New developments in treatment of neuromyelitis optica spectrum disorder (NMOSD) have opened up options for disease treatment in pediatric patients, but have led to some uncertainty and confusion as well.

At the2020 CNS-ICNA Conjoint Meeting, held virtually this year, presenters discussed some of the challenges of differential diagnosis and treatment choice in pediatric NMOSD, which is easily confused with multiple sclerosis.

NMOSD used to be considered a monophasic disease restricted to the optic nerve and spinal cord, but is now known to affect other regions of the central nervous system and to relapse in some patients.
 

Diagnosis

The disease is often mediated by antibodies to the aquaporin-4 (AQP-4) water channel, but about 30% of adult patients lack the antibody, and AQP-4 seronegativity is more common in the pediatric population. Another common antibody found in 40%–50% of children with NMOSD targets myelin oligodendrocyte glycoprotein (MOG).

It is important to be aware that false negatives can occur in serology assays, and false positives are common, particularly in ELISA assays, Silvia N. Tenembaum, MD, said during her presentation. For those reasons, serology is not enough for a diagnosis. “Patients should also have compatible symptoms and MRI findings,” said Dr. Tenembaum, director of the pediatric neuroimmunology program at National Pediatric Hospital in Buenos Aires.

According to international consensus criteria, to be diagnosed with NMOSD, AQP-4 seropositive patients should also have at least one core clinical symptom: optic neuritis, acute myelitis, area postrema syndrome, other acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic clinical syndrome, or symptomatic cerebral syndrome. AQP-4 seronegative patients or with unknown status should have at least two core symptoms, one of which must be optic neuritis, acute myelitis, or area postrema syndrome. Both conventional MRI and advanced new techniques are important for achieving differential diagnosis.

The most common symptom in children is optic neuritis, which occurs in 50%-70% of patients. Cerebral syndromes with or without encephalopathy and large tumefactive white matter lesions are also common, according to Dr. Tenembaum.

There are many conditions that mimic the spinal cord and optic nerve symptoms of NMOSD, which must be ruled out. One example is optic myelopathy and vision loss from late-onset biotinylase deficiency. It is critical to rule that out because it is treatable with supplements. Optic neuropathy, papillitis, and papilledema can also resemble NMOSD.

It is critical to achieve an early diagnosis of NMOSD in children, because some MS drugs can worsen NMOSD, according to Thaís Armangue, MD, PhD, head of neuroimmunology at SJD Barcelona Children’s Hospital, who also presented at the session. She pointed out that the MOG antibody, while common in children, is also associated with many demyelinating diseases. Some 50%-60% of children with acute disseminated encephalomyelitis (ADEM) have high titers of MOG antibodies. Although early studies suggested that persistent anti-MOG antibodies were associated with risk of developing MS, more recent studies show it predicts a non-MS disease course, particularly at titers greater than 1:1280, according to Dr. Tenembaum. Persistent anti-MOG antibodies are also associated with relapsing disease, but it is associated with other syndromes besides NMOSD. “The probability is that [MOG antibodies are] useful, but they cannot guide chronic immunotherapy, because even monophasic patients can last maybe 12 months before they become MOG negative, and we cannot wait so many months” to determine treatment course, said Dr. Tenembaum.

For monophasic ADEM or NMOSD, there is no need for chronic treatment. But children with MS and recurrent NMOSD require early chronic immunotherapy because specific therapies have been shown to improve prognosis.
 

Acute treatment

When it comes to acute treatment of NMOSD, the goal is to suppress the inflammatory attack but also to minimize long-term damage and optimize long-term neurological function. “The potential for irreversible injury with an attack is very high, and cumulative disabilities in NMOSD can result directly from attacks,” E. Ann Yeh, MD, director of the Pediatric MS and Neuroinflammatory Disorders Program at the Hospital for Sick Children at the University of Toronto, said during her talk.

IV steroids are generally the first choice, with a preference for methylprednisolone. Pediatric patients that are MOG antibody positive usually respond better and more quickly than do adults, with rapid daily improvements in mobility, vomiting, and eyesight. Dr. Yeh recommends weaning good responders off steroids because AQP-4 positive patients are likely to relapse without a steroid wean, and antibody testing may be unavailable or results may be delayed. The wean can range from 4 weeks to 4-6 months, depending on antibody status, likelihood of AQP-4 positivity, and clinical parameters.

Inadequate responses are usually pretty evident. If there is only light perception by day 4 or 5, or paralyzed patients are nonambulatory and achieve only twitchy movements by that time, second-line therapies should be considered, including therapeutic plasma exchange (TPE) with 5-7 exchanges or intravenous immunoglobulins (IVIg).

Dr. Yeh called for quick treatment. Whatever you do, “please do it sooner rather than later if you think there’s no response [to steroids],” Dr. Yeh said.

TPE is the first choice, according to Dr. Yeh. “There seems to be a fair amount of information that suggests that if you’re having difficulty getting a response to steroids, TPE can make a difference in these patients,” she said. But in some cases TPE may not be available, and IVIg can be attempted first. If it achieves no or only marginal improvement, TPE can be attempted later, but it must be kept in mind that TPE conducted too soon could wash out IVIg. Patients who get much better on IVIg can undergo a steroid wean, and then be evaluated for prophylactic therapy, said Dr. Yeh.

The evidence for IVIg is limited, reflecting the difficulty of studying treatments in rare populations. Still, when TPE is not available and the patient is quite impaired, IVIg makes sense to try. “Absence of evidence does not mean that the therapy doesn’t work, and I don’t think we should throw out the baby with the bath water,” said Dr. Yeh.

Although IVIg treatment is generally well tolerated, there have been a few serious adverse events, such as anaphylactic shock and aseptic meningitis, according to Andrea Savransky, MD, a pediatrician at National Pediatric Hospital in Buenos Aires, who also spoke at the session. “I think it is important to weigh the benefits against the risk,” Dr. Savransky said. She noted that TPE should not be taken lightly. One study showed more complications in pediatric patients than in adult patients, and it must be performed in specialized centers.
 

Emerging treaments

Tanuja Chitnis, MD, director of the Partners Pediatric MS Center at Massachusetts General Hospital, Boston, discussed some of the emerging treatments for pediatric NMOSD. Rituximab has been associated with success in some retrospective studies, but dosing should be personalized. Dr. Chitnis reported that B cells can return before 6 months, so she monitors B cells beginning 2 months after induction, redosing after 4 or 5 months rather than 6 if B cells return.

Nevertheless, relapses can still occur after rituximab therapy. “There is room for additional therapies to address this gap,” said Dr. Chitnis. Three new antibodies have received approval for treatment of NMOSD in adults. These include the complement inhibitor eculizumab, the IL-6 receptor antibody satralizumab, and the anti-CD19 antibody inebilizumab. Phase 3 clinical trials in children have been conducted for eculizumab and are in the planning stage for inebilizumab, and pediatric patients were included in pivotal trials for satralizumab.

Eculizumab treatment resulted in a 94.2% reduction in relapse risk in AQP4-positive adults. Satralizumab showed a 79% reduction in relapse risk among AQP-4 positive subjects with NMOSD or neuromyelitis optica and a 34% reduction in those who were AQP-4 negative. The pediatric subgroup had similar levels of response to adults, though the numbers were too small for a subgroup analysis.

In AQP-4 positive patients, inebilizumab treatment yielded a 77% reduction in relapse rate. In all patients, there was a 73% reduction.

For MOG antibody-positive patients with AQP-4 negative disease, novel therapies are at earlier stages of development. Typical MS therapies such as interferon beta and glatiramer acetate don’t seem to be effective. Some that have shown signs of efficacy include azathioprine, mycophenylate mofetil, rituximab, and IVIg infusion, but the state of the field is not encouraging. “This is an observation now being studied in larger cohorts, but in general I have not found that there’s a very strong response to any of these therapies, possibly with the exception of IVIg,” said Dr. Chitnis.

Dr. Tenembaum has no relevant financial disclosures. Dr. Armangue has received speaking honoraria from Novartis and travel expenses for scientific meetings from Merck, Biogen, and Roche. Dr. Yeh is on the scientific advisory board of Juno Therapeutics and has received research support from Biogen. Dr. Chitnis advises Biogen-Idec, Novartis, and Alexion, serves on clinical trial advisory boards for Novartis and Sanofi Aventis, and has received research support from Verily, EMD Serono, and Novartis. Dr. Savransky has received honoraria from Genzyme de Argentina SA.

New developments in treatment of neuromyelitis optica spectrum disorder (NMOSD) have opened up options for disease treatment in pediatric patients, but have led to some uncertainty and confusion as well.

At the2020 CNS-ICNA Conjoint Meeting, held virtually this year, presenters discussed some of the challenges of differential diagnosis and treatment choice in pediatric NMOSD, which is easily confused with multiple sclerosis.

NMOSD used to be considered a monophasic disease restricted to the optic nerve and spinal cord, but is now known to affect other regions of the central nervous system and to relapse in some patients.
 

Diagnosis

The disease is often mediated by antibodies to the aquaporin-4 (AQP-4) water channel, but about 30% of adult patients lack the antibody, and AQP-4 seronegativity is more common in the pediatric population. Another common antibody found in 40%–50% of children with NMOSD targets myelin oligodendrocyte glycoprotein (MOG).

It is important to be aware that false negatives can occur in serology assays, and false positives are common, particularly in ELISA assays, Silvia N. Tenembaum, MD, said during her presentation. For those reasons, serology is not enough for a diagnosis. “Patients should also have compatible symptoms and MRI findings,” said Dr. Tenembaum, director of the pediatric neuroimmunology program at National Pediatric Hospital in Buenos Aires.

According to international consensus criteria, to be diagnosed with NMOSD, AQP-4 seropositive patients should also have at least one core clinical symptom: optic neuritis, acute myelitis, area postrema syndrome, other acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic clinical syndrome, or symptomatic cerebral syndrome. AQP-4 seronegative patients or with unknown status should have at least two core symptoms, one of which must be optic neuritis, acute myelitis, or area postrema syndrome. Both conventional MRI and advanced new techniques are important for achieving differential diagnosis.

The most common symptom in children is optic neuritis, which occurs in 50%-70% of patients. Cerebral syndromes with or without encephalopathy and large tumefactive white matter lesions are also common, according to Dr. Tenembaum.

There are many conditions that mimic the spinal cord and optic nerve symptoms of NMOSD, which must be ruled out. One example is optic myelopathy and vision loss from late-onset biotinylase deficiency. It is critical to rule that out because it is treatable with supplements. Optic neuropathy, papillitis, and papilledema can also resemble NMOSD.

It is critical to achieve an early diagnosis of NMOSD in children, because some MS drugs can worsen NMOSD, according to Thaís Armangue, MD, PhD, head of neuroimmunology at SJD Barcelona Children’s Hospital, who also presented at the session. She pointed out that the MOG antibody, while common in children, is also associated with many demyelinating diseases. Some 50%-60% of children with acute disseminated encephalomyelitis (ADEM) have high titers of MOG antibodies. Although early studies suggested that persistent anti-MOG antibodies were associated with risk of developing MS, more recent studies show it predicts a non-MS disease course, particularly at titers greater than 1:1280, according to Dr. Tenembaum. Persistent anti-MOG antibodies are also associated with relapsing disease, but it is associated with other syndromes besides NMOSD. “The probability is that [MOG antibodies are] useful, but they cannot guide chronic immunotherapy, because even monophasic patients can last maybe 12 months before they become MOG negative, and we cannot wait so many months” to determine treatment course, said Dr. Tenembaum.

For monophasic ADEM or NMOSD, there is no need for chronic treatment. But children with MS and recurrent NMOSD require early chronic immunotherapy because specific therapies have been shown to improve prognosis.
 

Acute treatment

When it comes to acute treatment of NMOSD, the goal is to suppress the inflammatory attack but also to minimize long-term damage and optimize long-term neurological function. “The potential for irreversible injury with an attack is very high, and cumulative disabilities in NMOSD can result directly from attacks,” E. Ann Yeh, MD, director of the Pediatric MS and Neuroinflammatory Disorders Program at the Hospital for Sick Children at the University of Toronto, said during her talk.

IV steroids are generally the first choice, with a preference for methylprednisolone. Pediatric patients that are MOG antibody positive usually respond better and more quickly than do adults, with rapid daily improvements in mobility, vomiting, and eyesight. Dr. Yeh recommends weaning good responders off steroids because AQP-4 positive patients are likely to relapse without a steroid wean, and antibody testing may be unavailable or results may be delayed. The wean can range from 4 weeks to 4-6 months, depending on antibody status, likelihood of AQP-4 positivity, and clinical parameters.

Inadequate responses are usually pretty evident. If there is only light perception by day 4 or 5, or paralyzed patients are nonambulatory and achieve only twitchy movements by that time, second-line therapies should be considered, including therapeutic plasma exchange (TPE) with 5-7 exchanges or intravenous immunoglobulins (IVIg).

Dr. Yeh called for quick treatment. Whatever you do, “please do it sooner rather than later if you think there’s no response [to steroids],” Dr. Yeh said.

TPE is the first choice, according to Dr. Yeh. “There seems to be a fair amount of information that suggests that if you’re having difficulty getting a response to steroids, TPE can make a difference in these patients,” she said. But in some cases TPE may not be available, and IVIg can be attempted first. If it achieves no or only marginal improvement, TPE can be attempted later, but it must be kept in mind that TPE conducted too soon could wash out IVIg. Patients who get much better on IVIg can undergo a steroid wean, and then be evaluated for prophylactic therapy, said Dr. Yeh.

The evidence for IVIg is limited, reflecting the difficulty of studying treatments in rare populations. Still, when TPE is not available and the patient is quite impaired, IVIg makes sense to try. “Absence of evidence does not mean that the therapy doesn’t work, and I don’t think we should throw out the baby with the bath water,” said Dr. Yeh.

Although IVIg treatment is generally well tolerated, there have been a few serious adverse events, such as anaphylactic shock and aseptic meningitis, according to Andrea Savransky, MD, a pediatrician at National Pediatric Hospital in Buenos Aires, who also spoke at the session. “I think it is important to weigh the benefits against the risk,” Dr. Savransky said. She noted that TPE should not be taken lightly. One study showed more complications in pediatric patients than in adult patients, and it must be performed in specialized centers.
 

Emerging treaments

Tanuja Chitnis, MD, director of the Partners Pediatric MS Center at Massachusetts General Hospital, Boston, discussed some of the emerging treatments for pediatric NMOSD. Rituximab has been associated with success in some retrospective studies, but dosing should be personalized. Dr. Chitnis reported that B cells can return before 6 months, so she monitors B cells beginning 2 months after induction, redosing after 4 or 5 months rather than 6 if B cells return.

Nevertheless, relapses can still occur after rituximab therapy. “There is room for additional therapies to address this gap,” said Dr. Chitnis. Three new antibodies have received approval for treatment of NMOSD in adults. These include the complement inhibitor eculizumab, the IL-6 receptor antibody satralizumab, and the anti-CD19 antibody inebilizumab. Phase 3 clinical trials in children have been conducted for eculizumab and are in the planning stage for inebilizumab, and pediatric patients were included in pivotal trials for satralizumab.

Eculizumab treatment resulted in a 94.2% reduction in relapse risk in AQP4-positive adults. Satralizumab showed a 79% reduction in relapse risk among AQP-4 positive subjects with NMOSD or neuromyelitis optica and a 34% reduction in those who were AQP-4 negative. The pediatric subgroup had similar levels of response to adults, though the numbers were too small for a subgroup analysis.

In AQP-4 positive patients, inebilizumab treatment yielded a 77% reduction in relapse rate. In all patients, there was a 73% reduction.

For MOG antibody-positive patients with AQP-4 negative disease, novel therapies are at earlier stages of development. Typical MS therapies such as interferon beta and glatiramer acetate don’t seem to be effective. Some that have shown signs of efficacy include azathioprine, mycophenylate mofetil, rituximab, and IVIg infusion, but the state of the field is not encouraging. “This is an observation now being studied in larger cohorts, but in general I have not found that there’s a very strong response to any of these therapies, possibly with the exception of IVIg,” said Dr. Chitnis.

