Bavarian Nordic is abandoning its Covid-19 booster vaccine after Phase III results — even though it did hit the primary endpoint of the study — because it’s not as effective against newer variants of the virus.
Friday, September 1, 2023
Post-COVID Cognitive Deficits Linked With Clotting Proteins
Two distinct blood biomarker profiles predicted cognitive deficits 6 and 12 months after COVID-19, prospective U.K. data showed.
Both biomarker profiles featured proteins involved in coagulation, reported Maxime Taquet, PhD, of the University of Oxford in England, and co-authors in Nature Medicine.
Among 1,800 patients hospitalized for COVID-19 during the first wave of the pandemic, a blood profile that included high levels of fibrinogen correlated with both objective and subjective cognitive deficits. A second profile linked elevated D-dimer relative to C-reactive protein (CRP) with subjective cognitive deficits and occupational impact, which was partly mediated by fatigue and shortness of breath.
The results could not be explained by cognitive problems preceding the infection, nor by depression or anxiety, the researchers noted. The D-dimer relationship appeared specific to COVID infection, whereas high fibrinogen was a risk factor for cognitive deficits, regardless of the cause.
The findings provide a clue about one mechanism that might cause post-COVID cognitive deficits, Taquet told MedPage Today. "The observation that raised levels of fibrinogen and D-dimer relative to CRP levels are associated with later cognitive deficits suggests that hypercoagulation is likely to be involved," he said.
"Subsequent analyses and interpretations in our research suggest three potentially distinct mechanisms," Taquet added. "One involves blood clots in the brain directly affecting cognition; another relates to the direct effect of fibrinogen on the brain; and a third one involves blood clots in the lungs [that] might lead to subsequent hypoxia or fatigue, which can have cognitive manifestations."
Brain fog and other cognitive problems often persist after COVID -- especially among patients hospitalized with acute SARS-CoV-2 infection
-- but how and why they develop remain unknown.
Cognitive deficits appear to occur more frequently after COVID than other respiratory tract infections, Taquet noted. "In one of our studies, we showed they were 36% more common," he said. While they're less common after other infections, it's possible that mechanisms are similar: "COVID-19 may serve as a window into the possible brain consequences of respiratory infections," he suggested.
Taquet and colleagues studied 1,837 patients in the PHOSP-COVID cohort who had been hospitalized for COVID-19 in the U.K. between January 2020 and November 2021. Mean age was 58, and 37% were women.
The researchers used canonical correlation analysis to find covariation patterns between a set of six blood biomarkers measured on admission to hospital (CRP, D-dimer, fibrinogen, lymphocyte, and neutrophil and platelet counts) with a set of cognitive scores measured 6 and 12 months later. Cognitive scores included components of the Montreal Cognitive Assessment (MoCA) to assess objective deficits and cognitive items from the Patient Symptom Questionnaire (C-PSQ) to gauge subjective deficits.
In a subset of patients with C-PSQ scores before and after SARS-CoV-2 infection, subjective cognitive function declined at 6 and 12 months on average. High fibrinogen or high D-dimer levels relative to CRP were not more common in people with pre-existing cognitive deficits.
The researchers reproduced their analysis using electronic health records from a network of 57 healthcare organizations primarily in the U.S., and found that acute D-dimer level was significantly associated with post-COVID cognitive changes. Acutely raised fibrinogen level also was linked with post-COVID cognitive deficits.
The findings are limited to people who had COVID-19 in the first wave and who were ill enough to have been hospitalized, Taquet and colleagues emphasized. Blood samples were assessed only at the time of acute infection. Mechanisms are speculative, and further studies are needed to better delineate them, the researchers acknowledged.
"We're excited to see whether and how our findings will inform future research into possible treatments, which people currently living with post-COVID cognitive deficits urgently need," Taquet said.
Disclosures
This work was funded by MQ Mental Health Research, the Wolfson Foundation, UK Research and Innovation, National Institute of Health Research, and the National Institute for Health and Care Research Oxford Health Biomedical Research Centre.
The authors declared no competing interests.
