Clinical ShowCase™: Developing a Personalized Treatment Plan for a Patient with Sickle Cell Disease

Clinical Showcase Sickle Cell 

The FDA this week released a statement encouraging foreign importation of infant formula to the United States, among other flexibilities to help increase access to the much-needed product.

While the United States normally produces 98% of the infant formula the country consumes, other import sources traditionally come from trading partners in Mexico, Ireland, and the Netherlands. However, considering the increased shortage in infant formula seen across the country, the US Food and Drug Administration (FDA) has outlined a new process that the agency will use to allow importation of certain infant formula products intended for a foreign market or products manufactured in the United States usually for export. In the statement, the agency wrote that these flexibilities may help further increase access to formula products in the country.

Companies hoping to take advantage of the new flexibilities are encouraged to submit information to the FDA for quick evaluation of the product to assess its safety and nutritional value. This evaluation will include product labeling, nutritional adequacy information, safety testing, and facility inspection history, according to the statement. Additionally, the FDA intends to prioritize submissions that can demonstrate these points and have the largest volume of product available and those who can get product onto shelves the quickest.

Along with these recently announced flexibilities, the agency has also implemented a process streamlining the importation of infant formula at country ports so that products coming from abroad can more quickly be dispersed. As a result, the FDA wrote that more formula has come into the US.

This statement comes on the heels of the announcement reporting the potential reopening of Abbott Nutrition’s Sturgis, Michigan, facility, after its initial closure in February.

Only facilities experienced in and already making nutrition products are in a position to produce formula products that would not pose “significant health risks to consumers,” according to the FDA.

“Today’s action paves the way for companies who don’t normally distribute their infant formula products in the US to do so efficiently and safely,” said FDA Commissioner Robert M. Califf, MD, in the statement. “We are hopeful this call to the global market will be answered and that international businesses will rise to the occasion to assist in bolstering the supply of products that serve as the sole source of nutrition for many infants. With these flexibilities in place, we anticipate that those products that can quickly meet safety and nutrition standards could hit US stores in a matter of weeks.”

FDA encourages importation of safe infant formula and other flexibilities to further increase availability. FDA. Published May 16, 2022. Accessed May 17, 2022. 

https://www.fda.gov/news-events/press-announcements/fda-encourages-importation-safe-infant-formula-and-other-flexibilities-further-increase-availability?utm_medium=email&utm_source=govdelivery

Articles

This week, the agency announced it is encouraging importation of infant formula from usually unutilized foreign means in hopes of increasing access to the product in the wake of the country-wide shortage. 

FDA implements increased flexibilities for foreign importation of infant formula

 diagnostic tests, once a luxury at the beginning of the pandemic, are thankfully now more accessible in the US. Naso-pharyngeal RT-PCR tests are highly accurate, but for rapid results at home, some opt for rapid lateral flow antigen tests.

The need for inexpensive, reliable, rapid 

 is augmented by the relatively large proportion of children who are unvaccinated. One study, presented at this week’s 40th Annual Meeting of the European Society for Pediatric Infectious Diseases (

), assessed the performance of the “COVID-VIRO ALL IN” COVID-19 rapid test in children.

This cross-sectional, prospective, multicenter, real-life study was conducted from September 1, 2021-January 3, 2022. Children 0-15 years old were recruited after presenting to emergency departments and ambulatory settings. The children were either symptomatic for COVID-19 or had been exposed to an infected person.

All children were given a SARS-CoV-2 RT-PCR or rapid antigen test, and a self-test. Above the age of 6, the children could easily perform the self-tests themselves, whereas younger children required the help of a parent or other adult.

The COVID-VIRO ALL IN (AAZ-LMB, Boulogne Billancourt, France) test was used for this study, due to its short sampling device and soft sponge swab. The comfort of use allowed for long sampling (15 seconds per nostril). The investigators compared self-collected nasal swabs to RT-PCR tests, estimating the accuracy and acceptance of these tests for pediatric populations.

A total of 836 pediatric patients, aged an average of 4 years, completed the COVID-19 diagnostic tests. A total of 92.6% of the children were symptomatic, and the prevalence of COVID-19 was 18.4%.

In comparison to the RT-PCR test, the sensitivity of the self-collected nasal swab test was 72.6% during the period when the Delta variant was predominant, and 87.0% during the Omicron wave.

False negative self-tests were largely aligned with low viral loads. Low viral load was established by RT-PCR with a cycle threshold ≥33 and/or a SARS-CoV-2 rapid antigen test positive in more than 3 minutes. The youngest child confirmed positive with a self-test was 1 month old.

On a scale from 1-10, with 1 being “very pleasant” and 10 being “very unpleasant,” 77.9% of children rated the test ≤ 3.

