Each year in late summer, the Centers for Disease Control and Prevention (CDC) publishes its recommendations for the prevention of influenza for the upcoming season. The severity of each influenza season varies and is difficult to predict, which underscores the need to provide maximal vaccine coverage for at-risk patient populations.

Hoping for the best, planning for the worst. Over the past several decades the annual number of influenza-related hospitalizations has varied from approximately 55,000 to 431,000,¹ and the number of deaths from influenza has been as low as 3349 and as high as 48,614.² Infection rates are usually highest in children. Complications, hospitalizations, and deaths are highest in those ≥65 years, children<2 years, and patients with medical conditions known to increase risk for influenza complications. Those at high risk of complications appear in TABLE 1.³ The main recommendations for this coming year are the same as last year, including vaccinating everyone ≥6 months of age without a contraindication, starting vaccinations as soon as vaccine is available, and continuing throughout the influenza season for those who need it.

What’s new this year

An increasing number of influenza vaccine products are available; although to date, their effectiveness (which was determined to be 56% for all vaccines used last influenza season) 4 remains below what we would hope for. The CDC’s recommendations address these new types of vaccines, including ones that have 4 antigens instead of 3, and use new terminology to describe the vaccines.³

New terminology reflects changing vaccine formulations. Last influenza season there were 2 major categories of influenza vaccines: live-attenuated influenza vaccine (LAIV) and trivalent inactivated influenza vaccine (TIV). All products were produced using egg-culture methods and contained 2 influenza A antigen subtypes and 1 B subtype. Several products this year include 4 antigens (2 A subtypes and 2 B subtypes), and some are now produced with non–eggculture methods. This has led to a new system of classification, with the term inactivated influenza vaccine (IIV) replacing TIV. TABLE 2 lists the influenza vaccine categories and abbreviations. TABLE 3 lists the contraindications for the different vaccine types.³

The new products include Flumist Quadrivalent (MedImmune), a quadrivalent LAIV (LAIV4); Fluarix Quadrivalent (GlaxoSmithKline), a quadrivalent IIV (IIV4); Flucelvax (Novartis Vaccines and Diagnostics), a cell culture-based trivalent IIV (ccIIV3); and FluBlok (Protein Sciences), a trivalent recombinant hemagglutinin influenza vaccine (RIV3). Fluzone (Sanofi Pasteur), introduced last season in a trivalent formulation, is also available this season as a quadrivalent IIV (IIV4). As a group, influenza vaccine products now offer 3 routes of administration: intramuscular, subcutaneous, and intranasal. There is currently no evidence that any route offers an advantage over another, and the CDC states no preference for any particular product or route of administration.

Mercury content is not a problem
Even though there is no scientific controversy over the safety of the mercury-containing preservative thimerosal, some patients still have doubts and may ask for a thimerosalfree product. The only influenza products that contain any thimerosal are those that come in multidose vials. A description of each influenza vaccine product, including thimerosal content, indicated ages, and routes of administration, can be found on the CDC’s Web site³ (http://www.cdc.gov/flu/professionals/acip/2013-summary-recommendations.htm).

Options for those with egg allergy

There is now a product, RIV3 (FluBlok), that is manufactured without the use of eggs. It can be used in those 18 to 49 years of age with a history of egg allergy of any severity. Since 2011, the Advisory Committee on Immunization Practices (ACIP) has recommended that individuals with a history of mild egg allergy (those who experience only hives after egg exposure) may receive IIV, with additional safety precautions. Do not delay vaccination for these individuals if RIV is unavailable. Because of a lack of data demonstrating safety of LAIV for individuals with egg allergy, those allergic to eggs should receive RIV or IIV rather than LAIV.

Though the new ccIIV product, Flucelvax, is manufactured without the use of eggs, the seed viruses used to create the vaccine have been processed in eggs. The egg protein content in the vaccine is extremely low (<50 femtograms [5 × 10-14 g] per 0.5-mL dose), but the CDC does not consider it egg free. The FIGURE depicts the recommendations for those with a history of egg allergy.³

Other interventions for influenza prevention

Vaccination is only one tool available to prevent morbidity and mortality from influenza. Antiviral chemoprevention and treatment, and infection control practices can also be effective.

Antiviral chemoprevention is available for both pre- and post-exposure administration. In the past few years, the CDC has de-emphasized such use of antivirals for these indications out of concern for the supply of these agents and for the possibility that their use might lead to increased rates of viral resistance. Consider antiviral chemoprevention for those who have conditions that place them at risk for complications, and for those who are unvaccinated if they are at high risk for exposure to influenza (preexposure prophylaxis) or have been exposed (postexposure prophylaxis), if the medication can be started within 48 hours of exposure. Another option for unvaccinated high-risk patients is vigilant symptom monitoring with early treatment for influenza symptoms. Chemoprophylaxis is recommended in addition to vaccination to control influenza outbreaks at institutions that house patients at high risk for complications of influenza. Details on recommended antivirals including doses and duration of treatment can be found in a 2011 issue of Morbidity and Mortality Weekly Report.⁵

Antiviral treatment. The CDC recommends antiviral treatment for anyone with suspected or confirmed influenza who has progressive, severe, or complicated illness or is hospitalized for their illness.⁵ Treatment is also recommended for outpatients with suspected or confirmed influenza who are at higher risk for influenza complications. This latter group includes those in TABLE 1, particularly children 6 to 59 months and adults ≥50 years. Start antiviral treatment within 48 hours of the first symptoms. For hospitalized patients, however, begin treatment at any point regardless of duration of illness.

Infection control practices can prevent the spread of influenza in the health care setting and in the homes of those with influenza. These practices are also described on the CDC influenza Web site.⁶

Each year in late summer, the Centers for Disease Control and Prevention (CDC) publishes its recommendations for the prevention of influenza for the upcoming season. The severity of each influenza season varies and is difficult to predict, which underscores the need to provide maximal vaccine coverage for at-risk patient populations.

Hoping for the best, planning for the worst. Over the past several decades the annual number of influenza-related hospitalizations has varied from approximately 55,000 to 431,000,¹ and the number of deaths from influenza has been as low as 3349 and as high as 48,614.² Infection rates are usually highest in children. Complications, hospitalizations, and deaths are highest in those ≥65 years, children<2 years, and patients with medical conditions known to increase risk for influenza complications. Those at high risk of complications appear in TABLE 1.³ The main recommendations for this coming year are the same as last year, including vaccinating everyone ≥6 months of age without a contraindication, starting vaccinations as soon as vaccine is available, and continuing throughout the influenza season for those who need it.

What’s new this year

An increasing number of influenza vaccine products are available; although to date, their effectiveness (which was determined to be 56% for all vaccines used last influenza season) 4 remains below what we would hope for. The CDC’s recommendations address these new types of vaccines, including ones that have 4 antigens instead of 3, and use new terminology to describe the vaccines.³

New terminology reflects changing vaccine formulations. Last influenza season there were 2 major categories of influenza vaccines: live-attenuated influenza vaccine (LAIV) and trivalent inactivated influenza vaccine (TIV). All products were produced using egg-culture methods and contained 2 influenza A antigen subtypes and 1 B subtype. Several products this year include 4 antigens (2 A subtypes and 2 B subtypes), and some are now produced with non–eggculture methods. This has led to a new system of classification, with the term inactivated influenza vaccine (IIV) replacing TIV. TABLE 2 lists the influenza vaccine categories and abbreviations. TABLE 3 lists the contraindications for the different vaccine types.³

The new products include Flumist Quadrivalent (MedImmune), a quadrivalent LAIV (LAIV4); Fluarix Quadrivalent (GlaxoSmithKline), a quadrivalent IIV (IIV4); Flucelvax (Novartis Vaccines and Diagnostics), a cell culture-based trivalent IIV (ccIIV3); and FluBlok (Protein Sciences), a trivalent recombinant hemagglutinin influenza vaccine (RIV3). Fluzone (Sanofi Pasteur), introduced last season in a trivalent formulation, is also available this season as a quadrivalent IIV (IIV4). As a group, influenza vaccine products now offer 3 routes of administration: intramuscular, subcutaneous, and intranasal. There is currently no evidence that any route offers an advantage over another, and the CDC states no preference for any particular product or route of administration.

Mercury content is not a problem
Even though there is no scientific controversy over the safety of the mercury-containing preservative thimerosal, some patients still have doubts and may ask for a thimerosalfree product. The only influenza products that contain any thimerosal are those that come in multidose vials. A description of each influenza vaccine product, including thimerosal content, indicated ages, and routes of administration, can be found on the CDC’s Web site³ (http://www.cdc.gov/flu/professionals/acip/2013-summary-recommendations.htm).

Options for those with egg allergy

There is now a product, RIV3 (FluBlok), that is manufactured without the use of eggs. It can be used in those 18 to 49 years of age with a history of egg allergy of any severity. Since 2011, the Advisory Committee on Immunization Practices (ACIP) has recommended that individuals with a history of mild egg allergy (those who experience only hives after egg exposure) may receive IIV, with additional safety precautions. Do not delay vaccination for these individuals if RIV is unavailable. Because of a lack of data demonstrating safety of LAIV for individuals with egg allergy, those allergic to eggs should receive RIV or IIV rather than LAIV.

Though the new ccIIV product, Flucelvax, is manufactured without the use of eggs, the seed viruses used to create the vaccine have been processed in eggs. The egg protein content in the vaccine is extremely low (<50 femtograms [5 × 10-14 g] per 0.5-mL dose), but the CDC does not consider it egg free. The FIGURE depicts the recommendations for those with a history of egg allergy.³

Other interventions for influenza prevention

Vaccination is only one tool available to prevent morbidity and mortality from influenza. Antiviral chemoprevention and treatment, and infection control practices can also be effective.

Antiviral chemoprevention is available for both pre- and post-exposure administration. In the past few years, the CDC has de-emphasized such use of antivirals for these indications out of concern for the supply of these agents and for the possibility that their use might lead to increased rates of viral resistance. Consider antiviral chemoprevention for those who have conditions that place them at risk for complications, and for those who are unvaccinated if they are at high risk for exposure to influenza (preexposure prophylaxis) or have been exposed (postexposure prophylaxis), if the medication can be started within 48 hours of exposure. Another option for unvaccinated high-risk patients is vigilant symptom monitoring with early treatment for influenza symptoms. Chemoprophylaxis is recommended in addition to vaccination to control influenza outbreaks at institutions that house patients at high risk for complications of influenza. Details on recommended antivirals including doses and duration of treatment can be found in a 2011 issue of Morbidity and Mortality Weekly Report.⁵

Antiviral treatment. The CDC recommends antiviral treatment for anyone with suspected or confirmed influenza who has progressive, severe, or complicated illness or is hospitalized for their illness.⁵ Treatment is also recommended for outpatients with suspected or confirmed influenza who are at higher risk for influenza complications. This latter group includes those in TABLE 1, particularly children 6 to 59 months and adults ≥50 years. Start antiviral treatment within 48 hours of the first symptoms. For hospitalized patients, however, begin treatment at any point regardless of duration of illness.

Infection control practices can prevent the spread of influenza in the health care setting and in the homes of those with influenza. These practices are also described on the CDC influenza Web site.⁶

Each year in late summer, the Centers for Disease Control and Prevention (CDC) publishes its recommendations for the prevention of influenza for the upcoming season. The severity of each influenza season varies and is difficult to predict, which underscores the need to provide maximal vaccine coverage for at-risk patient populations.

Hoping for the best, planning for the worst. Over the past several decades the annual number of influenza-related hospitalizations has varied from approximately 55,000 to 431,000,¹ and the number of deaths from influenza has been as low as 3349 and as high as 48,614.² Infection rates are usually highest in children. Complications, hospitalizations, and deaths are highest in those ≥65 years, children<2 years, and patients with medical conditions known to increase risk for influenza complications. Those at high risk of complications appear in TABLE 1.³ The main recommendations for this coming year are the same as last year, including vaccinating everyone ≥6 months of age without a contraindication, starting vaccinations as soon as vaccine is available, and continuing throughout the influenza season for those who need it.

What’s new this year

An increasing number of influenza vaccine products are available; although to date, their effectiveness (which was determined to be 56% for all vaccines used last influenza season) 4 remains below what we would hope for. The CDC’s recommendations address these new types of vaccines, including ones that have 4 antigens instead of 3, and use new terminology to describe the vaccines.³

New terminology reflects changing vaccine formulations. Last influenza season there were 2 major categories of influenza vaccines: live-attenuated influenza vaccine (LAIV) and trivalent inactivated influenza vaccine (TIV). All products were produced using egg-culture methods and contained 2 influenza A antigen subtypes and 1 B subtype. Several products this year include 4 antigens (2 A subtypes and 2 B subtypes), and some are now produced with non–eggculture methods. This has led to a new system of classification, with the term inactivated influenza vaccine (IIV) replacing TIV. TABLE 2 lists the influenza vaccine categories and abbreviations. TABLE 3 lists the contraindications for the different vaccine types.³

The new products include Flumist Quadrivalent (MedImmune), a quadrivalent LAIV (LAIV4); Fluarix Quadrivalent (GlaxoSmithKline), a quadrivalent IIV (IIV4); Flucelvax (Novartis Vaccines and Diagnostics), a cell culture-based trivalent IIV (ccIIV3); and FluBlok (Protein Sciences), a trivalent recombinant hemagglutinin influenza vaccine (RIV3). Fluzone (Sanofi Pasteur), introduced last season in a trivalent formulation, is also available this season as a quadrivalent IIV (IIV4). As a group, influenza vaccine products now offer 3 routes of administration: intramuscular, subcutaneous, and intranasal. There is currently no evidence that any route offers an advantage over another, and the CDC states no preference for any particular product or route of administration.

