Search This Blog

Saturday, February 25, 2023

MI, TX: Not warned of contaminated soil, water shipments from Ohio train wreck

 Michigan and Texas officials are complaining that they were not told in advance about the shipment of contaminated soil and water from East Palestine, Ohio, — where a train derailment earlier this month has caused a public health and environmental crisis — to their states. 

Officials said they had not heard about the plan until after it was already set.

Rep. Debbie Dingell (D-Mich.), who represents the city of Ann Arbor and parts of the highly populated Wayne County in the House, said in a statement on Friday that she learned of the plan from a public update from Ohio Gov. Mike DeWine (R), which said contaminated soil from the site was being moved by truck to U.S. Ecology Wayne Disposal in the town of Belleville. 

“We were not given a heads up on this reported action. Our priority is to always keep the people we represent safe,” she said. 

Dingell said she is reaching out to the Environmental Protection Agency (EPA), Transportation Department (DOT), the train company Norfolk Southern, U.S. Ecology, the state of Ohio and others to learn what is being shipped. She also wants information on whether the facilities were approved to take the shipments, and on ways to keep Michigan residents safe. 

Wayne County Executive Warren Evans also said at a press conference on Friday that he was not notified about the toxic material being sent from the East Palestine site. He said county officials had not been officially informed but heard that trucks were on their way with liquid waste that was to be injected into a site in the Detroit suburb of Romulus and with solid waste set to go to a site in Van Buren Township. 

Evans said some of the shipments had already been delivered. 

“The fact that it’s here, and we haven’t been informed of the volume, we haven’t been informed of how it actually got here — Did it come by truck? Did it come by train? Did those transport vehicles, were they well-equipped to be able to deal with this?” he said. 

“I don’t know how you do that without contacting the local officials so that we can, number one, respond to our communities and, number two, give advice in terms of routes that you may take and those other sorts of things,” he added. 

The Michigan Department of Environment, Great Lakes & Energy (EGLE) said in a statement that the shipments were paused by the EPA following the objections from local officials.

The department said the U.S. Ecology hazardous waste landfill where the shipment was set to go is subject to multiple environmental programs that multiple government agencies carry out, and the department conducts unannounced inspections and “extensive monitoring” of the facility.

“We expect any shipment of Ohio soils and liquids to be handled in accordance with all laws and regulations as any other contaminated site material that is disposed of at the facilities, which are subject to extensive monitoring to ensure that hazardous waste does not present a threat to the environment or human health,” The EGLE statement reads.

Leaders and residents of one Texas county are also expressing concerns about shipments being sent to near their community, as Harris County Judge Lina Hidalgo confirmed that she was told that water used to fight fires at the site in East Palestine would be sent to Deer Park, one of the 34 cities in the county, to be disposed. 

She said she learned about this from a member of the press instead of any regulatory agency or official authority, which she called “unacceptable.” 

Hidalgo claimed the community does not know a lot of information about the situation that it should. She said “that doesn’t mean something is wrong,” but it is worth noting.

The judge added that she has spoken with the waste disposal company receiving the water, several officials at the EPA and DOT and other agencies and experts. 

Hidalgo said government officials have provided the information they have, but they don’t seem to have all of the details. 

I’m not clear on who has the full picture of what is happening here, and that is a problem,” she said. 

Cleanup of the Ohio site where the Norfolk Southern train derailed is continuing weeks after hazardous materials leaked into the air and forced thousands of people to evacuate from the area for about five days. 

State officials had said people could safely return home and use the water, but residents have reported rashes, difficulty breathing and feeling sick along with smelling noxious odors as they have come back. 

Federal officials then began stepping in to conduct their own testing to determine the safety of the area.

https://thehill.com/homenews/state-watch/3874008-michigan-texas-officials-complain-they-werent-warned-of-contaminated-soil-water-shipments-from-ohio-train-wreck/

Did U.S. Firms Help Propel China’s Balloon Fleet?

 by Susan Crabtree via RealClear Wire,

Sen. Mark Kelly, who previously served as a decorated space shuttle pilot with NASA, waded into the Chinese spy balloon uproar early this week after keeping publicly mum about it for several weeks.

