Guidelines

Psoriasis management in children involves attention not only to treatment of the physical condition but also psychosocial wellness and quality of life, according to a new clinical guideline on the management of pediatric psoriasis from the American Academy of Dermatology and the National Psoriasis Foundation.

Psoriasis affects approximately 1% of children, either alone or associated with comorbid conditions such as psoriatic arthritis (PsA), wrote Alan Menter, MD, of Baylor University Medical Center, Dallas, and coauthors of the guideline.

In the guideline, published in the Journal of the American Academy of Dermatology, the multidisciplinary work group identified screening tools to measure disease severity, strategies for management of comorbidities, and the safety and effectiveness of topical, systemic, and phototherapy treatments.

To assess disease severity, the work group recommended not only the use of body surface area (BSA), similar to measurement of severity in adults, but also the use of the Children’s Dermatology Life Quality Index, a 10-question quality of life survey, as BSA alone does not account for the potential negative impact of the disease on quality of life in terms of physical, emotional, social, and psychological function.

“For example, a child with psoriasis limited to the face or the entire scalp does not have severe disease based on BSA definitions, but if this involvement causes shame, social withdrawal, or bullying, it satisfies criteria for severe disease based on impact beyond the skin,” they said.

The work group stated that a variety of conditions may trigger or exacerbate psoriasis in children, including infections, cutaneous trauma, or physiological, emotional, and environmental stressors.

The majority of children with PsA develop joint inflammation before skin disease, the work group wrote. In addition, children with psoriasis are at increased risk for rheumatoid arthritis, so clinicians may need to distinguish between a combination of psoriasis and musculoskeletal issues and cases of either psoriatic or rheumatoid arthritis in young patients.

The cardiovascular risk factors associated with metabolic syndrome are greater in children with psoriasis, compared with children without psoriasis, the work group noted. In addition, pediatric psoriasis patients have a higher prevalence of obesity than children without psoriasis, and they recommended that children with psoriasis be monitored for the development of obesity, and that obese children with psoriasis should be referred for weight management.

The work group noted that data are insufficient in children to support the link between psoriasis and cardiovascular disease that has been documented in adults with psoriasis. However, “patients with pediatric psoriasis should have American Academy of Pediatrics (AAP)–recommended age-related cardiovascular screening regardless of the presence of signs or symptoms,” they said.

The guideline also recommends screening for dyslipidemia and hypertension according to AAP guidelines and educating pediatric psoriasis patients about the risk of diabetes and regularly screening for diabetes and insulin resistance in those who are obese. Overweight children with psoriasis may be screened at the provider’s discretion, they wrote. Patients with signs of inflammatory bowel disease, which also is associated with psoriasis in adults, should be considered for referral to a gastroenterologist, they noted.

Children with psoriasis should be screened regularly for mental health conditions regardless of age, and they should be asked about substance abuse, according to the guideline, and those with concerns should be referred for additional assessment and management.

The guideline divides treatment of psoriasis in children into three categories: topical, phototherapy and photochemotherapy, and systemic treatments (nonbiologic or biologic).

For topicals, the guideline recommendations include corticosteroids as an off-label therapy, as well as ultra-high-potency topical corticosteroids as monotherapy. Overall, “selection of a therapeutic routine (potency, delivery vehicle, frequency of application) should take into account sites of involvement, type and thickness of psoriasis, age of the patient, total BSA of application, anticipated occlusion, and disease acuity, among other patient-, disease-, and drug-related factors,” the authors wrote. Other topical options included in the recommendations: calcineurin inhibitors, topical vitamin D analogues, tazarotene (off label), anthralin, and coal tar.

Phototherapy has a history of use in psoriasis treatment and remains part of the current recommendations, although data in children are limited, and data on the use of phototherapy for pustular psoriasis in children are insufficient to make specific treatment and dosing recommendations, the work group noted. The researchers also noted that in-office phototherapy may not be feasible for many patients, but that in-home ultraviolet light equipment or natural sunlight in moderation could be recommended as an alternative.

The use of systemic, nonbiologic treatments for pediatric psoriasis should be “based on baseline severity of disease, subtype of psoriasis, speed of disease progression, lack of response to more conservative therapies such as topical agents and phototherapy (when appropriate), impaired physical or psychological functioning or [quality of life] due to disease extent, and the presence of comorbidities such as PsA,” the workgroup said.

Options for systemic treatment include methotrexate, cyclosporine (notably for pustular as well as plaque and erythrodermic psoriasis), and systemic retinoids. In addition, fumaric acid esters may be an option for children with moderate to severe psoriasis, with recommended clinical and laboratory monitoring.

The increasing safety and efficacy data on biologics in pediatric psoriasis patients support their consideration among first-line systemic treatments, the work group suggested. “Etanercept and ustekinumab are now [Food and Drug Administration] approved for patients with psoriasis 4 years and older and 12 years and older, respectively,” they said, and infliximab and adalimumab have been used off label in children.

The work group concluded that research and knowledge gaps about pediatric psoriasis persist and include mechanism of disease onset, development of comorbidities, and identification of ideal dosing for various treatments.

Finally, the work group emphasized the importance of collaboration between dermatologists and primary care providers for managing psoriasis in children, as well as the importance of patient education.

“Dermatologists should be mindful of the unique aspects of the emotional development of children and the social dynamics of having a visible difference,” they wrote. “Shared decision making with the patient (if age appropriate) and the caregivers is a useful approach, particularly as related to the use of off-label medications to treat severe disease,” they said.

“This is the first time that pediatric psoriasis has been discussed as an independent topic within the guideline,” said one of the guideline authors, Dawn M.R. Davis, MD, of the Mayo Clinic, Rochester, Minn., in an interview. “Children have unique physiology and psychosocial aspects to their care relative to adults. In addition, psoriasis has some clinical manifestations that are oftentimes distinctly seen in children,” she commented. “Creation of a guideline specific to children allows us to summarize the similarities and differences of disease presentation and management. It also allows an opportunity to clarify what research data (especially therapeutics) have been studied in children and their uses, safety profiles, and dosing,” she noted.

Psoriasis can be a psychosocially debilitating disease, she emphasized. “In children, for example, isolated or prominent facial involvement is common, which can be embarrassing and impact relationships.”

The take-home message for clinicians, Dr. Davis said, is to keep in mind the multisystemic nature of psoriasis. “It is not limited to the skin,” she said. “Treating a patient with psoriasis necessitates practicing whole-person care” and considering the multiple comorbidities that impact quality of life and overall health in children, as well as adults with psoriasis, she commented. “Dermatologists can empower patients and their caregivers by educating them on the multifocal, complex nature of the disease.” She added, “We have much to learn regarding psoriasis in the pediatric population. More research into therapeutics, topical and systemic, is necessary to optimize patient care.”

The guideline was based on studies published in the PubMed and MEDLINE databases from January 2011 through December 31, 2017.

Dr. Menter and Craig A. Elmets, MD, professor of dermatology, at the University of Alabama, Birmingham, were cochairs of the work group. The pediatric guideline is the latest in a multipart series of AAD-NPF guidelines on psoriasis being published this year in the Journal of the American Academy of Dermatology.

Many of the guideline authors, including lead author Dr. Menter, disclosed relationships with multiple companies; however, a minimum 51% of workgroup members had no relevant conflicts of interest in accordance with AAD policy. There was no funding source. Dr. Davis disclosed serving as an investigator for Regeneron, with no compensation.

SOURCE: Menter et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.08.049.

Psoriasis management in children involves attention not only to treatment of the physical condition but also psychosocial wellness and quality of life, according to a new clinical guideline on the management of pediatric psoriasis from the American Academy of Dermatology and the National Psoriasis Foundation.

Psoriasis affects approximately 1% of children, either alone or associated with comorbid conditions such as psoriatic arthritis (PsA), wrote Alan Menter, MD, of Baylor University Medical Center, Dallas, and coauthors of the guideline.

In the guideline, published in the Journal of the American Academy of Dermatology, the multidisciplinary work group identified screening tools to measure disease severity, strategies for management of comorbidities, and the safety and effectiveness of topical, systemic, and phototherapy treatments.

To assess disease severity, the work group recommended not only the use of body surface area (BSA), similar to measurement of severity in adults, but also the use of the Children’s Dermatology Life Quality Index, a 10-question quality of life survey, as BSA alone does not account for the potential negative impact of the disease on quality of life in terms of physical, emotional, social, and psychological function.

“For example, a child with psoriasis limited to the face or the entire scalp does not have severe disease based on BSA definitions, but if this involvement causes shame, social withdrawal, or bullying, it satisfies criteria for severe disease based on impact beyond the skin,” they said.

The work group stated that a variety of conditions may trigger or exacerbate psoriasis in children, including infections, cutaneous trauma, or physiological, emotional, and environmental stressors.

The majority of children with PsA develop joint inflammation before skin disease, the work group wrote. In addition, children with psoriasis are at increased risk for rheumatoid arthritis, so clinicians may need to distinguish between a combination of psoriasis and musculoskeletal issues and cases of either psoriatic or rheumatoid arthritis in young patients.

The cardiovascular risk factors associated with metabolic syndrome are greater in children with psoriasis, compared with children without psoriasis, the work group noted. In addition, pediatric psoriasis patients have a higher prevalence of obesity than children without psoriasis, and they recommended that children with psoriasis be monitored for the development of obesity, and that obese children with psoriasis should be referred for weight management.

The work group noted that data are insufficient in children to support the link between psoriasis and cardiovascular disease that has been documented in adults with psoriasis. However, “patients with pediatric psoriasis should have American Academy of Pediatrics (AAP)–recommended age-related cardiovascular screening regardless of the presence of signs or symptoms,” they said.

The guideline also recommends screening for dyslipidemia and hypertension according to AAP guidelines and educating pediatric psoriasis patients about the risk of diabetes and regularly screening for diabetes and insulin resistance in those who are obese. Overweight children with psoriasis may be screened at the provider’s discretion, they wrote. Patients with signs of inflammatory bowel disease, which also is associated with psoriasis in adults, should be considered for referral to a gastroenterologist, they noted.

Children with psoriasis should be screened regularly for mental health conditions regardless of age, and they should be asked about substance abuse, according to the guideline, and those with concerns should be referred for additional assessment and management.

The guideline divides treatment of psoriasis in children into three categories: topical, phototherapy and photochemotherapy, and systemic treatments (nonbiologic or biologic).

For topicals, the guideline recommendations include corticosteroids as an off-label therapy, as well as ultra-high-potency topical corticosteroids as monotherapy. Overall, “selection of a therapeutic routine (potency, delivery vehicle, frequency of application) should take into account sites of involvement, type and thickness of psoriasis, age of the patient, total BSA of application, anticipated occlusion, and disease acuity, among other patient-, disease-, and drug-related factors,” the authors wrote. Other topical options included in the recommendations: calcineurin inhibitors, topical vitamin D analogues, tazarotene (off label), anthralin, and coal tar.

Phototherapy has a history of use in psoriasis treatment and remains part of the current recommendations, although data in children are limited, and data on the use of phototherapy for pustular psoriasis in children are insufficient to make specific treatment and dosing recommendations, the work group noted. The researchers also noted that in-office phototherapy may not be feasible for many patients, but that in-home ultraviolet light equipment or natural sunlight in moderation could be recommended as an alternative.

The use of systemic, nonbiologic treatments for pediatric psoriasis should be “based on baseline severity of disease, subtype of psoriasis, speed of disease progression, lack of response to more conservative therapies such as topical agents and phototherapy (when appropriate), impaired physical or psychological functioning or [quality of life] due to disease extent, and the presence of comorbidities such as PsA,” the workgroup said.

Options for systemic treatment include methotrexate, cyclosporine (notably for pustular as well as plaque and erythrodermic psoriasis), and systemic retinoids. In addition, fumaric acid esters may be an option for children with moderate to severe psoriasis, with recommended clinical and laboratory monitoring.

The increasing safety and efficacy data on biologics in pediatric psoriasis patients support their consideration among first-line systemic treatments, the work group suggested. “Etanercept and ustekinumab are now [Food and Drug Administration] approved for patients with psoriasis 4 years and older and 12 years and older, respectively,” they said, and infliximab and adalimumab have been used off label in children.

The work group concluded that research and knowledge gaps about pediatric psoriasis persist and include mechanism of disease onset, development of comorbidities, and identification of ideal dosing for various treatments.

Finally, the work group emphasized the importance of collaboration between dermatologists and primary care providers for managing psoriasis in children, as well as the importance of patient education.

“Dermatologists should be mindful of the unique aspects of the emotional development of children and the social dynamics of having a visible difference,” they wrote. “Shared decision making with the patient (if age appropriate) and the caregivers is a useful approach, particularly as related to the use of off-label medications to treat severe disease,” they said.

“This is the first time that pediatric psoriasis has been discussed as an independent topic within the guideline,” said one of the guideline authors, Dawn M.R. Davis, MD, of the Mayo Clinic, Rochester, Minn., in an interview. “Children have unique physiology and psychosocial aspects to their care relative to adults. In addition, psoriasis has some clinical manifestations that are oftentimes distinctly seen in children,” she commented. “Creation of a guideline specific to children allows us to summarize the similarities and differences of disease presentation and management. It also allows an opportunity to clarify what research data (especially therapeutics) have been studied in children and their uses, safety profiles, and dosing,” she noted.

Psoriasis can be a psychosocially debilitating disease, she emphasized. “In children, for example, isolated or prominent facial involvement is common, which can be embarrassing and impact relationships.”

The take-home message for clinicians, Dr. Davis said, is to keep in mind the multisystemic nature of psoriasis. “It is not limited to the skin,” she said. “Treating a patient with psoriasis necessitates practicing whole-person care” and considering the multiple comorbidities that impact quality of life and overall health in children, as well as adults with psoriasis, she commented. “Dermatologists can empower patients and their caregivers by educating them on the multifocal, complex nature of the disease.” She added, “We have much to learn regarding psoriasis in the pediatric population. More research into therapeutics, topical and systemic, is necessary to optimize patient care.”

The guideline was based on studies published in the PubMed and MEDLINE databases from January 2011 through December 31, 2017.

Dr. Menter and Craig A. Elmets, MD, professor of dermatology, at the University of Alabama, Birmingham, were cochairs of the work group. The pediatric guideline is the latest in a multipart series of AAD-NPF guidelines on psoriasis being published this year in the Journal of the American Academy of Dermatology.

Many of the guideline authors, including lead author Dr. Menter, disclosed relationships with multiple companies; however, a minimum 51% of workgroup members had no relevant conflicts of interest in accordance with AAD policy. There was no funding source. Dr. Davis disclosed serving as an investigator for Regeneron, with no compensation.

SOURCE: Menter et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.08.049.

Psoriasis management in children involves attention not only to treatment of the physical condition but also psychosocial wellness and quality of life, according to a new clinical guideline on the management of pediatric psoriasis from the American Academy of Dermatology and the National Psoriasis Foundation.

Psoriasis affects approximately 1% of children, either alone or associated with comorbid conditions such as psoriatic arthritis (PsA), wrote Alan Menter, MD, of Baylor University Medical Center, Dallas, and coauthors of the guideline.

In the guideline, published in the Journal of the American Academy of Dermatology, the multidisciplinary work group identified screening tools to measure disease severity, strategies for management of comorbidities, and the safety and effectiveness of topical, systemic, and phototherapy treatments.

To assess disease severity, the work group recommended not only the use of body surface area (BSA), similar to measurement of severity in adults, but also the use of the Children’s Dermatology Life Quality Index, a 10-question quality of life survey, as BSA alone does not account for the potential negative impact of the disease on quality of life in terms of physical, emotional, social, and psychological function.

“For example, a child with psoriasis limited to the face or the entire scalp does not have severe disease based on BSA definitions, but if this involvement causes shame, social withdrawal, or bullying, it satisfies criteria for severe disease based on impact beyond the skin,” they said.

The work group stated that a variety of conditions may trigger or exacerbate psoriasis in children, including infections, cutaneous trauma, or physiological, emotional, and environmental stressors.

