Guidelines

The European Society for Medical Oncology (ESMO) has published a proposed scale that would rank molecular targets for various cancers by how well they can be treated with new or emerging drugs.

The ESMO Scale of Clinical Actionability for Molecular Targets is designed to “harmonize and standardize the reporting and interpretation of clinically relevant genomics data,” according to Joaquin Mateo, MD, PhD, from the Vall d’Hebron Institute of Oncology in Barcelona, Spain, and his fellow members of the ESMO Translational Research and Precision Medicine Working Group.

“A major challenge for oncologists in the clinic is to distinguish between findings that represent proven clinical value or potential value based on preliminary clinical or preclinical evidence from hypothetical gene-drug matches and findings that are currently irrelevant for clinical practice,” they wrote in Annals of Oncology.

The scale groups targets into one of six tiers based on levels of evidence ranging from the gold standard of prospective, randomized clinical trials to targets for which there are no evidence and only hypothetical actionability. The primary goal is to help oncologists assign priority to potential targets when they review results of gene-sequencing panels for individual patients, according to the developers.

Briefly, the six tiers are:

Tier I includes targets that are agreed to be suitable for routine use and a recommended specific drug when a specific molecular alteration is detected. Examples include trastuzumab for human epidermal growth factor receptor 2 (HER2)–positive breast cancer, and inhibitors of epidermal growth factor receptor (EGFR) in patients with non–small cell lung cancer positive for EGFR mutations.

Tier II includes “investigational targets that likely define a patient population that benefits from a targeted drug but additional data are needed.” This tier includes agents that work in the phosphatidylinostiol 3-kinase pathway.

Tier III is similar to Tier II, in that it includes investigational targets that define a patient population with proven benefit from a targeted therapy, but in this case the target is detected in a different tumor type that has not previously been studied. For example, the targeted agent vemurafenib (Zelboraf), which extends survival of patients with metastatic melanomas carrying the BRAF V600E mutation, has only limited activity against BRAF-mutated colorectal cancers.

Tier IV includes targets with preclinical evidence of actionability.

Tier V includes targets with “evidence of relevant antitumor activity, not resulting in clinical meaningful benefit as single treatment but supporting development of cotargeting approaches.” The authors cite the example of PIK3CA inhibitors in patients with estrogen receptor–positive, HER2-negative breast cancers who also have PIK3CA activating mutations. In clinical trials, this strategy led to objective responses but not change outcomes.

The final tier is not Tier VI, as might be expected, but Tier X, with the X in this case being the unknown – that is, alterations/mutations for which there is neither preclinical nor clinical evidence to support their hypothetical use as a drug target.

“This clinical benefit–centered classification system offers a common language for all the actors involved in clinical cancer drug development. Its implementation in sequencing reports, tumor boards, and scientific communication can enable precise treatment decisions and facilitate discussions with patients about novel therapeutic options,” Dr. Mateo and his associates wrote in their conclusion.

The development process was supported by ESMO. Multiple coauthors reported financial relationships with various companies as well as grants/support from other foundations or charities.

SOURCE: Mateo J et al. Ann Oncol. 2018 Aug 21. doi: 10.1093/annonc/mdy263.

The European Society for Medical Oncology (ESMO) has published a proposed scale that would rank molecular targets for various cancers by how well they can be treated with new or emerging drugs.

The ESMO Scale of Clinical Actionability for Molecular Targets is designed to “harmonize and standardize the reporting and interpretation of clinically relevant genomics data,” according to Joaquin Mateo, MD, PhD, from the Vall d’Hebron Institute of Oncology in Barcelona, Spain, and his fellow members of the ESMO Translational Research and Precision Medicine Working Group.

“A major challenge for oncologists in the clinic is to distinguish between findings that represent proven clinical value or potential value based on preliminary clinical or preclinical evidence from hypothetical gene-drug matches and findings that are currently irrelevant for clinical practice,” they wrote in Annals of Oncology.

The scale groups targets into one of six tiers based on levels of evidence ranging from the gold standard of prospective, randomized clinical trials to targets for which there are no evidence and only hypothetical actionability. The primary goal is to help oncologists assign priority to potential targets when they review results of gene-sequencing panels for individual patients, according to the developers.

Briefly, the six tiers are:

Tier I includes targets that are agreed to be suitable for routine use and a recommended specific drug when a specific molecular alteration is detected. Examples include trastuzumab for human epidermal growth factor receptor 2 (HER2)–positive breast cancer, and inhibitors of epidermal growth factor receptor (EGFR) in patients with non–small cell lung cancer positive for EGFR mutations.

Tier II includes “investigational targets that likely define a patient population that benefits from a targeted drug but additional data are needed.” This tier includes agents that work in the phosphatidylinostiol 3-kinase pathway.

Tier III is similar to Tier II, in that it includes investigational targets that define a patient population with proven benefit from a targeted therapy, but in this case the target is detected in a different tumor type that has not previously been studied. For example, the targeted agent vemurafenib (Zelboraf), which extends survival of patients with metastatic melanomas carrying the BRAF V600E mutation, has only limited activity against BRAF-mutated colorectal cancers.

Tier IV includes targets with preclinical evidence of actionability.

Tier V includes targets with “evidence of relevant antitumor activity, not resulting in clinical meaningful benefit as single treatment but supporting development of cotargeting approaches.” The authors cite the example of PIK3CA inhibitors in patients with estrogen receptor–positive, HER2-negative breast cancers who also have PIK3CA activating mutations. In clinical trials, this strategy led to objective responses but not change outcomes.

The final tier is not Tier VI, as might be expected, but Tier X, with the X in this case being the unknown – that is, alterations/mutations for which there is neither preclinical nor clinical evidence to support their hypothetical use as a drug target.

“This clinical benefit–centered classification system offers a common language for all the actors involved in clinical cancer drug development. Its implementation in sequencing reports, tumor boards, and scientific communication can enable precise treatment decisions and facilitate discussions with patients about novel therapeutic options,” Dr. Mateo and his associates wrote in their conclusion.

The development process was supported by ESMO. Multiple coauthors reported financial relationships with various companies as well as grants/support from other foundations or charities.

SOURCE: Mateo J et al. Ann Oncol. 2018 Aug 21. doi: 10.1093/annonc/mdy263.

The European Society for Medical Oncology (ESMO) has published a proposed scale that would rank molecular targets for various cancers by how well they can be treated with new or emerging drugs.

The ESMO Scale of Clinical Actionability for Molecular Targets is designed to “harmonize and standardize the reporting and interpretation of clinically relevant genomics data,” according to Joaquin Mateo, MD, PhD, from the Vall d’Hebron Institute of Oncology in Barcelona, Spain, and his fellow members of the ESMO Translational Research and Precision Medicine Working Group.

“A major challenge for oncologists in the clinic is to distinguish between findings that represent proven clinical value or potential value based on preliminary clinical or preclinical evidence from hypothetical gene-drug matches and findings that are currently irrelevant for clinical practice,” they wrote in Annals of Oncology.

The scale groups targets into one of six tiers based on levels of evidence ranging from the gold standard of prospective, randomized clinical trials to targets for which there are no evidence and only hypothetical actionability. The primary goal is to help oncologists assign priority to potential targets when they review results of gene-sequencing panels for individual patients, according to the developers.

Briefly, the six tiers are:

Tier I includes targets that are agreed to be suitable for routine use and a recommended specific drug when a specific molecular alteration is detected. Examples include trastuzumab for human epidermal growth factor receptor 2 (HER2)–positive breast cancer, and inhibitors of epidermal growth factor receptor (EGFR) in patients with non–small cell lung cancer positive for EGFR mutations.

Tier II includes “investigational targets that likely define a patient population that benefits from a targeted drug but additional data are needed.” This tier includes agents that work in the phosphatidylinostiol 3-kinase pathway.

Tier III is similar to Tier II, in that it includes investigational targets that define a patient population with proven benefit from a targeted therapy, but in this case the target is detected in a different tumor type that has not previously been studied. For example, the targeted agent vemurafenib (Zelboraf), which extends survival of patients with metastatic melanomas carrying the BRAF V600E mutation, has only limited activity against BRAF-mutated colorectal cancers.

Tier IV includes targets with preclinical evidence of actionability.

Tier V includes targets with “evidence of relevant antitumor activity, not resulting in clinical meaningful benefit as single treatment but supporting development of cotargeting approaches.” The authors cite the example of PIK3CA inhibitors in patients with estrogen receptor–positive, HER2-negative breast cancers who also have PIK3CA activating mutations. In clinical trials, this strategy led to objective responses but not change outcomes.

The final tier is not Tier VI, as might be expected, but Tier X, with the X in this case being the unknown – that is, alterations/mutations for which there is neither preclinical nor clinical evidence to support their hypothetical use as a drug target.

“This clinical benefit–centered classification system offers a common language for all the actors involved in clinical cancer drug development. Its implementation in sequencing reports, tumor boards, and scientific communication can enable precise treatment decisions and facilitate discussions with patients about novel therapeutic options,” Dr. Mateo and his associates wrote in their conclusion.

The development process was supported by ESMO. Multiple coauthors reported financial relationships with various companies as well as grants/support from other foundations or charities.

SOURCE: Mateo J et al. Ann Oncol. 2018 Aug 21. doi: 10.1093/annonc/mdy263.

Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.

The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.

The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.

Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.

“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”

The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.

The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.

The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.

Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.

In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.

The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.

“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.

The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.

SOURCE: Curry S et al. JAMA. 2018;320:911-7.

Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.

The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.

The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.

Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.

“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”

The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.

The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.

The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.

Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.

In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.

The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.

“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.

The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.

SOURCE: Curry S et al. JAMA. 2018;320:911-7.

Against the backdrop of a near doubling in the incidence of congenital syphilis in the United States, the U.S. Preventive Services Task Force has reaffirmed its 2009 recommendation to screen all pregnant women for syphilis as early as possible in pregnancy.

The advice was the task force’s primary recommendation, based on a systematic review of seven studies and backed by the highest grade of evidence, in a statement published in JAMA. Untreated syphilis can be transmitted to the fetus at any time during pregnancy or birth, and congenital syphilis is associated with significant neonatal morbidity – including bone deformities and neurologic impairment – as well as stillbirth and neonatal death.

The prevalence of congenital syphilis was in decline from 2008 to 2012, but then increased by 87% from 2012 to 2016 – from 8.4 cases per 100,000 live births in 2012 to 15.7 cases in 2016. The increase coincided with rising national rates of syphilis among women of reproductive age – from 0.9 cases of primary and secondary syphilis infection per 100,000 women in 2012 to 1.9 cases in 2016.

Additionally, the task force recommended that pregnant women who had not received prenatal care be screened at delivery.

“Although nearly 70% of infants with congenital syphilis are born to mothers who received prenatal care, detection, and treatment of maternal syphilis often occurs too late to treat the fetus and prevent congenital syphilis,” wrote Susan J. Curry, PhD, from the University of Iowa, Iowa City, and her coauthors. “Recent data suggest that while screening rates for syphilis infection are generally high, the proportion of women screened earlier in pregnancy remains low (for example, 20% of women are screened only at the time of delivery).”

The review pointed to an observational study of the impact of the introduction of syphilis screening during pregnancy in China. That study of more than 2 million women showed that screening for syphilis in pregnancy increased from 89.8% of women in 2002 to 97.2% of women in 2012 and was associated with a decrease in the incidence of congenital syphilis from 109.3 cases to 9.4 cases per 100,000 live births.

