View news from the 2021 SABCS, including session summaries, poster write-ups, and interviews with key opinion leaders.

Coverage of the 2021 San Antonio Breast Cancer Symposium

View news from the 2021 ACAAI Annual Scientific Meeting, including session summaries, poster write-ups, and interviews with key opinion leaders.

Coverage of 2021 ACAAI Annual Scientific Meeting

If 2020 was dominated by the news of how COVID-19 spread across the globe, then 2021 has so far been focused on ending the pandemic through vaccine distribution.

A Timeline of COVID-19 Vaccine Developments in 2021

This AJMC® Profiles in Care provides an in-depth look into the results of the outcomes-based agreement between Boehringer Ingelheim and Highmark Inc.

AJMC® Profiles in Care Launches

Circulating Interleukin-11 (IL-11) is difficult to detect in healthy individuals, but when it is present in various inflammatory diseases, it has an elevated presence in affected tissues, according to a literature review. The review, published online in 

, will appear in the January 2022 issue of the journal.

Whether the elevation of IL-11 is pathogenic or a natural host response to restore homeostasis has not been made clear for many diseases.

This review summarized the current literature describing roles for IL-11 in several inflammatory diseases and the emerging therapeutic interest in modulation of IL-11 signaling within these diseases.

IL-11 production by both immune and non-immune cells is not as well-characterized.

 In the overview of IL-11 signaling, the authors explained that the cytokine can exert various immunological activities within both the innate and adaptive immune processes. “IL-11 is a 19-kDa protein with a typical type-1 four α-helical bundle,” the authors explained, adding that it is part of the IL-6 family of cytokines.

IL-6 is the most comprehensively characterized member of the cytokine family, which also includes leukemia inhibitory factor, Oncostatin M, ciliary neurotrophic factor, cardiotrophin-1, cardiotrophin-like cytokine, neuropoietin, IL-27, and IL-31.

studies have shown that IL-11 can directly modulate macrophage activity through inhibition of TNF-α, IL-1β and IL-12 production,” they wrote. “Consistent with this, recombinant human IL-11 has been shown to down-regulate serum TNFα and IL-1β levels in a murine model of endotoxemia.”

This suggests IL-11 acts as an anti-inflammatory cytokine through modulation of the effector function of macrophages.

It also been shown to play a role in the differentiation of B and T cells, as IL-11 promoted immunoglobulin G (IgG) and M (IgM) production when B cells were co-cultured with T cells and macrophages. However, it did not directly effect purified B cells, which implies the promotion of antibody production was mediated indirectly through T cells or macrophages.

. The authors also outlined current literature surrounding IL-11 and autoimmune diseases, including rheumatoid arthritis (RA), multiple sclerosis, type 1 and type 2 diabetes, and systemic sclerosis. Additionally, inflammatory pathologies such as asthma, chronic obstructive pulmonary disease, inflammatory bowel disease, psoriasis, periodontitis, and pancreatitis were heavily covered in various publications.

gene has been detected in the synovial tissue and the IL-11 protein has been identified in the synovial fluid and is undetectable in healthy controls. Experts believe macrophages and fibroblasts are likely the main cellular sources.

“More recently, RNA-seq analysis showed that 

was one of the most highly upregulated genes produced by human synovial fibroblasts when co-cultured with a subtype of pro-inflammatory macrophage,” the authors said. “Interestingly, the increased 

expression was dependent on the EGFR signaling pathway, because the expression of 

was abolished when the human synovial fibroblasts were treated with an EGFR inhibitor.”

They also mentioned that IL-4—which promotes generation of Th2 cells—has been shown to inhibit IL-11 production by rheumatoid synovial cells. However, contributions of IL-11 signaling to the pathogenesis of RA is unclear, and the included studies on RA did not define how IL-11 modulated inflammation.

“A more detailed understanding of the biology of IL-11 is required in order to best determine whether inhibition of signaling by this cytokine is appropriate in different disease contexts,” the authors concluded.

Fung KY, Louis C, Metcalfe. RD, et al. Emerging roles for IL-11 in inflammatory diseases. 

. Published online doi:10.1016/j.cyto.2021.155750

Articles

Circulating Interleukin-11 is difficult to detect in healthy individuals, but when it is present in various inflammatory diseases, it has an elevated present in affected tissues, according to a literature review.

Review Explains Role of IL-11 in Inflammatory Diseases

Due to the rise of coordinated misinformation about vaccines, false beliefs about flu vaccines must be corrected immediately, according to Leslie Kantor, PhD, MPH, chair and professor of the Department of Urban-Global Public Health, Rutgers School of Public Health. 

