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Vertex Announces Positive Day 90 Data for the First Patient in the Phase 1/2 Clinical Trial Dosed With VX-880, a Novel Investigational Stem…

Posted: October 25, 2021 at 1:55 am


BOSTON--(BUSINESS WIRE)--Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced positive Day 90 data for the first patient from the Phase 1/2 clinical trial of VX-880, an investigational stem cell-derived, fully differentiated pancreatic islet cell replacement therapy for people with type 1 diabetes (T1D). This is the first demonstration of a patient with T1D achieving robust restoration of islet cell function from such a cell therapy.

The patient was treated with a single infusion of VX-880 at half the target dose in conjunction with immunosuppressive therapy. The patient achieved successful engraftment and demonstrated rapid and robust improvements in multiple measures, including increases in fasting and stimulated C-peptide, improvements in glycemic control, including HbA1c, and decreases in exogenous insulin requirement. VX-880 was generally well tolerated.

These results from the first patient treated with VX-880 are unprecedented. What makes these results truly remarkable is that they were achieved with treatment at half the target dose, said Bastiano Sanna, Ph.D., Executive Vice President and Chief of Cell and Genetic Therapies at Vertex. While still early, these results support the continued progression of our VX-880 clinical studies, as well as future studies using our encapsulated islet cells, which hold the potential to be used without the need for immunosuppression.

As a surgeon who has worked in the field of islet cell transplantation for decades, this approach, which obviates the need for an organ donor, could be a game changer, said James Markmann, M.D., Ph.D., Professor of Surgery and Chief of the Division of Transplant Surgery at Massachusetts General Hospital. We are excited to progress this unique and potentially transformative medicine through clinical trials and to patients.

More than a decade ago our lab had a vision for developing an islet cell replacement therapy to provide a functional cure to people suffering from T1D, said Doug Melton, Ph.D., Xander University Professor at Harvard and an Investigator of the Howard Hughes Medical Institute. These promising results bring great hope that stem cell-derived, fully differentiated islet cells could deliver a life-changing therapy for people who suffer from the relentless life-long burden of T1D.

Efficacy Results

The patient was diagnosed with T1D approximately 40 years ago and has been dependent on exogenous insulin. In the one year prior to treatment, the patient experienced 5 severe, potentially life-threatening hypoglycemic episodes. Prior to treatment with VX-880, the patients insulin dose was 34 units per day and fasting and stimulated C-peptide levels were undetectable, indicating that the patient was not making their own insulin. Per the study protocol, the patient received half the target dose of VX-880 through a hepatic portal vein infusion in combination with a standard regimen of immunosuppressive agents.

Fasting C-peptide, HbA1c and 7-day average daily insulin dose were measured at various intervals after VX-880 treatment through Day 90. Fasting C-peptide was detected early after treatment with VX-880 and increased rapidly to Day 90. In parallel, HbA1c and daily insulin dose decreased over time.

Islet cell function was evaluated at baseline and at Day 90 using a Mixed Meal Tolerance Test (MMTT) with quantification of C-peptide levels, a direct marker for insulin production. At baseline prior to VX-880 treatment, fasting and stimulated C-peptide levels were undetectable, indicating no endogenous insulin production. At Day 90 after VX-880 treatment, fasting C-peptide was 280 pmol/L, reflecting restored basal insulin production and increased after MMTT stimulation to a peak of 560 pmol/L, indicating that VX-880 restored glucose-responsive insulin production. Also at Day 90, HbA1c improved from 8.6% at baseline to 7.2%, and daily insulin dose decreased from 34 units per day prior to treatment with VX-880 to an average dose of 2.9 units per day over a 7-day period at the Day 90 visit, reflecting a 91% decrease in daily exogenous insulin use.

Baseline and Day 90 Measures of Islet Cell Function for Patient 1

Baseline before

VX-880 infusion

Day 90 after

VX-880 infusion

Fasting C-peptide (pmol/L)

Undetectable*

280

Peak Stimulated C-peptide with MMTT (pmol/L)

Undetectable*

560

HbA1c (%)

8.6

7.2

Daily insulin dose (units/day)**

34

2.9

*The lower limit of quantitation of the C-peptide assay is 13 pmol/L.**Daily insulin dose for baseline was measured on Day -3 prior to VX-880 infusion. For Day 90 post-infusion, average daily insulin dose was calculated over a 7-day period.

Safety Results

In this first patient, the safety of VX-880 was generally consistent with the immunosuppressive regimen used in this study. There were no serious adverse events (SAE) considered related to VX-880, and the majority of the adverse events were considered mild to moderate. The most common adverse events were severe hypoglycemic events, which were non-serious, not related to VX-880, and occurred in the perioperative period. Through Day 90, the patient had one SAE; this was a rash that was mild in severity, not related to VX-880, and resolved.

Next Steps

Based upon these data, Vertex plans to continue to progress the Phase 1/2 program for VX-880. There are multiple active sites in the U.S., and the Clinical Trial Application has been approved in Canada. Vertex is also progressing IND-enabling studies for its encapsulated islet cell program, which would potentially eliminate the requirement for immunosuppression, and plans to file an IND for this program in 2022.

About VX-880

VX-880 is an investigational allogeneic stem cell-derived, fully differentiated, insulin-producing islet cell therapy manufactured using proprietary technology. VX-880 is being evaluated for patients who have T1D with impaired hypoglycemic awareness and severe hypoglycemia. VX-880 has the potential to restore the bodys ability to regulate glucose levels by restoring pancreatic islet cell function, including glucose responsive insulin production. VX-880 is delivered by an infusion into the hepatic portal vein and requires chronic immunosuppressive therapy to protect the islet cells from immune rejection.

About the Phase 1/2 Clinical Trial

The clinical trial is a Phase 1/2, multi-center, single-arm, open-label study in patients who have T1D with impaired hypoglycemic awareness and severe hypoglycemia. This study is designed as a sequential, multi-part clinical trial to evaluate the safety and efficacy of VX-880. The first two patients will be treated with half the target dose, followed by dose escalation to the target dose in the subsequent patients. Approximately 17 patients will be enrolled in the clinical trial. Enrollment is ongoing in this study.

About Type 1 Diabetes

T1D results from the autoimmune destruction of insulin-producing islet cells in the pancreas, leading to loss of insulin production and impairment of blood glucose control. The absence of insulin leads to abnormalities in how the body processes nutrients, leading to high blood glucose levels. High blood glucose can lead to diabetic ketoacidosis and over time, to complications such as kidney disease/failure, eye disease (including vision loss), heart disease, stroke, nerve damage and even death.

Due to the limitations and complexities of insulin delivery systems, it can be difficult to achieve and maintain balance in glucose control in patients with T1D. Hypoglycemia often results because of the difficulty in balancing the different factors that impact glucose levels, including insulin, diet and exercise. Hypoglycemia remains a critical limiting factor in glycemic management, and severe hypoglycemia can cause loss of consciousness, coma, seizures, injury, and can be fatal. Over time, patients with T1D can develop impaired awareness of hypoglycemia, meaning they are no longer able to perceive the early signs of a hypoglycemic event, which can be dangerous and result in life threatening events.

Current standards of care do not address the underlying causes of the disease, and there are limited treatment options beyond insulin for the management of T1D.

About Vertex

Vertex is a global biotechnology company that invests in scientific innovation to create transformative medicines for people with serious diseases. The company has multiple approved medicines that treat the underlying cause of cystic fibrosis (CF) a rare, life-threatening genetic disease and has several ongoing clinical and research programs in CF. Beyond CF, Vertex has a robust pipeline of investigational small molecule medicines in other serious diseases where it has deep insight into causal human biology, including pain, alpha-1 antitrypsin deficiency and APOL1-mediated kidney diseases. In addition, Vertex has a rapidly expanding pipeline of cell and genetic therapies for diseases such as sickle cell disease, beta thalassemia, Duchenne muscular dystrophy and type 1 diabetes mellitus.

Founded in 1989 in Cambridge, Mass., Vertex's global headquarters is now located in Boston's Innovation District and its international headquarters is in London. Additionally, the company has research and development sites and commercial offices in North America, Europe, Australia and Latin America. Vertex is consistently recognized as one of the industry's top places to work, including 11 consecutive years on Science magazine's Top Employers list and a best place to work for LGBTQ equality by the Human Rights Campaign. For company updates and to learn more about Vertex's history of innovation, visit http://www.vrtx.com or follow us on Facebook, Twitter, LinkedIn, YouTube and Instagram.

Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, (i) statements by Bastiano Sanna, Ph.D., Dr. James Markmann, and Doug Melton, Ph.D. in this press release, (ii) our plans, expectations for, and the potential benefits of VX-880, (iii) our plans to continue to progress the Phase 1/2 program for VX-880 and IND-enabling studies for the encapsulated islet cell program, including anticipated regulatory filings in 2022, and (iv) our plans for dosing and enrollment of patients. While Vertex believes the forward-looking statements contained in this press release are accurate, these forward-looking statements represent the company's beliefs only as of the date of this press release and there are a number of risks and uncertainties that could cause actual events or results to differ materially from those expressed or implied by such forward-looking statements. Those risks and uncertainties include, among other things, that data from one patient may not be indicative of final clinical trial results, that data from the company's research and development programs may not support registration or further development of its compounds due to safety, efficacy, and other risks listed under the heading Risk Factors in Vertex's most recent annual report and subsequent quarterly reports filed with the Securities and Exchange Commission at http://www.sec.gov and available through the company's website at http://www.vrtx.com. You should not place undue reliance on these statements, or the scientific data presented. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX-GEN)

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Vertex Announces Positive Day 90 Data for the First Patient in the Phase 1/2 Clinical Trial Dosed With VX-880, a Novel Investigational Stem...

Shionogi Presents the Results of COVID-19 Therapeutic Agent at ISIRV-WHO Virtual Conference – Business Wire

Posted: at 1:55 am


OSAKA, Japan--(BUSINESS WIRE)--Shionogi & Co., Ltd. (Head Office: Osaka, Japan; President and CEO: Isao Teshirogi, Ph.D.; hereafter "Shionogi") presented results from non-clinical studies and from the Japanese Phase 1 clinical trial of S-217622, an investigational oral antiviral drug for COVID-19, caused by the novel coronavirus (SARS-CoV-2), at the International Society for Influenza and Other Respiratory Virus Diseases (ISIRV)-World Health Organization (WHO) Virtual Conference.

During ISIRV, the results of non-clinical drug efficacy and pharmacokinetic studies, and a summary of the results from the Japanese Phase 1 clinical trial1 which started in July 2021, were presented. The information presented is outlined below:

- S-217622 showed in vitro antiviral activity against a broad range of strains, including the strain.- A dose-dependent viral reduction effect of S-217622 was observed in multiple animal studies.- S-217622 showed a good drug metabolism and pharmacokinetics profile supporting oral dosing.

- Single oral administration of S-217622 to healthy Japanese subjects was safe and well tolerated.- The once-daily oral dosing of S-217622 was predicted to exceed the target concentration required for the viral reduction effect from the non-clinical studies.

Based on these results, S-217622 has the potential to reduce SARS-CoV-2 viral load with once-daily oral administration.

Shionogi is committed to Protect people worldwide from the threat of infectious diseases as our key focus. We are not only pursuing the research and development of therapeutics, but are also working toward total care for infectious diseases, through awareness building, epidemic monitoring, prevention, diagnosis, and addressing exacerbations, as well as the treating of the infection itself. As SARS-CoV-2 continues to have a major impact on peoples lives and represents a global threat, we will seek to contribute to re-establishing the safety and security of society by developing new products and services to address this pandemic, and will keep all stakeholders informed regarding the progress of our efforts. For more information on our COVID-19 initiatives, please visit our website.

About S-217622S-217622, an investigational therapeutic antiviral drug for COVID-19, is a 3CL protease inhibitor created through joint research between Hokkaido University and Shionogi. The novel coronavirus (SARS-CoV-2) has an enzyme called 3CL protease, which is essential for the replication of the virus. S-217622 suppresses the replication of SARS-CoV-2 by selectively inhibiting 3CL protease. In non-clinical studies using SARS-CoV-2 infected animals, it has been confirmed that the viral load is rapidly and significantly reduced. The Japanese Phase 1 clinical trials began in July 20211, and a Japanese Phase 2/3 clinical trial2 is currently underway in mild or asymptomatic COVID-19 patients.

About ShionogiShionogi & Co., Ltd. is a Japanese major research-driven pharmaceutical company dedicated to bringing benefits to patients based on its corporate philosophy of "supplying the best possible medicine to protect the health and wellbeing of the patients we serve. The company currently markets products in several therapeutic areas including anti-infectives, pain, cardiovascular diseases, and gastroenterology. Our pipeline is focused on infectious disease, pain, CNS, and oncology. For more information on Shionogi & Co., Ltd., visit https://www.shionogi.com/global/en/. Shionogi Inc. is the U.S. subsidiary of Shionogi & Co., Ltd. based in N.J. For more information on Shionogi Inc., please visit http://www.shionogi.com.

Forward-Looking StatementsThis announcement contains forward-looking statements. These statements are based on expectations in light of the information currently available, assumptions that are subject to risks and uncertainties which could cause actual results to differ materially from these statements. Risks and uncertainties include general domestic and international economic conditions such as general industry and market conditions, and changes of interest rate and currency exchange rate. These risks and uncertainties particularly apply with respect to product-related forward-looking statements. Product risks and uncertainties include, but are not limited to, completion and discontinuation of clinical trials; obtaining regulatory approvals; claims and concerns about product safety and efficacy; technological advances; adverse outcome of important litigation; domestic and foreign healthcare reforms and changes of laws and regulations. Also for existing products, there are manufacturing and marketing risks, which include, but are not limited to, inability to build production capacity to meet demand, lack of availability of raw materials and entry of competitive products. The company disclaims any intention or obligation to update or revise any forward-looking statements whether as a result of new information, future events or otherwise.

