Miriam E. Tucker

WASHINGTON – The International AIDS Society has officially shifted its focus from controlling to curing HIV infection.

Their seven-point plan called "The Inaugural Global Scientific Strategy Towards an HIV Cure" will be published online July 20 in the August issue of Nature Reviews/Immunology (vol. 12, pp. 607-14), and is outlined in a commentary published in Nature (vol. 487, pp. 293-4).

Miriam E. Tucker/IMNG Medical Media

The strategy merely represents the first step toward finding an AIDS cure, Dr. Steven Deeks emphasized at a press conference announcing the strategy. "No one thinks it’s going to be easy. Many people don’t even think it’s going to be possible. But, it’s certainly worth the investment."

"[Antiretroviral] drugs control the virus; they don’t eliminate it. In 2012, we now have 20-25 drugs, [used in] multiple combinations. They work very well, and people are now living much, much longer. But now that we’ve achieved what I think is the best that we can achieve with these drugs, we’re realizing some limitations," said Dr. Deeks, professor of medicine at the University of California, San Francisco.

HIV therapy is limited by problems of adherence, toxicity, cost, and lack of infrastructure in many countries for delivering drugs, he said. "Delivering drugs to the 33 million HIV-infected individuals worldwide – day in, day out, for decades and decades – is going to be a major challenge. ... So, now that we’ve achieved what we can with the current strategies, the field has shifted to what we think is the optimal intervention, which is to come up with a safe, affordable scalable intervention that will essentially either eliminate the virus completely or modify the immune system so that it can control the virus in the absence of therapy – a cure."

Fueling optimism about the possibility of a cure is the so-called "Berlin Patient," a man named Timothy Brown who received bone marrow from a naturally HIV-resistant donor. The Berlin Patient is now off all drugs at 5 years post transplant and remains virus free. "I don’t think anyone would want to go through what he went through to get that cure, but [the process] proved it could be done. This has really, truly inspired the field," said Dr. Deeks, cochair of the 34-member scientific panel that developed the strategy.

The seven research priorities described in the strategy for the cure are as follows:

• Determine the cellular and viral mechanisms that maintain HIV persistence.

• Determine the tissue and cellular sources of persistent HIV in individuals on long-term antiretroviral therapy.

• Determine the origin of immune activation and inflammation in the presence of antiretroviral therapy and the consequences for HIV persistence.

• Determine host and immune mechanisms that control infection but allow viral persistence.

• Study, compare, and validate assays to measure persistent infection.

• Develop and test therapeutic agents or immunologic strategies to eliminate latent infection in individuals on antiretroviral therapy.

• Develop and test strategies to enhance the capacity of the host response to control viral replication.

The panel was convened by the International AIDS Society with endorsements from major HIV-related organizations and institutions worldwide including amfAR, UNAIDS, the University of Pennsylvania, the Fred Hutchinson Cancer Research Center, and Monash University. The National Institutes of Health has recently undertaken targeted funding initiatives, including the Martin Delaney Collaboratory, which provides grants for research on a cure for HIV infection.

Other groups also are increasing research funding for a cure, including the French National Agency for Research on AIDS and Viral Hepatitis, the Canadian Institutes of Health Research and the Medical Research Council in the United Kingdom. Moreover, many pharmaceutical companies that had invested heavily in developing antiretroviral drugs are now also allocating resources toward pursuing a cure, according to an International AIDS Society statement.

Dr. Deeks disclosed that he has received grant support from Merck and Gilead, and has consulted in the past for Bristol-Myers Squibb, Merck, GlaxoSmithKline, and Gilead.

WASHINGTON – The International AIDS Society has officially shifted its focus from controlling to curing HIV infection.

Their seven-point plan called "The Inaugural Global Scientific Strategy Towards an HIV Cure" will be published online July 20 in the August issue of Nature Reviews/Immunology (vol. 12, pp. 607-14), and is outlined in a commentary published in Nature (vol. 487, pp. 293-4).

Miriam E. Tucker/IMNG Medical Media

The strategy merely represents the first step toward finding an AIDS cure, Dr. Steven Deeks emphasized at a press conference announcing the strategy. "No one thinks it’s going to be easy. Many people don’t even think it’s going to be possible. But, it’s certainly worth the investment."

"[Antiretroviral] drugs control the virus; they don’t eliminate it. In 2012, we now have 20-25 drugs, [used in] multiple combinations. They work very well, and people are now living much, much longer. But now that we’ve achieved what I think is the best that we can achieve with these drugs, we’re realizing some limitations," said Dr. Deeks, professor of medicine at the University of California, San Francisco.

HIV therapy is limited by problems of adherence, toxicity, cost, and lack of infrastructure in many countries for delivering drugs, he said. "Delivering drugs to the 33 million HIV-infected individuals worldwide – day in, day out, for decades and decades – is going to be a major challenge. ... So, now that we’ve achieved what we can with the current strategies, the field has shifted to what we think is the optimal intervention, which is to come up with a safe, affordable scalable intervention that will essentially either eliminate the virus completely or modify the immune system so that it can control the virus in the absence of therapy – a cure."

Fueling optimism about the possibility of a cure is the so-called "Berlin Patient," a man named Timothy Brown who received bone marrow from a naturally HIV-resistant donor. The Berlin Patient is now off all drugs at 5 years post transplant and remains virus free. "I don’t think anyone would want to go through what he went through to get that cure, but [the process] proved it could be done. This has really, truly inspired the field," said Dr. Deeks, cochair of the 34-member scientific panel that developed the strategy.

The seven research priorities described in the strategy for the cure are as follows:

• Determine the cellular and viral mechanisms that maintain HIV persistence.

• Determine the tissue and cellular sources of persistent HIV in individuals on long-term antiretroviral therapy.

• Determine the origin of immune activation and inflammation in the presence of antiretroviral therapy and the consequences for HIV persistence.

• Determine host and immune mechanisms that control infection but allow viral persistence.

• Study, compare, and validate assays to measure persistent infection.

• Develop and test therapeutic agents or immunologic strategies to eliminate latent infection in individuals on antiretroviral therapy.

• Develop and test strategies to enhance the capacity of the host response to control viral replication.

The panel was convened by the International AIDS Society with endorsements from major HIV-related organizations and institutions worldwide including amfAR, UNAIDS, the University of Pennsylvania, the Fred Hutchinson Cancer Research Center, and Monash University. The National Institutes of Health has recently undertaken targeted funding initiatives, including the Martin Delaney Collaboratory, which provides grants for research on a cure for HIV infection.

Other groups also are increasing research funding for a cure, including the French National Agency for Research on AIDS and Viral Hepatitis, the Canadian Institutes of Health Research and the Medical Research Council in the United Kingdom. Moreover, many pharmaceutical companies that had invested heavily in developing antiretroviral drugs are now also allocating resources toward pursuing a cure, according to an International AIDS Society statement.

Dr. Deeks disclosed that he has received grant support from Merck and Gilead, and has consulted in the past for Bristol-Myers Squibb, Merck, GlaxoSmithKline, and Gilead.

WASHINGTON – The International AIDS Society has officially shifted its focus from controlling to curing HIV infection.

Their seven-point plan called "The Inaugural Global Scientific Strategy Towards an HIV Cure" will be published online July 20 in the August issue of Nature Reviews/Immunology (vol. 12, pp. 607-14), and is outlined in a commentary published in Nature (vol. 487, pp. 293-4).

Miriam E. Tucker/IMNG Medical Media

The strategy merely represents the first step toward finding an AIDS cure, Dr. Steven Deeks emphasized at a press conference announcing the strategy. "No one thinks it’s going to be easy. Many people don’t even think it’s going to be possible. But, it’s certainly worth the investment."

"[Antiretroviral] drugs control the virus; they don’t eliminate it. In 2012, we now have 20-25 drugs, [used in] multiple combinations. They work very well, and people are now living much, much longer. But now that we’ve achieved what I think is the best that we can achieve with these drugs, we’re realizing some limitations," said Dr. Deeks, professor of medicine at the University of California, San Francisco.

HIV therapy is limited by problems of adherence, toxicity, cost, and lack of infrastructure in many countries for delivering drugs, he said. "Delivering drugs to the 33 million HIV-infected individuals worldwide – day in, day out, for decades and decades – is going to be a major challenge. ... So, now that we’ve achieved what we can with the current strategies, the field has shifted to what we think is the optimal intervention, which is to come up with a safe, affordable scalable intervention that will essentially either eliminate the virus completely or modify the immune system so that it can control the virus in the absence of therapy – a cure."

Fueling optimism about the possibility of a cure is the so-called "Berlin Patient," a man named Timothy Brown who received bone marrow from a naturally HIV-resistant donor. The Berlin Patient is now off all drugs at 5 years post transplant and remains virus free. "I don’t think anyone would want to go through what he went through to get that cure, but [the process] proved it could be done. This has really, truly inspired the field," said Dr. Deeks, cochair of the 34-member scientific panel that developed the strategy.

The seven research priorities described in the strategy for the cure are as follows:

• Determine the cellular and viral mechanisms that maintain HIV persistence.

• Determine the tissue and cellular sources of persistent HIV in individuals on long-term antiretroviral therapy.

• Determine the origin of immune activation and inflammation in the presence of antiretroviral therapy and the consequences for HIV persistence.

• Determine host and immune mechanisms that control infection but allow viral persistence.

• Study, compare, and validate assays to measure persistent infection.

• Develop and test therapeutic agents or immunologic strategies to eliminate latent infection in individuals on antiretroviral therapy.

• Develop and test strategies to enhance the capacity of the host response to control viral replication.

The panel was convened by the International AIDS Society with endorsements from major HIV-related organizations and institutions worldwide including amfAR, UNAIDS, the University of Pennsylvania, the Fred Hutchinson Cancer Research Center, and Monash University. The National Institutes of Health has recently undertaken targeted funding initiatives, including the Martin Delaney Collaboratory, which provides grants for research on a cure for HIV infection.

Other groups also are increasing research funding for a cure, including the French National Agency for Research on AIDS and Viral Hepatitis, the Canadian Institutes of Health Research and the Medical Research Council in the United Kingdom. Moreover, many pharmaceutical companies that had invested heavily in developing antiretroviral drugs are now also allocating resources toward pursuing a cure, according to an International AIDS Society statement.

Dr. Deeks disclosed that he has received grant support from Merck and Gilead, and has consulted in the past for Bristol-Myers Squibb, Merck, GlaxoSmithKline, and Gilead.

NATIONAL HARBOR, MD – The prognosis for older adult kidney transplant recipients has improved dramatically in recent years, and these individuals deserve to be referred for transplantation more often than they currently are, according to transplant surgeon, Dr. Dorry Segev.

Dr. Segev pointed to data from his own and other studies, showing that not only have survival rates among older adult kidney recipients improved, but the use of donor kidneys from older adults can in some cases be considered acceptable for younger recipients.

"What we knew about transplantation 20 years ago is completely different now. Immunosuppression agents are better, clinical protocols are better. ...Those aged 65 and older can have pretty good outcomes with transplantation," said Dr. Segev of the department of surgery at Johns Hopkins University, Baltimore.

Today, 2-year survival following kidney transplantation among those aged 65 and older is approximately 90%, based on data from 7,823 patients who were transplanted in 2009-2011, in contrast to about 80% among 1,153 who were transplanted in 1991-1993. And, older adults who do receive kidney transplants have almost double the survival benefit, compared with those who remain on the waiting list. "We’re transplanting more older adults, and they’re doing better," Dr. Segev said

Nevertheless, about 300,000 adults aged 65 years and older are currently on the waiting list for donor kidneys, and there is evidence that these individuals are referred for transplantation less often than younger individuals with chronic kidney disease. In another study from Dr. Segev’s group, national registry data on 6,988 Medicare recipients (aged 65 and older) of a first kidney transplant in 1999-2006 were compared with those of 128,850 older adults with end-stage renal disease in those same years who did not have absolute or relative contraindications to transplantation (J. Am. Geriatr. Soc. 2012;60:1-7).

Of the 11,756 who would be considered "excellent" candidates for transplantation (defined as greater than 87% predicted 3-year posttransplantation survival, corresponding to the top 20% of transplanted older adults), just 24% had access to transplantation and 13% actually received a kidney transplant. It was estimated that 11% of these candidates would have identified a suitable live donor had they been referred for kidney transplantation. "Those who should be transplanted are getting referred at an extremely low rate," Dr. Segev commented.

One way to counter the belief that donor kidneys are "wasted" on adults with lower remaining life expectancy is to consider kidney options that may not be appropriate for younger recipients, including "expanded criteria" donor kidneys, older living donors, and a special category designated by the Centers for Disease Control and Prevention as "infectious disease risk" donors.

"Expanded criteria" donors (ECDs) include those who are aged 60 years and older, or age 50-59 with two of the following three criteria: hypertension, stroke as the cause of death, or terminal creatinine greater than 1.5 mg/dL. There is a separate recipient waiting list for ECDs, of which "many are great kidneys," Dr. Segev said.

In a review of 142,907 first-time deceased-donor kidney registrants who were reported to UNOS (United Network for Organ Sharing) between 2003 and 2008, Dr. Segev and his associates found that just 67% of adults older than 65 years who were predicted to benefit from ECDs were listed for them, with huge variation (0% to 100%) by center (Am. J. Transplant. 2010;10:802-9).

Older living donors are another potential – but underutilized – source of donor kidneys for their peers. Among 219 healthy adults aged 70 and older who have donated kidneys at 80 U.S. transplantation centers, graft loss in the recipients was significantly higher than were matched 50- to 59-year-old, live-donor allografts, but were similar to matched, nonextended-criteria, 50- to 59-year-old, deceased-donor allografts. Mortality among the older living kidney donors was no higher than that among healthy matched controls, and in fact they lived longer (Clin. J. Am. Soc. Nephrol. 2011;6:2887-93).

"The study showed that donors do well and recipients do well, particularly older recipients. ... Many older adults have a social network of other older adults who would be willing to donate if they knew it was possible," Dr. Segev said.

Another source of alternative donor organs that might be appropriate for selected elderly patients are those from the Centers for Disease Control and Prevention’s "Infectious Risk Donors." These include men who have sex with men (MSM), injection drug users, hemophiliacs, prostitutes, those exposed to HIV, those who have had sex with anyone in the previous categories, and incarcerated individuals. Such donors account for nearly 10% of the donor pool, and their organs are discarded more often than other donor organs.

"It seems wasteful to discard these. There should be someone on the list who would benefit from them, even with higher infectious risk. The real diseases we worry about – HIV and HCV [hepatitis C virus] – take years for sequelae to develop," Dr. Segev said.

In two separate studies, the risk of infection from such an organ per 10,000 donors during the "window period" prior to positive test results for injection drug users was 4.9 for HIV and 32.4 for HCV. For MSM, those risks were 4.2 and 3.5, respectively, and for commercial sex workers, 2.7 and 12.3, respectively. The others incurred lower risks (Am. J. Transplant. 2011;1176-87; 11:1188-200).