The investigators concluded that the nasal self-test used in this study was reliable, particularly in more contagious children. They noted that it is vital to provide highly accurate tests that are less invasive and unpleasant to encourage families to test their children for COVID-19.

This study, “Diagnostic Accuracy of SARS-CoV-2 Antigen Detection Self-Test in Children: Vigil Study 3,” was presented during the 

40th Annual Meeting of the European Society for Pediatric Infectious Diseases (ESPID)

, held online and in Athens, Greece from May 9-13, 2022.

Originally published on our sister brand, 

A comparison of COVID-19 PCR tests and rapid self-tests found self-tests to be highly accurate and user-friendly for children.

Self-tests for COVID-19 are accurate and tolerable for children

 the FDA announced the amendment of the current emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine, now authorizing a single booster dose for children 5 to 11 years of age, at least 5 months after completing the primary Pfizer-BioNTech vaccine series.

This EUA amendment follows the January 3, 2022 authorization for adolescents aged 12 to 15 years and joins the approval of Comirnaty (COVID-19 vaccine, mRNA) for use in those aged 16 and older.

The agency analyzed immune response data in a subset of children age 5 to 11 collected from the ongoing randomized, placebo-controlled trial that supported the October 2021 authorization of the vaccine in this age group. Researchers evaluated antibody responses in 67 participants who received their booster dose 7 to 9 months following the completion of a 2-dose primary vaccine series.

Safety was assessed in 400 children who received a booster dose at least 5 months after their 2-dose primary series. The most commonly reported adverse effects included pain, injection site redness and swelling, and fatigue, headache, muscle or joint pain, and chills and fever.

“[T]he omicron wave has seen more kids getting sick with [COVID-19] and being hospitalized, and children may also experience longer term effects, even following initially mild disease,” said Robert M. Califf, MD, FDA Commissioner. “The FDA is authorizing the use of a single booster dose of the Pfizer-BioNTech COVID-19 vaccine for children 5 through 11 years of age to provide continued protection against COVID-19.”

“The Pfizer-BioNTech COVID-19 vaccine is effective in helping to prevent the most severe consequences of COVID-19 in individuals 5 years of age and older,” added Peter Marks, MD, PhD, director of the FDA Center for Biologics Evaluation and Research. “Since authorizing the vaccine for children down to 5 years of age in October 2021, emerging data suggest that vaccine effectiveness against COVID-19 wanes after the second dose…in all authorized populations.”

“The FDA has determined that the known and potential benefits of a single booster dose…for children 5 through 11 years of age at least 5 months after completing a primary series outweighs its known and potential risks and that a booster dose can help provide continued protection against COVID-19 in this and older age groups,” he continued.

Vaccination, Califf said, remains the most effective way to prevent COVID-19 and related severe consequences.

Coronavirus (COVID-19) update: FDA expands eligibility for Pfizer-BioNTech COVID-19 vaccine booster dose to children 5 through 11 years. News release. FDA. May 17, 2022. Accessed May 17, 2022. 

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-expands-eligibility-pfizer-biontech-covid-19-vaccine-booster-dose

Children may receive a single booster shot at least 5 months after completing their initial Pfizer-BioNTech 2-dose series.



FDA Authorizes Pfizer-BioNTech Booster Shot for Children Ages 5 to 11

The RESPONSE clinical trial (NCT04839601), a prospective single-arm study evaluating the safety and efficacy of NeuroPace’s Responsive Neurostimulation (RNS) System in adolescents aged 12 through 17 years with drug-resistant focal epilepsy, has commenced dosing.

According to clinicaltrials.gov, the study is expected to enroll 200 participants who will be followed for 2 years after placement of the RNS System. The primary outcome measure includes short-term serious adverse device effect (SADE) rate and responder rate at 12 months post-implant. The study design includes an interim analysis which will occur after the 75th implanted patient reaches 12 months post-implant. If the study achieves its primary safety and effectiveness end point goals at the interim analysis, the study will be considered successful and enrollment will be stopped.

Approved in 2013 for the treatment of medical refractory epilepsy, the RNS System remains the only brain-responsive neuromodulation system approved by the FDA. The closed-loop technology monitors and responds to a patient’s unique brain patterns to deliver therapy in real time prior to symptom onset.

"More than 1 million people are living with drug-resistant epilepsy," 

, pediatric neurologist and director, pediatric epilepsy program, Boston Children’s Health Physicians; and Patricia McGoldrick, NP, MPA, MSN, nurse practitioner and director, Pediatric Epilepsy Unit, Boston Children’s Health Physicians, said in a statement.

 “The RNS System has demonstrated unprecedented seizure reduction and improved quality of life in adults with drug-resistant focal epilepsy. Through this clinical study, we are looking forward to evaluating the RNS System in an expanded population of adolescent patients who have uncontrolled focal seizures, despite taking medications."