Mercury content is not a problem
Even though there is no scientific controversy over the safety of the mercury-containing preservative thimerosal, some patients still have doubts and may ask for a thimerosalfree product. The only influenza products that contain any thimerosal are those that come in multidose vials. A description of each influenza vaccine product, including thimerosal content, indicated ages, and routes of administration, can be found on the CDC’s Web site³ (http://www.cdc.gov/flu/professionals/acip/2013-summary-recommendations.htm).

Options for those with egg allergy

There is now a product, RIV3 (FluBlok), that is manufactured without the use of eggs. It can be used in those 18 to 49 years of age with a history of egg allergy of any severity. Since 2011, the Advisory Committee on Immunization Practices (ACIP) has recommended that individuals with a history of mild egg allergy (those who experience only hives after egg exposure) may receive IIV, with additional safety precautions. Do not delay vaccination for these individuals if RIV is unavailable. Because of a lack of data demonstrating safety of LAIV for individuals with egg allergy, those allergic to eggs should receive RIV or IIV rather than LAIV.

Though the new ccIIV product, Flucelvax, is manufactured without the use of eggs, the seed viruses used to create the vaccine have been processed in eggs. The egg protein content in the vaccine is extremely low (<50 femtograms [5 × 10-14 g] per 0.5-mL dose), but the CDC does not consider it egg free. The FIGURE depicts the recommendations for those with a history of egg allergy.³

Other interventions for influenza prevention

Vaccination is only one tool available to prevent morbidity and mortality from influenza. Antiviral chemoprevention and treatment, and infection control practices can also be effective.

Antiviral chemoprevention is available for both pre- and post-exposure administration. In the past few years, the CDC has de-emphasized such use of antivirals for these indications out of concern for the supply of these agents and for the possibility that their use might lead to increased rates of viral resistance. Consider antiviral chemoprevention for those who have conditions that place them at risk for complications, and for those who are unvaccinated if they are at high risk for exposure to influenza (preexposure prophylaxis) or have been exposed (postexposure prophylaxis), if the medication can be started within 48 hours of exposure. Another option for unvaccinated high-risk patients is vigilant symptom monitoring with early treatment for influenza symptoms. Chemoprophylaxis is recommended in addition to vaccination to control influenza outbreaks at institutions that house patients at high risk for complications of influenza. Details on recommended antivirals including doses and duration of treatment can be found in a 2011 issue of Morbidity and Mortality Weekly Report.⁵

Antiviral treatment. The CDC recommends antiviral treatment for anyone with suspected or confirmed influenza who has progressive, severe, or complicated illness or is hospitalized for their illness.⁵ Treatment is also recommended for outpatients with suspected or confirmed influenza who are at higher risk for influenza complications. This latter group includes those in TABLE 1, particularly children 6 to 59 months and adults ≥50 years. Start antiviral treatment within 48 hours of the first symptoms. For hospitalized patients, however, begin treatment at any point regardless of duration of illness.

Infection control practices can prevent the spread of influenza in the health care setting and in the homes of those with influenza. These practices are also described on the CDC influenza Web site.⁶

Illustrative case

A 10-year-old boy is brought in by his father for asthma follow-up. The child uses an albuterol inhaler, but has had increased coughing and wheezing recently. You are ready to step up his asthma therapy to include ICS. But the patient’s father questions this, noting that he recently read that steroids may reduce a child’s growth. How should you respond?

Inhaled corticosteroids (ICS) are a mainstay in the treatment of asthma ranging from mild persistent to severe. Standards of care for asthma treatment involve a stepwise approach, with ICS added if symptoms are not controlled with short-acting beta antagonists alone.² In addition, monotherapy with ICS is more effective for controlling symptoms than leukotriene inhibitors or other controller medications, while also decreasing hospitalizations and nocturnal awakenings and improving quality of life—with few side effects.³

What we know about ICS and children’s growth
One adverse effect of ICS, however, is that of “decreased linear growth velocity”⁴—ie, slowing the rate at which children grow. Until recently, children were thought to “catch up” later in life, either by growing for a longer period of time than they would had they not taken ICS or by growing at an increased velocity after ICS medications are discontinued.^4-6

Study summary: The effect on growth is small, but long-lasting

Kelly et al conducted a prospective observational cohort study that followed 943 (90.7%) participants in the Childhood Asthma Management Program (CAMP) in the years after the randomized controlled trial (RCT) ended.

A double-blind, placebo-controlled RCT, CAMP studied the linear growth of 1041 children with mild-to-moderate persistent asthma who were divided into 3 treatment groups: One group received 200 mcg inhaled budesonide twice daily; a second group received 8 mg inhaled nedocromil twice daily; and a third group received placebo. Albuterol was used symptomatically by all 3 groups.⁷ The children ranged in age from 5 to 13 years at the start of the study; 98 patients—split evenly among the 3 treatment arms—were lost to follow-up.

During the 4 to 6 years of the CAMP trial, the budesonide group received a mean total of 636 mg ICS, whereas the nedocromil and placebo groups received an average of 88.5 and 109.4 mg ICS, respectively. After the RCT ended, all participants had standardized asthma treatment, receiving mean adjusted total doses of ICS of 381 mg for the budesonide group, 347.9 mg for the nedocromil group, and 355 mg for the placebo group.

Patients’ height was measured every 6 months for the next 4.5 years, and once or twice a year thereafter until they reached adult height (at a mean age of 24.9±2.7 years).

ICS users were a half inch shorter
Long-term ICS use was linked to a lower adult height. The adjusted mean height was 171.1 cm for the budesonide group vs 172.3 cm for those on placebo, a difference of 1.2 cm, or 0.47 inch (95% confidence interval [CI], −1.9 to −0.5; P=.001); the mean adult height in the nedocromil group (172.1 cm) was similar to that of the placebo group (−0.2 cm; 95% CI, −0.9 to 0.5; P=.61).

The lower adult height in the ICS group did not vary significantly based on sex, age at trial entry, race, or duration of asthma prior to trial entry; however, dose was a key factor. A larger daily dose of budesonide—particularly in the first 2 years of the RCT—was associated with a lower adult height (about −0.1 cm for each mcg/kg in that 2-year time frame). This was consistent with results from studies that looked at other types of ICS (beclomethasone, fluticasone, and mometasone).^8-11

The study also showed that growth velocity was reduced in the first 2 years of assigned treatment with budesonide, and this was primarily among prepubertal participants. After the initial 2-year slowing in growth rate, the children resumed growing at normal speeds.

What’s new: Now we know: Children don’t “catch up"

Retrospective studies have reported that children on ICS for mild persistent to moderate asthma would have an initial slowing in growth velocity but then “catch up” by growing for a longer period of time.^3-5 This is the first prospective study with good follow-up to show that ICS use affects long-term growth and adult height. While the effect is not large, some children and their families might be concerned about it.

Caveats: ICS use was atypical

The randomized controlled portion of the study used a prescribed dose of budesonide without regard to symptoms. This is not the typical pattern of ICS use. In addition, compliance with ICS varies significantly.¹² Because the effect on adult height appears to be dose dependent, however, we think the results of this study are valid.

In addition, there was a placebo control group (and big differences in exposure to ICS) only for the duration of the RCT. During the subsequent study, all patients received equivalent doses of ICS. This means that the variation in mean adult height achieved can be primarily ascribed to participants’ use of ICS during the 4- to 6-year CAMP trial. Of note, the effect of ICS was greatest in prepubertal participants, so there may be a diminished effect as teens approach their final height.

The study did not look at the effect of ICS use in patients with severe asthma—the group most likely to use ICS. However, the benefits of ICS for those with severe asthma likely outweigh any negative effects on adult height.

Challenges to implementation: What to tell patients

The message we convey to patients (and parents) about ICS use is a nuanced one. We can stress that ICS remain very important in the treatment of asthma and, while it appears that their use causes a slight decrease in adult height, most children with persistent asthma benefit from ICS.

Acknowledgement

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

Illustrative case

A 10-year-old boy is brought in by his father for asthma follow-up. The child uses an albuterol inhaler, but has had increased coughing and wheezing recently. You are ready to step up his asthma therapy to include ICS. But the patient’s father questions this, noting that he recently read that steroids may reduce a child’s growth. How should you respond?

Inhaled corticosteroids (ICS) are a mainstay in the treatment of asthma ranging from mild persistent to severe. Standards of care for asthma treatment involve a stepwise approach, with ICS added if symptoms are not controlled with short-acting beta antagonists alone.² In addition, monotherapy with ICS is more effective for controlling symptoms than leukotriene inhibitors or other controller medications, while also decreasing hospitalizations and nocturnal awakenings and improving quality of life—with few side effects.³

What we know about ICS and children’s growth
One adverse effect of ICS, however, is that of “decreased linear growth velocity”⁴—ie, slowing the rate at which children grow. Until recently, children were thought to “catch up” later in life, either by growing for a longer period of time than they would had they not taken ICS or by growing at an increased velocity after ICS medications are discontinued.^4-6

Study summary: The effect on growth is small, but long-lasting

Kelly et al conducted a prospective observational cohort study that followed 943 (90.7%) participants in the Childhood Asthma Management Program (CAMP) in the years after the randomized controlled trial (RCT) ended.

A double-blind, placebo-controlled RCT, CAMP studied the linear growth of 1041 children with mild-to-moderate persistent asthma who were divided into 3 treatment groups: One group received 200 mcg inhaled budesonide twice daily; a second group received 8 mg inhaled nedocromil twice daily; and a third group received placebo. Albuterol was used symptomatically by all 3 groups.⁷ The children ranged in age from 5 to 13 years at the start of the study; 98 patients—split evenly among the 3 treatment arms—were lost to follow-up.

During the 4 to 6 years of the CAMP trial, the budesonide group received a mean total of 636 mg ICS, whereas the nedocromil and placebo groups received an average of 88.5 and 109.4 mg ICS, respectively. After the RCT ended, all participants had standardized asthma treatment, receiving mean adjusted total doses of ICS of 381 mg for the budesonide group, 347.9 mg for the nedocromil group, and 355 mg for the placebo group.

Patients’ height was measured every 6 months for the next 4.5 years, and once or twice a year thereafter until they reached adult height (at a mean age of 24.9±2.7 years).

ICS users were a half inch shorter
Long-term ICS use was linked to a lower adult height. The adjusted mean height was 171.1 cm for the budesonide group vs 172.3 cm for those on placebo, a difference of 1.2 cm, or 0.47 inch (95% confidence interval [CI], −1.9 to −0.5; P=.001); the mean adult height in the nedocromil group (172.1 cm) was similar to that of the placebo group (−0.2 cm; 95% CI, −0.9 to 0.5; P=.61).

The lower adult height in the ICS group did not vary significantly based on sex, age at trial entry, race, or duration of asthma prior to trial entry; however, dose was a key factor. A larger daily dose of budesonide—particularly in the first 2 years of the RCT—was associated with a lower adult height (about −0.1 cm for each mcg/kg in that 2-year time frame). This was consistent with results from studies that looked at other types of ICS (beclomethasone, fluticasone, and mometasone).^8-11

The study also showed that growth velocity was reduced in the first 2 years of assigned treatment with budesonide, and this was primarily among prepubertal participants. After the initial 2-year slowing in growth rate, the children resumed growing at normal speeds.

What’s new: Now we know: Children don’t “catch up"

Retrospective studies have reported that children on ICS for mild persistent to moderate asthma would have an initial slowing in growth velocity but then “catch up” by growing for a longer period of time.^3-5 This is the first prospective study with good follow-up to show that ICS use affects long-term growth and adult height. While the effect is not large, some children and their families might be concerned about it.

Caveats: ICS use was atypical

The randomized controlled portion of the study used a prescribed dose of budesonide without regard to symptoms. This is not the typical pattern of ICS use. In addition, compliance with ICS varies significantly.¹² Because the effect on adult height appears to be dose dependent, however, we think the results of this study are valid.

In addition, there was a placebo control group (and big differences in exposure to ICS) only for the duration of the RCT. During the subsequent study, all patients received equivalent doses of ICS. This means that the variation in mean adult height achieved can be primarily ascribed to participants’ use of ICS during the 4- to 6-year CAMP trial. Of note, the effect of ICS was greatest in prepubertal participants, so there may be a diminished effect as teens approach their final height.

The study did not look at the effect of ICS use in patients with severe asthma—the group most likely to use ICS. However, the benefits of ICS for those with severe asthma likely outweigh any negative effects on adult height.

Challenges to implementation: What to tell patients

The message we convey to patients (and parents) about ICS use is a nuanced one. We can stress that ICS remain very important in the treatment of asthma and, while it appears that their use causes a slight decrease in adult height, most children with persistent asthma benefit from ICS.

