Michele G. Sullivan

LAS VEGAS – Robot-assisted laparoscopic hysterectomy is just as quick and safe as standard laparoscopic hysterectomy – at least in the hands of an experienced surgeon, according to a surgical trial of 144 women.

The first prospective, randomized trial comparing the two techniques found no differences in operative time, intraoperative complications, postoperative pain, length of stay, or 12-week complications, Dr. Timothy Deimling reported at a meeting sponsored by the AAGL.

Michele Sullivan/Frontline Medical News

He did caution, however, that the single surgeon who performed all of the procedures was highly experienced with robotic surgery, having performed more than 600 cases in his career.

The trial included 144 women who underwent hysterectomy for benign conditions. There were 72 women in each surgical group. They were consented at the time of consult, but not randomized until the morning of surgery, said Dr. Deimling of the Penn State Milton S. Hershey Medical Center, in Hershey, Pa.

There were no significant between-group differences in any of the baseline characteristics, nor in any of the indications for surgery, with one exception: More women in the laparoscopic group had undergone prior cesarean sections (44% vs. 23%).

The primary outcome was mean operative time, which was considered initial incision to closure. This was similar in the robot-assisted and laparoscopic groups (74 vs. 75 minutes).

Secondary outcomes were also similar, including pain, which was scored on a 1-10 scale. The mean score was 3.9 in the laparoscopic group and 3.8 in the robotic group. Likewise length of stay was similar (mean 19.6 vs. 22 hours).

There was one serious intraoperative complication. A patient in the laparoscopic group experienced a ureteral injury after the insertion of the first trocar, which resulted in termination of the surgery. She later had a successful laparoscopic hysterectomy. Postoperative complications were also similar in the two groups.

But it’s unclear if the results are generalizable. Dr. Deimling noted that the single surgeon who performed all the cases was highly experienced in robotic surgery. Additionally, all cases were assisted by a surgical team of nurses and technicians who were highly trained in both laparoscopic and robotic gynecologic surgery.

Dr. Deimling reported having no relevant financial disclosures.

[email protected]

LAS VEGAS – Robot-assisted laparoscopic hysterectomy is just as quick and safe as standard laparoscopic hysterectomy – at least in the hands of an experienced surgeon, according to a surgical trial of 144 women.

The first prospective, randomized trial comparing the two techniques found no differences in operative time, intraoperative complications, postoperative pain, length of stay, or 12-week complications, Dr. Timothy Deimling reported at a meeting sponsored by the AAGL.

Michele Sullivan/Frontline Medical News

He did caution, however, that the single surgeon who performed all of the procedures was highly experienced with robotic surgery, having performed more than 600 cases in his career.

The trial included 144 women who underwent hysterectomy for benign conditions. There were 72 women in each surgical group. They were consented at the time of consult, but not randomized until the morning of surgery, said Dr. Deimling of the Penn State Milton S. Hershey Medical Center, in Hershey, Pa.

There were no significant between-group differences in any of the baseline characteristics, nor in any of the indications for surgery, with one exception: More women in the laparoscopic group had undergone prior cesarean sections (44% vs. 23%).

The primary outcome was mean operative time, which was considered initial incision to closure. This was similar in the robot-assisted and laparoscopic groups (74 vs. 75 minutes).

Secondary outcomes were also similar, including pain, which was scored on a 1-10 scale. The mean score was 3.9 in the laparoscopic group and 3.8 in the robotic group. Likewise length of stay was similar (mean 19.6 vs. 22 hours).

There was one serious intraoperative complication. A patient in the laparoscopic group experienced a ureteral injury after the insertion of the first trocar, which resulted in termination of the surgery. She later had a successful laparoscopic hysterectomy. Postoperative complications were also similar in the two groups.

But it’s unclear if the results are generalizable. Dr. Deimling noted that the single surgeon who performed all the cases was highly experienced in robotic surgery. Additionally, all cases were assisted by a surgical team of nurses and technicians who were highly trained in both laparoscopic and robotic gynecologic surgery.

Dr. Deimling reported having no relevant financial disclosures.

[email protected]

LAS VEGAS – Robot-assisted laparoscopic hysterectomy is just as quick and safe as standard laparoscopic hysterectomy – at least in the hands of an experienced surgeon, according to a surgical trial of 144 women.

The first prospective, randomized trial comparing the two techniques found no differences in operative time, intraoperative complications, postoperative pain, length of stay, or 12-week complications, Dr. Timothy Deimling reported at a meeting sponsored by the AAGL.

Michele Sullivan/Frontline Medical News

He did caution, however, that the single surgeon who performed all of the procedures was highly experienced with robotic surgery, having performed more than 600 cases in his career.

The trial included 144 women who underwent hysterectomy for benign conditions. There were 72 women in each surgical group. They were consented at the time of consult, but not randomized until the morning of surgery, said Dr. Deimling of the Penn State Milton S. Hershey Medical Center, in Hershey, Pa.

There were no significant between-group differences in any of the baseline characteristics, nor in any of the indications for surgery, with one exception: More women in the laparoscopic group had undergone prior cesarean sections (44% vs. 23%).

The primary outcome was mean operative time, which was considered initial incision to closure. This was similar in the robot-assisted and laparoscopic groups (74 vs. 75 minutes).

Secondary outcomes were also similar, including pain, which was scored on a 1-10 scale. The mean score was 3.9 in the laparoscopic group and 3.8 in the robotic group. Likewise length of stay was similar (mean 19.6 vs. 22 hours).

There was one serious intraoperative complication. A patient in the laparoscopic group experienced a ureteral injury after the insertion of the first trocar, which resulted in termination of the surgery. She later had a successful laparoscopic hysterectomy. Postoperative complications were also similar in the two groups.

But it’s unclear if the results are generalizable. Dr. Deimling noted that the single surgeon who performed all the cases was highly experienced in robotic surgery. Additionally, all cases were assisted by a surgical team of nurses and technicians who were highly trained in both laparoscopic and robotic gynecologic surgery.

Dr. Deimling reported having no relevant financial disclosures.

[email protected]

Updated guidelines regarding the treatment of patients with venous thromboembolism advise abandoning the routine use of compression stockings for prevention of postthrombotic syndrome in patients who have had an acute deep vein thrombosis, according to Dr. Clive Kearon, lead author of the American College of Chest Physicians’ 10th edition of “Antithrombotic Therapy for VTE Disease” (Chest. 2015. doi: 10.1016/j.chest.2015.11.026).

The VTE guidelines include 12 recommendations. Two other key changes from the previous guidelines include new treatment recommendations about which patients with isolated subsegmental pulmonary embolism (PE) should, and should not, receive anticoagulant therapy, and as a recommendation for the use of non–vitamin K antagonist oral anticoagulants (NOACs) instead of warfarin for initial and long-term treatment of VTE in patients without cancer.

It is another of the group’s “living guidelines,” intended to be flexible, easy-to-update recommendations … based on the best available evidence, and to identify gaps in our knowledge and areas for future research,” Dr. Kearon of McMaster University, Hamilton, Ont., said in an interview.

“Clinicians and guideline developers would like clinician decisions to be supported by very strong, or almost irrefutable, evidence,” he said. ”It’s difficult to do studies that provide irrefutable evidence, however,” and most of the updated recommendations are not based on the highest level of study evidence – large, randomized controlled trials.

Nevertheless, “the quality of evidence that supports guidelines and clinical decision making is much better now than it was 20 or 30 years ago,” Dr. Kearon said, mainly because more recent studies are considerably larger and involve multiple clinical centers. Plus, “we’re continually improving our skills at doing high-quality studies and studies that have a low potential for bias.”

The old recommendation to use graduated compression stockings for 2 years after DVT to reduce the risk of postthrombotic syndrome was mainly based on findings of two small single-center randomized trials, published in the Lancet and Annals of Internal Medicine, in which patients and study personnel were not blinded to stocking use. Since then, a much larger multicenter, placebo-controlled trial found that routine use of graduated compression stockings did not reduce postthrombotic syndrome or have other important benefits in 410 patients with a first proximal DVT randomized to receive either active or placebo compression stockings. The incidence of postthrombotic syndrome was 14% in the active group and 13% in the placebo group – a nonsignificant difference. The same study also found that routine use of graduated compression stockings did not reduce leg pain during the 3 months after a DVT – although the stockings were still able to reduce acute symptoms of DVT, and chronic symptoms in patients with postthrombotic syndrome.

The recommendation to replace warfarin with NOACs is based on new data suggesting that the agents are associated with a lower risk of bleeding, and on observations that NOACs are much easier for patients and clinicians to use. Several of the studies upon which earlier guidelines were based have been reanalyzed, Dr. Kearon and his coauthors wrote. There are also now extensive data on the comparative safety of NOACs and warfarin.