Primary Source
Nature Medicine
Source Reference: Taquet M, et al "Acute blood biomarker profiles predict cognitive deficits 6 and 12 months after COVID-19 hospitalization" Nat Med 2023; DOI: 10.1038/s41591-023-02525-y.
Extreme dietary habits for carbohydrates and fats affect life expectancy
A new study, published in The Journal of Nutrition, suggests that extreme dietary habits involving carbohydrates and fats affect life expectancy. Researchers from Nagoya University Graduate School of Medicine in Japan led by Dr. Takashi Tamura found that a low carbohydrate intake in men and a high carbohydrate intake in women are associated with a higher risk of all-cause and cancer-related mortality and that women with higher fat intake may have a lower risk of all-cause mortality. Their findings suggest that people should pursue a balanced diet rather than heavily restricting their carbohydrate or fat intake.
While low-carbohydrate and low-fat diets are becoming popular as a way to promote weight loss and improve blood glucose levels, their long-term effects on life expectancy are less clear. Interestingly, recent studies conducted in Western countries suggest that extreme dietary habits for carbohydrates and fats are associated with a higher risk of mortality. However, few studies have explored these associations in East Asian populations, including Japanese individuals who typically have relatively low fat and high-carbohydrate dietary intakes.
The authors conducted a follow-up survey over a period of 9 years with 81,333 Japanese people (34,893 men and 46,440 women) to evaluate the association between carbohydrate and fat intakes and the risk of mortality. Daily dietary intakes of carbohydrates, fats, and total energy were estimated using a food frequency questionnaire and calculated as a percentage of total energy intake for carbohydrates and fats. Carbohydrate intake quality (i.e., refined compared with minimally processed carbohydrate intake) and fat intake quality (i.e., saturated compared with unsaturated fat intake) were also assessed to examine the impact of food quality on the association with mortality.
They found that men who consumed less than 40% of their total energy from carbohydrates experienced significantly higher risks of all-cause and cancer-related mortality. The trend was observed regardless of whether refined or minimally processed carbohydrate were considered. On the other hand, among women with 5 years or longer of follow-up, those with a high carbohydrate intake of more than 65% had a higher risk of all-cause mortality. No clear association was observed between refined or minimally processed carbohydrate intake and the risk of mortality in women.
For fats, men with a high fat intake of more than 35% of their total energy from fats had a higher risk of cancer-related mortality. They also found that a low intake of unsaturated fat in men was associated with a higher risk of all-cause and cancer-related mortality. In contrast, total fat intake and saturated fat intake in women showed an inverse association with the risk of all-cause and cancer-related mortality. They concluded that this finding does not support the idea that high fat intake is detrimental to longevity in women.
“The finding that saturated fat intake was inversely associated with the risk of mortality only in women might partially explain the differences in the associations between the sexes,” Dr. Tamura stated. “Alternatively, components other than fat in the food sources of fat may be responsible for the observed inverse association between fat intake and mortality in women.”
This study is extremely important because restricting carbohydrates and fats, such as extremely low-carbohydrate and low-fat diets, are now popular dieting strategies aimed at improving health, including the management of metabolic syndrome. However, this study shows that low-carbohydrate and low-fat diets may not be the healthiest strategy for promoting longevity, as their short-term benefits could potentially be outweighed by long-term risk.
Overall, an unfavorable association with mortality was observed for low-carbohydrate intake in men and for high carbohydrate intake in women, whereas high fat intake could be associated with a lower mortality risk in women. The findings suggest that individuals should carefully consider how to balance their diet and ensure that they are taking in energy from a variety of food sources, while avoiding extremes.
Dr. Takashi Tamura, the lead researcher of this study
Credit: Department of Preventative Medicine, Nagoya University Graduate School of Medicine
The study, "Dietary carbohydrate and fat intakes and risk of mortality in the Japanese population: the Japan Multi-Institutional Collaborative Cohort Study," has been published in The Journal of Nutrition at DOI: 10.1016/j.tjnut.2023.05.027.