The group found convincing evidence that screening reduced both the incidence of congenital syphilis and the risk of adverse outcomes related to maternal infection and that the potential harms of screening – such as false positives – were small.

The paper also referenced guidelines from the Centers for Disease Control and Prevention, the American Academy of Pediatrics, and the American College of Obstetricians and Gynecologists that high-risk women – such as those living in areas or communities with a higher prevalence of syphilis, women with HIV, or with a history of incarceration or sex work – should also be rescreened early in the third trimester and again at delivery. Similarly, women who are exposed to an infected partner also should be rescreened.

Further, the task force recommended screening for nonpregnant adolescents and adults at increased risk of syphilis infection.

In terms of treatment, the CDC currently recommends parenteral penicillin G benzathine as the treatment of choice for syphilis in pregnant women. However, the task force recommended clinicians consult the CDC website for updates.

The authors noted that no studies that met the inclusion criteria examined whether penicillin use during pregnancy was associated with any harm or looked at serious adverse events in women with a history of penicillin allergy.

“Because the review was primarily focused on screening, it did not address the efficacy of alternative antibiotic treatments [e.g., ceftriaxone] in pregnant women [with or without penicillin allergies],” the authors wrote.

The research was funded by the U.S. Department of Health and Human Services. No conflicts of interest were reported.

SOURCE: Curry S et al. JAMA. 2018;320:911-7.

An updated set of practice guidelines developed by the American Academy of Neurology recommends that patients with prolonged disorders of consciousness, such as a vegetative state or minimally conscious state, first undergo treatment for other outside symptoms and conditions to increase the likelihood of initial accurate diagnosis. The AAN also recommends that patients be evaluated by multidisciplinary specialists using standardized neurobehavioral assessments.

sudok1/thinkstock

“People are sometimes misdiagnosed due to underlying impairments that can mask awareness,” guidelines first author Joseph T. Giacino, PhD, of Harvard Medical School, Boston, and Spaulding Rehabilitation Hospital, Charlestown, Mass., stated in a press release about the guidelines. “An inaccurate diagnosis can lead to inappropriate care decisions and poor health outcomes. Misdiagnosis may result in premature or inappropriate treatment withdrawal, failure to recommend beneficial rehabilitative treatments, and worse outcome. That is why an early and accurate diagnosis is so important.”

The practice guidelines, published Aug. 8 in Neurology, update the 1995 recommendations from the AAN on persistent vegetative state (VS) as well as a 2002 case definition of minimally conscious state (MCS) developed by the AAN, American Congress of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research. In the new document, these same organizations made 18 recommendations about prolonged disorders of consciousness (DoC) based on three levels of evidence: Level A evidence was defined as the strongest recommendation, Level B evidence consisted of recommendations with a confident rationale and a “favorable benefit-risk profile,” and Level C evidence was the lowest level of recommendation that was still useful to clinical practice. Evidence was grouped into four different classifications based on the modified Grading of Recommendations Assessment, Development, and Evaluation process in a systematic review and based on “strong related evidence, established principles of care, and inferences.”

In the guidelines, the committee made the following recommendations:

• Medically stable patients with DoC should be moved to multidisciplinary care settings where specialists can “optimize diagnostic evaluation, prognostication, and subsequent management, including effective medical monitoring and rehabilitative care” (Level B).
• Patients should receive care for confounding conditions, receive serial standardized assessments, and undergo care that “optimizes arousal” to maximize initial accurate diagnoses (Level B).
• Clinicians should communicate to families of patients with prolonged DoC that adult patients in an MCS caused by traumatic injury tend to have “more favorable outcomes,” compared with patients who are in a VS and patients with unresponsive wakefulness syndrome (UWS) caused by a nontraumatic injury (Level B).
• Clinicians must discuss long-term care with families of patients with prolonged DoC and a poor prognosis (Level A), indicate that not all patients of this type have a poor prognosis, administer Coma Recovery Scale–Revised, and perform imaging, such as structural MRI and single-photon emission CT, to determine prognosis in these patients (Level B).
• Regarding discussion of long-term care with families of children with prolonged DoC, clinicians should acknowledge that prognostic assessment, treatment, and natural history of recovery is not well-defined for children with prolonged DoC (Level B).
• In patients with traumatic VS, UWS, or MCS, amantadine should be prescribed (100-200 mg) between 4 weeks and 16 weeks after injury to lower the risk of disability and increase the likelihood of functional recovery (Level B).
• Clinicians should always assess and treat pain as well as discuss “evidence supporting treatment approaches” (Level B).

In addition, the subcommittee recommended changing the term permanent VS to chronic VS/UWS, citing Level B evidence. “Continued use of the term permanent VS is not justified. Use of this term implies irreversibility, which is not supported by the current research and has implications for family counseling, decision making, and the ethics of the field,” Dr. Giacino and his colleagues wrote.

In a separate summary of the guidelines, Dr. Giacino and his colleagues expressed concern about the lack of moderate or strong evidence for diagnostic assessment procedures in the literature, which they partially attributed to the inclusion of patients out 28 days or less from their injury in the systematic review for the guidelines. They further noted the lack of a gold-standard diagnostic approach for these patients, a lack of masking in diagnostic studies and tracking of recovery milestones and long-term functional outcomes for patients, and the limitations of the mainly retrospective analyses of outcomes in studies that they included. In addition, Dr. Giacino and his colleagues noted a lack of therapeutic studies with patients in inpatient rehabilitation centers and a “tendency by insurers to preferentially authorize rehabilitative care in lower-cost settings.” They excluded studies that had less than 20 patients, no control group, and were not “methodologically sound.”

Shorter lengths of stay in inpatient rehabilitation at academic medical centers have also led to problems in recruiting for placebo-controlled clinical trials, they noted.

“Under these circumstances, family members are often reticent to enroll patients with prolonged DoC in a placebo-controlled trial in view of the 50% likelihood of assignment to the placebo arm, preventing any possibility of active treatment during rehabilitation apart from routine physical, occupational, and speech therapies,” the authors wrote.

Several of the guidelines’ 16 authors disclosed ties to publishing houses and commercial or government entities, and participate in other activities related to the content of the published guidelines. Please see the full study for a complete list of disclosures.

An updated set of practice guidelines developed by the American Academy of Neurology recommends that patients with prolonged disorders of consciousness, such as a vegetative state or minimally conscious state, first undergo treatment for other outside symptoms and conditions to increase the likelihood of initial accurate diagnosis. The AAN also recommends that patients be evaluated by multidisciplinary specialists using standardized neurobehavioral assessments.

sudok1/thinkstock

“People are sometimes misdiagnosed due to underlying impairments that can mask awareness,” guidelines first author Joseph T. Giacino, PhD, of Harvard Medical School, Boston, and Spaulding Rehabilitation Hospital, Charlestown, Mass., stated in a press release about the guidelines. “An inaccurate diagnosis can lead to inappropriate care decisions and poor health outcomes. Misdiagnosis may result in premature or inappropriate treatment withdrawal, failure to recommend beneficial rehabilitative treatments, and worse outcome. That is why an early and accurate diagnosis is so important.”

The practice guidelines, published Aug. 8 in Neurology, update the 1995 recommendations from the AAN on persistent vegetative state (VS) as well as a 2002 case definition of minimally conscious state (MCS) developed by the AAN, American Congress of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research. In the new document, these same organizations made 18 recommendations about prolonged disorders of consciousness (DoC) based on three levels of evidence: Level A evidence was defined as the strongest recommendation, Level B evidence consisted of recommendations with a confident rationale and a “favorable benefit-risk profile,” and Level C evidence was the lowest level of recommendation that was still useful to clinical practice. Evidence was grouped into four different classifications based on the modified Grading of Recommendations Assessment, Development, and Evaluation process in a systematic review and based on “strong related evidence, established principles of care, and inferences.”

In the guidelines, the committee made the following recommendations:

• Medically stable patients with DoC should be moved to multidisciplinary care settings where specialists can “optimize diagnostic evaluation, prognostication, and subsequent management, including effective medical monitoring and rehabilitative care” (Level B).
• Patients should receive care for confounding conditions, receive serial standardized assessments, and undergo care that “optimizes arousal” to maximize initial accurate diagnoses (Level B).
• Clinicians should communicate to families of patients with prolonged DoC that adult patients in an MCS caused by traumatic injury tend to have “more favorable outcomes,” compared with patients who are in a VS and patients with unresponsive wakefulness syndrome (UWS) caused by a nontraumatic injury (Level B).
• Clinicians must discuss long-term care with families of patients with prolonged DoC and a poor prognosis (Level A), indicate that not all patients of this type have a poor prognosis, administer Coma Recovery Scale–Revised, and perform imaging, such as structural MRI and single-photon emission CT, to determine prognosis in these patients (Level B).
• Regarding discussion of long-term care with families of children with prolonged DoC, clinicians should acknowledge that prognostic assessment, treatment, and natural history of recovery is not well-defined for children with prolonged DoC (Level B).
• In patients with traumatic VS, UWS, or MCS, amantadine should be prescribed (100-200 mg) between 4 weeks and 16 weeks after injury to lower the risk of disability and increase the likelihood of functional recovery (Level B).
• Clinicians should always assess and treat pain as well as discuss “evidence supporting treatment approaches” (Level B).

In addition, the subcommittee recommended changing the term permanent VS to chronic VS/UWS, citing Level B evidence. “Continued use of the term permanent VS is not justified. Use of this term implies irreversibility, which is not supported by the current research and has implications for family counseling, decision making, and the ethics of the field,” Dr. Giacino and his colleagues wrote.

In a separate summary of the guidelines, Dr. Giacino and his colleagues expressed concern about the lack of moderate or strong evidence for diagnostic assessment procedures in the literature, which they partially attributed to the inclusion of patients out 28 days or less from their injury in the systematic review for the guidelines. They further noted the lack of a gold-standard diagnostic approach for these patients, a lack of masking in diagnostic studies and tracking of recovery milestones and long-term functional outcomes for patients, and the limitations of the mainly retrospective analyses of outcomes in studies that they included. In addition, Dr. Giacino and his colleagues noted a lack of therapeutic studies with patients in inpatient rehabilitation centers and a “tendency by insurers to preferentially authorize rehabilitative care in lower-cost settings.” They excluded studies that had less than 20 patients, no control group, and were not “methodologically sound.”

Shorter lengths of stay in inpatient rehabilitation at academic medical centers have also led to problems in recruiting for placebo-controlled clinical trials, they noted.

“Under these circumstances, family members are often reticent to enroll patients with prolonged DoC in a placebo-controlled trial in view of the 50% likelihood of assignment to the placebo arm, preventing any possibility of active treatment during rehabilitation apart from routine physical, occupational, and speech therapies,” the authors wrote.

Several of the guidelines’ 16 authors disclosed ties to publishing houses and commercial or government entities, and participate in other activities related to the content of the published guidelines. Please see the full study for a complete list of disclosures.

