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Stay up to date on the latest operating room and anesthesiology products as well as news and research from medical companies, government agencies, and more.
2024 – November 20 | November 19 | September | April | March | February | January
2023 – December | October | August | July | June | May | April | March | February | January
First american clade I mpox case reported
November 20
The California Department of Public Health confirmed, through laboratory testing, the first known case of clade I mpox in the United States. This case is related to an ongoing outbreak of clade I mpox in Central and Eastern Africa. The risk of clade I mpox to the public remains low, and there continue to be sporadic clade II mpox cases in the US.
The case was diagnosed in a person who recently traveled from Eastern Africa. The individual was treated shortly after returning to the US at a local medical facility and released. Since then, the person has isolated at home, is not on treatment specific for mpox, and symptoms are improving. Based on their travel history and symptoms, patient specimens were tested and confirmed for the presence of clade I monkeypox virus. Specimens are being sent to CDC for additional viral characterization. Additionally, CDC is working with the state to identify and follow up with potential contacts.
There are two types of mpox, clade I (with subclades Ia and Ib) and clade II (with subclades IIa and IIb; IIb caused the ongoing global outbreak). You can’t tell which type of mpox someone has by looking at them. Outbreaks from the different subclades can have different characteristics. Although clade II mpox has been circulating in the US since 2022, clade I mpox has never been reported in the US before now. Travel-associated cases of subclade Ib have been reported in Germany, India, Kenya, Sweden, Thailand, Zimbabwe, and the United Kingdom. Historically, clade I mpox has caused more severe illness and deaths than clade II mpox; however, recent data demonstrate that infections from clade I mpox in the current outbreak may not be as clinically severe as in previous outbreaks. While outbreaks of clade I mpox used to have death rates around 3%-11%, more recent outbreaks have had death rates as low as approximately 1% when patients received good medical oversight and supportive clinical care. Death rates are expected to be much lower in countries with stronger health care systems and treatment options, including the US. Current data supports that subclade Ib has a lower death rate of < 1% both in and outside of Africa. The recent travel-associated clade I mpox cases outside of Africa have all been attributed to subclade Ib; there have been no deaths associated with these cases and available data for a subset has detailed relatively mild disease courses.
People with mpox often get a rash that may be located on hands, feet, chest, face, mouth and/or near the genitals, including penis, testicles, labia, vagina, and anus. The incubation period is 3-17 days. During this time, a person does not have symptoms and may feel fine.
The anticipated overall risk of clade I mpox to the general population in the US from the outbreak in Central and Eastern Africa is low. Earlier this year CDC conducted a risk assessment which included epidemiologic data from Central and Eastern Africa, data from the ongoing mpox outbreak in the US caused by clade IIb, and historical data on clade I mpox outbreaks in DRC and other affected countries. In addition, CDC has simulated clade I mpox outbreaks. These simulations indicate that close-contact transmissions within and between households are unlikely to result in a large number of mpox clade I cases in the US. Additionally, in Sweden, Thailand, Germany, and India there was no apparent onward spread of the virus and the onward spread in the United Kingdom has been limited to close, household contacts so far.
CDC continues to work in Central and Eastern Africa to help stop mpox transmission at the source. This ongoing work includes laboratory training, supplies for diagnostic testing (including genetic sequencing), training of frontline health and epidemiologic workers, support for surveillance in people and animals, support for infection prevention and control, risk communication and community engagement, and direct technical assistance in outbreaks, as well as research collaborations.
CDC has more than two years of experience responding to mpox in the United States due to the ongoing 2022 global clade II mpox outbreak and has adjusted existing domestic public health systems and structures to respond to any outbreak of clade I mpox in the US. CDC issued guidance for travelers to countries in Central and Eastern Africa experiencing outbreaks earlier this year. CDC continues to recommend that clinicians request expedited clade specific testing for suspect clade I mpox cases with travel history to Central and Eastern Africa. CDC is also helping communities monitor the presence of both clades of mpox virus in wastewater samples. Data from samples can provide an early warning of mpox activity and spread in communities. CDC combines wastewater data with other data to decide if there is a need for further testing or other actions in collaboration with state and local public health partners.
CDC warns of measles surge
November 19
Worldwide, there were an estimated 10.3 million cases of measles in 2023, a 20% increase from 2022, according to new estimates from the World Health Organization (WHO) and the U.S. Centers for Disease Control and Prevention (CDC). Inadequate immunization coverage globally is driving the surge in cases.
Measles is preventable with two doses of the measles vaccine; yet more than 22 million children missed their first dose of the measles vaccine in 2023. Globally, an estimated 83% of children received their first dose of measles vaccine last year, while only 74% received the recommended second dose.
Coverage of 95% or greater of two doses of measles vaccine is needed in each country and community to prevent outbreaks and protect populations from one of the world’s most contagious human viruses.
As a result of global gaps in vaccination coverage, 57 countries experienced large or disruptive measles outbreaks in 2023, affecting all regions except the Americas, and representing a nearly 60% increase from 36 countries in the previous year. The WHO African, Eastern Mediterranean, European, Southeast Asia, and Western Pacific regions experienced a substantial upsurge in cases. Nearly half of all large or disruptive outbreaks occurred in the African region.
The new data show that an estimated 107,500 people, mostly children younger than 5 years of age, died due to measles in 2023. This is an 8% decrease from the previous year, mainly because the surge in cases occurred in countries and regions where children with measles have better nutritional status and access to health services.
Even when people survive measles, serious health effects can occur, including blindness, pneumonia, and encephalitis (an infection causing brain swelling and potentially brain damage).
As measles cases surge and outbreaks increase, the world’s elimination goal, as laid out in Immunization Agenda 2030, is under threat. Worldwide, 82 countries had achieved or maintained measles elimination at the end of 2023. Just this week, Brazil was reverified as having eliminated measles, making the WHO Americas Region once again free of endemic measles. With the exception of the African Region, at least 1 country in all WHO regions has eliminated the disease.
September
Location matters, even when it comes to suicide rates
September 24
A new CDC Vital Signs report released last week highlights the role that conditions in counties, such as insurance coverage, broadband internet access, and household income, can play in lowering suicide risk. Compared to counties with the lowest levels of these factors, suicide rates were:
- 26% lower in counties with the highest health insurance coverage
- 44% lower in counties where most homes have broadband internet access
- 13% lower in counties with the most household income
These findings reinforce other studies that show that the conditions where people are born, grow, live, work, and age can play an important role in shaping suicide prevention efforts.
Suicide rates have increased during the last 20 years and remain high. Tragically, more than 49,000 people died by suicide in 2022, and provisional data indicate a similar number of people died by suicide in 2023.
Suicide is the second leading cause of death for people ages 10-34, and other groups continue to have high rates: American Indian or Alaska Native (AI/AN) persons (27.1 per 100,000), males (23.0 per 100,000), rural residents (20.0 per 100,000), and people aged 45-64 (19 per 100,000).
April
Antibiotic enters European market
April 25
Pfizer Inc. announced that the European Commission (EC) has granted marketing authorization for EMBLAVEO® (aztreonam-avibactam) for the treatment of adult patients with complicated intra-abdominal infections, hospital-acquired pneumonia, including ventilator-associated pneumonia, and complicated urinary tract infections, including pyelonephritis. It is also indicated for the treatment of infections due to aerobic Gram-negative organisms in adult patients with limited treatment options.
“For health care teams treating patients with serious Gram-negative bacterial infections, the prospect of running out of effective treatment options is a daunting but very real threat,” said Yehuda Carmeli, Head, National Institute for Antibiotic Resistance and Infection Control, Tel Aviv Medical Center, Israel, and an investigator in the REVISIT study. “The approval of EMBLAVEO is welcome news for the infectious disease community and provides new hope to critically ill patients affected by antimicrobial resistance.”
Antimicrobial resistance (AMR) – when bacteria, viruses, fungi, and parasites change and find ways to resist the effects of antimicrobial drugs – is recognized as one of the biggest threats to global health. If AMR continues to rise unchecked, minor infections could become life-threatening, and many routine medical procedures such as caesarean sections and hip replacements could become too risky to perform. Multidrug-resistant Gram-negative bacteria are of particular concern due to the high rates of morbidity and mortality they cause. Metallo-β-lactamases (MBLs) are a type of enzyme produced by certain bacteria that can result in resistance to antibiotics, and MBL-producing Gram-negative bacteria are on the rise globally. Developing new treatments for infections caused by Gram-negative bacteria has been prioritized by the World Health Organization (WHO) as a critical area of focus due to their increasing spread.
“The European Medicines Agency’s accelerated review of EMBLAVEO reflects the urgent need for new treatments to address the threat of antimicrobial resistance,” said Alexandre de Germay, Chief International Commercial Officer, Executive Vice President, Pfizer. “With this approval, Pfizer is proud to take another step forward in its commitment to developing and bringing breakthrough health solutions to patients impacted by serious infectious diseases around the world.”
This approval is based on results from the previously reported Phase 3 program comprising the REVISIT (NCT03329092) and ASSEMBLE (NCT03580044) studies evaluating the efficacy, safety, and tolerability of EMBLAVEO in treating serious bacterial infections due to Gram-negative bacteria, including MBL-producing multidrug-resistant pathogens for which there are limited or no treatment options. Data support that EMBLAVEO is effective and well-tolerated, with no new safety findings and a similar safety profile to aztreonam alone.
The marketing authorization of EMBLAVEO is valid in all 27 European Union (EU) member states, as well as in Iceland, Liechtenstein, and Norway. Marketing authorization applications for EMBLAVEO are planned for submission in other countries.
Adding some fine print to OTC supplements
April 23
The Council for Responsible Nutrition (CRN), the leading trade association for the dietary supplement and functional food industry, announces the adoption of two sets of new voluntary guidelines: one focused on the formulation, labeling, and packaging of melatonin-containing dietary supplements marketed for sleep support, and another dedicated to the labeling of gummy dietary supplements.
The updated melatonin guidelines provide recommendations addressing intentional overages during manufacturing, child-deterrent packaging, and precautionary label statements for melatonin-containing products. These guidelines are designed to ensure that consumers have access to products that are responsibly formulated, labeled, and packaged.
With the growing popularity of gummy dietary supplements among consumers of all ages, CRN’s new guidelines for gummy supplements specifically address the unique aspects of these products. The new recommendations focus on labeling clarity, reducing unsupervised access by children, addressing potential choking hazards for small children, and ensuring products are used as intended.
Key Updated Recommendations for Melatonin Supplements:
Labeling Instructions: The revised melatonin guidelines call for cautionary label statements alerting consumers that melatonin may cause drowsiness, not to take with alcohol, and that the products are intended for intermittent or occasional use only.
Overages During Manufacturing: While recognizing that federal regulations require dietary supplement to contain at least 100 percent of their labeled amounts throughout shelf life, the guidelines recommend that any overages of melatonin added during manufacturing be informed by data to support stability and safety.
Child deterrent packaging: While federal regulations do not require child deterrent closures for melatonin-containing products, CRN’s revised guidelines call for industry members to adopt child deterrent packaging for products containing melatonin that are in flavored chewable forms that could be especially attractive to children. This recommendation provides parents and caregivers with a tool to prevent unsupervised access to these products.
CRN members are being asked to adopt these guidelines for melatonin-containing supplements within 18 months.
Key Recommendations for Gummy Form Supplements:
Targeted Advisories: Detailed labeling advisories for products aimed at both adults and children include specific considerations for gummy supplements intended for young children and underscore the importance of using these products under appropriate conditions and guidance.
Avoiding Potential Choking Hazards: For products intended for children under 4 years of age, the guidelines recommend a precautionary statement that if not chewed properly, the product could present a potential choking hazard.
Packaging Considerations: The recommendations ask manufacturers to consider packaging gummy products in containers with child deterrent closures (e.g., by evaluating various product attributes like ingredient profiles, serving amounts, and total package contents, when making their packaging choices).