Authors:
Takashi Tamura, Kenji Wakai, Yasufumi Kato, Yudai Tamada, Yoko Kubo, Rieko Okada, Mako Nagayoshi, Asahi Hishida, Nahomi Imaeda, Chiho Goto, Hiroaki Ikezaki, Jun Otonari, Megumi Hara, Keitaro Tanaka, Yohko Nakamura, Miho Kusakabe, Rie Ibusuki, Chihaya Koriyama, Isao Oze, Hidemi Ito, Sadao Suzuki,, Hiroko Nakagawa-Senda, Etsuko Ozaki, Daisuke Matsui, Kiyonori Kuriki, Keiko Kondo, Naoyuki Takashima, Takeshi Watanabe, Sakurako Katsuura-Kamano, and Keitaro Matsuo; for the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study
https://www.nagoya-u.ac.jp/researchinfo/result-en/2023/09/20230901-01.html
Why breast cancer survivors don’t take their meds
For roughly 80% of breast cancer survivors, treatment doesn’t end with surgery, radiation and chemotherapy. Instead, for the next five to 10 years, doctors recommend that they take medication to block sex hormones, which can fuel tumor growth and spark recurrence.
The drugs, no doubt, are life-saving: They’ve been shown to cut risk of cancer recurrence by as much as half in patients with hormone receptor-positive tumors (HR+)—the most common form of breast cancer. Yet despite their promised benefits, 40% of patients stop taking them early and a third take them less frequently than directed.
New CU Boulder research, published this month in the “Journal of Clinical Oncology,” sheds light on why that is and what doctors and the health care system can do about it.
It found that, overall, interventions can increase medication adherence by nearly 1.5 times. But some strategies work better than others.
“Our bottom-line finding is that there are strategies that do work in supporting women to take these life-extending medications, and that we as a cancer care community need to do better,” said senior author Joanna Arch, a professor in the Department of Psychology and Neuroscience and member of the CU Cancer Center on the Anschutz Medical Campus.
Arch noted these so-called “adjuvant endocrine therapies,” like the estrogen-blockers Tamoxifen and aromatase inhibitors, can be costly and come with a host of side effects, including weight gain, sexual side effects, joint pain, depression and sleeplessness.
“Imagine going from your normal estrogen activity to little or no estrogen within days. That’s what these medications do,” she said. “But the women who take them as prescribed also have lower recurrence rates and live longer. It’s a dilemma.”
As more next-generation cancer drugs, including chemotherapy agents, shift from infusions provided in a clinic to oral therapies taken at home, the medical community has grown increasingly interested in developing ways to make sure patients take their pills.
In a sweeping meta-analysis, Arch and her colleagues analyzed 25 studies representing about 368,000 women to gain insight into what works and what doesn’t.
Educational pamphlets are not enough
The study found that cost-cutting policy changes, such as providing generic alternatives or requiring insurance companies to cover pills at the same level as infusions, consistently worked. Such “oral parity laws” have been passed in 43 states in recent years.
In one study, participants were asked to create stickers to put on their pill boxes.
Mobile apps and texts to remind patients to take their medication and psychological/coping strategies also yielded modest improvements.
The study’s findings around managing side effects were complicated: Simply educating women on side effects, via pamphlets or verbal explanations, generally failed to increase the likelihood that women took their medication as directed.
But things such as physical therapy, exercise and behavioral counseling aimed at alleviating or managing side effects often worked.
“Education in and of itself is not enough. That is a clear finding,” said Arch, suggesting that doctors write referrals to practitioners who specialize in side effects and follow up with appointment reminders. “Most oncologists, I believe, don’t realize how low adherence is for these women. They assume that if they write the prescription, it’s being taken.”
Addressing mental health is key
One study included in the meta-analysis was Arch’s own.
In it, women were asked to identify their primary motivation for taking their medication—whether it was living to see their child or grandchild grow up, pursuing their art or running a marathon someday. Via an online program, they created a sticker with a photo representing that goal, and the words “I take this for…” below it. Then, they stuck it on their pill box.
Participants were more likely to take their pills, at least for the first month, than those who didn’t.
“Even just a tiny thing like this can help,” said Arch.
Notably, very few studies looked at whether treating depression can help. Arch, aiming to fill this gap, recently launched her own pilot trial.
“One of the most consistent predictors of not adhering to any medication is depression,” she said. “Depression taps motivation.”