Dr. Tenembaum has no relevant financial disclosures. Dr. Armangue has received speaking honoraria from Novartis and travel expenses for scientific meetings from Merck, Biogen, and Roche. Dr. Yeh is on the scientific advisory board of Juno Therapeutics and has received research support from Biogen. Dr. Chitnis advises Biogen-Idec, Novartis, and Alexion, serves on clinical trial advisory boards for Novartis and Sanofi Aventis, and has received research support from Verily, EMD Serono, and Novartis. Dr. Savransky has received honoraria from Genzyme de Argentina SA.

New developments in treatment of neuromyelitis optica spectrum disorder (NMOSD) have opened up options for disease treatment in pediatric patients, but have led to some uncertainty and confusion as well.

At the2020 CNS-ICNA Conjoint Meeting, held virtually this year, presenters discussed some of the challenges of differential diagnosis and treatment choice in pediatric NMOSD, which is easily confused with multiple sclerosis.

NMOSD used to be considered a monophasic disease restricted to the optic nerve and spinal cord, but is now known to affect other regions of the central nervous system and to relapse in some patients.
 

Diagnosis

The disease is often mediated by antibodies to the aquaporin-4 (AQP-4) water channel, but about 30% of adult patients lack the antibody, and AQP-4 seronegativity is more common in the pediatric population. Another common antibody found in 40%–50% of children with NMOSD targets myelin oligodendrocyte glycoprotein (MOG).

It is important to be aware that false negatives can occur in serology assays, and false positives are common, particularly in ELISA assays, Silvia N. Tenembaum, MD, said during her presentation. For those reasons, serology is not enough for a diagnosis. “Patients should also have compatible symptoms and MRI findings,” said Dr. Tenembaum, director of the pediatric neuroimmunology program at National Pediatric Hospital in Buenos Aires.

According to international consensus criteria, to be diagnosed with NMOSD, AQP-4 seropositive patients should also have at least one core clinical symptom: optic neuritis, acute myelitis, area postrema syndrome, other acute brainstem syndrome, symptomatic narcolepsy or acute diencephalic clinical syndrome, or symptomatic cerebral syndrome. AQP-4 seronegative patients or with unknown status should have at least two core symptoms, one of which must be optic neuritis, acute myelitis, or area postrema syndrome. Both conventional MRI and advanced new techniques are important for achieving differential diagnosis.

The most common symptom in children is optic neuritis, which occurs in 50%-70% of patients. Cerebral syndromes with or without encephalopathy and large tumefactive white matter lesions are also common, according to Dr. Tenembaum.

There are many conditions that mimic the spinal cord and optic nerve symptoms of NMOSD, which must be ruled out. One example is optic myelopathy and vision loss from late-onset biotinylase deficiency. It is critical to rule that out because it is treatable with supplements. Optic neuropathy, papillitis, and papilledema can also resemble NMOSD.

It is critical to achieve an early diagnosis of NMOSD in children, because some MS drugs can worsen NMOSD, according to Thaís Armangue, MD, PhD, head of neuroimmunology at SJD Barcelona Children’s Hospital, who also presented at the session. She pointed out that the MOG antibody, while common in children, is also associated with many demyelinating diseases. Some 50%-60% of children with acute disseminated encephalomyelitis (ADEM) have high titers of MOG antibodies. Although early studies suggested that persistent anti-MOG antibodies were associated with risk of developing MS, more recent studies show it predicts a non-MS disease course, particularly at titers greater than 1:1280, according to Dr. Tenembaum. Persistent anti-MOG antibodies are also associated with relapsing disease, but it is associated with other syndromes besides NMOSD. “The probability is that [MOG antibodies are] useful, but they cannot guide chronic immunotherapy, because even monophasic patients can last maybe 12 months before they become MOG negative, and we cannot wait so many months” to determine treatment course, said Dr. Tenembaum.

For monophasic ADEM or NMOSD, there is no need for chronic treatment. But children with MS and recurrent NMOSD require early chronic immunotherapy because specific therapies have been shown to improve prognosis.
 

Acute treatment

When it comes to acute treatment of NMOSD, the goal is to suppress the inflammatory attack but also to minimize long-term damage and optimize long-term neurological function. “The potential for irreversible injury with an attack is very high, and cumulative disabilities in NMOSD can result directly from attacks,” E. Ann Yeh, MD, director of the Pediatric MS and Neuroinflammatory Disorders Program at the Hospital for Sick Children at the University of Toronto, said during her talk.

IV steroids are generally the first choice, with a preference for methylprednisolone. Pediatric patients that are MOG antibody positive usually respond better and more quickly than do adults, with rapid daily improvements in mobility, vomiting, and eyesight. Dr. Yeh recommends weaning good responders off steroids because AQP-4 positive patients are likely to relapse without a steroid wean, and antibody testing may be unavailable or results may be delayed. The wean can range from 4 weeks to 4-6 months, depending on antibody status, likelihood of AQP-4 positivity, and clinical parameters.

Inadequate responses are usually pretty evident. If there is only light perception by day 4 or 5, or paralyzed patients are nonambulatory and achieve only twitchy movements by that time, second-line therapies should be considered, including therapeutic plasma exchange (TPE) with 5-7 exchanges or intravenous immunoglobulins (IVIg).

Dr. Yeh called for quick treatment. Whatever you do, “please do it sooner rather than later if you think there’s no response [to steroids],” Dr. Yeh said.

TPE is the first choice, according to Dr. Yeh. “There seems to be a fair amount of information that suggests that if you’re having difficulty getting a response to steroids, TPE can make a difference in these patients,” she said. But in some cases TPE may not be available, and IVIg can be attempted first. If it achieves no or only marginal improvement, TPE can be attempted later, but it must be kept in mind that TPE conducted too soon could wash out IVIg. Patients who get much better on IVIg can undergo a steroid wean, and then be evaluated for prophylactic therapy, said Dr. Yeh.

The evidence for IVIg is limited, reflecting the difficulty of studying treatments in rare populations. Still, when TPE is not available and the patient is quite impaired, IVIg makes sense to try. “Absence of evidence does not mean that the therapy doesn’t work, and I don’t think we should throw out the baby with the bath water,” said Dr. Yeh.

Although IVIg treatment is generally well tolerated, there have been a few serious adverse events, such as anaphylactic shock and aseptic meningitis, according to Andrea Savransky, MD, a pediatrician at National Pediatric Hospital in Buenos Aires, who also spoke at the session. “I think it is important to weigh the benefits against the risk,” Dr. Savransky said. She noted that TPE should not be taken lightly. One study showed more complications in pediatric patients than in adult patients, and it must be performed in specialized centers.
 

Emerging treaments

Tanuja Chitnis, MD, director of the Partners Pediatric MS Center at Massachusetts General Hospital, Boston, discussed some of the emerging treatments for pediatric NMOSD. Rituximab has been associated with success in some retrospective studies, but dosing should be personalized. Dr. Chitnis reported that B cells can return before 6 months, so she monitors B cells beginning 2 months after induction, redosing after 4 or 5 months rather than 6 if B cells return.

Nevertheless, relapses can still occur after rituximab therapy. “There is room for additional therapies to address this gap,” said Dr. Chitnis. Three new antibodies have received approval for treatment of NMOSD in adults. These include the complement inhibitor eculizumab, the IL-6 receptor antibody satralizumab, and the anti-CD19 antibody inebilizumab. Phase 3 clinical trials in children have been conducted for eculizumab and are in the planning stage for inebilizumab, and pediatric patients were included in pivotal trials for satralizumab.

Eculizumab treatment resulted in a 94.2% reduction in relapse risk in AQP4-positive adults. Satralizumab showed a 79% reduction in relapse risk among AQP-4 positive subjects with NMOSD or neuromyelitis optica and a 34% reduction in those who were AQP-4 negative. The pediatric subgroup had similar levels of response to adults, though the numbers were too small for a subgroup analysis.

In AQP-4 positive patients, inebilizumab treatment yielded a 77% reduction in relapse rate. In all patients, there was a 73% reduction.

For MOG antibody-positive patients with AQP-4 negative disease, novel therapies are at earlier stages of development. Typical MS therapies such as interferon beta and glatiramer acetate don’t seem to be effective. Some that have shown signs of efficacy include azathioprine, mycophenylate mofetil, rituximab, and IVIg infusion, but the state of the field is not encouraging. “This is an observation now being studied in larger cohorts, but in general I have not found that there’s a very strong response to any of these therapies, possibly with the exception of IVIg,” said Dr. Chitnis.

Dr. Tenembaum has no relevant financial disclosures. Dr. Armangue has received speaking honoraria from Novartis and travel expenses for scientific meetings from Merck, Biogen, and Roche. Dr. Yeh is on the scientific advisory board of Juno Therapeutics and has received research support from Biogen. Dr. Chitnis advises Biogen-Idec, Novartis, and Alexion, serves on clinical trial advisory boards for Novartis and Sanofi Aventis, and has received research support from Verily, EMD Serono, and Novartis. Dr. Savransky has received honoraria from Genzyme de Argentina SA.

After almost 2 decades of progress, the global state of measles vaccination and measles mortality is deteriorating. Vaccine hesitancy, natural disasters, geopolitical disruptions, and most recently the COVID-19 pandemic have combined to undermine efforts, which had aimed to eradicate measles by this year.

One of the most serious concerns of measles infection is its long-term neurological complications, including the fatal subacute sclerosing panencephalitis (SSPE) and measles inclusion-body encephalitis (MIBE), which is usually seen in immune deficient children. Although some efforts are being made to determine which patients might be most vulnerable to these outcomes, and to treat them, the best approach is still prevention and vaccination, according to Banu Anlar, MD, of Hacettepe University, Ankara, Turkey, who spoke during a session at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.

Worldwide vaccination strategies have slipped in recent years, leading to upticks in measles cases and vaccination rates. As a result, in 2018 the World Health Organization postponed its goal of eliminating measles by 2020. Future eradication goals will likely need to be modified, according to Anaita Udwadia Hegde MD, a pediatric neurologist in Mumbai, India, who also presented at the session.

After measles deaths dropped 74% between 2000 and 2010, coinciding with widespread increases in vaccination, the WHO felt emboldened to deal the disease a knockout blow. In 2010, it held a Global Technical Consultation to determine the feasibility of an eradication campaign, which concluded it should be possible by 2020. Several characteristics of measles made that a reasonable goal: It is passed only among humans, with no known animal reservoir; natural infection grants lifelong immunity; there is only one serotype; the virus is genetically stable; the vaccine is safe and leads to 95%-97% seroconversion after two doses, which provides long-term protection against known genotypes; the disease is easily recognized and tested for; and it had been successfully eliminated already in some regions of the world.

As of 2017, analyses showed that the vaccination program saved the lives of about 1.5 million children. That was a cause for celebration, but the goal of eradication has remained elusive. Vaccination rates have trailed targets. In 2018, UNICEF and WHO estimated that 86% of children globally received the first measles vaccine, unchanged from 2010 and below the goal of 95%. Only 69% of children received the second dose, below the goal of 80%. Four countries in Europe lost their measles elimination status in 2018.

Other attempts to eradicate diseases have met with mixed results. The only full success was smallpox, eliminated in 1977. Similar efforts with polio, malaria, guinea worm, and now measles have all come up short. Those failures could complicate future efforts because global agencies and donors may be leery of past failures because of potential harm to their reputations, according to Dr. Hegde.

Such programs require sustained financial commitment and political support as well as local trust. Nevertheless, they must continue for ethical reasons, said Dr. Hegde, but also for economic ones: Every $1 spent on vaccination programs saves $58 in future costs in low- and middle-income countries. Missed childhood vaccination also results in future vulnerable teenagers and young adults, and these populations are much harder to reach and can drive large outbreaks.

Several factors are contributing to the global regression in vaccine coverage, according to Kristen Feemster, MD, MPH, a pediatric infectious disease physician and the global director of medical affairs at Merck. Globalization has enabled the spread of the disease. Most cases in the United States are imported by travelers to countries where the disease is endemic. “Measles can happen anywhere in the world, and when it does it can travel and spread. If you have an unvaccinated traveler who is exposed to measles abroad, they can return home and spread it to anyone else who is unvaccinated or not otherwise immune. When we see cases they’ve been sporadic, but if you return to a community where immunization rates are low, you have the potential for more sustained spread,” Dr. Feemster said during her presentation.

Why are so many travelers unvaccinated? A key reason is that vaccine hesitance is growing. Most affected individuals involved in outbreaks are unvaccinated, usually by choice rather than for medical reasons. Concerns continue over the measles vaccine and autism, growing out of the debunked studies of Andrew Wakefield. In one example, a Somali community in Minnesota experienced a higher than usual number of autism cases and parents sought reasons to explain it. They discovered the supposed connection between vaccination and autism, and Wakefield himself met with a group of them. The result was a drop in vaccination and, in 2011 and 2017, sizable measles outbreaks.

2020 has of course brought a fresh challenge to measles vaccine with the COVID-19 pandemic, which has reduced access to health care and shifted scientific and health care interest away from measles and other vaccine-preventable diseases. On the positive side, social distancing, mask wearing, and restricted movement are likely reducing exposure to measles, but reduced vaccination rates are likely to result in future outbreaks. “There’s been a significant decrease in rates for routine immunizations globally, so there’s a potential for yet another resurgence of measles and other vaccine-preventable diseases,” said Dr. Feemster.

Dr. Feemster is an employee of Merck. Dr. Anlar and Dr. Hegde did not disclose any relevant financial relationships.

After almost 2 decades of progress, the global state of measles vaccination and measles mortality is deteriorating. Vaccine hesitancy, natural disasters, geopolitical disruptions, and most recently the COVID-19 pandemic have combined to undermine efforts, which had aimed to eradicate measles by this year.

One of the most serious concerns of measles infection is its long-term neurological complications, including the fatal subacute sclerosing panencephalitis (SSPE) and measles inclusion-body encephalitis (MIBE), which is usually seen in immune deficient children. Although some efforts are being made to determine which patients might be most vulnerable to these outcomes, and to treat them, the best approach is still prevention and vaccination, according to Banu Anlar, MD, of Hacettepe University, Ankara, Turkey, who spoke during a session at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.

Worldwide vaccination strategies have slipped in recent years, leading to upticks in measles cases and vaccination rates. As a result, in 2018 the World Health Organization postponed its goal of eliminating measles by 2020. Future eradication goals will likely need to be modified, according to Anaita Udwadia Hegde MD, a pediatric neurologist in Mumbai, India, who also presented at the session.

After measles deaths dropped 74% between 2000 and 2010, coinciding with widespread increases in vaccination, the WHO felt emboldened to deal the disease a knockout blow. In 2010, it held a Global Technical Consultation to determine the feasibility of an eradication campaign, which concluded it should be possible by 2020. Several characteristics of measles made that a reasonable goal: It is passed only among humans, with no known animal reservoir; natural infection grants lifelong immunity; there is only one serotype; the virus is genetically stable; the vaccine is safe and leads to 95%-97% seroconversion after two doses, which provides long-term protection against known genotypes; the disease is easily recognized and tested for; and it had been successfully eliminated already in some regions of the world.

As of 2017, analyses showed that the vaccination program saved the lives of about 1.5 million children. That was a cause for celebration, but the goal of eradication has remained elusive. Vaccination rates have trailed targets. In 2018, UNICEF and WHO estimated that 86% of children globally received the first measles vaccine, unchanged from 2010 and below the goal of 95%. Only 69% of children received the second dose, below the goal of 80%. Four countries in Europe lost their measles elimination status in 2018.

Other attempts to eradicate diseases have met with mixed results. The only full success was smallpox, eliminated in 1977. Similar efforts with polio, malaria, guinea worm, and now measles have all come up short. Those failures could complicate future efforts because global agencies and donors may be leery of past failures because of potential harm to their reputations, according to Dr. Hegde.

Such programs require sustained financial commitment and political support as well as local trust. Nevertheless, they must continue for ethical reasons, said Dr. Hegde, but also for economic ones: Every $1 spent on vaccination programs saves $58 in future costs in low- and middle-income countries. Missed childhood vaccination also results in future vulnerable teenagers and young adults, and these populations are much harder to reach and can drive large outbreaks.

