Key clinical point: Compared with radiofrequency ablation (RFA), microwave ablation (MWA) effectuates better 1- and 2-year disease-free survival (DFS) along with a lower risk of major complications in patients with hepatocellular carcinoma (HCC).

Main finding: Although both ablation therapies led to a similar 2-year overall survival (P = .573), MWA achieved better 1-year DFS (79.7% vs 60.7%; P = .035) and 2-year DFS (72.5% vs 45.4%; P = .02) rates than RFA. Concurrently, MWA showed a lower rate of major complications than RFA (14% vs 29%; P = .043).

Study details: Findings are from a retrospective cohort study involving 150 patients with HCC, including treatment-naïve and recurrent HCC, who were treated with either RFA (n=100) or MWA (n=50).

Disclosures: The study was sponsored by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. No conflict of interests was reported by the authors.

Source: Lee SK et al. J Clin Med. 2022 Jan 7. doi: 10.3390/jcm11020302.

Key clinical point: Compared with radiofrequency ablation (RFA), microwave ablation (MWA) effectuates better 1- and 2-year disease-free survival (DFS) along with a lower risk of major complications in patients with hepatocellular carcinoma (HCC).

Main finding: Although both ablation therapies led to a similar 2-year overall survival (P = .573), MWA achieved better 1-year DFS (79.7% vs 60.7%; P = .035) and 2-year DFS (72.5% vs 45.4%; P = .02) rates than RFA. Concurrently, MWA showed a lower rate of major complications than RFA (14% vs 29%; P = .043).

Study details: Findings are from a retrospective cohort study involving 150 patients with HCC, including treatment-naïve and recurrent HCC, who were treated with either RFA (n=100) or MWA (n=50).

Disclosures: The study was sponsored by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. No conflict of interests was reported by the authors.

Source: Lee SK et al. J Clin Med. 2022 Jan 7. doi: 10.3390/jcm11020302.

Key clinical point: Compared with radiofrequency ablation (RFA), microwave ablation (MWA) effectuates better 1- and 2-year disease-free survival (DFS) along with a lower risk of major complications in patients with hepatocellular carcinoma (HCC).

Main finding: Although both ablation therapies led to a similar 2-year overall survival (P = .573), MWA achieved better 1-year DFS (79.7% vs 60.7%; P = .035) and 2-year DFS (72.5% vs 45.4%; P = .02) rates than RFA. Concurrently, MWA showed a lower rate of major complications than RFA (14% vs 29%; P = .043).

Study details: Findings are from a retrospective cohort study involving 150 patients with HCC, including treatment-naïve and recurrent HCC, who were treated with either RFA (n=100) or MWA (n=50).

Disclosures: The study was sponsored by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. No conflict of interests was reported by the authors.

Source: Lee SK et al. J Clin Med. 2022 Jan 7. doi: 10.3390/jcm11020302.

Key clinical point: First-line radiofrequency ablation (RFA) is associated with worse long-term therapeutic outcomes for single periportal hepatocellular carcinoma (HCC) than for single nonperiportal HCC.

Main finding: At 1 and 5 years, periportal vs nonperiportal HCC was associated with significantly higher local tumor progression rates (15.7% and 46.9% vs 6.0% and 28.7%, respectively; P = .007) and worse overall survival rates (81.3% and 42.9% vs 99.3% and 78.1%, respectively; P < .0001).

Study details: The data come from a retrospective study involving 233 patients with HCC, either periportal (n=56) or nonperiportal (n=177), who underwent percutaneous RFA alone or combined with transarterial chemoembolization as first-line treatment.

Disclosures: The authors reported no funding source or conflict of interests.

Source: Cao S et al. Cancer Imaging. 2022 Jan 4. doi: 10.1186/s40644-021-00442-2.

Key clinical point: First-line radiofrequency ablation (RFA) is associated with worse long-term therapeutic outcomes for single periportal hepatocellular carcinoma (HCC) than for single nonperiportal HCC.

Main finding: At 1 and 5 years, periportal vs nonperiportal HCC was associated with significantly higher local tumor progression rates (15.7% and 46.9% vs 6.0% and 28.7%, respectively; P = .007) and worse overall survival rates (81.3% and 42.9% vs 99.3% and 78.1%, respectively; P < .0001).

Study details: The data come from a retrospective study involving 233 patients with HCC, either periportal (n=56) or nonperiportal (n=177), who underwent percutaneous RFA alone or combined with transarterial chemoembolization as first-line treatment.

Disclosures: The authors reported no funding source or conflict of interests.

Source: Cao S et al. Cancer Imaging. 2022 Jan 4. doi: 10.1186/s40644-021-00442-2.

Key clinical point: First-line radiofrequency ablation (RFA) is associated with worse long-term therapeutic outcomes for single periportal hepatocellular carcinoma (HCC) than for single nonperiportal HCC.

Main finding: At 1 and 5 years, periportal vs nonperiportal HCC was associated with significantly higher local tumor progression rates (15.7% and 46.9% vs 6.0% and 28.7%, respectively; P = .007) and worse overall survival rates (81.3% and 42.9% vs 99.3% and 78.1%, respectively; P < .0001).