Since its approval, the modality has been studied in several different settings, 

including 2 seminal studies published in 2020

. The first study, which included 150 patients with refractory epilepsy, showed median seizure reductions of 67% (IQR, 33-99) at 1 year, 75% (IQR, 50-94) at 2 years, 82% (IQR, 50-96) at 3 years or more, and 74% (IQR, 50-96) at last follow-up (mean, 2.3 years). Notably, 35% of patients treated with the device had at least a 90% reduction in seizure frequency, with 18% of patients reportedly seizure-free at last follow-up.

The second trial was a 9-year, long-term study that included 230 patients across 34 epilepsy centers with nearly 1900 patient-implant years of follow-up. At 9 years, the median percent reduction in seizure frequency was 75% (

 <.0001; Wilcoxon signed rank), the responder rate was 73%, and 35% had at least a 90% reduction in seizure frequency. Additionally, 18.4% of the cohort experienced at least 1 year of seizure freedom, with 62% of those seizure-free at the last follow-up.

"The RESPONSE study is an exciting opportunity to evaluate the safety and effectiveness of the RNS System in a younger population aged 12 through 17 [years], when seizures can profoundly impact school, social development, and self-esteem, as well as expose the teen to all of the risks of seizures themselves," 

, chief medical officer, NeuroPace, and primary investigator of RESPONSE, said in a statement.

 "Our recent announcement of nearly 11 yearsof battery life for the RNS System is especially beneficial to younger patients—fewer replacement procedures translates into lower health risk and lower cost for patients."

RESPONSE is one of the many ongoing studies further evaluating the efficacy and safety of the RNS System. In July 2021, the National Institutes of Health granted an investigational device exemption (IDE) to study the modulation device in 

 Months later, in November 2021, the company received another IDE to evaluate the RNS System in patients with 

 Dubbed NAUTILUS, that prospective, randomized pivotal study is the first to evaluate the effects of brain-responsive neuromodulation in this patient population.

NeuroPace announces first patient treated in pivotal study evaluating the RNS system in adolescents. News release. NeuroPace. May 4, 2022. Accessed May 10, 2022. https://www.neuropace.com/neuropace-announces-first-patient-treated-in-pivotal-study-evaluating-the-rns-system-in-adolescents/

RNS System RESPONSE Study (RESPONSE). Clinicaltrial.gov. https://clinicaltrials.gov/ct2/show/NCT04839601. Updated April 14, 2022. Accessed May 10, 2022.

Razavi B, Rao VR, Lin C, et al. Real-world experience with direct brain-responsive neurostimulation for focal onset seizures. 

 2020;61(8):1749-1757. doi:10.1111/epi.16593.Epub 2020. Jul 13.

Nair DR, Laxer KD, Weber PB. Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy. 

 2020;95(9)e1244-e1256. doi:10.1212/WNL.0000000000010154

NeuroPace awarded five-year NIH grant funding of more than $9M to study RNS system in Patients with Lennox-Gastaut Syndrome. News release. NeuroPace, Inc. June 30, 2021. Accessed May 10, 2022. https://www.globenewswire.com/news-release/2021/06/30/2255588/0/en/NeuroPace-Awarded-Five-Year-NIH-GraThent-Funding-of-More-than-9M-to-Study-RNS-System-in-Patients-with-Lennox-Gastaut-Syndrome.html

NeuroPace receives IDE approval to initiate NAUTILUS pivotal study of its RNS System for idiopathic generalized epilepsy. News release. November 10, 2021. Accessed May 10 2022. https://www.globenewswire.com/news-release/2021/11/10/2331968/0/en/NeuroPace-Receives-IDE-Approval-to-Initiate-NAUTILUS-Pivotal-Study-of-its-RNS-System-for-Idiopathic-Generalized-Epilepsy.html

Since its approval for the treatment of medical refractory epilepsy in 2013, the closed-loop neuromodulation device has had its efficacy and safety confirmed in several pivotal studies and will now be assessed in focal epilepsy in the RESPONSE trial.

First patient treated in adolescent epilepsy trial assessing NeuroPace RNS system

A recent investigation into obstructive sleep apnea (OSA) in pediatric patients with pulmonary hypertension (PH) found that a majority of patients were affected by the sleep disorder, prompting investigators to suggest routine screening for OSA in this population.

The new data was presented this weekend at 

the American Thoracic Society 2020 International Conference

 in San Francisco during the session, “Risk for Obstructive Sleep Apnea in Pediatric Patients with Pulmonary Hypertension”.

Obstructive sleep apnea has previously been associated with pulmonary hypertension in literature, with investigators citing a “complex and bidirectional relationship” between the 2 conditions.

