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I’m hearing a lot of concern about the impending changes in the Health Insurance Portability and Accountability Act (HIPAA) – which is understandable, since the Department of Health and Human Services has presented them as "the most sweeping ... since [the Act] was first implemented."

But after a careful perusal of the new rules – all 150 three-column pages of them – I can say with a modest degree of confidence that for most physicians, compliance will not be as challenging as some (such as those trying to sell you compliance-related materials) have warned.

However, you can’t simply ignore the new regulations; definitions will be more complex, security breaches more liberally defined, and potential penalties will be stiffer. Herewith the salient points:

• Business associates. The criteria for identifying "business associates" (BAs) remain the same: nonemployees, performing "functions or activities" on behalf of the "covered entity" (your practice), that involve "creating, receiving, maintaining, or transmitting" personal health information (PHI).

Typical BAs include answering and billing services, independent transcriptionists, hardware and software companies, and any other vendors involved in creating or maintaining your medical records. Practice management consultants, attorneys, companies that store or microfilm medical records, and record-shredding services are BAs if they must have direct access to PHI to do their jobs.

Mail carriers, package-delivery people, cleaning services, copier repairmen, bank employees, and the like are not considered BAs, even though they might conceivably come in contact with PHI on occasion. You are required to use "reasonable diligence" in limiting the PHI that these folks may encounter, but you do not need to enter into written BA agreements with them.

Independent contractors who work within your practice – aestheticians and physical therapists, for example – are not considered BAs either, and do not need to sign a BA agreement; just train them, as you do your employees. (I’ll have more on HIPAA and OSHA training in a future column.)

What is new is the additional onus placed on physicians for confidentiality breaches committed by their BAs. It’s not enough to simply have a BA contract. You are expected to use "reasonable diligence" in monitoring the work of your BAs. BAs and their subcontractors are directly responsible for their own actions, but the primary responsibility is ours. Let’s say that a contractor you hire to shred old medical records throws them into a trash bin instead; under the new rules, you must assume the worst-case scenario. Previously, you would only have to notify affected patients (and the government) if there was a "significant risk of financial or reputational harm," but now, any incident involving patient records is assumed to be a breach, and must be reported. Failure to do so could subject your practice, as well as the contractor, to significant fines – as high as $1 million in egregious cases.

• New patient rights. Patients will now be able to restrict the PHI shared with third-party insurers and health plans if they pay for the services themselves. They also have the right to request copies of their electronic health records, and you can bill the actual costs of responding to such a request. If you have EHR, now might be a good time to work out a system for doing this, because the response time has been decreased from 90 to 30 days – even less in some states.

• Marketing limitations. The new rule prohibits third-party-funded marketing to patients for products and services without their prior written authorization. You do not need prior authorization to market your own products and services, even when the communication is funded by a third party, but if there is any such funding, you will need to disclose it.

• Notice of privacy practices (NPP). You will need to revise your NPP to explain your relationships with BAs, and their status under the new rules. You will need to explain the breach notification process, too, as well as the new patient rights mentioned above. You must post your revised NPP in your office, and make copies available there, but you need not mail a copy to every patient.

• Get on it. The rules specify Sept. 23 as the effective date for the new regulations, although you have a year beyond that to revise your existing BA agreements. Extensions are possible, even likely.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J.

I’m hearing a lot of concern about the impending changes in the Health Insurance Portability and Accountability Act (HIPAA) – which is understandable, since the Department of Health and Human Services has presented them as "the most sweeping ... since [the Act] was first implemented."

But after a careful perusal of the new rules – all 150 three-column pages of them – I can say with a modest degree of confidence that for most physicians, compliance will not be as challenging as some (such as those trying to sell you compliance-related materials) have warned.

However, you can’t simply ignore the new regulations; definitions will be more complex, security breaches more liberally defined, and potential penalties will be stiffer. Herewith the salient points:

• Business associates. The criteria for identifying "business associates" (BAs) remain the same: nonemployees, performing "functions or activities" on behalf of the "covered entity" (your practice), that involve "creating, receiving, maintaining, or transmitting" personal health information (PHI).

