Key clinical point: Hispanic patients with a higher level of English language acculturation were less likely to use birth control and may require a more detailed discussion of the options for family planning.

Major finding: Hispanic women who reported using birth control had significantly lower English language acculturation compared to those who reported no birth control

Study details: The data come from surveys of 225 Hispanic women that combined the number of years lived in the U.S., the Short Acculturation Scale for Hispanics, and questions about family planning behaviors.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chamberlain R et al. Kans J Med. 2021 Apr 19. doi: 10.17161/kjm.vol1414845.

Key clinical point: Hispanic patients with a higher level of English language acculturation were less likely to use birth control and may require a more detailed discussion of the options for family planning.

Major finding: Hispanic women who reported using birth control had significantly lower English language acculturation compared to those who reported no birth control

Study details: The data come from surveys of 225 Hispanic women that combined the number of years lived in the U.S., the Short Acculturation Scale for Hispanics, and questions about family planning behaviors.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chamberlain R et al. Kans J Med. 2021 Apr 19. doi: 10.17161/kjm.vol1414845.

Key clinical point: Hispanic patients with a higher level of English language acculturation were less likely to use birth control and may require a more detailed discussion of the options for family planning.

Major finding: Hispanic women who reported using birth control had significantly lower English language acculturation compared to those who reported no birth control

Study details: The data come from surveys of 225 Hispanic women that combined the number of years lived in the U.S., the Short Acculturation Scale for Hispanics, and questions about family planning behaviors.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Chamberlain R et al. Kans J Med. 2021 Apr 19. doi: 10.17161/kjm.vol1414845.

Immediate postpartum long-acting reversible contraception (LARC) represents a safe and effective contraceptive strategy. Despite national guidelines recommending universal patient access, hospitals face significant barriers to offering inpatient LARCs. It is unclear why some hospitals successfully implement immediate postpartum LARCs, while others do not.

Moniz et al conducted a comparative, multiple case study of immediate postpartum LARC implementation at eleven “early adopter” U.S. hospitals and analyzed each hospital’s implementation strategy to produce generalizable knowledge about how and under what circumstances implementation of immediate postpartum LARCs unfold successfully. Between 2017-2018, the authors conducted single-day site visits and 78 semi-structured interviews with a variety of stakeholders (clinician champions, nurses, pharmacists, revenue cycle staff, and hospital administration). On average, sites used 18 (range 11-22) implementation strategies, including assessing institutional readiness for, and barriers to, implementation of immediate postpartum LARC, engaging reproductive justice experts and community resources to address social determinants of health, involving patients in implementation planning, and developing quality monitoring processes to evaluate clinical processes and outcomes. The researchers found that successful implementation of immediate postpartum LARC required three essential conditions: effective implementation champions who are supported by a multidisciplinary implementation team; creating an enabling financial environment; and engaging hospital administration. Additional findings from this study call for more support for individuals leading change in complex care settings, intentionally designing implementation interventions that take into account local contextual influences, and meaningfully engaging patients in the implementation process.

Of postpartum women, 61% in low- and middle-income countries (LMIC) have an unmet contraceptive need and many face high rates of short interpregnancy intervals (Moore). Additionally, 51%-96% of postpartum women in LMIC use short-acting methods of contraception (Moore), further highlighting the need for increased access to immediate postpartum LARC in LMIC. Data on the use and continuation of immediate postpartum LARC in LMIC is limited. Marchin et al conducted a systematic review and meta-analysis to determine 6-month continuation rates of immediate postpartum LARCs among women in 69 low-income countries that were enrolled in the Family Planning 2020 initiative. The meta-analysis ultimately focused on the copper IUD due to the absence of relevant studies on other LARC methods. The meta-analysis of 12 studies resulted in a pooled 6-month continuation rate for immediate postpartum copper IUDs of 87%, a rate comparable to continuation rates found in higher-income countries. This estimate had significant heterogeneity between studies. Secondary outcomes of expulsion, removal, and infection rates were low at 6%, 5%, and 0.2% respectively. High 6-month continuation rates and a low rate of adverse outcomes suggest immediate postpartum copper IUD insertion represents a feasible and acceptable postpartum contraceptive option for women living in LMIC.

In cases where contraception methods fail, are used incorrectly, or are not used at all, emergency contraception (EC) can be used after intercourse to prevent pregnancy. Timely access to, and accurate knowledge of, EC are especially important for rural women who are more likely to experience an unintended pregnancy resulting in a live birth compared to urban women. Milkowski et al analyzed publicly available data from the National Survey of Family Growth to estimate differences in oral EC use, access, and counseling by rural-urban county of residence among U.S. women aged 15-44 years. 10% of rural and 19% of urban women who had ever been sexually active reported ever using EC pills. Over the course of the study period (2006-2017), the percentage of women reporting ever-use of EC increased linearly in both rural and urban populations, with the prevalence of EC ever-use more than doubling in each group. This observation likely reflects an overall increase in EC use during a time period in which the federal government enacted several policies to improve access to EC. The study findings also highlight the need for improved patient counseling on EC. While the overall prevalence of EC counseling was low among all women, rural women were less likely to have received counseling on EC when compared to urban women.

Although many studies report weight gain in users of progestin-only hormonal contraception (POC), a recent Cochrane systematic review found that there was insufficient evidence to determine the effect of POCs on weight (Lopez). Beksinska et al conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial, which was an open label, prospective, randomized multicenter trial that compared the risk of HIV acquisition among women randomized to injectable contraception (DMPA), the copper IUD, or a second generation two rod levonorgestrel (LNG) implant Jadelle^Ò. This trial was conducted at 12 sites across four African countries between 2015 and 2018. Eligible study participants were nonpregnant, HIV negative, sexually active women aged 16-35 years who desired contraception. The final sample size included 7,014 women randomly assigned to receive DMPA (2,293), the LNG implant (2,372), or the copper IUD (2,349). Using a standardized protocol and calibrated equipment across all study sites, weight and height were measured at baseline and at study exit at 12, 15, or 18 months. The mean weight increased amongst all three contraceptive groups and was significantly different in magnitude, with the largest gain in the DMPA group (3.5 kg), 2.4 kg in the LNG implant group, and 1.5 kg in the copper IUD group. Unlike copper IUD users, women in the DMPA and LNG implant group continued to gain weight after 1 year of contraceptive use. It is noteworthy that, regardless of contraceptive method allocation, not all women gained weight and a small proportion of women lost weight. When choosing a contraceptive method, women using POCs should be counselled about the potential side effect of weight gain.

References:
Moniz MH, Bonawitz K, Wetmore MK, et al. Implementing immediate postpartum contraception: a comparative case study at 11 hospitals. Implement Sci Commun. 2021;2(1):42. Published 2021 Apr 12.

Moore Z, Pfitzer A, Gubin R, et al. Missed opportunities for family planning: an analysis of pregnancy risk and contraceptive method use among postpartum women in 21 low- and middle-income countries. Contraception 92 (2015): 31–39.
 

Marchin A, Moss A, Harrison M. A Meta-Analysis of Postpartum Copper IUD Continuation Rates in Low- and Middle-Income Countries. J Womens Health Dev. 2021;4(1):36-46.

Milkowski CM, Ziller EC, Ahrens KA. Rural-urban residence and emergency contraception use, access, and counseling in the United States, 2006-2017. Contracept X. 2021;3:100061.

Lopez L.M., Ramesh S., Chen M. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016 doi: 10.1002/14651858.CD008815.pub2.

Beksinska et al. “Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial. EClinicalMedicine. 2021;34:100800.

Immediate postpartum long-acting reversible contraception (LARC) represents a safe and effective contraceptive strategy. Despite national guidelines recommending universal patient access, hospitals face significant barriers to offering inpatient LARCs. It is unclear why some hospitals successfully implement immediate postpartum LARCs, while others do not.

Moniz et al conducted a comparative, multiple case study of immediate postpartum LARC implementation at eleven “early adopter” U.S. hospitals and analyzed each hospital’s implementation strategy to produce generalizable knowledge about how and under what circumstances implementation of immediate postpartum LARCs unfold successfully. Between 2017-2018, the authors conducted single-day site visits and 78 semi-structured interviews with a variety of stakeholders (clinician champions, nurses, pharmacists, revenue cycle staff, and hospital administration). On average, sites used 18 (range 11-22) implementation strategies, including assessing institutional readiness for, and barriers to, implementation of immediate postpartum LARC, engaging reproductive justice experts and community resources to address social determinants of health, involving patients in implementation planning, and developing quality monitoring processes to evaluate clinical processes and outcomes. The researchers found that successful implementation of immediate postpartum LARC required three essential conditions: effective implementation champions who are supported by a multidisciplinary implementation team; creating an enabling financial environment; and engaging hospital administration. Additional findings from this study call for more support for individuals leading change in complex care settings, intentionally designing implementation interventions that take into account local contextual influences, and meaningfully engaging patients in the implementation process.

Of postpartum women, 61% in low- and middle-income countries (LMIC) have an unmet contraceptive need and many face high rates of short interpregnancy intervals (Moore). Additionally, 51%-96% of postpartum women in LMIC use short-acting methods of contraception (Moore), further highlighting the need for increased access to immediate postpartum LARC in LMIC. Data on the use and continuation of immediate postpartum LARC in LMIC is limited. Marchin et al conducted a systematic review and meta-analysis to determine 6-month continuation rates of immediate postpartum LARCs among women in 69 low-income countries that were enrolled in the Family Planning 2020 initiative. The meta-analysis ultimately focused on the copper IUD due to the absence of relevant studies on other LARC methods. The meta-analysis of 12 studies resulted in a pooled 6-month continuation rate for immediate postpartum copper IUDs of 87%, a rate comparable to continuation rates found in higher-income countries. This estimate had significant heterogeneity between studies. Secondary outcomes of expulsion, removal, and infection rates were low at 6%, 5%, and 0.2% respectively. High 6-month continuation rates and a low rate of adverse outcomes suggest immediate postpartum copper IUD insertion represents a feasible and acceptable postpartum contraceptive option for women living in LMIC.

In cases where contraception methods fail, are used incorrectly, or are not used at all, emergency contraception (EC) can be used after intercourse to prevent pregnancy. Timely access to, and accurate knowledge of, EC are especially important for rural women who are more likely to experience an unintended pregnancy resulting in a live birth compared to urban women. Milkowski et al analyzed publicly available data from the National Survey of Family Growth to estimate differences in oral EC use, access, and counseling by rural-urban county of residence among U.S. women aged 15-44 years. 10% of rural and 19% of urban women who had ever been sexually active reported ever using EC pills. Over the course of the study period (2006-2017), the percentage of women reporting ever-use of EC increased linearly in both rural and urban populations, with the prevalence of EC ever-use more than doubling in each group. This observation likely reflects an overall increase in EC use during a time period in which the federal government enacted several policies to improve access to EC. The study findings also highlight the need for improved patient counseling on EC. While the overall prevalence of EC counseling was low among all women, rural women were less likely to have received counseling on EC when compared to urban women.

Although many studies report weight gain in users of progestin-only hormonal contraception (POC), a recent Cochrane systematic review found that there was insufficient evidence to determine the effect of POCs on weight (Lopez). Beksinska et al conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial, which was an open label, prospective, randomized multicenter trial that compared the risk of HIV acquisition among women randomized to injectable contraception (DMPA), the copper IUD, or a second generation two rod levonorgestrel (LNG) implant Jadelle^Ò. This trial was conducted at 12 sites across four African countries between 2015 and 2018. Eligible study participants were nonpregnant, HIV negative, sexually active women aged 16-35 years who desired contraception. The final sample size included 7,014 women randomly assigned to receive DMPA (2,293), the LNG implant (2,372), or the copper IUD (2,349). Using a standardized protocol and calibrated equipment across all study sites, weight and height were measured at baseline and at study exit at 12, 15, or 18 months. The mean weight increased amongst all three contraceptive groups and was significantly different in magnitude, with the largest gain in the DMPA group (3.5 kg), 2.4 kg in the LNG implant group, and 1.5 kg in the copper IUD group. Unlike copper IUD users, women in the DMPA and LNG implant group continued to gain weight after 1 year of contraceptive use. It is noteworthy that, regardless of contraceptive method allocation, not all women gained weight and a small proportion of women lost weight. When choosing a contraceptive method, women using POCs should be counselled about the potential side effect of weight gain.

References:
Moniz MH, Bonawitz K, Wetmore MK, et al. Implementing immediate postpartum contraception: a comparative case study at 11 hospitals. Implement Sci Commun. 2021;2(1):42. Published 2021 Apr 12.

Moore Z, Pfitzer A, Gubin R, et al. Missed opportunities for family planning: an analysis of pregnancy risk and contraceptive method use among postpartum women in 21 low- and middle-income countries. Contraception 92 (2015): 31–39.
 

Marchin A, Moss A, Harrison M. A Meta-Analysis of Postpartum Copper IUD Continuation Rates in Low- and Middle-Income Countries. J Womens Health Dev. 2021;4(1):36-46.

Milkowski CM, Ziller EC, Ahrens KA. Rural-urban residence and emergency contraception use, access, and counseling in the United States, 2006-2017. Contracept X. 2021;3:100061.

Lopez L.M., Ramesh S., Chen M. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016 doi: 10.1002/14651858.CD008815.pub2.

Beksinska et al. “Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial. EClinicalMedicine. 2021;34:100800.

Immediate postpartum long-acting reversible contraception (LARC) represents a safe and effective contraceptive strategy. Despite national guidelines recommending universal patient access, hospitals face significant barriers to offering inpatient LARCs. It is unclear why some hospitals successfully implement immediate postpartum LARCs, while others do not.

Moniz et al conducted a comparative, multiple case study of immediate postpartum LARC implementation at eleven “early adopter” U.S. hospitals and analyzed each hospital’s implementation strategy to produce generalizable knowledge about how and under what circumstances implementation of immediate postpartum LARCs unfold successfully. Between 2017-2018, the authors conducted single-day site visits and 78 semi-structured interviews with a variety of stakeholders (clinician champions, nurses, pharmacists, revenue cycle staff, and hospital administration). On average, sites used 18 (range 11-22) implementation strategies, including assessing institutional readiness for, and barriers to, implementation of immediate postpartum LARC, engaging reproductive justice experts and community resources to address social determinants of health, involving patients in implementation planning, and developing quality monitoring processes to evaluate clinical processes and outcomes. The researchers found that successful implementation of immediate postpartum LARC required three essential conditions: effective implementation champions who are supported by a multidisciplinary implementation team; creating an enabling financial environment; and engaging hospital administration. Additional findings from this study call for more support for individuals leading change in complex care settings, intentionally designing implementation interventions that take into account local contextual influences, and meaningfully engaging patients in the implementation process.

Of postpartum women, 61% in low- and middle-income countries (LMIC) have an unmet contraceptive need and many face high rates of short interpregnancy intervals (Moore). Additionally, 51%-96% of postpartum women in LMIC use short-acting methods of contraception (Moore), further highlighting the need for increased access to immediate postpartum LARC in LMIC. Data on the use and continuation of immediate postpartum LARC in LMIC is limited. Marchin et al conducted a systematic review and meta-analysis to determine 6-month continuation rates of immediate postpartum LARCs among women in 69 low-income countries that were enrolled in the Family Planning 2020 initiative. The meta-analysis ultimately focused on the copper IUD due to the absence of relevant studies on other LARC methods. The meta-analysis of 12 studies resulted in a pooled 6-month continuation rate for immediate postpartum copper IUDs of 87%, a rate comparable to continuation rates found in higher-income countries. This estimate had significant heterogeneity between studies. Secondary outcomes of expulsion, removal, and infection rates were low at 6%, 5%, and 0.2% respectively. High 6-month continuation rates and a low rate of adverse outcomes suggest immediate postpartum copper IUD insertion represents a feasible and acceptable postpartum contraceptive option for women living in LMIC.

In cases where contraception methods fail, are used incorrectly, or are not used at all, emergency contraception (EC) can be used after intercourse to prevent pregnancy. Timely access to, and accurate knowledge of, EC are especially important for rural women who are more likely to experience an unintended pregnancy resulting in a live birth compared to urban women. Milkowski et al analyzed publicly available data from the National Survey of Family Growth to estimate differences in oral EC use, access, and counseling by rural-urban county of residence among U.S. women aged 15-44 years. 10% of rural and 19% of urban women who had ever been sexually active reported ever using EC pills. Over the course of the study period (2006-2017), the percentage of women reporting ever-use of EC increased linearly in both rural and urban populations, with the prevalence of EC ever-use more than doubling in each group. This observation likely reflects an overall increase in EC use during a time period in which the federal government enacted several policies to improve access to EC. The study findings also highlight the need for improved patient counseling on EC. While the overall prevalence of EC counseling was low among all women, rural women were less likely to have received counseling on EC when compared to urban women.

Although many studies report weight gain in users of progestin-only hormonal contraception (POC), a recent Cochrane systematic review found that there was insufficient evidence to determine the effect of POCs on weight (Lopez). Beksinska et al conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial, which was an open label, prospective, randomized multicenter trial that compared the risk of HIV acquisition among women randomized to injectable contraception (DMPA), the copper IUD, or a second generation two rod levonorgestrel (LNG) implant Jadelle^Ò. This trial was conducted at 12 sites across four African countries between 2015 and 2018. Eligible study participants were nonpregnant, HIV negative, sexually active women aged 16-35 years who desired contraception. The final sample size included 7,014 women randomly assigned to receive DMPA (2,293), the LNG implant (2,372), or the copper IUD (2,349). Using a standardized protocol and calibrated equipment across all study sites, weight and height were measured at baseline and at study exit at 12, 15, or 18 months. The mean weight increased amongst all three contraceptive groups and was significantly different in magnitude, with the largest gain in the DMPA group (3.5 kg), 2.4 kg in the LNG implant group, and 1.5 kg in the copper IUD group. Unlike copper IUD users, women in the DMPA and LNG implant group continued to gain weight after 1 year of contraceptive use. It is noteworthy that, regardless of contraceptive method allocation, not all women gained weight and a small proportion of women lost weight. When choosing a contraceptive method, women using POCs should be counselled about the potential side effect of weight gain.

References:
Moniz MH, Bonawitz K, Wetmore MK, et al. Implementing immediate postpartum contraception: a comparative case study at 11 hospitals. Implement Sci Commun. 2021;2(1):42. Published 2021 Apr 12.

Moore Z, Pfitzer A, Gubin R, et al. Missed opportunities for family planning: an analysis of pregnancy risk and contraceptive method use among postpartum women in 21 low- and middle-income countries. Contraception 92 (2015): 31–39.
 

Marchin A, Moss A, Harrison M. A Meta-Analysis of Postpartum Copper IUD Continuation Rates in Low- and Middle-Income Countries. J Womens Health Dev. 2021;4(1):36-46.

Milkowski CM, Ziller EC, Ahrens KA. Rural-urban residence and emergency contraception use, access, and counseling in the United States, 2006-2017. Contracept X. 2021;3:100061.

Lopez L.M., Ramesh S., Chen M. Progestin-only contraceptives: effects on weight. Cochrane Database Syst Rev. 2016 doi: 10.1002/14651858.CD008815.pub2.

Beksinska et al. “Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial. EClinicalMedicine. 2021;34:100800.

Attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) often coexist in children and adults, but the range of cognitive abilities can vary widely in these patients. Researchers from around the world are leveraging symptom, cognitive assessment, and neurobiological measures to gain insights on how individuals with ADHD/ASD approach and solve problems.

Several experts discussed the progress of their research during the session, “Overlap and differences of ADHD and autism – new findings of functional imaging and cognition studies” at the World Congress on ADHD – Virtual Event.

“The overlap of these two disorders is a critical issue for our field,” said Sarah Karalunas, PhD, assistant professor of clinical psychology at Purdue University, West Lafayette, Ind., who moderated the session. Clinicians are often asked to make differential diagnoses between these two disorders. Only recently has the DSM-5 allowed their codiagnosis. “There’s increasing recognition that there may be shared cognitive and physiological features that reflect their shared risk and account for the high levels of symptom overlap,” said Dr. Karalunas.
 

Shared cognitive markers

Under the DSM’s change, “it’s now recognized that an estimated 20%-60% of children with ASD have comorbidities with ADHD, and around 20%-40% of children with ADHD have ASD symptoms,” said Beth Johnson, PhD, a research fellow with the Turner Institute for Brain and Mental Health at Monash University, Melbourne.

The shared overlap on genetic traits and comorbidities such as intellectual disability, anxiety, depression, and oppositional defiant disorder, make it difficult for clinicians to predict clinical outcomes, noted Dr. Johnson.

“We’re now understanding that they’re likely to be multiple autisms and ADHDs, that these symptoms exist on a spectrum of severity or ability,” she said. Dr. Johnson discussed a data-driven subtyping approach based on neurocognitive and symptom profiles in children with ADHD. The aim was to better understand how symptoms are managed across ADHD, ASD and comorbid ASD-ADHD.

As part of this research, her team recruited 295 controls and 117 children with ADHD who underwent clinical phenotyping and also completed working memory tasks, stop signal, and sustained attention tasks.

The researchers divided the children into four stable clusters based on the ADHD rating scale and autism questionnaire data: high ASD/ADHD traits, high ADHD/low ASD, low ADHD/moderate ASD, and low ADHD/ASD. Approximately half of the children with ADHD showed moderate to high ASD symptoms. Looking at neurocognition across the tasks, unsurprisingly, performance was lowest among the high-ASD/ADHD children, with performance on the stop signal being the most pronounced. “Notably, performance on the working memory task worsened with increasing ADHD symptoms,” she reported.
 

Drift model identifies information processing

Dr. Karalunas has also compared subgroups of ADHD and ASD children. “Our analysis examined whether cognitive impairments in ASD reflect a shared risk mechanism or co-occurring ADHD symptoms and why we see an overlap in these types of impairments,” she said.

Her study included 509 children with ADHD, 97 with ASD, and 301 controls (typical development). All three groups underwent a full cognitive assessment battery that measured attention arousal, basic processing speed, and working memory. Those tasks were collapsed into a series of variables as well as a set of tasks measuring response inhibition, switching, interference control, reward discounting, and measure of reaction time variability.