The new “Journal of Clinical Oncology” study is the first meta-analysis to show that interventions can be helpful, and that’s important, said Arch, because insurance companies need data to make decisions about what to cover.
But the study also showed that the effects are relatively modest and that there is room for improvement.
Arch said she hopes the study will spark more research into novel ways to support survivors:
“We have a lot of work to do.”
U.S. Unveils First 10 Drugs for Medicare Price Negotiations
The Centers for Medicare & Medicaid Services (CMS) took a historic step forward in its plans to negotiate the prices of Medicare's most costly prescription drugs by naming the first 10
up for negotiation on Tuesday.
The list of drugs to be negotiated includes:
- Apixaban (Eliquis): a blood thinner used to prevent stroke and blood clots
- Empagliflozin (Jardiance): a drug used to treat type 2 diabetes and heart failure
- Rivaroxaban (Xarelto): a blood thinner used to treat and prevent blood clots and reduce risks for patients with coronary or peripheral artery disease
- Sitagliptin (Januvia): a drug for treating type 2 diabetes
- Dapagliflozin (Farxiga): a drug for treating type 2 diabetes, heart failure, and chronic kidney disease
- Sacubitril/valsartan (Entresto): a drug for patients with chronic heart failure
- Etanercept (Enbrel): a drug for moderate to severe rheumatoid arthritis
- Ibrutinib (Imbruvica): a drug that is used to treat chronic lymphocytic leukemia/small lymphocytic lymphoma
- Ustekinumab (Stelara): a biologic that treats Crohn's disease, ulcerative colitis, psoriasis, and psoriatic arthritis
- Insulin aspart injection (NovoLog, among others): a drug for patients with diabetes mellitus
A 2003 law that expanded Medicare's prescription drug coverage also blocked CMS from negotiating drug prices. Under the landmark 2022 Inflation Reduction Act (IRA), CMS gained that authority for the first time.
"Today, my administration announced the first 10 Medicare Part D drugs that have been selected for price negotiation -- for the first time ever," Biden said. "We've reached this milestone because of the Inflation Reduction Act -- one of the most significant laws ever enacted, and one that passed with the leadership of Democrats in Congress."
Once implemented, the negotiated prices will lower costs for up to 9 million seniors, currently paying up to $6,497 in out-of-pocket costs annually for their medications, the president noted.
On top of the savings for seniors, the Congressional Budget Office estimates that the combined negotiation provisions and inflation rebate provisions of the IRA -- drugmakers must pay rebates to the federal government if they hike their prices above the level of inflation -- will save taxpayers $160 billion through reductions to Medicare spending.
The negotiations are slated to begin in 2023 and continue in 2024. Negotiated prices would then take effect at the start of 2026. Already, pharmaceutical companies and other industry players have filed as many as eight lawsuits to try to block or delay the negotiations from advancing, and more are expected.
The First Drugs Chosen for Negotiation
The 10 drugs chosen by CMS -- single-source brand-name drugs with no therapeutically equivalent generic or biosimilar competition -- were targeted for negotiation based on their total expenditures in the Medicare Part D program. These drugs are either costly, widely used, or both.
In terms of total Medicare Part D costs over the last year (June 2022 to May 2023), apixaban cost the most, at $16.5 billion for the 3.7 million enrollees taking the medication (total cost of $4,448 per enrollee). This was followed by empagliflozin ($7.1 billion), rivaroxaban ($6.0 billion), and sitagliptin ($4.1 billion).
The highest cost per enrollee went to ibrutinib ($133,178, with 20,000 enrollees over the previous year), followed by ustekinumab ($119,951, with 22,000 enrollees), and etanercept ($58,148, for 48,000 enrollees).
To be eligible for negotiation, drugs must be 7 years out from their FDA approval or licensure date for small-molecule drugs, or 11 years out for biologics, as of the date that the selected drugs list is published.
Senior administration officials, who spoke on background during a press call on Tuesday morning, said CMS "selected the 10 highest-spending drugs that qualify under the process that was described in the statute and the CMS program instruction."
The agency first identified the qualifying drugs under Medicare Part D as having been on the market for 7 to 11 years without competition, an official explained. Some drugs were excluded, including certain orphan drugs, low-spend drugs, or plasma-derived products.
