Gianna Melillo

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

As Rochelle Walensky, MD, MPH, prepares to assume the role of CDC director on January 20, the former professor of medicine at Harvard Medical School and infectious disease physician at Massachusetts General Hospital and Brigham Women’s Hospital faces a myriad of challenges wrought by the ongoing coronavirus disease 2019 (COVID-19) pandemic.

 since the first case of COVID-19 was reported in the United States, while current data indicate the country has surpassed 

. In comparison, the 1918 flu pandemic took 675,000 American lives, while the US reported a total of 405,000 fatalities during World War II.

Even at the unprecedented speed with which pharmaceutical companies have developed vaccines for COVID-19, rollout has been fragmented at the state level while 

racial disparities in administration rates

In an effort to improve the national rollout of COVID-19 vaccines, Walensky plans to increase the CDC’s communication to combat any 

 in receiving the vaccine, and indicated she wanted to increase media appearances above those made by current director Robert Redfield, MD, who departs with any remaining Trump administration officials Wednesday. She said making sure science-based communication is effectively disseminated to the public in layman’s terms is a top priority.

“Science is now conveyed through Twitter. Science is conveyed on social media, on podcasts, and in many different ways. And I think that's critical,” Walensky said during a livestreamed interview with 

Howard Bauchner, MD, the journal's editor-in-chief. When confronting vaccine hesitancy or anti-vaxxer sentiment on social media, “There's just this massive void and the right information, I think, is not getting out there… I want to make sure that the science is conveyed. We have to say it to one another. We have to say it to the public. And then we have to say it in other forms.”

Internally, Walensky hopes to bolster the voices of scientists already employed by the CDC. Under the Trump presidency, “they have been diminished. I think they've been muzzled,” Walensky said. “This top tier agency—world renowned—hasn't really been appreciated over the last 4 years, and really markedly over the last year. So I have to fix that.”

 in administering the allotment of COVID-19 vaccines they were given, many have reported 

. Part of the Biden administration’s plan to enhance rollout is to expand vaccine allocation to 4 key locations: federally qualified health centers, community vaccination centers (ie, stadiums), mobile units, and pharmacies.

“Part of the challenge with COVID-19 was that we had a frail public health infrastructure to start. It wasn't ready to tackle what it was given,” Walensky said. As director, she hopes to bring this reality to Congress’ attention. “We're in this because we had warnings for many, many other public health scares in the last 20 years and we didn't fix our public health infrastructure and our data infrastructure,” in response to those tests.

In order to meet President-elect Biden’s goal of 100 million vaccinations in 100 days, the constraints currently faced by federal and state governments need to be mitigated. “We have to titrate our supply and our eligibility so that we somehow hit the sweet spot, wherever it is we are, with how much supply we have and how many people are eligible,” Walensky said. 

While the CDC set the initial guidelines for vaccine eligibility and 

 this month, the Trump administration left actual rules and distribution processes to states, resulting in wide variation across the country. Some states adopted stricter standards that led to 

, while loose adherence has led to long lines and 

Expanding the population of those eligible to administer the vaccine can also help alleviate these roadblocks. These individuals can include retirees, the 

, medical military, upper level medical and nursing students, dentists and veterinarians.

Increasing both the number of vaccination sites and vaccinators will also help address the 

 brought to light by the pandemic. “We want to make sure that we can deliver volume, but also volume to the people in places that might be harder to reach.” In a collaborative approach, the federal government will step in at a state-by-state level and offer help based on each state’s unique challenges, Walensky said.

Articles

As Rochelle Walensky, MD, MPH, prepares to assume the role of CDC director on January 20, the  infectious disease specialist faces a myriad of challenges wrought by the ongoing coronavirus disease 2019 (COVID-19) pandemic. 

Incoming CDC Director to Prioritize Communication, COVID-19 Vaccine Rollout

Results from a prospective observational study showed aqueous transforming growth factor beta (TGF-β) and autotaxin (ATX) exhibited high diagnostic performance in detecting 

 subtypes and could serve as promising biomarkers for glaucoma. 

Progression of glaucoma depends on the disease’s subtype, the authors explained. Although high intraocular pressure (IOP) is characteristic in some types of glaucoma, it can vary and does not always give an exact diagnosis of subtype. “Therefore, there is an urgent and unmet need for biomarkers that can differentiate glaucoma subtypes and presume disease progression,” they wrote.

Elevations in IOP are thought to be the result of increased aqueous humor (AH) outflow resistance, primarily in the conventional pathway which consists of the trabecular meshwork (TM) and Schlemm’s canal (SC) tissues.