Four cognitive profiles emerged: a typically developing group, an ADHD group, an ASD group with low levels of ADHD symptoms and an ASD group with high levels of ADHD symptoms.

The ADHD group did worse on many of the tasks than the control group, and the ASD group with low ADHD levels also did poorly relative to the typically developing sample. This shows that autism – even in absence of co-occurring ADHD – demonstrates more cognitive impairment than typically developing kids. The ADHD group with high levels of autism did the most poorly across all of the tasks.

The findings also revealed a symptom severity pattern: the group with fewer symptoms did the best and the group with the most symptoms did the worst. “Overall, this reflects severity of impairment,” said Dr. Karalunas.

To identify measures more specific to either ADHD or autism, Dr. Karalunas and colleagues did a follow-up analysis to characterize cognitive performance. To accomplish this, they applied a drift-diffusion model to the same four cognitive profiles. The model assessed three parameters: drift rate, which relates to the speed or efficiency of information processing, boundary separation or speed accuracy trade-offs (impulsivity), and nondecision time such as motor preparation.

Using the same four cognitive profiles, they found that the ADHD group had slower drift rate relative to the control, although the two groups did not differ on boundary separation, which meant there were no differences on waiting to need to respond. The ADHD group had faster nondecision times. “This is a classic pattern, shown in the literature,” said Dr. Karalunas.
 

In other results, an interesting pattern began to evolve

Both ASD groups, for example, had much wider boundary separations, which meant they were waiting to be sure before they responded than the ADHD or typically developing groups. In contrast, the two ADHD groups had much faster non-decision times, whereas the two non-ADHD groups had similar nondecisions times.

Unlike the previous analysis, which saw a symptom severity pattern develop, “we’re getting two parameters that seem to track much more specifically to specific symptom domains,” observed Dr. Karalunas.

The results suggest there’s a substantial overlap in cognitive impairments in ADHD/ASD. “But we have pretty strong evidence at this point that these similarities are not accounted for by symptom overlap, especially for things like response and inhibition, working memory and processing speed. These seem to be independently related to ADHD and autism, regardless of the level of comorbid ADHD symptoms in the autism group,” said Dr. Karalunas.

The hope is to expand on these types of analyses to address the interaction of cognition-emotion and social cognition, and empirically define groups based on cognitive performance, she said.
 

Neurocognitive studies

Researchers have also been studying neural networks to assess ASD and ADHD. Roselyne Chauvin, PhD, a postdoctoral associate at Washington University, St. Louis, discussed the concept of “a task generic connectome,” in which researchers look for a common network between targeted task paradigms to get closer to a common alteration across impairments.

In her research, Dr. Chauvin and colleagues looked at connectivity modulations across three tasks: working memory, reward processing tasks, and stop signal tasks, comparing ADHD patients to siblings and controls. The ADHD group showed reduced sensitivity or a smaller number of connections modulated in the tasks compared with the other groups. Researchers wondered where those missed connections were located.

Dividing the cohorts into task generic and task specific groups, Dr. Chauvin and colleagues found that the ADHD group lacked common processing skills. They were also able to identify reproducible missing circuits in the ADHD participants. Among the cohorts, there was a higher modulation of task-specific edges in the ADHD group.

The ADHD patients seemed to be using more task-tailored alternative strategies that were more challenging and suboptimal.

She also previewed her ongoing work with the EU-AIMS Longitudinal European Autism Project (LEAP) database to study ASD-ADHD comorbidity. In this project, she and her colleagues looked at several tasks: probing emotion processing, inhibitory control, theory of mind, and reward anticipation. Comparing ASD groups with or without ADHD comorbidity or a shared connection, she and her team were able to devise a functional profile predictive of ADHD severity. As an example, “for the connection only used by the ASD with ADHD comorbidity, the more they were using those connections of higher amplitude in the modulation, inside this subset of connection, the higher they would have ADHD severity,” said Dr. Chauvin.

Neural correlates of different behavioral and cognitive profiles haven’t been widely studied, according to Charlotte Tye, PhD, who’s based at the Institute of Psychiatry, Psychology & Neuroscience, King’s College, London. Electroencephalography is a useful technique for understanding the neural correlates of cognitive impairments and teasing apart different models of co-occurrence in ASD and ADHD. 

Dr. Tye and colleagues tested this approach in a cohort of boys aged 8-13 years diagnosed with ASD and/or ADHD, measuring EEG while the children did various continuous performance tasks to assess changes in brain activity. Examining P3 amplitude (event-related potential components) they found that children with ADHD or ADHD+ASD showed an attenuated amplitude of the P3, compared with typically developing children and those with ASD.

“This suggests children with an ADHD diagnosis exhibited reduced inhibitory control,” said Dr. Tye. In contrast, children with ASD showed reduced conflict monitoring as indexed by altered N2 amplitude across task conditions.

These, and other studies conducted by Dr. Tye and colleagues indicate that children with ADHD show reduced neural responses during attentional processing, whereas autistic children show typical neural responses, supporting specific profiles.

“Autistic children with a diagnosis of ADHD appear to show the unique patterns of neural responses of autism and ADHD, supporting an additive co-occurrence rather than a distinct condition. This contributes to identification of transdiagnostic subgroups within neurodevelopmental conditions for targeting of personalized intervention, and suggests that children with co-occurring autism and ADHD require support for both conditions,” said Dr. Tye.

An important takeaway from all of these findings is “we can’t look just at how someone does overall on a single test,” said Dr. Karalunas in an interview. “There is a tremendous amount of variability between people who have the same diagnosis, and our research really needs to account for this.”

Attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) often coexist in children and adults, but the range of cognitive abilities can vary widely in these patients. Researchers from around the world are leveraging symptom, cognitive assessment, and neurobiological measures to gain insights on how individuals with ADHD/ASD approach and solve problems.

Several experts discussed the progress of their research during the session, “Overlap and differences of ADHD and autism – new findings of functional imaging and cognition studies” at the World Congress on ADHD – Virtual Event.

“The overlap of these two disorders is a critical issue for our field,” said Sarah Karalunas, PhD, assistant professor of clinical psychology at Purdue University, West Lafayette, Ind., who moderated the session. Clinicians are often asked to make differential diagnoses between these two disorders. Only recently has the DSM-5 allowed their codiagnosis. “There’s increasing recognition that there may be shared cognitive and physiological features that reflect their shared risk and account for the high levels of symptom overlap,” said Dr. Karalunas.
 

Shared cognitive markers

Under the DSM’s change, “it’s now recognized that an estimated 20%-60% of children with ASD have comorbidities with ADHD, and around 20%-40% of children with ADHD have ASD symptoms,” said Beth Johnson, PhD, a research fellow with the Turner Institute for Brain and Mental Health at Monash University, Melbourne.

The shared overlap on genetic traits and comorbidities such as intellectual disability, anxiety, depression, and oppositional defiant disorder, make it difficult for clinicians to predict clinical outcomes, noted Dr. Johnson.

“We’re now understanding that they’re likely to be multiple autisms and ADHDs, that these symptoms exist on a spectrum of severity or ability,” she said. Dr. Johnson discussed a data-driven subtyping approach based on neurocognitive and symptom profiles in children with ADHD. The aim was to better understand how symptoms are managed across ADHD, ASD and comorbid ASD-ADHD.

As part of this research, her team recruited 295 controls and 117 children with ADHD who underwent clinical phenotyping and also completed working memory tasks, stop signal, and sustained attention tasks.

The researchers divided the children into four stable clusters based on the ADHD rating scale and autism questionnaire data: high ASD/ADHD traits, high ADHD/low ASD, low ADHD/moderate ASD, and low ADHD/ASD. Approximately half of the children with ADHD showed moderate to high ASD symptoms. Looking at neurocognition across the tasks, unsurprisingly, performance was lowest among the high-ASD/ADHD children, with performance on the stop signal being the most pronounced. “Notably, performance on the working memory task worsened with increasing ADHD symptoms,” she reported.
 

Drift model identifies information processing

Dr. Karalunas has also compared subgroups of ADHD and ASD children. “Our analysis examined whether cognitive impairments in ASD reflect a shared risk mechanism or co-occurring ADHD symptoms and why we see an overlap in these types of impairments,” she said.

Her study included 509 children with ADHD, 97 with ASD, and 301 controls (typical development). All three groups underwent a full cognitive assessment battery that measured attention arousal, basic processing speed, and working memory. Those tasks were collapsed into a series of variables as well as a set of tasks measuring response inhibition, switching, interference control, reward discounting, and measure of reaction time variability.

Four cognitive profiles emerged: a typically developing group, an ADHD group, an ASD group with low levels of ADHD symptoms and an ASD group with high levels of ADHD symptoms.

The ADHD group did worse on many of the tasks than the control group, and the ASD group with low ADHD levels also did poorly relative to the typically developing sample. This shows that autism – even in absence of co-occurring ADHD – demonstrates more cognitive impairment than typically developing kids. The ADHD group with high levels of autism did the most poorly across all of the tasks.

The findings also revealed a symptom severity pattern: the group with fewer symptoms did the best and the group with the most symptoms did the worst. “Overall, this reflects severity of impairment,” said Dr. Karalunas.

To identify measures more specific to either ADHD or autism, Dr. Karalunas and colleagues did a follow-up analysis to characterize cognitive performance. To accomplish this, they applied a drift-diffusion model to the same four cognitive profiles. The model assessed three parameters: drift rate, which relates to the speed or efficiency of information processing, boundary separation or speed accuracy trade-offs (impulsivity), and nondecision time such as motor preparation.

Using the same four cognitive profiles, they found that the ADHD group had slower drift rate relative to the control, although the two groups did not differ on boundary separation, which meant there were no differences on waiting to need to respond. The ADHD group had faster nondecision times. “This is a classic pattern, shown in the literature,” said Dr. Karalunas.
 

In other results, an interesting pattern began to evolve

Both ASD groups, for example, had much wider boundary separations, which meant they were waiting to be sure before they responded than the ADHD or typically developing groups. In contrast, the two ADHD groups had much faster non-decision times, whereas the two non-ADHD groups had similar nondecisions times.

Unlike the previous analysis, which saw a symptom severity pattern develop, “we’re getting two parameters that seem to track much more specifically to specific symptom domains,” observed Dr. Karalunas.

The results suggest there’s a substantial overlap in cognitive impairments in ADHD/ASD. “But we have pretty strong evidence at this point that these similarities are not accounted for by symptom overlap, especially for things like response and inhibition, working memory and processing speed. These seem to be independently related to ADHD and autism, regardless of the level of comorbid ADHD symptoms in the autism group,” said Dr. Karalunas.

The hope is to expand on these types of analyses to address the interaction of cognition-emotion and social cognition, and empirically define groups based on cognitive performance, she said.
 

Neurocognitive studies

Researchers have also been studying neural networks to assess ASD and ADHD. Roselyne Chauvin, PhD, a postdoctoral associate at Washington University, St. Louis, discussed the concept of “a task generic connectome,” in which researchers look for a common network between targeted task paradigms to get closer to a common alteration across impairments.

In her research, Dr. Chauvin and colleagues looked at connectivity modulations across three tasks: working memory, reward processing tasks, and stop signal tasks, comparing ADHD patients to siblings and controls. The ADHD group showed reduced sensitivity or a smaller number of connections modulated in the tasks compared with the other groups. Researchers wondered where those missed connections were located.

Dividing the cohorts into task generic and task specific groups, Dr. Chauvin and colleagues found that the ADHD group lacked common processing skills. They were also able to identify reproducible missing circuits in the ADHD participants. Among the cohorts, there was a higher modulation of task-specific edges in the ADHD group.

The ADHD patients seemed to be using more task-tailored alternative strategies that were more challenging and suboptimal.

She also previewed her ongoing work with the EU-AIMS Longitudinal European Autism Project (LEAP) database to study ASD-ADHD comorbidity. In this project, she and her colleagues looked at several tasks: probing emotion processing, inhibitory control, theory of mind, and reward anticipation. Comparing ASD groups with or without ADHD comorbidity or a shared connection, she and her team were able to devise a functional profile predictive of ADHD severity. As an example, “for the connection only used by the ASD with ADHD comorbidity, the more they were using those connections of higher amplitude in the modulation, inside this subset of connection, the higher they would have ADHD severity,” said Dr. Chauvin.

Neural correlates of different behavioral and cognitive profiles haven’t been widely studied, according to Charlotte Tye, PhD, who’s based at the Institute of Psychiatry, Psychology & Neuroscience, King’s College, London. Electroencephalography is a useful technique for understanding the neural correlates of cognitive impairments and teasing apart different models of co-occurrence in ASD and ADHD. 

Dr. Tye and colleagues tested this approach in a cohort of boys aged 8-13 years diagnosed with ASD and/or ADHD, measuring EEG while the children did various continuous performance tasks to assess changes in brain activity. Examining P3 amplitude (event-related potential components) they found that children with ADHD or ADHD+ASD showed an attenuated amplitude of the P3, compared with typically developing children and those with ASD.

“This suggests children with an ADHD diagnosis exhibited reduced inhibitory control,” said Dr. Tye. In contrast, children with ASD showed reduced conflict monitoring as indexed by altered N2 amplitude across task conditions.

These, and other studies conducted by Dr. Tye and colleagues indicate that children with ADHD show reduced neural responses during attentional processing, whereas autistic children show typical neural responses, supporting specific profiles.

“Autistic children with a diagnosis of ADHD appear to show the unique patterns of neural responses of autism and ADHD, supporting an additive co-occurrence rather than a distinct condition. This contributes to identification of transdiagnostic subgroups within neurodevelopmental conditions for targeting of personalized intervention, and suggests that children with co-occurring autism and ADHD require support for both conditions,” said Dr. Tye.

An important takeaway from all of these findings is “we can’t look just at how someone does overall on a single test,” said Dr. Karalunas in an interview. “There is a tremendous amount of variability between people who have the same diagnosis, and our research really needs to account for this.”

Attention-deficit/hyperactivity disorder and autism spectrum disorder (ASD) often coexist in children and adults, but the range of cognitive abilities can vary widely in these patients. Researchers from around the world are leveraging symptom, cognitive assessment, and neurobiological measures to gain insights on how individuals with ADHD/ASD approach and solve problems.

Several experts discussed the progress of their research during the session, “Overlap and differences of ADHD and autism – new findings of functional imaging and cognition studies” at the World Congress on ADHD – Virtual Event.

“The overlap of these two disorders is a critical issue for our field,” said Sarah Karalunas, PhD, assistant professor of clinical psychology at Purdue University, West Lafayette, Ind., who moderated the session. Clinicians are often asked to make differential diagnoses between these two disorders. Only recently has the DSM-5 allowed their codiagnosis. “There’s increasing recognition that there may be shared cognitive and physiological features that reflect their shared risk and account for the high levels of symptom overlap,” said Dr. Karalunas.
 

Shared cognitive markers

Under the DSM’s change, “it’s now recognized that an estimated 20%-60% of children with ASD have comorbidities with ADHD, and around 20%-40% of children with ADHD have ASD symptoms,” said Beth Johnson, PhD, a research fellow with the Turner Institute for Brain and Mental Health at Monash University, Melbourne.

The shared overlap on genetic traits and comorbidities such as intellectual disability, anxiety, depression, and oppositional defiant disorder, make it difficult for clinicians to predict clinical outcomes, noted Dr. Johnson.

“We’re now understanding that they’re likely to be multiple autisms and ADHDs, that these symptoms exist on a spectrum of severity or ability,” she said. Dr. Johnson discussed a data-driven subtyping approach based on neurocognitive and symptom profiles in children with ADHD. The aim was to better understand how symptoms are managed across ADHD, ASD and comorbid ASD-ADHD.

As part of this research, her team recruited 295 controls and 117 children with ADHD who underwent clinical phenotyping and also completed working memory tasks, stop signal, and sustained attention tasks.

The researchers divided the children into four stable clusters based on the ADHD rating scale and autism questionnaire data: high ASD/ADHD traits, high ADHD/low ASD, low ADHD/moderate ASD, and low ADHD/ASD. Approximately half of the children with ADHD showed moderate to high ASD symptoms. Looking at neurocognition across the tasks, unsurprisingly, performance was lowest among the high-ASD/ADHD children, with performance on the stop signal being the most pronounced. “Notably, performance on the working memory task worsened with increasing ADHD symptoms,” she reported.
 

Drift model identifies information processing

Dr. Karalunas has also compared subgroups of ADHD and ASD children. “Our analysis examined whether cognitive impairments in ASD reflect a shared risk mechanism or co-occurring ADHD symptoms and why we see an overlap in these types of impairments,” she said.

Her study included 509 children with ADHD, 97 with ASD, and 301 controls (typical development). All three groups underwent a full cognitive assessment battery that measured attention arousal, basic processing speed, and working memory. Those tasks were collapsed into a series of variables as well as a set of tasks measuring response inhibition, switching, interference control, reward discounting, and measure of reaction time variability.

Four cognitive profiles emerged: a typically developing group, an ADHD group, an ASD group with low levels of ADHD symptoms and an ASD group with high levels of ADHD symptoms.

The ADHD group did worse on many of the tasks than the control group, and the ASD group with low ADHD levels also did poorly relative to the typically developing sample. This shows that autism – even in absence of co-occurring ADHD – demonstrates more cognitive impairment than typically developing kids. The ADHD group with high levels of autism did the most poorly across all of the tasks.

The findings also revealed a symptom severity pattern: the group with fewer symptoms did the best and the group with the most symptoms did the worst. “Overall, this reflects severity of impairment,” said Dr. Karalunas.

To identify measures more specific to either ADHD or autism, Dr. Karalunas and colleagues did a follow-up analysis to characterize cognitive performance. To accomplish this, they applied a drift-diffusion model to the same four cognitive profiles. The model assessed three parameters: drift rate, which relates to the speed or efficiency of information processing, boundary separation or speed accuracy trade-offs (impulsivity), and nondecision time such as motor preparation.

Using the same four cognitive profiles, they found that the ADHD group had slower drift rate relative to the control, although the two groups did not differ on boundary separation, which meant there were no differences on waiting to need to respond. The ADHD group had faster nondecision times. “This is a classic pattern, shown in the literature,” said Dr. Karalunas.
 

In other results, an interesting pattern began to evolve

Both ASD groups, for example, had much wider boundary separations, which meant they were waiting to be sure before they responded than the ADHD or typically developing groups. In contrast, the two ADHD groups had much faster non-decision times, whereas the two non-ADHD groups had similar nondecisions times.

Unlike the previous analysis, which saw a symptom severity pattern develop, “we’re getting two parameters that seem to track much more specifically to specific symptom domains,” observed Dr. Karalunas.

The results suggest there’s a substantial overlap in cognitive impairments in ADHD/ASD. “But we have pretty strong evidence at this point that these similarities are not accounted for by symptom overlap, especially for things like response and inhibition, working memory and processing speed. These seem to be independently related to ADHD and autism, regardless of the level of comorbid ADHD symptoms in the autism group,” said Dr. Karalunas.

The hope is to expand on these types of analyses to address the interaction of cognition-emotion and social cognition, and empirically define groups based on cognitive performance, she said.
 

Neurocognitive studies

Researchers have also been studying neural networks to assess ASD and ADHD. Roselyne Chauvin, PhD, a postdoctoral associate at Washington University, St. Louis, discussed the concept of “a task generic connectome,” in which researchers look for a common network between targeted task paradigms to get closer to a common alteration across impairments.

In her research, Dr. Chauvin and colleagues looked at connectivity modulations across three tasks: working memory, reward processing tasks, and stop signal tasks, comparing ADHD patients to siblings and controls. The ADHD group showed reduced sensitivity or a smaller number of connections modulated in the tasks compared with the other groups. Researchers wondered where those missed connections were located.

Dividing the cohorts into task generic and task specific groups, Dr. Chauvin and colleagues found that the ADHD group lacked common processing skills. They were also able to identify reproducible missing circuits in the ADHD participants. Among the cohorts, there was a higher modulation of task-specific edges in the ADHD group.

The ADHD patients seemed to be using more task-tailored alternative strategies that were more challenging and suboptimal.

She also previewed her ongoing work with the EU-AIMS Longitudinal European Autism Project (LEAP) database to study ASD-ADHD comorbidity. In this project, she and her colleagues looked at several tasks: probing emotion processing, inhibitory control, theory of mind, and reward anticipation. Comparing ASD groups with or without ADHD comorbidity or a shared connection, she and her team were able to devise a functional profile predictive of ADHD severity. As an example, “for the connection only used by the ASD with ADHD comorbidity, the more they were using those connections of higher amplitude in the modulation, inside this subset of connection, the higher they would have ADHD severity,” said Dr. Chauvin.

Neural correlates of different behavioral and cognitive profiles haven’t been widely studied, according to Charlotte Tye, PhD, who’s based at the Institute of Psychiatry, Psychology & Neuroscience, King’s College, London. Electroencephalography is a useful technique for understanding the neural correlates of cognitive impairments and teasing apart different models of co-occurrence in ASD and ADHD. 

Dr. Tye and colleagues tested this approach in a cohort of boys aged 8-13 years diagnosed with ASD and/or ADHD, measuring EEG while the children did various continuous performance tasks to assess changes in brain activity. Examining P3 amplitude (event-related potential components) they found that children with ADHD or ADHD+ASD showed an attenuated amplitude of the P3, compared with typically developing children and those with ASD.

“This suggests children with an ADHD diagnosis exhibited reduced inhibitory control,” said Dr. Tye. In contrast, children with ASD showed reduced conflict monitoring as indexed by altered N2 amplitude across task conditions.

These, and other studies conducted by Dr. Tye and colleagues indicate that children with ADHD show reduced neural responses during attentional processing, whereas autistic children show typical neural responses, supporting specific profiles.

“Autistic children with a diagnosis of ADHD appear to show the unique patterns of neural responses of autism and ADHD, supporting an additive co-occurrence rather than a distinct condition. This contributes to identification of transdiagnostic subgroups within neurodevelopmental conditions for targeting of personalized intervention, and suggests that children with co-occurring autism and ADHD require support for both conditions,” said Dr. Tye.

