Cheap Drug Eases Hot Flashes in Men With Prostate Cancer

 A widely available anticholinergic significantly improved hot flash symptoms in men taking androgen deprivation therapy (ADT) for their prostate cancer, a researcher reported here.

In a double-blind randomized trial of 81 men, twice-daily oxybutynin significantly reduced hot flash severity -- as measured by patient-reported hot flash scores -- as well as the frequency of the common and bothersome ADT side effect, according to findings presented by Brad Stish, MD, of the Mayo Clinic in Rochester, Minnesota, at the American Society of Clinical Oncologyopens in a new tab or window (ASCO) meeting here.

At baseline, patients had hot flash scores of approximately 18 points. At 6 weeks, twice-daily oxybutynin at doses of 5 mg and 2.5 mg led to average reductions of 13.95 and 9.94 points, respectively, as compared with a 4.85-point reduction with placebo (P=0.0019 and P=0.0732). Of note, a prespecified P value <0.1 was considered significant in the study.

And from averages of about 10 hot flashes per day at baseline, patients on the anticholinergic reported 6.89 and 4.77 fewer daily hot flashes at the lower and higher doses, respectively, as compared with 2.15 fewer with placebo (P<0.0001 and P=0.0236).

Furthermore, said Stish, oxybutynin was associated with improved patient quality of life and was well-tolerated.

"We think these results are very compelling and really believe that this demonstrates oxybutynin should be a reasonably considered clinical option for men who have bothersome hot flashes related to their androgen deprivation therapy," he said, adding that the anticholinergic is an attractive agent given that it's been around for decades, is widely available, and is very cost effective.

Hot flashes are the most predominant and commonly addressed problem in the clinic for men taking ADT for prostate cancer, said Stish in his introductory remarks. Used both in the non-metastatic and metastatic settings, ADT is given either temporarily, intermittently, or sometimes as a lifelong therapy in advanced disease.

Previous studies have shown that agents such as megestrol acetate, gabapentin, and venlafaxine can be effective for managing hot flash symptoms in men, but additional options are needed, he said.

Oxybutynin previously demonstrated effectiveness in a randomized placebo-controlled trialopens in a new tab or window for reducing hot flash symptoms and frequency in women, but studies have shown discordant results for men and women treated with the same agents for hot flashes, according to Stish.

Commenting on the new findings, ASCO-designated discussant Clark DuMontier, MD, MPH, of Brigham and Women's Hospital in Boston, noted the apparent dose-response effect with the anticholinergic and said "the data are strong to consider oxybutynin for hot flashes in men on androgen deprivation therapy, especially if venlafaxine is ineffective."

However, DuMontier noted there was low power to detect toxicity in the trial given the small sample size and called for larger head-to-head trials of oxybutynin and venlafaxine that include older and frailer patients to better evaluate the safety and effectiveness of the two agents for this patient population.

Stish presented primary findings of the double-blind Alliance A222001 trialopens in a new tab or window, which enrolled 88 men with frequent ADT-associated hot flashes (at least 28 per week) and randomized them 2:1 to 6 weeks of oxybutynin (2.5 mg or 5 mg twice daily) or matching placebo. Six patients withdrew before starting treatment and one was ineligible, leaving 81 for the primary analysis.

Stratification factors included hot flash frequency at baseline, duration of hot flashes, use of prior therapy for hot flashes, and planned radiation therapy during the study. Patients could be on abiraterone acetate (Zytiga) but not other newer androgen receptor pathway inhibitors -- enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa) -- that are CYP3A4 metabolized and may affect oxybutynin serum concentrations.

Patients in the study had a median age of 68, with 30% on abiraterone and 80% having an Eastern Cooperative Oncology Group performance status of 0.

The primary endpoint was change in hot flash score, a validated patient-reported scoring system that multiplies the frequency of hot flashes by their severity on a 0 to 4 scale (0 = none; 1 = mild; 2 = moderate; 3 = severe; and 4 = very severe). Secondary endpoints included quality of life on the Hot Flash-Related Daily Interference Scale (HFRDIS; a 0 to 100 scale where lower scores indicate less interference with life) and safety.