Typical BAs include answering and billing services, independent transcriptionists, hardware and software companies, and any other vendors involved in creating or maintaining your medical records. Practice management consultants, attorneys, companies that store or microfilm medical records, and record-shredding services are BAs if they must have direct access to PHI to do their jobs.

Mail carriers, package-delivery people, cleaning services, copier repairmen, bank employees, and the like are not considered BAs, even though they might conceivably come in contact with PHI on occasion. You are required to use "reasonable diligence" in limiting the PHI that these folks may encounter, but you do not need to enter into written BA agreements with them.

Independent contractors who work within your practice – aestheticians and physical therapists, for example – are not considered BAs either, and do not need to sign a BA agreement; just train them, as you do your employees. (I’ll have more on HIPAA and OSHA training in a future column.)

What is new is the additional onus placed on physicians for confidentiality breaches committed by their BAs. It’s not enough to simply have a BA contract. You are expected to use "reasonable diligence" in monitoring the work of your BAs. BAs and their subcontractors are directly responsible for their own actions, but the primary responsibility is ours. Let’s say that a contractor you hire to shred old medical records throws them into a trash bin instead; under the new rules, you must assume the worst-case scenario. Previously, you would only have to notify affected patients (and the government) if there was a "significant risk of financial or reputational harm," but now, any incident involving patient records is assumed to be a breach, and must be reported. Failure to do so could subject your practice, as well as the contractor, to significant fines – as high as $1 million in egregious cases.

• New patient rights. Patients will now be able to restrict the PHI shared with third-party insurers and health plans if they pay for the services themselves. They also have the right to request copies of their electronic health records, and you can bill the actual costs of responding to such a request. If you have EHR, now might be a good time to work out a system for doing this, because the response time has been decreased from 90 to 30 days – even less in some states.

• Marketing limitations. The new rule prohibits third-party-funded marketing to patients for products and services without their prior written authorization. You do not need prior authorization to market your own products and services, even when the communication is funded by a third party, but if there is any such funding, you will need to disclose it.

• Notice of privacy practices (NPP). You will need to revise your NPP to explain your relationships with BAs, and their status under the new rules. You will need to explain the breach notification process, too, as well as the new patient rights mentioned above. You must post your revised NPP in your office, and make copies available there, but you need not mail a copy to every patient.

• Get on it. The rules specify Sept. 23 as the effective date for the new regulations, although you have a year beyond that to revise your existing BA agreements. Extensions are possible, even likely.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J.

I’m hearing a lot of concern about the impending changes in the Health Insurance Portability and Accountability Act (HIPAA) – which is understandable, since the Department of Health and Human Services has presented them as "the most sweeping ... since [the Act] was first implemented."

But after a careful perusal of the new rules – all 150 three-column pages of them – I can say with a modest degree of confidence that for most physicians, compliance will not be as challenging as some (such as those trying to sell you compliance-related materials) have warned.

However, you can’t simply ignore the new regulations; definitions will be more complex, security breaches more liberally defined, and potential penalties will be stiffer. Herewith the salient points:

• Business associates. The criteria for identifying "business associates" (BAs) remain the same: nonemployees, performing "functions or activities" on behalf of the "covered entity" (your practice), that involve "creating, receiving, maintaining, or transmitting" personal health information (PHI).

Typical BAs include answering and billing services, independent transcriptionists, hardware and software companies, and any other vendors involved in creating or maintaining your medical records. Practice management consultants, attorneys, companies that store or microfilm medical records, and record-shredding services are BAs if they must have direct access to PHI to do their jobs.

Mail carriers, package-delivery people, cleaning services, copier repairmen, bank employees, and the like are not considered BAs, even though they might conceivably come in contact with PHI on occasion. You are required to use "reasonable diligence" in limiting the PHI that these folks may encounter, but you do not need to enter into written BA agreements with them.

Independent contractors who work within your practice – aestheticians and physical therapists, for example – are not considered BAs either, and do not need to sign a BA agreement; just train them, as you do your employees. (I’ll have more on HIPAA and OSHA training in a future column.)