The majority of children with PsA develop joint inflammation before skin disease, the work group wrote. In addition, children with psoriasis are at increased risk for rheumatoid arthritis, so clinicians may need to distinguish between a combination of psoriasis and musculoskeletal issues and cases of either psoriatic or rheumatoid arthritis in young patients.

The cardiovascular risk factors associated with metabolic syndrome are greater in children with psoriasis, compared with children without psoriasis, the work group noted. In addition, pediatric psoriasis patients have a higher prevalence of obesity than children without psoriasis, and they recommended that children with psoriasis be monitored for the development of obesity, and that obese children with psoriasis should be referred for weight management.

The work group noted that data are insufficient in children to support the link between psoriasis and cardiovascular disease that has been documented in adults with psoriasis. However, “patients with pediatric psoriasis should have American Academy of Pediatrics (AAP)–recommended age-related cardiovascular screening regardless of the presence of signs or symptoms,” they said.

The guideline also recommends screening for dyslipidemia and hypertension according to AAP guidelines and educating pediatric psoriasis patients about the risk of diabetes and regularly screening for diabetes and insulin resistance in those who are obese. Overweight children with psoriasis may be screened at the provider’s discretion, they wrote. Patients with signs of inflammatory bowel disease, which also is associated with psoriasis in adults, should be considered for referral to a gastroenterologist, they noted.

Children with psoriasis should be screened regularly for mental health conditions regardless of age, and they should be asked about substance abuse, according to the guideline, and those with concerns should be referred for additional assessment and management.

The guideline divides treatment of psoriasis in children into three categories: topical, phototherapy and photochemotherapy, and systemic treatments (nonbiologic or biologic).

For topicals, the guideline recommendations include corticosteroids as an off-label therapy, as well as ultra-high-potency topical corticosteroids as monotherapy. Overall, “selection of a therapeutic routine (potency, delivery vehicle, frequency of application) should take into account sites of involvement, type and thickness of psoriasis, age of the patient, total BSA of application, anticipated occlusion, and disease acuity, among other patient-, disease-, and drug-related factors,” the authors wrote. Other topical options included in the recommendations: calcineurin inhibitors, topical vitamin D analogues, tazarotene (off label), anthralin, and coal tar.

Phototherapy has a history of use in psoriasis treatment and remains part of the current recommendations, although data in children are limited, and data on the use of phototherapy for pustular psoriasis in children are insufficient to make specific treatment and dosing recommendations, the work group noted. The researchers also noted that in-office phototherapy may not be feasible for many patients, but that in-home ultraviolet light equipment or natural sunlight in moderation could be recommended as an alternative.

The use of systemic, nonbiologic treatments for pediatric psoriasis should be “based on baseline severity of disease, subtype of psoriasis, speed of disease progression, lack of response to more conservative therapies such as topical agents and phototherapy (when appropriate), impaired physical or psychological functioning or [quality of life] due to disease extent, and the presence of comorbidities such as PsA,” the workgroup said.

Options for systemic treatment include methotrexate, cyclosporine (notably for pustular as well as plaque and erythrodermic psoriasis), and systemic retinoids. In addition, fumaric acid esters may be an option for children with moderate to severe psoriasis, with recommended clinical and laboratory monitoring.

The increasing safety and efficacy data on biologics in pediatric psoriasis patients support their consideration among first-line systemic treatments, the work group suggested. “Etanercept and ustekinumab are now [Food and Drug Administration] approved for patients with psoriasis 4 years and older and 12 years and older, respectively,” they said, and infliximab and adalimumab have been used off label in children.

The work group concluded that research and knowledge gaps about pediatric psoriasis persist and include mechanism of disease onset, development of comorbidities, and identification of ideal dosing for various treatments.

Finally, the work group emphasized the importance of collaboration between dermatologists and primary care providers for managing psoriasis in children, as well as the importance of patient education.

“Dermatologists should be mindful of the unique aspects of the emotional development of children and the social dynamics of having a visible difference,” they wrote. “Shared decision making with the patient (if age appropriate) and the caregivers is a useful approach, particularly as related to the use of off-label medications to treat severe disease,” they said.

“This is the first time that pediatric psoriasis has been discussed as an independent topic within the guideline,” said one of the guideline authors, Dawn M.R. Davis, MD, of the Mayo Clinic, Rochester, Minn., in an interview. “Children have unique physiology and psychosocial aspects to their care relative to adults. In addition, psoriasis has some clinical manifestations that are oftentimes distinctly seen in children,” she commented. “Creation of a guideline specific to children allows us to summarize the similarities and differences of disease presentation and management. It also allows an opportunity to clarify what research data (especially therapeutics) have been studied in children and their uses, safety profiles, and dosing,” she noted.

Psoriasis can be a psychosocially debilitating disease, she emphasized. “In children, for example, isolated or prominent facial involvement is common, which can be embarrassing and impact relationships.”

The take-home message for clinicians, Dr. Davis said, is to keep in mind the multisystemic nature of psoriasis. “It is not limited to the skin,” she said. “Treating a patient with psoriasis necessitates practicing whole-person care” and considering the multiple comorbidities that impact quality of life and overall health in children, as well as adults with psoriasis, she commented. “Dermatologists can empower patients and their caregivers by educating them on the multifocal, complex nature of the disease.” She added, “We have much to learn regarding psoriasis in the pediatric population. More research into therapeutics, topical and systemic, is necessary to optimize patient care.”

The guideline was based on studies published in the PubMed and MEDLINE databases from January 2011 through December 31, 2017.

Dr. Menter and Craig A. Elmets, MD, professor of dermatology, at the University of Alabama, Birmingham, were cochairs of the work group. The pediatric guideline is the latest in a multipart series of AAD-NPF guidelines on psoriasis being published this year in the Journal of the American Academy of Dermatology.

Many of the guideline authors, including lead author Dr. Menter, disclosed relationships with multiple companies; however, a minimum 51% of workgroup members had no relevant conflicts of interest in accordance with AAD policy. There was no funding source. Dr. Davis disclosed serving as an investigator for Regeneron, with no compensation.

SOURCE: Menter et al. J Am Acad Dermatol. 2019. doi: 10.1016/j.jaad.2019.08.049.

The European League Against Rheumatism has released its first recommendations for the management of Sjögren’s syndrome with topical and systemic treatments.

First author Manuel Ramos-Casals, MD, PhD, of Hospital Clinic de Barcelona Institut Clinic de Medicina i Dermatologia and colleagues on the multinational, multispecialty EULAR Sjögren Syndrome Task Force Group said the EULAR recommendations “synthesize current thinking” of management for Sjögren’s syndrome, which is complicated by individualized treatment that does not address the systemic disease and for which therapeutic decisions are often made based on expert opinion and personal experience because of a lack of data.

“Sjögren’s syndrome is generally treated through symptom management,” noted Sara McCoy, MD, who is director of the University of Wisconsin Health Sjögren’s Syndrome Clinic and was not involved in the recommendations, which were published in Annals of the Rheumatic Diseases. “Although we have measures to address these symptoms, we do not have any approved therapy that ameliorates the driving cause.”

There is limited high-quality evidence for many of the therapies discussed in the recommendations: In total, 9 randomized controlled trials, 18 prospective studies, and 5 case-control studies were included as evidence in the recommendations, and many involved a small number of patients.

The first overarching recommendation says that patients with Sjögren’s syndrome should be managed at centers of expertise using a multidisciplinary approach, the authors wrote. Two other overarching recommendations focus on how to manage certain patient cases. In cases of dryness, first-line therapy should include topical therapies for symptomatic relief, while clinicians should consider systemic therapies for patients with active systemic disease. All three overarching recommendations had a high level of agreement among task force members.

The task force also offered 12 specific recommendations on disease management, which take an “algorithmic approach” to Sjögren’s syndrome management that is guided by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), Dr. McCoy said in an interview.

“The EULAR recommendations structure a clear approach to treatment of Sjögren’s manifestations, ranging from oral and ocular sicca management, to treatment of uncommon but severe systemic involvement of Sjögren’s,” she said.

Before treating patients for oral dryness symptoms, clinicians should evaluate salivary function at baseline using unstimulated whole salivary flows. First-line therapeutic approaches for oral dryness can include nonpharmacologic stimulation in cases of mild salivary gland dysfunction, pharmacologic stimulation in cases of moderate dysfunction, and substitution of saliva in cases of severe dysfunction, the authors said.

Ocular dryness should be assessed using ocular staining score followed by ocular surface–disease index, and once identified, it can be managed with artificial tears and ocular gels or ointments as first-line therapy. Topical immunosuppressive-containing drops and autologous serum eye drops are options for more severe or refractory ocular dryness.

Patients who have fatigue or pain associated with Sjögren’s syndrome should have their fatigue or pain scored with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), and any concomitant disease should also be evaluated. Clinicians should consider acetaminophen and NSAIDs for treatment of acute musculoskeletal pain and other pain-modifying agents, such as hydroxychloroquine in cases of articular pain, despite a lack of evidence showing its efficacy in trials.

For systemic disease, the task force advised matching treatment to the organ(s) involved and using the ESSDAI to evaluate disease severity., They said that “patients presenting with at least moderate activity in one clinical domain, or with a global moderate disease activity score” of 5 or higher can be considered for systemic therapy.

Although many clinicians use glucocorticoids (GCs) for managing Sjögren’s syndrome, there is no evidence of the treatment’s efficacy in systemic disease. The task force recommended using glucocorticoids such as methylprednisolone at the minimum dose and withdrawing use “as soon as possible” in patients with inactive disease. “Based on the potential development of chronic damage in patients with uncontrolled systemic disease, some patients may require long-term therapy with GCs, especially those with severe organ impairments,” Dr. Ramos-Casals and colleagues wrote. “In these patients, the addition of immunosuppressive agents as GC-sparing agents is justified, always weighing the potential benefits and risks.” Because of a lack of head-to-head studies of different immunosuppressive agents, the task force did not recommend one particular agent over another.

One recommendation that contained a high level of evidence was for the use of B-cell targeted therapies for patients with severe, refractory systemic disease. Efficacy of rituximab was mixed in studies totaling more than 400 patients, but generally showed a positive outcome in at least one of the following areas: global response, organ-specific response, ESSDAI reduction, and prednisone reduction. The task force recommended that rituximab “may be considered” in “patients with severe, refractory systemic disease” and may be best for those with symptoms linked to cryoglobulinemic-associated vasculitis, with the potential of using belimumab (Benlysta) as rescue therapy. While systemic organ-specific therapeutic approaches vary, the general rule should be to treat with GCs first, followed by immunosuppressive agents and biologics as second-line therapy in cases refractory to GCs, either sequentially or in combination, the authors said.

For patients with B-cell lymphoma, clinicians should use individualized treatment based on the World Health Organization 2016 histologic subtype and the stage of the disease. While some clinicians employ a “watchful waiting” approach to treating low-grade hematologic neoplasia, “the decision to treat low-grade lymphomas or not must be discussed in a multidisciplinary committee, taking into account the fact that they are linked to the disease activity and are the ultimate stage of autoimmune B-cell activation,” the authors wrote.

The task force also defined a number of future research agenda goals for Sjögren’s syndrome treatment management, including developing personalized therapeutic approaches, finding predictors of biological response to agents used in treatment, and identifying biomarkers of poor outcomes.

In addition, EULAR acknowledged some research gaps exist in the guidelines for particular symptoms of Sjögren’s syndrome, such as in the case of fatigue. “The EULAR recommendations mention the common association of fatigue with Sjögren’s syndrome, though acknowledge that fatigue is more commonly seen in the same demographic cohort as Sjögren’s,” Dr. McCoy said. “Aside from exercise, there remains little available to address this common and burdensome symptom amongst Sjögren’s patients. Overall, this is a pertinent gap in knowledge in our Sjögren’s patients.”

The Sjögren’s syndrome recommendations were funded by EULAR. Many task force members reported relationships with industry in the form of advisory board and speaker’s bureau memberships, consultancies, and grants. Dr. McCoy reported serving on a data monitoring committee for Bristol-Myers Squibb unrelated to the data in the EULAR recommendations.

SOURCE: Ramos-Casals M et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216114

The European League Against Rheumatism has released its first recommendations for the management of Sjögren’s syndrome with topical and systemic treatments.

First author Manuel Ramos-Casals, MD, PhD, of Hospital Clinic de Barcelona Institut Clinic de Medicina i Dermatologia and colleagues on the multinational, multispecialty EULAR Sjögren Syndrome Task Force Group said the EULAR recommendations “synthesize current thinking” of management for Sjögren’s syndrome, which is complicated by individualized treatment that does not address the systemic disease and for which therapeutic decisions are often made based on expert opinion and personal experience because of a lack of data.

“Sjögren’s syndrome is generally treated through symptom management,” noted Sara McCoy, MD, who is director of the University of Wisconsin Health Sjögren’s Syndrome Clinic and was not involved in the recommendations, which were published in Annals of the Rheumatic Diseases. “Although we have measures to address these symptoms, we do not have any approved therapy that ameliorates the driving cause.”

There is limited high-quality evidence for many of the therapies discussed in the recommendations: In total, 9 randomized controlled trials, 18 prospective studies, and 5 case-control studies were included as evidence in the recommendations, and many involved a small number of patients.

The first overarching recommendation says that patients with Sjögren’s syndrome should be managed at centers of expertise using a multidisciplinary approach, the authors wrote. Two other overarching recommendations focus on how to manage certain patient cases. In cases of dryness, first-line therapy should include topical therapies for symptomatic relief, while clinicians should consider systemic therapies for patients with active systemic disease. All three overarching recommendations had a high level of agreement among task force members.

The task force also offered 12 specific recommendations on disease management, which take an “algorithmic approach” to Sjögren’s syndrome management that is guided by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), Dr. McCoy said in an interview.

“The EULAR recommendations structure a clear approach to treatment of Sjögren’s manifestations, ranging from oral and ocular sicca management, to treatment of uncommon but severe systemic involvement of Sjögren’s,” she said.

Before treating patients for oral dryness symptoms, clinicians should evaluate salivary function at baseline using unstimulated whole salivary flows. First-line therapeutic approaches for oral dryness can include nonpharmacologic stimulation in cases of mild salivary gland dysfunction, pharmacologic stimulation in cases of moderate dysfunction, and substitution of saliva in cases of severe dysfunction, the authors said.

Ocular dryness should be assessed using ocular staining score followed by ocular surface–disease index, and once identified, it can be managed with artificial tears and ocular gels or ointments as first-line therapy. Topical immunosuppressive-containing drops and autologous serum eye drops are options for more severe or refractory ocular dryness.

Patients who have fatigue or pain associated with Sjögren’s syndrome should have their fatigue or pain scored with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), and any concomitant disease should also be evaluated. Clinicians should consider acetaminophen and NSAIDs for treatment of acute musculoskeletal pain and other pain-modifying agents, such as hydroxychloroquine in cases of articular pain, despite a lack of evidence showing its efficacy in trials.

For systemic disease, the task force advised matching treatment to the organ(s) involved and using the ESSDAI to evaluate disease severity., They said that “patients presenting with at least moderate activity in one clinical domain, or with a global moderate disease activity score” of 5 or higher can be considered for systemic therapy.

Although many clinicians use glucocorticoids (GCs) for managing Sjögren’s syndrome, there is no evidence of the treatment’s efficacy in systemic disease. The task force recommended using glucocorticoids such as methylprednisolone at the minimum dose and withdrawing use “as soon as possible” in patients with inactive disease. “Based on the potential development of chronic damage in patients with uncontrolled systemic disease, some patients may require long-term therapy with GCs, especially those with severe organ impairments,” Dr. Ramos-Casals and colleagues wrote. “In these patients, the addition of immunosuppressive agents as GC-sparing agents is justified, always weighing the potential benefits and risks.” Because of a lack of head-to-head studies of different immunosuppressive agents, the task force did not recommend one particular agent over another.

