RBC: Verastem Interim Analysis In Ovarian Cancer Reinforces Enthusiasm

 

• With the anticipation of a 2Q program update, Verastem Oncology 
  VSTM+11.1%+ Free Alerts
   announced that its interim analysis findings for the RAMP 201 program for recurrent low-grade serous ovarian cancer (LGSOC) continue evaluation in both monotherapy and combination regimens. 
• With incremental updates from ASCO, reiterated KOL enthusiasm, and more updates are upcoming in 2022 on a longer runway, RBC Capital continues to like the VSTM setup.
• The company plans to complete enrollment of all four trial cohorts in the second half of this year.
• It has reiterated the Outperform, Speculative Risk rating, and a price target of $5.
• RBC Capitals believes VSTM has exhibited differentiating safety profile exhibited thus far, all of which it finds reassuring.
• The analysts noted that around 6% had discontinued the trial based on treatment-related adverse events compared to ~30% for tyrosine kinase inhibitors' current standard of care.
• However, the update has generated interest in the clarity around the planned regulatory interactions, which are still pending and will guide go-forward dosing and trial design. 

https://www.benzinga.com/analyst-ratings/analyst-color/22/06/27595262/rbc-says-verastem-interim-analysis-in-ovarian-cancer-reinforces-enthusiasm

COVID-19 accounted for 62% of duty-related law enforcement deaths in 2020

 COVID-19 accounted for 62% of the 295 duty-related law enforcement deaths reported in 2020 to the National Law Enforcement Officer Memorial Fund database, which tracks law enforcement officers who died in the line of duty, according to a new University at Buffalo study.

The study, published last month in Policing: An International Journal, also found that COVID-19 accounted for 82% of deaths among Black members of law enforcement and 77% of deaths in Latinx officers, far higher than the 48% of deaths among white police officers.

These figures align with CDC data finding that race and ethnicity are risk markers for higher COVID-19 death rates, along with socioeconomic status, access to health care and exposure to the virus related to one’s occupation.

While the study looked specifically at COVID-19 deaths among members of law enforcement in 2020, there are important lessons for police and other first responder organizations going forward, said John Violanti, PhD, the study’s first author and research professor of epidemiology and environmental health in UB’s School of Public Health and Health Professions.

It’s the first study to examine law enforcement deaths from COVID-19 on a national level, demonstrating the widespread risk from COVID that officers face in their work.

Moreover, Violanti says, COVID has proven to be another source of stress for an occupational group that already faces numerous stressors that affect job performance and overall health. (Gunshots, automobile crashes, and physical stress were among the leading causes of death among law enforcement other than COVID-19.)

“The study’s finding that the majority of law enforcement deaths in 2020 were from COVID-19 reveals the added danger that law enforcement face during this pandemic,” added Violanti, a retired New York State Trooper and expert in police stress.

“Law enforcement were continuously exposed to the disease and were mandated to assist others in prevention and cure. The study should prompt police and other organizations to make informed decisions about preparation for any future disease outbreaks,” he said.

COVID-19 also accounted for deaths among corrections officers, Violanti and co-authors from the National Institute for Occupational Safety and Health, part of the Centers for Disease Control and Prevention, reported. Overcrowding in jails could be one possible explanation for COVID deaths among corrections officers given that incarcerated people are at higher risk for COVID-19 due to their proximity to one another, the researchers write. Another factor is the alarmingly high rate of corrections officers refusing to get vaccinated.

The majority of the law enforcement officers who died from COVID-19 were men (94%) over the age of 50 (61.6%) with more than 20 years of service (54%) and resided in Southern states.

In addition, the national rate of death due to COVID-19 — 12.8/100,000 officers — for law enforcement officers was higher compared to all other causes of death combined, at 8.0/100,000.

Given the complexity of personal exposures to COVID-19, the researchers point out that the percentage of COVID deaths attributed to duty may actually be higher or lower.

While this particular study looked only at law enforcement officers, the results suggest that other first responders, such as fire and EMT personnel, may also be disproportionately impacted, the researchers note.

“To help prevent the spread of COVID-19, the Occupational Safety and Health Administration  recommends that organizations implement multiple layers of controls including vaccinations, mask wearing, distancing, and increased ventilation in situations where police, first responders and other at-risk workers are more likely to be in prolonged, close contact with the public,” Violanti said.

---

JOURNAL

Policing An International Journal

DOI

10.1108/PIJPSM-02-2022-0022 

METHOD OF RESEARCH

Data/statistical analysis

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Proportionate mortality and national rate of death from COVID-19 among US law enforcement officers: 2020

ARTICLE PUBLICATION DATE

24-May-2022

COI STATEMENT

None

https://www.eurekalert.org/news-releases/955045

Cleveland Clinic: Sleep disturbances prevalent in post-acute sequelae of COVID-19

 Cleveland Clinic researchers found more than 40% of patients with Long COVID (Post-Acute Sequelae of COVID-19 or PASC) had moderate to severe sleep disturbances.