CRN members are being asked to adopt these guidelines for gummy supplements within 24 months.
March
New medication treats obesity-related liver disease
March 21
The approval of Madrigal Pharmaceuticals’ Rezdiffra (resmetirom) for metabolic dysfunction-associated steatohepatitis is expected to open doors for future therapies, while also setting the efficacy and safety bar for upcoming candidates, according to a Friday report from data analytics firm GlobalData.
Madrigal’s regulatory victory will help it “reap the benefits of the first-to-market therapy,” Sravani Meka, GlobalData senior pharma analyst, said in a statement. Rezdiffra will be able to enjoy market dominance while its competitors are still trialing their candidates, and the therapy will be able to establish itself in clinical guidelines and standards.
This advantage will help Madrigal carve out its own piece of the MASH market, which GlobalData estimates to reach nearly $26 billion in 2032 across the seven major markets—the U.S., France, Germany, Italy, Spain, the U.K., and Japan.
Rezdiffra will also “set the standard for all other treatments in development” and “future therapies will now have to meet or outperform the efficacy and safety data from resmetirom’s Phase III MAESTRO studies,” Meka said.
The FDA granted accelerated approval to Rezdiffra on Thursday, making it the first-ever authorized therapy for metabolic dysfunction-associated steatohepatitis (MASH). Rezdiffra can now be used alongside diet and exercise to treat patients with moderate to advanced liver fibrosis. The treatment’s continued approval may depend on a future confirmatory trial validating its clinical benefit.
Importantly, the FDA’s clearance does not require patients to have undergone liver biopsies to be treated with Rezdiffra.
Rezdiffra’s active ingredient is resmetirom, which is a small molecule, liver-directed drug that works by activating the thyroid hormone receptor beta (THR-β), which is highly enriched in the liver. The agonism of THR-β helps reduce intrahepatic triglyceride levels and boost lipid metabolism. According to Madrigal’s website, THR-β signaling is impaired in MASH patients, which triggers mitochondrial dysfunction, lipotoxicity, and fibrosis.
The FDA’s approval was supported by data from a comprehensive clinical development program that includes 18 clinical trials, four of which are late stage. The core of Madrigal’s program is MAESTRO-NASH, which hit both of its primary endpoints with both 80-mg and 100-mg doses of Rezdiffra eliciting significantly higher rates of MASH resolution and improvement in liver fibrosis compared to placebo.
By clearing the FDA’s regulatory hurdles, Rezdiffra has bested at least 20 other MASH programs that have been suspended or discontinued, including Intercept’s obeticholic acid tablets and Akero’s efruxifermin.
Still, other biotechs are on Madrigal’s heels developing their own MASH therapies with differentiated mechanisms of action. Among the potential competitors are Novo Nordisk and Eli Lilly, which are developing their respective top-selling GLP-1 receptor agonists semaglutide and tirzepatide for MASH.
Also hoping to target the lucrative market is 89bio, whose FGF21 analog pegozafermin met its Phase IIb primary histology endpoint in March 2023.
February
Waiting to exhale
February 21
After a late December surge, respiratory virus activity has been declining for weeks, with most indicators trending down. Weekly hospitalization rates for Covid-19, flu, and RSV declined through most of January.
However, respiratory disease activity remains elevated, and some flu activity indicators have increased again. Test positivity for flu rose nationally in late January and has leveled off since but continues to increase in parts of the country. Emergency department visits for flu have been going up in some areas of the country.
While the respiratory virus season is likely past its peak, it is definitely not over. There is still a lot of respiratory virus activity, according to the CDC’s update last Friday.
Hospitalizations and deaths are below last season’s
As we saw last season, Covid-19, flu, and RSV account for a large proportion of hospitalizations for respiratory viruses during the fall and winter months. This season, flu and RSV illnesses started increasing later in the fall, which is more like what was typical before the pandemic.
This season’s peak in combined Covid-19, flu, and RSV hospitalizations was not as high as last season’s. There were fewer reports of health care strain this season. Additionally, cumulative hospitalizations and deaths due to Covid-19 and flu are lower this season than they were at this time last season.
FDA approves novel therapy for treatment-resistant melanoma
February 20
Last week, the FDA approved Amtagvi, the first cellular therapy indicated for the treatment of adult patients with melanoma that is unresectable or metastatic, and previously treated with other therapies (i.e. a PD-1 blocking antibody, and if BRAF V600 mutation positive, a BRAF inhibitor with or without MEK inhibitor).
Although melanomas only represent approximately 1% of all skin cancers, they account for a significant number of cancer-related deaths. Melanoma can spread to other parts of the body if not detected and treated early, resulting in metastatic disease.
Treatment for unresectable or metastatic melanoma may include immunotherapy using PD-1 inhibitors, which are antibodies targeting certain proteins in the body to help the immune system fight off cancer cells. In addition, drugs targeting the BRAF gene, which helps with managing the growth and functioning of cells, may be used for treating melanoma associated with BRAF gene mutations. Those patients whose melanoma has progressed with these therapies have a high unmet medical need.
Amtagvi is a tumor-derived autologous T cell immunotherapy composed of a patient’s own T cells, a type of cell that helps the immune system fight cancer. A portion of the patient’s tumor tissue is removed during a surgical procedure prior to treatment. The patient’s T cells are separated from the tumor tissue, further manufactured, and then returned to the same patient as a single dose for infusion. This is the first FDA-approved tumor-derived T cell immunotherapy.
Amtagvi was approved through the Accelerated Approval pathway, under which the FDA may approve drugs for serious or life-threatening illnesses or conditions where there is an unmet medical need and the drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients (improving how patients feel or function, or whether they survive longer). This pathway generally gives patients the opportunity for earlier access to a promising therapy while the company conducts further trials to verify the predicted clinical benefit. A confirmatory trial is ongoing to verify Amtagvi’s clinical benefit.
The safety and effectiveness of Amtagvi was evaluated in a global, multicenter, multicohort clinical study including adult patients with unresectable or metastatic melanoma who had previously been treated with at least one systemic therapy, including a PD-1 blocking antibody, and if positive for the BRAF V600 mutation, a BRAF inhibitor or BRAF inhibitor with an MEK inhibitor. Effectiveness was established based on objective response rate to treatment and duration of response (measured from the date of confirmed initial objective response to the date of progression, death from any cause, starting a new anti-cancer treatment, or discontinuation from follow-up, whichever came first). Among the 73 patients treated with Amtagvi at the recommended dose, the objective response rate was 31.5%, including three (4.1%) patients with a complete response and 20 (27.4%) patients with a partial response. Among patients who were responsive to the treatment, 56.5%, 47.8%, and 43.5% continued to maintain responses without tumor progression or death at six, nine, and 12 months, respectively.
Patients treated with Amtagvi may exhibit prolonged severe low blood count, severe infection, cardiac disorder, or develop worsened respiratory or renal function or have fatal treatment-related complications. A Boxed Warning is included in the label containing information about these risks. Patients receiving this product should be closely monitored before and after infusion for signs and symptoms of adverse reactions. Treatment should be withheld or discontinued in the presence of these symptoms, as indicated.
The most common adverse reactions associated with Amtagvi included chills, fever, fatigue, tachycardia (abnormally fast heart rate), diarrhea, febrile neutropenia (fever associated with a low level of certain white blood cells), edema (swelling due to buildup of fluid in body tissues), rash, hypotension, hair loss, infection, hypoxia (abnormally low oxygen levels in the body), and feeling short of breath.
Amtagvi also received Orphan Drug, Regenerative Medicine Advanced Therapy, Fast Track, and Priority Review designations.
The FDA granted the approval of Amtagvi to Iovance Biotherapeutics Inc.
Neurologic aspects of long covid
February 16
Brain fog is one of the most common, persistent complaints in patients with long COVID. It affects as many as 46% of patients who also deal with other cognitive concerns like memory loss and difficulty concentrating.
Now, researchers believe they know why. A new study reported in Medscape has found that these symptoms may be the result of a viral-borne brain injury that may cause cognitive and mental health issues that persist for years.
Researchers found that 351 patients hospitalized with severe COVID-19 had evidence of a long-term brain injury — equivalent to 20 years of aging — a year after contracting the SARS-CoV-2 virus. The findings were based on a series of cognitive tests, self-reported symptoms, brain scans, and biomarkers.
The quest for early Alzheimer’s detection
February 14
An analysis of around 1,500 blood proteins has identified biomarkers that can be used to predict the risk of developing dementia up to 15 years before diagnosis.
The findings, reported this week in Nature Aging, are a step towards a tool that scientists have been in search of for decades: blood tests that can detect Alzheimer’s disease and other forms of dementia at a very early, pre-symptomatic stage.
Researchers screened blood samples from more than 50,000 healthy adults in the UK Biobank, 1,417 of whom developed dementia in a 14-year period.
They found that high blood levels of four proteins — GFAP, NEFL, GDF15, and LTBP2 — were strongly associated with dementia.
“Studies such as this are required if we are to intervene with disease-modifying therapies at the very earliest stage of dementia,” said Amanda Heslegrave, a neuroscientist at University College London, in a statement to the Science Media Centre in London.
By screening 1,463 proteins in blood samples from 52,645 people, the authors found that increased levels of GFAP, NEFL, GDF15 and LTBP2 were associated with dementia and Alzheimer’s disease. For some participants who developed dementia, blood levels of these proteins were outside normal ranges more than ten years before symptom onset.
GFAP, a protein that provides structural support to nerve cells called astrocytes, has already been proposed as a diagnostic marker for Alzheimer’s disease, as has GDF15.
The latest study finds that people with high levels of GFAP in their blood are more than twice as likely as people with normal levels to develop dementia, and are nearly three times as likely to develop Alzheimer’s.
The authors used machine learning to design predictive algorithms, combining levels of the four protein biomarkers with demographic factors such as age, sex, education level, and family history. They trained the model on information from two-thirds of the study participants, and tested its performance using data from the remaining 17,549 people.
The model predicted the incidence of three subtypes of dementia, including Alzheimer’s disease, with about 90% accuracy, using data from more than ten years before participants were officially diagnosed.
The authors say their findings could be used to develop blood tests that identify people at risk of developing dementia. Other researchers caution that the new biomarkers need further validation before being used as clinical screening tools.
The study “needs to be replicated and biomarkers that enable us not only to screen for disease risk but also to differentiate between diseases should be a priority,” said Heslegrave.
January
3D printing, the optic nerve, and intracranial pressure
January 12
Ultrasound measurement of optic nerve sheath diameter (ONSD) provides a valuable surrogate measure of intracranial pressure (ICP). However, the ability to perform reliable evaluations requires significant practice. Our group previously created and validated a training model in which a bisected table tennis ball (globe of eye) was secured to a pediatric endotracheal tube (optic nerve) and suspended in a cup of gelatine mixture (asamonitor.pub/3RXH8l5). By loading the endotracheal tube’s microcuff (optic nerve sheath) with various volumes of saline, we were able to dynamically model ONSD for reproducible ultrasound measurement from the surface of the cup.
Recently, we leveraged 3D printing to improve upon this initial model. We have now developed a 3D printed, detachable model of a skeletal head, in which the original ONSD model sits within two high-fidelity plastic orbits. This new model can be easily reproduced in any center with access to a 3D printer, ultrasound machine, and several household ingredients described in our initial publication, for an inexpensive and portable means of teaching and learning ONSD evaluation using ultrasound. Ultimately, we hope that this application of 3D printing will support the identification of patients with raised ICP.
Alleviating pincushion syndrome
January 11
The medical technology company BD (Becton, Dickinson and Company) has launched the PIVO™ Pro Needle-free Blood Collection Device, a needle-free blood draw technology with FDA clearance. The device is designed to be compatible with integrated catheters, specifically the new Nexiva™ Closed IV Catheter System with NearPort™ IV Access, expanding on its existing compatibility with traditional short peripheral I.V. catheters.