An important takeaway from all of these findings is “we can’t look just at how someone does overall on a single test,” said Dr. Karalunas in an interview. “There is a tremendous amount of variability between people who have the same diagnosis, and our research really needs to account for this.”

While it’s possible that residual effects of SARS-CoV-2 could lead to an eruption of attention-deficit/hyperactivity disorder (ADHD) cases, a debate at the World Congress on ADHD – Virtual Event underscored the fact that this is still a hypothesis. The bottom line is there needs to be more data, said Luis Augusto Rohde, MD, PhD, cochair of the congress’ scientific program committee and moderator of the session, “Residual effects of the 2019 pandemic will mirror the 1918 pandemic: Will we have lots of new ADHD cases?”

Considering the current pattern of the pandemic, there is not enough evidence for this to be a concern, Dr. Rohde said in an interview.

James Swanson, PhD, professor of pediatrics at the University of California, Irvine, opined that biological co-effects of COVID-19 are likely to have selective effects in children that may produce symptoms representative of ADHD. Using the 1918 Spanish flu pandemic as a historical reference, he estimated that COVID-19 would produce 5 million individuals with new-onset symptoms related to ADHD. “If these cases meet DSM-5 or ICD-11 criteria, there will be lots of new ADHD cases,” he predicted.

David Coghill, MD, a professor of child adolescent mental health at the University of Melbourne, observed that the sums Dr. Swanson presented “are based on maxing out the potential rather than looking at the sums more realistically.”
 

Could the 1918 pandemic offer clues?

In a commentary, Dr. Swanson and Nora D. Volkow, MD, wrote about “lessons learned” from the 1918 pandemic, and how residual sequelae in that era led to a condition labeled hyperkinetic syndrome in children. “It may be worthwhile to consider the hypothesis that the COVID-19 pandemic may result in a novel etiologic subtype of ADHD that clinicians may recognize in patients in the future,” wrote the commentators. 

In survivors of the 1918 pandemic, brain inflammation or encephalitis sometimes emerged as residual sequelae, said Dr. Swanson. In some adult cases, these symptoms were diagnosed as “encephalitis lethargica” (EL) and were associated with Parkinson’s disease. In 1930, based on patients evaluated after 1918, researchers Franz Kramer and Hans Pollnow at Charité Hospital in Berlin described the behavioral manifestation of EL in children as hyperkinetic syndrome, a condition that was characterized by symptoms similar to the properties of ADHD: lack of concentration, insufficient goal orientation, and increased distractibility. “They even reported on autopsy cases that described brain regions that we now know are associated with ADHD from decades of brain imaging studies,” said Dr. Swanson.

COVID-19 rarely results in severe respiratory problems in children but the absolute number requiring hospitalization has accumulated and is now relatively large, said Dr. Swanson. One study of 1,695 severe COVID-19 cases in children and adolescents used MRI and detected neural effects in specific brain regions such as basal ganglia and frontal lobes that previous research had associated with ADHD. Approximately 22% of these rare but severe cases had documented neurologic involvement, and studies of affected children with mild or none of the initial respiratory symptoms of COVID-19 also detected similar selective effects in these brain regions.

A recent survey of medical records of 80 million people that identified 240,000 COVID cases (mostly adults) revealed that a third had neurological and psychiatric sequelae. Dr. Swanson also mentioned an article he wrote more than a decade ago on environmental as well as genetic factors that resulted in etiologic subtypes of ADHD, which provided a model for the impact of COVID-19 on specific brain regions that are associated with ADHD.

So far, the COVID-19 pandemic has produced 150 million cases worldwide and there are about 100 million survivors, setting an estimate of a maximum number of cases with residual sequelae. “I think that severe COVID-19 will probably be related to severe residual sequelae, and that mild or asymptomatic COVID-19 may be associated with less severe residual sequelae, which may resemble ADHD” said Dr. Swanson. If one-third of the cases manifest in some neurologic or psychiatric systems, this means 27 million would have residual sequelae. If 20% have impaired concentration or brain fog, this could result in about 5 million ADHD cases, he said. 
 

Estimates aren’t evidence

The Swanson/Volkow commentary contains a lot of references to “might, could, and may,” said Dr. Coghill. While it’s true that COVID-19 could produce a novel etiologic subtype of ADHD, “the point here is at the moment, all of this is based on hypotheses,” he said.

The Spanish flu did produce mental health consequences – survivors reported depression, sleep disturbances, mental distraction, dizziness, and difficulties coping at work. In the United States, flu death rates from 1918 to 1920 were directly attributed to suicide rates. Unfortunately, these impacts weren’t widely researched, said Dr. Coghill.

It also seems clear that the 1918 Spanish flu outbreak was associated with significant neurological consequences, said Dr. Coghill. By 1919 and 1920, physicians and researchers in the United Kingdom were reporting increases in a variety of symptoms among some patients recovering from flu, such as neuropathy, neurasthenia, meningitis, degenerative changes in nerve cells, and a decline in visual acuity.

The EL cases Dr. Swanson mentioned did coincide with and reach epidemic proportions alongside the Spanish flu. “But still, a causal relationship is far from proven,” said Dr. Coghill.

Sol Levy, MD, described a “disease of criminals” following the 1918 pandemic, in which patients exhibited a high degree of general hyperkinesis, a difficulty in maintaining quiet attitudes, abruptness and clumsiness, and “explosive motor release of all voluntarily inhibited activities.”

However, these impairments suggest a much broader presentation typically seen in ADHD, noted Dr. Coghill.

Neurological complications occur more commonly than initially thought in severe COVID-19, with estimates ranging from 36% to 84%. But in a systematic review of neuropsychiatric complications of severe coronavirus infection, researchers found few psychiatric sequelae of these infections. While they did mention impaired concentration and difficulties with emotional ability, it’s very important to remember that these conditions “are cardinal symptoms of a wide range of psychiatric disorders,” said Dr. Coghill.

Overall, more neurological and neuropsychiatric symptoms largely confine to those with severe COVID-19, meaning they’re much less likely to occur in children and young adults, he said.

If there are severe effects of COVID-19, Dr. Swanson countered that “they might have more ADHD than the complex residual effects [Dr. Coghill] described. I hope that he’s right, but I do think there will be biological co-effects of COVID-19 that will produce symptoms that are more ADHD than other neurological disorders.”
 

Epigenetic effects

Researchers are now seeing transgenerational and intergenerational effects of potential infection. “So I certainly back high-quality studies looking at the effects of maternal and paternal infection on offspring,” said Dr. Coghill. Establishing clinical cohort studies to follow up on this population would be essential in understanding the risks of SARS-CoV-2. “That might be one way we’ll see an increase in ADHD,” said Dr. Coghill.

The reality is COVID-19 hasn’t been around for that long, and current knowledge about it is limited, he said. Rapid publications, cross-sectional or retrospective data, and poor methodological quality and rigor make generalizability difficult. In addition, limited testing and detection probably underestimate prevalence of neurological and neuropsychiatric complications.

“If history teaches us anything, it is that we should always be measured in how we glean lessons from the past. So let’s not get ahead of ourselves,” he cautioned.

An informal, post-discussion survey of session participants revealed that a slight majority – 55%-60% – expected residual effects of COVID-19 to lead to more ADHD, compared to 40%-45% who didn’t think this would happen.

Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA). Dr. Coghill worked for several pharmaceutical companies but had no disclosures relevant to this debate.

While it’s possible that residual effects of SARS-CoV-2 could lead to an eruption of attention-deficit/hyperactivity disorder (ADHD) cases, a debate at the World Congress on ADHD – Virtual Event underscored the fact that this is still a hypothesis. The bottom line is there needs to be more data, said Luis Augusto Rohde, MD, PhD, cochair of the congress’ scientific program committee and moderator of the session, “Residual effects of the 2019 pandemic will mirror the 1918 pandemic: Will we have lots of new ADHD cases?”

Considering the current pattern of the pandemic, there is not enough evidence for this to be a concern, Dr. Rohde said in an interview.

James Swanson, PhD, professor of pediatrics at the University of California, Irvine, opined that biological co-effects of COVID-19 are likely to have selective effects in children that may produce symptoms representative of ADHD. Using the 1918 Spanish flu pandemic as a historical reference, he estimated that COVID-19 would produce 5 million individuals with new-onset symptoms related to ADHD. “If these cases meet DSM-5 or ICD-11 criteria, there will be lots of new ADHD cases,” he predicted.

David Coghill, MD, a professor of child adolescent mental health at the University of Melbourne, observed that the sums Dr. Swanson presented “are based on maxing out the potential rather than looking at the sums more realistically.”
 

Could the 1918 pandemic offer clues?

In a commentary, Dr. Swanson and Nora D. Volkow, MD, wrote about “lessons learned” from the 1918 pandemic, and how residual sequelae in that era led to a condition labeled hyperkinetic syndrome in children. “It may be worthwhile to consider the hypothesis that the COVID-19 pandemic may result in a novel etiologic subtype of ADHD that clinicians may recognize in patients in the future,” wrote the commentators. 

In survivors of the 1918 pandemic, brain inflammation or encephalitis sometimes emerged as residual sequelae, said Dr. Swanson. In some adult cases, these symptoms were diagnosed as “encephalitis lethargica” (EL) and were associated with Parkinson’s disease. In 1930, based on patients evaluated after 1918, researchers Franz Kramer and Hans Pollnow at Charité Hospital in Berlin described the behavioral manifestation of EL in children as hyperkinetic syndrome, a condition that was characterized by symptoms similar to the properties of ADHD: lack of concentration, insufficient goal orientation, and increased distractibility. “They even reported on autopsy cases that described brain regions that we now know are associated with ADHD from decades of brain imaging studies,” said Dr. Swanson.

COVID-19 rarely results in severe respiratory problems in children but the absolute number requiring hospitalization has accumulated and is now relatively large, said Dr. Swanson. One study of 1,695 severe COVID-19 cases in children and adolescents used MRI and detected neural effects in specific brain regions such as basal ganglia and frontal lobes that previous research had associated with ADHD. Approximately 22% of these rare but severe cases had documented neurologic involvement, and studies of affected children with mild or none of the initial respiratory symptoms of COVID-19 also detected similar selective effects in these brain regions.

A recent survey of medical records of 80 million people that identified 240,000 COVID cases (mostly adults) revealed that a third had neurological and psychiatric sequelae. Dr. Swanson also mentioned an article he wrote more than a decade ago on environmental as well as genetic factors that resulted in etiologic subtypes of ADHD, which provided a model for the impact of COVID-19 on specific brain regions that are associated with ADHD.

So far, the COVID-19 pandemic has produced 150 million cases worldwide and there are about 100 million survivors, setting an estimate of a maximum number of cases with residual sequelae. “I think that severe COVID-19 will probably be related to severe residual sequelae, and that mild or asymptomatic COVID-19 may be associated with less severe residual sequelae, which may resemble ADHD” said Dr. Swanson. If one-third of the cases manifest in some neurologic or psychiatric systems, this means 27 million would have residual sequelae. If 20% have impaired concentration or brain fog, this could result in about 5 million ADHD cases, he said. 
 

Estimates aren’t evidence

The Swanson/Volkow commentary contains a lot of references to “might, could, and may,” said Dr. Coghill. While it’s true that COVID-19 could produce a novel etiologic subtype of ADHD, “the point here is at the moment, all of this is based on hypotheses,” he said.

The Spanish flu did produce mental health consequences – survivors reported depression, sleep disturbances, mental distraction, dizziness, and difficulties coping at work. In the United States, flu death rates from 1918 to 1920 were directly attributed to suicide rates. Unfortunately, these impacts weren’t widely researched, said Dr. Coghill.

It also seems clear that the 1918 Spanish flu outbreak was associated with significant neurological consequences, said Dr. Coghill. By 1919 and 1920, physicians and researchers in the United Kingdom were reporting increases in a variety of symptoms among some patients recovering from flu, such as neuropathy, neurasthenia, meningitis, degenerative changes in nerve cells, and a decline in visual acuity.

The EL cases Dr. Swanson mentioned did coincide with and reach epidemic proportions alongside the Spanish flu. “But still, a causal relationship is far from proven,” said Dr. Coghill.

Sol Levy, MD, described a “disease of criminals” following the 1918 pandemic, in which patients exhibited a high degree of general hyperkinesis, a difficulty in maintaining quiet attitudes, abruptness and clumsiness, and “explosive motor release of all voluntarily inhibited activities.”

However, these impairments suggest a much broader presentation typically seen in ADHD, noted Dr. Coghill.

Neurological complications occur more commonly than initially thought in severe COVID-19, with estimates ranging from 36% to 84%. But in a systematic review of neuropsychiatric complications of severe coronavirus infection, researchers found few psychiatric sequelae of these infections. While they did mention impaired concentration and difficulties with emotional ability, it’s very important to remember that these conditions “are cardinal symptoms of a wide range of psychiatric disorders,” said Dr. Coghill.

Overall, more neurological and neuropsychiatric symptoms largely confine to those with severe COVID-19, meaning they’re much less likely to occur in children and young adults, he said.

If there are severe effects of COVID-19, Dr. Swanson countered that “they might have more ADHD than the complex residual effects [Dr. Coghill] described. I hope that he’s right, but I do think there will be biological co-effects of COVID-19 that will produce symptoms that are more ADHD than other neurological disorders.”
 

Epigenetic effects

Researchers are now seeing transgenerational and intergenerational effects of potential infection. “So I certainly back high-quality studies looking at the effects of maternal and paternal infection on offspring,” said Dr. Coghill. Establishing clinical cohort studies to follow up on this population would be essential in understanding the risks of SARS-CoV-2. “That might be one way we’ll see an increase in ADHD,” said Dr. Coghill.

The reality is COVID-19 hasn’t been around for that long, and current knowledge about it is limited, he said. Rapid publications, cross-sectional or retrospective data, and poor methodological quality and rigor make generalizability difficult. In addition, limited testing and detection probably underestimate prevalence of neurological and neuropsychiatric complications.

“If history teaches us anything, it is that we should always be measured in how we glean lessons from the past. So let’s not get ahead of ourselves,” he cautioned.

An informal, post-discussion survey of session participants revealed that a slight majority – 55%-60% – expected residual effects of COVID-19 to lead to more ADHD, compared to 40%-45% who didn’t think this would happen.

Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA). Dr. Coghill worked for several pharmaceutical companies but had no disclosures relevant to this debate.

While it’s possible that residual effects of SARS-CoV-2 could lead to an eruption of attention-deficit/hyperactivity disorder (ADHD) cases, a debate at the World Congress on ADHD – Virtual Event underscored the fact that this is still a hypothesis. The bottom line is there needs to be more data, said Luis Augusto Rohde, MD, PhD, cochair of the congress’ scientific program committee and moderator of the session, “Residual effects of the 2019 pandemic will mirror the 1918 pandemic: Will we have lots of new ADHD cases?”

Considering the current pattern of the pandemic, there is not enough evidence for this to be a concern, Dr. Rohde said in an interview.

James Swanson, PhD, professor of pediatrics at the University of California, Irvine, opined that biological co-effects of COVID-19 are likely to have selective effects in children that may produce symptoms representative of ADHD. Using the 1918 Spanish flu pandemic as a historical reference, he estimated that COVID-19 would produce 5 million individuals with new-onset symptoms related to ADHD. “If these cases meet DSM-5 or ICD-11 criteria, there will be lots of new ADHD cases,” he predicted.

David Coghill, MD, a professor of child adolescent mental health at the University of Melbourne, observed that the sums Dr. Swanson presented “are based on maxing out the potential rather than looking at the sums more realistically.”
 

Could the 1918 pandemic offer clues?

In a commentary, Dr. Swanson and Nora D. Volkow, MD, wrote about “lessons learned” from the 1918 pandemic, and how residual sequelae in that era led to a condition labeled hyperkinetic syndrome in children. “It may be worthwhile to consider the hypothesis that the COVID-19 pandemic may result in a novel etiologic subtype of ADHD that clinicians may recognize in patients in the future,” wrote the commentators. 

In survivors of the 1918 pandemic, brain inflammation or encephalitis sometimes emerged as residual sequelae, said Dr. Swanson. In some adult cases, these symptoms were diagnosed as “encephalitis lethargica” (EL) and were associated with Parkinson’s disease. In 1930, based on patients evaluated after 1918, researchers Franz Kramer and Hans Pollnow at Charité Hospital in Berlin described the behavioral manifestation of EL in children as hyperkinetic syndrome, a condition that was characterized by symptoms similar to the properties of ADHD: lack of concentration, insufficient goal orientation, and increased distractibility. “They even reported on autopsy cases that described brain regions that we now know are associated with ADHD from decades of brain imaging studies,” said Dr. Swanson.

COVID-19 rarely results in severe respiratory problems in children but the absolute number requiring hospitalization has accumulated and is now relatively large, said Dr. Swanson. One study of 1,695 severe COVID-19 cases in children and adolescents used MRI and detected neural effects in specific brain regions such as basal ganglia and frontal lobes that previous research had associated with ADHD. Approximately 22% of these rare but severe cases had documented neurologic involvement, and studies of affected children with mild or none of the initial respiratory symptoms of COVID-19 also detected similar selective effects in these brain regions.

A recent survey of medical records of 80 million people that identified 240,000 COVID cases (mostly adults) revealed that a third had neurological and psychiatric sequelae. Dr. Swanson also mentioned an article he wrote more than a decade ago on environmental as well as genetic factors that resulted in etiologic subtypes of ADHD, which provided a model for the impact of COVID-19 on specific brain regions that are associated with ADHD.

So far, the COVID-19 pandemic has produced 150 million cases worldwide and there are about 100 million survivors, setting an estimate of a maximum number of cases with residual sequelae. “I think that severe COVID-19 will probably be related to severe residual sequelae, and that mild or asymptomatic COVID-19 may be associated with less severe residual sequelae, which may resemble ADHD” said Dr. Swanson. If one-third of the cases manifest in some neurologic or psychiatric systems, this means 27 million would have residual sequelae. If 20% have impaired concentration or brain fog, this could result in about 5 million ADHD cases, he said. 
 

Estimates aren’t evidence

The Swanson/Volkow commentary contains a lot of references to “might, could, and may,” said Dr. Coghill. While it’s true that COVID-19 could produce a novel etiologic subtype of ADHD, “the point here is at the moment, all of this is based on hypotheses,” he said.

The Spanish flu did produce mental health consequences – survivors reported depression, sleep disturbances, mental distraction, dizziness, and difficulties coping at work. In the United States, flu death rates from 1918 to 1920 were directly attributed to suicide rates. Unfortunately, these impacts weren’t widely researched, said Dr. Coghill.

It also seems clear that the 1918 Spanish flu outbreak was associated with significant neurological consequences, said Dr. Coghill. By 1919 and 1920, physicians and researchers in the United Kingdom were reporting increases in a variety of symptoms among some patients recovering from flu, such as neuropathy, neurasthenia, meningitis, degenerative changes in nerve cells, and a decline in visual acuity.

The EL cases Dr. Swanson mentioned did coincide with and reach epidemic proportions alongside the Spanish flu. “But still, a causal relationship is far from proven,” said Dr. Coghill.

Sol Levy, MD, described a “disease of criminals” following the 1918 pandemic, in which patients exhibited a high degree of general hyperkinesis, a difficulty in maintaining quiet attitudes, abruptness and clumsiness, and “explosive motor release of all voluntarily inhibited activities.”

However, these impairments suggest a much broader presentation typically seen in ADHD, noted Dr. Coghill.

Neurological complications occur more commonly than initially thought in severe COVID-19, with estimates ranging from 36% to 84%. But in a systematic review of neuropsychiatric complications of severe coronavirus infection, researchers found few psychiatric sequelae of these infections. While they did mention impaired concentration and difficulties with emotional ability, it’s very important to remember that these conditions “are cardinal symptoms of a wide range of psychiatric disorders,” said Dr. Coghill.

Overall, more neurological and neuropsychiatric symptoms largely confine to those with severe COVID-19, meaning they’re much less likely to occur in children and young adults, he said.

If there are severe effects of COVID-19, Dr. Swanson countered that “they might have more ADHD than the complex residual effects [Dr. Coghill] described. I hope that he’s right, but I do think there will be biological co-effects of COVID-19 that will produce symptoms that are more ADHD than other neurological disorders.”
 

Epigenetic effects

Researchers are now seeing transgenerational and intergenerational effects of potential infection. “So I certainly back high-quality studies looking at the effects of maternal and paternal infection on offspring,” said Dr. Coghill. Establishing clinical cohort studies to follow up on this population would be essential in understanding the risks of SARS-CoV-2. “That might be one way we’ll see an increase in ADHD,” said Dr. Coghill.

The reality is COVID-19 hasn’t been around for that long, and current knowledge about it is limited, he said. Rapid publications, cross-sectional or retrospective data, and poor methodological quality and rigor make generalizability difficult. In addition, limited testing and detection probably underestimate prevalence of neurological and neuropsychiatric complications.

“If history teaches us anything, it is that we should always be measured in how we glean lessons from the past. So let’s not get ahead of ourselves,” he cautioned.

An informal, post-discussion survey of session participants revealed that a slight majority – 55%-60% – expected residual effects of COVID-19 to lead to more ADHD, compared to 40%-45% who didn’t think this would happen.

Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA). Dr. Coghill worked for several pharmaceutical companies but had no disclosures relevant to this debate.

An examination of coffee consumption habits of almost 400,000 people suggests that those habits are largely driven by a person’s cardiovascular health.

©Elena Moiseeva/fotolia.com

Data from a large population database showed that people with essential hypertension, angina, or cardiac arrhythmias drank less coffee than people who had none of these conditions. When they did drink coffee, it tended to be decaffeinated.

The investigators, led by Elina Hyppönen, PhD, director of the Australian Centre for Precision Health at the University of South Australia, Adelaide, say that this predilection for avoiding coffee, which is known to produce jitteriness and heart palpitations, is based on genetics.

“If your body is telling you not to drink that extra cup of coffee, there’s likely a reason why,” Dr. Hyppönen said in an interview.

The study was published online in the American Journal of Clinical Nutrition.