"From there, we identified and ranked the top 50 qualifying single-source drugs with the highest gross costs to Medicare Part D, to determine the list of negotiation-eligible drugs ... and then finally from that, CMS selected the 10 highest-ranked negotiation-eligible drugs," the official said.
For the most part, experts said they anticipated that most of the drugs selected would be up for negotiation.
There were a "couple surprises," however, said Kelsey Lang, a principal in health policy at Avalere, a healthcare consulting firm based in the Washington, D.C.-Baltimore area. She attributed discrepancies between experts' predictions and the agency's list to differences in the data used in each of their analyses.
Dapagliflozin, sacubitril/valsartan, and ustekinumab seem to have jumped in spending, based on public data, which made them eligible for negotiation, she told MedPage Today in a phone interview during which a press representative was present.
Richard Frank, PhD, a senior fellow and director of the Brookings Schaeffer Initiative on Health Policy at the Brookings Institution, noted that "there are a bunch of drugs that have been on the market for a long time that have carried super high prices and have made tons of money, and I think those are the candidates where you can give taxpayers and consumers a real break, without really threatening the profitability of the product."
Apixaban has had global sales of $91 billion since it launched in 2013, he said. Even factoring in the cost of development -- roughly $3.5 billion -- there is still a significant amount of money to be made, he pointed out.
Adalimumab (Humira), an expensive biologic used to treat plaque psoriasis, was one drug some experts thought might be chosen for negotiation. A biosimilar adalimumab-atto (Amjevita) launched in January, but has not seen a great deal of uptake.
Frank suspects CMS saw "enough potential for competition that they kept it off the list."
A senior administration official on the press call said that "any of the drugs that you might have expected to see on the list that aren't selected here could be selected in future years under the exact same process."
Asked what impact price negotiations would have for patients, Madelaine Feldman, MD, vice president of advocacy and government affairs for the Coalition of State Rheumatology Organizations, told MedPage Today that patients often tend not to reap the benefits of drug pricing reforms.
However, because drug price negotiation has been paired with a $2,000 cap on annual out-of-pocket spending, expected to take effect in 2025, she said she is more optimistic.
"Someone's going to have to make up that difference that the patients used to pay," she said. And because much of the burden has shifted to Part D plans, they may be more incentivized to start putting lower priced drugs on their formularies, she added.
What Happens Next?
This fall, CMS will invite drug companies whose drugs have been selected for negotiation to meet with the agency regarding their data submissions. The agency will also host patient-focused listening sessions on the selected drugs.
Drug companies selected for the program will have until October 1 to sign an agreement to participate in the negotiation process for 2026, according to a timeline published by CMS on its Medicare Drug Price Negotiation Program.
By no later than October 2, those same companies must submit "manufacturer-specific data" to CMS that the agency will factor into its consideration of what is a "maximum fair price." These data may include costs of research and development, production costs, and sales and revenue data.
This date is also the deadline for the public to submit data to the agency regarding therapeutic alternatives to the selected drugs, as well as data on "unmet medical need" and impact on specific populations, according to an agency fact sheet.
By Feb. 1, 2024, CMS will share its initial maximum fair price offers with a justification, and companies will have 30 days to accept or suggest a counter-offer.
The negotiation period is slated to end Aug. 1, 2024. By September 1, CMS will publish the maximum fair prices that the agency has negotiated for these 10 drugs, and the negotiated prices will take effect beginning Jan. 1, 2026.
Looking ahead, CMS will choose up to 15 additional drugs for price negotiation for 2027, up to 15 more drugs (to include drugs covered under Medicare Part B) for 2028, and up to 20 more drugs for price negotiation each year after that, as stated in the IRA.
In addition to allowing Medicare to negotiate drug prices, the IRA looks to lower healthcare costs in other ways, including capping annual out-of-pocket expenses for Medicare Part D drug plans at $2,000, requiring drugmakers to cough up federal rebates if they hike prices above inflation levels, and maintaining the enhanced tax credits for those with Affordable Care Act coverage.