One recommendation that contained a high level of evidence was for the use of B-cell targeted therapies for patients with severe, refractory systemic disease. Efficacy of rituximab was mixed in studies totaling more than 400 patients, but generally showed a positive outcome in at least one of the following areas: global response, organ-specific response, ESSDAI reduction, and prednisone reduction. The task force recommended that rituximab “may be considered” in “patients with severe, refractory systemic disease” and may be best for those with symptoms linked to cryoglobulinemic-associated vasculitis, with the potential of using belimumab (Benlysta) as rescue therapy. While systemic organ-specific therapeutic approaches vary, the general rule should be to treat with GCs first, followed by immunosuppressive agents and biologics as second-line therapy in cases refractory to GCs, either sequentially or in combination, the authors said.

For patients with B-cell lymphoma, clinicians should use individualized treatment based on the World Health Organization 2016 histologic subtype and the stage of the disease. While some clinicians employ a “watchful waiting” approach to treating low-grade hematologic neoplasia, “the decision to treat low-grade lymphomas or not must be discussed in a multidisciplinary committee, taking into account the fact that they are linked to the disease activity and are the ultimate stage of autoimmune B-cell activation,” the authors wrote.

The task force also defined a number of future research agenda goals for Sjögren’s syndrome treatment management, including developing personalized therapeutic approaches, finding predictors of biological response to agents used in treatment, and identifying biomarkers of poor outcomes.

In addition, EULAR acknowledged some research gaps exist in the guidelines for particular symptoms of Sjögren’s syndrome, such as in the case of fatigue. “The EULAR recommendations mention the common association of fatigue with Sjögren’s syndrome, though acknowledge that fatigue is more commonly seen in the same demographic cohort as Sjögren’s,” Dr. McCoy said. “Aside from exercise, there remains little available to address this common and burdensome symptom amongst Sjögren’s patients. Overall, this is a pertinent gap in knowledge in our Sjögren’s patients.”

The Sjögren’s syndrome recommendations were funded by EULAR. Many task force members reported relationships with industry in the form of advisory board and speaker’s bureau memberships, consultancies, and grants. Dr. McCoy reported serving on a data monitoring committee for Bristol-Myers Squibb unrelated to the data in the EULAR recommendations.

SOURCE: Ramos-Casals M et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216114

The European League Against Rheumatism has released its first recommendations for the management of Sjögren’s syndrome with topical and systemic treatments.

First author Manuel Ramos-Casals, MD, PhD, of Hospital Clinic de Barcelona Institut Clinic de Medicina i Dermatologia and colleagues on the multinational, multispecialty EULAR Sjögren Syndrome Task Force Group said the EULAR recommendations “synthesize current thinking” of management for Sjögren’s syndrome, which is complicated by individualized treatment that does not address the systemic disease and for which therapeutic decisions are often made based on expert opinion and personal experience because of a lack of data.

“Sjögren’s syndrome is generally treated through symptom management,” noted Sara McCoy, MD, who is director of the University of Wisconsin Health Sjögren’s Syndrome Clinic and was not involved in the recommendations, which were published in Annals of the Rheumatic Diseases. “Although we have measures to address these symptoms, we do not have any approved therapy that ameliorates the driving cause.”

There is limited high-quality evidence for many of the therapies discussed in the recommendations: In total, 9 randomized controlled trials, 18 prospective studies, and 5 case-control studies were included as evidence in the recommendations, and many involved a small number of patients.

The first overarching recommendation says that patients with Sjögren’s syndrome should be managed at centers of expertise using a multidisciplinary approach, the authors wrote. Two other overarching recommendations focus on how to manage certain patient cases. In cases of dryness, first-line therapy should include topical therapies for symptomatic relief, while clinicians should consider systemic therapies for patients with active systemic disease. All three overarching recommendations had a high level of agreement among task force members.

The task force also offered 12 specific recommendations on disease management, which take an “algorithmic approach” to Sjögren’s syndrome management that is guided by the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI), Dr. McCoy said in an interview.

“The EULAR recommendations structure a clear approach to treatment of Sjögren’s manifestations, ranging from oral and ocular sicca management, to treatment of uncommon but severe systemic involvement of Sjögren’s,” she said.

Before treating patients for oral dryness symptoms, clinicians should evaluate salivary function at baseline using unstimulated whole salivary flows. First-line therapeutic approaches for oral dryness can include nonpharmacologic stimulation in cases of mild salivary gland dysfunction, pharmacologic stimulation in cases of moderate dysfunction, and substitution of saliva in cases of severe dysfunction, the authors said.

Ocular dryness should be assessed using ocular staining score followed by ocular surface–disease index, and once identified, it can be managed with artificial tears and ocular gels or ointments as first-line therapy. Topical immunosuppressive-containing drops and autologous serum eye drops are options for more severe or refractory ocular dryness.

Patients who have fatigue or pain associated with Sjögren’s syndrome should have their fatigue or pain scored with the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI), and any concomitant disease should also be evaluated. Clinicians should consider acetaminophen and NSAIDs for treatment of acute musculoskeletal pain and other pain-modifying agents, such as hydroxychloroquine in cases of articular pain, despite a lack of evidence showing its efficacy in trials.

For systemic disease, the task force advised matching treatment to the organ(s) involved and using the ESSDAI to evaluate disease severity., They said that “patients presenting with at least moderate activity in one clinical domain, or with a global moderate disease activity score” of 5 or higher can be considered for systemic therapy.

Although many clinicians use glucocorticoids (GCs) for managing Sjögren’s syndrome, there is no evidence of the treatment’s efficacy in systemic disease. The task force recommended using glucocorticoids such as methylprednisolone at the minimum dose and withdrawing use “as soon as possible” in patients with inactive disease. “Based on the potential development of chronic damage in patients with uncontrolled systemic disease, some patients may require long-term therapy with GCs, especially those with severe organ impairments,” Dr. Ramos-Casals and colleagues wrote. “In these patients, the addition of immunosuppressive agents as GC-sparing agents is justified, always weighing the potential benefits and risks.” Because of a lack of head-to-head studies of different immunosuppressive agents, the task force did not recommend one particular agent over another.

One recommendation that contained a high level of evidence was for the use of B-cell targeted therapies for patients with severe, refractory systemic disease. Efficacy of rituximab was mixed in studies totaling more than 400 patients, but generally showed a positive outcome in at least one of the following areas: global response, organ-specific response, ESSDAI reduction, and prednisone reduction. The task force recommended that rituximab “may be considered” in “patients with severe, refractory systemic disease” and may be best for those with symptoms linked to cryoglobulinemic-associated vasculitis, with the potential of using belimumab (Benlysta) as rescue therapy. While systemic organ-specific therapeutic approaches vary, the general rule should be to treat with GCs first, followed by immunosuppressive agents and biologics as second-line therapy in cases refractory to GCs, either sequentially or in combination, the authors said.

For patients with B-cell lymphoma, clinicians should use individualized treatment based on the World Health Organization 2016 histologic subtype and the stage of the disease. While some clinicians employ a “watchful waiting” approach to treating low-grade hematologic neoplasia, “the decision to treat low-grade lymphomas or not must be discussed in a multidisciplinary committee, taking into account the fact that they are linked to the disease activity and are the ultimate stage of autoimmune B-cell activation,” the authors wrote.

The task force also defined a number of future research agenda goals for Sjögren’s syndrome treatment management, including developing personalized therapeutic approaches, finding predictors of biological response to agents used in treatment, and identifying biomarkers of poor outcomes.

In addition, EULAR acknowledged some research gaps exist in the guidelines for particular symptoms of Sjögren’s syndrome, such as in the case of fatigue. “The EULAR recommendations mention the common association of fatigue with Sjögren’s syndrome, though acknowledge that fatigue is more commonly seen in the same demographic cohort as Sjögren’s,” Dr. McCoy said. “Aside from exercise, there remains little available to address this common and burdensome symptom amongst Sjögren’s patients. Overall, this is a pertinent gap in knowledge in our Sjögren’s patients.”

The Sjögren’s syndrome recommendations were funded by EULAR. Many task force members reported relationships with industry in the form of advisory board and speaker’s bureau memberships, consultancies, and grants. Dr. McCoy reported serving on a data monitoring committee for Bristol-Myers Squibb unrelated to the data in the EULAR recommendations.

SOURCE: Ramos-Casals M et al. Ann Rheum Dis. 2019 Oct 31. doi: 10.1136/annrheumdis-2019-216114

Regular colorectal cancer (CRC) screenings are indicated for asymptomatic patients aged 50-75 years, according to a new evidence-based guidance statement issued by the American College of Physicians.

Regular screening can be discontinued after age 75 years, Amir Qaseem, MD, president of clinical policy and the Center for Evidence Reviews at the American College of Physicians, and colleagues wrote in the Annals of Internal Medicine.

No one test is preferred over another, according to the guidance statement. Patients and physicians can select the test type together, based on individual needs and preferences, and each test carries its own screening interval. But regular testing has been proven time and again to reduce the risk of colorectal cancer mortality, and more people should have it, according to the guidance.

“Not enough people in the United States get screened for colorectal cancer,” ACP President Robert M. McLean, MD, said in a press statement. “Physicians should perform an individualized risk assessment for colorectal cancer in all adults. Doctors and patients should select the screening test based on a discussion of the benefits, harms, costs, availability, frequency, and patient preferences.”

The guidance is an attempt to balance existing guidelines authored by the U.S. Preventive Services Task Force and the Canadian Task Force on Preventive Health Care (CTFPHC), but it also was developed following critical review of those from the American Cancer Society and other organizations.

The ACP guidance is for adults at average risk for colorectal cancer who do not have symptoms; it does not apply to adults with a family history of colorectal cancer, a long-standing history of inflammatory bowel disease, genetic syndromes such as familial cancerous polyps, a personal history of previous colorectal cancer or benign polyps, or other risk factors.

The guidance was based on evaluations of stool-based tests, including the fecal immunochemical test (FIT), also called the immunochemical-based fecal occult blood test (FOBT), and direct visualization with endoscopic and radiologic tests, including flexible sigmoidoscopy, colonoscopy, and CT colonography. The guidance includes the following recommendations:
 

Clinicians should regularly screen for colorectal cancer in average-risk adults between the ages of 50 and 75 years.

This recommendation is in line with those made by the U.S. Preventive Services Task Force and the CTFPHC. Data suggest that regular screening reduces colorectal cancer–specific mortality in this age group, with those aged 65-75 years likely to garner the most benefit.

The absolute risk reduction increases with age and varies with test type. For every-other-year FOBT, it rises from 0.037% in those younger than 60 years to 0.20% in those aged 60 years or older. For flexible sigmoidoscopy, the risk reduction rises from 0.05% in the younger group to 0.29% in the older group.

Data from the CTFPHC show that the net benefit in those aged 50-59 years is small, however. This may influence the decision about when to start screening.


 

Clinicians should select the colorectal cancer screening test with the patient based on a discussion of benefits, harms, costs, availability, frequency, and patient preferences.

The FIT or FOBT should be performed every 2 years, colonoscopy every 10 years, and flexible sigmoidoscopy every 10 years, plus FIT every 2 years.

No data suggest a benefit of one test over another; however, “all screening tests are associated with potential benefits as well as harms,” the document states. “Clinical decisions need to be individualized using patient clinical characteristics, patient preferences, and screening test frequency and availability. Because many eligible patients have never been screened and some may not adhere to recommendations about subsequent screening or follow-up of positive findings on screening tests (such as colonoscopy after a positive result on a stool-based screening test), patient informed decision making and adherence are important factors in selection of a [colorectal cancer] screening test.”

Discussions with patients should include topics like the recommended frequency of each test, bowel preparation, anesthesia, transportation to and from testing site, time commitments, and the necessary steps if a test result is positive.
 

Clinicians should discontinue screening for colorectal cancer in average-risk adults older than 75 years or in adults with a life expectancy of 10 years or less.

While the benefit from screening increases with age, so do the risks for harm, especially serious harm. Data show the balance of harms and benefits reaching a tipping point at around 75 years of age. But again, this isn’t a universal recommendation, the statement says.

“Persons with no history of [colorectal cancer] screening may benefit from screening after age 75 years, whereas those who have received regular screening with negative results may not.”

Cessation of testing considers life expectancy after age 75 years. The average life expectancy for healthy 75-year-old men and women in the United States is 9.9 and 12 years, respectively. But among men and women with serious medical comorbidities, average life expectancy after age 70 years drops to 8.9 and 10.8 years, respectively.

“Therefore, most persons aged 75 years or older, as well as most adults who are younger than 75 years but have serious comorbid conditions [such as chronic renal failure], are unlikely to benefit from screening but would undergo unnecessary, burdensome, potentially harmful, and costly screening tests.”

As in any testing discussion, personal preferences are important, but not just to make patients feel comfortable about their choice. Mindset about colorectal cancer testing has a very big effect on compliance, the statement noted.

“For example, a biennial stool test is not a good screening strategy for patients who may be unwilling or unlikely to follow up every other year. In addition, given the tradeoffs between benefits and harms, some patients may want less intensive screening, such as screening that begins at a later age, stops at an earlier age, or recurs less frequently regardless of modality selected.”

[email protected]

SOURCE: Qassam A et al. Ann Intern Med. 2019;171:643-54.

Regular colorectal cancer (CRC) screenings are indicated for asymptomatic patients aged 50-75 years, according to a new evidence-based guidance statement issued by the American College of Physicians.

Regular screening can be discontinued after age 75 years, Amir Qaseem, MD, president of clinical policy and the Center for Evidence Reviews at the American College of Physicians, and colleagues wrote in the Annals of Internal Medicine.

No one test is preferred over another, according to the guidance statement. Patients and physicians can select the test type together, based on individual needs and preferences, and each test carries its own screening interval. But regular testing has been proven time and again to reduce the risk of colorectal cancer mortality, and more people should have it, according to the guidance.

“Not enough people in the United States get screened for colorectal cancer,” ACP President Robert M. McLean, MD, said in a press statement. “Physicians should perform an individualized risk assessment for colorectal cancer in all adults. Doctors and patients should select the screening test based on a discussion of the benefits, harms, costs, availability, frequency, and patient preferences.”

The guidance is an attempt to balance existing guidelines authored by the U.S. Preventive Services Task Force and the Canadian Task Force on Preventive Health Care (CTFPHC), but it also was developed following critical review of those from the American Cancer Society and other organizations.

The ACP guidance is for adults at average risk for colorectal cancer who do not have symptoms; it does not apply to adults with a family history of colorectal cancer, a long-standing history of inflammatory bowel disease, genetic syndromes such as familial cancerous polyps, a personal history of previous colorectal cancer or benign polyps, or other risk factors.

The guidance was based on evaluations of stool-based tests, including the fecal immunochemical test (FIT), also called the immunochemical-based fecal occult blood test (FOBT), and direct visualization with endoscopic and radiologic tests, including flexible sigmoidoscopy, colonoscopy, and CT colonography. The guidance includes the following recommendations:
 

Clinicians should regularly screen for colorectal cancer in average-risk adults between the ages of 50 and 75 years.

This recommendation is in line with those made by the U.S. Preventive Services Task Force and the CTFPHC. Data suggest that regular screening reduces colorectal cancer–specific mortality in this age group, with those aged 65-75 years likely to garner the most benefit.

The absolute risk reduction increases with age and varies with test type. For every-other-year FOBT, it rises from 0.037% in those younger than 60 years to 0.20% in those aged 60 years or older. For flexible sigmoidoscopy, the risk reduction rises from 0.05% in the younger group to 0.29% in the older group.

Data from the CTFPHC show that the net benefit in those aged 50-59 years is small, however. This may influence the decision about when to start screening.


 

Clinicians should select the colorectal cancer screening test with the patient based on a discussion of benefits, harms, costs, availability, frequency, and patient preferences.

The FIT or FOBT should be performed every 2 years, colonoscopy every 10 years, and flexible sigmoidoscopy every 10 years, plus FIT every 2 years.

No data suggest a benefit of one test over another; however, “all screening tests are associated with potential benefits as well as harms,” the document states. “Clinical decisions need to be individualized using patient clinical characteristics, patient preferences, and screening test frequency and availability. Because many eligible patients have never been screened and some may not adhere to recommendations about subsequent screening or follow-up of positive findings on screening tests (such as colonoscopy after a positive result on a stool-based screening test), patient informed decision making and adherence are important factors in selection of a [colorectal cancer] screening test.”