“People drink coffee as a pick-me-up when they’re feeling tired, or because it tastes good, or simply because it’s part of their daily routine, but what we don’t recognize is that people subconsciously self-regulate safe levels of caffeine based on how high their blood pressure is, and this is likely a result of a protective genetic mechanism, [meaning] that someone who drinks a lot of coffee is likely more genetically tolerant of caffeine, as compared to someone who drinks very little,” Dr. Hyppönen said.

“In addition, we’ve known from past research that when people feel unwell, they tend to drink less coffee. This type of phenomenon, where disease drives behavior, is called reverse causality,” Dr. Hyppönen said.

For this analysis, she and her team used information on 390,435 individuals of European ancestry from the UK Biobank, a large epidemiologic database. Habitual coffee consumption was self-reported, and systolic and diastolic blood pressure and heart rate were measured at baseline. Cardiovascular symptoms at baseline were gleaned from hospital diagnoses, primary care records, and/or self report, the authors note.

To look at the relationship of systolic BP, diastolic BP, and heart rate with coffee consumption, they used a strategy called Mendelian randomization, which allows genetic information such as variants reflecting higher blood pressures and heart rate to be used to provide evidence for a causal association.

Results showed that participants with essential hypertension, angina, or arrhythmia were “all more likely to drink less caffeinated coffee and to be nonhabitual or decaffeinated coffee drinkers compared with those who did not report related symptoms,” the authors write.

Those with higher systolic and diastolic BP based on their genetics tended to drink less caffeinated coffee at baseline, “with consistent genetic evidence to support a causal explanation across all methods,” they noted.

They also found that those people who have a higher resting heart rate due to their genes were more likely to choose decaffeinated coffee.

“These results have two major implications,” Dr. Hyppönen said. “Firstly, they show that our bodies can regulate behavior in ways that we may not realize, and that if something does not feel good to us, there is a likely to be a reason why.”

“Second, our results show that our health status in part regulates the amount of coffee we drink. This is important, because when disease drives behavior, it can lead to misleading health associations in observational studies, and indeed, create a false impression for health benefits if the group of people who do not drink coffee also includes more people who are unwell,” she said.

For now, doctors can tell their patients that this study provides an explanation as to why research on the health effects of habitual coffee consumption has been conflicting, Dr. Hyppönen said.

“Our study also highlights the uncertainty that underlies the claimed health benefits of coffee, but at the same time, it gives a positive message about the ability of our body to regulate our level of coffee consumption in a way that helps us avoid adverse effects.”

“The most common symptoms of excessive coffee consumption are palpitations and rapid heartbeat, also known as tachycardia,” Nieca Goldberg, MD, medical director of the NYU Women’s Heart Program at NYU Langone Health, said in an interview.

“This study was designed to see if cardiac symptoms affect coffee consumption, and it showed that people with hypertension, angina, history of arrhythmias, and poor health tend to be decaffeinated coffee drinkers or no coffee drinkers,” Dr. Goldberg said.

“People naturally alter their coffee intake base on their blood pressure and symptoms of palpitations and/or rapid heart rate,” she said.

The results also suggest that, “we cannot infer health benefit or harm based on the available coffee studies,” Dr. Goldberg added.

The study was funded by the National Health and Medical Research Council, Australia. Dr. Hyppönen and Dr. Goldberg have disclosed no relevant financial relationships.

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

An examination of coffee consumption habits of almost 400,000 people suggests that those habits are largely driven by a person’s cardiovascular health.

©Elena Moiseeva/fotolia.com

Data from a large population database showed that people with essential hypertension, angina, or cardiac arrhythmias drank less coffee than people who had none of these conditions. When they did drink coffee, it tended to be decaffeinated.

The investigators, led by Elina Hyppönen, PhD, director of the Australian Centre for Precision Health at the University of South Australia, Adelaide, say that this predilection for avoiding coffee, which is known to produce jitteriness and heart palpitations, is based on genetics.

“If your body is telling you not to drink that extra cup of coffee, there’s likely a reason why,” Dr. Hyppönen said in an interview.

The study was published online in the American Journal of Clinical Nutrition.

“People drink coffee as a pick-me-up when they’re feeling tired, or because it tastes good, or simply because it’s part of their daily routine, but what we don’t recognize is that people subconsciously self-regulate safe levels of caffeine based on how high their blood pressure is, and this is likely a result of a protective genetic mechanism, [meaning] that someone who drinks a lot of coffee is likely more genetically tolerant of caffeine, as compared to someone who drinks very little,” Dr. Hyppönen said.

“In addition, we’ve known from past research that when people feel unwell, they tend to drink less coffee. This type of phenomenon, where disease drives behavior, is called reverse causality,” Dr. Hyppönen said.

For this analysis, she and her team used information on 390,435 individuals of European ancestry from the UK Biobank, a large epidemiologic database. Habitual coffee consumption was self-reported, and systolic and diastolic blood pressure and heart rate were measured at baseline. Cardiovascular symptoms at baseline were gleaned from hospital diagnoses, primary care records, and/or self report, the authors note.

To look at the relationship of systolic BP, diastolic BP, and heart rate with coffee consumption, they used a strategy called Mendelian randomization, which allows genetic information such as variants reflecting higher blood pressures and heart rate to be used to provide evidence for a causal association.

Results showed that participants with essential hypertension, angina, or arrhythmia were “all more likely to drink less caffeinated coffee and to be nonhabitual or decaffeinated coffee drinkers compared with those who did not report related symptoms,” the authors write.

Those with higher systolic and diastolic BP based on their genetics tended to drink less caffeinated coffee at baseline, “with consistent genetic evidence to support a causal explanation across all methods,” they noted.

They also found that those people who have a higher resting heart rate due to their genes were more likely to choose decaffeinated coffee.

“These results have two major implications,” Dr. Hyppönen said. “Firstly, they show that our bodies can regulate behavior in ways that we may not realize, and that if something does not feel good to us, there is a likely to be a reason why.”

“Second, our results show that our health status in part regulates the amount of coffee we drink. This is important, because when disease drives behavior, it can lead to misleading health associations in observational studies, and indeed, create a false impression for health benefits if the group of people who do not drink coffee also includes more people who are unwell,” she said.

For now, doctors can tell their patients that this study provides an explanation as to why research on the health effects of habitual coffee consumption has been conflicting, Dr. Hyppönen said.

“Our study also highlights the uncertainty that underlies the claimed health benefits of coffee, but at the same time, it gives a positive message about the ability of our body to regulate our level of coffee consumption in a way that helps us avoid adverse effects.”

“The most common symptoms of excessive coffee consumption are palpitations and rapid heartbeat, also known as tachycardia,” Nieca Goldberg, MD, medical director of the NYU Women’s Heart Program at NYU Langone Health, said in an interview.

“This study was designed to see if cardiac symptoms affect coffee consumption, and it showed that people with hypertension, angina, history of arrhythmias, and poor health tend to be decaffeinated coffee drinkers or no coffee drinkers,” Dr. Goldberg said.

“People naturally alter their coffee intake base on their blood pressure and symptoms of palpitations and/or rapid heart rate,” she said.

The results also suggest that, “we cannot infer health benefit or harm based on the available coffee studies,” Dr. Goldberg added.

The study was funded by the National Health and Medical Research Council, Australia. Dr. Hyppönen and Dr. Goldberg have disclosed no relevant financial relationships.

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

An examination of coffee consumption habits of almost 400,000 people suggests that those habits are largely driven by a person’s cardiovascular health.

©Elena Moiseeva/fotolia.com

Data from a large population database showed that people with essential hypertension, angina, or cardiac arrhythmias drank less coffee than people who had none of these conditions. When they did drink coffee, it tended to be decaffeinated.

The investigators, led by Elina Hyppönen, PhD, director of the Australian Centre for Precision Health at the University of South Australia, Adelaide, say that this predilection for avoiding coffee, which is known to produce jitteriness and heart palpitations, is based on genetics.

“If your body is telling you not to drink that extra cup of coffee, there’s likely a reason why,” Dr. Hyppönen said in an interview.

The study was published online in the American Journal of Clinical Nutrition.

“People drink coffee as a pick-me-up when they’re feeling tired, or because it tastes good, or simply because it’s part of their daily routine, but what we don’t recognize is that people subconsciously self-regulate safe levels of caffeine based on how high their blood pressure is, and this is likely a result of a protective genetic mechanism, [meaning] that someone who drinks a lot of coffee is likely more genetically tolerant of caffeine, as compared to someone who drinks very little,” Dr. Hyppönen said.

“In addition, we’ve known from past research that when people feel unwell, they tend to drink less coffee. This type of phenomenon, where disease drives behavior, is called reverse causality,” Dr. Hyppönen said.

For this analysis, she and her team used information on 390,435 individuals of European ancestry from the UK Biobank, a large epidemiologic database. Habitual coffee consumption was self-reported, and systolic and diastolic blood pressure and heart rate were measured at baseline. Cardiovascular symptoms at baseline were gleaned from hospital diagnoses, primary care records, and/or self report, the authors note.

To look at the relationship of systolic BP, diastolic BP, and heart rate with coffee consumption, they used a strategy called Mendelian randomization, which allows genetic information such as variants reflecting higher blood pressures and heart rate to be used to provide evidence for a causal association.

Results showed that participants with essential hypertension, angina, or arrhythmia were “all more likely to drink less caffeinated coffee and to be nonhabitual or decaffeinated coffee drinkers compared with those who did not report related symptoms,” the authors write.

Those with higher systolic and diastolic BP based on their genetics tended to drink less caffeinated coffee at baseline, “with consistent genetic evidence to support a causal explanation across all methods,” they noted.

They also found that those people who have a higher resting heart rate due to their genes were more likely to choose decaffeinated coffee.

“These results have two major implications,” Dr. Hyppönen said. “Firstly, they show that our bodies can regulate behavior in ways that we may not realize, and that if something does not feel good to us, there is a likely to be a reason why.”

“Second, our results show that our health status in part regulates the amount of coffee we drink. This is important, because when disease drives behavior, it can lead to misleading health associations in observational studies, and indeed, create a false impression for health benefits if the group of people who do not drink coffee also includes more people who are unwell,” she said.

For now, doctors can tell their patients that this study provides an explanation as to why research on the health effects of habitual coffee consumption has been conflicting, Dr. Hyppönen said.

“Our study also highlights the uncertainty that underlies the claimed health benefits of coffee, but at the same time, it gives a positive message about the ability of our body to regulate our level of coffee consumption in a way that helps us avoid adverse effects.”

“The most common symptoms of excessive coffee consumption are palpitations and rapid heartbeat, also known as tachycardia,” Nieca Goldberg, MD, medical director of the NYU Women’s Heart Program at NYU Langone Health, said in an interview.

“This study was designed to see if cardiac symptoms affect coffee consumption, and it showed that people with hypertension, angina, history of arrhythmias, and poor health tend to be decaffeinated coffee drinkers or no coffee drinkers,” Dr. Goldberg said.

“People naturally alter their coffee intake base on their blood pressure and symptoms of palpitations and/or rapid heart rate,” she said.

The results also suggest that, “we cannot infer health benefit or harm based on the available coffee studies,” Dr. Goldberg added.

The study was funded by the National Health and Medical Research Council, Australia. Dr. Hyppönen and Dr. Goldberg have disclosed no relevant financial relationships.

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

Rheumatology News and the Coalition of State Rheumatology Organizations have partnered together to keep rheumatologists regularly informed on the advocacy issues of the day and perhaps inspire those who may be on the fence about finding “room” in their lives for action. This inaugural piece tells how CSRO President Dr. Madelaine (Mattie) A. Feldman views advocacy and how she found her way to action.

As a rheumatologist in private practice for 30 years, with husband and kids (and now grandkids), an active social life, and an exercise regimen, I realized if I were to become active in advocacy I would have to make room for it in my busy schedule. We all come up against the question of where will we find the time for a new hobby, exercise, joining a new organization, or even just eating right? Next comes the priority list discussion. How important is advocacy for my patients, my specialty, and my profession? Ultimately, how important is it for me? Where did that desire to get involved even come from? Why have I become so passionate about the issues?

For me, the answer to these questions goes back to the 1960s when I was growing up in New Orleans. My mom participated in civil rights protests, which did not make our family popular in the neighborhood, back when the KKK put flyers on everyone’s screen door. My mother didn’t care and told me that, no matter what people said, it was our duty to stand up for what was right. That was a long time ago and sadly my mom passed away just a year after I was old enough to vote. Her words have stayed with me and are more important now than ever.

Striving for justice despite how formidable the foe is requires an inner knowing that what you are doing is meaningful and will make a difference maybe not now, maybe not next year. At some point you must believe that your efforts will create a change for the better, small as it may be. My “saying” on Twitter (@MattieRheumMD) is “I’ll keep doing what I’m doing until my cynicism catches up to my passion.”

The story about my mom is just one of the many stories in my life taking me to where I am today. We all have them. I think the reason many of us go into rheumatology may be similar to the reasoning that leads one to advocacy efforts. At this point in time we can’t yet offer a cure, but we can point to a path that leads to improvements in the lives of our patients. I have to remind myself of that, every time there is an advocacy battle ahead, whether with insurance companies or the government ... increments are important.
 

The four Ps of advocacy

Living with compromise is hard, particularly when working within a system that needs a complete overhaul. Still, compromise is the key to getting anything done. Compromise is one of the four Ps of advocacy. I realize that compromise doesn’t start with a P, but it is such an integral part of advocacy, I am making allowances for it. The other Ps include patience, persistence/perseverance, and passion. I’m sure there are many others that could be part of the P family, like planning and performance, but let’s stick with these.

You don’t need to have all of these qualities when you start on the road to action in advocacy. For example, my passion came first. It developed when my patients could not get access to the treatments they needed. For many reasons, the medications were either unavailable (i.e., not on formulary, tiered very high) or unaffordable (i.e., copay too high, deductible too high). My passion deepened when I saw the hypocrisy within the drug-supply channel and the mistruths being told by those who profit from this channel. It wasn’t the “profit” part that bothered me, as I’m a believer in the free market. But this was not free market, and the companies were actually profiteering on the backs of my patients and justifying it by claiming they were saving the health care system billions of dollars. The fallacy of that claim and the players in this broken system are stories for another day.

Persistence came next for me. If you let up on the message, things might not only stay the same but could get worse. Perseverance is part of persistence because you need it to keep knocking on the same door even after that door is metaphorically (hopefully not literally) slammed in your face. Often, I will feel like a broken record and think that everyone has already heard the issues, not only from me but also from my fellow advocates. But never underestimate how many times a message, particularly on a difficult issue to understand, needs to be heard before it is fully comprehended.

Patience is one of the more difficult attributes to practice when you want action. I want things to happen yesterday – not tomorrow and definitely not next year. I have learned that the wheels of change turn quite slowly in this arena, sometimes pausing for inordinately long periods of time. I realize now that during the long wait, new facts can arise, allowing me to shape a different advocacy approach, one that ultimately bolsters my case. It still is very difficult to hear that a piece of legislation that seemed to be moving forward suddenly died and won’t be heard again until the next session. With patience you move forward with a smile, maybe a half-hearted one, but a smile nonetheless. This just makes life better.

Then there is compromise. This took me the longest to understand, particularly on the issues where my passion ran the deepest. Here is where passion could potentially get in the way of action. Feeling very strongly about an issue makes it difficult to let any piece of your ideal end result fall by the wayside. Here is where the saying “the perfect is the enemy of the good” comes into play. Just because you can’t have it all, doesn’t mean you can’t do good by achieving just part of what you have been striving for. Remember if you seek perfection, without compromise, you may lose the entire battle. Is there such a thing as compromising too much? I think so, but that may just be my passion speaking.

Rheumatology News and the Coalition of State Rheumatology Organizations started this column to keep you informed about current advocacy issues in rheumatology and perhaps inspire those who may be on the fence about finding “room” in their lives for action.

Advocacy doesn’t have to take up much room in your life. It can be as simple as clicking on CSRO.info/map, finding your state, and taking action by writing a letter to your representative on an important piece of legislation, like an accumulator adjustment ban (lots more on that in future columns). Or maybe just finding the time to read this column is all the action you have room for. We all have different amounts of space for any particular activity in our busy lives. It seems one of my stories from childhood created that space for advocacy in my life. I guess you could say it created a “Rheum” for Action.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is President of the CSRO, chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

Rheumatology News and the Coalition of State Rheumatology Organizations have partnered together to keep rheumatologists regularly informed on the advocacy issues of the day and perhaps inspire those who may be on the fence about finding “room” in their lives for action. This inaugural piece tells how CSRO President Dr. Madelaine (Mattie) A. Feldman views advocacy and how she found her way to action.

As a rheumatologist in private practice for 30 years, with husband and kids (and now grandkids), an active social life, and an exercise regimen, I realized if I were to become active in advocacy I would have to make room for it in my busy schedule. We all come up against the question of where will we find the time for a new hobby, exercise, joining a new organization, or even just eating right? Next comes the priority list discussion. How important is advocacy for my patients, my specialty, and my profession? Ultimately, how important is it for me? Where did that desire to get involved even come from? Why have I become so passionate about the issues?

For me, the answer to these questions goes back to the 1960s when I was growing up in New Orleans. My mom participated in civil rights protests, which did not make our family popular in the neighborhood, back when the KKK put flyers on everyone’s screen door. My mother didn’t care and told me that, no matter what people said, it was our duty to stand up for what was right. That was a long time ago and sadly my mom passed away just a year after I was old enough to vote. Her words have stayed with me and are more important now than ever.

Striving for justice despite how formidable the foe is requires an inner knowing that what you are doing is meaningful and will make a difference maybe not now, maybe not next year. At some point you must believe that your efforts will create a change for the better, small as it may be. My “saying” on Twitter (@MattieRheumMD) is “I’ll keep doing what I’m doing until my cynicism catches up to my passion.”

The story about my mom is just one of the many stories in my life taking me to where I am today. We all have them. I think the reason many of us go into rheumatology may be similar to the reasoning that leads one to advocacy efforts. At this point in time we can’t yet offer a cure, but we can point to a path that leads to improvements in the lives of our patients. I have to remind myself of that, every time there is an advocacy battle ahead, whether with insurance companies or the government ... increments are important.
 

The four Ps of advocacy

Living with compromise is hard, particularly when working within a system that needs a complete overhaul. Still, compromise is the key to getting anything done. Compromise is one of the four Ps of advocacy. I realize that compromise doesn’t start with a P, but it is such an integral part of advocacy, I am making allowances for it. The other Ps include patience, persistence/perseverance, and passion. I’m sure there are many others that could be part of the P family, like planning and performance, but let’s stick with these.

You don’t need to have all of these qualities when you start on the road to action in advocacy. For example, my passion came first. It developed when my patients could not get access to the treatments they needed. For many reasons, the medications were either unavailable (i.e., not on formulary, tiered very high) or unaffordable (i.e., copay too high, deductible too high). My passion deepened when I saw the hypocrisy within the drug-supply channel and the mistruths being told by those who profit from this channel. It wasn’t the “profit” part that bothered me, as I’m a believer in the free market. But this was not free market, and the companies were actually profiteering on the backs of my patients and justifying it by claiming they were saving the health care system billions of dollars. The fallacy of that claim and the players in this broken system are stories for another day.

Persistence came next for me. If you let up on the message, things might not only stay the same but could get worse. Perseverance is part of persistence because you need it to keep knocking on the same door even after that door is metaphorically (hopefully not literally) slammed in your face. Often, I will feel like a broken record and think that everyone has already heard the issues, not only from me but also from my fellow advocates. But never underestimate how many times a message, particularly on a difficult issue to understand, needs to be heard before it is fully comprehended.

Patience is one of the more difficult attributes to practice when you want action. I want things to happen yesterday – not tomorrow and definitely not next year. I have learned that the wheels of change turn quite slowly in this arena, sometimes pausing for inordinately long periods of time. I realize now that during the long wait, new facts can arise, allowing me to shape a different advocacy approach, one that ultimately bolsters my case. It still is very difficult to hear that a piece of legislation that seemed to be moving forward suddenly died and won’t be heard again until the next session. With patience you move forward with a smile, maybe a half-hearted one, but a smile nonetheless. This just makes life better.

Then there is compromise. This took me the longest to understand, particularly on the issues where my passion ran the deepest. Here is where passion could potentially get in the way of action. Feeling very strongly about an issue makes it difficult to let any piece of your ideal end result fall by the wayside. Here is where the saying “the perfect is the enemy of the good” comes into play. Just because you can’t have it all, doesn’t mean you can’t do good by achieving just part of what you have been striving for. Remember if you seek perfection, without compromise, you may lose the entire battle. Is there such a thing as compromising too much? I think so, but that may just be my passion speaking.

Rheumatology News and the Coalition of State Rheumatology Organizations started this column to keep you informed about current advocacy issues in rheumatology and perhaps inspire those who may be on the fence about finding “room” in their lives for action.

Advocacy doesn’t have to take up much room in your life. It can be as simple as clicking on CSRO.info/map, finding your state, and taking action by writing a letter to your representative on an important piece of legislation, like an accumulator adjustment ban (lots more on that in future columns). Or maybe just finding the time to read this column is all the action you have room for. We all have different amounts of space for any particular activity in our busy lives. It seems one of my stories from childhood created that space for advocacy in my life. I guess you could say it created a “Rheum” for Action.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is President of the CSRO, chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

Rheumatology News and the Coalition of State Rheumatology Organizations have partnered together to keep rheumatologists regularly informed on the advocacy issues of the day and perhaps inspire those who may be on the fence about finding “room” in their lives for action. This inaugural piece tells how CSRO President Dr. Madelaine (Mattie) A. Feldman views advocacy and how she found her way to action.

As a rheumatologist in private practice for 30 years, with husband and kids (and now grandkids), an active social life, and an exercise regimen, I realized if I were to become active in advocacy I would have to make room for it in my busy schedule. We all come up against the question of where will we find the time for a new hobby, exercise, joining a new organization, or even just eating right? Next comes the priority list discussion. How important is advocacy for my patients, my specialty, and my profession? Ultimately, how important is it for me? Where did that desire to get involved even come from? Why have I become so passionate about the issues?