However, “in open-angle glaucoma (OAG), primary open-angle glaucoma (POAG), secondary open-angle glaucoma (SOAG), and exfoliation glaucoma (XFG), an abnormal accumulation of extracellular matrix (ECM) is found along the conventional outflow pathway, leading to the disorganization and degeneration of the TM and SC as well as IOP elevation,” researchers explained.

Previous studies have found that upregulated or downregulated levels of TGF-β and ATX are present in patients with various forms of glaucoma. Based on these findings, the researchers hypothesized that “crosstalk may exist between ATX and TGF-βs, suggesting that concurrent levels of these mediators may be promising diagnostic biomarkers.”

To investigate the correlation between ATX and TGF-βs in different glaucoma subtypes, the investigators collected AH samples from patients with cataracts or glaucoma who were 20 years or older and who underwent surgery for these complications between March 2014 and December 2019. Participants presented at the University of Tokyo Hospital and 3 affiliated eye clinics. Machine learning was used to classify eyes into 3 groups depending on OAG diagnosis: POAG, SOAG, and XFG.

IOP was measured using Goldmann applanation tonometry, and maximum preoperative IOP was evaluated within 3 months prior to AH collection. In addition, the authors wrote, “[l]evels of ATX in the AH were determined via a two-site immunoenzymatic assay with an ATX assay reagent using a Tosoh AIA system. TGF-β levels in the AH were measured using a Bio-Plex Pro TGF-β assay.”

Two hundred and eighty-one eyes from as many patients were included in the study. Eighty-eight eyes were normal (without any ocular complications) while 97 had POAG, 48 had SOAG, and 48 had XFG. Researchers measured areas under the curve (AUC), sensitivity, and specify for 4 glaucoma indicators (ATX, TGF-β1, TGF-β2, and TGF-β3).

ATX, TGF-β1, and TGF-β3 were positively correlated with IOP.

ATX was significantly and negatively correlated with the mean deviation.

From least absolute shrinkage and selection operator regression analysis, the AUC values to distinguish each subgroup (normal, POAG, SOAG, and XFG) ranged between 0.675 (POAG vs normal) and 0.966 (XFG vs normal) when the 4 variables were used.

High AUC values were obtained with ATX for discriminating XFG from normal eyes and with TGF-β3 for discriminating XFG from normal eyes, POAG, or SOAG.

“Collectively, ATX and TGF-βs can be used as biomarkers to differentiate glaucoma subtypes; specifically, TGF-β3 and ATX have the ability to discriminate XFG from other subtypes or normal eyes…and ATX is effective in presuming severity in glaucoma,” the authors wrote. “If we can measure the levels of ATX and TGF-β1–β3 in the AH, it would provide information in addition to clinical findings to differentiate glaucoma subtypes.”

The lack of baseline IOP data, as most subjects had already been administered glaucoma eyedrops during their first visit to an outpatient facility, marks a limitation to the study. AH samples for SOAG included those from patients with elevated IOP due to various causes, meaning future studies could benefit from more discrimination. In addition, further in vitro or in vivo studies ought to be conducted to confirm the mechanisms underlying the changes in aqueous ATX and TGF-βs induced in glaucoma, the researchers concluded.

Igarashi N, Honjo M, Asaoka R, et al. Aqueous autotaxin and TGF-βs are promising diagnostic biomarkers for distinguishing open-angle glaucoma subtypes. 

. Published online January 14, 2021. doi:10.1038/s41598-021-81048-3

Results from a prospective observational study showed aqueous transforming growth factor beta and autotaxin exhibited high diagnostic performance in detecting glaucoma subtypes and could serve as promising biomarkers for glaucoma. 

Study Finds Potential Biomarkers for Distinguishing Glaucoma Subtypes 

Compared with triptan nonresponders, patients with 

 who report a response to at least 1 triptan have a higher likelihood of responding to treatment with erenumab, according to real-world data published in 

While acute migraine-specific treatments, most notably triptans, have been available since the 1990s, erenumab—a monoclonal antibody—was 

 by the FDA in 2018. It is administered monthly via self-injection of a 70- or 140-mg dose and blocks the calcitonin gene-related peptide (CGRP) receptor, which is believed to play a crucial role in migraine.

Similarly, “at the peripheral level, triptans constrict extracerebral blood vessels and reduce trigeminal sensory nerve activation, thus ultimately inhibiting vasoactive peptide release including substance P and CGRP,” authors wrote. Because triptans indirectly share their target with erenumab, researchers hypothesized that migraineurs who respond favorably to triptans might also respond to new preventive treatments.