New data from Dr. Segev’s group suggest that the risk of a poor outcome (defined as 33% or more of the year after the kidney transplantation that was spent hospitalized or dying) among older transplant recipients increases by an adjusted odds ratio of 1.42 per 10 years. Years on pretransplantation dialysis also was a significant predictor (1.11), whereas the receipt of a live donor organ was protective (0.59).

In all, the risks of kidney transplantation for older adults include the upfront risks of surgery, particularly among those with comorbidities; the risk of immunosuppression; and the ongoing need for medical follow-up. But the benefits can include longer survival and improved quality of life, Dr. Segev said.

Dr. Segev disclosed that he is a consultant, scientific advisor, and speaker for Sanofi.

NATIONAL HARBOR, MD – The prognosis for older adult kidney transplant recipients has improved dramatically in recent years, and these individuals deserve to be referred for transplantation more often than they currently are, according to transplant surgeon, Dr. Dorry Segev.

Dr. Segev pointed to data from his own and other studies, showing that not only have survival rates among older adult kidney recipients improved, but the use of donor kidneys from older adults can in some cases be considered acceptable for younger recipients.

"What we knew about transplantation 20 years ago is completely different now. Immunosuppression agents are better, clinical protocols are better. ...Those aged 65 and older can have pretty good outcomes with transplantation," said Dr. Segev of the department of surgery at Johns Hopkins University, Baltimore.

Today, 2-year survival following kidney transplantation among those aged 65 and older is approximately 90%, based on data from 7,823 patients who were transplanted in 2009-2011, in contrast to about 80% among 1,153 who were transplanted in 1991-1993. And, older adults who do receive kidney transplants have almost double the survival benefit, compared with those who remain on the waiting list. "We’re transplanting more older adults, and they’re doing better," Dr. Segev said

Nevertheless, about 300,000 adults aged 65 years and older are currently on the waiting list for donor kidneys, and there is evidence that these individuals are referred for transplantation less often than younger individuals with chronic kidney disease. In another study from Dr. Segev’s group, national registry data on 6,988 Medicare recipients (aged 65 and older) of a first kidney transplant in 1999-2006 were compared with those of 128,850 older adults with end-stage renal disease in those same years who did not have absolute or relative contraindications to transplantation (J. Am. Geriatr. Soc. 2012;60:1-7).

Of the 11,756 who would be considered "excellent" candidates for transplantation (defined as greater than 87% predicted 3-year posttransplantation survival, corresponding to the top 20% of transplanted older adults), just 24% had access to transplantation and 13% actually received a kidney transplant. It was estimated that 11% of these candidates would have identified a suitable live donor had they been referred for kidney transplantation. "Those who should be transplanted are getting referred at an extremely low rate," Dr. Segev commented.

One way to counter the belief that donor kidneys are "wasted" on adults with lower remaining life expectancy is to consider kidney options that may not be appropriate for younger recipients, including "expanded criteria" donor kidneys, older living donors, and a special category designated by the Centers for Disease Control and Prevention as "infectious disease risk" donors.

"Expanded criteria" donors (ECDs) include those who are aged 60 years and older, or age 50-59 with two of the following three criteria: hypertension, stroke as the cause of death, or terminal creatinine greater than 1.5 mg/dL. There is a separate recipient waiting list for ECDs, of which "many are great kidneys," Dr. Segev said.

In a review of 142,907 first-time deceased-donor kidney registrants who were reported to UNOS (United Network for Organ Sharing) between 2003 and 2008, Dr. Segev and his associates found that just 67% of adults older than 65 years who were predicted to benefit from ECDs were listed for them, with huge variation (0% to 100%) by center (Am. J. Transplant. 2010;10:802-9).

Older living donors are another potential – but underutilized – source of donor kidneys for their peers. Among 219 healthy adults aged 70 and older who have donated kidneys at 80 U.S. transplantation centers, graft loss in the recipients was significantly higher than were matched 50- to 59-year-old, live-donor allografts, but were similar to matched, nonextended-criteria, 50- to 59-year-old, deceased-donor allografts. Mortality among the older living kidney donors was no higher than that among healthy matched controls, and in fact they lived longer (Clin. J. Am. Soc. Nephrol. 2011;6:2887-93).

"The study showed that donors do well and recipients do well, particularly older recipients. ... Many older adults have a social network of other older adults who would be willing to donate if they knew it was possible," Dr. Segev said.

Another source of alternative donor organs that might be appropriate for selected elderly patients are those from the Centers for Disease Control and Prevention’s "Infectious Risk Donors." These include men who have sex with men (MSM), injection drug users, hemophiliacs, prostitutes, those exposed to HIV, those who have had sex with anyone in the previous categories, and incarcerated individuals. Such donors account for nearly 10% of the donor pool, and their organs are discarded more often than other donor organs.

"It seems wasteful to discard these. There should be someone on the list who would benefit from them, even with higher infectious risk. The real diseases we worry about – HIV and HCV [hepatitis C virus] – take years for sequelae to develop," Dr. Segev said.

In two separate studies, the risk of infection from such an organ per 10,000 donors during the "window period" prior to positive test results for injection drug users was 4.9 for HIV and 32.4 for HCV. For MSM, those risks were 4.2 and 3.5, respectively, and for commercial sex workers, 2.7 and 12.3, respectively. The others incurred lower risks (Am. J. Transplant. 2011;1176-87; 11:1188-200).

New data from Dr. Segev’s group suggest that the risk of a poor outcome (defined as 33% or more of the year after the kidney transplantation that was spent hospitalized or dying) among older transplant recipients increases by an adjusted odds ratio of 1.42 per 10 years. Years on pretransplantation dialysis also was a significant predictor (1.11), whereas the receipt of a live donor organ was protective (0.59).

In all, the risks of kidney transplantation for older adults include the upfront risks of surgery, particularly among those with comorbidities; the risk of immunosuppression; and the ongoing need for medical follow-up. But the benefits can include longer survival and improved quality of life, Dr. Segev said.

Dr. Segev disclosed that he is a consultant, scientific advisor, and speaker for Sanofi.

NATIONAL HARBOR, MD – The prognosis for older adult kidney transplant recipients has improved dramatically in recent years, and these individuals deserve to be referred for transplantation more often than they currently are, according to transplant surgeon, Dr. Dorry Segev.

Dr. Segev pointed to data from his own and other studies, showing that not only have survival rates among older adult kidney recipients improved, but the use of donor kidneys from older adults can in some cases be considered acceptable for younger recipients.

"What we knew about transplantation 20 years ago is completely different now. Immunosuppression agents are better, clinical protocols are better. ...Those aged 65 and older can have pretty good outcomes with transplantation," said Dr. Segev of the department of surgery at Johns Hopkins University, Baltimore.

Today, 2-year survival following kidney transplantation among those aged 65 and older is approximately 90%, based on data from 7,823 patients who were transplanted in 2009-2011, in contrast to about 80% among 1,153 who were transplanted in 1991-1993. And, older adults who do receive kidney transplants have almost double the survival benefit, compared with those who remain on the waiting list. "We’re transplanting more older adults, and they’re doing better," Dr. Segev said

Nevertheless, about 300,000 adults aged 65 years and older are currently on the waiting list for donor kidneys, and there is evidence that these individuals are referred for transplantation less often than younger individuals with chronic kidney disease. In another study from Dr. Segev’s group, national registry data on 6,988 Medicare recipients (aged 65 and older) of a first kidney transplant in 1999-2006 were compared with those of 128,850 older adults with end-stage renal disease in those same years who did not have absolute or relative contraindications to transplantation (J. Am. Geriatr. Soc. 2012;60:1-7).

Of the 11,756 who would be considered "excellent" candidates for transplantation (defined as greater than 87% predicted 3-year posttransplantation survival, corresponding to the top 20% of transplanted older adults), just 24% had access to transplantation and 13% actually received a kidney transplant. It was estimated that 11% of these candidates would have identified a suitable live donor had they been referred for kidney transplantation. "Those who should be transplanted are getting referred at an extremely low rate," Dr. Segev commented.

One way to counter the belief that donor kidneys are "wasted" on adults with lower remaining life expectancy is to consider kidney options that may not be appropriate for younger recipients, including "expanded criteria" donor kidneys, older living donors, and a special category designated by the Centers for Disease Control and Prevention as "infectious disease risk" donors.

"Expanded criteria" donors (ECDs) include those who are aged 60 years and older, or age 50-59 with two of the following three criteria: hypertension, stroke as the cause of death, or terminal creatinine greater than 1.5 mg/dL. There is a separate recipient waiting list for ECDs, of which "many are great kidneys," Dr. Segev said.

In a review of 142,907 first-time deceased-donor kidney registrants who were reported to UNOS (United Network for Organ Sharing) between 2003 and 2008, Dr. Segev and his associates found that just 67% of adults older than 65 years who were predicted to benefit from ECDs were listed for them, with huge variation (0% to 100%) by center (Am. J. Transplant. 2010;10:802-9).

Older living donors are another potential – but underutilized – source of donor kidneys for their peers. Among 219 healthy adults aged 70 and older who have donated kidneys at 80 U.S. transplantation centers, graft loss in the recipients was significantly higher than were matched 50- to 59-year-old, live-donor allografts, but were similar to matched, nonextended-criteria, 50- to 59-year-old, deceased-donor allografts. Mortality among the older living kidney donors was no higher than that among healthy matched controls, and in fact they lived longer (Clin. J. Am. Soc. Nephrol. 2011;6:2887-93).

"The study showed that donors do well and recipients do well, particularly older recipients. ... Many older adults have a social network of other older adults who would be willing to donate if they knew it was possible," Dr. Segev said.

Another source of alternative donor organs that might be appropriate for selected elderly patients are those from the Centers for Disease Control and Prevention’s "Infectious Risk Donors." These include men who have sex with men (MSM), injection drug users, hemophiliacs, prostitutes, those exposed to HIV, those who have had sex with anyone in the previous categories, and incarcerated individuals. Such donors account for nearly 10% of the donor pool, and their organs are discarded more often than other donor organs.

"It seems wasteful to discard these. There should be someone on the list who would benefit from them, even with higher infectious risk. The real diseases we worry about – HIV and HCV [hepatitis C virus] – take years for sequelae to develop," Dr. Segev said.

In two separate studies, the risk of infection from such an organ per 10,000 donors during the "window period" prior to positive test results for injection drug users was 4.9 for HIV and 32.4 for HCV. For MSM, those risks were 4.2 and 3.5, respectively, and for commercial sex workers, 2.7 and 12.3, respectively. The others incurred lower risks (Am. J. Transplant. 2011;1176-87; 11:1188-200).

New data from Dr. Segev’s group suggest that the risk of a poor outcome (defined as 33% or more of the year after the kidney transplantation that was spent hospitalized or dying) among older transplant recipients increases by an adjusted odds ratio of 1.42 per 10 years. Years on pretransplantation dialysis also was a significant predictor (1.11), whereas the receipt of a live donor organ was protective (0.59).

In all, the risks of kidney transplantation for older adults include the upfront risks of surgery, particularly among those with comorbidities; the risk of immunosuppression; and the ongoing need for medical follow-up. But the benefits can include longer survival and improved quality of life, Dr. Segev said.

Dr. Segev disclosed that he is a consultant, scientific advisor, and speaker for Sanofi.

The Food and Drug Administration has approved the use of the oral once-daily combination antiviral medication Truvada for prevention in uninfected people at high risk for acquiring HIV.

Gilead’s Truvada (emtricitabine and tenofovir disoproxil fumarate) has been on the U.S. market since 2004 for use in combination with other antiretroviral therapies for treatment of HIV-1 infected adults and children older than 12 years of age. The new indication, announced July 16 by the FDA, is the first ever for an HIV drug for "pre-exposure prophylaxis (PrEP)," and is to be used in combination with safer sex practices to reduce the risk of acquiring HIV infection among high-risk adults.

The studies were conducted in men who have sex with men and in heterosexual serodiscordant couples. But the new indication allows for use in other adults aged 18 years and older who are deemed to be at high risk, including those who have sex with people known to be HIV infected (who are not necessarily regular partners) and those who do not routinely use condoms, Dr. Debra Birnkrant, director of the FDA’s Division of Antiviral Products, said in a press briefing.

"These data show that treatment and new prevention methods are needed in order to have a major impact on the HIV epidemic in this country."

Truvada’s label will include new language in the boxed warning regarding the requirement for testing and documentation of a negative HIV test prior to prescribing for PrEP. Moreover, the medication will be contraindicated in people who have flulike symptoms, because that could indicate the presence of early acute but as yet undetectable HIV infection.

Testing for hepatitis B is also recommended, because worsening of hepatitis B has been reported in individuals with both HIV and hepatitis B when Truvada treatment was stopped. Individuals with a history of bone or kidney disease should be regularly monitored.

The approval comes with a risk evaluation and mitigation strategy (REMS) aimed at informing prescribers and potential users of the importance of daily use of the medication, regular HIV testing, and other infection risk-reducing measures. A training and education plan will also be made available to potential prescribers. This plan was made voluntary so as not to restrict access to Truvada for individuals who need it for HIV treatment, Dr. Birnkrant said.

Data supporting the approval of Truvada for PrEP primarily came from two large placebo-controlled trials: the Pre-Exposure Prophylaxis Initiative (iPrEx), sponsored by the National Institutes of Health and the Bill and Melinda Gates Foundation; and PartnersPrEP, sponsored by the University of Washington and funded by the Bill and Melinda Gates Foundation. In the iPrEx and PartnersPrEP trials, Truvada reduced the risk of acquiring HIV infection by 42% and 75%, respectively.

Dr. Birnkrant noted that Truvada was used in the studies in combination with other preventive strategies, such as safer sex practices, counseling, and regular testing. "Truvada alone should not be used to prevent HIV infection," she said.

About 50,000 adults and adolescents in the United States are newly diagnosed with HIV each year. While the overall rate of HIV infection has remained stable at least since 2004, the rates among men who have sex with men – particularly young minority men – have increased significantly.

"These data show that treatment and new prevention methods are needed in order to have a major impact on the HIV epidemic in this country," Dr. Birnkrant said.

The Food and Drug Administration has approved the use of the oral once-daily combination antiviral medication Truvada for prevention in uninfected people at high risk for acquiring HIV.

Gilead’s Truvada (emtricitabine and tenofovir disoproxil fumarate) has been on the U.S. market since 2004 for use in combination with other antiretroviral therapies for treatment of HIV-1 infected adults and children older than 12 years of age. The new indication, announced July 16 by the FDA, is the first ever for an HIV drug for "pre-exposure prophylaxis (PrEP)," and is to be used in combination with safer sex practices to reduce the risk of acquiring HIV infection among high-risk adults.