In the past, flu vaccinations were not quite as politicized, as we've seen with the COVID-19 vaccination. Do we think that that may be changing this year, and how do public health officials address that?

Yeah, it's very important that we all keep in mind that there is a very well-organized antivaccination effort all around the world. This is not just somebody’s crazy uncle making things up. There is a concerted effort to put misinformation out. It is then transmitted via bots all over the world. So, there's unfortunately a good chance that there will be additional misinformation about flu vaccines that we haven't seen in the past. Because the truth is, there is misinformation out there about just about every vaccine that's available right now. So, what do we need to do? We need to talk to our family and friends, our patients where we do have influence, and try to deal with that misinformation as soon as we hear about it.

Videos

Misinformation about flu vaccines must be dealt with immediately, according to 
Leslie Kantor, PhD, MPH, chair and professor of the Department of Urban-Global Public Health, Rutgers School of Public Health.

Dr Leslie Kantor on Responding to Misinformation About Flu Vaccines

 since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey. 

Appropriate management of lifestyle is likely to attenuate the severity of non-alcoholic fatty liver disease (

) and improve patients’ quality of life (QOL), according to authors of a review published in 

NAFLD is becoming a major health concern around the world, affecting approximately a quarter of the global adult population—an increase concurrent with epidemics of obesity and type 2 diabetes (T2D), researchers explained.

In addition to liver-related morbidity, NAFLD is associated with cardiovascular disease and malignancies, and is partially attributable to the modern Western lifestyle of unhealthy diet and lack of physical activity.

To better elucidate the potential effect of this lifestyle on NAFLD and to understand the effect of NAFLD on QoL, researchers summarized recently published evidence on these subjects.

One small pilot cross-sectional study revealed patients with NAFLD had a higher daily caloric intake than controls despite minimal differences in diet composition. Additional analyses found Western diets and intake of higher amounts of red meat and processed meat are associated with an increased prevalence and risk of the disease.

Sugar-sweetened beverages and soft drinks have also been linked with an increased likelihood of NAFLD, while one meta-analysis showed nuts were the only food group that provided a protective effect. Fruits, vegetables, whole grains, refined grains, fish, and legumes may also have potentially beneficial effects on NAFLD.

In contrast, macronutrients like saturated fatty acids, trans fat, preservatives and additives and fructose all likely lead to NAFLD development, researchers said. However, they cautioned “data on the association between dietary risk factors and NAFLD are based on observational studies; thus, a cause-effect relationship cannot be drawn.” Residual confounding and differing baseline participant characteristics serve as an important limitations on existing literature.

In addition to potential risks posed by individual foods, researchers outlined evidence pointing to an association between the type of cooking employed and NAFLD risk. For example, fried or well-don barbecue meat “may cause the formation of heterocyclic aromatic amines (HAAs) and advanced glycation-end products (AGEs), which have been associated with [insulin resistance] and oxidative stress, common contributors to the pathogenesis of NAFLD,” they said.

Another common feature of the Western diet—unhealthy snacking throughout the day— could contribute to increased triglyceride (TG) deposition in the liver.

Because overnutrition, poor nutritional quality, and decreased physical activity tend to co-exist, these factors can yield a synergistic effect non NAFLD development. Well-designed clinical trials and prospective cohort studies are warranted to better understand the effects of dietary/lifestyle interventions and modifications in these patients.

As no medications specifically licensed for NAFLD exist, “lifestyle adaptations are considered the mainstay of disease management and are recommended by all relevant guide- lines,” authors said.

Most of these adaptations focus on weight loss via diet change or regular exercise, while one cross-sectional study found that combined, high-quality diet and increased physical activity reduced NAFLD risk when compared to each action individually.

Low-fat, low-carbohydrate, and the Mediterranean Diets have also been evaluated in NAFLD and results indicate “the main driver of NAFLD improvement is likely to be energy restriction rather than diet composition.”

Several studies have highlighted potential benefits of the Mediterranean Diet on NAFLD. This diet consists of higher intake of whole grains, vegetables, fruits, nuts, olive oil, and fish and lower intake of red meat and alcohol.

However, high heterogeneity exists among studies and randomized controlled trials are needed. Until. Better evidence emerges, “reducing daily calorie intake, avoiding the aforementioned NAFLD-promoting foods, and following the [Mediterranean Diet] seems to be a sensible approach,” for patients, researchers noted.

When it comes to physical activity, repetitive, regular exercise can be beneficial in NAFLD even in the absence of significant weight loss. In patients with NAFLD, exercise can improve peripheral insulin sensitivity, suppresses liver fat synthesis, and potentially favor an anti-inflammatory state.

Although some aspects of exercise on NAFLD remain unclear, existing literature conclude any involvement in physical activity is superior to sedentary behavior.

