BOZEMAN, Mont. – In a busy downtown coffee shop, a drawing of a ski lift with intrauterine devices for chairs draws the eyes of sleepy customers getting their morning underway with a caffeine jolt.

The flyer touts the services of Bridgercare, a nonprofit reproductive health clinic a few miles up the road. The clinic offers wellness exams, birth control, and LGBTQ+ services – and, starting in April, it oversees the state’s multimillion-dollar share of federal family planning program funding.

In March, Bridgercare beat out the state health department to become administrator of Montana’s $2.3 million Title X program, which helps pay for family planning and preventive health services. The organization applied for the grant because its leaders were concerned about a new state law that sought to restrict which local providers are funded.

What is happening in Montana is the latest example of an ongoing power struggle between nonprofits and conservative-leaning states over who receives federal family planning money. That has intensified in recent years as the Title X program has increasingly become entangled with the politics of abortion.

This year, the federal government set aside $257 million for family planning and preventive care. The providers that get that funding often serve families with low incomes, and Title X is one of the few federal programs in which people without legal permission to be in the United States can participate.

“The program permeates into communities that otherwise would be unreached by public health efforts,” said Rebecca Kreitzer, an associate professor of public policy at the University of North Carolina at Chapel Hill.

The Montana Department of Public Health and Human Services controlled the distribution of the state’s Title X funds for decades. Bridgercare sought the administrator role to circumvent a Republican-sponsored law passed last year that required the state to prioritize the money for local health departments and federally qualified health centers. That would have put the nonprofit – which doesn’t provide abortion procedures – and similar organizations at the bottom of the list. The law also banned clinics that perform abortions from receiving Title X funds from the state health department.

Bridgercare Executive Director Stephanie McDowell said the group applied for the grant to try to protect the program from decisions coming out of the state capitol. “Because of the politicization of Title X, we’re seeing how it’s run, swinging back and forth based on partisan leadership,” Ms. McDowell said.

A U.S. Department of Health & Human Services spokesperson, Tara Broido, didn’t answer a question about whether the agency intentionally awarded grants to nonprofits to avoid state politics. Instead, she said in a statement that applicants were evaluated in a competitive process by a panel of independent reviewers based on criteria to deliver high-quality, client-centered services.

Federal law prohibits the money from being used to perform abortions. But it can cover other services provided by groups that offer abortions – the largest and best-known by far is Planned Parenthood. In recent years, conservative politicians have tried to keep such providers from receiving Title X funding.

In some cases, contraception has entered the debate around which family planning services government should help fund. Some abortion opponents have raised concerns that long-lasting forms of birth control, such as IUDs, lead to abortions. Those claims are disputed by reproductive health experts.

In 2019, the Trump administration introduced several new rules for Title X, including disqualifying from receiving the funding family planning clinics that also offered abortion services or referrals. Many clinics across the nation left the program instead of conforming to the rules. Simultaneously, the spread of COVID-19 interrupted routine care. The number of patients served by Title X plummeted.

The Biden administration reversed most of those rules, including allowing providers with abortion services back into the Title X program. States also try to influence the funding’s reach, either through legislation or budget rules.

The current Title X funding cycle is 5 years, and the amount of money available each year could shift based on the state’s network of providers or federal budget changes. Jon Ebelt, a spokesperson for the Montana Department of Public Health and Human Services, didn’t answer when asked whether the state planned to reapply to administer the funding in 2027. He said the department was disappointed with the Biden administration’s “refusal” to renew the state’s funding.

“We recognize, however, that recent proabortion federal rule changes have distorted Title X and conflict with Montana law,” he said.

Conservative states have been tangling with nonprofits and the federal government over Title X funding for more than a decade. In 2011, during the Obama administration, Texas whittled down the state’s family planning spending and prioritized sending the federal money to general primary care providers over reproductive health clinics. As a result, 25% of family planning clinics in Texas closed. In 2013, a nonprofit now called Every Body Texas joined the competition to distribute the state’s Title X dollars and won.

“Filling and rebuilding those holes have taken this last decade, essentially,” said Berna Mason, director of service delivery improvement for Every Body Texas.

In 2019, the governor of Nebraska proposed a budget that would have prohibited the money from going to any organization that provided abortions or referred patients for abortions outside of an emergency. It also would have required that funding recipients be legally and financially separate from such clinics, a restriction that would have gone further than the Trump administration’s rules. Afterward, a family planning council won the right to administer Title X money.

In 2017, the nonprofit Arizona Family Health Partnership lost its status as that state’s only Title X administrator when the state health department was given 25% of the funding to deliver to providers. That came after Arizona lawmakers ordered the department to apply for the funds and distribute them first to state- or county-owned clinics, with the remaining money going to primary care facilities. The change was backed by groups that were opposed to abortion, and reproductive health care providers saw it as an attempt to weaken clinics that offer abortion services.

However, the state left nearly all the money it received untouched, and although it’s still required by law to apply for Title X funding, it hasn’t received a portion of the grant since.

Bré Thomas, CEO of Arizona Family Health Partnership, said that, even though the nonprofit is the sole administrator of the Title X funding again, the threat remains that some or all could be taken away because of politics. “We’re at the will of who’s in charge,” Ms. Thomas said.

Nonprofits say they have an advantage over state agencies in expanding services because they have more flexibility in fundraising and fewer administrative hurdles.

In April, Mississippi nonprofit Converge took over administration of Title X funds, a role the state had held for decades. The organization’s founders said they weren’t worried that conservative politicians would restrict access to services but simply believed they could do a better job. “Service quality was very low, and it was very hard to get appointments,” said cofounder Danielle Lampton.

A Mississippi State Department of Health spokesperson, Liz Sharlot, said the agency looks forward to working with Converge.

In Montana, Bridgercare plans to restore funding to Planned Parenthood clinics that have been cut off from the program since 2019, recruit more health centers to participate, and expand the program’s reach in rural, frontier, and tribal communities using telehealth services, Ms. McDowell said.

The organization’s goal is to increase the number of patients benefiting from the federal program by at least 10% in each year of the 5-year grant cycle. The clinic also plans to apply to keep its Title X role beyond this grant.

“In 5 years, our grant application should be a clear front-runner for funding,” she said. “It’s less about ‘How do we beat someone in 5 years?’ And more about ‘How do we grow this program to serve patients?’”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

BOZEMAN, Mont. – In a busy downtown coffee shop, a drawing of a ski lift with intrauterine devices for chairs draws the eyes of sleepy customers getting their morning underway with a caffeine jolt.

The flyer touts the services of Bridgercare, a nonprofit reproductive health clinic a few miles up the road. The clinic offers wellness exams, birth control, and LGBTQ+ services – and, starting in April, it oversees the state’s multimillion-dollar share of federal family planning program funding.

In March, Bridgercare beat out the state health department to become administrator of Montana’s $2.3 million Title X program, which helps pay for family planning and preventive health services. The organization applied for the grant because its leaders were concerned about a new state law that sought to restrict which local providers are funded.

What is happening in Montana is the latest example of an ongoing power struggle between nonprofits and conservative-leaning states over who receives federal family planning money. That has intensified in recent years as the Title X program has increasingly become entangled with the politics of abortion.

This year, the federal government set aside $257 million for family planning and preventive care. The providers that get that funding often serve families with low incomes, and Title X is one of the few federal programs in which people without legal permission to be in the United States can participate.

“The program permeates into communities that otherwise would be unreached by public health efforts,” said Rebecca Kreitzer, an associate professor of public policy at the University of North Carolina at Chapel Hill.

The Montana Department of Public Health and Human Services controlled the distribution of the state’s Title X funds for decades. Bridgercare sought the administrator role to circumvent a Republican-sponsored law passed last year that required the state to prioritize the money for local health departments and federally qualified health centers. That would have put the nonprofit – which doesn’t provide abortion procedures – and similar organizations at the bottom of the list. The law also banned clinics that perform abortions from receiving Title X funds from the state health department.

Bridgercare Executive Director Stephanie McDowell said the group applied for the grant to try to protect the program from decisions coming out of the state capitol. “Because of the politicization of Title X, we’re seeing how it’s run, swinging back and forth based on partisan leadership,” Ms. McDowell said.

A U.S. Department of Health & Human Services spokesperson, Tara Broido, didn’t answer a question about whether the agency intentionally awarded grants to nonprofits to avoid state politics. Instead, she said in a statement that applicants were evaluated in a competitive process by a panel of independent reviewers based on criteria to deliver high-quality, client-centered services.

Federal law prohibits the money from being used to perform abortions. But it can cover other services provided by groups that offer abortions – the largest and best-known by far is Planned Parenthood. In recent years, conservative politicians have tried to keep such providers from receiving Title X funding.

In some cases, contraception has entered the debate around which family planning services government should help fund. Some abortion opponents have raised concerns that long-lasting forms of birth control, such as IUDs, lead to abortions. Those claims are disputed by reproductive health experts.

In 2019, the Trump administration introduced several new rules for Title X, including disqualifying from receiving the funding family planning clinics that also offered abortion services or referrals. Many clinics across the nation left the program instead of conforming to the rules. Simultaneously, the spread of COVID-19 interrupted routine care. The number of patients served by Title X plummeted.

The Biden administration reversed most of those rules, including allowing providers with abortion services back into the Title X program. States also try to influence the funding’s reach, either through legislation or budget rules.

The current Title X funding cycle is 5 years, and the amount of money available each year could shift based on the state’s network of providers or federal budget changes. Jon Ebelt, a spokesperson for the Montana Department of Public Health and Human Services, didn’t answer when asked whether the state planned to reapply to administer the funding in 2027. He said the department was disappointed with the Biden administration’s “refusal” to renew the state’s funding.

“We recognize, however, that recent proabortion federal rule changes have distorted Title X and conflict with Montana law,” he said.

Conservative states have been tangling with nonprofits and the federal government over Title X funding for more than a decade. In 2011, during the Obama administration, Texas whittled down the state’s family planning spending and prioritized sending the federal money to general primary care providers over reproductive health clinics. As a result, 25% of family planning clinics in Texas closed. In 2013, a nonprofit now called Every Body Texas joined the competition to distribute the state’s Title X dollars and won.

“Filling and rebuilding those holes have taken this last decade, essentially,” said Berna Mason, director of service delivery improvement for Every Body Texas.

In 2019, the governor of Nebraska proposed a budget that would have prohibited the money from going to any organization that provided abortions or referred patients for abortions outside of an emergency. It also would have required that funding recipients be legally and financially separate from such clinics, a restriction that would have gone further than the Trump administration’s rules. Afterward, a family planning council won the right to administer Title X money.

In 2017, the nonprofit Arizona Family Health Partnership lost its status as that state’s only Title X administrator when the state health department was given 25% of the funding to deliver to providers. That came after Arizona lawmakers ordered the department to apply for the funds and distribute them first to state- or county-owned clinics, with the remaining money going to primary care facilities. The change was backed by groups that were opposed to abortion, and reproductive health care providers saw it as an attempt to weaken clinics that offer abortion services.

However, the state left nearly all the money it received untouched, and although it’s still required by law to apply for Title X funding, it hasn’t received a portion of the grant since.

Bré Thomas, CEO of Arizona Family Health Partnership, said that, even though the nonprofit is the sole administrator of the Title X funding again, the threat remains that some or all could be taken away because of politics. “We’re at the will of who’s in charge,” Ms. Thomas said.

Nonprofits say they have an advantage over state agencies in expanding services because they have more flexibility in fundraising and fewer administrative hurdles.

In April, Mississippi nonprofit Converge took over administration of Title X funds, a role the state had held for decades. The organization’s founders said they weren’t worried that conservative politicians would restrict access to services but simply believed they could do a better job. “Service quality was very low, and it was very hard to get appointments,” said cofounder Danielle Lampton.

A Mississippi State Department of Health spokesperson, Liz Sharlot, said the agency looks forward to working with Converge.

In Montana, Bridgercare plans to restore funding to Planned Parenthood clinics that have been cut off from the program since 2019, recruit more health centers to participate, and expand the program’s reach in rural, frontier, and tribal communities using telehealth services, Ms. McDowell said.

The organization’s goal is to increase the number of patients benefiting from the federal program by at least 10% in each year of the 5-year grant cycle. The clinic also plans to apply to keep its Title X role beyond this grant.

“In 5 years, our grant application should be a clear front-runner for funding,” she said. “It’s less about ‘How do we beat someone in 5 years?’ And more about ‘How do we grow this program to serve patients?’”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

BOZEMAN, Mont. – In a busy downtown coffee shop, a drawing of a ski lift with intrauterine devices for chairs draws the eyes of sleepy customers getting their morning underway with a caffeine jolt.

The flyer touts the services of Bridgercare, a nonprofit reproductive health clinic a few miles up the road. The clinic offers wellness exams, birth control, and LGBTQ+ services – and, starting in April, it oversees the state’s multimillion-dollar share of federal family planning program funding.

In March, Bridgercare beat out the state health department to become administrator of Montana’s $2.3 million Title X program, which helps pay for family planning and preventive health services. The organization applied for the grant because its leaders were concerned about a new state law that sought to restrict which local providers are funded.

What is happening in Montana is the latest example of an ongoing power struggle between nonprofits and conservative-leaning states over who receives federal family planning money. That has intensified in recent years as the Title X program has increasingly become entangled with the politics of abortion.

This year, the federal government set aside $257 million for family planning and preventive care. The providers that get that funding often serve families with low incomes, and Title X is one of the few federal programs in which people without legal permission to be in the United States can participate.

“The program permeates into communities that otherwise would be unreached by public health efforts,” said Rebecca Kreitzer, an associate professor of public policy at the University of North Carolina at Chapel Hill.

The Montana Department of Public Health and Human Services controlled the distribution of the state’s Title X funds for decades. Bridgercare sought the administrator role to circumvent a Republican-sponsored law passed last year that required the state to prioritize the money for local health departments and federally qualified health centers. That would have put the nonprofit – which doesn’t provide abortion procedures – and similar organizations at the bottom of the list. The law also banned clinics that perform abortions from receiving Title X funds from the state health department.

Bridgercare Executive Director Stephanie McDowell said the group applied for the grant to try to protect the program from decisions coming out of the state capitol. “Because of the politicization of Title X, we’re seeing how it’s run, swinging back and forth based on partisan leadership,” Ms. McDowell said.

A U.S. Department of Health & Human Services spokesperson, Tara Broido, didn’t answer a question about whether the agency intentionally awarded grants to nonprofits to avoid state politics. Instead, she said in a statement that applicants were evaluated in a competitive process by a panel of independent reviewers based on criteria to deliver high-quality, client-centered services.

Federal law prohibits the money from being used to perform abortions. But it can cover other services provided by groups that offer abortions – the largest and best-known by far is Planned Parenthood. In recent years, conservative politicians have tried to keep such providers from receiving Title X funding.

In some cases, contraception has entered the debate around which family planning services government should help fund. Some abortion opponents have raised concerns that long-lasting forms of birth control, such as IUDs, lead to abortions. Those claims are disputed by reproductive health experts.

In 2019, the Trump administration introduced several new rules for Title X, including disqualifying from receiving the funding family planning clinics that also offered abortion services or referrals. Many clinics across the nation left the program instead of conforming to the rules. Simultaneously, the spread of COVID-19 interrupted routine care. The number of patients served by Title X plummeted.

The Biden administration reversed most of those rules, including allowing providers with abortion services back into the Title X program. States also try to influence the funding’s reach, either through legislation or budget rules.

The current Title X funding cycle is 5 years, and the amount of money available each year could shift based on the state’s network of providers or federal budget changes. Jon Ebelt, a spokesperson for the Montana Department of Public Health and Human Services, didn’t answer when asked whether the state planned to reapply to administer the funding in 2027. He said the department was disappointed with the Biden administration’s “refusal” to renew the state’s funding.

“We recognize, however, that recent proabortion federal rule changes have distorted Title X and conflict with Montana law,” he said.

Conservative states have been tangling with nonprofits and the federal government over Title X funding for more than a decade. In 2011, during the Obama administration, Texas whittled down the state’s family planning spending and prioritized sending the federal money to general primary care providers over reproductive health clinics. As a result, 25% of family planning clinics in Texas closed. In 2013, a nonprofit now called Every Body Texas joined the competition to distribute the state’s Title X dollars and won.

“Filling and rebuilding those holes have taken this last decade, essentially,” said Berna Mason, director of service delivery improvement for Every Body Texas.

In 2019, the governor of Nebraska proposed a budget that would have prohibited the money from going to any organization that provided abortions or referred patients for abortions outside of an emergency. It also would have required that funding recipients be legally and financially separate from such clinics, a restriction that would have gone further than the Trump administration’s rules. Afterward, a family planning council won the right to administer Title X money.

In 2017, the nonprofit Arizona Family Health Partnership lost its status as that state’s only Title X administrator when the state health department was given 25% of the funding to deliver to providers. That came after Arizona lawmakers ordered the department to apply for the funds and distribute them first to state- or county-owned clinics, with the remaining money going to primary care facilities. The change was backed by groups that were opposed to abortion, and reproductive health care providers saw it as an attempt to weaken clinics that offer abortion services.

However, the state left nearly all the money it received untouched, and although it’s still required by law to apply for Title X funding, it hasn’t received a portion of the grant since.