References

Our efforts against COVID-19, in addition to other valuable information regarding to COVID-19 may be found on our global website under Sustainability. We hope you find this information useful and of value: SHIONOGI website

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Shionogi Presents the Results of COVID-19 Therapeutic Agent at ISIRV-WHO Virtual Conference - Business Wire

LogicBio Therapeutics Announces Early Clinical Trial Results Demonstrating First-Ever In Vivo Genome Editing in Children – PRNewswire

Posted: at 1:55 am


LEXINGTON, Mass., Oct. 18, 2021 /PRNewswire/ --LogicBio Therapeutics, Inc.(Nasdaq:LOGC), a clinical-stage genetic medicine company, today announced clinical trial results demonstrating the first-ever in vivo genome editing in children. Early data from the company's Phase 1/2 SUNRISE clinical trial showed measurable levels of albumin-2A, a technology-related biomarker indicating site-specific gene insertion and protein expression. The SUNRISE trial is evaluating the safety, tolerability and preliminary efficacy of LB-001, the company's investigational, single-administration genome editing therapy, in pediatric patients with methylmalonic acidemia (MMA).

These results follow a recommendation from the independent Data Safety Monitoring Board (DSMB) overseeing the SUNRISE trial to continue the study without modification. The DSMB's recommendation was based on an evaluation of the safety data from the first two patients enrolled in the trial. Per the FDA-cleared protocol, albumin-2A detection together with the DSMB continuation recommendation enables LogicBio to begin enrolling two patients in the higher dose (1 x 1014 vg/kg) cohort (with ages ranging three to twelve years old) and two patients in the lower age (six months to two years old) cohort at the lower dose (5 x 1013 vg/kg) of LB-001.

"We are very excited to have achieved this significant milestone in the field of genetic medicine," said Fred Chereau, president and chief executive officer of LogicBio. "These early data indicate that we can precisely edit hepatocytes in vivo to treat a genetic liver disease with a single intravenous infusion using our proprietary GeneRide technology. Today's announcement is a demonstration that homologous recombination genome editing without the use of nucleases is a potential alternative to genome editing technologies in development that use nucleases, such as CRISPR. The ability to insert the correct version of a gene in a cell's genome without nucleases is an important step to unlocking the potential of GeneRide to treat a larger number of genetic diseases."

SUNRISE is a first-in-human, open-label, multi-center, Phase 1/2 clinical trial designed to assess the safety and tolerability of a single intravenous infusion of LB-001 in pediatric patients with MMA. LB-001 is designed to non-disruptively insert a corrective copy of the MMUT gene into the albumin locus to drive lifelong therapeutic levels of MMUT expression in the liver. LB-001 is based on the company's proprietary GeneRide technology, which uses homologous recombination, a natural DNA repair process, to enable precise editing of the genome without the need for exogenous nucleases and promoters that have been associated with an increased risk of immune response and cancer.

"MMA is a rare, life-threatening genetic disorder for which there are no treatments addressing the underlying cause of the disease. By demonstrating for the first time ever that in vivo, nuclease-free genome editing in pediatric patients is achievable, we are one step closer to bringing a safe and effective genetic medicine to children suffering from MMA and, potentially, other early onset genetic diseases where early intervention is critical to achieve optimal health outcomes," said Daniel Gruskin, MD, chief medical officer of LogicBio. "I would like to thank the patients, their families and the investigators who are participating in this landmark trial. We look forward to continuing to progress the clinical study to better understand the biochemical and clinical effect of this genome editing therapy."

The Company remains on track to present additional interim data by the end of 2021.

About the SUNRISE Trial

The SUNRISE trial is an open-label, multi-center, Phase 1/2 clinical trial designed to assess the safety and tolerability of a single intravenous infusion of LB-001 in pediatric patients with methylmalonic acidemia (MMA) characterized by methylmalonyl-CoA mutase gene (MMUT) mutations. Seven leading centers in the United States and one in Saudi Arabia are expected to participate in the trial. With the aim of evaluating LB-001 at an early age, the SUNRISE trial initially enrolled 3-12 year old patients and, following a recommendation from the trial's independent Data Safety Monitoring Board and detection of a biomarker indicating site-specific gene insertion, is permitted to enroll infants as young as 6 months old. The SUNRISE trial is designed to enroll up to 8 patients and evaluate a single administration of LB-001 at two dose levels.

About LB-001

LB-001 is an investigational, first-in-class, single-administration, genome editing therapy for early intervention in methylmalonic acidemia (MMA) using LogicBio's proprietary GeneRide drug development platform. GeneRide technology utilizes a natural DNA repair process called homologous recombination that enables precise editing of the genome without the need for exogenous nucleases and promoters that have been associated with an increased risk of immune response and cancer. LB-001 is designed to non-disruptively insert a corrective copy of the methylmalonyl-CoA mutase (MMUT) gene into the albumin locus to drive lifelong therapeutic levels of MMUT expression in the liver, the main site of MMUT expression and activity. LB-001 is delivered to hepatocytes intravenously via liver-targeted, engineered recombinant adeno-associated virus vector (rAAV-LK03). Preclinical studies found that LB-001 was safe and demonstrated transduction of hepatocytes, site-specific genomic integration, and transgene expression. LB-001corrected hepatocytes in a mouse model of MMA demonstrated preferential survival and expansion (selective advantage), thus contributing to a progressive increase in hepatic MMUT expression over time. LB-001 resulted in improved growth, metabolic stability, and survival in MMA mice. TheU.S. Food and Drug Administration(FDA) granted fast track designation, rare pediatric disease designation and orphan drug designation for LB-001 for the treatment of MMA. In addition, theEuropean Medicines Agency(EMA) granted orphan drug designation for LB-001 for the treatment of MMA.

About Methylmalonic Acidemia (MMA)

Methylmalonic acidemia (MMA) is a rare and life-threatening genetic disorder affecting approximately 1 in 50,000 newborns in the United States. In the most common form of MMA, a mutation in a gene called methylmalonyl-CoA mutase (MMUT) prevents the body from properly processing certain fats and proteins. As a result, toxic metabolites accumulate in the liver, in muscle tissue and in the brain. Symptoms include vomiting, lethargy, seizures, developmental delays and organ damage. There is no approved medical therapy addressing the underlying cause of the disease. To manage the symptoms, patients go on a severely restrictive, low-protein, high-calorie diet, often through a feeding tube. Even with aggressive management, these patients often experience life-threatening metabolic crises that can require recurrent hospitalizations and cause permanent neurocognitive damage. Because of this risk for irreversible damage, early intervention is critical and newborns are screened for MMA in every state in the United States.

AboutLogicBio Therapeutics

LogicBio Therapeuticsis a clinical-stage genetic medicine company pioneering genome editing and gene delivery platforms to address rare and serious diseases from infancy through adulthood. The Company's genome editing platform, GeneRide, is a new approach to precise gene insertion harnessing a cell's natural DNA repair process potentially leading to durable therapeutic protein expression levels. The Company's gene delivery platform, sAAVy, is an adeno-associated virus (AAV) capsid engineering platform designed to optimize gene delivery for treatments in a broad range of indications and tissues. The Company is based inLexington, MA.For more information, visitwww.logicbio.com, which does not form a part of this release.

Forward-Looking Statements

Statements in this press release regarding LogicBio's strategy, plans, prospects, expectations, beliefs, intentions and goals are forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, including but not limited to statements regarding early clinical results and the significance and interpretation thereof; homologous recombination genome editing without the use of nucleases as a potential alternative to genome editing technologies in development that use nucleases, such as CRISPR; the potential of the GeneRide platform, including the potential for genetic medicines based on the platform to be treatment options for genetic diseases; progressing the SUNRISE trial; the expected timing of announcing additional interim clinical data in the SUNRISE trial; the potential benefits of LB-001; and the sites expected to participate in the SUNRISE trial. The terms "demonstrating," "indicate," "look forward," "on track," "potential" and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement, including the risk that existing preclinical and clinical data, including early clinical data from a trial, may not be predictive of the results of ongoing or later clinical trials; the risk that clinical trials may not be successful or may be discontinued or delayed for any reason; the potential direct or indirect impact of the COVID-19 pandemic on our business, operations, and the markets and communities in which we and our partners, collaborators and vendors operate; manufacturing risks; risks associated with management and key personnel changes and transitional periods; the actual funding required to develop and commercialize product candidates, including for safety, tolerability, enrollment, manufacturing or economic reasons; the timing and content of decisions made by regulatory authorities; the actual time it takes to initiate and complete preclinical and clinical studies; the competitive landscape; changes in the economic and financial conditions of LogicBio; and LogicBio's ability to obtain, maintain and enforce patent and other intellectual property protection for LB-001 and any other product candidates. Other risks and uncertainties include those identified under the heading "Risk Factors" in LogicBio's Annual Report on Form 10-K for the year ended December 31, 2020 and other filings that LogicBio may make with the U.S. Securities and Exchange Commission in the future. These forward-looking statements (except as otherwise noted) speak only as of the date of this press release, and LogicBio does not undertake, and specifically disclaims, any obligation to update any forward-looking statements contained in this press release.

Investor Contacts:

Laurence Watts Gilmartin Group (619) 916-7620 [emailprotected]

Stephen Jasper Gilmartin Group (858) 525-2047 [emailprotected]

Media Contacts:

Jenna Urban Berry & Company Public Relations W: 212-253-8881 C: 203-218-9180 [emailprotected]

Bill Berry Berry & Company Public Relations W: 212-253-8881 C: 917-846-3862 [emailprotected]

SOURCE LogicBio Therapeutics, Inc.

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LogicBio Therapeutics Announces Early Clinical Trial Results Demonstrating First-Ever In Vivo Genome Editing in Children - PRNewswire

To study Zika, they offered their kids. Then they were forgotten. : Goats and Soda – NPR

Posted: at 1:55 am


Rochelle dos Santos embraces her daughter, who was born with microcephaly in 2016 after dos Santos contracted Zika during her pregnancy in midwest Brazil. Ueslie Marcilino/Undark Magazine hide caption

Rochelle dos Santos embraces her daughter, who was born with microcephaly in 2016 after dos Santos contracted Zika during her pregnancy in midwest Brazil.

Rochelle dos Santos learned that her daughter would probably be born with microcephaly a condition where a baby's head is much smaller than expected when she was seven months pregnant. It was 2016 and Brazil was going through an unprecedented microcephaly outbreak associated with the mosquito-borne virus Zika. After the baby was born and the diagnosis of congenital Zika syndrome was confirmed, several researchers approached dos Santos to see if she'd join relevant clinical studies. Eager to understand her daughter's condition, she agreed.

Dos Santos says she was surprised to learn through a social media post last year that an international study that she participated in had been published in the journal Brain & Development. The study took over a year to be completed, and dos Santos had taken her daughter multiple times to the hospital for evaluations. As the head of an association for families of children affected by Zika in Gois state in midwest Brazil, dos Santos wanted to share the findings with the other caregivers. She says she had to reach out directly to Hlio van der Linden, a neurologist at the Dr. Henrique Santillo State Center for Rehabilitation and Readaptation who authored the study in partnership with researchers in Brazil and the United States, to ask that a copy be shared with her. But she says he told her there was no point because it was written in English.

"Of course, we get upset," she recalled in her native Portuguese. "We want to have this feedback and better understand this situation that is new for everyone." Dos Santos who noted that while she speaks only a little English, her husband reads and speaks English capably said she feels used and that many other families share the same sentiment. "We know that COVID is now the priority," dos Santos adds, "but our children are still here, they still have needs."

The study's author sent her the article, and dos Santos says her husband translated it for her though she adds that she was also asked by van der Linden not to share it. (Van der Linden told Undark by email that while he did point out to dos Santos that the article was written in English, his main concern was running afoul of the journal's publishing rules. His request not to share it, he added, was for social media posts. "There was no problem in sharing the article with other mothers," he wrote, "but I believe this wasn't clear to the mother of the patient.")

Children with congenital Zika syndrome face numerous health issues, all originating from the peculiar way in which Zika attacks the developing brain. In addition to the condition's most pronounced feature reduced head size many have rigid muscles, difficulty swallowing and breathing and problems with the retina and optic nerve, as well as other symptoms that emerge as the children grow. "The doctors say that only time will tell how our children will be tomorrow," dos Santos says, "because there are no adults with this syndrome."

Dos Santos is not the only caregiver who felt left behind by scientists. Family groups like the one she heads have sprung up across the country, and members are increasingly at odds with the scientists who have used their children for research. The grandmother and caretaker of a boy with congenital Zika syndrome, Alessandra Hora dos Santos (no relation to Rochelle), launched one of these associations in Alagoas state in northeast Brazil in 2017. She says that lately she has been declining requests to participate in new studies although such invitations are becoming rare because there haven't been new outbreaks of the syndrome since 2016 and she noticed that other families are doing the same.

Scientists who conducted the studies on Zika during the peak and the aftermath of the outbreak admit that communicating the results to families is not always effective, and that it was not the top priority during the Zika crisis. In the rush to collect data, not all researchers took the time to explain in detail what their projects were about and set clear expectations. Busy caretakers, on the other hand, were hardly able to carefully read the informed consent forms they were signing to authorize investigators to collect data from their children. Over the last few years, these families have demanded to participate more actively in the scientific discussion around Zika.

"We feel diminished," says Alessandra Hora dos Santos. "It's like we were lab rats. They come in nicely, collect information, collect exams on the child, and in the end, we don't know of any results. It's like we are being used without even knowing why that is being done."

Left: Dos Santos helps her daughter, pictured, with physical therapy. Many children with congenital Zika disorder are physically disabled. Right: Due to difficulties swallowing, dos Santos' daughter uses a feeding tube, which is attached to her wheelchair. Ueslie Marcilino/Undark Magazine hide caption

Left: Dos Santos helps her daughter, pictured, with physical therapy. Many children with congenital Zika disorder are physically disabled. Right: Due to difficulties swallowing, dos Santos' daughter uses a feeding tube, which is attached to her wheelchair.

Left: Dos Santos' daughter uses leg braces to help her stand. Other symptoms of the disorder emerge as children grow. Right: Dos Santos guides her daughter to create a finger painting. "Our children are still here, they still have needs," she says. Ueslie Marcilino/Undark Magazine hide caption

Left: Dos Santos' daughter uses leg braces to help her stand. Other symptoms of the disorder emerge as children grow. Right: Dos Santos guides her daughter to create a finger painting. "Our children are still here, they still have needs," she says.