“Based on less bleeding with NOACs and greater convenience for patients and health care providers, we now suggest that a NOAC is used in preference to VKA [vitamin K antagonist] for the initial and long-term treatment of VTE in patients without cancer,” they wrote.

The recommendation to employ watchful waiting over anticoagulation in some patients with subsegmental pulmonary embolism is based on a compendium of clinical evidence rather than on large studies. A true subsegmental PE is unlikely to need anticoagulation, because it will have arisen from a small clot and thus carry a small risk of progression or recurrence.

“There is, however, high-quality evidence for the efficacy and safety of anticoagulant therapy in patients with larger PE, and this is expected to apply similarly to patients with subsegmental PE,” the authors wrote. “Whether the risk of progressive or recurrent VTE is high enough to justify anticoagulation in patients with subsegmental PE is uncertain.”

If clinical assessment suggests that anticoagulation isn’t appropriate, these patients should have a confirmatory bilateral ultrasound to rule out proximal DVTs, especially in high-risk locations. If a DVT is detected, clinicians may choose to conduct subsequent ultrasounds to identify and treat any evolving proximal clots.

The guideline has been endorsed by the American Association for Clinical Chemistry, the American College of Clinical Pharmacy, the International Society for Thrombosis and Haemostasis, and the American Society of Health-System Pharmacists.

Dr. Kearon has been compensated for speaking engagements sponsored by Boehringer Ingelheim and Bayer Healthcare related to VTE therapy. Some of the other guideline authors also disclosed relationships with pharmaceutical companies.

Updated guidelines regarding the treatment of patients with venous thromboembolism advise abandoning the routine use of compression stockings for prevention of postthrombotic syndrome in patients who have had an acute deep vein thrombosis, according to Dr. Clive Kearon, lead author of the American College of Chest Physicians’ 10th edition of “Antithrombotic Therapy for VTE Disease” (Chest. 2015. doi: 10.1016/j.chest.2015.11.026).

The VTE guidelines include 12 recommendations. Two other key changes from the previous guidelines include new treatment recommendations about which patients with isolated subsegmental pulmonary embolism (PE) should, and should not, receive anticoagulant therapy, and as a recommendation for the use of non–vitamin K antagonist oral anticoagulants (NOACs) instead of warfarin for initial and long-term treatment of VTE in patients without cancer.

It is another of the group’s “living guidelines,” intended to be flexible, easy-to-update recommendations … based on the best available evidence, and to identify gaps in our knowledge and areas for future research,” Dr. Kearon of McMaster University, Hamilton, Ont., said in an interview.

“Clinicians and guideline developers would like clinician decisions to be supported by very strong, or almost irrefutable, evidence,” he said. ”It’s difficult to do studies that provide irrefutable evidence, however,” and most of the updated recommendations are not based on the highest level of study evidence – large, randomized controlled trials.

Nevertheless, “the quality of evidence that supports guidelines and clinical decision making is much better now than it was 20 or 30 years ago,” Dr. Kearon said, mainly because more recent studies are considerably larger and involve multiple clinical centers. Plus, “we’re continually improving our skills at doing high-quality studies and studies that have a low potential for bias.”

The old recommendation to use graduated compression stockings for 2 years after DVT to reduce the risk of postthrombotic syndrome was mainly based on findings of two small single-center randomized trials, published in the Lancet and Annals of Internal Medicine, in which patients and study personnel were not blinded to stocking use. Since then, a much larger multicenter, placebo-controlled trial found that routine use of graduated compression stockings did not reduce postthrombotic syndrome or have other important benefits in 410 patients with a first proximal DVT randomized to receive either active or placebo compression stockings. The incidence of postthrombotic syndrome was 14% in the active group and 13% in the placebo group – a nonsignificant difference. The same study also found that routine use of graduated compression stockings did not reduce leg pain during the 3 months after a DVT – although the stockings were still able to reduce acute symptoms of DVT, and chronic symptoms in patients with postthrombotic syndrome.

The recommendation to replace warfarin with NOACs is based on new data suggesting that the agents are associated with a lower risk of bleeding, and on observations that NOACs are much easier for patients and clinicians to use. Several of the studies upon which earlier guidelines were based have been reanalyzed, Dr. Kearon and his coauthors wrote. There are also now extensive data on the comparative safety of NOACs and warfarin.

“Based on less bleeding with NOACs and greater convenience for patients and health care providers, we now suggest that a NOAC is used in preference to VKA [vitamin K antagonist] for the initial and long-term treatment of VTE in patients without cancer,” they wrote.

The recommendation to employ watchful waiting over anticoagulation in some patients with subsegmental pulmonary embolism is based on a compendium of clinical evidence rather than on large studies. A true subsegmental PE is unlikely to need anticoagulation, because it will have arisen from a small clot and thus carry a small risk of progression or recurrence.

“There is, however, high-quality evidence for the efficacy and safety of anticoagulant therapy in patients with larger PE, and this is expected to apply similarly to patients with subsegmental PE,” the authors wrote. “Whether the risk of progressive or recurrent VTE is high enough to justify anticoagulation in patients with subsegmental PE is uncertain.”

If clinical assessment suggests that anticoagulation isn’t appropriate, these patients should have a confirmatory bilateral ultrasound to rule out proximal DVTs, especially in high-risk locations. If a DVT is detected, clinicians may choose to conduct subsequent ultrasounds to identify and treat any evolving proximal clots.

The guideline has been endorsed by the American Association for Clinical Chemistry, the American College of Clinical Pharmacy, the International Society for Thrombosis and Haemostasis, and the American Society of Health-System Pharmacists.

Dr. Kearon has been compensated for speaking engagements sponsored by Boehringer Ingelheim and Bayer Healthcare related to VTE therapy. Some of the other guideline authors also disclosed relationships with pharmaceutical companies.

Updated guidelines regarding the treatment of patients with venous thromboembolism advise abandoning the routine use of compression stockings for prevention of postthrombotic syndrome in patients who have had an acute deep vein thrombosis, according to Dr. Clive Kearon, lead author of the American College of Chest Physicians’ 10th edition of “Antithrombotic Therapy for VTE Disease” (Chest. 2015. doi: 10.1016/j.chest.2015.11.026).

The VTE guidelines include 12 recommendations. Two other key changes from the previous guidelines include new treatment recommendations about which patients with isolated subsegmental pulmonary embolism (PE) should, and should not, receive anticoagulant therapy, and as a recommendation for the use of non–vitamin K antagonist oral anticoagulants (NOACs) instead of warfarin for initial and long-term treatment of VTE in patients without cancer.

It is another of the group’s “living guidelines,” intended to be flexible, easy-to-update recommendations … based on the best available evidence, and to identify gaps in our knowledge and areas for future research,” Dr. Kearon of McMaster University, Hamilton, Ont., said in an interview.

“Clinicians and guideline developers would like clinician decisions to be supported by very strong, or almost irrefutable, evidence,” he said. ”It’s difficult to do studies that provide irrefutable evidence, however,” and most of the updated recommendations are not based on the highest level of study evidence – large, randomized controlled trials.

Nevertheless, “the quality of evidence that supports guidelines and clinical decision making is much better now than it was 20 or 30 years ago,” Dr. Kearon said, mainly because more recent studies are considerably larger and involve multiple clinical centers. Plus, “we’re continually improving our skills at doing high-quality studies and studies that have a low potential for bias.”

The old recommendation to use graduated compression stockings for 2 years after DVT to reduce the risk of postthrombotic syndrome was mainly based on findings of two small single-center randomized trials, published in the Lancet and Annals of Internal Medicine, in which patients and study personnel were not blinded to stocking use. Since then, a much larger multicenter, placebo-controlled trial found that routine use of graduated compression stockings did not reduce postthrombotic syndrome or have other important benefits in 410 patients with a first proximal DVT randomized to receive either active or placebo compression stockings. The incidence of postthrombotic syndrome was 14% in the active group and 13% in the placebo group – a nonsignificant difference. The same study also found that routine use of graduated compression stockings did not reduce leg pain during the 3 months after a DVT – although the stockings were still able to reduce acute symptoms of DVT, and chronic symptoms in patients with postthrombotic syndrome.

The recommendation to replace warfarin with NOACs is based on new data suggesting that the agents are associated with a lower risk of bleeding, and on observations that NOACs are much easier for patients and clinicians to use. Several of the studies upon which earlier guidelines were based have been reanalyzed, Dr. Kearon and his coauthors wrote. There are also now extensive data on the comparative safety of NOACs and warfarin.

“Based on less bleeding with NOACs and greater convenience for patients and health care providers, we now suggest that a NOAC is used in preference to VKA [vitamin K antagonist] for the initial and long-term treatment of VTE in patients without cancer,” they wrote.