Though previous research has indicated a relationship between OSA and PH, little is known of the risk factors for the sleep disorder in younger populations. A better understanding of these risk factored could result in earlier and more meaningful treatment.

As such, and investigative team led by Daniel Ignatiuk, MD, of the Cincinnati Children’s Hospital, conducted an analysis of OSA risk factors documented in a 10-year cohort of pediatric patients with PH at the Cincinnati Children’s Hospital.

The team conducted a retrospective chart of patients 0-21 years with a documented diagnosis of PH who underwent diagnostic polysomnogram (PSG) between January 2010 and August 2020.

The first polysomnogram was analyzed in patients with multiple studies.

Exclusion criteria were PSG with sleep time less than four hours, tracheostomy tube, positive pressure ventilation, oxygen titration with less than 2 hours of diagnostic sleep time, and PSG more than 90 days before PH diagnosis or more than 90 days after PH resolution.

Meanwhile, PH was classified according to 6th World Symposium on PH criteria.

Only 2 patients with PH were excluded due to small group size.

Incidence of sleep disorders and OSA risk factors based on documented diagnoses and PH classification were the outcome variables.

A total of 403 patients were identified, with the final cohort including 89 patients with a median age of 3.6 years.

Classification of PH included group 1 (n=25, 28.1%), group 3 (n=31, 34.8%), and group 1/3 for patients meeting both group 1 and 3 criteria (n=33, 37.1%).

Diagnosed sleep disorders included OSA (n=79, 88.8%), central sleep apnea (n=11, 12.4%), hypoventilation (n=6, 6.7%), non-apneic hypoxemia (n=28, 31.5%), and periodic limb movement disorder (n=5, 5.6%).

Investigations observed that OSA risk was increased with a diagnosis of trisomy 21 (RR 1.24, 95% CI 1.09-1.42) (P<0.05).

Notably, OSA risk was decreased with group compared to group 1/3 PH (RR 0.84, 95% CI 0.71-0.99) (P<0.05) or group 3 PH (RR 0.81, 95% CI 0.68-0.96) (P<0.05), and no difference in OSA risk between group 1 and group 3 PH was seen.

Overall, OSA was diagnosed in a majority of pediatric patients in the study, most notably in patients with trisomy 21 or PS classification meeting both group 1 and 3 criteria.

“Our research supports routine screening for OSA in this population, and especially among patients with trisomy 21 or PH classification meeting both group 1 and 3 criteria,” the team wrote. “Further studies are needed to examine the impact of intervention on clinical outcomes.”

Significant OSA prevalence in pediatric patients with pulmonary hypertension

Each year, about 3400 infants die of sudden infant death syndrome (SIDS) in the United States, according to the Centers for Disease Control and Prevention.

 SIDS is categorized as the sudden or unexpected death of a baby aged less than 1 year in which the cause cannot be determined. These deaths happen most often during an infant’s sleep or in the sleeping area. Additionally, experts don’t know which babies are at risk for SIDS or what causes it. Now, a team of Australian investigators say they’ve discovered a piece of the puzzle into its cause, and they say it lies in an enzyme called butyrylcholiesterase (BChE).

, highlighted that autonomic dysfunction has been implicated in the pathophysiology of SIDS. BChE, they continued, is an enzyme of the cholinergic system, which is a major branch of the autonomic system and may provide a measure of autonomic (dys)function. With this in mind, a study was undertaken to measure BChE activity in infants and young children who had died from SIDS or Sudden Unexpected Death in Infancy (SUDI).

The study, which was case-controlled, measured BChE activity and total protein in the “eluate of 5μL spots punched from the dried blood spots [DBSs] taken at birth as part of the newborn screening program,” according to the investigators.

These DBSs were collected on post-natal day (PND) 2 to 4 on Whatman 903 filter paper over a 5-year period between 2016 to 2020. The samples where then stored at room temperature.

Children who were categorized as SUDI—who died less than 24 months old between July 20218 and July 2020—were identified using the databases of 3 New South Wales, Australia, forensic pathology sites.

The forensic pathologist’s death classification was used in the study in all but 5 cases. Two cases originally classified as SIDS were changed as SUDI because they were less than or equal to 3 weeks old, 1 case originally labeled SIDS was also changed to SUDI because the subject was more than 52 weeks old, and another 2 cases classified as unknown were changed to SIDS. The investigators noted that all non-SIDS cases had an identified cause of death.

For each SID or SUDI case, 10 date of birth or gender-matched samples of surviving children—who blood spot was taken on the day PND—were identified and used as study controls.

In total, they analyzed 722 DBS which included 67 DBS (58% male) from SUDI infants (26 SIDS, 41 non-SIDS), and 655 controls. The mean age at death for SIDS cases were reported as 15.7 (±8.1) weeks (4 to 36 weeks) and consisted of 54% male subjects. Of the non-SIDS cases, the mean age at death was 31.7 (±30) weeks (1-103 weeks), and was 64% male.