An updated set of practice guidelines developed by the American Academy of Neurology recommends that patients with prolonged disorders of consciousness, such as a vegetative state or minimally conscious state, first undergo treatment for other outside symptoms and conditions to increase the likelihood of initial accurate diagnosis. The AAN also recommends that patients be evaluated by multidisciplinary specialists using standardized neurobehavioral assessments.

sudok1/thinkstock

“People are sometimes misdiagnosed due to underlying impairments that can mask awareness,” guidelines first author Joseph T. Giacino, PhD, of Harvard Medical School, Boston, and Spaulding Rehabilitation Hospital, Charlestown, Mass., stated in a press release about the guidelines. “An inaccurate diagnosis can lead to inappropriate care decisions and poor health outcomes. Misdiagnosis may result in premature or inappropriate treatment withdrawal, failure to recommend beneficial rehabilitative treatments, and worse outcome. That is why an early and accurate diagnosis is so important.”

The practice guidelines, published Aug. 8 in Neurology, update the 1995 recommendations from the AAN on persistent vegetative state (VS) as well as a 2002 case definition of minimally conscious state (MCS) developed by the AAN, American Congress of Rehabilitation Medicine, and the National Institute on Disability, Independent Living, and Rehabilitation Research. In the new document, these same organizations made 18 recommendations about prolonged disorders of consciousness (DoC) based on three levels of evidence: Level A evidence was defined as the strongest recommendation, Level B evidence consisted of recommendations with a confident rationale and a “favorable benefit-risk profile,” and Level C evidence was the lowest level of recommendation that was still useful to clinical practice. Evidence was grouped into four different classifications based on the modified Grading of Recommendations Assessment, Development, and Evaluation process in a systematic review and based on “strong related evidence, established principles of care, and inferences.”

In the guidelines, the committee made the following recommendations:

• Medically stable patients with DoC should be moved to multidisciplinary care settings where specialists can “optimize diagnostic evaluation, prognostication, and subsequent management, including effective medical monitoring and rehabilitative care” (Level B).
• Patients should receive care for confounding conditions, receive serial standardized assessments, and undergo care that “optimizes arousal” to maximize initial accurate diagnoses (Level B).
• Clinicians should communicate to families of patients with prolonged DoC that adult patients in an MCS caused by traumatic injury tend to have “more favorable outcomes,” compared with patients who are in a VS and patients with unresponsive wakefulness syndrome (UWS) caused by a nontraumatic injury (Level B).
• Clinicians must discuss long-term care with families of patients with prolonged DoC and a poor prognosis (Level A), indicate that not all patients of this type have a poor prognosis, administer Coma Recovery Scale–Revised, and perform imaging, such as structural MRI and single-photon emission CT, to determine prognosis in these patients (Level B).
• Regarding discussion of long-term care with families of children with prolonged DoC, clinicians should acknowledge that prognostic assessment, treatment, and natural history of recovery is not well-defined for children with prolonged DoC (Level B).
• In patients with traumatic VS, UWS, or MCS, amantadine should be prescribed (100-200 mg) between 4 weeks and 16 weeks after injury to lower the risk of disability and increase the likelihood of functional recovery (Level B).
• Clinicians should always assess and treat pain as well as discuss “evidence supporting treatment approaches” (Level B).

In addition, the subcommittee recommended changing the term permanent VS to chronic VS/UWS, citing Level B evidence. “Continued use of the term permanent VS is not justified. Use of this term implies irreversibility, which is not supported by the current research and has implications for family counseling, decision making, and the ethics of the field,” Dr. Giacino and his colleagues wrote.

In a separate summary of the guidelines, Dr. Giacino and his colleagues expressed concern about the lack of moderate or strong evidence for diagnostic assessment procedures in the literature, which they partially attributed to the inclusion of patients out 28 days or less from their injury in the systematic review for the guidelines. They further noted the lack of a gold-standard diagnostic approach for these patients, a lack of masking in diagnostic studies and tracking of recovery milestones and long-term functional outcomes for patients, and the limitations of the mainly retrospective analyses of outcomes in studies that they included. In addition, Dr. Giacino and his colleagues noted a lack of therapeutic studies with patients in inpatient rehabilitation centers and a “tendency by insurers to preferentially authorize rehabilitative care in lower-cost settings.” They excluded studies that had less than 20 patients, no control group, and were not “methodologically sound.”

Shorter lengths of stay in inpatient rehabilitation at academic medical centers have also led to problems in recruiting for placebo-controlled clinical trials, they noted.

“Under these circumstances, family members are often reticent to enroll patients with prolonged DoC in a placebo-controlled trial in view of the 50% likelihood of assignment to the placebo arm, preventing any possibility of active treatment during rehabilitation apart from routine physical, occupational, and speech therapies,” the authors wrote.

Several of the guidelines’ 16 authors disclosed ties to publishing houses and commercial or government entities, and participate in other activities related to the content of the published guidelines. Please see the full study for a complete list of disclosures.

An update to the first-ever guideline on adult congenital heart disease, released today, provides new recommendations and a more nuanced classification system based on data and expertise accrued in the field over the past decade.

Better road map

The document is intended to provide a “better road map” for all providers who will see such patients in their practice, said Dr. Daniels, director of the adult congenital heart disease and pulmonary hypertension program at Ohio State University Heart Center and Nationwide Children’s Hospital, Columbus.

“There are not enough adult congenital heart disease cardiologists and programs in the country to care for the almost 1.5 million adults with congenital heart disease in the United States, so we know these patients are cared for by general cardiologists,” Dr. Daniels said in an interview. “Having some guidelines about when to refer to those patients was a huge part of the purpose of these updated guidelines.”

The revamped classification system underlying the new guidelines seeks to better characterize disease severity based on the complexity of its anatomy and physiology, according to Dr. Daniels.

Previous documents, including the original 2008 AHA/ACC guideline (Circulation. 2008 Nov 7;118:e714-833), focused mainly on anatomic classifications to rank severity, he said.

“Traditionally, we’ve based the severity of congenital heart disease based on the complexity of anatomy they were born with, but that goes only so far,” Dr. Daniels said in an interview.

More than just anatomy

In the new system, anatomy is classified as simple (I, e.g., isolated small atrial septal defect), moderately complex (II, e.g., coarctation of the aorta), or greatly complex (III, e.g., cyanotic congenital heart defect), while physiologic stages range from A to D, increasing along with the severity of physiologic variables such as New York Heart Association functional class; exercise capacity; aortic enlargement; arrhythmias; renal, hepatic, or pulmonary function; and venal or arterial stenosis.

A normotensive patient with repaired coarctation of the aorta would be classified as IIA if she had normal end-organ function and exercise capacity, whereas a similar patient with an ascending aortic diameter of 4.0 cm would be classified as IIB, and with the addition of moderate aortic stenosis, would be classified as IIIC, according to an example provided in the guidelines.

Congenital heart disease specialist Robert “Jake” Jaquiss, MD, said in an interview that consideration of physiology alongside anatomy is one of the most important features of the new guidelines.

“This is a way of thinking about patients that involves not just their anatomy, but also considering a variety of domains in which there may be physiologic dysfunction that can modify the underlying anatomy,” said Dr. Jaquiss, chief of pediatric and congenital heart surgery at Children’s Medical Center/University of Texas Southwestern Medical Center, Dallas. “I think that is a more clinically relevant way to think about patients and patient evaluation management, and I commend the authors for that focus.”

For example, one patient who has undergone a Fontan procedure may be fully functional, whereas another with nearly identical anatomy may be burdened by arrhythmias, fluid retention, and impaired exercise function. “If we don’t grasp the physiologic difference, we treat the two patients the same way, which is obviously inappropriate,” Dr. Jaquiss said.

Research directions

Much more research needs to be done, according to guideline authors, who list 60 unresolved research questions that represent evidence gaps and future directions for study.

For example, outstanding questions related to tetralogy of Fallot focus on the optimal timing for pulmonary valve replacement, the role of pulmonary valve replacement and ventricular tachycardia ablation in decreasing sudden cardiac death risk, and whether implantable cardioverter-defibrillators reduce mortality.

“These are the kinds of evolutionary sort of understandings and alterations in the intervention, both at the original operation and for assessment of care, and what we think about it and how we think about it in 2018 is quite different than how we thought in 2008, and I dare say it’ll be even more different in 2028,” Dr. Jaquiss said.

The AHA/ACC guideline was developed in association with the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

Dr. Daniels reported a relevant relationship with Actelion. Guideline coauthors reported relevant relationships in that same category with Actelion, Boehringer Ingelheim, Cormatrix, Edward Lifesciences, Gilead, Medtronic, Novartis, Sorin (LivaNova), St. Jude Medical, and United Therapeutics. No other disclosures were reported.

SOURCE: Stout KK et al. J Am Coll Cardiol. 2018 Aug 16. Copublished in Circulation.

An update to the first-ever guideline on adult congenital heart disease, released today, provides new recommendations and a more nuanced classification system based on data and expertise accrued in the field over the past decade.

Better road map

The document is intended to provide a “better road map” for all providers who will see such patients in their practice, said Dr. Daniels, director of the adult congenital heart disease and pulmonary hypertension program at Ohio State University Heart Center and Nationwide Children’s Hospital, Columbus.

“There are not enough adult congenital heart disease cardiologists and programs in the country to care for the almost 1.5 million adults with congenital heart disease in the United States, so we know these patients are cared for by general cardiologists,” Dr. Daniels said in an interview. “Having some guidelines about when to refer to those patients was a huge part of the purpose of these updated guidelines.”

The revamped classification system underlying the new guidelines seeks to better characterize disease severity based on the complexity of its anatomy and physiology, according to Dr. Daniels.

Previous documents, including the original 2008 AHA/ACC guideline (Circulation. 2008 Nov 7;118:e714-833), focused mainly on anatomic classifications to rank severity, he said.

“Traditionally, we’ve based the severity of congenital heart disease based on the complexity of anatomy they were born with, but that goes only so far,” Dr. Daniels said in an interview.

More than just anatomy

In the new system, anatomy is classified as simple (I, e.g., isolated small atrial septal defect), moderately complex (II, e.g., coarctation of the aorta), or greatly complex (III, e.g., cyanotic congenital heart defect), while physiologic stages range from A to D, increasing along with the severity of physiologic variables such as New York Heart Association functional class; exercise capacity; aortic enlargement; arrhythmias; renal, hepatic, or pulmonary function; and venal or arterial stenosis.

A normotensive patient with repaired coarctation of the aorta would be classified as IIA if she had normal end-organ function and exercise capacity, whereas a similar patient with an ascending aortic diameter of 4.0 cm would be classified as IIB, and with the addition of moderate aortic stenosis, would be classified as IIIC, according to an example provided in the guidelines.

Congenital heart disease specialist Robert “Jake” Jaquiss, MD, said in an interview that consideration of physiology alongside anatomy is one of the most important features of the new guidelines.

“This is a way of thinking about patients that involves not just their anatomy, but also considering a variety of domains in which there may be physiologic dysfunction that can modify the underlying anatomy,” said Dr. Jaquiss, chief of pediatric and congenital heart surgery at Children’s Medical Center/University of Texas Southwestern Medical Center, Dallas. “I think that is a more clinically relevant way to think about patients and patient evaluation management, and I commend the authors for that focus.”

For example, one patient who has undergone a Fontan procedure may be fully functional, whereas another with nearly identical anatomy may be burdened by arrhythmias, fluid retention, and impaired exercise function. “If we don’t grasp the physiologic difference, we treat the two patients the same way, which is obviously inappropriate,” Dr. Jaquiss said.

Research directions

Much more research needs to be done, according to guideline authors, who list 60 unresolved research questions that represent evidence gaps and future directions for study.