Several factors are contributing to the global regression in vaccine coverage, according to Kristen Feemster, MD, MPH, a pediatric infectious disease physician and the global director of medical affairs at Merck. Globalization has enabled the spread of the disease. Most cases in the United States are imported by travelers to countries where the disease is endemic. “Measles can happen anywhere in the world, and when it does it can travel and spread. If you have an unvaccinated traveler who is exposed to measles abroad, they can return home and spread it to anyone else who is unvaccinated or not otherwise immune. When we see cases they’ve been sporadic, but if you return to a community where immunization rates are low, you have the potential for more sustained spread,” Dr. Feemster said during her presentation.

Why are so many travelers unvaccinated? A key reason is that vaccine hesitance is growing. Most affected individuals involved in outbreaks are unvaccinated, usually by choice rather than for medical reasons. Concerns continue over the measles vaccine and autism, growing out of the debunked studies of Andrew Wakefield. In one example, a Somali community in Minnesota experienced a higher than usual number of autism cases and parents sought reasons to explain it. They discovered the supposed connection between vaccination and autism, and Wakefield himself met with a group of them. The result was a drop in vaccination and, in 2011 and 2017, sizable measles outbreaks.

2020 has of course brought a fresh challenge to measles vaccine with the COVID-19 pandemic, which has reduced access to health care and shifted scientific and health care interest away from measles and other vaccine-preventable diseases. On the positive side, social distancing, mask wearing, and restricted movement are likely reducing exposure to measles, but reduced vaccination rates are likely to result in future outbreaks. “There’s been a significant decrease in rates for routine immunizations globally, so there’s a potential for yet another resurgence of measles and other vaccine-preventable diseases,” said Dr. Feemster.

Dr. Feemster is an employee of Merck. Dr. Anlar and Dr. Hegde did not disclose any relevant financial relationships.

After almost 2 decades of progress, the global state of measles vaccination and measles mortality is deteriorating. Vaccine hesitancy, natural disasters, geopolitical disruptions, and most recently the COVID-19 pandemic have combined to undermine efforts, which had aimed to eradicate measles by this year.

One of the most serious concerns of measles infection is its long-term neurological complications, including the fatal subacute sclerosing panencephalitis (SSPE) and measles inclusion-body encephalitis (MIBE), which is usually seen in immune deficient children. Although some efforts are being made to determine which patients might be most vulnerable to these outcomes, and to treat them, the best approach is still prevention and vaccination, according to Banu Anlar, MD, of Hacettepe University, Ankara, Turkey, who spoke during a session at the 2020 CNS-ICNA Conjoint Meeting, held virtually this year.

Worldwide vaccination strategies have slipped in recent years, leading to upticks in measles cases and vaccination rates. As a result, in 2018 the World Health Organization postponed its goal of eliminating measles by 2020. Future eradication goals will likely need to be modified, according to Anaita Udwadia Hegde MD, a pediatric neurologist in Mumbai, India, who also presented at the session.

After measles deaths dropped 74% between 2000 and 2010, coinciding with widespread increases in vaccination, the WHO felt emboldened to deal the disease a knockout blow. In 2010, it held a Global Technical Consultation to determine the feasibility of an eradication campaign, which concluded it should be possible by 2020. Several characteristics of measles made that a reasonable goal: It is passed only among humans, with no known animal reservoir; natural infection grants lifelong immunity; there is only one serotype; the virus is genetically stable; the vaccine is safe and leads to 95%-97% seroconversion after two doses, which provides long-term protection against known genotypes; the disease is easily recognized and tested for; and it had been successfully eliminated already in some regions of the world.

As of 2017, analyses showed that the vaccination program saved the lives of about 1.5 million children. That was a cause for celebration, but the goal of eradication has remained elusive. Vaccination rates have trailed targets. In 2018, UNICEF and WHO estimated that 86% of children globally received the first measles vaccine, unchanged from 2010 and below the goal of 95%. Only 69% of children received the second dose, below the goal of 80%. Four countries in Europe lost their measles elimination status in 2018.

Other attempts to eradicate diseases have met with mixed results. The only full success was smallpox, eliminated in 1977. Similar efforts with polio, malaria, guinea worm, and now measles have all come up short. Those failures could complicate future efforts because global agencies and donors may be leery of past failures because of potential harm to their reputations, according to Dr. Hegde.

Such programs require sustained financial commitment and political support as well as local trust. Nevertheless, they must continue for ethical reasons, said Dr. Hegde, but also for economic ones: Every $1 spent on vaccination programs saves $58 in future costs in low- and middle-income countries. Missed childhood vaccination also results in future vulnerable teenagers and young adults, and these populations are much harder to reach and can drive large outbreaks.

Several factors are contributing to the global regression in vaccine coverage, according to Kristen Feemster, MD, MPH, a pediatric infectious disease physician and the global director of medical affairs at Merck. Globalization has enabled the spread of the disease. Most cases in the United States are imported by travelers to countries where the disease is endemic. “Measles can happen anywhere in the world, and when it does it can travel and spread. If you have an unvaccinated traveler who is exposed to measles abroad, they can return home and spread it to anyone else who is unvaccinated or not otherwise immune. When we see cases they’ve been sporadic, but if you return to a community where immunization rates are low, you have the potential for more sustained spread,” Dr. Feemster said during her presentation.

Why are so many travelers unvaccinated? A key reason is that vaccine hesitance is growing. Most affected individuals involved in outbreaks are unvaccinated, usually by choice rather than for medical reasons. Concerns continue over the measles vaccine and autism, growing out of the debunked studies of Andrew Wakefield. In one example, a Somali community in Minnesota experienced a higher than usual number of autism cases and parents sought reasons to explain it. They discovered the supposed connection between vaccination and autism, and Wakefield himself met with a group of them. The result was a drop in vaccination and, in 2011 and 2017, sizable measles outbreaks.

2020 has of course brought a fresh challenge to measles vaccine with the COVID-19 pandemic, which has reduced access to health care and shifted scientific and health care interest away from measles and other vaccine-preventable diseases. On the positive side, social distancing, mask wearing, and restricted movement are likely reducing exposure to measles, but reduced vaccination rates are likely to result in future outbreaks. “There’s been a significant decrease in rates for routine immunizations globally, so there’s a potential for yet another resurgence of measles and other vaccine-preventable diseases,” said Dr. Feemster.

Dr. Feemster is an employee of Merck. Dr. Anlar and Dr. Hegde did not disclose any relevant financial relationships.

Over 44,000 more children were diagnosed with COVID-19 in the last week, bringing the total number of child cases to almost three-quarters of a million in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.

The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.

Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.

California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.

Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
 

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Over 44,000 more children were diagnosed with COVID-19 in the last week, bringing the total number of child cases to almost three-quarters of a million in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.

The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.

Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.

California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.

Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
 

[email protected]

Over 44,000 more children were diagnosed with COVID-19 in the last week, bringing the total number of child cases to almost three-quarters of a million in the United States, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The total number of COVID-19 cases among children was 741,891 as of Oct. 15, which puts the cumulative proportion at 10.9% of the 6.8 million cases reported in all ages by 49 states (New York does not report ages), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP and CHA said in their weekly COVID-19 report.

The 44,258 new cases in children represented 13.3% of all cases reported during the week ending Oct. 15, down from 14.6% the previous week (children make up almost 23% of the total U.S. population), the AAP/CHA data show.

Those data also indicate that there have been almost 986 cases of COVID-19 per 100,000 children in the United States. Corresponding rates among the states range from 181 per 100,000 in Vermont to 2,581 per 100,000 in North Dakota. Tennessee (2,277) and South Carolina (2,212) are the only other states above 2,000, according to the report.

California has reported the most child cases, 89,843 (1,010 per 100,000 children), so far, followed by Florida (44,199), Illinois (42,132), and Tennessee (40,137). Seven other states have had over 20,000 cases each, the AAP and CHA noted.

Measures of severe illness continue to be low, although the data are less comprehensive. Children represent only 1.7% of all COVID-19 hospitalizations (24 states and N.Y.C. reporting) and 0.07% of all deaths (42 states and N.Y.C. reporting). Thirteen states and D.C. have had no deaths yet, while Texas has reported three times as many (27) as any other state (Arizona is next with 9, although N.Y.C. has had 15), the AAP/CHA report said.
 

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Patients with systemic sclerosis have variable disease progression but often experience debilitating fatigue, pain, and digestive issues – and they’re extremely concerned about progressive organ damage, according to those who spoke at and provided input at a public meeting on patient-focused drug development for the disease.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The virtual meeting was part of the Food and Drug Administration’s Patient-Focused Drug Development (PFDD) initiative, which began in 2012 and aims to provide a systematic way for patients’ experiences, needs, and priorities to be “captured and meaningfully incorporated” into drug development and evaluation.
 

Patients rate their most impactful symptoms

Dinesh Khanna, MBBS, MSc, a rheumatologist who directs a scleroderma research program at the University of Michigan, Ann Arbor, attended the meeting after giving an opening presentation on the disease to FDA officials, patients, and other participants. In a later interview, he said that patients’ ratings of their most impactful symptoms was especially striking.

Raynaud’s phenomenon, digestive symptoms, and fatigue were the top three answers to a poll question that asked patients what symptom had the most significant impact on daily life, he noted, “and none of these are being [strongly] addressed right now [in clinical trials] apart from Raynaud’s phenomenon, for which there are some trials ongoing.”

He and other researchers are “struggling with what outcomes measures to use [in their studies],” said Dr. Khanna, the Frederick G.L. Huetwell Professor of Rheumatology at the University. “My takeaway from the meeting as a clinical trialist is that we should be paying close attention to the symptoms that patients tell us are the most important. We should be including these in our trial designs as secondary endpoints, if not primary endpoints. We have not done that [thus far], really.”

Approximately 200,000 patients in the United States have scleroderma, and approximately 75,000-80,000 of these patients have systemic scleroderma, or systemic sclerosis, Dr. Khanna said in his opening presentation. Each year, he estimates, about 6,000 new diagnoses of systemic sclerosis are made.

More than 200 people – patients, FDA officials, and others – participated in the PFDD meeting. Patients participated in one of two panels – one focused on health effects and daily impacts, and the other on treatments – or submitted input electronically. All were invited to answer poll questions.

Raj Nair, MD, one of eight FDA leaders attending the meeting, noted in closing remarks that the pain experienced by patients with systemic sclerosis includes severe pain from Raynaud’s phenomenon and pain caused by digital ulcers and by calcinosis. “We heard about how paralyzing the pain from calcinosis is, and that there are very few options for alleviating this pain,” said Dr. Nair, of the division of rheumatology and transplant medicine.

Another takeaway, he said, is that the “fatigue can be severe and debilitating, leading to days where it is impossible to get out of bed,” and that digestive symptoms can also be severe. “Reflux,” he noted, “requires significant medical intervention.”
 

Patients describe their experiences

Rosemary Lyons, diagnosed with scleroderma 35 years ago, explained that while her skin is no longer hardened, she is overly sensitive to fabrics and skin care products and has difficulty with sleeping and eating. She moved away from family in the Northeast to live in the South where the climate is warmer, but even on a 90-degree night she needs a blanket and two comforters to curb the cold and attempt to sleep.

Impaired gastrointestinal motility has made food her “biggest problem” for the past 10 years, and because of GI symptoms, she can eat only one meal a day. She also experiences fainting, brain fog, and severe fatigue. On a good day, Ms. Lyons noted, she sometimes opts to do some house chores “knowing that I’ll have 1-3 days of recovery.”

Another patient, Amy Harding, said that 22 years after her scleroderma diagnosis, “the calcinosis I get in my fingers, elbows, toes, and ears tops all the prior symptoms.” The skin tightening and digital ulcers that she experienced in the first 10 years have tapered off, and while Raynaud’s symptoms and heartburn have worsened, they are at least partly manageable with medications, unlike the pain from calcinosis.
 

Treating symptoms vs. disease may be key in risk-benefit analysis

In questions after patient presentations, FDA officials probed for more perspective on issues such as how fatigue should be assessed, the differences between fatigue and brain fog, the impact of calcinosis on functioning, and how much risk patients would be willing to assume from treatments that have side effects and that may or may not modulate the disease and slow disease progression.

Most patients said in response to an FDA poll question that they definitely (almost 40%) or possibly (almost 50%) would be willing to try a hypothetical new self-injectable medication if it were shown to reduce their most impactful symptoms but had side effects.

“I think what [we’ve been hearing] today is that whether we’re working on the symptoms or the disease itself is [the key]” to patients’ risk-benefit analysis, said meeting moderator Capt. Robyn Bent, RN, MS, of the U.S. Public Health Service, and director of the PFDD.

Anita Devine, diagnosed 13 years ago with systemic sclerosis, was one of several panel members who said she would accept more bothersome treatment side effects and risks “if the gain was control of disease progression and overall quality of life ... and organ preservation.” Ms. Devine, who has needed kidney dialysis and multiple hand surgeries, noted that she previously took anti-neoplastic and anti-inflammatory agents “to try to stem the course of my disease, but unfortunately the disease did not abate.”

Treatments for systemic sclerosis include vasodilators, immunosuppressive medications, antifibrotic therapies, and stem cell transplants, Dr. Khanna said in his opening remarks.

Trials of drugs for scleroderma have focused on early disease that may be amenable to treatment, with the exception of trials for pulmonary arterial hypertension, which affects some patients with systemic sclerosis. There are multiple FDA-approved drugs for pulmonary arterial hypertension and more trials are underway.

Outcomes such as pain and fatigue are included in many of the trials currently underway, but they tend to be lower-level secondary outcomes measures that cannot be incorporated into drug labeling or are more “exploratory in nature,” Dr. Khanna said in the interview.

Dr. Khanna disclosed that he is the chief medical officer (an equity position) for CiVi Biopharma/Eicos Sciences Inc., which is developing a drug for Raynaud’s, and serves as a consultant and grant recipient for numerous companies that make or are developing drugs for systemic sclerosis.

The FDA will accept patient comments until Dec. 15, 2020, at which time comments will be compiled into a summary report, Ms. Bent said.

Patients with systemic sclerosis have variable disease progression but often experience debilitating fatigue, pain, and digestive issues – and they’re extremely concerned about progressive organ damage, according to those who spoke at and provided input at a public meeting on patient-focused drug development for the disease.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The virtual meeting was part of the Food and Drug Administration’s Patient-Focused Drug Development (PFDD) initiative, which began in 2012 and aims to provide a systematic way for patients’ experiences, needs, and priorities to be “captured and meaningfully incorporated” into drug development and evaluation.
 

Patients rate their most impactful symptoms

Dinesh Khanna, MBBS, MSc, a rheumatologist who directs a scleroderma research program at the University of Michigan, Ann Arbor, attended the meeting after giving an opening presentation on the disease to FDA officials, patients, and other participants. In a later interview, he said that patients’ ratings of their most impactful symptoms was especially striking.

Raynaud’s phenomenon, digestive symptoms, and fatigue were the top three answers to a poll question that asked patients what symptom had the most significant impact on daily life, he noted, “and none of these are being [strongly] addressed right now [in clinical trials] apart from Raynaud’s phenomenon, for which there are some trials ongoing.”

He and other researchers are “struggling with what outcomes measures to use [in their studies],” said Dr. Khanna, the Frederick G.L. Huetwell Professor of Rheumatology at the University. “My takeaway from the meeting as a clinical trialist is that we should be paying close attention to the symptoms that patients tell us are the most important. We should be including these in our trial designs as secondary endpoints, if not primary endpoints. We have not done that [thus far], really.”

Approximately 200,000 patients in the United States have scleroderma, and approximately 75,000-80,000 of these patients have systemic scleroderma, or systemic sclerosis, Dr. Khanna said in his opening presentation. Each year, he estimates, about 6,000 new diagnoses of systemic sclerosis are made.

More than 200 people – patients, FDA officials, and others – participated in the PFDD meeting. Patients participated in one of two panels – one focused on health effects and daily impacts, and the other on treatments – or submitted input electronically. All were invited to answer poll questions.

Raj Nair, MD, one of eight FDA leaders attending the meeting, noted in closing remarks that the pain experienced by patients with systemic sclerosis includes severe pain from Raynaud’s phenomenon and pain caused by digital ulcers and by calcinosis. “We heard about how paralyzing the pain from calcinosis is, and that there are very few options for alleviating this pain,” said Dr. Nair, of the division of rheumatology and transplant medicine.