By the time physicians started to notice a surge in microcephaly in Brazil in mid-2015, researchers had to scramble to design studies, get funding and conduct analyses. Eventually, scientists from multiple institutions coalesced in the Microcephaly Epidemic Research Group (MERG). They began the research efforts even before the link with Zika had been established and had a crucial role in guiding public health strategies to tackle the epidemic. "There was a lot of pressure coming from the media and the health ministry," says infectious disease expert Demcrito de Barros Miranda-Filho, a member of MERG and a professor at the University of Pernambuco. "We had to develop all the projects from scratch and submit them to the ethics committees within a deadline," he says, adding that there was also pressure to give answers to the families.

One of the group's concerns was to immediately share individual results of tests and clinical evaluations that could directly impact the child's treatment. But when it comes to the general findings at the end of the study, says Miranda-Filho, the researchers didn't properly communicate them to the participants.

"It is very complex to decode biological questions and put them into a more understandable language," says Thlia Velho Barreto de Arajo, an epidemiologist at the Federal University of Pernambuco and a member of MERG. "We haven't figured out a way to do that yet, and we would need research resources to get advice for transforming technical language into something palatable." Ricardo Arraes de Alencar Ximenes, an epidemiologist at both the University of Pernambuco and the Federal University of Pernambuco, notes that one of the obstacles to develop well-thought-out communication strategies is getting dedicated funding.

Physician Camila Ventura, one of the coordinators of an ambitious project with the goal of evaluating the neurodevelopment of about 200 children with congenital Zika syndrome over five years, says she is familiar with the families' demands and agrees with them. But there are other obstacles beyond adequate funding, she says. For example, with funding from the United States National Institutes of Health, the project is being developed at the Altino Ventura Foundation, a Brazilian health nonprofit, in partnership with the U.S. research organization RTI International. Because the project is done in partnership with other organizations, Ventura says it's not solely up to her to provide this feedback.

"This criticism applies to our own institution and I try my best to push for these answers" from our research partners, says Ventura. "The mothers see that we're collecting data and they want to know: What about my kid?" she adds. "Is he getting better?"

Van der Linden wrote that when he invites a family to participate in a study, he tries to make it clear that the goal is to better understand the condition and that the findings might not benefit the participants themselves. "I explain that after the study is done, there won't be a 'result.' Sincerely, I don't offer or promise to call each one to explain the details, etc. I always make it clear that it is for science," he wrote to Undark by email. "I believe there might have been an over-expectation, or an unrealistic expectation of something that was never promised."

Soraya Fleischer, an anthropologist at the University of Braslia who coordinates a research project on the impact of Zika on the lives of families, says it's also important to consider what these mothers mean when they ask for study results. "For the researchers, the result is what is published in a well-qualified scientific journal or goes into their resume," she says. But for the families, says Fleischer, sometimes the result is a simple blood test that confirms that the child's disabilities were caused by Zika an important document that grants access to certain social benefits reserved for children with the syndrome, which can be difficult to get via the public health system.

Not every parent has had a bad experience with Zika researchers. Jaqueline Silva de Oliveira, the mother of a 5-year-old girl with congenital Zika syndrome, says that whenever she needs these types of reports in order to claim social benefits, she reaches out to the scientist who enrolled her family in a genetics study. The girl's twin brother was not affected by Zika, which caught the attention of a group at the Human Genome and Stem Cell Research Center at the University of So Paulo that wanted to try to identify potential protective genes.

"I participated to be able to help prevent other children from having microcephaly," says de Oliveira. She says she can't explain in her words what the results of the study were and she didn't receive a document describing them. But overall, she thinks having participated in the study was a positive experience. She continues to have a connection with the researchers, and they helped her find a neurologist, one of the best in the state, she says, who managed to control her daughter's epilepsy crises. "I helped the researcher on the study," she says, "and when I needed it, she helped me."

During the initial 2015 Zika outbreak and the years that followed, participation in the Brazilian Zika studies could be difficult. Luciana Lira, a medical anthropologist at the Federal University of Pernambuco, recalls accompanying two mothers to an event in 2018 in Recife, in Pernambuco state, one of the epicenters of the congenital Zika syndrome outbreak. The event was organized by a local university and an association for families of children with rare diseases. While the other mothers attended talks and participated in conversation circles, the mothers of children with congenital Zika syndrome were directed to a hall where researchers organized a task force to collect blood for a research project.

On that occasion, Lira says she watched while a nurse approached a mother to participate in the study. The mother "was so agitated that, when the nurse approached her and started explaining the study, she clearly wasn't paying full attention because there were more urgent things to deal with. Her daughter was having a crying fit, she had to fix her feeding tube, all of that," says Lira. "Then she agreed to participate, signed a paper and that's it. This type of situation has become very commonplace."

The researcher behind the project was Nilson Antonio de Assuno, a chemistry professor at the Federal University of So Paulo who was then studying the biochemical characteristics of blood among children with Zika. The study hasn't been published yet, de Assuno says, adding that he is aware that some families don't fully understand the purpose of his research when they agree to participate. "They get nervous because they are at an event, these are humble people, their children are crying and they end up not understanding very well what we're explaining."

De Assuno says there isn't much to be done about creating better strategies to communicate with families of children participating in studies. "I have been noticing this distrust in families," he says, "but those who end up losing are the families themselves." He says that he has previously tried to explain and educate the population about his work. "No matter what you do," he adds, "there will always be this distrust."

Lira and her colleagues have been observing the relationship between caregivers of children with Zika and biomedical scientists in Recife. Silvana Matos, also an anthropologist at the Federal University of Pernambuco, says that initially the caregivers welcomed the attention from scientists because they wanted to understand what had happened to their children. "The thing they complained the most about, right after this initial period," she says, "was that the test results never came back to them and the researchers, from Brazil or abroad, never reached out again to tell them what happened."

The families' experiences with the medical trials made them wary of researchers more broadly. By the time the anthropologists started working with the families in late 2016, they had to redesign their work to deal with this research fatigue and gain trust, says Lira. The families "had been overwhelmed both by scientists trying to collect organic samples, and by journalists and researchers wanting to interview them," says Fleischer. "There was an eagerness to learn what was happening" among the scientists and journalists, she adds, and the families "were the source."

Lira spent several months following caregivers around before doing any interviews. Fleischer, who is not based in Recife, decided to come back to the city several times over the years to revisit the families and show them what had been produced with the data they had collected before for example, an article or a newspaper story. Realizing that the caretakers were too busy to read long articles, Fleischer's group created a blog to publish short stories about life with Zika that they would print out and distribute to the participants during their visits. The fact that the researchers kept coming back and reporting what they were doing made the families feel respected, according to Fleischer, and it was essential to build trust.

Dos Santos, left, with her daughters. Dos Santos says she feels used and that many other families share the same sentiment. Medical anthropologist Luciana Lira says the families became overwhelmed by scientists and journalists, and that she had to change her approach to gain the families' trust. Ueslie Marcilino/Undark Magazine hide caption

Dos Santos, left, with her daughters. Dos Santos says she feels used and that many other families share the same sentiment. Medical anthropologist Luciana Lira says the families became overwhelmed by scientists and journalists, and that she had to change her approach to gain the families' trust.

In Brazil, the ethical and legal framework for research involving human subjects was established in 1996 through a resolution by the Brazilian National Council of Health. To conduct a study involving human subjects in Brazil, researchers have to submit their proposal to a research ethics committee, much like in the U.S. Every research organization may constitute its own committee, which responds to the National Commission for Research Ethics (CONEP, by its Portuguese acronym).

Before entering a study, participants must sign a free and informed consent form, a document that describes the study, its goals and possible risks and benefits of participating. According to the commission, the document should be written in clear and accessible language.

The need to share the findings with participants, which is at the core of the caregivers' complaints, is not directly covered by the 1996 resolution. But the current ethical norms, in force since 2012, do state that research findings should be communicated to the community if there's a potential to benefit the population, notes biologist Maria Mercedes Bendati, who retired from the municipal health department of Porto Alegre, in southern Brazil, in 2017 and is a CONEP member. "It already says that it is important to give this feedback," she says. The next step, she adds, is to implement the requirement "and make it very clear in the academic education of the researchers that they should fulfill their social role, and know that the research implies giving these answers to the participants."

Bendati participated in the Pan American Health Organization Zika Ethics Consultation in April 2016, which originated an ethics guidance on key issues raised by the Zika outbreak.

Florencia Luna, the chair of the Zika Ethics Consultation, says the goal of the guidance was precisely to prevent situations like the ones the caregivers described. "We were very concerned about doing this research at that moment in the middle of the outbreak. So it's a little bit like now, with COVID," she says. "Even if you want to do [research] fast and quick, and you should do it like that, that doesn't mean you have to avoid ethical standards."

Luna, who is also the director of the bioethics program at the Latin American Faculty of Social Sciences in Argentina, believes that returning to the participants with the results is an ethical obligation. "Personally, I do think it is very important to come back and tell the good or the bad news," she says, especially with Zika, which involves mothers and babies with health conditions. "At least to send them a letter, to call them on the phone," she adds. "Maybe not to make them go to the clinic because it would be too burdensome for them, but there are other ways where you can communicate nowadays, with smartphones, with the internet."

According to the International Ethical Guidelines for Health-related Research Involving Humans, a 2016 document prepared by the Council for International Organizations of Medical Sciences in collaboration with the World Health Organization, researchers "should engage potential participants and communities in a meaningful participatory process" which includes the dissemination of the study's results.

Despite such guidelines, not communicating results to participants is seen by some researchers as business as usual. Carl Elliott, an expert in bioethics and a professor of philosophy at the University of Minnesota, says the situation narrated by Rochelle dos Santos, where the investigator hesitated to send her the study for which her daughter had collaborated, didn't surprise him.

"If I were the research subject or the mother of the research subject, it would offend me and I think justifiably," he says. "That said, I think the vast majority of research subjects don't do that sort of follow-up. They don't ask or are not even particularly interested in the papers." Elliot says he doesn't think the investigator gave the right response, but he imagines he was probably surprised by the request.

In any case, Elliott says he believes that, if a participant actively asks, the researcher must provide the results: "It's shameful that it takes so much effort, and often money, for the public to get access to the results of scientific studies published in the medical literature."

Bioethics expert Carl Elliot says that the situation Rochelle dos Santos (pictured) described, where the investigator hesitated to send her the study for which her daughter had collaborated, didn't surprise him. Ueslie Marcilino/Undark Magazine hide caption

Bioethics expert Carl Elliot says that the situation Rochelle dos Santos (pictured) described, where the investigator hesitated to send her the study for which her daughter had collaborated, didn't surprise him.

In September 2018, the Brazilian caregivers' discontent culminated at the annual Congress of the Brazilian Society of Tropical Medicine in Recife. That year, the program included several sessions about congenital Zika syndrome. According to a paper written by Lira, none of the families' associations had been invited.

During one of the sessions on the main stage, Germana Soares, the mother of a boy with congenital Zika syndrome and the president of one of the largest family associations, requested to speak. She read aloud a letter to the event's organizers. "We believe there is a lack of empathy and sensitivity to our reality, and a lack of respect in the fact that we were underestimated. As if we the mothers, relatives and caretakers would lack the understanding to participate in a technical event to discuss a topic that is of our biggest interest," the letter stated. "Are we mothers so ignorant, without the least bit of education, that we cannot understand a scientific article or a lecture? Or should the researchers be the ones to use a language that is more comprehensible? Are we totally wrong to demand a discussion about ethics in biomedical research? Are we just numbers?"

The organizers were apparently caught by surprise, as Soares' speech wasn't in the program. One of the speakers at the session called Sinval Pinto Brando Filho, the president of the Society, to ask him what to do about it. He advised him to let Soares speak. "Our organization welcomes this debate with great satisfaction because we study the tropical diseases, in terms of controlling them," says Brando Filho, adding that every year the Brazilian Society of Tropical Medicine invites patients of neglected diseases to a public forum during the congress to discuss the problems they face. "I see this as something specific that was immediately recognized that it should be more sensitively incorporated into the tribute session."

Today, only sporadic cases of congenital Zika syndrome still occur, which makes it difficult to get funding for research, scientists say. The research focus has shifted to COVID-19, but the Zika health emergency might have left a legacy when it comes to research ethics.

"My personal reflection about the Zika experience in ethics committees is that perhaps there should have been a dialogue with the researchers to ask them how the findings would be shared with the participants," says Bendati. "When it comes to COVID-19, the CONEP is now being very clear on the need for a proposal of feedback to be given to participants." Learning from the mistakes of Zika might have contributed to this evolution, Bendati adds.

Luna says she's aware that sometimes ethics are viewed as an obstacle to science. Tracking down the participants can be difficult, and researchers who might have moved on to another project often lack the time and the energy to pursue it. "But it's part of what we have to do in order to build trust, to continue working," she says. "If not, these women will not collaborate in any other research in their lives because they were disappointed."

Mariana Lenharo is a science and health journalist whose writing has appeared in Scientific American, Mother Jones, Elemental, BBC News Brazil, among other publications. She is currently based in So Paulo, Brazil.

Continued here:
To study Zika, they offered their kids. Then they were forgotten. : Goats and Soda - NPR

Frequency Therapeutics Announces First Subject Dosed in FX-322 Phase 2b Acquired Sensorineural Hearing Loss (SNHL) Study and FDA Agreement on Speech…

Posted: at 1:55 am


LEXINGTON, Mass.--(BUSINESS WIRE)--Frequency Therapeutics, Inc. (Nasdaq: FREQ), a clinical-stage regenerative medicine company focused on developing therapeutics to activate a persons innate regenerative potential to restore function, today announced that the first subject has been dosed in a new FX-322 Phase 2b study (FX-322-208) being conducted in a refined population of individuals with SNHL.

FX-322-208 is a randomized, placebo-controlled, multi-center study designed to evaluate the impact of a single administration of FX-322 on speech perception in approximately 124 subjects with SNHL. The studys primary endpoint is speech perception, a measure of sound clarity and understanding speech. The Phase 2b studys inclusion criteria are designed to enroll subjects with the same hearing loss severities and etiologies as those subjects in which statistically significant improvements in speech perception were observed in prior FX-322 clinical studies. FX-322-208 will include subjects with hearing loss associated with either noise-induced or sudden SNHL.