The studies were conducted in men who have sex with men and in heterosexual serodiscordant couples. But the new indication allows for use in other adults aged 18 years and older who are deemed to be at high risk, including those who have sex with people known to be HIV infected (who are not necessarily regular partners) and those who do not routinely use condoms, Dr. Debra Birnkrant, director of the FDA’s Division of Antiviral Products, said in a press briefing.

"These data show that treatment and new prevention methods are needed in order to have a major impact on the HIV epidemic in this country."

Truvada’s label will include new language in the boxed warning regarding the requirement for testing and documentation of a negative HIV test prior to prescribing for PrEP. Moreover, the medication will be contraindicated in people who have flulike symptoms, because that could indicate the presence of early acute but as yet undetectable HIV infection.

Testing for hepatitis B is also recommended, because worsening of hepatitis B has been reported in individuals with both HIV and hepatitis B when Truvada treatment was stopped. Individuals with a history of bone or kidney disease should be regularly monitored.

The approval comes with a risk evaluation and mitigation strategy (REMS) aimed at informing prescribers and potential users of the importance of daily use of the medication, regular HIV testing, and other infection risk-reducing measures. A training and education plan will also be made available to potential prescribers. This plan was made voluntary so as not to restrict access to Truvada for individuals who need it for HIV treatment, Dr. Birnkrant said.

Data supporting the approval of Truvada for PrEP primarily came from two large placebo-controlled trials: the Pre-Exposure Prophylaxis Initiative (iPrEx), sponsored by the National Institutes of Health and the Bill and Melinda Gates Foundation; and PartnersPrEP, sponsored by the University of Washington and funded by the Bill and Melinda Gates Foundation. In the iPrEx and PartnersPrEP trials, Truvada reduced the risk of acquiring HIV infection by 42% and 75%, respectively.

Dr. Birnkrant noted that Truvada was used in the studies in combination with other preventive strategies, such as safer sex practices, counseling, and regular testing. "Truvada alone should not be used to prevent HIV infection," she said.

About 50,000 adults and adolescents in the United States are newly diagnosed with HIV each year. While the overall rate of HIV infection has remained stable at least since 2004, the rates among men who have sex with men – particularly young minority men – have increased significantly.

"These data show that treatment and new prevention methods are needed in order to have a major impact on the HIV epidemic in this country," Dr. Birnkrant said.

The Food and Drug Administration has approved the use of the oral once-daily combination antiviral medication Truvada for prevention in uninfected people at high risk for acquiring HIV.

Gilead’s Truvada (emtricitabine and tenofovir disoproxil fumarate) has been on the U.S. market since 2004 for use in combination with other antiretroviral therapies for treatment of HIV-1 infected adults and children older than 12 years of age. The new indication, announced July 16 by the FDA, is the first ever for an HIV drug for "pre-exposure prophylaxis (PrEP)," and is to be used in combination with safer sex practices to reduce the risk of acquiring HIV infection among high-risk adults.

The studies were conducted in men who have sex with men and in heterosexual serodiscordant couples. But the new indication allows for use in other adults aged 18 years and older who are deemed to be at high risk, including those who have sex with people known to be HIV infected (who are not necessarily regular partners) and those who do not routinely use condoms, Dr. Debra Birnkrant, director of the FDA’s Division of Antiviral Products, said in a press briefing.

"These data show that treatment and new prevention methods are needed in order to have a major impact on the HIV epidemic in this country."

Truvada’s label will include new language in the boxed warning regarding the requirement for testing and documentation of a negative HIV test prior to prescribing for PrEP. Moreover, the medication will be contraindicated in people who have flulike symptoms, because that could indicate the presence of early acute but as yet undetectable HIV infection.

Testing for hepatitis B is also recommended, because worsening of hepatitis B has been reported in individuals with both HIV and hepatitis B when Truvada treatment was stopped. Individuals with a history of bone or kidney disease should be regularly monitored.

The approval comes with a risk evaluation and mitigation strategy (REMS) aimed at informing prescribers and potential users of the importance of daily use of the medication, regular HIV testing, and other infection risk-reducing measures. A training and education plan will also be made available to potential prescribers. This plan was made voluntary so as not to restrict access to Truvada for individuals who need it for HIV treatment, Dr. Birnkrant said.

Data supporting the approval of Truvada for PrEP primarily came from two large placebo-controlled trials: the Pre-Exposure Prophylaxis Initiative (iPrEx), sponsored by the National Institutes of Health and the Bill and Melinda Gates Foundation; and PartnersPrEP, sponsored by the University of Washington and funded by the Bill and Melinda Gates Foundation. In the iPrEx and PartnersPrEP trials, Truvada reduced the risk of acquiring HIV infection by 42% and 75%, respectively.

Dr. Birnkrant noted that Truvada was used in the studies in combination with other preventive strategies, such as safer sex practices, counseling, and regular testing. "Truvada alone should not be used to prevent HIV infection," she said.

About 50,000 adults and adolescents in the United States are newly diagnosed with HIV each year. While the overall rate of HIV infection has remained stable at least since 2004, the rates among men who have sex with men – particularly young minority men – have increased significantly.

"These data show that treatment and new prevention methods are needed in order to have a major impact on the HIV epidemic in this country," Dr. Birnkrant said.

A man’s life expectancy should serve as the basis for determining, on a case-by-case basis, whether prostate-specific antigen screening is appropriate, according to a new provisional clinical opinion issued by the American Society of Clinical Oncology.

Specifically, for men who are not expected to live longer than 10 years, ASCO agrees with the May 2012 guideline from the U.S. Preventive Services Task Force (USPSTF) that the risks brought on by PSA screening outweigh the benefits (Ann. Intern Med. 2012 May 22 [epub ahead of print]).

For men with a longer life expectancy, however, "it is recommended that physicians discuss with their patients whether PSA testing for prostate cancer screening is appropriate for them. PSA testing may save lives but is associated with harms, including complications from unnecessary biopsy, surgery, or radiation treatment," ASCO panel cochair Dr. Ethan Basch and his associates wrote (J. Clin. Oncol. 2012 July 16 [doi:10.1200/JCO.2012.43.3441]).

The ASCO panel also recommended that information written in lay language be available to clinicians and their patients to facilitate the discussion of the benefits and harms associated with PSA testing before the routine ordering of a PSA test. A "decision aid," based on the ASCO provisional clinical opinion (PCO), was to be made available at www.asco.org/pco/psa.

Calculation of life expectancy is based on multiple individual factors and circumstances. The PCO mentions one available life expectancy calculator as an example, but the ASCO panel does not endorse any one calculator over another.

ASCO Differs on PSAs for Younger Men

In an interview, Dr. Basch said that the ASCO panel evaluated essentially the same data as did the USPSTF. This included screening studies and treatment studies in which men who screened positive for cancer based on PSA testing were randomly assigned to either prostate surgery or watchful waiting. The multidisciplinary ASCO panel, which includes individuals with clinical expertise in medical oncology, urology, radiation oncology, and statistics, paid particular attention to subgroup analyses and statistical issues, however.

"For older men or those with shorter life expectancy, our current recommendations are the same as [those of] the USPSTF. For younger men there is a divergence, in an area where research results are complex and the balance between risks and benefits is close.

"Ultimately, it was the judgment of the ASCO panel that the balance between risks and harms for younger men depends on individual values and preferences, and therefore must be evaluated on a case-by-case basis by a patient and his physician, and must be well informed by scientifically accurate decision tools," said Dr. Basch, a medical oncologist specializing in prostate cancer at Memorial Sloan-Kettering Cancer Center, New York.

USPSTF Official Sees Similarities

Although urologists denounced the USPSTF recommendations at the annual meeting of the American Urological Association, and delegates to the American Medical Association did likewise at their meeting, ASCO agrees more than it disagrees with the controversial guideline, according to Dr. Michael L. LeFevre, co–vice chair of the task force.

"I’m struck by the similarities between the recommendations more than the differences," he said in an interview.

"ASCO concluded that the benefits don’t outweigh the harms, and even with [fewer than] 10 years’ life expectancy, the benefits might not outweigh the harms. ... We certainly also say that that assessment doesn’t mean that an individual clinician cannot offer screening, nor that an individual man can’t request screening,"

"The similarity between the two guidelines is that anybody doing PSA screening should be doing it as an informed choice," added Dr. LeFevre, the Future of Family Medicine professor and vice chair of the department of family and community medicine at the University of Missouri, Columbia.

The USPSTF tries to update its recommendations every 5 years, but may update earlier if important studies are published, as happened in this case. Two major studies are not yet published, Dr. Lefevre noted: PIVOT (Prostate Cancer Intervention Vs. Observation Trial) probably won’t prompt an update, but the PROTECT study "is large enough that I’m really hoping it will inform some of the unanswered questions that we have today."

Two Trials Key to ASCO Opinion

A "provisional clinical opinion" (PCO) is ASCO’s evidence-based approach to offering rapid responses to emerging data in clinical oncology. It is intended "to offer timely clinical direction to ASCO members after publication or presentation of potentially practice-changing data from major studies." In this case, the authors used the Agency for Health Research and Quality’s (AHRQ’s) review, which was also the basis for the USPSTF’s review.

Of the five randomized controlled trials identified, the ASCO panel deemed only two to be of sufficient quality. The PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer) screening trial, involving 76,685 men aged 55-74 years, showed no statistically significant differences in overall or prostate cancer–specific mortality at 7 years between men who were offered annual PSA screens and those who received usual care. However, half of the "usual care" group also received PSA screenings (J. Natl. Cancer Inst. 2012;104:125-32).

In contrast, in the multicenter ERSPC (European Randomized Study of Screening for Prostate Cancer) trial, which involved 182,160 men aged 50-74 years, those aged 55-69 who received PSA testing once every 4 years had a 20% reduction in prostate cancer–specific mortality (but not overall mortality) at 9 years, with the result maintained at 11 years (N. Engl. J. Med. 2009;360:1320-8).

In a subanalysis of the Swedish ERSPC center involving 20,000 men after 14 years of follow-up, statistically significant differences in prostate cancer–specific mortality of up to 56% were detected in favor of the PSA-screened (Lancet Oncol. 2010;11:725-32).

The AHRQ systematic review reported that the false-positive rates associated with PSA screening were 12.9% in the PLCO trial after four rounds of screening, and 12.5% in one center of the ERSPC after three rounds of screening. In PLCO, harms associated with diagnostic evaluations, including biopsy, were reported to be infection, bleeding, and urinary difficulty (68 events per 10,000 evaluations). In one center of the ERSPC trial, among 5,802 biopsies performed, reported harms were fever (3.5%), urinary retention (0.4%), hospitalization for signs of prostatitis or urosepsis (0.5%), and hematuria (22.6%) and hematospermia (50.4%) more than 3 days after biopsy.

"It is important to recognize that risk-benefit ratios can be substantially affected in studies and in practice by altering screening strategies, by changing treatment strategies, by changing measurement approaches, and by considering different lengths of follow-up.

"The ASCO guideline suggests that we can improve outcomes by becoming wiser about how we screen, wiser about who we treat, wiser about avoiding and managing harms of treatment, and wiser about how we communicate with patients," Dr. Basch said in the interview.

He added that physicians should not offer or order PSA screening unless they are "prepared to engage in shared decision making that enables an informed choice by patients." The current decision aid, designed to assist in that conversation, is a first version. "It is ASCO’s hope that it will be tested and refined in the future to become as efficient and useful as possible. It is also a hope that provision of accurate information to clarify decision making will make the PSA discussion more efficient and meaningful."

Hopefully, this process will be made easier in the future with new screening tests and new ways of using the PSA test that are currently under evaluation. Also, Dr. Basch said, "more mature results of ongoing screening studies, final results of treatment studies, and investigations of active surveillance approaches are all likely to improve our understanding of how screening and treatment can be optimized."

Dr. Basch reported no relevant disclosures, but one other ASCO panel member, Dr. Andrew Vickers, disclosed financial ties to GlaxoSmithKline and Genomic Health. USPHTF members such as Dr. LeFevre are vetted for disclosure.

A man’s life expectancy should serve as the basis for determining, on a case-by-case basis, whether prostate-specific antigen screening is appropriate, according to a new provisional clinical opinion issued by the American Society of Clinical Oncology.

Specifically, for men who are not expected to live longer than 10 years, ASCO agrees with the May 2012 guideline from the U.S. Preventive Services Task Force (USPSTF) that the risks brought on by PSA screening outweigh the benefits (Ann. Intern Med. 2012 May 22 [epub ahead of print]).

For men with a longer life expectancy, however, "it is recommended that physicians discuss with their patients whether PSA testing for prostate cancer screening is appropriate for them. PSA testing may save lives but is associated with harms, including complications from unnecessary biopsy, surgery, or radiation treatment," ASCO panel cochair Dr. Ethan Basch and his associates wrote (J. Clin. Oncol. 2012 July 16 [doi:10.1200/JCO.2012.43.3441]).

The ASCO panel also recommended that information written in lay language be available to clinicians and their patients to facilitate the discussion of the benefits and harms associated with PSA testing before the routine ordering of a PSA test. A "decision aid," based on the ASCO provisional clinical opinion (PCO), was to be made available at www.asco.org/pco/psa.

Calculation of life expectancy is based on multiple individual factors and circumstances. The PCO mentions one available life expectancy calculator as an example, but the ASCO panel does not endorse any one calculator over another.

ASCO Differs on PSAs for Younger Men

In an interview, Dr. Basch said that the ASCO panel evaluated essentially the same data as did the USPSTF. This included screening studies and treatment studies in which men who screened positive for cancer based on PSA testing were randomly assigned to either prostate surgery or watchful waiting. The multidisciplinary ASCO panel, which includes individuals with clinical expertise in medical oncology, urology, radiation oncology, and statistics, paid particular attention to subgroup analyses and statistical issues, however.

"For older men or those with shorter life expectancy, our current recommendations are the same as [those of] the USPSTF. For younger men there is a divergence, in an area where research results are complex and the balance between risks and benefits is close.

"Ultimately, it was the judgment of the ASCO panel that the balance between risks and harms for younger men depends on individual values and preferences, and therefore must be evaluated on a case-by-case basis by a patient and his physician, and must be well informed by scientifically accurate decision tools," said Dr. Basch, a medical oncologist specializing in prostate cancer at Memorial Sloan-Kettering Cancer Center, New York.

USPSTF Official Sees Similarities

Although urologists denounced the USPSTF recommendations at the annual meeting of the American Urological Association, and delegates to the American Medical Association did likewise at their meeting, ASCO agrees more than it disagrees with the controversial guideline, according to Dr. Michael L. LeFevre, co–vice chair of the task force.

"I’m struck by the similarities between the recommendations more than the differences," he said in an interview.

"ASCO concluded that the benefits don’t outweigh the harms, and even with [fewer than] 10 years’ life expectancy, the benefits might not outweigh the harms. ... We certainly also say that that assessment doesn’t mean that an individual clinician cannot offer screening, nor that an individual man can’t request screening,"

"The similarity between the two guidelines is that anybody doing PSA screening should be doing it as an informed choice," added Dr. LeFevre, the Future of Family Medicine professor and vice chair of the department of family and community medicine at the University of Missouri, Columbia.