To determine if previous response to triptans predicts the efficacy of erenumab, if the loss of efficacy of triptans over time predicts erenumab’s ineffectiveness, and if erenumab treatment improves the efficacy of triptans, researchers analyzed data of all patients treated with erenumab between January 2019 through March 2020 at several headache centers in Italy.

All participants were between ages 18 and 65, had a diagnosis of migraine with or without aura, and were consecutively treated with erenumab for chronic or high-frequency (≥8 monthly headache days) episodic migraine. Information on triptan use prior to erenumab was collected via a data collection form administered during a telephone interview.

“Patients who reported use of at least one triptan for at least 3 migraine attacks were considered triptan users,” researchers wrote. “Triptan users were classified as ‘triptan responders’ if they were headache-free within 2 hours after treating at least 3 migraine attacks with one triptan; the remaining patients were classified as ‘triptan non-responders.’” Non-responders were asked about decreased response over time and whether the efficacy of triptans improved after erenumab treatment began.

‘Erenumab responders’ were defined as patients who reported a mean ≥ 50% reduction in monthly migraine days from baseline to months 4 to 6 of treatment.

Of the 105 patients treated with erenumab who answered the data collection form, 91 (86.6%) were considered triptan users. Of these patients, 58 (63.7%) were erenumab responders, 33 (32.3%) were erenumab nonresponders, 73 (80.2%) were triptan responders, and 18 (19.8%) were triptan non-responders. Researchers found no significant differences in baseline characteristics between the erenumab responders and nonresponders, apart from triptan use.

Among erenumab responders, 51 (87.9%) were triptan responders while among erenumab non-responders, 22 (66.7%) were triptan responders

The odds ratio (OR) of being an erenumab responder was 3.64 (95% CI, 1.25–10.64) for triptan responders compared with nonresponders (

The OR of being an erenumab responder was 0.78 (95% CI, 0.33–1.83) for patients reporting triptan wear-off compared with those not reporting triptan wear-off (

After starting erenumab treatment, 52 patients (57.1%) continued using triptans; 36 of them (69.2%) were erenumab responders and 16 (30.8%) were erenumab nonresponders

The proportion of patients reporting an improvement in triptan effectiveness was similar in erenumab responders and erenumab nonresponders (52.8% vs 62.5%; OR 0.67; 95% CI, 0.20–2.24; 

Although the findings may be used in clinical practice to advise patients about their chances of response to erenumab, researchers cautioned previous response to triptans alone should not represent a strict criterion to select patients for erenumab, given many triptan non-responders did respond to erenumab.

A limited number of participants, in addition to the potential for recall bias in the study’s design, mark limitations.

Overall, “improving responsiveness to acute medication is a goal of migraine prevention and might be an additional parameter to test the efficacy of preventative drugs,” researchers concluded. “This information is relevant to improve our understanding of migraine and its treatments and to predict the efficacy of migraine-specific preventatives.”

Frattale I, Caponnetto V, Casalena A, et al. Association between response to triptans and response to erenumab: real-life data. 

Published online January 6, 2021. doi:10.1186/s10194-020-01213-3

Compared with triptan nonresponders, patients with migraine who report a response to at least 1 triptan have a higher likelihood of responding to treatment with erenumab, according to real-world data published in The Journal of Headache and Pain.

Data Show Migraineurs Who Respond to Triptans More Likely to Respond to Erenumab

 showed an activin type II receptor (ActRII) blockade, achieved via bimagrumab, led to significant loss of fat mass (FM), gain in lean mass (LM), and metabolic improvements among patients with type 2 

Overweight and obesity are often accompanied by insulin resistance, chronic inflammation, and related comorbid diseases, but the combination of lifestyle management and pharmacotherapy has been increasingly recognized as an effective and safe treatment option for affected patients, researchers explained. Currently, 5 medications are approved for long-term use by the FDA for patients with overweight or obesity.

Bimagrumab, developed by Novartis, is a fully human monoclonal antibody that binds to the ActRII and thus prevents the actions of natural ligands that negatively regulate skeletal muscle growth. However, the underlying mechanisms linking ActRII inhibition with reductions in FM and the mechanisms of improved insulin sensitivity are largely unknown.