All DBSs were examined for BChE activity and total protein content and BChE specific activity (BChEsa) was calculated. They saw good correlation between the BChE activity of plasma QCs and corresponding DBS QCs (r .84). They noted, however, that the recovery of BChE in DBS QC compared to plasma QC was lower (23.4 ± 2%) than in previous studies. Due to several excluded samples, the study population was reduced to 30 non-SID cases (mean age of death: 23.5 [±30] weeks, range 1-103 weeks; 57% male).

Investigators normalized BChE activity to total protein content to overcome variability in punch location and hematocrit. In turn, there was good recovery of total protein in plasma QC vs its corresponding DBS QC (96.25 ± 11.8%).

Additionally, they reported: “Mean values (± Standard Deviation) for BChEsa for SIDS cases (n = 26) and their controls (n = 254) was 5·6 (±2·1) vs 7·7 (±3·6), respectively, and for non-SIDS cases (n = 30) and their controls (n=291) was 8·5 (±4·2) vs 8·5 (±3·4), respectively.”

Conditional logistic regression showed strong evidence of interaction between BChEsa and cause of death case outcome or control status (

 = ·0061). In response to this finding, separate models for SIDS and non-SIDS groups were performed, concluding that the SIDS death group had strong evidence that lower BChEsa was associated with death (OR= 73 per U/mg, 95% CI .60-.89, P = .0014) and the non-SIDS death group had no evidence of a linear association between BChEsa and death (OR= 1.001 per U/mg, 95% CI .89-1.13, 

Additionally, “there was no evidence of an association between any of the predictors (BCHEsa, gender and cause of death) and age at death, in either univariable or multivariable models,” investigators wrote.

Results showed that a decrease in BChEsa was a biochemical marker distinguishing infants who succumb to SIDs from controls and infants with known causes of death. Investigators hypothesize that these findings are evidence of an altered cholinergic homeostasis and postulate that one could “plausibly produce functional alterations to an infant's autonomic and arousal responses to an exogenous stressor leaving them vulnerable to sudden death.”

Study limitations included difficulties comparing study findings of BChEsa with known BChE reference intervals and that the samples used were 2 years old and would not accurately reflect BChEsa in fresh DBSs. They tried to minimize the effect of long storage times by including 10 date of birth and gender matched, surviving controls per SIDS or non-SIDS case.

Study investigators acknowledged the need for further investigation to determine whether BChE could potentially be used as a biomarker to identify and prevent SIDS deaths.

About SUID and SIDS. Centers for Disease Control and Prevention. Accessed May 16, 2022. 

Harrington CT, Hafid NA, Waters KA. Butyrylcholinesterase is a potential biomarker for sudden infant death syndrome. 

Investigators may have found a piece of the puzzle into what causes sudden infant death syndrome. 

Butyrylcholiesterase may be key biomarker in SIDS identification, prevention

A study on best practices in the identification and management of perinatal depression raised more questions than answers.

The study aimed to examine the guidelines for managing perinatal depression in obstetric and pediatric settings, as well as the evidence supporting these guidelines. To do this, the investigators conducted a search for best practices in the Guideline International Network using the term 

; conducted additional searches on Google and other websites; and had discussions with experts in perinatal depression. To be included, guidelines had to describe the management of perinatal depression in obstetric or pediatric care settings; be written in English; and have been published between 1990 and 2021. The investigators found 25 guidelines published by 17 organizations—with 6 organizations publishing more than 1 guideline—that met the aforementioned criteria for inclusion. They then examined the research supporting these guidelines through searches in PubMed and Google Scholar, and conducted a literature review.

The investigators found that most guidelines (n =18, 72%) made recommendations for screening for perinatal depression, and 16 (89%) made several recommendations, including for screening timeframe, setting, and instrumentation. Just over one-third of the guidelines (n = 9, 36%) recommended assessment by severity and instrumentation to confirm depression after screening, and 3 (33%) made several recommendations. Suicide assessment was also analyzed, with 13 guidelines (52%) addressing suicide assessment, 6 (46%) of which recommended immediate evaluation. More than 50% of the guidelines (n = 7, 54%) recommended referring the patient to a psychiatrist or other mental health clinician to monitor the patient’s well-being.

