree," said Gregory. "It was just like ..."

"Wait a minute," I interrupt, "you don’t mean ..."

"Yes indeed," says Greg, with a twinkle. "She handed me an apple." Kate laughs in agreement.

There you have it – life imitating Scripture. Although there’s nothing in the Good Book about Adam and Eve hiding under the Tree of Knowledge to keep from getting wet.

Here’s to happy endings, however they start out.

Dr. Rockoff practices dermatology in Brookline, Mass. To respond to this column, e-mail him at our editorial offices at [email protected]. 

CHICAGO – Donepezil proved no better than placebo at improving overall cognitive function among 198 patients who had undergone partial or whole brain irradiation for brain tumors, investigators reported at the annual meeting of the American Society of Clinical Oncology.

A randomized, double-blind, multicenter phase III trial found no significant differences between donepezil (Aricept) and placebo in either cognitive composite scores after 12 or 24 weeks of therapy – the study’s primary end point – or in domains of attention/concentration, motor speed/dexterity, learning, or memory, said Stephen R. Rapp, Ph.D., professor of psychiatry and behavioral medicine at Wake Forest Baptist Medical Center in Winston-Salem, N.C.

Among patients with more cognitive problems at baseline, however, there was a significant benefit in verbal memory for patients on donepezil, compared with controls (P = .005), and a trend toward preservation of motor speed and dexterity, Dr. Rapp said.

"We have to continue looking for effective treatments for cognitive symptoms in this population. It has a big impact on patients," he said.

Previous studies indicated that more than half of patients who receive partial or whole brain irradiation for tumors will have cognitive deficits, and that about 12% will develop some form of dementia. Cognitive problems have a major impact on patient quality of life, and anything clinicians can do to preserve or improve patient mental faculties is important, Dr. Rapp said.

The study was designed to test whether donepezil, an acetylcholinesterase inhibitor indicated for treatment of mild-to-moderate cognitive decline from Alzheimer’s disease, could have a similar neuroprotective effect following whole brain irradiation.

Investigators enrolled 198 patients 6 months after they received at least 30 Gy of brain irradiation. Following a baseline evaluation, patients were randomized to receive either 5-10 mg daily of oral donepezil or placebo for 24 weeks, with an interim assessment performed at 12 weeks.

The study looked at the effect of the drug on cognitive functioning and on measures of fatigue, mood, and quality of life.

The patients were assessed at baseline for cognitive function, and at 12 and 24 weeks with the Hopkins Verbal Learning Test-Revised, Rey-Osterreith Complex Figure-modified (a measure of visual spatial ability, memory, and planning ability), Trail Making Test, Digit Span, Controlled Oral Word Association, and Grooved Pegboard (a measure of dexterity and motor control).

Both study arms showed significant improvement in cognitive composite scores over baseline (P less than .01 for both), but the degree of improvement did not differ significantly between arms. Similarly, there were no significant differences between the treatment arms in any of the test domains, Dr. Rapp said.

Among patients with greater baseline cognitive deficits, as measured by a score of less than 51 on the FACT Brain subscale, there was also significant improvement over baseline but no between-group difference, he reported.

Donepezil was significantly better than placebo control in this subgroup for improvement in performance on the recognition portion of the Hopkins Verbal Learning Test, which measures verbal memory, and donepezil danced on the edge of significance at preserving motor speed and dexterity as measured by the Grooved Pegboard-Dominant Hand test but never crossed the line (P = .06), he said.

Adverse events were similar between the groups, and the patients assigned to donepezil appeared to tolerate it well, Dr. Rapp said.

Dr. Robin Grant of the Center for Clinical Brain Sciences at the University of Edinburgh, the invited discussant, said that the study was very well designed. He noted, however, "that there was no specified level of cognitive deficit at the time of [study] entry, and I think if you look at moderate to severely affected patients then you’re more likely to be able to show a change there," he said.

He added that it would be interesting to see results from the Grooved Pegboard test performed with the contralateral rather than dominant hand.

The study was funded by the National Institutes of Health and by Eisai, maker of donepezil. Dr. Rapp disclosed receiving research funding from the company. Dr. Grant reported having no financial disclosures.

CHICAGO – Donepezil proved no better than placebo at improving overall cognitive function among 198 patients who had undergone partial or whole brain irradiation for brain tumors, investigators reported at the annual meeting of the American Society of Clinical Oncology.

A randomized, double-blind, multicenter phase III trial found no significant differences between donepezil (Aricept) and placebo in either cognitive composite scores after 12 or 24 weeks of therapy – the study’s primary end point – or in domains of attention/concentration, motor speed/dexterity, learning, or memory, said Stephen R. Rapp, Ph.D., professor of psychiatry and behavioral medicine at Wake Forest Baptist Medical Center in Winston-Salem, N.C.

Among patients with more cognitive problems at baseline, however, there was a significant benefit in verbal memory for patients on donepezil, compared with controls (P = .005), and a trend toward preservation of motor speed and dexterity, Dr. Rapp said.

"We have to continue looking for effective treatments for cognitive symptoms in this population. It has a big impact on patients," he said.

Previous studies indicated that more than half of patients who receive partial or whole brain irradiation for tumors will have cognitive deficits, and that about 12% will develop some form of dementia. Cognitive problems have a major impact on patient quality of life, and anything clinicians can do to preserve or improve patient mental faculties is important, Dr. Rapp said.

The study was designed to test whether donepezil, an acetylcholinesterase inhibitor indicated for treatment of mild-to-moderate cognitive decline from Alzheimer’s disease, could have a similar neuroprotective effect following whole brain irradiation.