The device allows for high-quality blood samples to be drawn directly from a patient’s peripheral I.V. line, reducing the need for additional needlesticks. As needle phobia affects over 60% of adults, the new solution aims to improve the patient experience by minimizing fear and anxiety associated with repetitive needlesticks.
The technology has the potential to optimize I.V. performance, reduce sample errors, and decrease complications.
December 2023
FDA approves two gene therapies to treat sickle cell disease
December 21
The U.S. Food and Drug Administration (FDA) approved two milestone treatments, Casgevy and Lyfgenia, representing the first cell-based gene therapies for the treatment of sickle cell disease (SCD) in patients 12 years and older. Additionally, one of these therapies, Casgevy, is the first FDA-approved treatment to utilize a type of novel genome editing technology, signaling an innovative advancement in the field of gene therapy.
Sickle cell disease is a group of inherited blood disorders affecting approximately 100,000 people in the U.S. It is most common in African Americans and, while less prevalent, also affects Hispanic Americans. The primary problem in sickle cell disease is a mutation in hemoglobin, a protein found in red blood cells that delivers oxygen to the body’s tissues. This mutation causes red blood cells to develop a crescent or “sickle” shape. These sickled red blood cells restrict the flow in blood vessels and limit oxygen delivery to the body’s tissues, leading to severe pain and organ damage called vaso-occlusive events (VOEs) or vaso-occlusive crises (VOCs). The recurrence of these events or crises can lead to life-threatening disabilities and/or early death.
Casgevy, a cell-based gene therapy, is approved for the treatment of sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises. Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology. Patients’ hematopoietic (blood) stem cells are modified by genome editing using CRISPR/Cas9 technology.
CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. The modified blood stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery. In patients with sickle cell disease, increased levels of HbF prevent the sickling of red blood cells.
Lyfgenia is a cell-based gene therapy. Lyfgenia uses a lentiviral vector (gene delivery vehicle) for genetic modification and is approved for the treatment of patients 12 years of age and older with sickle cell disease and a history of vaso-occlusive events. With Lyfgenia, the patient’s blood stem cells are genetically modified to produce HbAT87Q, a gene-therapy derived hemoglobin that functions similarly to hemoglobin A, which is the normal adult hemoglobin produced in persons not affected by sickle cell disease. Red blood cells containing HbAT87Q have a lower risk of sickling and occluding blood flow. These modified stem cells are then delivered to the patient.
Both products are made from the patients’ own blood stem cells, which are modified, and are given back as a one-time, single-dose infusion as part of a hematopoietic (blood) stem cell transplant. Prior to treatment, a patients’ own stem cells are collected, and then the patient must undergo myeloablative conditioning (high-dose chemotherapy), a process that removes cells from the bone marrow so they can be replaced with the modified cells in Casgevy and Lyfgenia. Patients who received Casgevy or Lyfgenia will be followed in a long-term study to evaluate each product’s safety and effectiveness.
“These approvals represent an important medical advance with the use of innovative cell-based gene therapies to target potentially devastating diseases and improve public health,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s actions follow rigorous evaluations of the scientific and clinical data needed to support approval, reflecting the FDA’s commitment to facilitating development of safe and effective treatments for conditions with severe impacts on human health.”
Data Supporting Casgevy
The safety and effectiveness of Casgevy were evaluated in an ongoing single-arm, multi-center trial in adult and adolescent patients with SCD. Patients had a history of at least two protocol-defined severe VOCs during each of the two years prior to screening. The primary efficacy outcome was freedom from severe VOC episodes for at least 12 consecutive months during the 24-month follow-up period. A total of 44 patients were treated with Casgevy. Of the 31 patients with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. All treated patients achieved successful engraftment with no patients experiencing graft failure or graft rejection.
The most common side effects were low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache and itching.
Data Supporting Lyfgenia
The safety and effectiveness of Lyfgenia is based on the analysis of data from a single-arm, 24-month multicenter study in patients with sickle cell disease and history of VOEs between the ages of 12- and 50- years old. Effectiveness was evaluated based on complete resolution of VOEs (VOE-CR) between 6 and 18 months after infusion with Lyfgenia. In total, 88% of 32 patients achieved VOE-CR during this time period.
The most common side effects included stomatitis (mouth sores of the lips, mouth, and throat), low levels of platelets, white blood cells, and red blood cells, and febrile neutropenia (fever and low white blood cell count), consistent with chemotherapy and underlying disease.
Hematologic malignancy (blood cancer) has occurred in patients treated with Lyfgenia. A black box warning is included in the label for Lyfgenia with information regarding this risk. Patients receiving this product should have lifelong monitoring for these malignancies.
Both the Casgevy and Lyfgenia applications received Priority Review, Orphan Drug, Fast Track and Regenerative Medicine Advanced Therapy designations.
The FDA granted approval of Casgevy to Vertex Pharmaceuticals Inc. and approval of Lyfgenia to Bluebird Bio Inc.
lower vaccinations, higher illness rates: a bad combination
December 20
The Centers for Disease Control and Prevention (CDC) is issuing a Health Alert Network (HAN) Health Advisory to alert health care providers to low vaccination rates against influenza, Covid-19, and RSV. Low vaccination rates, coupled with ongoing increases in national and international respiratory disease activity caused by multiple pathogens, including influenza viruses, SARS-CoV-2, and RSV, could lead to more severe disease and increased health care capacity strain in the coming weeks.
In addition, a recent increase in cases of multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection in the United States has been reported.
In the past four weeks, hospitalizations among all age groups increased by 200% for influenza, 51% for Covid-19, and 60% for RSV.
- Influenza vaccination: Vaccination coverage for the seasonal 2023-2024 influenza vaccine is low in all age groups compared with the same period of the 2022–2023 season. As of November 18, 2023, there were 7.4 million fewer influenza vaccine doses administered to adults in pharmacies and physician offices compared with the 2022–2023 influenza season.
- Covid-19 vaccination: Vaccination coverage for the updated 2023-2024 Covid-19 vaccine remains low. As of December 2, 2023, the percent of the population reporting receipt of this vaccine was 7.7% in children 6 months-17 years (including 2.8% in children 6 months-4 years), 17.2% in adults ≥18 years (including 36% in adults ≥65 years), and 9.6% in pregnant persons.
- RSV vaccination: As of December 2, 2023, 15.9% of U.S. adults aged ≥60 years reported receiving an RSV vaccine.
Key reasons for low vaccination uptake of influenza, Covid-19, and RSV vaccines, based on survey results from a nationally representative sample of U.S. adults (Ipsos KnowledgePanel and NORC AmeriSpeak Omnibus Surveys), include:
- Lack of provider recommendation
- Concerns or issues about unknown or serious side effects
- Occurrence of mild side effects
- Lack of time or forgetting to get vaccinated.
FDA clears plating system
December 6
Johnson & Johnson MedTech’s DePuy Synthes has achieved FDA clearance for its TriLEAP™ Lower Extremity Anatomic Plating System. The system is tailored to the requirements of orthopedic surgeons, podiatrists, and foot and ankle specialists, providing a solution for various elective foot surgeries such as bunionectomy. Bunions affect a substantial portion of the U.S. population, with one in four individuals suffering from this progressive foot disorder.
The TriLEAP™ System addresses the need for stability and effective fixation in bunionectomies, osteotomies, fusions, and foot or ankle fractures. This system offers an array of procedure-specific plate options, along with multiple screw shaft diameters and other instruments for the reduction, internal fixation, and fusion of bones and bone fragments, empowering surgeons with a range of intraoperative choices. DePuy Synthes anticipates that the TriLEAP™ System will be available in the United States in 2024.
October 2023
New developments in Covid vaccination
October 26
The U.S. Food and Drug Administration (FDA) amended the emergency use authorization (EUA) of the Novavax Covid-19 Vaccine, Adjuvanted for use in individuals 12 years of age and older to include the 2023-24 formula. Individuals 12 years of age and older previously vaccinated with a Covid-19 vaccine (and who have not already been vaccinated with a recently updated mRNA Covid-19 vaccine) are eligible to receive one dose and unvaccinated individuals receive two doses.
The updated vaccine addresses currently circulating variants to provide better protection against serious consequences of Covid-19, including hospitalization and death. Consistent with the totality of the evidence and input from the FDA’s expert advisors, the Novavax Covid-19 Vaccine, Adjuvanted, a monovalent vaccine, has been updated to include the spike protein from the SARS-CoV-2 omicron variant lineage XBB.1.5 (2023-2024 formula).
This authorization follows the FDA’s recent approvals and authorizations of updated mRNA Covid-19 vaccines for 2023-24 manufactured by ModernaTX Inc. and Pfizer Inc.
“The Covid-19 vaccines have saved countless lives and have prevented serious outcomes of Covid-19 caused by the SARS-CoV-2 virus,” said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research. “Today’s authorization provides an additional Covid-19 vaccine option that meets the FDA’s standards for safety, effectiveness, and manufacturing quality needed to support emergency use authorization. As we head into the fall season and transition into 2024, we strongly encourage those who are eligible to consider receiving an updated Covid-19 vaccine to provide better protection against currently circulating variants.”
The FDA evaluated manufacturing data to support the change to the 2023-24 formula of the Novavax Covid-19 Vaccine, Adjuvanted. Additionally, the FDA evaluated non-clinical immune response data suggesting that the vaccine provides protection against the currently circulating Covid-19 variants. The agency also relied on its evaluation of safety and effectiveness data from clinical trials of Novavax Covid-19 Vaccine, Adjuvanted (Original monovalent) and investigational monovalent and bivalent Novavax Covid-19 adjuvanted vaccines, as well as postmarketing data. The data accrued with these Novavax Covid-19 vaccines are relevant to Novavax Covid-19 Vaccine, Adjuvanted (2023-2024 Formula) as the vaccines are manufactured using a similar process.
The FDA has determined that the Novavax Covid-19 Vaccine, Adjuvanted (2023-2024 Formula) has met the statutory criteria for issuance of an EUA, and that the known and potential benefits of the vaccine outweigh its known and potential risks in individuals 12 years of age and older.
As part of this action, the Novavax Covid-19 Vaccine, Adjuvanted (Original monovalent) is no longer authorized for use in the U.S.
Using AI to develop a ‘pain signature’ for each patient
October 25
According to an October 4 article in Medical Design & Outsourcing, commercial-stage pain management technology company Medasense Biometrics has developed an AI-powered patient monitoring solution to help clinicians manage physiological pain.
Medasense’s pain monitoring solution uses physiological parameters and derivatives to analyze the nonlinear relationship between them using AI, creating a unique pain signature for each patient. This allows for a personalized approach to pain monitoring, considering factors like medication, surgery type, and individual patient response.
Medasense’s flagship device, the PMD-200, uses the company’s Nociception Level Index (NOL), a technology employed to monitor a patient’s pain level during surgery. The PMD-200 has a finger probe connected to the patient and monitors different physiological responses to pain, including pulse waves, sweating, movement, and peripheral temperature changes. The data collected by the probe is analyzed to produce a number between zero and 100 for the pain level the patient is experiencing.
The NOL technology is wired to a bedside monitor in the operating room, which displays the patient’s index number. The threshold for intervention is set at 25, which means that if the patient’s index number is above 25 for more than 60 seconds, the anesthesiologist should consider giving more medication. Beyond the operating room, Medasense’s pain monitoring solution has broader implications for critical care. In ICUs, for example, it could assist in managing pain for patients who may be unable to communicate their discomfort, such as those under sedation or on ventilators. The system’s real-time feedback ensures that pain management remains tailored to the patient’s condition, preventing unnecessary suffering and complications.