The HFRDIS showed significant improvement with both doses of oxybutynin over placebo, with scores decreasing by about 21 points with the 5-mg dose, about 14 points with the 2.5-mg dose, and about 3 points with placebo (P=0.0012 and P=0.0419, respectively).

Grade ≥3 adverse events (AEs) occurred in 7% of patients on 2.5-mg oxybutynin, 4% of those on the 5-mg dose, and 8% of those on placebo (P=0.86). These included decreased lymphocyte count, urinary tract infection, and anemia in the oxybutynin recipients, and tachycardia and syncope in the placebo recipients, with none considered related to treatment.

Dry mouth was the most common oxybutynin-related grade 2 AE (9%), which was not surprising and typically transient, said Stish. The drug is used for bladder symptoms, and dry mouth is a commonly reported side effect.

Grade 2 events of urinary retention (4%), urinary frequency (2%), urinary tract infection (2%), gastroesophageal reflux disease (2%), and fatigue (2%) were also considered possibly or probably related to oxybutynin.

Oxybutynin was delivered in the study via a syrup with a concentration of 1 mg/mL, allowing for easy titrating of dose if tolerance issues emerged, said Stish, though twice-daily pills and long-acting forms are also available.

Disclosures

This study was sponsored by the Alliance for Clinical Trials in Oncology.

Stish disclosed research funding from Varian Medical Systems.

DuMontier reported stock ownership in Eli Lilly.

Primary Source

American Society of Clinical Oncology

Source Reference: opens in a new tab or windowStish BJ "Alliance A222001: A randomized, double-blind, placebo controlled phase II study of oxybutynin versus placebo for the treatment of hot flashes in men receiving androgen deprivation therapy" ASCO 2024; Abstract LBA12004.

https://www.medpagetoday.com/meetingcoverage/asco/110457

'Co-Locating COVID Vaccines, Infection Testing With Syringe Services Shows Success'

 Co-locating COVID-19 vaccination and infectious disease testing with a syringe services program boosted engagement among people who injected drugs, according to an analysis of the Baltimore-based initiative.

Among 347 participants across 10 co-located clinics participating in the Baltimore City Health Department Syringe Services Program from April 2021 to June 2022, 63% received at least one dose of the COVID vaccine and 58% received one infectious disease test, reported Omeid Heidari, PhD, MPH, of the University of Washington in Seattle, and co-authors in Health Affairsopens in a new tab or window.

"The most important finding for us is that co-location worked," Heidari told MedPage Today.

Overall, 94% of participants completed primary vaccination with either mRNA or viral vector vaccines, a rate that outpaces the general population (88%),opens in a new tab or window Heidari and co-authors noted.

"The prevailing thought is that for people who are using and injecting drugs, it's hard to do follow-up care, but this is a population that when you have the right messenger -- someone they trust in -- they'll come back for follow-up services and even complete important preventive care," Heidari said.

Those "trusted messengers" were the syringe exchange services staff, who have a lot of empathy for this population, which is lacking in the traditional medical system, he added.

Even though all participants were eligible for a booster at the time of data analysis, only 30% received a booster dose, which is lower than the general public.

Heidari believes the discrepancy is due in part to a lag between when the primary series was offered and when the clinics restarted and boosters became available.

"When you are not there and present, people are not going to come as often," he said, underscoring the need for consistent engagement.

As for infectious disease testing, 86% of participants received a point-of-care HIV test, 64% received a hepatitis C test, 38% received a syphilis test, 34% received a throat swab for gonorrhea and chlamydia, and 25% received a genital swab for gonorrhea and chlamydia.

Of the eight people with positive HIV tests (5% of those tested), all received treatment. One additional person, who reported HIV exposure within 72 hours, tested negative using a rapid test. That individual received a prescription for postexposure prophylaxis and a referral for clinical services.

Among 21 people who tested positive for hepatitis C (16% of those tested), only six were documented as having a successful referral visit. For the six people who had a confirmed positive syphilis test, all were successfully linked to treatment when it was deemed necessary.

No one tested positive for chlamydia or gonorrhea. One individual tested positive for trichomoniasis and was successfully treated.

This collaborative program was run through a partnership with the Johns Hopkins mobile vaccine unit and the Center for Infectious Disease and Nursing Innovation, which provides testing for HIV, hepatitis C, and other sexually transmitted infections, as well as linkages to care.