For example, outstanding questions related to tetralogy of Fallot focus on the optimal timing for pulmonary valve replacement, the role of pulmonary valve replacement and ventricular tachycardia ablation in decreasing sudden cardiac death risk, and whether implantable cardioverter-defibrillators reduce mortality.

“These are the kinds of evolutionary sort of understandings and alterations in the intervention, both at the original operation and for assessment of care, and what we think about it and how we think about it in 2018 is quite different than how we thought in 2008, and I dare say it’ll be even more different in 2028,” Dr. Jaquiss said.

The AHA/ACC guideline was developed in association with the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

Dr. Daniels reported a relevant relationship with Actelion. Guideline coauthors reported relevant relationships in that same category with Actelion, Boehringer Ingelheim, Cormatrix, Edward Lifesciences, Gilead, Medtronic, Novartis, Sorin (LivaNova), St. Jude Medical, and United Therapeutics. No other disclosures were reported.

SOURCE: Stout KK et al. J Am Coll Cardiol. 2018 Aug 16. Copublished in Circulation.

An update to the first-ever guideline on adult congenital heart disease, released today, provides new recommendations and a more nuanced classification system based on data and expertise accrued in the field over the past decade.

Better road map

The document is intended to provide a “better road map” for all providers who will see such patients in their practice, said Dr. Daniels, director of the adult congenital heart disease and pulmonary hypertension program at Ohio State University Heart Center and Nationwide Children’s Hospital, Columbus.

“There are not enough adult congenital heart disease cardiologists and programs in the country to care for the almost 1.5 million adults with congenital heart disease in the United States, so we know these patients are cared for by general cardiologists,” Dr. Daniels said in an interview. “Having some guidelines about when to refer to those patients was a huge part of the purpose of these updated guidelines.”

The revamped classification system underlying the new guidelines seeks to better characterize disease severity based on the complexity of its anatomy and physiology, according to Dr. Daniels.

Previous documents, including the original 2008 AHA/ACC guideline (Circulation. 2008 Nov 7;118:e714-833), focused mainly on anatomic classifications to rank severity, he said.

“Traditionally, we’ve based the severity of congenital heart disease based on the complexity of anatomy they were born with, but that goes only so far,” Dr. Daniels said in an interview.

More than just anatomy

In the new system, anatomy is classified as simple (I, e.g., isolated small atrial septal defect), moderately complex (II, e.g., coarctation of the aorta), or greatly complex (III, e.g., cyanotic congenital heart defect), while physiologic stages range from A to D, increasing along with the severity of physiologic variables such as New York Heart Association functional class; exercise capacity; aortic enlargement; arrhythmias; renal, hepatic, or pulmonary function; and venal or arterial stenosis.

A normotensive patient with repaired coarctation of the aorta would be classified as IIA if she had normal end-organ function and exercise capacity, whereas a similar patient with an ascending aortic diameter of 4.0 cm would be classified as IIB, and with the addition of moderate aortic stenosis, would be classified as IIIC, according to an example provided in the guidelines.

Congenital heart disease specialist Robert “Jake” Jaquiss, MD, said in an interview that consideration of physiology alongside anatomy is one of the most important features of the new guidelines.

“This is a way of thinking about patients that involves not just their anatomy, but also considering a variety of domains in which there may be physiologic dysfunction that can modify the underlying anatomy,” said Dr. Jaquiss, chief of pediatric and congenital heart surgery at Children’s Medical Center/University of Texas Southwestern Medical Center, Dallas. “I think that is a more clinically relevant way to think about patients and patient evaluation management, and I commend the authors for that focus.”

For example, one patient who has undergone a Fontan procedure may be fully functional, whereas another with nearly identical anatomy may be burdened by arrhythmias, fluid retention, and impaired exercise function. “If we don’t grasp the physiologic difference, we treat the two patients the same way, which is obviously inappropriate,” Dr. Jaquiss said.

Research directions

Much more research needs to be done, according to guideline authors, who list 60 unresolved research questions that represent evidence gaps and future directions for study.

For example, outstanding questions related to tetralogy of Fallot focus on the optimal timing for pulmonary valve replacement, the role of pulmonary valve replacement and ventricular tachycardia ablation in decreasing sudden cardiac death risk, and whether implantable cardioverter-defibrillators reduce mortality.

“These are the kinds of evolutionary sort of understandings and alterations in the intervention, both at the original operation and for assessment of care, and what we think about it and how we think about it in 2018 is quite different than how we thought in 2008, and I dare say it’ll be even more different in 2028,” Dr. Jaquiss said.

The AHA/ACC guideline was developed in association with the American Association for Thoracic Surgery, American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons.

Dr. Daniels reported a relevant relationship with Actelion. Guideline coauthors reported relevant relationships in that same category with Actelion, Boehringer Ingelheim, Cormatrix, Edward Lifesciences, Gilead, Medtronic, Novartis, Sorin (LivaNova), St. Jude Medical, and United Therapeutics. No other disclosures were reported.

SOURCE: Stout KK et al. J Am Coll Cardiol. 2018 Aug 16. Copublished in Circulation.

The National Comprehensive Cancer Network (NCCN) has issued its first-ever clinical practice guidelines for the treatment of gestational trophoblastic neoplasia (GTN), a rare, serious complication of pregnancy that can often be cured, but can have devastating consequences if mismanaged or if treatment is needlessly delayed.

David Mutch, MD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, who heads the NCCN Clinical Practice Guidelines in Oncology Committee for GTN, explained the critical importance of the GTN guidelines.

“It’s a rare disease, people weren’t that familiar with it, and they often are patients treated with single-agent therapy when they should be treated with multi-agent therapy,” he said in an interview.

“There wasn’t a clear understanding of what to do except by those people who treated these patients regularly. The only thing most people knew was that it was very chemosensitive and should be curable, but it’s only curable if you follow the appropriate algorithms,” he continued.

The algorithms he referred to were established by a handful of centers with expertise and experience in diagnosing and treating these rare conditions, including noninvasive hydatidiform mole, invasive mole, and choriocarcinoma, the most aggressive form of GTN.

Neil Horowitz, MD, director of clinical research in gynecologic oncology at the Dana-Farber Cancer Institute in Boston, works with colleagues in one of those referral centers, the New England Trophoblastic Disease Center, and is familiar with the new guidelines. As with other rare malignancies, there are data to suggest that patients with GTN who are treated in centers of excellence with higher patient volumes have better outcomes than do similar patients treated in a community setting, he said in an interview.
 

Placental origins

GTNs arise from placental rather than maternal tissue. They most commonly present with vaginal bleeding and a rapidly enlarging uterus, and may be accompanied by pelvic pain or pressure, anemia, severe nausea/vomiting (hyperemesis gravidarum), hyperthyroidism, or early-pregnancy preeclampsia.

The overall reported incidence of GTN in the United States, including hydatidiform mole, is approximately 110 to 120 per 100,000 pregnancies, and the reported incidence of choriocarcinoma is about 2 to 7 per 100,000, according to the National Cancer Institute.

The GTN guidelines provide evidence-based recommendations about optimal approaches to GTN in all of its known forms. For example, the section on noninvasive hydatidiform mole recommends the tests that should be routinely performed during workup, followed by surgery with either suction, dilation and curettage – preferably under ultrasound guidance – or hysterectomy for women who are older or who do not wish to preserve fertility.

The guidelines also specify steps that should be taken for diagnosis and staging of GTN as well as risk-based therapeutic approaches.

For example, the guidelines recommend therapy with either methotrexate alone or alternating with leucovorin, or dactinomycin alone for patients with confirmed low risk GTN, defined as a prognostic score less than 7.

The prognostic scoring index, also included in the guidelines, considers risk factors such as age, prior pregnancies, interval from an index pregnancy, pretreatment human chorionic gonadotropin (hCG) levels, site and number of metastases, largest tumor size, and previous chemotherapy failure.

For patients with high-risk GTN, defined as FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stages II-III with a prognostic score of 7 or greater, or FIGO stage IV, chemotherapy with the EMA/CO regimen is recommended. This aggressive regimen consists of etoposide, methotrexate, dactinomycin (the “EMA “component) plus cyclophosphamide and vincristine (the “CO” component).

“In my mind, the most important part of the guidelines is reiterating how the diagnosis of GTN should be made, and importantly, how the score should be calculated so that women are put in the appropriate low-risk or high-risk category, so they get the right treatment,” Dr. Horowitz said.
 

Reassuring insurers

Dr. Mutch said that he and his colleagues in GTN centers sometimes treat patients with intermediate or high-risk disease who were started on single-agent therapy or suboptimal therapies and present with advanced, drug-resistant disease.

“These guidelines were established so that people could see exactly what needs to be done when,” he said.

The guidelines also are critical for convincing third-party payers about the need for specific treatments, he added.

“I had a high-risk patient who needed EMA/CO, and the insurance company said ‘well, there’s no NCCN guidelines – we won’t approve it.’ So then I had to wait 3 days while it went through peer review. Meanwhile, the tumor doubled in size, and then the nurse who was reviewing it declined the ‘CO’ part, so that was delayed a week, and it really jeopardized this patient’s survival,” Dr. Mutch said.

The guidelines also include recommendations for patients with special clinical situations, such as women with clinical responses to EMA/CO who continue to have plateauing low levels of hCG or have a re-elevation of hCG levels after having a complete response to EMA/CO.

There are also specific recommendations for treatment of two even rarer intermediate trophoblastic tumor types: placental-site trophoblastic tumor and epithelioid trophoblastic tumor.

The guidelines are supported by the NCCN. Dr. Mutch reported consulting/advisory board participation for Clovis. Dr. Horowitz reported having no relationships to disclose.

SOURCE: Gestational Trophoblastic Neoplasia. NCCN.org, Version 1.2019, published Aug. 9, 2018.

The National Comprehensive Cancer Network (NCCN) has issued its first-ever clinical practice guidelines for the treatment of gestational trophoblastic neoplasia (GTN), a rare, serious complication of pregnancy that can often be cured, but can have devastating consequences if mismanaged or if treatment is needlessly delayed.

David Mutch, MD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, who heads the NCCN Clinical Practice Guidelines in Oncology Committee for GTN, explained the critical importance of the GTN guidelines.

“It’s a rare disease, people weren’t that familiar with it, and they often are patients treated with single-agent therapy when they should be treated with multi-agent therapy,” he said in an interview.

“There wasn’t a clear understanding of what to do except by those people who treated these patients regularly. The only thing most people knew was that it was very chemosensitive and should be curable, but it’s only curable if you follow the appropriate algorithms,” he continued.

The algorithms he referred to were established by a handful of centers with expertise and experience in diagnosing and treating these rare conditions, including noninvasive hydatidiform mole, invasive mole, and choriocarcinoma, the most aggressive form of GTN.

Neil Horowitz, MD, director of clinical research in gynecologic oncology at the Dana-Farber Cancer Institute in Boston, works with colleagues in one of those referral centers, the New England Trophoblastic Disease Center, and is familiar with the new guidelines. As with other rare malignancies, there are data to suggest that patients with GTN who are treated in centers of excellence with higher patient volumes have better outcomes than do similar patients treated in a community setting, he said in an interview.
 

Placental origins

GTNs arise from placental rather than maternal tissue. They most commonly present with vaginal bleeding and a rapidly enlarging uterus, and may be accompanied by pelvic pain or pressure, anemia, severe nausea/vomiting (hyperemesis gravidarum), hyperthyroidism, or early-pregnancy preeclampsia.