What Next After Early End of MOSAICO HIV Vaccine Trial?

 The abrupt and early end of the MOSAICO HIV vaccine trial

opens in a new tab or window, announced last month, was the topic of a special session at the Conference on Retroviruses and Opportunistic Infectionsopens in a new tab or window here.

Results of the 3,800-participant trial were negative, with an identical 113 individuals in the vaccine regimen and placebo groups becoming infected with HIV in just under 2 years (incidence of 4.1 per 100 person-years), reported Susan Buchbinder, MD, of the San Francisco Department of Public Health and co-chair of the HIV Vaccine Trials Network. She noted that infection was highest among young people ages 18-20.

"No safety issues with the vaccine regimen were identified, but the regimen was not efficacious in preventing HIV acquisition," said Buchbinder.

"We learned," said Lawrence Corey, MD, of Fred Hutchinson Cancer Research Center in Seattle and principal investigator of the HIV Vaccine Trials Network. "We're not going to go down that road anymore. It's time to try another route," he told MedPage Today in an interview. "It didn't fail. We got a result that we didn't like."

Rather than working on inducing non-neutralizing antibodies, research now will focus on delivering more potent broadly neutralizing HIV-1 antibodies (bnAb), Corey said. His new mantra, inspired by Yogi Berra, he said, is to concentrate on the positive: "When there's a fork in the road, take it."

"The HIV virus has set up an amazing array of diversionary strategies," Corey said. "Making an HIV vaccine is scientifically hard -- likely the hardest antibody-mediated vaccine in the virologic world."

But there's no doubt a vaccine is needed: "The reality is we've never controlled a disease in a population without a vaccine. We're not going to give a hundred million people long-acting antiretrovirals for 10 years during their most highest-risk sexual time," he said.

Protecting against HIV will require a vaccine with sequential vaccination, Corey explained. "Unlike the COVID-19 vaccine, which has essentially the same immunogen in each shot, the HIV vaccine will be done in sequence." It will start with a germline priming shot, then "shepherding" of memory B cells, boosting and polishing them, and then a final step with plasma cells that secrete broadly neutralizing antibodies, he said.

Several phase I trials are investigating possible avenues of such research, including one that has made headway in germline priming, including mRNA-1644opens in a new tab or window, which is evaluating the safety and immunogenicity of the eOD-GT8 60mer mRNA vaccine as a "germline-targeting" immunogen.

MOSAICO involved the use of a tetravalent intramuscular vaccine candidate -- adenovirus serotype 26 Mosaic4 human immunodeficiency virus (Ad26.Mos4.HIV) -- given alone first, and then combined with a Clade C and Mosaic gp140 HIV bivalent vaccine.

"This was a valiant attempt to look at a Mosaic immunogen to try to counter the diversity of HIV, by inducing non-neutralizing antibodies," said Katharine Bar, MD, director of the Virology Core at Penn Center for AIDS Research in Philadelphia. "I think we now have another piece of evidence that non-neutralizing antibodies are not going to be broadly protective against HIV acquisition."

"Even though it's a novel approach to responding to a diverse range of viruses, it still was aiming for non-neutralizing antibodies," she told MedPage Today. "It's really challenging, but there are multiple approaches for iterative bnAb development, where we're taking focused immunogens that have just the specific epitope we're looking to generate an antibody against, and they're targeting specific B cells. The hope is that with this process, we can prime the right B cells to make very specific broadly neutralizing antibody lineages, and through these multiple attempts at the same concept, we can hopefully start inducing broadly neutralizing antibodies -- i.e., antibodies that neutralize the virus, not just bind [to it] -- and antibodies that are able to target a range of viruses across circulating variants."

"We know it's a big task, but [it's] informed by good rationale," Bar said.