The syringe services program, which has its own mobile van, visits neighborhoods with high overdose rates, providing harm reduction counseling and naloxone (Narcan) training. A second mobile vaccine unit provided mRNA (Moderna or Pfizer-BioNTech) or viral vector (Janssen) COVID vaccines.

While it was discussed whether it would be more convenient for this population to receive only the one-dose Janssen vaccine, shortly before staff went into the field, a potential link between the Janssen vaccine and an increased risk of blood clotsopens in a new tab or window was found. Therefore, the team decided to offer people the option of any one of the three vaccines.

"I think providing individuals the autonomy to make that decision for themselves really just showed that we were partners who cared about their health and well-being, and not just picking services for them," Heidari noted.

At the start of the program, participants received a $10 gift card for every completed infectious disease test. After the first five clinics, the incentive was changed to a single $20 gift card regardless of the number of tests. Gift cards were not offered for COVID vaccinations until after FDA approvalopens in a new tab or window in August 2021.

Any prescriptions provided were billed to participants' insurance, and uninsured individuals were connected to the city's sexual health clinic for free treatment.

With regard to harm reduction, an average 3,057 syringes were distributed and 1,437 syringes were returned across eight co-located clinics that had available data. Additionally, an average of 24 naloxone kits were distributed and accompanied by training.

Of the 347 people who received at least one COVID vaccine or infectious disease test at one of the 10 clinics, mean age was 51, 69% were men, 76% were Black, 15% were white, and 3% were Hispanic or Latino. In all, 40% were insured, 23% were uninsured, and 37% did not specify.

In the future, Heidari said he would like to see programs include more robust services on site. For example, for people with hepatitis C, staff could potentially also provide confirmatory testing and have clinicians available to prescribe curative therapy, in addition to first-line testing.

"You could feasibly have a lot of the services provided in primary care embedded within syringe services of harm reduction sites," he noted.

Other novel approaches that leverage co-location and trusted partners might include providing pre-exposure prophylaxis for HIV, wound care, diabetes and hypertension screening and treatment, mental health counseling, and medications for opioid use disorder, Heidari and team said.

Heidari hopes the study findings will lead payers and government agencies to place more value on this type of care and encourage them to reimburse it appropriately.

A limitation to the study was that it involved self-evaluation: Heidari and his team were involved in both implementing the program and assessing it.

Disclosures

This program received support from the Early Intervention Services Grant through the Baltimore City Health Department; the Johns Hopkins University School of Nursing Center for Infectious Disease and Nursing Innovation Community Support Grant; and the Urban Health Institute at Johns Hopkins University.

Heidari received a grant from the National Center for Advancing Translational Sciences.

The authors reported no conflicts of interest.

Primary Source

Health Affairs

Source Reference: opens in a new tab or windowHeidari O, et al "Colocating syringe services, COVID-19 vaccination, and infectious disease testing: Baltimore's experience" Health Aff 2024; DOI:10.1377/hlthaff.2024.00032.

https://www.medpagetoday.com/publichealthpolicy/publichealth/110451

'FDA Panel to Consider Which COVID Strain to Target in an Updated Vaccine'

 The current predominant strain of COVID-19 should be a key consideration during the upcoming meeting of an FDA advisory committee tasked with making recommendations about the next COVID vaccine, agency staff said in a briefing document

opens in a new tab or window released Monday.

"Although JN.1 sublineages were predominant through spring 2024 in the U.S., the KP.2 subvariant has now become the predominant circulating strain," the authors noted. "Because the antigenic distance between JN.1 and JN.1-derived subvariants such as KP.2 subvariants is not far, it is possible that vaccines developed against JN.1 may adequately protect against KP.2. However, further SARS-CoV-2 evolution may lead to further divergence from JN.1, and consideration may need to be given to the selection of the subvariant that is currently predominant to assure the best possible match as the virus further evolves."

The document was released in advance of Wednesday's meetingopens in a new tab or window of the agency's Vaccines and Related Biological Products Advisory Committee. Following presentations and committee discussion, committee members will be asked to vote "Yes," "No," or "Abstain" on the question, "For the 2024-2025 formula of COVID-19 vaccines in the U.S., does the committee recommend a monovalent JN.1-lineage vaccine composition?" Presenters will include staff from the FDA and CDC; representatives of vaccine manufacturers Moderna, Pfizer, and Novavax; and a representative of the WHO's Technical Advisory Group on Coronavirus Vaccines (TAG-CO-VAC).