The recommendation to employ watchful waiting over anticoagulation in some patients with subsegmental pulmonary embolism is based on a compendium of clinical evidence rather than on large studies. A true subsegmental PE is unlikely to need anticoagulation, because it will have arisen from a small clot and thus carry a small risk of progression or recurrence.

“There is, however, high-quality evidence for the efficacy and safety of anticoagulant therapy in patients with larger PE, and this is expected to apply similarly to patients with subsegmental PE,” the authors wrote. “Whether the risk of progressive or recurrent VTE is high enough to justify anticoagulation in patients with subsegmental PE is uncertain.”

If clinical assessment suggests that anticoagulation isn’t appropriate, these patients should have a confirmatory bilateral ultrasound to rule out proximal DVTs, especially in high-risk locations. If a DVT is detected, clinicians may choose to conduct subsequent ultrasounds to identify and treat any evolving proximal clots.

The guideline has been endorsed by the American Association for Clinical Chemistry, the American College of Clinical Pharmacy, the International Society for Thrombosis and Haemostasis, and the American Society of Health-System Pharmacists.

Dr. Kearon has been compensated for speaking engagements sponsored by Boehringer Ingelheim and Bayer Healthcare related to VTE therapy. Some of the other guideline authors also disclosed relationships with pharmaceutical companies.

More than half of HIV infections in Dutch men who have sex with men (MSM) could have been prevented with a combination of regular testing and pre-exposure antiretrovirals for HIV-negative men, and early antiretroviral treatment for those with new infections, according to a new study.

The results of the national database study suggest that dramatic reductions in HIV infections could be achieved with a combination of improved HIV testing and immediate implementation of the World Health Organization’s newly revised 2016 HIV treatment guidelines, Dr. Oliver Ratmann and his colleagues reported (Sci Transl Med. 2016 Jan 6;8[320]. doi: 10.1126/scitranslmed.aad1863).

©jarun011/thinkstockphotos.com

The WHO guidelines call for providing immediate antiretroviral treatment (ART) to all HIV-infected MSM and pre-exposure antiretrovirals (PrEP) to at least half of all HIV-negative MSM younger than 30 years.

Dr. Ratmann of the School of Public Health at Imperial College, London, and his coauthors used national cohort studies to identify 617 patients who were in the first year of an HIV infection from 1996-2010. By matching their HIV strains with infected men in the overall analysis, they determined that most of the transmissions (71%) came from men with undiagnosed HIV, and 22% from men who were diagnosed but not yet treated. Only 6% were from men who had initiated antiretroviral therapy, and 1% were from men who had not had health care treatment in the last 18 months. Nearly half of the infections (43%) were passed on by men who were in their first year of an HIV infection.

When the research team considered annual testing, they found that only 17% of transmitters had an HIV test in the year before diagnosis. “If half of all transmitters had been tested annually, immediate ART and PrEP to half of all MSM age 30 years or younger who test negative could have averted 45% of infections. Comprehensive rollout of PrEP to half of all men testing negative irrespective of their age would have [averted] 66% of infections,” the investigators wrote.

Regular testing will be a key part of success when the 2016 WHO guidelines are adopted, Dr. Ratmann and his colleagues noted. “Without substantial increases in current annual testing coverage, ART and PrEP (also offered), the revised guidelines could not have prevented more than a third of all infections in our transmission cohort. Strategies such as self-testing, community-based testing, and more provider-initiated routine testing in general practices and at medical admissions ... need to be expanded alongside biomedical interventions,” they wrote.

The study was supported by a grant from the Netherlands Ministry of Health, Welfare and Sport through its Centre for Infectious Disease Control–National Institute for Public Health and the Environment. Dr. Ratmann declared financial support from the Wellcome Trust, while two of his coauthors disclosed funding from the European Research Council, the Bill & Melinda Gates Foundation, Bristol-Myers Squibb, ViiV Healthcare, Gilead Sciences, Janssen Pharmaceuticals Inc., and Merck & Co.

[email protected]

More than half of HIV infections in Dutch men who have sex with men (MSM) could have been prevented with a combination of regular testing and pre-exposure antiretrovirals for HIV-negative men, and early antiretroviral treatment for those with new infections, according to a new study.

The results of the national database study suggest that dramatic reductions in HIV infections could be achieved with a combination of improved HIV testing and immediate implementation of the World Health Organization’s newly revised 2016 HIV treatment guidelines, Dr. Oliver Ratmann and his colleagues reported (Sci Transl Med. 2016 Jan 6;8[320]. doi: 10.1126/scitranslmed.aad1863).

©jarun011/thinkstockphotos.com

The WHO guidelines call for providing immediate antiretroviral treatment (ART) to all HIV-infected MSM and pre-exposure antiretrovirals (PrEP) to at least half of all HIV-negative MSM younger than 30 years.

Dr. Ratmann of the School of Public Health at Imperial College, London, and his coauthors used national cohort studies to identify 617 patients who were in the first year of an HIV infection from 1996-2010. By matching their HIV strains with infected men in the overall analysis, they determined that most of the transmissions (71%) came from men with undiagnosed HIV, and 22% from men who were diagnosed but not yet treated. Only 6% were from men who had initiated antiretroviral therapy, and 1% were from men who had not had health care treatment in the last 18 months. Nearly half of the infections (43%) were passed on by men who were in their first year of an HIV infection.

When the research team considered annual testing, they found that only 17% of transmitters had an HIV test in the year before diagnosis. “If half of all transmitters had been tested annually, immediate ART and PrEP to half of all MSM age 30 years or younger who test negative could have averted 45% of infections. Comprehensive rollout of PrEP to half of all men testing negative irrespective of their age would have [averted] 66% of infections,” the investigators wrote.

Regular testing will be a key part of success when the 2016 WHO guidelines are adopted, Dr. Ratmann and his colleagues noted. “Without substantial increases in current annual testing coverage, ART and PrEP (also offered), the revised guidelines could not have prevented more than a third of all infections in our transmission cohort. Strategies such as self-testing, community-based testing, and more provider-initiated routine testing in general practices and at medical admissions ... need to be expanded alongside biomedical interventions,” they wrote.

The study was supported by a grant from the Netherlands Ministry of Health, Welfare and Sport through its Centre for Infectious Disease Control–National Institute for Public Health and the Environment. Dr. Ratmann declared financial support from the Wellcome Trust, while two of his coauthors disclosed funding from the European Research Council, the Bill & Melinda Gates Foundation, Bristol-Myers Squibb, ViiV Healthcare, Gilead Sciences, Janssen Pharmaceuticals Inc., and Merck & Co.

[email protected]

More than half of HIV infections in Dutch men who have sex with men (MSM) could have been prevented with a combination of regular testing and pre-exposure antiretrovirals for HIV-negative men, and early antiretroviral treatment for those with new infections, according to a new study.

The results of the national database study suggest that dramatic reductions in HIV infections could be achieved with a combination of improved HIV testing and immediate implementation of the World Health Organization’s newly revised 2016 HIV treatment guidelines, Dr. Oliver Ratmann and his colleagues reported (Sci Transl Med. 2016 Jan 6;8[320]. doi: 10.1126/scitranslmed.aad1863).

©jarun011/thinkstockphotos.com

The WHO guidelines call for providing immediate antiretroviral treatment (ART) to all HIV-infected MSM and pre-exposure antiretrovirals (PrEP) to at least half of all HIV-negative MSM younger than 30 years.

Dr. Ratmann of the School of Public Health at Imperial College, London, and his coauthors used national cohort studies to identify 617 patients who were in the first year of an HIV infection from 1996-2010. By matching their HIV strains with infected men in the overall analysis, they determined that most of the transmissions (71%) came from men with undiagnosed HIV, and 22% from men who were diagnosed but not yet treated. Only 6% were from men who had initiated antiretroviral therapy, and 1% were from men who had not had health care treatment in the last 18 months. Nearly half of the infections (43%) were passed on by men who were in their first year of an HIV infection.

When the research team considered annual testing, they found that only 17% of transmitters had an HIV test in the year before diagnosis. “If half of all transmitters had been tested annually, immediate ART and PrEP to half of all MSM age 30 years or younger who test negative could have averted 45% of infections. Comprehensive rollout of PrEP to half of all men testing negative irrespective of their age would have [averted] 66% of infections,” the investigators wrote.

Regular testing will be a key part of success when the 2016 WHO guidelines are adopted, Dr. Ratmann and his colleagues noted. “Without substantial increases in current annual testing coverage, ART and PrEP (also offered), the revised guidelines could not have prevented more than a third of all infections in our transmission cohort. Strategies such as self-testing, community-based testing, and more provider-initiated routine testing in general practices and at medical admissions ... need to be expanded alongside biomedical interventions,” they wrote.

