Jeff Temple, PhD, licensed psychologist, vice dean for research, UTMB School of Nursing, discusses the rising mental health crisis in adolescents and strategies for community stakeholders to mitigate this issue with AJMC® Associate Editor Matthew Gavidia.

Take a DEEP DIVE Into Medical World News

AJMC Associate Editor Matthew Gavidia sat down with Shannon Burke, SVP and general manager of health systems at Synchrony Health & Wellness, to discuss the importance of exercise on her physical and mental health and how it has improved her productivity.

Find Out What Managed Care Experts Like to Do AFTER HOURS

For our latest After Hours interview, Traci Thompson, MD, MBA, chief medical officer, Humana Healthy Horizons of Florida, discusses her drive to improve health equity in underserved east Tampa, with AJMC® Associate Editor Matthew Gavidia.

Learn About Managed Care Experts' AFTER HOURS Pursuits

 Dr Pitt, building on that, SGLT2 inhibitors and finerenone have improved outcomes for patients with CKD [chronic kidney disease]. We’ve discussed this in the clinical trial results. Is there a potential role to use these agents in combination to promote a reduction in disease progression or in CV [cardiovascular] risk?

 It’s still very early in the game, but there are preclinical data that if you take a low dose of finerenone and a low dose of an SGLT2 inhibitor, such as empagliflozin, at least in an animal model, you get better results than with either one alone, and you reduce mortality. We’ve already talked about the fact that when you add an SGLT2 to an MRA [mineralocorticoid receptor antagonist], you have less hyperkalemia. There are lots of reasons to think that this combination is going to be very useful in not only treating CKD and heart failure but also preventing them.

I’d like to make a few comments [regarding things] that maybe were already alluded to. Dr Agarwal talked about hyperkalemia, but of people who discontinue these agents, only about 1% or so discontinue the agents because of hyperkalemia. With our old friends, the steroidal MRAs, it was a much higher percentage who discontinue, and many people don’t start. If you aren’t on an MRA, at least with heart failure, you have a tremendous increase in risk. The increased tolerability that you get with agents such as finerenone is important.

Another thing I’d like to mention is that when you start an agent such as finerenone, you sometimes have a rise in creatinine, which is a hemodynamically mediated effect because of the small drop in blood pressure. Some clinicians have become nervous and stop agents because of the rise in creatinine, but if you persist, you protect the kidneys and the heart. This is transient hemodynamics. This is an important point. You shouldn’t get nervous when you see a slight increase in creatinine when you start these agents because [it helps] in the long run.

We’ve said a lot of good things about these agents. Dr Agarwal said that maybe there isn’t much new, but there’s a need for new things. We talked about these patients with diabetes, and Dr Feldman said all the good things that we do, but one thing that we haven’t done is reduce stroke. There isn’t any evidence that SGLT2 inhibitors have reduced stroke, nor did we find that finerenone reduces stroke. In a patient with diabetes, especially with renal disease or heart failure, stroke is a major thing that we have to think about. There are new drugs and opportunities coming that will be able to reduce stroke. The game isn’t [over]. It’s very exciting, but there’s more to come.

 Excellent overview. It’s exciting. There’s more to come, and we have to modernize the way we’re treating these patients early.

I now want to hear from our payer colleague, Paul, because as we introduce new therapies, we provide great outcomes for patients, but we also introduce new costs when we think about managing the covered lives and the per member, per million standpoint. Paul, how are payers balancing these high costs of new treatments for CKD with the risk of disease progression and total cost of care? Are there barriers from a utilization management standpoint? Are there patients who could benefit from these therapies but might not have access due to utilization management strategies or payer policies?

 That’s a great question, Ryan. It isn’t really what I work in on the utilization management point, and not being a clinician, I probably shouldn’t answer the clinical questions. We have 3 great clinical panelists here. But the talk about utilization management is looking at the appropriateness of care and making sure our providers understand the testing, screenings, and the new therapies that are available. One thing we have to do as a payer is balance the cost of care with the treatment of the member to make sure it’s the appropriate care for the member. We have clinical experts throughout Humana who look at that. That isn’t something I work on. But it’s making sure we’re educating providers on the appropriateness and what’s the right medication.

All of our physician colleagues here have talked about the challenges, such as medication adherence. When we look at a member, we’re looking at how likely they are to understand why they’re doing that therapy, why they’re taking that medication, the risks, how they need to change behavior to make sure those medications remain appropriate, and that they aren’t doing something that counteracts the medication or fights against what they’re doing. Utilization management from our standpoint is looking at the appropriateness and making sure physicians are educated on the right end. I’ll let the clinical people on our end talk about those patients who could benefit from it who aren’t able to get it for whatever reason. I’ll leave it at that. It’s looking at appropriateness and making sure there’s education and helping the physicians and providers understand the why behind what’s being offered to the member.

Videos

Dr Bertram Pitt explains the possibility of combining SGLT2 inhibitors and MRAs when treating CKD and CV, and Paul Sapia, MHA, discusses how payers balance cost of care with disease progression and health disparities.

Combination Therapy and Payer Perspective on CKD Therapies

Maggie is an editor for The American Journal of Managed Care® (AJMC®) and produces written, video, and podcast content covering several disease states. She joined AJMC® in 2019, and has been with AJMC®’s parent company, MJH Life Sciences®, since 2014, when she started as a copy editor.