For me, the answer to these questions goes back to the 1960s when I was growing up in New Orleans. My mom participated in civil rights protests, which did not make our family popular in the neighborhood, back when the KKK put flyers on everyone’s screen door. My mother didn’t care and told me that, no matter what people said, it was our duty to stand up for what was right. That was a long time ago and sadly my mom passed away just a year after I was old enough to vote. Her words have stayed with me and are more important now than ever.

Striving for justice despite how formidable the foe is requires an inner knowing that what you are doing is meaningful and will make a difference maybe not now, maybe not next year. At some point you must believe that your efforts will create a change for the better, small as it may be. My “saying” on Twitter (@MattieRheumMD) is “I’ll keep doing what I’m doing until my cynicism catches up to my passion.”

The story about my mom is just one of the many stories in my life taking me to where I am today. We all have them. I think the reason many of us go into rheumatology may be similar to the reasoning that leads one to advocacy efforts. At this point in time we can’t yet offer a cure, but we can point to a path that leads to improvements in the lives of our patients. I have to remind myself of that, every time there is an advocacy battle ahead, whether with insurance companies or the government ... increments are important.
 

The four Ps of advocacy

Living with compromise is hard, particularly when working within a system that needs a complete overhaul. Still, compromise is the key to getting anything done. Compromise is one of the four Ps of advocacy. I realize that compromise doesn’t start with a P, but it is such an integral part of advocacy, I am making allowances for it. The other Ps include patience, persistence/perseverance, and passion. I’m sure there are many others that could be part of the P family, like planning and performance, but let’s stick with these.

You don’t need to have all of these qualities when you start on the road to action in advocacy. For example, my passion came first. It developed when my patients could not get access to the treatments they needed. For many reasons, the medications were either unavailable (i.e., not on formulary, tiered very high) or unaffordable (i.e., copay too high, deductible too high). My passion deepened when I saw the hypocrisy within the drug-supply channel and the mistruths being told by those who profit from this channel. It wasn’t the “profit” part that bothered me, as I’m a believer in the free market. But this was not free market, and the companies were actually profiteering on the backs of my patients and justifying it by claiming they were saving the health care system billions of dollars. The fallacy of that claim and the players in this broken system are stories for another day.

Persistence came next for me. If you let up on the message, things might not only stay the same but could get worse. Perseverance is part of persistence because you need it to keep knocking on the same door even after that door is metaphorically (hopefully not literally) slammed in your face. Often, I will feel like a broken record and think that everyone has already heard the issues, not only from me but also from my fellow advocates. But never underestimate how many times a message, particularly on a difficult issue to understand, needs to be heard before it is fully comprehended.

Patience is one of the more difficult attributes to practice when you want action. I want things to happen yesterday – not tomorrow and definitely not next year. I have learned that the wheels of change turn quite slowly in this arena, sometimes pausing for inordinately long periods of time. I realize now that during the long wait, new facts can arise, allowing me to shape a different advocacy approach, one that ultimately bolsters my case. It still is very difficult to hear that a piece of legislation that seemed to be moving forward suddenly died and won’t be heard again until the next session. With patience you move forward with a smile, maybe a half-hearted one, but a smile nonetheless. This just makes life better.

Then there is compromise. This took me the longest to understand, particularly on the issues where my passion ran the deepest. Here is where passion could potentially get in the way of action. Feeling very strongly about an issue makes it difficult to let any piece of your ideal end result fall by the wayside. Here is where the saying “the perfect is the enemy of the good” comes into play. Just because you can’t have it all, doesn’t mean you can’t do good by achieving just part of what you have been striving for. Remember if you seek perfection, without compromise, you may lose the entire battle. Is there such a thing as compromising too much? I think so, but that may just be my passion speaking.

Rheumatology News and the Coalition of State Rheumatology Organizations started this column to keep you informed about current advocacy issues in rheumatology and perhaps inspire those who may be on the fence about finding “room” in their lives for action.

Advocacy doesn’t have to take up much room in your life. It can be as simple as clicking on CSRO.info/map, finding your state, and taking action by writing a letter to your representative on an important piece of legislation, like an accumulator adjustment ban (lots more on that in future columns). Or maybe just finding the time to read this column is all the action you have room for. We all have different amounts of space for any particular activity in our busy lives. It seems one of my stories from childhood created that space for advocacy in my life. I guess you could say it created a “Rheum” for Action.

Dr. Feldman is a rheumatologist in private practice with The Rheumatology Group in New Orleans. She is President of the CSRO, chair of the Alliance for Safe Biologic Medicines, and a past member of the American College of Rheumatology insurance subcommittee. You can reach her at [email protected].

William of Ockham would have been proud because, at this year’s American Gastroenterological Association’s Shark Tank pitch competition, one product clearly demonstrated Ockham’s razor – that sometimes the simplest solution is best – and came away as the winner at the 2021 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology.

Courtesy Dr. Toufic Kachaamy

Out of five innovative products, ranging from an educational app to a high-tech anorectal sensor, all aimed at improving outcomes in patients with gastrointestinal disorders, the winner was ... drumroll please ...

A needle.

That’s it. A needle. But not like any other needle.


 

Winner: Toufic Kachaamy, MD, FASGE, AGAF – An EUS-guided access needle

This EUS-guided access needle, invented by Dr. Kachaamy, enterprise clinical leader at Cancer Treatment Centers of America, Phoenix, is a simple device that overcomes a longstanding challenge presented by endoscopic retrograde cholangiopancreatography (ERCP): biliary access.

Many “ERCPs are considered difficult, and sometimes fail, depending on the center and the endoscopist,” Dr. Kachaamy said during a virtual presentation. “Most failures are due to failed initial access to the bile duct.”

Indeed, one study cited a failure rate in ductal cannulation of 5%-15% even among experienced hands.

Failure can have several consequences, Dr. Kachaamy noted, including increased complications, higher cost, delayed care, longer hospitalization, and greater likelihood of patient transfer.

He went on to explain why biliary access can be so challenging and how this EUS-guided access needle helps address these issues.

“[The] two main limitations [during endoscopic ultrasound–guided biliary access] are directing the wire into the narrowed areas and the wire shearing as we are manipulating the wire to get it to where we want it,” Dr. Kachaamy said. “[This EUS-guided access needle] is a 19-22 gauge, rotatable needle with a smooth, side exit for the wire to allow wire manipulation and direction without shearing.”

Dr. Kachaamy highlighted the simple design, which will keep the production cost below $300 per unit, and suggested that failed ERCPs are just the first potential indication of many. Future uses may include gallbladder access, peri-GI collection, gastrojejunostomy, and others.

In an interview, Dr. Kachaamy reacted to the win, which follows 2 years of collaborative development with Cancer Treatment Centers of America.

“For people who are innovators, there’s nothing that feels more rewarding than their ideas being recognized as adding something to the field and potentially helping people and patients,” Dr. Kachaamy said. “So [this is] very, very, very exciting. Very rewarding. Pride would probably be the best way I’d describe it.”

Dr. Kachaamy anticipates that this EUS-guided access needle will be commercially available within 1-2 years, pending regulatory approval. In the meantime, he and his colleagues are seeking a strategic partner.


 

A shark speaks

V. Raman Muthusamy, MD, AGAF, immediate past chair of the AGA Center for GI Innovation and Technology and director of endoscopy at UCLA Health System, moderated the Shark Tank session, calling it “the highlight” of the AGA Tech Summit.

Dr. Muthusamy and four other “sharks,” including a gastroenterologist, venture capitalist, regulatory device reviewer, and entrepreneur, scored the pitches using three equally weighted categories: the quality of the pitch, the level of innovation and impact on the field, and the quality of the business plan and overall feasibility.

“We saw a full spectrum [of innovations],” Dr. Muthusamy said. “I think it was an enjoyable session.”

Behind closed doors, the sharks narrowed the field to two top contenders. Ultimately, however, there could be only one winner: Dr. Kachaamy. Their decision aligned with a “Fan Favorite” audience poll.

“A lot of [Dr. Kachaamy’s win] had to do with the potential applications and commonality of the problem,” Dr. Muthusamy said in an interview. He highlighted how the EUS-guided access needle allows for an immediate response to ERCP failure without the need for a second procedure.

Dr. Muthusamy also noted that several product designs previously failed to achieve what the EUS-guided access needle has the potential to do.

“I think the feeling was that this seemed to be a way that may address some of the limitations and challenges that we’ve had with earlier [attempts at solving this problem],” Dr. Muthusamy said.

For innovators who didn’t make the cut this year, or those with products still in development, Dr. Muthusamy suggested applying next year.

“We encourage our colleagues and members of the AGA to continue to apply to this program,” Dr. Muthusamy said.
 

Other fish in the sea

Four other innovators entered the AGA Shark Tank this year. Here are snippets of their pitches:

Hans Gregersen, MD, PhD, MPH – Fecobionics
“Fecobionics is a simulated electronic stool with the consistency and shape of normal stool,” Dr. Gregersen said.

The balloon device, which contains multiple sensors, provides “real-time, quantitative, and mechanistic insights by simulating defecation.”

“It ... is inserted into the rectum,” Dr. Gregersen said. “It measures multiple pressures; it has gyroscopes that measure orientation; we can compute the bending of the device; and we can calculate the shape of the device.”

According to Dr. Gregersen, Fecobionics has “diagnostic potential for patients with fecal incontinence and for subtyping patients with constipation.” He highlighted fewer false-positives than current technology, alongside greater efficiency and lower cost.

Dr. Gregersen is a research professor at California Medical Innovations Institute, San Diego.

Mary J. Pattison, RN – Trans-Abdominal Gastric Surgical System (TAGSS)
TAGSS is a trans-abdominal gastric access device that “represents a novel and exciting means to address multiple gastrointestinal conditions that are without a standardized approach,” Ms. Pattison said. “Placed as simply as a [percutaneous endoscopic gastrostomy tube], TAGSS offers disruptive technology to address [gastroesophageal reflux disease], fundoplication, achalasia, gastroparesis, gastric tumors, and even obesity in a safe, efficient, and cost effective manner. TAGSS offers the first true hybrid approach for endoscopic/laparoscopic collaboration.”

Ms. Pattison is a nurse clinician and endoscopy assistant at WestGlen GI Consultants, Weston, Mo.

Pankaj Rajvanshi, MD, FAASLD – Healthswim App
“At this time, most patient education is provided by Dr. Google,” Dr. Rajvanshi said, “and we want to change that. We have built a platform which allows you, the physician, to create custom, curated, credible content that can be delivered seamlessly to your patients on an ongoing basis.”

Through the Healthswim app, patients subscribe to their providers, allowing access physician-approved content. Subscribers also receive provider updates through their social media feeds.

Dr. Rajvanshi is a gastroenterologist at Swedish Medical Center, Seattle.

Ali S. Karakurum, MD, FACP, FACG – A Device for Removal of Esophageal Food Impactions
“I would like to propose a device which consists of a clear overtube, a collapsible plastic cylindrical basket secured to the distal end of the overtube ... and a snare wire attached to the distal end of the basket which is controlled by the snare handle externally,” Dr. Karakurum said. “The device is ... gradually advanced over the scope for the basket to encompass the food bolus under direct visualization. Once the food bolus is within the basket, the wire loop at the end of the basket is closed via the external handle, securing the food bolus in the basket for safe removal.”

Dr. Karakurum is a gastroenterologist at Advanced Gastroenterology & Endoscopy, Port Jefferson, N.Y.

This article was updated 5/14/21.

William of Ockham would have been proud because, at this year’s American Gastroenterological Association’s Shark Tank pitch competition, one product clearly demonstrated Ockham’s razor – that sometimes the simplest solution is best – and came away as the winner at the 2021 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology.

Courtesy Dr. Toufic Kachaamy

Out of five innovative products, ranging from an educational app to a high-tech anorectal sensor, all aimed at improving outcomes in patients with gastrointestinal disorders, the winner was ... drumroll please ...

A needle.

That’s it. A needle. But not like any other needle.


 

Winner: Toufic Kachaamy, MD, FASGE, AGAF – An EUS-guided access needle

This EUS-guided access needle, invented by Dr. Kachaamy, enterprise clinical leader at Cancer Treatment Centers of America, Phoenix, is a simple device that overcomes a longstanding challenge presented by endoscopic retrograde cholangiopancreatography (ERCP): biliary access.

Many “ERCPs are considered difficult, and sometimes fail, depending on the center and the endoscopist,” Dr. Kachaamy said during a virtual presentation. “Most failures are due to failed initial access to the bile duct.”

Indeed, one study cited a failure rate in ductal cannulation of 5%-15% even among experienced hands.

Failure can have several consequences, Dr. Kachaamy noted, including increased complications, higher cost, delayed care, longer hospitalization, and greater likelihood of patient transfer.

He went on to explain why biliary access can be so challenging and how this EUS-guided access needle helps address these issues.

“[The] two main limitations [during endoscopic ultrasound–guided biliary access] are directing the wire into the narrowed areas and the wire shearing as we are manipulating the wire to get it to where we want it,” Dr. Kachaamy said. “[This EUS-guided access needle] is a 19-22 gauge, rotatable needle with a smooth, side exit for the wire to allow wire manipulation and direction without shearing.”

Dr. Kachaamy highlighted the simple design, which will keep the production cost below $300 per unit, and suggested that failed ERCPs are just the first potential indication of many. Future uses may include gallbladder access, peri-GI collection, gastrojejunostomy, and others.

In an interview, Dr. Kachaamy reacted to the win, which follows 2 years of collaborative development with Cancer Treatment Centers of America.

“For people who are innovators, there’s nothing that feels more rewarding than their ideas being recognized as adding something to the field and potentially helping people and patients,” Dr. Kachaamy said. “So [this is] very, very, very exciting. Very rewarding. Pride would probably be the best way I’d describe it.”

Dr. Kachaamy anticipates that this EUS-guided access needle will be commercially available within 1-2 years, pending regulatory approval. In the meantime, he and his colleagues are seeking a strategic partner.


 

A shark speaks

V. Raman Muthusamy, MD, AGAF, immediate past chair of the AGA Center for GI Innovation and Technology and director of endoscopy at UCLA Health System, moderated the Shark Tank session, calling it “the highlight” of the AGA Tech Summit.

Dr. Muthusamy and four other “sharks,” including a gastroenterologist, venture capitalist, regulatory device reviewer, and entrepreneur, scored the pitches using three equally weighted categories: the quality of the pitch, the level of innovation and impact on the field, and the quality of the business plan and overall feasibility.

“We saw a full spectrum [of innovations],” Dr. Muthusamy said. “I think it was an enjoyable session.”

Behind closed doors, the sharks narrowed the field to two top contenders. Ultimately, however, there could be only one winner: Dr. Kachaamy. Their decision aligned with a “Fan Favorite” audience poll.

“A lot of [Dr. Kachaamy’s win] had to do with the potential applications and commonality of the problem,” Dr. Muthusamy said in an interview. He highlighted how the EUS-guided access needle allows for an immediate response to ERCP failure without the need for a second procedure.

Dr. Muthusamy also noted that several product designs previously failed to achieve what the EUS-guided access needle has the potential to do.

“I think the feeling was that this seemed to be a way that may address some of the limitations and challenges that we’ve had with earlier [attempts at solving this problem],” Dr. Muthusamy said.

For innovators who didn’t make the cut this year, or those with products still in development, Dr. Muthusamy suggested applying next year.

“We encourage our colleagues and members of the AGA to continue to apply to this program,” Dr. Muthusamy said.
 

Other fish in the sea

Four other innovators entered the AGA Shark Tank this year. Here are snippets of their pitches:

Hans Gregersen, MD, PhD, MPH – Fecobionics
“Fecobionics is a simulated electronic stool with the consistency and shape of normal stool,” Dr. Gregersen said.

The balloon device, which contains multiple sensors, provides “real-time, quantitative, and mechanistic insights by simulating defecation.”

“It ... is inserted into the rectum,” Dr. Gregersen said. “It measures multiple pressures; it has gyroscopes that measure orientation; we can compute the bending of the device; and we can calculate the shape of the device.”

According to Dr. Gregersen, Fecobionics has “diagnostic potential for patients with fecal incontinence and for subtyping patients with constipation.” He highlighted fewer false-positives than current technology, alongside greater efficiency and lower cost.

Dr. Gregersen is a research professor at California Medical Innovations Institute, San Diego.

Mary J. Pattison, RN – Trans-Abdominal Gastric Surgical System (TAGSS)
TAGSS is a trans-abdominal gastric access device that “represents a novel and exciting means to address multiple gastrointestinal conditions that are without a standardized approach,” Ms. Pattison said. “Placed as simply as a [percutaneous endoscopic gastrostomy tube], TAGSS offers disruptive technology to address [gastroesophageal reflux disease], fundoplication, achalasia, gastroparesis, gastric tumors, and even obesity in a safe, efficient, and cost effective manner. TAGSS offers the first true hybrid approach for endoscopic/laparoscopic collaboration.”

Ms. Pattison is a nurse clinician and endoscopy assistant at WestGlen GI Consultants, Weston, Mo.

Pankaj Rajvanshi, MD, FAASLD – Healthswim App
“At this time, most patient education is provided by Dr. Google,” Dr. Rajvanshi said, “and we want to change that. We have built a platform which allows you, the physician, to create custom, curated, credible content that can be delivered seamlessly to your patients on an ongoing basis.”

Through the Healthswim app, patients subscribe to their providers, allowing access physician-approved content. Subscribers also receive provider updates through their social media feeds.

Dr. Rajvanshi is a gastroenterologist at Swedish Medical Center, Seattle.

Ali S. Karakurum, MD, FACP, FACG – A Device for Removal of Esophageal Food Impactions
“I would like to propose a device which consists of a clear overtube, a collapsible plastic cylindrical basket secured to the distal end of the overtube ... and a snare wire attached to the distal end of the basket which is controlled by the snare handle externally,” Dr. Karakurum said. “The device is ... gradually advanced over the scope for the basket to encompass the food bolus under direct visualization. Once the food bolus is within the basket, the wire loop at the end of the basket is closed via the external handle, securing the food bolus in the basket for safe removal.”

Dr. Karakurum is a gastroenterologist at Advanced Gastroenterology & Endoscopy, Port Jefferson, N.Y.

This article was updated 5/14/21.

William of Ockham would have been proud because, at this year’s American Gastroenterological Association’s Shark Tank pitch competition, one product clearly demonstrated Ockham’s razor – that sometimes the simplest solution is best – and came away as the winner at the 2021 AGA Tech Summit sponsored by the AGA Center for GI Innovation and Technology.

Courtesy Dr. Toufic Kachaamy

Out of five innovative products, ranging from an educational app to a high-tech anorectal sensor, all aimed at improving outcomes in patients with gastrointestinal disorders, the winner was ... drumroll please ...

A needle.

That’s it. A needle. But not like any other needle.


 

Winner: Toufic Kachaamy, MD, FASGE, AGAF – An EUS-guided access needle

This EUS-guided access needle, invented by Dr. Kachaamy, enterprise clinical leader at Cancer Treatment Centers of America, Phoenix, is a simple device that overcomes a longstanding challenge presented by endoscopic retrograde cholangiopancreatography (ERCP): biliary access.

Many “ERCPs are considered difficult, and sometimes fail, depending on the center and the endoscopist,” Dr. Kachaamy said during a virtual presentation. “Most failures are due to failed initial access to the bile duct.”

Indeed, one study cited a failure rate in ductal cannulation of 5%-15% even among experienced hands.

Failure can have several consequences, Dr. Kachaamy noted, including increased complications, higher cost, delayed care, longer hospitalization, and greater likelihood of patient transfer.

He went on to explain why biliary access can be so challenging and how this EUS-guided access needle helps address these issues.

“[The] two main limitations [during endoscopic ultrasound–guided biliary access] are directing the wire into the narrowed areas and the wire shearing as we are manipulating the wire to get it to where we want it,” Dr. Kachaamy said. “[This EUS-guided access needle] is a 19-22 gauge, rotatable needle with a smooth, side exit for the wire to allow wire manipulation and direction without shearing.”

Dr. Kachaamy highlighted the simple design, which will keep the production cost below $300 per unit, and suggested that failed ERCPs are just the first potential indication of many. Future uses may include gallbladder access, peri-GI collection, gastrojejunostomy, and others.

In an interview, Dr. Kachaamy reacted to the win, which follows 2 years of collaborative development with Cancer Treatment Centers of America.

“For people who are innovators, there’s nothing that feels more rewarding than their ideas being recognized as adding something to the field and potentially helping people and patients,” Dr. Kachaamy said. “So [this is] very, very, very exciting. Very rewarding. Pride would probably be the best way I’d describe it.”

Dr. Kachaamy anticipates that this EUS-guided access needle will be commercially available within 1-2 years, pending regulatory approval. In the meantime, he and his colleagues are seeking a strategic partner.


 

A shark speaks

V. Raman Muthusamy, MD, AGAF, immediate past chair of the AGA Center for GI Innovation and Technology and director of endoscopy at UCLA Health System, moderated the Shark Tank session, calling it “the highlight” of the AGA Tech Summit.

Dr. Muthusamy and four other “sharks,” including a gastroenterologist, venture capitalist, regulatory device reviewer, and entrepreneur, scored the pitches using three equally weighted categories: the quality of the pitch, the level of innovation and impact on the field, and the quality of the business plan and overall feasibility.

“We saw a full spectrum [of innovations],” Dr. Muthusamy said. “I think it was an enjoyable session.”

Behind closed doors, the sharks narrowed the field to two top contenders. Ultimately, however, there could be only one winner: Dr. Kachaamy. Their decision aligned with a “Fan Favorite” audience poll.

“A lot of [Dr. Kachaamy’s win] had to do with the potential applications and commonality of the problem,” Dr. Muthusamy said in an interview. He highlighted how the EUS-guided access needle allows for an immediate response to ERCP failure without the need for a second procedure.

Dr. Muthusamy also noted that several product designs previously failed to achieve what the EUS-guided access needle has the potential to do.