The USPSTF tries to update its recommendations every 5 years, but may update earlier if important studies are published, as happened in this case. Two major studies are not yet published, Dr. Lefevre noted: PIVOT (Prostate Cancer Intervention Vs. Observation Trial) probably won’t prompt an update, but the PROTECT study "is large enough that I’m really hoping it will inform some of the unanswered questions that we have today."

Two Trials Key to ASCO Opinion

A "provisional clinical opinion" (PCO) is ASCO’s evidence-based approach to offering rapid responses to emerging data in clinical oncology. It is intended "to offer timely clinical direction to ASCO members after publication or presentation of potentially practice-changing data from major studies." In this case, the authors used the Agency for Health Research and Quality’s (AHRQ’s) review, which was also the basis for the USPSTF’s review.

Of the five randomized controlled trials identified, the ASCO panel deemed only two to be of sufficient quality. The PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer) screening trial, involving 76,685 men aged 55-74 years, showed no statistically significant differences in overall or prostate cancer–specific mortality at 7 years between men who were offered annual PSA screens and those who received usual care. However, half of the "usual care" group also received PSA screenings (J. Natl. Cancer Inst. 2012;104:125-32).

In contrast, in the multicenter ERSPC (European Randomized Study of Screening for Prostate Cancer) trial, which involved 182,160 men aged 50-74 years, those aged 55-69 who received PSA testing once every 4 years had a 20% reduction in prostate cancer–specific mortality (but not overall mortality) at 9 years, with the result maintained at 11 years (N. Engl. J. Med. 2009;360:1320-8).

In a subanalysis of the Swedish ERSPC center involving 20,000 men after 14 years of follow-up, statistically significant differences in prostate cancer–specific mortality of up to 56% were detected in favor of the PSA-screened (Lancet Oncol. 2010;11:725-32).

The AHRQ systematic review reported that the false-positive rates associated with PSA screening were 12.9% in the PLCO trial after four rounds of screening, and 12.5% in one center of the ERSPC after three rounds of screening. In PLCO, harms associated with diagnostic evaluations, including biopsy, were reported to be infection, bleeding, and urinary difficulty (68 events per 10,000 evaluations). In one center of the ERSPC trial, among 5,802 biopsies performed, reported harms were fever (3.5%), urinary retention (0.4%), hospitalization for signs of prostatitis or urosepsis (0.5%), and hematuria (22.6%) and hematospermia (50.4%) more than 3 days after biopsy.

"It is important to recognize that risk-benefit ratios can be substantially affected in studies and in practice by altering screening strategies, by changing treatment strategies, by changing measurement approaches, and by considering different lengths of follow-up.

"The ASCO guideline suggests that we can improve outcomes by becoming wiser about how we screen, wiser about who we treat, wiser about avoiding and managing harms of treatment, and wiser about how we communicate with patients," Dr. Basch said in the interview.

He added that physicians should not offer or order PSA screening unless they are "prepared to engage in shared decision making that enables an informed choice by patients." The current decision aid, designed to assist in that conversation, is a first version. "It is ASCO’s hope that it will be tested and refined in the future to become as efficient and useful as possible. It is also a hope that provision of accurate information to clarify decision making will make the PSA discussion more efficient and meaningful."

Hopefully, this process will be made easier in the future with new screening tests and new ways of using the PSA test that are currently under evaluation. Also, Dr. Basch said, "more mature results of ongoing screening studies, final results of treatment studies, and investigations of active surveillance approaches are all likely to improve our understanding of how screening and treatment can be optimized."

Dr. Basch reported no relevant disclosures, but one other ASCO panel member, Dr. Andrew Vickers, disclosed financial ties to GlaxoSmithKline and Genomic Health. USPHTF members such as Dr. LeFevre are vetted for disclosure.

A man’s life expectancy should serve as the basis for determining, on a case-by-case basis, whether prostate-specific antigen screening is appropriate, according to a new provisional clinical opinion issued by the American Society of Clinical Oncology.

Specifically, for men who are not expected to live longer than 10 years, ASCO agrees with the May 2012 guideline from the U.S. Preventive Services Task Force (USPSTF) that the risks brought on by PSA screening outweigh the benefits (Ann. Intern Med. 2012 May 22 [epub ahead of print]).

For men with a longer life expectancy, however, "it is recommended that physicians discuss with their patients whether PSA testing for prostate cancer screening is appropriate for them. PSA testing may save lives but is associated with harms, including complications from unnecessary biopsy, surgery, or radiation treatment," ASCO panel cochair Dr. Ethan Basch and his associates wrote (J. Clin. Oncol. 2012 July 16 [doi:10.1200/JCO.2012.43.3441]).

The ASCO panel also recommended that information written in lay language be available to clinicians and their patients to facilitate the discussion of the benefits and harms associated with PSA testing before the routine ordering of a PSA test. A "decision aid," based on the ASCO provisional clinical opinion (PCO), was to be made available at www.asco.org/pco/psa.

Calculation of life expectancy is based on multiple individual factors and circumstances. The PCO mentions one available life expectancy calculator as an example, but the ASCO panel does not endorse any one calculator over another.

ASCO Differs on PSAs for Younger Men

In an interview, Dr. Basch said that the ASCO panel evaluated essentially the same data as did the USPSTF. This included screening studies and treatment studies in which men who screened positive for cancer based on PSA testing were randomly assigned to either prostate surgery or watchful waiting. The multidisciplinary ASCO panel, which includes individuals with clinical expertise in medical oncology, urology, radiation oncology, and statistics, paid particular attention to subgroup analyses and statistical issues, however.

"For older men or those with shorter life expectancy, our current recommendations are the same as [those of] the USPSTF. For younger men there is a divergence, in an area where research results are complex and the balance between risks and benefits is close.

"Ultimately, it was the judgment of the ASCO panel that the balance between risks and harms for younger men depends on individual values and preferences, and therefore must be evaluated on a case-by-case basis by a patient and his physician, and must be well informed by scientifically accurate decision tools," said Dr. Basch, a medical oncologist specializing in prostate cancer at Memorial Sloan-Kettering Cancer Center, New York.

USPSTF Official Sees Similarities

Although urologists denounced the USPSTF recommendations at the annual meeting of the American Urological Association, and delegates to the American Medical Association did likewise at their meeting, ASCO agrees more than it disagrees with the controversial guideline, according to Dr. Michael L. LeFevre, co–vice chair of the task force.

"I’m struck by the similarities between the recommendations more than the differences," he said in an interview.

"ASCO concluded that the benefits don’t outweigh the harms, and even with [fewer than] 10 years’ life expectancy, the benefits might not outweigh the harms. ... We certainly also say that that assessment doesn’t mean that an individual clinician cannot offer screening, nor that an individual man can’t request screening,"

"The similarity between the two guidelines is that anybody doing PSA screening should be doing it as an informed choice," added Dr. LeFevre, the Future of Family Medicine professor and vice chair of the department of family and community medicine at the University of Missouri, Columbia.

The USPSTF tries to update its recommendations every 5 years, but may update earlier if important studies are published, as happened in this case. Two major studies are not yet published, Dr. Lefevre noted: PIVOT (Prostate Cancer Intervention Vs. Observation Trial) probably won’t prompt an update, but the PROTECT study "is large enough that I’m really hoping it will inform some of the unanswered questions that we have today."

Two Trials Key to ASCO Opinion

A "provisional clinical opinion" (PCO) is ASCO’s evidence-based approach to offering rapid responses to emerging data in clinical oncology. It is intended "to offer timely clinical direction to ASCO members after publication or presentation of potentially practice-changing data from major studies." In this case, the authors used the Agency for Health Research and Quality’s (AHRQ’s) review, which was also the basis for the USPSTF’s review.

Of the five randomized controlled trials identified, the ASCO panel deemed only two to be of sufficient quality. The PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer) screening trial, involving 76,685 men aged 55-74 years, showed no statistically significant differences in overall or prostate cancer–specific mortality at 7 years between men who were offered annual PSA screens and those who received usual care. However, half of the "usual care" group also received PSA screenings (J. Natl. Cancer Inst. 2012;104:125-32).

In contrast, in the multicenter ERSPC (European Randomized Study of Screening for Prostate Cancer) trial, which involved 182,160 men aged 50-74 years, those aged 55-69 who received PSA testing once every 4 years had a 20% reduction in prostate cancer–specific mortality (but not overall mortality) at 9 years, with the result maintained at 11 years (N. Engl. J. Med. 2009;360:1320-8).

In a subanalysis of the Swedish ERSPC center involving 20,000 men after 14 years of follow-up, statistically significant differences in prostate cancer–specific mortality of up to 56% were detected in favor of the PSA-screened (Lancet Oncol. 2010;11:725-32).

The AHRQ systematic review reported that the false-positive rates associated with PSA screening were 12.9% in the PLCO trial after four rounds of screening, and 12.5% in one center of the ERSPC after three rounds of screening. In PLCO, harms associated with diagnostic evaluations, including biopsy, were reported to be infection, bleeding, and urinary difficulty (68 events per 10,000 evaluations). In one center of the ERSPC trial, among 5,802 biopsies performed, reported harms were fever (3.5%), urinary retention (0.4%), hospitalization for signs of prostatitis or urosepsis (0.5%), and hematuria (22.6%) and hematospermia (50.4%) more than 3 days after biopsy.

"It is important to recognize that risk-benefit ratios can be substantially affected in studies and in practice by altering screening strategies, by changing treatment strategies, by changing measurement approaches, and by considering different lengths of follow-up.

"The ASCO guideline suggests that we can improve outcomes by becoming wiser about how we screen, wiser about who we treat, wiser about avoiding and managing harms of treatment, and wiser about how we communicate with patients," Dr. Basch said in the interview.

He added that physicians should not offer or order PSA screening unless they are "prepared to engage in shared decision making that enables an informed choice by patients." The current decision aid, designed to assist in that conversation, is a first version. "It is ASCO’s hope that it will be tested and refined in the future to become as efficient and useful as possible. It is also a hope that provision of accurate information to clarify decision making will make the PSA discussion more efficient and meaningful."

Hopefully, this process will be made easier in the future with new screening tests and new ways of using the PSA test that are currently under evaluation. Also, Dr. Basch said, "more mature results of ongoing screening studies, final results of treatment studies, and investigations of active surveillance approaches are all likely to improve our understanding of how screening and treatment can be optimized."

Dr. Basch reported no relevant disclosures, but one other ASCO panel member, Dr. Andrew Vickers, disclosed financial ties to GlaxoSmithKline and Genomic Health. USPHTF members such as Dr. LeFevre are vetted for disclosure.

NATIONAL HARBOR, MD. – Facebook is being used to directly solicit living kidney donors, and some aspects of that use raise privacy and ethical issues, according to Dr. Alex Chang.

The social networking site has been widely praised since its May 1 launch of a program allowing users to add organ donor status to their timelines and facilitating users’ linking to their state or national organ donor registries. However, its use for directly soliciting living donors raises issues of concern that organ transplant programs need to recognize and respond to, said Dr. Chang, a nephrology fellow at Loyola University Medical Center, Maywood, Ill.

"What I like about what Facebook has done is that it increases organ donation awareness and makes it personal. ... Facebook, I think, will dramatically increase organ registries if this is implemented well. However, careful consideration of the risks and benefits should be taken prior to being a living kidney donor," Dr. Chang said in an interview at a meeting sponsored by the National Kidney Foundation.

In their poster presentation at the meeting, Dr. Chang and his colleagues analyzed 144 English-language pages on Facebook devoted to soliciting a living kidney donor for a specific person in need. Potential organ recipients ranged in age from 2 to 69 years, and included all racial and ethnic groups and blood types. Of the pages for which the relationships between the page creator and the patient could be determined, 37% were created by the patients themselves, 31% by their children, and 32% by other family or friends.

People posted a range of information from one-sentence requests to explicit medical histories, as well as photographs of family and of the patient receiving hemodialysis.

"Much more careful consideration of the ethical implications of using social media is needed. The privacy issue is huge. ... Many people do not realize the vast amount of information that can be garnered from their Facebook pages, and when you add medical information to that, the risk is increased more," he said.

Although the contribution of Facebook in soliciting donors couldn’t be determined, 30% of the pages reported that donors had been tested, and 12% that a kidney transplant had been received. Individuals for whom donors were tested were significantly more likely to be white and to have more than 50 posts by others on their sites.

The risks of kidney donation were mentioned by 5% of the pages; only 11% mentioned associated costs. "I thought that was pretty astonishing since you are asking a very serious favor of your friends and family and/or strangers, and there is little mention of the actual risks and costs. Oftentimes, donors are caught unaware of certain financial costs such as missing 2 weeks of work and [the fact that] the long-term consequences of living kidney donation are still not totally certain. I believe this deserves fair mention if this method of media is being used for this purpose," Dr. Chang said.

Also of concern: Offers to sell kidneys were posted on 3% of pages.

"In my view I think it is premature to promote using Facebook to solicit living kidney donors. However it is happening and will continue to happen. I think that transplant programs have to recognize this and come up with plans on how to deal with social media–mediated living kidney transplant."

Dr. Chang said he had no relevant financial disclosures.

NATIONAL HARBOR, MD. – Facebook is being used to directly solicit living kidney donors, and some aspects of that use raise privacy and ethical issues, according to Dr. Alex Chang.

The social networking site has been widely praised since its May 1 launch of a program allowing users to add organ donor status to their timelines and facilitating users’ linking to their state or national organ donor registries. However, its use for directly soliciting living donors raises issues of concern that organ transplant programs need to recognize and respond to, said Dr. Chang, a nephrology fellow at Loyola University Medical Center, Maywood, Ill.

"What I like about what Facebook has done is that it increases organ donation awareness and makes it personal. ... Facebook, I think, will dramatically increase organ registries if this is implemented well. However, careful consideration of the risks and benefits should be taken prior to being a living kidney donor," Dr. Chang said in an interview at a meeting sponsored by the National Kidney Foundation.

In their poster presentation at the meeting, Dr. Chang and his colleagues analyzed 144 English-language pages on Facebook devoted to soliciting a living kidney donor for a specific person in need. Potential organ recipients ranged in age from 2 to 69 years, and included all racial and ethnic groups and blood types. Of the pages for which the relationships between the page creator and the patient could be determined, 37% were created by the patients themselves, 31% by their children, and 32% by other family or friends.

People posted a range of information from one-sentence requests to explicit medical histories, as well as photographs of family and of the patient receiving hemodialysis.

"Much more careful consideration of the ethical implications of using social media is needed. The privacy issue is huge. ... Many people do not realize the vast amount of information that can be garnered from their Facebook pages, and when you add medical information to that, the risk is increased more," he said.