The study was supported by a grant from the Netherlands Ministry of Health, Welfare and Sport through its Centre for Infectious Disease Control–National Institute for Public Health and the Environment. Dr. Ratmann declared financial support from the Wellcome Trust, while two of his coauthors disclosed funding from the European Research Council, the Bill & Melinda Gates Foundation, Bristol-Myers Squibb, ViiV Healthcare, Gilead Sciences, Janssen Pharmaceuticals Inc., and Merck & Co.

[email protected]

Cervical cancer screening should begin at age 21 years and continue even beyond a woman’s reproductive years, but yearly testing is neither necessary nor recommended for most women, according to new guidelines issued by the American College of Obstetricians and Gynecologists.

Since cervical cancer is “a rather indolent disease,” more frequent testing is much more likely to result in anxiety and unnecessary treatment than in preventing cancers, according to the document, which was published online in Obstetrics and Gynecology (2016 Dec 22;127:e1-20).

“Annual screening leads to a very small increase in cases of cancer prevented at the cost of a very large excess of procedures and treatments and should not be performed,” members of the ACOG Committee on Practice Bulletins-Gynecology wrote. Excisional procedures can confer an increased risk of preterm birth – another serious consideration when determining the frequency of screening.

And, wrote the committee, the psychosocial aspects of earlier screening must also be taken into account.

“The emotional effect of labeling an adolescent with a sexually transmitted infection and potential precancer must be considered, because adolescence is a time of heightened concern for self-image and emerging sexuality,” they wrote.

Recommendations in this set of guidelines differ slightly from those published in 2015 by the Society of Gynecologic Oncology (SGO) and the American Society for Colposcopy and Cervical Pathology (ASCCP). Both the SGO and ACOG documents take into account the recently approved HPV DNA test, which is indicated as a primary cervical cancer screening tool.

©xrender/Thinkstock.com

The test detects 14 high-risk HPV types, and specifically identifies HPV 16 and 18. A positive result for either of those types should prompt a colposcopy; women who test positive for any of the other 12 high-risk types should have a Pap test.

The SGO guidelines say that primary HPV testing alone can be considered for women beginning at age 25 years. The ACOG document also notes that HPV testing alone can be considered an alternative for women older than 25 years but stresses that cytology alone or co-testing remain the options specifically recommended in current major society guidelines. If screening with the primary HPV test is used, it should be performed according to the SGO guidance, the ACOG document states.

Dr. Jill Rabin favors the ACOG recommendations over HPV-only testing. She is a professor of obstetrics and gynecology and cochief of the division of ambulatory care, Women’s Health Programs–Prenatal Care Assistance Program Services at Northwell Health, New Hyde Park, N.Y.

“I know certain groups – and not just SGO – go with just the HPV-only test, but I can’t bring myself to do that,” she said in an interview. “Most of the literature agrees that you need to look at both cytology and HPV testing to get the best results. And all cervical cancer is not driven by HPV infections.”

The ACOG document stresses that sexual initiation – whatever the age – should not be the precipitating factor for the first cervical cancer screening. HPV infections are normally acquired very quickly after vaginal intercourse begins, although nearly all cases are naturally cleared within a couple of years. From ages 21-29 years, cervical cytology alone is sufficient for these women, and primary HPV co-testing is not appropriate. The recommended screening interval is every 3 years.

HPV testing is more sensitive than is cytology but less specific, the authors said. And because women in this age group often have noncarcinogenic, transient HPV infections, co-testing could drive more testing and interventions without decreasing cancer incidence.

For women aged 30-65 years, however, HPV testing combined with cervical cytology is the optimum choice and should be conducted every 5 years. If cytology alone is performed, however, the recommended interval is every 3 years.

Any woman in this age group who has an HPV-positive co-test with negative cytology should be retested with both methods in 12 months. A colposcopy is recommended if the repeat cervical cytology test result is unspecified atypical squamous cells or higher, or if the HPV test result is still positive. Otherwise, the next co-testing can occur 3 years later.

As an alternative strategy, an immediate HPV genotyping can be performed; if high-risk strains are present, an immediate colposcopy is indicated.

A history of having had the HPV vaccine series doesn’t obviate the need for screening or change the basic recommendations for screening type or interval, according to the ACOG document. Even the 9-valent vaccine doesn’t cover all cancer-associated HPV. And many women may have had the series after already acquiring an HPV infection, which reduces the vaccine’s efficacy.

Finally, the ACOG committee noted that, “long-term efficacy of the vaccine remains incompletely established. Although HPV vaccination is an important step toward cervical cancer prevention, it does not remove the need for routine cervical cancer screening.”

After age 65 years, screening can be discontinued for women with who have had consecutive negative testing in the prior 10 years. For women who have had grade 2 or 3 cervical intraepithelial neoplasia (CIN), or adenocarcinoma in situ, screening needs to continue for 20 years after spontaneous regression or treatment.

“Women aged 65 years and older do get cervical cancer,” the ACOG committee members wrote. “Women in this age group represent 14% of the U.S. female population but have 19.6% of the new cases of cervical cancer.”

However, since most cases occur in inadequately or unscreened women, and because of the long latency of HPV-driven cancers, “screening women in this age group would prevent very few cases ... [and the slight gain] would come at significant cost, including an increase in required colposcopy procedures.”

Changes in most risk factors, including new sexual partners, are not a reason to start screening again in older women because of the long disease latency, according to the ACOG recommendations. Dr. Rabin added, “I reconsider this in certain instances if their status changes, especially if there is immunosuppression, being with a high-risk partner, or having multiple sexual partners.” *

The guidelines recommend more frequent screening for women previously treated for CIN 2, CIN 3, or cancer; those with HIV infection; those who are immunocompromised, including have received solid organ transplants; and those who were exposed to diethylstilbestrol in utero.

Women who’ve had a total hysterectomy and no history of CIN 2 or greater don’t need screening, but those who have had a high-grade CIN should continue it, as there can be a recurrence in the vaginal cuff even years later.

*Clarification, 1/8/2016: An earlier version of this story misstated Dr. Jill Rabin's position on when to screen women age 65 and older. 

[email protected]

Cervical cancer screening should begin at age 21 years and continue even beyond a woman’s reproductive years, but yearly testing is neither necessary nor recommended for most women, according to new guidelines issued by the American College of Obstetricians and Gynecologists.

Since cervical cancer is “a rather indolent disease,” more frequent testing is much more likely to result in anxiety and unnecessary treatment than in preventing cancers, according to the document, which was published online in Obstetrics and Gynecology (2016 Dec 22;127:e1-20).

“Annual screening leads to a very small increase in cases of cancer prevented at the cost of a very large excess of procedures and treatments and should not be performed,” members of the ACOG Committee on Practice Bulletins-Gynecology wrote. Excisional procedures can confer an increased risk of preterm birth – another serious consideration when determining the frequency of screening.

And, wrote the committee, the psychosocial aspects of earlier screening must also be taken into account.

“The emotional effect of labeling an adolescent with a sexually transmitted infection and potential precancer must be considered, because adolescence is a time of heightened concern for self-image and emerging sexuality,” they wrote.

Recommendations in this set of guidelines differ slightly from those published in 2015 by the Society of Gynecologic Oncology (SGO) and the American Society for Colposcopy and Cervical Pathology (ASCCP). Both the SGO and ACOG documents take into account the recently approved HPV DNA test, which is indicated as a primary cervical cancer screening tool.

©xrender/Thinkstock.com

The test detects 14 high-risk HPV types, and specifically identifies HPV 16 and 18. A positive result for either of those types should prompt a colposcopy; women who test positive for any of the other 12 high-risk types should have a Pap test.

The SGO guidelines say that primary HPV testing alone can be considered for women beginning at age 25 years. The ACOG document also notes that HPV testing alone can be considered an alternative for women older than 25 years but stresses that cytology alone or co-testing remain the options specifically recommended in current major society guidelines. If screening with the primary HPV test is used, it should be performed according to the SGO guidance, the ACOG document states.

Dr. Jill Rabin favors the ACOG recommendations over HPV-only testing. She is a professor of obstetrics and gynecology and cochief of the division of ambulatory care, Women’s Health Programs–Prenatal Care Assistance Program Services at Northwell Health, New Hyde Park, N.Y.

“I know certain groups – and not just SGO – go with just the HPV-only test, but I can’t bring myself to do that,” she said in an interview. “Most of the literature agrees that you need to look at both cytology and HPV testing to get the best results. And all cervical cancer is not driven by HPV infections.”

The ACOG document stresses that sexual initiation – whatever the age – should not be the precipitating factor for the first cervical cancer screening. HPV infections are normally acquired very quickly after vaginal intercourse begins, although nearly all cases are naturally cleared within a couple of years. From ages 21-29 years, cervical cytology alone is sufficient for these women, and primary HPV co-testing is not appropriate. The recommended screening interval is every 3 years.