She has a BA in English from Penn State University. You can connect with Maggie on 

General anesthesia use and the potential for greater risk of adverse outcomes among pediatric patients who have idiopathic 

 (IPAH) and undergo right heart catheterization (RHC) make it necessary for them to receive specialized pediatric cardiology care, according to new study findings 

In this new retrospective study, outcomes were compared between 2 population cohorts: 469 patients with congenital heart disease–PAH (CHD-PAH) and 122 patients with IPAH. Median (IQR) ages were 8.8 (3.3-13.3) and 9.0 (5.0-12.9) years, respectively, and 60.4% were female patients. All underwent diagnostic RHC between 2005 and 2020, and the most common New York Heart Association functional class prior to RHC was class III-IV in 7.9% of the CHD-PAH group and 27% of the IPAH group. Syncope was present in 1.5% and 27%, respectively.

“RHC is generally considered a low-risk procedure, with a rate of complications of around 1% in adult patients. However, pediatric patients tend to have higher risks due to low weight, respiratory depression, anesthetic sensitivity, and relatively unstable hemodynamic status,” the study investigators wrote. “This study therefore set out to investigate the clinical characteristics and hemodynamics of Chinese pediatric patients with PAH from one of the largest pediatric PAH referral centers, and further, to quantify the safety and efficiency of RHC in this vulnerable population.”

Overall, all of the patients in the CHD-PAH group underwent RHC, representing 79.4% of these procedures during the study. Among these patients, the median time from symptom onset to diagnosis was twice that of the IPAH cohort: 24 (6-68) months vs 12 (4-25.5) months.

General anesthesia was used in approximately two-thirds of the RHC procedures, with 18 patients experiencing an adverse event (AE) during their procedure; among these patients, 14 were from the IPAH study cohort and 4 were from the CHD-PAH study cohort, and 2 patients were under local anesthesia whereas 16 were under general anesthesia. Seventeen of the AEs were a pulmonary hypertensive crisis (PHC), and these developed during anesthesia induction (n = 5), during RHC (n = 10), and after pulmonary angiography (n = 2). One patient died almost 3 days after the procedure.

Ketamine, propofol, dexmedetomidine, or opioids were the anesthetics used, “at the anesthetist’s discretion,” the authors wrote.

Several factors were associated with a significantly higher risk of developing a PHC. These were the following:

Presence of IPAH: 1302% higher risk (odds ratio [OR], 14.02; 95% CI, 4.49-43.85; 

Atrial blood gas pH below 7.35: 1150.4% higher risk (OR, 12.504; 95% CI, 3.545-44.102; 

Right atrial pressure above 14 mm Hg: 963.6% higher risk (OR, 10.636; 95% CI, 3.668-30.847; 

The authors’ investigation also determined that the most common reason for a referral for RHC was made following an abnormal physical exam in 60.3% of the CHD-PAH group and decreased exercise tolerance in 44.3% of the IPAH cohort, as well as that PHC was seen more often in patients who did not have an intracardiac shunt.

“Overall, our data reveal that RHC is a safe procedure in pediatric patients with CHD-PAH, while the probability of AEs, especially PHC, was relatively higher in IPAH patients and correlated with poor cardiac functional class and poor hemodynamic condition, history of syncope, lower pH value, and necessity of general anesthesia,” the investigators concluded. “However, with timely aggressive treatments, most pediatric patients can complete the procedures safely.”

Their ultimate recommendation is for the procedure to be performed at a large referral pediatric cardiology center.

Xu Z, Zhang H, Arvanitaki A, et al. Right heart catheterization in pediatric pulmonary arterial hypertension: insights and outcome from a large tertiary center. 

. Published online September 13, 2022. doi:10.3390/jcm11185374

Articles

Outcomes following right heart catheterization in a pediatric patient population were analyzed, with emphasis placed on risk of adverse outcomes following the procedure, especially the development of pulmonary hypertensive crisis (PHC).

Potential for PHC Necessitates Pediatric Cardiology Care for Children With PAH

 Dr Feldman, hearing these positive results, how do you use finerenone at your practice? Are you starting to consider it for unique patients? Are you starting to use it in combination with SGLT2 inhibitors based on some of the data that we’ve seen thus far?

What Dr Agarwal alluded to is that the IDNT and RENAAL trials were in 2000 and 2001, and there are multiple other drugs that were tried between 2001 and 2015 or 2016 when SGLT2 inhibitors came on, and then last year when finerenone came on. [Before SGLT2 inhibitors and finerenone,] they all were dreadfully unsuccessful, and we had nothing in our toolbox to slow the process.

One thing is that when a patient comes to me, they think the first thing I’m going to do is say, “You’re ready for dialysis.” Basically, I use the guideline-directed therapy to slow the loss of renal function—what Dr Agarwal said—the decrease in serum creatinine by doubling, the [reduction] of eGFR [estimated glomerular filtration rate] by 57%. You now look at the eGFR over time.

One of Dr Agarwal’s colleagues…says graceful aging is when after the age of 35—I like to think it’s 40, but he says 35—you lose about 0.8 to 1 mL/min of eGFR per year. If you’re hypertensive, that can go up to 6 or 8 mL/min. RENAAL and IDNT slowed it a little. SGLT2 inhibitors drop it down to about 2.8 mL/min. On top of what Dr Agarwal said, with ACE [angiotensin-converting enzyme] inhibitors, ARBs [angiotensin receptor blockers], SGLT2 inhibitors, and adding MRAs [mineralocorticoid receptor antagonists], you can probably drop it down to 1.5 mL/min. That means that if somebody comes to me with an eGFR of 45 mL/min and I use combination therapy, normal loss of renal function in a diabetic with hypertension would be 4 or 5 mL/min a year. They would have been looking at dialysis in about 5 or 6 years. In addition, as their eGFR drops, they’re at risk for heart failure and coronary events and strokes.