Discussions with patients should include topics like the recommended frequency of each test, bowel preparation, anesthesia, transportation to and from testing site, time commitments, and the necessary steps if a test result is positive.
 

Clinicians should discontinue screening for colorectal cancer in average-risk adults older than 75 years or in adults with a life expectancy of 10 years or less.

While the benefit from screening increases with age, so do the risks for harm, especially serious harm. Data show the balance of harms and benefits reaching a tipping point at around 75 years of age. But again, this isn’t a universal recommendation, the statement says.

“Persons with no history of [colorectal cancer] screening may benefit from screening after age 75 years, whereas those who have received regular screening with negative results may not.”

Cessation of testing considers life expectancy after age 75 years. The average life expectancy for healthy 75-year-old men and women in the United States is 9.9 and 12 years, respectively. But among men and women with serious medical comorbidities, average life expectancy after age 70 years drops to 8.9 and 10.8 years, respectively.

“Therefore, most persons aged 75 years or older, as well as most adults who are younger than 75 years but have serious comorbid conditions [such as chronic renal failure], are unlikely to benefit from screening but would undergo unnecessary, burdensome, potentially harmful, and costly screening tests.”

As in any testing discussion, personal preferences are important, but not just to make patients feel comfortable about their choice. Mindset about colorectal cancer testing has a very big effect on compliance, the statement noted.

“For example, a biennial stool test is not a good screening strategy for patients who may be unwilling or unlikely to follow up every other year. In addition, given the tradeoffs between benefits and harms, some patients may want less intensive screening, such as screening that begins at a later age, stops at an earlier age, or recurs less frequently regardless of modality selected.”

[email protected]

SOURCE: Qassam A et al. Ann Intern Med. 2019;171:643-54.

Regular colorectal cancer (CRC) screenings are indicated for asymptomatic patients aged 50-75 years, according to a new evidence-based guidance statement issued by the American College of Physicians.

Regular screening can be discontinued after age 75 years, Amir Qaseem, MD, president of clinical policy and the Center for Evidence Reviews at the American College of Physicians, and colleagues wrote in the Annals of Internal Medicine.

No one test is preferred over another, according to the guidance statement. Patients and physicians can select the test type together, based on individual needs and preferences, and each test carries its own screening interval. But regular testing has been proven time and again to reduce the risk of colorectal cancer mortality, and more people should have it, according to the guidance.

“Not enough people in the United States get screened for colorectal cancer,” ACP President Robert M. McLean, MD, said in a press statement. “Physicians should perform an individualized risk assessment for colorectal cancer in all adults. Doctors and patients should select the screening test based on a discussion of the benefits, harms, costs, availability, frequency, and patient preferences.”

The guidance is an attempt to balance existing guidelines authored by the U.S. Preventive Services Task Force and the Canadian Task Force on Preventive Health Care (CTFPHC), but it also was developed following critical review of those from the American Cancer Society and other organizations.

The ACP guidance is for adults at average risk for colorectal cancer who do not have symptoms; it does not apply to adults with a family history of colorectal cancer, a long-standing history of inflammatory bowel disease, genetic syndromes such as familial cancerous polyps, a personal history of previous colorectal cancer or benign polyps, or other risk factors.

The guidance was based on evaluations of stool-based tests, including the fecal immunochemical test (FIT), also called the immunochemical-based fecal occult blood test (FOBT), and direct visualization with endoscopic and radiologic tests, including flexible sigmoidoscopy, colonoscopy, and CT colonography. The guidance includes the following recommendations:
 

Clinicians should regularly screen for colorectal cancer in average-risk adults between the ages of 50 and 75 years.

This recommendation is in line with those made by the U.S. Preventive Services Task Force and the CTFPHC. Data suggest that regular screening reduces colorectal cancer–specific mortality in this age group, with those aged 65-75 years likely to garner the most benefit.

The absolute risk reduction increases with age and varies with test type. For every-other-year FOBT, it rises from 0.037% in those younger than 60 years to 0.20% in those aged 60 years or older. For flexible sigmoidoscopy, the risk reduction rises from 0.05% in the younger group to 0.29% in the older group.

Data from the CTFPHC show that the net benefit in those aged 50-59 years is small, however. This may influence the decision about when to start screening.


 

Clinicians should select the colorectal cancer screening test with the patient based on a discussion of benefits, harms, costs, availability, frequency, and patient preferences.

The FIT or FOBT should be performed every 2 years, colonoscopy every 10 years, and flexible sigmoidoscopy every 10 years, plus FIT every 2 years.

No data suggest a benefit of one test over another; however, “all screening tests are associated with potential benefits as well as harms,” the document states. “Clinical decisions need to be individualized using patient clinical characteristics, patient preferences, and screening test frequency and availability. Because many eligible patients have never been screened and some may not adhere to recommendations about subsequent screening or follow-up of positive findings on screening tests (such as colonoscopy after a positive result on a stool-based screening test), patient informed decision making and adherence are important factors in selection of a [colorectal cancer] screening test.”

Discussions with patients should include topics like the recommended frequency of each test, bowel preparation, anesthesia, transportation to and from testing site, time commitments, and the necessary steps if a test result is positive.
 

Clinicians should discontinue screening for colorectal cancer in average-risk adults older than 75 years or in adults with a life expectancy of 10 years or less.

While the benefit from screening increases with age, so do the risks for harm, especially serious harm. Data show the balance of harms and benefits reaching a tipping point at around 75 years of age. But again, this isn’t a universal recommendation, the statement says.

“Persons with no history of [colorectal cancer] screening may benefit from screening after age 75 years, whereas those who have received regular screening with negative results may not.”

Cessation of testing considers life expectancy after age 75 years. The average life expectancy for healthy 75-year-old men and women in the United States is 9.9 and 12 years, respectively. But among men and women with serious medical comorbidities, average life expectancy after age 70 years drops to 8.9 and 10.8 years, respectively.

“Therefore, most persons aged 75 years or older, as well as most adults who are younger than 75 years but have serious comorbid conditions [such as chronic renal failure], are unlikely to benefit from screening but would undergo unnecessary, burdensome, potentially harmful, and costly screening tests.”

As in any testing discussion, personal preferences are important, but not just to make patients feel comfortable about their choice. Mindset about colorectal cancer testing has a very big effect on compliance, the statement noted.

“For example, a biennial stool test is not a good screening strategy for patients who may be unwilling or unlikely to follow up every other year. In addition, given the tradeoffs between benefits and harms, some patients may want less intensive screening, such as screening that begins at a later age, stops at an earlier age, or recurs less frequently regardless of modality selected.”

[email protected]

SOURCE: Qassam A et al. Ann Intern Med. 2019;171:643-54.

Recommendations for the diagnosis and management of acute and chronic graft-versus-host disease (GVHD) are the central focus of the first National Comprehensive Cancer Network (NCCN) guideline on hematopoietic cell transplantation.

The guideline presents detailed recommendations for the evaluation of hematopoietic cell transplant (HCT) recipients, and an extensive section on the diagnosis and workup of GVHD, including information on staging and grading of acute GVHD, grading of chronic GVHD, treatment response criteria, and suggested systemic therapies for steroid-refractory disease.

“We wanted to both build on the commonly used approach to stage and treat graft-versus-host disease, and make sure that this information is readily available for physicians-in-training and young physicians who are learning about transplants,” said guideline committee chair Ayman Saad, MB BCh, of The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute in Columbus, Ohio.

In an interview, Dr. Saad emphasized that an important goal of the guidelines is to encourage general oncologists to recognize early signs of GVHD and refer potential candidates to transplant centers for further evaluation.

“We also urge oncologists who may be caring for patients after HCT to familiarize themselves with the varied manifestations of GVHD – a very common and significant posttransplant complication – and to consult with transplant providers to optimize their ongoing care. The guidelines explain how to diagnose and treat this condition in order to achieve the best possible outcomes,” guideline panel member Alison W. Loren, MD, director of blood and marrow transplantation at Abraham Cancer Center, University of Pennsylvania, Philadelphia, said in a statement.

The guideline includes links to other NCCN guidelines for diseases where HCT is a common therapeutic option, including leukemias, myeloid malignancies, lymphomas, central nervous system cancers, and testicular cancer.

The HCT guideline includes:

• Pretransplant recipient evaluation with recommendations for clinical assessment and imaging.
• Diagnosis and workup of GVHD, with separate algorithms for suspected acute or chronic GVHD.
• Specific interventions for management of acute GVHD with corticosteroids or other systemic agents.
• Chronic GVHD diagnosis by organ site and symptoms, with a severity scoring system.
• Chronic GVHD steroid response definitions and criteria.
• Suggested systemic agents for steroid-refractory GVHD.

One feature that is unusual for an NCCN guideline document is a page of photographs to assist clinicians in diagnosing range-of-motion abnormalities in the shoulder, elbow, hand, and ankle of patients with suspected or confirmed GVHD. Dr. Saad said that future iterations of the guideline will include additional photos to help clinicians develop a visual repertoire of potential GVHD signs.

Future versions will also include a discussion section and more comprehensive information on other common complications following HCT transplant, as well as management of posttransplant relapse.

Ideally, the guideline will help clinicians document and justify clinical decisions surrounding HCT and GVHD management in discussions with third-party payers, Dr. Saad said.

“Sometimes we struggle with payers when we want to use a certain modality to treat GVHD, and they respond ‘that’s not approved,’ or ‘that’s not a common indication,’ et cetera,” he said. “What we’re trying to put here are the commonly used therapies that most, but not all, experts agree on, and we can use this to negotiate with payers.”

He also emphasized that the guideline is meant to be instructive rather than prescriptive and is not meant to hinder innovations that may emerge from clinical trials.

“We would appreciate any feedback from non-NCCN centers as well as experts at NCCN centers, and we’ll be more than happy to address any concerns or criticisms they have,” he said.

Dr. Saad reported financial relationships with Actinium and Incysus Biomedical. Dr. Loren has previously reported having no disclosures.

Recommendations for the diagnosis and management of acute and chronic graft-versus-host disease (GVHD) are the central focus of the first National Comprehensive Cancer Network (NCCN) guideline on hematopoietic cell transplantation.

The guideline presents detailed recommendations for the evaluation of hematopoietic cell transplant (HCT) recipients, and an extensive section on the diagnosis and workup of GVHD, including information on staging and grading of acute GVHD, grading of chronic GVHD, treatment response criteria, and suggested systemic therapies for steroid-refractory disease.

“We wanted to both build on the commonly used approach to stage and treat graft-versus-host disease, and make sure that this information is readily available for physicians-in-training and young physicians who are learning about transplants,” said guideline committee chair Ayman Saad, MB BCh, of The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute in Columbus, Ohio.

In an interview, Dr. Saad emphasized that an important goal of the guidelines is to encourage general oncologists to recognize early signs of GVHD and refer potential candidates to transplant centers for further evaluation.

“We also urge oncologists who may be caring for patients after HCT to familiarize themselves with the varied manifestations of GVHD – a very common and significant posttransplant complication – and to consult with transplant providers to optimize their ongoing care. The guidelines explain how to diagnose and treat this condition in order to achieve the best possible outcomes,” guideline panel member Alison W. Loren, MD, director of blood and marrow transplantation at Abraham Cancer Center, University of Pennsylvania, Philadelphia, said in a statement.

The guideline includes links to other NCCN guidelines for diseases where HCT is a common therapeutic option, including leukemias, myeloid malignancies, lymphomas, central nervous system cancers, and testicular cancer.

The HCT guideline includes:

• Pretransplant recipient evaluation with recommendations for clinical assessment and imaging.
• Diagnosis and workup of GVHD, with separate algorithms for suspected acute or chronic GVHD.
• Specific interventions for management of acute GVHD with corticosteroids or other systemic agents.
• Chronic GVHD diagnosis by organ site and symptoms, with a severity scoring system.
• Chronic GVHD steroid response definitions and criteria.
• Suggested systemic agents for steroid-refractory GVHD.

One feature that is unusual for an NCCN guideline document is a page of photographs to assist clinicians in diagnosing range-of-motion abnormalities in the shoulder, elbow, hand, and ankle of patients with suspected or confirmed GVHD. Dr. Saad said that future iterations of the guideline will include additional photos to help clinicians develop a visual repertoire of potential GVHD signs.

Future versions will also include a discussion section and more comprehensive information on other common complications following HCT transplant, as well as management of posttransplant relapse.

Ideally, the guideline will help clinicians document and justify clinical decisions surrounding HCT and GVHD management in discussions with third-party payers, Dr. Saad said.

“Sometimes we struggle with payers when we want to use a certain modality to treat GVHD, and they respond ‘that’s not approved,’ or ‘that’s not a common indication,’ et cetera,” he said. “What we’re trying to put here are the commonly used therapies that most, but not all, experts agree on, and we can use this to negotiate with payers.”

He also emphasized that the guideline is meant to be instructive rather than prescriptive and is not meant to hinder innovations that may emerge from clinical trials.

“We would appreciate any feedback from non-NCCN centers as well as experts at NCCN centers, and we’ll be more than happy to address any concerns or criticisms they have,” he said.

Dr. Saad reported financial relationships with Actinium and Incysus Biomedical. Dr. Loren has previously reported having no disclosures.

Recommendations for the diagnosis and management of acute and chronic graft-versus-host disease (GVHD) are the central focus of the first National Comprehensive Cancer Network (NCCN) guideline on hematopoietic cell transplantation.

The guideline presents detailed recommendations for the evaluation of hematopoietic cell transplant (HCT) recipients, and an extensive section on the diagnosis and workup of GVHD, including information on staging and grading of acute GVHD, grading of chronic GVHD, treatment response criteria, and suggested systemic therapies for steroid-refractory disease.

“We wanted to both build on the commonly used approach to stage and treat graft-versus-host disease, and make sure that this information is readily available for physicians-in-training and young physicians who are learning about transplants,” said guideline committee chair Ayman Saad, MB BCh, of The Ohio State University Comprehensive Cancer Center, James Cancer Hospital and Solove Research Institute in Columbus, Ohio.

In an interview, Dr. Saad emphasized that an important goal of the guidelines is to encourage general oncologists to recognize early signs of GVHD and refer potential candidates to transplant centers for further evaluation.

“We also urge oncologists who may be caring for patients after HCT to familiarize themselves with the varied manifestations of GVHD – a very common and significant posttransplant complication – and to consult with transplant providers to optimize their ongoing care. The guidelines explain how to diagnose and treat this condition in order to achieve the best possible outcomes,” guideline panel member Alison W. Loren, MD, director of blood and marrow transplantation at Abraham Cancer Center, University of Pennsylvania, Philadelphia, said in a statement.

The guideline includes links to other NCCN guidelines for diseases where HCT is a common therapeutic option, including leukemias, myeloid malignancies, lymphomas, central nervous system cancers, and testicular cancer.

The HCT guideline includes:

• Pretransplant recipient evaluation with recommendations for clinical assessment and imaging.
• Diagnosis and workup of GVHD, with separate algorithms for suspected acute or chronic GVHD.
• Specific interventions for management of acute GVHD with corticosteroids or other systemic agents.
• Chronic GVHD diagnosis by organ site and symptoms, with a severity scoring system.
• Chronic GVHD steroid response definitions and criteria.
• Suggested systemic agents for steroid-refractory GVHD.

One feature that is unusual for an NCCN guideline document is a page of photographs to assist clinicians in diagnosing range-of-motion abnormalities in the shoulder, elbow, hand, and ankle of patients with suspected or confirmed GVHD. Dr. Saad said that future iterations of the guideline will include additional photos to help clinicians develop a visual repertoire of potential GVHD signs.

Future versions will also include a discussion section and more comprehensive information on other common complications following HCT transplant, as well as management of posttransplant relapse.

Ideally, the guideline will help clinicians document and justify clinical decisions surrounding HCT and GVHD management in discussions with third-party payers, Dr. Saad said.