HPV testing is more sensitive than is cytology but less specific, the authors said. And because women in this age group often have noncarcinogenic, transient HPV infections, co-testing could drive more testing and interventions without decreasing cancer incidence.

For women aged 30-65 years, however, HPV testing combined with cervical cytology is the optimum choice and should be conducted every 5 years. If cytology alone is performed, however, the recommended interval is every 3 years.

Any woman in this age group who has an HPV-positive co-test with negative cytology should be retested with both methods in 12 months. A colposcopy is recommended if the repeat cervical cytology test result is unspecified atypical squamous cells or higher, or if the HPV test result is still positive. Otherwise, the next co-testing can occur 3 years later.

As an alternative strategy, an immediate HPV genotyping can be performed; if high-risk strains are present, an immediate colposcopy is indicated.

A history of having had the HPV vaccine series doesn’t obviate the need for screening or change the basic recommendations for screening type or interval, according to the ACOG document. Even the 9-valent vaccine doesn’t cover all cancer-associated HPV. And many women may have had the series after already acquiring an HPV infection, which reduces the vaccine’s efficacy.

Finally, the ACOG committee noted that, “long-term efficacy of the vaccine remains incompletely established. Although HPV vaccination is an important step toward cervical cancer prevention, it does not remove the need for routine cervical cancer screening.”

After age 65 years, screening can be discontinued for women with who have had consecutive negative testing in the prior 10 years. For women who have had grade 2 or 3 cervical intraepithelial neoplasia (CIN), or adenocarcinoma in situ, screening needs to continue for 20 years after spontaneous regression or treatment.

“Women aged 65 years and older do get cervical cancer,” the ACOG committee members wrote. “Women in this age group represent 14% of the U.S. female population but have 19.6% of the new cases of cervical cancer.”

However, since most cases occur in inadequately or unscreened women, and because of the long latency of HPV-driven cancers, “screening women in this age group would prevent very few cases ... [and the slight gain] would come at significant cost, including an increase in required colposcopy procedures.”

Changes in most risk factors, including new sexual partners, are not a reason to start screening again in older women because of the long disease latency, according to the ACOG recommendations. Dr. Rabin added, “I reconsider this in certain instances if their status changes, especially if there is immunosuppression, being with a high-risk partner, or having multiple sexual partners.” *

The guidelines recommend more frequent screening for women previously treated for CIN 2, CIN 3, or cancer; those with HIV infection; those who are immunocompromised, including have received solid organ transplants; and those who were exposed to diethylstilbestrol in utero.

Women who’ve had a total hysterectomy and no history of CIN 2 or greater don’t need screening, but those who have had a high-grade CIN should continue it, as there can be a recurrence in the vaginal cuff even years later.

*Clarification, 1/8/2016: An earlier version of this story misstated Dr. Jill Rabin's position on when to screen women age 65 and older. 

[email protected]

Cervical cancer screening should begin at age 21 years and continue even beyond a woman’s reproductive years, but yearly testing is neither necessary nor recommended for most women, according to new guidelines issued by the American College of Obstetricians and Gynecologists.

Since cervical cancer is “a rather indolent disease,” more frequent testing is much more likely to result in anxiety and unnecessary treatment than in preventing cancers, according to the document, which was published online in Obstetrics and Gynecology (2016 Dec 22;127:e1-20).

“Annual screening leads to a very small increase in cases of cancer prevented at the cost of a very large excess of procedures and treatments and should not be performed,” members of the ACOG Committee on Practice Bulletins-Gynecology wrote. Excisional procedures can confer an increased risk of preterm birth – another serious consideration when determining the frequency of screening.

And, wrote the committee, the psychosocial aspects of earlier screening must also be taken into account.

“The emotional effect of labeling an adolescent with a sexually transmitted infection and potential precancer must be considered, because adolescence is a time of heightened concern for self-image and emerging sexuality,” they wrote.

Recommendations in this set of guidelines differ slightly from those published in 2015 by the Society of Gynecologic Oncology (SGO) and the American Society for Colposcopy and Cervical Pathology (ASCCP). Both the SGO and ACOG documents take into account the recently approved HPV DNA test, which is indicated as a primary cervical cancer screening tool.

©xrender/Thinkstock.com

The test detects 14 high-risk HPV types, and specifically identifies HPV 16 and 18. A positive result for either of those types should prompt a colposcopy; women who test positive for any of the other 12 high-risk types should have a Pap test.

The SGO guidelines say that primary HPV testing alone can be considered for women beginning at age 25 years. The ACOG document also notes that HPV testing alone can be considered an alternative for women older than 25 years but stresses that cytology alone or co-testing remain the options specifically recommended in current major society guidelines. If screening with the primary HPV test is used, it should be performed according to the SGO guidance, the ACOG document states.

Dr. Jill Rabin favors the ACOG recommendations over HPV-only testing. She is a professor of obstetrics and gynecology and cochief of the division of ambulatory care, Women’s Health Programs–Prenatal Care Assistance Program Services at Northwell Health, New Hyde Park, N.Y.

“I know certain groups – and not just SGO – go with just the HPV-only test, but I can’t bring myself to do that,” she said in an interview. “Most of the literature agrees that you need to look at both cytology and HPV testing to get the best results. And all cervical cancer is not driven by HPV infections.”

The ACOG document stresses that sexual initiation – whatever the age – should not be the precipitating factor for the first cervical cancer screening. HPV infections are normally acquired very quickly after vaginal intercourse begins, although nearly all cases are naturally cleared within a couple of years. From ages 21-29 years, cervical cytology alone is sufficient for these women, and primary HPV co-testing is not appropriate. The recommended screening interval is every 3 years.

HPV testing is more sensitive than is cytology but less specific, the authors said. And because women in this age group often have noncarcinogenic, transient HPV infections, co-testing could drive more testing and interventions without decreasing cancer incidence.

For women aged 30-65 years, however, HPV testing combined with cervical cytology is the optimum choice and should be conducted every 5 years. If cytology alone is performed, however, the recommended interval is every 3 years.

Any woman in this age group who has an HPV-positive co-test with negative cytology should be retested with both methods in 12 months. A colposcopy is recommended if the repeat cervical cytology test result is unspecified atypical squamous cells or higher, or if the HPV test result is still positive. Otherwise, the next co-testing can occur 3 years later.

As an alternative strategy, an immediate HPV genotyping can be performed; if high-risk strains are present, an immediate colposcopy is indicated.

A history of having had the HPV vaccine series doesn’t obviate the need for screening or change the basic recommendations for screening type or interval, according to the ACOG document. Even the 9-valent vaccine doesn’t cover all cancer-associated HPV. And many women may have had the series after already acquiring an HPV infection, which reduces the vaccine’s efficacy.

Finally, the ACOG committee noted that, “long-term efficacy of the vaccine remains incompletely established. Although HPV vaccination is an important step toward cervical cancer prevention, it does not remove the need for routine cervical cancer screening.”

After age 65 years, screening can be discontinued for women with who have had consecutive negative testing in the prior 10 years. For women who have had grade 2 or 3 cervical intraepithelial neoplasia (CIN), or adenocarcinoma in situ, screening needs to continue for 20 years after spontaneous regression or treatment.

“Women aged 65 years and older do get cervical cancer,” the ACOG committee members wrote. “Women in this age group represent 14% of the U.S. female population but have 19.6% of the new cases of cervical cancer.”

However, since most cases occur in inadequately or unscreened women, and because of the long latency of HPV-driven cancers, “screening women in this age group would prevent very few cases ... [and the slight gain] would come at significant cost, including an increase in required colposcopy procedures.”

Changes in most risk factors, including new sexual partners, are not a reason to start screening again in older women because of the long disease latency, according to the ACOG recommendations. Dr. Rabin added, “I reconsider this in certain instances if their status changes, especially if there is immunosuppression, being with a high-risk partner, or having multiple sexual partners.” *

The guidelines recommend more frequent screening for women previously treated for CIN 2, CIN 3, or cancer; those with HIV infection; those who are immunocompromised, including have received solid organ transplants; and those who were exposed to diethylstilbestrol in utero.

Women who’ve had a total hysterectomy and no history of CIN 2 or greater don’t need screening, but those who have had a high-grade CIN should continue it, as there can be a recurrence in the vaginal cuff even years later.

*Clarification, 1/8/2016: An earlier version of this story misstated Dr. Jill Rabin's position on when to screen women age 65 and older. 

[email protected]

While 2015 might not have been the year of the blockbuster Alzheimer’s drug, it did lay a few more paving stones on the road to understanding the disease.

Federal funding boosts, new-generation collaborative drug trials, and advances in tau imaging are some of the biggest boons of 2015, according to Dr. Neil Buckholtzof the National Institute on Aging, who in an interview addressed some of the points summarized in the NIA’s annual report on Alzheimer’s disease, the 2014-2015 Alzheimer’s Disease Progress Report: Advancing Research Toward a Cure.