The analysis also showed patients with moderate-to-severe compared with normal-to-mild sleep disturbances had higher body mass indices, were more likely to be Black, and had worse general anxiety disorder. After adjusting for demographics, Black patients were three times more likely to experience moderate-to-severe sleep disturbances. The findings were presented on June 6 at the SLEEP 2022 meeting of the Associated Professional Sleep Societies.

 

The team analyzed data collected from 962 patients with PASC in Cleveland Clinic’s reCOVer Clinic between February 2021 to April 2022. The patients were recovered from COVID-19 and completed the sleep disturbance and fatigue questionnaires of the Patient-Reported Outcomes Measurement Information System. More than two-thirds of patients (67.2%) reported at least moderate fatigue, while 21.8% indicated severe fatigue. Eight percent of patients reported severe sleep disturbances while 41.3% reported moderate sleep disturbances.

“Sleep difficulties are prevalent and debilitating symptoms reported in patients with long COVID,” said Cinthya Pena Orbea, MD, a staff physician in Cleveland Clinic’s Sleep Disorders Center. “So we leveraged data from Cleveland Clinic’s reCOVer Clinic for people with long COVID to further elucidate these associations.”

https://www.eurekalert.org/news-releases/954933

Why COVID-19 antibody treatments aren’t as effective for new variants

 A new study published in today’s issue of Biochemistry is the first to explore the effects of multiple mutations in the evolution of SARS-CoV-2 variants. The findings can help scientists better understand the properties of current and new variants.

The results can also be used to better inform the development of vaccines and therapeutics to counter the threats posed by variants.

“Earlier studies, including ours, have focused on explaining the effect of single mutations and not the mechanism underlying the co-evolution of mutations,” said the paper’s corresponding author Krishna Mallela, PhD, professor in the department of pharmaceutical sciences at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences located on the University of Colorado Anschutz Medical Campus.

“Our study helps explain the concept of convergent evolution by balancing positive and negative selection pressures,” he adds.

The new paper, co-authored by Vaibhav Upadhyay, Casey Patrick and Alexandra Lucas from Mallela’s lab, was featured on the journal’s cover. The paper provides the physical basis for why approved antibody therapeutics are not working in neutralizing the recent variants of concern, such as Omicron and its subvariants.

“Understanding the mechanisms underlying the antibody escape and the location of mutations in the spike protein will help in developing new antibody therapeutics that will work against new variants by targeting epitopes with minimal mutations or developing broad neutralizing antibodies that target multiple epitopes,” said Mallela.

The study found that certain mutations appear repeatedly in emerging variants showing convergent evolution. One such evolution occurs at three amino acid positions K417, E484 and N501 in the spike protein’s receptor binding domain (RBD). Nearly half of 4.3 million variant sequences in GISAID database that contain any of these three mutations have all three occurring together. Although individual mutations have both beneficial and deleterious/adverse effects, when they come together, deleterious/adverse effects get canceled out, leading to improved selection of the mutations together. 

The researchers examined the physical mechanisms underlying the convergent evolution of the three mutations by delineating the individual and collective effects of mutations on binding to angiotensin converting enzyme 2 receptor, immune escape from neutralizing antibodies, protein stability and expression.

They found the three RBD mutations perform very distinct and specific roles that contribute toward improving the virus fitness and build the case for their positive selection, even though individual mutations have deleterious effects that make them prone to negative selection. Compared to the wild-type, K417T escapes Class 1 antibodies and has increased stability and expression; however, it has decreased ACE2 receptor binding. E484K escapes Class 2 antibodies; however, it has decreased receptor binding, stability and expression. N501Y increases receptor binding; however, it has decreased stability and expression. When these mutations come together, the deleterious effects are mitigated due to the presence of compensatory effects. Triple mutant K417T/E484K/N501Y has increased ACE2 receptor binding, escapes both Class 1 and Class 2 antibodies and has similar stability and expression as that of the wild-type.

The authors conclude the collective effect of these mutations is far more advantageous for virus fitness than the individual mutations and the presence of multiple mutations improves the selection of individual mutations.

Mallela concludes, “As SARS-CoV-2 has evolved from Alpha to Omicron, more and more mutations are accumulating. We hope that by providing research that understands the role of these mutations, we can help further propel research and the development of new therapies to better combat new variants.”