“I think the feeling was that this seemed to be a way that may address some of the limitations and challenges that we’ve had with earlier [attempts at solving this problem],” Dr. Muthusamy said.

For innovators who didn’t make the cut this year, or those with products still in development, Dr. Muthusamy suggested applying next year.

“We encourage our colleagues and members of the AGA to continue to apply to this program,” Dr. Muthusamy said.
 

Other fish in the sea

Four other innovators entered the AGA Shark Tank this year. Here are snippets of their pitches:

Hans Gregersen, MD, PhD, MPH – Fecobionics
“Fecobionics is a simulated electronic stool with the consistency and shape of normal stool,” Dr. Gregersen said.

The balloon device, which contains multiple sensors, provides “real-time, quantitative, and mechanistic insights by simulating defecation.”

“It ... is inserted into the rectum,” Dr. Gregersen said. “It measures multiple pressures; it has gyroscopes that measure orientation; we can compute the bending of the device; and we can calculate the shape of the device.”

According to Dr. Gregersen, Fecobionics has “diagnostic potential for patients with fecal incontinence and for subtyping patients with constipation.” He highlighted fewer false-positives than current technology, alongside greater efficiency and lower cost.

Dr. Gregersen is a research professor at California Medical Innovations Institute, San Diego.

Mary J. Pattison, RN – Trans-Abdominal Gastric Surgical System (TAGSS)
TAGSS is a trans-abdominal gastric access device that “represents a novel and exciting means to address multiple gastrointestinal conditions that are without a standardized approach,” Ms. Pattison said. “Placed as simply as a [percutaneous endoscopic gastrostomy tube], TAGSS offers disruptive technology to address [gastroesophageal reflux disease], fundoplication, achalasia, gastroparesis, gastric tumors, and even obesity in a safe, efficient, and cost effective manner. TAGSS offers the first true hybrid approach for endoscopic/laparoscopic collaboration.”

Ms. Pattison is a nurse clinician and endoscopy assistant at WestGlen GI Consultants, Weston, Mo.

Pankaj Rajvanshi, MD, FAASLD – Healthswim App
“At this time, most patient education is provided by Dr. Google,” Dr. Rajvanshi said, “and we want to change that. We have built a platform which allows you, the physician, to create custom, curated, credible content that can be delivered seamlessly to your patients on an ongoing basis.”

Through the Healthswim app, patients subscribe to their providers, allowing access physician-approved content. Subscribers also receive provider updates through their social media feeds.

Dr. Rajvanshi is a gastroenterologist at Swedish Medical Center, Seattle.

Ali S. Karakurum, MD, FACP, FACG – A Device for Removal of Esophageal Food Impactions
“I would like to propose a device which consists of a clear overtube, a collapsible plastic cylindrical basket secured to the distal end of the overtube ... and a snare wire attached to the distal end of the basket which is controlled by the snare handle externally,” Dr. Karakurum said. “The device is ... gradually advanced over the scope for the basket to encompass the food bolus under direct visualization. Once the food bolus is within the basket, the wire loop at the end of the basket is closed via the external handle, securing the food bolus in the basket for safe removal.”

Dr. Karakurum is a gastroenterologist at Advanced Gastroenterology & Endoscopy, Port Jefferson, N.Y.

This article was updated 5/14/21.

Among patients with locally advanced resectable esophageal or junctional cancer, the overall survival benefit conferred by preoperative chemoradiotherapy persists for at least 10 years, according to long-term results of the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study (CROSS). As a result of earlier publication of CROSS data, chemoradiotherapy followed by surgery has become one of the standards of care for patients with locally advanced resectable esophageal cancer, stated lead author Ben M. Eyck, MD, of Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues in the Journal of Clinical Oncology.

In the multicenter, randomized trial, initiated in 2004, 178 patients randomized to chemoradiotherapy with subsequent surgery and 188 patients randomized to surgery alone were followed with overall survival as the primary, and cause-specific survival and risks of locoregional and distant relapse as the secondary endpoints. Chemoradiotherapy consisted of 5 weekly cycles of carboplatin (area under the curve of 2 mg/mL/min) and paclitaxel (50 mg/m² body surface area on days 1, 8, 15, 22, and 29) with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week. Mean age was 60 years (around 78% male), with squamous cell carcinoma (23%) and adenocarcinoma (75%) as the predominant histologies.

The first analysis showed low short-term toxicity and 2-year survival increased from 50% for patients receiving surgery alone to 67% for neoadjuvant chemoradiotherapy plus surgery. Five-year follow-up data were consistent with initial reporting. Long-term benefits and harms of this regimen remain unclear, according to the researchers. Neoadjuvant chemoradiotherapy’s side effects could lead to long-term death from other causes than esophageal cancer, and may not be preventing but rather merely postponing cancer-related death. The aim of the current analysis was to determine whether the observed benefits persisted beyond 5 years.

As of Dec. 31, 2018, 117/178 patients in the chemoradiotherapy-surgery arm and 144/188 in the surgery arm had died. Median follow-up for surviving patients was 147 months. Patients in the chemoradiotherapy surgery arm had better overall survival than patients in the surgery arm (hazard ratio, 0.70; 95% confidence interval, 0.55-0.89; P = .004), with a 10-year overall survival of 38% (95% CI, 31-45) and 25% (95% CI, 19-32), respectively. No significant subgroup differences were observed for overall survival. Also, there was no evidence of a time-dependent effect of neoadjuvant chemoradiotherapy on overall survival. The major effect of neoadjuvant chemoradiotherapy, landmark analyses showed, was in the first 5 years of follow-up, with the effect on overall survival stabilized thereafter, with a hazard ratio approaching 1.00.
 

Cause-specific mortality

Eighty-four of 178 patients in the chemoradiotherapy-surgery arm died of esophageal cancer, with 32 dying of other causes. In the surgery arm, 121/188 died of esophageal cancer and 22 of other causes. The hazard ratio for esophageal cancer death in the chemoradiotherapy-surgery arm was 0.60 (95% CI, 0.46 to 0.80), with 10-year absolute risks of 47% (95% CI, 40-54) and 64% (95% CI,57-71), respectively, in the two arms. Death from other causes was comparable, with 10-year absolute risks of 15% (95% CI, 10-21) and 11% (95% CI, 7-16), respectively, for chemoradiotherapy-surgery versus surgery alone.

Locoregional relapse

Locoregional relapse rates were 8% (15/178) and 18% (33/188) in the chemoradiotherapy-surgery and surgery arms, respectively (HR, 0.39; 95% CI, 0.21-0.72). Eighty-seven percent of those developed within 3 years of follow-up in the chemoradiotherapy arm, with the median relapse-free interval at 3.9 months. In the surgery arm, 28 of 33 relapses (85%) developed within 3 years and the median relapse-free interval was 7.1 months. Beyond 6 years, there were no further relapses in either arm.

While synchronous distant plus locoregional relapse developed in 23 of 178 patients (13%) in the chemoradiotherapy-surgery arm and in 42 of 188 patients (22%) in the surgery arm (HR, 0.43; 95% CI, 0.26-0.72), isolated distant relapse developed at similar rates (around 27.5%) in both groups. Risk of distant relapse (with or without locoregional relapse) was lower in the chemoradiotherapy-surgery arm (HR, 0.61; 95%CI, 0.45-0.84). The median relapse-free interval was 15.1 months (interquartile range, 9.3-27.6) in the chemoradiotherapy-surgery arm and 9.0 months (IQR, 5.3-19.7) in the surgery arm.
 

Safety and health-related quality of life

The combination of paclitaxel and carboplatin with concurrent 41.4 Gy radiotherapy before surgery seems safe in the long term and does not significantly increase the risk of toxicity-related death, the researchers stated. Within the CROSS trial, short-term and long-term health-related quality of life after neoadjuvant chemoradiotherapy plus surgery for surviving patients was comparable to that after surgery alone.

Long-term persistent overall survival benefit

Ten-year CROSS results show that “for locally advanced resectable cancer of the esophagus or esophagogastric junction, preoperative chemoradiotherapy induces a long-term persistent improvement in overall survival.” Also, neoadjuvant chemoradiotherapy does not lead to an increased risk of death from other causes, and the survival benefit of long-term survivors is not compromised, compared with surgery alone. Furthermore, neoadjuvant chemoradiotherapy plus surgery according to CROSS can still be regarded as a standard of care, the researchers added.

Dr. Eyck and colleagues are currently performing the phase II TNT-OES-1 trial. It combines FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) chemotherapy followed by CROSS chemoradiotherapy in patients with advanced esophageal and junctional adenocarcinoma. If this regimen appears to be safe in advanced cancer, they plan to perform a phase III trial with this regimen in locally advanced cancer. In addition, they are currently evaluating the implementation of adjuvant nivolumab in clinical practice for patients with pathologically residual disease after CROSS + surgery, based on the recently published CheckMate 577 trial .

“If possible, we prefer adding better systemic therapy to chemoradiotherapy rather than replacing chemoradiotherapy with systemic therapy alone,” Dr. Eyck said in an interview. “The reason for this is that we would like to allow patients with a complete response to neoadjuvant therapy to undergo active surveillance instead of surgery in the near future. … Since the pathologically complete response rate after regimens containing radiotherapy is substantially higher, we still prefer the addition of radiotherapy.”

The study was funded by the Dutch Cancer Foundation (KWF Kankerbestrijding). Dr. Eyck reported no disclosures. Several of the coauthors reported consulting and advisory roles with a variety of pharmaceutical companies.

Among patients with locally advanced resectable esophageal or junctional cancer, the overall survival benefit conferred by preoperative chemoradiotherapy persists for at least 10 years, according to long-term results of the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study (CROSS). As a result of earlier publication of CROSS data, chemoradiotherapy followed by surgery has become one of the standards of care for patients with locally advanced resectable esophageal cancer, stated lead author Ben M. Eyck, MD, of Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues in the Journal of Clinical Oncology.

In the multicenter, randomized trial, initiated in 2004, 178 patients randomized to chemoradiotherapy with subsequent surgery and 188 patients randomized to surgery alone were followed with overall survival as the primary, and cause-specific survival and risks of locoregional and distant relapse as the secondary endpoints. Chemoradiotherapy consisted of 5 weekly cycles of carboplatin (area under the curve of 2 mg/mL/min) and paclitaxel (50 mg/m² body surface area on days 1, 8, 15, 22, and 29) with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week. Mean age was 60 years (around 78% male), with squamous cell carcinoma (23%) and adenocarcinoma (75%) as the predominant histologies.

The first analysis showed low short-term toxicity and 2-year survival increased from 50% for patients receiving surgery alone to 67% for neoadjuvant chemoradiotherapy plus surgery. Five-year follow-up data were consistent with initial reporting. Long-term benefits and harms of this regimen remain unclear, according to the researchers. Neoadjuvant chemoradiotherapy’s side effects could lead to long-term death from other causes than esophageal cancer, and may not be preventing but rather merely postponing cancer-related death. The aim of the current analysis was to determine whether the observed benefits persisted beyond 5 years.

As of Dec. 31, 2018, 117/178 patients in the chemoradiotherapy-surgery arm and 144/188 in the surgery arm had died. Median follow-up for surviving patients was 147 months. Patients in the chemoradiotherapy surgery arm had better overall survival than patients in the surgery arm (hazard ratio, 0.70; 95% confidence interval, 0.55-0.89; P = .004), with a 10-year overall survival of 38% (95% CI, 31-45) and 25% (95% CI, 19-32), respectively. No significant subgroup differences were observed for overall survival. Also, there was no evidence of a time-dependent effect of neoadjuvant chemoradiotherapy on overall survival. The major effect of neoadjuvant chemoradiotherapy, landmark analyses showed, was in the first 5 years of follow-up, with the effect on overall survival stabilized thereafter, with a hazard ratio approaching 1.00.
 

Cause-specific mortality

Eighty-four of 178 patients in the chemoradiotherapy-surgery arm died of esophageal cancer, with 32 dying of other causes. In the surgery arm, 121/188 died of esophageal cancer and 22 of other causes. The hazard ratio for esophageal cancer death in the chemoradiotherapy-surgery arm was 0.60 (95% CI, 0.46 to 0.80), with 10-year absolute risks of 47% (95% CI, 40-54) and 64% (95% CI,57-71), respectively, in the two arms. Death from other causes was comparable, with 10-year absolute risks of 15% (95% CI, 10-21) and 11% (95% CI, 7-16), respectively, for chemoradiotherapy-surgery versus surgery alone.

Locoregional relapse

Locoregional relapse rates were 8% (15/178) and 18% (33/188) in the chemoradiotherapy-surgery and surgery arms, respectively (HR, 0.39; 95% CI, 0.21-0.72). Eighty-seven percent of those developed within 3 years of follow-up in the chemoradiotherapy arm, with the median relapse-free interval at 3.9 months. In the surgery arm, 28 of 33 relapses (85%) developed within 3 years and the median relapse-free interval was 7.1 months. Beyond 6 years, there were no further relapses in either arm.

While synchronous distant plus locoregional relapse developed in 23 of 178 patients (13%) in the chemoradiotherapy-surgery arm and in 42 of 188 patients (22%) in the surgery arm (HR, 0.43; 95% CI, 0.26-0.72), isolated distant relapse developed at similar rates (around 27.5%) in both groups. Risk of distant relapse (with or without locoregional relapse) was lower in the chemoradiotherapy-surgery arm (HR, 0.61; 95%CI, 0.45-0.84). The median relapse-free interval was 15.1 months (interquartile range, 9.3-27.6) in the chemoradiotherapy-surgery arm and 9.0 months (IQR, 5.3-19.7) in the surgery arm.
 

Safety and health-related quality of life

The combination of paclitaxel and carboplatin with concurrent 41.4 Gy radiotherapy before surgery seems safe in the long term and does not significantly increase the risk of toxicity-related death, the researchers stated. Within the CROSS trial, short-term and long-term health-related quality of life after neoadjuvant chemoradiotherapy plus surgery for surviving patients was comparable to that after surgery alone.

Long-term persistent overall survival benefit

Ten-year CROSS results show that “for locally advanced resectable cancer of the esophagus or esophagogastric junction, preoperative chemoradiotherapy induces a long-term persistent improvement in overall survival.” Also, neoadjuvant chemoradiotherapy does not lead to an increased risk of death from other causes, and the survival benefit of long-term survivors is not compromised, compared with surgery alone. Furthermore, neoadjuvant chemoradiotherapy plus surgery according to CROSS can still be regarded as a standard of care, the researchers added.

Dr. Eyck and colleagues are currently performing the phase II TNT-OES-1 trial. It combines FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) chemotherapy followed by CROSS chemoradiotherapy in patients with advanced esophageal and junctional adenocarcinoma. If this regimen appears to be safe in advanced cancer, they plan to perform a phase III trial with this regimen in locally advanced cancer. In addition, they are currently evaluating the implementation of adjuvant nivolumab in clinical practice for patients with pathologically residual disease after CROSS + surgery, based on the recently published CheckMate 577 trial .

“If possible, we prefer adding better systemic therapy to chemoradiotherapy rather than replacing chemoradiotherapy with systemic therapy alone,” Dr. Eyck said in an interview. “The reason for this is that we would like to allow patients with a complete response to neoadjuvant therapy to undergo active surveillance instead of surgery in the near future. … Since the pathologically complete response rate after regimens containing radiotherapy is substantially higher, we still prefer the addition of radiotherapy.”

The study was funded by the Dutch Cancer Foundation (KWF Kankerbestrijding). Dr. Eyck reported no disclosures. Several of the coauthors reported consulting and advisory roles with a variety of pharmaceutical companies.

Among patients with locally advanced resectable esophageal or junctional cancer, the overall survival benefit conferred by preoperative chemoradiotherapy persists for at least 10 years, according to long-term results of the Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study (CROSS). As a result of earlier publication of CROSS data, chemoradiotherapy followed by surgery has become one of the standards of care for patients with locally advanced resectable esophageal cancer, stated lead author Ben M. Eyck, MD, of Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues in the Journal of Clinical Oncology.

In the multicenter, randomized trial, initiated in 2004, 178 patients randomized to chemoradiotherapy with subsequent surgery and 188 patients randomized to surgery alone were followed with overall survival as the primary, and cause-specific survival and risks of locoregional and distant relapse as the secondary endpoints. Chemoradiotherapy consisted of 5 weekly cycles of carboplatin (area under the curve of 2 mg/mL/min) and paclitaxel (50 mg/m² body surface area on days 1, 8, 15, 22, and 29) with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week. Mean age was 60 years (around 78% male), with squamous cell carcinoma (23%) and adenocarcinoma (75%) as the predominant histologies.

The first analysis showed low short-term toxicity and 2-year survival increased from 50% for patients receiving surgery alone to 67% for neoadjuvant chemoradiotherapy plus surgery. Five-year follow-up data were consistent with initial reporting. Long-term benefits and harms of this regimen remain unclear, according to the researchers. Neoadjuvant chemoradiotherapy’s side effects could lead to long-term death from other causes than esophageal cancer, and may not be preventing but rather merely postponing cancer-related death. The aim of the current analysis was to determine whether the observed benefits persisted beyond 5 years.

As of Dec. 31, 2018, 117/178 patients in the chemoradiotherapy-surgery arm and 144/188 in the surgery arm had died. Median follow-up for surviving patients was 147 months. Patients in the chemoradiotherapy surgery arm had better overall survival than patients in the surgery arm (hazard ratio, 0.70; 95% confidence interval, 0.55-0.89; P = .004), with a 10-year overall survival of 38% (95% CI, 31-45) and 25% (95% CI, 19-32), respectively. No significant subgroup differences were observed for overall survival. Also, there was no evidence of a time-dependent effect of neoadjuvant chemoradiotherapy on overall survival. The major effect of neoadjuvant chemoradiotherapy, landmark analyses showed, was in the first 5 years of follow-up, with the effect on overall survival stabilized thereafter, with a hazard ratio approaching 1.00.
 

Cause-specific mortality

Eighty-four of 178 patients in the chemoradiotherapy-surgery arm died of esophageal cancer, with 32 dying of other causes. In the surgery arm, 121/188 died of esophageal cancer and 22 of other causes. The hazard ratio for esophageal cancer death in the chemoradiotherapy-surgery arm was 0.60 (95% CI, 0.46 to 0.80), with 10-year absolute risks of 47% (95% CI, 40-54) and 64% (95% CI,57-71), respectively, in the two arms. Death from other causes was comparable, with 10-year absolute risks of 15% (95% CI, 10-21) and 11% (95% CI, 7-16), respectively, for chemoradiotherapy-surgery versus surgery alone.

Locoregional relapse

Locoregional relapse rates were 8% (15/178) and 18% (33/188) in the chemoradiotherapy-surgery and surgery arms, respectively (HR, 0.39; 95% CI, 0.21-0.72). Eighty-seven percent of those developed within 3 years of follow-up in the chemoradiotherapy arm, with the median relapse-free interval at 3.9 months. In the surgery arm, 28 of 33 relapses (85%) developed within 3 years and the median relapse-free interval was 7.1 months. Beyond 6 years, there were no further relapses in either arm.

While synchronous distant plus locoregional relapse developed in 23 of 178 patients (13%) in the chemoradiotherapy-surgery arm and in 42 of 188 patients (22%) in the surgery arm (HR, 0.43; 95% CI, 0.26-0.72), isolated distant relapse developed at similar rates (around 27.5%) in both groups. Risk of distant relapse (with or without locoregional relapse) was lower in the chemoradiotherapy-surgery arm (HR, 0.61; 95%CI, 0.45-0.84). The median relapse-free interval was 15.1 months (interquartile range, 9.3-27.6) in the chemoradiotherapy-surgery arm and 9.0 months (IQR, 5.3-19.7) in the surgery arm.
 

Safety and health-related quality of life

The combination of paclitaxel and carboplatin with concurrent 41.4 Gy radiotherapy before surgery seems safe in the long term and does not significantly increase the risk of toxicity-related death, the researchers stated. Within the CROSS trial, short-term and long-term health-related quality of life after neoadjuvant chemoradiotherapy plus surgery for surviving patients was comparable to that after surgery alone.

Long-term persistent overall survival benefit

Ten-year CROSS results show that “for locally advanced resectable cancer of the esophagus or esophagogastric junction, preoperative chemoradiotherapy induces a long-term persistent improvement in overall survival.” Also, neoadjuvant chemoradiotherapy does not lead to an increased risk of death from other causes, and the survival benefit of long-term survivors is not compromised, compared with surgery alone. Furthermore, neoadjuvant chemoradiotherapy plus surgery according to CROSS can still be regarded as a standard of care, the researchers added.

Dr. Eyck and colleagues are currently performing the phase II TNT-OES-1 trial. It combines FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) chemotherapy followed by CROSS chemoradiotherapy in patients with advanced esophageal and junctional adenocarcinoma. If this regimen appears to be safe in advanced cancer, they plan to perform a phase III trial with this regimen in locally advanced cancer. In addition, they are currently evaluating the implementation of adjuvant nivolumab in clinical practice for patients with pathologically residual disease after CROSS + surgery, based on the recently published CheckMate 577 trial .

“If possible, we prefer adding better systemic therapy to chemoradiotherapy rather than replacing chemoradiotherapy with systemic therapy alone,” Dr. Eyck said in an interview. “The reason for this is that we would like to allow patients with a complete response to neoadjuvant therapy to undergo active surveillance instead of surgery in the near future. … Since the pathologically complete response rate after regimens containing radiotherapy is substantially higher, we still prefer the addition of radiotherapy.”

The study was funded by the Dutch Cancer Foundation (KWF Kankerbestrijding). Dr. Eyck reported no disclosures. Several of the coauthors reported consulting and advisory roles with a variety of pharmaceutical companies.

Participants in the Alliance for Headache Disorders Advocacy session requested federal funding for headache research and treatment. While patients told their stories, a noted advocate said headache is “an eminently solvable problem, but the urgency is now.”

It is going to take more than a pandemic to stop key headache advocacy stakeholders from raising awareness of the devastating impact of migraine and cluster headache and to motivate Congress to act.