Another takeaway, he said, is that the “fatigue can be severe and debilitating, leading to days where it is impossible to get out of bed,” and that digestive symptoms can also be severe. “Reflux,” he noted, “requires significant medical intervention.”
 

Patients describe their experiences

Rosemary Lyons, diagnosed with scleroderma 35 years ago, explained that while her skin is no longer hardened, she is overly sensitive to fabrics and skin care products and has difficulty with sleeping and eating. She moved away from family in the Northeast to live in the South where the climate is warmer, but even on a 90-degree night she needs a blanket and two comforters to curb the cold and attempt to sleep.

Impaired gastrointestinal motility has made food her “biggest problem” for the past 10 years, and because of GI symptoms, she can eat only one meal a day. She also experiences fainting, brain fog, and severe fatigue. On a good day, Ms. Lyons noted, she sometimes opts to do some house chores “knowing that I’ll have 1-3 days of recovery.”

Another patient, Amy Harding, said that 22 years after her scleroderma diagnosis, “the calcinosis I get in my fingers, elbows, toes, and ears tops all the prior symptoms.” The skin tightening and digital ulcers that she experienced in the first 10 years have tapered off, and while Raynaud’s symptoms and heartburn have worsened, they are at least partly manageable with medications, unlike the pain from calcinosis.
 

Treating symptoms vs. disease may be key in risk-benefit analysis

In questions after patient presentations, FDA officials probed for more perspective on issues such as how fatigue should be assessed, the differences between fatigue and brain fog, the impact of calcinosis on functioning, and how much risk patients would be willing to assume from treatments that have side effects and that may or may not modulate the disease and slow disease progression.

Most patients said in response to an FDA poll question that they definitely (almost 40%) or possibly (almost 50%) would be willing to try a hypothetical new self-injectable medication if it were shown to reduce their most impactful symptoms but had side effects.

“I think what [we’ve been hearing] today is that whether we’re working on the symptoms or the disease itself is [the key]” to patients’ risk-benefit analysis, said meeting moderator Capt. Robyn Bent, RN, MS, of the U.S. Public Health Service, and director of the PFDD.

Anita Devine, diagnosed 13 years ago with systemic sclerosis, was one of several panel members who said she would accept more bothersome treatment side effects and risks “if the gain was control of disease progression and overall quality of life ... and organ preservation.” Ms. Devine, who has needed kidney dialysis and multiple hand surgeries, noted that she previously took anti-neoplastic and anti-inflammatory agents “to try to stem the course of my disease, but unfortunately the disease did not abate.”

Treatments for systemic sclerosis include vasodilators, immunosuppressive medications, antifibrotic therapies, and stem cell transplants, Dr. Khanna said in his opening remarks.

Trials of drugs for scleroderma have focused on early disease that may be amenable to treatment, with the exception of trials for pulmonary arterial hypertension, which affects some patients with systemic sclerosis. There are multiple FDA-approved drugs for pulmonary arterial hypertension and more trials are underway.

Outcomes such as pain and fatigue are included in many of the trials currently underway, but they tend to be lower-level secondary outcomes measures that cannot be incorporated into drug labeling or are more “exploratory in nature,” Dr. Khanna said in the interview.

Dr. Khanna disclosed that he is the chief medical officer (an equity position) for CiVi Biopharma/Eicos Sciences Inc., which is developing a drug for Raynaud’s, and serves as a consultant and grant recipient for numerous companies that make or are developing drugs for systemic sclerosis.

The FDA will accept patient comments until Dec. 15, 2020, at which time comments will be compiled into a summary report, Ms. Bent said.

Patients with systemic sclerosis have variable disease progression but often experience debilitating fatigue, pain, and digestive issues – and they’re extremely concerned about progressive organ damage, according to those who spoke at and provided input at a public meeting on patient-focused drug development for the disease.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

The virtual meeting was part of the Food and Drug Administration’s Patient-Focused Drug Development (PFDD) initiative, which began in 2012 and aims to provide a systematic way for patients’ experiences, needs, and priorities to be “captured and meaningfully incorporated” into drug development and evaluation.
 

Patients rate their most impactful symptoms

Dinesh Khanna, MBBS, MSc, a rheumatologist who directs a scleroderma research program at the University of Michigan, Ann Arbor, attended the meeting after giving an opening presentation on the disease to FDA officials, patients, and other participants. In a later interview, he said that patients’ ratings of their most impactful symptoms was especially striking.

Raynaud’s phenomenon, digestive symptoms, and fatigue were the top three answers to a poll question that asked patients what symptom had the most significant impact on daily life, he noted, “and none of these are being [strongly] addressed right now [in clinical trials] apart from Raynaud’s phenomenon, for which there are some trials ongoing.”

He and other researchers are “struggling with what outcomes measures to use [in their studies],” said Dr. Khanna, the Frederick G.L. Huetwell Professor of Rheumatology at the University. “My takeaway from the meeting as a clinical trialist is that we should be paying close attention to the symptoms that patients tell us are the most important. We should be including these in our trial designs as secondary endpoints, if not primary endpoints. We have not done that [thus far], really.”

Approximately 200,000 patients in the United States have scleroderma, and approximately 75,000-80,000 of these patients have systemic scleroderma, or systemic sclerosis, Dr. Khanna said in his opening presentation. Each year, he estimates, about 6,000 new diagnoses of systemic sclerosis are made.

More than 200 people – patients, FDA officials, and others – participated in the PFDD meeting. Patients participated in one of two panels – one focused on health effects and daily impacts, and the other on treatments – or submitted input electronically. All were invited to answer poll questions.

Raj Nair, MD, one of eight FDA leaders attending the meeting, noted in closing remarks that the pain experienced by patients with systemic sclerosis includes severe pain from Raynaud’s phenomenon and pain caused by digital ulcers and by calcinosis. “We heard about how paralyzing the pain from calcinosis is, and that there are very few options for alleviating this pain,” said Dr. Nair, of the division of rheumatology and transplant medicine.

Another takeaway, he said, is that the “fatigue can be severe and debilitating, leading to days where it is impossible to get out of bed,” and that digestive symptoms can also be severe. “Reflux,” he noted, “requires significant medical intervention.”
 

Patients describe their experiences

Rosemary Lyons, diagnosed with scleroderma 35 years ago, explained that while her skin is no longer hardened, she is overly sensitive to fabrics and skin care products and has difficulty with sleeping and eating. She moved away from family in the Northeast to live in the South where the climate is warmer, but even on a 90-degree night she needs a blanket and two comforters to curb the cold and attempt to sleep.

Impaired gastrointestinal motility has made food her “biggest problem” for the past 10 years, and because of GI symptoms, she can eat only one meal a day. She also experiences fainting, brain fog, and severe fatigue. On a good day, Ms. Lyons noted, she sometimes opts to do some house chores “knowing that I’ll have 1-3 days of recovery.”

Another patient, Amy Harding, said that 22 years after her scleroderma diagnosis, “the calcinosis I get in my fingers, elbows, toes, and ears tops all the prior symptoms.” The skin tightening and digital ulcers that she experienced in the first 10 years have tapered off, and while Raynaud’s symptoms and heartburn have worsened, they are at least partly manageable with medications, unlike the pain from calcinosis.
 

Treating symptoms vs. disease may be key in risk-benefit analysis

In questions after patient presentations, FDA officials probed for more perspective on issues such as how fatigue should be assessed, the differences between fatigue and brain fog, the impact of calcinosis on functioning, and how much risk patients would be willing to assume from treatments that have side effects and that may or may not modulate the disease and slow disease progression.

Most patients said in response to an FDA poll question that they definitely (almost 40%) or possibly (almost 50%) would be willing to try a hypothetical new self-injectable medication if it were shown to reduce their most impactful symptoms but had side effects.

“I think what [we’ve been hearing] today is that whether we’re working on the symptoms or the disease itself is [the key]” to patients’ risk-benefit analysis, said meeting moderator Capt. Robyn Bent, RN, MS, of the U.S. Public Health Service, and director of the PFDD.

Anita Devine, diagnosed 13 years ago with systemic sclerosis, was one of several panel members who said she would accept more bothersome treatment side effects and risks “if the gain was control of disease progression and overall quality of life ... and organ preservation.” Ms. Devine, who has needed kidney dialysis and multiple hand surgeries, noted that she previously took anti-neoplastic and anti-inflammatory agents “to try to stem the course of my disease, but unfortunately the disease did not abate.”

Treatments for systemic sclerosis include vasodilators, immunosuppressive medications, antifibrotic therapies, and stem cell transplants, Dr. Khanna said in his opening remarks.

Trials of drugs for scleroderma have focused on early disease that may be amenable to treatment, with the exception of trials for pulmonary arterial hypertension, which affects some patients with systemic sclerosis. There are multiple FDA-approved drugs for pulmonary arterial hypertension and more trials are underway.

Outcomes such as pain and fatigue are included in many of the trials currently underway, but they tend to be lower-level secondary outcomes measures that cannot be incorporated into drug labeling or are more “exploratory in nature,” Dr. Khanna said in the interview.

Dr. Khanna disclosed that he is the chief medical officer (an equity position) for CiVi Biopharma/Eicos Sciences Inc., which is developing a drug for Raynaud’s, and serves as a consultant and grant recipient for numerous companies that make or are developing drugs for systemic sclerosis.

The FDA will accept patient comments until Dec. 15, 2020, at which time comments will be compiled into a summary report, Ms. Bent said.

People who have undergone bariatric surgery appear less likely to suffer an aortic dissection than other adults with obesity, researchers say.

The finding is the latest in a series of benefits researchers have linked to the surgery, not all of which appear to directly result from weight loss.

“It has an incredible impact on hyperlipidemia and hypertension,” said Luis Felipe Okida, MD, from Cleveland Clinic Florida, Weston. “Those are the main risk factors for aortic dissection.”

He presented the finding at the virtual American Congress of Surgeons Clinical Congress 2020. The study was also published online in the Journal of the American College of Surgeons.

Although uncommon, acute aortic dissection proves fatal to half the people it strikes if patients do not receive treatment within 72 hours, Dr. Okida said in an interview.

To learn whether there is an association between bariatric surgery and risk for aortic dissection, Dr. Okida and colleagues analyzed data from the National Inpatient Sample (NIS) database from 2010 to 2015. The NIS comprises about 20% of hospital inpatient admissions in the United States.

Among the patients in the sample, 296,041 adults had undergone bariatric surgery, and 2,004,804 adults had obesity (body mass index ≥35 kg/m²) but had never undergone bariatric surgery. This latter group represented the control group.

Among the control group, 1,411 patients (.070%) experienced aortic dissection; among the bariatric surgery group, 94 patients (0.032%) experienced aortic dissection. This was a statistically significant difference (P < .0001).

The groups differed significantly in many ways. The mean age of the patients in the control group was 54.4 years, which was a mean of 2.5 years older than the bariatric surgery group. Additionally, the control group included a higher percentage of women and a lower percentage of White persons.

Those in the control group were also more likely to have a history of tobacco use, hypertension (64.2% vs. 48.9% in the surgery group), hyperlipidemia (32.7% vs. 18.3%), diabetes, aortic aneurysm (20.6% vs. 12.0%), and bicuspid aortic valves but were less likely to have Marfan/Ehlers-Danlos syndrome.

A multivariate analysis showed that gender, age, history of tobacco use, hypertension, hyperlipidemia, and Marfan/Ehlers-Danlos syndrome were associated with an increased risk for aortic dissection. Diabetes was associated with a lower risk. All of these findings had previously been reported in the literature, Dr. Okida said, but the reasons for the negative association with diabetes is not well understood.

The association between the surgery and aortic dissection applied to younger patients as well as older ones.

“In elderly patients, the main risk factor for aortic dissection is hypertension, and in younger patients, below 40 years old, the main risk factors are diseases of the collagen and diseases of the aorta,” said Dr. Okida during his presentation. “But these younger patients still have a high prevalence of hypertension, and that’s why bariatric surgery is beneficial.”

Although the finding regarding risk for aortic dissection supports the value of bariatric surgery, it does not in itself provide justification for undergoing the procedure. “It’s not even one of the comorbidities that insurance companies would recognize as key in approving this procedure,” said senior author Emanuele Lo Menzo, MD, PhD, also from the Cleveland Clinic Florida.

“I don’t think a physician would ever recommend this procedure specifically to avoid aortic dissection,” he said in an interview. “It’s sort of an extended benefit.”

The study raises interesting questions about the effects of the surgery, said Shanu Kothari, MD, president-elect of the American Society for Metabolic and Bariatric Surgery.

“We’ve known for a long time that patients with chronic obesity who undergo weight-loss surgery live longer than those who don’t,” he said in an interview. “They have less cardiovascular disease and cancer. Is this one more reason that they live longer?”

Bariatric surgery produces benefits for people with diabetes the day after the surgery, long before patients lose weight as a result of the procedure, Dr. Kothari said.

The effects on metabolism are complex, he added. Besides caloric restriction, they include changes in bile salt absorption and the gut microbiome, which in turn can affect hormones and inflammation.

A key question is how long after the surgery the risk for aortic dissection starts to decline, said Dr. Kothari.

The study could not answer such questions, and Dr. Okida could not find any previous studies that explored the association. He also couldn’t find any study that examined whether weight loss by other means might also reduce the risk for aortic dissection.

Dr. Okida, Dr. Lo Menzo, and Dr. Kothari disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

People who have undergone bariatric surgery appear less likely to suffer an aortic dissection than other adults with obesity, researchers say.

The finding is the latest in a series of benefits researchers have linked to the surgery, not all of which appear to directly result from weight loss.

“It has an incredible impact on hyperlipidemia and hypertension,” said Luis Felipe Okida, MD, from Cleveland Clinic Florida, Weston. “Those are the main risk factors for aortic dissection.”

He presented the finding at the virtual American Congress of Surgeons Clinical Congress 2020. The study was also published online in the Journal of the American College of Surgeons.

Although uncommon, acute aortic dissection proves fatal to half the people it strikes if patients do not receive treatment within 72 hours, Dr. Okida said in an interview.

To learn whether there is an association between bariatric surgery and risk for aortic dissection, Dr. Okida and colleagues analyzed data from the National Inpatient Sample (NIS) database from 2010 to 2015. The NIS comprises about 20% of hospital inpatient admissions in the United States.

Among the patients in the sample, 296,041 adults had undergone bariatric surgery, and 2,004,804 adults had obesity (body mass index ≥35 kg/m²) but had never undergone bariatric surgery. This latter group represented the control group.

Among the control group, 1,411 patients (.070%) experienced aortic dissection; among the bariatric surgery group, 94 patients (0.032%) experienced aortic dissection. This was a statistically significant difference (P < .0001).

The groups differed significantly in many ways. The mean age of the patients in the control group was 54.4 years, which was a mean of 2.5 years older than the bariatric surgery group. Additionally, the control group included a higher percentage of women and a lower percentage of White persons.

Those in the control group were also more likely to have a history of tobacco use, hypertension (64.2% vs. 48.9% in the surgery group), hyperlipidemia (32.7% vs. 18.3%), diabetes, aortic aneurysm (20.6% vs. 12.0%), and bicuspid aortic valves but were less likely to have Marfan/Ehlers-Danlos syndrome.

A multivariate analysis showed that gender, age, history of tobacco use, hypertension, hyperlipidemia, and Marfan/Ehlers-Danlos syndrome were associated with an increased risk for aortic dissection. Diabetes was associated with a lower risk. All of these findings had previously been reported in the literature, Dr. Okida said, but the reasons for the negative association with diabetes is not well understood.

The association between the surgery and aortic dissection applied to younger patients as well as older ones.

“In elderly patients, the main risk factor for aortic dissection is hypertension, and in younger patients, below 40 years old, the main risk factors are diseases of the collagen and diseases of the aorta,” said Dr. Okida during his presentation. “But these younger patients still have a high prevalence of hypertension, and that’s why bariatric surgery is beneficial.”

Although the finding regarding risk for aortic dissection supports the value of bariatric surgery, it does not in itself provide justification for undergoing the procedure. “It’s not even one of the comorbidities that insurance companies would recognize as key in approving this procedure,” said senior author Emanuele Lo Menzo, MD, PhD, also from the Cleveland Clinic Florida.