Making clinical progress toward slowing or stopping Alzheimer’s development has been a tough slog, said Dr. Buckholtz, director of NIA’s Division of Neuroscience. It’s a problem that will be solved only by the collaborative efforts of many minds and many institutions, and all of these efforts are the product of a single common denominator: money. Things have improved considerably along that front, he said.

“In 2014, we received an additional appropriation from Congress of $100 million specifically for Alzheimer’s research. In 2015, we got another additional appropriation of $25 million,” which will give Alzheimer’s research an immediate boost in 2016.

“What that extra money has allowed us to do is fund Alzheimer’s applications beyond the regular funding line,” he said. “And that’s a really big deal. We’ve been able to use that money to double our funding for Alzheimer’s research applications from 8% to 18%” of the proposals submitted.

Two new programs arose from the additional monies, Dr. Buckholtz said: theNIH Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome Initiativeand the Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer’s Disease program.

The Down syndrome initiative will provide $35 million to two large projects studying early Alzheimer’s-like brain changes in people with Down syndrome. Because the amyloid precursor protein gene is also overexpressed in Down syndrome, these patients accumulate beta-amyloid at a greatly accelerated rate and will, inevitably, develop Alzheimer’s dementia. Thus, they represent an ideal population in which to study AD pathology from its earliest manifestations. The two projects will examine structural brain changes with MRI, amyloid, and tau imaging; search for new biomarkers, including blood-based biomarkers; and follow patients long term for changes in their medical, cognitive, and memory status.

The vascular program awarded a total of $4 million for research on how both the systemic vasculature and microvascular systems influence the development not only of Alzheimer’s but of other dementias as well.

Dr. Buckholtz also pointed to work on four large drug trials in presymptomatic patients: the Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Treatment Trial, the Dominantly Inherited Alzheimer Network Trial, the APOE4 Treatment Trial, and the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) trial.

The first three will test anti-amyloid drugs in subjects with strong genetic risk factors for Alzheimer’s, and the A4 study will examine anti-amyloid treatment in subjects who are cognitively normal but have imaging evidence of beta-amyloid brain plaques.

These trials are clinically unique because each one could show whether early intervention in amyloid accumulation has any effect on disease development or progression. Logistically, they are unique because each relies on public/private partnerships involving three-way collaborations of academia, federal, and pharmaceutical dollars.

“We’re providing funds, but these trials take a lot of money – a lot. And working with pharmaceutical companies is one way that we can get the money we need to make them happen,” Dr. Buckholtz said. “We are seeing more and more of these interactions with government, academia, and industry, and I think this is what it will take to get something going. There’s still a lot of hard work to be done by independent researchers, but these kinds of partnerships will be needed to really move this forward.”

Clinically, Dr. Buckholtz said, one of the year’s most striking areas of research is tau imaging. New radioligands are being developed that allow PET imaging of tau tangles. Like amyloid imaging, tau imaging has the potential to redefine the way clinical trials are created and conducted, and could, in the future, become a useful tool for diagnosis and for tracking both disease progression and modification.

Tau imaging may also untangle the complicated relationship of tau, amyloid, and cognition. “It’s been very difficult to answer this question,” Dr. Buckholtz said. “Tau normally builds up very slowly in the medial temporal lobe with age, and in general, it doesn’t have a major deleterious effect. But when beta-amyloid comes along, it somehow exacerbates this increase, and tau moves out into the temporal cortex. That is the proximal thing that produces neurodegeneration and cognitive decline. We have never been able to observe this as a dynamic process, but now that we have imaging ligands for both amyloid and tau, we will be able to look at both of these at the same time in the same person, over a long period.”

At least three of the large anti-amyloid trials will be adding tau imaging to the existing protocol, Dr. Buckholtz added.

Preclinically, he said, the induction of pluripotent stem cells into neurons with an aging phenotype was a very important step in creating in vitro models of human aging (Cell Stem Cell. 2015 Dec 3;17[6]:705-18). Before this discovery, stem cell–induced neurons didn’t re-create human aging; in fact, induction somehow seemed to rejuvenate them, even if the progenitor cells were from an elderly person.

“Making these neurons with an aging phenotype is going to be very important as we look at aging – the biggest single risk factor for Alzheimer’s,” Dr. Buckholtz said.

Sleep is another emerging story, he said. “The relationship between sleep and beta-amyloid is fascinating. Some studies indicate that amyloid disrupts slow-wave sleep, which is needed for memory formation.”

And, despite the decades-old knowledge that the apolipoprotein E epsilon-4 allele confers various levels of Alzheimer’s risk, little is known about the mechanics of that relationship. Dr. Buckholtz hopes that will change in the near future.

Finally, work continues on what he called one of Alzheimer’s Holy Grails: a validated, blood-based biomarker. “The search hasn’t gone as well as we hoped it would. We still don’t have a reliable one, but no one is sure if that’s because there are just so many things that affect blood proteins or because we simply don’t have a good way to look at it. I’m hopeful, though. An accurate blood-based biomarker would bring Alzheimer’s screening into the primary care office. It would be an enormous step.”

[email protected]

On Twitter @Alz_Gal

While 2015 might not have been the year of the blockbuster Alzheimer’s drug, it did lay a few more paving stones on the road to understanding the disease.

Federal funding boosts, new-generation collaborative drug trials, and advances in tau imaging are some of the biggest boons of 2015, according to Dr. Neil Buckholtzof the National Institute on Aging, who in an interview addressed some of the points summarized in the NIA’s annual report on Alzheimer’s disease, the 2014-2015 Alzheimer’s Disease Progress Report: Advancing Research Toward a Cure.

Making clinical progress toward slowing or stopping Alzheimer’s development has been a tough slog, said Dr. Buckholtz, director of NIA’s Division of Neuroscience. It’s a problem that will be solved only by the collaborative efforts of many minds and many institutions, and all of these efforts are the product of a single common denominator: money. Things have improved considerably along that front, he said.

“In 2014, we received an additional appropriation from Congress of $100 million specifically for Alzheimer’s research. In 2015, we got another additional appropriation of $25 million,” which will give Alzheimer’s research an immediate boost in 2016.

“What that extra money has allowed us to do is fund Alzheimer’s applications beyond the regular funding line,” he said. “And that’s a really big deal. We’ve been able to use that money to double our funding for Alzheimer’s research applications from 8% to 18%” of the proposals submitted.

Two new programs arose from the additional monies, Dr. Buckholtz said: theNIH Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome Initiativeand the Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer’s Disease program.

The Down syndrome initiative will provide $35 million to two large projects studying early Alzheimer’s-like brain changes in people with Down syndrome. Because the amyloid precursor protein gene is also overexpressed in Down syndrome, these patients accumulate beta-amyloid at a greatly accelerated rate and will, inevitably, develop Alzheimer’s dementia. Thus, they represent an ideal population in which to study AD pathology from its earliest manifestations. The two projects will examine structural brain changes with MRI, amyloid, and tau imaging; search for new biomarkers, including blood-based biomarkers; and follow patients long term for changes in their medical, cognitive, and memory status.

The vascular program awarded a total of $4 million for research on how both the systemic vasculature and microvascular systems influence the development not only of Alzheimer’s but of other dementias as well.

Dr. Buckholtz also pointed to work on four large drug trials in presymptomatic patients: the Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Treatment Trial, the Dominantly Inherited Alzheimer Network Trial, the APOE4 Treatment Trial, and the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) trial.

The first three will test anti-amyloid drugs in subjects with strong genetic risk factors for Alzheimer’s, and the A4 study will examine anti-amyloid treatment in subjects who are cognitively normal but have imaging evidence of beta-amyloid brain plaques.

These trials are clinically unique because each one could show whether early intervention in amyloid accumulation has any effect on disease development or progression. Logistically, they are unique because each relies on public/private partnerships involving three-way collaborations of academia, federal, and pharmaceutical dollars.

“We’re providing funds, but these trials take a lot of money – a lot. And working with pharmaceutical companies is one way that we can get the money we need to make them happen,” Dr. Buckholtz said. “We are seeing more and more of these interactions with government, academia, and industry, and I think this is what it will take to get something going. There’s still a lot of hard work to be done by independent researchers, but these kinds of partnerships will be needed to really move this forward.”

Clinically, Dr. Buckholtz said, one of the year’s most striking areas of research is tau imaging. New radioligands are being developed that allow PET imaging of tau tangles. Like amyloid imaging, tau imaging has the potential to redefine the way clinical trials are created and conducted, and could, in the future, become a useful tool for diagnosis and for tracking both disease progression and modification.