Acknowledgement

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

Illustrative case

A 10-year-old boy is brought in by his father for asthma follow-up. The child uses an albuterol inhaler, but has had increased coughing and wheezing recently. You are ready to step up his asthma therapy to include ICS. But the patient’s father questions this, noting that he recently read that steroids may reduce a child’s growth. How should you respond?

Inhaled corticosteroids (ICS) are a mainstay in the treatment of asthma ranging from mild persistent to severe. Standards of care for asthma treatment involve a stepwise approach, with ICS added if symptoms are not controlled with short-acting beta antagonists alone.² In addition, monotherapy with ICS is more effective for controlling symptoms than leukotriene inhibitors or other controller medications, while also decreasing hospitalizations and nocturnal awakenings and improving quality of life—with few side effects.³

What we know about ICS and children’s growth
One adverse effect of ICS, however, is that of “decreased linear growth velocity”⁴—ie, slowing the rate at which children grow. Until recently, children were thought to “catch up” later in life, either by growing for a longer period of time than they would had they not taken ICS or by growing at an increased velocity after ICS medications are discontinued.^4-6

Study summary: The effect on growth is small, but long-lasting

Kelly et al conducted a prospective observational cohort study that followed 943 (90.7%) participants in the Childhood Asthma Management Program (CAMP) in the years after the randomized controlled trial (RCT) ended.

A double-blind, placebo-controlled RCT, CAMP studied the linear growth of 1041 children with mild-to-moderate persistent asthma who were divided into 3 treatment groups: One group received 200 mcg inhaled budesonide twice daily; a second group received 8 mg inhaled nedocromil twice daily; and a third group received placebo. Albuterol was used symptomatically by all 3 groups.⁷ The children ranged in age from 5 to 13 years at the start of the study; 98 patients—split evenly among the 3 treatment arms—were lost to follow-up.

During the 4 to 6 years of the CAMP trial, the budesonide group received a mean total of 636 mg ICS, whereas the nedocromil and placebo groups received an average of 88.5 and 109.4 mg ICS, respectively. After the RCT ended, all participants had standardized asthma treatment, receiving mean adjusted total doses of ICS of 381 mg for the budesonide group, 347.9 mg for the nedocromil group, and 355 mg for the placebo group.

Patients’ height was measured every 6 months for the next 4.5 years, and once or twice a year thereafter until they reached adult height (at a mean age of 24.9±2.7 years).

ICS users were a half inch shorter
Long-term ICS use was linked to a lower adult height. The adjusted mean height was 171.1 cm for the budesonide group vs 172.3 cm for those on placebo, a difference of 1.2 cm, or 0.47 inch (95% confidence interval [CI], −1.9 to −0.5; P=.001); the mean adult height in the nedocromil group (172.1 cm) was similar to that of the placebo group (−0.2 cm; 95% CI, −0.9 to 0.5; P=.61).

The lower adult height in the ICS group did not vary significantly based on sex, age at trial entry, race, or duration of asthma prior to trial entry; however, dose was a key factor. A larger daily dose of budesonide—particularly in the first 2 years of the RCT—was associated with a lower adult height (about −0.1 cm for each mcg/kg in that 2-year time frame). This was consistent with results from studies that looked at other types of ICS (beclomethasone, fluticasone, and mometasone).^8-11

The study also showed that growth velocity was reduced in the first 2 years of assigned treatment with budesonide, and this was primarily among prepubertal participants. After the initial 2-year slowing in growth rate, the children resumed growing at normal speeds.

What’s new: Now we know: Children don’t “catch up"

Retrospective studies have reported that children on ICS for mild persistent to moderate asthma would have an initial slowing in growth velocity but then “catch up” by growing for a longer period of time.^3-5 This is the first prospective study with good follow-up to show that ICS use affects long-term growth and adult height. While the effect is not large, some children and their families might be concerned about it.

Caveats: ICS use was atypical

The randomized controlled portion of the study used a prescribed dose of budesonide without regard to symptoms. This is not the typical pattern of ICS use. In addition, compliance with ICS varies significantly.¹² Because the effect on adult height appears to be dose dependent, however, we think the results of this study are valid.

In addition, there was a placebo control group (and big differences in exposure to ICS) only for the duration of the RCT. During the subsequent study, all patients received equivalent doses of ICS. This means that the variation in mean adult height achieved can be primarily ascribed to participants’ use of ICS during the 4- to 6-year CAMP trial. Of note, the effect of ICS was greatest in prepubertal participants, so there may be a diminished effect as teens approach their final height.

The study did not look at the effect of ICS use in patients with severe asthma—the group most likely to use ICS. However, the benefits of ICS for those with severe asthma likely outweigh any negative effects on adult height.

Challenges to implementation: What to tell patients

The message we convey to patients (and parents) about ICS use is a nuanced one. We can stress that ICS remain very important in the treatment of asthma and, while it appears that their use causes a slight decrease in adult height, most children with persistent asthma benefit from ICS.

Acknowledgement

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

"If it ain’t broke, don’t fix it" or "A stitch in time saves nine"—which do you prefer?

When I taught epidemiology at the University of Chicago, I asked first-year medical students that question before discussing the science of screening for early detection of disease. Each year, the class was about evenly divided. Their split response reinforced to me the need for shared decision making when we offer screening tests to our patients.

Shared decision making is especially important in light of new evidence about the effectiveness (or lack thereof) of some screening tests. Several bread-and-butter screening procedures and tests promoted for years have been debunked as having no value (routine testicular exam and monthly self-breast exam), having harms that might outweigh the benefits (PSA for prostate cancer), or having marginal benefit for those in certain age groups (mammography in women younger than 50). And, as treatments for cancer get better and better, screening will have less and less value. What would a 30-year-old do if he found out he has a gene that makes him susceptible to Alzheimer's disease?

The biggest screening test challenge, however— genome screening—is still to come. Genomic sequencing analysis is already useful for the diagnosis of certain genetic disorders and for treatment decisions in certain cancers. Genomic sequencing to screen for disease, however, is fraught with ethical challenges and the absolute need for shared decision making.

What if gene analysis uncovers "incidental findings" about risk faced by asymptomatic patients, like the "incidentalomas" described in "When to worry about incidental renal and adrenal masses"? The debate about what to do with incidental findings from genetic analysis is heating up because of the American College of Medical Genetics and Genomics' recent recommendations¹ to automatically screen for 56 genes that may contain "potentially important" findings when genome sequencing is done for any reason.

Talk about Pandora’s box! Suppose a 30-year-old finds he carries a gene that makes him susceptible to Alzheimer’s disease. What would he do with that information, other than get depressed when he realizes there are not yet any effective early interventions?

Family physicians are likely to be asked more and more questions about genome analysis.* Be prepared. You can start by asking patients whether they adhere to an "If it ain’t broke…" " or "A stitch in time…" approach.

"If it ain’t broke, don’t fix it" or "A stitch in time saves nine"—which do you prefer?

When I taught epidemiology at the University of Chicago, I asked first-year medical students that question before discussing the science of screening for early detection of disease. Each year, the class was about evenly divided. Their split response reinforced to me the need for shared decision making when we offer screening tests to our patients.

Shared decision making is especially important in light of new evidence about the effectiveness (or lack thereof) of some screening tests. Several bread-and-butter screening procedures and tests promoted for years have been debunked as having no value (routine testicular exam and monthly self-breast exam), having harms that might outweigh the benefits (PSA for prostate cancer), or having marginal benefit for those in certain age groups (mammography in women younger than 50). And, as treatments for cancer get better and better, screening will have less and less value. What would a 30-year-old do if he found out he has a gene that makes him susceptible to Alzheimer's disease?

The biggest screening test challenge, however— genome screening—is still to come. Genomic sequencing analysis is already useful for the diagnosis of certain genetic disorders and for treatment decisions in certain cancers. Genomic sequencing to screen for disease, however, is fraught with ethical challenges and the absolute need for shared decision making.

What if gene analysis uncovers "incidental findings" about risk faced by asymptomatic patients, like the "incidentalomas" described in "When to worry about incidental renal and adrenal masses"? The debate about what to do with incidental findings from genetic analysis is heating up because of the American College of Medical Genetics and Genomics' recent recommendations¹ to automatically screen for 56 genes that may contain "potentially important" findings when genome sequencing is done for any reason.

Talk about Pandora’s box! Suppose a 30-year-old finds he carries a gene that makes him susceptible to Alzheimer’s disease. What would he do with that information, other than get depressed when he realizes there are not yet any effective early interventions?

Family physicians are likely to be asked more and more questions about genome analysis.* Be prepared. You can start by asking patients whether they adhere to an "If it ain’t broke…" " or "A stitch in time…" approach.

"If it ain’t broke, don’t fix it" or "A stitch in time saves nine"—which do you prefer?

When I taught epidemiology at the University of Chicago, I asked first-year medical students that question before discussing the science of screening for early detection of disease. Each year, the class was about evenly divided. Their split response reinforced to me the need for shared decision making when we offer screening tests to our patients.

Shared decision making is especially important in light of new evidence about the effectiveness (or lack thereof) of some screening tests. Several bread-and-butter screening procedures and tests promoted for years have been debunked as having no value (routine testicular exam and monthly self-breast exam), having harms that might outweigh the benefits (PSA for prostate cancer), or having marginal benefit for those in certain age groups (mammography in women younger than 50). And, as treatments for cancer get better and better, screening will have less and less value. What would a 30-year-old do if he found out he has a gene that makes him susceptible to Alzheimer's disease?

The biggest screening test challenge, however— genome screening—is still to come. Genomic sequencing analysis is already useful for the diagnosis of certain genetic disorders and for treatment decisions in certain cancers. Genomic sequencing to screen for disease, however, is fraught with ethical challenges and the absolute need for shared decision making.

What if gene analysis uncovers "incidental findings" about risk faced by asymptomatic patients, like the "incidentalomas" described in "When to worry about incidental renal and adrenal masses"? The debate about what to do with incidental findings from genetic analysis is heating up because of the American College of Medical Genetics and Genomics' recent recommendations¹ to automatically screen for 56 genes that may contain "potentially important" findings when genome sequencing is done for any reason.

Talk about Pandora’s box! Suppose a 30-year-old finds he carries a gene that makes him susceptible to Alzheimer’s disease. What would he do with that information, other than get depressed when he realizes there are not yet any effective early interventions?

Family physicians are likely to be asked more and more questions about genome analysis.* Be prepared. You can start by asking patients whether they adhere to an "If it ain’t broke…" " or "A stitch in time…" approach.

Microbiome refers to all the microbial life that exists in a specific niche. In the case of humans that means a lot of bacteria, viruses, fungi, parasites, and a very old class of single-celled organisms called archaea. The organisms include commensals and pathogenic microorganisms. Many articles distinguish "microbiome" and "microbiota" to differentiate the collective genomes of the microorganisms or the microorganisms themselves, respectively. However, these terms are largely synonymous.

A number of advances have allowed scientists to make major advances in understanding the microbiome. Specifically, we now have the molecular tools to perform gene expression analysis for an entire microbial community in the new discipline of metagenomics and analyze the massive results with new methods of mathematical analysis.

The human body contains over 10 times more microorganisms than human cells. The existence of a remarkably diverse and enormously large microbial world on us and in us first began to come to light in the late 1990s. We are learning more and more about the individual locations of the human host that have different populations of microbes and about differences among humans that contribute to or account for susceptibility to infectious diseases as well as autoimmune diseases and even obesity and cancer.

The nasopharyngeal microbiome has become an area of research by our group led by Qingfu Xu, Ph.D., at the Rochester (N.Y.) General Hospital Research Institute in collaboration with Melinda M. Pettigrew, Ph.D., at the Yale School of Public Health, New Haven, Conn., and Dr. Janet R. Casey at Legacy Pediatrics, also in Rochester. The traditional view of the immune system is undergoing reassessment as we learn that our microbiota has coevolved with our immune system, and each exerts influence over the other. Our group has a special interest in the impact of the nasopharyngeal microbiome on the innate immune response in that physiologic niche, and the way the innate immune system modifies the microbiome. With a special interest in the bacteria that cause respiratory infections such as acute otitis media, acute sinusitis, bronchopneumonia, and pneumonia, we have identified how microbes like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis compete and synergize in the nasopharynx to cause infections.

Also, we seek to better understand how respiratory viruses like respiratory syncytial virus (RSV), influenzae, parainfluenzae, rhinovirus, and others facilitate the overgrowth of S. pneumoniae, H. flu, and M. catarrhalis in the nose such that they convert from commensals to pathogens. But the synergy goes both ways, as we have recently found that S. pneumoniae facilitates upper respiratory viral infections.

Up to now most of the work on the human microbiome has focused on the gut, and nearly all studies have occurred in adults. Perhaps readers are aware of the use of "fecal microbiota transplantation" as a treatment/cure for Clostridium difficile infection. Unhealthy gut microbiota in premature neonates are a major contributing factor in necrotizing enterocolitis.