By using these medicines and slowing the loss of renal function, the loss of eGFR, on a yearly basis, you can assure people that they will have fewer cardiovascular events and less heart failure, and probably prevent the need for dialysis if they live that long.

People used to get a transplant. When I started transplants, it would last for 8 or 10 years. We called that dialysis vacation. Now we have medications to do the same thing that transplants do, and they should be used in combination, because the combination on top of ACEs and ARBs with SGLT2 inhibitors and MRAs, you can reduce the loss of eGFR filtration, decrease the albumin-to-creatinine ratio, and bring it into a more normal range, hopefully someday down to about 1.5 or even 1 mL/min with newer stuff coming onto the market, ie, GLP-1 RAs [receptor agonists], which are most likely also renoprotective.

 [I have] a brief question for you. Have your patients provided any feedback as you’ve started to use finerenone on its ease of use or tolerability compared with previous treatments?

As Dr Agarwal alluded to, unfortunately, these are still MRAs, and hyperkalemia is a real issue. I’ll close out the session with the economic value; we do have treatment for hyperkalemia so you don’t have to stop these medicines. You can continue the medicines and use the alluded-to potassium binders, a low potassium diet, and keep the patients on their medicines, and they feel better. Patients tell me they feel better, particularly if they’ve had heart failure and symptoms of fatigue and weakness. The patients notice a difference, and it’s [usually] with combination-type therapy.

Dr Jeffrey Feldman discusses finerenone trial data and the role that it and SGLT2 inhibitors have played in patients with CKD.

Using Published Data to Consider SGLT2 Inhibitors and MRAs in CKD Management

Laura is the vice president of content for The American Journal of Managed Care® (AJMC®) and all its brands, including The American Journal of Accountable Care®, Evidence-Based Oncology™, and The Center for Biosimilars®. She has been working on AJMC® since 2014 and has been with AJMC®’s parent company, MJH Life Sciences®, since 2011.

She has an MA in business and economic reporting from New York University. You can connect with Laura on 

A drug to treat early Alzheimer disease has shown success in reducing cognitive and functional decline. Eisai and Biogen announced topline results from a large global page 3 confirmatory trial of lecanemab that met both the primary endpoint and all secondary endpoints.

Biogen also developed aducanumab (Aduhelm), which was the first drug approved for Alzheimer disease (AD) in 18 years. The approval of aducanumab 

, but trials showed that the drug could cause brain swelling or brain bleeding. Despite the advisory panel for the FDA voting that the evidence for aducanumab wasn’t enough to approve the drug, the FDA ultimately did approve it.

However, the topline results of the phase 3 confirmatory CLARITY AD clinical trial of lecanemab have shown that the drug reduced cognitive and functional decline by 27% at 18 months compared with placebo. The trial used the Clinical Dementia Rating-Sum of Boxes (CDR-SB).

As early as 6 months on treatment there were highly statistically significant changes in CDR-SB from baseline compared with placebo.

“These are the most encouraging results in clinical trials treating the underlying causes of Alzheimer’s to date,” the Alzheimer’s Association said 

Lecanemab is an investigational anti-amyloid beta protofibril antibody for the treatment of early AD—or mild cognitive impairment due to AD and mild AD—with confirmed presence of amyloid pathology in the brain. CLARITY AD was a placebo-controlled, double-blind, parallel-group, randomized study of 1795 people with early AD. Patients were randomized 1:1 to receive either placebo or 10 mg/kg bi-weekly of lecanemab.

Among patients taking lecanemab, the incidence of amyloid-related imaging abnormalities–edema/effusion (ARIA-E) was 12.5% vs 1.7% in the placebo group. The rate of ARIA cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis (ARIA-H) was 17.0% in the lecanemab compared with 8.7% in the placebo group.

The FDA accepted a Biologics License Application for lecanemab under the accelerated approval pathway in July 2022, and it granted Priority Review. A decision on lecanemab is expected by January 6, 2023.

“Today’s announcement gives patients and their families hope that lecanemab, if approved, can potentially slow the progression of Alzheimer’s disease, and provide a clinically meaningful impact on cognition and function,” Michel Vounatsos, CEO at Biogen, 

. “Importantly, the study shows that removal of aggregated amyloid beta in the brain is associated with a slowing of disease in patients at the early stage of the disease.

Eisai and Biogen highlighted the inclusion of ethnic and racial populations in the United States in the CLARITY AD trial, making the trial population comparable to the country’s Medicare population. Approximately 25% of participants were Hispanic and Black. This diversity is important because the trials for aducanumab had come under fire for their lack of diversity—only 0.6% of participants were Black and 3% were Hispanic.

However, if the drug is approved, it will be subject to a coverage decision put in place by CMS after the approval of aducanumab. With concerns over the effectiveness of aducanumab and a high price tag for the drug, CMS implemented a National Coverage Determination (NCD) for approved monoclonal antibodies directed against amyloid for the treatment of AD.

As a result, CMS will only cover aducanumab for patients in “qualifying” clinical trials that meet specific criteria set by CMS. For now, aducanumab is the only approved drug that falls into this category, but lecanemab would also be affected by the decision if it was approved. In addition, donanemab from Eli Lilly is in the pipeline and being investigated for the treatment of early AD.

The Alzheimer’s Association noted in its statement that CMS has indicated it will modify the NCD if warranted by evidence.

“If full CLARITY AD results are in line with today’s topline announcement and the FDA approves this treatment, Medicare beneficiaries living with Alzheimer’s, a terminal, progressive disease, deserve the same immediate, full coverage under Medicare afforded to those with other terminal diseases,” the association said.