The majority of guidelines (n = 21, 84%) made recommendations for treatment, with most (n = 20, 95%) offering several recommendations and 14 (67%) making recommendations by severity. Most (90%) recommended psychosocial interventions such as cognitive behavioral therapy or psychodynamic therapy; 60% recommended pharmacological treatment such as selective serotonin reuptake inhibitors (SSRIs) or serotonin and norepinephrine reuptake inhibitors (SNRIs); 40% recommended psychoeducation throughout the perinatal period; and 19% recommended alternative treatments like bright light therapy and electronic mental health support (ie, self-guided applications). The investigators also noted that literature on reassessment, remission, and care management was limited, and that they identified no literature discussing treatment adjustments for perinatal depression that was unresponsive to psychotherapy or pharmacology.

Overall, the investigators noted that evidence was inadequate or contradictory across all areas, and that of the limited number of studies available, most include small sample sizes or are not of sufficient quality to meaningfully inform clinical practice. 

They concluded: “Clinicians may use these recommendations to guide their practice, but they should be aware of the limitations of the evidence supporting these guidelines and remain alert to new evidence. There is a clear need for researchers and policymakers to prioritize this area in order to develop evidence-based guidelines for managing perinatal depression.”

Management of depression during the perinatal period: state of the evidence

Recommendations are often vague, contradictory, according to investigators.

Study examines best practices for managing perinatal depression

Whether it be avoiding infection at the surgical site, or a chance for a patient to bleed out, there is no question that seconds matter during any surgical procedure.

At the American College of Mohs Surgery (ACMS) 54th annual meeting being held this week in Philadelphia, Pennsylvania, a group of researchers from Emory University in Atlanta, Georgia, presented a pearl that is designed to help surgeons save those precious seconds during Mohs surgery. The technique that was discussed has applicability to many types of surgical procedures.

Latrice Hogue, MD, set up her presentation with a common problem faced by Mohs surgeons: “You are scrubbed in and need to request assistance—more suture, etc.—from team members who are outside of the room, what do you do?”

Hogue and colleagues noted that many Mohs surgical suites are not equipped with buzzers/buttons to call for assistance, and that often in these scenarios, other people in the room are usually scrubbed in as well and would have to scrub out, which leads to a potential wasting of resources, for example, staff time, and also the risk of contamination of having that person leaving the room. And of course, there is also the potential of lost time, which could lead to a delay in surgical procedure to stop and locate assistance.

To address this potential problem, the Emory team tried out an innovative solution, which is to initiate the “walkie talkie” feature on their digital watch, pull sterile gloves over their digital watch prior to the surgery, and then be empowered to communicate to their teams through this push-to-talk technology.

This has proven a useful tool for their team, Hogue explained, as most team members have these digital watches, just like most of the world.

“Digital watches are currently used by over 100 million people worldwide,” Hogue said, quoting an article from Techradar.com.

The push-to-talk feature on these phones allows the surgeon to communicate via one tap and an immediate voice message to the recipient, and the range for the technology includes anywhere an internet connection is available.

From apps that are designed to prepare patients for their surgeries, to headset use by surgeons in the operating theatre during procedures, technology hacks like the ones offered from Emory are quickly changing the way that patients are treated, and ultimately, helping surgeons perform their jobs in a more timely and safer way.

Hogue L, Lim J, Blalock T, Team communication tool during Mohs surgery. Presented at: American College of Mohs Surgery. Held May 12-15, 2022. Philadelphia, PA.

Presenters highlight the possible solutions to communication between the scrubbed-in surgery team and outside help that could save time.

Seconds Matter: A Pearl for Improving Communication During Surgery

Acne vulgaris is a skin condition caused by the dysfunction of the pilosebaceous unit which causes red bumps on the face and truck. Commonly, adolescents battle with this skin condition, but this patient age group is also more susceptible to misinformation. A recent article looked into the issue of the amount of misinformation on the internet by compiling a qualitative review of misinformation and conspiracy theories in acne.

The reason why adolescents are often more likely to believe misinformation is due to age, stress about the condition, and the amount of time spent on the internet. The researchers performed a review in March 2022 of PubMed that used the terms ‘acne’ AND ‘misinformation’ OR ‘disinformation’ OR ‘conspiracy theory’ in which 1,024 abstracts were found and then analyzed to see if they should be included as misinformation. After the analysis, 5 were included. After, a Google search was conducted using combinations of the terms ‘acne’ and ‘misinformation’, ‘disinformation’ and ‘conspiracy theories’. After that, TikTok, Twitter, Facebook, and Instagram were also investigated.

The common categories of the false content were diet and other ‘causes’ of acne, distrust of traditional acne therapies, and the use of nonconventional treatments. The dietary causes of acne, in these misinformation posts, included exposure to dairy products, high-fat foods, and chocolate. Other supposed causes included poor hygiene, contagion, systemic infections such as Candida, and fluoridated water, the researchers explained. For cures, veganism was often cited along with natural topical treatments, and nutritional supplements like diindolylmethane.