Although it has taken 30 years to get to this point, the next series of phase I studies are already showing promise to stimulate the right B cells and start the process of generating these early antibody precursors, she continued. "There's promise in this field, but it is still a really daunting task. At least the end goal for these bnAb vaccines is something we believe to be effective. We just have to ... find a pathway. We have to figure out how to get through those multiple steps."

Corey predicted it will take about 5 years to determine how to construct an effective vaccine, after which trials need to be done.

"I think in a decade we can have an effective HIV vaccine," he said.

The multisite, multinational MOSAICO trial enrolled 3,800 cisgender men and transgender individuals (ages 18-60) at risk for HIV. Participants came from Argentina, Spain, Peru, Mexico, Brazil, the U.S., and other countries. They were randomized 1:1 to placebo or the vaccine regimen, with Ad26.Mos4.HIV given via intramuscular injection at day 1 and at 3 months, and then combined with the Clade C and Mosaic gp140 HIV bivalent vaccine intramuscularly at months 6 and 12.

A total of 99.6% of the participants were male at birth, 91.5% were male at screening, and the rest identified as transgender, gender queer, female, or gender variant. Most (86.6%) were Hispanic or Latino.

A unique feature of the trial, said Buchbinder, was that during recruitment all potential participants were given information about PrEP, and could opt for PrEP services instead of participating in the trial. Once in the trial, participants could switch to PrEP and remain in the trial.

"Despite ongoing risk reduction counseling and linkage to PrEP [pre-exposure prophylaxis], HIV incidence, particularly in young participants in Latin America, was very high," she said. "This is a population in great need of additional effective HIV prevention modalities."

Disclosures

Buchbinder reported relationships with Gilead Sciences and ViiV Healthcare.

Corey disclosed no financial relationships.

Primary Source

Conference on Retroviruses and Opportunistic Infections

Source Reference: opens in a new tab or window"Results from the MOSAICO HIV vaccine trial and future directions for HIV vaccines" CROI 2023; Special Session SS-1.


https://www.medpagetoday.com/meetingcoverage/croi/103269

What Clinicians Need to Know About Loperamide Misuse

 Loperamide, the active ingredient in Imodium, is readily available in over-the-counter (OTC) anti-diarrheal agents that are safe when used as directed. Sources have reported cases of people misusing extreme high doses of loperamide to act as an opioid substitute or to self-manage their opioid withdrawal, which can come with serious health risks.

Through my work as the assistant clinical director at the Upstate New York Poison Center, I was involved in 2012 in the second-known reported caseopens in a new tab or window of loperamide-induced cardiac toxicity and published the first case series of patients with ventricular arrhythmias in connection with loperamide misuse. In the years following, poison control centers and medical examiners saw an increased number of cases with toxicity and death due to high doses of loperamide; however, recent poison center data shows a slight decrease in the number of casesopens in a new tab or window.

It is promising that the number of loperamide cases have declined, however, deaths from opioids remain a public health crisis. The CDC reported a 31% increase

opens in a new tab or window in drug overdose mortality from 2019 through 2020 with these numbers expected to continue to rise. Tragically, in the 12 months ending in April 2021, more than 100,000 people diedopens in a new tab or window from drug overdoses, with more than 70,000 deaths due to synthetic opioids, specifically fentanyl. Despite increased efforts towards harm reduction, resources are still unavailable for many. With that, some may turn to alternative opioid substitutes -- and clinicians need to be aware of these agents.

Let's discuss why healthcare providers need to be aware of cardiac toxicity from loperamide misuse and current initiatives designed to help mitigate misuse and abuse.