“I don’t think a physician would ever recommend this procedure specifically to avoid aortic dissection,” he said in an interview. “It’s sort of an extended benefit.”

The study raises interesting questions about the effects of the surgery, said Shanu Kothari, MD, president-elect of the American Society for Metabolic and Bariatric Surgery.

“We’ve known for a long time that patients with chronic obesity who undergo weight-loss surgery live longer than those who don’t,” he said in an interview. “They have less cardiovascular disease and cancer. Is this one more reason that they live longer?”

Bariatric surgery produces benefits for people with diabetes the day after the surgery, long before patients lose weight as a result of the procedure, Dr. Kothari said.

The effects on metabolism are complex, he added. Besides caloric restriction, they include changes in bile salt absorption and the gut microbiome, which in turn can affect hormones and inflammation.

A key question is how long after the surgery the risk for aortic dissection starts to decline, said Dr. Kothari.

The study could not answer such questions, and Dr. Okida could not find any previous studies that explored the association. He also couldn’t find any study that examined whether weight loss by other means might also reduce the risk for aortic dissection.

Dr. Okida, Dr. Lo Menzo, and Dr. Kothari disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

People who have undergone bariatric surgery appear less likely to suffer an aortic dissection than other adults with obesity, researchers say.

The finding is the latest in a series of benefits researchers have linked to the surgery, not all of which appear to directly result from weight loss.

“It has an incredible impact on hyperlipidemia and hypertension,” said Luis Felipe Okida, MD, from Cleveland Clinic Florida, Weston. “Those are the main risk factors for aortic dissection.”

He presented the finding at the virtual American Congress of Surgeons Clinical Congress 2020. The study was also published online in the Journal of the American College of Surgeons.

Although uncommon, acute aortic dissection proves fatal to half the people it strikes if patients do not receive treatment within 72 hours, Dr. Okida said in an interview.

To learn whether there is an association between bariatric surgery and risk for aortic dissection, Dr. Okida and colleagues analyzed data from the National Inpatient Sample (NIS) database from 2010 to 2015. The NIS comprises about 20% of hospital inpatient admissions in the United States.

Among the patients in the sample, 296,041 adults had undergone bariatric surgery, and 2,004,804 adults had obesity (body mass index ≥35 kg/m²) but had never undergone bariatric surgery. This latter group represented the control group.

Among the control group, 1,411 patients (.070%) experienced aortic dissection; among the bariatric surgery group, 94 patients (0.032%) experienced aortic dissection. This was a statistically significant difference (P < .0001).

The groups differed significantly in many ways. The mean age of the patients in the control group was 54.4 years, which was a mean of 2.5 years older than the bariatric surgery group. Additionally, the control group included a higher percentage of women and a lower percentage of White persons.

Those in the control group were also more likely to have a history of tobacco use, hypertension (64.2% vs. 48.9% in the surgery group), hyperlipidemia (32.7% vs. 18.3%), diabetes, aortic aneurysm (20.6% vs. 12.0%), and bicuspid aortic valves but were less likely to have Marfan/Ehlers-Danlos syndrome.

A multivariate analysis showed that gender, age, history of tobacco use, hypertension, hyperlipidemia, and Marfan/Ehlers-Danlos syndrome were associated with an increased risk for aortic dissection. Diabetes was associated with a lower risk. All of these findings had previously been reported in the literature, Dr. Okida said, but the reasons for the negative association with diabetes is not well understood.

The association between the surgery and aortic dissection applied to younger patients as well as older ones.

“In elderly patients, the main risk factor for aortic dissection is hypertension, and in younger patients, below 40 years old, the main risk factors are diseases of the collagen and diseases of the aorta,” said Dr. Okida during his presentation. “But these younger patients still have a high prevalence of hypertension, and that’s why bariatric surgery is beneficial.”

Although the finding regarding risk for aortic dissection supports the value of bariatric surgery, it does not in itself provide justification for undergoing the procedure. “It’s not even one of the comorbidities that insurance companies would recognize as key in approving this procedure,” said senior author Emanuele Lo Menzo, MD, PhD, also from the Cleveland Clinic Florida.

“I don’t think a physician would ever recommend this procedure specifically to avoid aortic dissection,” he said in an interview. “It’s sort of an extended benefit.”

The study raises interesting questions about the effects of the surgery, said Shanu Kothari, MD, president-elect of the American Society for Metabolic and Bariatric Surgery.

“We’ve known for a long time that patients with chronic obesity who undergo weight-loss surgery live longer than those who don’t,” he said in an interview. “They have less cardiovascular disease and cancer. Is this one more reason that they live longer?”

Bariatric surgery produces benefits for people with diabetes the day after the surgery, long before patients lose weight as a result of the procedure, Dr. Kothari said.

The effects on metabolism are complex, he added. Besides caloric restriction, they include changes in bile salt absorption and the gut microbiome, which in turn can affect hormones and inflammation.

A key question is how long after the surgery the risk for aortic dissection starts to decline, said Dr. Kothari.

The study could not answer such questions, and Dr. Okida could not find any previous studies that explored the association. He also couldn’t find any study that examined whether weight loss by other means might also reduce the risk for aortic dissection.

Dr. Okida, Dr. Lo Menzo, and Dr. Kothari disclosed no relevant financial relationships.

A version of this article originally appeared on Medscape.com.

An updated European Society for Medical Oncology (ESMO) clinical practice guidelines were released to provide key recommendations on the management of chronic lymphocytic leukemia (CLL).

The guidelines were developed by a multidisciplinary group of experts from different institutions and countries in Europe and provide levels of evidence and grades of recommendation where applicable for issues regarding prognosis and treatment decisions in CLL. Such decisions depend on genetic and clinical factors such as age, stage, and comorbidities. The guidelines also focus on new therapies targeting B-cell-receptor pathways or defect mechanism of apoptosis, which have been found to induce long-lasting remissions. The guidelines were endorsed by the European Hematology Association (EHA) through the Scientific Working Group on CLL/European Research Initiative on CLL (ERIC), according to the report published online the Annals of Oncology.

These clinical practice guidelines were developed in accordance with the ESMO standard operating procedures for clinical practice guidelines development with use of relevant literature selected by the expert authors. Statements without grading were considered justified as standard clinical practice by the experts and the ESMO faculty.

Below are some highlights of the guidelines, which cover a wide array of topics regarding the diagnosis, staging, treatment, and progression of CLL disease.
 

Diagnosis

The guidelines indicate that CLL diagnosis is usually possible by immunophenotyping of peripheral blood only and that lymph node (LN) biopsy and/or bone marrow biopsy may be helpful if immunophenotyping is not conclusive for the diagnosis of CLL, according to Barbara Eichhorst, MD, of the University of Cologne (Germany) and colleagues on behalf of the ESMO guidelines committee.

Staging and risk assessment

Early asymptomatic-stage disease does not need further risk assessment, but after the first year, when all patients should be seen at 3-monthly intervals, patients can be followed every 3-12 months. The interval would depend on burden and dynamics of the disease obtained by the using history and physical examinations, including a careful palpation of all LN areas, spleen, and liver, as well as assessing complete blood cell count and differential count, according to the report.

Advanced- and symptomatic-stage disease requires a broader examination including imaging, history and status of relevant infections, and fluorescent in situ hybridization (FISH) assays for the detection of deletion of the chromosome 17 (del[17p]) affecting the tumor protein p53 expression and, in the absence of del(17p), TP53 sequencing for detection of TP53 gene mutation, according to the authors.

Prognostication

Two clinical staging systems are typically used in CLL. Both Binet and Rai staging systems separate three groups of patients with different prognosis, although “as a consequence of more effective therapy, the overall survival (OS) of patients with advanced stage has improved and the relevance of the staging systems for prognostication has decreased,” according to the report.

The recent addition of genetic markers has also proved highly relevant to identifying patients with different prognoses and to guide treatment.
 

Therapy

Although CLL is an incurable disease, choice and application of treatment are strongly tied to the length of survival, according to the authors. The guidelines recommend Binet and Rai staging with clinical symptoms as relevant for treatment indication. In addition, the identification of del(17p), TP53 mutations, and IGHV status are relevant for choice of therapy and should be assessed prior to treatment.

The guidelines discuss specific treatment modalities for various stages of the disease, from early stages to relapse.

For frontline therapy, different treatment strategies are available including continuous treatment with Bruton tyrosine kinase (BTK)–inhibitors, such as ibrutinib, until progression or time-limited therapy with ChT backbone and CD20 antibodies. In addition, the Food and Drug Administration and European Medicines Agency have recently approved the combination of venetoclax plus obinutuzumab for first-line therapy of CLL.

Treatment decisions should include an assessment of IGHV and TP53 status, as well as patient-related factors such as comedication, comorbidities, preferences, drug availability, and potential of treatment adherence, according to the guidelines.

In case of symptomatic relapse within 3 years after fixed-duration therapy or nonresponse to therapy, the guidelines recommend that the therapeutic regimen should be changed, regardless of the type of first-line either to venetoclax plus rituximab for 24 months or to ibrutinib, acalabrutinib, or other BTK inhibitors (if available) as continuous therapy.

The guidelines also discuss the possible roles for hematopoietic stem cell transplantation and cellular therapies, as well as the treatment of the various complications that can arise in patients with CLL, and dealing with various aspects of disease progression.

No external funds were provided for the production of the guidelines. The authors of the report and members of the ESMO Guidelines Committee reported numerous disclosures regarding pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Eichhorst B et al. Ann Oncol. 2020 Oct 19. doi: 10.1016/j.annonc.2020.09.019.

An updated European Society for Medical Oncology (ESMO) clinical practice guidelines were released to provide key recommendations on the management of chronic lymphocytic leukemia (CLL).

The guidelines were developed by a multidisciplinary group of experts from different institutions and countries in Europe and provide levels of evidence and grades of recommendation where applicable for issues regarding prognosis and treatment decisions in CLL. Such decisions depend on genetic and clinical factors such as age, stage, and comorbidities. The guidelines also focus on new therapies targeting B-cell-receptor pathways or defect mechanism of apoptosis, which have been found to induce long-lasting remissions. The guidelines were endorsed by the European Hematology Association (EHA) through the Scientific Working Group on CLL/European Research Initiative on CLL (ERIC), according to the report published online the Annals of Oncology.

These clinical practice guidelines were developed in accordance with the ESMO standard operating procedures for clinical practice guidelines development with use of relevant literature selected by the expert authors. Statements without grading were considered justified as standard clinical practice by the experts and the ESMO faculty.

Below are some highlights of the guidelines, which cover a wide array of topics regarding the diagnosis, staging, treatment, and progression of CLL disease.
 

Diagnosis

The guidelines indicate that CLL diagnosis is usually possible by immunophenotyping of peripheral blood only and that lymph node (LN) biopsy and/or bone marrow biopsy may be helpful if immunophenotyping is not conclusive for the diagnosis of CLL, according to Barbara Eichhorst, MD, of the University of Cologne (Germany) and colleagues on behalf of the ESMO guidelines committee.

Staging and risk assessment

Early asymptomatic-stage disease does not need further risk assessment, but after the first year, when all patients should be seen at 3-monthly intervals, patients can be followed every 3-12 months. The interval would depend on burden and dynamics of the disease obtained by the using history and physical examinations, including a careful palpation of all LN areas, spleen, and liver, as well as assessing complete blood cell count and differential count, according to the report.

Advanced- and symptomatic-stage disease requires a broader examination including imaging, history and status of relevant infections, and fluorescent in situ hybridization (FISH) assays for the detection of deletion of the chromosome 17 (del[17p]) affecting the tumor protein p53 expression and, in the absence of del(17p), TP53 sequencing for detection of TP53 gene mutation, according to the authors.

Prognostication

Two clinical staging systems are typically used in CLL. Both Binet and Rai staging systems separate three groups of patients with different prognosis, although “as a consequence of more effective therapy, the overall survival (OS) of patients with advanced stage has improved and the relevance of the staging systems for prognostication has decreased,” according to the report.

The recent addition of genetic markers has also proved highly relevant to identifying patients with different prognoses and to guide treatment.
 

Therapy

Although CLL is an incurable disease, choice and application of treatment are strongly tied to the length of survival, according to the authors. The guidelines recommend Binet and Rai staging with clinical symptoms as relevant for treatment indication. In addition, the identification of del(17p), TP53 mutations, and IGHV status are relevant for choice of therapy and should be assessed prior to treatment.

The guidelines discuss specific treatment modalities for various stages of the disease, from early stages to relapse.

For frontline therapy, different treatment strategies are available including continuous treatment with Bruton tyrosine kinase (BTK)–inhibitors, such as ibrutinib, until progression or time-limited therapy with ChT backbone and CD20 antibodies. In addition, the Food and Drug Administration and European Medicines Agency have recently approved the combination of venetoclax plus obinutuzumab for first-line therapy of CLL.

Treatment decisions should include an assessment of IGHV and TP53 status, as well as patient-related factors such as comedication, comorbidities, preferences, drug availability, and potential of treatment adherence, according to the guidelines.

In case of symptomatic relapse within 3 years after fixed-duration therapy or nonresponse to therapy, the guidelines recommend that the therapeutic regimen should be changed, regardless of the type of first-line either to venetoclax plus rituximab for 24 months or to ibrutinib, acalabrutinib, or other BTK inhibitors (if available) as continuous therapy.

The guidelines also discuss the possible roles for hematopoietic stem cell transplantation and cellular therapies, as well as the treatment of the various complications that can arise in patients with CLL, and dealing with various aspects of disease progression.

No external funds were provided for the production of the guidelines. The authors of the report and members of the ESMO Guidelines Committee reported numerous disclosures regarding pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Eichhorst B et al. Ann Oncol. 2020 Oct 19. doi: 10.1016/j.annonc.2020.09.019.

An updated European Society for Medical Oncology (ESMO) clinical practice guidelines were released to provide key recommendations on the management of chronic lymphocytic leukemia (CLL).

The guidelines were developed by a multidisciplinary group of experts from different institutions and countries in Europe and provide levels of evidence and grades of recommendation where applicable for issues regarding prognosis and treatment decisions in CLL. Such decisions depend on genetic and clinical factors such as age, stage, and comorbidities. The guidelines also focus on new therapies targeting B-cell-receptor pathways or defect mechanism of apoptosis, which have been found to induce long-lasting remissions. The guidelines were endorsed by the European Hematology Association (EHA) through the Scientific Working Group on CLL/European Research Initiative on CLL (ERIC), according to the report published online the Annals of Oncology.

These clinical practice guidelines were developed in accordance with the ESMO standard operating procedures for clinical practice guidelines development with use of relevant literature selected by the expert authors. Statements without grading were considered justified as standard clinical practice by the experts and the ESMO faculty.

Below are some highlights of the guidelines, which cover a wide array of topics regarding the diagnosis, staging, treatment, and progression of CLL disease.
 

Diagnosis

The guidelines indicate that CLL diagnosis is usually possible by immunophenotyping of peripheral blood only and that lymph node (LN) biopsy and/or bone marrow biopsy may be helpful if immunophenotyping is not conclusive for the diagnosis of CLL, according to Barbara Eichhorst, MD, of the University of Cologne (Germany) and colleagues on behalf of the ESMO guidelines committee.

Staging and risk assessment

Early asymptomatic-stage disease does not need further risk assessment, but after the first year, when all patients should be seen at 3-monthly intervals, patients can be followed every 3-12 months. The interval would depend on burden and dynamics of the disease obtained by the using history and physical examinations, including a careful palpation of all LN areas, spleen, and liver, as well as assessing complete blood cell count and differential count, according to the report.

Advanced- and symptomatic-stage disease requires a broader examination including imaging, history and status of relevant infections, and fluorescent in situ hybridization (FISH) assays for the detection of deletion of the chromosome 17 (del[17p]) affecting the tumor protein p53 expression and, in the absence of del(17p), TP53 sequencing for detection of TP53 gene mutation, according to the authors.

Prognostication

Two clinical staging systems are typically used in CLL. Both Binet and Rai staging systems separate three groups of patients with different prognosis, although “as a consequence of more effective therapy, the overall survival (OS) of patients with advanced stage has improved and the relevance of the staging systems for prognostication has decreased,” according to the report.

The recent addition of genetic markers has also proved highly relevant to identifying patients with different prognoses and to guide treatment.
 