The posts said treatments like antibiotics were poisonous, and isotretinoin was toxic and devasting to the patient. Other misinformation about common treatments included an over exaggeration of cases of depression, inflammatory bowel disease, organ failure, infertility, and sexual dysfunction.

The researchers found that the websites in which these pieces of content were found often were associated with companies that were selling products that were advertised to cure acne in a short amount of time.

“Dermatologists should be aware of the nature of acne-related misinformation available online, and be prepared to counter it with scientific principles and facts,” the researchers concluded.

O’Connor C, O’Grady C, Murphy M. Spotting fake news: a qualitative review of misinformation and conspiracy theories in acne vulgaris. 

. Published online April 18, 2022:ced.15222. doi:10.1111/ced.15222

Teenagers were the most likely to be affected by targeted misinformation.

Misinformation and acne

Cortical/cerebral visual impairment (CVI), a condition related to brain injury, is visual impairment resulting from damage to the visual pathways in the brain. Unfortunately, CVI is all too common although not as commonly diagnosed.

CVI is the number 1 cause of pediatric visual impairment and blindness in the US and developed countries worldwide,

 according to Lotfi Merabet, OD, PhD, MPH, who is associate professor of ophthalmology, Harvard Medical School and Director, the Laboratory for Visual Neuroplasticity, Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston; and on the Board of Directors Education Committee and the CVI Steering Committee of the Perkins School for the Blind, Watertown, MA.

“There has been a fundamental shift in the clinical profile of visual impairment in pediatric populations and the Perkins population mirrors this perfectly,” he commented.

In the 1950s to 1980s, children enrolled in the school were typically profoundly blind due to a disease or pathology at the ocular level, i.e., infection, inherited disease, or retinopathy of prematurity.

Over the past couple of decades, a shift occurred with children presenting with a more complex profile—they were visual impaired and often had learning disabilities and motor and/or language issues. The source of those issues was not in the eye but from brain damage, he explained.

“This difference in pediatric blindness is important both from clinical and scientific standpoints as well as an educational standpoint,” Merabet emphasized.

Recognition of the source of the brain-based visual disabilities is the key to the early intervention in affected children.

In light of that, Merabet and other researchers are attempting to determine the inherent differences in these children. Specifically, how visual impairment caused by damage to the brain is different from visual impairment at the level of the eye.

What has been determined is that affected children may have sustained a neurologic complication or brain injury during the time of development, i.e., around the time of birth or shortly thereafter.

Some children may have had a stroke in utero or were born prematurely. Other causes include seizure disorder, trauma, and genetic/metabolic disorders.

Because of medical advances in neonatal care, many more of these children are surviving today than in the mid-20th century. In addition, there currently is greater recognition of their perceptual and learning issues at the research level.

However, the focus today is extending that recognition into the clinics.

In a typical scenario, parents may report that their child cannot locate a favorite toy or cross the street or becomes overwhelmed in crowds or a busy classroom. In contrast, the child’s vision may be only moderately impaired or even normal based on a Snellen chart evaluation or visual perimetry, and the eyes appear healthy on slit-lamp evaluation.

This scenario often can lead the parents into the weeds with suggestions of possible diagnoses including autism, development delays, or psychiatric issues when the clinician does not recognize that the visual impairment is not based on the eye, but is localized to the brain. This is the point at which these children begin to fall through the cracks.

Merabet and colleagues, in collaboration with Boston Children’s Hospital, Perkins, and Boston University Medical Center, are currently studying the brain scans of children with CVI to correlate any identified structural changes in the brain to the manifesting developmental and behavioral deficits and comparing the scans to those obtained from children with normal vision and those with other forms of ocular blindness.

In their study, children are divided based on age, 7 years and older and 14 years and older.

For the younger group, virtual reality and eye tracking are used to obtain an idea of their visual perceptual abilities by assessing functional vision.

In this group, the children are tasked with, for example, finding a certain toy in the toy box or a particular person in a crowded hallway, and the complexity of the environment and the child’s reaction to it is assessed.

As the environment increases in complexity, despite good visual acuity, their vision becomes very confusing swirl of colors that prevents the differentiation of objects/persons (see 

Merabet uses virtual reality to create functional vision assessment tools that surpass the standard eye chart and tests performed in an ophthalmology or optometry clinic.

“We found that the children are very sensitive to clutter, crowding, complex motion, and more interestingly, to visual demands," he explained. "As the task becomes much more difficult, that is as we make the assessment harder, their visual system breaks down."

This point is important because while a visual assessment during a standard vision test indicates that these children may have normal visual acuity, when put into a situation in which the visual system is taxed, that is the point at which the system can break down and the hidden visual impairment manifests itself.

“This breaking down of the visual system in the setting of high visual demands and complexity is the telltale sign of CVI, and highlights the difference between visual function and functional vision. We need to gain a better understanding of how these children use their vision in the real world,” he stated.