About the University of Colorado Anschutz Medical Campus

The University of Colorado Anschutz Medical Campus is a world-class medical destination at the forefront of transformative science, medicine, education and patient care. The campus encompasses the University of Colorado health professional schools, more than 60 centers and institutes, and two nationally ranked independent hospitals - UCHealth University of Colorado Hospital and Children's Hospital Colorado - that treat more than two million adult and pediatric patients each year. Innovative, interconnected and highly collaborative, the University of Colorado Anschutz Medical Campus delivers life-changing treatments, patient care and professional training and conducts world-renowned research fueled by over $650 million in research grants. For more information, visit www.cuanschutz.edu.

https://www.eurekalert.org/news-releases/955029

Why High Density of MS Patients in Wisconsin?

 Large numbers of multiple sclerosis (MS) patients appear to be clustered in southeastern Wisconsin, and researchers are trying to find out why.

Healthcare records showed densities of MS patients as high as 1,000 cases per 100,000 persons in some Wisconsin zip codes, about three times the norm of 353 per 100,000 population in the Midwest, reported Ahmed Obeidat, MD, PhD, of the Medical College of Wisconsin and Froedtert Hospital in Milwaukee, in a platform session at the 2022 annual meeting of the Consortium of Multiple Sclerosis Centers.

"The numbers were eye-opening," Obeidat told MedPage Today.

Some clusters of MS patients lived in areas near aluminum manufacturers, he observed.

"I noticed a large number of patients who came to see me in the clinic from areas that are at a distance from my practice location," Obeidat said. "Frequently I saw people coming from the same town or the same zip code, so I asked the question: is there a clustering of MS cases in Wisconsin?"

"When I looked at the areas where these patients came from, I noticed aluminum manufacturing plants," he continued. "I reviewed the literature and found previous reports of large amounts of aluminum in brain tissue of people living with MS and other neurodegenerative disorders."

Within 100 km of the Medical College of Wisconsin MS center, the density of MS patients per 100,000 population was 240. But in that 100-km radius, some areas reflected densities as high as 1,105 per 100,000. Ten zip codes had densities over 478 per 100,000. Overall, 67 of 110 zip codes within 100 km showed a density higher than 240 per 100,000.

Obeidat and colleagues used files from MS patients in the Froedtert Hospital and Medical College of Wisconsin Health Network and incorporated 2010 census data to compile population numbers. Zip codes further than 100 km away from the MS center or with fewer than 10 diagnosed MS patients were excluded.

"If anything, we are underestimating the overall numbers, because we have access only to the cases we follow at our health system," Obeidat noted.

The researchers identified 6,697 MS patients (73% female), then generated heat maps for total MS patients and MS patients per 100,000 population. Dense groups of patients lived near the MS center, but clusters also emerged in other areas.

"We noted several other areas with higher densities that cannot be solely explained by proximity," Obeidat said. "Two manufacturers near each other had clusters of MS patients."

People in Wisconsin are disproportionately affected by regional factors, including less vitamin D due to lower sun exposure, Obeidat noted. But variables like that would affect latitudes across the entire state and would not account for specific differences in southeast Wisconsin, he pointed out. Smoking, obesity, and Epstein-Barr virus also have been tied to MS development.

The findings call for an investigation of local environmental factors, Obeidat stated.

"Our plan is to further explore the chemicals used in aluminum factories and study candidates for immune dysregulation," he said. "We think aluminum is a plausible associated chemical."

Disclosures

This study received no funding.

Obeidat reported relationships with Biogen, Biologix, Bristol Myers Squibb, Celgene, EMD Serono, Genentech, GW Pharma, Horizon, Novartis, Sanofi/Genzyme, TG Therapeutics, Viela Bio, Atara Biotherapeutics, Jazz Pharma, and AbbVie.

Primary Source

Consortium of Multiple Sclerosis Centers

Source Reference: Porwal MH, et al "Disproportionate residence of multiple sclerosis patients in southeast Wisconsin: A clue to environmental factors?" CMSC 2022 platform session.

https://www.medpagetoday.com/meetingcoverage/cmsc/99103

Physician Group Releases Guidance on Cardiovascular Issues in Long COVID

 Risks for cardiovascular complications, including pulmonary embolism, arterial and venous thromboses, myocardial infarction, and stroke, are higher in patients with post-acute sequelae of SARS-CoV-2 (PASC), or long COVID, highlighting the need for greater awareness of these conditions among clinicians, according to a consensus statement released by the American Academy of Physical Medicine & Rehabilitation (AAPM&R).

Cardiovascular complications may arise weeks or months after a patient's initial COVID-19 infection, with severity of the symptoms ranging from "mild to incapacitating," according to the PASC Collaborative, a multidisciplinary group of physicians, clinicians, and patient advocates, who developed the statement. They noted that 5% to 29% of COVID-19 survivors complain of cardiovascular symptoms such as chest pain, dyspnea, or palpitations months after their recovery from the acute infection.

"Unfortunately, many people could have chronic cardiovascular conditions due to COVID-19 infection -- even patients without previous cardiovascular disease, comorbidities, and otherwise low risk of cardiovascular disease," said ​​lead author Jonathan Whiteson, MD, of NYU Langone Health in New York City, in a press release. "Because of the chronic nature of cardiovascular conditions, there will likely be long-lasting consequences for patients and health systems worldwide."