With regard to QOL, limited data indicate NAFLD mainly impacts physical health, although increasing evidence has pointed to a variety of symptoms including anxiety, depression, and cognitive impairment. According to authors, this suggests “NAFLD may in fact be a symptomatic disease, albeit with non-specific symptoms, and not a ‘silent disease.’” Previous research also indicates QoL tends to deteriorate as the disease progresses.

“The modern Western lifestyle, characterized by unhealthy eating habits and inadequate physical activity, is frequently associated with development of metabolic diseases, including NAFLD,” authors concluded.

Vachliotis I, Goulas A, Papaioannidou P, Polyzos SA. Nonalcoholic fatty liver disease: lifestyle and quality of life. 

. Published online December 1, 2021. doi: 10.1007/s42000-021-00339-6

Authors of a review published in Hormones outlined the benefits of healthy eating and physical activity to prevent and improve non-alcoholic fatty liver disease.

Healthy Eating, Exercise Encouraged to Help Improve QOL in NAFLD

To date, just a small number of cases have documented 

 (PV) in pregnant women. This rare myeloproliferative neoplasm poses a particular risk of thrombosis in these patients and requires anti-platelet treatment. A group of researchers looked at the case of a pregnant women with PV to add to the limited information of managing the condition in these patients.

Three years after being diagnosed with JAK2-positive marked PV, the 38-year-old patient became pregnant. In addition to receiving her current medication, the patient began anticoagulant treatment while being closely monitored by both her obstetrician and hematologist.

“The particularity of the case of PV in pregnancy presented herein embodies the difficulties in diagnosis of this pathology in a woman of fertile age, and the need for interdisciplinary collaboration in order to obtain a good and safe outcome for both mother and child,” emphasized the researchers, writing in 

. “A young age for PV, but an advanced maternal age is the most challenging background for a high‐risk pregnancy with multiple and complex associated diseases.”

On the 23­rd week of pregnancy, cytoreductive treatment was reduced to pegylated interferon‐α twice a week, owing to the favorable evolution of PV. While hydroxyurea is typically the preferred drug for initial PV treatment due to its efficacy, limited toxicity, and low cost, young patients and pregnant patients often instead receive interferon‐α because it offers the possibility of a cytogenic remission. The treatment also offers favorable safety in pregnant patients compared to hydroxyurea.

Throughout the pregnancy, ultrasound showed normal fetal growth and normal amniotic fluid index, and the patient experienced no thrombotic events. The baby was born with no neonatal complications.

“To the best of our knowledge, there are limited studies available in the literature debating the management of PV in pregnancy,” wrote the researchers. “A recent study by Robinson 

concluded that it is essential for the optimal fetal prognosis to act actively in the hemogram balance.”

Based on the European Collaboration on Low‐Dose Aspirin in Polycythemia Vera trial, it is suggested that 100 mg of aspirin daily reduces the risk of non‐fatal myocardial infarction, non‐fatal stroke, pulmonary embolism, major venous thrombosis, or death from cardiovascular causes. In the current case study, 150 mg of aspirin was considered based on screening and preventing pre-eclampsia and other fetal and maternal complications. Enoxaparin was added due to peripheral venous insufficiency with a high risk of thrombosis. According to the researchers, the case study suggests that better results are achieved when using cytoreductive treatment and low-dose aspirin.

Bohiltea R, Niculescu-mizil E, Mihai B, et al. Polycythemia vera in pregnancy represents a challenge for a multidisciplinary collaboration: A case report and literature review. 

 2022;23(1):19. doi: 10.3892/etm.2021.10941

According to the researchers, the case study suggests that better results are achieved when using cytoreductive treatment and low-dose aspirin.



Case Report Suggests Improved Outcomes of PV During Pregnancy With Cytoreductive Treatment, Aspirin

With special considerations needed for the treatment of elderly or unfit patients with 

 (CLL), researchers have compiled the available evidence for using certain treatment approaches in this population, with an aim to improve survival and quality of life.

The researchers outlined potential treatment options for this patient population since the emergence and uptake of targeted treatments, offering preferred options that are a better fit for such patients, compared with more traditional chemotherapy approaches.

“In the era of targeted therapies, treatment of elderly/unfit patients with CLL must be a balance between efficacy and safety,” commented the researchers. “Although it is not possible to make direct comparisons between results of different studies, some considerations may guide the choice toward the best treatment option in elderly patients, considering both quality of life and life expectancy.”