Bré Thomas, CEO of Arizona Family Health Partnership, said that, even though the nonprofit is the sole administrator of the Title X funding again, the threat remains that some or all could be taken away because of politics. “We’re at the will of who’s in charge,” Ms. Thomas said.

Nonprofits say they have an advantage over state agencies in expanding services because they have more flexibility in fundraising and fewer administrative hurdles.

In April, Mississippi nonprofit Converge took over administration of Title X funds, a role the state had held for decades. The organization’s founders said they weren’t worried that conservative politicians would restrict access to services but simply believed they could do a better job. “Service quality was very low, and it was very hard to get appointments,” said cofounder Danielle Lampton.

A Mississippi State Department of Health spokesperson, Liz Sharlot, said the agency looks forward to working with Converge.

In Montana, Bridgercare plans to restore funding to Planned Parenthood clinics that have been cut off from the program since 2019, recruit more health centers to participate, and expand the program’s reach in rural, frontier, and tribal communities using telehealth services, Ms. McDowell said.

The organization’s goal is to increase the number of patients benefiting from the federal program by at least 10% in each year of the 5-year grant cycle. The clinic also plans to apply to keep its Title X role beyond this grant.

“In 5 years, our grant application should be a clear front-runner for funding,” she said. “It’s less about ‘How do we beat someone in 5 years?’ And more about ‘How do we grow this program to serve patients?’”
 

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

In a European Society for Medical Oncology Virtual Plenary session, Dr Paz-Ares and colleagues presented interim analysis of the PEARLS/KEYNOTE-091 study of adjuvant pembrolizumab. In this triple-blind phase 3 trial, 1177 patients with stage IB (tumor ≥ 4 cm) to IIIA non–small cell lung cancer (NSCLC) (per American Joint Committee on Cancer [AJCC], version 7) were randomly assigned to receive pembrolizumab vs placebo. The dual primary endpoints were disease-free survival (DFS) in the overall population and in the population with high programmed death-ligand 1 (PD-L1) (tumor proportion score [TPS] ≥ 50%). The study met its primary endpoint where improved DFS was observed in the overall population that included lung cancers, whether they were PD-L1–negative (TPS = 0%) or –positive (TPS  ≥ 1%) (53.6 months in the pembrolizumab group vs 42.0 months in the placebo group [hazard ratio (HR) 0.76; P = .0014]). Overall survival data are not yet clear. Of note, in the interim analysis presented, the subset of patients with high PD-L1 NSCLC (TPS ≥ 50%) did not show a DFS benefit whereas in other adjuvant and neoadjuvant studies, such as IMpower010 and CheckMate 816, the subset of high PD-L1 patients appeared to derive the most benefit. The results from the high PD-L1 subset and other subsets may change with future updated analyses as more events occur. The major co-primary endpoint was clearly met with the overall population clearly showing a positive DFS benefit. The results of the PEARLS trial adds to the current landscape of systemic treatment of early-stage NSCLC where neoadjuvant chemotherapy plus nivolumab is US Food and Drug Administration (FDA)–approved for stage IB (≥ 4 cm) to IIIA resected NSCLC regardless of level of PD-L1 expression, as is adjuvant atezolizumab after consideration of adjuvant chemotherapy in patients that are PD-L1–positive (≥ 1%) on the basis of a DFS benefit observed in this population.^1,2 For the future, it is important to see if the DFS benefit observed in these studies translates into a meaningful overall survival benefit.

Plasma cfDNA Levels as a Prognostic Marker in ALK+ NSCLC in the ALEX Trial

The ALEX trial is a pivotal global phase 3 randomized control trial that demonstrated superior progression-free survival (PFS) with the next-generation ALK inhibitor alectinib compared with the first-generation ALK inhibitor crizotinib as first-line treatment of ALK-positive NSCLC (HR 0.43; 95% CI 0.32-0.58; median PFS 34.8 vs 10.9 months crizotinib).³ In a study recently published in Clinical Cancer Research, Dr Dziadziuszko and colleagues retrospectively assessed the prognostic value of baseline cell-free DNA (cfDNA) levels in patients treated in the ALEX trial. Baseline plasma for cfDNA was quantified by the Foundation ACT next-generation sequencing assay. Clinical outcomes were assessed by quantitative cfDNA level stratified by the median value. In both the alectinib and crizotinib treatment arms, patients with cfDNA levels above the median were more likely to experience disease progression (alectinib adjusted HR 2.04; 95% CI 1.07-3.89; P = .03 and crizotinib adjusted HR 1.83; 95% CI 1.11-3.00, P = .016). Though survival data are incomplete, the study also suggested survival probability was lower when baseline cfDNA was above the median in both the alectinib and crizotinib treatment arms. Regardless of cfDNA levels, PFS was improved with alectinib compared with crizotinib. Previous studies have shown the value of cfDNA analysis at the time of progression to guide further treatment and target resistance mechanisms to ALK tyrosine kinase inhibitors (TKI), such as G1202R, or bypass tract pathways, such as MET amplification.^4,5 Assessment of the EML4-ALK variant type (V1 vs V3) has been shown to associate with certain types of resistance mechanisms (ie, on target ALK mutations, such as G1202R in V3) and clinical activity of specific ALK TKI (V3 > V1 for PFS with lorlatinib).⁶ This study examining baseline cfDNA levels and clinical outcomes on the ALEX trial shows the potential utility of baseline cfDNA levels as a prognostic factor for ALK TKI.

Lorlatinib in ROS1-Rearranged NSCLC After Progression on Prior ROS1 TKI

ROS1 rearrangements represent about 1.5% of lung adenocarcinoma. In advanced disease, both crizotinib and entrectinib are FDA-approved as agents targeting ROS1 with robust PFS. The third-generation TKI lorlatinib is approved and has substantial activity in ALK-rearranged NSCLC. In a recently published retrospective real-world cohort study by Girard and colleagues (LORLATU), 80 patients with ROS1-rearranged NSCLC were treated with lorlatinib as second-line treatment or beyond and after failure on at least one prior ROS1 TKI. Median PFS was 7.1 months (95% CI 5.0-9.9) and median overall survival was 19.6 months (95% CI 12.3-27.5). The overall response rate was 45% and the disease control rate was 82%. The central nervous system response rate was 72%. There were no new safety signals. This retrospective cohort study demonstrates that lorlatinib is a major targeted therapy treatment option in ROS1-rearranged NSCLC.

Checkmate 816: Neoadjuvant Nivolumab Plus Chemotherapy in Resectable NSCLC

In this open-label, phase 3 trial, 358 patients with stage IB (T ³ 4cm) to IIIA (per AJCC v7) resectable NSCLC were randomized 1:1 to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone for three cycles, followed by surgical resection. The primary endpoints were event-free survival (EFS) and pathological complete response (pCR) (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. The median EFS was significantly increased in the nivolumab plus chemotherapy arm compared to chemotherapy alone: 31.6 months (95% CI 30.2 to not reached) vs 20.8 months (95% CI 14.0 to 26.7) (HR 0.63; 97.38% CI 0.43 to 0.91; P = .005). pCR rate was also increased in the nivolumab plus chemotherapy arm (24.0% vs 2.2%, respectively; odds ratio 13.94; 99% CI 3.49 to 55.75; P < .001). At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI 0.30 to 1.07), which currently does not meet the criterion for statistical significance. Of the randomized patients, 83.2% of those in the nivolumab-plus chemotherapy group and 75.4% of those in the chemotherapy-alone group were able to undergo surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. In an exploratory analysis, EFS was longer in patients with pCR than patients without a pCR. In a subset analysis, patients with high PD-L1 expression (³50%) stood out in terms of particular benefit (HR 0.24, 95% CI 0.10–0.61). The Checkmate 816 trial is a landmark study. Neoadjuvant nivolumab plus chemotherapy represents a new standard of care in the systemic treatment of resectable NSCLC that is at a stage that warrants systemic treatment. It is FDA approved regardless of PD-L1 expression level including PD-L1 negative (0%) patients.² Adjuvant atezolizumab after adjuvant chemotherapy is also an FDA-approved treatment option for patients that are PD-L1 positive (³1%) based upon the IMpower 010 study.¹ It will be important to assess the overall survival benefit as the trial data matures, which seems to be trending in the right direction. Additional neoadjuvant clinical trials with chemoimmunotherapy have completed accrual and some of these trials also continued PD-(L)1 immune checkpoint inhibitor therapy in the adjuvant setting after surgery. An important question for the future is if combination of PD-(L)1 immune checkpoint blockade with chemotherapy in the neoadjuvant setting along with continuation of immunotherapy in the adjuvant setting post-surgery will further improve clinical outcomes.

References

1. Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-57. Doi: 10.1016/S0140-6736(21)02098-5  Source

2. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. April 11, 2022. Doi: 10.1056/NEJMoa2202170 Source
    
3. Mok T, Camige DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31:1056-1064. Doi: 10.1016/j.annonc.2020.04.478 Source

4. Shaw AT, Solomon BJ, Chiari R, et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2019;20:1691-1701. Doi: 10.1016/S1470-2045(19)30655-2 Source
    
5. Lawrence MN, Tamen RM, Martinez P, et al. SPACEWALK: A remote participation study of ALK resistance leveraging plasma cell-free DNA genotyping. JTO Clin Res Rep. 2021;2:100151. Doi: 10.1016/j.jtocrr.2021.100151 Source
    
6. Lin JJ, Zhu VW, Yoda S, et al. Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer. J Clin Oncol. 2018;36:1199-1206. Doi: 10.1200/JCO.2017.76.2294 Source

In a European Society for Medical Oncology Virtual Plenary session, Dr Paz-Ares and colleagues presented interim analysis of the PEARLS/KEYNOTE-091 study of adjuvant pembrolizumab. In this triple-blind phase 3 trial, 1177 patients with stage IB (tumor ≥ 4 cm) to IIIA non–small cell lung cancer (NSCLC) (per American Joint Committee on Cancer [AJCC], version 7) were randomly assigned to receive pembrolizumab vs placebo. The dual primary endpoints were disease-free survival (DFS) in the overall population and in the population with high programmed death-ligand 1 (PD-L1) (tumor proportion score [TPS] ≥ 50%). The study met its primary endpoint where improved DFS was observed in the overall population that included lung cancers, whether they were PD-L1–negative (TPS = 0%) or –positive (TPS  ≥ 1%) (53.6 months in the pembrolizumab group vs 42.0 months in the placebo group [hazard ratio (HR) 0.76; P = .0014]). Overall survival data are not yet clear. Of note, in the interim analysis presented, the subset of patients with high PD-L1 NSCLC (TPS ≥ 50%) did not show a DFS benefit whereas in other adjuvant and neoadjuvant studies, such as IMpower010 and CheckMate 816, the subset of high PD-L1 patients appeared to derive the most benefit. The results from the high PD-L1 subset and other subsets may change with future updated analyses as more events occur. The major co-primary endpoint was clearly met with the overall population clearly showing a positive DFS benefit. The results of the PEARLS trial adds to the current landscape of systemic treatment of early-stage NSCLC where neoadjuvant chemotherapy plus nivolumab is US Food and Drug Administration (FDA)–approved for stage IB (≥ 4 cm) to IIIA resected NSCLC regardless of level of PD-L1 expression, as is adjuvant atezolizumab after consideration of adjuvant chemotherapy in patients that are PD-L1–positive (≥ 1%) on the basis of a DFS benefit observed in this population.^1,2 For the future, it is important to see if the DFS benefit observed in these studies translates into a meaningful overall survival benefit.

Plasma cfDNA Levels as a Prognostic Marker in ALK+ NSCLC in the ALEX Trial

The ALEX trial is a pivotal global phase 3 randomized control trial that demonstrated superior progression-free survival (PFS) with the next-generation ALK inhibitor alectinib compared with the first-generation ALK inhibitor crizotinib as first-line treatment of ALK-positive NSCLC (HR 0.43; 95% CI 0.32-0.58; median PFS 34.8 vs 10.9 months crizotinib).³ In a study recently published in Clinical Cancer Research, Dr Dziadziuszko and colleagues retrospectively assessed the prognostic value of baseline cell-free DNA (cfDNA) levels in patients treated in the ALEX trial. Baseline plasma for cfDNA was quantified by the Foundation ACT next-generation sequencing assay. Clinical outcomes were assessed by quantitative cfDNA level stratified by the median value. In both the alectinib and crizotinib treatment arms, patients with cfDNA levels above the median were more likely to experience disease progression (alectinib adjusted HR 2.04; 95% CI 1.07-3.89; P = .03 and crizotinib adjusted HR 1.83; 95% CI 1.11-3.00, P = .016). Though survival data are incomplete, the study also suggested survival probability was lower when baseline cfDNA was above the median in both the alectinib and crizotinib treatment arms. Regardless of cfDNA levels, PFS was improved with alectinib compared with crizotinib. Previous studies have shown the value of cfDNA analysis at the time of progression to guide further treatment and target resistance mechanisms to ALK tyrosine kinase inhibitors (TKI), such as G1202R, or bypass tract pathways, such as MET amplification.^4,5 Assessment of the EML4-ALK variant type (V1 vs V3) has been shown to associate with certain types of resistance mechanisms (ie, on target ALK mutations, such as G1202R in V3) and clinical activity of specific ALK TKI (V3 > V1 for PFS with lorlatinib).⁶ This study examining baseline cfDNA levels and clinical outcomes on the ALEX trial shows the potential utility of baseline cfDNA levels as a prognostic factor for ALK TKI.

Lorlatinib in ROS1-Rearranged NSCLC After Progression on Prior ROS1 TKI

ROS1 rearrangements represent about 1.5% of lung adenocarcinoma. In advanced disease, both crizotinib and entrectinib are FDA-approved as agents targeting ROS1 with robust PFS. The third-generation TKI lorlatinib is approved and has substantial activity in ALK-rearranged NSCLC. In a recently published retrospective real-world cohort study by Girard and colleagues (LORLATU), 80 patients with ROS1-rearranged NSCLC were treated with lorlatinib as second-line treatment or beyond and after failure on at least one prior ROS1 TKI. Median PFS was 7.1 months (95% CI 5.0-9.9) and median overall survival was 19.6 months (95% CI 12.3-27.5). The overall response rate was 45% and the disease control rate was 82%. The central nervous system response rate was 72%. There were no new safety signals. This retrospective cohort study demonstrates that lorlatinib is a major targeted therapy treatment option in ROS1-rearranged NSCLC.

Checkmate 816: Neoadjuvant Nivolumab Plus Chemotherapy in Resectable NSCLC

In this open-label, phase 3 trial, 358 patients with stage IB (T ³ 4cm) to IIIA (per AJCC v7) resectable NSCLC were randomized 1:1 to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone for three cycles, followed by surgical resection. The primary endpoints were event-free survival (EFS) and pathological complete response (pCR) (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. The median EFS was significantly increased in the nivolumab plus chemotherapy arm compared to chemotherapy alone: 31.6 months (95% CI 30.2 to not reached) vs 20.8 months (95% CI 14.0 to 26.7) (HR 0.63; 97.38% CI 0.43 to 0.91; P = .005). pCR rate was also increased in the nivolumab plus chemotherapy arm (24.0% vs 2.2%, respectively; odds ratio 13.94; 99% CI 3.49 to 55.75; P < .001). At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI 0.30 to 1.07), which currently does not meet the criterion for statistical significance. Of the randomized patients, 83.2% of those in the nivolumab-plus chemotherapy group and 75.4% of those in the chemotherapy-alone group were able to undergo surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. In an exploratory analysis, EFS was longer in patients with pCR than patients without a pCR. In a subset analysis, patients with high PD-L1 expression (³50%) stood out in terms of particular benefit (HR 0.24, 95% CI 0.10–0.61). The Checkmate 816 trial is a landmark study. Neoadjuvant nivolumab plus chemotherapy represents a new standard of care in the systemic treatment of resectable NSCLC that is at a stage that warrants systemic treatment. It is FDA approved regardless of PD-L1 expression level including PD-L1 negative (0%) patients.² Adjuvant atezolizumab after adjuvant chemotherapy is also an FDA-approved treatment option for patients that are PD-L1 positive (³1%) based upon the IMpower 010 study.¹ It will be important to assess the overall survival benefit as the trial data matures, which seems to be trending in the right direction. Additional neoadjuvant clinical trials with chemoimmunotherapy have completed accrual and some of these trials also continued PD-(L)1 immune checkpoint inhibitor therapy in the adjuvant setting after surgery. An important question for the future is if combination of PD-(L)1 immune checkpoint blockade with chemotherapy in the neoadjuvant setting along with continuation of immunotherapy in the adjuvant setting post-surgery will further improve clinical outcomes.