For decades, physicians have been taught that obesity is a problem derived from excessive caloric intake and inadequate caloric consumption through activity, plus vaguely defined differences in "metabolism." As a consequence, we checked for hypothyroidism � I never found a case. New research has shown that there is a difference in the "metabolism" of obese patients, but the difference is how the individual gut microbiota metabolizes our food. It turns out the thinner individuals have a microbiota that is less efficient in breaking down the food we ingest to allow efficient absorption into the bloodstream, whereas obese individuals have a more efficient microbiota that facilitates absorption of a greater percentage of the proteins, carbohydrates, and fats that are ingested. So the pathway to treatment of obesity may lie in the study of the microbiome!

It turns out that the microbiota of the skin is highly diverse. The microbiota colonizing the antecubital fossa is different from that of the forearm or biceps or axillae. When atopic dermatitis flares, it is often in the antecubital fossa, and it is caused by overgrowth of Staphylococcus aureus. The microbiome of a patient with atopic dermatitis is different from that of a person without atopic dermatitis, and the former microbiota is more permissive to S. aureus becoming a pathogen rather than a commensal of the skin.

Prevention of urogenital infections in girls depends on a healthy vaginal microbiota. Bacterial vaginosis requires the establishment of overgrowth by Gardnerella vaginalis and Peptostreptococcus anaerobius that can only occur if the resident microbiota is unable to control the proliferation of these bacteria. Only if the microbiota of the perineum, urethra, and bladder will allow potential urinary tract infection pathogens access to epithelial attachment sites can infection become established.

A last topic for this column is the role of the microbiota in autoimmune diseases. In particular, I find it fascinating to learn that aberrant, unstable intestinal microbiota can lead to a leaky intestinal mucosal barrier. Combined with inadequate innate immune responses in the gut, progression may occur that allows antigens from microbes that cross-react with antigens of self in the pancreas to stimulate autoimmune antibodies. Similar pathogenic mechanisms may contribute to inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and other autoimmune diseases.

I anticipate future research will establish the makeup of a healthy microbiota associated with protection from the diseases mentioned here. With that knowledge, the next efforts in research will focus on how to convert an unhealthy microbiota to a healthy one. If the efforts succeed, I see new promising treatments in the future.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. The microbiome research at the Rochester General Hospital Research Institute is supported by the National Institutes of Health and the National Institute for Deafness and Communication Disorders. To comment, e-mail him at pdnews@ frontlinemedcom.com.

Microbiome refers to all the microbial life that exists in a specific niche. In the case of humans that means a lot of bacteria, viruses, fungi, parasites, and a very old class of single-celled organisms called archaea. The organisms include commensals and pathogenic microorganisms. Many articles distinguish "microbiome" and "microbiota" to differentiate the collective genomes of the microorganisms or the microorganisms themselves, respectively. However, these terms are largely synonymous.

A number of advances have allowed scientists to make major advances in understanding the microbiome. Specifically, we now have the molecular tools to perform gene expression analysis for an entire microbial community in the new discipline of metagenomics and analyze the massive results with new methods of mathematical analysis.

The human body contains over 10 times more microorganisms than human cells. The existence of a remarkably diverse and enormously large microbial world on us and in us first began to come to light in the late 1990s. We are learning more and more about the individual locations of the human host that have different populations of microbes and about differences among humans that contribute to or account for susceptibility to infectious diseases as well as autoimmune diseases and even obesity and cancer.

The nasopharyngeal microbiome has become an area of research by our group led by Qingfu Xu, Ph.D., at the Rochester (N.Y.) General Hospital Research Institute in collaboration with Melinda M. Pettigrew, Ph.D., at the Yale School of Public Health, New Haven, Conn., and Dr. Janet R. Casey at Legacy Pediatrics, also in Rochester. The traditional view of the immune system is undergoing reassessment as we learn that our microbiota has coevolved with our immune system, and each exerts influence over the other. Our group has a special interest in the impact of the nasopharyngeal microbiome on the innate immune response in that physiologic niche, and the way the innate immune system modifies the microbiome. With a special interest in the bacteria that cause respiratory infections such as acute otitis media, acute sinusitis, bronchopneumonia, and pneumonia, we have identified how microbes like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis compete and synergize in the nasopharynx to cause infections.

Also, we seek to better understand how respiratory viruses like respiratory syncytial virus (RSV), influenzae, parainfluenzae, rhinovirus, and others facilitate the overgrowth of S. pneumoniae, H. flu, and M. catarrhalis in the nose such that they convert from commensals to pathogens. But the synergy goes both ways, as we have recently found that S. pneumoniae facilitates upper respiratory viral infections.

Up to now most of the work on the human microbiome has focused on the gut, and nearly all studies have occurred in adults. Perhaps readers are aware of the use of "fecal microbiota transplantation" as a treatment/cure for Clostridium difficile infection. Unhealthy gut microbiota in premature neonates are a major contributing factor in necrotizing enterocolitis.

For decades, physicians have been taught that obesity is a problem derived from excessive caloric intake and inadequate caloric consumption through activity, plus vaguely defined differences in "metabolism." As a consequence, we checked for hypothyroidism � I never found a case. New research has shown that there is a difference in the "metabolism" of obese patients, but the difference is how the individual gut microbiota metabolizes our food. It turns out the thinner individuals have a microbiota that is less efficient in breaking down the food we ingest to allow efficient absorption into the bloodstream, whereas obese individuals have a more efficient microbiota that facilitates absorption of a greater percentage of the proteins, carbohydrates, and fats that are ingested. So the pathway to treatment of obesity may lie in the study of the microbiome!

It turns out that the microbiota of the skin is highly diverse. The microbiota colonizing the antecubital fossa is different from that of the forearm or biceps or axillae. When atopic dermatitis flares, it is often in the antecubital fossa, and it is caused by overgrowth of Staphylococcus aureus. The microbiome of a patient with atopic dermatitis is different from that of a person without atopic dermatitis, and the former microbiota is more permissive to S. aureus becoming a pathogen rather than a commensal of the skin.

Prevention of urogenital infections in girls depends on a healthy vaginal microbiota. Bacterial vaginosis requires the establishment of overgrowth by Gardnerella vaginalis and Peptostreptococcus anaerobius that can only occur if the resident microbiota is unable to control the proliferation of these bacteria. Only if the microbiota of the perineum, urethra, and bladder will allow potential urinary tract infection pathogens access to epithelial attachment sites can infection become established.

A last topic for this column is the role of the microbiota in autoimmune diseases. In particular, I find it fascinating to learn that aberrant, unstable intestinal microbiota can lead to a leaky intestinal mucosal barrier. Combined with inadequate innate immune responses in the gut, progression may occur that allows antigens from microbes that cross-react with antigens of self in the pancreas to stimulate autoimmune antibodies. Similar pathogenic mechanisms may contribute to inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and other autoimmune diseases.

I anticipate future research will establish the makeup of a healthy microbiota associated with protection from the diseases mentioned here. With that knowledge, the next efforts in research will focus on how to convert an unhealthy microbiota to a healthy one. If the efforts succeed, I see new promising treatments in the future.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. The microbiome research at the Rochester General Hospital Research Institute is supported by the National Institutes of Health and the National Institute for Deafness and Communication Disorders. To comment, e-mail him at pdnews@ frontlinemedcom.com.

Microbiome refers to all the microbial life that exists in a specific niche. In the case of humans that means a lot of bacteria, viruses, fungi, parasites, and a very old class of single-celled organisms called archaea. The organisms include commensals and pathogenic microorganisms. Many articles distinguish "microbiome" and "microbiota" to differentiate the collective genomes of the microorganisms or the microorganisms themselves, respectively. However, these terms are largely synonymous.

A number of advances have allowed scientists to make major advances in understanding the microbiome. Specifically, we now have the molecular tools to perform gene expression analysis for an entire microbial community in the new discipline of metagenomics and analyze the massive results with new methods of mathematical analysis.

The human body contains over 10 times more microorganisms than human cells. The existence of a remarkably diverse and enormously large microbial world on us and in us first began to come to light in the late 1990s. We are learning more and more about the individual locations of the human host that have different populations of microbes and about differences among humans that contribute to or account for susceptibility to infectious diseases as well as autoimmune diseases and even obesity and cancer.

The nasopharyngeal microbiome has become an area of research by our group led by Qingfu Xu, Ph.D., at the Rochester (N.Y.) General Hospital Research Institute in collaboration with Melinda M. Pettigrew, Ph.D., at the Yale School of Public Health, New Haven, Conn., and Dr. Janet R. Casey at Legacy Pediatrics, also in Rochester. The traditional view of the immune system is undergoing reassessment as we learn that our microbiota has coevolved with our immune system, and each exerts influence over the other. Our group has a special interest in the impact of the nasopharyngeal microbiome on the innate immune response in that physiologic niche, and the way the innate immune system modifies the microbiome. With a special interest in the bacteria that cause respiratory infections such as acute otitis media, acute sinusitis, bronchopneumonia, and pneumonia, we have identified how microbes like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis compete and synergize in the nasopharynx to cause infections.

Also, we seek to better understand how respiratory viruses like respiratory syncytial virus (RSV), influenzae, parainfluenzae, rhinovirus, and others facilitate the overgrowth of S. pneumoniae, H. flu, and M. catarrhalis in the nose such that they convert from commensals to pathogens. But the synergy goes both ways, as we have recently found that S. pneumoniae facilitates upper respiratory viral infections.

Up to now most of the work on the human microbiome has focused on the gut, and nearly all studies have occurred in adults. Perhaps readers are aware of the use of "fecal microbiota transplantation" as a treatment/cure for Clostridium difficile infection. Unhealthy gut microbiota in premature neonates are a major contributing factor in necrotizing enterocolitis.

For decades, physicians have been taught that obesity is a problem derived from excessive caloric intake and inadequate caloric consumption through activity, plus vaguely defined differences in "metabolism." As a consequence, we checked for hypothyroidism � I never found a case. New research has shown that there is a difference in the "metabolism" of obese patients, but the difference is how the individual gut microbiota metabolizes our food. It turns out the thinner individuals have a microbiota that is less efficient in breaking down the food we ingest to allow efficient absorption into the bloodstream, whereas obese individuals have a more efficient microbiota that facilitates absorption of a greater percentage of the proteins, carbohydrates, and fats that are ingested. So the pathway to treatment of obesity may lie in the study of the microbiome!

It turns out that the microbiota of the skin is highly diverse. The microbiota colonizing the antecubital fossa is different from that of the forearm or biceps or axillae. When atopic dermatitis flares, it is often in the antecubital fossa, and it is caused by overgrowth of Staphylococcus aureus. The microbiome of a patient with atopic dermatitis is different from that of a person without atopic dermatitis, and the former microbiota is more permissive to S. aureus becoming a pathogen rather than a commensal of the skin.

Prevention of urogenital infections in girls depends on a healthy vaginal microbiota. Bacterial vaginosis requires the establishment of overgrowth by Gardnerella vaginalis and Peptostreptococcus anaerobius that can only occur if the resident microbiota is unable to control the proliferation of these bacteria. Only if the microbiota of the perineum, urethra, and bladder will allow potential urinary tract infection pathogens access to epithelial attachment sites can infection become established.

A last topic for this column is the role of the microbiota in autoimmune diseases. In particular, I find it fascinating to learn that aberrant, unstable intestinal microbiota can lead to a leaky intestinal mucosal barrier. Combined with inadequate innate immune responses in the gut, progression may occur that allows antigens from microbes that cross-react with antigens of self in the pancreas to stimulate autoimmune antibodies. Similar pathogenic mechanisms may contribute to inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and other autoimmune diseases.

I anticipate future research will establish the makeup of a healthy microbiota associated with protection from the diseases mentioned here. With that knowledge, the next efforts in research will focus on how to convert an unhealthy microbiota to a healthy one. If the efforts succeed, I see new promising treatments in the future.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. The microbiome research at the Rochester General Hospital Research Institute is supported by the National Institutes of Health and the National Institute for Deafness and Communication Disorders. To comment, e-mail him at pdnews@ frontlinemedcom.com.

Red blood cell culture showing
Staphylococcus infection
Credit: Bill Branson

The US Food and Drug Administration (FDA) has approved the first mass spectrometer system for automated identification of bacteria and yeasts that are known to cause serious illnesses in humans.

The system, called VITEK MS, can identify 193 different microorganisms and perform up to 192 different tests, each of which takes about 1 minute.

The VITEK MS can identify yeasts and bacteria associated with skin infections, pneumonia, meningitis, and bloodstream infections.

Patients whose immune systems are compromised or weakened by HIV/AIDS, cancer treatment, or antirejection therapy following transplants are particularly vulnerable to these infections.

“The ability for laboratories to use 1 device to identify almost 200 different microorganisms is a significant advance in the timely identification of pathogenic microorganisms,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health at FDA’s Center for Devices and Radiological Health.

The VITEK MS incorporates a technology called matrix-assisted laser desorption/ionization–time of flight mass spectrometry. The technology uses a laser to break yeast and bacteria specimens into small particles that form a pattern unique to the microorganism.

The VITEK MS automatically compares the microorganism pattern to 193 known yeasts and bacteria in the system’s database to identify the microorganism.

Compared to other identification methods that require abundant organism growth for testing, mass spectrometry requires only a small amount of yeast or bacterial growth.