Treatment approaches outlined by the group include chemoimmunotherapy, B-cell receptor (BCR) inhibitors, and venetoclax.

 approaches are decreasing in use among the elderly population as more chemotherapy-free options become available. For older patients (aged 65 years and older) that are considered fit, bendamustine with anti-CD20 antibodies, rituximab in particular, is still considered as an option. The bendamustine-rituximab combination has established a better risk-benefit profile than fludarabine–cyclophosphamide and rituximab, despite its inferior progression-free survival (PFS), because of its lower toxicity. Bendamustine has also been studied with obinutuzumab; together, the combination showed a complete response (CR) rate of 32% in patients that were a median age of 68 years. However, the combination also led to tumor lysis syndrome (TLS).

used in this patient population include ibrutinib, acalabrutinib, and a combination of idelalisib and rituximab. Approved for CLL in the relapsed/refractory setting, and for patients with del (17)/TP53 in the first-line setting, ibrutinib has shown superiority over chlorambucil frontline and ofatumumab, although there have been identified side effects of concern in elderly/unfit patients, including atrial fibrillation, hypertension, and bleeding.

In a trial of elderly/unfit patients aged a median of 74 years, acalabrutinib, with or without obinutuzumab, demonstrated improved overall survival rate (ORR) over chlorambucil–obinutuzumab, and in another trial showed superior PFS compared with bendamustine–rituximab and idelalisib-rituximab. In the latter trial, acalabrutinib alone was associated with serious adverse events in 29% of patients compared with 56% of patients treated with ibrutinib-rituximab and 26% of patients receiving bendamustine–rituximab.

in older patients was studied in a large, real-life trial of over 300 patients with relapsed/refractory CLL. Compared results in patients aged over 75 years and patients aged under 75 years, the study demonstrated no differences in ORR (81% vs 82%), 1-year PFS (79% vs 73%), or 1-year overall survival (77% vs 83%). Similar safety results were also found, with TLS being reported in 3% of patients in both age groups.

Fresa A, Autore F, Galli, et al. Treatment options for elderly/unfit patients with chronic lymphocytic leukemia in the era of targeted drugs: A comprehensive review. 

. 2021;10(21):5104. doi: 10.3390/jcm10215104

The researchers outlined potential treatment options for this patient population since the emergence and uptake of targeted treatments.


Targeted Therapies Offer Attractive Treatment Approach for Elderly/Unfit Patients With CLL

Samsung Bioepis launched a new white paper ‘Improving the Understanding and Acceptance of Biosimilars in the United States.’ The new white paper, developed based on research in 2021, highlights current perceptions, knowledge gaps, and barriers within the U.S. healthcare environment that are stymying adoption of biosimilars, and outlines potential strategies and incentives to help expand biosimilars’ use to help reduce healthcare costs while maintaining a high standard of patient care. The report is informed by the insights of key opinion leaders and subject matter experts, including doctors, pharmacists, nurses, patient advocates, and drug policy experts, who participated in three virtual expert panel sessions held in June-July 2021.

Link to Press Release on Samsung Bioepis website

Samsung Bioepis launches white paper highlighting barriers and opportunities to drive biosimilar adoption in the United States.

Improving Understanding and Acceptance of Biosimilars in the United States

® since 2019 after receiving his Bachelor's degree at Rutgers University–New Brunswick in journalism and economics.

US adults with atopic dermatitis (AD) may be at greater risk of psychiatric, autoimmune, and systemic comorbidities than the general population, according to study findings published in the

Journal of the American Academy of Dermatology

 as the leading cause of disability among skin conditions, is characterized by a complex etiology that shares systemic implications. Notably, studies investigating the comorbidity burden in patients with AD have focused mostly on inpatient populations, despite the condition being primarily seen in the ambulatory population.

“There is a need to better characterize AD and its comorbidities in a more representative, real-world setting to better guide counseling and management of patients with AD,” said the study authors.

Examining an ambulatory population derived from the MarketScan Commercial Claims and Encounters database between January 1, 2017, and December 31, 2017, researchers conducted a retrospective analysis to better characterize the real-world comorbidities present in AD populations.

In the study, the comorbidity burden of adult patients with AD (n = 39,779; mean [SD] age, 42.5 [13.7] years; 63.9% female) was compared with age- and sex-matched controls from the general population (n = 353,743) via multivariable logistic regressions.

Compared with the control group, patients with AD exhibited an extensively greater risk of comorbidities overall:

Psychiatric conditions: obsessive-compulsive disorder (odds ratio [OR], 2.01), schizophrenia (OR, 1.45), anxiety (OR, 1.44), attention-deficit hyperactivity disorder (OR, 1.43), eating disorder (OR, 1.33), and mood disorder (OR, 1.31).

