'AMD Strongly Associated With Heart Disease and Stroke'

 Subretinal drusenoid deposits (SDD) had a significant association with underlying cardiovascular disease (CVD), adding a missing link between age-related macular degeneration (AMD) and CVD, according to a prospective study presented at the American Society of Retina Specialists (ASRS) meeting.

In this exclusive video, study author R. Theodore Smith, MD, PhD, of Mount Sinai Health System in New York City, discusses the study and the clinical implications.

The following is a transcript of his remarks:

A connection between these three diseases [SDD, AMD, and CVD] has been suspected for decades, but it's never been pinned down. The way we approached the problem was to look at AMD as two separate diseases -- one involving the classic drusen pathways and the other one involving what we call the subretinal drusenoid deposits. And drusen are under the RPE [retinal pigment epithelium], and the subretinal deposits are above the RPE, and they're very different. They're very different genetics, lipid content, risk factors, and so on.

So we chose to segregate a group of 200 AMD patients into 100 approximately with, and another 100 without, the subretinal deposits. And then we looked at their cardiovascular history. And we were pleasantly surprised and almost shocked to find that of the 200 patients, there were 47 in that entire group that had serious cardiovascular disease -- such as cardiac infarction, a severe valvular disease, compromising circulation, or the stroke patients who had significant stenosis of their internal carotid artery, and this blocks the circulation to the eye.

So all these things in common have is that the perfusion eventually getting to the eye is insufficient. Out of these 47 subjects with these severe conditions, 40 out of the 47 showed subretinal deposits in their eyes, and only seven did not. And when we do the odds ratios, the odds of a patient having high-risk vascular disease, given the presence of these deposits in their eyes, is basically 9 to 1, with a very nice confidence interval from like 4 to 15.

So you put these together, we can detect ongoing -- not future, but present -- severe vascular disease in patients with a simple OCT [optical coherence tomography] scan, which is very simply done in our ophthalmology clinics. And we add that to some severe risk factors like HDL [high-density lipoprotein] and so forth, we can even do it more accurately. This promises to change everything.

In clinical practice, once all this has been formulated and codified, it is possible that we could have these fairly inexpensive retinal cameras available through[out] the medical world so that patients can be screened by them as part of their routine medical care. And then they could be told immediately whether or not they have these high-risk features, which means they should then have further workup -- let's say an echocardiogram, carotid Doppler -- and then take it to the next level to find out what may be hiding. But as a screening tool, that's where we really like to take it.

https://www.medpagetoday.com/meetingcoverage/asrsvideopearls/100153

Early Look at 2023 Cost-Of-Living Adjustments and Maximum Contribution Base

 The BLS reported this morning:

The Consumer Price Index for Urban Wage Earners and Clerical Workers (CPI-W) increased 9.1 percent over the last 12 months to an index level of 292.219 (1982-84=100). For the month, the index declined 0.1 percent prior to seasonal adjustment.

CPI-W is the index that is used to calculate the Cost-Of-Living Adjustments (COLA). The calculation dates have changed over time (see Cost-of-Living Adjustments), but the current calculation uses the average CPI-W for the three months in Q3 (July, August, September) and compares to the average for the highest previous average of Q3 months. Note: this is not the headline CPI-U and is not seasonally adjusted (NSA).

• In 2021, the Q3 average of CPI-W was 268.421.

The 2021 Q3 average was the highest Q3 average, so we only have to compare Q3 this year to last year.

Click on graph for larger image.

This graph shows CPI-W since January 2000. The red lines are the Q3 average of CPI-W for each year.

Note: The year labeled is for the calculation, and the adjustment is effective for December of that year (received by beneficiaries in January of the following year).

CPI-W was up 9.1% year-over-year in July, and although this is early - we need the data for July, August and September - my early guess is COLA will probably be around 8.5% to 9.0% this year, the largest increase since 11.2% in 1981 (and larger than the 7.4% increase in 1982).

Contribution and Benefit Base

The contribution base will be adjusted using the National Average Wage Index. This is based on a one-year lag. The National Average Wage Index is not available for 2021 yet, but wages probably increased again in 2021. If wages increased 4% in 2021, then the contribution base next year will increase to around $153,000 in 2023, from the current $147,000.

Remember - this is an early look. What matters is average CPI-W, NSA, for all three months in Q3 (July, August and September).

https://www.calculatedriskblog.com/2022/08/early-look-at-2023-cost-of-living.html

Allogene cut to Market Perform from Outperform by Raymond James

 Target to $9 from $32

https://finviz.com/quote.ashx?t=ALLO&ty=c&ta=1&p=d

Will low-dose vaccination stretch the monkeypox vaccine supply, or backfire?