So testing can start as soon as growth is visible, generally within 18 to 24 hours. Traditional methods can take up to 5 days to produce the same identification results.

The FDA reviewed the VITEK MS through its de novo classification process, a regulatory pathway for some novel, low-to-moderate-risk medical devices that are not substantially equivalent to an already legally marketed device.

The FDA based its decision on the results of a study of 7068 microorganisms. When compared to sequencing and biochemical testing, the VITEK MS correctly identified the scientific group or family 93.6% of the time (with 87.5% of microorganisms identified to species level).

The system provided a “no identification” result for 3.2% of the microorganisms in the study, 0.8% of the test results were incorrect, and 2.4% were low discrimination with no correct result.

The VITEK MS is manufactured by bioMerieux, Inc., located in Durham, North Carolina.

Red blood cell culture showing
Staphylococcus infection
Credit: Bill Branson

The US Food and Drug Administration (FDA) has approved the first mass spectrometer system for automated identification of bacteria and yeasts that are known to cause serious illnesses in humans.

The system, called VITEK MS, can identify 193 different microorganisms and perform up to 192 different tests, each of which takes about 1 minute.

The VITEK MS can identify yeasts and bacteria associated with skin infections, pneumonia, meningitis, and bloodstream infections.

Patients whose immune systems are compromised or weakened by HIV/AIDS, cancer treatment, or antirejection therapy following transplants are particularly vulnerable to these infections.

“The ability for laboratories to use 1 device to identify almost 200 different microorganisms is a significant advance in the timely identification of pathogenic microorganisms,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health at FDA’s Center for Devices and Radiological Health.

The VITEK MS incorporates a technology called matrix-assisted laser desorption/ionization–time of flight mass spectrometry. The technology uses a laser to break yeast and bacteria specimens into small particles that form a pattern unique to the microorganism.

The VITEK MS automatically compares the microorganism pattern to 193 known yeasts and bacteria in the system’s database to identify the microorganism.

Compared to other identification methods that require abundant organism growth for testing, mass spectrometry requires only a small amount of yeast or bacterial growth.

So testing can start as soon as growth is visible, generally within 18 to 24 hours. Traditional methods can take up to 5 days to produce the same identification results.

The FDA reviewed the VITEK MS through its de novo classification process, a regulatory pathway for some novel, low-to-moderate-risk medical devices that are not substantially equivalent to an already legally marketed device.

The FDA based its decision on the results of a study of 7068 microorganisms. When compared to sequencing and biochemical testing, the VITEK MS correctly identified the scientific group or family 93.6% of the time (with 87.5% of microorganisms identified to species level).

The system provided a “no identification” result for 3.2% of the microorganisms in the study, 0.8% of the test results were incorrect, and 2.4% were low discrimination with no correct result.

The VITEK MS is manufactured by bioMerieux, Inc., located in Durham, North Carolina.

Red blood cell culture showing
Staphylococcus infection
Credit: Bill Branson

The US Food and Drug Administration (FDA) has approved the first mass spectrometer system for automated identification of bacteria and yeasts that are known to cause serious illnesses in humans.

The system, called VITEK MS, can identify 193 different microorganisms and perform up to 192 different tests, each of which takes about 1 minute.

The VITEK MS can identify yeasts and bacteria associated with skin infections, pneumonia, meningitis, and bloodstream infections.

Patients whose immune systems are compromised or weakened by HIV/AIDS, cancer treatment, or antirejection therapy following transplants are particularly vulnerable to these infections.

“The ability for laboratories to use 1 device to identify almost 200 different microorganisms is a significant advance in the timely identification of pathogenic microorganisms,” said Alberto Gutierrez, PhD, director of the Office of In Vitro Diagnostics and Radiological Health at FDA’s Center for Devices and Radiological Health.

The VITEK MS incorporates a technology called matrix-assisted laser desorption/ionization–time of flight mass spectrometry. The technology uses a laser to break yeast and bacteria specimens into small particles that form a pattern unique to the microorganism.

The VITEK MS automatically compares the microorganism pattern to 193 known yeasts and bacteria in the system’s database to identify the microorganism.

Compared to other identification methods that require abundant organism growth for testing, mass spectrometry requires only a small amount of yeast or bacterial growth.

So testing can start as soon as growth is visible, generally within 18 to 24 hours. Traditional methods can take up to 5 days to produce the same identification results.

The FDA reviewed the VITEK MS through its de novo classification process, a regulatory pathway for some novel, low-to-moderate-risk medical devices that are not substantially equivalent to an already legally marketed device.

The FDA based its decision on the results of a study of 7068 microorganisms. When compared to sequencing and biochemical testing, the VITEK MS correctly identified the scientific group or family 93.6% of the time (with 87.5% of microorganisms identified to species level).

The system provided a “no identification” result for 3.2% of the microorganisms in the study, 0.8% of the test results were incorrect, and 2.4% were low discrimination with no correct result.

The VITEK MS is manufactured by bioMerieux, Inc., located in Durham, North Carolina.

Carmen Bugan read her poems to her family. Her father had been imprisoned by Securitate, the Romanian secret police, for anticommunist rhetoric that he distributed on leaflets to people’s mailboxes. Securitate tracked him down by examining the leaflets for identifying typescript that they linked to one of his typewriters. He buried his other typewriter in the garden to escape detection. He would dig it up when he wanted to write serious anticommunist literature, then rebury it again in the garden.

"It is not important that the poem stays or goes," Carmen writes. "I discover a way to relieve our family’s suffering even though when I read the poems to Mom and my sister it seems that I create more pain at first.

"Mom loves the words, loves explanations of feelings to negotiate pain, and I can provide this for her. My sister says her feelings are exteriorized, articulated by the emotions in the poem and I can help bring things out" ("Burying the Typewriter," Minneapolis: Graywolf Press, 2012, p. 124).

Carmen created a poetic narrative to help her family manage their suffering. In this way, she helped her family become close and share a sense of belonging together. Carmen was able to transmute the family’s experience of trauma into a story that articulated their survival. Her poems became a written narrative of her family’s history. Resilience was created and passed along through the generations. This is the intergenerational transmission of resilience.

Intergenerational transmission has been shown in trauma; antisocial behavior; violence; religion; politics; substance abuse (J. Res. Adolesc. 1995;5:225-52); depression (J. Fam. Psychol. 2003;17:545-56); attachment (Psychol. Bull. 1995;117:387-403); perfectionism (J. Fam. Psychol. 2005;19:358-66); poverty; being on welfare; teenage pregnancy; education; and family life trajectories ("Intergenerational Transmission of Behavioral Patterns: Similarity of Parents’ and Children’s Family-Life Trajectories," Netherlands Interdisciplinary Demographical Institute, The Hague, 2006).

In short, there is evidence for the intergenerational transmission of everything bad. It is time to create evidence of the intergenerational transmission of resilience.

Researchers who study intergenerational legacies have discovered that children who know the most about their families have a strong sense of control over their lives, higher self-esteem, and the strongest "intergenerational self," compared with children who know less about their families. Marshall P. Duke, Ph.D., and his colleagues developed a measure called "Do You Know?" that asks children questions about their family. Examples of questions are "Do you know where your grandparents grew up? Do you know where your mom and dad went to high school?" (Psychotherapy 2008;45,268-72).

Dr. Duke identifies three common family narratives:

• The ascending family narrative: "Son, when we came to this country, we had nothing. Our family worked. We opened a store. Your grandfather went to high school. Your father went to college. And now you ... "

• The descending narrative: "Sweetheart, we used to have it all. Then we lost everything."

• The oscillating family narrative: "Dear, let me tell you, we’ve had ups and downs in our family. We built a family business. Your grandfather was a pillar of the community. Your mother was on the board of the hospital. But we also had setbacks. You had an uncle who was once arrested. We had a house burn down. Your father lost a job. But no matter what happened, we always stuck together as a family."

Healing narratives are prominent in American Indian and folk medicine traditions but also exist in modern medicine. In psychiatry, one of the tenets of the Recovery Movement is to focus on strengths and a positive sense of identity that is not linked to a psychiatric diagnosis. Communities such as Alcoholics Anonymous, Narcotics Anonymous, and Al-Anon foster resilience through communion and sharing. Narrative therapy, developed by Australian therapist Michael White and his collaborator David Epston of New Zealand in 1989 (Context 2009;105:57-58), is a type of psychotherapy that seeks and promotes a healthy, successful personal narrative to replace a dominant repressive illness narrative.

How can the psychiatrist, during a routine office visit, help patients develop a positive, resilient family narrative? Patients can benefit from an exploration of patterns of behavior or ways of relating that might have been passed down through the generations. Understanding the motivations, difficulties, and aspirations of their parents and grandparents provides patients with a historical perspective on their current difficulties. If patients can understand their difficulties in the context of the larger family system, they develop a more nuanced and less harsh understanding of the challenges they face.

When Sarah presented with depression, it became clear that her family dynamics were troubling. She felt happy and competent at work. In passing, she remarked that she felt intimidated by her teenage daughter, so I inquired about her family system to see what generational narratives might be at play. Over several sessions, we uncovered the covert negative messages she had received as a child. She had fought not to pass these on to her children, by being "more permissive and hands off." In response, her children chided her for being overly anxious, sensing that she was conflicted and troubled, although the source remained mysterious to everyone. Using a family systems approach to understand the intergenerational inheritance, the family came to understand the strong generational forces at work. This lessened her guilt and anguish, and increased the children’s understanding and empathy for their mother.

A family systems approach allows a family legacy to be revealed, reworked, and rewritten. A new family narrative that carries the family forward and allows the telling of a positive family narrative can be created. We can guide patients to find the positive aspects of their family stories and thus promote family resilience.

Here are a few questions we should ask our patients: "What did your parents teach you that you want to pass along? What values did your parents have? How have you lived or not lived those values? How has the relationship with your parents affected your relationship with your children? How did your parents resolve problems, and how do you resolve problems? How do your children resolve problems? What were the motivations that drove your parents? What countries do your relatives come from? What was it like for them growing up? Did they experience deprivation? War? How has that affected you and your siblings? Are there family secrets? What do you want to take away from this legacy? What do you want to pass along to the next generation?" Asking these questions allows the patient to see their current struggles and conflicts with a longer lens.

The novelist Laila Lalami, who did not know her mother, was surprised when her husband gave her a DNA test kit so that she could find out her genetic inheritance. When the results came in, Laila remarked: "So it was that, in just a few moments, I found myself returning to those childhood days when I used to dream up different families, and different fates, for my mother. What science gave me, in the end, was no different from what my own imagination had fed me for many years – stories. The search was not over. The search would never be over. And not even science could help fill out the abyss I grew up with. Only stories could." ("My Fictional Grandparents," The New York Times, July 26, 2013)

We are all part of our own family narrative that stretches back in time and forward into the future. We are creating a family story for ourselves in the present that our children will carry forward with them into their future. These narratives have many strands. Let’s help our patients pick out the strands that help them build family resilience.

Dr. Heru is with the department of psychiatry at the University of Colorado at Denver, Aurora. She is editor of the recently published book, "Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals" (New York: Routledge, 2013).

Carmen Bugan read her poems to her family. Her father had been imprisoned by Securitate, the Romanian secret police, for anticommunist rhetoric that he distributed on leaflets to people’s mailboxes. Securitate tracked him down by examining the leaflets for identifying typescript that they linked to one of his typewriters. He buried his other typewriter in the garden to escape detection. He would dig it up when he wanted to write serious anticommunist literature, then rebury it again in the garden.

"It is not important that the poem stays or goes," Carmen writes. "I discover a way to relieve our family’s suffering even though when I read the poems to Mom and my sister it seems that I create more pain at first.

"Mom loves the words, loves explanations of feelings to negotiate pain, and I can provide this for her. My sister says her feelings are exteriorized, articulated by the emotions in the poem and I can help bring things out" ("Burying the Typewriter," Minneapolis: Graywolf Press, 2012, p. 124).

Carmen created a poetic narrative to help her family manage their suffering. In this way, she helped her family become close and share a sense of belonging together. Carmen was able to transmute the family’s experience of trauma into a story that articulated their survival. Her poems became a written narrative of her family’s history. Resilience was created and passed along through the generations. This is the intergenerational transmission of resilience.

Intergenerational transmission has been shown in trauma; antisocial behavior; violence; religion; politics; substance abuse (J. Res. Adolesc. 1995;5:225-52); depression (J. Fam. Psychol. 2003;17:545-56); attachment (Psychol. Bull. 1995;117:387-403); perfectionism (J. Fam. Psychol. 2005;19:358-66); poverty; being on welfare; teenage pregnancy; education; and family life trajectories ("Intergenerational Transmission of Behavioral Patterns: Similarity of Parents’ and Children’s Family-Life Trajectories," Netherlands Interdisciplinary Demographical Institute, The Hague, 2006).

In short, there is evidence for the intergenerational transmission of everything bad. It is time to create evidence of the intergenerational transmission of resilience.

Researchers who study intergenerational legacies have discovered that children who know the most about their families have a strong sense of control over their lives, higher self-esteem, and the strongest "intergenerational self," compared with children who know less about their families. Marshall P. Duke, Ph.D., and his colleagues developed a measure called "Do You Know?" that asks children questions about their family. Examples of questions are "Do you know where your grandparents grew up? Do you know where your mom and dad went to high school?" (Psychotherapy 2008;45,268-72).