Medasense displayed its intraoperative pain management with nociception monitoring solution at ANESTHESIOLOGY® 2023.
AI strikes again
October 20
GE HealthCare and Mass General Brigham announced, as part of its initial collaboration, the co-development of an artificial intelligence (AI) algorithm that will help increase operations effectiveness and productivity. The first innovative AI application from the collaboration is the schedule predictions dashboard of the Radiology Operations Module (ROM), a digital imaging tool that helps optimize scheduling, reduce cost, and free providers from administrative burden, allowing more time for the clinician-patient relationship.
ROM is commercially available to health care institutions. The actionable insights driven by AI and machine learning are designed to help improve both departmental and enterprise-wide productivity and administrative efficiency.
By 2025, the U.S. is estimated to have a shortage of approximately 446,000 home health aides, 95,000 nursing assistants, 98,700 medical and lab technologists and technicians, and more than 29,000 nurse practitioners, according to a report conducted by industry market analytic firm Mercer. Health systems will need to rely on technology to help solve some of these challenges.
Operational AI-enabled tools can address challenges that often pose a threat to patient care such as cost of care and hospital inefficiencies. When a patient misses an appointment, fails to schedule a follow-up, or is late, also known as missed care opportunities, the impact can be significant.
The co-developed algorithm is intended to predict missed care opportunities and late arrivals, which could help increase flexibility and streamline administrative operations, improve patient satisfaction, and better accommodate urgent care, inpatients, or walk-in appointments.
In preliminary tests, the algorithm was able to predict the missed care opportunity correctly, at rates of up to 96%, with limited false positives.
“Utilizing operational AI and machine learning can bring providers together and streamline data sets,” said Keith Dreyer, Chief Data Science Officer, Mass General Brigham. “The strategic use of AI offers great potential for the future of health care, and we’re proud to be at the forefront of the movement. This technology has the potential to reduce burnout and allow physicians to spend more time with patients, which may ultimately lead to better outcomes.”
August 2023
Malaria in Maryland? Really?
August 25
The Maryland Department of Health has confirmed and reported a positive case of locally acquired malaria in a Maryland resident. The individual was hospitalized and is now recovering. The individual did not travel recently outside of the United States nor to other U.S. states with recent locally acquired malaria cases.
“Malaria was once common in the United States, including in Maryland, but we have not seen a case in Maryland that was not related to travel in over 40 years,” said Maryland Department of Health Secretary Laura Herrera Scott.
Malaria is a mosquito-borne disease caused by a parasite. More than 2,000 cases of malaria are reported annually in the U.S., according to the CDC, with most cases occurring in people returning from international travel. Symptoms of malaria usually appear 7 to 30 days after an infective bite and include high fever, chills, body aches, diarrhea, and vomiting.
Long-term PPI use linked to higher dementia risk
August 17
People who take proton pump inhibitors (PPI) for 4.5 years or more may have a higher risk of dementia compared to people who do not take these medications, according to new research published in a recent issue of Neurology, the medical journal of the American Academy of Neurology.
The study only looked at prescription medications. Over-the-counter medications were excluded. This study does not prove that acid reflux drugs cause dementia; it only shows an association.
“Proton pump inhibitors are a useful tool to help control acid reflux, however, long-term use has been linked in previous studies to a higher risk of stroke, bone fractures, and chronic kidney disease,” said study author Kamakshi Lakshminarayan, MBBS, PhD, of the University of Minnesota School of Public Health in Minneapolis.
The study included 5,712 people, age 45 and older, who did not have dementia at the start of the study. They had an average age of 75.
Participants were then followed for a median duration of 5.5 years. During this time, 585 people, or 10%, developed dementia.
Of the 4,222 people who did not take the drugs, 415 people developed dementia, or 19 cases per 1,000 person-years. Person-years represent both the number of people in the study and the amount of time each person spends in the study. Of the 497 people who took the drugs for more than 4.4 years, 58 people developed dementia, or 24 cases per 1,000 person-years.
After adjusting for factors such as age, sex, and race, as well as health-related factors such as high blood pressure and diabetes, researchers found people who had been taking acid reflux drugs for more than 4.4 years had a 33% higher risk of developing dementia than people who never took the drugs.
Researchers did not find a higher risk of dementia for people who took the drugs for fewer than 4.4 years.
A limitation of the study was that participants were asked once a year about medication use, so researchers estimated use between annual check-ins. If participants stopped and restarted acid reflux drugs in between check-ins, estimation of their use may have been inaccurate. The authors were also unable to assess if participants took over-the-counter acid reflux drugs.
World health organization (WHO) updates lists of essential medications
August 3
The WHO published the new editions of the Model Lists of Essential Medicines (EML) and Essential Medicines for Children (EMLc) which include important new medicines for the treatment of multiple sclerosis, cancer, infectious diseases, and cardiovascular conditions, among others.
For the 2023 update, 85 applications, encompassing over one hundred medicines and formulations, were considered by the WHO Expert Committee on Selection and Use of Essential Medicines. The recommended changes bring the total number of medicines on the EML and EMLc to 502 and 361, respectively.
Multiple sclerosis (MS). Until now, no medicines for its treatment have been included on the EML. In 2023, three medicines that can delay or slow its progression - cladribine, glatiramer acetate, and rituximab - are added to the EML.
Cardiovascular medicines. Fixed-dose combinations of multiple medicines (commonly called ‘polypills’) for the prevention of diseases of the heart and blood vessels, notably cholesterol-lowering agents with one or more blood pressure-lowering agents with and without acetylsalicylic acid (aspirin), have been added to the EML for the first time.
Infectious diseases. New medicines listed for infectious diseases include:
- ceftolozane + tazobactam, a ‘reserve’ group antibiotic effective against multidrug-resistant bacteria, including difficult-to-treat infections caused by carbapenem-resistant Pseudomonas aeruginosa
- pretomanid for treatment of multidrug-resistant or rifampicin-resistant tuberculosis
- ravidasvir (to be used in combination with sofosbuvir) for the treatment of chronic hepatitis C virus infection in adults
- monoclonal antibodies for Ebola virus disease.
Cancer medicines. Two new cancer treatments have been added: pegylated liposomal doxorubicin for Kaposi sarcoma; and pegfilgrastim to stimulate the production of white blood cells and reduce the toxic effect of some cancer medicines on the bone marrow.
Pfizer developing Group B Streptococcus (GBS) maternal vaccine
August 1
Pfizer Inc. announced data from a Phase 2 study investigating its hexavalent capsular polysaccharide (CPS) conjugate, and Group B Streptococcus (GBS) vaccine candidate, GBS6, being developed for maternal administration to protect infants against invasive GBS disease. In stage two of the three-part study, which enrolled 360 healthy pregnant individuals, GBS6 generated robust maternal antibody responses against the six GBS CPS serotypes included in the vaccine, and these antibodies were efficiently transferred to infants at ratios of ~0.4-1.3 depending on GBS6 group. Based on a parallel natural history study conducted in South Africa, the Phase 2 study immunogenicity data suggest that GBS6 may offer meaningful protection against invasive GBS disease in newborns and young infants. The results were published in The New England Journal of Medicine (NEJM) and will inform a planned Phase 3 clinical development program.
In both the mothers and infants, the safety profile was similar between the vaccine and placebo groups. Local reactions were generally mild or moderate and of short duration, with pain at the injection site being the most frequently reported event. Solicited systemic events were similar among the GBS6 groups and the placebo group, with most events being mild or moderate. Overall, 2%-8% of participants in the GBS6 groups, depending on dose, and 5% of those in the placebo group, reported fever. Among pregnant individuals, adverse events (AEs) occurred in 45%-70% of the participants in the GBS6 groups, depending on dose, and in 61% of those in the placebo group. The most common AEs and serious adverse events (SAEs) were conditions that are related to pregnancy. Among the infants, AEs occurred in 62%-75% of the participants in the GBS6 groups, depending on dose, and in 74% of those in the placebo group. None of the SAEs were deemed related to the vaccine candidate.
July 2023
Novel technology to assist neurosurgeons
July 27
Stryker has commercially launched its Q Guidance System with Cranial Guidance Software to provide surgeons with an image-based planning and intraoperative guidance system that assists in positioning instruments and identifying patient anatomy during cranial surgery. The software can be used for craniotomies, skull base and transsphenoidal procedures, shunt placements, and biopsies.
The system offers neurosurgeons have more surgical planning and guidance capabilities, with a special focus on biopsies and shunt placements.
The Q Guidance System with Cranial Guidance Software uses both active and passive tracking technology to provide groundbreaking planning and guidance capabilities that include:
- A proprietary camera: Stryker’s new 4th generation FP8000 camera offers increased speeds compared to products currently offered in the market.
- Dual PC system: One PC powers the operating system’s applications while the other provides real-time patient data.
- Diffusion Tensor Imaging (DTI) and tractography: DTI uses anisotropic diffusion to estimate the brain’s axonal organization, reconstructed in 3D.
- Precision Targeting System: Enables navigated biopsy of cranial tissue by using comprehensive guidance data and imaging to pre-plan an approach for entry point.
- Electromagnetic catheter placement: Enables pinless shunt procedures.
“With Stryker’s new camera technology, we were able to quickly register patients using the CranialMask Tracker,” said J.D. Day, MD, UAMS Health in Little Rock, Arkansas. “The new user interface and workflows are slick, and our staff loves the intuitive new views like 3D targeting and the new skull stripping feature.”
The Q Guidance System with Cranial Guidance Software was used at six early product surveillance sites in May 2023.
New drug to prevent RSV in babies and toddlers
July 21
The FDA approved Beyfortus for the prevention of RSV in neonates and infants born during or entering their first RSV season, and in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.
RSV is a virus that causes acute respiratory infection in individuals of all age groups. While most infants and young children experience mild, cold-like symptoms, some infants, especially with their first infection, develop lower respiratory tract disease such as pneumonia and bronchiolitis (swelling of the small airway passages in the lungs) that often leads to an emergency department or physician office visit. Premature infants, and those with chronic lung disease of prematurity or significant congenital heart disease, are at highest risk for severe RSV disease. Approximately 1%-3% of children under 12 months of age in the U.S. are hospitalized each year due to RSV, according to the American Academy of Pediatrics.
Beyfortus is a monoclonal antibody with activity against RSV. Monoclonal antibodies are laboratory-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses. One dose of Beyfortus, administered as a single intramuscular injection prior to or during RSV season, may provide protection during the RSV season.
The safety and efficacy of Beyfortus were supported by three clinical trials. The key measure of efficacy was the incidence of medically attended RSV lower respiratory tract infection (MA RSV LRTI), evaluated during the 150 days after Beyfortus administration. Among infants who were treated with Beyfortus, 12 (1.2%) experienced MA RSV LRTI compared with 25 (5.0%) infants who received placebo. Beyfortus reduced the risk of MA RSV LRTI by approximately 75% relative to placebo.
Possible side effects of Beyfortus include rash and injection site reactions. Beyfortus should not be given to infants and children with a history of serious hypersensitivity reactions to Beyfortus’ active ingredients or any of its excipients.
Beyfortus comes with warnings and precautions about serious hypersensitivity reactions, including anaphylaxis, which have been observed with other human IgG1 monoclonal antibodies. Beyfortus should be given with caution to infants and children with clinically significant bleeding disorders.
Beyfortus received a Fast Track designation for this indication.
The FDA granted this approval to AstraZeneca.
Alzheimer’s drug receives FDA approval
July 13
The FDA converted Leqembi, indicated to treat adult patients with Alzheimer’s disease, to traditional approval following a determination that a confirmatory trial verified clinical benefit. Leqembi is the first amyloid beta-directed antibody to be converted from an accelerated approval to a traditional approval for the treatment of Alzheimer’s disease. The drug works by reducing amyloid plaques that form in the brain, a defining pathophysiological feature of the disease.