Building on clinical findings of a 10-week study that showed “a single intravenous dose of bimagrumab…not only increased lean mass but significantly reduced total body fat mass (FM) and improved insulin sensitivity compared with placebo,” researchers conducted a phase 2 trial to determine the treatment’s efficacy and safety in adult patients with T2D and overweight or obesity. In comparison, the previous study tested bimagrumab in healthy volunteers with insulin resistance who were not dieting.

The randomized clinical trial took place across 9 sites in the United States and United Kingdom between 2017 and 2019. A total of 75 patients aged between 18 and 75 years, with glycated hemoglobin (A1C) between 6.5% and 10%, and with a body mass index (BMI) between 28 and 40 were enrolled in the study; 58 patients completed the trial.

All participants also had a stable body weight between 65 and 140 kg and “were not taking antidiabetic therapy at the time of screening or were receiving stable metformin monotherapy, dipeptidyl peptidase 4 (DPP4) inhibitor monotherapy, or combination therapy of metformin and a DPP4 inhibitor,” as these medications generally have weight-neutral effects.

Patients were randomized 1:1 to receive 10 mg/kg (up to a maximum of 1200 mg in 5% dextrose solution) of bimagrumab (n = 37) or placebo (n = 38) every 4 weeks for 48 weeks, for a total of 12 doses. Doses were administered via a 30-minute intravenous infusion, and the treatment period ended approximately 4 weeks after the last dose administration. All patients had a follow-up period of 8 weeks, met with a registered dietitian at each monthly study visit, and received counseling for physical activity.

The majority of patients randomized to bimagrumab were women (62.2%) compared with 31.6% in the placebo group. At baseline, patients exhibited a “mean (SD) age of 60.4 (7.7) years; mean BMI of 32.9 (3.4); mean body weight (BW) of 93.6 (14.9) kg; mean FM of 35.4 (7.5) kg; and mean A1C level of 7.8% (1.0%).”

Of the 58 participants who completed the trial, researchers found the following changes at week 48 for the bimagrumab arm vs placebo group, respectively:

FM: −20.5% (−7.5 kg [80% CI, −8.3 to −6.6 kg]) vs −0.5% (−0.18 kg [80% CI, −0.99 to 0.63 kg]) (

LM: 3.6% (1.70 kg [80% CI, 1.1 to 2.3 kg]) vs −0.8% (−0.4 kg [80% CI, −1.0 to 0.1 kg]) (

Waist circumference: −9.0 cm (80% CI, −10.3 to −7.7 cm) vs 0.5 cm (80% CI, −0.8 to 1.7 cm) (

A1C level: −0.76 percentage points (80% CI, −1.05 to −0.48 percentage points) vs −0.04 percentage points (80% CI, −0.23 to 0.31 percentage points) (

BW: −6.5% (−5.9 kg [80% CI, −7.1 to −4.7 kg]) vs −0.8% (−0.8 kg [80% CI, −1.9 to 0.3 kg]) (

8 adverse events leading to study discontinuation occurred in 5 patients in the bimagrumab group and none in the placebo group.

Six patients reported 9 serious adverse events, including pancreatitis and pneumonia; overall, “adverse events were reported by 31 of 37 patients (83.8%) in the bimagrumab group and 31 of 38 (81.6%) in the placebo group.” Adverse events reported by the treatment group included mild diarrhea and muscle spasms, and 1 patient in the treatment group reported the development of acne, which has been reported in prior studies of bimagrumab.

The relatively small sample size and gender imbalance across groups mark limitations to this study.

However, results confirm “that inhibition of this receptor in human participants leads to not only increases in lean mass but profound decreases in body fat, along with improvements in glycemic control. Inhibition of ActRII may provide a novel pathway for the pharmacologic management of excess adiposity and accompanying metabolic disturbances,” the researchers concluded.

Heymsfield SB, Coleman LA, Miller R, et al. Effect of bimagrumab vs placebo on body fat mass among adults with type 2 diabetes and obesity: a phase 2 randomized clinical trial.

. 2021;4(1):e2033457. doi:10.1001/jamanetworkopen.2020.33457

Results of a phase 2 trial showed that an activin type II receptor blockade, achieved via bimagrumab, led to significant loss of fat mass, gain in lean mass, and metabolic improvements among patients with type 2 diabetes (T2D) and overweight or obesity. 

Gianna Melillo

Articles

Incoming CDC Director to Prioritize Communication, COVID-19 Vaccine Rollout

Study Finds Potential Biomarkers for Distinguishing Glaucoma Subtypes

Data Show Migraineurs Who Respond to Triptans More Likely to Respond to Erenumab

Trial Finds Bimagrumab Aids Weight Loss in Patients With T2D, Obesity