In the briefing document, the FDA staff gave a brief history of coronavirus vaccines, noting that two COVID vaccines -- Moderna's Spikevax and Pfizer's Comirnaty -- have been approved for COVID-19 prevention in persons 12 and older, while three other vaccines -- one from Moderna, one from Pfizer, and one from Novavax -- have emergency use authorizations for COVID prevention in various age groups. The document's authors emphasized that any recommendation for updating the vaccines' antigenic composition "must consider the time needed for manufacturers to implement and deliver" a new vaccine.

Since the introduction of the 2023-2024 updated vaccine, COVID-19 "has continued evolving into distinct sublineages by acquiring additional mutations," the briefing document said. "Although real-world effectiveness studies suggest that currently approved/authorized COVID-19 vaccines (2023-2024 formula) continue to provide protection against more currently circulating XBB sublineages, in prior years there appears to have been an inverse relationship between the time since vaccination and vaccine effectiveness, such that COVID-19 vaccine effectiveness against SARS-CoV-2 sublineages appears to wane over time and that better matching of the vaccine to circulating strains is associated with improved neutralizing antibody titers."

"Consistent with this observation, a decrease in effectiveness of COVID-19 vaccines (2023-2024 Formula) against COVID-19 caused by JN.1 lineage viruses has been reported," the authors wrote. "Available data suggest that updating the current formula of COVID-19 vaccines to more closely match currently circulating JN.1 lineage viruses is warranted for the anticipated 2024-2025 respiratory virus season in the U.S."

The authors also cautioned that the virus continues to evolve. "SARS-CoV-2 evolution continues to be complex and remains unpredictable," they wrote. "There is no indication that SARS-CoV-2 evolution is slowing, though immunity appears to be mitigating severe clinical outcomes, particularly in younger populations. Intrinsic viral factors, including mutation rate and recombination potential, generate possibilities for increased transmissibility and adaptation to the host. At the same time, host immune responses and other factors contribute to selection of variants."

The briefing document also discusses recommendations made by the WHO advisory group. In an April 26 statement, the group recommended that "As the virus is expected to continue to evolve from JN.1, the TAG-CO-VAC advises the use of a monovalent JN.1 lineage as the antigen in future formulations of COVID-19 vaccines." However, the briefing document added, "The TAG-CO-VAC recommendation for a monovalent JN.1 lineage vaccine was made at a time when JN.1 was almost completely dominant and before JN.1 lineage-derived virus variants with FLiRT mutations, such as KP.2, became dominant in the U.S. This change in epidemiology warrants consideration."

FDA officials will take the advisory panel's recommendation into account when it considers which updated vaccines to approve and/or authorize. The agency does not have to follow its advisory panels' recommendations, but often does. The CDC's Advisory Committee on Immunization Practices (ACIP) will also weigh in with recommendations on use of the vaccines.

The FDA advisory committee meeting comes at a time when vaccine uptake is low. As of May 11 -- the latest date for which figures were available -- 22.5% of adults reported receiving an updated COVID vaccine since mid-September 2023, and 14.4% of children ages 6 months to 17 years were reportedly up to date on their COVID shots, according to the CDCopens in a new tab or window.

https://www.medpagetoday.com/infectiousdisease/covid19vaccine/110458

Louisiana Lawmakers Approve Surgical Castration for Sex Crimes Against Kids

 A person found guilty of a sex crime against a child in Louisiana could soon be ordered to undergo surgical castration, in addition to prison time.

Louisiana lawmakers gave final approval to a bill Monday that would allow judges the option to sentence someone to surgical castration after the person has been convicted of certain aggravated sex crimes -- including rape, incest, and molestation -- against a child younger than age 13. Several states, including Louisiana, currently can order such criminals to receive chemical castration, which uses medications that block testosterone production in order to decrease sex drive. However, surgical castration is a more invasive procedure.

If an offender "fails to appear or refuses to undergo" castration after a judge orders the procedure, they could be hit with a "failure to comply" charge and face an additional 3-5 years in prison, based on the bill's language.