Study details: The data come from a retrospective study involving 233 patients with HCC, either periportal (n=56) or nonperiportal (n=177), who underwent percutaneous RFA alone or combined with transarterial chemoembolization as first-line treatment.

Disclosures: The authors reported no funding source or conflict of interests.

Source: Cao S et al. Cancer Imaging. 2022 Jan 4. doi: 10.1186/s40644-021-00442-2.

Key clinical point: As initial treatment, hepatic arterial infusion chemotherapy (HAIC) effectuates a greater survival and radiological response than transarterial chemoembolization (TACE) among patients with infiltrative hepatocellular carcinoma (HCC).

Main finding: HIAC vs TACE led to a longer median overall survival (13.3 months vs 10.8 months; P = .043) and progression-free survival (7.8 months vs 4.0 months; P = .035) along with higher objective response (34.8% vs 11.8%; P = .001) and disease control (54.3% vs 36.8%; P = .028) rates.

Study details: Findings are from a retrospective real-world study including 160 adult patients with large infiltrative HCCs who underwent either HAIC (n=92) or TACE (n=68) as initial treatment.

Disclosures: The authors declared receiving no financial assistance for the study and having no potential conflict of interests.

Source: An C et al. Front Oncol. 2021 Dec 16. doi: 10.3389/fonc.2021.747496.

Key clinical point: As initial treatment, hepatic arterial infusion chemotherapy (HAIC) effectuates a greater survival and radiological response than transarterial chemoembolization (TACE) among patients with infiltrative hepatocellular carcinoma (HCC).

Main finding: HIAC vs TACE led to a longer median overall survival (13.3 months vs 10.8 months; P = .043) and progression-free survival (7.8 months vs 4.0 months; P = .035) along with higher objective response (34.8% vs 11.8%; P = .001) and disease control (54.3% vs 36.8%; P = .028) rates.

Study details: Findings are from a retrospective real-world study including 160 adult patients with large infiltrative HCCs who underwent either HAIC (n=92) or TACE (n=68) as initial treatment.

Disclosures: The authors declared receiving no financial assistance for the study and having no potential conflict of interests.

Source: An C et al. Front Oncol. 2021 Dec 16. doi: 10.3389/fonc.2021.747496.

Key clinical point: As initial treatment, hepatic arterial infusion chemotherapy (HAIC) effectuates a greater survival and radiological response than transarterial chemoembolization (TACE) among patients with infiltrative hepatocellular carcinoma (HCC).

Main finding: HIAC vs TACE led to a longer median overall survival (13.3 months vs 10.8 months; P = .043) and progression-free survival (7.8 months vs 4.0 months; P = .035) along with higher objective response (34.8% vs 11.8%; P = .001) and disease control (54.3% vs 36.8%; P = .028) rates.

Study details: Findings are from a retrospective real-world study including 160 adult patients with large infiltrative HCCs who underwent either HAIC (n=92) or TACE (n=68) as initial treatment.

Disclosures: The authors declared receiving no financial assistance for the study and having no potential conflict of interests.

Source: An C et al. Front Oncol. 2021 Dec 16. doi: 10.3389/fonc.2021.747496.

Key clinical point: Modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined objective response (OR) and early tumor shrinkage (ETS) may serve as independent prognostic factors for overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) on sorafenib monotherapy.

Main finding: OR assessed by mRECIST (adjusted hazard ratio [aHR], 0.32; P < .001) and ETS (aHR, 0.44; P < .001) were independent prognostic factors for OS. A longer median OS was shown by responders vs nonresponders (30.3 months vs 11.4 months; P < .001) and by patients with ETS ≥20% vs those with ETS <20% (22.1 months vs 11.4 months; P < .001).

Study details: This was a post hoc analysis of data from the phase 2 SORAMIC trial and included 115 patients with advanced HCC receiving sorafenib monotherapy.

Disclosures: The study was sponsored by Sirtex Medical and Bayer Healthcare. Some of the authors declared receiving personal fees and research grants from various sources including Bayer and Sirtex.

Source: Öcal O et al. Cancer Imaging. 2022 Jan 4. doi: 10.1186/s40644-021-00439-x.

Key clinical point: Modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined objective response (OR) and early tumor shrinkage (ETS) may serve as independent prognostic factors for overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) on sorafenib monotherapy.

Main finding: OR assessed by mRECIST (adjusted hazard ratio [aHR], 0.32; P < .001) and ETS (aHR, 0.44; P < .001) were independent prognostic factors for OS. A longer median OS was shown by responders vs nonresponders (30.3 months vs 11.4 months; P < .001) and by patients with ETS ≥20% vs those with ETS <20% (22.1 months vs 11.4 months; P < .001).

Study details: This was a post hoc analysis of data from the phase 2 SORAMIC trial and included 115 patients with advanced HCC receiving sorafenib monotherapy.

Disclosures: The study was sponsored by Sirtex Medical and Bayer Healthcare. Some of the authors declared receiving personal fees and research grants from various sources including Bayer and Sirtex.

Source: Öcal O et al. Cancer Imaging. 2022 Jan 4. doi: 10.1186/s40644-021-00439-x.