Therapy

Although CLL is an incurable disease, choice and application of treatment are strongly tied to the length of survival, according to the authors. The guidelines recommend Binet and Rai staging with clinical symptoms as relevant for treatment indication. In addition, the identification of del(17p), TP53 mutations, and IGHV status are relevant for choice of therapy and should be assessed prior to treatment.

The guidelines discuss specific treatment modalities for various stages of the disease, from early stages to relapse.

For frontline therapy, different treatment strategies are available including continuous treatment with Bruton tyrosine kinase (BTK)–inhibitors, such as ibrutinib, until progression or time-limited therapy with ChT backbone and CD20 antibodies. In addition, the Food and Drug Administration and European Medicines Agency have recently approved the combination of venetoclax plus obinutuzumab for first-line therapy of CLL.

Treatment decisions should include an assessment of IGHV and TP53 status, as well as patient-related factors such as comedication, comorbidities, preferences, drug availability, and potential of treatment adherence, according to the guidelines.

In case of symptomatic relapse within 3 years after fixed-duration therapy or nonresponse to therapy, the guidelines recommend that the therapeutic regimen should be changed, regardless of the type of first-line either to venetoclax plus rituximab for 24 months or to ibrutinib, acalabrutinib, or other BTK inhibitors (if available) as continuous therapy.

The guidelines also discuss the possible roles for hematopoietic stem cell transplantation and cellular therapies, as well as the treatment of the various complications that can arise in patients with CLL, and dealing with various aspects of disease progression.

No external funds were provided for the production of the guidelines. The authors of the report and members of the ESMO Guidelines Committee reported numerous disclosures regarding pharmaceutical and biotechnology companies.

[email protected]

SOURCE: Eichhorst B et al. Ann Oncol. 2020 Oct 19. doi: 10.1016/j.annonc.2020.09.019.

Have you ever done something where you’re not quite sure why you did it at the time, but later on you realize it was part of some larger cosmic purpose, and you go, “Ahhh, now I understand…that’s why!”? Call it a fortuitous coincidence. Or a subconscious act of anticipation. Maybe a little push from God.

Last summer, as SHM’s Practice Analysis Committee was planning the State of Hospital Medicine survey for 2020, we received a request from SHM’s Diversity, Equity & Inclusion (DEI) Special Interest Group (SIG) to include a series of questions related to hospitalist gender, race and ethnic distribution in the new survey. We’ve generally resisted doing things like this because the SoHM is designed to capture data at the group level, not the individual level – and honestly, it’s as much as a lot of groups can do to tell us reliably how many FTEs they have, much less provide details about individual providers. In addition, the survey is already really long, and we are always looking for ways to make it shorter and easier for participants while still collecting the information report users care most about.

But we wanted to take the asks from the DEI SIG seriously, and as we considered their request, we realized that though it wasn’t practical to collect this information for individual hospital medicine group (HMG) members, we could collect it for group leaders. Little did we know last summer that issues of gender and racial diversity and equity would be so front-and-center right now, as we prepare to release the 2020 SoHM Report in early September. Ahhh, now I understand…that’s why – with the prompting of the DEI SIG – we so fortuitously chose to include those questions this year!

Here’s a sneak preview of what we learned. Among SoHM respondents, 57.1% reported that the highest-ranking leader in their HMG is White, and 23.5% of highest-ranking leaders are Asian. Only 5.5% of HMG leaders were Black/African American. Ethnicity was a separate question, and only 2.2% of HMG leaders were reported as Hispanic/Latino.

I have been profoundly moved by the wretched deaths of George Floyd and other people of color at the hands of police in recent months, and by the subsequent protests and our growing national reckoning over issues of racial equity and justice. In my efforts to understand more about race in America, I have been challenged by my friend Ryan Brown, MD, specialty medical director for hospital medicine with Atrium Health in Charlotte, N.C., and others to go beyond just learning about these issues. I want to use my voice to advocate for change, and my actions to participate in effecting change, within the context of my sphere of influence.

So, what does that have to do with the SoHM data on HMG leader demographics? Well, it’s clear that Black and brown people are woefully underrepresented in the ranks of hospital medicine leadership.

• Create and sponsor a mentoring program in which hospitalists volunteer to mentor minority junior high and high school students and help them prepare to pursue a career in medicine.
• Develop a formal, structured advocacy or collaboration effort with organizations like AAMC and the Accreditation Council for Graduate Medical Education designed to promote meaningful increases in the proportion of medical school students and residents who are people of color, and in the proportion who choose primary care – and ultimately, hospital medicine.
• Work hard to collect reliable racial, ethnic and gender information about SHM members and consider collaborating with MGMA to incorporate demographic questions into its survey tool for individual hospitalist compensation and productivity data. Challenge us on the Practice Analysis Committee who are responsible for the SoHM survey to continue surveying leadership demographics, and to consider how we can expand our collection of DEI information in 2022.
• Undertake a public relations campaign to highlight to health systems and other employers the under-representation of Black and Latino hospitalists in leadership positions, and to promote conscious efforts to increase those ranks.
• Create scholarships for hospitalists from underrepresented racial and ethnic groups to attend SHM-sponsored leadership development programs such as Leadership Academy, Academic Hospitalist Academy, and Quality and Safety Educators Academy, with the goal of increasing their ranks in positions of influence throughout healthcare. A scholarship program might even include raising funds to help minority hospitalists pursue Master’s-level programs such as an MBA, MHA, or MMM.
• Develop an educational track, mentoring program, or other support initiative for early-career hospitalist leaders and those interested in developing leadership skills, and ensure it gives specific attention to strategies for increasing the proportion of hospitalists of color in leadership positions.
• Review and revise existing SHM documents such as The Key Principles and Characteristics of an Effective Hospital Medicine Group, the Core Competencies in Hospital Medicine, and various white papers and position statements to ensure they address diversity, equity and inclusion – both with regard to the hospital medicine workforce and leadership, and with regard to patient care and eliminating health disparities.

I’m sure there are plenty of other similar actions we can take that I haven’t thought of. But we need to start the conversation about concrete steps our Society, and the medical specialty we represent, can take to foster real change. And then, we need to follow our words up with actions.

Ms. Flores is a partner at Nelson Flores Hospital Medicine Consultants in La Quinta, Calif. She serves on SHM’s Practice Analysis and Annual Conference Committees and helps to coordinate SHM’s biannual State of Hospital Medicine survey.

Have you ever done something where you’re not quite sure why you did it at the time, but later on you realize it was part of some larger cosmic purpose, and you go, “Ahhh, now I understand…that’s why!”? Call it a fortuitous coincidence. Or a subconscious act of anticipation. Maybe a little push from God.

Last summer, as SHM’s Practice Analysis Committee was planning the State of Hospital Medicine survey for 2020, we received a request from SHM’s Diversity, Equity & Inclusion (DEI) Special Interest Group (SIG) to include a series of questions related to hospitalist gender, race and ethnic distribution in the new survey. We’ve generally resisted doing things like this because the SoHM is designed to capture data at the group level, not the individual level – and honestly, it’s as much as a lot of groups can do to tell us reliably how many FTEs they have, much less provide details about individual providers. In addition, the survey is already really long, and we are always looking for ways to make it shorter and easier for participants while still collecting the information report users care most about.

But we wanted to take the asks from the DEI SIG seriously, and as we considered their request, we realized that though it wasn’t practical to collect this information for individual hospital medicine group (HMG) members, we could collect it for group leaders. Little did we know last summer that issues of gender and racial diversity and equity would be so front-and-center right now, as we prepare to release the 2020 SoHM Report in early September. Ahhh, now I understand…that’s why – with the prompting of the DEI SIG – we so fortuitously chose to include those questions this year!

Here’s a sneak preview of what we learned. Among SoHM respondents, 57.1% reported that the highest-ranking leader in their HMG is White, and 23.5% of highest-ranking leaders are Asian. Only 5.5% of HMG leaders were Black/African American. Ethnicity was a separate question, and only 2.2% of HMG leaders were reported as Hispanic/Latino.

I have been profoundly moved by the wretched deaths of George Floyd and other people of color at the hands of police in recent months, and by the subsequent protests and our growing national reckoning over issues of racial equity and justice. In my efforts to understand more about race in America, I have been challenged by my friend Ryan Brown, MD, specialty medical director for hospital medicine with Atrium Health in Charlotte, N.C., and others to go beyond just learning about these issues. I want to use my voice to advocate for change, and my actions to participate in effecting change, within the context of my sphere of influence.

So, what does that have to do with the SoHM data on HMG leader demographics? Well, it’s clear that Black and brown people are woefully underrepresented in the ranks of hospital medicine leadership.

• Create and sponsor a mentoring program in which hospitalists volunteer to mentor minority junior high and high school students and help them prepare to pursue a career in medicine.
• Develop a formal, structured advocacy or collaboration effort with organizations like AAMC and the Accreditation Council for Graduate Medical Education designed to promote meaningful increases in the proportion of medical school students and residents who are people of color, and in the proportion who choose primary care – and ultimately, hospital medicine.
• Work hard to collect reliable racial, ethnic and gender information about SHM members and consider collaborating with MGMA to incorporate demographic questions into its survey tool for individual hospitalist compensation and productivity data. Challenge us on the Practice Analysis Committee who are responsible for the SoHM survey to continue surveying leadership demographics, and to consider how we can expand our collection of DEI information in 2022.
• Undertake a public relations campaign to highlight to health systems and other employers the under-representation of Black and Latino hospitalists in leadership positions, and to promote conscious efforts to increase those ranks.
• Create scholarships for hospitalists from underrepresented racial and ethnic groups to attend SHM-sponsored leadership development programs such as Leadership Academy, Academic Hospitalist Academy, and Quality and Safety Educators Academy, with the goal of increasing their ranks in positions of influence throughout healthcare. A scholarship program might even include raising funds to help minority hospitalists pursue Master’s-level programs such as an MBA, MHA, or MMM.
• Develop an educational track, mentoring program, or other support initiative for early-career hospitalist leaders and those interested in developing leadership skills, and ensure it gives specific attention to strategies for increasing the proportion of hospitalists of color in leadership positions.
• Review and revise existing SHM documents such as The Key Principles and Characteristics of an Effective Hospital Medicine Group, the Core Competencies in Hospital Medicine, and various white papers and position statements to ensure they address diversity, equity and inclusion – both with regard to the hospital medicine workforce and leadership, and with regard to patient care and eliminating health disparities.

I’m sure there are plenty of other similar actions we can take that I haven’t thought of. But we need to start the conversation about concrete steps our Society, and the medical specialty we represent, can take to foster real change. And then, we need to follow our words up with actions.

Ms. Flores is a partner at Nelson Flores Hospital Medicine Consultants in La Quinta, Calif. She serves on SHM’s Practice Analysis and Annual Conference Committees and helps to coordinate SHM’s biannual State of Hospital Medicine survey.

Have you ever done something where you’re not quite sure why you did it at the time, but later on you realize it was part of some larger cosmic purpose, and you go, “Ahhh, now I understand…that’s why!”? Call it a fortuitous coincidence. Or a subconscious act of anticipation. Maybe a little push from God.

Last summer, as SHM’s Practice Analysis Committee was planning the State of Hospital Medicine survey for 2020, we received a request from SHM’s Diversity, Equity & Inclusion (DEI) Special Interest Group (SIG) to include a series of questions related to hospitalist gender, race and ethnic distribution in the new survey. We’ve generally resisted doing things like this because the SoHM is designed to capture data at the group level, not the individual level – and honestly, it’s as much as a lot of groups can do to tell us reliably how many FTEs they have, much less provide details about individual providers. In addition, the survey is already really long, and we are always looking for ways to make it shorter and easier for participants while still collecting the information report users care most about.

But we wanted to take the asks from the DEI SIG seriously, and as we considered their request, we realized that though it wasn’t practical to collect this information for individual hospital medicine group (HMG) members, we could collect it for group leaders. Little did we know last summer that issues of gender and racial diversity and equity would be so front-and-center right now, as we prepare to release the 2020 SoHM Report in early September. Ahhh, now I understand…that’s why – with the prompting of the DEI SIG – we so fortuitously chose to include those questions this year!

Here’s a sneak preview of what we learned. Among SoHM respondents, 57.1% reported that the highest-ranking leader in their HMG is White, and 23.5% of highest-ranking leaders are Asian. Only 5.5% of HMG leaders were Black/African American. Ethnicity was a separate question, and only 2.2% of HMG leaders were reported as Hispanic/Latino.

I have been profoundly moved by the wretched deaths of George Floyd and other people of color at the hands of police in recent months, and by the subsequent protests and our growing national reckoning over issues of racial equity and justice. In my efforts to understand more about race in America, I have been challenged by my friend Ryan Brown, MD, specialty medical director for hospital medicine with Atrium Health in Charlotte, N.C., and others to go beyond just learning about these issues. I want to use my voice to advocate for change, and my actions to participate in effecting change, within the context of my sphere of influence.

So, what does that have to do with the SoHM data on HMG leader demographics? Well, it’s clear that Black and brown people are woefully underrepresented in the ranks of hospital medicine leadership.

• Create and sponsor a mentoring program in which hospitalists volunteer to mentor minority junior high and high school students and help them prepare to pursue a career in medicine.
• Develop a formal, structured advocacy or collaboration effort with organizations like AAMC and the Accreditation Council for Graduate Medical Education designed to promote meaningful increases in the proportion of medical school students and residents who are people of color, and in the proportion who choose primary care – and ultimately, hospital medicine.
• Work hard to collect reliable racial, ethnic and gender information about SHM members and consider collaborating with MGMA to incorporate demographic questions into its survey tool for individual hospitalist compensation and productivity data. Challenge us on the Practice Analysis Committee who are responsible for the SoHM survey to continue surveying leadership demographics, and to consider how we can expand our collection of DEI information in 2022.
• Undertake a public relations campaign to highlight to health systems and other employers the under-representation of Black and Latino hospitalists in leadership positions, and to promote conscious efforts to increase those ranks.
• Create scholarships for hospitalists from underrepresented racial and ethnic groups to attend SHM-sponsored leadership development programs such as Leadership Academy, Academic Hospitalist Academy, and Quality and Safety Educators Academy, with the goal of increasing their ranks in positions of influence throughout healthcare. A scholarship program might even include raising funds to help minority hospitalists pursue Master’s-level programs such as an MBA, MHA, or MMM.
• Develop an educational track, mentoring program, or other support initiative for early-career hospitalist leaders and those interested in developing leadership skills, and ensure it gives specific attention to strategies for increasing the proportion of hospitalists of color in leadership positions.
• Review and revise existing SHM documents such as The Key Principles and Characteristics of an Effective Hospital Medicine Group, the Core Competencies in Hospital Medicine, and various white papers and position statements to ensure they address diversity, equity and inclusion – both with regard to the hospital medicine workforce and leadership, and with regard to patient care and eliminating health disparities.

I’m sure there are plenty of other similar actions we can take that I haven’t thought of. But we need to start the conversation about concrete steps our Society, and the medical specialty we represent, can take to foster real change. And then, we need to follow our words up with actions.

Ms. Flores is a partner at Nelson Flores Hospital Medicine Consultants in La Quinta, Calif. She serves on SHM’s Practice Analysis and Annual Conference Committees and helps to coordinate SHM’s biannual State of Hospital Medicine survey.

Free CME Credit 

Hemolytic disease of the fetus and newborn (HDFN) is a rare condition with an estimated 3 to 80 cases per 100,000 persons annually in the United States. Nonetheless, the complexity and increased risk for adverse outcomes in such cases requires more targeted approaches to HDFN that minimize or negate the risks associated with intrauterine transfusion.
This article focuses on the pathophysiology underlying fetal/newborn allo- and autoimmune diseases, especially HDFN and the current/evolving diagnostic and treatment regimens for HDFN.

Click here to read the article.

CME CREDITS: .25 CREDITS
To receive CME credit, please read the articles and go to www.omniaeducation.com/HDFN to access the post-test and evaluation.

Free CME Credit 

Hemolytic disease of the fetus and newborn (HDFN) is a rare condition with an estimated 3 to 80 cases per 100,000 persons annually in the United States. Nonetheless, the complexity and increased risk for adverse outcomes in such cases requires more targeted approaches to HDFN that minimize or negate the risks associated with intrauterine transfusion.
This article focuses on the pathophysiology underlying fetal/newborn allo- and autoimmune diseases, especially HDFN and the current/evolving diagnostic and treatment regimens for HDFN.