1. Manly JJ, Glymour MM. What the aducanumab approval reveals about Alzheimer disease research. 

. 2021;78(11):1305-1306. doi:10.1001/jamaneurol.2021.3404

The topline results showed the phase 3 trial met both the primary endpoint and all secondary endpoints.

Alzheimer Disease Drug Lecanemab Successfully Reduces Cognitive, Functional Decline

Dr Noble discusses recent ATS guidelines regarding the use of pirfenidone in ILD. 

Utilizing Pirfenidone in ILD Treatment Strategy

There has been a sea change in how retina specialists treat retinal diseases, with a progressive shift toward more utilization of anti–vascular endothelial growth factor (VEGF), said Paul Hahn, MD, vitreoretinal surgeon at NJRetina.

Over the years of running the ASRS Preferences and Trends survey, have you seen any large shifts in responses to trends that are worth highlighting?

With the PAT survey, year over a year, we repeat some key questions to try to highlight important trends. Trends that we're often most interested in learning about are new technologies, new therapies that might be rapidly changing. For example, a couple of years ago, the FDA approval of the first ILM [internal limiting membrane]–staining agent—it’s a staining agent to help us perform macular surgery more effectively—this first agent was FDA approved, and prior to that, we were using an off-label agent. Over the past couple of years in the US, we saw rapid uptake in the utilization of this agent. This agent was actually approved earlier internationally, and over those prior years, we saw similar rapid increase in its uptake.

There have been some slower trends that we've been following closely as well. In the treatment of retinal diseases, there have really been sea changes in the way we perform things. For example, over the past 15 years, there has been a progressive shift toward utilization of more anti-VEGF therapy for treatment of retinal diseases, and we capture that with the PAT survey. Currently, there's a move toward, potentially, use of anti-VEGF therapy for treatment of retinal diseases that we previously did not treat, such as for severe nonproliferative diabetic retinopathy, something that we previously monitored. The PAT survey is in the process of capturing whether there really is a sea change or whether people will stick with their current habits.

Dr Paul Hahn Highlights Shifting Trends Among Retina Specialists

Biogen Agrees to Payout to Settle Kickback Allegations

 to pay $900 million to resolve allegations that it caused the submission of false claims to Medicare and Medicaid through kickback payments to physicians for prescribing Biogen drugs. This payment resolves a lawsuit that was filed by a former Biogen employee under the False Claims Act. The lawsuit alleged that Biogen paid physicians kickbacks to entice them to prescribe Biogen’s drugs for multiple sclerosis from January 1, 2009, to March 18, 2014. Biogen will be paying the United States government $843,805,187 and 15 states will receive $56,194,813.

American Cancer Society Expresses Concern About Fertility Preservation

 that fertility preservation options for patients with cancer could be at risk in a post–

 world. Gene testing and storage and disposal of embryos could be areas where restrictions are imposed in the future, according to the American Cancer Society. Researchers found that of more than 120,000 patients aged 15 to 44 years who were diagnosed with cancer in 2018, 68% of them needed fertility preservation services. Of those, there were 32,000 patients who lived in the 22 states where abortion bans exist or are expected to be passed.

Supreme Court to Hear Case on Ability to Sue Medicaid Providers

 to hear a case on Medicaid recipients’ ability to sue providers, which could potentially open the door to further rollback of the program’s benefits. The decision will determine whether tens of millions of beneficiaries of public welfare programs can sue their providers if their essential needs like health care and food are at risk, which would be more efficient than waiting on the federal government. Conservative judges and lawyers have argued that health care providers or individuals should not be able to sue in cases of Medicaid coverage. Arguments in the current case, 

Biogen Inc agreed to pay $900 million to settle allegations about improper physician payments; the American Cancer Society warns that fertility preservation for patients with cancer is at risk after the overturn of Roe v Wade; the Supreme Court will hear a case about Medicaid recipients’ ability to sue their providers.

What We’re Reading: Biogen Agrees to Settlement; Fertility Preservation for Patients With Cancer; Supreme Court Medicaid Case

Ophthalmology is image heavy, which has made the specialty amenable to telemedicine and the implementation of artificial intelligence (AI), said Grayson Armstrong, MD, medical director, ophthalmic emergency services at Massachusetts Eye and Ear, and instructor in ophthalmology at Harvard Medical School.

You'll be presenting on telemedicine and artificial intelligence for eye care at the AAO meeting. What are some of the key points you'll be talking about?

I'm incredibly excited to be talking about telemedicine and AI this upcoming AAO meeting. Ophthalmology as a specialty is incredibly amenable to telemedicine and AI implementation. We're an incredibly imaging heavy specialty. We have a lot of images and a lot of data that makes this possible. We're always on the cutting edge of technology. And we're, in many ways, the early adopters across all of medicine, in both pharma, technology, innovation, AI.

A few of the talks that I'll be speaking at—the first is called “Innovations in Telemedicine and AI From Around the World,” where I'll be on a panel with Michael Chiang, MD, the director of the National Eye Institute, and also Daniel Shu Wei Ting from the National University of Singapore, where we're talking about how to implement new technologies and AI in the clinics with your patients. This is mainly for young ophthalmologists, but anyone can attend. It's talking about where we currently stand as a field, where we're going, and how to use this in your day-to-day practice.

We're also talking about integration of AI tech and patient care, broadly. And the last session is called “Optimizing Telemedicine and AI for Both International and Domestic Use.” This is going to be during the 11:30 to 12:45 pm session on Sunday. This coincides with 

, where Jim Madara, MD, who's the CEO of the American Medical Association, is also talking about technology for patient care. I think it's going to be pretty innovating to hear how someone in charge of an organization as big as the AMA is thinking about these things, and how it can be applied to the field of ophthalmology.