Key clinical point: Modified Response Evaluation Criteria in Solid Tumors (mRECIST)-determined objective response (OR) and early tumor shrinkage (ETS) may serve as independent prognostic factors for overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) on sorafenib monotherapy.

Main finding: OR assessed by mRECIST (adjusted hazard ratio [aHR], 0.32; P < .001) and ETS (aHR, 0.44; P < .001) were independent prognostic factors for OS. A longer median OS was shown by responders vs nonresponders (30.3 months vs 11.4 months; P < .001) and by patients with ETS ≥20% vs those with ETS <20% (22.1 months vs 11.4 months; P < .001).

Study details: This was a post hoc analysis of data from the phase 2 SORAMIC trial and included 115 patients with advanced HCC receiving sorafenib monotherapy.

Disclosures: The study was sponsored by Sirtex Medical and Bayer Healthcare. Some of the authors declared receiving personal fees and research grants from various sources including Bayer and Sirtex.

Source: Öcal O et al. Cancer Imaging. 2022 Jan 4. doi: 10.1186/s40644-021-00439-x.

Key clinical point: Lowering the current United Network for Organ Sharing-recommended alpha-fetoprotein (AFP) level threshold for exclusion from liver transplant (LT) to ≥500 ng/mL for all patients with hepatocellular carcinoma (HCC) instead of only for those with AFP levels >1000 ng/mL could improve post-LT outcomes.

Main finding: After multivariable adjustment, an AFP level ≥500 ng/mL at LT was associated with an elevated risk of post-LT mortality (adjusted hazard ratio [aHR], 1.5; P = .02) and HCC recurrence (aHR, 1.88; P = .02) compared with an AFP level <100 ng/mL.

Study details: This was a retrospective cohort study involving 1,766 adult patients with HCC who had undergone LT and had listing AFP levels between 100 ng/mL and 999 ng/mL at initial model for end-stage liver disease exception.

Disclosures: The study was funded by the UCSF Clinical and Translational Science Institute Research Funding Award and UCSF Liver Center. Some of the authors reported being on the advisory board of or receiving research grants from various organizations.

Source: Goldman ML et al. Liver Transpl. 2021 Dec 20. doi: 10.1002/lt.26392.

Key clinical point: Lowering the current United Network for Organ Sharing-recommended alpha-fetoprotein (AFP) level threshold for exclusion from liver transplant (LT) to ≥500 ng/mL for all patients with hepatocellular carcinoma (HCC) instead of only for those with AFP levels >1000 ng/mL could improve post-LT outcomes.

Main finding: After multivariable adjustment, an AFP level ≥500 ng/mL at LT was associated with an elevated risk of post-LT mortality (adjusted hazard ratio [aHR], 1.5; P = .02) and HCC recurrence (aHR, 1.88; P = .02) compared with an AFP level <100 ng/mL.

Study details: This was a retrospective cohort study involving 1,766 adult patients with HCC who had undergone LT and had listing AFP levels between 100 ng/mL and 999 ng/mL at initial model for end-stage liver disease exception.

Disclosures: The study was funded by the UCSF Clinical and Translational Science Institute Research Funding Award and UCSF Liver Center. Some of the authors reported being on the advisory board of or receiving research grants from various organizations.

Source: Goldman ML et al. Liver Transpl. 2021 Dec 20. doi: 10.1002/lt.26392.

Key clinical point: Lowering the current United Network for Organ Sharing-recommended alpha-fetoprotein (AFP) level threshold for exclusion from liver transplant (LT) to ≥500 ng/mL for all patients with hepatocellular carcinoma (HCC) instead of only for those with AFP levels >1000 ng/mL could improve post-LT outcomes.

Main finding: After multivariable adjustment, an AFP level ≥500 ng/mL at LT was associated with an elevated risk of post-LT mortality (adjusted hazard ratio [aHR], 1.5; P = .02) and HCC recurrence (aHR, 1.88; P = .02) compared with an AFP level <100 ng/mL.

Study details: This was a retrospective cohort study involving 1,766 adult patients with HCC who had undergone LT and had listing AFP levels between 100 ng/mL and 999 ng/mL at initial model for end-stage liver disease exception.

Disclosures: The study was funded by the UCSF Clinical and Translational Science Institute Research Funding Award and UCSF Liver Center. Some of the authors reported being on the advisory board of or receiving research grants from various organizations.

Source: Goldman ML et al. Liver Transpl. 2021 Dec 20. doi: 10.1002/lt.26392.

Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.

In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.

However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.

In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).

Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).

The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).

Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.

The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.

However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
 

Data may inform clinical decisions

“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.

“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.

The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.

However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.

The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.

In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.

However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.

In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).

Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).

The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).

Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.

The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.

However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
 

Data may inform clinical decisions

“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.

“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.

The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.

However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.

The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Approximately 3% of youth who tested positive for COVID-19 in an emergency department setting had severe outcomes after 2 weeks, but this risk was 0.5% among those not admitted to the hospital, based on data from more than 3,000 individuals aged 18 and younger.

In the early stages of the COVID-19 pandemic, youth younger than 18 years accounted for fewer than 5% of reported cases, but now account for approximately 25% of positive cases, wrote Anna L. Funk, PhD, of the University of Calgary, Alberta, Canada, and colleagues.