The U.S. Food and Drug Administration (FDA), in a recent Type-C meeting with the Company, agreed that speech perception is an acceptable primary efficacy endpoint. A variety of other listening tests, including multiple measures of speech perception and pure tone thresholds, will also be assessed.

The FX-322-208 Phase 2b study incorporates learnings from all of our prior studies, enabling us to identify targeted patient populations and prior responder groups for evaluation. We are testing FX-322 in subjects with hearing loss severities and etiologies where we have seen improvements in past trials. We have also applied key additional design elements to the study to mitigate potential bias and help ensure the consistency of baseline hearing assessments, said David L. Lucchino, Frequencys Chief Executive Officer. Moreover, we are very pleased to have obtained alignment with the FDA on speech perception as the primary endpoint for our upcoming studies, given the important need for treatments that can provide greater hearing clarity. In a recently held externally-led Patient Focused Drug Development program with FDA, sponsored by the Hearing Loss Association of America, patients made clear that medicines that could restore hearing and that can enable greater speech perception were critical to advancing the current standard of care. We believe we now have a clear path forward to deliver on this common goal.

Mr. Lucchino continued: In November, we look forward to presenting the detailed clinical findings that support the design of FX-322-208, as well as discussing our broader R&D efforts as we expand our pipeline in hearing loss as well as other disease areas where we have seen real promise from our technology.

In two previous clinical studies, the Company observed statistically significant improvements in speech perception scores in individuals with acquired sensorineural hearing loss. These studies are FX-322-201, a randomized placebo-controlled study of subjects with mild to moderately severe SNHL, and FX-322-111, an open-label study evaluating different FX-322 administration conditions, where nine of 32 subjects that completed the study showed speech perception improvements between 90 days and one year following administration. To date, more than 175 individuals have been dosed with FX-322 across previous studies and no drug-related serious adverse events have been reported.

The Company will maintain flexibility in the overall FX-322-208 design in order to be able to include additional etiologies and severities based on pending results from its ongoing FX-322 study in severe subjects (FX-322-113).

FX-322-208 is expected to be conducted at approximately 25 U.S.-based study sites consisting of both private ENT clinics and academic medical centers. Additional study details are available at clinicaltrials.gov (NCT05086276).

Frequency plans to host an R&D event on November 9, 2021, where the Company will review detailed FX-322 clinical results and discuss the data supporting the design and inclusion criteria for FX-322-208.

Patients with hearing loss who may be interested in participating in FX-322-208 may visit this link, which is also available on the study page at clinicaltrials.gov under Additional Information.

About Frequency Therapeutics

Frequency Therapeutics is leading a new category in regenerative medicine that aims to restore human function first in hearing loss and then in multiple sclerosis (MS) by developing therapeutics that activate a persons innate regenerative potential within the body through the activation of progenitor cells. Frequencys hearing research focuses on cochlear restoration and auditory repair, and its lead asset, FX-322, is a small-molecule product candidate that is the first to show statistically significant and clinically meaningful hearing improvements in clinical trials for sensorineural hearing loss. Frequency is also following early restorative signals in MS to develop medicines with the same underlying regenerative science being brought to hearing loss.

Headquartered in Lexington, Mass., Frequency has an ex-U.S. license and collaboration agreement with Astellas Pharma Inc. for FX-322, as well as additional collaboration and licensing agreements with academic and nonprofit research organizations including Massachusetts Eye and Ear, Mass General Brigham, the Massachusetts Institute of Technology, the Scripps Research Institute and Cambridge Enterprises Limited. For more information, visit http://www.frequencytx.com and follow Frequency on Twitter @Frequencytx.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements regarding the design of the new Phase 2b trial of FX-322, including the number of patients that will be enrolled, the type of SNHL that these patients will have, the number of study sites, and the measurements used in the study, the interpretation and implications of the results and learnings of other FX-322 clinical studies, including the FX-322-111, FX-322-201 and FX-322-113 studies, the acceptance by the FDA of particular endpoints in the Companys trials, the treatment potential of FX-322, the timing of and topics to be discussed during the R&D event, our program to develop a product candidate for the treatment of multiple sclerosis, the ability of our technology platform to provide patient benefit, the ability to continue to develop our Progenitor Cell Activation (PCA) platform and identify additional product candidates, and the potential application of the PCA platform to other diseases.

These forward-looking statements are based on managements current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: the impact of COVID-19 on the Companys ongoing and planned clinical trials; research and development and manufacturing activities, the relocation of the Companys offices and laboratory facilities, the Companys business and financial markets; the Company has incurred and will continue to incur significant losses and is not and may never be profitable; the Companys need for additional funding to complete development and commercialization of any product candidate; the Companys dependence on the development of FX-322; the unproven approach of the PCA platform; the lengthy, expensive and uncertain process of clinical drug development and regulatory approval; limited experience successfully obtaining marketing approval for and commercializing product candidates; the results of earlier clinical trials not being indicative of the results from later clinical trials; differences between preliminary or interim data and final data; adverse events or undesirable side effects; disruptions at the FDA and other regulatory agencies; failure to identify additional product candidates; new or changed legislation; failure to maintain Fast Track designation for FX-322 and such designation failing to result in faster development or regulatory review or approval; costly and damaging litigation, including related to product liability or intellectual property or brought by stockholders; dependence on Astellas Pharma Inc. for the development and commercialization of FX-322 outside of the United States; misconduct by employees or independent contractors; reliance on third parties, including to conduct clinical trials and manufacture product candidates; compliance with laws and regulations, including healthcare and environmental, health, and safety laws and regulations; failure to obtain, maintain and enforce protection of patents and other intellectual property; security breaches or failure to protect private personal information; attracting and retaining key personnel; and ability to manage growth.

These and other important factors discussed under the caption Risk factors in the Companys Form 10-Q filed with the Securities and Exchange Commission (SEC) on August 12, 2021 and its other reports filed with the SEC could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent managements estimates as of the date of this press release. While the Company may elect to update such forward-looking statements at some point in the future, it disclaims any obligation to do so, even if subsequent events cause its views to change. These forward-looking statements should not be relied upon as representing the Companys views as of any date subsequent to the date of this press release.

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Frequency Therapeutics Announces First Subject Dosed in FX-322 Phase 2b Acquired Sensorineural Hearing Loss (SNHL) Study and FDA Agreement on Speech...

Addressing Resistance to Targeted Therapies in Metastatic Colorectal Cancer – Cancer Network

Posted: at 1:55 am


Metastatic colorectal cancer (mCRC) is the second most common cause of cancer-related death worldwide.1 In the mid-1980s, the median overall survival (OS) for patients with mCRC ranged from 10 to 12 months from the time of initial diagnosis.2 In more recent studies, this median has more than doubled and is commonly reported at more than 25 to 30 months.3 These improvements are due, in large part, to the introduction of multiple novel agents during the last 3 decades. Despite these improvements, however, nearly all patients treated with palliative chemotherapy will eventually develop resistance and ultimately succumb to progression of metastatic disease. Understanding the mechanisms by which malignant cells evade treatment could unlock novel therapeutic strategies that overcome resistance and improve survival. In this review, we will discuss some of the drivers of therapeutic resistance in patients with mCRC and present some novel strategies to overcome resistance.

Therapeutic resistance develops in nearly all patients with advanced cancer who are treated with palliative systemic therapy. Resistance to cancer-directed therapy is generally divided into primary and secondary (acquired) resistance. Primary resistance is defined as a lack of objective clinical or radiographic response to therapy. Secondary resistance is defined as therapeutic resistance that emerges after a period of disease stability or response.4 Although these terms will be used throughout this review, it is important to note that this simple division becomes less clear as the precision of surveillance imaging and/or blood-based tests improves. For example, biochemical or molecular assessment of response may be discordant with imaging studies, which may either be a function of disease natural history, imaging frequency, orin the case of immunotherapypseudoprogression. Despite these caveats, it is helpful to understand therapeutic resistance fundamentally in terms of whether a therapy is not effective or no longer effective in order to better understand and target the underlying mechanisms driving resistance.

Until recently, there have been few attempts to study secondary therapeutic resistance in large-scale clinical trials. We will outline a few of the reasons why this research has been difficult to conduct but also why, in the age of targeted therapeutics, it is of utmost importance. The established clinical trial infrastructure is designed to assess the safety and efficacy of drugs largely based on objective response, progression-free survival (PFS), and OS. If a drug is effective at decreasing or controlling disease for an extended period of time, it is generally felt to be a positive outcome, which can lead to a regulatory approval. As clinical trials move more to response-based end points, it is possible that we will see more drugs that demonstrate excellent initial responses but lead to rapid development of secondary resistance. The need for rapid drug approval in this setting will have to be balanced against long-term outcomes of patients treated with novel therapeutics.

Historically, objective response rate (ORR) has been considered a surrogate for clinical benefit, even where OS benefit is unknown. However, therapies that are designed to target a single aberrant growth signal are susceptible to rapid outgrowth of resistant subclones, limiting the durability of response. The promise of targeted therapytargeting only the gene or protein that is driving cellular proliferationmay become a liability when resistant subclones drive signaling through alternate pathways. A recurring challenge for drug development in mCRC is the rapid development of treatment resistance. For the vast majority of colon cancers, targeting a single mutation is either ineffective (primary resistance) or leads to relatively rapid disease progression after a period of response (secondary resistance). The future of clinical trials for mCRC will need to shift to dynamic assessment of not only primary resistance mechanisms but also those that develop in response to therapeutic inhibition.

Understanding mechanisms of secondary resistance is of utmost importance, but until recently such understanding has relied almost exclusively on postprogression tissue biopsies. Given the invasive nature of these biopsies, it is understandable that it has been difficult to conduct these ancillary studies in large-scale clinical trials. However, serial tissue biopsies are neither cost-effective nor practical. Furthermore, a single-site tumor biopsy is a relatively poor representation of the spectrum of intra- and intertumoral heterogeneity.5 If we are to successfully reach the ultimate goal of practicing precision oncology, we must understand the dynamic interplay between preexisting mutational profiles and those that are induced or unmasked by treatment. Fortunately, circulating tumor DNA (ctDNA) is a technology that can be harnessed to overcome most of these shortcomings and to provide a diagnostic tool for longitudinal, dynamic disease monitoring.

Although the presence of cell-free DNA (cfDNA) was initially described in 1948 in healthy individuals, it was not until the past decade that commercial ctDNA assays have become incorporated into routine clinical practice.6 The most obvious benefit of ctDNA-based molecular testing is its ability to provide a noninvasive mechanism for monitoring dynamic mutational profiles. The fact that ctDNA is noninvasive allows for repeated, longitudinal testing without the associated morbidity that tissue biopsies entail. As tumors progress, metastasize, or are exposed to stressors such as targeted inhibitors or chemotherapy, they develop acquired mutations; these are not uniformly distributed throughout single tumors or within multiple tumors in the same patient.7 This intra- and intertumoral heterogeneity cannot be accounted for in single-site tissue biopsies. In this situation, ctDNA can actually provide a better understanding of the fluid molecular landscape of cancers, because it is exposed to therapy in real time as resistance mechanisms are developing. Indeed, this approach has allowed for the design of multiple novel clinical trial platforms that are tailored not only to a specific disease state or line of therapy but to underpinnings of molecular resistance. Two such efforts are the Colorectal and Liquid Biopsy Molecularly Assigned Therapy (COLOMATE) umbrella trial (NCT03765736) and the Guardant Originates in Zipangu Liquid biopsy Arrival (GOZILA) trial (UMIN000016343). In these trials, patients with refractory mCRC undergo ctDNA-based screening and are assigned to one of several molecularly selected treatment arms. Patients are also offered molecular screening at the time of trial discontinuation. Although complete discussion of the COLOMATE and GOZILA trials is outside of the scope of this article, their design and implementation serve as a road map for future trial platforms. Herein, we will outline some of the most common mechanisms of resistance to targeted therapies in the treatment of mCRC.

EGFR is commonly overexpressed in CRC.8 This knowledge led to the initial development, and ultimately approval, of the monoclonal antibodies cetuximab (Erbitux) and panitumumab (Vectibix) to treat mCRC.9,10 Despite these approvals, a large proportion of patients did not gain significant benefit from treatment with cetuximab or panitumumab. Multiple reports later identified KRAS mutations as driving primary resistance to EGFR blockade.11-13 While initial reports investigated only KRAS exon 2 mutations, the negative predictive effect of KRAS exon 3 and 4 mutations as well as of NRAS exon 2, 3, and 4 mutations were later found to have a similar negative predictive value.14,15 These findings eventually led to revised approvals of these drugs, limiting treatment to patients with KRAS and NRAS (RAS) wild-type disease. RAS mutations remain the strongest negative predictor of response to anti-EGFR therapy.