Ophthalmology is image heavy, which has made the specialty amenable to telemedicine and the implementation of artificial intelligence, said Grayson Armstrong, MD, medical director, ophthalmic emergency services at Massachusetts Eye and Ear, and instructor in ophthalmology at Harvard Medical School.

Dr Grayson Armstrong Highlights How Ophthalmologists Are Early Adopters of Innovation

M. "Tonette" Krousel-Wood, MD, MSPH, FACPM, is president of the American College of Preventive Medicine.

Throughout the year, we mark important HIV awareness days focused on youth, women, and girls, vaccine research, and disproportionate impact on Black, Native, Latinx, National Asian, and Pacific Islander populations. In September, we highlight both National HIV/AIDS and Aging Awareness Day and National Gay Men’s HIV/AIDS Awareness Day. Each of these days gives us a chance as physicians and public health experts to raise awareness and encourage adults and adolescents to get tested for HIV. 

This outreach, for some, can be lifesaving—reducing the stigma associated with HIV and the anxiety that may come from requesting a test from one’s doctor or local community health services providers. But what happens when dedicated days of awareness are over?

As preventive medicine physicians, we understand that milestone days can go a long way toward building awareness around critical public health issues. However, the importance of HIV testing and the empowerment gained by “knowing your status” should be embraced and promoted throughout the year. We must all work consistently to promote the availability, convenience, and personal and public health importance of testing for HIV infection.

1.2 million Americans are living with HIV. Of those, more than 150,000 don’t even know it.

 For that 13% of individuals, one single test can be the difference between maintaining an undetectable level of HIV or progressing to late-stage HIV or AIDS. An early HIV diagnosis can help patients receive timely antiretroviral therapy that can prevent the virus from damaging the immune system and can greatly improve a patient's quality of life over the long term. In fact, with early detection and treatment, someone who is HIV positive can have a similar life expectancy to an HIV-negative individual. Therefore, as physicians, we must stress the importance of testing and follow-up treatment for HIV positive individuals. Early detection provides the opportunity for early action with lifesaving results.

Demetre Daskalakis, MD, director of HIV prevention at the CDC, said it best, “The only way we can truly end HIV in the United States is by eliminating the barriers that prevent equitable access to HIV prevention.” Testing is a critical step for HIV prevention. It is of utmost importance to make testing easily accessible and encouraged among people of all races, sexual orientations and gender identities, and socioeconomic backgrounds. The 

 that everyone between the ages of 13 and 64 years gets tested at least once as part of routine health care, with those more at risk for HIV testing at least annually.

As preventive medicine specialists, we are working on the front lines in the fight against HIV and AIDS. Ensuring access to testing and treatment, getting patients into regular testing, and encouraging the use of pre- and postexposure prophylaxis (PrEP and PEP) are critical. For many, the solution starts with meaningful conversations to reduce the stigma associated with HIV and the important measures available to prevent infection. It will take all of us in the health care community to help drive these conversations—yes, on awareness days and every single day of the year.

Contributor: Every Day Is HIV Awareness Day—The Importance of Motivating People to Get Tested for HIV

Rose is a freelance writer for The American Journal of Managed Care® (AJMC®), where she previously worked as an editor.

She has a BA in journalism & media studies and Spanish from Rutgers University. You can connect with Rose on 

Pregnant patients with inherited bleeding disorders face an elevated risk of life-threatening bleeding during pregnancy, delivery, and the postpartum period, making the identification and management of these disorders crucial to the mother and newborn’s health. A recent 

 details current knowledge on mitigating the risk for carrying mothers with 

 or von Willebrand disease (VWD) and their children.

Although healthy women experience changes to the hemostatic system throughout pregnancy, childbirth, and the postpartum period that support coagulation to minimize bleeding, these changes might not fully protect patients with hemophilia or VWD. Understanding the inheritance patterns of bleeding disorders and being aware of normal levels of procoagulant and anticoagulant factors in newborns is another key aspect of management.

Hemophilia is characterized by low levels of coagulant factors VIII or IX, and factor VIII in particular increases throughout pregnancy. Although the increase is normally sufficient in healthy women, the increase is inconsistent between women with hemophilia and may not be enough to prevent postpartum bleeding. Treatment by a multidisciplinary team at a care center affiliated with a hemophilia treatment center (HTC) is the ideal scenario for this patient group to reduce the risk of complications. Contextual information about the mother’s family and prepregnancy counseling on the potential for genetic transmission would ideally be in place at the HTC.

To assure sufficient levels of coagulant factors are present at delivery, factor levels should be checked early in pregnancy and at least at 28 to 34 weeks of pregnancy. Desmopressin (DDAVP) or factor replacement therapy is recommended for patients whose factor levels are lower than 50% by week 34 of pregnancy, although factor replacement is the first choice if needed due to the potential risk of neonatal or maternal hyponatremia with DDAVP. The factor level target should be 100% to 150%.

Determining the gender of the fetus is also important, as males carry a 50% risk of inheriting the disease and being at risk of neonatal bleeding while females have a 50% chance of being carriers with mildly low factor levels and little risk of neonatal bleeding. Chorionic villus sampling (CVS) or amniocentesis to evaluate fetal DNA is suggested for mothers of male fetuses. At birth, intracranial hemorrhage is the greatest concern for a newborn with hemophilia.