"This is a consequence," Republican state Sen. Valarie Hodges said during a committee hearing on the bill in April. "It's a step over and beyond just going to jail and getting out."

The bill now heads to the desk of conservative Gov. Jeff Landry (R), who will decide whether to sign it into law or veto it.

Currently, there are 2,224 people imprisoned in Louisiana for sex crimes against children younger than 13. However, if the bill becomes law, it can only be applied to those who have convicted a crime that occurred on or after Aug. 1, 2024.

The sponsor of the bill, Democratic state Sen. Regina Barrow, has said it would be an extra step in punishment for horrific crimes. She hopes the legislation will serve as a deterrent to such offenses against children.

"We are talking about babies who are being violated by somebody," Barrow said during an April committee meeting. "That is inexcusable."

While castration is often associated with men, Barrow said the law could be applied to women, too. She also stressed that imposing the punishment would be by individual cases and at the discretion of judges. The punishment is not automatic.

The proposed law also stipulates that a medical expert must "determine whether that offender is an appropriate candidate" for the procedure before it's carried out.

A handful of states -- including California, Florida, and Texas -- have laws in place allowing for chemical castration, but in some of those states offenders can opt for the surgical procedure if they prefer. The National Conference of State Legislatures said they are unaware of any states that currently have laws in place, like the bill proposed in Louisiana, that would specifically allow judges to impose surgical castration.

Louisiana's current chemical castration law has been in place since 2008, however very few offenders have had the punishment passed handed down to them -- with officials saying from 2010 to 2019opens in a new tab or window, they could only think of one or two cases.

The bill, and chemical castration bills, have received pushback, with opponents saying it is "cruel and unusual punishment" and questioned the effectiveness of the procedure. Additionally some Louisiana lawmakers have questioned if the punishment was too harsh for someone who may have a single offense.

"For me, when I think about a child, one time is too many," Barrow responded.

https://www.medpagetoday.com/surgery/generalsurgery/110459

FibroGen Agreement with Regeneron to Evaluate FibroGen’s Immuno-Oncology Assets in Trials

 

• FibroGen to evaluate FG-3165, an anti-galectin 9 (Gal9) monoclonal antibody (mAb), as monotherapy treatment as well as in combination with LIBTAYO® in patients with select solid tumors
• FibroGen to evaluate FG-3175, an anti-c-c motif chemokine receptor 8 (CCR8) mAb, as monotherapy treatment as well as in combination with LIBTAYO® in patients with select solid tumors
• Both FG-3165 and FG-3175 have demonstrated complementary mechanisms of action with PD-1 inhibitors in preclinical studies

https://www.globenewswire.com/news-release/2024/06/03/2892583/33525/en/FibroGen-Announces-Clinical-Trial-Supply-Agreement-with-Regeneron-Pharmaceuticals-to-Evaluate-FibroGen-s-Immuno-Oncology-Assets-FG-3165-anti-Galectin-9-and-FG-3175-anti-CCR8-in-Com.html

10 Reason Why Student Debt Cancellation Is Extremely Unfair

 A recent Tweet by Elizabeth Warren and a short rebuttal to her inspired this post. Let’s take a look at the Tweet and my 10 reasons.

Deeply Unfair

10 Reasons Why Student Debt Cancellation is Unfair

1. It is unfair to those who sacrificed to pay off their student loans and it’s unfair to those who foot the bill.
2. It is an upward transfer of wealth. The plumber pays for someone  else’s college education.
3. It encourages going to college when there might be better choices such as learning a trade. And It creates incentive to take on new student loans.
4. It is blatant election year bribe to college students and college graduates.
5. It creates creates a moral hazard for college administrators to sell useless degrees creating another overhang of new student debt.
6. It creates a moral hazard for students who might feel that their debt should be forgiven in the future
7. It subsidizes poor decision-making such as majoring in useless degrees including gender studies, anthropology, archeology, art history, music, culinary arts, fashion design, philosophy, etc.
8. The president has no power to forgive student loans. Doing so creates another precedent for presidential rule by decree. This is too big a financial decision not to involve Congress. The current student loan program was authorized by Congress and contains no such authority to the president.
9. Biden is openly fluting the Supreme court, another dangerous precedent.
10. Free money is highly inflationary.