Tau imaging may also untangle the complicated relationship of tau, amyloid, and cognition. “It’s been very difficult to answer this question,” Dr. Buckholtz said. “Tau normally builds up very slowly in the medial temporal lobe with age, and in general, it doesn’t have a major deleterious effect. But when beta-amyloid comes along, it somehow exacerbates this increase, and tau moves out into the temporal cortex. That is the proximal thing that produces neurodegeneration and cognitive decline. We have never been able to observe this as a dynamic process, but now that we have imaging ligands for both amyloid and tau, we will be able to look at both of these at the same time in the same person, over a long period.”

At least three of the large anti-amyloid trials will be adding tau imaging to the existing protocol, Dr. Buckholtz added.

Preclinically, he said, the induction of pluripotent stem cells into neurons with an aging phenotype was a very important step in creating in vitro models of human aging (Cell Stem Cell. 2015 Dec 3;17[6]:705-18). Before this discovery, stem cell–induced neurons didn’t re-create human aging; in fact, induction somehow seemed to rejuvenate them, even if the progenitor cells were from an elderly person.

“Making these neurons with an aging phenotype is going to be very important as we look at aging – the biggest single risk factor for Alzheimer’s,” Dr. Buckholtz said.

Sleep is another emerging story, he said. “The relationship between sleep and beta-amyloid is fascinating. Some studies indicate that amyloid disrupts slow-wave sleep, which is needed for memory formation.”

And, despite the decades-old knowledge that the apolipoprotein E epsilon-4 allele confers various levels of Alzheimer’s risk, little is known about the mechanics of that relationship. Dr. Buckholtz hopes that will change in the near future.

Finally, work continues on what he called one of Alzheimer’s Holy Grails: a validated, blood-based biomarker. “The search hasn’t gone as well as we hoped it would. We still don’t have a reliable one, but no one is sure if that’s because there are just so many things that affect blood proteins or because we simply don’t have a good way to look at it. I’m hopeful, though. An accurate blood-based biomarker would bring Alzheimer’s screening into the primary care office. It would be an enormous step.”

[email protected]

On Twitter @Alz_Gal

While 2015 might not have been the year of the blockbuster Alzheimer’s drug, it did lay a few more paving stones on the road to understanding the disease.

Federal funding boosts, new-generation collaborative drug trials, and advances in tau imaging are some of the biggest boons of 2015, according to Dr. Neil Buckholtzof the National Institute on Aging, who in an interview addressed some of the points summarized in the NIA’s annual report on Alzheimer’s disease, the 2014-2015 Alzheimer’s Disease Progress Report: Advancing Research Toward a Cure.

Making clinical progress toward slowing or stopping Alzheimer’s development has been a tough slog, said Dr. Buckholtz, director of NIA’s Division of Neuroscience. It’s a problem that will be solved only by the collaborative efforts of many minds and many institutions, and all of these efforts are the product of a single common denominator: money. Things have improved considerably along that front, he said.

“In 2014, we received an additional appropriation from Congress of $100 million specifically for Alzheimer’s research. In 2015, we got another additional appropriation of $25 million,” which will give Alzheimer’s research an immediate boost in 2016.

“What that extra money has allowed us to do is fund Alzheimer’s applications beyond the regular funding line,” he said. “And that’s a really big deal. We’ve been able to use that money to double our funding for Alzheimer’s research applications from 8% to 18%” of the proposals submitted.

Two new programs arose from the additional monies, Dr. Buckholtz said: theNIH Biomarkers of Alzheimer’s Disease in Adults with Down Syndrome Initiativeand the Interdisciplinary Research to Understand the Vascular Contributions to Alzheimer’s Disease program.

The Down syndrome initiative will provide $35 million to two large projects studying early Alzheimer’s-like brain changes in people with Down syndrome. Because the amyloid precursor protein gene is also overexpressed in Down syndrome, these patients accumulate beta-amyloid at a greatly accelerated rate and will, inevitably, develop Alzheimer’s dementia. Thus, they represent an ideal population in which to study AD pathology from its earliest manifestations. The two projects will examine structural brain changes with MRI, amyloid, and tau imaging; search for new biomarkers, including blood-based biomarkers; and follow patients long term for changes in their medical, cognitive, and memory status.

The vascular program awarded a total of $4 million for research on how both the systemic vasculature and microvascular systems influence the development not only of Alzheimer’s but of other dementias as well.

Dr. Buckholtz also pointed to work on four large drug trials in presymptomatic patients: the Alzheimer’s Prevention Initiative Autosomal Dominant Alzheimer’s Disease Treatment Trial, the Dominantly Inherited Alzheimer Network Trial, the APOE4 Treatment Trial, and the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) trial.

The first three will test anti-amyloid drugs in subjects with strong genetic risk factors for Alzheimer’s, and the A4 study will examine anti-amyloid treatment in subjects who are cognitively normal but have imaging evidence of beta-amyloid brain plaques.

These trials are clinically unique because each one could show whether early intervention in amyloid accumulation has any effect on disease development or progression. Logistically, they are unique because each relies on public/private partnerships involving three-way collaborations of academia, federal, and pharmaceutical dollars.

“We’re providing funds, but these trials take a lot of money – a lot. And working with pharmaceutical companies is one way that we can get the money we need to make them happen,” Dr. Buckholtz said. “We are seeing more and more of these interactions with government, academia, and industry, and I think this is what it will take to get something going. There’s still a lot of hard work to be done by independent researchers, but these kinds of partnerships will be needed to really move this forward.”

Clinically, Dr. Buckholtz said, one of the year’s most striking areas of research is tau imaging. New radioligands are being developed that allow PET imaging of tau tangles. Like amyloid imaging, tau imaging has the potential to redefine the way clinical trials are created and conducted, and could, in the future, become a useful tool for diagnosis and for tracking both disease progression and modification.

Tau imaging may also untangle the complicated relationship of tau, amyloid, and cognition. “It’s been very difficult to answer this question,” Dr. Buckholtz said. “Tau normally builds up very slowly in the medial temporal lobe with age, and in general, it doesn’t have a major deleterious effect. But when beta-amyloid comes along, it somehow exacerbates this increase, and tau moves out into the temporal cortex. That is the proximal thing that produces neurodegeneration and cognitive decline. We have never been able to observe this as a dynamic process, but now that we have imaging ligands for both amyloid and tau, we will be able to look at both of these at the same time in the same person, over a long period.”

At least three of the large anti-amyloid trials will be adding tau imaging to the existing protocol, Dr. Buckholtz added.

Preclinically, he said, the induction of pluripotent stem cells into neurons with an aging phenotype was a very important step in creating in vitro models of human aging (Cell Stem Cell. 2015 Dec 3;17[6]:705-18). Before this discovery, stem cell–induced neurons didn’t re-create human aging; in fact, induction somehow seemed to rejuvenate them, even if the progenitor cells were from an elderly person.

“Making these neurons with an aging phenotype is going to be very important as we look at aging – the biggest single risk factor for Alzheimer’s,” Dr. Buckholtz said.

Sleep is another emerging story, he said. “The relationship between sleep and beta-amyloid is fascinating. Some studies indicate that amyloid disrupts slow-wave sleep, which is needed for memory formation.”

And, despite the decades-old knowledge that the apolipoprotein E epsilon-4 allele confers various levels of Alzheimer’s risk, little is known about the mechanics of that relationship. Dr. Buckholtz hopes that will change in the near future.

Finally, work continues on what he called one of Alzheimer’s Holy Grails: a validated, blood-based biomarker. “The search hasn’t gone as well as we hoped it would. We still don’t have a reliable one, but no one is sure if that’s because there are just so many things that affect blood proteins or because we simply don’t have a good way to look at it. I’m hopeful, though. An accurate blood-based biomarker would bring Alzheimer’s screening into the primary care office. It would be an enormous step.”

[email protected]

On Twitter @Alz_Gal

Patients with Alzheimer’s disease (AD) who performed poorly on early cognitive tests seemed to progress more rapidly than those with less baseline impairment, a study showed.

Age was also an indicator of progression, with younger patients declining at a more rapid pace, according to the study published in the December issue of the American Journal of Alzheimer’s Disease & Other Dementias.

But no single test – even those routinely used as diagnostic tools – successfully predicted the rate of decline, reported Jennifer N. Travis Seidl and Paul J. Massman, Ph.D.

Agnieszka Letowska/Thinkstock

“Tests that differed between the rapidly and slowly progressing groups tended to measure higher-order cognitive skills such as executive functioning, memory, and visuospatial construction,” wrote Ms. Seidl of the University of Houston and Dr. Massman of the Baylor College of Medicine, Houston. “This indicates that a full neuropsychological evaluation, rather than sole use of a global screening measure such as the MMSE [Mini-Mental State Exam] or ADAS-cog [Alzheimer’s Disease Assessment Scale–Cognitive], may be useful for predicting future cognitive decline.”