However, the risk of severe outcomes of youth with COVID-19 remains poorly understood and data from large studies are lacking, they noted.

In a prospective cohort study published in JAMA Network Open, the researchers reviewed data from 3,221 children and adolescents who were tested for COVID-19 at one of 41 emergency departments in 10 countries including Argentina, Australia, Canada, Costa Rica, Italy, New Zealand, Paraguay, Singapore, Spain, and the United States between March 2020 and June 2021. Positive infections were confirmed by polymerase chain reaction (PCR) testing. At 14 days’ follow-up after a positive test, 735 patients (22.8%), were hospitalized, 107 (3.3%) had severe outcomes, and 4 (0.12%) had died. Severe outcomes were significantly more likely in children aged 5-10 years and 10-18 years vs. less than 1 year (odds ratios, 1.60 and 2.39, respectively), and in children with a self-reported chronic illness (OR, 2.34) or a prior episode of pneumonia (OR, 3.15).

Severe outcomes were more likely in patients who presented with symptoms that started 4-7 days before seeking care, compared with those whose symptoms started 0-3 days before seeking care (OR, 2.22).

The researchers also reviewed data from a subgroup of 2,510 individuals who were discharged home from the ED after initial testing. At 14 days’ follow-up, 50 of these patients (2.0%) were hospitalized and 12 (0.5%) had severe outcomes. In addition, the researchers found that the risk of severe outcomes among hospitalized COVID-19–positive youth was nearly four times higher, compared with hospitalized youth who tested negative for COVID-19 (risk difference, 3.9%).

Previous retrospective studies of severe outcomes in children and adolescents with COVID-19 have yielded varying results, in part because of the variation in study populations, the researchers noted in their discussion of the findings. “Our study population provides a risk estimate for youths brought for ED care.” Therefore, “Our lower estimate of severe disease likely reflects our stringent definition, which required the occurrence of complications or specific invasive interventions,” they said.

The study limitations included the potential overestimation of the risk of severe outcomes because patients were recruited in the ED, the researchers noted. Other limitations included variation in regional case definitions, screening criteria, and testing capacity among different sites and time periods. “Thus, 5% of our SARS-CoV-2–positive participants were asymptomatic – most of whom were tested as they were positive contacts of known cases or as part of routine screening procedures,” they said. The findings also are not generalizable to all community EDs and did not account for variants, they added.

However, the results were strengthened by the ability to compare outcomes for children with positive tests to similar children with negative tests, and add to the literature showing an increased risk of severe outcomes for those hospitalized with positive tests, the researchers concluded.
 

Data may inform clinical decisions

“The data [in the current study] are concerning for severe outcomes for children even prior to the Omicron strain,” said Margaret Thew, DNP, FP-BC, of Children’s Wisconsin-Milwaukee Hospital, in an interview. “Presently, the number of children infected with the Omicron strain is much higher and hospitalizations among children are at their highest since COVID-19 began,” she said. “For medical providers caring for this population, the study sheds light on pediatric patients who may be at higher risk of severe illness when they become infected with COVID-19,” she added.

“I was surprised by how high the number of pediatric patients hospitalized (22%) and the percentage (3%) with severe disease were during this time,” given that the timeline for these data preceded the spread of the Omicron strain, said Ms. Thew. “The risk of prior pneumonia was quite surprising. I do not recall seeing prior pneumonia as a risk factor for more severe COVID-19 with children or adults,” she added.

The take-home messaging for clinicians caring for children and adolescents is the added knowledge of the risk factors for severe outcomes from COVID-19, including the 10-18 age range, chronic illness, prior pneumonia, and longer symptom duration before seeking care in the ED, Ms. Thew emphasized.

However, additional research is needed on the impact of the new strains of COVID-19 on pediatric and adolescent hospitalizations, Ms. Thew said. Research also is needed on the other illnesses that have resulted from COVID-19, including illness requiring antibiotic use or medical interventions or treatments, and on the risk of combined COVID-19 and influenza viruses, she noted.

The study was supported by the Canadian Institutes of Health Research, Alberta Innovates, the Alberta Health Services University of Calgary Clinical Research Fund, the Alberta Children’s Hospital Research Institute, the COVID-19 Research Accelerator Funding Track (CRAFT) Program at the University of California, Davis, and the Cincinnati Children’s Hospital Medical Center Division of Emergency Medicine Small Grants Program. Lead author Dr. Funk was supported by the University of Calgary Eyes-High Post-Doctoral Research Fund, but had no financial conflicts to disclose. Ms. Thew had no financial conflicts to disclose and serves on the Editorial Advisory Board of Pediatric News.

Key clinical point: Individuals with persistent or incident body fatness show an increased risk of developing hepatocellular carcinoma (HCC).

Main finding: Compared with their persistent no-fatness counterparts, both general fatness (persistent: adjusted hazard ratio [aHR], 1.28; 95% CI, 1.23-1.34; incident: aHR, 1.10; 95% CI, 1.01-1.20) and central fatness (persistent: aHR, 1.33; 95% CI, 1.26-1.40; incident: aHR, 1.19; 95% CI, 1.11-1.27) were associated with an increased risk of HCC.