With COVID-19 still very much a part of our lives, the Alliance for Headache Disorders Advocacy (AHDA)—a nonprofit dedicated to advocating for equitable policies for people with headache disorders—moved forward with its annual Headache on the Hill advocacy day, which took place virtually for the first time via videoconferencing on March 23, 2021.

While participants missed the opportunity to travel to Washington to meet with key legislators face-to-face, optimists saw it as a chance to involve more patients, providers, researchers, and caregivers who otherwise would not be able to participate. Indeed, more were involved than ever before: 217 individuals from 47 states and 178 Congressional districts attended, meeting with influential lawmakers, including Senator Patrick Leahy (D-VT), chair of the Appropriations Committee; Senator Richard Shelby (R-AL), vice chair of the Appropriations Committee; Rep. Rose DeLauro (D-CT), chair of the House Committee on Appropriations; Senator Jon Tester (D-MT), chair of Senate Committee on Veterans’ Affairs; Senator Jerry Moran (R-KS), ranking member of the Senate Committee on Veterans’ Affairs; Senator Patty Murray (D-WA), chair of the Senate HELP Committee; and Senator Richard Burr (R-NC), ranking member of the Senate HELP Committee.

I have had the privilege of being a part of Headache on the Hill for 13 years and was pleased to participate in this year’s virtual event. Though the setting was different, our mission remained the same: to make our important legislative requests (“asks”) of as many offices in Congress as possible. This year, we had 2 asks that aim to improve headache research and access to treatment, especially for our Veterans:

• Increased research funding: The group requested that the National Institutes of Health (NIH) Helping to End Addiction Long-Term (HEAL) initiative focus on headache disorders to reduce disease burden and opioid prescribing. This would make more funding available for headache research.

• Improved treatment access: The group also asked Congress to fully fund Veterans Health Administration (VHA) Headache Disorders Centers of Excellence (HCoE), facilitating equitable access to care for disabled veterans. This would double the number of VA Centers of Excellence to treat headache disorders in our veterans.

Of course, getting results means more than simply asking. The request to our congresspeople and their staff is more likely to succeed if it is well-reasoned and backed by evidence; and the Headache on the Hill contingent delivered on these requirements.

Why Congress should direct HEAL to focus on headache disorders:

• Headache disorders are extraordinarily burdensome. As most of us know (but not all legislators are aware), 60 million Americans suffer from migraine headache; it is the second leading cause of disability lifetime in the world.¹ Additionally, cluster headache is thought to be the most severe type of pain humans can experience.²

• There is a critical need for more effective and safer treatments for headache disorders. Opioid use is known to worsen migraine frequency and severity for some and make medications for headache less effective.³ Guidelines uniformly recommend against treating migraine with opioids; yet somehow 10% of migraine sufferers actively use opioids,⁴ and nearly 60% receive opioids during visits to the emergency room.⁵

• NIH has underfunded research on headache disorders. NIH has not prioritized programs for headache disorders research despite the fact that since 2009, 17 appropriations report language statements have strongly urged NIH to do so.⁶ In fact, headache is the least-funded research area among the most burdensome diseases.^7,8 Instead, other important disorders were funded, even though Headache on the Hill advocacy arranged for the report language for headache.

• Statutory authority for the HEAL initiative calls for disease burden to be a “crucial consideration” in prioritizing research programs. Less than 1% of HEAL grants have been for headache disorders research.¹⁰ If disease burden was used as the only gauge for funding, NIH investment for migraine research would likely be 15 times higher than the roughly $20 million that has historically been allocated.⁹ We hope our work this year will get us where we need to be.

Why Congress should fully fund VHA Headache Disorders Centers of Excellence  

• Headache disorders are a major health issue for veterans. Some 350,000 Global War on Terror (GWOT) veterans have sustained traumatic brain injuries. Many of them experience headaches. In fact, research shows that half of these veterans reported 15 or more headache days per month 4 to 11 years after sustaining traumatic brain injury. Nine of every 10 veterans met the criteria for migraine.¹⁰ Moreover, 3 million GWOT veterans have been exposed to toxic open burn pits.¹¹ These individuals have been found to be twice as likely to experience functional limitations due to migraine than those who did not have burn pit duties.¹²

• Headache Centers of Excellence (HCoEs) work. In 2018, $10 million was appropriated to establish at least 5 HCoEs that provided 1) comprehensive direct patient specialized headache medicine care within the VHA; 2) consultation and referral specialized headache care centers within the VHA; 3) education and training of VHA healthcare providers in headache medicine; and 4) research to improve the quality of headache disorders care for veterans and civilians.¹³

• Fourteen sites now exist, and success continues to be demonstrated. Last year more than 400,000 veterans sought specialty care for headache disorders from the VHA.¹⁴ However, only half of these vets are within reasonable reach of a HCoE.

The asks

Armed with this evidence, we made specific asks of the House and Senate with respect to annual appropriations spending bills:

1. Legislators were asked to sign on to a letter or send their own letter to officials on the House and Senate Labor, Health and Human Services, Education, and Related Agencies appropriations subcommittees to allocate $50 million from the HEAL initiative for headache disorders research in fiscal year 2022.

2. Similarly, lawmakers were asked to sign onto a letter or send their own letter to members of the Military Construction and Veterans Affairs subcommittee to appropriate $25 million to fund a doubling of HCoEs from 14 to 28 to improve access to those seeking care for headache disorders.

Stories from Americans nationwide

Headache on the Hill is about more than just presenting evidence and making requests. If that were the case, there is a pretty good chance that, before long, legislators would be looking at their watches, checking their smartphones, and flashing knowing glances at their aides in an effort to cut things short. However, humanizing the topic by sharing stories of the toll migraine and cluster headaches take on individuals is compelling testimony that hopefully will lead to meaningful action and positive outcomes. Here is a sampling of the stories told during and after the Headache on the Hill session:

• Rachel Koh and Ronetta Stokes: Koh registered for both the 2019 and 2020 Headache on the Hill sessions, only to be forced to cancel due to migraine attacks. But this year, according to the American Migraine Foundation, she was able to participate virtually and tell her representatives why increased funding was important for her, as well as veterans, including her father and uncle. Meanwhile, Stokes, a first-time participant, said she was struck by the conversations she had with legislators. Most knew someone with migraine, and some were sufferers themselves. “The more we share and spread the word, the sooner we can end the stigma,” Stokes told the American Migraine Foundation.

• Mia Maysack: Maysack wrote about her experience in a column for Pain News Network. “I live with both migraine disease and cluster headaches, which are called ‘suicide headaches’ for good reason,” she wrote. “There’s no limit to the chaos, interruption, inconvenience, and discomfort these conditions have caused in my life, requiring my full-time attention just to manage the symptoms. The difficult experiences I and countless others have faced in seeking, finding, and attempting different forms of treatment is why I continue to advocate—even when I don't feel up to it.” Maysack added that although it is relatively easy for her to receive a medication prescription for her condition, she’d like to see more consideration given to treatments such as water therapy, massage, oxygen, and mindful meditation.

• Chloe Vruno: Vruno, a 21-year-old college student, has suffered with migraine since the age of 15. “Some days are worse than others,” she noted in an article in her local newspaper, the Steuben County, IN Herald Republican. “Most days I have to push through a migraine to make it to class, but some days are so severe that I cannot make it to classes. On days I cannot make it, I use my accommodation for attendance flexibility, or now with COVID, I Zoom into class from my room.” Vruno wanted to make her representatives aware of these types of disruptions, a regular occurrence for migraine sufferers like her. This was her second Headache on the Hill event, and she found lawmakers whom she spoke with to be “extremely attentive, engaged, and excited.”

“A moral imperative”

Stories like these from regular individuals across the United States who suffer from headache disorders go a long way in convincing legislators to act. It also helps to tap into a celebrity’s endorsement when you can. Headache on the Hill did not disappoint in this regard, with Jon Stewart, the former host of The Daily Show, appearing as a special guest during a policy panel discussion on chronic headache disorders and toxic exposure. The session, which took place virtually as part of Headache on the Hill, featured Stewart, a national advocate for service personnel with toxic exposures, and Rep. Mark Takano (D-CA), who delivered the keynote address. The panel discussion included first responders, veterans, and clinicians.

Stewart summed up the sentiments of all Headache on the Hill stakeholders this way: “This is an eminently solvable problem, but the urgency is now. People will continue to suffer needlessly if we don’t get this done. It is a moral imperative that we pass a bill on presumption as soon as possible.”

I always enjoy going to Washington on cold days in February to be part of Headache on the Hill, and I hope we will be back in-person next year. We have tripled the number of attendees over the last 13 years and have a higher percentage of great patients and advocates now. I have to give a special thanks to Dr. Bob Shapiro, Professor of Neurology at the University of Vermont, who started and has guided this phenomenal effort over the years, to Dr. Chris Gottschalk, Professor of Neurology at Yale, who is gradually taking over the reins, and to Katie MacDonald who runs the entire show, even though she suffers from chronic migraine on a daily basis.

Participants in the Alliance for Headache Disorders Advocacy session requested federal funding for headache research and treatment. While patients told their stories, a noted advocate said headache is “an eminently solvable problem, but the urgency is now.”

It is going to take more than a pandemic to stop key headache advocacy stakeholders from raising awareness of the devastating impact of migraine and cluster headache and to motivate Congress to act.

With COVID-19 still very much a part of our lives, the Alliance for Headache Disorders Advocacy (AHDA)—a nonprofit dedicated to advocating for equitable policies for people with headache disorders—moved forward with its annual Headache on the Hill advocacy day, which took place virtually for the first time via videoconferencing on March 23, 2021.

While participants missed the opportunity to travel to Washington to meet with key legislators face-to-face, optimists saw it as a chance to involve more patients, providers, researchers, and caregivers who otherwise would not be able to participate. Indeed, more were involved than ever before: 217 individuals from 47 states and 178 Congressional districts attended, meeting with influential lawmakers, including Senator Patrick Leahy (D-VT), chair of the Appropriations Committee; Senator Richard Shelby (R-AL), vice chair of the Appropriations Committee; Rep. Rose DeLauro (D-CT), chair of the House Committee on Appropriations; Senator Jon Tester (D-MT), chair of Senate Committee on Veterans’ Affairs; Senator Jerry Moran (R-KS), ranking member of the Senate Committee on Veterans’ Affairs; Senator Patty Murray (D-WA), chair of the Senate HELP Committee; and Senator Richard Burr (R-NC), ranking member of the Senate HELP Committee.

I have had the privilege of being a part of Headache on the Hill for 13 years and was pleased to participate in this year’s virtual event. Though the setting was different, our mission remained the same: to make our important legislative requests (“asks”) of as many offices in Congress as possible. This year, we had 2 asks that aim to improve headache research and access to treatment, especially for our Veterans:

• Increased research funding: The group requested that the National Institutes of Health (NIH) Helping to End Addiction Long-Term (HEAL) initiative focus on headache disorders to reduce disease burden and opioid prescribing. This would make more funding available for headache research.

• Improved treatment access: The group also asked Congress to fully fund Veterans Health Administration (VHA) Headache Disorders Centers of Excellence (HCoE), facilitating equitable access to care for disabled veterans. This would double the number of VA Centers of Excellence to treat headache disorders in our veterans.

Of course, getting results means more than simply asking. The request to our congresspeople and their staff is more likely to succeed if it is well-reasoned and backed by evidence; and the Headache on the Hill contingent delivered on these requirements.

Why Congress should direct HEAL to focus on headache disorders:

• Headache disorders are extraordinarily burdensome. As most of us know (but not all legislators are aware), 60 million Americans suffer from migraine headache; it is the second leading cause of disability lifetime in the world.¹ Additionally, cluster headache is thought to be the most severe type of pain humans can experience.²

• There is a critical need for more effective and safer treatments for headache disorders. Opioid use is known to worsen migraine frequency and severity for some and make medications for headache less effective.³ Guidelines uniformly recommend against treating migraine with opioids; yet somehow 10% of migraine sufferers actively use opioids,⁴ and nearly 60% receive opioids during visits to the emergency room.⁵

• NIH has underfunded research on headache disorders. NIH has not prioritized programs for headache disorders research despite the fact that since 2009, 17 appropriations report language statements have strongly urged NIH to do so.⁶ In fact, headache is the least-funded research area among the most burdensome diseases.^7,8 Instead, other important disorders were funded, even though Headache on the Hill advocacy arranged for the report language for headache.

• Statutory authority for the HEAL initiative calls for disease burden to be a “crucial consideration” in prioritizing research programs. Less than 1% of HEAL grants have been for headache disorders research.¹⁰ If disease burden was used as the only gauge for funding, NIH investment for migraine research would likely be 15 times higher than the roughly $20 million that has historically been allocated.⁹ We hope our work this year will get us where we need to be.

Why Congress should fully fund VHA Headache Disorders Centers of Excellence  

• Headache disorders are a major health issue for veterans. Some 350,000 Global War on Terror (GWOT) veterans have sustained traumatic brain injuries. Many of them experience headaches. In fact, research shows that half of these veterans reported 15 or more headache days per month 4 to 11 years after sustaining traumatic brain injury. Nine of every 10 veterans met the criteria for migraine.¹⁰ Moreover, 3 million GWOT veterans have been exposed to toxic open burn pits.¹¹ These individuals have been found to be twice as likely to experience functional limitations due to migraine than those who did not have burn pit duties.¹²

• Headache Centers of Excellence (HCoEs) work. In 2018, $10 million was appropriated to establish at least 5 HCoEs that provided 1) comprehensive direct patient specialized headache medicine care within the VHA; 2) consultation and referral specialized headache care centers within the VHA; 3) education and training of VHA healthcare providers in headache medicine; and 4) research to improve the quality of headache disorders care for veterans and civilians.¹³

• Fourteen sites now exist, and success continues to be demonstrated. Last year more than 400,000 veterans sought specialty care for headache disorders from the VHA.¹⁴ However, only half of these vets are within reasonable reach of a HCoE.

The asks

Armed with this evidence, we made specific asks of the House and Senate with respect to annual appropriations spending bills:

1. Legislators were asked to sign on to a letter or send their own letter to officials on the House and Senate Labor, Health and Human Services, Education, and Related Agencies appropriations subcommittees to allocate $50 million from the HEAL initiative for headache disorders research in fiscal year 2022.

2. Similarly, lawmakers were asked to sign onto a letter or send their own letter to members of the Military Construction and Veterans Affairs subcommittee to appropriate $25 million to fund a doubling of HCoEs from 14 to 28 to improve access to those seeking care for headache disorders.

Stories from Americans nationwide

Headache on the Hill is about more than just presenting evidence and making requests. If that were the case, there is a pretty good chance that, before long, legislators would be looking at their watches, checking their smartphones, and flashing knowing glances at their aides in an effort to cut things short. However, humanizing the topic by sharing stories of the toll migraine and cluster headaches take on individuals is compelling testimony that hopefully will lead to meaningful action and positive outcomes. Here is a sampling of the stories told during and after the Headache on the Hill session:

• Rachel Koh and Ronetta Stokes: Koh registered for both the 2019 and 2020 Headache on the Hill sessions, only to be forced to cancel due to migraine attacks. But this year, according to the American Migraine Foundation, she was able to participate virtually and tell her representatives why increased funding was important for her, as well as veterans, including her father and uncle. Meanwhile, Stokes, a first-time participant, said she was struck by the conversations she had with legislators. Most knew someone with migraine, and some were sufferers themselves. “The more we share and spread the word, the sooner we can end the stigma,” Stokes told the American Migraine Foundation.

• Mia Maysack: Maysack wrote about her experience in a column for Pain News Network. “I live with both migraine disease and cluster headaches, which are called ‘suicide headaches’ for good reason,” she wrote. “There’s no limit to the chaos, interruption, inconvenience, and discomfort these conditions have caused in my life, requiring my full-time attention just to manage the symptoms. The difficult experiences I and countless others have faced in seeking, finding, and attempting different forms of treatment is why I continue to advocate—even when I don't feel up to it.” Maysack added that although it is relatively easy for her to receive a medication prescription for her condition, she’d like to see more consideration given to treatments such as water therapy, massage, oxygen, and mindful meditation.

• Chloe Vruno: Vruno, a 21-year-old college student, has suffered with migraine since the age of 15. “Some days are worse than others,” she noted in an article in her local newspaper, the Steuben County, IN Herald Republican. “Most days I have to push through a migraine to make it to class, but some days are so severe that I cannot make it to classes. On days I cannot make it, I use my accommodation for attendance flexibility, or now with COVID, I Zoom into class from my room.” Vruno wanted to make her representatives aware of these types of disruptions, a regular occurrence for migraine sufferers like her. This was her second Headache on the Hill event, and she found lawmakers whom she spoke with to be “extremely attentive, engaged, and excited.”

“A moral imperative”

Stories like these from regular individuals across the United States who suffer from headache disorders go a long way in convincing legislators to act. It also helps to tap into a celebrity’s endorsement when you can. Headache on the Hill did not disappoint in this regard, with Jon Stewart, the former host of The Daily Show, appearing as a special guest during a policy panel discussion on chronic headache disorders and toxic exposure. The session, which took place virtually as part of Headache on the Hill, featured Stewart, a national advocate for service personnel with toxic exposures, and Rep. Mark Takano (D-CA), who delivered the keynote address. The panel discussion included first responders, veterans, and clinicians.

Stewart summed up the sentiments of all Headache on the Hill stakeholders this way: “This is an eminently solvable problem, but the urgency is now. People will continue to suffer needlessly if we don’t get this done. It is a moral imperative that we pass a bill on presumption as soon as possible.”

I always enjoy going to Washington on cold days in February to be part of Headache on the Hill, and I hope we will be back in-person next year. We have tripled the number of attendees over the last 13 years and have a higher percentage of great patients and advocates now. I have to give a special thanks to Dr. Bob Shapiro, Professor of Neurology at the University of Vermont, who started and has guided this phenomenal effort over the years, to Dr. Chris Gottschalk, Professor of Neurology at Yale, who is gradually taking over the reins, and to Katie MacDonald who runs the entire show, even though she suffers from chronic migraine on a daily basis.

Participants in the Alliance for Headache Disorders Advocacy session requested federal funding for headache research and treatment. While patients told their stories, a noted advocate said headache is “an eminently solvable problem, but the urgency is now.”

It is going to take more than a pandemic to stop key headache advocacy stakeholders from raising awareness of the devastating impact of migraine and cluster headache and to motivate Congress to act.

With COVID-19 still very much a part of our lives, the Alliance for Headache Disorders Advocacy (AHDA)—a nonprofit dedicated to advocating for equitable policies for people with headache disorders—moved forward with its annual Headache on the Hill advocacy day, which took place virtually for the first time via videoconferencing on March 23, 2021.

While participants missed the opportunity to travel to Washington to meet with key legislators face-to-face, optimists saw it as a chance to involve more patients, providers, researchers, and caregivers who otherwise would not be able to participate. Indeed, more were involved than ever before: 217 individuals from 47 states and 178 Congressional districts attended, meeting with influential lawmakers, including Senator Patrick Leahy (D-VT), chair of the Appropriations Committee; Senator Richard Shelby (R-AL), vice chair of the Appropriations Committee; Rep. Rose DeLauro (D-CT), chair of the House Committee on Appropriations; Senator Jon Tester (D-MT), chair of Senate Committee on Veterans’ Affairs; Senator Jerry Moran (R-KS), ranking member of the Senate Committee on Veterans’ Affairs; Senator Patty Murray (D-WA), chair of the Senate HELP Committee; and Senator Richard Burr (R-NC), ranking member of the Senate HELP Committee.

I have had the privilege of being a part of Headache on the Hill for 13 years and was pleased to participate in this year’s virtual event. Though the setting was different, our mission remained the same: to make our important legislative requests (“asks”) of as many offices in Congress as possible. This year, we had 2 asks that aim to improve headache research and access to treatment, especially for our Veterans:

• Increased research funding: The group requested that the National Institutes of Health (NIH) Helping to End Addiction Long-Term (HEAL) initiative focus on headache disorders to reduce disease burden and opioid prescribing. This would make more funding available for headache research.

• Improved treatment access: The group also asked Congress to fully fund Veterans Health Administration (VHA) Headache Disorders Centers of Excellence (HCoE), facilitating equitable access to care for disabled veterans. This would double the number of VA Centers of Excellence to treat headache disorders in our veterans.

Of course, getting results means more than simply asking. The request to our congresspeople and their staff is more likely to succeed if it is well-reasoned and backed by evidence; and the Headache on the Hill contingent delivered on these requirements.

Why Congress should direct HEAL to focus on headache disorders:

• Headache disorders are extraordinarily burdensome. As most of us know (but not all legislators are aware), 60 million Americans suffer from migraine headache; it is the second leading cause of disability lifetime in the world.¹ Additionally, cluster headache is thought to be the most severe type of pain humans can experience.²

• There is a critical need for more effective and safer treatments for headache disorders. Opioid use is known to worsen migraine frequency and severity for some and make medications for headache less effective.³ Guidelines uniformly recommend against treating migraine with opioids; yet somehow 10% of migraine sufferers actively use opioids,⁴ and nearly 60% receive opioids during visits to the emergency room.⁵

• NIH has underfunded research on headache disorders. NIH has not prioritized programs for headache disorders research despite the fact that since 2009, 17 appropriations report language statements have strongly urged NIH to do so.⁶ In fact, headache is the least-funded research area among the most burdensome diseases.^7,8 Instead, other important disorders were funded, even though Headache on the Hill advocacy arranged for the report language for headache.

• Statutory authority for the HEAL initiative calls for disease burden to be a “crucial consideration” in prioritizing research programs. Less than 1% of HEAL grants have been for headache disorders research.¹⁰ If disease burden was used as the only gauge for funding, NIH investment for migraine research would likely be 15 times higher than the roughly $20 million that has historically been allocated.⁹ We hope our work this year will get us where we need to be.