Leqembi was approved in January under the Accelerated Approval pathway, which allows the FDA to approve drugs for serious conditions where there is an unmet medical need, based on clinical data demonstrating the drug’s effect on a surrogate endpoint. In the case of Leqembi, reducing amyloid plaques in the brain is reasonably likely to predict a clinical benefit to patients. As a post-marketing requirement of the accelerated approval, the FDA required the applicant to conduct a clinical trial, often referred to as a confirmatory study, to verify the anticipated clinical benefit of Leqembi. The efficacy of Leqembi was evaluated using the results of Study 301 (CLARITY AD), a Phase 3 randomized, controlled clinical trial.
“Today’s action is the first verification that a drug targeting the underlying disease process of Alzheimer’s disease has shown clinical benefit in this devastating disease,” said Teresa Buracchio, acting director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “This confirmatory study verified that it is a safe and effective treatment for patients with Alzheimer’s disease.”
Study 301 was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that enrolled 1,795 patients with Alzheimer’s disease. Treatment was initiated in patients with mild cognitive impairment or mild dementia stage of disease and confirmed presence of amyloid beta pathology. Patients were randomized in a 1:1 ratio to receive placebo or Leqembi at a dose of 10 milligrams (mg)/kilograms (kg), once every two weeks. Leqembi demonstrated a statistically significant and clinically meaningful reduction of decline from baseline to 18 months on the primary endpoint, the Clinical Dementia Rating Scale Sum of Boxes score, compared to placebo. Statistically significant differences between treatment groups were also demonstrated on all secondary endpoints, which included the Alzheimer’s Disease Assessment Scale Cognitive Subscale 14, and the Alzheimer’s Disease Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment.
On June 9, the FDA convened the Peripheral and Central Nervous System Drugs Advisory Committee to discuss whether Study 301 provided evidence of clinical benefit of Leqembi for the treatment of Alzheimer’s disease. All committee members voted affirmatively that the results of the study verified the clinical benefit of Leqembi for the indicated use.
The most common side effects of Leqembi were headache, infusion-related reactions, and amyloid-related imaging abnormalities (ARIA), a side effect known to occur with the class of antibodies targeting amyloid. ARIA most commonly presents as temporary swelling in areas of the brain seen in imaging studies that usually resolves over time and may be accompanied by small spots of bleeding in or on the surface of the brain.
Although ARIA is often not associated with any symptoms, symptoms can occur and include headache, confusion, dizziness, vision changes, and nausea. ARIA can also infrequently present with serious and life-threatening brain edema that can be associated with seizures and other severe neurological symptoms. Intracerebral hemorrhages can occur in patients treated with this class of medications and can be fatal. A boxed warning is included in the prescribing information to alert patients and caregivers to the potential risks associated with ARIA.
Patients treated with Leqembi who are homozygous for the ApoE ε4 allele have a higher incidence of ARIA, including symptomatic, serious, and severe ARIA, compared to heterozygotes and noncarriers. The prescribing information states that testing for ApoE ε4 status should be performed before starting treatment with Leqembi to inform the risk of developing ARIA.
Use of anticoagulant medication was associated with an increased number of intracerebral hemorrhages in patients taking Leqembi compared to placebo. The prescribing information recommends caution when considering use of Leqembi in patients taking anticoagulants or with other risk factors for intracerebral hemorrhage.
Leqembi is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of its inactive ingredients. Adverse reactions may include angioedema (swelling) and anaphylaxis (allergic reaction).
Leqembi should be initiated in patients with mild cognitive impairment or mild dementia stage of Alzheimer’s disease—the population in which treatment was studied in clinical trials. The labeling states that there are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.
The approval of Leqembi was granted to Eisai Inc.
June 2023
New device designed to optimize epidural placement
June 27
The Israeli medical tech company Omeq Medical has obtained regulatory approval from the FDA for its EpiFinder device, which helps physicians precisely place an epidural needle while conducting the standard loss of resistance (LOR) technique. It is a sensor-driven, battery-operated, single-use epidural placement device that can be used for “safe, accurate epidural injections.” Users can place the device between a standard needle and a syringe. It eliminates the need for capital equipment and is compatible with existing epidural syringes. EpiFinder also has the capability to monitor tissue resistance at the needle tip to accurately identify penetration of the needle into the epidural space, thereby safeguarding the patient from complications arising from misplacement. In a first-in-human clinical trial conducted by Omeq, the EpiFinder was able to securely provide successful epidural blocks in each of 31 patients.
AMA backs away from BMI
June 22
Delegates at the Annual Meeting of the American Medical Association (AMA) House of Delegates adopted policy aimed at clarifying how body mass index (BMI) can be used as a measure in medicine. The new policy was part of the AMA Council on Science and Public Health report which evaluated the problematic history with BMI and explored alternatives. The report also outlined the harms and benefits of using BMI and pointed to BMI as an imperfect way to measure body fat in multiple groups given that it does not account for differences across race/ethnic groups, sexes, genders, and age-span. Given the report’s findings, the new policy supports the AMA in educating physicians on the issues with BMI and alternative measures for diagnosing obesity.
Under the newly adopted policy, the AMA recognizes issues with using BMI as a measurement due to its historical harm, its use for racist exclusion, and because BMI is based primarily on data collected from previous generations of non-Hispanic white populations. Due to significant limitations associated with the widespread use of BMI in clinical settings, the AMA suggests that it be used in conjunction with other valid measures of risk such as, but not limited to, measurements of visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic/metabolic factors. The policy noted that BMI is significantly correlated with the amount of fat mass in the general population but loses predictability when applied on the individual level. The AMA also recognizes that relative body shape and composition differences across race/ethnic groups, sexes, genders, and age-span are essential to consider when applying BMI as a measure of adiposity and that BMI should not be used as a sole criterion to deny appropriate insurance reimbursement.
FDA recommends single-strain Covid boosters come autumn
June 21
The FDA recommended that Covid-19 vaccine manufacturers make single-strain booster shots for this fall that would target the currently circulating Omicron subvariant XBB.1.5. This vaccine would drop protection against the original strain of the virus that emerged in China in late 2019 to focus on the current circulating variants.
On June 15, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) unanimously voted that the vaccine composition be updated to a monovalent Covid-19 vaccine with an XBB-lineage of the Omicron variant. Following discussion of the evidence, the committee expressed a preference for XBB.1.5.
Based on the totality of the evidence, the FDA has advised manufacturers who will be updating their Covid-19 vaccines that they should develop vaccines with a monovalent XBB.1.5 composition.
Additional information: Recommendation for the 2023-2024 Formula of Covid-19 vaccines in the U.S.
RSV prevention options for infants endorsed by FDA
June 16
The U.S. Food and Drug Administration Antimicrobial Drugs Advisory Committee (AMDAC) has voted unanimously 21 to 0 that AstraZeneca and Sanofi’s nirsevimab has a favorable benefit risk profile for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease (LRTD) in newborns and infants born during or entering their first RSV season. The committee also voted 19 to 2 in support of nirsevimab’s favorable benefit risk profile for children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season.
Nirsevimab has the potential to protect the broad infant population through its first RSV season, including those born healthy at term or preterm, or with specific health conditions that make them vulnerable to RSV disease. The single dose can be flexibly administered at the beginning of the RSV season or at birth for newborns born during the RSV season.
The FDA accepted the Biologics License Application (BLA) for nirsevimab in 2022 and the agency has indicated it will work to expedite its review. The Prescription Drug User Fee Act date is in the third quarter of 2023. If approved by that time, nirsevimab will be available in the U.S. ahead of the 2023-4 RSV season.
In the U.S., RSV is the leading cause of hospitalization for babies under one. About 75% of infants hospitalized for RSV in the U.S. were born at term with no underlying conditions.
The AMDAC based its recommendation on the nirsevimab clinical development program spanning three pivotal late-stage clinical trials, including results from the MELODY Phase III trial recently published in The New England Journal of Medicine. Across all clinical endpoints, a single dose of nirsevimab demonstrated sustained and consistent reduction in RSV LRTD requiring medical care vs. placebo through the entire RSV season. Nirsevimab was generally well tolerated with a favorable safety profile that was consistent across all clinical trials. The overall rates of adverse events were comparable between nirsevimab and placebo and the majority of adverse events were mild or moderate in severity. The most common adverse events were rash, fever, and injection site reactions.
2023 was a particularly harsh winter for RSV. Read more in this In the Know article.
NIH’s ComboMATCH initiative will pilot novel drug combinations
June 9
The National Cancer Institute (NCI) has launched a large precision medicine cancer initiative to test the effectiveness of treating adults and children with new drug combinations that target specific tumor alterations. Known as the Combination Therapy Platform Trial with Molecular Analysis for Therapy Choice (ComboMATCH), the initiative is the largest of its kind to test combinations of cancer drugs guided by tumor biology. The endeavor aims to identify promising treatments that can advance to larger, more definitive clinical trials outside of ComboMATCH. NCI is part of the National Institutes of Health.
ComboMATCH comprises numerous phase 2 treatment trials that will each evaluate a drug combination—usually either two targeted drugs or a targeted drug plus a chemotherapy drug. Some trials will include patients with specific changes in their cancer cells, no matter where the cancer arose in the body, whereas others will enroll patients with specific cancer types.
“The majority of treatments that patients get nowadays are not genomically determined,” said James H. Doroshow, MD, director of NCI’s Division of Cancer Treatment and Diagnosis. “With ComboMATCH, we’re trying to show that genomic abnormalities can be used to determine the most effective treatment combinations for patients.”
ComboMATCH is a cross-group collaboration among NCI and all five U.S. clinical trial groups within NCI’s National Clinical Trials Network (NCTN). ComboMATCH is a successor to NCI-MATCH, NCI’s groundbreaking precision medicine clinical trial. In NCI-MATCH, people were assigned to treatment based on genetic changes in their tumor rather than their type of cancer. For the most part, NCI-MATCH evaluated single drugs targeting the mutation thought to be driving the growth of a patient’s tumor. However, many patients quickly developed resistance to these single drugs.
“With ComboMATCH, we’re hoping that by attacking both the genetic driver and the mechanisms of resistance, we will obtain more durable clinical responses and more benefit to patients,” said Jeffrey Moscow, MD, of the Investigational Drug Branch in NCI’s Division of Cancer Treatment and Diagnosis and a co-leader of ComboMATCH.
The combinations will include both U.S. Food and Drug Administration-approved drugs and investigational agents contributed by pharmaceutical companies. Hundreds of thousands of potential drug combinations exist, so one challenge has been to narrow down and prioritize the most promising ones.
There are several ways in which patients with locally advanced or metastatic solid tumors will be identified for possible participation in ComboMATCH. In recent years, genomic testing of tumors has become a standard part of care for people with many cancer types. A doctor at any of the community hospitals and cancer centers participating in ComboMATCH can refer their patient for additional eligibility screening if the patient’s test results show that they have a particular alteration being investigated in one of the treatment trials. Any one of the nearly 35 designated commercial and academic labs that are conducting genomic testing as part of standard of care can also identify patients who might be eligible for a ComboMATCH trial.
HIV Rates Decline Among 13-24 Year Olds
June 1
Estimated annual new HIV infections were 12% lower in 2021 compared to 2017—dropping from about 36,500 infections to about 32,100—according to new CDC data published May 23. The decline was driven by a 34% decrease in new infections among 13- to 24-year-olds, mostly among gay and bisexual males.
According to CDC’s latest estimates, annual HIV infections dropped from 9,300 in 2017 to 6,100 in 2021 among 13- to 24-year-olds. Declines among young gay and bisexual males (who account for roughly 80% of new infections in this age group) drove the trend, falling from an estimated 7,400 infections to about 4,900 during the timeframe.