Study details: The data come from a nationwide population-based cohort study including 6,789,472 individuals aged 20 years or older who were not previously diagnosed with HCC and underwent health examinations twice with a gap of 2 years.

Disclosures: The study was sponsored by the Research Supporting Program of The Korean Association for the Study of the Liver and the Korean Liver Foundation. The authors declared no conflict of interests.

Source: Kim MN et al. Int J Cancer. 2021 Dec 26. doi: 10.1002/ijc.33920.

Key clinical point: Individuals with persistent or incident body fatness show an increased risk of developing hepatocellular carcinoma (HCC).

Main finding: Compared with their persistent no-fatness counterparts, both general fatness (persistent: adjusted hazard ratio [aHR], 1.28; 95% CI, 1.23-1.34; incident: aHR, 1.10; 95% CI, 1.01-1.20) and central fatness (persistent: aHR, 1.33; 95% CI, 1.26-1.40; incident: aHR, 1.19; 95% CI, 1.11-1.27) were associated with an increased risk of HCC.

Study details: The data come from a nationwide population-based cohort study including 6,789,472 individuals aged 20 years or older who were not previously diagnosed with HCC and underwent health examinations twice with a gap of 2 years.

Disclosures: The study was sponsored by the Research Supporting Program of The Korean Association for the Study of the Liver and the Korean Liver Foundation. The authors declared no conflict of interests.

Source: Kim MN et al. Int J Cancer. 2021 Dec 26. doi: 10.1002/ijc.33920.

Key clinical point: Individuals with persistent or incident body fatness show an increased risk of developing hepatocellular carcinoma (HCC).

Main finding: Compared with their persistent no-fatness counterparts, both general fatness (persistent: adjusted hazard ratio [aHR], 1.28; 95% CI, 1.23-1.34; incident: aHR, 1.10; 95% CI, 1.01-1.20) and central fatness (persistent: aHR, 1.33; 95% CI, 1.26-1.40; incident: aHR, 1.19; 95% CI, 1.11-1.27) were associated with an increased risk of HCC.

Study details: The data come from a nationwide population-based cohort study including 6,789,472 individuals aged 20 years or older who were not previously diagnosed with HCC and underwent health examinations twice with a gap of 2 years.

Disclosures: The study was sponsored by the Research Supporting Program of The Korean Association for the Study of the Liver and the Korean Liver Foundation. The authors declared no conflict of interests.

Source: Kim MN et al. Int J Cancer. 2021 Dec 26. doi: 10.1002/ijc.33920.

Key clinical point: Patients with small hepatocellular carcinoma (HCC) show a comparable improvement in recurrence-free survival (RFS) after undergoing surgery or radiofrequency ablation (RFA).

Main finding: The median RFS of patients who had undergone surgery was not significantly different from that of patients receiving RFA (3.46 years vs 3.04 years; hazard ratio, 0.92; P = .58).

Study details: Findings are from the phase 3 SURF-trial including 301 patients aged between 20 and 80 years with the largest HCC diameter ≤3 cm and ≤3 HCC nodules who were randomly assigned (1:1) to undergo either surgery (n=150) or RFA (n=151).

Disclosures: The study was sponsored by the Japanese Foundation for Multidisciplinary Treatment of Cancer and the Health and Labor Sciences Research Grant for Clinical Cancer Research. Some of the authors declared receiving lecture fees or research funds from or serving as an advisor for various companies. A few authors reported being on the editorial team/board of Liver Cancer.

Source: Takayama T et al. Liver Cancer. 2021 Dec 29. doi: 10.1159/000521665.

Key clinical point: Patients with small hepatocellular carcinoma (HCC) show a comparable improvement in recurrence-free survival (RFS) after undergoing surgery or radiofrequency ablation (RFA).

Main finding: The median RFS of patients who had undergone surgery was not significantly different from that of patients receiving RFA (3.46 years vs 3.04 years; hazard ratio, 0.92; P = .58).

Study details: Findings are from the phase 3 SURF-trial including 301 patients aged between 20 and 80 years with the largest HCC diameter ≤3 cm and ≤3 HCC nodules who were randomly assigned (1:1) to undergo either surgery (n=150) or RFA (n=151).

Disclosures: The study was sponsored by the Japanese Foundation for Multidisciplinary Treatment of Cancer and the Health and Labor Sciences Research Grant for Clinical Cancer Research. Some of the authors declared receiving lecture fees or research funds from or serving as an advisor for various companies. A few authors reported being on the editorial team/board of Liver Cancer.

Source: Takayama T et al. Liver Cancer. 2021 Dec 29. doi: 10.1159/000521665.

Key clinical point: Patients with small hepatocellular carcinoma (HCC) show a comparable improvement in recurrence-free survival (RFS) after undergoing surgery or radiofrequency ablation (RFA).

Main finding: The median RFS of patients who had undergone surgery was not significantly different from that of patients receiving RFA (3.46 years vs 3.04 years; hazard ratio, 0.92; P = .58).

Study details: Findings are from the phase 3 SURF-trial including 301 patients aged between 20 and 80 years with the largest HCC diameter ≤3 cm and ≤3 HCC nodules who were randomly assigned (1:1) to undergo either surgery (n=150) or RFA (n=151).