VWD is a more heterogeneous condition than hemophilia, although some management aspects are similar. During pregnancy, von Willebrand factor (VWF) levels increase to mitigate bleeding at delivery, but there is significant variation in VWF levels in expectant mothers with VWD. Those with type 1 VWD tend to show bleeding profile improvement throughout pregnancy as factor levels increase. Those with type 2 VWD show an increase in defective endogenous VWF, but not in VW activity. In women with type 3 VWD, the most severe form, both VWF and factor VIII typically remain low during pregnancy. Factor replacement therapy can help compensate for the lack of natural factor level increases.

As in hemophilia, target factor levels should be a minimum of 50%, targeting 100% to 150% at delivery. Factor replacement therapy with VWF containing plasma-derived factor VIII concentrate has been the most used intervention, although recombinant VWF may be more effective, the study authors note. To manage the risk of postpartum hemorrhage, prophylaxis with antifibrinolytics is recommended, and postpartum tranexamic acid is recommended when the patient’s bleeding score is high or there is a history of postpartum hemorrhage. As with hemophilia, DDAVP is another treatment option but carries concerns of maternal hyponatremia.

With hemophilia and VWD, the safety of neuraxial anesthesia has been called into question. Although it is still debated, experts agree that it should not be administered when factor activity is below 50%. In newborns, the greatest concern regarding bleeding complications is for those with type 2 or 3 VWD.

Overall, the review emphasizes the importance of early and accurate diagnosis of bleeding disorders in pregnant women and the fetuses they carry. Additionally, appropriate treatment for insufficient factor levels is crucial to uneventful pregnancy and birth. Treatment by a multidisciplinary care team and ideally involving an HTC are both key to improving the likelihood of a safe delivery for mothers and newborns.

Janbain M, Kouides P. Managing pregnant women with hemophilia and von Willebrand disease: How do we provide optimum care and prevent complications? 

. 2022;14:1307-1313. doi:10.2147/IJWH.S273043

A recent review details strategies for mitigating the risks faced by pregnant patients with hemophilia or von Willebrand disease and their children.


Managing Bleeding Disorders in Pregnancy Requires Early Diagnosis, Multidisciplinary Care

the journal of the American Academy of Pediatrics, provides guidance on evaluating children for 

 The recommendations aim to make this type of evaluation more consistent in cases when children have suspicious bruising or intracranial hemorrhage (ICH).

“When bleeding or bruising is suspicious for child abuse, careful consideration of medical and nonmedical causes is important,” the authors wrote. “Mistaken diagnosis, whether an inappropriate finding of abuse, a missed case of abuse, or overlooking of a medical cause, can cause harm to the child and his or her family.”

Infants are at an increased risk of abusive bruising or bleeding, but their presentation of bleeding disorders can be similar to abusive bruising or injury. Contextual information about the patient’s medical and family history of bleeding or bruising is also not sufficient to rule out a bleeding disorder. Laboratory evaluation is often needed to confirm bleeding disorders, but even when a disorder is present, it is still possible for abuse to be the cause.

The clinical recommendations in the report are informed by a technical report published in tandem with the recommendations,

 with data that include evidence differentiating accidental bruising vs abusive bruising in healthy children and the types of bruising seen in children with bleeding disorders.

The first recommendation is to conduct thorough medical, trauma, and family history assessments on children with bruising or bleeding that is suspicious for abuse. Notably, medical history cannot rule out bleeding disorders. If there is a specific bleeding disorder within a child’s family history, testing for that disorder should be completed. If possible, information on a child’s history should be obtained directly from the child and away from caregivers.

Recommendations 2 through 4 address the characteristics of bruising and specific medical history information that would indicate the need for a laboratory test to identify or rule out bleeding disorders. The need for laboratory testing should be based on the location and pattern of the bruising, the reasoning provided for the bruising, and the child’s developmental status and mobility level. For example, certain bruising patterns, such as hand-patterned bruising or bruising to the ears, neck, or genitals, are highly consistent with abuse and generally indicate that testing for a bleeding disorder is unnecessary.

Testing for bleeding disorders is addressed in recommendations 5, 6, 8, 9, 9a, and 9b. The type of testing should be informed by the prevalence of various conditions and the findings on the child that led to suspicion of a disorder. This can be based on patient medical history and characteristics, as well as physical findings. Whole blood clotting assays, such as thromboelastograph or rotational thromboelastography, should not be used in testing when abuse is possible. The report authors note that children with ICH often receive transfusions, so testing for bleeding disorders should be delayed until any transfused blood clotting elements have been eliminated.

Recommendation 7 suggests that when a physician does not have the necessary resources or comfort level to evaluate children for bleeding disorders in cases of possible abuse, they consult with a child abuse pediatrician or pediatric hematologist. This especially concerns cases of subdural hemorrhage and any instances where ICH is present. Testing for prothrombin time, activated partial thromboplastin time, von Willebrand factor antigen, von Willebrand factor activity, clotting factor VIII activity level, clotting factor IX activity level, and a complete blood count with platelet count are recommended in cases of suspicious bruising.

Even if laboratory testing indicates a bleeding disorder, Recommendation 8a emphasizes that abuse should not be eliminated as a possibility. Following up in a home setting is suggested to gather information that may help determine the likelihood that a bleeding disorder alone led to the suspicious findings.

Overall, the recommendations emphasize a need for thorough assessment of children with bleeding or bruising that could be caused by a bleeding disorder. Due to the rarity of bleeding disorders overall, identifying significant characteristics of these disorders prior to testing is recommended.

“Children who present with bleeding and bruising concerning for abuse require careful evaluation for the potential of bleeding disorders as a cause. No single panel of tests rules out every possible bleeding disorder,” the authors wrote. “Given the rarity of most bleeding disorders and the possible presence of specific clinical factors that decrease the likelihood of a bleeding disorder causing a child’s findings, extensive laboratory evaluation is usually not necessary.”