BRAF V600E mutations, occurring downstream of KRAS, appear to have a similar negative predictive effect to EGFR inhibitor (EGFRi) therapy. Di Nicolantonio and colleagues initially described a cohort of 79 patients with mCRC treated with panitumumab or cetuximab. The response rate in 11 patients with BRAF V600Emutant mCRC was 0% compared with 32% in those patients with BRAF V600E and KRAS wild-type mCRC.16 This finding has been subsequently bolstered by multiple retrospective reviews; however, given the relative rarity of BRAF V600E mutations in mCRC, there was insufficient statistical evidence to preclude benefit from anti-EGFR therapies in this patient subset.17,18

HER2 amplification has also been implicated as a driver of primary resistance to EGFRi therapy.18,19 Similar to BRAF, the rarity of HER2 amplification in mCRC has limited the ability to make definitive conclusions regarding its role in EGFR resistance. Nonetheless, HER2 amplification is associated with significantly worse outcomes in patients treated with EGFR antibodies with or without cytotoxic chemotherapy.20,21 In one retrospective analysis, 74 patients with HER2-amplified mCRC had significantly worse ORRs (31.2% vs 46.9%) and median PFS times (5.7 vs 7.0 months).21

All the causes of primary resistance mentioned above can also lead to secondary resistance in patients who are treated with EGFR antibodies. One novel class of mutations that develops as a mechanism of secondary resistance to EGFRi are the so-called EGFR ectodomain mutations, which arise within the receptor region of EGFR and alter cetuximab or panitumumab binding.22,23 Based on mathematical modeling, one can assume that there are numerous subclonal mutations in all patients with mCRC.24 The fact that these mutations generally remain subclonal suggests that they have some inherent growth disadvantage compared with the dominant (wild-type) clone in most cases. This dynamic is changed in the setting of targeted therapy, in which the dominant clone is selectively inhibited; this allows for growth of subclonal populations that are resistant to the inhibitor. When this selective pressure is removed, subclonal resistance mutations rapidly decay. This interplay between dominant and subclonal populations has been shown in a number of elegant preclinical and clinical studies.25-27 In one study that included 135 patients with RAS/BRAF wild-type mCRC who had progressed on anti-EGFR therapy, researchers were able to quantify the half-life of exponential decay of acquired mutations after withdrawal of an EGFRi. The half-life of clonal decay of acquired RAS mutations was 3.4 months, and the half-life of EGFR mutations was 6.9 months. Further, the investigators showed a nearly 20% improvement in ORR between those patients who were retreated with anti-EGFR therapy less than 1 half-life vs those who were retreated after more than 2 half-lives.25

The knowledge that acquired mutations decay after withdrawal of anti-EGFR therapy has spurred multiple trials aimed at EGFR rechallenge in patients who have developed secondary resistance to EGFRi. Two recent single-arm trials have provided evidence that EGFR rechallenge is a feasible and effective strategy for treatment of refractory mCRC. The 2 trials had similar designs and included patients who had an initial response to cetuximab-based chemotherapy followed by development of secondary resistance and exposure to a cetuximab-free regimen. In the CRICKET trial (NCT02296203), 28 patients were treated with cetuximab and irinotecan rechallenge. Although ctDNA was collected at the time of enrollment, patients were not excluded based on the presence of RAS, BRAF, or EGFR ectodomain mutations. The ORR and disease control rate (DCR) were 21% and 54%, respectively. In the CHRONOS trial (NCT03227926), patients with RAS, BRAF, or EGFR ectodomain mutations were excluded from EGFR rechallenge. In this trial, 27 patients were treated with single-agent panitumumab. The ORR and DCR were 30% and 63%, respectively. The COLOMATE companion trial PULSE (NCT03992456) will assess panitumumab rechallenge in patients with mCRC who have progressed on prior anti-EGFR therapy and who meet rigorous molecular eligibility based on cfDNA profiling. Enrollment is ongoing.

HER2 amplification occurs in approximately 3% of patients with mCRC.28 Multiple trials have evaluated different antiHER2-based therapies in patients with mCRC with varying degrees of success.29-31 Despite the impressive activity of this therapeutic strategy, nearly all patients develop primary or secondary resistance. The HERACLES trial (NCT03225937) evaluated trastuzumab (Herceptin) and lapatinib (Tykerb) in patients with refractory, HER2-positive mCRC. Utilizing ctDNA, these patients were evaluated pre- and post treatment to determine the molecular alterations associated with primary and secondary resistance. Baseline RAS or BRAF mutations were detected in 6 of 7 patients (86%) with primary resistance to anti-HER2 therapy, as compared with 3 of 22 patients (14%) who had clinical benefit from therapy.32 At the time of progression, alterations in a known resistance pathway were identified in all but 1 patient. These acquired alterations included PIK3CA mutations (4 patients), HER2 mutations (3 patients), KRAS mutations (2 patients), EGFR mutation (1 patient), and MET amplification (3 patients). Similar results were reported in the MyPathway trial (NCT02091141), in which patients were treated with trastuzumab and pertuzumab (Perjeta). The ORR was significantly lower in patients with a baseline KRAS mutation vs those with wild-type disease (8% vs 40%).30 In addition to KRAS mutations, those patients with PIK3CA mutations also had significantly worse ORR than those without (13% vs 43%, respectively).

Because patients with HER2-amplified mCRC with concomitant RAS, BRAF, and/or PIK3CA mutations experience limited benefit from selective anti-HER2 strategies, a novel therapeutic strategy is needed. The current standard of care for these patientsregorafenib (Stivarga) and TAS-102 (trifluridinetipiracil)offers only limited survival benefit.33,34 The combination of tucatinib (Tukysa) and trastuzumab is active against RAS wild-type and HER2-amplified mCRC,35 but this selective anti-HER2 combination is unlikely to provide benefit in patients with concomitant resistance mutations. To target resistance mutations and HER2 amplification simultaneously, the 3T study will evaluate the safety, tolerability, and preliminary efficacy of tucatinib, trastuzumab, and TAS-102 in patients with PIK3CA-, RAS-, or BRAF-mutated and HER2-amplified mCRC. This will also be a COLOMATE companion trial.

BRAFV600E mutations occur in approximately 7% of patients with mCRC, and they are associated with significantly worse response to chemotherapy and poor prognosis.36,37 Several studies have sought to target BRAF V600Emutated mCRC. Unlike patients with BRAFV600Emutated melanoma, patients with mCRC appear to derive modest benefit, if any, from single-agent BRAF inhibitors.38,39 The mechanism of this primary resistance is due to EGFR-mediated reactivation of MAPK signaling through RAS, CRAF, and BRAF heterodimerization.40,41 Indeed, the combination of EGFR and BRAF inhibitors have led to significant improvements in responses, yet these responses tend to be short-lived due to relatively rapid development of secondary resistance. In the phase 3 BEACON trial, patients were treated with a combination of the BRAF inhibitor encorafenib (Braftovi) and cetuximab with or without the MEK inhibitor binimetinib (Mektovi) vs a control arm of irinotecan-based chemotherapy. ORRs (27% vs 20% vs 2%), median PFS (4.5 vs 4.3 vs 1.5 months) and median OS (9.3 vs 9.3 vs 5.9 months) were all improved with the targeted inhibitor combinations.42 Somewhat surprisingly, there was not a clinically significant difference in outcomes between patients who received triplet (BRAF, MEK, EGFR) vs doublet inhibition (BRAF, EGFR) despite a numerically increased response rate with the addition of MEK inhibition.

As mentioned above, the development of secondary resistance in patients treated with targeted BRAF inhibitors is inevitable and generally rapid when compared with other targeted therapy approaches. Multiple pathways of secondary resistance have been identified in both in vitro and patient samples. The most common of these is the development of acquired RAS mutations or amplifications, which accounts for approximately 70% of patients who develop secondary resistance.27,43 Other documented causes of resistance include BRAF and MET amplifications, MAP2K1 mutations, and ARAF mutations as well as BRAF exon 2-8 deletions and EGFR ectodomain mutations, both of which decrease the affinity of BRAF and EGFRi binding.43 The common theme of all these alterations is reactivation of signaling through the MAPK pathway, which bypasses inhibition.

Since resistance mutations decay upon withdrawal of anti-EGFR therapies, it is hypothesized that similar changes would occur in BRAFV600Emutant mCRC as well. Using this rationale, we have designed the BRAFV600Erechallenge arm of the COLOMATE trial, which will enroll patients with BRAF V600Emutant mCRC who develop secondary resistance to targeted inhibition, are subsequently treated with chemotherapy, and are then rechallenged with encorafenib, cetuximab, and binimetinib. The addition of binimetinib in this setting allows for negative selective pressure downstream of BRAF, which will hopefully decrease the reemergence of secondary resistance mutations that bypass BRAF signaling.

Non-V600 BRAF (BRAFnon-V600) mutations occur in approximately 2% of all patients with mCRC, and these patients have a significantly better prognosis than those with the more common BRAF V600E mutations.44 BRAF non-V600 mutations are functionally divided into class II or class III, based upon their mechanism of signaling and RAS activation dependence. Whereas BRAF V600E mutations signal as RAS independent, activated monomer, class II BRAF non-V600 mutants signal as constitutively active mutant BRAF dimers that are relatively insensitive to negative RAS feedback inhibition.45 Class III BRAF non-V600mutants have impaired or even absent kinase activity, but they can still amplify MAPK signaling in a RAS-dependent fashion through increased mutant/wild-type RAF heterodimerization.46

As mentioned above, class II BRAF non-V600 variants signal as constitutively activated dimers that are largely independent of RAS activation at baseline. Xenografts derived from patients with class II BRAF non-V600 variants who were exposed to dual BRAF/MEK inhibition showed significant shrinkage in 17 of 19 (89%) of tumors.47 Despite the preclinical evidence of benefit in this patient population, there has been limited success thus far in clinical trials evaluating dual BRAF-MEK inhibition in patients with class II mutations. One potential cause of resistance in patients with mCRC is EGFR upregulation/reactivation. Class II mutants are relatively insensitive to upstream activation (EGFR, RAS) at baseline due to ERK-mediated feedback suppression. However, in situations where this feedback suppression is eased, such as in the case of effective MEK/BRAF inhibition, one would expect rapid feedback reactivation as is seen in BRAF V600E mutations. Current RAF inhibitors selectively inhibit BRAF V600Emutant monomers, but this can lead to modest ERK inhibition in patients with class II mutations. This is due to binding of the RAF inhibitor to one site in the dimer pair, leading to inhibition of that protomer while the other protomer remains activated. By itself, this modest inhibition is unlikely to provide any level of disease control; however, we hypothesize that the combination of modest BRAF inhibition combined with MEK and EGFR inhibition to prevent feedback reactivation will lead to improved disease control compared with other approved therapies.

Class III BRAF non-V600 mutations activate ERK signaling through amplification of mutant/wild-type RAF heterodimers. Class III mutants bind to RAS more effectively and activate wild-type CRAF, leading to downstream ERK activation.46 ERK activation in these mutants requires upstream activation by RAS,either by activating mutation or increased EGFR activity. This reliance on upstream activation can be exploited by effective EFGR inhibition in patients with RAS wild-type disease.48,49 EGFR inhibition significantly decreases RAS signaling, while MEK inhibition has the potential to not only decrease downstream signaling but also to reduce the competitive advantage of emergent RAS or other upstream mutations. BRAF inhibitor treatment in this setting offsets toxicity from the MEK and EGFRi as it has opposing effects in normal tissues. These patients with class II and class III BRAF non-V600 mutations will be eligible for the COLOMATE Umbrella trial to Evaluate Anti-BRAF Treatment Strategies, which will assess the safety and effectiveness of the combination of encorafenib, cetuximab, and binimetinib.

Although the mechanisms listed above are some of the most common pathways of resistance, they do not account for all the therapeutic targets driving secondary resistance. Noninvasive, longitudinal monitoring with ctDNA will continue to revolutionize clinical trial design. These advances have the opportunity to usher in new trials that allow for dynamic and adaptive treatment arms. In these studies, patients can be started on one trial and seamlessly switched to another at the first signs of resistance. This clinical trial approach will require rethinking clinical trial and statistical design, but it could offer a novel approach to overcoming resistance. We look forward to innovative clinical trial designs that will allow for this level of precision care for patients with mCRC.

Author Affiliations: Mayo Clinic, Jacksonville, FL, USA; Vanderbilt University Medical Center, Nashville, TN, USA; Emory University School of Medicine, Atlanta, GA, USA; 4Mayo Clinic, Scottsdale, AZ, USA; 5Duke University Medical Center, Durham, North Carolina, USA.

JJ receives consulting fees and education grants from AstraZeneca, Bayer, E.R. Squibb & Sons, and OncLive. KC has research grants to her institution from Array, Bristol Myers Squibb, Daiichi Sankyo, Incyte, Merck, Nucana, Pfizer/Calithera. She receives consulting fees from Array, Foundation Medicine, Merck, Natera, Taiho, Pfizer. CW receives research grants to her institution from Boston Biomedical Inc, INHBRX, Lycera, Rapt Therapeutics, Seattle Genetics, Symphogen, and Vaccinex. She has consulting fees and education grants from Nova Research, Oncology Learning Network, and PrecisCA. JS is a consultant for AbbVie, Amgen, AstraZeneca, Bayer, Biopharma, Inivata, Mereo, Natera, Pfizer, Seagen, Silverback Therapeutics, and Viatris. He has received research grants to his institution from AbbVie, Amgen, AStar D3, Bayer, Curegenix, Daiichi Sankyo, Gossamer Bio, Nektar, Roche/Genentech, Sanofi, and Seagen. TBS receives research funding to his instiution from Abgenomics, Agios, Amgen, Arcus, Arys, Atreca, Bayer, Boston Biomedical, Bristol Myers Squibb, Celgene, Clovis, Incyte, Ipsen, Genentech, Lilly, Merck, Merus, Mirati, Novartis, Pfizer, and Seattle Genetics,. Hereceives consulting fees to his institution from Arcus, Array Biopharma, AstraZeneca, Bayer, Daiichi Sankyo, Eisai, Foundation Medicine Genentech, Incyte, Ipsen, Pfizer, Seattle Genetics, and Merck. Hereceives consulting fees (to self) from AbbVie, Beigene, Boehringer Ingelheim, Celularity, Exact Science, Janssen, Kanaph, Natera, Sobi, TreosBio, and Xilis. He serves on an Independent Data Monitoring Committee/Data and Safety Monitoring Board (IDMC/DSMB) (to self) for AstraZeneca, Exelixis, Lilly, PanCan, and 1Globe. He is on the Scientific Advisory Board for Imugene, Immuneering, and Sun Biopharma. He holds inventions/patents of WO/2018/183488; WO/2019/055687.

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Addressing Resistance to Targeted Therapies in Metastatic Colorectal Cancer - Cancer Network

Red Cross urges action for Papua New Guinea as COVID-19 overwhelms health system – Reuters

Posted: at 1:53 am


A woman holds a small bottle labelled with a "Coronavirus COVID-19 Vaccine" sticker and a medical syringe in this illustration taken October 30, 2020. REUTERS/Dado Ruvic

Oct 25 (Reuters) - Concerted international action is needed to support Papua New Guinea as a surge in COVID-19 cases overwhelms the Pacific country's health system, the International Federation of Red Cross and Red Crescent Societies said on Monday.

Coronavirus cases in the island nation of 9 million have been surging in recent weeks, with 385 new cases recorded on Thursday, according to latest available government data.

There have been 26,731 officially confirmed cases and 329 deaths in the country 150 km (90 miles) north of Australia.

Less than 1% of the population has been fully vaccinated, according to Our World in Data figures, although the government anticipated months ago that it would have enough shots by now for everyone who wanted to be vaccinated.