References

1. Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-57. Doi: 10.1016/S0140-6736(21)02098-5  Source

2. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. April 11, 2022. Doi: 10.1056/NEJMoa2202170 Source
    
3. Mok T, Camige DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31:1056-1064. Doi: 10.1016/j.annonc.2020.04.478 Source

4. Shaw AT, Solomon BJ, Chiari R, et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2019;20:1691-1701. Doi: 10.1016/S1470-2045(19)30655-2 Source
    
5. Lawrence MN, Tamen RM, Martinez P, et al. SPACEWALK: A remote participation study of ALK resistance leveraging plasma cell-free DNA genotyping. JTO Clin Res Rep. 2021;2:100151. Doi: 10.1016/j.jtocrr.2021.100151 Source
    
6. Lin JJ, Zhu VW, Yoda S, et al. Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer. J Clin Oncol. 2018;36:1199-1206. Doi: 10.1200/JCO.2017.76.2294 Source

In a European Society for Medical Oncology Virtual Plenary session, Dr Paz-Ares and colleagues presented interim analysis of the PEARLS/KEYNOTE-091 study of adjuvant pembrolizumab. In this triple-blind phase 3 trial, 1177 patients with stage IB (tumor ≥ 4 cm) to IIIA non–small cell lung cancer (NSCLC) (per American Joint Committee on Cancer [AJCC], version 7) were randomly assigned to receive pembrolizumab vs placebo. The dual primary endpoints were disease-free survival (DFS) in the overall population and in the population with high programmed death-ligand 1 (PD-L1) (tumor proportion score [TPS] ≥ 50%). The study met its primary endpoint where improved DFS was observed in the overall population that included lung cancers, whether they were PD-L1–negative (TPS = 0%) or –positive (TPS  ≥ 1%) (53.6 months in the pembrolizumab group vs 42.0 months in the placebo group [hazard ratio (HR) 0.76; P = .0014]). Overall survival data are not yet clear. Of note, in the interim analysis presented, the subset of patients with high PD-L1 NSCLC (TPS ≥ 50%) did not show a DFS benefit whereas in other adjuvant and neoadjuvant studies, such as IMpower010 and CheckMate 816, the subset of high PD-L1 patients appeared to derive the most benefit. The results from the high PD-L1 subset and other subsets may change with future updated analyses as more events occur. The major co-primary endpoint was clearly met with the overall population clearly showing a positive DFS benefit. The results of the PEARLS trial adds to the current landscape of systemic treatment of early-stage NSCLC where neoadjuvant chemotherapy plus nivolumab is US Food and Drug Administration (FDA)–approved for stage IB (≥ 4 cm) to IIIA resected NSCLC regardless of level of PD-L1 expression, as is adjuvant atezolizumab after consideration of adjuvant chemotherapy in patients that are PD-L1–positive (≥ 1%) on the basis of a DFS benefit observed in this population.^1,2 For the future, it is important to see if the DFS benefit observed in these studies translates into a meaningful overall survival benefit.

Plasma cfDNA Levels as a Prognostic Marker in ALK+ NSCLC in the ALEX Trial

The ALEX trial is a pivotal global phase 3 randomized control trial that demonstrated superior progression-free survival (PFS) with the next-generation ALK inhibitor alectinib compared with the first-generation ALK inhibitor crizotinib as first-line treatment of ALK-positive NSCLC (HR 0.43; 95% CI 0.32-0.58; median PFS 34.8 vs 10.9 months crizotinib).³ In a study recently published in Clinical Cancer Research, Dr Dziadziuszko and colleagues retrospectively assessed the prognostic value of baseline cell-free DNA (cfDNA) levels in patients treated in the ALEX trial. Baseline plasma for cfDNA was quantified by the Foundation ACT next-generation sequencing assay. Clinical outcomes were assessed by quantitative cfDNA level stratified by the median value. In both the alectinib and crizotinib treatment arms, patients with cfDNA levels above the median were more likely to experience disease progression (alectinib adjusted HR 2.04; 95% CI 1.07-3.89; P = .03 and crizotinib adjusted HR 1.83; 95% CI 1.11-3.00, P = .016). Though survival data are incomplete, the study also suggested survival probability was lower when baseline cfDNA was above the median in both the alectinib and crizotinib treatment arms. Regardless of cfDNA levels, PFS was improved with alectinib compared with crizotinib. Previous studies have shown the value of cfDNA analysis at the time of progression to guide further treatment and target resistance mechanisms to ALK tyrosine kinase inhibitors (TKI), such as G1202R, or bypass tract pathways, such as MET amplification.^4,5 Assessment of the EML4-ALK variant type (V1 vs V3) has been shown to associate with certain types of resistance mechanisms (ie, on target ALK mutations, such as G1202R in V3) and clinical activity of specific ALK TKI (V3 > V1 for PFS with lorlatinib).⁶ This study examining baseline cfDNA levels and clinical outcomes on the ALEX trial shows the potential utility of baseline cfDNA levels as a prognostic factor for ALK TKI.

Lorlatinib in ROS1-Rearranged NSCLC After Progression on Prior ROS1 TKI

ROS1 rearrangements represent about 1.5% of lung adenocarcinoma. In advanced disease, both crizotinib and entrectinib are FDA-approved as agents targeting ROS1 with robust PFS. The third-generation TKI lorlatinib is approved and has substantial activity in ALK-rearranged NSCLC. In a recently published retrospective real-world cohort study by Girard and colleagues (LORLATU), 80 patients with ROS1-rearranged NSCLC were treated with lorlatinib as second-line treatment or beyond and after failure on at least one prior ROS1 TKI. Median PFS was 7.1 months (95% CI 5.0-9.9) and median overall survival was 19.6 months (95% CI 12.3-27.5). The overall response rate was 45% and the disease control rate was 82%. The central nervous system response rate was 72%. There were no new safety signals. This retrospective cohort study demonstrates that lorlatinib is a major targeted therapy treatment option in ROS1-rearranged NSCLC.

Checkmate 816: Neoadjuvant Nivolumab Plus Chemotherapy in Resectable NSCLC

In this open-label, phase 3 trial, 358 patients with stage IB (T ³ 4cm) to IIIA (per AJCC v7) resectable NSCLC were randomized 1:1 to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone for three cycles, followed by surgical resection. The primary endpoints were event-free survival (EFS) and pathological complete response (pCR) (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. The median EFS was significantly increased in the nivolumab plus chemotherapy arm compared to chemotherapy alone: 31.6 months (95% CI 30.2 to not reached) vs 20.8 months (95% CI 14.0 to 26.7) (HR 0.63; 97.38% CI 0.43 to 0.91; P = .005). pCR rate was also increased in the nivolumab plus chemotherapy arm (24.0% vs 2.2%, respectively; odds ratio 13.94; 99% CI 3.49 to 55.75; P < .001). At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI 0.30 to 1.07), which currently does not meet the criterion for statistical significance. Of the randomized patients, 83.2% of those in the nivolumab-plus chemotherapy group and 75.4% of those in the chemotherapy-alone group were able to undergo surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. In an exploratory analysis, EFS was longer in patients with pCR than patients without a pCR. In a subset analysis, patients with high PD-L1 expression (³50%) stood out in terms of particular benefit (HR 0.24, 95% CI 0.10–0.61). The Checkmate 816 trial is a landmark study. Neoadjuvant nivolumab plus chemotherapy represents a new standard of care in the systemic treatment of resectable NSCLC that is at a stage that warrants systemic treatment. It is FDA approved regardless of PD-L1 expression level including PD-L1 negative (0%) patients.² Adjuvant atezolizumab after adjuvant chemotherapy is also an FDA-approved treatment option for patients that are PD-L1 positive (³1%) based upon the IMpower 010 study.¹ It will be important to assess the overall survival benefit as the trial data matures, which seems to be trending in the right direction. Additional neoadjuvant clinical trials with chemoimmunotherapy have completed accrual and some of these trials also continued PD-(L)1 immune checkpoint inhibitor therapy in the adjuvant setting after surgery. An important question for the future is if combination of PD-(L)1 immune checkpoint blockade with chemotherapy in the neoadjuvant setting along with continuation of immunotherapy in the adjuvant setting post-surgery will further improve clinical outcomes.

References

1. Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-57. Doi: 10.1016/S0140-6736(21)02098-5  Source

2. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. April 11, 2022. Doi: 10.1056/NEJMoa2202170 Source
    
3. Mok T, Camige DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31:1056-1064. Doi: 10.1016/j.annonc.2020.04.478 Source

4. Shaw AT, Solomon BJ, Chiari R, et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2019;20:1691-1701. Doi: 10.1016/S1470-2045(19)30655-2 Source
    
5. Lawrence MN, Tamen RM, Martinez P, et al. SPACEWALK: A remote participation study of ALK resistance leveraging plasma cell-free DNA genotyping. JTO Clin Res Rep. 2021;2:100151. Doi: 10.1016/j.jtocrr.2021.100151 Source
    
6. Lin JJ, Zhu VW, Yoda S, et al. Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer. J Clin Oncol. 2018;36:1199-1206. Doi: 10.1200/JCO.2017.76.2294 Source

Functional abdominal pain in childhood and adolescence is extremely stressful for patients and a therapeutic challenge for the physicians treating them. A meta-analysis of 33 randomized-controlled studies published in JAMA Pediatrics shows that cognitive-behavioral therapy or hypnotherapy promises the greatest therapy success.

“If children or adolescents complain about chronic abdominal pain and a detailed diagnostic does not reveal any somatic cause, this is referred to as functional abdominal pain,” Burkhard Rodeck, MD, general secretary of the German Society of Pediatrics and Adolescent Medicine in Berlin, told this news organization.
 

Signal perception disorder

It is still not completely clear what causes functional abdominal pain. But it is assumed to be a disruption in the communication between the gastrointestinal tract and the brain. “These patients are experiencing a signal perception disorder: normal body signals, such as a slight stomach rumble, are assigned to the pain category for them much more quickly than for other people,” said Dr. Rodeck. “The meta-analysis provides confirmation of this – functional abdominal pain is actually a biopsychosocial matter.”

In the standard therapy of functional abdominal pain, however, it is also possible to choose a medicinal approach. “Studies show that herbal preparations such as peppermint oil capsules have some efficacy, since they attenuate the strength of the signals being sent from the gastrointestinal tract to the brain, with the result that they are not perceived so quickly as pain. Probiotics can also potentially help,” added Dr. Rodeck.

“If this is unsuccessful, the child must be offered a psychologic/psychotherapeutic measure, usually cognitive-behavioral therapy.”
 

Comparison of psychosocial therapies

The meta-analysis was carried out by a research team at the University of Central Lancashire, Preston, United Kingdom. It included 2,657 children and adolescents between the ages of 7 and 17 years, of which two-thirds were girls.

Various psychosocial therapy approaches for functional abdominal pain, such as cognitive-behavioral therapy, educational assistance, hypnotherapy (directed at the digestive system), guided meditation with relaxation, yoga, or (visceral) osteopathy were investigated and compared in the studies – sometimes against each other and sometimes against no intervention.

Lead author Morris Gordon, MBChB, PhD, professor of evidence synthesis and systematic review at the University of Central Lancashire, and his colleagues reported that cognitive-behavioral therapy was 2.37-times more likely to result in therapy success than no intervention. To treat functional abdominal pain successfully in one child or adolescent, five children needed to be treated with cognitive-behavioral therapy.
 

Rarer, milder pain

The children and adolescents treated with cognitive-behavioral therapy also experienced less frequent and less severe abdominal pain than the children and adolescents who did not receive any intervention. The rate of side effect–related therapy discontinuations did not differ between the groups.

Hypnotherapy could also be associated with an improved outcome, compared with no intervention, added Dr. Gordon and his colleagues. Hypnotherapy was 2.86-times more likely to result in therapy success, and the number needed to treat was five.

The other therapeutic approaches investigated did not perform any better in the studies than no intervention. However, the authors noted that evidence of the effectiveness of cognitive-behavioral therapy and hypnotherapy is moderate or weak, especially owing to the high bias risk.

“The therapy for functional abdominal pain cannot be compared with the therapy for scarlet fever, for example, where penicillin is administered in the knowledge that recovery is guaranteed. There is evidence that cognitive-behavioral therapy and possibly also hypnotherapy may help, but this is not true for every patient,” said Dr. Rodeck.
 

Start with the pediatrician

Dr. Gordon and his co-authors suggested considering cognitive-behavioral therapy and hypnotherapy for the treatment of functional abdominal pain in children and adolescents. But they added that further randomized controlled studies are necessary to improve the quality of evidence and therefore the reliability of these results.

Children and adolescents with functional abdominal pain do not need to be sent directly to the psychologist for treatment, said Dr. Rodeck. The pediatric or adolescent medicine specialist can also administer the initial behavioral therapy measures. “Some patients manage with the behavioral therapy approaches we offer as pediatric and adolescent medicine specialists; others require professional support with psychologic expertise,” said Dr. Rodeck. Should outpatient treatment be unsuccessful, inpatient therapy in special psychosomatic clinics or wards remains an option.
 

Education offers relief

For many patients, being informed about the connections and mechanisms that play a role in functional abdominal pain can offer a lot of relief, said Dr. Rodeck. Offering coping strategies that can be used in the event of acute symptoms is also a part of this education.

“If patients have functional abdominal pain for which no organic cause can be found, this can lead to frustration, sadness, and despair. The problem can become even worse if they feel that they are not being taken seriously by the physician,” said Dr. Rodeck. These negative experiences can further exacerbate the pain perception disorder. The aim of behavioral therapy measures is therefore to interrupt and downregulate this vicious cycle.

“Constant investigations are not always helpful for patients with functional abdominal pain. Time must be taken with these patients to talk and explore the options. They have definite abdominal pain, they are not imagining it. They must be taken seriously,” he emphasized.

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

Functional abdominal pain in childhood and adolescence is extremely stressful for patients and a therapeutic challenge for the physicians treating them. A meta-analysis of 33 randomized-controlled studies published in JAMA Pediatrics shows that cognitive-behavioral therapy or hypnotherapy promises the greatest therapy success.

“If children or adolescents complain about chronic abdominal pain and a detailed diagnostic does not reveal any somatic cause, this is referred to as functional abdominal pain,” Burkhard Rodeck, MD, general secretary of the German Society of Pediatrics and Adolescent Medicine in Berlin, told this news organization.
 

Signal perception disorder

It is still not completely clear what causes functional abdominal pain. But it is assumed to be a disruption in the communication between the gastrointestinal tract and the brain. “These patients are experiencing a signal perception disorder: normal body signals, such as a slight stomach rumble, are assigned to the pain category for them much more quickly than for other people,” said Dr. Rodeck. “The meta-analysis provides confirmation of this – functional abdominal pain is actually a biopsychosocial matter.”

In the standard therapy of functional abdominal pain, however, it is also possible to choose a medicinal approach. “Studies show that herbal preparations such as peppermint oil capsules have some efficacy, since they attenuate the strength of the signals being sent from the gastrointestinal tract to the brain, with the result that they are not perceived so quickly as pain. Probiotics can also potentially help,” added Dr. Rodeck.

“If this is unsuccessful, the child must be offered a psychologic/psychotherapeutic measure, usually cognitive-behavioral therapy.”
 

Comparison of psychosocial therapies

The meta-analysis was carried out by a research team at the University of Central Lancashire, Preston, United Kingdom. It included 2,657 children and adolescents between the ages of 7 and 17 years, of which two-thirds were girls.

Various psychosocial therapy approaches for functional abdominal pain, such as cognitive-behavioral therapy, educational assistance, hypnotherapy (directed at the digestive system), guided meditation with relaxation, yoga, or (visceral) osteopathy were investigated and compared in the studies – sometimes against each other and sometimes against no intervention.

Lead author Morris Gordon, MBChB, PhD, professor of evidence synthesis and systematic review at the University of Central Lancashire, and his colleagues reported that cognitive-behavioral therapy was 2.37-times more likely to result in therapy success than no intervention. To treat functional abdominal pain successfully in one child or adolescent, five children needed to be treated with cognitive-behavioral therapy.
 

Rarer, milder pain

The children and adolescents treated with cognitive-behavioral therapy also experienced less frequent and less severe abdominal pain than the children and adolescents who did not receive any intervention. The rate of side effect–related therapy discontinuations did not differ between the groups.

Hypnotherapy could also be associated with an improved outcome, compared with no intervention, added Dr. Gordon and his colleagues. Hypnotherapy was 2.86-times more likely to result in therapy success, and the number needed to treat was five.

The other therapeutic approaches investigated did not perform any better in the studies than no intervention. However, the authors noted that evidence of the effectiveness of cognitive-behavioral therapy and hypnotherapy is moderate or weak, especially owing to the high bias risk.

“The therapy for functional abdominal pain cannot be compared with the therapy for scarlet fever, for example, where penicillin is administered in the knowledge that recovery is guaranteed. There is evidence that cognitive-behavioral therapy and possibly also hypnotherapy may help, but this is not true for every patient,” said Dr. Rodeck.
 

Start with the pediatrician

Dr. Gordon and his co-authors suggested considering cognitive-behavioral therapy and hypnotherapy for the treatment of functional abdominal pain in children and adolescents. But they added that further randomized controlled studies are necessary to improve the quality of evidence and therefore the reliability of these results.

Children and adolescents with functional abdominal pain do not need to be sent directly to the psychologist for treatment, said Dr. Rodeck. The pediatric or adolescent medicine specialist can also administer the initial behavioral therapy measures. “Some patients manage with the behavioral therapy approaches we offer as pediatric and adolescent medicine specialists; others require professional support with psychologic expertise,” said Dr. Rodeck. Should outpatient treatment be unsuccessful, inpatient therapy in special psychosomatic clinics or wards remains an option.
 