1. Anderst JD, Carpenter SL, Killough E, Abshire TC. Evaluation for bleeding disorders in suspected child abuse. 

 Published online September 19, 2022. doi:10.1542/peds.2022-059276

2. Carpenter SL, Abshire TC, Killough E, Anderst JD. Evaluating for suspected child abuse: Conditions that predispose to bleeding. 

. Published online September 19, 2022. doi:10.1542/peds.2022-059277

The recommendations aim to make this type of evaluation more consistent in cases when children have suspicious bruising or bleeding patterns. 

Guidance for Evaluating for Bleeding Disorders in Suspected Child Abuse 

Julia is an associate editor for The American Journal of Managed Care® (AJMC®) and joined AJMC® in 2022. She produces written and video content covering multiple disease states, and assists in the screening process for manuscripts submitted to AJMC®.

She has a BA in English language and literature from Rutgers University. You can connect with Julia on 

The proportion of people who underwent a 

 transplant in The Netherlands were able to work, and well, according to a new report 

Clinical Journal of the American Society of Nephrology

This study also found that these patients functioned better at work after the surgery compared with before the transplant.

The study used data from the TransplantLines Biobank and Cohort study, which were collected from June 2015 to May 2021. Participants were invited to participate if they were adult solid organ transplant recipients or donors. Kidney transplant recipients with a functioning allograft and potential kidney donors were included.

Data on work were obtained through self-formulated questions, with work functioning measured using the Work Role Functioning Questionnaire (WRFQ). Adverse effects of immunosuppressive therapy also were assessed with a questionnaire.

Data from the WRFQ were available for 668 kidney transplant recipients, 246 potential kidney donors, and 553 community-dwelling employed adults. Adults with a transplant kidney received the organ from a living donor more frequently and underwent the procedure on a preemptive basis more frequently vs those who received a kidney transplant and did not fill out the questionnaires. The mean (SD) age of the group was 51 (11) years, median (IQR) time after transplantation was 3 (2-10) years, and 59% of participants were men.

The prevalence of men was lower in the potential kidney donors group (43%) and higher in community-dwelling adults (70%), and the mean age was higher among potential kidney donors and lower in community-dwelling employed adults, at 53 (9) and 45 (11) years.

Fifty-six percent of the participants who underwent a kidney transplant were employed compared with 79% of the potential kidney donors, with 62% of employed men and 48% of employed being transplant recipients. Kidney transplant recipients were most often employed on a permanent contract (72%), worked more than 32 hours a week (58%), and had mentally demanding tasks (44%). Eight percent reported sickness-related absence at the time of inclusion in the study, with 17% receiving a supplementary disability pension as well.

The median (IQR) total score of the WRFQ was lower compared with employed potential kidney donors, at 91 (76-98) vs 94 (85-99), but it was higher compared with community-dwelling adults who were employed, whose score was 88 (79-95).

Twenty-four percent, 23%, and 53%  of the kidney transplant recipients reported low, medium, and high work functioning, respectively. Of the entire work time in patients who underwent kidney transplants, work scheduling demands were met a median of 94% (63%-100%), output demands were met a median of 88% (63%-100%), physical demands were met 100% (88%-100%), mental and social demands were met 96% (82%-100%), and flexibility demands were met 95% (85%-100%).

There were some limitations to this study. Causal relationships could not be assessed due to the observational study design, and selection bias favoring healthy patients was possible. Causes of unemployment and how many kidney transplant recipients were unemployed prior to transplant also were not available in any data.

Knobbe TJ, Kremer D, Abma FI, et al. Employment status and work functioning among kidney transplant recipients. 

. Published online September 26, 2022. doi:10.2215/CJN.05560522

A recent report found that 56% of patients from The Netherlands who underwent a kidney transplant were able to work and functioned well while working.

Kidney Transplant Recipients Able to Find Stable Work Post Surgery

Young people’s sleep patterns have changed worldwide in recent years, leading investigators to assess the relationship between 

 and academic performance in Norway, where a negative trend in academic achievement in math and science was reported alongside the shift in sleep patterns. A study published in 

 found that there was an association between sleep deficits and academic performance in math and science specifically.

The study used data from the Trends in International Mathematics and Science Study (TIMSS) from 2015 and 2019. The sample includes Norwegian ninth grade students and their mathematics and science teachers who participated in TIMSS. The TIMSS measures mathematics and science competence in Norwegian grades 5 and 9 and also includes information collected from students and teachers through questionnaires.

Teachers were asked how much they felt that students suffering from not enough sleep were limiting their ability to teach the class. Students were asked how often they felt sleepy when they arrived at school in the 2019 data.

Teachers’ reports of changes in the way students’ lack of sleep affected their ability to teach were compared from 2015 to 2019. In 2015, 37.8% of science teachers reported that students’ sleepiness did not affect their ability to teach. This decreased to 23.6% in 2019. There were also 10% fewer math teachers who reported sleep deficit as an issue in 2015 compared with 2019.

The researchers found that sleepiness affected mathematics and science achievements significantly. An increase of 8 score points in math was associated with students’ reports of being less sleepy, equivalent to a little less than half of a year of schooling in Norway. Feeling sleepy was also associated with a decrease of 5 score points in science academic performance.

Sleep deficits reported by teachers were also found to be associated with math and science performance. An increase in sleep deficit was associated with a decrease of 10 score points in math in 2015 and 9 score points in 2019. Similar results were found with performance in science, with a sleep deficit associated with a decrease in approximately 10 score points in 2015 and approximately 6 score points in 2019.