Disclosures: The study was sponsored by the Japanese Foundation for Multidisciplinary Treatment of Cancer and the Health and Labor Sciences Research Grant for Clinical Cancer Research. Some of the authors declared receiving lecture fees or research funds from or serving as an advisor for various companies. A few authors reported being on the editorial team/board of Liver Cancer.

Source: Takayama T et al. Liver Cancer. 2021 Dec 29. doi: 10.1159/000521665.

Key clinical point: The oncological outcome in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT) is strongly affected by the ABO blood group system.

Main finding: Blood group A showed an independent association with increased tumor recurrence risk (adjusted hazard ratio [aHR], 1.574; P = .034) with group A vs non-A recipients having higher 5-year tumor recurrence rates (20.1% vs 13.2%; aHR, 1.66; P = .011) and lower 5-year recurrence-free survival rates (66.8% vs 71.3%; aHR, 1.38; P = .045).

Study details: The data are derived from a multicentric retrospective observational study including 925 adult patients with HCC who underwent LT, of whom 406, 94, 380, and 45 had blood group A, B, O, and AB, respectively.

Disclosures: The authors reported no funding source or conflict of interests.

Source: Kayvan M et al. Transplantation. 2021 Dec 27. doi: 10.1097/TP.0000000000004004.

Key clinical point: The oncological outcome in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT) is strongly affected by the ABO blood group system.

Main finding: Blood group A showed an independent association with increased tumor recurrence risk (adjusted hazard ratio [aHR], 1.574; P = .034) with group A vs non-A recipients having higher 5-year tumor recurrence rates (20.1% vs 13.2%; aHR, 1.66; P = .011) and lower 5-year recurrence-free survival rates (66.8% vs 71.3%; aHR, 1.38; P = .045).

Study details: The data are derived from a multicentric retrospective observational study including 925 adult patients with HCC who underwent LT, of whom 406, 94, 380, and 45 had blood group A, B, O, and AB, respectively.

Disclosures: The authors reported no funding source or conflict of interests.

Source: Kayvan M et al. Transplantation. 2021 Dec 27. doi: 10.1097/TP.0000000000004004.

Key clinical point: The oncological outcome in patients with hepatocellular carcinoma (HCC) who underwent liver transplantation (LT) is strongly affected by the ABO blood group system.

Main finding: Blood group A showed an independent association with increased tumor recurrence risk (adjusted hazard ratio [aHR], 1.574; P = .034) with group A vs non-A recipients having higher 5-year tumor recurrence rates (20.1% vs 13.2%; aHR, 1.66; P = .011) and lower 5-year recurrence-free survival rates (66.8% vs 71.3%; aHR, 1.38; P = .045).

Study details: The data are derived from a multicentric retrospective observational study including 925 adult patients with HCC who underwent LT, of whom 406, 94, 380, and 45 had blood group A, B, O, and AB, respectively.

Disclosures: The authors reported no funding source or conflict of interests.

Source: Kayvan M et al. Transplantation. 2021 Dec 27. doi: 10.1097/TP.0000000000004004.

Intranasal ketamine may be a viable treatment option for acute cluster headache attacks, a pilot study has found, though it did not reduce pain intensity as quickly as initially anticipated.

“In clinical practice, intranasal ketamine might be a valuable tool for severely affected patients with insufficient response or intolerance to current first-line treatment,” wrote Anja S. Petersen, MD, of the Danish Headache Center at Rigshospitalet-Glostrup (Denmark) and her coauthors. The study was published online ahead of print in Headache.

To assess ketamine’s safety and efficacy in treating cluster headache attacks, the researchers launched a single-center, open-label, proof-of-concept study of 23 Danish patients with chronic cluster headache. Their average age was 51, 70% were males, and their mean disease duration was 18 years. Twenty of the participants suffered a spontaneous attack while under in-hospital observation and were treated with 15 mg of intranasal ketamine every 6 minutes to a maximum of five times.

Fifteen minutes after ketamine was administered, mean pain intensity (±SD) was reduced from 7.2 (±1.3) to 6.1 (±3.1) on an 11-point numeric rating scale, equivalent to a 15% reduction and well below the primary endpoint of a 50% or greater reduction. Only 4 of the 20 participants had a reduction of 50% or more, and 4 patients chose rescue medication at 15 minutes. However, at 30 minutes pain intensity was reduced by 59% (mean difference 4.3, 95% confidence interval, 2.4-6.2, P > 0.001), with 11 out of 16 participants scoring a 4 or below.

Eight of the 20 participants reported feeling complete relief from the ketamine nasal spray, while 6 participants reported feeling no effects. Half of the patients said they preferred ketamine to oxygen and/or sumatriptan injection. Seventeen patients (83%) reported side effects, but 12 of them classified their side effects as “few.” No serious adverse events were identified, with the most common adverse events being dizziness, lightheadedness, nausea/vomiting, and paresthesia.
 

Debating ketamine’s potential for cluster headache patients

“I’m not crazy about the prospects,” said Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., in an interview. “It was an admirable proof-of-concept trial, and well worth doing. These are desperate patients. But if the aim was to decrease pain intensity within 15 minutes for cluster patients without side effects, this clearly did not do that,” Dr. Tepper said.