Education offers relief

For many patients, being informed about the connections and mechanisms that play a role in functional abdominal pain can offer a lot of relief, said Dr. Rodeck. Offering coping strategies that can be used in the event of acute symptoms is also a part of this education.

“If patients have functional abdominal pain for which no organic cause can be found, this can lead to frustration, sadness, and despair. The problem can become even worse if they feel that they are not being taken seriously by the physician,” said Dr. Rodeck. These negative experiences can further exacerbate the pain perception disorder. The aim of behavioral therapy measures is therefore to interrupt and downregulate this vicious cycle.

“Constant investigations are not always helpful for patients with functional abdominal pain. Time must be taken with these patients to talk and explore the options. They have definite abdominal pain, they are not imagining it. They must be taken seriously,” he emphasized.

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

Functional abdominal pain in childhood and adolescence is extremely stressful for patients and a therapeutic challenge for the physicians treating them. A meta-analysis of 33 randomized-controlled studies published in JAMA Pediatrics shows that cognitive-behavioral therapy or hypnotherapy promises the greatest therapy success.

“If children or adolescents complain about chronic abdominal pain and a detailed diagnostic does not reveal any somatic cause, this is referred to as functional abdominal pain,” Burkhard Rodeck, MD, general secretary of the German Society of Pediatrics and Adolescent Medicine in Berlin, told this news organization.
 

Signal perception disorder

It is still not completely clear what causes functional abdominal pain. But it is assumed to be a disruption in the communication between the gastrointestinal tract and the brain. “These patients are experiencing a signal perception disorder: normal body signals, such as a slight stomach rumble, are assigned to the pain category for them much more quickly than for other people,” said Dr. Rodeck. “The meta-analysis provides confirmation of this – functional abdominal pain is actually a biopsychosocial matter.”

In the standard therapy of functional abdominal pain, however, it is also possible to choose a medicinal approach. “Studies show that herbal preparations such as peppermint oil capsules have some efficacy, since they attenuate the strength of the signals being sent from the gastrointestinal tract to the brain, with the result that they are not perceived so quickly as pain. Probiotics can also potentially help,” added Dr. Rodeck.

“If this is unsuccessful, the child must be offered a psychologic/psychotherapeutic measure, usually cognitive-behavioral therapy.”
 

Comparison of psychosocial therapies

The meta-analysis was carried out by a research team at the University of Central Lancashire, Preston, United Kingdom. It included 2,657 children and adolescents between the ages of 7 and 17 years, of which two-thirds were girls.

Various psychosocial therapy approaches for functional abdominal pain, such as cognitive-behavioral therapy, educational assistance, hypnotherapy (directed at the digestive system), guided meditation with relaxation, yoga, or (visceral) osteopathy were investigated and compared in the studies – sometimes against each other and sometimes against no intervention.

Lead author Morris Gordon, MBChB, PhD, professor of evidence synthesis and systematic review at the University of Central Lancashire, and his colleagues reported that cognitive-behavioral therapy was 2.37-times more likely to result in therapy success than no intervention. To treat functional abdominal pain successfully in one child or adolescent, five children needed to be treated with cognitive-behavioral therapy.
 

Rarer, milder pain

The children and adolescents treated with cognitive-behavioral therapy also experienced less frequent and less severe abdominal pain than the children and adolescents who did not receive any intervention. The rate of side effect–related therapy discontinuations did not differ between the groups.

Hypnotherapy could also be associated with an improved outcome, compared with no intervention, added Dr. Gordon and his colleagues. Hypnotherapy was 2.86-times more likely to result in therapy success, and the number needed to treat was five.

The other therapeutic approaches investigated did not perform any better in the studies than no intervention. However, the authors noted that evidence of the effectiveness of cognitive-behavioral therapy and hypnotherapy is moderate or weak, especially owing to the high bias risk.

“The therapy for functional abdominal pain cannot be compared with the therapy for scarlet fever, for example, where penicillin is administered in the knowledge that recovery is guaranteed. There is evidence that cognitive-behavioral therapy and possibly also hypnotherapy may help, but this is not true for every patient,” said Dr. Rodeck.
 

Start with the pediatrician

Dr. Gordon and his co-authors suggested considering cognitive-behavioral therapy and hypnotherapy for the treatment of functional abdominal pain in children and adolescents. But they added that further randomized controlled studies are necessary to improve the quality of evidence and therefore the reliability of these results.

Children and adolescents with functional abdominal pain do not need to be sent directly to the psychologist for treatment, said Dr. Rodeck. The pediatric or adolescent medicine specialist can also administer the initial behavioral therapy measures. “Some patients manage with the behavioral therapy approaches we offer as pediatric and adolescent medicine specialists; others require professional support with psychologic expertise,” said Dr. Rodeck. Should outpatient treatment be unsuccessful, inpatient therapy in special psychosomatic clinics or wards remains an option.
 

Education offers relief

For many patients, being informed about the connections and mechanisms that play a role in functional abdominal pain can offer a lot of relief, said Dr. Rodeck. Offering coping strategies that can be used in the event of acute symptoms is also a part of this education.

“If patients have functional abdominal pain for which no organic cause can be found, this can lead to frustration, sadness, and despair. The problem can become even worse if they feel that they are not being taken seriously by the physician,” said Dr. Rodeck. These negative experiences can further exacerbate the pain perception disorder. The aim of behavioral therapy measures is therefore to interrupt and downregulate this vicious cycle.

“Constant investigations are not always helpful for patients with functional abdominal pain. Time must be taken with these patients to talk and explore the options. They have definite abdominal pain, they are not imagining it. They must be taken seriously,” he emphasized.

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

New research suggests physicians face a Herculean task to get Americans with atherosclerotic cardiovascular disease (ASCVD) to take high-intensity statins, despite multiple professional guidelines giving the therapy their highest level recommendation.

Results from more 600,000 commercially insured patients with established ASCVD showed:

• Only one in five patients (22.5%) were taking a high-intensity statin.
• 27.6% were taking a low- or moderate-intensity statin.
• One-half (49.9%) were not taking any statin.

“It’s embarrassing,” senior author Christopher B. Granger, MD, Duke Clinical Research Institute, Durham, N.C., told this news organization. “It should be embarrassing for anybody in health care that we do such a terrible job with something so simple and effective.”

The results were published in the Journal of the American College of Cardiology.

Statins have been shown to reduce the risk for ASCVD events by about 30%, with an added 15% reduction with a high-intensity formulation. The class I recommendation for high-intensity statin use in ASCVD patients younger than 75 years in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines prompted a jump in prescriptions that plateaued by 2017.

A class II recommendation was added to the 2018 guideline update for high-intensity statins in adults older than 75 years with ASCVD. But underuse persists, despite falling prices with generic availability and initiatives to improve statin adoption, the authors noted.

“There are a lot of barriers for patients to statin use, including the misinformation on the Internet and elsewhere that statins have all kinds of side effects,” Dr. Granger said. “They have uncommon side effects, but when we look at it carefully, only about 10% of patients, even with statin intolerance, have true intolerance.”

Efforts are needed to better understand and address these barriers, particularly for younger and female patients, he noted.

In multivariate analyses, patients who were middle-aged (odds ratio, 2.66) or at least 75 years of age (OR, 2.09) were more than twice as likely as patients younger than 45 years to be on any statin.

Not surprisingly, women were 30% less likely than men to receive a statin (OR, 0.70), Dr. Granger said. A high Charlson comorbidity score (OR, 0.72) and peripheral artery disease (OR, 0.55) also reduced the odds of a statin prescription.

Among statin users, middle-aged (OR, 0.83) and older (OR, 0.44) patients were less likely to be on a high-intensity statin, as were women (OR, 0.68) and patients with peripheral artery disease (OR, 0.43).

Visiting a cardiologist in the previous 12 months, however, increased the odds a patient was on a high-intensity statin (OR, 1.21), as did the use of other LDL-cholesterol-lowering drugs (OR, 1.44).

“With no evidence of heterogeneity in efficacy by sex, ongoing work must not only address misperceptions and barriers to the prescription of high-intensity statins in women, but also further understand (and address) differences in tolerability, which may be related to sex-based variation in statin metabolism,” wrote the authors, led by Adam J. Nelson, MBBS, MBA, MPH, also from Duke.

The study involved 601,934 patients (mean age, 67.5 years) who had a diagnosis of ASCVD between Jan. 31, 2018, and an index date of Jan. 31, 2019, and were enrolled in the HealthCore Integrated Research Environment database.

Two-thirds (70.9%) of patients visited a cardiologist in the 12 months prior to the index date, and three-fourths (81.3%) visited a primary care provider.

Pharmacy claims for the 12 months after the index date showed 82.8% of high-intensity users at index achieved coverage for at least 75% of days. Those with the least adherence (< 50% of days covered) included younger patients, as well as those with chronic kidney disease or depression.

“We need implementation research. What are the tools and the methods that we can use to improve the proportion of patients who are having the life-saving benefits from statins?” Dr. Granger said.

He noted that the team has submitted a National Institutes of Health grant to try to use pharmacists, as a mechanism within the context of health systems and payer systems, to improve the appropriate use of statins in a randomized trial. “I think that’s a win.”

Salim S. Virani, MD, PhD, Baylor College of Medicine, and Michael DeBakey VA Medical Center, Houston, and colleagues point out in a related editorial that the rates of statin usage in the study are “considerably lower” than in other contemporary studies, where about 80% and 50% of ASCVD patients are receiving statins and high-intensity statins, respectively.

Possible explanations are the use of rule-out codes, a short medication fill window from the index date, or issues with medication capture, they said. “Nevertheless, the findings are largely consistent with other work highlighting low use of statin therapy.”

The editorialists said social media, statin-related adverse effects, and therapeutic inertia are key drivers of non–guideline-concordant statin use. Possible solutions include improving guideline dissemination, leveraging team-based care, using smart clinical decision-support tools at the point of care, and identifying trustworthy and easily understood sources of information for patients.

“We can only hope that the fate of statin therapy is not repeated with sodium-glucose cotranspoerter-2 inhibitors or glucagon-like peptide-1 receptor agonists in another 30 years, or worse yet, that continued gaps in statin therapy use in patients with ASCVD persist 30 years from now,” Dr. Virani and colleagues concluded.

A sliver of optimism?

A research letter by Colantonio et al. in the same issue of JACC points to some positive steps, at least among patients having a myocardial infarction (MI). It reported that the percentage of patients who received a high-intensity statin as their first statin prescription 30 days after MI jumped from 30.7% in the first quarter of 2011 to 78.6% in the fourth quarter of 2019.

Similar increases were reported by race/ethnicity, despite statin use previously shown to be lower among non-Hispanic Black patients with ASCVD. In each calendar year, however, high-intensity statin therapy was lower among patients older than 75 years and among women.

Dr. Granger disclosed ties with Boehringer Ingelheim, Bristol Myers Squibb, Janssen Pharmaceuticals, Pfizer, AKROS, Apple, AstraZeneca, Daiichi Sankyo, Food and Drug Administration, GlaxoSmithKline, Medtronic Foundation, Novartis Pharmaceuticals, AbbVie, Bayer, Boston Scientific, CeleCor Therapeutics, Correvio, Espero BioPharma, Medscape, Medtronic, Merck, National Institutes of Health, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Virani disclosed ties with the Department of Veterans Affairs, the National Institutes of Health, the World Heart Federation, and the Jooma and Tahir Family, and the American College of Cardiology.

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

New research suggests physicians face a Herculean task to get Americans with atherosclerotic cardiovascular disease (ASCVD) to take high-intensity statins, despite multiple professional guidelines giving the therapy their highest level recommendation.

Results from more 600,000 commercially insured patients with established ASCVD showed:

• Only one in five patients (22.5%) were taking a high-intensity statin.
• 27.6% were taking a low- or moderate-intensity statin.
• One-half (49.9%) were not taking any statin.

“It’s embarrassing,” senior author Christopher B. Granger, MD, Duke Clinical Research Institute, Durham, N.C., told this news organization. “It should be embarrassing for anybody in health care that we do such a terrible job with something so simple and effective.”

The results were published in the Journal of the American College of Cardiology.

Statins have been shown to reduce the risk for ASCVD events by about 30%, with an added 15% reduction with a high-intensity formulation. The class I recommendation for high-intensity statin use in ASCVD patients younger than 75 years in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines prompted a jump in prescriptions that plateaued by 2017.

A class II recommendation was added to the 2018 guideline update for high-intensity statins in adults older than 75 years with ASCVD. But underuse persists, despite falling prices with generic availability and initiatives to improve statin adoption, the authors noted.

“There are a lot of barriers for patients to statin use, including the misinformation on the Internet and elsewhere that statins have all kinds of side effects,” Dr. Granger said. “They have uncommon side effects, but when we look at it carefully, only about 10% of patients, even with statin intolerance, have true intolerance.”

Efforts are needed to better understand and address these barriers, particularly for younger and female patients, he noted.

In multivariate analyses, patients who were middle-aged (odds ratio, 2.66) or at least 75 years of age (OR, 2.09) were more than twice as likely as patients younger than 45 years to be on any statin.

Not surprisingly, women were 30% less likely than men to receive a statin (OR, 0.70), Dr. Granger said. A high Charlson comorbidity score (OR, 0.72) and peripheral artery disease (OR, 0.55) also reduced the odds of a statin prescription.

Among statin users, middle-aged (OR, 0.83) and older (OR, 0.44) patients were less likely to be on a high-intensity statin, as were women (OR, 0.68) and patients with peripheral artery disease (OR, 0.43).

Visiting a cardiologist in the previous 12 months, however, increased the odds a patient was on a high-intensity statin (OR, 1.21), as did the use of other LDL-cholesterol-lowering drugs (OR, 1.44).

“With no evidence of heterogeneity in efficacy by sex, ongoing work must not only address misperceptions and barriers to the prescription of high-intensity statins in women, but also further understand (and address) differences in tolerability, which may be related to sex-based variation in statin metabolism,” wrote the authors, led by Adam J. Nelson, MBBS, MBA, MPH, also from Duke.

The study involved 601,934 patients (mean age, 67.5 years) who had a diagnosis of ASCVD between Jan. 31, 2018, and an index date of Jan. 31, 2019, and were enrolled in the HealthCore Integrated Research Environment database.

Two-thirds (70.9%) of patients visited a cardiologist in the 12 months prior to the index date, and three-fourths (81.3%) visited a primary care provider.

Pharmacy claims for the 12 months after the index date showed 82.8% of high-intensity users at index achieved coverage for at least 75% of days. Those with the least adherence (< 50% of days covered) included younger patients, as well as those with chronic kidney disease or depression.

“We need implementation research. What are the tools and the methods that we can use to improve the proportion of patients who are having the life-saving benefits from statins?” Dr. Granger said.

He noted that the team has submitted a National Institutes of Health grant to try to use pharmacists, as a mechanism within the context of health systems and payer systems, to improve the appropriate use of statins in a randomized trial. “I think that’s a win.”

Salim S. Virani, MD, PhD, Baylor College of Medicine, and Michael DeBakey VA Medical Center, Houston, and colleagues point out in a related editorial that the rates of statin usage in the study are “considerably lower” than in other contemporary studies, where about 80% and 50% of ASCVD patients are receiving statins and high-intensity statins, respectively.

Possible explanations are the use of rule-out codes, a short medication fill window from the index date, or issues with medication capture, they said. “Nevertheless, the findings are largely consistent with other work highlighting low use of statin therapy.”

The editorialists said social media, statin-related adverse effects, and therapeutic inertia are key drivers of non–guideline-concordant statin use. Possible solutions include improving guideline dissemination, leveraging team-based care, using smart clinical decision-support tools at the point of care, and identifying trustworthy and easily understood sources of information for patients.

“We can only hope that the fate of statin therapy is not repeated with sodium-glucose cotranspoerter-2 inhibitors or glucagon-like peptide-1 receptor agonists in another 30 years, or worse yet, that continued gaps in statin therapy use in patients with ASCVD persist 30 years from now,” Dr. Virani and colleagues concluded.

A sliver of optimism?

A research letter by Colantonio et al. in the same issue of JACC points to some positive steps, at least among patients having a myocardial infarction (MI). It reported that the percentage of patients who received a high-intensity statin as their first statin prescription 30 days after MI jumped from 30.7% in the first quarter of 2011 to 78.6% in the fourth quarter of 2019.

Similar increases were reported by race/ethnicity, despite statin use previously shown to be lower among non-Hispanic Black patients with ASCVD. In each calendar year, however, high-intensity statin therapy was lower among patients older than 75 years and among women.

Dr. Granger disclosed ties with Boehringer Ingelheim, Bristol Myers Squibb, Janssen Pharmaceuticals, Pfizer, AKROS, Apple, AstraZeneca, Daiichi Sankyo, Food and Drug Administration, GlaxoSmithKline, Medtronic Foundation, Novartis Pharmaceuticals, AbbVie, Bayer, Boston Scientific, CeleCor Therapeutics, Correvio, Espero BioPharma, Medscape, Medtronic, Merck, National Institutes of Health, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Virani disclosed ties with the Department of Veterans Affairs, the National Institutes of Health, the World Heart Federation, and the Jooma and Tahir Family, and the American College of Cardiology.