Investigators enrolled 198 patients 6 months after they received at least 30 Gy of brain irradiation. Following a baseline evaluation, patients were randomized to receive either 5-10 mg daily of oral donepezil or placebo for 24 weeks, with an interim assessment performed at 12 weeks.

The study looked at the effect of the drug on cognitive functioning and on measures of fatigue, mood, and quality of life.

The patients were assessed at baseline for cognitive function, and at 12 and 24 weeks with the Hopkins Verbal Learning Test-Revised, Rey-Osterreith Complex Figure-modified (a measure of visual spatial ability, memory, and planning ability), Trail Making Test, Digit Span, Controlled Oral Word Association, and Grooved Pegboard (a measure of dexterity and motor control).

Both study arms showed significant improvement in cognitive composite scores over baseline (P less than .01 for both), but the degree of improvement did not differ significantly between arms. Similarly, there were no significant differences between the treatment arms in any of the test domains, Dr. Rapp said.

Among patients with greater baseline cognitive deficits, as measured by a score of less than 51 on the FACT Brain subscale, there was also significant improvement over baseline but no between-group difference, he reported.

Donepezil was significantly better than placebo control in this subgroup for improvement in performance on the recognition portion of the Hopkins Verbal Learning Test, which measures verbal memory, and donepezil danced on the edge of significance at preserving motor speed and dexterity as measured by the Grooved Pegboard-Dominant Hand test but never crossed the line (P = .06), he said.

Adverse events were similar between the groups, and the patients assigned to donepezil appeared to tolerate it well, Dr. Rapp said.

Dr. Robin Grant of the Center for Clinical Brain Sciences at the University of Edinburgh, the invited discussant, said that the study was very well designed. He noted, however, "that there was no specified level of cognitive deficit at the time of [study] entry, and I think if you look at moderate to severely affected patients then you’re more likely to be able to show a change there," he said.

He added that it would be interesting to see results from the Grooved Pegboard test performed with the contralateral rather than dominant hand.

The study was funded by the National Institutes of Health and by Eisai, maker of donepezil. Dr. Rapp disclosed receiving research funding from the company. Dr. Grant reported having no financial disclosures.

CHICAGO – Donepezil proved no better than placebo at improving overall cognitive function among 198 patients who had undergone partial or whole brain irradiation for brain tumors, investigators reported at the annual meeting of the American Society of Clinical Oncology.

A randomized, double-blind, multicenter phase III trial found no significant differences between donepezil (Aricept) and placebo in either cognitive composite scores after 12 or 24 weeks of therapy – the study’s primary end point – or in domains of attention/concentration, motor speed/dexterity, learning, or memory, said Stephen R. Rapp, Ph.D., professor of psychiatry and behavioral medicine at Wake Forest Baptist Medical Center in Winston-Salem, N.C.

Among patients with more cognitive problems at baseline, however, there was a significant benefit in verbal memory for patients on donepezil, compared with controls (P = .005), and a trend toward preservation of motor speed and dexterity, Dr. Rapp said.

"We have to continue looking for effective treatments for cognitive symptoms in this population. It has a big impact on patients," he said.

Previous studies indicated that more than half of patients who receive partial or whole brain irradiation for tumors will have cognitive deficits, and that about 12% will develop some form of dementia. Cognitive problems have a major impact on patient quality of life, and anything clinicians can do to preserve or improve patient mental faculties is important, Dr. Rapp said.

The study was designed to test whether donepezil, an acetylcholinesterase inhibitor indicated for treatment of mild-to-moderate cognitive decline from Alzheimer’s disease, could have a similar neuroprotective effect following whole brain irradiation.

Investigators enrolled 198 patients 6 months after they received at least 30 Gy of brain irradiation. Following a baseline evaluation, patients were randomized to receive either 5-10 mg daily of oral donepezil or placebo for 24 weeks, with an interim assessment performed at 12 weeks.

The study looked at the effect of the drug on cognitive functioning and on measures of fatigue, mood, and quality of life.

The patients were assessed at baseline for cognitive function, and at 12 and 24 weeks with the Hopkins Verbal Learning Test-Revised, Rey-Osterreith Complex Figure-modified (a measure of visual spatial ability, memory, and planning ability), Trail Making Test, Digit Span, Controlled Oral Word Association, and Grooved Pegboard (a measure of dexterity and motor control).

Both study arms showed significant improvement in cognitive composite scores over baseline (P less than .01 for both), but the degree of improvement did not differ significantly between arms. Similarly, there were no significant differences between the treatment arms in any of the test domains, Dr. Rapp said.

Among patients with greater baseline cognitive deficits, as measured by a score of less than 51 on the FACT Brain subscale, there was also significant improvement over baseline but no between-group difference, he reported.

Donepezil was significantly better than placebo control in this subgroup for improvement in performance on the recognition portion of the Hopkins Verbal Learning Test, which measures verbal memory, and donepezil danced on the edge of significance at preserving motor speed and dexterity as measured by the Grooved Pegboard-Dominant Hand test but never crossed the line (P = .06), he said.

Adverse events were similar between the groups, and the patients assigned to donepezil appeared to tolerate it well, Dr. Rapp said.

Dr. Robin Grant of the Center for Clinical Brain Sciences at the University of Edinburgh, the invited discussant, said that the study was very well designed. He noted, however, "that there was no specified level of cognitive deficit at the time of [study] entry, and I think if you look at moderate to severely affected patients then you’re more likely to be able to show a change there," he said.

He added that it would be interesting to see results from the Grooved Pegboard test performed with the contralateral rather than dominant hand.

The study was funded by the National Institutes of Health and by Eisai, maker of donepezil. Dr. Rapp disclosed receiving research funding from the company. Dr. Grant reported having no financial disclosures.