Although the contribution of Facebook in soliciting donors couldn’t be determined, 30% of the pages reported that donors had been tested, and 12% that a kidney transplant had been received. Individuals for whom donors were tested were significantly more likely to be white and to have more than 50 posts by others on their sites.

The risks of kidney donation were mentioned by 5% of the pages; only 11% mentioned associated costs. "I thought that was pretty astonishing since you are asking a very serious favor of your friends and family and/or strangers, and there is little mention of the actual risks and costs. Oftentimes, donors are caught unaware of certain financial costs such as missing 2 weeks of work and [the fact that] the long-term consequences of living kidney donation are still not totally certain. I believe this deserves fair mention if this method of media is being used for this purpose," Dr. Chang said.

Also of concern: Offers to sell kidneys were posted on 3% of pages.

"In my view I think it is premature to promote using Facebook to solicit living kidney donors. However it is happening and will continue to happen. I think that transplant programs have to recognize this and come up with plans on how to deal with social media–mediated living kidney transplant."

Dr. Chang said he had no relevant financial disclosures.

NATIONAL HARBOR, MD. – Facebook is being used to directly solicit living kidney donors, and some aspects of that use raise privacy and ethical issues, according to Dr. Alex Chang.

The social networking site has been widely praised since its May 1 launch of a program allowing users to add organ donor status to their timelines and facilitating users’ linking to their state or national organ donor registries. However, its use for directly soliciting living donors raises issues of concern that organ transplant programs need to recognize and respond to, said Dr. Chang, a nephrology fellow at Loyola University Medical Center, Maywood, Ill.

"What I like about what Facebook has done is that it increases organ donation awareness and makes it personal. ... Facebook, I think, will dramatically increase organ registries if this is implemented well. However, careful consideration of the risks and benefits should be taken prior to being a living kidney donor," Dr. Chang said in an interview at a meeting sponsored by the National Kidney Foundation.

In their poster presentation at the meeting, Dr. Chang and his colleagues analyzed 144 English-language pages on Facebook devoted to soliciting a living kidney donor for a specific person in need. Potential organ recipients ranged in age from 2 to 69 years, and included all racial and ethnic groups and blood types. Of the pages for which the relationships between the page creator and the patient could be determined, 37% were created by the patients themselves, 31% by their children, and 32% by other family or friends.

People posted a range of information from one-sentence requests to explicit medical histories, as well as photographs of family and of the patient receiving hemodialysis.

"Much more careful consideration of the ethical implications of using social media is needed. The privacy issue is huge. ... Many people do not realize the vast amount of information that can be garnered from their Facebook pages, and when you add medical information to that, the risk is increased more," he said.

Although the contribution of Facebook in soliciting donors couldn’t be determined, 30% of the pages reported that donors had been tested, and 12% that a kidney transplant had been received. Individuals for whom donors were tested were significantly more likely to be white and to have more than 50 posts by others on their sites.

The risks of kidney donation were mentioned by 5% of the pages; only 11% mentioned associated costs. "I thought that was pretty astonishing since you are asking a very serious favor of your friends and family and/or strangers, and there is little mention of the actual risks and costs. Oftentimes, donors are caught unaware of certain financial costs such as missing 2 weeks of work and [the fact that] the long-term consequences of living kidney donation are still not totally certain. I believe this deserves fair mention if this method of media is being used for this purpose," Dr. Chang said.

Also of concern: Offers to sell kidneys were posted on 3% of pages.

"In my view I think it is premature to promote using Facebook to solicit living kidney donors. However it is happening and will continue to happen. I think that transplant programs have to recognize this and come up with plans on how to deal with social media–mediated living kidney transplant."

Dr. Chang said he had no relevant financial disclosures.

ATLANTA – The 13-valent pneumococcal conjugate vaccine should be given to all immunocompromised adults aged 19 years and older, according to new recommendations from the Centers for Disease Control and Prevention.

In a unanimous vote at its June meeting, the CDC’s Advisory Committee on Immunization Practices said that the 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13]) is recommended for the same adults who are currently advised to receive two doses of the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax]), including those with immunocompromising conditions. Patients who are immunocompromised include individuals with HIV infection, hematologic cancer, solid cancer, organ transplant, chronic renal failure/nephrotic syndrome, and diseases requiring treatment with immunosuppressive drugs, as well as patients with functional or anatomic asplenia, cerebrospinal fluid leaks, and cochlear implants.

The new recommendation calls for the use of PCV13 in addition to PPSV23.

According to Dr. Sandra A. Fryhofer, the liaison to the Advisory Committee on Immunization Practices (ACIP) from the American College of Physicians, "We’re very excited that there’s finally some guidance for internists about what to do with immunocompromised patients. Of course, we don’t have all the data yet. ... But this is the best we could do for now. On the surface it’s a very complicated recommendation schedule, but I think as we get more experience with it, maybe it will get easier in the implementation," she said in an interview.

Immunocompromised individuals are at significantly elevated risk for invasive pneumococcal disease (IPD). According to one study, that risk is 173-fold higher among HIV-infected individuals and 186 times higher in those with hematologic cancer compared with age-matched controls (J. Infect. Dis. 2005;192:377-86).

A cost-effectiveness analysis presented at the meeting found that use of PCV13 was cost saving for all the immunocompromised groups together, and for dialysis patients specifically. For HIV-infected patients, the cost per quality-adjusted life year gained was $3,206, well within the bounds of what is considered cost effective, according to the CDC’s Dr. Charles Stoecker.

However, Dr. Fryhofer, of Emory University in Atlanta, noted that the relative costs of PCV13 and PPSV23 – $124.37 versus $55.02 per dose in 2009 – are also likely to factor into the decision about a broader recommendation for PCV13. "This vaccine is more than twice the price of the vaccine we’ve been using. Cost effectiveness is important, and we have to think about stewardship in our resources. But certainly, pneumococcal disease is a leading killer."

The decision for the use of PCV13 in immunocompromised people was made despite the fact that the only study on vaccine efficacy in such individuals investigated the previous 7-valent formulation of the vaccine (PCV7), and was conducted in HIV-infected adults in Malawi (N. Engl. J. Med. 2010;362:812-22). "The only data we have are quite limited and not always applicable to the population we’re looking at, but we believe the data are sufficient to determine that the vaccine may be beneficial in these populations and will not cause harm," ACIP pneumococcal working group chair Dr. Nancy M. Bennett said in an interview. No further vaccine efficacy data are anticipated for the immunocompromised groups, she noted.

The vote for use of PCV13 in immunocompromised adults was taken in two parts, one for those aged 19 and older who have never received a pneumococcal vaccine, and the other for those who already received one or more doses of PPSV23. The former group should receive a single dose of PCV13, followed by a dose of PPSV23 at least 8 weeks later. After that, the current recommendations remain unchanged: a second dose of PPSV23 5 years later, and another one at age 65 or later.

For immunocompromised adults aged 19 and older who have already received one or more doses of PPSV23, the recommendation is to give PCV13 1 year or longer after the most recent PPSV23 dose. A second dose of PPSV23 is recommended 1 or more years after the first PCV13 dose and 5 or more years after the first PPSV23 dose.

Prevnar 13 is licensed for the prevention of IPD in children aged 6 weeks through 5 years, and for the prevention of both IPD and pneumococcal pneumonia in adults aged 50 years and older. The adult licensure, announced by the Food and Drug Administration on Dec. 30, 2011, was based on data showing noninferior immunogenicity compared with PPSV23.

Wider Use Under Consideration

At its February 2012 meeting, the ACIP decided to defer a vote on recommending PCV13 for all adults aged 50 years and older until additional data become available. That vote could come as early as February 2013, but it is more likely to be made at the June 2013 ACIP meeting, said Dr. Bennett, professor of medicine and community and preventive medicine at the University of Rochester (N.Y.).

Specifically, the committee is awaiting two pieces of data before deciding whether to recommend the routine use of PCV13 in adults aged 50 years and older. One is the indirect impact on adults – the so-called herd effect – of the now-routine use of PCV13 in children. Data collected thus far suggest that there has already been a decline in IPD cases since PCV13 was introduced in 2010, specifically due to the PCV13 strains 19A and 7F, the CDC’s Dr. Matthew Moore said.

The committee is also waiting for PCV13 vaccine efficacy data from a large trial in the Netherlands titled CAPITA (Community Acquired Pneumonia Immunization Trial in Adults), which aims to establish the efficacy of PCV13 in the prevention of a first episode of vaccine-serotype specific pneumococcal CAP in 85,000 community-dwelling adults aged 65 years and older (Neth. J. Med. 2008;66:378-83).

"We are interested in whether or not this vaccine should be used in the general population over the age of 50," said Dr. Bennett. "Pneumococcal pneumonia is really the holy grail. That is what we would like to be preventing since it’s much more pervasive than invasive pneumococcal disease. But unfortunately, most studies look at [IPD] as the outcome rather than pneumonia. So [the CAPITA study] is very very important, because if we can show that the vaccine prevents pneumonia in adults – something that’s been very difficult to show with any of the pneumococcal vaccines – then we would really have good evidence upon which to base the recommendation."

All of the sources for this story reported that they had no conflicts of interest.

ATLANTA – The 13-valent pneumococcal conjugate vaccine should be given to all immunocompromised adults aged 19 years and older, according to new recommendations from the Centers for Disease Control and Prevention.

In a unanimous vote at its June meeting, the CDC’s Advisory Committee on Immunization Practices said that the 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13]) is recommended for the same adults who are currently advised to receive two doses of the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax]), including those with immunocompromising conditions. Patients who are immunocompromised include individuals with HIV infection, hematologic cancer, solid cancer, organ transplant, chronic renal failure/nephrotic syndrome, and diseases requiring treatment with immunosuppressive drugs, as well as patients with functional or anatomic asplenia, cerebrospinal fluid leaks, and cochlear implants.

The new recommendation calls for the use of PCV13 in addition to PPSV23.

According to Dr. Sandra A. Fryhofer, the liaison to the Advisory Committee on Immunization Practices (ACIP) from the American College of Physicians, "We’re very excited that there’s finally some guidance for internists about what to do with immunocompromised patients. Of course, we don’t have all the data yet. ... But this is the best we could do for now. On the surface it’s a very complicated recommendation schedule, but I think as we get more experience with it, maybe it will get easier in the implementation," she said in an interview.

Immunocompromised individuals are at significantly elevated risk for invasive pneumococcal disease (IPD). According to one study, that risk is 173-fold higher among HIV-infected individuals and 186 times higher in those with hematologic cancer compared with age-matched controls (J. Infect. Dis. 2005;192:377-86).

A cost-effectiveness analysis presented at the meeting found that use of PCV13 was cost saving for all the immunocompromised groups together, and for dialysis patients specifically. For HIV-infected patients, the cost per quality-adjusted life year gained was $3,206, well within the bounds of what is considered cost effective, according to the CDC’s Dr. Charles Stoecker.

However, Dr. Fryhofer, of Emory University in Atlanta, noted that the relative costs of PCV13 and PPSV23 – $124.37 versus $55.02 per dose in 2009 – are also likely to factor into the decision about a broader recommendation for PCV13. "This vaccine is more than twice the price of the vaccine we’ve been using. Cost effectiveness is important, and we have to think about stewardship in our resources. But certainly, pneumococcal disease is a leading killer."

The decision for the use of PCV13 in immunocompromised people was made despite the fact that the only study on vaccine efficacy in such individuals investigated the previous 7-valent formulation of the vaccine (PCV7), and was conducted in HIV-infected adults in Malawi (N. Engl. J. Med. 2010;362:812-22). "The only data we have are quite limited and not always applicable to the population we’re looking at, but we believe the data are sufficient to determine that the vaccine may be beneficial in these populations and will not cause harm," ACIP pneumococcal working group chair Dr. Nancy M. Bennett said in an interview. No further vaccine efficacy data are anticipated for the immunocompromised groups, she noted.

The vote for use of PCV13 in immunocompromised adults was taken in two parts, one for those aged 19 and older who have never received a pneumococcal vaccine, and the other for those who already received one or more doses of PPSV23. The former group should receive a single dose of PCV13, followed by a dose of PPSV23 at least 8 weeks later. After that, the current recommendations remain unchanged: a second dose of PPSV23 5 years later, and another one at age 65 or later.

For immunocompromised adults aged 19 and older who have already received one or more doses of PPSV23, the recommendation is to give PCV13 1 year or longer after the most recent PPSV23 dose. A second dose of PPSV23 is recommended 1 or more years after the first PCV13 dose and 5 or more years after the first PPSV23 dose.

Prevnar 13 is licensed for the prevention of IPD in children aged 6 weeks through 5 years, and for the prevention of both IPD and pneumococcal pneumonia in adults aged 50 years and older. The adult licensure, announced by the Food and Drug Administration on Dec. 30, 2011, was based on data showing noninferior immunogenicity compared with PPSV23.

Wider Use Under Consideration

At its February 2012 meeting, the ACIP decided to defer a vote on recommending PCV13 for all adults aged 50 years and older until additional data become available. That vote could come as early as February 2013, but it is more likely to be made at the June 2013 ACIP meeting, said Dr. Bennett, professor of medicine and community and preventive medicine at the University of Rochester (N.Y.).

Specifically, the committee is awaiting two pieces of data before deciding whether to recommend the routine use of PCV13 in adults aged 50 years and older. One is the indirect impact on adults – the so-called herd effect – of the now-routine use of PCV13 in children. Data collected thus far suggest that there has already been a decline in IPD cases since PCV13 was introduced in 2010, specifically due to the PCV13 strains 19A and 7F, the CDC’s Dr. Matthew Moore said.

The committee is also waiting for PCV13 vaccine efficacy data from a large trial in the Netherlands titled CAPITA (Community Acquired Pneumonia Immunization Trial in Adults), which aims to establish the efficacy of PCV13 in the prevention of a first episode of vaccine-serotype specific pneumococcal CAP in 85,000 community-dwelling adults aged 65 years and older (Neth. J. Med. 2008;66:378-83).

"We are interested in whether or not this vaccine should be used in the general population over the age of 50," said Dr. Bennett. "Pneumococcal pneumonia is really the holy grail. That is what we would like to be preventing since it’s much more pervasive than invasive pneumococcal disease. But unfortunately, most studies look at [IPD] as the outcome rather than pneumonia. So [the CAPITA study] is very very important, because if we can show that the vaccine prevents pneumonia in adults – something that’s been very difficult to show with any of the pneumococcal vaccines – then we would really have good evidence upon which to base the recommendation."

All of the sources for this story reported that they had no conflicts of interest.

ATLANTA – The 13-valent pneumococcal conjugate vaccine should be given to all immunocompromised adults aged 19 years and older, according to new recommendations from the Centers for Disease Control and Prevention.