Infectious conditions: methicillin-resistant 

Autoimmune diseases: alopecia areata (OR, 6.01), vitiligo (OR, 4.44), dermatopolymyositis (OR, 3.54), systemic lupus erythematosus (OR 2.46), connective tissue disease (OR, 2.34), and Sjögren syndrome (OR, 2.17).

Systemic conditions: atherosclerosis (OR, 1.69), 

 (OR, 1.52), metabolic syndrome (OR, 1.47), hyperlipidemia (OR, 1.37), chronic kidney disease (OR, 1.28), and sleep disorders (OR, 1.52)

Increased risk of oncologic, dermatologic/allergic, and neurologic/ocular conditions, as well as other comorbidities of the aforementioned disease types, was also identified in patients with AD compared with the general population.

Several limitations were noted regarding the study findings, including its retrospective study design and use of health care claims data that prevented controlling for other potential confounders, such as ethnicity, race, and AD severity.

“Real-world, ambulatory adults with AD were associated with a wide range of psychiatric, dermatologic, and extracutaneous comorbidities, highlighting the systemic nature of this disease,” they concluded. “Increased awareness of the comorbidity burden and modifiable risk factors in AD can help guide 311 effective counseling, workup, and management of these patients.”

Roh YS, Huang AH, Sutaria N, et al. Real-world comorbidities of atopic dermatitis in the U.S. adult ambulatory population. 

. Published online November 17, 2021. doi:10.1016/j.jaad.2021.11.014

A high comorbidity burden, including psychiatric, autoimmune, and systemic conditions, was found in US adult ambulatory populations with atopic dermatitis.

Higher Risk of Systemic, Psychiatric Conditions Found in Patients With Atopic Dermatitis

High levels of nitric oxide (NO) and carbon monoxide (CO) suctioned out from the nasal-paranasal sinuses can be used to distinguish 

 from healthy controls, according to study results published in 

Although no pathophysiological origin of migraine has been identified, numerous theories have been proposed, including the sinus hypoxic nitric oxide hypothesis, which purports that diffused sinus NO (dsNO) in the nasal mucosa causes migraine, researchers explained.

“Hypoxia leads to increase production of NO and CO, which have vasodilatory and anti–inflammatory actions,” they added, while “administration of intranasal NO scavengers has been proven to neutralize nasal NO and reduce migraine attacks and the severity.”

In the current analysis, investigators in Sri Lanka studied the levels of NO and CO in the air sucked out from the nasal-paranasal sinuses in migraine patients and healthy individuals.

All study participants were between ages 16 and 19 years. Those with migraine underwent the procedure during an acute episode and all samples were taken within 6 hours of headache onset. None had taken acute treatment for migraine prior to the procedure.

“Three normal oral breathings were taken before the breath test for NO and CO to wash out paranasal gases. Then, after maximal oral inspiration, subjects were instructed to exhale into the device mouthpiece of the NO and CO analyzer,” authors wrote.

A normal exhaled NO level was defined as 5 to 10 ppb, and 1.01 ± 0.12 ppm was considered normal for CO. A total of 20 migraineurs and 22 healthy participants completed the study. Participants also reported their general headache pain before and after suction using a standard pain rating scale (0 being pain free and 10 being severe pain).

Patients had comparatively high values compared with controls for paranasal NO (both left and right sides), paranasal CO (both left and right sides), fraction exhaled NO (FeNO), and fraction exhaled CO (FeCO).

Patients had median paranasal NO contents of 132.5 ppb and 154 ppb on left and right sides, respectively, compared with 36 ppb and 34.5 ppb corresponding values in controls (

A similar pattern was observed with paranasal CO (

FeNO and FeCO content were also higher in migraineurs (

Receiver operating characteristic curves of all gas measurements showed that they all could classify patients and controls effectively and NO was the most effective followed by paranasal CO.

With paranasal sinus NO, all patients had values above 50 ppb and controls had values below 50 ppb.

With paranasal sinus CO, all patients had values of 1 ppm or above, but all controls had this value less than 1 ppm but recorded as 1 ppm.

After air suction, the mean pain scores of general headache and tenderness dropped by a very large margin in migraine patients (

Overall, “these data strongly indicated that migraine patients in general have comparatively 4-5 times higher values of NO in paranasal air compared to controls,” the authors wrote. They continued, “CO concentration in paranasal air was also very high (

 < .0001) in migraine patients than controls, where patients had a median CO level of 2 ppm (both left and right sides) compared to 1 ppm (both left and right sides) in controls.”

Currently, no specific laboratory test has been established for the diagnosis of migraine, and researchers suggest that these exhalation tests may help aid diagnosis in difficult situations—for instance, when headache symptoms overlap with other.