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

New research suggests physicians face a Herculean task to get Americans with atherosclerotic cardiovascular disease (ASCVD) to take high-intensity statins, despite multiple professional guidelines giving the therapy their highest level recommendation.

Results from more 600,000 commercially insured patients with established ASCVD showed:

• Only one in five patients (22.5%) were taking a high-intensity statin.
• 27.6% were taking a low- or moderate-intensity statin.
• One-half (49.9%) were not taking any statin.

“It’s embarrassing,” senior author Christopher B. Granger, MD, Duke Clinical Research Institute, Durham, N.C., told this news organization. “It should be embarrassing for anybody in health care that we do such a terrible job with something so simple and effective.”

The results were published in the Journal of the American College of Cardiology.

Statins have been shown to reduce the risk for ASCVD events by about 30%, with an added 15% reduction with a high-intensity formulation. The class I recommendation for high-intensity statin use in ASCVD patients younger than 75 years in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines prompted a jump in prescriptions that plateaued by 2017.

A class II recommendation was added to the 2018 guideline update for high-intensity statins in adults older than 75 years with ASCVD. But underuse persists, despite falling prices with generic availability and initiatives to improve statin adoption, the authors noted.

“There are a lot of barriers for patients to statin use, including the misinformation on the Internet and elsewhere that statins have all kinds of side effects,” Dr. Granger said. “They have uncommon side effects, but when we look at it carefully, only about 10% of patients, even with statin intolerance, have true intolerance.”

Efforts are needed to better understand and address these barriers, particularly for younger and female patients, he noted.

In multivariate analyses, patients who were middle-aged (odds ratio, 2.66) or at least 75 years of age (OR, 2.09) were more than twice as likely as patients younger than 45 years to be on any statin.

Not surprisingly, women were 30% less likely than men to receive a statin (OR, 0.70), Dr. Granger said. A high Charlson comorbidity score (OR, 0.72) and peripheral artery disease (OR, 0.55) also reduced the odds of a statin prescription.

Among statin users, middle-aged (OR, 0.83) and older (OR, 0.44) patients were less likely to be on a high-intensity statin, as were women (OR, 0.68) and patients with peripheral artery disease (OR, 0.43).

Visiting a cardiologist in the previous 12 months, however, increased the odds a patient was on a high-intensity statin (OR, 1.21), as did the use of other LDL-cholesterol-lowering drugs (OR, 1.44).

“With no evidence of heterogeneity in efficacy by sex, ongoing work must not only address misperceptions and barriers to the prescription of high-intensity statins in women, but also further understand (and address) differences in tolerability, which may be related to sex-based variation in statin metabolism,” wrote the authors, led by Adam J. Nelson, MBBS, MBA, MPH, also from Duke.

The study involved 601,934 patients (mean age, 67.5 years) who had a diagnosis of ASCVD between Jan. 31, 2018, and an index date of Jan. 31, 2019, and were enrolled in the HealthCore Integrated Research Environment database.

Two-thirds (70.9%) of patients visited a cardiologist in the 12 months prior to the index date, and three-fourths (81.3%) visited a primary care provider.

Pharmacy claims for the 12 months after the index date showed 82.8% of high-intensity users at index achieved coverage for at least 75% of days. Those with the least adherence (< 50% of days covered) included younger patients, as well as those with chronic kidney disease or depression.

“We need implementation research. What are the tools and the methods that we can use to improve the proportion of patients who are having the life-saving benefits from statins?” Dr. Granger said.

He noted that the team has submitted a National Institutes of Health grant to try to use pharmacists, as a mechanism within the context of health systems and payer systems, to improve the appropriate use of statins in a randomized trial. “I think that’s a win.”

Salim S. Virani, MD, PhD, Baylor College of Medicine, and Michael DeBakey VA Medical Center, Houston, and colleagues point out in a related editorial that the rates of statin usage in the study are “considerably lower” than in other contemporary studies, where about 80% and 50% of ASCVD patients are receiving statins and high-intensity statins, respectively.

Possible explanations are the use of rule-out codes, a short medication fill window from the index date, or issues with medication capture, they said. “Nevertheless, the findings are largely consistent with other work highlighting low use of statin therapy.”

The editorialists said social media, statin-related adverse effects, and therapeutic inertia are key drivers of non–guideline-concordant statin use. Possible solutions include improving guideline dissemination, leveraging team-based care, using smart clinical decision-support tools at the point of care, and identifying trustworthy and easily understood sources of information for patients.

“We can only hope that the fate of statin therapy is not repeated with sodium-glucose cotranspoerter-2 inhibitors or glucagon-like peptide-1 receptor agonists in another 30 years, or worse yet, that continued gaps in statin therapy use in patients with ASCVD persist 30 years from now,” Dr. Virani and colleagues concluded.

A sliver of optimism?

A research letter by Colantonio et al. in the same issue of JACC points to some positive steps, at least among patients having a myocardial infarction (MI). It reported that the percentage of patients who received a high-intensity statin as their first statin prescription 30 days after MI jumped from 30.7% in the first quarter of 2011 to 78.6% in the fourth quarter of 2019.

Similar increases were reported by race/ethnicity, despite statin use previously shown to be lower among non-Hispanic Black patients with ASCVD. In each calendar year, however, high-intensity statin therapy was lower among patients older than 75 years and among women.

Dr. Granger disclosed ties with Boehringer Ingelheim, Bristol Myers Squibb, Janssen Pharmaceuticals, Pfizer, AKROS, Apple, AstraZeneca, Daiichi Sankyo, Food and Drug Administration, GlaxoSmithKline, Medtronic Foundation, Novartis Pharmaceuticals, AbbVie, Bayer, Boston Scientific, CeleCor Therapeutics, Correvio, Espero BioPharma, Medscape, Medtronic, Merck, National Institutes of Health, Novo Nordisk, Rhoshan Pharmaceuticals, and Roche Diagnostics. Dr. Virani disclosed ties with the Department of Veterans Affairs, the National Institutes of Health, the World Heart Federation, and the Jooma and Tahir Family, and the American College of Cardiology.

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

Symptom timelines surrounding COVID infection tend to center on either the immediate 5-day quarantine protocols for acute infection or the long-COVID symptoms that can last a month or potentially far longer.

But some patients report a “middle-range” COVID that will resolve before it becomes long COVID, yet still lasts longer than is typical for viral infections. People may return to work or daily routines, but something is off: What had been simple exercise regimens become onerous. Everyday tasks take more effort.

Does this ill-defined subset point to a “medium COVID?”

Farha Ikramuddin, MD, MHA, a physiatrist and rehabilitation specialist at the University of Minnesota and M Health Fairview in Minneapolis, points out there is no definition or diagnostic code or shared official understanding of a middle category for COVID.

“But am I seeing that? Absolutely,” she said in an interview.

“I have seen patients who are younger, healthier, [and] with not so many comorbidities have either persistence of symptoms or reappearance after the initial infection is done,” she said.

Some patients report they had very low infection or were nonsymptomatic and returned to their normal health fairly quickly after infection. Then a week later they began experiencing fatigue, lost appetite, loss of smell, and feeling full after a few bites, Dr. Ikramuddin said.

Part of the trouble in categorizing the space between returning to normal after a week and having symptoms for months is that organizations can’t agree on a timeline for when symptoms warrant a “long-COVID” label.

For instance, the Centers for Disease Control and Prevention defines it as 4 or more weeks after infection. The World Health Organization defines it as starting 3 months after COVID-19 symptom onset.

“I’m seeing ‘medium COVID’ – as one would call it – in younger and healthier patients. I’m also noticing that these symptoms are not severe enough to warrant stopping their job or changing their job schedules,” Dr. Ikramuddin said.

They go back to work, she said, but start noticing something is off.

“I am seeing that.”

“I discharge at least two patients a week from my clinic because they have moved on and no longer have symptoms,” Dr. Ikramuddin said.

In a story from Kaiser Health News published last month, WHYY health reporter Nina Feldman writes: “What I’ve come to think of as my ‘medium COVID’ affected my life. I couldn’t socialize much, drink, or stay up past 9:30 p.m. It took me 10 weeks to go for my first run – I’d been too afraid to try.”

She described a dinner with a friend after ending initial isolation protocols: “One glass of wine left me feeling like I’d had a whole bottle. I was bone-achingly exhausted but couldn’t sleep.”
 

Medical mystery

Dr. Ikramuddin notes the mechanism behind prolonged COVID-19 symptoms is still a medical mystery.

“In one scenario,” she said, “the question is being asked about whether the virus is staying dormant, similar to herpes zoster or HIV.”

“Right now, instead of getting more answers, we’re getting more questions,” Dr. Ikramuddin  said.

Mouhib Naddour, MD, a pulmonary specialist with Sharp HealthCare in San Diego, said he’s seeing that it’s taking some patients who have had COVID longer to recover than it would for other viral infections.

Some patients fall between those recovering within 2-3 weeks and patients having long COVID. Those patients in the gap could be lumped into a middle-range COVID, he told this news organization.

“We try to put things into tables and boxes but it is hard with this disease,” Dr. Naddour said.

He agrees there’s no medical definition for “medium” COVID, but he said the idea should bring hope for patients to know that, if their symptoms are persisting they don’t necessarily have long COVID – and their symptoms may still disappear.

“This is an illness that may take longer to completely recover from,” he said. “The majority of patients we’re seeing in this group could be healthy young patients who get COVID, then 2-3 weeks after they test negative, still have lingering symptoms.”
 

Common symptoms

Some commonly reported symptoms of those with enduring illness, which often overlap with other stages of COVID, are difficulty breathing, chest tightness, dry cough, chest pain, muscle and joint pain, fatigue, difficulty sleeping, and mood swings, Dr. Naddour said. 

“We need to do an extensive assessment to make sure there’s no other problem causing these symptoms,” he said.

Still, there is no set timeline for the medium-COVID range, he noted, so checking in with a primary care physician is important for people experiencing symptoms.
 

It’s a continuum, not a category

Fernando Carnavali, MD, coordinator for Mount Sinai’s Center for Post-COVID Care in New York, said he is not ready to recognize a separate category for a “medium” COVID.

He noted that science can’t even agree on a name for lasting post-COVID symptoms, whether it’s “long COVID” or “long-haul COVID,” “post-COVID syndrome” or “post-acute sequelae of COVID-19 (PASC ).” There’s no agreed-upon pathophysiology or biomarker.

“That creates these gaps of understanding on where we are,” Dr. Carnavali said in an interview.

He said he understands people’s need to categorize symptoms, but rather than a middle ground he sees a continuum.

It doesn’t mean what others may call COVID’s middle ground doesn’t exist, Dr. Carnavali said: “We are in the infancy of defining this. Trying to classify them may create more anxiety.”

The clinicians interviewed for this story report no relevant financial relationships.

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

Symptom timelines surrounding COVID infection tend to center on either the immediate 5-day quarantine protocols for acute infection or the long-COVID symptoms that can last a month or potentially far longer.

But some patients report a “middle-range” COVID that will resolve before it becomes long COVID, yet still lasts longer than is typical for viral infections. People may return to work or daily routines, but something is off: What had been simple exercise regimens become onerous. Everyday tasks take more effort.

Does this ill-defined subset point to a “medium COVID?”

Farha Ikramuddin, MD, MHA, a physiatrist and rehabilitation specialist at the University of Minnesota and M Health Fairview in Minneapolis, points out there is no definition or diagnostic code or shared official understanding of a middle category for COVID.

“But am I seeing that? Absolutely,” she said in an interview.

“I have seen patients who are younger, healthier, [and] with not so many comorbidities have either persistence of symptoms or reappearance after the initial infection is done,” she said.

Some patients report they had very low infection or were nonsymptomatic and returned to their normal health fairly quickly after infection. Then a week later they began experiencing fatigue, lost appetite, loss of smell, and feeling full after a few bites, Dr. Ikramuddin said.

Part of the trouble in categorizing the space between returning to normal after a week and having symptoms for months is that organizations can’t agree on a timeline for when symptoms warrant a “long-COVID” label.

For instance, the Centers for Disease Control and Prevention defines it as 4 or more weeks after infection. The World Health Organization defines it as starting 3 months after COVID-19 symptom onset.

“I’m seeing ‘medium COVID’ – as one would call it – in younger and healthier patients. I’m also noticing that these symptoms are not severe enough to warrant stopping their job or changing their job schedules,” Dr. Ikramuddin said.

They go back to work, she said, but start noticing something is off.

“I am seeing that.”

“I discharge at least two patients a week from my clinic because they have moved on and no longer have symptoms,” Dr. Ikramuddin said.

In a story from Kaiser Health News published last month, WHYY health reporter Nina Feldman writes: “What I’ve come to think of as my ‘medium COVID’ affected my life. I couldn’t socialize much, drink, or stay up past 9:30 p.m. It took me 10 weeks to go for my first run – I’d been too afraid to try.”

She described a dinner with a friend after ending initial isolation protocols: “One glass of wine left me feeling like I’d had a whole bottle. I was bone-achingly exhausted but couldn’t sleep.”
 

Medical mystery

Dr. Ikramuddin notes the mechanism behind prolonged COVID-19 symptoms is still a medical mystery.

“In one scenario,” she said, “the question is being asked about whether the virus is staying dormant, similar to herpes zoster or HIV.”

“Right now, instead of getting more answers, we’re getting more questions,” Dr. Ikramuddin  said.

Mouhib Naddour, MD, a pulmonary specialist with Sharp HealthCare in San Diego, said he’s seeing that it’s taking some patients who have had COVID longer to recover than it would for other viral infections.

Some patients fall between those recovering within 2-3 weeks and patients having long COVID. Those patients in the gap could be lumped into a middle-range COVID, he told this news organization.

“We try to put things into tables and boxes but it is hard with this disease,” Dr. Naddour said.

He agrees there’s no medical definition for “medium” COVID, but he said the idea should bring hope for patients to know that, if their symptoms are persisting they don’t necessarily have long COVID – and their symptoms may still disappear.

“This is an illness that may take longer to completely recover from,” he said. “The majority of patients we’re seeing in this group could be healthy young patients who get COVID, then 2-3 weeks after they test negative, still have lingering symptoms.”
 

Common symptoms

Some commonly reported symptoms of those with enduring illness, which often overlap with other stages of COVID, are difficulty breathing, chest tightness, dry cough, chest pain, muscle and joint pain, fatigue, difficulty sleeping, and mood swings, Dr. Naddour said. 

“We need to do an extensive assessment to make sure there’s no other problem causing these symptoms,” he said.

Still, there is no set timeline for the medium-COVID range, he noted, so checking in with a primary care physician is important for people experiencing symptoms.
 

It’s a continuum, not a category

Fernando Carnavali, MD, coordinator for Mount Sinai’s Center for Post-COVID Care in New York, said he is not ready to recognize a separate category for a “medium” COVID.

He noted that science can’t even agree on a name for lasting post-COVID symptoms, whether it’s “long COVID” or “long-haul COVID,” “post-COVID syndrome” or “post-acute sequelae of COVID-19 (PASC ).” There’s no agreed-upon pathophysiology or biomarker.

“That creates these gaps of understanding on where we are,” Dr. Carnavali said in an interview.

He said he understands people’s need to categorize symptoms, but rather than a middle ground he sees a continuum.

It doesn’t mean what others may call COVID’s middle ground doesn’t exist, Dr. Carnavali said: “We are in the infancy of defining this. Trying to classify them may create more anxiety.”

The clinicians interviewed for this story report no relevant financial relationships.

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

Symptom timelines surrounding COVID infection tend to center on either the immediate 5-day quarantine protocols for acute infection or the long-COVID symptoms that can last a month or potentially far longer.

But some patients report a “middle-range” COVID that will resolve before it becomes long COVID, yet still lasts longer than is typical for viral infections. People may return to work or daily routines, but something is off: What had been simple exercise regimens become onerous. Everyday tasks take more effort.

Does this ill-defined subset point to a “medium COVID?”

Farha Ikramuddin, MD, MHA, a physiatrist and rehabilitation specialist at the University of Minnesota and M Health Fairview in Minneapolis, points out there is no definition or diagnostic code or shared official understanding of a middle category for COVID.

“But am I seeing that? Absolutely,” she said in an interview.

“I have seen patients who are younger, healthier, [and] with not so many comorbidities have either persistence of symptoms or reappearance after the initial infection is done,” she said.

Some patients report they had very low infection or were nonsymptomatic and returned to their normal health fairly quickly after infection. Then a week later they began experiencing fatigue, lost appetite, loss of smell, and feeling full after a few bites, Dr. Ikramuddin said.

Part of the trouble in categorizing the space between returning to normal after a week and having symptoms for months is that organizations can’t agree on a timeline for when symptoms warrant a “long-COVID” label.

For instance, the Centers for Disease Control and Prevention defines it as 4 or more weeks after infection. The World Health Organization defines it as starting 3 months after COVID-19 symptom onset.

“I’m seeing ‘medium COVID’ – as one would call it – in younger and healthier patients. I’m also noticing that these symptoms are not severe enough to warrant stopping their job or changing their job schedules,” Dr. Ikramuddin said.

They go back to work, she said, but start noticing something is off.

“I am seeing that.”

“I discharge at least two patients a week from my clinic because they have moved on and no longer have symptoms,” Dr. Ikramuddin said.