Click here to read the article.

CME CREDITS: .25 CREDITS
To receive CME credit, please read the articles and go to www.omniaeducation.com/HDFN to access the post-test and evaluation.

Free CME Credit 

Hemolytic disease of the fetus and newborn (HDFN) is a rare condition with an estimated 3 to 80 cases per 100,000 persons annually in the United States. Nonetheless, the complexity and increased risk for adverse outcomes in such cases requires more targeted approaches to HDFN that minimize or negate the risks associated with intrauterine transfusion.
This article focuses on the pathophysiology underlying fetal/newborn allo- and autoimmune diseases, especially HDFN and the current/evolving diagnostic and treatment regimens for HDFN.

Click here to read the article.

CME CREDITS: .25 CREDITS
To receive CME credit, please read the articles and go to www.omniaeducation.com/HDFN to access the post-test and evaluation.

Rejuvenation of the lower face often involves treatment of the submentum and the jowls. Energy-based devices such as lasers, radiofrequency, radiofrequency microneedling, CoolSculpting, and ultrasound have been used in the tightening of the neck and jowls.

Lily Talakoub, MD

However, the only noninvasive injectable treatment approved for the reduction of submental fat is deoxycholic acid (Kybella). The mechanism of action of deoxycholic acid has been documented as adipocyte lysis, followed by a local tissue response with neutrophil infiltration, septal thickening, neocollagenesis, and neovascularization within the subcutaneous layer, with no adverse changes in the dermis or epidermis. This treatment, which has a dose-dependent response, is highly effective for submental fat reduction and jaw contouring.

In my practice, I have found that multiple consecutive treatments with deoxycholic acid (an off-label use) are effective in permanently reducing the jowl overhang with minimal adverse effects.

Jowl fat is a common cause of sagging of the jowls, and there are few alternatives to treatment with surgery or liposuction. Jowl overhang results from multiple factors related to aging, including skeletal resorption, subcutaneous atrophy, superior and inferior fat pad compartment displacement, or mandibular septum dehiscence, which allows for the accumulation of fat pockets to migrate into the neck.

A prospective study published earlier this year describes results in 66 adults with excess jowl fat, who were treated with 2 mg/cm² of deoxycholic acid. Injections were done in patients with “pinchable fat on the jawline” and “relatively” minimal skin laxity of 0.2 mL spaced approximately 1 cm apart or 0.1 mL spaced 0.5 cm-0.75 cm apart; the mean injection volume was 0.8 mL. After 6 months, 98% of the patients experienced improvement with a mean of 1.8 treatments. Common injection site adverse events included edema, numbness, tenderness, and bruising.

In my experience, injection volumes from 1.0 mL to 1.5 mL of deoxycholic acid can be used in each jowl with minimal adverse events if proper landmarks are followed. It is crucial that the correct patient is selected (one with minimal skin laxity), and that during injection, the fat and skin are pinched away from the underlying musculature and neurovascular structures to avoid injection near the marginal mandibular nerve. Volumes less than 1.0 mL have minimal visible improvements and will require more than 3-4 treatment sessions for optimal results.

Jowl contouring with deoxycholic acid (with or without treatment of the submental fat pads) should be considered in the treatment options for lower face rejuvenation. I often see a marked improvement in patients who present prominent marionette lines who have been unhappy with fillers in the lower face. Often, the marionette lines are a result of significant overhang from jowl fat and hyaluronic acid fillers are a temporary and often unsatisfactory treatment option. The use of deoxycholic acid in the treatment of the jowl fat is a highly effective option to minimize the appearance of marionette lines caused by displaced fat pockets in the aging lower face.
 

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected] . They had no relevant disclosures.

Rejuvenation of the lower face often involves treatment of the submentum and the jowls. Energy-based devices such as lasers, radiofrequency, radiofrequency microneedling, CoolSculpting, and ultrasound have been used in the tightening of the neck and jowls.

Lily Talakoub, MD

However, the only noninvasive injectable treatment approved for the reduction of submental fat is deoxycholic acid (Kybella). The mechanism of action of deoxycholic acid has been documented as adipocyte lysis, followed by a local tissue response with neutrophil infiltration, septal thickening, neocollagenesis, and neovascularization within the subcutaneous layer, with no adverse changes in the dermis or epidermis. This treatment, which has a dose-dependent response, is highly effective for submental fat reduction and jaw contouring.

In my practice, I have found that multiple consecutive treatments with deoxycholic acid (an off-label use) are effective in permanently reducing the jowl overhang with minimal adverse effects.

Jowl fat is a common cause of sagging of the jowls, and there are few alternatives to treatment with surgery or liposuction. Jowl overhang results from multiple factors related to aging, including skeletal resorption, subcutaneous atrophy, superior and inferior fat pad compartment displacement, or mandibular septum dehiscence, which allows for the accumulation of fat pockets to migrate into the neck.

A prospective study published earlier this year describes results in 66 adults with excess jowl fat, who were treated with 2 mg/cm² of deoxycholic acid. Injections were done in patients with “pinchable fat on the jawline” and “relatively” minimal skin laxity of 0.2 mL spaced approximately 1 cm apart or 0.1 mL spaced 0.5 cm-0.75 cm apart; the mean injection volume was 0.8 mL. After 6 months, 98% of the patients experienced improvement with a mean of 1.8 treatments. Common injection site adverse events included edema, numbness, tenderness, and bruising.

In my experience, injection volumes from 1.0 mL to 1.5 mL of deoxycholic acid can be used in each jowl with minimal adverse events if proper landmarks are followed. It is crucial that the correct patient is selected (one with minimal skin laxity), and that during injection, the fat and skin are pinched away from the underlying musculature and neurovascular structures to avoid injection near the marginal mandibular nerve. Volumes less than 1.0 mL have minimal visible improvements and will require more than 3-4 treatment sessions for optimal results.

Jowl contouring with deoxycholic acid (with or without treatment of the submental fat pads) should be considered in the treatment options for lower face rejuvenation. I often see a marked improvement in patients who present prominent marionette lines who have been unhappy with fillers in the lower face. Often, the marionette lines are a result of significant overhang from jowl fat and hyaluronic acid fillers are a temporary and often unsatisfactory treatment option. The use of deoxycholic acid in the treatment of the jowl fat is a highly effective option to minimize the appearance of marionette lines caused by displaced fat pockets in the aging lower face.
 

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected] . They had no relevant disclosures.

Rejuvenation of the lower face often involves treatment of the submentum and the jowls. Energy-based devices such as lasers, radiofrequency, radiofrequency microneedling, CoolSculpting, and ultrasound have been used in the tightening of the neck and jowls.

Lily Talakoub, MD

However, the only noninvasive injectable treatment approved for the reduction of submental fat is deoxycholic acid (Kybella). The mechanism of action of deoxycholic acid has been documented as adipocyte lysis, followed by a local tissue response with neutrophil infiltration, septal thickening, neocollagenesis, and neovascularization within the subcutaneous layer, with no adverse changes in the dermis or epidermis. This treatment, which has a dose-dependent response, is highly effective for submental fat reduction and jaw contouring.

In my practice, I have found that multiple consecutive treatments with deoxycholic acid (an off-label use) are effective in permanently reducing the jowl overhang with minimal adverse effects.

Jowl fat is a common cause of sagging of the jowls, and there are few alternatives to treatment with surgery or liposuction. Jowl overhang results from multiple factors related to aging, including skeletal resorption, subcutaneous atrophy, superior and inferior fat pad compartment displacement, or mandibular septum dehiscence, which allows for the accumulation of fat pockets to migrate into the neck.

A prospective study published earlier this year describes results in 66 adults with excess jowl fat, who were treated with 2 mg/cm² of deoxycholic acid. Injections were done in patients with “pinchable fat on the jawline” and “relatively” minimal skin laxity of 0.2 mL spaced approximately 1 cm apart or 0.1 mL spaced 0.5 cm-0.75 cm apart; the mean injection volume was 0.8 mL. After 6 months, 98% of the patients experienced improvement with a mean of 1.8 treatments. Common injection site adverse events included edema, numbness, tenderness, and bruising.

In my experience, injection volumes from 1.0 mL to 1.5 mL of deoxycholic acid can be used in each jowl with minimal adverse events if proper landmarks are followed. It is crucial that the correct patient is selected (one with minimal skin laxity), and that during injection, the fat and skin are pinched away from the underlying musculature and neurovascular structures to avoid injection near the marginal mandibular nerve. Volumes less than 1.0 mL have minimal visible improvements and will require more than 3-4 treatment sessions for optimal results.

Jowl contouring with deoxycholic acid (with or without treatment of the submental fat pads) should be considered in the treatment options for lower face rejuvenation. I often see a marked improvement in patients who present prominent marionette lines who have been unhappy with fillers in the lower face. Often, the marionette lines are a result of significant overhang from jowl fat and hyaluronic acid fillers are a temporary and often unsatisfactory treatment option. The use of deoxycholic acid in the treatment of the jowl fat is a highly effective option to minimize the appearance of marionette lines caused by displaced fat pockets in the aging lower face.
 

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected] . They had no relevant disclosures.

Children with complex medical conditions are living longer, many with the help of interventions and technology, such as gastrostomy tubes, tracheostomies, ventilator support, and parenteral nutrition. Children with medical complexity and technology account for over 80% of hospital days in pediatric academic centers.¹

Hospitalists need communication skills and clinical information to guide discussions with patients and families about whether to pursue these measures. Tracheostomy discussions can be particularly challenging. Over 4,000 infants and children undergo tracheostomy each year, with related hospital charges of more than $2 billion, a 30-day readmission rate of 24.9%, and a median length of stay for pneumonia or tracheitis of 4 days.² There is limited research on prognosis, outcomes, decision-making, and effects on quality of life, especially in the population of children who have significant neurological impairment (NI) and/or progressive or deteriorating neurological conditions. Physician biases may also influence this discussion.

This article will examine the question: How can a hospitalist guide decision-making discussions with families about tracheostomy placement for children with NI? A literature search was performed on Medline and Web of Science using the key terms tracheostomy, prognosis, neurologically impaired children, and decision-making. Articles included were relevant to the clinical question and published in the last 5 years. One article was included outside this timeframe given the scarcity of data.

Indications for tracheostomy include airway obstruction and the need for prolonged ventilation support.³ The number of tracheostomies placed has been increasing over the last 30 years, especially at tertiary care centers.³ Primary indications for tracheostomy include prolonged ventilation particularly in the context of underlying conditions such as congenital or acquired respiratory disease, congenital or acquired neurologic disease, cardiopulmonary disease, and primary anatomic airway obstruction.^3,4 Children who undergo tracheostomy often have multiple medical conditions that impact their overall health and prognosis, with 41% having three or more complex chronic health conditions.⁵ This article will focus on children who have a primary indication of NI and in whom tracheostomy is often used as a life-prolonging measure.

Discussions about tracheostomy should include information about risks, benefits, and prognosis. Prognosis discussions can be challenging given that many children for whom this intervention is being considered have multiple and complex medical conditions with uncertain or even known poor prognoses. Mortality rates ranging from 3% to 11% have been reported during the initial tracheostomy admission, with NI increasing the risk for mortality during the tracheostomy admission.^5,6 Children with NI also have higher mortality beyond the initial hospital stay, lower decannulation rates, and more frequent admissions with longer lengths of stay than do children receiving a tracheostomy for upper airway obstruction (Table 1).^6,7

For most children in this population, prognosis is related more to the underlying disease process than to the risk of the surgery for tracheostomy placement itself. Discussions with families should include the anticipated prognosis of the underlying disease, as well as current available data on outcomes for children with neurological impairment who have undergone tracheostomy placement. Most patients who receive a tracheostomy are children with complex medical conditions who have an acute event that leads to airway compromise and respiratory failure underscoring the importance of advance care planning.⁵

Clinicians face challenges when initiating advance care planning discussions, including prognostic uncertainty, the perception that families may not want to engage in these discussions, and the complexity and time these discussions can take. In one study of more than 300 chronically ill children, only 17% of parents had discussed advance directives, although 49% reported they would like to create one for their child.⁹ A small study found that, although parents find these discussions difficult, they also find them important. They value a step by step approach with consideration for hope and nonmedical concerns.¹⁰ Advance care planning discussions should be viewed as a time out to clarify what the family sees as the best path forward before initiation of a tracheostomy discussion and decision.

Determining goals of care is a cornerstone of any discussion about tracheostomy placement, especially when a child has a condition that is life limiting. The decision to pursue tracheostomy should involve shared decision-making. This decision-making process is the preferred communication model when multiple options could be pursued, each with its own risks and benefits.¹⁰

In this model of decision-making, the family’s goals and values should be determined in the context of the medical intervention that is being pursued. Medical information such as prognosis, risk, benefits, and impact of the intervention on quality of life should all be shared with the family. Ideally, shared decision-making allows the practitioner and family to make a decision together that matches the family’s goals and values with the best option available. If the family’s goal is to prolong life and they feel their child has good quality of life, tracheostomy placement may be the most appropriate option. However, it is also possible that the family’s goals may align more with less invasive treatment options or a transition to comfort care.

Discussions regarding goals of care can be challenging, and involving an interdisciplinary team and a Palliative Care consultant can be helpful.

Research on what parents find helpful in discussions about tracheostomy is limited. One study of 56 caregivers found that parents did not feel they could make a “free choice” because the alternative to tracheostomy was death.¹¹ In interviews with caregivers following tracheostomy, this same study found several themes in caregiver perspectives on their decision for tracheostomy (Table 2); caregivers saw a benefit to “health and well-being” from tracheostomy even though they reported feeling unprepared for the caregiving aspect at home or the potential negative side effects. Half the children in this study had a neurologic diagnosis, and only families who chose tracheostomy placement were included. To this author’s knowledge, there are currently no studies that look at decisional themes, satisfaction, or outcomes for families that chose to not pursue tracheostomy.

There is limited literature about how providers discuss tracheostomy. One single-center study of practitioners found that providers focused more often on the benefits of tracheostomy rather than burdens (72% vs 28%).¹² A common benefit theme was the provider “suggesting life with a tracheostomy might not be as difficult as families fear in that the child may have the ability to regain speech, engage in normal activities, and have the tracheostomy reversed once the child’s health improved.” However, decannulation rates and recovery trajectories for children with NI do not support this general expectation (Table 1). These provider communication themes may help to explain the family’s perspective that they feel unprepared for the burdens of a tracheostomy or the intensity of home caregiving. Given the limited data, it is difficult to generalize. Comparing communication and decision-making themes side by side does draw attention to how providers might better communicate with families about this decision (Table 2).

The difficult aspects of caregiving deserve special attention. A study of 25 parents showed reduced parental quality of life after their child’s tracheostomy placement related to overwhelming medical care, fear of death of the child requiring constant vigilance, and financial and psychological stressors.¹³ Most (72%) families in this study reported decisional regret at 3 months.Resources and support for a child with this level of care varies based on the child’s community. Exploration and discussion of what is available for each family, including home nursing, respite, and/or a skilled nursing facility, should be completed prior to tracheostomy placement. Honest discussions about the potential effects of this intervention on the family’s life can help inform their decision.

Decision-making tools for tracheostomy could be valuable for both families and clinicians. These tools allow for a more systematic approach to the decision-making process that takes into account the multidimensional aspects of this decision. The “Child Tracheostomy Decision Guide,” published by the Winnipeg Regional Health Authority, is one available tool.¹⁴ This tool guides families through the factors that may affect their decision-making and includes thoughts about goals of care, quality of life, prognosis, care at home, and other options such as comfort care. The Courageous Parents Network has also developed parent videos giving the perspective of parents who have chosen or not chosen tracheostomy.¹⁵ Currently, there are no studies that examine the usefulness of decision-making tools.

A common theme throughout the literature is the lack of a unifying classification system for reporting outcomes data. Each study utilizes different primary indications for tracheostomy and often different definitions for NI. There is very little literature that focuses specifically on outcomes for children with NI who receive tracheostomy as a life-prolonging measure. These gaps present challenges for obtaining meaningful prognosis data to share with families. Outcomes data for children who do not receive tracheostomy is also lacking. Additional studies on how families make this decision and their decisional satisfaction could help inform the decision-making process for both parents and clinicians. Research regarding the helpfulness and outcomes with decision-making tools would be useful.