What is new is the additional onus placed on physicians for confidentiality breaches committed by their BAs. It’s not enough to simply have a BA contract. You are expected to use "reasonable diligence" in monitoring the work of your BAs. BAs and their subcontractors are directly responsible for their own actions, but the primary responsibility is ours. Let’s say that a contractor you hire to shred old medical records throws them into a trash bin instead; under the new rules, you must assume the worst-case scenario. Previously, you would only have to notify affected patients (and the government) if there was a "significant risk of financial or reputational harm," but now, any incident involving patient records is assumed to be a breach, and must be reported. Failure to do so could subject your practice, as well as the contractor, to significant fines – as high as $1 million in egregious cases.

• New patient rights. Patients will now be able to restrict the PHI shared with third-party insurers and health plans if they pay for the services themselves. They also have the right to request copies of their electronic health records, and you can bill the actual costs of responding to such a request. If you have EHR, now might be a good time to work out a system for doing this, because the response time has been decreased from 90 to 30 days – even less in some states.

• Marketing limitations. The new rule prohibits third-party-funded marketing to patients for products and services without their prior written authorization. You do not need prior authorization to market your own products and services, even when the communication is funded by a third party, but if there is any such funding, you will need to disclose it.

• Notice of privacy practices (NPP). You will need to revise your NPP to explain your relationships with BAs, and their status under the new rules. You will need to explain the breach notification process, too, as well as the new patient rights mentioned above. You must post your revised NPP in your office, and make copies available there, but you need not mail a copy to every patient.

• Get on it. The rules specify Sept. 23 as the effective date for the new regulations, although you have a year beyond that to revise your existing BA agreements. Extensions are possible, even likely.

Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J.

Children and teenagers take longer to recover from a concussion if they’ve had one before, especially within the past year, Boston Children’s Hospital emergency department physicians found in a study of 280 of their concussed patients published June 10 in Pediatrics.

The median duration of symptoms, assessed by the serial Rivermead Post-Concussion Symptoms Questionnaire (RPSQ) over a period of 3 months, climbed from 12 days in patients who hadn’t been concussed before to 24 days in those who had. The median symptom duration was 28 days in patients with multiple previous concussions, and 35 days in those who’d been concussed within the previous year, "nearly three times the median duration [for] those who had no previous concussions," according to Dr. Matthew A. Eisenberg and his associates at the hospital (Pediatrics 2013 [doi:10.1542/peds.2013-0432]).

"Similarly, patients with two or more previous concussions had more than double the median symptom duration [of] patients with zero or one previous concussion," they found.

On multivariate analysis, previous concussion, maintaining consciousness, being 13 years or older, and an initial RPSQ of 18 or higher all predicted prolonged recovery. Among all comers, 77% had symptoms at 1 week, 32% at 4 weeks, and 15% at 3 months. The mean age in the trial was 14.3 years (range, 11-22 years).

The findings were statistically significant and have "direct implications on the management of athletes and other at-risk individuals who sustain concussions, supporting the concept that sufficient time to recover from a concussion may improve long-term outcomes," the investigators said.

"However, we did not find an association between physician-advised cognitive or physical rest and duration of symptoms, which may reflect the limitations of our observational study," they added. "A randomized [controlled] trial will likely be necessary to address the utility of this intervention."

Sixty-six percent of the subjects were enrolled the day they were injured; 24.7% were enrolled 1 day later, 7.2% 2 days later, and 1.7% 3 days later. The majority (63.8%) had been injured playing hockey, soccer, football, basketball or some other sport.

The investigators defined concussion broadly to include either altered mental status following blunt head trauma or, within 4 hours of it, any of the following symptoms that were not present before the injury: headache, nausea, vomiting, dizziness/balance problems, fatigue, drowsiness, blurred vision, memory difficulty, or trouble concentrating.

The most common symptoms in the study were headache (85.1%), fatigue (64.7%), and dizziness (63.0%); 4.3% of subjects had altered gait or balance, and 2.4% had altered mental status. There were no abnormalities in the 20.8% of kids who got neuroimaging.

On discharge, 65.9% were prescribed a period of cognitive rest and 92.4% were told to take time off from sports; 63.8% were also told to follow up with their primary care doctor, 45.5% with a sports concussion clinic, and 6.2% with a specialist.

In contrast to prior studies, loss of consciousness seemed to protect against a prolonged recovery (HR, 0.648; P = .02). Maybe the 22% of kids who got knocked out were more likely to follow their doctors’ advice to rest, "thus speeding recovery from their injury. We cannot, however, eliminate the possibility that there is a biological basis to this finding," the team noted.