In a unanimous vote at its June meeting, the CDC’s Advisory Committee on Immunization Practices said that the 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13]) is recommended for the same adults who are currently advised to receive two doses of the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Pneumovax]), including those with immunocompromising conditions. Patients who are immunocompromised include individuals with HIV infection, hematologic cancer, solid cancer, organ transplant, chronic renal failure/nephrotic syndrome, and diseases requiring treatment with immunosuppressive drugs, as well as patients with functional or anatomic asplenia, cerebrospinal fluid leaks, and cochlear implants.

The new recommendation calls for the use of PCV13 in addition to PPSV23.

According to Dr. Sandra A. Fryhofer, the liaison to the Advisory Committee on Immunization Practices (ACIP) from the American College of Physicians, "We’re very excited that there’s finally some guidance for internists about what to do with immunocompromised patients. Of course, we don’t have all the data yet. ... But this is the best we could do for now. On the surface it’s a very complicated recommendation schedule, but I think as we get more experience with it, maybe it will get easier in the implementation," she said in an interview.

Immunocompromised individuals are at significantly elevated risk for invasive pneumococcal disease (IPD). According to one study, that risk is 173-fold higher among HIV-infected individuals and 186 times higher in those with hematologic cancer compared with age-matched controls (J. Infect. Dis. 2005;192:377-86).

A cost-effectiveness analysis presented at the meeting found that use of PCV13 was cost saving for all the immunocompromised groups together, and for dialysis patients specifically. For HIV-infected patients, the cost per quality-adjusted life year gained was $3,206, well within the bounds of what is considered cost effective, according to the CDC’s Dr. Charles Stoecker.

However, Dr. Fryhofer, of Emory University in Atlanta, noted that the relative costs of PCV13 and PPSV23 – $124.37 versus $55.02 per dose in 2009 – are also likely to factor into the decision about a broader recommendation for PCV13. "This vaccine is more than twice the price of the vaccine we’ve been using. Cost effectiveness is important, and we have to think about stewardship in our resources. But certainly, pneumococcal disease is a leading killer."

The decision for the use of PCV13 in immunocompromised people was made despite the fact that the only study on vaccine efficacy in such individuals investigated the previous 7-valent formulation of the vaccine (PCV7), and was conducted in HIV-infected adults in Malawi (N. Engl. J. Med. 2010;362:812-22). "The only data we have are quite limited and not always applicable to the population we’re looking at, but we believe the data are sufficient to determine that the vaccine may be beneficial in these populations and will not cause harm," ACIP pneumococcal working group chair Dr. Nancy M. Bennett said in an interview. No further vaccine efficacy data are anticipated for the immunocompromised groups, she noted.

The vote for use of PCV13 in immunocompromised adults was taken in two parts, one for those aged 19 and older who have never received a pneumococcal vaccine, and the other for those who already received one or more doses of PPSV23. The former group should receive a single dose of PCV13, followed by a dose of PPSV23 at least 8 weeks later. After that, the current recommendations remain unchanged: a second dose of PPSV23 5 years later, and another one at age 65 or later.

For immunocompromised adults aged 19 and older who have already received one or more doses of PPSV23, the recommendation is to give PCV13 1 year or longer after the most recent PPSV23 dose. A second dose of PPSV23 is recommended 1 or more years after the first PCV13 dose and 5 or more years after the first PPSV23 dose.

Prevnar 13 is licensed for the prevention of IPD in children aged 6 weeks through 5 years, and for the prevention of both IPD and pneumococcal pneumonia in adults aged 50 years and older. The adult licensure, announced by the Food and Drug Administration on Dec. 30, 2011, was based on data showing noninferior immunogenicity compared with PPSV23.

Wider Use Under Consideration

At its February 2012 meeting, the ACIP decided to defer a vote on recommending PCV13 for all adults aged 50 years and older until additional data become available. That vote could come as early as February 2013, but it is more likely to be made at the June 2013 ACIP meeting, said Dr. Bennett, professor of medicine and community and preventive medicine at the University of Rochester (N.Y.).

Specifically, the committee is awaiting two pieces of data before deciding whether to recommend the routine use of PCV13 in adults aged 50 years and older. One is the indirect impact on adults – the so-called herd effect – of the now-routine use of PCV13 in children. Data collected thus far suggest that there has already been a decline in IPD cases since PCV13 was introduced in 2010, specifically due to the PCV13 strains 19A and 7F, the CDC’s Dr. Matthew Moore said.

The committee is also waiting for PCV13 vaccine efficacy data from a large trial in the Netherlands titled CAPITA (Community Acquired Pneumonia Immunization Trial in Adults), which aims to establish the efficacy of PCV13 in the prevention of a first episode of vaccine-serotype specific pneumococcal CAP in 85,000 community-dwelling adults aged 65 years and older (Neth. J. Med. 2008;66:378-83).

"We are interested in whether or not this vaccine should be used in the general population over the age of 50," said Dr. Bennett. "Pneumococcal pneumonia is really the holy grail. That is what we would like to be preventing since it’s much more pervasive than invasive pneumococcal disease. But unfortunately, most studies look at [IPD] as the outcome rather than pneumonia. So [the CAPITA study] is very very important, because if we can show that the vaccine prevents pneumonia in adults – something that’s been very difficult to show with any of the pneumococcal vaccines – then we would really have good evidence upon which to base the recommendation."

All of the sources for this story reported that they had no conflicts of interest.

PHILADELPHIA – Closed-loop insulin therapy improved nocturnal glycemic control among 10 children with type 1 diabetes who were younger than 7 years of age, Dr. Andrew Dauber reported at the annual scientific sessions of the American Diabetes Association.

The effectiveness of closed-loop insulin delivery using a pump combined with a continuous glucose sensor and a controller algorithm – the so-called "artificial pancreas" – has been shown to improve glycemic control in patients with type 1 diabetes, but no studies have been conducted in children younger than 7 years old. They are at increased risk for hypoglycemia, particularly at night, and there is particular concern that repeated hypoglycemic episodes could lead to neurocognitive deficits in that age group, Dr. Dauber said. Both eating and activity patterns among young children tend to be erratic and unpredictable, making accurate insulin dosing difficult, he added.

"We believe this is an underrepresented group in research studies and that they need dedicated research in the development of an artificial pancreas," said Dr. Dauber, a pediatric endocrinologist at Children’s Hospital Boston.

The 10 children were aged 2.0-6.8 years (mean 5.1) and had a diabetes duration of 0.5-4.7 years (mean 2.1). At baseline, their hemoglobin A1_c levels ranged from 7.1% to 8.9%, with a mean of 8.1%. Seven of the 10 children had HbA1_c values of less than 8.5%, the American Diabetes Association’s target for children in that age group. Average daily insulin doses ranged from 0.61 to 1.0 units/kg (mean 0.72).

The closed-loop system included a physiological insulin delivery algorithm using proportional-integral-derivative terms that were modified by insulin feedback. During the overnight (10 p.m. to 8 a.m.) control period, basal rates were manually adjusted every 20 minutes based on the sensor readings. During the morning (8 a.m. to noon), mini-boluses of insulin were given every minute based on sensor readings. Target blood sugars were 150 mg/dL during 10 p.m. to 6 a.m. and 120 mg/dL during 6 a.m. to noon. The afternoon was spent in standard pump therapy.

The children were admitted to the research unit for 48 hours and given identical meals each day. No meal boluses were given during the closed-loop period. Each child spent one day on the closed-loop system during the overnight and morning, and another day with standard pump therapy (in random order).

Time spent in target glucose range of 110-200 mg/dL overnight was higher with the closed-loop system, 3.2 vs. 5.3 hours, but this did not reach statistical significance (P = .12). However, the closed-loop system significantly reduced the time spent with blood glucose levels above 300 mg/dL (0.18 vs. 1.3 hours, P = .035) and the noon glucose values (189 vs. 273 mg/dL, P = .009). Postprandial peaks were nearly identical (367 mg/dL closed-loop vs. 353 mg/dL open-loop) as were the number of interventions needed to treat hypoglycemia (5 vs. 4).

"Closed-loop therapy decreased the degree of nocturnal hyperglycemia in young children without increasing the incidence of hypoglycemia, and improved prelunch blood sugars. We believe closed-loop therapy has the potential to improve diabetes care for very young children," Dr. Dauber said.

Dr. Dauber received research support from Abbott Diabetes Care, Animas Corporation, and HemoCue Inc. which provided supplies for the study. The companies played no role in the design and conduct of the study, or in the collection, management, or interpretation of the data, he reported.

PHILADELPHIA – Closed-loop insulin therapy improved nocturnal glycemic control among 10 children with type 1 diabetes who were younger than 7 years of age, Dr. Andrew Dauber reported at the annual scientific sessions of the American Diabetes Association.

The effectiveness of closed-loop insulin delivery using a pump combined with a continuous glucose sensor and a controller algorithm – the so-called "artificial pancreas" – has been shown to improve glycemic control in patients with type 1 diabetes, but no studies have been conducted in children younger than 7 years old. They are at increased risk for hypoglycemia, particularly at night, and there is particular concern that repeated hypoglycemic episodes could lead to neurocognitive deficits in that age group, Dr. Dauber said. Both eating and activity patterns among young children tend to be erratic and unpredictable, making accurate insulin dosing difficult, he added.

"We believe this is an underrepresented group in research studies and that they need dedicated research in the development of an artificial pancreas," said Dr. Dauber, a pediatric endocrinologist at Children’s Hospital Boston.

The 10 children were aged 2.0-6.8 years (mean 5.1) and had a diabetes duration of 0.5-4.7 years (mean 2.1). At baseline, their hemoglobin A1_c levels ranged from 7.1% to 8.9%, with a mean of 8.1%. Seven of the 10 children had HbA1_c values of less than 8.5%, the American Diabetes Association’s target for children in that age group. Average daily insulin doses ranged from 0.61 to 1.0 units/kg (mean 0.72).

The closed-loop system included a physiological insulin delivery algorithm using proportional-integral-derivative terms that were modified by insulin feedback. During the overnight (10 p.m. to 8 a.m.) control period, basal rates were manually adjusted every 20 minutes based on the sensor readings. During the morning (8 a.m. to noon), mini-boluses of insulin were given every minute based on sensor readings. Target blood sugars were 150 mg/dL during 10 p.m. to 6 a.m. and 120 mg/dL during 6 a.m. to noon. The afternoon was spent in standard pump therapy.

The children were admitted to the research unit for 48 hours and given identical meals each day. No meal boluses were given during the closed-loop period. Each child spent one day on the closed-loop system during the overnight and morning, and another day with standard pump therapy (in random order).

Time spent in target glucose range of 110-200 mg/dL overnight was higher with the closed-loop system, 3.2 vs. 5.3 hours, but this did not reach statistical significance (P = .12). However, the closed-loop system significantly reduced the time spent with blood glucose levels above 300 mg/dL (0.18 vs. 1.3 hours, P = .035) and the noon glucose values (189 vs. 273 mg/dL, P = .009). Postprandial peaks were nearly identical (367 mg/dL closed-loop vs. 353 mg/dL open-loop) as were the number of interventions needed to treat hypoglycemia (5 vs. 4).

"Closed-loop therapy decreased the degree of nocturnal hyperglycemia in young children without increasing the incidence of hypoglycemia, and improved prelunch blood sugars. We believe closed-loop therapy has the potential to improve diabetes care for very young children," Dr. Dauber said.

Dr. Dauber received research support from Abbott Diabetes Care, Animas Corporation, and HemoCue Inc. which provided supplies for the study. The companies played no role in the design and conduct of the study, or in the collection, management, or interpretation of the data, he reported.

PHILADELPHIA – Closed-loop insulin therapy improved nocturnal glycemic control among 10 children with type 1 diabetes who were younger than 7 years of age, Dr. Andrew Dauber reported at the annual scientific sessions of the American Diabetes Association.

The effectiveness of closed-loop insulin delivery using a pump combined with a continuous glucose sensor and a controller algorithm – the so-called "artificial pancreas" – has been shown to improve glycemic control in patients with type 1 diabetes, but no studies have been conducted in children younger than 7 years old. They are at increased risk for hypoglycemia, particularly at night, and there is particular concern that repeated hypoglycemic episodes could lead to neurocognitive deficits in that age group, Dr. Dauber said. Both eating and activity patterns among young children tend to be erratic and unpredictable, making accurate insulin dosing difficult, he added.

"We believe this is an underrepresented group in research studies and that they need dedicated research in the development of an artificial pancreas," said Dr. Dauber, a pediatric endocrinologist at Children’s Hospital Boston.

The 10 children were aged 2.0-6.8 years (mean 5.1) and had a diabetes duration of 0.5-4.7 years (mean 2.1). At baseline, their hemoglobin A1_c levels ranged from 7.1% to 8.9%, with a mean of 8.1%. Seven of the 10 children had HbA1_c values of less than 8.5%, the American Diabetes Association’s target for children in that age group. Average daily insulin doses ranged from 0.61 to 1.0 units/kg (mean 0.72).

The closed-loop system included a physiological insulin delivery algorithm using proportional-integral-derivative terms that were modified by insulin feedback. During the overnight (10 p.m. to 8 a.m.) control period, basal rates were manually adjusted every 20 minutes based on the sensor readings. During the morning (8 a.m. to noon), mini-boluses of insulin were given every minute based on sensor readings. Target blood sugars were 150 mg/dL during 10 p.m. to 6 a.m. and 120 mg/dL during 6 a.m. to noon. The afternoon was spent in standard pump therapy.

The children were admitted to the research unit for 48 hours and given identical meals each day. No meal boluses were given during the closed-loop period. Each child spent one day on the closed-loop system during the overnight and morning, and another day with standard pump therapy (in random order).

Time spent in target glucose range of 110-200 mg/dL overnight was higher with the closed-loop system, 3.2 vs. 5.3 hours, but this did not reach statistical significance (P = .12). However, the closed-loop system significantly reduced the time spent with blood glucose levels above 300 mg/dL (0.18 vs. 1.3 hours, P = .035) and the noon glucose values (189 vs. 273 mg/dL, P = .009). Postprandial peaks were nearly identical (367 mg/dL closed-loop vs. 353 mg/dL open-loop) as were the number of interventions needed to treat hypoglycemia (5 vs. 4).

"Closed-loop therapy decreased the degree of nocturnal hyperglycemia in young children without increasing the incidence of hypoglycemia, and improved prelunch blood sugars. We believe closed-loop therapy has the potential to improve diabetes care for very young children," Dr. Dauber said.

Dr. Dauber received research support from Abbott Diabetes Care, Animas Corporation, and HemoCue Inc. which provided supplies for the study. The companies played no role in the design and conduct of the study, or in the collection, management, or interpretation of the data, he reported.

NATIONAL HARBOR, MD. – Contrary to current practice trends, evidence suggests that kidney dialysis can – and perhaps should – be delayed in older adults with chronic kidney disease.

"Older adults, like their younger counterparts, should not initiate dialysis on the basis of [estimated glomerular filtration] alone, but can wait to delay dialysis initiation until more traditional clinical indicators appear, such as fluid overload that can’t be managed with diuretics; uremic symptoms which interfere with quality of life; or electrolyte disturbances," said Dr. Manjula Kurella Tamura.