Pharmacology of Loperamide

First made available in the U.S. as an OTC product in the late 1980s, loperamide was considered to be free of abuse potentialopens in a new tab or window despite being a mu opioid receptor agonist. At therapeutic doses, loperamide has limited oral bioavailability (<1%) and does not cross the blood-brain barrier. Loperamide is structurally similar to haloperidol (Haldol) and methadone. Although it is an opioid agonist, doses of up to 16 mg do not cause central opioid effects in adults. If taken concurrently with a P-glycoprotein inhibitor or in excessive dosing, opioid effects do occur.

review

opens in a new tab or window of the FDA MedWatch system from 1976 through December 2015 described 48 casesopens in a new tab or window of loperamide abuse with serious cardiac events and 10 deaths with a median daily dose of 250 mg (range: 70 mg–1,600 mg). The cardiac toxicity typically occurs with chronic dosing rather than acute overdose.

At high plasma concentrations, loperamide and its metabolite, n-desmethyl-loperamide, interfere with cardiac conduction by blocking both sodium and potassium channels, resulting in widening of the QRS complex and the QT interval and subsequent ventricular arrhythmias. There also have been reports of bradycardiaopens in a new tab or window that suggest a direct myocardial depressant effect.

Efforts to Mitigate Loperamide Misuse

In 2016, the FDA released a warningopens in a new tab or window about the risks of cardiac toxicity and death after supratherapeutic dosing. In addition, in 2018, FDA and the OTC medicine industry announced packaging limits on solid forms of OTC loperamide. The products can only be sold in unit-dose blister packages and in no more than a maximum of 24 tablets (48 mg). Liquid products are still sold in 4- and 8-oz sizes, with no more than 32 mg of loperamide in 8 oz.

The Consumer Healthcare Products Association (CHPA) formed a national advisory board with multiple experts, including myself and other healthcare providers, FDA, pharmaceutical companies, patients, and advocates. Through this work, CHPA developed a national campaign to educate

opens in a new tab or window healthcare providers and at-risk patients about loperamide abuse and misuse.

The exact incidence of ongoing loperamide misuse is impossible to quantify. Fortunately, cases of loperamide toxicity in the literature appear to have declined since 2020 and the National Poison Data Center has reported declines in intentional loperamide exposures every year since 2017. Anecdotally, calls to my poison center have decreased since 2020.

The Role of Clinicians and Health Systems

There is no specific antidote for patients with loperamide-induced cardiac toxicity, and the mainstay of care is supportive care. For patients with life-threatening arrhythmias, standard advanced cardiac life support management should be employedopens in a new tab or window. Sodium bicarbonate at doses of 1-2 meq/kg IV bolus may be considered. However, close monitoring of serum potassium is needed because hypokalemia may worsen QT prolongation.

Deaths from drug overdose, the majority of which involve opioids, is a public health crisis. Harm reduction measures, including access to medications for opioid use disorder, need to be readily available and accessible. Clinicians should consider loperamide in the differential diagnosis in patients with opioid use disorder and unexplained syncope or an abnormal electrocardiogram. Clinicians should share the dangers of loperamide misuse and abuse with vulnerable patients, their families, and all members of the healthcare team. For any potential case of loperamide toxicity, call the regional poison center at 1-800-222-1222.

Jeanna M. Marraffa, PharmD, MPH,opens in a new tab or window is the assistant clinical director of the Upstate New York Poison Center and a clinical professor in the Department of Emergency Medicine at Upstate Medical University, University Hospital in Syracuse, New York. She currently serves as president-elect for the American Academy of Clinical Toxicology.

https://www.medpagetoday.com/opinion/second-opinions/103217

Sublingual Immunotherapy Appears Viable in Treating Peanut Allergies in Kids

 Peanut sublingual immunotherapy (SLIT) achieved clinically significant desensitization to peanut allergens in the majority of children in an open-label, prospective study.

Among 47 kids who completed therapy and the 48-month double-blind, placebo-controlled food challenge, 70% achieved clinically significant desensitization (successfully consumed dose [SCD] >800 mg), and 36% achieved full desensitization (SCD 5,000 mg), reported Edwin H. Kim, MD, MS, of the University of North Carolina School of Medicine in Chapel Hill, and co-authors.