“Sometimes we struggle with payers when we want to use a certain modality to treat GVHD, and they respond ‘that’s not approved,’ or ‘that’s not a common indication,’ et cetera,” he said. “What we’re trying to put here are the commonly used therapies that most, but not all, experts agree on, and we can use this to negotiate with payers.”

He also emphasized that the guideline is meant to be instructive rather than prescriptive and is not meant to hinder innovations that may emerge from clinical trials.

“We would appreciate any feedback from non-NCCN centers as well as experts at NCCN centers, and we’ll be more than happy to address any concerns or criticisms they have,” he said.

Dr. Saad reported financial relationships with Actinium and Incysus Biomedical. Dr. Loren has previously reported having no disclosures.

Guidelines on the management of acute upper gastrointestinal bleeding have been updated, including recommendations on managing patients on antiplatelet or anticoagulant therapy and on use of endoscopy and new therapeutic approaches.

Writing in Annals of Internal Medicine, an international group of experts published an update to the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding, with a focus on resuscitation and risk assessment; pre-endoscopic, endoscopic, and pharmacologic management; and secondary prophylaxis.

Alan N. Barkun, MDCM, MSc, from McGill University, Montreal, and coauthors first recommended that fluid resuscitation should be initiated in patients with acute upper gastrointestinal bleeding and hemodynamic instability to avoid hemorrhagic shock and restore end-organ perfusion and tissue oxygenation while the bleeding is brought under control.

They acknowledged the uncertainty around whether colloid or crystalloid fluid should be used, but suggested routine use of colloids was not justified because they were more expensive and did not appear to increase survival.

On the question of whether the resuscitation should be aggressive or restrictive in its timing and rate, the group said there was not enough evidence to support a recommendation on this. “The important issue in patients with hemorrhagic shock due to trauma or UGIB [upper gastrointestinal bleeding] is to stop the bleeding while minimizing hemodynamic compromise,” they wrote.

They also advised blood transfusions in patients with a hemoglobin level below 80 g/L who did not have underlying cardiovascular disease, but suggested a higher hemoglobin threshold for those with underlying cardiovascular disease.

The second recommendation was that patients with a Glasgow Blatchford score of 1 or less were at very low risk for rebleeding and mortality, and these patients may therefore not need hospitalization or inpatient endoscopy. They advised against using the AIMS65 prognostic score for this purpose because it was designed to identify patients at high risk of death, not those at low risk for safe discharge.

In regard to endoscopic management, they advocated that all patients with acute upper gastrointestinal bleeding – whether low or high risk – undergo endoscopy within 24 hours of presentation. This was even more urgent in patients being treated with anticoagulants. “Because of the recognized benefits of early endoscopy, coagulopathy should be treated as necessary but endoscopy should not be delayed,” they wrote.

Patients with acutely bleeding ulcers with high-risk stigmata should undergo endoscopic therapy preferably with thermocoagulation or sclerosant injection, or with hemoclips depending on the bleeding location and patient characteristics.

The group also included two conditional recommendations, based on very-low-quality evidence, that patients with actively bleeding ulcers receive TC-325 hemostatic powder as temporizing therapy to stop the bleeding if conventional endoscopic therapies aren’t available or fail. However, they stressed that TC-325 should not be used as a single therapeutic strategy.

Because of a lack of efficacy data and low availability of expertise in the technology, the authors said they could not make a recommendation for or against using a Doppler endoscopic probe (DEP) to assess the need for further endoscopic therapy.

“The group generally agreed that although making a recommendation for or against using DEP to manage UGIB is premature, DEP has the potential to alter the usual approach to visually assessing bleeding lesion risk when evaluating the need for, and adequacy of, endoscopic hemostasis.”

The guidelines also addressed the issue of pharmacologic management of acute upper gastrointestinal bleeding. They strongly recommended that patients with bleeding ulcers and high-risk stigmata who have undergone successful endoscopic therapy should then receive an intravenous loading dose of proton pump inhibitor (PPI) therapy, followed by continuous intravenous infusion.

“Cost-effectiveness studies have suggested that high-dose intravenous PPIs after successful endoscopic hemostasis improve outcomes at a modest cost increase relative to non–high-dose intravenous or oral PPI strategies,” they wrote.

A second conditional recommendation, based on very-low-quality evidence, was that patients with a bleeding ulcer who were at high risk for rebleeding be also treated twice-daily with oral PPIs for 2 weeks, then once-daily. They also recommended patients on cardiovascular prophylaxis with single or dual antiplatelet therapy or anticoagulant therapy be given PPIs.

“The consensus group concluded that, for high-risk patients with an ongoing need for anticoagulants, the evidence suggests that the benefits of secondary prophylaxis outweigh the risks.”

The group was supported by a grant from CIHR Institute of Nutrition, Metabolism and Diabetes and from the Saudi Gastroenterology Association. Nine authors declared grants, personal fees, honoraria and other funding from the pharmaceutical and medical device sector outside the submitted work. No other conflicts of interest were declared.

SOURCE: Barkun A et al. Ann Intern Med 2019, October 22. doi: 10.7326/M19-1795.

Guidelines on the management of acute upper gastrointestinal bleeding have been updated, including recommendations on managing patients on antiplatelet or anticoagulant therapy and on use of endoscopy and new therapeutic approaches.

Writing in Annals of Internal Medicine, an international group of experts published an update to the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding, with a focus on resuscitation and risk assessment; pre-endoscopic, endoscopic, and pharmacologic management; and secondary prophylaxis.

Alan N. Barkun, MDCM, MSc, from McGill University, Montreal, and coauthors first recommended that fluid resuscitation should be initiated in patients with acute upper gastrointestinal bleeding and hemodynamic instability to avoid hemorrhagic shock and restore end-organ perfusion and tissue oxygenation while the bleeding is brought under control.

They acknowledged the uncertainty around whether colloid or crystalloid fluid should be used, but suggested routine use of colloids was not justified because they were more expensive and did not appear to increase survival.

On the question of whether the resuscitation should be aggressive or restrictive in its timing and rate, the group said there was not enough evidence to support a recommendation on this. “The important issue in patients with hemorrhagic shock due to trauma or UGIB [upper gastrointestinal bleeding] is to stop the bleeding while minimizing hemodynamic compromise,” they wrote.

They also advised blood transfusions in patients with a hemoglobin level below 80 g/L who did not have underlying cardiovascular disease, but suggested a higher hemoglobin threshold for those with underlying cardiovascular disease.

The second recommendation was that patients with a Glasgow Blatchford score of 1 or less were at very low risk for rebleeding and mortality, and these patients may therefore not need hospitalization or inpatient endoscopy. They advised against using the AIMS65 prognostic score for this purpose because it was designed to identify patients at high risk of death, not those at low risk for safe discharge.

In regard to endoscopic management, they advocated that all patients with acute upper gastrointestinal bleeding – whether low or high risk – undergo endoscopy within 24 hours of presentation. This was even more urgent in patients being treated with anticoagulants. “Because of the recognized benefits of early endoscopy, coagulopathy should be treated as necessary but endoscopy should not be delayed,” they wrote.

Patients with acutely bleeding ulcers with high-risk stigmata should undergo endoscopic therapy preferably with thermocoagulation or sclerosant injection, or with hemoclips depending on the bleeding location and patient characteristics.

The group also included two conditional recommendations, based on very-low-quality evidence, that patients with actively bleeding ulcers receive TC-325 hemostatic powder as temporizing therapy to stop the bleeding if conventional endoscopic therapies aren’t available or fail. However, they stressed that TC-325 should not be used as a single therapeutic strategy.

Because of a lack of efficacy data and low availability of expertise in the technology, the authors said they could not make a recommendation for or against using a Doppler endoscopic probe (DEP) to assess the need for further endoscopic therapy.

“The group generally agreed that although making a recommendation for or against using DEP to manage UGIB is premature, DEP has the potential to alter the usual approach to visually assessing bleeding lesion risk when evaluating the need for, and adequacy of, endoscopic hemostasis.”

The guidelines also addressed the issue of pharmacologic management of acute upper gastrointestinal bleeding. They strongly recommended that patients with bleeding ulcers and high-risk stigmata who have undergone successful endoscopic therapy should then receive an intravenous loading dose of proton pump inhibitor (PPI) therapy, followed by continuous intravenous infusion.

“Cost-effectiveness studies have suggested that high-dose intravenous PPIs after successful endoscopic hemostasis improve outcomes at a modest cost increase relative to non–high-dose intravenous or oral PPI strategies,” they wrote.

A second conditional recommendation, based on very-low-quality evidence, was that patients with a bleeding ulcer who were at high risk for rebleeding be also treated twice-daily with oral PPIs for 2 weeks, then once-daily. They also recommended patients on cardiovascular prophylaxis with single or dual antiplatelet therapy or anticoagulant therapy be given PPIs.

“The consensus group concluded that, for high-risk patients with an ongoing need for anticoagulants, the evidence suggests that the benefits of secondary prophylaxis outweigh the risks.”

The group was supported by a grant from CIHR Institute of Nutrition, Metabolism and Diabetes and from the Saudi Gastroenterology Association. Nine authors declared grants, personal fees, honoraria and other funding from the pharmaceutical and medical device sector outside the submitted work. No other conflicts of interest were declared.

SOURCE: Barkun A et al. Ann Intern Med 2019, October 22. doi: 10.7326/M19-1795.

Guidelines on the management of acute upper gastrointestinal bleeding have been updated, including recommendations on managing patients on antiplatelet or anticoagulant therapy and on use of endoscopy and new therapeutic approaches.

Writing in Annals of Internal Medicine, an international group of experts published an update to the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding, with a focus on resuscitation and risk assessment; pre-endoscopic, endoscopic, and pharmacologic management; and secondary prophylaxis.

Alan N. Barkun, MDCM, MSc, from McGill University, Montreal, and coauthors first recommended that fluid resuscitation should be initiated in patients with acute upper gastrointestinal bleeding and hemodynamic instability to avoid hemorrhagic shock and restore end-organ perfusion and tissue oxygenation while the bleeding is brought under control.

They acknowledged the uncertainty around whether colloid or crystalloid fluid should be used, but suggested routine use of colloids was not justified because they were more expensive and did not appear to increase survival.

On the question of whether the resuscitation should be aggressive or restrictive in its timing and rate, the group said there was not enough evidence to support a recommendation on this. “The important issue in patients with hemorrhagic shock due to trauma or UGIB [upper gastrointestinal bleeding] is to stop the bleeding while minimizing hemodynamic compromise,” they wrote.

They also advised blood transfusions in patients with a hemoglobin level below 80 g/L who did not have underlying cardiovascular disease, but suggested a higher hemoglobin threshold for those with underlying cardiovascular disease.

The second recommendation was that patients with a Glasgow Blatchford score of 1 or less were at very low risk for rebleeding and mortality, and these patients may therefore not need hospitalization or inpatient endoscopy. They advised against using the AIMS65 prognostic score for this purpose because it was designed to identify patients at high risk of death, not those at low risk for safe discharge.

In regard to endoscopic management, they advocated that all patients with acute upper gastrointestinal bleeding – whether low or high risk – undergo endoscopy within 24 hours of presentation. This was even more urgent in patients being treated with anticoagulants. “Because of the recognized benefits of early endoscopy, coagulopathy should be treated as necessary but endoscopy should not be delayed,” they wrote.

Patients with acutely bleeding ulcers with high-risk stigmata should undergo endoscopic therapy preferably with thermocoagulation or sclerosant injection, or with hemoclips depending on the bleeding location and patient characteristics.

The group also included two conditional recommendations, based on very-low-quality evidence, that patients with actively bleeding ulcers receive TC-325 hemostatic powder as temporizing therapy to stop the bleeding if conventional endoscopic therapies aren’t available or fail. However, they stressed that TC-325 should not be used as a single therapeutic strategy.

Because of a lack of efficacy data and low availability of expertise in the technology, the authors said they could not make a recommendation for or against using a Doppler endoscopic probe (DEP) to assess the need for further endoscopic therapy.

“The group generally agreed that although making a recommendation for or against using DEP to manage UGIB is premature, DEP has the potential to alter the usual approach to visually assessing bleeding lesion risk when evaluating the need for, and adequacy of, endoscopic hemostasis.”

The guidelines also addressed the issue of pharmacologic management of acute upper gastrointestinal bleeding. They strongly recommended that patients with bleeding ulcers and high-risk stigmata who have undergone successful endoscopic therapy should then receive an intravenous loading dose of proton pump inhibitor (PPI) therapy, followed by continuous intravenous infusion.

“Cost-effectiveness studies have suggested that high-dose intravenous PPIs after successful endoscopic hemostasis improve outcomes at a modest cost increase relative to non–high-dose intravenous or oral PPI strategies,” they wrote.

A second conditional recommendation, based on very-low-quality evidence, was that patients with a bleeding ulcer who were at high risk for rebleeding be also treated twice-daily with oral PPIs for 2 weeks, then once-daily. They also recommended patients on cardiovascular prophylaxis with single or dual antiplatelet therapy or anticoagulant therapy be given PPIs.

“The consensus group concluded that, for high-risk patients with an ongoing need for anticoagulants, the evidence suggests that the benefits of secondary prophylaxis outweigh the risks.”

The group was supported by a grant from CIHR Institute of Nutrition, Metabolism and Diabetes and from the Saudi Gastroenterology Association. Nine authors declared grants, personal fees, honoraria and other funding from the pharmaceutical and medical device sector outside the submitted work. No other conflicts of interest were declared.

SOURCE: Barkun A et al. Ann Intern Med 2019, October 22. doi: 10.7326/M19-1795.

A new draft guideline for the diagnosis and management of thrombocytopenic purpura (TTP) was recently released by the International Society on Thrombosis and Hemostasis (ISTH).

Svisio/Thinkstock

According to the panel of experts involved, the ISTH guideline takes into account the latest TTP findings, offering a more up-to-date resource for clinicians than the two previously published guidelines in 2012 from the British Committee for Standards in Haematology and in 2017 from the TTP group of Japan’s Blood Coagulation Abnormalities Research Team.

“Since the publication of these guidelines, there have been significant developments in the diagnosis and treatment of TTP, and an increase in published data on how management strategies affect objective health outcomes,” the panel members wrote in the guideline, which is available at ISTH.org.

Despite these advancements, TTP remains a challenging condition for both clinicians and patients for a variety of reasons, the panel noted, which was led by clinical cochair X. Long Zheng, MD, PhD, of the University of Alabama in Birmingham and method cochair Sara K. Vesely, PhD, of the University of Oklahoma, Oklahoma City.

The ISTH guideline provides recommendations for adult patients with either immune or hereditary TTP, from acute events through remission, including diagnostic steps to determine if a case of thrombotic microangiopathy is in fact TTP.

Nearly all the recommendations are based on very-low-certainty evidence. Some of the key treatment recommendations include the following:

• For patients with immune TTP experiencing a first acute event, add corticosteroids to therapeutic plasma exchange (TPE), rather than treating with TPE alone. This is a strong recommendation.
• For patients with immune TTP experiencing a first acute event, add rituximab to corticosteroids and TPE, rather than corticosteroids and TPE alone. This is a conditional recommendation.
• For patients with immune TTP experiencing a relapse, add corticosteroids to TPE, rather than TPE alone. This is a strong recommendation.
• For patients with immune TTP experiencing a relapse, add rituximab to corticosteroids and TPE, rather than steroids and TPE alone. This is a conditional recommendation.
• For patients with immune TTP experiencing an acute event – either a first event or a relapse – use caplacizumab. This is a conditional recommendation based on moderate-certainty evidence.
• For patients with immune TTP who are in remission and have low plasma ADAMTS13 activity but no other symptoms of TMA, use rituximab for prophylaxis. This is a conditional recommendation.
• For patients with hereditary TTP who are in remission, plasma infusion or a watch-and-wait strategy is recommended. This is a conditional recommendation.
• For patients with hereditary TTP who are in remission, do not use factor VIII concentrate infusions. A watch-and-wait strategy is advised. This is a conditional recommendation.
• For patients with immune TTP who are pregnant and have decreased plasma ADAMTS13 activity but no symptoms of TMA, use prophylactic treatment. This is a strong recommendation.
• For patients with hereditary TTP who are pregnant, use prophylactic treatment. This is a strong recommendation. The panel further recommended treatment with plasma infusion rather than factor VIII products, which was a conditional recommendation.