“Our nation’s HIV prevention efforts continue to move in the right direction,” said CDC Director Rochelle P. Walensky, MD, MPH “Longstanding factors, such as systemic inequities, social and economic marginalization and residential segregation, however, stand between highly effective HIV treatment and prevention and people who could benefit from them. Efforts must be accelerated and strengthened for progress to reach all groups faster and equitably.”
Data suggest that improved reach of HIV testing, treatment, and pre-exposure prophylaxis (PrEP) has contributed to progress in HIV prevention among young gay and bisexual males.
May 2023
Horrific complications linked to artificial eye drops
May 25
As of May 15, 2023, CDC, in partnership with state and local health departments, identified 81 patients in 18 states with VIM-GES-CRPA, a rare strain of extensively drug-resistant P. aeruginosa. The outbreak strain had never been reported in the United States prior to this outbreak.
Most patients reported using artificial tears. Patients reported over 10 different brands of artificial tears, and some patients used multiple brands. EzriCare Artificial Tears, a preservative-free, over-the-counter product packaged in multidose bottles, was the brand most reported.
1.63 million excess deaths in Black Americans
May 24
A recent JAMA study questioned how many excess deaths and years of potential life are lost for the Black population, compared with the white population, occurred in the United States from 1999 through 2020. Findings were somewhat surprising during a period of focus on health disparities.
From 1999 to 2011, the age-adjusted excess mortality rate declined from 404 to 211 excess deaths per 100,000 individuals among Black males. However, the rate plateaued from 2011 through 2019 and increased in 2020 to 395 excess deaths — rates not seen since 2000.
Heart disease had the highest excess mortality rate, and the excess years of potential life lost rates were highest among Black infants and middle-aged adults.
No more Johnson & Johnson vaccine
May 19
Janssen Covid-19 vaccine is no longer available in the U.S. All remaining U.S. government stock of Janssen Covid-19 vaccine expired May 7, 2023. Dispose of any remaining Janssen Covid-19 vaccine in accordance with local, state, and federal regulations.
People ages 18 years and older who received one dose of Janssen Covid-19 vaccine should be considered to have received a single-dose Janssen primary series.
People ages 18 years and older who received one or two Janssen Covid-19 vaccine doses are recommended to receive 1 bivalent mRNA dose (Moderna or Pfizer-BioNTech) at least two months after completion of the previous dose.
Treatment-resistant ringworm emerges in New York
May 12
Tinea is a common, highly contagious, superficial infection of the skin, hair, or nails caused by dermatophyte molds. During the past decade, an epidemic of severe, antifungal-resistant tinea has emerged in South Asia because of the rapid spread of Trichophyton indotineae, a novel dermatophyte species; the epidemic has likely been driven by misuse and overuse of topical antifungals and corticosteroids. T. indotineae infections are highly transmissible and characterized by widespread, inflamed, pruritic plaques on the body (tinea corporis), the crural fold, pubic region, and adjacent thigh (tinea cruris), or the face (tinea faciei). T. indotineae isolates are frequently resistant to terbinafine, a mainstay of tinea treatment. T. indotineae infections have been reported throughout Asia and in Europe and Canada but have not previously been described in the U.S.
On February 28, 2023, a New York City dermatologist notified public health officials of two patients who had severe tinea that did not improve with oral terbinafine treatment, raising concern for potential T. indotineae infection; these patients shared no epidemiologic links. Skin culture isolates from each patient were previously identified by a clinical laboratory as Trichophyton mentagrophytes and were subsequently forwarded to the Wadsworth Center, New York State Department of Health, for further review and analysis. Sanger sequencing of the internal transcribed spacer region of the ribosomal gene, followed by phylogenetic analysis performed during March 2023, identified the isolates as T. indotineae. Activity related to this investigation was reviewed by the CDC and was conducted consistent with applicable federal law and CDC policy.
Patient A, a woman aged 28 years, developed a widespread pruritic eruption during summer 2021. She had a first dermatologic evaluation in December 2021, at which time she was in her third trimester of pregnancy. She had no other underlying medical conditions, no known exposures to a person with a similar rash, and no recent international travel history. Dermatologists noted large, annular, scaly, pruritic plaques over the neck, abdomen, pubic region, and buttocks. She received a diagnosis of tinea and began oral terbinafine therapy in January 2022 after the birth of her baby. Because her eruptions did not improve after two weeks of therapy, terbinafine was discontinued, and she began itraconazole treatment. The rash resolved completely after completing a four-week course of itraconazole; however, she is being monitored for potential recurrence of infection and the need for resumption of itraconazole.
Patient B, a woman aged 47 years with no major medical conditions, developed a widespread, pruritic eruption in summer 2022 while in Bangladesh. There, she received treatment with topical antifungal and steroid combination creams and noted that several family members were experiencing similar eruptions. After returning to the United States, she visited an emergency department three times during autumn 2022. She was prescribed hydrocortisone 2.5% ointment and diphenhydramine (visit 1), clotrimazole cream (visit 2), and terbinafine cream (visit 3) with no improvement. In December 2022, she was evaluated by dermatologists who noted widespread, discrete, scaly, annular, pruritic plaques affecting the thighs and buttocks. She received a four-week course of oral terbinafine, but her symptoms did not improve. She then received a four-week course of griseofulvin therapy, resulting in approximately 80% improvement. Itraconazole therapy is being considered pending further evaluation given the recent confirmation of suspected T. indotineae infection. Her son and husband, who live in the same house and report similar eruptions, are currently undergoing evaluation.
Both cases highlight several important points. Patient A had no recent international travel history, suggesting potential local U.S. transmission of T. indotineae. Health care providers should consider T. indotineae infection in patients with widespread tinea, particularly when eruptions do not improve with first-line topical antifungal agents or oral terbinafine. Culture-based identification techniques used by most clinical laboratories typically misidentify T. indotineae as T. mentographytes or T. interdigitale; correct identification requires genomic sequencing. Health care providers who suspect T. indotineae infection should contact their state or local public health department for assistance with testing, which is available at certain public health laboratories and specialized academic and commercial laboratories. Successful treatment using oral itraconazole, a triazole antifungal, has been documented. However, physicians should be aware of challenges with itraconazole absorption, which can lead to variable serum drug concentrations. Itraconazole’s interactions with other drugs, the need for up to 12 weeks of therapy, and the documented emergence of triazole resistance must also be considered.
Antimicrobial stewardship efforts are essential to minimize the misuse and overuse of prescribed and over-the-counter antifungal drugs and corticosteroids. In addition, health care providers can educate patients about strategies to prevent the spread of the dermatophytes that cause tinea. Finally, public health surveillance efforts and increased testing could help detect and monitor the spread of T. indotineae.
Fentanyl-related deaths in children have skyrocketed
May 10
An important study was published last week in JAMA Pediatrics with regard to the current direction of the opioid crisis. To date, there has been little research about opioid poisonings in children younger than 10.
Mirroring trends seen among adults, pediatric deaths from fentanyl began to increase substantially in 2013, resulting in a more than 30-fold increase in mortality between 2013 and 2021. A surge that began in 2018 has led to a nearly threefold increase in deaths among older adolescents and a nearly sixfold increase among children younger than 5 years. Across age groups, annual deaths peaked in 2020 and 2021, suggesting that the Covid-19 pandemic exacerbated this public health crisis.
The primary limitation of this research is that it relied on population-based death certificate data, including provisional 2021 data. The quality of this information depends on the accuracy and completeness of the investigations conducted at the time of death.
Findings from this study suggest that the pediatric opioid crisis is changing in ways that will make it harder to combat. Commonsense solutions (e.g., safe storage and disposal) are still needed to prevent pediatric exposures to opioids, but a greater emphasis on harm reduction strategies is necessary, including parental and adolescent treatment for opioid use disorder and improving access to naloxone in homes, which is where most pediatric deaths from fentanyl occur.
Role of 3D Printing in Obstetric Anesthesia
May 4
Parents bringing cell phones into the OR during cesarean delivery to capture the baby’s first moments is the rule, rather than the exception anymore. It’s more complicated than it sounds to hold a phone and many ask to keep them on the anesthesia cart or machine.
Tufts Medical Center has found a workaround. In this article, authors describe their 3D phone holder, which is conveniently attached to an I.V. pole and easily accessible to the patient and her support person. The phone holder was designed using CAD software (Autodesk Fusion 360, San Francisco) and printed on a fused deposition modeling 3D printer (Prusa Research i3 MKs+, Prague, Czech Republic) in PETG filament.
Authors say these 3D-printed objects are clean, nontoxic, and can be fabricated into myriad shapes. Importantly, these are cheaper than what’s available online and their use at Tufts Medical Center has increased patient satisfaction.
April 2023
Blastomycosis Outbreak in Michigan
April 27
Investigations continue on an outbreak of blastomycosis, a fungal infection, associated with the Escanaba Billerud Paper Mill in Michigan.
To date, there have been a total of 104 cases (confirmed and probable) of blastomycosis identified. Thirteen out of the 104 cases have been hospitalized and one person has died. All 104 cases are employees, contractors, or visitors of Escanaba Billerud Paper Mill.
Blastomycosis is caused by a fungus, Blastomyces, that lives in the environment, especially in moist soil and decomposing matter like wood or leaves, according to the CDC. It is predominantly found in the Midwest and the South, particularly around the Ohio and Mississippi Rivers and the Great Lakes.
People can breathe in these microscopic fungal spores, and although most won’t get sick, some will develop symptoms like a fever or cough between three weeks and three months later, the CDC says. Other symptoms may include chest pain, trouble breathing, night sweats, fatigue, weight loss, and muscle or joint pain, according to Public Health Delta & Menominee Counties. In rare cases, the infection can spread outside the lungs to places like the skin, bones, brain, and spinal cord.
Blastomycosis does not spread from person to person. It’s treated with antifungal medication that must be taken for a period ranging from six months to a year, depending on the severity of the illness and the person’s overall health.
STI cases rose in U.S. throughout 2021, study says
April 25
Reported cases of the sexually transmitted infections (STIs) chlamydia, gonorrhea, and syphilis all increased between 2020 and 2021 — reaching a total of more than 2.5 million reported cases — according to CDC’s final surveillance data.
The new report provides final surveillance data for 2021, and shows that overall, in a single year (2020-2021):
- Gonorrhea rates increased more than 4%
- Syphilis rates surged, increasing nearly 32% for combined stages of the infection. Among the syphilis data, cases of congenital syphilis rose by an alarming 32% and resulted in 220 stillbirths and infant deaths.
- Chlamydia rates increased nearly 4%, but – unlike gonorrhea and syphilis – still did not return to pre-pandemic levels. This raises concerns that screening continued to be impacted by Covid-19 related disruptions the second year of the pandemic, because the infection is often asymptomatic.
While STIs are common in all U.S. regions and across all groups, the 2021 data show STIs continue to disproportionately affect gay and bisexual men, and younger people. Additionally, a disproportionate number of cases were diagnosed among Black and American Indian/Alaska Native people.
Janssen Pharmaceutical introduces once-daily prostate cancer tablets
April 18
The Janssen Pharmaceutical Companies of Johnson & Johnson announced the availability of an additional tablet strength of ERLEADA® (apalutamide) in the United States. The introduction of the 240mg tablet provides the first-and-only option for a once-daily, single-tablet Androgen Receptor Inhibitor (ARI) approved for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).
With two strengths available, health care professionals may prescribe the approved 240mg once-daily dose of ERLEADA® in either one 240mg tablet or four 60mg tablets. The single-tablet option may be preferable for patients in need of reducing their total number of daily pills.
ERLEADA® remains the only ARI with labeling to include approved alternate methods of administration for patients who have difficulty swallowing tablets whole. The 60mg tablets continue to have an approved option for dispersing with applesauce, while the 240mg tablet is approved for dispersing in orange juice, water, or applesauce. The 240mg tablet may also be administered through a feeding tube.