The mean SCD of peanut protein during the food challenge increased from 48.4 mg at baseline to 2,723 mg after 48 months (P<0.0001), and desensitization lasted more than 17 weeks following treatment discontinuation, they noted in the Journal of Allergy and Clinical Immunology

opens in a new tab or window.

As of 2021, it has been estimatedopens in a new tab or window that about 4.6 million adults in the U.S. have some form of peanut allergy, with 800,000 having developed the allergy during adulthood. Approximately 200,000 people in the U.S.opens in a new tab or window are sent to the emergency department following a food-related allergic reaction each year.

"The typical approach of strict allergen avoidance has been shown to greatly reduce the frequency of allergic reactions; however, over time most patients experience accidental ingestions with unpredictable and sometimes severe symptoms," Kim and team wrote. "Furthermore, strict allergen avoidance has led to the unintended consequence of a significant decrease in quality of life driven by factors such as anxiety, social isolation, restricted daily activities, and financial burden. Immunotherapy has been the best studied approach to treatment with numerous positive studies of oral immunotherapy (OIT) leading to the recent regulatory approval of the first product for peanut OIT."

In the study, peanut skin prick testing for the per-protocol population was significantly decreased by 12 months of treatment and remained this way over the course of treatment, from a mean wheal size of 16.5 mm at baseline to 9.1 mm after 48 months (P<0.0001).

Peanut-specific immunoglobulin E levels had significantly decreased by 24 months and through the duration of treatment, from a mean baseline level of 213.0 kUA/L to 60.7 kUA/L after 48 months (P<0.0001), following an initial increase from baseline to 6 months. Peanut-specific immunoglobulin G4, however, increased from an average of 0.8 mg/L at baseline to an average of 20.6 mg/L after 48 months (P<0.0001).

Mean percentage of CD63+ basophils decreased from baseline at both the 10 ng/mL dilution, which was significant throughout the 48 months, and the 1 ng/mL dilution, which was significant at the 24- and 48-month time points.

TH2 cytokine levels after peanut stimulation also decreased over time, with average IL-4, IL-5, IL-13, and IFN-gamma levels significantly reduced over 48 months.

"With the goal of peanut allergy treatment increasingly focused on protection from accidental ingestions of peanut, our data for peanut SLIT supports a treatment response in the majority of patients that importantly appears to be able to withstand lapses in therapy of up to several weeks," Kim and colleagues wrote.

"When considering that tolerance does not appear likely with food immunotherapy and that treatment is likely to be required long-term if not indefinitely, these results demonstrating the feasibility and safety of keeping up the daily peanut SLIT regimen for multiple years take on particular importance," they added.

For this study, 54 peanut-allergic children ages 1 to 11 years (mean age 7.1, 63% boys, 90.7% white) were treated with open-label 4-mg peanut SLIT for 48 months, and 47 completed therapy. At baseline, 70.4% of children reported atopic dermatitis, 59.3% reported allergic rhinitis, 40.7% reported asthma, and 27.8% reported other food allergies. Dosing compliance was high, with 97.6% of doses administered.

Desensitization after SLIT was assessed by a 5,000-mg double-blind, placebo-controlled food challenge. A randomly assigned avoidance period between 1-17 weeks was followed by a food challenge. Skin prick testing, immunoglobulins, basophil activation testing, TH1, TH2, and IL-10 cytokines were measured longitudinally. Safety was assessed through patient-reported diaries.

Symptoms were reported after 4% of home-administered doses. Lip swelling and oropharyngeal itching were the most common symptoms, occurring with 3.7% of doses. Belly pain, vomiting, diarrhea, and skin symptoms were reported with 0.1% of doses. Three participants withdrew as the result of abdominal reactions or food aversion. While 0.14% of the administered doses required the use of antihistamines, epinephrine was not given at any point during the course of the study.

Kim and team noted that there was no blinding of the treatment or avoidance phases of the study, which was a limitation. Children can also "spontaneously outgrow" a peanut allergy, though the authors said this was unlikely in their cohort.

Disclosures

This study was supported by funding from the National Institutes of Health and the National Center for Advancing Translational Sciences.