Why Congress should fully fund VHA Headache Disorders Centers of Excellence  

• Headache disorders are a major health issue for veterans. Some 350,000 Global War on Terror (GWOT) veterans have sustained traumatic brain injuries. Many of them experience headaches. In fact, research shows that half of these veterans reported 15 or more headache days per month 4 to 11 years after sustaining traumatic brain injury. Nine of every 10 veterans met the criteria for migraine.¹⁰ Moreover, 3 million GWOT veterans have been exposed to toxic open burn pits.¹¹ These individuals have been found to be twice as likely to experience functional limitations due to migraine than those who did not have burn pit duties.¹²

• Headache Centers of Excellence (HCoEs) work. In 2018, $10 million was appropriated to establish at least 5 HCoEs that provided 1) comprehensive direct patient specialized headache medicine care within the VHA; 2) consultation and referral specialized headache care centers within the VHA; 3) education and training of VHA healthcare providers in headache medicine; and 4) research to improve the quality of headache disorders care for veterans and civilians.¹³

• Fourteen sites now exist, and success continues to be demonstrated. Last year more than 400,000 veterans sought specialty care for headache disorders from the VHA.¹⁴ However, only half of these vets are within reasonable reach of a HCoE.

The asks

Armed with this evidence, we made specific asks of the House and Senate with respect to annual appropriations spending bills:

1. Legislators were asked to sign on to a letter or send their own letter to officials on the House and Senate Labor, Health and Human Services, Education, and Related Agencies appropriations subcommittees to allocate $50 million from the HEAL initiative for headache disorders research in fiscal year 2022.

2. Similarly, lawmakers were asked to sign onto a letter or send their own letter to members of the Military Construction and Veterans Affairs subcommittee to appropriate $25 million to fund a doubling of HCoEs from 14 to 28 to improve access to those seeking care for headache disorders.

Stories from Americans nationwide

Headache on the Hill is about more than just presenting evidence and making requests. If that were the case, there is a pretty good chance that, before long, legislators would be looking at their watches, checking their smartphones, and flashing knowing glances at their aides in an effort to cut things short. However, humanizing the topic by sharing stories of the toll migraine and cluster headaches take on individuals is compelling testimony that hopefully will lead to meaningful action and positive outcomes. Here is a sampling of the stories told during and after the Headache on the Hill session:

• Rachel Koh and Ronetta Stokes: Koh registered for both the 2019 and 2020 Headache on the Hill sessions, only to be forced to cancel due to migraine attacks. But this year, according to the American Migraine Foundation, she was able to participate virtually and tell her representatives why increased funding was important for her, as well as veterans, including her father and uncle. Meanwhile, Stokes, a first-time participant, said she was struck by the conversations she had with legislators. Most knew someone with migraine, and some were sufferers themselves. “The more we share and spread the word, the sooner we can end the stigma,” Stokes told the American Migraine Foundation.

• Mia Maysack: Maysack wrote about her experience in a column for Pain News Network. “I live with both migraine disease and cluster headaches, which are called ‘suicide headaches’ for good reason,” she wrote. “There’s no limit to the chaos, interruption, inconvenience, and discomfort these conditions have caused in my life, requiring my full-time attention just to manage the symptoms. The difficult experiences I and countless others have faced in seeking, finding, and attempting different forms of treatment is why I continue to advocate—even when I don't feel up to it.” Maysack added that although it is relatively easy for her to receive a medication prescription for her condition, she’d like to see more consideration given to treatments such as water therapy, massage, oxygen, and mindful meditation.

• Chloe Vruno: Vruno, a 21-year-old college student, has suffered with migraine since the age of 15. “Some days are worse than others,” she noted in an article in her local newspaper, the Steuben County, IN Herald Republican. “Most days I have to push through a migraine to make it to class, but some days are so severe that I cannot make it to classes. On days I cannot make it, I use my accommodation for attendance flexibility, or now with COVID, I Zoom into class from my room.” Vruno wanted to make her representatives aware of these types of disruptions, a regular occurrence for migraine sufferers like her. This was her second Headache on the Hill event, and she found lawmakers whom she spoke with to be “extremely attentive, engaged, and excited.”

“A moral imperative”

Stories like these from regular individuals across the United States who suffer from headache disorders go a long way in convincing legislators to act. It also helps to tap into a celebrity’s endorsement when you can. Headache on the Hill did not disappoint in this regard, with Jon Stewart, the former host of The Daily Show, appearing as a special guest during a policy panel discussion on chronic headache disorders and toxic exposure. The session, which took place virtually as part of Headache on the Hill, featured Stewart, a national advocate for service personnel with toxic exposures, and Rep. Mark Takano (D-CA), who delivered the keynote address. The panel discussion included first responders, veterans, and clinicians.

Stewart summed up the sentiments of all Headache on the Hill stakeholders this way: “This is an eminently solvable problem, but the urgency is now. People will continue to suffer needlessly if we don’t get this done. It is a moral imperative that we pass a bill on presumption as soon as possible.”

I always enjoy going to Washington on cold days in February to be part of Headache on the Hill, and I hope we will be back in-person next year. We have tripled the number of attendees over the last 13 years and have a higher percentage of great patients and advocates now. I have to give a special thanks to Dr. Bob Shapiro, Professor of Neurology at the University of Vermont, who started and has guided this phenomenal effort over the years, to Dr. Chris Gottschalk, Professor of Neurology at Yale, who is gradually taking over the reins, and to Katie MacDonald who runs the entire show, even though she suffers from chronic migraine on a daily basis.

For children with attention-deficit/hyperactivity disorder, taking a weekend or summer break from methylphenidate may have some benefits. A drug “holiday” can help assess whether a drug is still useful and possibly help with drug tolerance, weight gain, and growth suppression. But drug holidays are not without their problems, Lily Hechtman, MD, FRCP, professor at the department of psychiatry, McGill University, Montreal, said during a session at the World Congress on ADHD – Virtual Event.

Ceasing a medication can have repercussions from a health and social standpoint, cautioned Dr. Hechtman, a presenter and moderator of the session, “Unsolved mysteries in the treatment of ADHD with psychostimulants.”

The rate of drug holidays is somewhere between 30% and 40% in ADHD patients. Patients have multiple reasons for taking them, said Dr. Hechtman. The American Academy of Child & Adolescent Psychology as well as the National Institute for Health and Clinical Excellence recommend this method to assess whether a medication is still necessary. Parents may opt for a drug holiday because most would prefer their children to take less medication.

A drug holiday can counteract some of the key side effects of stimulant medication such as decreased appetite and weight loss, and the moodiness and irritability that accompanies the medication, as well as sleep problems.

It may also be used to avoid drug tolerance, the need to increase dosage as medication continues. A 2002 study of 166 children and adolescents treated with methylphenidate revealed that 60% had developed drug tolerance. Drug tolerance increases with duration. “So, the longer the child is on medication, the more likely he or she will develop some drug tolerance,” said Dr. Hechtman.

It is hypothesized that a drug holiday results in the resensitization of the neurons in the brain because they aren’t exposed to the stimulation of dopamine release and dopamine exposure.

The minimum time a patient needs a drug holiday to deal with some drug tolerance is about a month. “Even if you have a drug holiday and your drug tolerance has been decreased, it can reoccur with increasing dosages, once medication resumes” after the holiday, said Dr. Hechtman.
 

The growth factor

A drug holiday can also address concerns about growth suppression. “Some studies show that drug holidays help with growth suppression and others do not,” said Dr. Hechtman.

The Multimodal Treatment of ADHD (MTA) study, which followed children with ADHD from childhood to adolescence into adulthood, offers some key insights on the effects of treatment on growth.

Over a 10-year period, “you could see that the rate of medication use decreased significantly with time” among participants, said Dr. Hechtman, a coauthor of the MTA research. Only 10% who began the study aged 7-9 years were still using stimulants 10 years later. Looking at short-term effects on growth among these children, those who never went on stimulants to begin with had no growth suppression at all, whereas those who underwent early and consistent treatment experienced the greatest growth suppression.

Comparatively, inconsistently medicated participants had less growth suppression than those who remained on medication. “They were pretty close to the controls,” said Dr. Hechtman.

These patterns continued in a 16-year follow-up, as these patients became adults. Based on the results in the inconsistently treated group, this suggests that drug holidays can limit the effects of growth suppression, at least to a certain extent, said Dr. Hechtman.

Other studies have yielded varying results on the impact of drug holidays on height and weight. “The evidence for the utility of drug holidays for medication side effects is there for decreased appetite and weight, but not so much for decreased height,” summarized Dr. Hechtman.

One recent study of 230 children by James Waxmonsky and colleagues that examined drug holidays on weekends and summers showed that drug holidays did increase weight but interestingly, not height. Older studies Dr. Hechtman cited had inconsistent results on height and weight gain and loss. A 2012 study suggested that drug holidays resulted in a slight improvement in appetite for both weekend and school holidays. But only 9% of the children in the sample (n = 51) saw their appetite return to normal levels.
 

‘Negative things can happen’

The downside of drug holidays is parents may rationalize that their child is doing fine without the medication, and discontinue it. The process of stopping and starting medication can lead to other problems. “Negative things can happen during drug holidays,” said Dr. Hechtman.

The large variability of doses over the weekend can result in rebound and side effects.

A child may go from a full dose, which could be 50-60 mg of stimulant to zero from Friday to Saturday. As a result they have a lot of rebound on that Saturday. Similarly, they go from zero on Sunday to full dose on the Monday, causing lots of side effects. “Also, they will never have a stable effective dose because of the roller-coaster effect of being on and off the drugs,” she noted.

The lack of consistency and accommodation to the side effects can lead to discontinuation of the medication.

Off medication, the child may be more accident prone or have more injuries. “Their behavior off the medication may be such that it leads to social problems,” Dr. Hechtman continued. Weekend activities that require medication such as homework or school projects, family or religious gatherings, or sports and social activities with family and peers may be affected. If the child is behaving poorly off the medication, they may be expelled from such activities. If it’s a summer drug holiday, they may get kicked out of camp or the swimming pool.

If the child’s condition is already worsening, and a drug holiday takes place on top of this, the child may experience a rebound or relapse, in which the condition looks a lot worse than it did with the drugs.
 

Do drug holidays matter?

Another session speaker, James Swanson, PhD, who noted that the “emergence of tolerance may limit and eventually undermine initial relative benefit” of stimulants, said there may be instances in which drug holidays may be impractical.

Given the poor adherence to ADHD medication, “most treated ADHD cases stop medication anyway and these patients do not have an opportunity for drug holidays,” he said in an interview.

“If tolerance does emerge, then for long-term treatment the concept of drug holiday seems difficult to evaluate to me,” said Dr. Swanson, director of the Child Development Center at the University of California, Irvine.

Planned medication breaks may not be a good way to evaluate efficacy unless it is performed under “double-blind” conditions, he offered. The MTA used an approach of switching between short periods of time, with and without medication. “We did this to compare medication to placebo and to compare doses of medication to optimize the short-term benefit,” said Dr. Swanson, a coauthor of the MTA study.

Dr. Hechtman receives funding from The Canadian Institutes of Health Research. Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA).

For children with attention-deficit/hyperactivity disorder, taking a weekend or summer break from methylphenidate may have some benefits. A drug “holiday” can help assess whether a drug is still useful and possibly help with drug tolerance, weight gain, and growth suppression. But drug holidays are not without their problems, Lily Hechtman, MD, FRCP, professor at the department of psychiatry, McGill University, Montreal, said during a session at the World Congress on ADHD – Virtual Event.

Ceasing a medication can have repercussions from a health and social standpoint, cautioned Dr. Hechtman, a presenter and moderator of the session, “Unsolved mysteries in the treatment of ADHD with psychostimulants.”

The rate of drug holidays is somewhere between 30% and 40% in ADHD patients. Patients have multiple reasons for taking them, said Dr. Hechtman. The American Academy of Child & Adolescent Psychology as well as the National Institute for Health and Clinical Excellence recommend this method to assess whether a medication is still necessary. Parents may opt for a drug holiday because most would prefer their children to take less medication.

A drug holiday can counteract some of the key side effects of stimulant medication such as decreased appetite and weight loss, and the moodiness and irritability that accompanies the medication, as well as sleep problems.

It may also be used to avoid drug tolerance, the need to increase dosage as medication continues. A 2002 study of 166 children and adolescents treated with methylphenidate revealed that 60% had developed drug tolerance. Drug tolerance increases with duration. “So, the longer the child is on medication, the more likely he or she will develop some drug tolerance,” said Dr. Hechtman.

It is hypothesized that a drug holiday results in the resensitization of the neurons in the brain because they aren’t exposed to the stimulation of dopamine release and dopamine exposure.

The minimum time a patient needs a drug holiday to deal with some drug tolerance is about a month. “Even if you have a drug holiday and your drug tolerance has been decreased, it can reoccur with increasing dosages, once medication resumes” after the holiday, said Dr. Hechtman.
 

The growth factor

A drug holiday can also address concerns about growth suppression. “Some studies show that drug holidays help with growth suppression and others do not,” said Dr. Hechtman.

The Multimodal Treatment of ADHD (MTA) study, which followed children with ADHD from childhood to adolescence into adulthood, offers some key insights on the effects of treatment on growth.

Over a 10-year period, “you could see that the rate of medication use decreased significantly with time” among participants, said Dr. Hechtman, a coauthor of the MTA research. Only 10% who began the study aged 7-9 years were still using stimulants 10 years later. Looking at short-term effects on growth among these children, those who never went on stimulants to begin with had no growth suppression at all, whereas those who underwent early and consistent treatment experienced the greatest growth suppression.

Comparatively, inconsistently medicated participants had less growth suppression than those who remained on medication. “They were pretty close to the controls,” said Dr. Hechtman.

These patterns continued in a 16-year follow-up, as these patients became adults. Based on the results in the inconsistently treated group, this suggests that drug holidays can limit the effects of growth suppression, at least to a certain extent, said Dr. Hechtman.

Other studies have yielded varying results on the impact of drug holidays on height and weight. “The evidence for the utility of drug holidays for medication side effects is there for decreased appetite and weight, but not so much for decreased height,” summarized Dr. Hechtman.

One recent study of 230 children by James Waxmonsky and colleagues that examined drug holidays on weekends and summers showed that drug holidays did increase weight but interestingly, not height. Older studies Dr. Hechtman cited had inconsistent results on height and weight gain and loss. A 2012 study suggested that drug holidays resulted in a slight improvement in appetite for both weekend and school holidays. But only 9% of the children in the sample (n = 51) saw their appetite return to normal levels.
 

‘Negative things can happen’

The downside of drug holidays is parents may rationalize that their child is doing fine without the medication, and discontinue it. The process of stopping and starting medication can lead to other problems. “Negative things can happen during drug holidays,” said Dr. Hechtman.

The large variability of doses over the weekend can result in rebound and side effects.

A child may go from a full dose, which could be 50-60 mg of stimulant to zero from Friday to Saturday. As a result they have a lot of rebound on that Saturday. Similarly, they go from zero on Sunday to full dose on the Monday, causing lots of side effects. “Also, they will never have a stable effective dose because of the roller-coaster effect of being on and off the drugs,” she noted.

The lack of consistency and accommodation to the side effects can lead to discontinuation of the medication.

Off medication, the child may be more accident prone or have more injuries. “Their behavior off the medication may be such that it leads to social problems,” Dr. Hechtman continued. Weekend activities that require medication such as homework or school projects, family or religious gatherings, or sports and social activities with family and peers may be affected. If the child is behaving poorly off the medication, they may be expelled from such activities. If it’s a summer drug holiday, they may get kicked out of camp or the swimming pool.

If the child’s condition is already worsening, and a drug holiday takes place on top of this, the child may experience a rebound or relapse, in which the condition looks a lot worse than it did with the drugs.
 

Do drug holidays matter?

Another session speaker, James Swanson, PhD, who noted that the “emergence of tolerance may limit and eventually undermine initial relative benefit” of stimulants, said there may be instances in which drug holidays may be impractical.

Given the poor adherence to ADHD medication, “most treated ADHD cases stop medication anyway and these patients do not have an opportunity for drug holidays,” he said in an interview.

“If tolerance does emerge, then for long-term treatment the concept of drug holiday seems difficult to evaluate to me,” said Dr. Swanson, director of the Child Development Center at the University of California, Irvine.

Planned medication breaks may not be a good way to evaluate efficacy unless it is performed under “double-blind” conditions, he offered. The MTA used an approach of switching between short periods of time, with and without medication. “We did this to compare medication to placebo and to compare doses of medication to optimize the short-term benefit,” said Dr. Swanson, a coauthor of the MTA study.

Dr. Hechtman receives funding from The Canadian Institutes of Health Research. Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA).

For children with attention-deficit/hyperactivity disorder, taking a weekend or summer break from methylphenidate may have some benefits. A drug “holiday” can help assess whether a drug is still useful and possibly help with drug tolerance, weight gain, and growth suppression. But drug holidays are not without their problems, Lily Hechtman, MD, FRCP, professor at the department of psychiatry, McGill University, Montreal, said during a session at the World Congress on ADHD – Virtual Event.

Ceasing a medication can have repercussions from a health and social standpoint, cautioned Dr. Hechtman, a presenter and moderator of the session, “Unsolved mysteries in the treatment of ADHD with psychostimulants.”

The rate of drug holidays is somewhere between 30% and 40% in ADHD patients. Patients have multiple reasons for taking them, said Dr. Hechtman. The American Academy of Child & Adolescent Psychology as well as the National Institute for Health and Clinical Excellence recommend this method to assess whether a medication is still necessary. Parents may opt for a drug holiday because most would prefer their children to take less medication.

A drug holiday can counteract some of the key side effects of stimulant medication such as decreased appetite and weight loss, and the moodiness and irritability that accompanies the medication, as well as sleep problems.

It may also be used to avoid drug tolerance, the need to increase dosage as medication continues. A 2002 study of 166 children and adolescents treated with methylphenidate revealed that 60% had developed drug tolerance. Drug tolerance increases with duration. “So, the longer the child is on medication, the more likely he or she will develop some drug tolerance,” said Dr. Hechtman.

It is hypothesized that a drug holiday results in the resensitization of the neurons in the brain because they aren’t exposed to the stimulation of dopamine release and dopamine exposure.

The minimum time a patient needs a drug holiday to deal with some drug tolerance is about a month. “Even if you have a drug holiday and your drug tolerance has been decreased, it can reoccur with increasing dosages, once medication resumes” after the holiday, said Dr. Hechtman.
 

The growth factor

A drug holiday can also address concerns about growth suppression. “Some studies show that drug holidays help with growth suppression and others do not,” said Dr. Hechtman.

The Multimodal Treatment of ADHD (MTA) study, which followed children with ADHD from childhood to adolescence into adulthood, offers some key insights on the effects of treatment on growth.

Over a 10-year period, “you could see that the rate of medication use decreased significantly with time” among participants, said Dr. Hechtman, a coauthor of the MTA research. Only 10% who began the study aged 7-9 years were still using stimulants 10 years later. Looking at short-term effects on growth among these children, those who never went on stimulants to begin with had no growth suppression at all, whereas those who underwent early and consistent treatment experienced the greatest growth suppression.

Comparatively, inconsistently medicated participants had less growth suppression than those who remained on medication. “They were pretty close to the controls,” said Dr. Hechtman.

These patterns continued in a 16-year follow-up, as these patients became adults. Based on the results in the inconsistently treated group, this suggests that drug holidays can limit the effects of growth suppression, at least to a certain extent, said Dr. Hechtman.

Other studies have yielded varying results on the impact of drug holidays on height and weight. “The evidence for the utility of drug holidays for medication side effects is there for decreased appetite and weight, but not so much for decreased height,” summarized Dr. Hechtman.

One recent study of 230 children by James Waxmonsky and colleagues that examined drug holidays on weekends and summers showed that drug holidays did increase weight but interestingly, not height. Older studies Dr. Hechtman cited had inconsistent results on height and weight gain and loss. A 2012 study suggested that drug holidays resulted in a slight improvement in appetite for both weekend and school holidays. But only 9% of the children in the sample (n = 51) saw their appetite return to normal levels.
 

‘Negative things can happen’

The downside of drug holidays is parents may rationalize that their child is doing fine without the medication, and discontinue it. The process of stopping and starting medication can lead to other problems. “Negative things can happen during drug holidays,” said Dr. Hechtman.

The large variability of doses over the weekend can result in rebound and side effects.

A child may go from a full dose, which could be 50-60 mg of stimulant to zero from Friday to Saturday. As a result they have a lot of rebound on that Saturday. Similarly, they go from zero on Sunday to full dose on the Monday, causing lots of side effects. “Also, they will never have a stable effective dose because of the roller-coaster effect of being on and off the drugs,” she noted.

The lack of consistency and accommodation to the side effects can lead to discontinuation of the medication.

Off medication, the child may be more accident prone or have more injuries. “Their behavior off the medication may be such that it leads to social problems,” Dr. Hechtman continued. Weekend activities that require medication such as homework or school projects, family or religious gatherings, or sports and social activities with family and peers may be affected. If the child is behaving poorly off the medication, they may be expelled from such activities. If it’s a summer drug holiday, they may get kicked out of camp or the swimming pool.

If the child’s condition is already worsening, and a drug holiday takes place on top of this, the child may experience a rebound or relapse, in which the condition looks a lot worse than it did with the drugs.
 

Do drug holidays matter?

Another session speaker, James Swanson, PhD, who noted that the “emergence of tolerance may limit and eventually undermine initial relative benefit” of stimulants, said there may be instances in which drug holidays may be impractical.

Given the poor adherence to ADHD medication, “most treated ADHD cases stop medication anyway and these patients do not have an opportunity for drug holidays,” he said in an interview.

“If tolerance does emerge, then for long-term treatment the concept of drug holiday seems difficult to evaluate to me,” said Dr. Swanson, director of the Child Development Center at the University of California, Irvine.

Planned medication breaks may not be a good way to evaluate efficacy unless it is performed under “double-blind” conditions, he offered. The MTA used an approach of switching between short periods of time, with and without medication. “We did this to compare medication to placebo and to compare doses of medication to optimize the short-term benefit,” said Dr. Swanson, a coauthor of the MTA study.

Dr. Hechtman receives funding from The Canadian Institutes of Health Research. Dr. Swanson has two patents: (PIXA4), which uses a “time-of-flight” camera to measure growth on infants, and a provisional patent on the mechanism of tolerance to stimulant medication (PATSMTA).