FDA will mandate pre-paid mailers to facilitate outpatient opioid returns
April 7
Earlier this week, the U.S. Food and Drug Administration announced it is requiring manufacturers of opioid analgesics dispensed in outpatient settings to make pre-paid mail-back envelopes available to outpatient pharmacies and other dispensers as an additional opioid analgesic disposal option for patients.
“Expanding impactful opioid disposal options, such as mail-back envelopes and in-home disposal, for patients to safely and securely dispose of their unused opioid medications is part of the agency’s comprehensive approach to addressing the overdose crisis,” said FDA Commissioner Robert M. Califf, MD. “We believe these efforts will not only increase convenient disposal options for many Americans, but also reduce unfortunate opportunities for nonmedical use, accidental exposure, overdose and potential new cases of opioid use disorder. We’re pleased to take this first critical step to increase mail-back envelope options in partnership with the U.S. Postal Service.”
The FDA issued notice to all manufacturers of opioid analgesics used in outpatient settings that they are required to submit the proposed modification to the Opioid Analgesic Risk Evaluation and Mitigation Strategy (OA REMS) within 180 days of the date of the notification letter. The agency anticipates approval of the modified REMS in 2024. When implemented, outpatient pharmacies and other dispensers will have the option to order prepaid mail-back envelopes from opioid analgesic manufacturers, which they may then provide to patients prescribed opioid analgesics. The REMS modification also requires manufacturers to develop educational materials for patients on safe disposal of opioid analgesics, which outpatient pharmacies and other dispensers may also provide to patients.
This action follows a Federal Register notice issued in April 2022 that sought public comment on a potential modification of the OA REMS to require that mail-back envelopes be dispensed and education on safe disposal be provided with opioid analgesics dispensed in an outpatient setting.
Patients commonly report having unused opioid analgesics following surgical procedures and many Americans gain access to opioids through friends or relatives who have unused opioids. Data show educating patients about disposal options may increase the disposal rate of unused opioids and that providing a disposal option along with education could further increase that rate.
Currently, there are multiple mail-back envelope programs operating in the U.S. and mail-back envelopes are commercially available from multiple entities. There are long-standing regulations and policies, under the Drug Enforcement Administration and United States Postal Service, in place to ensure that mail-back envelopes are nondescript, fit for purpose, and can safely and securely transport unused medicines from the patient’s home to the location where they will be destroyed.
The FDA continues to consider additional ways to increase safe disposal of unused opioid analgesics. Specifically, the agency is exploring whether manufacturers of opioid analgesics should also be required to make in-home disposal products available to patients who are prescribed opioid analgesics. The FDA has also issued a Federal Register notice to seek information and comments from the public to aid the agency’s assessment of in-home disposal methods.
These collective efforts are part of the agency’s implementation of the FDA Overdose Prevention Framework that aims to prevent drug overdoses, and reduce deaths through impactful and creative actions. The FDA remains focused on responding to all facets of substance use, misuse, substance use disorders, overdose and death in the U.S. through the four priorities of the framework, including supporting primary prevention by eliminating unnecessary initial prescription drug exposure and inappropriate prolonged prescribing, encouraging harm reduction through innovation and education, advancing development of evidence-based treatments for substance use disorders, and protecting the public from unapproved, diverted, or counterfeit drugs presenting overdose risks.
March 2023
TB Cases Increase 5% in 2022
March 31
Preliminary TB data released by CDC show that the number of U.S. TB disease cases increased 5% in 2022 to 8,300 cases. CDC is calling on health care providers and communities disproportionately affected by TB to Think. Test. Treat TB.
TB disease cases in 2022 increased but did not return to pre-pandemic levels. Some public health officials were concerned about delayed or missed diagnoses of TB disease in 2020, following a substantial 20% decline that year. Now, CDC data signal a rebound in cases and show considerable increases among some groups, including:
- Children aged 4 and under: cases in this age group are particularly concerning because they usually result from recent transmission versus reactivation of long-standing latent TB infection.
- People who are incarcerated: highlighting the importance of entry and annual screening and prompt evaluation of people with TB symptoms in a setting that increases the risk for outbreaks.
- People from some racial and ethnic groups: underscoring the importance of increasing TB prevention services in communities at risk for TB.
Autism Diagnoses Rise, despite Covid-related delays in detection
March 30
One in 36 (2.8%) 8-year-old children have been identified with autism spectrum disorder (ASD), according to an analysis published in CDC’s Morbidity and Mortality Weekly Report (MMWR). The new findings are higher than the previous 2018 estimate that found a prevalence of 1 in 44 (2.3%). The data come from 11 communities in the Autism and Developmental Disabilities Monitoring (ADDM) Network and are not representative of the entire United States.
A second report on 4-year-old children in the same 11 communities highlights the impact of Covid-19, showing disruptions in progress in early autism detection. In the early months of the pandemic, 4-year-old children were less likely to have an evaluation or be identified with ASD than 8-year-old children when they were the same age. This coincides with the interruptions in childcare and health care services during the Covid-19 pandemic.
ASD prevalence among Asian, Black, and Hispanic children was at least 30% higher in 2020 than 2018, and ASD prevalence among White children was 14.6% higher than in 2018. For the first time, the percentage of 8-year-old Asian or Pacific Islander (3.3%), Hispanic (3.2%), and Black (2.9%) children identified with autism was higher than among 8-year-old White children (2.4%). This is the opposite of racial and ethnic differences observed in previous ADDM reports for 8-year-olds. These shifts may reflect improved screening, awareness, and access to services among historically underserved groups.
Additionally, disparities for co-occurring intellectual disability have persisted. A higher percentage of Black children with autism were identified with intellectual disability compared with White, Hispanic, or Asian or Pacific Islander children with autism. These differences could relate in part to access to services that diagnose and support children with autism.
Overall, autism prevalence within the ADDM sites was nearly four times higher for boys than girls. Still, this is the first ADDM report in which the prevalence of autism among 8-year-old girls has exceeded 1%.
DEA issues warning for illicit fentanyl mixed with xylazine
March 29
The U.S. Drug Enforcement Administration is warning the American public of a sharp increase in the trafficking of fentanyl mixed with xylazine.
Xylazine, also known as “Tranq,” is a powerful sedative that the U.S. Food and Drug Administration has approved for veterinary use.
“Xylazine is making the deadliest drug threat our country has ever faced, fentanyl, even deadlier,” said Administrator Milgram. “DEA has seized xylazine and fentanyl mixtures in 48 of 50 States. The DEA Laboratory System is reporting that, in 2022, approximately 23% of fentanyl powder and 7% of fentanyl pills seized by the DEA contained xylazine.”
Xylazine and fentanyl drug mixtures place users at a higher risk of suffering fatal drug poisoning. Because xylazine is not an opioid, naloxone (Narcan) does not reverse its effects. Still, experts always recommend administering naloxone if someone might be suffering from drug poisoning. People who inject drug mixtures containing xylazine also can develop severe wounds, including necrosis—the rotting of human tissue—that may lead to amputation.
According to the CDC, 107,735 Americans died between August 2021 and August 2022 from drug poisonings, with 66 percent of those deaths involving synthetic opioids like fentanyl. The Sinaloa Cartel and Jalisco Cartel in Mexico, using chemicals largely sourced from China, are primarily responsible for the vast majority of the fentanyl that is being trafficked in communities across the United States.
FDA recently communicated to health care providers about the risks to patients exposed to xylazine in illicit drugs.
EPA Proposes First National Standards on Drinking Water
March 17
Earlier this week, the Biden-Harris Administration proposed the first-ever national drinking water standard for six per- and polyfluoroalkyl substances (PFAS) in the latest action under President Biden’s plan to combat PFAS pollution and Administrator Regan’s PFAS Strategic Roadmap. Through this action, the U.S. Environmental Protection Agency (EPA) aims to protect public health from PFAS pollution, leveraging the latest science and complementing state efforts to limit PFAS by proposing to establish legally enforceable levels for six PFAS known to occur in drinking water.
This proposal builds on other key milestones to combat PFAS, including EPA’s proposal to designate two PFAS as CERCLA hazardous substances; enhancing data on PFAS under EPA’s National PFAS Testing Strategy and through nationwide sampling for 29 PFAS in public drinking water systems; and initiating the distribution of $10 billion in funding to address emerging contaminants under the Bipartisan Infrastructure Law (BIL).
The proposal, if finalized, would regulate PFOA and PFOS as individual contaminants, and will regulate four other PFAS – PFNA, PFHxS, PFBS, and GenX Chemicals – as a mixture.
- PFOA and PFOS: EPA is proposing to regulate PFOA and PFOS at a level they can be reliably measured at 4 parts per trillion.
- PFNA, PFHxS, PFBS, and GenX Chemicals: EPA is also proposing a regulation to limit any mixture containing one or more of PFNA, PFHxS, PFBS, and/or GenX Chemicals. For these PFAS, water systems would use an established approach called a hazard index calculation, defined in the proposed rule, to determine if the combined levels of these PFAS pose a potential risk.
If finalized, the proposed regulation will require public water systems to monitor for these chemicals. It will also require systems to notify the public and reduce PFAS contamination if levels exceed the proposed regulatory standards. EPA anticipates that, if fully implemented, the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses. This action establishes nationwide protection from PFAS pollution for all people, including environmental justice communities.
In February 2023, EPA announced the availability of $2 billion from President Biden’s Bipartisan Infrastructure Law to address emerging contaminants, including PFAS, in drinking water across the country. These funds will promote access to safe and clean water in small, rural, and disadvantaged communities while supporting local economies. EPA requests input on the proposal from all stakeholders, including the public, water system managers, and public health professionals. Comments may be submitted through the public docket, identified by Docket ID No. EPA-HQ-OW-2022-0114.
Colorectal Cancer Rates Rising in Adults Younger than 55
March 9
According to the American Cancer Society, colorectal cancer is the third most commonly diagnosed cancer and the third most common cause of cancer-related death in both men and women in the United States. However, it ranks second in cancer-related deaths overall, and is the leading cause of death in men younger than age 50.
Findings from a new report by the American Cancer Society show that the proportion of individuals diagnosed with advanced-stage colorectal cancer increased from 52% in the mid-2000s to 60% in 2019. The number of people younger than age 55 diagnosed with colorectal cancer doubled from 11% (1 in 10) in 1995 to 20% (1 in 5) in 2019. There was also a shift to left-sided tumors, with the proportion of rectal cancer increasing from 27% in 1995 to 31% in 2019. Racial and ethnic disparities in this cancer continue, with Native Americans, Alaskan Natives, and Black individuals experiencing the highest incidence and mortality rates compared to White patients.
“Dr. Gearhead” Compares Portable EKG Sensors
March 7
Authors of ASA Monitor’s “Dr. Gearhead” column weigh in on ECG/EKG sensors on the current market. This informal discussion compares the capabilities for capturing EKG information from portable devices at home, or whenever a patient may experience symptoms.
Highlighted products include:
- Smart watches (Apple watch, Withings ScanWatch)
- EKG stethoscope (Eko DUO)
- Wearable EKG Patch (Zio Patch)
- Wallet sized EKG devices (Kardia Mobile 6L)
Read this ASA Monitor article to learn which product had the closest correlation with the 12-lead intervals and was most accurate in overall evaluation such as QRS morphology and QTc duration, as well as which has an automatic atrial fibrillation algorithm with the fewest uninterpretable results, and which offers the unique ability to detect heart murmurs.