The overall reported incidence of GTN in the United States, including hydatidiform mole, is approximately 110 to 120 per 100,000 pregnancies, and the reported incidence of choriocarcinoma is about 2 to 7 per 100,000, according to the National Cancer Institute.

The GTN guidelines provide evidence-based recommendations about optimal approaches to GTN in all of its known forms. For example, the section on noninvasive hydatidiform mole recommends the tests that should be routinely performed during workup, followed by surgery with either suction, dilation and curettage – preferably under ultrasound guidance – or hysterectomy for women who are older or who do not wish to preserve fertility.

The guidelines also specify steps that should be taken for diagnosis and staging of GTN as well as risk-based therapeutic approaches.

For example, the guidelines recommend therapy with either methotrexate alone or alternating with leucovorin, or dactinomycin alone for patients with confirmed low risk GTN, defined as a prognostic score less than 7.

The prognostic scoring index, also included in the guidelines, considers risk factors such as age, prior pregnancies, interval from an index pregnancy, pretreatment human chorionic gonadotropin (hCG) levels, site and number of metastases, largest tumor size, and previous chemotherapy failure.

For patients with high-risk GTN, defined as FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stages II-III with a prognostic score of 7 or greater, or FIGO stage IV, chemotherapy with the EMA/CO regimen is recommended. This aggressive regimen consists of etoposide, methotrexate, dactinomycin (the “EMA “component) plus cyclophosphamide and vincristine (the “CO” component).

“In my mind, the most important part of the guidelines is reiterating how the diagnosis of GTN should be made, and importantly, how the score should be calculated so that women are put in the appropriate low-risk or high-risk category, so they get the right treatment,” Dr. Horowitz said.
 

Reassuring insurers

Dr. Mutch said that he and his colleagues in GTN centers sometimes treat patients with intermediate or high-risk disease who were started on single-agent therapy or suboptimal therapies and present with advanced, drug-resistant disease.

“These guidelines were established so that people could see exactly what needs to be done when,” he said.

The guidelines also are critical for convincing third-party payers about the need for specific treatments, he added.

“I had a high-risk patient who needed EMA/CO, and the insurance company said ‘well, there’s no NCCN guidelines – we won’t approve it.’ So then I had to wait 3 days while it went through peer review. Meanwhile, the tumor doubled in size, and then the nurse who was reviewing it declined the ‘CO’ part, so that was delayed a week, and it really jeopardized this patient’s survival,” Dr. Mutch said.

The guidelines also include recommendations for patients with special clinical situations, such as women with clinical responses to EMA/CO who continue to have plateauing low levels of hCG or have a re-elevation of hCG levels after having a complete response to EMA/CO.

There are also specific recommendations for treatment of two even rarer intermediate trophoblastic tumor types: placental-site trophoblastic tumor and epithelioid trophoblastic tumor.

The guidelines are supported by the NCCN. Dr. Mutch reported consulting/advisory board participation for Clovis. Dr. Horowitz reported having no relationships to disclose.

SOURCE: Gestational Trophoblastic Neoplasia. NCCN.org, Version 1.2019, published Aug. 9, 2018.

The National Comprehensive Cancer Network (NCCN) has issued its first-ever clinical practice guidelines for the treatment of gestational trophoblastic neoplasia (GTN), a rare, serious complication of pregnancy that can often be cured, but can have devastating consequences if mismanaged or if treatment is needlessly delayed.

David Mutch, MD, of the Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, who heads the NCCN Clinical Practice Guidelines in Oncology Committee for GTN, explained the critical importance of the GTN guidelines.

“It’s a rare disease, people weren’t that familiar with it, and they often are patients treated with single-agent therapy when they should be treated with multi-agent therapy,” he said in an interview.

“There wasn’t a clear understanding of what to do except by those people who treated these patients regularly. The only thing most people knew was that it was very chemosensitive and should be curable, but it’s only curable if you follow the appropriate algorithms,” he continued.

The algorithms he referred to were established by a handful of centers with expertise and experience in diagnosing and treating these rare conditions, including noninvasive hydatidiform mole, invasive mole, and choriocarcinoma, the most aggressive form of GTN.

Neil Horowitz, MD, director of clinical research in gynecologic oncology at the Dana-Farber Cancer Institute in Boston, works with colleagues in one of those referral centers, the New England Trophoblastic Disease Center, and is familiar with the new guidelines. As with other rare malignancies, there are data to suggest that patients with GTN who are treated in centers of excellence with higher patient volumes have better outcomes than do similar patients treated in a community setting, he said in an interview.
 

Placental origins

GTNs arise from placental rather than maternal tissue. They most commonly present with vaginal bleeding and a rapidly enlarging uterus, and may be accompanied by pelvic pain or pressure, anemia, severe nausea/vomiting (hyperemesis gravidarum), hyperthyroidism, or early-pregnancy preeclampsia.

The overall reported incidence of GTN in the United States, including hydatidiform mole, is approximately 110 to 120 per 100,000 pregnancies, and the reported incidence of choriocarcinoma is about 2 to 7 per 100,000, according to the National Cancer Institute.

The GTN guidelines provide evidence-based recommendations about optimal approaches to GTN in all of its known forms. For example, the section on noninvasive hydatidiform mole recommends the tests that should be routinely performed during workup, followed by surgery with either suction, dilation and curettage – preferably under ultrasound guidance – or hysterectomy for women who are older or who do not wish to preserve fertility.

The guidelines also specify steps that should be taken for diagnosis and staging of GTN as well as risk-based therapeutic approaches.

For example, the guidelines recommend therapy with either methotrexate alone or alternating with leucovorin, or dactinomycin alone for patients with confirmed low risk GTN, defined as a prognostic score less than 7.

The prognostic scoring index, also included in the guidelines, considers risk factors such as age, prior pregnancies, interval from an index pregnancy, pretreatment human chorionic gonadotropin (hCG) levels, site and number of metastases, largest tumor size, and previous chemotherapy failure.

For patients with high-risk GTN, defined as FIGO (Fédération Internationale de Gynécologie et d’Obstétrique) stages II-III with a prognostic score of 7 or greater, or FIGO stage IV, chemotherapy with the EMA/CO regimen is recommended. This aggressive regimen consists of etoposide, methotrexate, dactinomycin (the “EMA “component) plus cyclophosphamide and vincristine (the “CO” component).

“In my mind, the most important part of the guidelines is reiterating how the diagnosis of GTN should be made, and importantly, how the score should be calculated so that women are put in the appropriate low-risk or high-risk category, so they get the right treatment,” Dr. Horowitz said.
 

Reassuring insurers

Dr. Mutch said that he and his colleagues in GTN centers sometimes treat patients with intermediate or high-risk disease who were started on single-agent therapy or suboptimal therapies and present with advanced, drug-resistant disease.

“These guidelines were established so that people could see exactly what needs to be done when,” he said.

The guidelines also are critical for convincing third-party payers about the need for specific treatments, he added.

“I had a high-risk patient who needed EMA/CO, and the insurance company said ‘well, there’s no NCCN guidelines – we won’t approve it.’ So then I had to wait 3 days while it went through peer review. Meanwhile, the tumor doubled in size, and then the nurse who was reviewing it declined the ‘CO’ part, so that was delayed a week, and it really jeopardized this patient’s survival,” Dr. Mutch said.

The guidelines also include recommendations for patients with special clinical situations, such as women with clinical responses to EMA/CO who continue to have plateauing low levels of hCG or have a re-elevation of hCG levels after having a complete response to EMA/CO.

There are also specific recommendations for treatment of two even rarer intermediate trophoblastic tumor types: placental-site trophoblastic tumor and epithelioid trophoblastic tumor.

The guidelines are supported by the NCCN. Dr. Mutch reported consulting/advisory board participation for Clovis. Dr. Horowitz reported having no relationships to disclose.

SOURCE: Gestational Trophoblastic Neoplasia. NCCN.org, Version 1.2019, published Aug. 9, 2018.

Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for patients with chronic lymphocytic leukemia who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on chronic lymphocytic leukemia (CLL) to include “significant” developments in treatment. They were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the department of oncology at the University of Oxford (England), and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who could not take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients could also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended. TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib with rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote. However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplantation should be considered as a treatment option for patients who have either failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have a Richter transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5%-10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum is a registered charity that receives funding from a number of pharmaceutical companies.

SOURCE: Schuh AH et al. Br J Haematol. 2018 Jul 15. doi: 10.1111/bjh.15460.

Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for patients with chronic lymphocytic leukemia who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on chronic lymphocytic leukemia (CLL) to include “significant” developments in treatment. They were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the department of oncology at the University of Oxford (England), and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who could not take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients could also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended. TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib with rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote. However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplantation should be considered as a treatment option for patients who have either failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have a Richter transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5%-10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum is a registered charity that receives funding from a number of pharmaceutical companies.

SOURCE: Schuh AH et al. Br J Haematol. 2018 Jul 15. doi: 10.1111/bjh.15460.

Fludarabine, cyclophosphamide, and rituximab are recommended as initial therapy for patients with chronic lymphocytic leukemia who do not have TP53 disruption, according to new guidelines from the British Society for Haematology.

The guidelines update the 2012 recommendations on chronic lymphocytic leukemia (CLL) to include “significant” developments in treatment. They were published in the British Journal of Haematology.

Anna H. Schuh, MD, of the department of oncology at the University of Oxford (England), and her coauthors noted that, while these guidelines apply to treatments available outside clinical trials, wherever possible patients with CLL should be treated within the clinical trial setting.

While recommending fludarabine, cyclophosphamide, and rituximab as first-line therapy, the guideline authors acknowledged that the combination of bendamustine and rituximab is an acceptable alternative for patients who could not take the triple therapy because of comorbidities such as advanced age, renal impairment, or issues with marrow capacity.

Similarly, less-fit patients could also be considered for chlorambucil-obinutuzumab or chlorambucil-ofatumumab combinations.

All patients diagnosed with CLL should be tested for TP53 deletions and mutations before each line of therapy, the guideline committee recommended. TP53 disruption makes chemoimmunotherapy ineffective because of either a deletion of chromosome 17p or a mutation in the TP53 gene. However, there is compelling evidence for the efficacy of ibrutinib in these patients, or idelalisib and rituximab for those with cardiac disease or receiving vitamin K antagonists.

With respect to maintenance therapy, the guidelines noted that this was not routinely recommended in CLL as “it is unclear to what extent the progression-free survival benefit is offset by long-term toxicity.”

Patients who are refractory to chemoimmunotherapy, who have relapsed, or who cannot be retreated with chemoimmunotherapy should be treated with idelalisib with rituximab or ibrutinib monotherapy, the guidelines suggested.

“Deciding whether ibrutinib or idelalisib with rituximab is most appropriate for an individual patient depends on a range of factors, including toxicity profile and convenience of delivery,” the authors wrote. However, they noted that the value of adding bendamustine to either option was unclear as research had not shown significant, associated gains in median progression-free survival.

Allogeneic stem cell transplantation should be considered as a treatment option for patients who have either failed chemotherapy, have a TP53 disruption and have not responded to B-cell receptor signaling pathway inhibitors such as ibrutinib, or have a Richter transformation.

The guidelines also addressed the issue of autoimmune cytopenias, which occur in 5%-10% of patients with CLL and can actually precede the diagnosis of CLL in about 9% of cases.