The multidisciplinary expert panel included hematologists and pathologists with expertise in TTP, neurologists, nephrologists, intensive care specialists, and patient representatives. The panel followed the GRADE approach and the Population, Intervention, Comparison, Outcome (PICO) framework, and adhered to standards set forth by the Health and Medicine Division (HMD) of the National Academies of Sciences, Engineering, and Medicine and the GIN-McMaster Guideline Development Checklist.

Even with an experienced group of physicians and a structured plan, however, the creation of guidelines for rare diseases like TTP presents a unique set of obstacles, according to the panel members. Challenges include a small body of relevant evidence that is often inconsistent and lacking in high certainty and studies that do not address outcomes important to patients. These shortcomings can make it difficult for guideline developers to issue strong recommendations.

“However, well-developed clinical practice guidelines are vital in rare diseases; these conditions are, by their nature, encountered very infrequently by individual clinicians, who may feel unprepared to address their diagnosis and treatment,” the panelists wrote. “Well-synthesized evidence and clear recommendations play an important role in supporting clinical decision making. Systematically created guidelines can also highlight areas where evidence is uncertain, clinical judgement is required, and future research in the area is warranted.”

The guideline was supported by ISTH. Fifty percent of the panel members had no or minimal conflict of interest; those with conflicts of interest abstained from voting on recommendations relevant to their conflicts.

A new draft guideline for the diagnosis and management of thrombocytopenic purpura (TTP) was recently released by the International Society on Thrombosis and Hemostasis (ISTH).

Svisio/Thinkstock

According to the panel of experts involved, the ISTH guideline takes into account the latest TTP findings, offering a more up-to-date resource for clinicians than the two previously published guidelines in 2012 from the British Committee for Standards in Haematology and in 2017 from the TTP group of Japan’s Blood Coagulation Abnormalities Research Team.

“Since the publication of these guidelines, there have been significant developments in the diagnosis and treatment of TTP, and an increase in published data on how management strategies affect objective health outcomes,” the panel members wrote in the guideline, which is available at ISTH.org.

Despite these advancements, TTP remains a challenging condition for both clinicians and patients for a variety of reasons, the panel noted, which was led by clinical cochair X. Long Zheng, MD, PhD, of the University of Alabama in Birmingham and method cochair Sara K. Vesely, PhD, of the University of Oklahoma, Oklahoma City.

The ISTH guideline provides recommendations for adult patients with either immune or hereditary TTP, from acute events through remission, including diagnostic steps to determine if a case of thrombotic microangiopathy is in fact TTP.

Nearly all the recommendations are based on very-low-certainty evidence. Some of the key treatment recommendations include the following:

• For patients with immune TTP experiencing a first acute event, add corticosteroids to therapeutic plasma exchange (TPE), rather than treating with TPE alone. This is a strong recommendation.
• For patients with immune TTP experiencing a first acute event, add rituximab to corticosteroids and TPE, rather than corticosteroids and TPE alone. This is a conditional recommendation.
• For patients with immune TTP experiencing a relapse, add corticosteroids to TPE, rather than TPE alone. This is a strong recommendation.
• For patients with immune TTP experiencing a relapse, add rituximab to corticosteroids and TPE, rather than steroids and TPE alone. This is a conditional recommendation.
• For patients with immune TTP experiencing an acute event – either a first event or a relapse – use caplacizumab. This is a conditional recommendation based on moderate-certainty evidence.
• For patients with immune TTP who are in remission and have low plasma ADAMTS13 activity but no other symptoms of TMA, use rituximab for prophylaxis. This is a conditional recommendation.
• For patients with hereditary TTP who are in remission, plasma infusion or a watch-and-wait strategy is recommended. This is a conditional recommendation.
• For patients with hereditary TTP who are in remission, do not use factor VIII concentrate infusions. A watch-and-wait strategy is advised. This is a conditional recommendation.
• For patients with immune TTP who are pregnant and have decreased plasma ADAMTS13 activity but no symptoms of TMA, use prophylactic treatment. This is a strong recommendation.
• For patients with hereditary TTP who are pregnant, use prophylactic treatment. This is a strong recommendation. The panel further recommended treatment with plasma infusion rather than factor VIII products, which was a conditional recommendation.

The multidisciplinary expert panel included hematologists and pathologists with expertise in TTP, neurologists, nephrologists, intensive care specialists, and patient representatives. The panel followed the GRADE approach and the Population, Intervention, Comparison, Outcome (PICO) framework, and adhered to standards set forth by the Health and Medicine Division (HMD) of the National Academies of Sciences, Engineering, and Medicine and the GIN-McMaster Guideline Development Checklist.

Even with an experienced group of physicians and a structured plan, however, the creation of guidelines for rare diseases like TTP presents a unique set of obstacles, according to the panel members. Challenges include a small body of relevant evidence that is often inconsistent and lacking in high certainty and studies that do not address outcomes important to patients. These shortcomings can make it difficult for guideline developers to issue strong recommendations.

“However, well-developed clinical practice guidelines are vital in rare diseases; these conditions are, by their nature, encountered very infrequently by individual clinicians, who may feel unprepared to address their diagnosis and treatment,” the panelists wrote. “Well-synthesized evidence and clear recommendations play an important role in supporting clinical decision making. Systematically created guidelines can also highlight areas where evidence is uncertain, clinical judgement is required, and future research in the area is warranted.”

The guideline was supported by ISTH. Fifty percent of the panel members had no or minimal conflict of interest; those with conflicts of interest abstained from voting on recommendations relevant to their conflicts.

A new draft guideline for the diagnosis and management of thrombocytopenic purpura (TTP) was recently released by the International Society on Thrombosis and Hemostasis (ISTH).

Svisio/Thinkstock

According to the panel of experts involved, the ISTH guideline takes into account the latest TTP findings, offering a more up-to-date resource for clinicians than the two previously published guidelines in 2012 from the British Committee for Standards in Haematology and in 2017 from the TTP group of Japan’s Blood Coagulation Abnormalities Research Team.

“Since the publication of these guidelines, there have been significant developments in the diagnosis and treatment of TTP, and an increase in published data on how management strategies affect objective health outcomes,” the panel members wrote in the guideline, which is available at ISTH.org.

Despite these advancements, TTP remains a challenging condition for both clinicians and patients for a variety of reasons, the panel noted, which was led by clinical cochair X. Long Zheng, MD, PhD, of the University of Alabama in Birmingham and method cochair Sara K. Vesely, PhD, of the University of Oklahoma, Oklahoma City.

The ISTH guideline provides recommendations for adult patients with either immune or hereditary TTP, from acute events through remission, including diagnostic steps to determine if a case of thrombotic microangiopathy is in fact TTP.

Nearly all the recommendations are based on very-low-certainty evidence. Some of the key treatment recommendations include the following:

• For patients with immune TTP experiencing a first acute event, add corticosteroids to therapeutic plasma exchange (TPE), rather than treating with TPE alone. This is a strong recommendation.
• For patients with immune TTP experiencing a first acute event, add rituximab to corticosteroids and TPE, rather than corticosteroids and TPE alone. This is a conditional recommendation.
• For patients with immune TTP experiencing a relapse, add corticosteroids to TPE, rather than TPE alone. This is a strong recommendation.
• For patients with immune TTP experiencing a relapse, add rituximab to corticosteroids and TPE, rather than steroids and TPE alone. This is a conditional recommendation.
• For patients with immune TTP experiencing an acute event – either a first event or a relapse – use caplacizumab. This is a conditional recommendation based on moderate-certainty evidence.
• For patients with immune TTP who are in remission and have low plasma ADAMTS13 activity but no other symptoms of TMA, use rituximab for prophylaxis. This is a conditional recommendation.
• For patients with hereditary TTP who are in remission, plasma infusion or a watch-and-wait strategy is recommended. This is a conditional recommendation.
• For patients with hereditary TTP who are in remission, do not use factor VIII concentrate infusions. A watch-and-wait strategy is advised. This is a conditional recommendation.
• For patients with immune TTP who are pregnant and have decreased plasma ADAMTS13 activity but no symptoms of TMA, use prophylactic treatment. This is a strong recommendation.
• For patients with hereditary TTP who are pregnant, use prophylactic treatment. This is a strong recommendation. The panel further recommended treatment with plasma infusion rather than factor VIII products, which was a conditional recommendation.

The multidisciplinary expert panel included hematologists and pathologists with expertise in TTP, neurologists, nephrologists, intensive care specialists, and patient representatives. The panel followed the GRADE approach and the Population, Intervention, Comparison, Outcome (PICO) framework, and adhered to standards set forth by the Health and Medicine Division (HMD) of the National Academies of Sciences, Engineering, and Medicine and the GIN-McMaster Guideline Development Checklist.

Even with an experienced group of physicians and a structured plan, however, the creation of guidelines for rare diseases like TTP presents a unique set of obstacles, according to the panel members. Challenges include a small body of relevant evidence that is often inconsistent and lacking in high certainty and studies that do not address outcomes important to patients. These shortcomings can make it difficult for guideline developers to issue strong recommendations.

“However, well-developed clinical practice guidelines are vital in rare diseases; these conditions are, by their nature, encountered very infrequently by individual clinicians, who may feel unprepared to address their diagnosis and treatment,” the panelists wrote. “Well-synthesized evidence and clear recommendations play an important role in supporting clinical decision making. Systematically created guidelines can also highlight areas where evidence is uncertain, clinical judgement is required, and future research in the area is warranted.”

The guideline was supported by ISTH. Fifty percent of the panel members had no or minimal conflict of interest; those with conflicts of interest abstained from voting on recommendations relevant to their conflicts.

An international panel of neurologists has drafted a consensus statement on the diagnosis, prognosis, and treatment of stridor in patients with multiple system atrophy (MSA). The statement was published Oct. 1 in Neurology. In addition to reviewing the literature on the topic and providing recommendations, the authors described several areas for future research.

MSA is a rare neurodegenerative disorder that entails autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor has a high positive predictive value in the diagnosis of MSA, but consensus about its definition and clinical implications had not been established previously. The Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) delle Scienze Neurologiche di Bologna (Italy) convened a consensus conference of experts in 2017 to determine diagnostic criteria for stridor in MSA, define its prognostic value, suggest treatment options, and indicate subjects for future research. The neurologists reviewed studies of any design that reported original data. They based their statements on 34 published articles, most of which were class III or IV.

The authors defined stridor in MSA as “a strained, high-pitched, harsh respiratory sound, mainly inspiratory, caused by laryngeal dysfunction leading to narrowing of the rima glottidis.” Stridor may occur exclusively during sleep or during sleep and wakefulness. It may be recognized during a clinical examination, through witness report, or through an audio recording. Neurologists may consider laryngoscopy to exclude mechanical lesions or functional vocal cord abnormalities related to other neurologic conditions, wrote the authors. Drug-induced sleep endoscopy and video polysomnography also may be considered.

Whether stridor, or certain features of stridor, affects survival in MSA is uncertain. “Stridor within 3 years of motor or autonomic symptom onset may shorten survival,” according to the statement. “However, identification of stridor onset may be difficult.” Moreover, stridor during wakefulness is considered to reflect a more advanced stage of disease, compared with stridor during sleep. Although stridor can be distressing for the patient and his or her caregivers, its influence on health-related quality of life has yet to be determined, according to the statement.

Continuous positive airway pressure (CPAP) during sleep can be a useful symptomatic treatment and should be considered a first-line therapy for stridor, wrote the authors. Tracheostomy, another effective symptomatic treatment, bypasses upper-airway obstruction at the larynx. “Persistent and severe stridor may require tracheostomy,” according to the statement. It is not certain whether CPAP improves survival in patients with MSA and stridor, and tracheostomy may improve survival. The literature contains insufficient evidence about whether minimally invasive procedures or botulinum toxin injections are effective symptomatic treatments for stridor, wrote the authors.

During their review of the literature, the authors identified what they considered to be several research gaps. The diagnosis of stridor remains challenging, and investigators should develop a questionnaire for detecting stridor, they wrote. A smartphone application also could be developed to recognize stridor automatically. “The relationship between stridor and other breathing disorders (i.e., central apneas and breathing rate abnormalities) and their respective contributions to disease prognosis and survival should be determined through a multicenter prospective study,” according to the statement. Finally, randomized controlled trials comparing CPAP and tracheostomy for various degrees of stridor could guide physicians’ choice of treatment.

The IRCCS funded the study. One of the authors is a section editor for Neurology, and other authors reported receiving honoraria from various companies such as Novartis, Sanofi, and UCB.

[email protected]

SOURCE: Cortelli P et al. Neurology. 2019;93(14):630-9.

An international panel of neurologists has drafted a consensus statement on the diagnosis, prognosis, and treatment of stridor in patients with multiple system atrophy (MSA). The statement was published Oct. 1 in Neurology. In addition to reviewing the literature on the topic and providing recommendations, the authors described several areas for future research.

MSA is a rare neurodegenerative disorder that entails autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor has a high positive predictive value in the diagnosis of MSA, but consensus about its definition and clinical implications had not been established previously. The Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) delle Scienze Neurologiche di Bologna (Italy) convened a consensus conference of experts in 2017 to determine diagnostic criteria for stridor in MSA, define its prognostic value, suggest treatment options, and indicate subjects for future research. The neurologists reviewed studies of any design that reported original data. They based their statements on 34 published articles, most of which were class III or IV.

The authors defined stridor in MSA as “a strained, high-pitched, harsh respiratory sound, mainly inspiratory, caused by laryngeal dysfunction leading to narrowing of the rima glottidis.” Stridor may occur exclusively during sleep or during sleep and wakefulness. It may be recognized during a clinical examination, through witness report, or through an audio recording. Neurologists may consider laryngoscopy to exclude mechanical lesions or functional vocal cord abnormalities related to other neurologic conditions, wrote the authors. Drug-induced sleep endoscopy and video polysomnography also may be considered.

Whether stridor, or certain features of stridor, affects survival in MSA is uncertain. “Stridor within 3 years of motor or autonomic symptom onset may shorten survival,” according to the statement. “However, identification of stridor onset may be difficult.” Moreover, stridor during wakefulness is considered to reflect a more advanced stage of disease, compared with stridor during sleep. Although stridor can be distressing for the patient and his or her caregivers, its influence on health-related quality of life has yet to be determined, according to the statement.

Continuous positive airway pressure (CPAP) during sleep can be a useful symptomatic treatment and should be considered a first-line therapy for stridor, wrote the authors. Tracheostomy, another effective symptomatic treatment, bypasses upper-airway obstruction at the larynx. “Persistent and severe stridor may require tracheostomy,” according to the statement. It is not certain whether CPAP improves survival in patients with MSA and stridor, and tracheostomy may improve survival. The literature contains insufficient evidence about whether minimally invasive procedures or botulinum toxin injections are effective symptomatic treatments for stridor, wrote the authors.

During their review of the literature, the authors identified what they considered to be several research gaps. The diagnosis of stridor remains challenging, and investigators should develop a questionnaire for detecting stridor, they wrote. A smartphone application also could be developed to recognize stridor automatically. “The relationship between stridor and other breathing disorders (i.e., central apneas and breathing rate abnormalities) and their respective contributions to disease prognosis and survival should be determined through a multicenter prospective study,” according to the statement. Finally, randomized controlled trials comparing CPAP and tracheostomy for various degrees of stridor could guide physicians’ choice of treatment.

The IRCCS funded the study. One of the authors is a section editor for Neurology, and other authors reported receiving honoraria from various companies such as Novartis, Sanofi, and UCB.

[email protected]

SOURCE: Cortelli P et al. Neurology. 2019;93(14):630-9.

An international panel of neurologists has drafted a consensus statement on the diagnosis, prognosis, and treatment of stridor in patients with multiple system atrophy (MSA). The statement was published Oct. 1 in Neurology. In addition to reviewing the literature on the topic and providing recommendations, the authors described several areas for future research.