Reactions and Expected Backlash
Nancy LeaMond, executive vice president and chief advocacy and engagement officer of the AARP (formerly known as the American Association of Retired Persons), praised the administration for taking action to "bring down out-of-control prescription drug prices."
"For too long, big drug companies have fleeced our country and padded their profits by setting outrageous prices, all at the expense of American lives," LeaMond said in a statement to press. "The number one reason seniors skip or ration their prescriptions is because they can't afford them. This must stop."
"We cannot overstate how monumental this law is for older Americans' financial stability and overall health," she added.
Pharmaceutical companies have already taken aim at the new law by launching a "blizzard of lawsuits" to try and block it, including AstraZeneca, Astellas, Bristol Myers Squibb, Johnson & Johnson, and Merck, as well as the drug industry's trade group, the Pharmaceutical Research and Manufacturers of America.
"Today is a regrettable milestone in the implementation of the Inflation Reduction Act's price control provisions, which will result in harmful reductions in biomedical innovation while failing to address the root causes of high out-of-pocket costs," said John Stanford, executive director of Incubate, a group of venture capital firms, in an emailed statement.
"Government price setting throws a wrench in the successful market-based drug development ecosystem that patients count on to deliver life-saving therapies," he added. "The uncertainty created by price controls will force many early-stage life sciences investors to direct their funds elsewhere."
https://www.medpagetoday.com/washington-watch/washington-watch/106102
CDC: Deaths From Counterfeit Pills, Notably Fentanyl, Rising
Fatal overdoses from counterfeit pharmaceuticals, particularly pills found to contain fentanyls, more than doubled in recent years, the CDC reported.
Among more than 100,000 recent overdose deaths in the U.S., the percentage caused by pills disguised as legitimate pharmaceutical products increased from 2.0% in the third quarter of 2019 to 4.7% in the last quarter of 2021.
The proportion of those deaths involving illicitly manufactured fentanyls jumped to 93.0% from 72.2%, while illicit benzodiazepines also rose to 5.3% from 1.4%. Fake fentanyl was the sole drug involved in 41.4% of counterfeit pill-related deaths, compared with 19.5% of overdose deaths without evidence of counterfeit pill use.
Western states drove the increase in deaths with evidence of counterfeit pill use, with a rise from 4.7% to 14.7% across the study period, whereas percentages remained below 4% elsewhere, reported Julie O'Donnell, PhD, of the CDC, and colleagues in Morbidity and Mortality Weekly Report
"The proliferation of counterfeit pills, which are not manufactured by pharmaceutical companies, but are typically made to look like legitimate pharmaceutical pills (frequently oxycodone or alprazolam [Xanax]), is complicating the illicit drug market and potentially contributing to [overdose] deaths," O'Donnell and colleagues wrote.
And it may unintentionally expose new populations to highly potent drugs.
"Counterfeit pills often contain illicitly manufactured fentanyls (IMFs), illicit benzodiazepines (e.g., bromazolam, etizolam, and flualprazolam), or other illicit drugs, and can increase overdose risk because the pills might expose persons to drugs they did not intend to use," they added.
The findings come against a backdrop of an overall increase in drug overdose death rates involving fentanyl, methamphetamine, and cocaine from 2016 through 2021, as previously reported by the CDC without respect to counterfeit status.
Prevention and education efforts "that are tailored to persons most at risk, and include outreach to those who do not frequent traditional harm reduction services, might be most successful," they wrote.
Effective messaging by public health entities might include highlighting the dangers of pills obtained and taken without a prescription, as well as encouraging drug product testing, O'Donnell and colleagues added.
Data examined for the study came from jurisdictions participating in CDC's State Unintentional Drug Overdose Reporting System (SUDORS), which included 29 states and the District of Columbia from July 2019 to December 2021, with an additional five states reporting data during 2021. Jurisdictions entered information about unintentional and undetermined intent overdose deaths from death certificates, post-mortem toxicology reports, and medical examiner and coroner reports.
As for means of drug use, smoking was the most common non-ingestion route among deaths with evidence of counterfeit pill use (39.5%) and was highest in western jurisdictions (55.1%).