Dr. Duke identifies three common family narratives:

• The ascending family narrative: "Son, when we came to this country, we had nothing. Our family worked. We opened a store. Your grandfather went to high school. Your father went to college. And now you ... "

• The descending narrative: "Sweetheart, we used to have it all. Then we lost everything."

• The oscillating family narrative: "Dear, let me tell you, we’ve had ups and downs in our family. We built a family business. Your grandfather was a pillar of the community. Your mother was on the board of the hospital. But we also had setbacks. You had an uncle who was once arrested. We had a house burn down. Your father lost a job. But no matter what happened, we always stuck together as a family."

Healing narratives are prominent in American Indian and folk medicine traditions but also exist in modern medicine. In psychiatry, one of the tenets of the Recovery Movement is to focus on strengths and a positive sense of identity that is not linked to a psychiatric diagnosis. Communities such as Alcoholics Anonymous, Narcotics Anonymous, and Al-Anon foster resilience through communion and sharing. Narrative therapy, developed by Australian therapist Michael White and his collaborator David Epston of New Zealand in 1989 (Context 2009;105:57-58), is a type of psychotherapy that seeks and promotes a healthy, successful personal narrative to replace a dominant repressive illness narrative.

How can the psychiatrist, during a routine office visit, help patients develop a positive, resilient family narrative? Patients can benefit from an exploration of patterns of behavior or ways of relating that might have been passed down through the generations. Understanding the motivations, difficulties, and aspirations of their parents and grandparents provides patients with a historical perspective on their current difficulties. If patients can understand their difficulties in the context of the larger family system, they develop a more nuanced and less harsh understanding of the challenges they face.

When Sarah presented with depression, it became clear that her family dynamics were troubling. She felt happy and competent at work. In passing, she remarked that she felt intimidated by her teenage daughter, so I inquired about her family system to see what generational narratives might be at play. Over several sessions, we uncovered the covert negative messages she had received as a child. She had fought not to pass these on to her children, by being "more permissive and hands off." In response, her children chided her for being overly anxious, sensing that she was conflicted and troubled, although the source remained mysterious to everyone. Using a family systems approach to understand the intergenerational inheritance, the family came to understand the strong generational forces at work. This lessened her guilt and anguish, and increased the children’s understanding and empathy for their mother.

A family systems approach allows a family legacy to be revealed, reworked, and rewritten. A new family narrative that carries the family forward and allows the telling of a positive family narrative can be created. We can guide patients to find the positive aspects of their family stories and thus promote family resilience.

Here are a few questions we should ask our patients: "What did your parents teach you that you want to pass along? What values did your parents have? How have you lived or not lived those values? How has the relationship with your parents affected your relationship with your children? How did your parents resolve problems, and how do you resolve problems? How do your children resolve problems? What were the motivations that drove your parents? What countries do your relatives come from? What was it like for them growing up? Did they experience deprivation? War? How has that affected you and your siblings? Are there family secrets? What do you want to take away from this legacy? What do you want to pass along to the next generation?" Asking these questions allows the patient to see their current struggles and conflicts with a longer lens.

The novelist Laila Lalami, who did not know her mother, was surprised when her husband gave her a DNA test kit so that she could find out her genetic inheritance. When the results came in, Laila remarked: "So it was that, in just a few moments, I found myself returning to those childhood days when I used to dream up different families, and different fates, for my mother. What science gave me, in the end, was no different from what my own imagination had fed me for many years – stories. The search was not over. The search would never be over. And not even science could help fill out the abyss I grew up with. Only stories could." ("My Fictional Grandparents," The New York Times, July 26, 2013)

We are all part of our own family narrative that stretches back in time and forward into the future. We are creating a family story for ourselves in the present that our children will carry forward with them into their future. These narratives have many strands. Let’s help our patients pick out the strands that help them build family resilience.

Dr. Heru is with the department of psychiatry at the University of Colorado at Denver, Aurora. She is editor of the recently published book, "Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals" (New York: Routledge, 2013).

Carmen Bugan read her poems to her family. Her father had been imprisoned by Securitate, the Romanian secret police, for anticommunist rhetoric that he distributed on leaflets to people’s mailboxes. Securitate tracked him down by examining the leaflets for identifying typescript that they linked to one of his typewriters. He buried his other typewriter in the garden to escape detection. He would dig it up when he wanted to write serious anticommunist literature, then rebury it again in the garden.

"It is not important that the poem stays or goes," Carmen writes. "I discover a way to relieve our family’s suffering even though when I read the poems to Mom and my sister it seems that I create more pain at first.

"Mom loves the words, loves explanations of feelings to negotiate pain, and I can provide this for her. My sister says her feelings are exteriorized, articulated by the emotions in the poem and I can help bring things out" ("Burying the Typewriter," Minneapolis: Graywolf Press, 2012, p. 124).

Carmen created a poetic narrative to help her family manage their suffering. In this way, she helped her family become close and share a sense of belonging together. Carmen was able to transmute the family’s experience of trauma into a story that articulated their survival. Her poems became a written narrative of her family’s history. Resilience was created and passed along through the generations. This is the intergenerational transmission of resilience.

Intergenerational transmission has been shown in trauma; antisocial behavior; violence; religion; politics; substance abuse (J. Res. Adolesc. 1995;5:225-52); depression (J. Fam. Psychol. 2003;17:545-56); attachment (Psychol. Bull. 1995;117:387-403); perfectionism (J. Fam. Psychol. 2005;19:358-66); poverty; being on welfare; teenage pregnancy; education; and family life trajectories ("Intergenerational Transmission of Behavioral Patterns: Similarity of Parents’ and Children’s Family-Life Trajectories," Netherlands Interdisciplinary Demographical Institute, The Hague, 2006).

In short, there is evidence for the intergenerational transmission of everything bad. It is time to create evidence of the intergenerational transmission of resilience.

Researchers who study intergenerational legacies have discovered that children who know the most about their families have a strong sense of control over their lives, higher self-esteem, and the strongest "intergenerational self," compared with children who know less about their families. Marshall P. Duke, Ph.D., and his colleagues developed a measure called "Do You Know?" that asks children questions about their family. Examples of questions are "Do you know where your grandparents grew up? Do you know where your mom and dad went to high school?" (Psychotherapy 2008;45,268-72).

Dr. Duke identifies three common family narratives:

• The ascending family narrative: "Son, when we came to this country, we had nothing. Our family worked. We opened a store. Your grandfather went to high school. Your father went to college. And now you ... "

• The descending narrative: "Sweetheart, we used to have it all. Then we lost everything."

• The oscillating family narrative: "Dear, let me tell you, we’ve had ups and downs in our family. We built a family business. Your grandfather was a pillar of the community. Your mother was on the board of the hospital. But we also had setbacks. You had an uncle who was once arrested. We had a house burn down. Your father lost a job. But no matter what happened, we always stuck together as a family."

Healing narratives are prominent in American Indian and folk medicine traditions but also exist in modern medicine. In psychiatry, one of the tenets of the Recovery Movement is to focus on strengths and a positive sense of identity that is not linked to a psychiatric diagnosis. Communities such as Alcoholics Anonymous, Narcotics Anonymous, and Al-Anon foster resilience through communion and sharing. Narrative therapy, developed by Australian therapist Michael White and his collaborator David Epston of New Zealand in 1989 (Context 2009;105:57-58), is a type of psychotherapy that seeks and promotes a healthy, successful personal narrative to replace a dominant repressive illness narrative.

How can the psychiatrist, during a routine office visit, help patients develop a positive, resilient family narrative? Patients can benefit from an exploration of patterns of behavior or ways of relating that might have been passed down through the generations. Understanding the motivations, difficulties, and aspirations of their parents and grandparents provides patients with a historical perspective on their current difficulties. If patients can understand their difficulties in the context of the larger family system, they develop a more nuanced and less harsh understanding of the challenges they face.

When Sarah presented with depression, it became clear that her family dynamics were troubling. She felt happy and competent at work. In passing, she remarked that she felt intimidated by her teenage daughter, so I inquired about her family system to see what generational narratives might be at play. Over several sessions, we uncovered the covert negative messages she had received as a child. She had fought not to pass these on to her children, by being "more permissive and hands off." In response, her children chided her for being overly anxious, sensing that she was conflicted and troubled, although the source remained mysterious to everyone. Using a family systems approach to understand the intergenerational inheritance, the family came to understand the strong generational forces at work. This lessened her guilt and anguish, and increased the children’s understanding and empathy for their mother.

A family systems approach allows a family legacy to be revealed, reworked, and rewritten. A new family narrative that carries the family forward and allows the telling of a positive family narrative can be created. We can guide patients to find the positive aspects of their family stories and thus promote family resilience.

Here are a few questions we should ask our patients: "What did your parents teach you that you want to pass along? What values did your parents have? How have you lived or not lived those values? How has the relationship with your parents affected your relationship with your children? How did your parents resolve problems, and how do you resolve problems? How do your children resolve problems? What were the motivations that drove your parents? What countries do your relatives come from? What was it like for them growing up? Did they experience deprivation? War? How has that affected you and your siblings? Are there family secrets? What do you want to take away from this legacy? What do you want to pass along to the next generation?" Asking these questions allows the patient to see their current struggles and conflicts with a longer lens.

The novelist Laila Lalami, who did not know her mother, was surprised when her husband gave her a DNA test kit so that she could find out her genetic inheritance. When the results came in, Laila remarked: "So it was that, in just a few moments, I found myself returning to those childhood days when I used to dream up different families, and different fates, for my mother. What science gave me, in the end, was no different from what my own imagination had fed me for many years – stories. The search was not over. The search would never be over. And not even science could help fill out the abyss I grew up with. Only stories could." ("My Fictional Grandparents," The New York Times, July 26, 2013)

We are all part of our own family narrative that stretches back in time and forward into the future. We are creating a family story for ourselves in the present that our children will carry forward with them into their future. These narratives have many strands. Let’s help our patients pick out the strands that help them build family resilience.

Dr. Heru is with the department of psychiatry at the University of Colorado at Denver, Aurora. She is editor of the recently published book, "Working With Families in Medical Settings: A Multidisciplinary Guide for Psychiatrists and Other Health Professionals" (New York: Routledge, 2013).

Drugs in vials
Credit: Bill Branson

The French National Health Authority’s Transparency Commission has granted market access for the antineoplastic drug pixantrone (Pixuvri).

The drug is intended for use as monotherapy to treat adult patients with aggressive B-cell non-Hodgkin lymphoma who have failed 2 or 3 prior lines of therapy.

Pixantrone has already gained conditional marketing authorization for this indication within the European Union.

In the fourth quarter of 2012, the drug was made available to patients in 8 countries—Sweden, Denmark, Finland, Austria, Norway, Germany, the UK, and the Netherlands.

And last month, pixantrone was granted market access in Italy.

Now, the drug’s developers, Cell Therapeutics Inc., announced that pixantrone has been granted market access in France.
 
The next steps in France’s pharmaceutical reimbursement process are inclusion on the list of medicines approved for hospital use and subsequent publication in the Journal Officiel. And Cell Therapeutics intends to pursue these final goals.

All registered pharmaceuticals in France are subjected to a process known as Evaluation of Therapeutic Benefit, with the resulting evaluation expressed as a classification between 1 and 6. 

The Transparency Commission rated pixantrone at level 5, which allows the drug to be included in the reimbursed drugs list for hospital use. The commission will reassess the rating for the drug within 2 years.

France’s authorization and the European Commission’s conditional marketing authorization are based on data from the phase 3 EXTEND PIX301 trial. Although pixantrone prompted positive results in this trial, the US Food and Drug Administration (FDA) has expressed concerns about the number of patients included.

In fact, the FDA rejected a new drug application for pixantrone in 2010. Cell Therapeutics later resubmitted an application for the drug but withdrew it in January of last year. The company has not confirmed plans to refile with the FDA.

As for the European Commission’s conditional approval of pixantrone, it will be renewed on a yearly basis until Cell Therapeutics fullfills its committment to

provide additional data on patients

treated with pixantrone who previously received rituximab. The company said it expects to

have the results of this research by mid-2015.

Pixantrone is a novel aza-anthracenedione that forms stable DNA adducts. The drug was designed so that it cannot bind iron and perpetuate oxygen radical production or form a long-lived hydroxyl metabolite—both of which are the putative mechanisms for anthracycline-induced acute and chronic cardiotoxicity.

For full prescribing information for pixantrone, including the safety and efficacy profile in the approved indication, visit www.pixuvri.eu.

Drugs in vials
Credit: Bill Branson

The French National Health Authority’s Transparency Commission has granted market access for the antineoplastic drug pixantrone (Pixuvri).

The drug is intended for use as monotherapy to treat adult patients with aggressive B-cell non-Hodgkin lymphoma who have failed 2 or 3 prior lines of therapy.

Pixantrone has already gained conditional marketing authorization for this indication within the European Union.

In the fourth quarter of 2012, the drug was made available to patients in 8 countries—Sweden, Denmark, Finland, Austria, Norway, Germany, the UK, and the Netherlands.