“In a sense, this study was to evaluate whether glutamate might be a target for chronic cluster headache, to determine if blocking NMDA glutamate receptors by ketamine would be effective,” Dr. Tepper said. “And I must say, I’m not very impressed.”

He noted his concerns about the study – including 30 minutes being an “unacceptable” wait for patients undergoing a cluster attack, the 20% of patients who required a rescue at 15 minutes, and the various side effects that come with ketamine in nasal form – and said the results did not sway him to consider ketamine a practical option for cluster headache patients.

“You add all of that up, and I would say this was an equivocal study,” he said. “There might be enough there to be worth studying in episodic cluster rather than chronic cluster; there might be enough to consider a randomized, placebo-controlled trial. But it’s not something that I would ring the bell at Wall Street about.”

“The acute treatment of a patient with chronic cluster headache is a real problem for us headache specialists,” added Alan Rapoport, MD, professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, in an interview. “Cluster headache is probably the worst pain we deal with; women who’ve gone through childbirth say that cluster headache is worse. So it’s very reasonable to have tried.”

“It’s not an impressive finding,” he said, “but it does indicate that there’s some value here. Maybe they need to change the dose; maybe they need to get it in faster by doing something tricky like combining the drug with another substance that will make it attach to the nasal mucosa better. I urge them to study it again, and I hope that they come up with better results the next time, because what they attempted to study is absolutely vital.”

The authors acknowledged their study’s limitations, including a homogeneous patient population and the lack of placebo-controlled verification of effect after 30 minutes. They added, however, that a pilot study like this provides “critical information and paves the way for subsequent placebo-controlled studies.” They also admitted that “daily usage [of ketamine] seems suboptimal” because of the potential of patients becoming addicted.

The study was funded by CCH Pharmaceuticals. Several authors reported receiving speaker’s fees and being subinvestigators in trials run by various pharmaceutical companies, including CCH Pharmaceuticals.

Intranasal ketamine may be a viable treatment option for acute cluster headache attacks, a pilot study has found, though it did not reduce pain intensity as quickly as initially anticipated.

“In clinical practice, intranasal ketamine might be a valuable tool for severely affected patients with insufficient response or intolerance to current first-line treatment,” wrote Anja S. Petersen, MD, of the Danish Headache Center at Rigshospitalet-Glostrup (Denmark) and her coauthors. The study was published online ahead of print in Headache.

To assess ketamine’s safety and efficacy in treating cluster headache attacks, the researchers launched a single-center, open-label, proof-of-concept study of 23 Danish patients with chronic cluster headache. Their average age was 51, 70% were males, and their mean disease duration was 18 years. Twenty of the participants suffered a spontaneous attack while under in-hospital observation and were treated with 15 mg of intranasal ketamine every 6 minutes to a maximum of five times.

Fifteen minutes after ketamine was administered, mean pain intensity (±SD) was reduced from 7.2 (±1.3) to 6.1 (±3.1) on an 11-point numeric rating scale, equivalent to a 15% reduction and well below the primary endpoint of a 50% or greater reduction. Only 4 of the 20 participants had a reduction of 50% or more, and 4 patients chose rescue medication at 15 minutes. However, at 30 minutes pain intensity was reduced by 59% (mean difference 4.3, 95% confidence interval, 2.4-6.2, P > 0.001), with 11 out of 16 participants scoring a 4 or below.

Eight of the 20 participants reported feeling complete relief from the ketamine nasal spray, while 6 participants reported feeling no effects. Half of the patients said they preferred ketamine to oxygen and/or sumatriptan injection. Seventeen patients (83%) reported side effects, but 12 of them classified their side effects as “few.” No serious adverse events were identified, with the most common adverse events being dizziness, lightheadedness, nausea/vomiting, and paresthesia.
 

Debating ketamine’s potential for cluster headache patients

“I’m not crazy about the prospects,” said Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., in an interview. “It was an admirable proof-of-concept trial, and well worth doing. These are desperate patients. But if the aim was to decrease pain intensity within 15 minutes for cluster patients without side effects, this clearly did not do that,” Dr. Tepper said.

“In a sense, this study was to evaluate whether glutamate might be a target for chronic cluster headache, to determine if blocking NMDA glutamate receptors by ketamine would be effective,” Dr. Tepper said. “And I must say, I’m not very impressed.”

He noted his concerns about the study – including 30 minutes being an “unacceptable” wait for patients undergoing a cluster attack, the 20% of patients who required a rescue at 15 minutes, and the various side effects that come with ketamine in nasal form – and said the results did not sway him to consider ketamine a practical option for cluster headache patients.

“You add all of that up, and I would say this was an equivocal study,” he said. “There might be enough there to be worth studying in episodic cluster rather than chronic cluster; there might be enough to consider a randomized, placebo-controlled trial. But it’s not something that I would ring the bell at Wall Street about.”

“The acute treatment of a patient with chronic cluster headache is a real problem for us headache specialists,” added Alan Rapoport, MD, professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, in an interview. “Cluster headache is probably the worst pain we deal with; women who’ve gone through childbirth say that cluster headache is worse. So it’s very reasonable to have tried.”