More than half of deaths with evidence of counterfeit pill use involved counterfeit oxycodone, either alone (55.2%) or with counterfeit alprazolam (3.9%), researchers reported.
Decedents with evidence of counterfeit pill use were younger than those without such evidence (57.1% vs 28.1% under age 35) and more were Hispanic or Latino (18.7% vs 9.4%, respectively). Additionally, a higher percentage of deaths with evidence of counterfeit pill use were in people with a history of prescription drug misuse compared with those without such evidence (27.0% vs 9.4%).
Deaths involving oxycodone and alprazolam combined involved people of the youngest average age (26 years).
"Counterfeit pills have been marketed toward younger persons, who might have more recently started using drugs and have lower tolerance," O'Donnell and colleagues wrote. "Younger persons might also exhibit more risk-taking behaviors than do older persons, and engage less with harm reduction services."
"The higher percentage of Hispanic decedents could reflect the younger age of this population and the demographics of western states where evidence of counterfeit pill use was more common; nonetheless, it might still have implications for access to and use of prevention messaging materials and harm reduction services," they added, such as tailoring these messages and services to address potential engagement, language, or other barriers.
Limitations of the study included that analyses might not be generalizable beyond jurisdictions that were included, and that documentation of counterfeit pill use is likely underestimated, the researchers noted.
Furthermore, the definition for evidence of counterfeit pill use included pills found or reported to be at the overdose scene, and some overdose deaths might be included as having evidence of such use even if the decedent did not use the pills.
Disclosures
The authors reported no conflicts of interest.
Primary Source
Morbidity and Mortality Weekly Report
Source Reference: O'Donnell J, et al "Drug overdose deaths with evidence of counterfeit pill use -- United States, July 2019–December 2021" Morb Mortal Wkly Rep 2023; DOI: 10.15585/mmwr.mm7235a3.
https://www.medpagetoday.com/publichealthpolicy/publichealth/106153
CDC Details 2021 Multidrug-Resistant TB Outbreak in Kansas
An outbreak of multidrug-resistant tuberculosis (TB) developed in Kansas in November 2021, and included multiple children who were born in the U.S. and became infected in the state, CDC researchers reported.
The outbreak involved 13 people across four households in Kansas City and spanned 1 year. While a majority of the seven adults identified were born outside the U.S. in a country that had experienced a multidrug-resistant TB outbreak with the same genotype in 2007-2009, most of the six children were U.S.-born, noted Elizabeth Groenweghe, MPH, of the Unified Government Public Health Department in Kansas City, and colleagues in the Morbidity and Mortality Weekly Report.
"This outbreak is ... a cautionary tale, reminding other low TB incidence jurisdictions that sustained declines in TB incidence are not assured," they wrote. "Successful TB treatment and prevention requires ongoing identification and treatment of [latent TB infection] and a swift multifaceted public health response for each person newly diagnosed with TB."
Nine additional people in the four affected households were diagnosed with latent infections, and one child in a neighboring state with an epidemiologic connection to the Kansas outbreak was also identified in July 2022.
All of the active infection isolates were resistant to rifampin, isoniazid, pyrazinamide, and ethambutol -- all first-line treatments -- but susceptible to second-line therapeutics, Groenweghe and co-authors said.
The outbreak began when an infant was hospitalized with pulmonary and meningeal TB. DNA sequencing confirmed that the infective strain was resistant to all four of the first-line drugs. An investigation by the local health department found four latent infections and four more active infections in the same household (household A), including a severely ill adult with pulmonary cavitary disease, who had exhibited symptoms since June 2021.
In January 2022, another case emerged, this time in a young child living in a different household (household B) in the same apartment building. Members of the two families socialized together extensively, shared a car, and commuted together to the same workplace.
The child was hospitalized with pulmonary TB and lymphadenitis; isolates had the same drug resistance profile as those from household A. The child's mother, who was pregnant, was soon diagnosed with pulmonary multidrug-resistant TB. Investigators found four more people in household B with active infection, including a severely ill young adult with pulmonary cavitary lesions, who had been symptomatic since September 2021.