In patients where autoimmune cytopenia is the dominant clinical feature, they should be treated with corticosteroids, intravenous immunoglobulin, or rituximab. However, for patients where the cytopenia is triggered by CLL therapy, the guidelines recommended halting treatment and beginning immunosuppression.

The guideline development was supported by the British Society for Haematology. The UK CLL Forum is a registered charity that receives funding from a number of pharmaceutical companies.

SOURCE: Schuh AH et al. Br J Haematol. 2018 Jul 15. doi: 10.1111/bjh.15460.

For adult patients with HIV, earlier treatment results in faster and more likely virologic suppression along with greater linkage to care, according to the 2018 Recommendations of the International Antiviral Society-USA (IAS-USA).

The updated treatment and prevention guidelines also have outlined drug selection, including three-drug therapy (usually as a single-tablet combination) and two-drug switch therapy, as well as discouragement of cash incentives for treatment. The guidelines, written by Michael S. Saag, MD, of the University of Alabama at Birmingham and his coauthors, were published in JAMA.

Since the previous IAS-USA guidelines were published in 2016 (JAMA. 2016;316(2):191-210), multiple studies have investigated the importance of timely antiretroviral therapy (ART). In one study, patients with HIV began ART within 24 hours of diagnosis. These patients achieved virologic suppression (fewer than 200 HIV RNA copies/mL) quicker than patients treated according to previous guidelines (medians, 1.8 months vs. 4.3 months; P = .0001). Another study found that patients who began ART immediately were more likely to achieve viral suppression at 12 months (50% vs. 34%; P = .007) and become linked to care at 3 months (68% vs. 43%). As such, the updated guidelines recommended that ART should be started as soon as possible (even without supporting laboratory results). Exceptions were maintained for patients not ready to start therapy and those at risk for immune reconstitution syndrome.

With regard to initial treatment selection, three-drug therapy is recommended, incorporating an integrase single-strand transfer inhibitor (InSTI) with 2 nucleoside reverse transcriptase inhibitors.

Single-tablet formulations are effective, well tolerated, and promote medication adherence. Dolutegravir is not recommended in women who are pregnant or may become pregnant because it may increase the risk of neural tube defects. It is unclear whether other InSTIs pose similar risks. Although two-drug regimens are not recommended for initial therapy, they may be considered as switch therapy to reduce cost and complications.

The 2018 guidelines have discouraged cash incentives for ART adherence because such programs have proven ineffective. Conversely, noncash incentives are likely to be beneficial. Further recommendations to improve outcomes were wide ranging and included identification of patients subject to food scarcity or psychiatric disorders. For the latter, chronic depression has been associated with worse outcomes – including a two-fold mortality risk – and so appropriate treatment is recommended.

The researchers concluded with a brief review of future directions for HIV treatment and prevention. Long-acting injectable and oral antiretrovirals are under investigation, along with implantable and nanoparticle therapies.

“Clinicians who care for patients with HIV have a major role in advocating for programs and their patients at the local, national, and international levels,” the authors wrote. “Advocacy should go beyond access to ART and include access to mental health and substance abuse services, as well as efforts to end policies such as HIV criminalization that impede the ability to provide evidence-based care and prevention services.”

The authors reported support from Gilead, ViiV, Merck, and other sources. The current guidelines were funded by IAS-USA.

SOURCE: Saag MS et al. JAMA. 2018;320[4]:379-96.

For adult patients with HIV, earlier treatment results in faster and more likely virologic suppression along with greater linkage to care, according to the 2018 Recommendations of the International Antiviral Society-USA (IAS-USA).

The updated treatment and prevention guidelines also have outlined drug selection, including three-drug therapy (usually as a single-tablet combination) and two-drug switch therapy, as well as discouragement of cash incentives for treatment. The guidelines, written by Michael S. Saag, MD, of the University of Alabama at Birmingham and his coauthors, were published in JAMA.

Since the previous IAS-USA guidelines were published in 2016 (JAMA. 2016;316(2):191-210), multiple studies have investigated the importance of timely antiretroviral therapy (ART). In one study, patients with HIV began ART within 24 hours of diagnosis. These patients achieved virologic suppression (fewer than 200 HIV RNA copies/mL) quicker than patients treated according to previous guidelines (medians, 1.8 months vs. 4.3 months; P = .0001). Another study found that patients who began ART immediately were more likely to achieve viral suppression at 12 months (50% vs. 34%; P = .007) and become linked to care at 3 months (68% vs. 43%). As such, the updated guidelines recommended that ART should be started as soon as possible (even without supporting laboratory results). Exceptions were maintained for patients not ready to start therapy and those at risk for immune reconstitution syndrome.

With regard to initial treatment selection, three-drug therapy is recommended, incorporating an integrase single-strand transfer inhibitor (InSTI) with 2 nucleoside reverse transcriptase inhibitors.

Single-tablet formulations are effective, well tolerated, and promote medication adherence. Dolutegravir is not recommended in women who are pregnant or may become pregnant because it may increase the risk of neural tube defects. It is unclear whether other InSTIs pose similar risks. Although two-drug regimens are not recommended for initial therapy, they may be considered as switch therapy to reduce cost and complications.

The 2018 guidelines have discouraged cash incentives for ART adherence because such programs have proven ineffective. Conversely, noncash incentives are likely to be beneficial. Further recommendations to improve outcomes were wide ranging and included identification of patients subject to food scarcity or psychiatric disorders. For the latter, chronic depression has been associated with worse outcomes – including a two-fold mortality risk – and so appropriate treatment is recommended.

The researchers concluded with a brief review of future directions for HIV treatment and prevention. Long-acting injectable and oral antiretrovirals are under investigation, along with implantable and nanoparticle therapies.

“Clinicians who care for patients with HIV have a major role in advocating for programs and their patients at the local, national, and international levels,” the authors wrote. “Advocacy should go beyond access to ART and include access to mental health and substance abuse services, as well as efforts to end policies such as HIV criminalization that impede the ability to provide evidence-based care and prevention services.”

The authors reported support from Gilead, ViiV, Merck, and other sources. The current guidelines were funded by IAS-USA.

SOURCE: Saag MS et al. JAMA. 2018;320[4]:379-96.

For adult patients with HIV, earlier treatment results in faster and more likely virologic suppression along with greater linkage to care, according to the 2018 Recommendations of the International Antiviral Society-USA (IAS-USA).

The updated treatment and prevention guidelines also have outlined drug selection, including three-drug therapy (usually as a single-tablet combination) and two-drug switch therapy, as well as discouragement of cash incentives for treatment. The guidelines, written by Michael S. Saag, MD, of the University of Alabama at Birmingham and his coauthors, were published in JAMA.

Since the previous IAS-USA guidelines were published in 2016 (JAMA. 2016;316(2):191-210), multiple studies have investigated the importance of timely antiretroviral therapy (ART). In one study, patients with HIV began ART within 24 hours of diagnosis. These patients achieved virologic suppression (fewer than 200 HIV RNA copies/mL) quicker than patients treated according to previous guidelines (medians, 1.8 months vs. 4.3 months; P = .0001). Another study found that patients who began ART immediately were more likely to achieve viral suppression at 12 months (50% vs. 34%; P = .007) and become linked to care at 3 months (68% vs. 43%). As such, the updated guidelines recommended that ART should be started as soon as possible (even without supporting laboratory results). Exceptions were maintained for patients not ready to start therapy and those at risk for immune reconstitution syndrome.

With regard to initial treatment selection, three-drug therapy is recommended, incorporating an integrase single-strand transfer inhibitor (InSTI) with 2 nucleoside reverse transcriptase inhibitors.

Single-tablet formulations are effective, well tolerated, and promote medication adherence. Dolutegravir is not recommended in women who are pregnant or may become pregnant because it may increase the risk of neural tube defects. It is unclear whether other InSTIs pose similar risks. Although two-drug regimens are not recommended for initial therapy, they may be considered as switch therapy to reduce cost and complications.

The 2018 guidelines have discouraged cash incentives for ART adherence because such programs have proven ineffective. Conversely, noncash incentives are likely to be beneficial. Further recommendations to improve outcomes were wide ranging and included identification of patients subject to food scarcity or psychiatric disorders. For the latter, chronic depression has been associated with worse outcomes – including a two-fold mortality risk – and so appropriate treatment is recommended.

The researchers concluded with a brief review of future directions for HIV treatment and prevention. Long-acting injectable and oral antiretrovirals are under investigation, along with implantable and nanoparticle therapies.

“Clinicians who care for patients with HIV have a major role in advocating for programs and their patients at the local, national, and international levels,” the authors wrote. “Advocacy should go beyond access to ART and include access to mental health and substance abuse services, as well as efforts to end policies such as HIV criminalization that impede the ability to provide evidence-based care and prevention services.”

The authors reported support from Gilead, ViiV, Merck, and other sources. The current guidelines were funded by IAS-USA.

SOURCE: Saag MS et al. JAMA. 2018;320[4]:379-96.

Transcatheter aortic valve replacement has entered a new stage of development, and so needed a tweaked set of standards for how existing programs operate and what new program need to open, said a panel of experts formed by the four U.S. societies with the closest links to this procedure.

U.S. transcatheter aortic valve replacement (TAVR) programs have “matured as a therapeutic option” since its commercial U.S. introduction in 2012, said a revised statement of operator and institutional recommendations and requirements issued on July 18 by the American Association for Thoracic Surgery, the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. A writing panel formed by these four groups prepared the revision, published online in the Journal of the American College of Cardiology on July 18, to replace the first set of recommendations for running U.S. TAVR programs that came out in 2012 (J Am Coll Cardiol. 2012 May 29;59[22]:2028-42).

“The main thrust is to ensure and allow for the metrics of quality TAVR,” said Joseph E. Bavaria, MD, cochair of the writing panel and professor of surgery and codirector of the transcatheter valve program at the University of Pennsylvania in Philadelphia. “We’re trying to force continuous quality improvement across U.S. TAVR teams,” Dr. Bavaria explained in an interview.

The key to this change will be the data collected on every U.S. TAVR patient in the Transcatheter Valve Therapy registry maintained by the American College of Cardiology and the Society of Thoracic Surgeons, which now has data on more than 120,000 patients who have undergone TAVR at what are now 582 active U.S. TAVR programs, noted Carl L. Tommaso, MD, an interventional cardiologist with NorthShore Medical Group in Bannockburn, Ill., and cochair of the writing panel. “You need to do risk adjustment to measure quality of care,” and the robust database that now exists has begun to make this possible, said Dr. Tommaso, who neither performs TAVR procedures nor participates on a TAVR team. Statistical analyses based on this substantial and always-expanding database of TAVR patients now allows for risk-adjusted assessment of in hospital and 30-day mortality, and risk-adjusted evaluation of 1-year mortality and quality-of-life outcomes are expected within the next couple of years.

“We’re still not yet at the point of having good, risk-adjusted models” for all these measures, but our hope is that in the next 2-7 years we can move completely to quality measures, as has already been done for percutaneous coronary interventions” and away from procedure volume, which currently serves as a surrogate marker for a TAVR program’s competence.

The new document continues to call for TAVR programs to average at least 50 TAVR procedures a year or at least 100 every 2 years, but primarily to insure that each TAVR program can generate enough data about its performance to produce statistically reliable numbers.

“The volume floors are only there because you can’t measure quality without volume,” said Dr. Bavaria. “It’s impossible to measure quality without a certain procedure volume.”