As the study was only carried out among those aged 16 through 19, results may not be generalizable to the wider adult population, marking a limitation.

“Further studies are needed to conclude that NO and CO can be a causative molecule for migraine headache,” researchers concluded.

Bandara SMR, Samita S, Kiridana AM, and Herath HMMTB. Elevated nitric oxide and carbon monoxide concentration in nasal-paranasal sinus air as a diagnostic tool of migraine: a case – control study. 

. Published online October 26, 2021. doi:10.1186/s12883-021-02434-y

In a small study, researchers identified high nasal-paranasal sinus nitric oxide and carbon monoxide levels as potential migraine biomarkers. 

Researchers Find Potential Diagnostic for Migraine in Sinuses

An analysis of CDC data from 2018 revealed more US children are being diagnosed with autism and at younger ages, the Associated Press 

. Among 8-year-olds in 2018, 1 in 44 had been diagnosed with autism, while in 2016, that rate was lower at 1 in 54. According to experts, the rise reflects more awareness of the developmental condition and wider availability of treatment services as opposed to a true increase in those affected. Additional CDC data showed that children up to age 4 were 50% more likely to be diagnosed with autism in 2018 compared with 2014. However, rates vary depending on geographic locations, with 1 in 26 children diagnosed in California and 1 in 60 in Missouri.

Private Health Insurance to Cover COVID-19 Tests 

As part of President Joe Biden’s strategy to track the 

 of COVID-19 and tackle a potential winter surge, the administration announced it would seek to require private health plans to cover at-home COVID-19 tests, POLITICO 

 If enacted, more than 150 million Americans with private health plans would be reimbursed for the tests if they submit expenses to their insurance provider. Some authorities within the Families First Coronavirus Response Act direct private insurers to provide coverage and prohibit them from imposing cost sharing of the diagnostic tests during the public health emergency, according to POLITICO. HHS and the Labor and Treasury departments have yet to issue official guidance on the reimbursement requirement.

 suggest lead, mercury, and other pollutants could affect the ratio of boys to girls born each year, NBC News 

. The study included data from around half of the US population and the entire Swedish population and found that pollution in different geographic regions could affect children before they are born. Different pollutants may prevent some pregnancies from being carried to term, which could result in imbalances in how they affect each sex, experts said. According to authors, regions with higher mercury exposure produced a slightly higher ratio of boys; areas with lead in the soil were linked with higher proportions of girls born.

New data suggest more children are being diagnosed with autism in the United States; Biden pushes for coverage of at-home COVID-19 tests; different pollutants may affect the ratio of boys to girls born. 

What We’re Reading: US Autism Prevalence; Coverage for At-Home COVID-19 Tests; Pollutants May Affect Birth Ratios

 found that participants with chronic cough tolerated and saw improvements in symptoms after transcutaneous electrical nerve stimulation (TENS) treatment.

The study also pointed out that participants experienced minimal adverse effects during and after treatment.

“Patient-reported stimulation of the appropriate anatomic area that corresponded to their symptoms demonstrated feasibility,” the study authors said. “This study can inform future research by providing evidence of tolerable TENS device settings and methods for application.”

TENS is a form of electroanalgesia used for neuropathic pain disorders; in healthy participants, it has been found to increase the somatosensory threshold throughout the stimulated receptive field of the applied current. Availability, affordability, ease of use, and relative lack of side effects or drug interactions are all advantages of TENS. While this noninvasive treatment may have a more pronounced effect on hypersensitive neurons compared with normal neurons, that effect is theorized to underlie its efficacy in treating neuropathic conditions.

The study only included 5 participants with refractory chronic cough; all participants were female with a mean age of 73 years. One participant was White, 2 were Black, and 2 were Hispanic or Latin American.

All participants completed the Cough Severity Index (CSI) and Newcastle Laryngeal Hypersensitivity Questionnaire (NLHQ) to evaluate the baseline characteristics of their cough. The mean CSI score was 25.6 and the mean NLHQ score was 14.8.

For the TENS treatment, participants were seated in a semi-reclining position and the cricoid cartilage, thyroid cartilage, hyoid bone, and thyrohyoid membrane were identified. The researchers used the TENS LGMedSupply LG-3000 unit and attached lead wires to self-adhesive electrode pads.

“For all patients, the cathode was placed over the left thyrohyoid membrane, approximating the location of internal branch of the superior laryngeal nerve, and the anode was placed over the left paramedian cricothyroid space,” the authors explained. “Leads were applied unilaterally to the left side to avoid possible bradycardia through stimulation of the right vagus nerve.”