The investigation also identified two additional households (C and D) with connections to households A and B, although located in a different neighborhood. Household C had two latent cases and two active cases, including a teen who had spent time in both households A and B; the teen was diagnosed with pulmonary multidrug-resistant TB and extrapulmonary TB vasculitis. Household D had three adults with latent infections.
Public health officials then investigated other contacts, a school, and a workplace. Potential contacts underwent an interferon-gamma release assay blood test or tuberculin skin test 8 weeks after their most recent exposure to any of those with TB.
Investigators thought the outbreak was contained within these four households until July 2022, when a child in a neighboring state was diagnosed with multidrug-resistant TB (household E).
"Additional investigation confirmed that the young adult from household B was also known to household E and had spent time in the home of household E while infectious," Groenweghe and team wrote.
Clinicians constructed individual treatment regimens for each person. Most of the adults (median age 29 years) and an older teenager in household A received 26 weeks of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM). The pregnant woman was treated with bedaquiline, linezolid, moxifloxacin, and clofazimine. After her baby was born and she stopped breastfeeding, she was switched to the BPaLM regimen for 6 more months.
"The infant, young child, other children, and young teenager presented a unique treatment challenge because BPaLM has not been studied in children aged <15 years," the authors noted.
Three of these children, ages 9-13, received 26 weeks of bedaquiline, linezolid, moxifloxacin, and delamanid. Delamanid is a multidrug-resistant TB medication used in Europe. The FDA granted a compassionate use authorization for these cases.
The infant and young child received bedaquiline, cycloserine, levofloxacin, and linezolid.
Length of treatment was clinically determined and differed in each case, but by September 2023, 13 of the 14 patients had completed treatment.
"One adult who received a clinical diagnosis of extrapulmonary TB disease declined treatment despite extensive measures on the part of public health and clinicians. Local public health staff members continue to maintain careful communication and relationship with this person, should they desire treatment, or should their disease progress further and pose a health risk to the community," Groenweghe and co-authors wrote.
The nine patients diagnosed with latent TB infections were all treated with 6 months of daily moxifloxacin. All completed treatment and none developed disease or complications. Local public health officials will continue to monitor all of the patients every 6 months for at least 2 years. This includes chest x-rays, review of signs and symptoms, and a physical exam.
The CDC's National TB Molecular Surveillance Center performed whole-genome sequencing on isolates from nine of those with culture-confirmed active TB. Whole-genome single nucleotide polymorphism (SNP) analysis showed that these isolates were very similar, differing only by up to three SNPs. This finding supported the investigators' hypothesis that the outbreak was locally transmitted within the social setting of these families.
The whole-genome SNP analysis also genetically tied the isolates to outbreaks that had occurred in the Federated States of Micronesia during 2007-2009 and Guam during 2009-2016. Some of the adults in the outbreak lived in those regions during those times.
"Both sentinel events of TB disease in the infant and young child included a plausible source within the household (i.e., a non-U.S.-born adult with a lengthy illness course and infectious period)," Groenweghe and team wrote. "At least one of these adults was likely infected overseas years earlier and then experienced progression to active TB disease after moving to Kansas. Unfortunately, neither of the plausible source persons received a diagnosis for many months, leading to further transmission."
"This outbreak in an urban, at-risk community resulted in tremendous financial, staffing, and capacity strain on the local public health department, where capacity was already diminished after nearly 2 years of COVID-19 pandemic response; however, recent collaborations established during COVID-19 prevention activities led to many positive working relationships with community partners such as the schools and hospitals, which facilitated efficient coordination of the outbreak response," the authors noted.
Disclosures
Groenweghe had no financial disclosures. Co-authors disclosed relationships with the Pacific Islands Tuberculosis Controllers Association Conference, the Heartland National Tuberculosis Center, the American Academy of HIV Medicine, the Advisory Counsel for the Elimination of Tuberculosis, and the Kansas Department of Health and Environment.
Primary Source
Morbidity and Mortality Weekly Report
Source Reference: Groenweghe E, et al "Outbreak of multidrug-resistant tuberculosis -- Kansas, 2021-2022" MMWR 2023; DOI: 10.15585/mmwr.mm7235a4.
https://www.medpagetoday.com/infectiousdisease/tuberculosis/106166
Subscribe to:
Posts (Atom)