The trend analyses found that the effect of time on science and math achievement was 13.01 and 8.42 score points, respectively, from 2015 to 2019.

There were some limitations to this study. Students were not asked about sleepiness in 2015. Teachers were not asked if their students had had enough sleep but instead were asked if their sleepiness limited their ability to teach, making it an indirect measure. A scale with several items measuring sleep deficit and sleepiness would have been ideal but was not used for this study. The questions regarding sleep were focused on quantity rather than quality of sleep.

The researchers concluded that there has been an increase in sleep deficits in students from Norway from 2015 to 2019. There was a negative association between sleep deficits and performance in math and science, with performance decreasing from 2015 to 2019 due to an increase in sleep deficits.

Vik FN, Nilsen T, Overby NC. Associations between sleep deficit and academic achievement – triangulation across time and subject domains among students and teachers in TIMSS in Norway. 

. 2022;22:1790. doi:10.1186/s12889-022-14161-1

A trend study found that adolescents in Norway had poor academic performance in science and math when they were sleep deprived.

Sleep Deficits Associated With Poor Academic Performance Among Norwegian Youth

During the Parker Health Lecture at the American Academy of Ophthalmology (AAO) annual meeting, James Madara, MD, CEO of the American Medical Association (AMA), will discuss the 3 arcs of the AMA’s strategic framework and the innovation that needs to occur.

Can you give a preview of what you'll discuss during the Parker Health Lecture at the AAO annual meeting?

I will discuss a couple of things. One is the strategic framework of the AMA, and it has 3 arcs. Those arcs represent what I would call precompetitive positions. One is chronic disease, one is lifelong learning, and one is removing obstacles from physician-patient interactions. And when you think about that, in the terms of precompetitive, the reason it’s precompetitive is that it doesn't really matter what health system we have, in the mid-century, if we don't have the workforce trained for the 21st century, if we haven't dealt with the problem of chronic disease that’s growing—it's now more than 90% of our $4 trillion health care spend and growing—and if we haven't removed the obstacles so that physicians can better interact with patients, none of those potential health systems would work very well in the mid-21st century. So, in that sense, these are precompetitive needs.

The second point I'll make is that a lot of innovation has to occur under these 3 arcs. Some of that innovation is done internally, some of it is that our venture company formation in Silicon Valley, Health2047. What unites all the work done here and there is that the problem definition has to be at the right site. Too often, the tools and services we have in health care have a starting problem definition at the administrative level. Then the solution is thrown over the transom into the clinic, and we get a series of point solutions that don't interact very well. We need to define a problem where we think the truth of the health system is, and that's between the patient and the physician.

I hope to make those points, and obviously they all require partnering, because these are big problems larger than any one organization can solve.

AMA’s Dr James Madara to Discuss Precompetitive Positions and Innovation Needs at AAO

The American Academy of Ophthalmology (AAO) annual meeting will present cutting-edge topics on retinal disease, as well as feature a presentation from historian Doris Kearns Goodwin, said Ravi Goel, MD, spokesperson for AAO and ophthalmologist at Regional Eye Associates in New Jersey.

Can you highlight 1 or 2 of the sessions you will be chairing and what attendees can look forward to at them?

I am excited about AAO 2022. After 2 years of the COVID-19 pandemic, and then numerous aspects that the academy has gone to, to make the venue safe and a world-class facility, I'm looking forward to meeting with colleagues and exchanging ideas. There are a few sessions that I'm particularly interested in. One of the sessions is on Innovations in Ophthalmology From Around the World. This is cosponsored by the AMA Ophthalmology Section Council, and we will have 4 dynamic speakers, 

, and he's the CEO and executive vice president of the American Medical Association, and he'll be speaking about the future of medicine.

We'll also have cutting-edge topics on retinal disease, and also one of our speakers from Duke travels internationally, mostly to Africa, to deal with indigent and ophthalmic care in third-world countries. We'll also have a 

, who is a faculty member at Harvard Medical School and Mass Eye and Ear, talking about the future of telemedicine. So, the Innovations in Ophthalmology From Around the World, cosponsored by the AMA Ophthalmology Section Council, is a must-visit event.

As an ophthalmologist, and as a student of history, I am most excited actually about the closing session. Historian Doris Kearns Goodwin is going to be speaking about 

. I'm not trying to sell her book, but I think she is a fascinating speaker, and she's a fascinating writer. As someone who's read her book, including 

, and is a fan of Abraham Lincoln and John F. Kennedy, and she worked for Lyndon Johnson. Her talks are always fascinating. And I would encourage colleagues to show up at the closing session and to hear Doris Kearns Goodwin speak. In addition, Scott Turow is going to be speaking at the opening session. So, I look forward to seeing colleagues there.

What's the importance of having annual meetings with in-person attendance vs only virtual attendance?

One of the hidden benefits in ophthalmology is that there has been an explosion of education, through online sites and educational media, webinars, etc, over the last 2 years. I noticed that when I returned to New Orleans last year, and we were fully vaccinated, and the Academy did a wonderful job of making sure everyone was safe. It was wonderful to get to be in the same room with colleagues, to exchange ideas often in the hallway, you can talk about a challenging case. That's where innovation occurs, not only in the sessions but also in sidebar conversations. And what I love about the Academy's annual meeting now is that we have 75-minute blocks with intermissions, so that attendees and speakers can move more easily between sessions. There is in-person and there is virtual at the annual meeting, and I think that there are some sessions which I’ll attend in person, there are some sessions which may be across the convention center, and available either virtual or on demand, and I'll attend them virtual or on demand. For me, I'm looking forward to seeing colleagues and learning about the future of ophthalmology.