To assess tolerability, the researchers performed a flexible laryngoscopy prior to TENS activation. They did not use an intranasal lidocaine or decongestant in order to prevent topical anesthesia from being an uncontrolled variable. Visual inspection of the external anterior cervical musculature was used to measure contractions. To assess feasibility, visual inspection was used to measure pad movement.

“As the TENS unit was powered on and gradually increased to the maximum tolerated intensity, the larynx was monitored for any abnormal motion, spasm, or muscle contraction deemed outside of the normal range of motion on a standard laryngologist assessment,” the authors noted. “After the maximum tolerated intensity was reached, the flexible laryngoscope was withdrawn, and the patient underwent continued TENS treatment.”

TENS treatment consisted of two 15 minute sessions with a 2 minute break in between.

During each 15 minute session, the unit was kept at a frequency of 120 Hz and a short pulse duration of 120 µs. Intensity slowly increased to the maximum tolerated intensity, which was then maintained for the duration of each session.

Participants rated symptoms before, during, and after TENS treatment using a 5-point Likert scale ranging from 0 to 4, with 4 being the highest severity of chronic cough symptoms.

Each participant rated their symptoms before, during, and after treatment, respectively, as follows:

The mean rating before, during, and after TENS treatment was 2, 1.2, and 1, respectively.

Participant 4 was the only one to report an increase in symptoms. This was noted as new-onset mild hoarseness that had completely resolved within 24 hours after treatment, though the exact duration was not reported. The researchers observed normal vocal cord motion and did not observe any signs of laryngospasm or involuntary vocal fold adduction or contraction.

While acknowledging the small and homogenous sample in the study, the authors still said TENS treatment for chronic cough it tolerable, feasible, and demonstrated a trend toward improved symptoms during and immediately after treatment.

“Future studies that are designed to evaluate the long-term benefits of TENS application in a controlled office setting would be beneficial,” they said. “Additionally, since there is currently no evidence substantiating TENS as a standalone treatment for neuropathic cough, it would also be beneficial to study TENS administration as an adjunct treatment.”

Michalowski A, Haines A, Shaparin N, et al. Transcutaneous electrical nerve stimulation as a treatment for neuropathic cough: a tolerability and feasibility study. 

. Published online May 18, 2021. doi:0.1007/s40120-021-00255-2

A small study found that patients with chronic cough saw improvements in symptoms following transcutaneous electrical nerve stimulation treatment, with minimal adverse effects.

TENS Has Potential as a Treatment for Chronic Cough, Small Study Finds

Nearly 2 million new cancers were expected to be diagnosed in the United States in 2021, with an estimated 608,570 cancer-related deaths. Despite significant advances in detection and treatment, cancer remains the second leading cause of death in the United States after cardiovascular disease (with the exception of temporal changes due to COVID-19).

Delays in early diagnosis and treatment during the COVID-19 pandemic may further increase the burden of cancer in the coming years.

 Direct US medical costs for cancer in 2020 were an estimated $200.

 billion (in 2019 dollars), an increase of 10% since 2015.

 Given the aging population, costs are expected to reach $246 billion by 2030.

Between 1991 and 2018, the age-adjusted cancer mortality rate in the United States declined 31%, due, in part, to declines in smoking, improvements in early detection, and advancements in treatment for some cancers. That translates to about 3.2 million fewer cancer deaths.1 Those trends are largely driven by improvements in lung, colorectal, breast, and prostate cancer deaths. Many others (eg, pancreatic, ovarian, and liver) are primarily diagnosed in the later stages; thus, there are still disappointing 5-year survival rates. The 5-year relative survival rate (defined as the ratio of observed survival in a population to the expected or background survival rate) for pancreatic cancer, for instance, is just 10%.

Earlier diagnosis has the potential to reduce cancer-related deaths. One study estimated 15% fewer cancer-related deaths if those with stage IV cancers had been diagnosed at stage III.

Other research predicts that early cancer detection could increase 5-year survival rates to 90%.

 In lung cancer, which was the leading cause of cancer death in the United States, patients diagnosed in the earliest stages have a 59% 5-year relative survival rate, while those diagnosed in stage IV have a 6% survival rate.

However, a study that implemented population-based ovarian cancer screening found earlier diagnosis did not reduce cancer-related deaths.

This result is a reminder that shifts in stage at diagnosis may not always correlate with mortality reductions. Studies that measure both are important in establishing the efficacy of early detection efforts.

The US Preventive Services Task Force (USPSTF) recommends population-based screening for breast, colorectal, and cervical cancers.7 For prostate cancer, the Task Force recommends an individual decision based on a discussion of potential harms and benefits.

The Task Force also recommends screening certain smokers for lung cancer.

 contains a summary of cancer screening tests and recommendations from the USPSTF. Early detection as well as advances in treatment are likely behind the declining mortality rates for these cancers. However, cancers without recommended screening tests account for 71% of cancer deaths in the United States.