“It’s not an impressive finding,” he said, “but it does indicate that there’s some value here. Maybe they need to change the dose; maybe they need to get it in faster by doing something tricky like combining the drug with another substance that will make it attach to the nasal mucosa better. I urge them to study it again, and I hope that they come up with better results the next time, because what they attempted to study is absolutely vital.”

The authors acknowledged their study’s limitations, including a homogeneous patient population and the lack of placebo-controlled verification of effect after 30 minutes. They added, however, that a pilot study like this provides “critical information and paves the way for subsequent placebo-controlled studies.” They also admitted that “daily usage [of ketamine] seems suboptimal” because of the potential of patients becoming addicted.

The study was funded by CCH Pharmaceuticals. Several authors reported receiving speaker’s fees and being subinvestigators in trials run by various pharmaceutical companies, including CCH Pharmaceuticals.

Intranasal ketamine may be a viable treatment option for acute cluster headache attacks, a pilot study has found, though it did not reduce pain intensity as quickly as initially anticipated.

“In clinical practice, intranasal ketamine might be a valuable tool for severely affected patients with insufficient response or intolerance to current first-line treatment,” wrote Anja S. Petersen, MD, of the Danish Headache Center at Rigshospitalet-Glostrup (Denmark) and her coauthors. The study was published online ahead of print in Headache.

To assess ketamine’s safety and efficacy in treating cluster headache attacks, the researchers launched a single-center, open-label, proof-of-concept study of 23 Danish patients with chronic cluster headache. Their average age was 51, 70% were males, and their mean disease duration was 18 years. Twenty of the participants suffered a spontaneous attack while under in-hospital observation and were treated with 15 mg of intranasal ketamine every 6 minutes to a maximum of five times.

Fifteen minutes after ketamine was administered, mean pain intensity (±SD) was reduced from 7.2 (±1.3) to 6.1 (±3.1) on an 11-point numeric rating scale, equivalent to a 15% reduction and well below the primary endpoint of a 50% or greater reduction. Only 4 of the 20 participants had a reduction of 50% or more, and 4 patients chose rescue medication at 15 minutes. However, at 30 minutes pain intensity was reduced by 59% (mean difference 4.3, 95% confidence interval, 2.4-6.2, P > 0.001), with 11 out of 16 participants scoring a 4 or below.

Eight of the 20 participants reported feeling complete relief from the ketamine nasal spray, while 6 participants reported feeling no effects. Half of the patients said they preferred ketamine to oxygen and/or sumatriptan injection. Seventeen patients (83%) reported side effects, but 12 of them classified their side effects as “few.” No serious adverse events were identified, with the most common adverse events being dizziness, lightheadedness, nausea/vomiting, and paresthesia.
 

Debating ketamine’s potential for cluster headache patients

“I’m not crazy about the prospects,” said Stewart J. Tepper, MD, professor of neurology at the Geisel School of Medicine at Dartmouth, Hanover, N.H., in an interview. “It was an admirable proof-of-concept trial, and well worth doing. These are desperate patients. But if the aim was to decrease pain intensity within 15 minutes for cluster patients without side effects, this clearly did not do that,” Dr. Tepper said.

“In a sense, this study was to evaluate whether glutamate might be a target for chronic cluster headache, to determine if blocking NMDA glutamate receptors by ketamine would be effective,” Dr. Tepper said. “And I must say, I’m not very impressed.”

He noted his concerns about the study – including 30 minutes being an “unacceptable” wait for patients undergoing a cluster attack, the 20% of patients who required a rescue at 15 minutes, and the various side effects that come with ketamine in nasal form – and said the results did not sway him to consider ketamine a practical option for cluster headache patients.

“You add all of that up, and I would say this was an equivocal study,” he said. “There might be enough there to be worth studying in episodic cluster rather than chronic cluster; there might be enough to consider a randomized, placebo-controlled trial. But it’s not something that I would ring the bell at Wall Street about.”

“The acute treatment of a patient with chronic cluster headache is a real problem for us headache specialists,” added Alan Rapoport, MD, professor of neurology at University of California, Los Angeles, and past president of the International Headache Society, in an interview. “Cluster headache is probably the worst pain we deal with; women who’ve gone through childbirth say that cluster headache is worse. So it’s very reasonable to have tried.”

“It’s not an impressive finding,” he said, “but it does indicate that there’s some value here. Maybe they need to change the dose; maybe they need to get it in faster by doing something tricky like combining the drug with another substance that will make it attach to the nasal mucosa better. I urge them to study it again, and I hope that they come up with better results the next time, because what they attempted to study is absolutely vital.”

The authors acknowledged their study’s limitations, including a homogeneous patient population and the lack of placebo-controlled verification of effect after 30 minutes. They added, however, that a pilot study like this provides “critical information and paves the way for subsequent placebo-controlled studies.” They also admitted that “daily usage [of ketamine] seems suboptimal” because of the potential of patients becoming addicted.

The study was funded by CCH Pharmaceuticals. Several authors reported receiving speaker’s fees and being subinvestigators in trials run by various pharmaceutical companies, including CCH Pharmaceuticals.