Subjects who were 13 years or older might have taken longer to recover (HR, 1.404; P = .04) because games "between older children involve more contact and higher-force impacts," although neurobiologic differences between older and younger kids might have played a role, as well, the investigators said.

"Female patients" – about 43% of the study total – "had more severe symptoms at presentation in our study (mean initial RPSQ of 21.3 vs. 17.0 in male patients, P = .02). ... Whether this finding is indicative of the fact that female patients have more severe symptoms from concussion in general, as suggested in several previous studies, or is due to referral bias in which female individuals preferentially present to the ED when symptoms are more severe ... cannot be ascertained from our data," they noted.

Female gender fell out on multivariate analysis as a predictor of prolonged recovery (HR, 1.294; P= 0.11).

The investigators said they had no relevant financial disclosures.

Children and teenagers take longer to recover from a concussion if they’ve had one before, especially within the past year, Boston Children’s Hospital emergency department physicians found in a study of 280 of their concussed patients published June 10 in Pediatrics.

The median duration of symptoms, assessed by the serial Rivermead Post-Concussion Symptoms Questionnaire (RPSQ) over a period of 3 months, climbed from 12 days in patients who hadn’t been concussed before to 24 days in those who had. The median symptom duration was 28 days in patients with multiple previous concussions, and 35 days in those who’d been concussed within the previous year, "nearly three times the median duration [for] those who had no previous concussions," according to Dr. Matthew A. Eisenberg and his associates at the hospital (Pediatrics 2013 [doi:10.1542/peds.2013-0432]).

"Similarly, patients with two or more previous concussions had more than double the median symptom duration [of] patients with zero or one previous concussion," they found.

On multivariate analysis, previous concussion, maintaining consciousness, being 13 years or older, and an initial RPSQ of 18 or higher all predicted prolonged recovery. Among all comers, 77% had symptoms at 1 week, 32% at 4 weeks, and 15% at 3 months. The mean age in the trial was 14.3 years (range, 11-22 years).

The findings were statistically significant and have "direct implications on the management of athletes and other at-risk individuals who sustain concussions, supporting the concept that sufficient time to recover from a concussion may improve long-term outcomes," the investigators said.

"However, we did not find an association between physician-advised cognitive or physical rest and duration of symptoms, which may reflect the limitations of our observational study," they added. "A randomized [controlled] trial will likely be necessary to address the utility of this intervention."

Sixty-six percent of the subjects were enrolled the day they were injured; 24.7% were enrolled 1 day later, 7.2% 2 days later, and 1.7% 3 days later. The majority (63.8%) had been injured playing hockey, soccer, football, basketball or some other sport.

The investigators defined concussion broadly to include either altered mental status following blunt head trauma or, within 4 hours of it, any of the following symptoms that were not present before the injury: headache, nausea, vomiting, dizziness/balance problems, fatigue, drowsiness, blurred vision, memory difficulty, or trouble concentrating.

The most common symptoms in the study were headache (85.1%), fatigue (64.7%), and dizziness (63.0%); 4.3% of subjects had altered gait or balance, and 2.4% had altered mental status. There were no abnormalities in the 20.8% of kids who got neuroimaging.

On discharge, 65.9% were prescribed a period of cognitive rest and 92.4% were told to take time off from sports; 63.8% were also told to follow up with their primary care doctor, 45.5% with a sports concussion clinic, and 6.2% with a specialist.

In contrast to prior studies, loss of consciousness seemed to protect against a prolonged recovery (HR, 0.648; P = .02). Maybe the 22% of kids who got knocked out were more likely to follow their doctors’ advice to rest, "thus speeding recovery from their injury. We cannot, however, eliminate the possibility that there is a biological basis to this finding," the team noted.

Subjects who were 13 years or older might have taken longer to recover (HR, 1.404; P = .04) because games "between older children involve more contact and higher-force impacts," although neurobiologic differences between older and younger kids might have played a role, as well, the investigators said.

"Female patients" – about 43% of the study total – "had more severe symptoms at presentation in our study (mean initial RPSQ of 21.3 vs. 17.0 in male patients, P = .02). ... Whether this finding is indicative of the fact that female patients have more severe symptoms from concussion in general, as suggested in several previous studies, or is due to referral bias in which female individuals preferentially present to the ED when symptoms are more severe ... cannot be ascertained from our data," they noted.