MSA is a rare neurodegenerative disorder that entails autonomic failure, cerebellar ataxia, and parkinsonism. Laryngeal stridor has a high positive predictive value in the diagnosis of MSA, but consensus about its definition and clinical implications had not been established previously. The Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) delle Scienze Neurologiche di Bologna (Italy) convened a consensus conference of experts in 2017 to determine diagnostic criteria for stridor in MSA, define its prognostic value, suggest treatment options, and indicate subjects for future research. The neurologists reviewed studies of any design that reported original data. They based their statements on 34 published articles, most of which were class III or IV.

The authors defined stridor in MSA as “a strained, high-pitched, harsh respiratory sound, mainly inspiratory, caused by laryngeal dysfunction leading to narrowing of the rima glottidis.” Stridor may occur exclusively during sleep or during sleep and wakefulness. It may be recognized during a clinical examination, through witness report, or through an audio recording. Neurologists may consider laryngoscopy to exclude mechanical lesions or functional vocal cord abnormalities related to other neurologic conditions, wrote the authors. Drug-induced sleep endoscopy and video polysomnography also may be considered.

Whether stridor, or certain features of stridor, affects survival in MSA is uncertain. “Stridor within 3 years of motor or autonomic symptom onset may shorten survival,” according to the statement. “However, identification of stridor onset may be difficult.” Moreover, stridor during wakefulness is considered to reflect a more advanced stage of disease, compared with stridor during sleep. Although stridor can be distressing for the patient and his or her caregivers, its influence on health-related quality of life has yet to be determined, according to the statement.

Continuous positive airway pressure (CPAP) during sleep can be a useful symptomatic treatment and should be considered a first-line therapy for stridor, wrote the authors. Tracheostomy, another effective symptomatic treatment, bypasses upper-airway obstruction at the larynx. “Persistent and severe stridor may require tracheostomy,” according to the statement. It is not certain whether CPAP improves survival in patients with MSA and stridor, and tracheostomy may improve survival. The literature contains insufficient evidence about whether minimally invasive procedures or botulinum toxin injections are effective symptomatic treatments for stridor, wrote the authors.

During their review of the literature, the authors identified what they considered to be several research gaps. The diagnosis of stridor remains challenging, and investigators should develop a questionnaire for detecting stridor, they wrote. A smartphone application also could be developed to recognize stridor automatically. “The relationship between stridor and other breathing disorders (i.e., central apneas and breathing rate abnormalities) and their respective contributions to disease prognosis and survival should be determined through a multicenter prospective study,” according to the statement. Finally, randomized controlled trials comparing CPAP and tracheostomy for various degrees of stridor could guide physicians’ choice of treatment.

The IRCCS funded the study. One of the authors is a section editor for Neurology, and other authors reported receiving honoraria from various companies such as Novartis, Sanofi, and UCB.

[email protected]

SOURCE: Cortelli P et al. Neurology. 2019;93(14):630-9.

New consensus statements, released by a group of 36 experts, provide specific recommendations related to monitoring bleeding and assessing efficacy of treatment in patients with acquired hemophilia.

Svisio/Thinkstock

A global survey was developed by a nine-member steering committee with expertise in the hemostatic management of patients with acquired hemophilia. The Delphi methodology was used to obtain consensus on a list of statements on the location-specific treatment of bleeding in acquired hemophilia.

“The initial survey was circulated via email for refinement and was formally corroborated at a face-to-face meeting,” wrote Andreas Tiede, MD, PhD, of Hannover (Germany) Medical School and fellow experts. The report is published in Haemophilia.

The key areas outlined include the initial management of bleeding, and management of location-specific bleeding, including urological, gastrointestinal, muscle, and pharyngeal bleeds, as well as intracranial and postpartum hemorrhage.

If an expert hematologist is not available, and the bleeding event is life‐threatening, the emergency physician should initiate treatment in accordance with local or national recommendations, according to the initial management guidelines.

With respect to urological bleeds, the best interval for evaluating successful achievement of hemostasis is every 6-12 hours. The experts also reported that, if first-line hemostatic therapy is not effective, more intensive treatment should be considered every 6-12 hours.

In the management of intracranial hemorrhage, the frequency of clinical evaluation is subject to the particular scenario, and it can vary from every 2 hours (for clinical assessment) to every 24 hours (for imaging studies), they wrote.

If initial hemostatic treatment is not effective, more intensive therapy should be considered every 6 hours, they recommended.

“The statement addressing optimal frequency for assessing hemostasis in intracranial bleeds was the subject of much deliberation among the steering committee regarding timing of assessment,” the experts acknowledged.

The geographic diversity and global representation of expert participants were major strengths of these recommendations. However, these statements did not consider socioeconomic parameters or geopolitical differences that could affect patient care. As a result, they may not be applicable to all patient populations.

The manuscript was funded by Novo Nordisk AG. The authors reported having financial affiliations with Novo Nordisk and several other companies.

SOURCE: Tiede A et al. Haemophilia. 2019 Sep 13. doi: 10.1111/hae.13844.

New consensus statements, released by a group of 36 experts, provide specific recommendations related to monitoring bleeding and assessing efficacy of treatment in patients with acquired hemophilia.

Svisio/Thinkstock

A global survey was developed by a nine-member steering committee with expertise in the hemostatic management of patients with acquired hemophilia. The Delphi methodology was used to obtain consensus on a list of statements on the location-specific treatment of bleeding in acquired hemophilia.

“The initial survey was circulated via email for refinement and was formally corroborated at a face-to-face meeting,” wrote Andreas Tiede, MD, PhD, of Hannover (Germany) Medical School and fellow experts. The report is published in Haemophilia.

The key areas outlined include the initial management of bleeding, and management of location-specific bleeding, including urological, gastrointestinal, muscle, and pharyngeal bleeds, as well as intracranial and postpartum hemorrhage.

If an expert hematologist is not available, and the bleeding event is life‐threatening, the emergency physician should initiate treatment in accordance with local or national recommendations, according to the initial management guidelines.

With respect to urological bleeds, the best interval for evaluating successful achievement of hemostasis is every 6-12 hours. The experts also reported that, if first-line hemostatic therapy is not effective, more intensive treatment should be considered every 6-12 hours.

In the management of intracranial hemorrhage, the frequency of clinical evaluation is subject to the particular scenario, and it can vary from every 2 hours (for clinical assessment) to every 24 hours (for imaging studies), they wrote.

If initial hemostatic treatment is not effective, more intensive therapy should be considered every 6 hours, they recommended.

“The statement addressing optimal frequency for assessing hemostasis in intracranial bleeds was the subject of much deliberation among the steering committee regarding timing of assessment,” the experts acknowledged.

The geographic diversity and global representation of expert participants were major strengths of these recommendations. However, these statements did not consider socioeconomic parameters or geopolitical differences that could affect patient care. As a result, they may not be applicable to all patient populations.

The manuscript was funded by Novo Nordisk AG. The authors reported having financial affiliations with Novo Nordisk and several other companies.

SOURCE: Tiede A et al. Haemophilia. 2019 Sep 13. doi: 10.1111/hae.13844.

New consensus statements, released by a group of 36 experts, provide specific recommendations related to monitoring bleeding and assessing efficacy of treatment in patients with acquired hemophilia.

Svisio/Thinkstock

A global survey was developed by a nine-member steering committee with expertise in the hemostatic management of patients with acquired hemophilia. The Delphi methodology was used to obtain consensus on a list of statements on the location-specific treatment of bleeding in acquired hemophilia.

“The initial survey was circulated via email for refinement and was formally corroborated at a face-to-face meeting,” wrote Andreas Tiede, MD, PhD, of Hannover (Germany) Medical School and fellow experts. The report is published in Haemophilia.

The key areas outlined include the initial management of bleeding, and management of location-specific bleeding, including urological, gastrointestinal, muscle, and pharyngeal bleeds, as well as intracranial and postpartum hemorrhage.

If an expert hematologist is not available, and the bleeding event is life‐threatening, the emergency physician should initiate treatment in accordance with local or national recommendations, according to the initial management guidelines.

With respect to urological bleeds, the best interval for evaluating successful achievement of hemostasis is every 6-12 hours. The experts also reported that, if first-line hemostatic therapy is not effective, more intensive treatment should be considered every 6-12 hours.

In the management of intracranial hemorrhage, the frequency of clinical evaluation is subject to the particular scenario, and it can vary from every 2 hours (for clinical assessment) to every 24 hours (for imaging studies), they wrote.

If initial hemostatic treatment is not effective, more intensive therapy should be considered every 6 hours, they recommended.

“The statement addressing optimal frequency for assessing hemostasis in intracranial bleeds was the subject of much deliberation among the steering committee regarding timing of assessment,” the experts acknowledged.

The geographic diversity and global representation of expert participants were major strengths of these recommendations. However, these statements did not consider socioeconomic parameters or geopolitical differences that could affect patient care. As a result, they may not be applicable to all patient populations.

The manuscript was funded by Novo Nordisk AG. The authors reported having financial affiliations with Novo Nordisk and several other companies.

SOURCE: Tiede A et al. Haemophilia. 2019 Sep 13. doi: 10.1111/hae.13844.

All adult patients with primary sclerosing cholangitis should be screened at least annually for cholangiocarcinoma and gallbladder cancer, particularly in the first year after their diagnosis, according to a clinical practice update published in Clinical Gastroenterology and Hepatology.

Individuals with primary sclerosing cholangitis have a 400-fold higher risk of cholangiocarcinoma, compared with the general population, and around one-third of cancers are detected within 1 year of the cholangitis diagnosis, Christopher L. Bowlus, MD, of the University of California, Davis, and coauthors wrote.

The clinical practice update from the American Gastroenterological Association was in response to the observation that, while there is significant evidence for an increasing incidence of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplant listing among patients with primary sclerosing cholangitis, there is a lack of good evidence to guide cholangiocarcinoma surveillance in these patients.

“The low prevalence and long duration of PSC [primary sclerosing cholangitis] present substantial barriers to better understanding risk stratification, developing biomarkers, and measuring the impact surveillance has on clinical outcomes,” they wrote.

The first recommendation was that surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with primary sclerosing cholangitis, regardless of their disease stage. The authors especially emphasized the importance of surveillance in the first year after a diagnosis of primary sclerosing cholangitis, in patients who also have ulcerative colitis, and in those diagnosed at an older age.

They cited one study that found regular surveillance of patients with primary sclerosing cholangitis was associated with significantly higher 5-year survival rates, compared with those no regular screening (68% vs. 20%; P less than .0061).

In terms of surveillance modalities, the update suggested 6- to 12-monthly imaging of the biliary tree with ultrasound computed tomography, computed tomography, or magnetic resonance imaging – with or without serum carbohydrate antigen 19-9. However the authors wrote that MRI was often preferred to CT because of its superior sensitivity.

They advised against endoscopic retrograde cholangiopancreatography with brush cytology for routine surveillance because of procedural risks. On the other hand, they suggested this procedure, with or without fluorescence in situ hybridization analysis and/or cholangioscopy, could be used for investigation.

“In addition to ERCP [endoscopic retrograde cholangiopancreatography] with brushings, endoscopic ultrasound, intraductal ultrasonography, and cholangioscopy may be used to direct biopsy sampling,” they wrote. Symptoms such as increasing cholestatic biochemistry values, jaundice, fever, right upper quadrant pain, or pruritus should trigger evaluation for cholangiocarcinoma.

However the authors advised “great caution” with the use of fine-needle aspiration of perihilar biliary strictures in liver transplant candidates because of the risk of tumor seeding if the lesion turned out to be cholangiocarcinoma.

On the question of cholangiocarcinoma surveillance in pediatric patients and those with small-duct primary sclerosing cholangitis, the authors wrote that cholangiocarcinoma was so rare in these patients that routine cholangiocarcinoma surveillance was not required.

The clinical update also looked at the prevalence and risk factors for gallbladder cancer, which affects around 2% of individuals with primary sclerosing cholangitis. Two studies found gallbladder polyps in 10%-17% of patients, but the authors noted that “the optimal modality for diagnosis of gallbladder polyps in PSC remains unknown”.

“Because of the high risk of malignancy in gallbladder mass lesions and a 5-year survival rate of 5% to 10% for gallbladder cancer, patients should undergo annual US [ultrasound] screening,” they wrote.

They said the question of whether to perform a cholecystectomy in patients with gallbladder polyps should be guided by the size and growth of the polyps because there is an increased risk of gallbladder cancer in polyps larger than 8 mm and by the clinical status of the patient.

Finally, the update examined the issue of hepatocellular carcinoma in patients with primary sclerosing cholangitis, which – while rare – may increase with the presence of cirrhosis.

The authors advised that patients with primary sclerosing cholangitis and cirrhosis should undergo surveillance for hepatocellular carcinoma every 6 months with ultrasound, CT, or MRI.

“We anticipate that with the development of large patient cohorts, advances in uncovering genetic and other risk factors for cholangiocarcinoma, and development of effective treatments for PSC, further refinement of this practice update will be required.”

Two authors declared consultancies, grants and research contracts with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Bowlus C et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi 10.1016/j.cgh.2019.07.011.

All adult patients with primary sclerosing cholangitis should be screened at least annually for cholangiocarcinoma and gallbladder cancer, particularly in the first year after their diagnosis, according to a clinical practice update published in Clinical Gastroenterology and Hepatology.

Individuals with primary sclerosing cholangitis have a 400-fold higher risk of cholangiocarcinoma, compared with the general population, and around one-third of cancers are detected within 1 year of the cholangitis diagnosis, Christopher L. Bowlus, MD, of the University of California, Davis, and coauthors wrote.

The clinical practice update from the American Gastroenterological Association was in response to the observation that, while there is significant evidence for an increasing incidence of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplant listing among patients with primary sclerosing cholangitis, there is a lack of good evidence to guide cholangiocarcinoma surveillance in these patients.

“The low prevalence and long duration of PSC [primary sclerosing cholangitis] present substantial barriers to better understanding risk stratification, developing biomarkers, and measuring the impact surveillance has on clinical outcomes,” they wrote.

The first recommendation was that surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with primary sclerosing cholangitis, regardless of their disease stage. The authors especially emphasized the importance of surveillance in the first year after a diagnosis of primary sclerosing cholangitis, in patients who also have ulcerative colitis, and in those diagnosed at an older age.

They cited one study that found regular surveillance of patients with primary sclerosing cholangitis was associated with significantly higher 5-year survival rates, compared with those no regular screening (68% vs. 20%; P less than .0061).

In terms of surveillance modalities, the update suggested 6- to 12-monthly imaging of the biliary tree with ultrasound computed tomography, computed tomography, or magnetic resonance imaging – with or without serum carbohydrate antigen 19-9. However the authors wrote that MRI was often preferred to CT because of its superior sensitivity.

They advised against endoscopic retrograde cholangiopancreatography with brush cytology for routine surveillance because of procedural risks. On the other hand, they suggested this procedure, with or without fluorescence in situ hybridization analysis and/or cholangioscopy, could be used for investigation.

“In addition to ERCP [endoscopic retrograde cholangiopancreatography] with brushings, endoscopic ultrasound, intraductal ultrasonography, and cholangioscopy may be used to direct biopsy sampling,” they wrote. Symptoms such as increasing cholestatic biochemistry values, jaundice, fever, right upper quadrant pain, or pruritus should trigger evaluation for cholangiocarcinoma.

However the authors advised “great caution” with the use of fine-needle aspiration of perihilar biliary strictures in liver transplant candidates because of the risk of tumor seeding if the lesion turned out to be cholangiocarcinoma.

On the question of cholangiocarcinoma surveillance in pediatric patients and those with small-duct primary sclerosing cholangitis, the authors wrote that cholangiocarcinoma was so rare in these patients that routine cholangiocarcinoma surveillance was not required.

The clinical update also looked at the prevalence and risk factors for gallbladder cancer, which affects around 2% of individuals with primary sclerosing cholangitis. Two studies found gallbladder polyps in 10%-17% of patients, but the authors noted that “the optimal modality for diagnosis of gallbladder polyps in PSC remains unknown”.