In a story from Kaiser Health News published last month, WHYY health reporter Nina Feldman writes: “What I’ve come to think of as my ‘medium COVID’ affected my life. I couldn’t socialize much, drink, or stay up past 9:30 p.m. It took me 10 weeks to go for my first run – I’d been too afraid to try.”

She described a dinner with a friend after ending initial isolation protocols: “One glass of wine left me feeling like I’d had a whole bottle. I was bone-achingly exhausted but couldn’t sleep.”
 

Medical mystery

Dr. Ikramuddin notes the mechanism behind prolonged COVID-19 symptoms is still a medical mystery.

“In one scenario,” she said, “the question is being asked about whether the virus is staying dormant, similar to herpes zoster or HIV.”

“Right now, instead of getting more answers, we’re getting more questions,” Dr. Ikramuddin  said.

Mouhib Naddour, MD, a pulmonary specialist with Sharp HealthCare in San Diego, said he’s seeing that it’s taking some patients who have had COVID longer to recover than it would for other viral infections.

Some patients fall between those recovering within 2-3 weeks and patients having long COVID. Those patients in the gap could be lumped into a middle-range COVID, he told this news organization.

“We try to put things into tables and boxes but it is hard with this disease,” Dr. Naddour said.

He agrees there’s no medical definition for “medium” COVID, but he said the idea should bring hope for patients to know that, if their symptoms are persisting they don’t necessarily have long COVID – and their symptoms may still disappear.

“This is an illness that may take longer to completely recover from,” he said. “The majority of patients we’re seeing in this group could be healthy young patients who get COVID, then 2-3 weeks after they test negative, still have lingering symptoms.”
 

Common symptoms

Some commonly reported symptoms of those with enduring illness, which often overlap with other stages of COVID, are difficulty breathing, chest tightness, dry cough, chest pain, muscle and joint pain, fatigue, difficulty sleeping, and mood swings, Dr. Naddour said. 

“We need to do an extensive assessment to make sure there’s no other problem causing these symptoms,” he said.

Still, there is no set timeline for the medium-COVID range, he noted, so checking in with a primary care physician is important for people experiencing symptoms.
 

It’s a continuum, not a category

Fernando Carnavali, MD, coordinator for Mount Sinai’s Center for Post-COVID Care in New York, said he is not ready to recognize a separate category for a “medium” COVID.

He noted that science can’t even agree on a name for lasting post-COVID symptoms, whether it’s “long COVID” or “long-haul COVID,” “post-COVID syndrome” or “post-acute sequelae of COVID-19 (PASC ).” There’s no agreed-upon pathophysiology or biomarker.

“That creates these gaps of understanding on where we are,” Dr. Carnavali said in an interview.

He said he understands people’s need to categorize symptoms, but rather than a middle ground he sees a continuum.

It doesn’t mean what others may call COVID’s middle ground doesn’t exist, Dr. Carnavali said: “We are in the infancy of defining this. Trying to classify them may create more anxiety.”

The clinicians interviewed for this story report no relevant financial relationships.

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

New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) confirm a small but statistically significant increased risk for Guillain-Barré syndrome (GBS) in the 3 weeks after receipt of the Janssen/Johnson & Johnson COVID-19 vaccine.

The Janssen vaccine (Ad26.COV2.S) is a replication-incompetent adenoviral vector vaccine.

The data show no increased risk of GBS with the Pfizer (BNT162b2) or Moderna (mRNA-1273) shots – both mRNA vaccines.

“Our findings support the current guidance from U.S. health officials that preferentially recommend use of mRNA COVID-19 vaccines for primary and booster doses,” Nicola Klein, MD, PhD, with Kaiser Permanente Vaccine Study Center, Oakland, Calif., told this news organization.

“Individuals who choose to receive Janssen/J&J COVID-19 vaccine should be informed of the potential safety risks, including GBS,” Dr. Klein said.

The study was published online in JAMA Network Open.
 

Eleven cases

Between mid-December 2020 and mid-November 2021, roughly 15.1 million doses of COVID-19 vaccine were administered to nearly 7.9 million adults in the United States.

This includes roughly 483,000 doses of the Janssen vaccine, 8.8 million doses of the Pfizer vaccine, and 5.8 million doses of the Moderna vaccine.

The researchers confirmed 11 cases of GBS after the Janssen vaccine.

The unadjusted incidence of GBS (per 100,000 person-years) was 32.4 in the first 21 days after the Janssen vaccine – substantially higher than the expected background rate of 1 to 2 cases per 100,000 person-years.

There were 36 confirmed cases of GBS after mRNA vaccines. The unadjusted incidence in the first 21 days after mRNA vaccination was 1.3 per 100,000 person-years, similar to the overall expected background rate.

In an adjusted head-to-head comparison, GBS incidence during the 21 days after receipt of the Janssen vaccine was 20.6 times higher than the GBS incidence during the 21 days after the Pfizer or Moderna mRNA vaccines, amounting to 15.5 excess cases per million Janssen vaccine recipients.

Most cases of GBS after the Janssen vaccine occurred during the 1- to 21-day risk interval, with the period of greatest risk in the 1-14 days after vaccination.

The findings of this analysis of surveillance data of COVID-19 vaccines are “consistent with an elevated risk of GBS after primary Ad26.COV2.S vaccination,” the authors wrote.
 

Novel presentation?

The researchers note that nearly all individuals who developed GBS after the Janssen vaccine had facial weakness or paralysis, in addition to weakness and decreased reflexes in the limbs, suggesting that the presentation of GBS after COVID-19 adenoviral vector vaccine may be novel.

“More research is needed to determine if the presentation of GBS after adenoviral vector vaccine differs from GBS after other exposures such as Campylobacter jejuni, and to investigate the mechanism for how adenoviral vector vaccines may cause GBS,” Dr. Klein and colleagues said.

“The Vaccine Safety Datalink continues to conduct safety surveillance for all COVID-19 vaccines, including monitoring for GBS and other serious health outcomes after vaccination,” Dr. Klein said in an interview.

This study was supported by the Centers for Disease Control and Prevention. Dr. Klein reported receiving grants from Pfizer research support for a COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work.

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

New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) confirm a small but statistically significant increased risk for Guillain-Barré syndrome (GBS) in the 3 weeks after receipt of the Janssen/Johnson & Johnson COVID-19 vaccine.

The Janssen vaccine (Ad26.COV2.S) is a replication-incompetent adenoviral vector vaccine.

The data show no increased risk of GBS with the Pfizer (BNT162b2) or Moderna (mRNA-1273) shots – both mRNA vaccines.

“Our findings support the current guidance from U.S. health officials that preferentially recommend use of mRNA COVID-19 vaccines for primary and booster doses,” Nicola Klein, MD, PhD, with Kaiser Permanente Vaccine Study Center, Oakland, Calif., told this news organization.

“Individuals who choose to receive Janssen/J&J COVID-19 vaccine should be informed of the potential safety risks, including GBS,” Dr. Klein said.

The study was published online in JAMA Network Open.
 

Eleven cases

Between mid-December 2020 and mid-November 2021, roughly 15.1 million doses of COVID-19 vaccine were administered to nearly 7.9 million adults in the United States.

This includes roughly 483,000 doses of the Janssen vaccine, 8.8 million doses of the Pfizer vaccine, and 5.8 million doses of the Moderna vaccine.

The researchers confirmed 11 cases of GBS after the Janssen vaccine.

The unadjusted incidence of GBS (per 100,000 person-years) was 32.4 in the first 21 days after the Janssen vaccine – substantially higher than the expected background rate of 1 to 2 cases per 100,000 person-years.

There were 36 confirmed cases of GBS after mRNA vaccines. The unadjusted incidence in the first 21 days after mRNA vaccination was 1.3 per 100,000 person-years, similar to the overall expected background rate.

In an adjusted head-to-head comparison, GBS incidence during the 21 days after receipt of the Janssen vaccine was 20.6 times higher than the GBS incidence during the 21 days after the Pfizer or Moderna mRNA vaccines, amounting to 15.5 excess cases per million Janssen vaccine recipients.

Most cases of GBS after the Janssen vaccine occurred during the 1- to 21-day risk interval, with the period of greatest risk in the 1-14 days after vaccination.

The findings of this analysis of surveillance data of COVID-19 vaccines are “consistent with an elevated risk of GBS after primary Ad26.COV2.S vaccination,” the authors wrote.
 

Novel presentation?

The researchers note that nearly all individuals who developed GBS after the Janssen vaccine had facial weakness or paralysis, in addition to weakness and decreased reflexes in the limbs, suggesting that the presentation of GBS after COVID-19 adenoviral vector vaccine may be novel.

“More research is needed to determine if the presentation of GBS after adenoviral vector vaccine differs from GBS after other exposures such as Campylobacter jejuni, and to investigate the mechanism for how adenoviral vector vaccines may cause GBS,” Dr. Klein and colleagues said.

“The Vaccine Safety Datalink continues to conduct safety surveillance for all COVID-19 vaccines, including monitoring for GBS and other serious health outcomes after vaccination,” Dr. Klein said in an interview.

This study was supported by the Centers for Disease Control and Prevention. Dr. Klein reported receiving grants from Pfizer research support for a COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work.

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

New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) confirm a small but statistically significant increased risk for Guillain-Barré syndrome (GBS) in the 3 weeks after receipt of the Janssen/Johnson & Johnson COVID-19 vaccine.

The Janssen vaccine (Ad26.COV2.S) is a replication-incompetent adenoviral vector vaccine.

The data show no increased risk of GBS with the Pfizer (BNT162b2) or Moderna (mRNA-1273) shots – both mRNA vaccines.

“Our findings support the current guidance from U.S. health officials that preferentially recommend use of mRNA COVID-19 vaccines for primary and booster doses,” Nicola Klein, MD, PhD, with Kaiser Permanente Vaccine Study Center, Oakland, Calif., told this news organization.

“Individuals who choose to receive Janssen/J&J COVID-19 vaccine should be informed of the potential safety risks, including GBS,” Dr. Klein said.

The study was published online in JAMA Network Open.
 

Eleven cases

Between mid-December 2020 and mid-November 2021, roughly 15.1 million doses of COVID-19 vaccine were administered to nearly 7.9 million adults in the United States.

This includes roughly 483,000 doses of the Janssen vaccine, 8.8 million doses of the Pfizer vaccine, and 5.8 million doses of the Moderna vaccine.

The researchers confirmed 11 cases of GBS after the Janssen vaccine.

The unadjusted incidence of GBS (per 100,000 person-years) was 32.4 in the first 21 days after the Janssen vaccine – substantially higher than the expected background rate of 1 to 2 cases per 100,000 person-years.

There were 36 confirmed cases of GBS after mRNA vaccines. The unadjusted incidence in the first 21 days after mRNA vaccination was 1.3 per 100,000 person-years, similar to the overall expected background rate.

In an adjusted head-to-head comparison, GBS incidence during the 21 days after receipt of the Janssen vaccine was 20.6 times higher than the GBS incidence during the 21 days after the Pfizer or Moderna mRNA vaccines, amounting to 15.5 excess cases per million Janssen vaccine recipients.

Most cases of GBS after the Janssen vaccine occurred during the 1- to 21-day risk interval, with the period of greatest risk in the 1-14 days after vaccination.

The findings of this analysis of surveillance data of COVID-19 vaccines are “consistent with an elevated risk of GBS after primary Ad26.COV2.S vaccination,” the authors wrote.
 

Novel presentation?

The researchers note that nearly all individuals who developed GBS after the Janssen vaccine had facial weakness or paralysis, in addition to weakness and decreased reflexes in the limbs, suggesting that the presentation of GBS after COVID-19 adenoviral vector vaccine may be novel.

“More research is needed to determine if the presentation of GBS after adenoviral vector vaccine differs from GBS after other exposures such as Campylobacter jejuni, and to investigate the mechanism for how adenoviral vector vaccines may cause GBS,” Dr. Klein and colleagues said.

“The Vaccine Safety Datalink continues to conduct safety surveillance for all COVID-19 vaccines, including monitoring for GBS and other serious health outcomes after vaccination,” Dr. Klein said in an interview.

This study was supported by the Centers for Disease Control and Prevention. Dr. Klein reported receiving grants from Pfizer research support for a COVID vaccine clinical trial as well as other unrelated studies, grants from Merck, grants from GlaxoSmithKline, grants from Sanofi Pasteur, and grants from Protein Science (now Sanofi Pasteur) outside the submitted work.

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

Mental disorders were significantly more likely in children whose mothers had one of five common autoimmune diseases, a new study found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as attention-deficit/hyperactivity disorder (ADHD), but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been “scattered and limited,” which “hampered an overall understanding” of the link, Fei Li, MD, the corresponding author of the study, told this news organization.

Dr. Li, of Shanghai Jiao Tong University China, and colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks of mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country’s National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5,460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs. 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR,], 1.16), with an incidence of 9.38 vs. 7.91 per 1,000 person-years, the researchers reported.

The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.11), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19).

The five autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium, (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.54), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk of autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers wrote.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk of obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, they added.

The study findings were limited by several factors, including the lack of data on potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers noted. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria over the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and ability to consider a range of confounders, the researchers said.

“This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring’s mental disorders from childhood through early adulthood,” Dr. Li said in an interview.

For clinicians, Dr. Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

“Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well,” she said.
 

Pay early attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history – problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Dr. Jay, who was not involved in the research.

“It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options,” Dr. Jay added.

The authors have reported no relevant financial relationships.

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

Mental disorders were significantly more likely in children whose mothers had one of five common autoimmune diseases, a new study found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as attention-deficit/hyperactivity disorder (ADHD), but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been “scattered and limited,” which “hampered an overall understanding” of the link, Fei Li, MD, the corresponding author of the study, told this news organization.

Dr. Li, of Shanghai Jiao Tong University China, and colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks of mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country’s National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5,460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs. 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR,], 1.16), with an incidence of 9.38 vs. 7.91 per 1,000 person-years, the researchers reported.

The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.11), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19).

The five autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium, (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.54), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk of autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers wrote.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk of obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, they added.

The study findings were limited by several factors, including the lack of data on potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers noted. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria over the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and ability to consider a range of confounders, the researchers said.

“This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring’s mental disorders from childhood through early adulthood,” Dr. Li said in an interview.

For clinicians, Dr. Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

“Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well,” she said.
 

Pay early attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history – problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Dr. Jay, who was not involved in the research.

“It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options,” Dr. Jay added.

The authors have reported no relevant financial relationships.

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

Mental disorders were significantly more likely in children whose mothers had one of five common autoimmune diseases, a new study found.

Previous research has linked both maternal and paternal autoimmune diseases and specific mental disorders, such as attention-deficit/hyperactivity disorder (ADHD), but most of these studies focused on specific conditions in relatively small populations. The new study included data on more than 2 million births, making it one of the largest efforts to date to examine the association, according to the researchers, whose findings were published in JAMA Network Open.

Previous evidence of the possible association between certain maternal autoimmune diseases and mental disorders in offspring has been “scattered and limited,” which “hampered an overall understanding” of the link, Fei Li, MD, the corresponding author of the study, told this news organization.

Dr. Li, of Shanghai Jiao Tong University China, and colleagues reviewed data from a Danish registry cohort of singleton births with up to 38 years of follow-up. They explored associations between a range of maternal autoimmune diseases diagnosed before childbirth and the risks of mental disorders in children in early childhood through young adulthood.

The study population included 2,254,234 births and 38,916,359 person-years. Data on mental health were collected from the Psychiatric Central Research Register and the country’s National Patient Register. The median age of the children at the time of assessment was 16.7 years; approximately half were male.

A total of 50,863 children (2.26%) were born to mothers who had been diagnosed with autoimmune diseases before childbirth. During the follow-up period, 5,460 children of mothers with autoimmune diseases and 303,092 children of mothers without autoimmune diseases were diagnosed with a mental disorder (10.73% vs. 13.76%), according to the researchers.

The risk of being diagnosed with a mental disorder was significantly higher among children of mothers with any autoimmune disease (hazard ratio [HR,], 1.16), with an incidence of 9.38 vs. 7.91 per 1,000 person-years, the researchers reported.

The increased risk persisted when the results were classified by organ system, including connective tissue (HR, 1.11), endocrine (HR, 1.19), gastrointestinal (HR, 1.11), blood (HR, 1.10), nervous (HR, 1.17), and skin (HR, 1.19).

The five autoimmune diseases in mothers that were most commonly associated mental health disorders in children were type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and psoriasis vulgaris.

The greatest risk for children of mothers with any autoimmune disease was observed for organic conditions such as delirium, (HR, 1.54), followed by obsessive-compulsive disorder (HR, 1.42), schizophrenia (HR, 1.54), and mood problems (HR, 1.12).

Children of mothers with any autoimmune disorder also had a significantly increased risk of autism (HR, 1.21), intellectual disability (HR, 1.19), and ADHD (HR, 1.19).

The results add to evidence that activation of the maternal immune system may drive changes in the brain and behavioral problems, which has been observed in animal studies, the researchers wrote.

Potential underlying mechanisms in need of more exploration include genetic risk factors, maternal transmission of autoantibodies to the fetus during pregnancy, and the increased risk of obstetric complications, such as preterm birth, for women with autoimmune disorders that could affect mental development in children, they added.