 The U.S. heath secretary recently declared monkeypox as a public health emergency, paving the way for emergency use authorizations of additional vaccines or vaccine regimens to fight the disease.

The same day, Food and Drug Administration Commissioner Robert Califf said that the U.S. government is seriously considering stretching the very limited supply of Bavarian Nordic’s Jynneos vaccine — the only vaccine licensed against monkeypox in the U.S. — by changing the way it is given. Instead of giving a full dose subcutaneously (into the fat layer under the skin), a lower dose of the vaccine could be given intradermally (injecting the vaccine within the skin). The FDA may soon issue an emergency authorization for Jynneos to be administered in this way.

Given the precarious state of affairs with respect to the U.S. stockpile for Jynneos and Bavarian Nordic’s limited capacity to quickly make more doses, the U.S. has limited options. This dose-sparing strategy could begin to address a public health need for men who have sex with men, who are at higher risk for acquiring the infection. If the vaccine can be administered at lower doses at no risk to effectiveness, lower-dose intradermal injections make sense.

But this strategy could also backfire. If there is a risk to effectiveness, it may be better to focus the available full doses of vaccine on individuals at highest risk — men who have sex with multiple male partners — to provide the best chance of getting the outbreak under control.

Uncertainties in the effectiveness of Jynneos will be magnified by switching to a new mode of administering a lower dose outside of a clinical trial. While the data support Jynneos as effective in reducing the severity of monkeypox, the data do not show that it prevents mild disease or transmission of the monkeypox virus. Indeed, in animal studies performed by Bavarian Nordic, even at the time of peak immune response, two doses of Jynneos did not prevent monkeypox infection or disease, though they did prevent the most severe disease and deaths. In addition, the vaccine’s ability to prevent monkeypox in the current outbreak, where a very high dose of virus infects people via mucosal surfaces (as occurs in sexual transmission), has not been studied in humans or animals. The existing studies provide even less confidence about effectiveness after just one dose — peak immune response is not achieved until two weeks after the second dose.

The largest study to support the proposed strategy of intradermal immunization involved a total of about 150 people who received both doses. About 20% of first-dose recipients didn’t get their second doses, likely related to high local reaction rates after the first dose. Study participants were evaluated for antibody responses to the vaccine strain virus (vaccinia) that are expected to track monkeypox antibody responses. Antibody levels were similar between recipients of the low-dose intradermal vaccine and those who received the normally delivered full-dose vaccine, although the criteria for the comparisons were less rigorous than the FDA normally uses for this type of comparison.

These antibody responses on their own, however, don’t predict protection against monkeypox.

In other studies, two doses of the Jynneos vaccine induced antibody titers in humans similar to one dose of the ACAM2000 vaccine (which is based on the vaccine that was used to eradicate smallpox), but the ACAM2000 vaccine proved much more protective against monkeypox challenge in vaccinated animals. There is also an uncertain relationship between the doses given in this study and that of the current vaccine, which can vary over an eightfold range, so using a 20% dose of vaccine for intradermal inoculation could either substantially underdose recipients (with a risk of lower effectiveness) or overdose them (with the potential for more side effects) relative to the vaccine given in the study of intradermal administration.

This study also reported lower long-term immune responses in those who received the lower-dose intradermal vaccine, raising concerns about the overall immune response to the intradermal lower dose vaccine.

Switching to intradermal administration is also complicated. Vaccines are not typically given intradermally in the U.S., and there is little margin for error. Mistakes could cause a lower dose of the vaccine to be delivered deeper than intended, with likely lower effectiveness. That’s why the worldwide vaccination campaign that led to the eradication of smallpox used a special needle, called a bifurcated needle, to provide consistent dosing, and why developers are exploring more reliable methods than needles and syringes for other vaccines that could be administered intradermally.

People who administer the vaccine intradermally would need special training, and even then may make mistakes. The FDA normally regulates vaccines paired with unusual delivery devices as combination products, which involve an extra set of assurances that the correct dose will be delivered to the right part of the body — assurances that likely would not be present in this case.

Vaccines by themselves won’t solve the monkeypox outbreak. Concern over stigma associated with monkeypox has made it more difficult to target messaging to the groups at highest risk both of getting monkeypox and sustaining transmission — individuals who have many sexual partners who, so far, have predominantly been men who have sex with men. While there are spillover cases to people not in this risk group, the likelihood that sustained transmission will arise from these other cases is presently low.