Laughable Explanations to Difficult Question

Everything this president does is inflationary. Yet, Biden and economists refuse to admit this.

January 11, 2024: Is Inflation Down? That’s What President Biden Says

February 20, 2024: The CBO Revised the Cost of Biden’s Energy Policies Up by $466 Billion

April 12, 2024: How the Inflation Reduction Act Failed to Reduced Electricity Costs in Pictures

May 11, 2024: What’s the Inflation Rate Under Biden vs 7 Previous Presidents?

Any Questions?

https://mishtalk.com/economics/student-debt-cancellation-is-extremely-unfair-here-are-10-reasons-why/

'Biden campaign looks to mobilize LGBTQ voters with Pride Month media blitz'

 President Biden’s reelection campaign on Monday announced plans to launch new organizing efforts and a paid media blitz aimed at attracting LGBTQ voters during Pride Month. 

The campaign plans to have a presence at more than 200 Pride events in 23 states, including each of the battleground states that will decide November’s election, according to a news release. The campaign’s LGBTQ voter initiative, Out for Biden-Harris, will work with LGBTQ clubs, caucuses, councils and grassroots networks across the country to mobilize voters and leverage the administration’s relationships with influential LGBTQ rights advocates. 

At the end of the month, Biden and first lady Jill Biden, who kicked off Pride Month with an appearance at Pittsburgh’s annual Pride festival on Sunday, will host an LGBTQ fundraising event in New York City. 

“Thanks to the tireless work of LGBTQ+ organizers, our community has made enormous strides to equality, and thanks to President Biden, we haven’t just undone the harm imposed by Trump, we’ve taken more action than ever to expand rights and freedoms for every single American,” said Sam Alleman, the Biden-Harris campaign’s national LGBTQ+ engagement director. “All of that progress is on the line this November.” 

Biden, who frequently touts himself and his administration as the most pro-LGBTQ in history, expanded during his first term federal nondiscrimination protections for LGBTQ people and condemned violence and threats made against the community. In 2022, Biden signed legislation safeguarding marriage equality. 

But the president has fallen short on some promises made to LGBTQ voters, including a pledge to safeguard access to gender-affirming health care as more Republican-led states move to ban treatment for minors. 

On the other hand, former President Trump has promised to enact at least a dozen policies targeting transgender rights if he is reelected, including a nationwide ban on transgender student-athletes competing in accordance with their gender identity and a federal law that recognizes only two genders. He has also vowed to punish health care providers who administer gender-affirming medical care to minors and roll back new transgender student protections “on day one” of his presidency. 

Trump as president barred transgender individuals from serving openly in the military, gutted Obama-era nondiscrimination protections for LGBTQ people and rejected requests from U.S. embassies to fly rainbow flags during Pride Month. But he’s still been able to rally LGBTQ conservatives to his side: His run in 2020 was endorsed by the Log Cabin Republicans, a conservative LGBTQ advocacy group.

Recent polling suggests the former president leads Biden in key battleground states and maintains a slight 1.1 percentage point advantage nationally, based on The Hill/Decision Desk HQ’s average of 725 polls pitting the two against each other. Nearly 70 percent of LGBTQ likely voters surveyed in January by the LGBTQ media advocacy group GLAAD said they preferred Biden over Trump. 

In the same survey, more than half of voters said they would not vote for a candidate that supports restricting transgender rights. 

LGBTQ voters played a key role in Biden’s victory in 2020, a Washington Post analysis found. More than 7 percent of U.S. adults in a March Gallup poll said they identify as lesbian, gay, bisexual, transgender or “something other than heterosexual,” including more than 20 percent of Americans aged 18-25. 

But while LGBTQ voters are more likely to support Democrats in elections, not all of them are set on voting for Biden this year. The Human Rights Campaign, the nation’s largest LGBTQ advocacy group, in May committed $15 million to help reelect the president, noting that roughly a third of “equality voters” — who prioritize LGBTQ rights at the ballot box — are at risk of not voting. 

https://thehill.com/homenews/lgbtq/4700827-biden-campaign-looks-to-mobilize-lgbtq-voters-with-pride-month-media-blitz/