"An individualized approach to these decisions that accounts for the patient’s burden of symptoms and trajectory of kidney function decline is probably wise until more clinical trials are conducted in the older adult population," continued Dr. Tamura of the division of nephrology at Stanford (Calif.) University.

Two striking patterns have emerged over time. First, in all age groups, dialysis is being initiated at a higher estimated glomerular filtration rate (eGFR) today, compared with a decade ago, which is generally viewed as representing earlier initiation of dialysis over time (Kidney Int. 2009;76:257-61).

Secondl older patients are initiating dialysis earlier in the course of kidney disease than are younger patients. This was true one decade ago and is even more so today, when more than 50% of patients older than age 75 years begin dialysis with an eGFR greater than 10 mL/min per 1.73 m² (Arch. Intern. Med. 2011;171:1663-9).

One rationale often cited for starting older patients on dialysis sooner is that they have a lower tolerance for uremia. However, Dr. Tamura said, "I looked back through the literature to find out where this idea came from. It certainly has a lot of face validity, but is there evidence that it’s true? I couldn’t find it. I just kept seeing it repeated over and over, that older patients need to start sooner. But I couldn’t find an explanation."

And in fact, increasing evidence suggests that the opposite may be true. In one study of 112 adults older than age 75 with GFR of 5-7 mL/min, there were no differences in survival between those who were randomized to dialysis or those on a very low protein diet with delayed dialysis initiation (median follow-up, 26.5 months). There also were no differences between the two groups in the causes of death, and there were actually fewer hospitalizations and total hospital days in the diet group (Am. J. Kidney Dis. 2007;49:569-80).

That study excluded patients with diabetes, an ejection fraction less than 30%, urine protein excretion greater than 3 g/day, active malignancy, and uremic symptoms, she noted.

Subsequently, the multicenter IDEAL (Initiating Dialysis Early and Late) study was conducted in Australia and New Zealand, in which 828 adults (mean age, 60 years) with progressive chronic kidney disease were randomized to "early start" of dialysis, with planned initiation when eGFR was 10.0-14.0 mL/min, or "late start," at eGFR of 5.0-7.0 mL/min. Earlier initiation of dialysis was permitted based on the discretion of the treating physician (N. Engl. J. Med. 2010;363:609-19).

Owing to the development of symptoms, 75% of the "late start" group was initiated on dialysis with an eGFR of greater than 7.0 mL/min, with a mean of 9.8 mL/min and a median delay of 6 months, compared with the "early start" group, who initiated dialysis with a mean eGFR of 12 mL/min. There were no differences in survival between the early and late groups (median follow-up, 3.6 years). Subgroup analysis showed that there also were no differences between the early vs. late groups among patients older than 60 years, Dr. Tamura said.

The IDEAL authors concluded that "with careful clinical management, dialysis may be delayed until either the GFR drops below 7 mL/min or more traditional clinical indicators for the initiation of dialysis are present."

However, the question of whether the IDEAL findings can be applied to older patients prompted controversy, given that the patients included in the study were younger than the overall dialysis population and relatively healthy, and therefore less susceptible to the potential complications of later initiation of dialysis (N. Engl. J. Med. 2010;363:2368).

To address that issue, Dr. Tamura and her associates retrospectively examined the timing of initiation of dialysis in a population of 2,402 nursing home residents who initiated dialysis in 1998-2000. The median eGFR at the time of dialysis initiation was 9.8 mL/min. The likelihood of earlier dialysis initiation (eGFR of 15 mL/min or greater) was associated with having one or more signs and symptoms of volume overload, cognitive decline, increased dependence in activities of daily living, and weight loss. However, those factors altogether accounted for only 31% of the early dialysis initiations (Am. J. Kidney Dis. 2010;56:1117-26).

"Certainly, the factors that contribute to early dialysis initiation are complex and may not always be clinical. But again, it makes you think that perhaps some of these patients are not started early because they have symptoms, but for other reasons, and perhaps it’s just the nervousness of the nephrologist caring for a very frail patient," she commented.

Indeed, urgent indications accounted for just 10% of the patients in the late-start arm of the IDEAL study who ended up initiating dialysis at greater than the target eGFR, with "uremia" and "physician discretion" accounting for 80%. However, Dr. Tamura pointed out, the uremic syndrome can be difficult to diagnose in elderly patients with other chronic conditions. No biomarker is sufficiently specific, and symptoms of uremia can overlap with other conditions. For example, nausea may result from diabetic gastroparesis, fatigue may be from cardiopulmonary disease or depression, and cognitive impairment might be cause by medications or dementia.

Moreover, conditions commonly observed in advanced chronic kidney disease – such as malnutrition, low functional status, pruritis, and restless leg syndrome – not always improve with dialysis initiation.

Also complicating the decision of when to initiate dialysis in the elderly is the fact that estimated equations for GFR tend to be less accurate in the elderly due to sarcopenia and fluid retention, and that acute kidney injury is more common in older patients, she said.

Given all this, Dr. Tamura advises that it is appropriate to delay dialysis initiation in older asymptomatic adults with an eGFR greater than 10 mL/min. As for when it is appropriate to initiate dialysis, "there are still more questions than answers. Clinical judgment will continue to guide practice, but hopefully symptom burden and patient preferences will have a stronger influence."

Dr. Tamura reported having no conflicts of interest.

NATIONAL HARBOR, MD. – Contrary to current practice trends, evidence suggests that kidney dialysis can – and perhaps should – be delayed in older adults with chronic kidney disease.

"Older adults, like their younger counterparts, should not initiate dialysis on the basis of [estimated glomerular filtration] alone, but can wait to delay dialysis initiation until more traditional clinical indicators appear, such as fluid overload that can’t be managed with diuretics; uremic symptoms which interfere with quality of life; or electrolyte disturbances," said Dr. Manjula Kurella Tamura.

"An individualized approach to these decisions that accounts for the patient’s burden of symptoms and trajectory of kidney function decline is probably wise until more clinical trials are conducted in the older adult population," continued Dr. Tamura of the division of nephrology at Stanford (Calif.) University.

Two striking patterns have emerged over time. First, in all age groups, dialysis is being initiated at a higher estimated glomerular filtration rate (eGFR) today, compared with a decade ago, which is generally viewed as representing earlier initiation of dialysis over time (Kidney Int. 2009;76:257-61).

Secondl older patients are initiating dialysis earlier in the course of kidney disease than are younger patients. This was true one decade ago and is even more so today, when more than 50% of patients older than age 75 years begin dialysis with an eGFR greater than 10 mL/min per 1.73 m² (Arch. Intern. Med. 2011;171:1663-9).

One rationale often cited for starting older patients on dialysis sooner is that they have a lower tolerance for uremia. However, Dr. Tamura said, "I looked back through the literature to find out where this idea came from. It certainly has a lot of face validity, but is there evidence that it’s true? I couldn’t find it. I just kept seeing it repeated over and over, that older patients need to start sooner. But I couldn’t find an explanation."

And in fact, increasing evidence suggests that the opposite may be true. In one study of 112 adults older than age 75 with GFR of 5-7 mL/min, there were no differences in survival between those who were randomized to dialysis or those on a very low protein diet with delayed dialysis initiation (median follow-up, 26.5 months). There also were no differences between the two groups in the causes of death, and there were actually fewer hospitalizations and total hospital days in the diet group (Am. J. Kidney Dis. 2007;49:569-80).

That study excluded patients with diabetes, an ejection fraction less than 30%, urine protein excretion greater than 3 g/day, active malignancy, and uremic symptoms, she noted.

Subsequently, the multicenter IDEAL (Initiating Dialysis Early and Late) study was conducted in Australia and New Zealand, in which 828 adults (mean age, 60 years) with progressive chronic kidney disease were randomized to "early start" of dialysis, with planned initiation when eGFR was 10.0-14.0 mL/min, or "late start," at eGFR of 5.0-7.0 mL/min. Earlier initiation of dialysis was permitted based on the discretion of the treating physician (N. Engl. J. Med. 2010;363:609-19).

Owing to the development of symptoms, 75% of the "late start" group was initiated on dialysis with an eGFR of greater than 7.0 mL/min, with a mean of 9.8 mL/min and a median delay of 6 months, compared with the "early start" group, who initiated dialysis with a mean eGFR of 12 mL/min. There were no differences in survival between the early and late groups (median follow-up, 3.6 years). Subgroup analysis showed that there also were no differences between the early vs. late groups among patients older than 60 years, Dr. Tamura said.

The IDEAL authors concluded that "with careful clinical management, dialysis may be delayed until either the GFR drops below 7 mL/min or more traditional clinical indicators for the initiation of dialysis are present."

However, the question of whether the IDEAL findings can be applied to older patients prompted controversy, given that the patients included in the study were younger than the overall dialysis population and relatively healthy, and therefore less susceptible to the potential complications of later initiation of dialysis (N. Engl. J. Med. 2010;363:2368).

To address that issue, Dr. Tamura and her associates retrospectively examined the timing of initiation of dialysis in a population of 2,402 nursing home residents who initiated dialysis in 1998-2000. The median eGFR at the time of dialysis initiation was 9.8 mL/min. The likelihood of earlier dialysis initiation (eGFR of 15 mL/min or greater) was associated with having one or more signs and symptoms of volume overload, cognitive decline, increased dependence in activities of daily living, and weight loss. However, those factors altogether accounted for only 31% of the early dialysis initiations (Am. J. Kidney Dis. 2010;56:1117-26).

"Certainly, the factors that contribute to early dialysis initiation are complex and may not always be clinical. But again, it makes you think that perhaps some of these patients are not started early because they have symptoms, but for other reasons, and perhaps it’s just the nervousness of the nephrologist caring for a very frail patient," she commented.

Indeed, urgent indications accounted for just 10% of the patients in the late-start arm of the IDEAL study who ended up initiating dialysis at greater than the target eGFR, with "uremia" and "physician discretion" accounting for 80%. However, Dr. Tamura pointed out, the uremic syndrome can be difficult to diagnose in elderly patients with other chronic conditions. No biomarker is sufficiently specific, and symptoms of uremia can overlap with other conditions. For example, nausea may result from diabetic gastroparesis, fatigue may be from cardiopulmonary disease or depression, and cognitive impairment might be cause by medications or dementia.

Moreover, conditions commonly observed in advanced chronic kidney disease – such as malnutrition, low functional status, pruritis, and restless leg syndrome – not always improve with dialysis initiation.

Also complicating the decision of when to initiate dialysis in the elderly is the fact that estimated equations for GFR tend to be less accurate in the elderly due to sarcopenia and fluid retention, and that acute kidney injury is more common in older patients, she said.

Given all this, Dr. Tamura advises that it is appropriate to delay dialysis initiation in older asymptomatic adults with an eGFR greater than 10 mL/min. As for when it is appropriate to initiate dialysis, "there are still more questions than answers. Clinical judgment will continue to guide practice, but hopefully symptom burden and patient preferences will have a stronger influence."

Dr. Tamura reported having no conflicts of interest.

NATIONAL HARBOR, MD. – Contrary to current practice trends, evidence suggests that kidney dialysis can – and perhaps should – be delayed in older adults with chronic kidney disease.

"Older adults, like their younger counterparts, should not initiate dialysis on the basis of [estimated glomerular filtration] alone, but can wait to delay dialysis initiation until more traditional clinical indicators appear, such as fluid overload that can’t be managed with diuretics; uremic symptoms which interfere with quality of life; or electrolyte disturbances," said Dr. Manjula Kurella Tamura.

"An individualized approach to these decisions that accounts for the patient’s burden of symptoms and trajectory of kidney function decline is probably wise until more clinical trials are conducted in the older adult population," continued Dr. Tamura of the division of nephrology at Stanford (Calif.) University.

Two striking patterns have emerged over time. First, in all age groups, dialysis is being initiated at a higher estimated glomerular filtration rate (eGFR) today, compared with a decade ago, which is generally viewed as representing earlier initiation of dialysis over time (Kidney Int. 2009;76:257-61).

Secondl older patients are initiating dialysis earlier in the course of kidney disease than are younger patients. This was true one decade ago and is even more so today, when more than 50% of patients older than age 75 years begin dialysis with an eGFR greater than 10 mL/min per 1.73 m² (Arch. Intern. Med. 2011;171:1663-9).

One rationale often cited for starting older patients on dialysis sooner is that they have a lower tolerance for uremia. However, Dr. Tamura said, "I looked back through the literature to find out where this idea came from. It certainly has a lot of face validity, but is there evidence that it’s true? I couldn’t find it. I just kept seeing it repeated over and over, that older patients need to start sooner. But I couldn’t find an explanation."

And in fact, increasing evidence suggests that the opposite may be true. In one study of 112 adults older than age 75 with GFR of 5-7 mL/min, there were no differences in survival between those who were randomized to dialysis or those on a very low protein diet with delayed dialysis initiation (median follow-up, 26.5 months). There also were no differences between the two groups in the causes of death, and there were actually fewer hospitalizations and total hospital days in the diet group (Am. J. Kidney Dis. 2007;49:569-80).

That study excluded patients with diabetes, an ejection fraction less than 30%, urine protein excretion greater than 3 g/day, active malignancy, and uremic symptoms, she noted.

Subsequently, the multicenter IDEAL (Initiating Dialysis Early and Late) study was conducted in Australia and New Zealand, in which 828 adults (mean age, 60 years) with progressive chronic kidney disease were randomized to "early start" of dialysis, with planned initiation when eGFR was 10.0-14.0 mL/min, or "late start," at eGFR of 5.0-7.0 mL/min. Earlier initiation of dialysis was permitted based on the discretion of the treating physician (N. Engl. J. Med. 2010;363:609-19).

Owing to the development of symptoms, 75% of the "late start" group was initiated on dialysis with an eGFR of greater than 7.0 mL/min, with a mean of 9.8 mL/min and a median delay of 6 months, compared with the "early start" group, who initiated dialysis with a mean eGFR of 12 mL/min. There were no differences in survival between the early and late groups (median follow-up, 3.6 years). Subgroup analysis showed that there also were no differences between the early vs. late groups among patients older than 60 years, Dr. Tamura said.

The IDEAL authors concluded that "with careful clinical management, dialysis may be delayed until either the GFR drops below 7 mL/min or more traditional clinical indicators for the initiation of dialysis are present."

However, the question of whether the IDEAL findings can be applied to older patients prompted controversy, given that the patients included in the study were younger than the overall dialysis population and relatively healthy, and therefore less susceptible to the potential complications of later initiation of dialysis (N. Engl. J. Med. 2010;363:2368).