Without public health campaigns that provide clear information to the core high-risk group, there is even a possibility that vaccination will increase the incidence of risky behaviors — and a vaccine that is not highly effective could actually make things worse.

Other vaccines, including the ACAM2000 (which has been associated with heart complications) and the Japanese LC16m8 vaccines, may have an important role to play as well, but like Jynneos they are in short supply.

Monkeypox isn’t going away, so the U.S. government needs to urgently evaluate alternative strategies to augment the supply of monkeypox vaccines and deploy it effectively. In addition, more information is needed about antiviral drugs that might treat monkeypox, including antibody-based treatments such as vaccinia immune globulin.

The U.S. needs a concerted effort to make sure enough vaccines and therapeutics are available to address these needs and to reduce suffering. A hasty decision to try an unproven and risky strategy to stretch the existing vaccine supply may interfere with developing a national plan to quell this outbreak.

Philip Krause is an infectious diseases physician, a consultant to the World Health Organization, and a former deputy director of the U.S. Food and Drug Administration’s Office of Vaccines Research and Review. Luciana L. Borio is an infectious disease physician, a senior fellow for global health at the Council on Foreign Relations, and former director for medical and biodefense preparedness policy at the National Security Council. The authors have no links to any companies producing or evaluating any of the vaccines mentioned in this article. The opinions expressed here are their own, and not necessarily those of the organizations they are affiliated with.

https://www.statnews.com/2022/08/09/will-low-dose-vaccination-stretch-the-monkeypox-vaccine-supply-or-backfire/

As monkeypox spreads, university campuses prepare for another outbreak

 Public health experts are urging universities to prepare for the arrival of monkeypox before students return to campus in the coming weeks.

As the current outbreak has rapidly spread around the U.S., five campuses already confirmed cases this summer, even with most students away. Monkeypox is a viral infection that is primarily transmitted through close skin-to-skin contact. It is currently concentrated among communities of gay, bisexual, and other men who have sex with men, but it is not limited to those populations. Schools need to develop a clear communication strategy and plan to identify suspect cases, access testing and vaccines for students and staff, and provide contact tracing services, public health experts said.

“I think universities really do need to prepare, and we’re going to see outbreaks at universities,” said Lawrence Gostin, a professor of global health law at Georgetown University in Washington, one of the five schools where cases have been reported. The others are George Washington University, also in Washington; the University of Texas at Austin; and Bucknell and West Chester universities in Pennsylvania.

“I’m particularly worried about contact sports, wrestling, football, locker rooms, and particularly sex in dormitories,” Gostin said. While there is guidance from the Centers for Disease Control and Prevention about containing spread in congregate settings, it’s not targeted to colleges and universities. “I think that CDC and local health departments should develop a specific set of guidance for higher education,” he said. “They did that with Covid-19 and I think it’s critically important, particularly because this academic year is just around the corner. We really needed the guidance yesterday.”

Rachel Cox, an assistant professor at MGH Institute of Health Professions who studies infectious disease epidemiology, said parties, dancing, or sharing towels and bedding in dorms can all increase risk of transmission as students seek a traditional college experience. Speaking about the CDC guidelines, she added, “It’s really going to be up to the schools to figure out the best way to disseminate this information to their students.”

Many schools have begun preparing for cases. A spokesperson for Georgetown said the university’s Student Health Center and university hospital will work together “to identify, test, and manage suspected and confirmed cases.” Students and staff will be able to get tested at the campus health center.

A spokesperson for Johns Hopkins University said administrators are “closely monitoring the situation and having conversations with the Maryland Department of Health regarding monitoring of cases, testing, contact tracing, and procedures for treatment of infected individuals.” Like with Covid, they have also assembled a group of public health and medical professionals to guide their response.

Cox said that schools should prepare onsite clinicians for testing and try to acquire tests from large lab service providers. The American Clinical Laboratory Association said on Sunday that five laboratories nationally have capacity to test up to 70,000 patient samples per week, which is more than current demand.

Cox also said colleges should stockpile gloves and gowns that would be required when treating a student with monkeypox, find local sites that offer vaccinations, and establish protocols for in-house contact tracing and isolating students safely.

The University of North Florida put up an informational website, focusing on guidance for students who suspect they have the virus based on initial viral symptoms like having a headache, fever, sore throat, chills, or upon spotting lesions. Valerie Morrison, director of Student Health Services, said UNF will rely on some of the same health experts, committees, contact tracing, and deep cleaning protocols put together over the last two years for Covid to formulate a monkeypox response plan.