Dr. Bavaria stressed, however, that the goal of the new document is not to limit TAVR programs based on their procedure volume, especially because another goal of the document is to ensure reasonable geographic access to TAVR for U.S. patients. “This document does not advocate for any program to shut down,” he declared. On top of that, “we have no problem with new programs,” although the document noted that “the major threat to low volume sites growing and achieving higher levels of experience is the opening of additional sites in the same geographic region.”

In 2017, 204 of the 525 sites (39%) performing TAVR at that time were performing fewer than 50 procedures annually, the document said, but added that many TAVR centers now operate in what are predominantly rural regions “and it is important that they remain active if they can document acceptable quality even if they should fall below volume thresholds to maintain patient access to care.”

Dr. Tommaso said that perhaps a TAVR center in Alaska, for example, might not meet the 50 cases/year standard, “but I don’t think anyone would worry if the volume was low because we’re serving patients in Alaska.” Currently, 84% of TAVR centers that have been operating for more than 2 years meet the 50 procedures/year threshold, he added. And TAVR centers now operate in 49 of the 50 states, with only Wyoming lacking a TAVR facility within its borders. Despite this, use of TAVR among Wyoming residents is comparable to the rate in Illinois, Dr. Bavaria said.

Both cochairs also highlighted that, with TAVR now approved for patients at moderate risk for aortic-valve surgery, the number of patients who are TAVR candidates has grown, and it’s possible that pending trial results will soon broaden TAVR’s availability to low-risk patients, a step that would greatly further expand the potential patient pool for the procedure.

The revised recommendations and requirements will make it “a little easier to start a new program, except now, for the first time, you need to start with an operator who is already experienced with TAVR,” noted Dr. Bavaria. “The TAVR technology is now mature enough that it’s inappropriate to have learning-curve mortality.” But aside from this the new standards lower the bar a bit for a center’s volume of percutaneous coronary interventions and surgical aortic valve replacements. The revision also maintains that an examination by and consultation with a single cardiac surgeon by a prospective TAVR patient is adequate, similar to the 2012 document, although the Center for Medicare & Medicaid Services mandated in its coverage decision that prospective TAVR patients consult with two cardiac surgeons, the so-called “two-surgeon rule.” If CMS eliminated the two-surgeon rule it would “streamline” the process that patients go through when being assessed for TAVR, Dr. Tommaso observed, and both he and Dr. Bavaria expressed hope that the new document might prompt CMS to reconsider this guidance.

“We felt that two surgeons weren’t needed,” but the document specifies that both the surgeon and the cardiologist whom a prospective patient consults before finalizing plans for the intervention should both be members of the multidisciplinary team that performs the procedure. Until now, these clinicians weren’t specified as necessarily members of the TAVR team, Dr. Bavaria said.

One additional new element in the revised document is specification of shared decision making as the mechanism patients should go through when considering TAVR relative to their other management options, Dr. Tommaso said.Dr. Bavaria and Dr. Tommaso had no disclosures.

[email protected]
 

SOURCE: Bavaria JE et al. JACC. 2018 Jul18. doi:10.1016/j.jacc.2018.07.002.
 

Transcatheter aortic valve replacement has entered a new stage of development, and so needed a tweaked set of standards for how existing programs operate and what new program need to open, said a panel of experts formed by the four U.S. societies with the closest links to this procedure.

U.S. transcatheter aortic valve replacement (TAVR) programs have “matured as a therapeutic option” since its commercial U.S. introduction in 2012, said a revised statement of operator and institutional recommendations and requirements issued on July 18 by the American Association for Thoracic Surgery, the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. A writing panel formed by these four groups prepared the revision, published online in the Journal of the American College of Cardiology on July 18, to replace the first set of recommendations for running U.S. TAVR programs that came out in 2012 (J Am Coll Cardiol. 2012 May 29;59[22]:2028-42).

“The main thrust is to ensure and allow for the metrics of quality TAVR,” said Joseph E. Bavaria, MD, cochair of the writing panel and professor of surgery and codirector of the transcatheter valve program at the University of Pennsylvania in Philadelphia. “We’re trying to force continuous quality improvement across U.S. TAVR teams,” Dr. Bavaria explained in an interview.

The key to this change will be the data collected on every U.S. TAVR patient in the Transcatheter Valve Therapy registry maintained by the American College of Cardiology and the Society of Thoracic Surgeons, which now has data on more than 120,000 patients who have undergone TAVR at what are now 582 active U.S. TAVR programs, noted Carl L. Tommaso, MD, an interventional cardiologist with NorthShore Medical Group in Bannockburn, Ill., and cochair of the writing panel. “You need to do risk adjustment to measure quality of care,” and the robust database that now exists has begun to make this possible, said Dr. Tommaso, who neither performs TAVR procedures nor participates on a TAVR team. Statistical analyses based on this substantial and always-expanding database of TAVR patients now allows for risk-adjusted assessment of in hospital and 30-day mortality, and risk-adjusted evaluation of 1-year mortality and quality-of-life outcomes are expected within the next couple of years.

“We’re still not yet at the point of having good, risk-adjusted models” for all these measures, but our hope is that in the next 2-7 years we can move completely to quality measures, as has already been done for percutaneous coronary interventions” and away from procedure volume, which currently serves as a surrogate marker for a TAVR program’s competence.

The new document continues to call for TAVR programs to average at least 50 TAVR procedures a year or at least 100 every 2 years, but primarily to insure that each TAVR program can generate enough data about its performance to produce statistically reliable numbers.

“The volume floors are only there because you can’t measure quality without volume,” said Dr. Bavaria. “It’s impossible to measure quality without a certain procedure volume.”

Dr. Bavaria stressed, however, that the goal of the new document is not to limit TAVR programs based on their procedure volume, especially because another goal of the document is to ensure reasonable geographic access to TAVR for U.S. patients. “This document does not advocate for any program to shut down,” he declared. On top of that, “we have no problem with new programs,” although the document noted that “the major threat to low volume sites growing and achieving higher levels of experience is the opening of additional sites in the same geographic region.”

In 2017, 204 of the 525 sites (39%) performing TAVR at that time were performing fewer than 50 procedures annually, the document said, but added that many TAVR centers now operate in what are predominantly rural regions “and it is important that they remain active if they can document acceptable quality even if they should fall below volume thresholds to maintain patient access to care.”

Dr. Tommaso said that perhaps a TAVR center in Alaska, for example, might not meet the 50 cases/year standard, “but I don’t think anyone would worry if the volume was low because we’re serving patients in Alaska.” Currently, 84% of TAVR centers that have been operating for more than 2 years meet the 50 procedures/year threshold, he added. And TAVR centers now operate in 49 of the 50 states, with only Wyoming lacking a TAVR facility within its borders. Despite this, use of TAVR among Wyoming residents is comparable to the rate in Illinois, Dr. Bavaria said.

Both cochairs also highlighted that, with TAVR now approved for patients at moderate risk for aortic-valve surgery, the number of patients who are TAVR candidates has grown, and it’s possible that pending trial results will soon broaden TAVR’s availability to low-risk patients, a step that would greatly further expand the potential patient pool for the procedure.

The revised recommendations and requirements will make it “a little easier to start a new program, except now, for the first time, you need to start with an operator who is already experienced with TAVR,” noted Dr. Bavaria. “The TAVR technology is now mature enough that it’s inappropriate to have learning-curve mortality.” But aside from this the new standards lower the bar a bit for a center’s volume of percutaneous coronary interventions and surgical aortic valve replacements. The revision also maintains that an examination by and consultation with a single cardiac surgeon by a prospective TAVR patient is adequate, similar to the 2012 document, although the Center for Medicare & Medicaid Services mandated in its coverage decision that prospective TAVR patients consult with two cardiac surgeons, the so-called “two-surgeon rule.” If CMS eliminated the two-surgeon rule it would “streamline” the process that patients go through when being assessed for TAVR, Dr. Tommaso observed, and both he and Dr. Bavaria expressed hope that the new document might prompt CMS to reconsider this guidance.

“We felt that two surgeons weren’t needed,” but the document specifies that both the surgeon and the cardiologist whom a prospective patient consults before finalizing plans for the intervention should both be members of the multidisciplinary team that performs the procedure. Until now, these clinicians weren’t specified as necessarily members of the TAVR team, Dr. Bavaria said.

One additional new element in the revised document is specification of shared decision making as the mechanism patients should go through when considering TAVR relative to their other management options, Dr. Tommaso said.Dr. Bavaria and Dr. Tommaso had no disclosures.

[email protected]
 

SOURCE: Bavaria JE et al. JACC. 2018 Jul18. doi:10.1016/j.jacc.2018.07.002.
 

Transcatheter aortic valve replacement has entered a new stage of development, and so needed a tweaked set of standards for how existing programs operate and what new program need to open, said a panel of experts formed by the four U.S. societies with the closest links to this procedure.

U.S. transcatheter aortic valve replacement (TAVR) programs have “matured as a therapeutic option” since its commercial U.S. introduction in 2012, said a revised statement of operator and institutional recommendations and requirements issued on July 18 by the American Association for Thoracic Surgery, the American College of Cardiology, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. A writing panel formed by these four groups prepared the revision, published online in the Journal of the American College of Cardiology on July 18, to replace the first set of recommendations for running U.S. TAVR programs that came out in 2012 (J Am Coll Cardiol. 2012 May 29;59[22]:2028-42).

“The main thrust is to ensure and allow for the metrics of quality TAVR,” said Joseph E. Bavaria, MD, cochair of the writing panel and professor of surgery and codirector of the transcatheter valve program at the University of Pennsylvania in Philadelphia. “We’re trying to force continuous quality improvement across U.S. TAVR teams,” Dr. Bavaria explained in an interview.

The key to this change will be the data collected on every U.S. TAVR patient in the Transcatheter Valve Therapy registry maintained by the American College of Cardiology and the Society of Thoracic Surgeons, which now has data on more than 120,000 patients who have undergone TAVR at what are now 582 active U.S. TAVR programs, noted Carl L. Tommaso, MD, an interventional cardiologist with NorthShore Medical Group in Bannockburn, Ill., and cochair of the writing panel. “You need to do risk adjustment to measure quality of care,” and the robust database that now exists has begun to make this possible, said Dr. Tommaso, who neither performs TAVR procedures nor participates on a TAVR team. Statistical analyses based on this substantial and always-expanding database of TAVR patients now allows for risk-adjusted assessment of in hospital and 30-day mortality, and risk-adjusted evaluation of 1-year mortality and quality-of-life outcomes are expected within the next couple of years.

“We’re still not yet at the point of having good, risk-adjusted models” for all these measures, but our hope is that in the next 2-7 years we can move completely to quality measures, as has already been done for percutaneous coronary interventions” and away from procedure volume, which currently serves as a surrogate marker for a TAVR program’s competence.

The new document continues to call for TAVR programs to average at least 50 TAVR procedures a year or at least 100 every 2 years, but primarily to insure that each TAVR program can generate enough data about its performance to produce statistically reliable numbers.

“The volume floors are only there because you can’t measure quality without volume,” said Dr. Bavaria. “It’s impossible to measure quality without a certain procedure volume.”

Dr. Bavaria stressed, however, that the goal of the new document is not to limit TAVR programs based on their procedure volume, especially because another goal of the document is to ensure reasonable geographic access to TAVR for U.S. patients. “This document does not advocate for any program to shut down,” he declared. On top of that, “we have no problem with new programs,” although the document noted that “the major threat to low volume sites growing and achieving higher levels of experience is the opening of additional sites in the same geographic region.”