Although the individual course of Alzheimer’s dementia is notoriously unpredictable, the ability to predict the rate of decline would be immensely helpful to patients and caregivers, as well as medical staff, the investigators noted (Am J Alzheimers Dis Other Demen. 2015. doi: 10.1177/1533317515617720).

“Prediction of rate of decline among patients with [Alzheimer’s disease] may allow caregivers and physicians to make more informed decisions about future care of the patient,” they wrote.

The team examined dementia progression over a period of 2 years in a cohort of 110 Alzheimer’s patients who were seen at the Baylor College of Medicine Alzheimer’s Disease and Memory Disorders Center in Houston. Of these, half were slow progressers and the other half, rapid progressers.

The group was assessed by baseline and 2-year scores on 14 neuropsychological tests, including some of the most widely used: Mini-Mental State Examination, Clinical Dementia Rating scale (CDR), Alzheimer ’s Disease Assessment Scale–Cognitive subscale, and the Instrumental Activities of Daily Living (IADL). Other tests measured overall intelligence, memory and verbal fluency, executive function, and physical function.

At baseline, fast progression was significantly associated with younger age (72 vs. 77 years). Sex, ADAS-cog and MMSE scores, and apolipoprotein E epsilon 4 genetic status were not different between the groups. Functional status as measured by IADL was similar. The baseline CDR, however, was significantly different, with 48% of the slow progressers being at 0.5, compared with 24% of the rapid progressers.

The finding of no difference between the groups on baseline performance on the ADAS-cog or MMSE “indicates that these global measures are not as useful for predicting rate of decline as are more specific measures of neuropsychological functioning.”

Many of the more specific tests did accurately differentiate the groups. The rapid progressers had significantly poorer scores on the Logical Memory, Verbal Series Attention Test, Controlled Oral Word Association Test verbal fluency, and block design in the Wechsler Adult Intelligence Scale.

There were also persistent significant differences for the Boston Naming Test and Rey-Osterrieth Complex.

The investigators suggested that future research examine the predictive value of performance in tests that measure higher-order thinking skills “to determine whether the differences in the rate of progression observed in the current study occur throughout the course of the disease.”

They received no outside funding for the study and did not have any financial disclosures.

[email protected]

On Twitter @Alz_Gal

Patients with Alzheimer’s disease (AD) who performed poorly on early cognitive tests seemed to progress more rapidly than those with less baseline impairment, a study showed.

Age was also an indicator of progression, with younger patients declining at a more rapid pace, according to the study published in the December issue of the American Journal of Alzheimer’s Disease & Other Dementias.

But no single test – even those routinely used as diagnostic tools – successfully predicted the rate of decline, reported Jennifer N. Travis Seidl and Paul J. Massman, Ph.D.

Agnieszka Letowska/Thinkstock

“Tests that differed between the rapidly and slowly progressing groups tended to measure higher-order cognitive skills such as executive functioning, memory, and visuospatial construction,” wrote Ms. Seidl of the University of Houston and Dr. Massman of the Baylor College of Medicine, Houston. “This indicates that a full neuropsychological evaluation, rather than sole use of a global screening measure such as the MMSE [Mini-Mental State Exam] or ADAS-cog [Alzheimer’s Disease Assessment Scale–Cognitive], may be useful for predicting future cognitive decline.”

Although the individual course of Alzheimer’s dementia is notoriously unpredictable, the ability to predict the rate of decline would be immensely helpful to patients and caregivers, as well as medical staff, the investigators noted (Am J Alzheimers Dis Other Demen. 2015. doi: 10.1177/1533317515617720).

“Prediction of rate of decline among patients with [Alzheimer’s disease] may allow caregivers and physicians to make more informed decisions about future care of the patient,” they wrote.

The team examined dementia progression over a period of 2 years in a cohort of 110 Alzheimer’s patients who were seen at the Baylor College of Medicine Alzheimer’s Disease and Memory Disorders Center in Houston. Of these, half were slow progressers and the other half, rapid progressers.

The group was assessed by baseline and 2-year scores on 14 neuropsychological tests, including some of the most widely used: Mini-Mental State Examination, Clinical Dementia Rating scale (CDR), Alzheimer ’s Disease Assessment Scale–Cognitive subscale, and the Instrumental Activities of Daily Living (IADL). Other tests measured overall intelligence, memory and verbal fluency, executive function, and physical function.

At baseline, fast progression was significantly associated with younger age (72 vs. 77 years). Sex, ADAS-cog and MMSE scores, and apolipoprotein E epsilon 4 genetic status were not different between the groups. Functional status as measured by IADL was similar. The baseline CDR, however, was significantly different, with 48% of the slow progressers being at 0.5, compared with 24% of the rapid progressers.

The finding of no difference between the groups on baseline performance on the ADAS-cog or MMSE “indicates that these global measures are not as useful for predicting rate of decline as are more specific measures of neuropsychological functioning.”

Many of the more specific tests did accurately differentiate the groups. The rapid progressers had significantly poorer scores on the Logical Memory, Verbal Series Attention Test, Controlled Oral Word Association Test verbal fluency, and block design in the Wechsler Adult Intelligence Scale.

There were also persistent significant differences for the Boston Naming Test and Rey-Osterrieth Complex.

The investigators suggested that future research examine the predictive value of performance in tests that measure higher-order thinking skills “to determine whether the differences in the rate of progression observed in the current study occur throughout the course of the disease.”

They received no outside funding for the study and did not have any financial disclosures.

[email protected]

On Twitter @Alz_Gal

Patients with Alzheimer’s disease (AD) who performed poorly on early cognitive tests seemed to progress more rapidly than those with less baseline impairment, a study showed.

Age was also an indicator of progression, with younger patients declining at a more rapid pace, according to the study published in the December issue of the American Journal of Alzheimer’s Disease & Other Dementias.

But no single test – even those routinely used as diagnostic tools – successfully predicted the rate of decline, reported Jennifer N. Travis Seidl and Paul J. Massman, Ph.D.

Agnieszka Letowska/Thinkstock

“Tests that differed between the rapidly and slowly progressing groups tended to measure higher-order cognitive skills such as executive functioning, memory, and visuospatial construction,” wrote Ms. Seidl of the University of Houston and Dr. Massman of the Baylor College of Medicine, Houston. “This indicates that a full neuropsychological evaluation, rather than sole use of a global screening measure such as the MMSE [Mini-Mental State Exam] or ADAS-cog [Alzheimer’s Disease Assessment Scale–Cognitive], may be useful for predicting future cognitive decline.”

Although the individual course of Alzheimer’s dementia is notoriously unpredictable, the ability to predict the rate of decline would be immensely helpful to patients and caregivers, as well as medical staff, the investigators noted (Am J Alzheimers Dis Other Demen. 2015. doi: 10.1177/1533317515617720).

“Prediction of rate of decline among patients with [Alzheimer’s disease] may allow caregivers and physicians to make more informed decisions about future care of the patient,” they wrote.

The team examined dementia progression over a period of 2 years in a cohort of 110 Alzheimer’s patients who were seen at the Baylor College of Medicine Alzheimer’s Disease and Memory Disorders Center in Houston. Of these, half were slow progressers and the other half, rapid progressers.

The group was assessed by baseline and 2-year scores on 14 neuropsychological tests, including some of the most widely used: Mini-Mental State Examination, Clinical Dementia Rating scale (CDR), Alzheimer ’s Disease Assessment Scale–Cognitive subscale, and the Instrumental Activities of Daily Living (IADL). Other tests measured overall intelligence, memory and verbal fluency, executive function, and physical function.

At baseline, fast progression was significantly associated with younger age (72 vs. 77 years). Sex, ADAS-cog and MMSE scores, and apolipoprotein E epsilon 4 genetic status were not different between the groups. Functional status as measured by IADL was similar. The baseline CDR, however, was significantly different, with 48% of the slow progressers being at 0.5, compared with 24% of the rapid progressers.

The finding of no difference between the groups on baseline performance on the ADAS-cog or MMSE “indicates that these global measures are not as useful for predicting rate of decline as are more specific measures of neuropsychological functioning.”

Many of the more specific tests did accurately differentiate the groups. The rapid progressers had significantly poorer scores on the Logical Memory, Verbal Series Attention Test, Controlled Oral Word Association Test verbal fluency, and block design in the Wechsler Adult Intelligence Scale.

There were also persistent significant differences for the Boston Naming Test and Rey-Osterrieth Complex.

The investigators suggested that future research examine the predictive value of performance in tests that measure higher-order thinking skills “to determine whether the differences in the rate of progression observed in the current study occur throughout the course of the disease.”

They received no outside funding for the study and did not have any financial disclosures.

[email protected]

On Twitter @Alz_Gal