And last month, pixantrone was granted market access in Italy.

Now, the drug’s developers, Cell Therapeutics Inc., announced that pixantrone has been granted market access in France.
 
The next steps in France’s pharmaceutical reimbursement process are inclusion on the list of medicines approved for hospital use and subsequent publication in the Journal Officiel. And Cell Therapeutics intends to pursue these final goals.

All registered pharmaceuticals in France are subjected to a process known as Evaluation of Therapeutic Benefit, with the resulting evaluation expressed as a classification between 1 and 6. 

The Transparency Commission rated pixantrone at level 5, which allows the drug to be included in the reimbursed drugs list for hospital use. The commission will reassess the rating for the drug within 2 years.

France’s authorization and the European Commission’s conditional marketing authorization are based on data from the phase 3 EXTEND PIX301 trial. Although pixantrone prompted positive results in this trial, the US Food and Drug Administration (FDA) has expressed concerns about the number of patients included.

In fact, the FDA rejected a new drug application for pixantrone in 2010. Cell Therapeutics later resubmitted an application for the drug but withdrew it in January of last year. The company has not confirmed plans to refile with the FDA.

As for the European Commission’s conditional approval of pixantrone, it will be renewed on a yearly basis until Cell Therapeutics fullfills its committment to

provide additional data on patients

treated with pixantrone who previously received rituximab. The company said it expects to

have the results of this research by mid-2015.

Pixantrone is a novel aza-anthracenedione that forms stable DNA adducts. The drug was designed so that it cannot bind iron and perpetuate oxygen radical production or form a long-lived hydroxyl metabolite—both of which are the putative mechanisms for anthracycline-induced acute and chronic cardiotoxicity.

For full prescribing information for pixantrone, including the safety and efficacy profile in the approved indication, visit www.pixuvri.eu.

Drugs in vials
Credit: Bill Branson

The French National Health Authority’s Transparency Commission has granted market access for the antineoplastic drug pixantrone (Pixuvri).

The drug is intended for use as monotherapy to treat adult patients with aggressive B-cell non-Hodgkin lymphoma who have failed 2 or 3 prior lines of therapy.

Pixantrone has already gained conditional marketing authorization for this indication within the European Union.

In the fourth quarter of 2012, the drug was made available to patients in 8 countries—Sweden, Denmark, Finland, Austria, Norway, Germany, the UK, and the Netherlands.

And last month, pixantrone was granted market access in Italy.

Now, the drug’s developers, Cell Therapeutics Inc., announced that pixantrone has been granted market access in France.
 
The next steps in France’s pharmaceutical reimbursement process are inclusion on the list of medicines approved for hospital use and subsequent publication in the Journal Officiel. And Cell Therapeutics intends to pursue these final goals.

All registered pharmaceuticals in France are subjected to a process known as Evaluation of Therapeutic Benefit, with the resulting evaluation expressed as a classification between 1 and 6. 

The Transparency Commission rated pixantrone at level 5, which allows the drug to be included in the reimbursed drugs list for hospital use. The commission will reassess the rating for the drug within 2 years.

France’s authorization and the European Commission’s conditional marketing authorization are based on data from the phase 3 EXTEND PIX301 trial. Although pixantrone prompted positive results in this trial, the US Food and Drug Administration (FDA) has expressed concerns about the number of patients included.

In fact, the FDA rejected a new drug application for pixantrone in 2010. Cell Therapeutics later resubmitted an application for the drug but withdrew it in January of last year. The company has not confirmed plans to refile with the FDA.

As for the European Commission’s conditional approval of pixantrone, it will be renewed on a yearly basis until Cell Therapeutics fullfills its committment to

provide additional data on patients

treated with pixantrone who previously received rituximab. The company said it expects to

have the results of this research by mid-2015.

Pixantrone is a novel aza-anthracenedione that forms stable DNA adducts. The drug was designed so that it cannot bind iron and perpetuate oxygen radical production or form a long-lived hydroxyl metabolite—both of which are the putative mechanisms for anthracycline-induced acute and chronic cardiotoxicity.

For full prescribing information for pixantrone, including the safety and efficacy profile in the approved indication, visit www.pixuvri.eu.

SAN FRANCISCO – Postoperative troponin elevation and myocardial infarction both impact 5-year survival following vascular surgery procedures, the results of a large long-term study showed.

In fact, troponin elevation increased the hazard of death by 50% while myocardial infarction increased the hazard of death by nearly threefold, Dr. Jessica P. Simons reported at the annual meeting of the Society for Vascular Surgery. "Future studies are needed to assess the nature of this association as well as the utility of routine postoperative screening for myocardial ischemia," said Dr. Simons of the division of vascular and endovascular surgery at the University of Massachusetts, Worcester.

In a study that she presented on behalf of the Vascular Study Group of New England (VSGNE), Dr. Simons and her associates set out to determine the association of postoperative troponin elevation with long-term survival in patients undergoing vascular surgical procedures. "Postoperative myocardial infarction has been shown to impact short- and long-term mortality," she said. "In addition, troponin elevations have also been shown to negatively impact survival for a wide range of diagnoses. This has been seen in critical care medical literature and also in the general surgical population."

The researchers identified 16,363 VSGNE patients who underwent carotid revascularization, open AAA repair, endovascular AAA repair, or lower-extremity bypass between 2003 and 2011. The exposure variable of interest was postoperative myocardial ischemia, which was categorized as either no ischemia, troponin elevation, or myocardial infarction. The primary end point was survival during the first 5 years postoperatively. They used Kaplan-Meier analyses and Cox proportional hazards models to evaluate the effect of postoperative troponin elevation and myocardial infarction.

Of the 16,363 patients, 15,888 (97.1%) had no ischemia, 211 (1.3%) had troponin elevation, and 264 (1.6%) had myocardial infarction. When this was broken down by procedure type, open AAA had the highest rates of postoperative myocardial ischemia (9%), troponin elevation (3.9%), and myocardial infarction (5.1%), compared with carotid revascularization, endovascular aneurysm repair, and lower-extremity bypass.

The rate of 5-year survival for all procedures was 73% among those with no ischemia, 54% among those with troponin elevation, and 33% among those with myocardial infarction. This difference reached statistical significance with a P value of less than .0001. After adjusting for covariates, the researchers found a similar trend. In this analysis the rate of 5-year survival was 78% among those with no ischemia, 48% among those with troponin elevation, and 35% among those with myocardial infarction. This also reached statistical significance with a P value of less than .0001.

"We performed a subgroup analysis by procedure type, and the trend was the same across all procedure types," Dr. Simons said.

In Cox modeling the researchers found that postoperative ischemia in the form of a troponin elevation increased the hazard of death at 5 years by 45% (HR, 1.45; P =.01) while myocardial infarction nearly tripled the hazard of death (HR, 2.93; P =.0001).

"We have shown an association between postoperative myocardial ischemia and worse survival, but does postoperative myocardial ischemia worsen long-term survival, or does postoperative myocardial ischemia simply identify a high-risk subset of patients?" Dr. Simons asked. "If postoperative myocardial ischemia worsens long-term survival, then efforts should focus on better preoperative medical optimization and perioperative prevention of ischemia. If postoperative myocardial ischemia is simply identifying a high-risk subset of patients, then efforts should focus on better preoperative risk stratification and postoperative medical surveillance."

She concluded that postoperative myocardial ischemia, "whether a troponin elevation or a myocardial infarction, is associated with lower survival. This effect is seen across all procedure types and persists out to 5 years postoperatively."

Dr. Simons said she had no relevant financial disclosures.

[email protected]

SAN FRANCISCO – Postoperative troponin elevation and myocardial infarction both impact 5-year survival following vascular surgery procedures, the results of a large long-term study showed.

In fact, troponin elevation increased the hazard of death by 50% while myocardial infarction increased the hazard of death by nearly threefold, Dr. Jessica P. Simons reported at the annual meeting of the Society for Vascular Surgery. "Future studies are needed to assess the nature of this association as well as the utility of routine postoperative screening for myocardial ischemia," said Dr. Simons of the division of vascular and endovascular surgery at the University of Massachusetts, Worcester.

In a study that she presented on behalf of the Vascular Study Group of New England (VSGNE), Dr. Simons and her associates set out to determine the association of postoperative troponin elevation with long-term survival in patients undergoing vascular surgical procedures. "Postoperative myocardial infarction has been shown to impact short- and long-term mortality," she said. "In addition, troponin elevations have also been shown to negatively impact survival for a wide range of diagnoses. This has been seen in critical care medical literature and also in the general surgical population."

The researchers identified 16,363 VSGNE patients who underwent carotid revascularization, open AAA repair, endovascular AAA repair, or lower-extremity bypass between 2003 and 2011. The exposure variable of interest was postoperative myocardial ischemia, which was categorized as either no ischemia, troponin elevation, or myocardial infarction. The primary end point was survival during the first 5 years postoperatively. They used Kaplan-Meier analyses and Cox proportional hazards models to evaluate the effect of postoperative troponin elevation and myocardial infarction.

Of the 16,363 patients, 15,888 (97.1%) had no ischemia, 211 (1.3%) had troponin elevation, and 264 (1.6%) had myocardial infarction. When this was broken down by procedure type, open AAA had the highest rates of postoperative myocardial ischemia (9%), troponin elevation (3.9%), and myocardial infarction (5.1%), compared with carotid revascularization, endovascular aneurysm repair, and lower-extremity bypass.

The rate of 5-year survival for all procedures was 73% among those with no ischemia, 54% among those with troponin elevation, and 33% among those with myocardial infarction. This difference reached statistical significance with a P value of less than .0001. After adjusting for covariates, the researchers found a similar trend. In this analysis the rate of 5-year survival was 78% among those with no ischemia, 48% among those with troponin elevation, and 35% among those with myocardial infarction. This also reached statistical significance with a P value of less than .0001.

"We performed a subgroup analysis by procedure type, and the trend was the same across all procedure types," Dr. Simons said.

In Cox modeling the researchers found that postoperative ischemia in the form of a troponin elevation increased the hazard of death at 5 years by 45% (HR, 1.45; P =.01) while myocardial infarction nearly tripled the hazard of death (HR, 2.93; P =.0001).

"We have shown an association between postoperative myocardial ischemia and worse survival, but does postoperative myocardial ischemia worsen long-term survival, or does postoperative myocardial ischemia simply identify a high-risk subset of patients?" Dr. Simons asked. "If postoperative myocardial ischemia worsens long-term survival, then efforts should focus on better preoperative medical optimization and perioperative prevention of ischemia. If postoperative myocardial ischemia is simply identifying a high-risk subset of patients, then efforts should focus on better preoperative risk stratification and postoperative medical surveillance."

She concluded that postoperative myocardial ischemia, "whether a troponin elevation or a myocardial infarction, is associated with lower survival. This effect is seen across all procedure types and persists out to 5 years postoperatively."

Dr. Simons said she had no relevant financial disclosures.

[email protected]

SAN FRANCISCO – Postoperative troponin elevation and myocardial infarction both impact 5-year survival following vascular surgery procedures, the results of a large long-term study showed.

In fact, troponin elevation increased the hazard of death by 50% while myocardial infarction increased the hazard of death by nearly threefold, Dr. Jessica P. Simons reported at the annual meeting of the Society for Vascular Surgery. "Future studies are needed to assess the nature of this association as well as the utility of routine postoperative screening for myocardial ischemia," said Dr. Simons of the division of vascular and endovascular surgery at the University of Massachusetts, Worcester.

In a study that she presented on behalf of the Vascular Study Group of New England (VSGNE), Dr. Simons and her associates set out to determine the association of postoperative troponin elevation with long-term survival in patients undergoing vascular surgical procedures. "Postoperative myocardial infarction has been shown to impact short- and long-term mortality," she said. "In addition, troponin elevations have also been shown to negatively impact survival for a wide range of diagnoses. This has been seen in critical care medical literature and also in the general surgical population."

The researchers identified 16,363 VSGNE patients who underwent carotid revascularization, open AAA repair, endovascular AAA repair, or lower-extremity bypass between 2003 and 2011. The exposure variable of interest was postoperative myocardial ischemia, which was categorized as either no ischemia, troponin elevation, or myocardial infarction. The primary end point was survival during the first 5 years postoperatively. They used Kaplan-Meier analyses and Cox proportional hazards models to evaluate the effect of postoperative troponin elevation and myocardial infarction.

Of the 16,363 patients, 15,888 (97.1%) had no ischemia, 211 (1.3%) had troponin elevation, and 264 (1.6%) had myocardial infarction. When this was broken down by procedure type, open AAA had the highest rates of postoperative myocardial ischemia (9%), troponin elevation (3.9%), and myocardial infarction (5.1%), compared with carotid revascularization, endovascular aneurysm repair, and lower-extremity bypass.

The rate of 5-year survival for all procedures was 73% among those with no ischemia, 54% among those with troponin elevation, and 33% among those with myocardial infarction. This difference reached statistical significance with a P value of less than .0001. After adjusting for covariates, the researchers found a similar trend. In this analysis the rate of 5-year survival was 78% among those with no ischemia, 48% among those with troponin elevation, and 35% among those with myocardial infarction. This also reached statistical significance with a P value of less than .0001.