To address that issue, Dr. Tamura and her associates retrospectively examined the timing of initiation of dialysis in a population of 2,402 nursing home residents who initiated dialysis in 1998-2000. The median eGFR at the time of dialysis initiation was 9.8 mL/min. The likelihood of earlier dialysis initiation (eGFR of 15 mL/min or greater) was associated with having one or more signs and symptoms of volume overload, cognitive decline, increased dependence in activities of daily living, and weight loss. However, those factors altogether accounted for only 31% of the early dialysis initiations (Am. J. Kidney Dis. 2010;56:1117-26).

"Certainly, the factors that contribute to early dialysis initiation are complex and may not always be clinical. But again, it makes you think that perhaps some of these patients are not started early because they have symptoms, but for other reasons, and perhaps it’s just the nervousness of the nephrologist caring for a very frail patient," she commented.

Indeed, urgent indications accounted for just 10% of the patients in the late-start arm of the IDEAL study who ended up initiating dialysis at greater than the target eGFR, with "uremia" and "physician discretion" accounting for 80%. However, Dr. Tamura pointed out, the uremic syndrome can be difficult to diagnose in elderly patients with other chronic conditions. No biomarker is sufficiently specific, and symptoms of uremia can overlap with other conditions. For example, nausea may result from diabetic gastroparesis, fatigue may be from cardiopulmonary disease or depression, and cognitive impairment might be cause by medications or dementia.

Moreover, conditions commonly observed in advanced chronic kidney disease – such as malnutrition, low functional status, pruritis, and restless leg syndrome – not always improve with dialysis initiation.

Also complicating the decision of when to initiate dialysis in the elderly is the fact that estimated equations for GFR tend to be less accurate in the elderly due to sarcopenia and fluid retention, and that acute kidney injury is more common in older patients, she said.

Given all this, Dr. Tamura advises that it is appropriate to delay dialysis initiation in older asymptomatic adults with an eGFR greater than 10 mL/min. As for when it is appropriate to initiate dialysis, "there are still more questions than answers. Clinical judgment will continue to guide practice, but hopefully symptom burden and patient preferences will have a stronger influence."

Dr. Tamura reported having no conflicts of interest.

ATLANTA – The 2012-2013 influenza vaccination statement from the Centers for Disease Control and Prevention’s vaccine advisory panel is expected to contain a new algorithm for children aged 6 months through 8 years to determine whether they need one or two doses.

The CDC’s Advisory Committee on Immunization Practices voted to approve the same algorithm approved by the American Academy of Pediatrics’ Committee on Infectious Disease earlier this year:

© Yarinca/istockphoto.com

• First, has the child ever received influenza vaccine?

• If yes, did the child receive two or more total doses of seasonal vaccine since July 2010?

• If yes, give one dose. If not, or if the information isn’t known, give two doses.

• If the child has never received influenza vaccine or the information isn’t known, give two doses.

The algorithm was necessary because children younger than 9 years of age need two doses of seasonal vaccine in order to establish immune system priming, and two out of the three influenza strains included in the 2012-2013 influenza vaccine – A/Victoria/361/2011 (H3N2) and B/Wisconsin/1/2010 – are different from those of the 2011-2012 vaccine. The one that remains the same is the 2009 pandemic strain A/California/7/2009, which was available in 2009 as a monovalent vaccine and then was included in the seasonal 2010-2011 and 2011-2012 flu vaccines, said Dr. Lisa Grohskopf of the CDC’s Influenza Division.

The algorithm was designed to be simple, the AAP’s liaison Dr. Michael T. Brady said in an interview. "Thirty-five percent or so of children receive vaccines outside of their medical home. That creates a problem with access to the information. Also, many pediatricians will set up vaccine clinics designed to move children through quickly. ... You’d like to make it so that any child who needs two gets two [doses of the flu vaccine]."

But, he said, if the information is available, then the option is still there to use it. "The option is, do you want to put the onus on the pediatrician to try to track everything down, or do you want to try to make it more fail-safe so that it’s easier? What this does in general is make it simple. But if you want to get the information and avoid an extra dose, that’s fine," said Dr. Brady, professor and chair of pediatrics at the Ohio State University and Nationwide Children’s Hospital, both in Columbus.

Once adopted by the CDC and published in the CDC’s Morbidity and Mortality Report, the influenza vaccine statement will also contain information about the strains selected for 2012-2013, a reiteration of the universal recommendation for flu vaccine for all individuals aged 6 months and older, and an acknowledgement of the recently-approved quadrivalent live attenuated vaccine, which is expected to be available for the 2013-2014.

The statement also will include an update of an investigation into an increased risk for febrile seizures associated with receipt of the trivalent inactivated influenza vaccine (TIV) in conjunction with the 13-valent pneumococcal conjugate vaccine. The elevated risk was seen for seizures following TIV in children aged 6-23 months in surveillance data for 2011-2012 among children aged 6-23 months, but not in those aged 24-59 months.

At the meeting, the committee also voted use of the vaccine via the new algorithm into the federal Vaccines for Children Program.

As a CDC employee, Dr. Grohskopf has no disclosures. Dr. Brady stated that he has no relevant financial disclosures.

ATLANTA – The 2012-2013 influenza vaccination statement from the Centers for Disease Control and Prevention’s vaccine advisory panel is expected to contain a new algorithm for children aged 6 months through 8 years to determine whether they need one or two doses.

The CDC’s Advisory Committee on Immunization Practices voted to approve the same algorithm approved by the American Academy of Pediatrics’ Committee on Infectious Disease earlier this year:

© Yarinca/istockphoto.com

• First, has the child ever received influenza vaccine?

• If yes, did the child receive two or more total doses of seasonal vaccine since July 2010?

• If yes, give one dose. If not, or if the information isn’t known, give two doses.

• If the child has never received influenza vaccine or the information isn’t known, give two doses.

The algorithm was necessary because children younger than 9 years of age need two doses of seasonal vaccine in order to establish immune system priming, and two out of the three influenza strains included in the 2012-2013 influenza vaccine – A/Victoria/361/2011 (H3N2) and B/Wisconsin/1/2010 – are different from those of the 2011-2012 vaccine. The one that remains the same is the 2009 pandemic strain A/California/7/2009, which was available in 2009 as a monovalent vaccine and then was included in the seasonal 2010-2011 and 2011-2012 flu vaccines, said Dr. Lisa Grohskopf of the CDC’s Influenza Division.

The algorithm was designed to be simple, the AAP’s liaison Dr. Michael T. Brady said in an interview. "Thirty-five percent or so of children receive vaccines outside of their medical home. That creates a problem with access to the information. Also, many pediatricians will set up vaccine clinics designed to move children through quickly. ... You’d like to make it so that any child who needs two gets two [doses of the flu vaccine]."

But, he said, if the information is available, then the option is still there to use it. "The option is, do you want to put the onus on the pediatrician to try to track everything down, or do you want to try to make it more fail-safe so that it’s easier? What this does in general is make it simple. But if you want to get the information and avoid an extra dose, that’s fine," said Dr. Brady, professor and chair of pediatrics at the Ohio State University and Nationwide Children’s Hospital, both in Columbus.

Once adopted by the CDC and published in the CDC’s Morbidity and Mortality Report, the influenza vaccine statement will also contain information about the strains selected for 2012-2013, a reiteration of the universal recommendation for flu vaccine for all individuals aged 6 months and older, and an acknowledgement of the recently-approved quadrivalent live attenuated vaccine, which is expected to be available for the 2013-2014.

The statement also will include an update of an investigation into an increased risk for febrile seizures associated with receipt of the trivalent inactivated influenza vaccine (TIV) in conjunction with the 13-valent pneumococcal conjugate vaccine. The elevated risk was seen for seizures following TIV in children aged 6-23 months in surveillance data for 2011-2012 among children aged 6-23 months, but not in those aged 24-59 months.

At the meeting, the committee also voted use of the vaccine via the new algorithm into the federal Vaccines for Children Program.

As a CDC employee, Dr. Grohskopf has no disclosures. Dr. Brady stated that he has no relevant financial disclosures.

ATLANTA – The 2012-2013 influenza vaccination statement from the Centers for Disease Control and Prevention’s vaccine advisory panel is expected to contain a new algorithm for children aged 6 months through 8 years to determine whether they need one or two doses.

The CDC’s Advisory Committee on Immunization Practices voted to approve the same algorithm approved by the American Academy of Pediatrics’ Committee on Infectious Disease earlier this year:

© Yarinca/istockphoto.com

• First, has the child ever received influenza vaccine?

• If yes, did the child receive two or more total doses of seasonal vaccine since July 2010?

• If yes, give one dose. If not, or if the information isn’t known, give two doses.

• If the child has never received influenza vaccine or the information isn’t known, give two doses.

The algorithm was necessary because children younger than 9 years of age need two doses of seasonal vaccine in order to establish immune system priming, and two out of the three influenza strains included in the 2012-2013 influenza vaccine – A/Victoria/361/2011 (H3N2) and B/Wisconsin/1/2010 – are different from those of the 2011-2012 vaccine. The one that remains the same is the 2009 pandemic strain A/California/7/2009, which was available in 2009 as a monovalent vaccine and then was included in the seasonal 2010-2011 and 2011-2012 flu vaccines, said Dr. Lisa Grohskopf of the CDC’s Influenza Division.

The algorithm was designed to be simple, the AAP’s liaison Dr. Michael T. Brady said in an interview. "Thirty-five percent or so of children receive vaccines outside of their medical home. That creates a problem with access to the information. Also, many pediatricians will set up vaccine clinics designed to move children through quickly. ... You’d like to make it so that any child who needs two gets two [doses of the flu vaccine]."

But, he said, if the information is available, then the option is still there to use it. "The option is, do you want to put the onus on the pediatrician to try to track everything down, or do you want to try to make it more fail-safe so that it’s easier? What this does in general is make it simple. But if you want to get the information and avoid an extra dose, that’s fine," said Dr. Brady, professor and chair of pediatrics at the Ohio State University and Nationwide Children’s Hospital, both in Columbus.

Once adopted by the CDC and published in the CDC’s Morbidity and Mortality Report, the influenza vaccine statement will also contain information about the strains selected for 2012-2013, a reiteration of the universal recommendation for flu vaccine for all individuals aged 6 months and older, and an acknowledgement of the recently-approved quadrivalent live attenuated vaccine, which is expected to be available for the 2013-2014.

The statement also will include an update of an investigation into an increased risk for febrile seizures associated with receipt of the trivalent inactivated influenza vaccine (TIV) in conjunction with the 13-valent pneumococcal conjugate vaccine. The elevated risk was seen for seizures following TIV in children aged 6-23 months in surveillance data for 2011-2012 among children aged 6-23 months, but not in those aged 24-59 months.

At the meeting, the committee also voted use of the vaccine via the new algorithm into the federal Vaccines for Children Program.

As a CDC employee, Dr. Grohskopf has no disclosures. Dr. Brady stated that he has no relevant financial disclosures.

A new combination vaccine protects infants and children against both meningococcal and Haemophilus influenzae type b infections.

The Food and Drug Administration on June 14 approved GlaxoSmithKline Biologicals’ Menhibrix, a combination vaccine for infants and children aged 6 weeks through 18 months, for prevention of invasive disease caused by Neisseria meningitidis serogroups C and Y and Haemophilus influenzae type b. It is the first meningococcal vaccine that can be given starting as young as 6 weeks of age, Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement.

The effectiveness of Menhibrix was based on immune responses in several hundred U.S. infants and toddlers who received the vaccine. For the Hib component of the vaccine, immune responses in infants and toddlers following vaccination with Menhibrix were found to be comparable to immune responses in infants and toddlers who received another FDA-approved vaccine against invasive Hib disease. For the meningococcal component, data showed that the vaccine induced the production of antibodies at levels considered to be predictive of protection against invasive meningococcal disease caused by serogroups C and Y, the FDA said.

Safety data for Menhibrix were obtained from about 7,500 infants and toddlers in the United States, Mexico, and Australia. Common adverse reactions reported after administration of Menhibrix were pain, redness, and swelling at the injection site, irritability, and fever.

Menhibrix is given as a four-dose series at 2, 4, 6 and 12 through 15 months of age. The first dose may be given as early as 6 weeks of age, and the fourth dose may be given as late as 18 months of age.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention is scheduled to address the subject of meningococcal vaccines at its meeting on June 20.

A new combination vaccine protects infants and children against both meningococcal and Haemophilus influenzae type b infections.

The Food and Drug Administration on June 14 approved GlaxoSmithKline Biologicals’ Menhibrix, a combination vaccine for infants and children aged 6 weeks through 18 months, for prevention of invasive disease caused by Neisseria meningitidis serogroups C and Y and Haemophilus influenzae type b. It is the first meningococcal vaccine that can be given starting as young as 6 weeks of age, Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement.

The effectiveness of Menhibrix was based on immune responses in several hundred U.S. infants and toddlers who received the vaccine. For the Hib component of the vaccine, immune responses in infants and toddlers following vaccination with Menhibrix were found to be comparable to immune responses in infants and toddlers who received another FDA-approved vaccine against invasive Hib disease. For the meningococcal component, data showed that the vaccine induced the production of antibodies at levels considered to be predictive of protection against invasive meningococcal disease caused by serogroups C and Y, the FDA said.

Safety data for Menhibrix were obtained from about 7,500 infants and toddlers in the United States, Mexico, and Australia. Common adverse reactions reported after administration of Menhibrix were pain, redness, and swelling at the injection site, irritability, and fever.

Menhibrix is given as a four-dose series at 2, 4, 6 and 12 through 15 months of age. The first dose may be given as early as 6 weeks of age, and the fourth dose may be given as late as 18 months of age.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention is scheduled to address the subject of meningococcal vaccines at its meeting on June 20.

A new combination vaccine protects infants and children against both meningococcal and Haemophilus influenzae type b infections.

The Food and Drug Administration on June 14 approved GlaxoSmithKline Biologicals’ Menhibrix, a combination vaccine for infants and children aged 6 weeks through 18 months, for prevention of invasive disease caused by Neisseria meningitidis serogroups C and Y and Haemophilus influenzae type b. It is the first meningococcal vaccine that can be given starting as young as 6 weeks of age, Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in a statement.

The effectiveness of Menhibrix was based on immune responses in several hundred U.S. infants and toddlers who received the vaccine. For the Hib component of the vaccine, immune responses in infants and toddlers following vaccination with Menhibrix were found to be comparable to immune responses in infants and toddlers who received another FDA-approved vaccine against invasive Hib disease. For the meningococcal component, data showed that the vaccine induced the production of antibodies at levels considered to be predictive of protection against invasive meningococcal disease caused by serogroups C and Y, the FDA said.

Safety data for Menhibrix were obtained from about 7,500 infants and toddlers in the United States, Mexico, and Australia. Common adverse reactions reported after administration of Menhibrix were pain, redness, and swelling at the injection site, irritability, and fever.

Menhibrix is given as a four-dose series at 2, 4, 6 and 12 through 15 months of age. The first dose may be given as early as 6 weeks of age, and the fourth dose may be given as late as 18 months of age.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention is scheduled to address the subject of meningococcal vaccines at its meeting on June 20.