Kim reported relationships with ALK-Abello, DBV Technologies, Kenota Health, Ukko, AllerGenis, Allergy Therapeutics, Belhaven Biopharma, Duke Clinical Research Institute, Genentech, and Nutricia. He also reported receiving grant support to his institution from the National Institute of Allergy and Infectious Diseases and Food Allergy Research & Education.

Co-authors reported multiple relationships with industry and government organizations.

Primary Source

Journal of Allergy and Clinical Immunology

Source Reference: opens in a new tab or windowKim EH, et al "Open-label study of the efficacy, safety and durability of peanut sublingual immunotherapy in peanut-allergic children" J Allergy Clin Immunol 2023; DOI: 10.1016/j.jaci.2023.01.036.

https://www.medpagetoday.com/allergyimmunology/allergy/103271

Extensively Drug-Resistant Shigellosis on the Rise in the U.S.

 Healthcare professionals should be on the lookout for an increase in extensively drug-resistant (XDR) Shigella infections (shigellosis) and should report cases to local or state health departments, the CDC said in a health advisory Friday

opens in a new tab or window.Given that Shigella bacteria are easily transmissible (through as few as 10-100 organisms) and antimicrobial treatment options are limited, the agency also asked healthcare providers to educate patients and communities at increased risk about prevention and transmission.

Historically, the infection has been most common in children ages 1 to 4 years in the U.S., but the CDC has reported a rise in antimicrobial-resistant Shigella infections among men who have sex with men, people experiencing homelessness, international travelers, and people with HIV in recent years

opens in a new tab or window

The agency detected a recent rise in XDR Shigella infections through national surveillance systems, with 5% of infections caused by XDR strains in 2022, up from 0% in 2015. From 2015 to Jan. 22, 2023, CDC has received reports of 239 XDR Shigella isolates.

Among the recent infections, median age of patients was 42 years. Of the 232 patients with available information, 82% were men, 13% were women, and 5% were children. Of the 41 patients who provided information about recent sexual activity, 88% reported male-to-male sexual contact.

This acute enteric infection can cause "inflammatory diarrhea that can be bloody and may also lead to fever, abdominal cramping, and tenesmus," the agency noted.

XDR strains can also spread antimicrobial resistance genes to other enteric bacteria, adding to the "potentially serious public health concerns," the CDC said.

Healthcare professionals should consider shigellosis in the differential diagnosis of acute diarrhea, especially in patients at higher risk, and should ask patients about relevant exposures and social history, including sexual history and travel.

Shigella bacteria are transmitted by the fecal-oral route, person-to-person contact including sex, and through contaminated food and water. The CDC said patients with shigellosis should stay home; abstain from sex; wash hands often, especially around sexual activity; not prepare food for others; and stay out of recreational water.

"Currently, there are no data from clinical studies of treatment of XDR Shigella to inform recommendations for the optimal antimicrobial treatment of these infections," the agency wrote. "As such, CDC does not have recommendations for optimal antimicrobial treatment of XDR Shigella infections."

XDR Shigella bacteria are resistant to azithromycin, ciprofloxacin, ceftriaxone, trimethoprim-sulfamethoxazole, and ampicillin.

According to the CDC's National Antimicrobial Resistance Monitoring Systemopens in a new tab or window, which shows predicted antimicrobial resistance based on preliminary data, Shigella isolates tested in 2023 with the most resistance to ciprofloxacin are concentrated in Washington state, and, to a lesser extent, Utah and New Mexico.

While most patients recover from shigellosis without treatment with antimicrobials, the CDC recommended antimicrobial susceptibility testing to guide antimicrobial treatment selection when needed. Though options for XDR shigellosis are lacking in the U.S., a U.K. study

opens in a new tab or window suggested a potential strategy of oral pivmecillinam (not commercially available in the U.S.) and fosfomycin, or IV carbapenems and colistin.

https://www.medpagetoday.com/infectiousdisease/generalinfectiousdisease/103275