Although there are limited data on outcomes specific to the children with NI and tracheostomy, existing literature shows a higher mortality, lower decannulation rate, higher hospitalization rate, and longer length of stay than that for children who receive tracheostomy for other indications. Tracheostomy is often a life-prolonging measure for children with NI. Shared decision-making should be the preferred communication process and include defining goals of care, as well as anticipated prognosis with balanced information about risks and benefits. Further research about the decision-making process and communication would be beneficial.

Dr Shaw has nothing to disclose.

Children with complex medical conditions are living longer, many with the help of interventions and technology, such as gastrostomy tubes, tracheostomies, ventilator support, and parenteral nutrition. Children with medical complexity and technology account for over 80% of hospital days in pediatric academic centers.¹

Hospitalists need communication skills and clinical information to guide discussions with patients and families about whether to pursue these measures. Tracheostomy discussions can be particularly challenging. Over 4,000 infants and children undergo tracheostomy each year, with related hospital charges of more than $2 billion, a 30-day readmission rate of 24.9%, and a median length of stay for pneumonia or tracheitis of 4 days.² There is limited research on prognosis, outcomes, decision-making, and effects on quality of life, especially in the population of children who have significant neurological impairment (NI) and/or progressive or deteriorating neurological conditions. Physician biases may also influence this discussion.

This article will examine the question: How can a hospitalist guide decision-making discussions with families about tracheostomy placement for children with NI? A literature search was performed on Medline and Web of Science using the key terms tracheostomy, prognosis, neurologically impaired children, and decision-making. Articles included were relevant to the clinical question and published in the last 5 years. One article was included outside this timeframe given the scarcity of data.

Indications for tracheostomy include airway obstruction and the need for prolonged ventilation support.³ The number of tracheostomies placed has been increasing over the last 30 years, especially at tertiary care centers.³ Primary indications for tracheostomy include prolonged ventilation particularly in the context of underlying conditions such as congenital or acquired respiratory disease, congenital or acquired neurologic disease, cardiopulmonary disease, and primary anatomic airway obstruction.^3,4 Children who undergo tracheostomy often have multiple medical conditions that impact their overall health and prognosis, with 41% having three or more complex chronic health conditions.⁵ This article will focus on children who have a primary indication of NI and in whom tracheostomy is often used as a life-prolonging measure.

Discussions about tracheostomy should include information about risks, benefits, and prognosis. Prognosis discussions can be challenging given that many children for whom this intervention is being considered have multiple and complex medical conditions with uncertain or even known poor prognoses. Mortality rates ranging from 3% to 11% have been reported during the initial tracheostomy admission, with NI increasing the risk for mortality during the tracheostomy admission.^5,6 Children with NI also have higher mortality beyond the initial hospital stay, lower decannulation rates, and more frequent admissions with longer lengths of stay than do children receiving a tracheostomy for upper airway obstruction (Table 1).^6,7

For most children in this population, prognosis is related more to the underlying disease process than to the risk of the surgery for tracheostomy placement itself. Discussions with families should include the anticipated prognosis of the underlying disease, as well as current available data on outcomes for children with neurological impairment who have undergone tracheostomy placement. Most patients who receive a tracheostomy are children with complex medical conditions who have an acute event that leads to airway compromise and respiratory failure underscoring the importance of advance care planning.⁵

Clinicians face challenges when initiating advance care planning discussions, including prognostic uncertainty, the perception that families may not want to engage in these discussions, and the complexity and time these discussions can take. In one study of more than 300 chronically ill children, only 17% of parents had discussed advance directives, although 49% reported they would like to create one for their child.⁹ A small study found that, although parents find these discussions difficult, they also find them important. They value a step by step approach with consideration for hope and nonmedical concerns.¹⁰ Advance care planning discussions should be viewed as a time out to clarify what the family sees as the best path forward before initiation of a tracheostomy discussion and decision.

Determining goals of care is a cornerstone of any discussion about tracheostomy placement, especially when a child has a condition that is life limiting. The decision to pursue tracheostomy should involve shared decision-making. This decision-making process is the preferred communication model when multiple options could be pursued, each with its own risks and benefits.¹⁰

In this model of decision-making, the family’s goals and values should be determined in the context of the medical intervention that is being pursued. Medical information such as prognosis, risk, benefits, and impact of the intervention on quality of life should all be shared with the family. Ideally, shared decision-making allows the practitioner and family to make a decision together that matches the family’s goals and values with the best option available. If the family’s goal is to prolong life and they feel their child has good quality of life, tracheostomy placement may be the most appropriate option. However, it is also possible that the family’s goals may align more with less invasive treatment options or a transition to comfort care.

Discussions regarding goals of care can be challenging, and involving an interdisciplinary team and a Palliative Care consultant can be helpful.

Research on what parents find helpful in discussions about tracheostomy is limited. One study of 56 caregivers found that parents did not feel they could make a “free choice” because the alternative to tracheostomy was death.¹¹ In interviews with caregivers following tracheostomy, this same study found several themes in caregiver perspectives on their decision for tracheostomy (Table 2); caregivers saw a benefit to “health and well-being” from tracheostomy even though they reported feeling unprepared for the caregiving aspect at home or the potential negative side effects. Half the children in this study had a neurologic diagnosis, and only families who chose tracheostomy placement were included. To this author’s knowledge, there are currently no studies that look at decisional themes, satisfaction, or outcomes for families that chose to not pursue tracheostomy.

There is limited literature about how providers discuss tracheostomy. One single-center study of practitioners found that providers focused more often on the benefits of tracheostomy rather than burdens (72% vs 28%).¹² A common benefit theme was the provider “suggesting life with a tracheostomy might not be as difficult as families fear in that the child may have the ability to regain speech, engage in normal activities, and have the tracheostomy reversed once the child’s health improved.” However, decannulation rates and recovery trajectories for children with NI do not support this general expectation (Table 1). These provider communication themes may help to explain the family’s perspective that they feel unprepared for the burdens of a tracheostomy or the intensity of home caregiving. Given the limited data, it is difficult to generalize. Comparing communication and decision-making themes side by side does draw attention to how providers might better communicate with families about this decision (Table 2).

The difficult aspects of caregiving deserve special attention. A study of 25 parents showed reduced parental quality of life after their child’s tracheostomy placement related to overwhelming medical care, fear of death of the child requiring constant vigilance, and financial and psychological stressors.¹³ Most (72%) families in this study reported decisional regret at 3 months.Resources and support for a child with this level of care varies based on the child’s community. Exploration and discussion of what is available for each family, including home nursing, respite, and/or a skilled nursing facility, should be completed prior to tracheostomy placement. Honest discussions about the potential effects of this intervention on the family’s life can help inform their decision.

Decision-making tools for tracheostomy could be valuable for both families and clinicians. These tools allow for a more systematic approach to the decision-making process that takes into account the multidimensional aspects of this decision. The “Child Tracheostomy Decision Guide,” published by the Winnipeg Regional Health Authority, is one available tool.¹⁴ This tool guides families through the factors that may affect their decision-making and includes thoughts about goals of care, quality of life, prognosis, care at home, and other options such as comfort care. The Courageous Parents Network has also developed parent videos giving the perspective of parents who have chosen or not chosen tracheostomy.¹⁵ Currently, there are no studies that examine the usefulness of decision-making tools.

A common theme throughout the literature is the lack of a unifying classification system for reporting outcomes data. Each study utilizes different primary indications for tracheostomy and often different definitions for NI. There is very little literature that focuses specifically on outcomes for children with NI who receive tracheostomy as a life-prolonging measure. These gaps present challenges for obtaining meaningful prognosis data to share with families. Outcomes data for children who do not receive tracheostomy is also lacking. Additional studies on how families make this decision and their decisional satisfaction could help inform the decision-making process for both parents and clinicians. Research regarding the helpfulness and outcomes with decision-making tools would be useful.

Although there are limited data on outcomes specific to the children with NI and tracheostomy, existing literature shows a higher mortality, lower decannulation rate, higher hospitalization rate, and longer length of stay than that for children who receive tracheostomy for other indications. Tracheostomy is often a life-prolonging measure for children with NI. Shared decision-making should be the preferred communication process and include defining goals of care, as well as anticipated prognosis with balanced information about risks and benefits. Further research about the decision-making process and communication would be beneficial.

Dr Shaw has nothing to disclose.

Children with complex medical conditions are living longer, many with the help of interventions and technology, such as gastrostomy tubes, tracheostomies, ventilator support, and parenteral nutrition. Children with medical complexity and technology account for over 80% of hospital days in pediatric academic centers.¹

Hospitalists need communication skills and clinical information to guide discussions with patients and families about whether to pursue these measures. Tracheostomy discussions can be particularly challenging. Over 4,000 infants and children undergo tracheostomy each year, with related hospital charges of more than $2 billion, a 30-day readmission rate of 24.9%, and a median length of stay for pneumonia or tracheitis of 4 days.² There is limited research on prognosis, outcomes, decision-making, and effects on quality of life, especially in the population of children who have significant neurological impairment (NI) and/or progressive or deteriorating neurological conditions. Physician biases may also influence this discussion.

This article will examine the question: How can a hospitalist guide decision-making discussions with families about tracheostomy placement for children with NI? A literature search was performed on Medline and Web of Science using the key terms tracheostomy, prognosis, neurologically impaired children, and decision-making. Articles included were relevant to the clinical question and published in the last 5 years. One article was included outside this timeframe given the scarcity of data.

Indications for tracheostomy include airway obstruction and the need for prolonged ventilation support.³ The number of tracheostomies placed has been increasing over the last 30 years, especially at tertiary care centers.³ Primary indications for tracheostomy include prolonged ventilation particularly in the context of underlying conditions such as congenital or acquired respiratory disease, congenital or acquired neurologic disease, cardiopulmonary disease, and primary anatomic airway obstruction.^3,4 Children who undergo tracheostomy often have multiple medical conditions that impact their overall health and prognosis, with 41% having three or more complex chronic health conditions.⁵ This article will focus on children who have a primary indication of NI and in whom tracheostomy is often used as a life-prolonging measure.

Discussions about tracheostomy should include information about risks, benefits, and prognosis. Prognosis discussions can be challenging given that many children for whom this intervention is being considered have multiple and complex medical conditions with uncertain or even known poor prognoses. Mortality rates ranging from 3% to 11% have been reported during the initial tracheostomy admission, with NI increasing the risk for mortality during the tracheostomy admission.^5,6 Children with NI also have higher mortality beyond the initial hospital stay, lower decannulation rates, and more frequent admissions with longer lengths of stay than do children receiving a tracheostomy for upper airway obstruction (Table 1).^6,7

For most children in this population, prognosis is related more to the underlying disease process than to the risk of the surgery for tracheostomy placement itself. Discussions with families should include the anticipated prognosis of the underlying disease, as well as current available data on outcomes for children with neurological impairment who have undergone tracheostomy placement. Most patients who receive a tracheostomy are children with complex medical conditions who have an acute event that leads to airway compromise and respiratory failure underscoring the importance of advance care planning.⁵

Clinicians face challenges when initiating advance care planning discussions, including prognostic uncertainty, the perception that families may not want to engage in these discussions, and the complexity and time these discussions can take. In one study of more than 300 chronically ill children, only 17% of parents had discussed advance directives, although 49% reported they would like to create one for their child.⁹ A small study found that, although parents find these discussions difficult, they also find them important. They value a step by step approach with consideration for hope and nonmedical concerns.¹⁰ Advance care planning discussions should be viewed as a time out to clarify what the family sees as the best path forward before initiation of a tracheostomy discussion and decision.

Determining goals of care is a cornerstone of any discussion about tracheostomy placement, especially when a child has a condition that is life limiting. The decision to pursue tracheostomy should involve shared decision-making. This decision-making process is the preferred communication model when multiple options could be pursued, each with its own risks and benefits.¹⁰

In this model of decision-making, the family’s goals and values should be determined in the context of the medical intervention that is being pursued. Medical information such as prognosis, risk, benefits, and impact of the intervention on quality of life should all be shared with the family. Ideally, shared decision-making allows the practitioner and family to make a decision together that matches the family’s goals and values with the best option available. If the family’s goal is to prolong life and they feel their child has good quality of life, tracheostomy placement may be the most appropriate option. However, it is also possible that the family’s goals may align more with less invasive treatment options or a transition to comfort care.

Discussions regarding goals of care can be challenging, and involving an interdisciplinary team and a Palliative Care consultant can be helpful.

Research on what parents find helpful in discussions about tracheostomy is limited. One study of 56 caregivers found that parents did not feel they could make a “free choice” because the alternative to tracheostomy was death.¹¹ In interviews with caregivers following tracheostomy, this same study found several themes in caregiver perspectives on their decision for tracheostomy (Table 2); caregivers saw a benefit to “health and well-being” from tracheostomy even though they reported feeling unprepared for the caregiving aspect at home or the potential negative side effects. Half the children in this study had a neurologic diagnosis, and only families who chose tracheostomy placement were included. To this author’s knowledge, there are currently no studies that look at decisional themes, satisfaction, or outcomes for families that chose to not pursue tracheostomy.

There is limited literature about how providers discuss tracheostomy. One single-center study of practitioners found that providers focused more often on the benefits of tracheostomy rather than burdens (72% vs 28%).¹² A common benefit theme was the provider “suggesting life with a tracheostomy might not be as difficult as families fear in that the child may have the ability to regain speech, engage in normal activities, and have the tracheostomy reversed once the child’s health improved.” However, decannulation rates and recovery trajectories for children with NI do not support this general expectation (Table 1). These provider communication themes may help to explain the family’s perspective that they feel unprepared for the burdens of a tracheostomy or the intensity of home caregiving. Given the limited data, it is difficult to generalize. Comparing communication and decision-making themes side by side does draw attention to how providers might better communicate with families about this decision (Table 2).

The difficult aspects of caregiving deserve special attention. A study of 25 parents showed reduced parental quality of life after their child’s tracheostomy placement related to overwhelming medical care, fear of death of the child requiring constant vigilance, and financial and psychological stressors.¹³ Most (72%) families in this study reported decisional regret at 3 months.Resources and support for a child with this level of care varies based on the child’s community. Exploration and discussion of what is available for each family, including home nursing, respite, and/or a skilled nursing facility, should be completed prior to tracheostomy placement. Honest discussions about the potential effects of this intervention on the family’s life can help inform their decision.

Decision-making tools for tracheostomy could be valuable for both families and clinicians. These tools allow for a more systematic approach to the decision-making process that takes into account the multidimensional aspects of this decision. The “Child Tracheostomy Decision Guide,” published by the Winnipeg Regional Health Authority, is one available tool.¹⁴ This tool guides families through the factors that may affect their decision-making and includes thoughts about goals of care, quality of life, prognosis, care at home, and other options such as comfort care. The Courageous Parents Network has also developed parent videos giving the perspective of parents who have chosen or not chosen tracheostomy.¹⁵ Currently, there are no studies that examine the usefulness of decision-making tools.

A common theme throughout the literature is the lack of a unifying classification system for reporting outcomes data. Each study utilizes different primary indications for tracheostomy and often different definitions for NI. There is very little literature that focuses specifically on outcomes for children with NI who receive tracheostomy as a life-prolonging measure. These gaps present challenges for obtaining meaningful prognosis data to share with families. Outcomes data for children who do not receive tracheostomy is also lacking. Additional studies on how families make this decision and their decisional satisfaction could help inform the decision-making process for both parents and clinicians. Research regarding the helpfulness and outcomes with decision-making tools would be useful.

Although there are limited data on outcomes specific to the children with NI and tracheostomy, existing literature shows a higher mortality, lower decannulation rate, higher hospitalization rate, and longer length of stay than that for children who receive tracheostomy for other indications. Tracheostomy is often a life-prolonging measure for children with NI. Shared decision-making should be the preferred communication process and include defining goals of care, as well as anticipated prognosis with balanced information about risks and benefits. Further research about the decision-making process and communication would be beneficial.

Dr Shaw has nothing to disclose.