The Task Force’s decisions on screening recommendations are based on 4 factors

Evidence related to beneﬁts and harms from randomized clinical trials and observational studies.

Whether benefits outweigh harms and, if so, by how much and in which populations.

The degree of certainty the evidence provides for both beneﬁts and harms.

Ages and other risk factors needed to specify when to begin and when to stop offering the service and in which populations.

As new data become available, the USPSTF continues to update its guidance. In 2021, it changed the 2013 screening recommendation for lung cancer by expanding the eligibility pool for low-dose computed tomography (LDCT) scans from adults aged 55 to 80 years with a 30 pack-year smoking history to those aged 50 to 80 years with a 20 pack-year history.

The same year, it also revised the 2016 colorectal screening recommendations from adults aged 50 years or older at average risk of colorectal cancer to those aged 45 years in light of increasing rates of the cancer being diagnosed in younger people.

Federal goals for 2030 are highlighted in Table 2.

Despite well-publicized guidelines, screening uptake in the United States remains below goals (Table 2). Numerous barriers, including financial, a lack of awareness about screening as well as provider recommendations, psychosocial and logistical barriers, a lack of trust in the healthcare system, and access, contribute to this result.

 Screening for cervical and breast cancer declined between 2011 and 2019 in insured populations; additionally, for cervical and colorectal cancers, screening declined in uninsured populations.

A recent analysis of the Surveillance, Epidemiology, and End Results (SEER) Program database presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2021 virtual meeting found an increased incidence in cervical cancer among women younger than 50 years and a significant decrease in the 5-year survival rate, though the authors did not correlate it with the lower screening rate.

Results of a study based on the 2018 Behavioral Risk Factor Surveillance System data found significant differences in meeting breast, cervical, and colorectal cancer screening guidelines among women based on age, race, and ethnicity, as well as socioeconomic and insurance status. For example, women without health insurance had a 26% to 39% lower prevalence of breast cancer screening compared with those with insurance. Overall, women with annual household incomes less than $50,000, education below the college level, those who live in rural counties, those without insurance, or those who could not pay for healthcare were less likely to be screened.

A recent retrospective claims analysis of a large commercial and Medicare Advantage database from 2008 to February 2020 presented at Academy of Managed Care Pharmacists (AMCP) Nexus 2021 found cancer screening rates of 1.2%, 11.7%, 20.8%, 51.4%, and 64.4% for lung, prostate, colorectal, cervical, and breast cancers, respectively, based on guidelines during that period.

The COVID-19 pandemic exacerbated screening barriers. Early in the pandemic, medical centers closed to elective procedures, including screenings; individuals were loath to go to those still open (and even after they reopened) given fears of infection; nearly 2.7 million people lost employer-provided health insurance between April 23, 2020, and December 21, 2020, and thus coverage for screenings.

In addition, several medical societies recommended postponing screening.

One large tertiary center saw 20.6% of its mammogram appointments cancelled in March 2020, before decreasing to 7% in August of that year.

A retrospective cohort screening of about 60 million Medicare Advantage and commercially insured individuals found a sharp decline in screening for breast, colorectal, and prostate cancers (90.8%, 79.3%, and 63.4%, respectively) between March 2020 and May 2020 compared with the same time in 2018 and 2019. Based on these declines, the authors estimated an absolute deficit in screening in the United States of 9.4 million people in 2020 (3.9 million, breast; 3.8 million, colorectal; and 1.6 million, prostate).

Cancer remains the second leading cause of death in the United States despite decades of treatment advances. While death rates have fallen for breast, cervical, and colorectal cancers, death rates remain high for the majority of malignancies, primarily given the late stage at which they are diagnosed. The US Preventive Services Task Force currently recommends routine screening for just 4 cancers: breast, cervical, colorectal, and lung (for high-risk individuals); for prostate cancer, recommendations support individual decision making. However, cancers without recommended screening tests account for 71% of cancer deaths in the United States. In addition, screening rates remain below national goals, with numerous barriers to population-based screening. Recently, initial results of studies on blood-based multicancer early detection tests, which rely on measurement of a range of analytes, demonstrate the potential to identify multiple cancers in a single blood test and detect many cancers for which no screening tests are currently recommended. Blood-based tests have the potential to be more accessible and easier to disseminate than organ-specific tests. However, it remains unclear if their use can reduce deaths from these cancers. Other issues include cost-effectiveness, the impact of false-positive and false-negative results on patients and costs, and uptake among individuals and clinicians. Research and development of blood-based multicancer early detection tests continue.