CDC Issues Alert on Drug-Resistant Shigellosis in the United States
March 2
The Centers for Disease Control and Prevention (CDC) has been monitoring an increase in extensively drug-resistant (XDR) Shigella infections (shigellosis) reported through national surveillance systems. In 2022, about 5% of Shigella infections reported to CDC were caused by XDR strains, compared with 0% in 2015. Clinicians treating patients infected with XDR strains have limited antimicrobial treatment options. Shigella bacteria are easily transmissible. XDR Shigella strains can spread antimicrobial resistance genes to other enteric bacteria. Given these potentially serious public health concerns, the CDC asks health care professionals to be vigilant about suspecting and reporting cases of XDR Shigella infection to their local or state health department and educating patients and communities at increased risk about prevention and transmission.
Shigellosis is an acute enteric infection that is an important cause of domestically acquired and travel- associated bacterial diarrhea in the United States. Shigellosis usually causes inflammatory diarrhea that can be bloody and may also lead to fever, abdominal cramping, and tenesmus. Infections are generally self-limiting; however, antimicrobial treatment may be indicated to prevent complications or shorten the duration of illness. CDC defines XDR Shigella bacteria as strains that are resistant to all commonly recommended empiric and alternative antibiotics — azithromycin, ciprofloxacin, ceftriaxone, trimethoprim sulfamethoxazole (TMP-SMX), and ampicillin. Currently, there is no data from clinical studies of treatment of XDR Shigella to inform recommendations for the optimal antimicrobial treatment of these infections. As such, the CDC does not have recommendations for optimal antimicrobial treatment of XDR Shigella infections.
February 2023
1 in 5 Children/Adolescents Classified with Disordered Eating, JAMA Pediatrics Study Says
February 28
In a worldwide JAMA Pediatrics study published last week, 22% reported that children and adolescents showed disordered eating. The proportion was further elevated among girls, older adolescents, and those with higher body mass index. Disordered eating became more elevated with increasing age and body mass index. This high proportion is worrisome from a public health perspective and highlights the need to implement strategies for preventing eating disorders.
New Stroke Treatment
February 23
Nature recently reported results from two participants in a first-in-human study using electrical stimulation of cervical spinal circuits to facilitate arm and hand motor control in chronic post-stroke hemiparesis. Authors found that continuous stimulation through selected contacts improved strength, kinematics, and functional movements, thereby enabling participants to perform movements that they could not perform without spinal cord stimulation. Both participants retained some of these improvements even without stimulation and no serious adverse events were reported.
Black and Hispanic Patients on Dialysis Have Higher Rates of Staph Bloodstream Infections
February 17
Adults on dialysis treatment for end-stage kidney disease were 100 times more likely to have a Staphylococcus aureus (staph) bloodstream infection than adults not on dialysis during 2017–2020, according to a new Vital Signs report released today by the Centers for Disease Control and Prevention (CDC) (asamonitor.pub/40UyXK8).
More than half of people in the U.S. receiving dialysis belong to a racial or ethnic minority group—about one in every three people receiving dialysis is Black and one in every five is Hispanic. CDC data found patients on dialysis in these groups have higher rates of staph bloodstream infections than White patients on dialysis.
Dialysis treatment, although necessary and lifesaving, comes with risks. Health care providers use needles or catheters to connect a patient to a dialysis machine, and germs, like staph, can get into a patient’s bloodstream. Staph bloodstream infections can be serious and even deadly. Some infections are resistant to some of the most common antibiotics used to treat them, making the drugs ineffective.
CDC data confirmed one of the key ways health care providers can reduce the risk of infection is by using lower-risk alternatives, such as fistulas and grafts, to replace central venous catheters to connect patients’ blood circulation to dialysis machines for treatment.
Hispanic patients on dialysis had a 40% higher risk of staph bloodstream infections than White patients on dialysis between 2017 and 2020. Other challenges for many patients on dialysis include:
- Lack of access to preventive care for conditions like diabetes and high blood pressure, which increase the risk of developing end-stage kidney disease.
- Lack of patient education about treatment options for end-stage kidney disease.
- Extended use of a central venous catheter to connect a patient’s blood circulation to a dialysis machine for treatment (also known as a vascular access type). Catheters have the highest risk of infection among all vascular access types.
- Socioeconomic factors, including poverty, household crowding, and lower education levels.
Moderate or Reduced Alcohol Consumption Reduces Dementia Risk, Study Says
February 9
JAMA (JAMA Netw Open 2023;6:e2254771) recently published a cohort study of 3,933,382 individuals in Korea, maintaining that mild to moderate alcohol consumption was associated with a decreased risk of dementia compared with sustained nondrinking. Sustained heavy drinking of alcohol was associated with an increased risk of dementia. Reduction of drinking from a heavy to a moderate level and initiation of mild drinking were associated with a decreased risk of dementia compared with a sustained level of drinking.
Alcohol consumption level was categorized into none (0 g per day), mild (<15 g per day), moderate (15-29.9 g per day), and heavy (≥30 g per day) drinking. On the basis of changes in alcohol consumption level from 2009 to 2011, participants were categorized into the following groups: nondrinker, quitter, reducer, sustainer, and increaser.
These findings suggest that the threshold of alcohol consumption for dementia risk reduction is low.
January 2023
Weight-loss surgery linked to longer lifespans, study says
January 31
In a recent study, lower all-cause mortality was reported for male bariatric surgery patients as well as female patients when compared with sex-matched non-surgery participants (Obesity (Silver Spring) 2023; 31: 574- 85).
Similar studies have reported lower all-cause mortality among patients who have undergone bariatric surgery when compared with BMI-matched patients who have not undergone bariatric surgery. This study extends follow up to 40 years and includes almost 22,000 surgical patients representing all four major types of bariatric procedures performed today.
This study is important because it confirms decades long durability of bariatric surgery in reducing death from all causes and those related to cardiovascular disease, cancer, and diabetes when compared with matched participants with severe obesity. These findings may not only increase interest in bariatric surgery treatment for patients with severe obesity, but further stimulate important research related to the discovery of physiologic and biomolecular mechanisms leading to nonsurgical treatment that results in weight loss and improved mortality similar to that achieved by bariatric surgery.
Massachusetts Department of Public Health announces first cases of concerning gonorrhea strain
January 27
The Department of Public Health (DPH) announced it has detected a novel strain of gonorrhea in a Massachusetts resident that showed reduced response to multiple antibiotics and another case with genetic markers that indicate a similar drug response (asamonitor.pub/3ZMsmkm). This is the first time that resistance or reduced response to five classes of antibiotics has been identified in gonorrhea in the United States.
Both cases in Massachusetts were successfully cured with ceftriaxone, the antibiotic currently recommended to treat gonorrhea. To date, no direct connection between the two individuals has been identified.
Gonorrhea is a bacterial sexually transmitted infection. It may present without symptoms, and if left untreated, can result in pelvic inflammatory disease, infertility, and other health problems.
This strain of gonorrhea has been previously seen in Asia-Pacific countries and in the United Kingdom, but not in the U.S. A genetic marker common to these two Massachusetts residents was also previously seen in a case in Nevada, though that strain retained sensitivity to at least one class of antibiotics. Overall, these cases are an important reminder that strains of gonorrhea in the U.S. are becoming less responsive to a limited arsenal of antibiotics.
The Massachusetts cases were detected by DPH’s State Public Health Laboratory as part of disease surveillance activities. Field epidemiologists in DPH’s Division of Sexually Transmitted Disease Prevention are conducting contact tracing to determine if other individuals have acquired this infection. Working with the US Centers for Disease Control and Prevention (CDC) and local hospitals and health centers, DPH is expanding its testing of gonorrhea specimens for evidence of this strain in other patients.
DPH has issued an alert to clinicians and laboratories to raise awareness of this new strain. The alert recommends increased use of laboratory culture testing for individuals with symptoms of gonorrhea to detect antibiotic resistance and reminds providers of the process for submission of gonorrhea specimens to the State Public Health Laboratory to support DPH’s and CDC’s surveillance of further resistance in this organism. This alert also reinforces the CDC’s recommendation to use high doses of the antibiotic ceftriaxone for the treatment of all gonorrhea cases and to perform follow-up tests to ensure all patients with gonorrhea are successfully treated.
“The discovery of this strain of gonorrhea is a serious public health concern which DPH, the CDC, and other health departments have been vigilant about detecting in the US,” said Public Health Commissioner Margret Cooke. “We urge all sexually active people to be regularly tested for sexually transmitted infections and to consider reducing the number of their sexual partners and increasing their use of condoms when having sex. Clinicians are advised to review the clinical alert and assist with our expanded surveillance efforts.”
Gonorrhea has been increasing in Massachusetts and nationally, adding to concerns about the potential spread of this strain which is more difficult to treat. In Massachusetts, laboratory-confirmed cases of gonorrhea have increased 312% since a low point of 1,976 cases in 2009 to 8,133 in 2021. Nationally, confirmed cases have risen by 131% between 2009 and 2021, with 696,764 cases reported in the US in 2021 according to preliminary data released by the CDC.
FDA Moves to Simplify Covid Vaccine Schedule and match strains annually
January 24
In recently published guidance, the Food and Drug Administration (FDA) plans to simplify the Covid-19 immunization schedule and periodically update the composition of Covid-19 vaccines as needed. The FDA anticipates conducting an assessment of SARS-CoV-2 strains at least annually and engaging the Vaccines and Related Biological Products Advisory Committee (VRBPAC) in about early June of each year regarding strain selection for the fall season.
Read more in the FDA’s media statement.
FDA approves Tzield to delay onset of stage 3 type 1 diabetes
January 19
The U.S. Food and Drug Administration (FDA) has approved Tzield (teplizumab-mzwv) injection to delay the onset of stage 3 type 1 diabetes in adults and pediatric patients 8 years and older who currently have stage 2 type 1 diabetes. Type 1 diabetes occurs when the immune system attacks and destroys the cells that make insulin. People with a type 1 diabetes diagnosis have increased glucose that requires insulin shots to survive and must check their blood sugar levels regularly. Type 1 diabetes is usually diagnosed in children and young adults but can appear at any age. Tzield binds to certain immune system cells and delays progression to stage 3 type 1 diabetes. Tzield may deactivate the immune cells that attack insulin-producing cells, while increasing the proportion of cells that help moderate the immune response. The safety and efficacy of the drug were evaluated in a randomized, double-blind, event-driven, placebo-controlled trial with 76 patients with stage 2 type 1 diabetes. Patients randomly received Tzield or a placebo once daily via intravenous infusion for14 days. The trial results showed that over an average follow-up of 51 months, 45% of the 44 patients who received Tzield were later diagnosed with stage 3 type 1 diabetes, compared to 72% of the 32 patients who received a placebo. The mid-range time from randomization to stage 3 type 1 diabetes diagnosis was 50 months for the patients who received Tzield and 25 months for those who received a placebo.
Source: asamonitor.pub/3VKd7G0
Major digital health initiative for children and adolescents combines advanced movement tracking and AI
January 12
The World Health Organization (WHO), the Ministry of Public Health of Qatar, and FIFA are launching a digital app designed to help increase physical activity and improve the health and well-being of children and adolescents. GenMove, Season1 is a games app that uses advanced movement tracking and artificial intelligence (AI) technology to provide 8–15-year-olds with a vigorous game experience. The games call for a range of different movements that develop different physical skills and are suitable for children with all levels of fitness.
WHO recommends all children and adolescents get an average of 60 minutes of moderate-intensity aerobic physical activity per day, including activities that strengthen muscles and bones at least 3 times a week. Yet, more than 80% of adolescents do not meet these recommendations and can spend more than 8 hours of their waking day being sedentary and inactive. The app is hoped to spur activeness in children around the world. GenMove games are built around popular sports such as football and involve actions such as jumping, reaching, and kicking to build kids’ confidence and enjoyment of moving. The games can be played inside or outside and need only a mobile phone or tablet (IOS or Android) and a small space to get children active. GenMove Season 1 is available in English, Arabic, Chinese, French, Russian, and Spanish.
Source: asamonitor.pub/3gM1MGF