The 14-year and older children undergo magnetic resonance imaging of the brain to see how their brains are “wired” (i.e., white matter connectivity) and activate as a function of performing virtual reality tasks.

“We found that their brains are very different from children with typical neurologic development and from those who are blind from other causes, emphasizing the need for education,” he said.

Another factor under investigation is why some children benefit from intervention and others do not and the time line of improvement.

Part of the challenge here is determining how the cause of the CVI—brain injury, trauma, infection, seizure, or a genetic or metabolic disorder relates to underlying visual impairment.

“This makes for a complicated patient profile and every child is unique in terms of their challenges,” he pointed out.

No specific treatment exists currently for CVI. Early diagnosis of brain-based visual impairment and implementation of strategies to promote maximal brain development are the current focus, but there is no strong evidence yet to support what does and does not benefit these patients.

“This is a great challenge because much more than vision can be involved. It is important to use a multi-level approach that does not just consider vision but also language and increasing cognitive function and self-awareness in general. The goal is to promote as much brain development as possible,” he advised.

In his lab, the researchers attempt to develop novel assessment tools and compensatory strategies to better understand the difficulties that the children face and work around their challenges.

Perkins has created the CVI Center at Perkins to bring researchers, educators, medical professionals, and parents together to make a concerted effort to recognize the brain impairment in these children as quickly as possible and ensure they have access to the effective interventions they need, while driving groundbreaking research in the field.

At Perkins, the resources are being focused on how to assess and educate children with CVI and how this disorder is fundamentally different from children with eye-based visual impairment. Fifty-two percent of the Perkins population has CVI.

Jessie Cronan, senior director of Perkins CVI, described a new ambitious 2-parteffort spearheaded by Perkins, the first phase of which will be released in May 2022.

“The protocol is a ground-breaking digital assessment tool that was created out of a series of symposia with leaders in CVI that convened beginning in 2018,” she described.

The collaborations among the experts highlighted the huge gap that exists around CVI knowledge and diagnosis and that it is a problem approaching epidemic proportions that is largely unknown even by experts in visual impairment.

The challenge identified is two-fold: providing both education about CVI and functional baseline assessments and diagnostic tools for families, teachers, and physicians, she explained.

This recognition generated the Perkins CVI Protocol, which fills the education gap and provides a database of information to support educators and physicians in the US and worldwide.

“The teaching and diagnostic assessment tool that was created has enough embedded educational resources for educators to learn about the disorder, easily accessible, and sufficiently well-structured to be reliably valid and useful for those with all levels of understanding about CVI,” Cronan explained.

This tool is designed to provide more of a “whole-child” diagnostic assessment of CVI than previously available and identify children who may not have been previously diagnosed.

Part 1 is an anonymous data medical file review that compiles all the basic information about each patient and facilitates amassment of demographic information in the database that can be shared with researchers.

From this database, a lengthy list of questions was compiled to be used with parents that looks at 16 visual behaviors, the result of which is a functional visional assessment (customized student sketch) of the individual’s visual behaviors, what the experienced behaviors may mean, and recommendations for that patient.

The tool includes links to videos/articles about the visual behaviors and scientific reports, tutorials, and lists of online learning courses.

This part also generates a letter to be sent to patients’ eye care providers to include them in the assessment of possible CVI to access care.

Part 2 is an education roadmap that is currently under development and validation and is expected to be rolled out in early 2023. It will incorporate everything from part 1 and create a series of recommendations for observations and direct assessments that will generate an in-depth report and provide a set of educational recommendations.

“This report will inform independent educational plans, which are core to special education,” Cronan explained.

A conference on CVI is scheduled for June 26-28, 2022, in Boston.

https://www.perkins.org/event/cvi-collab-conference/#register

“The goal is to identify and diagnose these children earlier and follow them closely to obtain the best benefit. Identifying them when they are in their teens may mean that valuable time has been lost although it is never too late,” Merabet said.

Merabet has no financial interest in this subject matter; Cronan is an employee of Perkins School for the Blind.

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Martín MB, Santos-Lozano A, Martín-Hernández J, et al. Cerebral versus ocular visual impairment: the impact on developmental neuroplasticity. 

Bauer CM, Heidary G, Koo BB, et al. Abnormal white matter tractography of visual pathways detected by high-angular-resolution diffusion imaging (HARDI) corresponds to visual dysfunction in cortical/cerebral visual impairment. J AAPOS 2014;18 398–401. 10.1016/j.jaapos.2014.03.004;https://doi.org/10.1016/j.jaapos.2014.03.004

Hirsch GV, Bauer CM, Merabet LB. Using structural and functional brain imaging to uncover how the brain adapts to blindness. 

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