“Covid really set out a great template of how community resources need to work together,” she said. “We have a great mechanism in place.”

A University of South Florida spokesperson said the school is focused on promoting messaging about safe sex. If a case is identified, the Florida Department of Health would be contacted to conduct contact tracing.

Northwestern University released a statement stating that it does not expect a large number of monkeypox cases on campus. It will provide initial assessment, diagnosis, and treatment, but refer students to community partners for vaccination and contact tracing. Students living in on-campus housing must isolate off campus for the two- to four-week recovery time when they are contagious from the time symptoms of lesions start until all rashes or lesions have fully healed. There will be a limited number of rooms for students to isolate on or near campus.

With more information about monkeypox (which isn’t a novel disease like Covid), an approved vaccine (though the supply is limited), and medications already available, campuses should be better equipped to handle the situation.

“It’s really important to learn from mistakes and pitfalls we made during Covid … not moving quickly enough to kind of contain spread,” Cox said. “I think it’s really important that campuses get committees together to discuss the best way to get this going before students come to campus in the fall.”

Unlike Covid, there is not a need to regularly test all students. There is, however, a greater need for cleaning surfaces and stigma-free messaging.

“The first thing we need is really good public health communication and messaging in ways that’s informative, but at the same time, supportive and non-stigmatizing,” said Gostin, who is also a director of the World Health Organization’s Center on Global Health. He said communication needs to include messaging focused on individuals at highest risk. Having lived through the AIDS pandemic, he said this “deeper engagement with affected communities is the absolute secret sauce to an effective strategy.”

“The monkeypox virus is targeting a certain community [now] … but this is a virus that anybody can get, and we are very clear on that in our social media posts,” Morrison said.

https://www.statnews.com/2022/08/09/monkeypox-spreads-university-campuses-prepare-for-another-outbreak/

Eisai steps up beyond-the-pill approach to dementia

 More and more pharma companies are looking “beyond the pill” when it comes to providing care for patients, few more so than Eisai, which is developing a package of products and services in Japan for people living with dementia.

Its latest venture is an alliance with Tokyo-based Lifenet Insurance Co, which aims to develop a series of insurance products specifically for people with dementia and other aging-related diseases, with the aim of reducing “the burden of medical and nursing care” they face.

Eisai has a long history of developing drug therapies for dementia, starting with the cholinesterase inhibitor Aricept (donepezil) which was approved for Alzheimer’s disease in the 1990s and latterly with Biogen-partnered amyloid-targeted therapies Aduhelm (aducanumab) and lecanemab.

The company has been moving beyond that core drug development activity in recent years however, for example launching a collaboration NTT IT in 2016 to develop a cloud-based system to allow doctors and caregivers to share treatment plans and medical and lifestyle information for elderly patients being treated at home.

Pilot testing of the system suggested it encouraged changes to lifestyle habits and nursing care and encouraged greater levels of communication between patients, carers and doctors.

That initiative stemmed from the need to respond to a ticking timebomb among Japan’s increasingly ageing population, with estimates suggesting one in five elderly Japanese people will have dementia by the middle of the decade.

In 2019, the Japanese government launched a new national strategy to try to prepare for high rates of dementia, focused on providing care in the community to prevent the nursing home sector from becoming overwhelmed.

Eisai is increasingly looking at assisting that objective through the use of digital technologies. Earlier this year, for example, it started rolling out a smartphone-based app called NouKNOW that allows people to self-assess their cognitive performance and spot declines that may signal the onset of dementia.

It has also partnered with Fujitsu spin-out FCNT, which makes smartphones aimed at older consumers, to pre-install the app on one of its Raku Raku smartphone models.

The latest alliance – which kicks off with a 300 million yen purchase of Lifenet stock by the pharma company – adds yet another dimension to Eisai’s beyond-the-pill strategy.

In a statement (PDF), Eisai noted that it ties into a medium-term business plan announced last year which expands its role in healthcare.

“We should contribute not only to people in the medical domain but also to people in the daily living domain,” it said.

“Eisai aims to evolve into a company that empowers them ‘to realise their fullest life’ by creating solutions based on science and data in the fields with high unmet medical needs where Eisai has the greatest strength, through an ecosystem developed in collaboration with other industries.”

https://pharmaphorum.com/news/eisai-steps-up-beyond-the-pill-approach-to-dementia-in-japan/

MindMed started at Overweight by Cantor

 Target $3

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