Misinformation, public apprehension, and logistical challenges with the rollout have slowed down vaccinations, the Red Cross said.

"Urgent efforts and further support are needed in healthcare to prevent a massive loss of life in the coming days and weeks," Uvenama Rova, PNG Red Cross secretary general, said in a statement.

According to the PNG National Control Centre for COVID-19, all major hospitals have been hit with rising cases.

"We're at the moment barely managing with the existing load," Gary Nou, team leader for Emergency Medical Team at the National Centre, was quoted as saying last week in a statement on the centre's website.

A medical team from Australia arrived in Port Moresby this month, and Britain was also to send a team.

While some other nations in the Pacific region, such as the Solomon Islands and Kiribati, have also had sluggish vaccine rollouts, the tiny nation of Palau had 99% of its population over 12 vaccinated by mid-October, while Fiji had 96% of eligible people with one dose, the Red Cross said this month.

Reporting by Lidia Kelly in Melbourne; Editing by William Mallard

Our Standards: The Thomson Reuters Trust Principles.

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NY Jets humiliated by Patriots in 54-13 loss. Zach Wilson’s health is all that matters now – NorthJersey.com

Posted: at 1:53 am


FOXBOROUGH, Mass. Sunday provided yet another reminder that things can always get worse for the New York Jets. Especially when they're on the same field as the Patriots.

The Jets were humiliated by the Patriots,54-13at Gillette Stadium in one of the most lopsided lossesin franchise history.

"This is the NFL," Jets coach Robert Saleh said. "You give up 50 points, it's embarrassing."

And that wasn't even the worst part of this brutal afternoon.

That moment came early in the second quarter when rookie quarterback Zach Wilson injured his right kneetaking a big hit from Patriots linebacker Matthew Judon. A few minutes later, Wilson was limping back to the locker room and no one knows for sure when he'll be back on the field.

Saleh said the initial prognosis for Wilson's injury is"good." And according to Wilson,the belief is he suffered a PCL injury, which he called the "best-case" scenario.

The Jets won't know anything for sure until Wilson gets an MRI on Monday. But the Jets season hinges on what comes next.

If Wilson has an injury that keeps him out a significant amount of time, the Jets are staring a lost season in the face.Their unquestioned top priority was to develop their young quarterback this season, and every snap he can't be on the field is a missed opportunity.

But Sunday showed us just how big of a priority Wilson's development is, because it's the only thing the Jets have to look forward to this season. Even if Wilson was healthy and playing better, this team has done nothing to prove it can be consistently competitive because the roster just isn't good enough.

Saleh put the blame on himself and the coaches, not the players. The normally ubeat coach was clearly downtrodden and perhaps a little shell-shocked in the aftermath of this loss.

"I don't think I've had this feeling after a game since 2017 against Dallas," Saleh said, referring to a 40-10 loss to the Cowboys when he was the 49ers' defensive coordinator. "A helpless feeling where you're just watching, you're trying to figure something out. I'll be honest. We talk about adversity. Everyone was asking [when it would come]. You can chalk this one up, it's here.

NY JETS: Coach Robert Saleh says It's time to 'put up or shut up' early on offense

"This [loss] is from coaches all the way down. NFL doesn't really give a flying [expletive] excuse my language in terms of scheduling. We got to line up the next week and for the 11 or 12, whatever we got left. I know we got the right men in that locker room. I know we got the right people in that locker room. I know we'll come back strong. But we got to get it going."

But do the Jets have the right players in their locker room?

General manager Joe Douglas has been on the job for more than two years and it's hard to argue that this team is significantly better from top to bottom than it was back then. There are certainly some promising young players on the roster, and the Jets have improved, especially on the defensive line.

But they have the only offense in the NFLthat has yet to score a point in the first quarter of a game this season. And their defense just allowed the Patriots to score 50-plus points on them for the first time since 1979.

Let's just pause a moment to appreciate how bad this defensive performance was: According to the CBS broadcast, the Jets had gone 420 games without allowing 50 points; the last time it happened was a 52-14 loss to Miami in 1995. They couldn't stop anything, allowing rookie quarterback Mac Jones to go over 300 yards passing for the first time in his career. They also allowed backup Brian Hoyer to rack up 69 passing yards on a late drive.

The Jets defense' surrendered 551 yards on Sunday, the last time they gave up more than that was 1998.

A lack of talent has to be part of the reason for that. Yes, the Jets had to play without C.J. Mosley, who had helped them be surprisingly effective early in the season. But something is wrong if everything falls apart without him on the field.

"Did it hurt? Obviously, yeah," Saleh said. "Should it have hurt this bad? No."

Some of that is on coaching. Saleh is clearly still learning the ropes in his first year. But the talent on this roster is not consistently improving. And if the Jets keep having days like Sunday, Douglas is going to be under some major pressure to upgrade the roster. Quickly. Because what we saw on Sunday looked a lot like what we've been seeing from the Jets for the past decade.

At halftime, the Patriots honored former defensive lineman Richard Seymour by inducting him into their hall of fame. Seymour spoke on the field during the break and told a roaring crowd that he could have picked any game he wanted for this moment, but he picked the "homecoming game against the Jets."

That jab was right on target. The Jets have lost 12 straight games to the Patriots dating back to their last win in 2015. They haven't beaten the Patriots in Foxborough since the 2010 playoffs.

And Sundayshows just how far the Jets still have to come. It was bad on every level and it even had their normally optimistic coach swearing after the game. Multiple times.

"Everyonce in a while you get your [expletive] excuse my language you get your teeth knocked in," Saleh said. "Sorry."

This was an inexcusable performance.

And it was even harder to stomach without Wilson out there growing. That's why it's so important for the Jets young quarterback to miss as little time as possible. Because if he's out for a while, there could be a lot of hopeless Sundays in the very near future.

Andy Vasquezis the Jetsbeat writer for NorthJersey.com. For unlimited access to all Jets analysis, news, trades and more, pleasesubscribe todayanddownload our app.

Email:vasqueza@northjersey.com

Twitter:@andy_vasquez

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$15M donation to expand Calvin University health care education, partnerships – MiBiz: West Michigan Business News

Posted: at 1:53 am


GRAND RAPIDS Forming a new school with the backing of a $15 million gift from an anonymous donor will enable Calvin University to elevate academic programs in health care.

Programs that are now spread across several departments at the Grand Rapids-based Christian liberal arts college will become part of the planned School of Health.

The new school will allow the university to better organize, coordinate and support undergraduate and graduate degree programs in health sciences. It will also expand academics, upgrade facilities and form stronger partnerships with care providers in the market, Calvin University President Michael Le Roy told MiBiz.

Calvin has always had real strengths in the natural sciences and the health sciences at the undergraduate level, and I think that were building on that strength, Le Roy said. This will turn some heads and help them to see that we have some concerted strategy for growth and development and meeting the educational needs of people who want to work in these fields.

A steering committee consisting of faculty, staff and administrators has started work to define the full scope of the new Calvin School of Health that initially would feature existing academic programs in nursing, kinesiology, exercise science, speech pathology and audiology, and public health.

In the coming months, the steering committee will assess market demand and identify new undergraduate and graduate programs for Calvin. The university hopes to launch three new masters programs in health-related fields by the fall of 2022.

The School of Health will also develop certification programs for non-degree students already working in health care, Le Roy said. Clinical professions such as occupational and physical therapists and physician assistants are among the new programs the School of Health could develop, he said.

This school will really allow us to evaluate the demand and the opportunity, he said. Theres a long list of opportunities, and part of what we want to identify is what are the most urgent needs and how we meet those fairly quickly.

The university will soon begin searching for a dean for the new School of Health and work to redesign existing space for the programs.

Meanwhile, the School of Health should allow Calvin to expand partnerships with medical schools at Michigan State University, the University of Michigan and Wayne State University, as well as with care providers and other health sciences programs at colleges in West Michigan, said Calvin Provost Noah Toly.

It does give us a better platform to partner with providers of health and health sciences education ... and be part of a network of partners that features not only other educators but also organizations and employers, Toly said. Everyone in that network benefits from all of its players doing the things that distinguishes them.

Calvin, with a student population of 3,300, envisioned forming the School of Health under a master plan put in place after transitioning in 2019 from a college to a university.

The master plan involves imagining the organization of the whole university and academic structure and what schools would likely be a part of this, Le Roy said.

The university proceeded with establishing the School of Health after securing the $15 million donation from a donor with whom Cavin has a long-standing relationship, he said. The donation will go to support academic programming and support leadership, personnel, labs, and undergraduate and graduate training, Le Roy said.

The donor is someone who is very familiar with Calvin and its programming in the health sciences, and somebody who was acquainted with our vision and the goals we have over the next decade to become a global university thats serving a wide variety of students, he said.

The familiarity with that vision catalyzed some imagination, said Le Roy, who described the donation as a real affirmation of the work faculty have been doing in the health sciences area, and it will be a catalyst for us in our vision going forward.

The gift for the School of Health was the second-largest single contribution ever for Calvin, behind a nearly $22.3 million donation in 2020 to form the new School of Business.

University officials hope the two contributions and creation of both schools will spur other benefactors to get behind areas of our programming where they have great affinity and support the universitys Vision 2030 strategic plan, Toly said.

We had always been hoping that the vision, plus the launching schools, would lead other donors to see how their gift would make a difference, he said.

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Oswego Health increases starting hourly rate to $15 – WSYR

Posted: at 1:53 am


Posted: Oct 24, 2021 / 07:06 PM EDT / Updated: Oct 24, 2021 / 09:12 PM EDT

OSWEGO, N.Y. (WSYR-TV) Oswego Health has increased its starting hourly rate to $15.00, which is their new minimum. This comes after New York State announced it would raise the minimum wage from $12.50 to $13.20 effective January 1, 2022.

The recent staffing challenges are impacting all industries, especially healthcare and long-term care. The ongoing COVID-19 pandemic has made it difficult to find people willing to work in the medical field. Oswego Health is one of Oswego Countys largest employers, with over 1,200 employees.

This change in starting rate impacts several positions at Oswego Health, including nursing assistants, certified nurse aids, environmental service techs, house keeping, unit helpers and other positions. Oswego Health says this wage increase is an effort to recruit new employees, as well as show appreciation to its current employees.

We want to continue our philosophy of paying them a fair wage for the great work that they do and we really made this decision to go above and beyond what the minimum wage was. It goes up to $13.20 across the state in January and we said you know what, lets do something more here. Lets really show our employees how we feel and show them we want to pay them a fair wage for the great work they do, says Marq Brown, VP of Human Resources.

Oswego Health says their staffing is stable right now, and they are able to give the care thats needed to their patients. But they are still looking to hire.

Across the board we are looking for positions, certainly for registered nurses, nursing assistants, CT tech, ultra sound techs, people that work in the back office. We have positions open everywhere, says Michael Harlovic, President and CEO at Oswego Health.

Click here for more details about Oswego Health.

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Oswego Health increases starting hourly rate to $15 - WSYR

How Entrepreneurs Can Protect Their Mental Health While Being Their Own Boss – Entrepreneur

Posted: at 1:53 am


Opinions expressed by Entrepreneur contributors are their own.

Entrepreneurship tends to be thought of as a glitzy way of life. A lot of that can be attributed to whats posted and seen on social media from the most successful entrepreneurs who show off their freedom and upscale lifestyle.

What people fail to understand is that this kind oflife makes up a very small minority of entrepreneurs, and almost all of them didnt get to that point of success without years of struggle and financial hardship while building their companies.

In addition, whats shown on social media also isnt always a depiction of a persons real lifestyle.

Being an entrepreneur isnt about waking up on a remote island and sending out a few emails before hopping on a private jet to Italy. The business is a daily grind, even for those who have successfully built their company into a money-making revenue machine.

Its not easy deciding to start and build a business, reflected in a study where72% of entrepreneurs self-reported mental health concerns. The study also noted that entrepreneurs were significantly more likely to report a lifetime history of depression, ADHD, substance use and bipolar diagnosis.

A newly formed small business cant grow or make money in the early stages if its leader doesnt have the hustle mentality to grind day in and day out.

Here are a few ways that entrepreneurs can protect their mental health throughout the stressful, but rewarding journey of creating and building their own business.

Like in any area of life,financial issues are the number one reported cause for stress and anxiety among entrepreneurs. Some people put their entire life savings into the startup with nothing to fall back on.

According to smallbizgenius.net, 39% of small business owners use cash to fund their companies.While thats a method that has worked for a few, its not recommended and could leave someone in a tough spot if the company doesnt work out.

The start-up journey is stressful enough to begin with, and putting everything into a basketthat fails 90% of the time is not smart. Its important to make sure theres a financial cushion to live on for at least three to six months.

If thats not possible, consider working a part-time job that allows for flexible hours. Another idea is having a side hustle that brings income like having a rental company or curating an investment portfolio.

The biggest takeaway is to try and leave as much money on the table to take care of the personal side of things and find a way to still bring in an additional income stream at the same time.

Related:EntrepreneurshipIs All About Overcoming Obstacles

Another quick way to overheat and face an even higher level of stress is trying to do everything by yourself.Even if the startup isnt in a place to take on full-time employees quite yet, there are endless resources available to help a business outsource certain tasks.

This is important because burnout can happen very quickly when a business is forming, and that process tends to speed itself up if the founder is trying to do everything on their own.

Another option to avoid wearing down is going into business with a partner. Typically, each person would be an expert in a certain area of the company which would not only take things off ones plate, but also be beneficial in driving the business forward.

Related:Here We Explore the Core ofEntrepreneurship

When beginning the entrepreneur journey, its important for a persons mental well-being that they are surrounded by positive influences.

There will be some friends and family members that question the decision to leave corporate life with a steady paycheck behind. Remember, they come from a position of care and love, but they arent entrepreneurs.

Surround yourself with mentors who have been successful as entrepreneurs. Ask them for advice and guidance through the beginning of the start-up journey and continue to develop that relationship and expand a professional network as the business grows.

Mental health can easily deteriorate with the wrong people giving the wrong advice or pushing ones self to the point of burnout. Following the above tips and frequently checking in with ones emotions will help to ensure that self-care stays a top priority.

Related:Are You Cut ForEntrepreneurship?