“Because of the high risk of malignancy in gallbladder mass lesions and a 5-year survival rate of 5% to 10% for gallbladder cancer, patients should undergo annual US [ultrasound] screening,” they wrote.

They said the question of whether to perform a cholecystectomy in patients with gallbladder polyps should be guided by the size and growth of the polyps because there is an increased risk of gallbladder cancer in polyps larger than 8 mm and by the clinical status of the patient.

Finally, the update examined the issue of hepatocellular carcinoma in patients with primary sclerosing cholangitis, which – while rare – may increase with the presence of cirrhosis.

The authors advised that patients with primary sclerosing cholangitis and cirrhosis should undergo surveillance for hepatocellular carcinoma every 6 months with ultrasound, CT, or MRI.

“We anticipate that with the development of large patient cohorts, advances in uncovering genetic and other risk factors for cholangiocarcinoma, and development of effective treatments for PSC, further refinement of this practice update will be required.”

Two authors declared consultancies, grants and research contracts with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Bowlus C et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi 10.1016/j.cgh.2019.07.011.

All adult patients with primary sclerosing cholangitis should be screened at least annually for cholangiocarcinoma and gallbladder cancer, particularly in the first year after their diagnosis, according to a clinical practice update published in Clinical Gastroenterology and Hepatology.

Individuals with primary sclerosing cholangitis have a 400-fold higher risk of cholangiocarcinoma, compared with the general population, and around one-third of cancers are detected within 1 year of the cholangitis diagnosis, Christopher L. Bowlus, MD, of the University of California, Davis, and coauthors wrote.

The clinical practice update from the American Gastroenterological Association was in response to the observation that, while there is significant evidence for an increasing incidence of cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver transplant listing among patients with primary sclerosing cholangitis, there is a lack of good evidence to guide cholangiocarcinoma surveillance in these patients.

“The low prevalence and long duration of PSC [primary sclerosing cholangitis] present substantial barriers to better understanding risk stratification, developing biomarkers, and measuring the impact surveillance has on clinical outcomes,” they wrote.

The first recommendation was that surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with primary sclerosing cholangitis, regardless of their disease stage. The authors especially emphasized the importance of surveillance in the first year after a diagnosis of primary sclerosing cholangitis, in patients who also have ulcerative colitis, and in those diagnosed at an older age.

They cited one study that found regular surveillance of patients with primary sclerosing cholangitis was associated with significantly higher 5-year survival rates, compared with those no regular screening (68% vs. 20%; P less than .0061).

In terms of surveillance modalities, the update suggested 6- to 12-monthly imaging of the biliary tree with ultrasound computed tomography, computed tomography, or magnetic resonance imaging – with or without serum carbohydrate antigen 19-9. However the authors wrote that MRI was often preferred to CT because of its superior sensitivity.

They advised against endoscopic retrograde cholangiopancreatography with brush cytology for routine surveillance because of procedural risks. On the other hand, they suggested this procedure, with or without fluorescence in situ hybridization analysis and/or cholangioscopy, could be used for investigation.

“In addition to ERCP [endoscopic retrograde cholangiopancreatography] with brushings, endoscopic ultrasound, intraductal ultrasonography, and cholangioscopy may be used to direct biopsy sampling,” they wrote. Symptoms such as increasing cholestatic biochemistry values, jaundice, fever, right upper quadrant pain, or pruritus should trigger evaluation for cholangiocarcinoma.

However the authors advised “great caution” with the use of fine-needle aspiration of perihilar biliary strictures in liver transplant candidates because of the risk of tumor seeding if the lesion turned out to be cholangiocarcinoma.

On the question of cholangiocarcinoma surveillance in pediatric patients and those with small-duct primary sclerosing cholangitis, the authors wrote that cholangiocarcinoma was so rare in these patients that routine cholangiocarcinoma surveillance was not required.

The clinical update also looked at the prevalence and risk factors for gallbladder cancer, which affects around 2% of individuals with primary sclerosing cholangitis. Two studies found gallbladder polyps in 10%-17% of patients, but the authors noted that “the optimal modality for diagnosis of gallbladder polyps in PSC remains unknown”.

“Because of the high risk of malignancy in gallbladder mass lesions and a 5-year survival rate of 5% to 10% for gallbladder cancer, patients should undergo annual US [ultrasound] screening,” they wrote.

They said the question of whether to perform a cholecystectomy in patients with gallbladder polyps should be guided by the size and growth of the polyps because there is an increased risk of gallbladder cancer in polyps larger than 8 mm and by the clinical status of the patient.

Finally, the update examined the issue of hepatocellular carcinoma in patients with primary sclerosing cholangitis, which – while rare – may increase with the presence of cirrhosis.

The authors advised that patients with primary sclerosing cholangitis and cirrhosis should undergo surveillance for hepatocellular carcinoma every 6 months with ultrasound, CT, or MRI.

“We anticipate that with the development of large patient cohorts, advances in uncovering genetic and other risk factors for cholangiocarcinoma, and development of effective treatments for PSC, further refinement of this practice update will be required.”

Two authors declared consultancies, grants and research contracts with the pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Bowlus C et al. Clin Gastroenterol Hepatol. 2019 Jul 12. doi 10.1016/j.cgh.2019.07.011.

Patients 50-79 years old with a demonstrably low risk of developing the disease within 15 years probably don’t need to be screened for colorectal cancer. But if their risk of disease is at least 3% over 15 years, patients should be screened, Lise M. Helsingen, MD, and colleagues wrote in BMJ (2019;367:l5515 doi: 10.1136/bmj.l5515).

For these patients, “We suggest screening with one of the four screening options: fecal immunochemical test (FIT) every year, FIT every 2 years, a single sigmoidoscopy, or a single colonoscopy,” wrote Dr. Helsingen of the University of Oslo, and her team.

She chaired a 22-member international panel that developed a collaborative effort from the MAGIC research and innovation program as a part of the BMJ Rapid Recommendations project. The team reviewed 12 research papers comprising almost 1.4 million patients from Denmark, Italy, the Netherlands, Norway, Poland, Spain, Sweden, the United Kingdom, and the United States. Follow-up ranged from 0 to 19.5 years for colorectal cancer incidence and up to 30 years for mortality.

Because of the dearth of relevant data in some studies, however, the projected outcomes had to be simulated, with benefits and harms calculations based on 100% screening adherence. However, the team noted, it’s impossible to achieve complete adherence. Most studies of colorectal screening don’t exceed a 50% adherence level.

“All the modeling data are of low certainty. It is a useful indication, but there is a high chance that new evidence will show a smaller or larger benefit, which in turn may alter these recommendations.”

Compared with no screening, all four screening models reduced the risk of colorectal cancer mortality to a similar level.

• FIT every year, 59%.
• FIT every 2 years, 50%.
• Single sigmoidoscopy, 52%.
• Single colonoscopy, 67%.

Screening had less of an impact on reducing the incidence of colorectal cancer:

• FIT every 2 years, 0.05%.
• FIT every year, 0.15%.
• Single sigmoidoscopy, 27%.
• Single colonoscopy, 34%.

The panel also assessed potential harms. Among almost 1 million patients, the colonoscopy-related mortality rate was 0.03 per 1,000 procedures. The perforation rate was 0.8 per 1,000 colonoscopies after a positive fecal test, and 1.4 per 1,000 screened with sigmoidoscopy. The bleeding rate was 1.9 per 1,000 colonoscopies performed after a positive fecal test, and 3-4 per 1,000 screened with sigmoidoscopy.

Successful implementation of these recommendations hinges on accurate risk assessment, however. The team recommended the QCancer platform as “one of the best performing models for both men and women.”

The calculator includes age, sex, ethnicity, smoking status, alcohol use, family history of gastrointestinal cancer, personal history of other cancers, diabetes, ulcerative colitis, colonic polyps, and body mass index.

“We suggest this model because it is available as an online calculator; includes only risk factors available in routine health care; has been validated in a population separate from the derivation population; has reasonable discriminatory ability; and has a good fit between predicted and observed outcomes. In addition, it is the only online risk calculator we know of that predicts risk over a 15-year time horizon.”

The team stressed that their recommendations can’t be applied to all patients. Because evidence for both screening recommendations was weak – largely because of the dearth of supporting data – patients and physicians should cocreate a personalized screening plan.

“Several factors influence individuals’ decisions whether to be screened, even when they are presented with the same information,” the authors said. These include variation in an individual’s values and preferences, a close balance of benefits versus harms and burdens, and personal preference.

“Some individuals may value a minimally invasive test such as FIT, and the possibility of invasive screening with colonoscopy might put them off screening altogether. Those who most value preventing colorectal cancer or avoiding repeated testing are likely to choose sigmoidoscopy or colonoscopy.”

The authors had no financial conflicts of interest.

SOURCE: BMJ 2019;367:l5515. doi: 10.1136/bmj.l5515.

Patients 50-79 years old with a demonstrably low risk of developing the disease within 15 years probably don’t need to be screened for colorectal cancer. But if their risk of disease is at least 3% over 15 years, patients should be screened, Lise M. Helsingen, MD, and colleagues wrote in BMJ (2019;367:l5515 doi: 10.1136/bmj.l5515).

For these patients, “We suggest screening with one of the four screening options: fecal immunochemical test (FIT) every year, FIT every 2 years, a single sigmoidoscopy, or a single colonoscopy,” wrote Dr. Helsingen of the University of Oslo, and her team.

She chaired a 22-member international panel that developed a collaborative effort from the MAGIC research and innovation program as a part of the BMJ Rapid Recommendations project. The team reviewed 12 research papers comprising almost 1.4 million patients from Denmark, Italy, the Netherlands, Norway, Poland, Spain, Sweden, the United Kingdom, and the United States. Follow-up ranged from 0 to 19.5 years for colorectal cancer incidence and up to 30 years for mortality.

Because of the dearth of relevant data in some studies, however, the projected outcomes had to be simulated, with benefits and harms calculations based on 100% screening adherence. However, the team noted, it’s impossible to achieve complete adherence. Most studies of colorectal screening don’t exceed a 50% adherence level.

“All the modeling data are of low certainty. It is a useful indication, but there is a high chance that new evidence will show a smaller or larger benefit, which in turn may alter these recommendations.”

Compared with no screening, all four screening models reduced the risk of colorectal cancer mortality to a similar level.

• FIT every year, 59%.
• FIT every 2 years, 50%.
• Single sigmoidoscopy, 52%.
• Single colonoscopy, 67%.

Screening had less of an impact on reducing the incidence of colorectal cancer:

• FIT every 2 years, 0.05%.
• FIT every year, 0.15%.
• Single sigmoidoscopy, 27%.
• Single colonoscopy, 34%.

The panel also assessed potential harms. Among almost 1 million patients, the colonoscopy-related mortality rate was 0.03 per 1,000 procedures. The perforation rate was 0.8 per 1,000 colonoscopies after a positive fecal test, and 1.4 per 1,000 screened with sigmoidoscopy. The bleeding rate was 1.9 per 1,000 colonoscopies performed after a positive fecal test, and 3-4 per 1,000 screened with sigmoidoscopy.

Successful implementation of these recommendations hinges on accurate risk assessment, however. The team recommended the QCancer platform as “one of the best performing models for both men and women.”

The calculator includes age, sex, ethnicity, smoking status, alcohol use, family history of gastrointestinal cancer, personal history of other cancers, diabetes, ulcerative colitis, colonic polyps, and body mass index.

“We suggest this model because it is available as an online calculator; includes only risk factors available in routine health care; has been validated in a population separate from the derivation population; has reasonable discriminatory ability; and has a good fit between predicted and observed outcomes. In addition, it is the only online risk calculator we know of that predicts risk over a 15-year time horizon.”

The team stressed that their recommendations can’t be applied to all patients. Because evidence for both screening recommendations was weak – largely because of the dearth of supporting data – patients and physicians should cocreate a personalized screening plan.

“Several factors influence individuals’ decisions whether to be screened, even when they are presented with the same information,” the authors said. These include variation in an individual’s values and preferences, a close balance of benefits versus harms and burdens, and personal preference.

“Some individuals may value a minimally invasive test such as FIT, and the possibility of invasive screening with colonoscopy might put them off screening altogether. Those who most value preventing colorectal cancer or avoiding repeated testing are likely to choose sigmoidoscopy or colonoscopy.”

The authors had no financial conflicts of interest.

SOURCE: BMJ 2019;367:l5515. doi: 10.1136/bmj.l5515.

Patients 50-79 years old with a demonstrably low risk of developing the disease within 15 years probably don’t need to be screened for colorectal cancer. But if their risk of disease is at least 3% over 15 years, patients should be screened, Lise M. Helsingen, MD, and colleagues wrote in BMJ (2019;367:l5515 doi: 10.1136/bmj.l5515).

For these patients, “We suggest screening with one of the four screening options: fecal immunochemical test (FIT) every year, FIT every 2 years, a single sigmoidoscopy, or a single colonoscopy,” wrote Dr. Helsingen of the University of Oslo, and her team.

She chaired a 22-member international panel that developed a collaborative effort from the MAGIC research and innovation program as a part of the BMJ Rapid Recommendations project. The team reviewed 12 research papers comprising almost 1.4 million patients from Denmark, Italy, the Netherlands, Norway, Poland, Spain, Sweden, the United Kingdom, and the United States. Follow-up ranged from 0 to 19.5 years for colorectal cancer incidence and up to 30 years for mortality.

Because of the dearth of relevant data in some studies, however, the projected outcomes had to be simulated, with benefits and harms calculations based on 100% screening adherence. However, the team noted, it’s impossible to achieve complete adherence. Most studies of colorectal screening don’t exceed a 50% adherence level.

“All the modeling data are of low certainty. It is a useful indication, but there is a high chance that new evidence will show a smaller or larger benefit, which in turn may alter these recommendations.”

Compared with no screening, all four screening models reduced the risk of colorectal cancer mortality to a similar level.

• FIT every year, 59%.
• FIT every 2 years, 50%.
• Single sigmoidoscopy, 52%.
• Single colonoscopy, 67%.

Screening had less of an impact on reducing the incidence of colorectal cancer:

• FIT every 2 years, 0.05%.
• FIT every year, 0.15%.
• Single sigmoidoscopy, 27%.
• Single colonoscopy, 34%.

The panel also assessed potential harms. Among almost 1 million patients, the colonoscopy-related mortality rate was 0.03 per 1,000 procedures. The perforation rate was 0.8 per 1,000 colonoscopies after a positive fecal test, and 1.4 per 1,000 screened with sigmoidoscopy. The bleeding rate was 1.9 per 1,000 colonoscopies performed after a positive fecal test, and 3-4 per 1,000 screened with sigmoidoscopy.

Successful implementation of these recommendations hinges on accurate risk assessment, however. The team recommended the QCancer platform as “one of the best performing models for both men and women.”

The calculator includes age, sex, ethnicity, smoking status, alcohol use, family history of gastrointestinal cancer, personal history of other cancers, diabetes, ulcerative colitis, colonic polyps, and body mass index.

“We suggest this model because it is available as an online calculator; includes only risk factors available in routine health care; has been validated in a population separate from the derivation population; has reasonable discriminatory ability; and has a good fit between predicted and observed outcomes. In addition, it is the only online risk calculator we know of that predicts risk over a 15-year time horizon.”

The team stressed that their recommendations can’t be applied to all patients. Because evidence for both screening recommendations was weak – largely because of the dearth of supporting data – patients and physicians should cocreate a personalized screening plan.

“Several factors influence individuals’ decisions whether to be screened, even when they are presented with the same information,” the authors said. These include variation in an individual’s values and preferences, a close balance of benefits versus harms and burdens, and personal preference.

“Some individuals may value a minimally invasive test such as FIT, and the possibility of invasive screening with colonoscopy might put them off screening altogether. Those who most value preventing colorectal cancer or avoiding repeated testing are likely to choose sigmoidoscopy or colonoscopy.”

The authors had no financial conflicts of interest.

SOURCE: BMJ 2019;367:l5515. doi: 10.1136/bmj.l5515.