Whiteson and colleagues noted that the new consensus statement, the fourth in a series of guidance statements released by AAPM&R, was created to help improve awareness and understanding about this new and widespread condition. The PASC Collaborative was designed to share the best collective knowledge from across medical fields in one place for providers who are tasked with identifying long COVID and its many manifestations.

The goal of the consensus statement was to help providers address patient needs in whatever specialty they are practicing, explained co-author Alba Azola, MD, co-director of the Post-Acute COVID-19 Team at Johns Hopkins Medicine in Baltimore.

"We are not enough," Azola told MedPage Today. "In terms of the post-COVID clinics, there's just not enough for the millions and millions of Americans that are affected."

The guidance, in a nutshell, recommends that physicians become more vigilant about the potential for cardiovascular disease caused by long COVID, especially in patients with no history of cardiovascular complications, calling for targeted education of both healthcare professionals and patients with long COVID.

Whiteson and team advised that all stakeholders learn about the heterogeneity of long COVID symptoms, the likelihood of developing long COVID, the difference between expected symptoms and clinical red flags, lifestyle changes to help ease symptoms, and the connection between the cardiovascular and nervous systems.

This will help both physicians and patients identify the risk factors for cardiovascular complications related to long COVID, they said. Specifically, they noted that patients may experience shortness of breath, fatigue, chest pain, palpitations, dizziness, abdominal bloating, leg swelling, and reduced tolerance for exercise or activity.

To help physicians diagnose and treat patients with long COVID who may present with these symptoms, Whiteson and team outlined several best practices. First, they recommended that a full patient history be taken, including details about any previous COVID-19 infections, such as severity of initial infection and need for ventilator or extra-corporeal membrane oxygenation. Physicians should also note any common or worsening cardiac complaints. In addition, the authors recommended the use of all relevant testing, such as electrocardiograms, echocardiograms, cardiac stress tests, and standard lab tests.

The authors stressed that physicians should focus on modification strategies for risk factors, including hypertension, diabetes, obesity, tobacco use, and sedentary behavior. These modifiable risk factors are associated with greater morbidity and mortality in patients with COVID-19. New research is attempting to define their effects in patients with long COVID.

If patients are experiencing severe cardiovascular complications or disorders, such as arrhythmias, coronary artery disease, or ventricular dysfunction, the next recommended step would be to refer them to the appropriate specialist or a cardiac or long COVID rehabilitation center, the guidance states.

"I think the future will entail a state where we are talking about COVID as a risk factor," Whiteson said. "If someone has had COVID, they may develop cardiovascular disease even in the absence of other risk factors, so look carefully and interpret symptoms cautiously because it's not something you want to miss."

Disclosures

Several co-authors disclosed funding from organizations and institutions. The only author receiving funding for this specific manuscript was Sampsel, who is under contract to AAPM&R to support the writing and submission of each Consensus Guidance Statement.

Primary Source

American Academy of Physical Medicine & Rehabilitation

Source Reference: Whiteson J, et al "Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cardiovascular complications in patients with post-acute sequelae of SARS-CoV-2 infection (PASC)" AAPM&R 2022.

https://www.medpagetoday.com/special-reports/exclusives/99112

4 destinations added to COVID travel warning list

 The Centers for Disease Control and Prevention (CDC) has added four destinations to its list of “high-risk” travel locations regarding COVID-19 statistics.

Guyana, Mongolia, Namibia and St. Kitts and Nevis were all deemed a Level 3 travel risk on Monday, according to the CDC. They were previously categorized at Level 2, or “moderate” risk.

“Make sure you are up to date with your COVID-19 vaccines before traveling to these destinations. If you are not up to date with your COVID-19 vaccines, avoid travel to these destinations,” the CDC warned about Level 3 locations.

To be considered a Level 3 or high-risk destination, countries must have more than 100 new COVID-19 cases per 100,000 residents over the past 28 days.

Level 4 is known as “Special Circumstances/Do Not Travel.” No locations are currently on that list. 

In April, the agency removed all destinations from the Level 4 risk category, saying it would reserve “Level 4” warnings “for special circumstances, such as rapidly escalating case trajectory or extremely high case counts, emergence of a new variant of concern, or healthcare infrastructure collapse.” 

“With this new configuration, travelers will have a more actionable alert for when they should not travel to a certain destination (Level 4), regardless of vaccination status, until we have a clearer understanding of the COVID-19 situation at that destination,” the statement added.

In the U.S., cases are on a slightly upward trend, with a national daily case average of more than 98,000, the CDC’s data showed as of Monday. 

https://thehill.com/policy/international/3514517-four-destinations-added-to-covid-travel-warning-list/