"We performed a subgroup analysis by procedure type, and the trend was the same across all procedure types," Dr. Simons said.

In Cox modeling the researchers found that postoperative ischemia in the form of a troponin elevation increased the hazard of death at 5 years by 45% (HR, 1.45; P =.01) while myocardial infarction nearly tripled the hazard of death (HR, 2.93; P =.0001).

"We have shown an association between postoperative myocardial ischemia and worse survival, but does postoperative myocardial ischemia worsen long-term survival, or does postoperative myocardial ischemia simply identify a high-risk subset of patients?" Dr. Simons asked. "If postoperative myocardial ischemia worsens long-term survival, then efforts should focus on better preoperative medical optimization and perioperative prevention of ischemia. If postoperative myocardial ischemia is simply identifying a high-risk subset of patients, then efforts should focus on better preoperative risk stratification and postoperative medical surveillance."

She concluded that postoperative myocardial ischemia, "whether a troponin elevation or a myocardial infarction, is associated with lower survival. This effect is seen across all procedure types and persists out to 5 years postoperatively."

Dr. Simons said she had no relevant financial disclosures.

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SAN FRANCISCO – One-third of perioperative deaths and complications after elective endovascular repair of abdominal aortic aneurysms occur post discharge, results from a large analysis showed.

"Improved predischarge surveillance and close postdischarge follow-up of identified high-risk patients may further improve 30-day outcomes after EVAR," Dr. Prateek K. Gupta said at the Society for Vascular Surgery annual meeting.

Outcome improvement in the field of aortic surgery, specifically endovascular repair of abdominal aortic aneurysms, "has received much attention," said Dr. Gupta of the department of surgery at the University of Wisconsin Hospital and Clinics, Madison. "With EVAR, the index hospital stay after aortic surgery has decreased significantly, leaving a need for better understanding of postdischarge outcomes, which is necessary to improve quality and reduce readmission rates with implementation of targeted outpatient interventions."

In an effort to examine postdischarge 30-day outcomes after elective EVAR, Dr. Gupta and his associates identified 11,229 patients from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database who underwent an elective EVAR for AAA between 2005 and 2010. The primary outcome of interest was postdischarge mortality, while the secondary outcome was postdischarge overall morbidity. The researchers performed univariate and multiple logistic regression analysis to assess factors associated with the primary and secondary study outcomes.

Of the 11,229 patient 83% were male and their mean age was 75 years. Dr. Gupta reported that 117 patients died within 30 days of EVAR, for a rate of 1%. Of these deaths, 31% occurred after hospital discharge, and the median time to death was 9 days. At the same time, 1,204 patients experienced complications within 30 days of EVAR, for a rate of 11%. Of these, 500 (40%) occurred post discharge, and the median time for a complication to occur was 3 days.

Only 20% of patients (7/36) who died post discharge experienced an in-hospital complication. Compared with patients who did not develop a postdischarge complication, those who had more than a sixfold likelihood of reoperation (20.4% vs. 3.1%, respectively; P less than .0001) and death (3.0% vs. 0.2%; P less than .0001) within 30 days of surgery.

Multivariable analysis revealed the following factors that were independently and significantly associated with postdischarge mortality: preoperative heart failure (adjusted odds ratio, 4.7), admission from a skilled nursing facility (AOR, 2.2), increase in age per year (AOR, 1.09), postdischarge renal failure requiring dialysis (AOR, 72.5), postdischarge cardiac arrest/MI (AOR, 46.6), and postdischarge pneumonia (AOR, 26.5).

Dr. Gupta reported that the 30-day postdischarge rate among patients admitted from a nursing facility or acute care was 2.5%. "In contrast to patients who survived after EVAR, patients who died post discharge were more likely to have been admitted from a nursing facility or acute care (13.9% vs. 1.8%; P less than .0001)," he said.

The 30-day post-discharge mortality was highest among patients who had postdischarge renal failure (27%),postdischarge MI (19%), and postdischarge pneumonia (15%).

The researchers also found that patients with a history of peripheral artery disease (PAD) had a significantly higher post-discharge complication rate after EVAR (7.1% vs. 4.3%; P = .001). This also correlated with a higher wound infection rate (3.2% vs. 1.7%; P = .01). A previous cardiac surgery also predisposed patients toward a higher overall postdischarge complication rate (5.3% vs. 4.2%; P = .007).

"Usually, patients undergoing EVAR are followed up at 2 weeks for wound evaluation, or at 1 month with a CT scan," Dr. Gupta said. "In the present study, the median occurrence for most of the postdischarge complications was within the first 10 days after surgery. The interquartile range was 11-22 days for the diagnosis of a wound infection after EVAR. These data suggest that earlier follow-up of high-risk patients may help identify and possibly prevent some of these complications and subsequently decrease readmissions. A standardized protocol for triage and surveillance of high-risk patients post EVAR is needed."

Limitations of the study include that fact that causality could not be determined because it was a retrospective analysis. "In addition, the timing of the operation is not specified in NSQIP," so it could either be a predischarge event or it could have occurred on readmission, Dr. Gupta said. "Data on readmission is not available from the 2005-2010 data sets."

Dr. Gupta said that he had no relevant financial disclosures to make.

[email protected]

SAN FRANCISCO – One-third of perioperative deaths and complications after elective endovascular repair of abdominal aortic aneurysms occur post discharge, results from a large analysis showed.

"Improved predischarge surveillance and close postdischarge follow-up of identified high-risk patients may further improve 30-day outcomes after EVAR," Dr. Prateek K. Gupta said at the Society for Vascular Surgery annual meeting.

Outcome improvement in the field of aortic surgery, specifically endovascular repair of abdominal aortic aneurysms, "has received much attention," said Dr. Gupta of the department of surgery at the University of Wisconsin Hospital and Clinics, Madison. "With EVAR, the index hospital stay after aortic surgery has decreased significantly, leaving a need for better understanding of postdischarge outcomes, which is necessary to improve quality and reduce readmission rates with implementation of targeted outpatient interventions."

In an effort to examine postdischarge 30-day outcomes after elective EVAR, Dr. Gupta and his associates identified 11,229 patients from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database who underwent an elective EVAR for AAA between 2005 and 2010. The primary outcome of interest was postdischarge mortality, while the secondary outcome was postdischarge overall morbidity. The researchers performed univariate and multiple logistic regression analysis to assess factors associated with the primary and secondary study outcomes.

Of the 11,229 patient 83% were male and their mean age was 75 years. Dr. Gupta reported that 117 patients died within 30 days of EVAR, for a rate of 1%. Of these deaths, 31% occurred after hospital discharge, and the median time to death was 9 days. At the same time, 1,204 patients experienced complications within 30 days of EVAR, for a rate of 11%. Of these, 500 (40%) occurred post discharge, and the median time for a complication to occur was 3 days.

Only 20% of patients (7/36) who died post discharge experienced an in-hospital complication. Compared with patients who did not develop a postdischarge complication, those who had more than a sixfold likelihood of reoperation (20.4% vs. 3.1%, respectively; P less than .0001) and death (3.0% vs. 0.2%; P less than .0001) within 30 days of surgery.

Multivariable analysis revealed the following factors that were independently and significantly associated with postdischarge mortality: preoperative heart failure (adjusted odds ratio, 4.7), admission from a skilled nursing facility (AOR, 2.2), increase in age per year (AOR, 1.09), postdischarge renal failure requiring dialysis (AOR, 72.5), postdischarge cardiac arrest/MI (AOR, 46.6), and postdischarge pneumonia (AOR, 26.5).

Dr. Gupta reported that the 30-day postdischarge rate among patients admitted from a nursing facility or acute care was 2.5%. "In contrast to patients who survived after EVAR, patients who died post discharge were more likely to have been admitted from a nursing facility or acute care (13.9% vs. 1.8%; P less than .0001)," he said.

The 30-day post-discharge mortality was highest among patients who had postdischarge renal failure (27%),postdischarge MI (19%), and postdischarge pneumonia (15%).

The researchers also found that patients with a history of peripheral artery disease (PAD) had a significantly higher post-discharge complication rate after EVAR (7.1% vs. 4.3%; P = .001). This also correlated with a higher wound infection rate (3.2% vs. 1.7%; P = .01). A previous cardiac surgery also predisposed patients toward a higher overall postdischarge complication rate (5.3% vs. 4.2%; P = .007).

"Usually, patients undergoing EVAR are followed up at 2 weeks for wound evaluation, or at 1 month with a CT scan," Dr. Gupta said. "In the present study, the median occurrence for most of the postdischarge complications was within the first 10 days after surgery. The interquartile range was 11-22 days for the diagnosis of a wound infection after EVAR. These data suggest that earlier follow-up of high-risk patients may help identify and possibly prevent some of these complications and subsequently decrease readmissions. A standardized protocol for triage and surveillance of high-risk patients post EVAR is needed."

Limitations of the study include that fact that causality could not be determined because it was a retrospective analysis. "In addition, the timing of the operation is not specified in NSQIP," so it could either be a predischarge event or it could have occurred on readmission, Dr. Gupta said. "Data on readmission is not available from the 2005-2010 data sets."

Dr. Gupta said that he had no relevant financial disclosures to make.

[email protected]

SAN FRANCISCO – One-third of perioperative deaths and complications after elective endovascular repair of abdominal aortic aneurysms occur post discharge, results from a large analysis showed.

"Improved predischarge surveillance and close postdischarge follow-up of identified high-risk patients may further improve 30-day outcomes after EVAR," Dr. Prateek K. Gupta said at the Society for Vascular Surgery annual meeting.

Outcome improvement in the field of aortic surgery, specifically endovascular repair of abdominal aortic aneurysms, "has received much attention," said Dr. Gupta of the department of surgery at the University of Wisconsin Hospital and Clinics, Madison. "With EVAR, the index hospital stay after aortic surgery has decreased significantly, leaving a need for better understanding of postdischarge outcomes, which is necessary to improve quality and reduce readmission rates with implementation of targeted outpatient interventions."

In an effort to examine postdischarge 30-day outcomes after elective EVAR, Dr. Gupta and his associates identified 11,229 patients from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database who underwent an elective EVAR for AAA between 2005 and 2010. The primary outcome of interest was postdischarge mortality, while the secondary outcome was postdischarge overall morbidity. The researchers performed univariate and multiple logistic regression analysis to assess factors associated with the primary and secondary study outcomes.

Of the 11,229 patient 83% were male and their mean age was 75 years. Dr. Gupta reported that 117 patients died within 30 days of EVAR, for a rate of 1%. Of these deaths, 31% occurred after hospital discharge, and the median time to death was 9 days. At the same time, 1,204 patients experienced complications within 30 days of EVAR, for a rate of 11%. Of these, 500 (40%) occurred post discharge, and the median time for a complication to occur was 3 days.

Only 20% of patients (7/36) who died post discharge experienced an in-hospital complication. Compared with patients who did not develop a postdischarge complication, those who had more than a sixfold likelihood of reoperation (20.4% vs. 3.1%, respectively; P less than .0001) and death (3.0% vs. 0.2%; P less than .0001) within 30 days of surgery.

Multivariable analysis revealed the following factors that were independently and significantly associated with postdischarge mortality: preoperative heart failure (adjusted odds ratio, 4.7), admission from a skilled nursing facility (AOR, 2.2), increase in age per year (AOR, 1.09), postdischarge renal failure requiring dialysis (AOR, 72.5), postdischarge cardiac arrest/MI (AOR, 46.6), and postdischarge pneumonia (AOR, 26.5).

Dr. Gupta reported that the 30-day postdischarge rate among patients admitted from a nursing facility or acute care was 2.5%. "In contrast to patients who survived after EVAR, patients who died post discharge were more likely to have been admitted from a nursing facility or acute care (13.9% vs. 1.8%; P less than .0001)," he said.

The 30-day post-discharge mortality was highest among patients who had postdischarge renal failure (27%),postdischarge MI (19%), and postdischarge pneumonia (15%).

The researchers also found that patients with a history of peripheral artery disease (PAD) had a significantly higher post-discharge complication rate after EVAR (7.1% vs. 4.3%; P = .001). This also correlated with a higher wound infection rate (3.2% vs. 1.7%; P = .01). A previous cardiac surgery also predisposed patients toward a higher overall postdischarge complication rate (5.3% vs. 4.2%; P = .007).

"Usually, patients undergoing EVAR are followed up at 2 weeks for wound evaluation, or at 1 month with a CT scan," Dr. Gupta said. "In the present study, the median occurrence for most of the postdischarge complications was within the first 10 days after surgery. The interquartile range was 11-22 days for the diagnosis of a wound infection after EVAR. These data suggest that earlier follow-up of high-risk patients may help identify and possibly prevent some of these complications and subsequently decrease readmissions. A standardized protocol for triage and surveillance of high-risk patients post EVAR is needed."

Limitations of the study include that fact that causality could not be determined because it was a retrospective analysis. "In addition, the timing of the operation is not specified in NSQIP," so it could either be a predischarge event or it could have occurred on readmission, Dr. Gupta said. "Data on readmission is not available from the 2005-2010 data sets."

Dr. Gupta said that he had no relevant financial disclosures to make.

[email protected]