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How Entrepreneurs Can Protect Their Mental Health While Being Their Own Boss - Entrepreneur

Free program aims to tackle home health-care needs on Staten Island – SILive.com

Posted: at 1:53 am


STATEN ISLAND, N.Y. In response to the growing need for home health-care workers on Staten Island amid the continuing coronavirus (COVID-19) pandemic and vaccine mandates, a local non-profit will soon kick off its first virtual home health aide training program.

Staten Island Performing Provider System (PPS) received more than 200 responses to its initial outreach seeking enrollment for its free Certified Home Health Aide Training Program, taught by the City University of New York City College of Technology.

The programs initial five-week class will begin the first week of November, and is comprised of 20 students, according to Joseph Conte, executive director of PPS.

Home health aides are traditionally supervised by medical practitioners, usually nurses, and may work with therapists and other medical staff. These aides keep records and report changes in the clients condition to supervisors. They are often the only ones preserving the quality of life of their home-bound patients.

About a dozen Licensed Home Care Services Agencies and Certified Home Health Agencies employed nearly 7,000 home health-care aides on Staten Island prior to the Oct. 7 vaccine mandate, which caused staffs to shrink, managers said.

Conte said he anticipates the new programs growth and continuance in filling this critical gap, though its initial enrollment period is currently closed. We hope to run classes throughout 2022, and get up to 100 trained in that cycle, he said.

Results will be twofold, he said.

Graduates will fill a gap in health care created by the COVID-19 pandemic, as many care givers stopped work for personal reasons or sought a new career when vaccines became a requirement in the field in New York City. Additionally, the program will create sorely-needed jobs on Staten Island.

The program offers a high level of professionalism by including an expanded number of hours above the minimum requirements, said Mary Han, director of continuing care and quality management for PPS. In addition, all graduates will receive full professional attire, including a uniform, stethoscope and medical kit at their commencement, she said.

At the conclusion of the course, SafeHarbor Healthcare Services will be providing participants with a two-day, in-person skills training session.

Han said she learned a lot from speaking with the applicants.

There are many who have a nursing degree from a different country, but no certification here, she said. Some are new immigrants, and many have lost their jobs due to COVID. The common theme among these discussions is the urgency to find employment after going through their own challenges.

Conte said that the majority of people responding to the programs initial text outreach hail from the North Shore: 38 candidates from ZIP code 10304, 33 from 10301 and 27 from 10303.

Its all along the North Shore corridor, he said. I think were reaching a lot of individuals who have lost employment during COVID individuals who have decided they wanted to switch careers into an entry level health-care role.

Conte said the entry-level jobs start people on a sturdy career ladder toward roles as licensed practical nurses, patient care associates in a hospital setting or certified nursing assistants in nursing homes.

I think it really has the potential to fill hundreds of roles in the coming year or two, and thats an important start, Conte said.

In looking ahead, PPS representatives said they plan to work with the Staten Island Chamber of Commerce and the Jewish Community Center in order to expand the program to meet the employment and health-care needs on the Island.

Though PPS has funding for initial classes thanks to Northwell Heath and other sources, it is currently working with FundRISING to obtain additional monetary support through the Apprenticeship State Expansion Grant of the New York State Department of Labor, Division of Employment and Workforce Solutions.

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Conn. Health Officials Warn Parents to Take Precautions Against Respiratory Viruses – NBC Connecticut

Posted: at 1:53 am


Health officials in Connecticut are reminding parents to take precautions against respiratory viruses this fall due to an increase in cases.

The state Department of Public Health, along with pediatric providers from Connecticut Children's and Yale New Haven Children's Hospital, said that these precautions are not only against COVID-19, but also the flu and respiratory syncytial virus, also known as RSV.

RSV made an early impact over the summer in Connecticut, and that could be a sign of things to come this winter, said DPH Commissioner Manisha Juthani.

RSV causes 2.1 million outpatient visits and 58,000 hospitalization annually in children under the age of 5, according to the Centers for Disease Control and Prevention.

We have seen more RSV infections at Connecticut Childrens than usual for this time of year, said Juan Salazar, physician-in-chief and pediatric infectious disease specialist at Connecticut Childrens. This is likely because safety measures relaxed over the summer and people started getting together again."

The virus is easily spread through mouth and nose droplets when a person coughs or sneezes, according to Salazar. It can also survive on surfaces and infect anyone who touches a contaminated surface.

The associate medical director for infection prevention at Yale New Haven Children's Hospital, Thomas Murray, said said RSV usually causes milder symptoms for most babies and infants. This includes congestion, runny nose, cough and fever.

"However, for some younger children, especially those born prematurely or with underlying health conditions, the virus can cause more severe symptoms such as difficulty breathing, Murray said.

RSV is a leading cause of hospitalization in the winter months in childrens hospitals, but now we are seeing it in the late summer and fall. Hospitalized children with RSV typically go home within a few days but the most serious cases can last a week or longer," he continued.

Health officials emphasized that the spread of respiratory viruses can be prevented through hand washing and measures such as masking, avoiding crows and social distancing.

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Conn. Health Officials Warn Parents to Take Precautions Against Respiratory Viruses - NBC Connecticut

To support youth mental health in the Roaring Fork Valley, organizers look to the internet – Aspen Times

Posted: at 1:53 am


This months Time to Talk mental health support group met somewhere its never convened before: the metaverse.

Its a virtual world in which avatars all represent real people who gather on platforms like Decentraland, which hosted the Oct. 13 meeting by broadcasting it on a virtual screen in a virtual movie theater.

Thats a whole lot of online, but the challenges users face offline, like anxiety and depression, are very much the same as those they might face in the digital sphere too, said Andy Godfrey, who leads the monthly meetings organized through the mental health advocacy organization Aspen Strong.

One of the questions from one of the avatars was, Why are you doing this? Why did you pick this venue? I think many of those real world problems that we have here will be similar problems in the metaverse, Godfrey said. The platform also adds another level of anonymity because participants can choose their usernames and avatars.

Godfrey chose the metaverse as a new venue for the support group in hopes it might widen the audience from its usual half dozen or so Zoom participants, and it worked: the meeting garnered 30 unique viewers, he said. Part of the aim, too, is to reach younger audiences by meeting teens and young adults where they are: the internet.

Its one of a number of initiatives Aspen Strong has launched to reach and provide mental health support for a younger demographic. The organization helped plan a yoga series led by high schoolers this summer; theres also a series that will combine activities that might include fly fishing or jewelry making with conversations about mental health and plans to offer a nutrition course in the works, according to Aspen Strong Executive Director Angilina Taylor.

But Taylor recognizes that the activities the organization launches with young people in mind might not always reach their target audience. Its one of the reasons Aspen Strong is looking to assemble a board of younger mental health advocates who can inform the organization on what types of events and programs kids and young adults will actually engage in.

From the adult perspective, were like, These are so cool. Oh my gosh, I wish I had this when I was a youth, Taylor said. But when you think about when you were younger, would you have gone, and what would have gotten you to go? If theyre not going to show up, whats the point?

Taylor recognizes there may be barriers like approachability that are standing between young people and resources that could help support them through mental health challenges. Aspen Strong focuses on fostering conversations and reducing the stigma surrounding mental health, but theres a different dialogue and perhaps a different stigma among teenagers and young adults.

Look, I think weve come a long way. I think that they have a much broader understanding of mental health than we did when we were their age (but) were still seeing a lot of people struggling, she said.

It wont be easy to reach every young person in this valley and beyond who is struggling with mental health. But for every different avenue, there might be one or two more people who now have more tools and resources to cope with mental health.

Its not about the quantity thats showing up. Its about the quality (of the) interactions that were having with the people that do come. Maybe that has a ripple effect, Taylor said.

Taylor isnt the only one hoping for that ripple effect.

The same phrase describes the aspirations of Nikki Beinstein, a Carbondale-based educator who founded The Serious Type, a social media-like website for youth between the ages of 13 and 23.

Users of which there are about 50 so far from as near as Aspen and as far as Karnataka, India submit writing, videos and other creative works based on categories like Arts, Culture and Media and Sustainability and Justice.

The site itself evolved from what was originally intended to be an in-classroom sustainable business project; once the pandemic hit, Beinstein had to shift her plan and also expand the scope beyond its founding premise to cover all topics and a variety of mediums.

Sustainability, in this case, means a lot more than just recycling and renewable energy or a long-term business plan that stays in the black. Beinstein said theres also a people piece that drives the ethos behind the site.

If you dont deal with the people, you know, their views, their opinions, perspectives, their mental health, you know, how they treat one another, then you cant really get to the environmental piece, she said. We have to kind of go inward.

The level of intention and purpose baked into The Serious Type contributes to that introspective, purposeful atmosphere, Beinstein suggested.

Submissions are curated on the front end by a group of editors to ensure the works are polished, appropriate and constructive, Beinstein said. And unlike Facebook or Instagram, there are no likes, comments or followers, only views, a forum for submitters and a platform for considerate self-expression.

For me, the mental health aspect kind of goes hand in hand with the sustainability (aspect) and being able to express themselves fully, Beinstein said. And once they can express themselves and connect with each other on a deeper, deeper level, then I believe they can really start to make true change and difference in the world. This was one of the solutions to help kids to find their purpose, finally, connect at a deeper level, and then they could really begin to shift the culture in a real sustainable way.

kwilliams@aspentimes.com

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To support youth mental health in the Roaring Fork Valley, organizers look to the internet - Aspen Times

The Watchdog: If you need mental health therapy in Dallas-Fort Worth, get in line. A very long line – Denton Record Chronicle

Posted: at 1:53 am


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The Watchdog: If you need mental health therapy in Dallas-Fort Worth, get in line. A very long line - Denton Record Chronicle

Gardens for health, self-sufficiency and rooted friendships | Pamelas Food Service Diary – SILive.com

Posted: at 1:53 am


STATEN ISLAND, N.Y. The pandemic permanently drilled a few lessons into my mindset. There is the importance of self-sufficiency with the peace of mind in having a continuous food supply. Also during COVID, especially in the quarantine days, the only reliable thing in our housebound state (and beyond) was our garden. Flowers kept blooming and nature kept going even when the world seemed to stop.

With that, I want to emphasize the importance of tending a garden. And on many levels, the boroughs four garden clubs illustrate that great matter in their work around Staten Island. Consider them quiet sets of helping hands that keep the beauty going in the Borough of Parks.

Susan Marretta, left, with Bernadette Sullivan at The Staaten. (Staten Island Advance/ Pamela Silvestri)Pamela Silvestri

Gardening is my sanity. I love watching things grow and eating healthy, said Susan Marretta, member of the Richmond Ever-Green Garden Club established in 1985. This group, by the way, is involved with community beautification projects to name a few the Garibaldi-Meucci Museum, Fr. Capodanno Chapel at Fort Wadsworth, St. Nicholas Chapel as well as an historic preservation project and garden restoration at Silver Mount Cemetery, Silver Lake.

At a recent luncheon at The Staaten for the four organizations, there were faces attached to those mothers of nature.

- Garden club members gathered at The Staaten for the first time in almost two years for their biggest annual fundraiser. The speaker of the day wasChristine Donck-Guelton, right, a Sogetsu School Instructor and board member NY chapter Soghetsu School and Ikebana International. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Heading up the Castle Manor Garden Club are Lucille Bauer and Evelia Foster, a crew who loves gardening and protecting the local environment. They tend dozens of community endeavors the Blue Star By-Way Memorial Garden at Fort Wadsworth and the Manresa Council 9/11 garden.

Graceann Morawek is at the helm of the Great Kills Garden Club, founded in 1954. Her fellow ladies maintain the entrance to Bloomingdale Park. Their monthly meetings include chats about nature, flower design and offer a hands-on make-it-and-take-it workshops.

- Garden club members gathered at The Staaten for the first time in almost two years for their biggest annual fundraiser. Pamela SilvestriPamela Silvestri

And heres an interesting tidbit: the oldest club on the Isle of Staaten the Staten Island Garden Club was founded in 1914 by Alice Austen herself. This modern group of 34 members-strong grooms the Alice Austin House Museum grounds of Clear Comfort in Rosebank plus the famed photographers grave site at Moravian Cemetery. Among the many projects around the North Shore, this club champions frogs. The effort that raises awareness of the declining, bug-eating frog and amphibian populations.

We encourage novice gardeners with our moments and non-competitive flower arrangement workshops. The only membership requirement is an interest in gardening, a love of flowers and an appreciation of natural beauty, notes president S.I. Garden Club prez Josephine Fedele.

Enjoying a day with gardening on their mind at The Staaten. (Pamela Silvestri)Pamela Silvestri

Then, there is the Richmond Ever-Green Garden Club.

Says its president Suzanne Quinn, We create wreaths for the women who have completed the program at Amethyst House. We keep current with speakers on horticulture, history of The Island and tours of gardens. This is a small part of what we do. We support each other and the camaraderie is wonderful and are always looking for new members to join.

Quinn is a native Staten Islander who grew up on the South Shore with a garden cultivated by her father.

This was just a way of life as we were [living among] the farms of the borough. My fathers parents had turkeys and chickens and my mother had rabbits and chickens. Shes from the Westerleigh area, said Quinn. Her mom is a spry 100 and she attributes the longevity to the self-sufficient home canning, jarring and preserving natures bounty from the yard.

- Garden club members gathered at The Staaten for the first time in almost two years for their biggest annual fundraiser. (Pamela Silvestri)Pamela Silvestri

I just love it. Its being outside. We enjoyed seeing things grow during the pandemic on my fathers garden that had been left empty for quite a few years. My husband who never really did vegetable gardening took that over and that was a nice thing to see my fathers garden resurrected, said Quinn.

Long live our Islands garden clubs for the next generations!

Here is the contact information and meeting schedule for the four garden clubs. Hopefully you are encouraged to join to one of them to keep the garden community rooted, so to speak:

Castle Manor Garden Club

Co-presidents: Lucille Bauer and Evelia Foster

Meets: Second Wednesday of each month at 1 p.m.

Contact: lucillebauer@hotmail.com

Staten Island Garden Club

President: Josephine Fedele

Meets: Fourth Wednesday of the month

Contact: jofedele@yahoo.com

Great Kills Garden Club

President: Graceann Morawek

Meets: Third Tuesday of the month at 10 a.m.