The study findings were limited by several factors, including the lack of data on potential exacerbation of autoimmune disease activity during pregnancy and its effect on the fetus, the researchers noted. Other limitations included potential detection bias, lack of data on mental disorders in adulthood, and potential changes in diagnostic criteria over the long study period.

The results were strengthened by the use of a population-based registry, the large sample size, and ability to consider a range of confounders, the researchers said.

“This study could help acquire a comprehensive compilation of the associations between maternal autoimmune disorders diagnosed before childbirth and offspring’s mental disorders from childhood through early adulthood,” Dr. Li said in an interview.

For clinicians, Dr. Li said, the findings suggest that the offspring of mothers with autoimmune diseases may benefit from long-term surveillance for mental health disorders.

“Further studies should provide more evidence on the detailed associations of specific maternal autoimmune diseases with a full spectrum of mental disorders in offspring, and more research on underlying mechanisms is needed as well,” she said.
 

Pay early attention

M. Susan Jay, MD, an adjunct professor of pediatrics at the Medical College of Wisconsin, Milwaukee, said previous efforts to examine the association between maternal autoimmunity were hampered by study design, small samples, and self-report of disease history – problems the new research avoids.

The large patient population allowed for detailed subgroup analysis of different conditions and outcomes. Another advantage was the availability of sociodemographic and clinical information, which allowed for the elimination of confounding factors, said Dr. Jay, who was not involved in the research.

“It would be prudent to follow children of mothers with autoimmune disorders before or during pregnancy for mental health issues, and if identified clinically, to offer psychological and developmental behavioral support options,” Dr. Jay added.

The authors have reported no relevant financial relationships.

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

LISBON – A shift toward broader-spectrum antibiotics and increasing antibiotic resistance has led to high levels of mortality and neurodevelopmental impacts in surviving babies, according to a large international study conducted on four continents.

Results of the 3-year study were presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

The observational study, NeoOBS, conducted by the Global Antibiotic Research and Development Partnership (GARDP) and key partners from 2018 to 2020, explored the outcomes of more than 3,200 newborns, finding an overall mortality of 11% in those with suspected neonatal sepsis. The mortality rate increased to 18% in newborns in whom a pathogen was detected in blood culture.

More than half of infection-related deaths (59%) were due to hospital-acquired infections. Klebsiella pneumoniae was the most common pathogen isolated and is usually associated with hospital-acquired infections, which are increasingly resistant to existing antibiotic treatments, said a report produced by GARDP to accompany the results.

The study also identified a worrying trend: Hospitals are frequently using last-line agents such as carbapenems because of the high degree of antibiotic resistance in their facilities. Of note, 15% of babies with neonatal sepsis were given last-line antibiotics.

Pediatrician Julia Bielicki, MD, PhD, senior lecturer, Paediatric Infectious Diseases Research Group, St. George’s University of London, and clinician at the University of Basel Children’s Hospital, Switzerland, was a coinvestigator on the NeoOBS study.

In an interview, she explained that, as well as reducing mortality, the research is about managing infections better to prevent long-term events and improve the quality of life for survivors of neonatal sepsis. “It can have life-changing impacts for so many babies,” Dr. Bielicki said. “Improving care is much more than just making sure the baby survives the episode of sepsis – it’s about ensuring these babies can become children and adults and go on to lead productive lives.”

Also, only a minority of patients (13%) received the World Health Organization guidelines for standard of care use of ampicillin and gentamicin, and there was increasing use of last-line agents such as carbapenems and even polymyxins in some settings in low- and middle-income countries. “This is alarming and foretells the impending crisis of a lack of antibiotics to treat sepsis caused by multidrug-resistant organisms,” according to the GARDP report.

There was wide variability in antibiotic combinations used across sites in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Uganda, and Vietnam, and often such use was not supported by underlying data.

Dr. Bielicki remarked that there was a shift toward broad-spectrum antibiotic use. “In a high-income country, you have more restrictive patterns of antibiotic use, but it isn’t necessarily less antibiotic exposure of neonates to antibiotics, but on the whole, usually narrow-spectrum agents are used.”

In Africa and Asia, on the other hand, clinicians often have to use a broader-spectrum antibiotic empirically and may need to switch to another antibiotic very quickly. “Sometimes alternatives are not available,” she pointed out.

“Local physicians are very perceptive of this problem of antibiotic resistance in their daily practice, especially in centers with high mortality,” said Dr. Bielicki, emphasizing that it is not their fault, but is “due to the limitations in terms of the weapons available to treat these babies, which strongly demonstrates the growing problem of antimicrobial resistance affecting these babies on a global scale.”

Tim Jinks, PhD, Head of Drug Resistant Infections Priority Program at Wellcome Trust, commented on the study in a series of text messages to this news organization. “This research provides further demonstration of the urgent need for improved treatment of newborns suffering with sepsis and particularly the requirement for new antibiotics that overcome the burden of drug-resistant infections caused by [antimicrobial resistance].”

“The study is a hugely important contribution to our understanding of the burden of neonatal sepsis in low- and middle- income countries,” he added, “and points toward ways that patient treatment can be improved to save more lives.”
 

High-, middle-, and low-income countries

The NeoOBS study gathered data from 19 hospitals in 11 high-, middle-, and low-income countries and assessed which antibiotics are currently being used to treat neonatal sepsis, as well as the degree of drug resistance associated with them. Sites included some in Italy and Greece, where most of the neonatal sepsis data currently originate, and this helped to anchor the data, Dr. Bielicki said.

The study identified babies with clinical sepsis over a 4-week period and observed how these patients were managed, particularly with respect to antibiotics, as well as outcomes including whether they recovered, remained in hospital, or died. Investigators obtained bacterial cultures from the patients and grew them to identify which organisms were causing the sepsis.

Of note, mortality varied widely between hospitals, ranging from 1% to 27%. Dr. Bielicki explained that the investigators were currently exploring the reasons behind this wide range of mortality. “There are lots of possible reasons for this, including structural factors such as how care is delivered, which is complex to measure,” she said. “It isn’t trivial to measure why, in a certain setting, mortality is low and why in another setting of comparable income range, mortality is much higher.”

Aside from the mortality results, Dr. Bielicki also emphasized that the survivors of neonatal sepsis frequently experience neurodevelopmental impacts. “A hospital may have low mortality, but many of these babies may have neurodevelopment problems, and this has a long-term impact.”

“Even though mortality might be low in a certain hospital, it might not be low in terms of morbidity,” she added.

The researchers also collected isolates from the cohort of neonates to determine which antibiotic combinations work against the pathogens. “This will help us define what sort of antibiotic regimen warrants further investigation,” Dr. Bielicki said.

Principal Investigator, Mike Sharland, MD, also from St. George’s, University of London, who is also the Antimicrobial Resistance Program Lead at Penta Child Health Research, said, in a press release, that the study had shown that antibiotic resistance is now one of the major threats to neonatal health globally. “There are virtually no studies underway on developing novel antibiotic treatments for babies with sepsis caused by multidrug-resistant infections.”

“This is a major problem for babies in all countries, both rich and poor,” he stressed.
 

NeoSep-1 trial to compare multiple different treatments

The results have paved the way for a major new global trial of multiple established and new antibiotics with the goal of reducing mortality from neonatal sepsis – the NeoSep1 trial.

“This is a randomized trial with a specific design that allows us to rank different treatments against each other in terms of effectiveness, safety, and costs,” Dr. Bielicki explained.

Among the antibiotics in the study are amikacin, flomoxef and amikacin, or fosfomycin and flomoxef in babies with sepsis 28 days old or younger. Similar to the NeoOBS study, patients will be recruited from all over the world, and in particular from low- and middle-income countries such as Kenya, South Africa, and other countries in Africa and Southeast Asia.

Ultimately, the researchers want to identify modifiable risk factors and enact change in practice. But Dr. Bielicki was quick to point out that it was difficult to disentangle those factors that can easily be changed. “Some can be changed in theory, but in practice it is actually difficult to change them. One modifiable risk factor that can be changed is probably infection control, so when resistant bacteria appear in a unit, we need to ensure that there is no or minimal transmission between babies.”

Luregn Schlapbach, MD, PhD, Head, department of intensive care and neonatology, University Children’s Hospital Zurich, Switzerland, welcomed the study, saying recent recognition of pediatric and neonatal sepsis was an urgent problem worldwide.

She referred to the 2017 WHO resolution recognizing that sepsis represents a leading cause of mortality and morbidity worldwide, affecting patients of all ages, across all continents and health care systems but that many were pediatric. “At that time, our understanding of the true burden of sepsis was limited, as was our knowledge of current epidemiology,” she said in an email interview. “The Global Burden of Disease study in 2020 revealed that about half of the approximatively 50 million global sepsis cases affect pediatric age groups, many of those during neonatal age.”

The formal acknowledgment of this extensive need emphasizes the “urgency to design preventive and therapeutic interventions to reduce this devastating burden,” Dr. Schlapbach said. “In this context, the work led by GARDP is of great importance – it is designed to improve our understanding of current practice, risk factors, and burden of neonatal sepsis across low- to middle-income settings and is essential to design adequately powered trials testing interventions such as antimicrobials to improve patient outcomes and reduce the further emergence of antimicrobial resistance.”

Dr. Bielicki and Dr. Schlapbach have disclosed no relevant financial relationships.

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

LISBON – A shift toward broader-spectrum antibiotics and increasing antibiotic resistance has led to high levels of mortality and neurodevelopmental impacts in surviving babies, according to a large international study conducted on four continents.

Results of the 3-year study were presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

The observational study, NeoOBS, conducted by the Global Antibiotic Research and Development Partnership (GARDP) and key partners from 2018 to 2020, explored the outcomes of more than 3,200 newborns, finding an overall mortality of 11% in those with suspected neonatal sepsis. The mortality rate increased to 18% in newborns in whom a pathogen was detected in blood culture.

More than half of infection-related deaths (59%) were due to hospital-acquired infections. Klebsiella pneumoniae was the most common pathogen isolated and is usually associated with hospital-acquired infections, which are increasingly resistant to existing antibiotic treatments, said a report produced by GARDP to accompany the results.

The study also identified a worrying trend: Hospitals are frequently using last-line agents such as carbapenems because of the high degree of antibiotic resistance in their facilities. Of note, 15% of babies with neonatal sepsis were given last-line antibiotics.

Pediatrician Julia Bielicki, MD, PhD, senior lecturer, Paediatric Infectious Diseases Research Group, St. George’s University of London, and clinician at the University of Basel Children’s Hospital, Switzerland, was a coinvestigator on the NeoOBS study.

In an interview, she explained that, as well as reducing mortality, the research is about managing infections better to prevent long-term events and improve the quality of life for survivors of neonatal sepsis. “It can have life-changing impacts for so many babies,” Dr. Bielicki said. “Improving care is much more than just making sure the baby survives the episode of sepsis – it’s about ensuring these babies can become children and adults and go on to lead productive lives.”

Also, only a minority of patients (13%) received the World Health Organization guidelines for standard of care use of ampicillin and gentamicin, and there was increasing use of last-line agents such as carbapenems and even polymyxins in some settings in low- and middle-income countries. “This is alarming and foretells the impending crisis of a lack of antibiotics to treat sepsis caused by multidrug-resistant organisms,” according to the GARDP report.

There was wide variability in antibiotic combinations used across sites in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Uganda, and Vietnam, and often such use was not supported by underlying data.

Dr. Bielicki remarked that there was a shift toward broad-spectrum antibiotic use. “In a high-income country, you have more restrictive patterns of antibiotic use, but it isn’t necessarily less antibiotic exposure of neonates to antibiotics, but on the whole, usually narrow-spectrum agents are used.”

In Africa and Asia, on the other hand, clinicians often have to use a broader-spectrum antibiotic empirically and may need to switch to another antibiotic very quickly. “Sometimes alternatives are not available,” she pointed out.

“Local physicians are very perceptive of this problem of antibiotic resistance in their daily practice, especially in centers with high mortality,” said Dr. Bielicki, emphasizing that it is not their fault, but is “due to the limitations in terms of the weapons available to treat these babies, which strongly demonstrates the growing problem of antimicrobial resistance affecting these babies on a global scale.”

Tim Jinks, PhD, Head of Drug Resistant Infections Priority Program at Wellcome Trust, commented on the study in a series of text messages to this news organization. “This research provides further demonstration of the urgent need for improved treatment of newborns suffering with sepsis and particularly the requirement for new antibiotics that overcome the burden of drug-resistant infections caused by [antimicrobial resistance].”

“The study is a hugely important contribution to our understanding of the burden of neonatal sepsis in low- and middle- income countries,” he added, “and points toward ways that patient treatment can be improved to save more lives.”
 

High-, middle-, and low-income countries

The NeoOBS study gathered data from 19 hospitals in 11 high-, middle-, and low-income countries and assessed which antibiotics are currently being used to treat neonatal sepsis, as well as the degree of drug resistance associated with them. Sites included some in Italy and Greece, where most of the neonatal sepsis data currently originate, and this helped to anchor the data, Dr. Bielicki said.

The study identified babies with clinical sepsis over a 4-week period and observed how these patients were managed, particularly with respect to antibiotics, as well as outcomes including whether they recovered, remained in hospital, or died. Investigators obtained bacterial cultures from the patients and grew them to identify which organisms were causing the sepsis.

Of note, mortality varied widely between hospitals, ranging from 1% to 27%. Dr. Bielicki explained that the investigators were currently exploring the reasons behind this wide range of mortality. “There are lots of possible reasons for this, including structural factors such as how care is delivered, which is complex to measure,” she said. “It isn’t trivial to measure why, in a certain setting, mortality is low and why in another setting of comparable income range, mortality is much higher.”

Aside from the mortality results, Dr. Bielicki also emphasized that the survivors of neonatal sepsis frequently experience neurodevelopmental impacts. “A hospital may have low mortality, but many of these babies may have neurodevelopment problems, and this has a long-term impact.”

“Even though mortality might be low in a certain hospital, it might not be low in terms of morbidity,” she added.

The researchers also collected isolates from the cohort of neonates to determine which antibiotic combinations work against the pathogens. “This will help us define what sort of antibiotic regimen warrants further investigation,” Dr. Bielicki said.

Principal Investigator, Mike Sharland, MD, also from St. George’s, University of London, who is also the Antimicrobial Resistance Program Lead at Penta Child Health Research, said, in a press release, that the study had shown that antibiotic resistance is now one of the major threats to neonatal health globally. “There are virtually no studies underway on developing novel antibiotic treatments for babies with sepsis caused by multidrug-resistant infections.”

“This is a major problem for babies in all countries, both rich and poor,” he stressed.
 

NeoSep-1 trial to compare multiple different treatments

The results have paved the way for a major new global trial of multiple established and new antibiotics with the goal of reducing mortality from neonatal sepsis – the NeoSep1 trial.

“This is a randomized trial with a specific design that allows us to rank different treatments against each other in terms of effectiveness, safety, and costs,” Dr. Bielicki explained.

Among the antibiotics in the study are amikacin, flomoxef and amikacin, or fosfomycin and flomoxef in babies with sepsis 28 days old or younger. Similar to the NeoOBS study, patients will be recruited from all over the world, and in particular from low- and middle-income countries such as Kenya, South Africa, and other countries in Africa and Southeast Asia.

Ultimately, the researchers want to identify modifiable risk factors and enact change in practice. But Dr. Bielicki was quick to point out that it was difficult to disentangle those factors that can easily be changed. “Some can be changed in theory, but in practice it is actually difficult to change them. One modifiable risk factor that can be changed is probably infection control, so when resistant bacteria appear in a unit, we need to ensure that there is no or minimal transmission between babies.”

Luregn Schlapbach, MD, PhD, Head, department of intensive care and neonatology, University Children’s Hospital Zurich, Switzerland, welcomed the study, saying recent recognition of pediatric and neonatal sepsis was an urgent problem worldwide.

She referred to the 2017 WHO resolution recognizing that sepsis represents a leading cause of mortality and morbidity worldwide, affecting patients of all ages, across all continents and health care systems but that many were pediatric. “At that time, our understanding of the true burden of sepsis was limited, as was our knowledge of current epidemiology,” she said in an email interview. “The Global Burden of Disease study in 2020 revealed that about half of the approximatively 50 million global sepsis cases affect pediatric age groups, many of those during neonatal age.”

The formal acknowledgment of this extensive need emphasizes the “urgency to design preventive and therapeutic interventions to reduce this devastating burden,” Dr. Schlapbach said. “In this context, the work led by GARDP is of great importance – it is designed to improve our understanding of current practice, risk factors, and burden of neonatal sepsis across low- to middle-income settings and is essential to design adequately powered trials testing interventions such as antimicrobials to improve patient outcomes and reduce the further emergence of antimicrobial resistance.”

Dr. Bielicki and Dr. Schlapbach have disclosed no relevant financial relationships.

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

LISBON – A shift toward broader-spectrum antibiotics and increasing antibiotic resistance has led to high levels of mortality and neurodevelopmental impacts in surviving babies, according to a large international study conducted on four continents.

Results of the 3-year study were presented at this week’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID).