In 2017, 204 of the 525 sites (39%) performing TAVR at that time were performing fewer than 50 procedures annually, the document said, but added that many TAVR centers now operate in what are predominantly rural regions “and it is important that they remain active if they can document acceptable quality even if they should fall below volume thresholds to maintain patient access to care.”

Dr. Tommaso said that perhaps a TAVR center in Alaska, for example, might not meet the 50 cases/year standard, “but I don’t think anyone would worry if the volume was low because we’re serving patients in Alaska.” Currently, 84% of TAVR centers that have been operating for more than 2 years meet the 50 procedures/year threshold, he added. And TAVR centers now operate in 49 of the 50 states, with only Wyoming lacking a TAVR facility within its borders. Despite this, use of TAVR among Wyoming residents is comparable to the rate in Illinois, Dr. Bavaria said.

Both cochairs also highlighted that, with TAVR now approved for patients at moderate risk for aortic-valve surgery, the number of patients who are TAVR candidates has grown, and it’s possible that pending trial results will soon broaden TAVR’s availability to low-risk patients, a step that would greatly further expand the potential patient pool for the procedure.

The revised recommendations and requirements will make it “a little easier to start a new program, except now, for the first time, you need to start with an operator who is already experienced with TAVR,” noted Dr. Bavaria. “The TAVR technology is now mature enough that it’s inappropriate to have learning-curve mortality.” But aside from this the new standards lower the bar a bit for a center’s volume of percutaneous coronary interventions and surgical aortic valve replacements. The revision also maintains that an examination by and consultation with a single cardiac surgeon by a prospective TAVR patient is adequate, similar to the 2012 document, although the Center for Medicare & Medicaid Services mandated in its coverage decision that prospective TAVR patients consult with two cardiac surgeons, the so-called “two-surgeon rule.” If CMS eliminated the two-surgeon rule it would “streamline” the process that patients go through when being assessed for TAVR, Dr. Tommaso observed, and both he and Dr. Bavaria expressed hope that the new document might prompt CMS to reconsider this guidance.

“We felt that two surgeons weren’t needed,” but the document specifies that both the surgeon and the cardiologist whom a prospective patient consults before finalizing plans for the intervention should both be members of the multidisciplinary team that performs the procedure. Until now, these clinicians weren’t specified as necessarily members of the TAVR team, Dr. Bavaria said.

One additional new element in the revised document is specification of shared decision making as the mechanism patients should go through when considering TAVR relative to their other management options, Dr. Tommaso said.Dr. Bavaria and Dr. Tommaso had no disclosures.

[email protected]
 

SOURCE: Bavaria JE et al. JACC. 2018 Jul18. doi:10.1016/j.jacc.2018.07.002.
 

Rituximab should be included in first-line chemotherapy when treating mantle cell lymphoma, according to a new management guideline from the British Society for Haematology.

The best outcome data is for the R-CHOP regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by maintenance treatment with rituximab, wrote Pamela McKay, MD, of Beatson West of Scotland Cancer Centre in Glasgow, and her colleagues. The report was published in the British Journal of Haematology. But the combination of rituximab and bendamustine is also effective and a more favorable safety profile, according to the guideline. Single agent rituximab is not recommended.

At relapse, the guideline calls on physicians to take an individualized approach based on age, comorbidities, performance status, and response to prior therapy. Some options to consider include ibrutinib as a single agent or rituximab plus chemotherapy. The authors cautioned that there is little evidence to support maintenance rituximab after relapse treatment.

The guideline also explores the role of autologous stem cell transplantation (ASCT) and allogeneic SCT (alloSCT). The authors recommend that ASCT be considered as consolidation of first-line therapy for patients who are fit for intensive therapy. AlloSCT is a viable option in second remission among fit patients who have an appropriate donor and it may also be effective as a rescue therapy for patients who relapse after ASCT. But alloSCT is appropriate only as a first-line therapy for high-risk patients and is best used as part of a clinical trial, according to the recommendations.

The British Society of Haematology previously issued guidance on mantle cell lymphoma in 2012, but the updated document includes new drug therapeutic options and transplant data. The guideline includes a therapeutic algorithm to assist physicians in choosing first-line therapy, options after first relapse, and management in the case of higher relapse.

The guideline authors reported having no conflicts of interest.

[email protected]

SOURCE: McKay P et al. Br J Haematol. 2018 Jul;182(1):46-62.

Rituximab should be included in first-line chemotherapy when treating mantle cell lymphoma, according to a new management guideline from the British Society for Haematology.

The best outcome data is for the R-CHOP regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by maintenance treatment with rituximab, wrote Pamela McKay, MD, of Beatson West of Scotland Cancer Centre in Glasgow, and her colleagues. The report was published in the British Journal of Haematology. But the combination of rituximab and bendamustine is also effective and a more favorable safety profile, according to the guideline. Single agent rituximab is not recommended.

At relapse, the guideline calls on physicians to take an individualized approach based on age, comorbidities, performance status, and response to prior therapy. Some options to consider include ibrutinib as a single agent or rituximab plus chemotherapy. The authors cautioned that there is little evidence to support maintenance rituximab after relapse treatment.

The guideline also explores the role of autologous stem cell transplantation (ASCT) and allogeneic SCT (alloSCT). The authors recommend that ASCT be considered as consolidation of first-line therapy for patients who are fit for intensive therapy. AlloSCT is a viable option in second remission among fit patients who have an appropriate donor and it may also be effective as a rescue therapy for patients who relapse after ASCT. But alloSCT is appropriate only as a first-line therapy for high-risk patients and is best used as part of a clinical trial, according to the recommendations.

The British Society of Haematology previously issued guidance on mantle cell lymphoma in 2012, but the updated document includes new drug therapeutic options and transplant data. The guideline includes a therapeutic algorithm to assist physicians in choosing first-line therapy, options after first relapse, and management in the case of higher relapse.

The guideline authors reported having no conflicts of interest.

[email protected]

SOURCE: McKay P et al. Br J Haematol. 2018 Jul;182(1):46-62.

Rituximab should be included in first-line chemotherapy when treating mantle cell lymphoma, according to a new management guideline from the British Society for Haematology.

The best outcome data is for the R-CHOP regimen (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) followed by maintenance treatment with rituximab, wrote Pamela McKay, MD, of Beatson West of Scotland Cancer Centre in Glasgow, and her colleagues. The report was published in the British Journal of Haematology. But the combination of rituximab and bendamustine is also effective and a more favorable safety profile, according to the guideline. Single agent rituximab is not recommended.

At relapse, the guideline calls on physicians to take an individualized approach based on age, comorbidities, performance status, and response to prior therapy. Some options to consider include ibrutinib as a single agent or rituximab plus chemotherapy. The authors cautioned that there is little evidence to support maintenance rituximab after relapse treatment.

The guideline also explores the role of autologous stem cell transplantation (ASCT) and allogeneic SCT (alloSCT). The authors recommend that ASCT be considered as consolidation of first-line therapy for patients who are fit for intensive therapy. AlloSCT is a viable option in second remission among fit patients who have an appropriate donor and it may also be effective as a rescue therapy for patients who relapse after ASCT. But alloSCT is appropriate only as a first-line therapy for high-risk patients and is best used as part of a clinical trial, according to the recommendations.

The British Society of Haematology previously issued guidance on mantle cell lymphoma in 2012, but the updated document includes new drug therapeutic options and transplant data. The guideline includes a therapeutic algorithm to assist physicians in choosing first-line therapy, options after first relapse, and management in the case of higher relapse.

The guideline authors reported having no conflicts of interest.

[email protected]

SOURCE: McKay P et al. Br J Haematol. 2018 Jul;182(1):46-62.

The Agency for Healthcare Research and Quality has announced that after July 16, 2018, its National Guideline Clearinghouse (NGC) website (guideline.gov) will no longer be available because its federal funding will be discontinued. According to the NGC website, its mission is to provide “an accessible mechanism for obtaining objective, detailed information on clinical practice guidelines and to further their dissemination, implementation, and use.”

Its services, all free to use, included providing summaries of each guideline, side-by-side comparisons of two or more guidelines, and syntheses of guidelines covering similar topics, highlighting areas of similarity and difference.

Update, July 17, 2018: Now that the guidelines are no longer available on the government site, ECRI Institute, the independent nonprofit that developed and maintained the National Guidelines Clearinghouse since its inception 20 years ago, “announced plans to continue providing this critical service to the healthcare community.” The ECRI Institute stated that they will launch an interim website this Fall “with many additional features planned for the near future.” Participating guideline developers will be able to access and contribute to the website free of charge, according to the company, while others will be charged a fee. In addition, as a temporary stop-gap, Fred Trotter, founder and CTO of CareSet Systems, a Medicare data use site, voluntarily cloned the complete guidelines before the government site shut down and made them available for public use here: https://github.com/CareSet/AHRQ_search_clone.

[email protected]

The Agency for Healthcare Research and Quality has announced that after July 16, 2018, its National Guideline Clearinghouse (NGC) website (guideline.gov) will no longer be available because its federal funding will be discontinued. According to the NGC website, its mission is to provide “an accessible mechanism for obtaining objective, detailed information on clinical practice guidelines and to further their dissemination, implementation, and use.”

Its services, all free to use, included providing summaries of each guideline, side-by-side comparisons of two or more guidelines, and syntheses of guidelines covering similar topics, highlighting areas of similarity and difference.

Update, July 17, 2018: Now that the guidelines are no longer available on the government site, ECRI Institute, the independent nonprofit that developed and maintained the National Guidelines Clearinghouse since its inception 20 years ago, “announced plans to continue providing this critical service to the healthcare community.” The ECRI Institute stated that they will launch an interim website this Fall “with many additional features planned for the near future.” Participating guideline developers will be able to access and contribute to the website free of charge, according to the company, while others will be charged a fee. In addition, as a temporary stop-gap, Fred Trotter, founder and CTO of CareSet Systems, a Medicare data use site, voluntarily cloned the complete guidelines before the government site shut down and made them available for public use here: https://github.com/CareSet/AHRQ_search_clone.

[email protected]

The Agency for Healthcare Research and Quality has announced that after July 16, 2018, its National Guideline Clearinghouse (NGC) website (guideline.gov) will no longer be available because its federal funding will be discontinued. According to the NGC website, its mission is to provide “an accessible mechanism for obtaining objective, detailed information on clinical practice guidelines and to further their dissemination, implementation, and use.”

Its services, all free to use, included providing summaries of each guideline, side-by-side comparisons of two or more guidelines, and syntheses of guidelines covering similar topics, highlighting areas of similarity and difference.

Update, July 17, 2018: Now that the guidelines are no longer available on the government site, ECRI Institute, the independent nonprofit that developed and maintained the National Guidelines Clearinghouse since its inception 20 years ago, “announced plans to continue providing this critical service to the healthcare community.” The ECRI Institute stated that they will launch an interim website this Fall “with many additional features planned for the near future.” Participating guideline developers will be able to access and contribute to the website free of charge, according to the company, while others will be charged a fee. In addition, as a temporary stop-gap, Fred Trotter, founder and CTO of CareSet Systems, a Medicare data use site, voluntarily cloned the complete guidelines before the government site shut down and made them available for public use here: https://github.com/CareSet/AHRQ_search_clone.

[email protected]