Contact: 917-992-9719

Richmond Ever-Green Garden Club

President: Suzanne Quinn

Meets: Second Monday of the month at 6:30 p.m.

Contact: suzanne@tquinn.com

- Garden club members gathered at The Staaten for the first time in almost two years for their biggest annual fundraiser. (Pamela Silvestri)Pamela Silvestri

Suzaannne Quinn of the Richmond Ever-Green Garden Club, left, and Evelia Foster of the Castle Manor Garden Club. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Catching up over gardening talk (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Chocolate Halloween cake was among the goodies for sale for the garden clubs' annual big fundraiser. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

- Garden club members gathered at The Staaten for the first time in almost two years for their biggest annual fundraiser. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Some of the helping hands in the community who tend to the beautification of the Borough of Parks. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Garden club members gathered at The Staaten for the first time in almost two years for their biggest annual fundraiser. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

From left to right: Carol Boylan, Graceann Morawek, Josephine Fedele and Suzanne Quinn. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Garden club members gathered at The Staaten for the first time in almost two years for their biggest annual fundraiser. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

A fabulous carrot cake donated to the sale table at The Staaten for a fundraiser for the four garden clubs of Staten Island. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Garden club members mingle at The Staaten. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Selling raffles to benefit the borough's gardening community. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Carol Berardi addresses the room. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

From left to right: Betty LaFemina and Carol Boylan. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Suzanne Quinn, left, and Evalia Foster (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Garden Club members enjoy a luncheon for fellowship and a fundraiser. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

Garden club members gathered at The Staaten for the first time in almost two years for their biggest annual fundraiser. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

At lunch with the borough's gardening groups. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

In a luncheon at The Staaten, the borough's most avid gardeners gathered on Thursday, Oct. 21, 2021. (Staten Island Advance/Pamela Silvestri)Pamela Silvestri

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Community Health Network collects 1,100 pounds of medicine on ‘Drug Take Back Day’ – WTHR

Posted: at 1:53 am


INDIANAPOLIS More than 1,100 pounds of medication were collected at Community Health Network sites around central Indiana during a nationwide drug take-back day on Saturday.

The Drug Enforcement Administration sponsored the 21st "Prescription Drug Take Back" on Oct. 23. The initiative allows people to properly dispose of prescription drugs while also helping prevent prescription drug abuse and theft.

Sites around the state accepted expired, unused, and unwanted prescription drugs and covered both pills and liquid medications.

Community Health Network had locations across central Indiana that were participating in the effort, and those locations ultimately collected more than 1,100 pounds of medication.

All of this medicine will be properly disposed of. Community Health Network explained that proper medication disposal helps prevent children and pets from being accidentally poisoned, and it also ensures people's personal information on prescription bottles wont be used for identity theft.

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Community Health Network collects 1,100 pounds of medicine on 'Drug Take Back Day' - WTHR

WHO and partners call for action to better protect health and care workers from COVID-19 – World Health Organization

Posted: at 1:53 am


The World Health Organization and partners[i] have issued an urgent call for concrete action to better protect health and care workers worldwide from COVID-19 and other health issues.

The organizations are concerned that large numbers of health and care workers have died from COVID-19, but also that an increasing proportion of the workforce are suffering from burnout, stress, anxiety and fatigue.

In a Joint Statement issued this week, WHO and partners are calling on all Member State governments and stakeholders to strengthen the monitoring and reporting of COVID-19 infections, ill-health and deaths among health and care workers. They should also include disaggregation by age, gender and occupation as a standard procedure, to enable decision makers and scientists to identify and implement mitigation measures that will further reduce the risk of infections and ill-health.

The Statement also urges political leaders and policy makers to do all within their power to make regulatory, policy and investment decisions that ensure the protection of health and care workers. It highlights the opportunity to align this with a forthcoming global health and care worker compact and the International Labour Organizations call for a human-centered recovery from the COVID-19 crisis.

Finally, the partners call upon leaders and policy makers to ensure equitable access to vaccines so that health and care workers are prioritized in the uptake of COVID-19 vaccinations. Available data from 119 countries suggest that by September 2021, 2 in 5 health and care workers were fully vaccinated on average, with considerable difference across regions and economic groupings. Less than 1 in 10 have been fully vaccinated in the African region while 22 mostly high-income countries reported that above 80% of their health and care workers are fully vaccinated. These rates only account for data reported to WHO through the standard mechanisms.

We have a moral obligation to protect all health and care workers, ensure their rights and provide them with decent work in a safe and enabling practice environment. This must include access to vaccines, said Jim Campbell, Director of the WHO Health Workforce Department. Beyond vaccines , economic recovery and all new investments in emergency preparedness and response must prioritize the education and employment of health and care workers, linking to the UN Secretary-Generals Global Accelerator for Jobs and Social Protection, he added.

A new WHO working paperestimates that between 80 000 to 180 000 health and care workers could have died from COVID-19 in the period between January 2020 to May 2021, converging to a medium scenario of 115 500 deaths. These estimates are derived from the 3.45 million COVID-19 related deaths reported to WHO as at May 2021; a number by itself considered to be much lower than the real death toll (60% or more than what is reported to WHO).

This WHO working paper provides a stark number to stimulate greater action; we cannot afford to lose more health and care workers and our world will not recover from the pandemic without long-term, sustainable investments in the health workforce, said Catherine Duggan, Chief Executive Officer of the International Pharmaceutical Federation and one of several members of the World Health Professions Alliance allied with the Joint Statement.

WHO is currently leading efforts to develop a global health and care worker compact, based on existing legal instruments, conventions and resolutions. The compact aims to provide Member States, stakeholders and institutions with comprehensive guidance on their existing obligations to protect health and care workers, safeguard their rights, and to promote and ensure decent work, free from gender, racial and all other forms of discrimination. The guidance will be presented to the 75th World Health Assembly in May 2022.

[i] Frontline Health Workers Coalition; Global Health Workforce Network; Health Service Executive, Ireland; International Council of Nurses; International Pharmaceutical Federation; International Labour Organization; OECD; Public Services International and the World Medical Association.

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WHO and partners call for action to better protect health and care workers from COVID-19 - World Health Organization

Kylar’s Riders charity gives to families in the NICU at UnityPoint – Health St. Luke’s – KTIV

Posted: at 1:53 am


SIOUX CITY (KTIV) - Some families in the NICU at Unity Point Health - St. Luke's got a surprise from Kylar's Riders Sunday.

After raising money from their charity motorcycle poker run during Hubbard Hoot Owl Days back in August, the organization was able to give close to $2,000 to families in the NICU.

The donation came in form of Visa gift cards so families can use the donations in any way they need.

Co-Founder of Kyler's Riders Brandon Woltman said seeing not only the biker community but the Siouxland community as a whole come together to help these families filled their hearts.

"Just giving them some positive light in this. They are struggling through a hard time, a hard season and we hope that this will help a little bit. And the words will hit a little bit more. And we want to continue to do this every year," said Woltman.

The donation hits close to home for Woltman and his wife as they started Kyler's Riders in Honor of their late daughter who passed away in the NICU and to give back to those families battling the same fight they did more than seven years ago.

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Kylar's Riders charity gives to families in the NICU at UnityPoint - Health St. Luke's - KTIV

Health care workers exhausted: Were fighting this battle, and it just keeps coming and coming – Hamilton Journal News

Posted: at 1:53 am


The first year was difficult, Ali said. After January, when we had the vaccine, it was more depression because a lot of people we lost, we felt like this is preventable loss.

After treating coronavirus patients for going on 20 months, hospital staff see no end in sight as they face a younger patient population and increasing abuse from those who embrace misinformation and view them as the enemy. This is on top of the stressful conditions they have endured throughout the pandemic, like wearing personal protective equipment for long hours, the fear of taking the virus home, less than optimal staffing levels and working extra shifts to care for the large influx of high-need patients.

Health care workers exhausted, burned out

As of Friday, 269 inpatients in the region had COVID-19. At the peak of the current surge, just over 400 hospitalized patients in the region had COVID-19. Even as this fourth wave abates somewhat, workers treating coronavirus patients are still overwhelmed and fearful of more waves.

Vicki Laywell is a registered respiratory therapist at Kettering Health where she's treated COVID-19 patients throughout the pandemic. She said she recently treated a patient in their 20s who had to transfer to another hospital to be put on life support. "To see someone in their 20s and they have their whole life ahead of them, and to hug the mother and knowing that she may see her son again alive and she may not, it's just very emotionally draining for us," she said. Submitted photo.

Vicki Laywell, a respiratory therapist at Kettering Medical Center, said it feels like theyre in a war zone.

Were fighting this battle and it just keeps coming and coming, Laywell said. I feel like if the public could go through a COVID ICU and see what these people are dealing with, it would change their perspective on wearing masks, getting vaccinated, hand washing, limiting your inner circle of family and friends. You want to be around next year and if you get this COVID theres so many that are not surviving, and when they do survive, sometimes they have lifetime altered changes to their physical health.

Patricia OMalley, a nurse researcher at Premier Health, said coronavirus has turned hospitals into field hospital-like environments.

We know that continuous exposure to all of this high acuity over this period of time does result in moral distress, moral suffering, anxiety, exhaustion and sadness, OMalley said. And the idea that so much of what we are seeing now with our unvaccinated population is unnecessary is particularly difficult.

A nationwide survey of more than 5,000 registered nurses released last month by National Nurses United, found that about 42% of nurses feel sad or depressed more often than they did before the pandemic, and more than a third feel traumatized by their experiences caring for patients.

Too many tasks, too little time for self care, too much stress, said Bernadette Melnyk, dean of the Ohio State University College of Nursing. And all of that is affecting our nurses, physicians and other health care workers, and its compromising quality and safety of care.

Sable Morgan, a nurse team leader in the intensive care unit at Miami Valley Hospital, was feeling so burned out that she went from full-time to part-time in February.

Dealing with the amount of death that were seeing, it really takes a toll on you, Morgan said. Its emotional because no matter how hard we fight, its just kind of a never-ending fight. Its exhausting. Its not seeing the light at the end of the tunnel that makes it the hardest And it was kind of, I need to step down a little bit or I dont know if I can keep nursing.

Sable Morgan, a nurse in the intensive care unit at Miami Valley Hospital, said, "Its emotional because no matter how hard we fight, it's just kind of a never ending fight. It's exhausting. It's not seeing the light at the end of the tunnel I think is what makes it the hardest." Submitted photo.

Credit: William J Jones

Credit: William J Jones

Misinformation and abuse

We get a lot of hate, we get a lot of bullying, we get a lot of people yelling at us, and its all political, said Kelly Schlotterbeck, a respiratory therapist working at The Christ Hospital in Cincinnati and Miami Valley South.

Schlotterbeck and other area health care workers said the number of patients asking for dangerous, untested treatments they saw online has gotten out of control.

Somebody asked if we could nebulize hydrogen peroxide because apparently theres a TikTok video where somebody says that nebulizing hydrogen peroxide will help COVID, she said. That would be incredibly dangerous, its a free radical. It is completely not recommended. And these are the things that people are asking for. Ive had people tell us, Youre not doing enough to help me.

She said another patient treated by a colleague refused a badly needed blood transfusion unless the staff could prove the blood came from a donor who was not vaccinated against COVID-19.

What worries me is the amount of distrust from the public, Schlotterbeck said. An opinion is not an experts opinion. And I feel like the public anymore thinks that because theyve read it, they can demand what happens in their care, no matter how ludicrous it is, and I am really concerned as to when this is going to stop.

Nurses and other health care workers were revered as heroes at the beginning of the pandemic, Morgan said, but now theyre treated like the enemy for encouraging vaccination.

The National Nurses United survey found that 31% of hospital nurses had faced workplace violence, up from 22% in their March survey.

Peoples fears about vaccines and the virus are valid, OMalley said, but misinformation especially the belief that natural immunity is enough or an untested substance will treat coronavirus is a threat to public health.

Patients hospitalized with COVID-19 and their families are understandably desperate for anything to give them hope, Laywell said.

And its so sad, because the vaccine is the hope that they should have turned to before, said Laywell as she choked back tears. It just became such a political situation, and its when youre up there, you see people gasping for breath and trying to decide, Should I go on a ventilator because I probably wont wake up, theres nothing political about it.

Karen Davis is a nurse in the Intensive Care Unit at Dayton Children's Hospital. MARSHALL GORBYSTAFF

Patients leave forever changed

Area hospital workers warn that even the patients who survive COVID-19 hospitalization are forever changed by the experience. The reality further depresses staff as many cases of patients saved dont feel like a victory.

People are constantly talking about the 99% survival rate, Schlotterbeck said. I really wish that the public realized that even the people that leave on oxygen, or awaiting lung transplants or leave on dialysis with chronic kidney disease afterward, theyre included in that 99%. But their life is going to be so impacted.

Never able to work again. Remaining on ventilators the rest of their lives. Never walking again.

I wish that the public knew more of that, Schlotterbeck said. I had a patient last night thats been there for like four months. Hes COVID resolved but hes still on a ventilator, and were having a hard time getting him off.

Chronic symptoms like brain fog, shortness of breath, loss of taste and smell can last a long time after contracting COVID-19, Ali said.

I still see in my pulmonary clinic a good number of these patients who have scar tissue in their lungs, he said.

A study from June found that 45% of patients hospitalized for COVID-19 still suffered related health issues when they were discharged.

Karen Davis, a nurse in the intensive care unit at Dayton Childrens Hospital, said being hospitalized for COVID-19 is a life-changing experience for children.

The patients that I took care of, the youngest was 9 and the oldest was 17. They all had trouble breathing, she said. The one that stands out to me the most was a young man that was 17, and I took care of him in the beginning phase of his disease process. And it was just hard to watch him he got very anxious because he couldnt breathe, and Im trying to tell him Try to slow your breathing down. The whole time I knew he couldnt breathe. Its just hard to watch them struggle They become aware of their own mortality, and thats a little young to be aware of that.

Have questions about COVID-19, face masks, vaccines, testing, quarantining or anything else pandemic-related? Send them to jordan.laird@coxinc.com. Answers will be published regularly in print and online.

See the original post here:
Health care workers exhausted: Were fighting this battle, and it just keeps coming and coming - Hamilton Journal News

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