Female gender fell out on multivariate analysis as a predictor of prolonged recovery (HR, 1.294; P= 0.11).

The investigators said they had no relevant financial disclosures.

Children and teenagers take longer to recover from a concussion if they’ve had one before, especially within the past year, Boston Children’s Hospital emergency department physicians found in a study of 280 of their concussed patients published June 10 in Pediatrics.

The median duration of symptoms, assessed by the serial Rivermead Post-Concussion Symptoms Questionnaire (RPSQ) over a period of 3 months, climbed from 12 days in patients who hadn’t been concussed before to 24 days in those who had. The median symptom duration was 28 days in patients with multiple previous concussions, and 35 days in those who’d been concussed within the previous year, "nearly three times the median duration [for] those who had no previous concussions," according to Dr. Matthew A. Eisenberg and his associates at the hospital (Pediatrics 2013 [doi:10.1542/peds.2013-0432]).

"Similarly, patients with two or more previous concussions had more than double the median symptom duration [of] patients with zero or one previous concussion," they found.

On multivariate analysis, previous concussion, maintaining consciousness, being 13 years or older, and an initial RPSQ of 18 or higher all predicted prolonged recovery. Among all comers, 77% had symptoms at 1 week, 32% at 4 weeks, and 15% at 3 months. The mean age in the trial was 14.3 years (range, 11-22 years).

The findings were statistically significant and have "direct implications on the management of athletes and other at-risk individuals who sustain concussions, supporting the concept that sufficient time to recover from a concussion may improve long-term outcomes," the investigators said.

"However, we did not find an association between physician-advised cognitive or physical rest and duration of symptoms, which may reflect the limitations of our observational study," they added. "A randomized [controlled] trial will likely be necessary to address the utility of this intervention."

Sixty-six percent of the subjects were enrolled the day they were injured; 24.7% were enrolled 1 day later, 7.2% 2 days later, and 1.7% 3 days later. The majority (63.8%) had been injured playing hockey, soccer, football, basketball or some other sport.

The investigators defined concussion broadly to include either altered mental status following blunt head trauma or, within 4 hours of it, any of the following symptoms that were not present before the injury: headache, nausea, vomiting, dizziness/balance problems, fatigue, drowsiness, blurred vision, memory difficulty, or trouble concentrating.

The most common symptoms in the study were headache (85.1%), fatigue (64.7%), and dizziness (63.0%); 4.3% of subjects had altered gait or balance, and 2.4% had altered mental status. There were no abnormalities in the 20.8% of kids who got neuroimaging.

On discharge, 65.9% were prescribed a period of cognitive rest and 92.4% were told to take time off from sports; 63.8% were also told to follow up with their primary care doctor, 45.5% with a sports concussion clinic, and 6.2% with a specialist.

In contrast to prior studies, loss of consciousness seemed to protect against a prolonged recovery (HR, 0.648; P = .02). Maybe the 22% of kids who got knocked out were more likely to follow their doctors’ advice to rest, "thus speeding recovery from their injury. We cannot, however, eliminate the possibility that there is a biological basis to this finding," the team noted.

Subjects who were 13 years or older might have taken longer to recover (HR, 1.404; P = .04) because games "between older children involve more contact and higher-force impacts," although neurobiologic differences between older and younger kids might have played a role, as well, the investigators said.

"Female patients" – about 43% of the study total – "had more severe symptoms at presentation in our study (mean initial RPSQ of 21.3 vs. 17.0 in male patients, P = .02). ... Whether this finding is indicative of the fact that female patients have more severe symptoms from concussion in general, as suggested in several previous studies, or is due to referral bias in which female individuals preferentially present to the ED when symptoms are more severe ... cannot be ascertained from our data," they noted.

Female gender fell out on multivariate analysis as a predictor of prolonged recovery (HR, 1.294; P= 0.11).

The investigators said they had no relevant financial disclosures.

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 pdnews@frontlinemedcom.com.

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 pdnews@frontlinemedcom.com.

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 pdnews@frontlinemedcom.com.

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.