The observational study, NeoOBS, conducted by the Global Antibiotic Research and Development Partnership (GARDP) and key partners from 2018 to 2020, explored the outcomes of more than 3,200 newborns, finding an overall mortality of 11% in those with suspected neonatal sepsis. The mortality rate increased to 18% in newborns in whom a pathogen was detected in blood culture.

More than half of infection-related deaths (59%) were due to hospital-acquired infections. Klebsiella pneumoniae was the most common pathogen isolated and is usually associated with hospital-acquired infections, which are increasingly resistant to existing antibiotic treatments, said a report produced by GARDP to accompany the results.

The study also identified a worrying trend: Hospitals are frequently using last-line agents such as carbapenems because of the high degree of antibiotic resistance in their facilities. Of note, 15% of babies with neonatal sepsis were given last-line antibiotics.

Pediatrician Julia Bielicki, MD, PhD, senior lecturer, Paediatric Infectious Diseases Research Group, St. George’s University of London, and clinician at the University of Basel Children’s Hospital, Switzerland, was a coinvestigator on the NeoOBS study.

In an interview, she explained that, as well as reducing mortality, the research is about managing infections better to prevent long-term events and improve the quality of life for survivors of neonatal sepsis. “It can have life-changing impacts for so many babies,” Dr. Bielicki said. “Improving care is much more than just making sure the baby survives the episode of sepsis – it’s about ensuring these babies can become children and adults and go on to lead productive lives.”

Also, only a minority of patients (13%) received the World Health Organization guidelines for standard of care use of ampicillin and gentamicin, and there was increasing use of last-line agents such as carbapenems and even polymyxins in some settings in low- and middle-income countries. “This is alarming and foretells the impending crisis of a lack of antibiotics to treat sepsis caused by multidrug-resistant organisms,” according to the GARDP report.

There was wide variability in antibiotic combinations used across sites in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Uganda, and Vietnam, and often such use was not supported by underlying data.

Dr. Bielicki remarked that there was a shift toward broad-spectrum antibiotic use. “In a high-income country, you have more restrictive patterns of antibiotic use, but it isn’t necessarily less antibiotic exposure of neonates to antibiotics, but on the whole, usually narrow-spectrum agents are used.”

In Africa and Asia, on the other hand, clinicians often have to use a broader-spectrum antibiotic empirically and may need to switch to another antibiotic very quickly. “Sometimes alternatives are not available,” she pointed out.

“Local physicians are very perceptive of this problem of antibiotic resistance in their daily practice, especially in centers with high mortality,” said Dr. Bielicki, emphasizing that it is not their fault, but is “due to the limitations in terms of the weapons available to treat these babies, which strongly demonstrates the growing problem of antimicrobial resistance affecting these babies on a global scale.”

Tim Jinks, PhD, Head of Drug Resistant Infections Priority Program at Wellcome Trust, commented on the study in a series of text messages to this news organization. “This research provides further demonstration of the urgent need for improved treatment of newborns suffering with sepsis and particularly the requirement for new antibiotics that overcome the burden of drug-resistant infections caused by [antimicrobial resistance].”

“The study is a hugely important contribution to our understanding of the burden of neonatal sepsis in low- and middle- income countries,” he added, “and points toward ways that patient treatment can be improved to save more lives.”
 

High-, middle-, and low-income countries

The NeoOBS study gathered data from 19 hospitals in 11 high-, middle-, and low-income countries and assessed which antibiotics are currently being used to treat neonatal sepsis, as well as the degree of drug resistance associated with them. Sites included some in Italy and Greece, where most of the neonatal sepsis data currently originate, and this helped to anchor the data, Dr. Bielicki said.

The study identified babies with clinical sepsis over a 4-week period and observed how these patients were managed, particularly with respect to antibiotics, as well as outcomes including whether they recovered, remained in hospital, or died. Investigators obtained bacterial cultures from the patients and grew them to identify which organisms were causing the sepsis.

Of note, mortality varied widely between hospitals, ranging from 1% to 27%. Dr. Bielicki explained that the investigators were currently exploring the reasons behind this wide range of mortality. “There are lots of possible reasons for this, including structural factors such as how care is delivered, which is complex to measure,” she said. “It isn’t trivial to measure why, in a certain setting, mortality is low and why in another setting of comparable income range, mortality is much higher.”

Aside from the mortality results, Dr. Bielicki also emphasized that the survivors of neonatal sepsis frequently experience neurodevelopmental impacts. “A hospital may have low mortality, but many of these babies may have neurodevelopment problems, and this has a long-term impact.”

“Even though mortality might be low in a certain hospital, it might not be low in terms of morbidity,” she added.

The researchers also collected isolates from the cohort of neonates to determine which antibiotic combinations work against the pathogens. “This will help us define what sort of antibiotic regimen warrants further investigation,” Dr. Bielicki said.

Principal Investigator, Mike Sharland, MD, also from St. George’s, University of London, who is also the Antimicrobial Resistance Program Lead at Penta Child Health Research, said, in a press release, that the study had shown that antibiotic resistance is now one of the major threats to neonatal health globally. “There are virtually no studies underway on developing novel antibiotic treatments for babies with sepsis caused by multidrug-resistant infections.”

“This is a major problem for babies in all countries, both rich and poor,” he stressed.
 

NeoSep-1 trial to compare multiple different treatments

The results have paved the way for a major new global trial of multiple established and new antibiotics with the goal of reducing mortality from neonatal sepsis – the NeoSep1 trial.

“This is a randomized trial with a specific design that allows us to rank different treatments against each other in terms of effectiveness, safety, and costs,” Dr. Bielicki explained.

Among the antibiotics in the study are amikacin, flomoxef and amikacin, or fosfomycin and flomoxef in babies with sepsis 28 days old or younger. Similar to the NeoOBS study, patients will be recruited from all over the world, and in particular from low- and middle-income countries such as Kenya, South Africa, and other countries in Africa and Southeast Asia.

Ultimately, the researchers want to identify modifiable risk factors and enact change in practice. But Dr. Bielicki was quick to point out that it was difficult to disentangle those factors that can easily be changed. “Some can be changed in theory, but in practice it is actually difficult to change them. One modifiable risk factor that can be changed is probably infection control, so when resistant bacteria appear in a unit, we need to ensure that there is no or minimal transmission between babies.”

Luregn Schlapbach, MD, PhD, Head, department of intensive care and neonatology, University Children’s Hospital Zurich, Switzerland, welcomed the study, saying recent recognition of pediatric and neonatal sepsis was an urgent problem worldwide.

She referred to the 2017 WHO resolution recognizing that sepsis represents a leading cause of mortality and morbidity worldwide, affecting patients of all ages, across all continents and health care systems but that many were pediatric. “At that time, our understanding of the true burden of sepsis was limited, as was our knowledge of current epidemiology,” she said in an email interview. “The Global Burden of Disease study in 2020 revealed that about half of the approximatively 50 million global sepsis cases affect pediatric age groups, many of those during neonatal age.”

The formal acknowledgment of this extensive need emphasizes the “urgency to design preventive and therapeutic interventions to reduce this devastating burden,” Dr. Schlapbach said. “In this context, the work led by GARDP is of great importance – it is designed to improve our understanding of current practice, risk factors, and burden of neonatal sepsis across low- to middle-income settings and is essential to design adequately powered trials testing interventions such as antimicrobials to improve patient outcomes and reduce the further emergence of antimicrobial resistance.”

Dr. Bielicki and Dr. Schlapbach have disclosed no relevant financial relationships.

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

The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. However, a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.

The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.

The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD-only at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.

In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told this news organization. “I think this is another reason to try to be more generous in offering ablation to women.”

Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings April 30 at the Heart Rhythm Society 2022 Scientific Sessions, conducted virtually and live in San Francisco.

Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”

It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ontario, who is not a coauthor.

“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.

Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.

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

The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. However, a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.

The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.

The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD-only at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.

In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told this news organization. “I think this is another reason to try to be more generous in offering ablation to women.”

Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings April 30 at the Heart Rhythm Society 2022 Scientific Sessions, conducted virtually and live in San Francisco.

Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”

It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ontario, who is not a coauthor.

“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.

Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.

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

The risk for dementia goes up in patients with atrial fibrillation (AFib), but some evidence suggests that risk can be blunted with therapies that restore sinus rhythm. However, a new cohort study suggests that the treatment effect’s magnitude might depend on the rhythm control strategy. It hinted that AFib catheter ablation might be more effective than pharmacologic rhythm control alone at cutting the risk for dementia.

The case-matched study of more than 38,000 adults with AFib saw a 41% reduction (P < .0001) in risk for dementia among those who underwent catheter ablation after attempted rhythm control with antiarrhythmic drugs (AAD), compared with those managed with pharmacologic rhythm control therapy alone.

The observational study comprising 20 years of data comes with big limitations and can’t say for sure whether catheter ablation is better than AAD-only at cutting the dementia risk in AFib. But it and other evidence support the idea, which has yet to be explored in a randomized fashion.

In a secondary finding, the analysis showed a similar reduction in dementia risk from catheter ablation, compared with AAD, in women and in men by 40% and 45%, respectively (P < .0001 for both). The findings are particularly relevant “given the higher life-long risk of dementia among women and the lower likelihood that women will be offered ablation, which has been demonstrated repeatedly,” Emily P. Zeitler, MD, MHS, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, told this news organization. “I think this is another reason to try to be more generous in offering ablation to women.”

Management of AFib certainly evolved in important ways from 2000 to 2021, the period covered by the study. But a sensitivity analysis based on data from 2010 to 2021 showed “no meaningful differences” in the results, said Dr. Zeitler, who is slated to present the findings April 30 at the Heart Rhythm Society 2022 Scientific Sessions, conducted virtually and live in San Francisco.

Dr. Zeitler acknowledged that the observational study, even with its propensity-matched ablation and AAD cohorts, can only hint at a preference for ablation over AAD for lowering risk for AFib-associated dementia. “We know there’s unmeasured and unfixable confounding between those two groups, so we see this really as hypothesis-generating.”

It was “a well-done analysis,” and the conclusion that the dementia risk was lower with catheter ablation is “absolutely correct,” but only as far as the study and its limitations allow, agreed David Conen, MD, MPH, McMaster University, Hamilton, Ontario, who is not a coauthor.

“Even with propensity matching, you can get rid of some sorts of confounding, but you can never get rid of all selection bias issues.” That, he said when interviewed, takes randomized trials.

Dr. Conen, who is studying cognitive decline in AFib as a SWISS-AF trial principal investigator, pointed to a secondary finding of the analysis as evidence for such confounding. He said the ablation group’s nearly 50% drop (P < .0001) in competing risk for death, compared with patients managed with AAD, isn’t plausible.

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

The latest upward trend in new COVID-19 cases among children picked up steam, but there was also some movement in the vaccination effort in the past week.

Moderna submitted a request to the Food and Drug administration for emergency use authorization of its COVID-19 vaccine in children under the age of 6 years, according to this news organization, and Pfizer/BioNTech officially applied for authorization of a booster dose in children aged 5-11, the companies announced.

The FDA has tentatively scheduled meetings of its Vaccines and Related Biological Products Advisory Committee in June to consider the applications, saying that it “understands the urgency to authorize a vaccine for age groups who are not currently eligible for vaccination and will work diligently to complete our evaluation of the data. Should any of the submissions be completed in a timely manner and the data support a clear path forward following our evaluation, the FDA will act quickly” to convene the necessary meetings.

The need for greater access to vaccines seems to be increasing, as new pediatric COVID cases rose for the third consecutive week. April 22-28 saw over 53,000 new cases reported in children, up 43.5% from the previous week and up 105% since cases started rising again after dipping under 26,000 during the week of April 1-7, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Hospital admissions involving diagnosed COVID also ticked up over the latter half of April, although the most recent 7-day average (April 24-30) of 112 per day was lower than the 117 reported for the previous week (April 17-23), the Centers for Disease Control and Prevention said, also noting that figures for the latest week “should be interpreted with caution.”

Vaccinations also were up slightly in children aged 5-11 years, with 52,000 receiving their first dose during the week of April 21-27, compared with 48,000 the week before. There was a slight dip, however, among 12- to 17-year-olds, who received 34,000 first doses during April 21-27, versus 35,000 the previous week, the AAP said in a separate report.

Cumulatively, almost 69% of all children aged 12-17 years have received at least one dose of the COVID-19 vaccine and 59% are fully vaccinated. Those aged 5-11 are well short of those figures, with just over 35% having received at least one dose and 28.5% fully vaccinated, the CDC said on its COVID Data Tracker.

A look at recent activity shows that children are not gaining on adults, who are much more likely to be vaccinated – full vaccination in those aged 50-64, for example, is 80%. During the 2 weeks from April 17-30, the 5- to 11-year-olds represented 10.5% of those who had initiated a first dose and 12.4% of those who gained full-vaccination status, both of which were well below the oldest age groups, the CDC reported.

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The latest upward trend in new COVID-19 cases among children picked up steam, but there was also some movement in the vaccination effort in the past week.

Moderna submitted a request to the Food and Drug administration for emergency use authorization of its COVID-19 vaccine in children under the age of 6 years, according to this news organization, and Pfizer/BioNTech officially applied for authorization of a booster dose in children aged 5-11, the companies announced.

The FDA has tentatively scheduled meetings of its Vaccines and Related Biological Products Advisory Committee in June to consider the applications, saying that it “understands the urgency to authorize a vaccine for age groups who are not currently eligible for vaccination and will work diligently to complete our evaluation of the data. Should any of the submissions be completed in a timely manner and the data support a clear path forward following our evaluation, the FDA will act quickly” to convene the necessary meetings.

The need for greater access to vaccines seems to be increasing, as new pediatric COVID cases rose for the third consecutive week. April 22-28 saw over 53,000 new cases reported in children, up 43.5% from the previous week and up 105% since cases started rising again after dipping under 26,000 during the week of April 1-7, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Hospital admissions involving diagnosed COVID also ticked up over the latter half of April, although the most recent 7-day average (April 24-30) of 112 per day was lower than the 117 reported for the previous week (April 17-23), the Centers for Disease Control and Prevention said, also noting that figures for the latest week “should be interpreted with caution.”

Vaccinations also were up slightly in children aged 5-11 years, with 52,000 receiving their first dose during the week of April 21-27, compared with 48,000 the week before. There was a slight dip, however, among 12- to 17-year-olds, who received 34,000 first doses during April 21-27, versus 35,000 the previous week, the AAP said in a separate report.

Cumulatively, almost 69% of all children aged 12-17 years have received at least one dose of the COVID-19 vaccine and 59% are fully vaccinated. Those aged 5-11 are well short of those figures, with just over 35% having received at least one dose and 28.5% fully vaccinated, the CDC said on its COVID Data Tracker.

A look at recent activity shows that children are not gaining on adults, who are much more likely to be vaccinated – full vaccination in those aged 50-64, for example, is 80%. During the 2 weeks from April 17-30, the 5- to 11-year-olds represented 10.5% of those who had initiated a first dose and 12.4% of those who gained full-vaccination status, both of which were well below the oldest age groups, the CDC reported.

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The latest upward trend in new COVID-19 cases among children picked up steam, but there was also some movement in the vaccination effort in the past week.

Moderna submitted a request to the Food and Drug administration for emergency use authorization of its COVID-19 vaccine in children under the age of 6 years, according to this news organization, and Pfizer/BioNTech officially applied for authorization of a booster dose in children aged 5-11, the companies announced.

The FDA has tentatively scheduled meetings of its Vaccines and Related Biological Products Advisory Committee in June to consider the applications, saying that it “understands the urgency to authorize a vaccine for age groups who are not currently eligible for vaccination and will work diligently to complete our evaluation of the data. Should any of the submissions be completed in a timely manner and the data support a clear path forward following our evaluation, the FDA will act quickly” to convene the necessary meetings.

The need for greater access to vaccines seems to be increasing, as new pediatric COVID cases rose for the third consecutive week. April 22-28 saw over 53,000 new cases reported in children, up 43.5% from the previous week and up 105% since cases started rising again after dipping under 26,000 during the week of April 1-7, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Hospital admissions involving diagnosed COVID also ticked up over the latter half of April, although the most recent 7-day average (April 24-30) of 112 per day was lower than the 117 reported for the previous week (April 17-23), the Centers for Disease Control and Prevention said, also noting that figures for the latest week “should be interpreted with caution.”

Vaccinations also were up slightly in children aged 5-11 years, with 52,000 receiving their first dose during the week of April 21-27, compared with 48,000 the week before. There was a slight dip, however, among 12- to 17-year-olds, who received 34,000 first doses during April 21-27, versus 35,000 the previous week, the AAP said in a separate report.

Cumulatively, almost 69% of all children aged 12-17 years have received at least one dose of the COVID-19 vaccine and 59% are fully vaccinated. Those aged 5-11 are well short of those figures, with just over 35% having received at least one dose and 28.5% fully vaccinated, the CDC said on its COVID Data Tracker.

A look at recent activity shows that children are not gaining on adults, who are much more likely to be vaccinated – full vaccination in those aged 50-64, for example, is 80%. During the 2 weeks from April 17-30, the 5- to 11-year-olds represented 10.5% of those who had initiated a first dose and 12.4% of those who gained full-vaccination status, both of which were well below the oldest age groups, the CDC reported.

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