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

For our latest After Hours interview, Crystal Denlinger, MD, FACP, chief scientific officer, NCCN, discusses how how she rekindled her love for sailing during the pandemic, with AJMC® Associate Editor Matthew Gavidia.

Learn About Managed Care Experts' AFTER HOURS Interests

 had lower endothelial function than healthy controls, regardless of whether participants had physiological confirmation of the disease. 

also showed that that participants with asthma who regularly used short-acting beta agonist (SABA) medications had increased arterial stiffness than those who did not use SABA.

Researchers aimed to compare markers of cardiovascular risk, specifically endothelial function, arterial stiffness, and systemic inflammation, among those with confirmed asthma, unconfirmed asthma, and healthy controls. Researchers also aimed to investigate the effect of SABA use on these vascular outcomes.

This cross-sectional study included 26 patients with confirmed asthma, 15 patients with unconfirmed asthma, and 26 healthy controls all recruited from the Edmonton, Canada metropolitan area. All participants in the study were aged between 18 to 45 years and current nonsmokers.

Participants completed a pulmonary function test and evaluation for asthma. Physiological evidence of asthma was defined as a clinical history of symptoms such as recurrent wheezing, cough, and/or chest tightness. Physiological evidence also includes a reversibility in forced expiratory volume in 1 second (FEV

) of ≥12% and 200mL, a ≥20% reduction in FEV

 after a methacholine challenge, or a ≥10% reduction in FEV

Participants were labeled with confirmed asthma if they had a clinical history and physiological evidence of asthma. Those labelled with unconfirmed asthma had a clinical history but no physiological evidence of asthma. Healthy controls had no evidence of asthma. Researchers compared endothelial function, arterial stiffness, and systemic inflammation between these three groups of participants.

Researchers assessed participants’ endothelial function as flow-mediated dilation (FMD) after 5 minutes of supra-systolic forearm occlusion distal to the imaging site. A 1% decreased in FMD correlates with a 7% increase in cardiovascular risk.

Participants’ arterial stiffness was assessed using pulse wave velocity (PWV). PWV was measured between the carotid and radial artery. A 1 m/s increased in PWV corresponds to about a 16% increase in cardiovascular risk.

Systematic inflammation was assessed by C-reactive protein (CRP) levels in serum after venous blood was collected from the participants. CRP levels have been linked with cardiovascular risk, even for those without underlying cardiovascular morbidity.

Endothelial function was significantly lower in both confirmed and unconfirmed asthma groups than compared to healthy controls. There was no significant difference in FMD between the confirmed and unconfirmed asthma groups.

There was no significant difference found in arterial stiffness and systemic inflammation among both asthma groups and the controls.

Participants with bot confirmed and unconfirmed asthma were grouped together and then split based on SABA use. SABA was used by 19 participants and not used by 22 participants in the last year. There was no significant difference between in endothelial function and systemic inflammation between these two groups. However, SABA users had a significantly higher arterial stiffness by an average of 1.5 m/s than those not using SABA.

Limitations of this study include the small sample size and the inability to account for seasonal fluctuations in asthma symptoms due to the cross-sectional design. Also, this study did not adjust for other variables that can impact vascular outcomes.

Reduced vascular function was seen in participants with asthma regardless of physiological confirmation of asthma, suggesting that the link between asthma and cardiovascular risk may be due to factors other than asthma pathophysiology and perhaps due to asthma symptomatology, the researchers noted. The researchers also noted that this study highlights the need for proper asthma management to avoid inappropriate SABA use in patients with unconfirmed physiological asthma.

Henry SL, Moore LE, Brotto AR, Rowland S, Fuhr D, Stickland MK. Systemic vascular health is comprised in both confirmed and unconfirmed asthma. 

Articles

Patients with symptoms of asthma, regardless of physiological confirmation, experienced worse vascular outcomes and greater cardiovascular risk, which may be due to short-acting beta agonist (SABA) use, according to the results of a recent study.

Worse Vascular Outcomes Found in Patients With Asthma

There is evidence for a causal link between 

 and cardiovascular disease (CVD), suggesting the importance of early monitoring of cardiovascular risk in patients with psoriasis, according to a study recently 

Although patients with psoriasis are known to have a higher risk for CVD, this study builds upon previous research by investigating a causal link between psoriasis and CVD.

“A large number of observational studies showed that patients with psoriasis have a higher risk of CVD, but most studies did not fully adjust for confounding factors, so it is not clear whether the risk of CVD is directly attributed to psoriasis,” wrote the authors.

They conducted a 2-sample Mendelian randomization to evaluate the potential causal relationship between psoriasis and CVD using genetic evidence. Genetic instruments from the genome-wide association study of European descent for psoriasis were used to investigate the relationship. Inverse variance-weighted Mendelian randomization analyses were used, in addition to a variety of other methods.

The analysis indicated that genetic susceptibility to psoriasis was associated with a higher risk of multiple CVDs. Psoriasis was associated with a higher risk of heart failure (odds ratio [OR], 1.04; 95% CI, 1.01-1.06; 

 = 2.72E-03), atrial fibrillation (OR, 1.04; 95% CI, 1.02-1.07; 

 = 3.27E04), myocardial infarction (OR, 1.07; 95% CI, 1.01-1.12; 

 = .01), valvular heart disease (OR, 1.001; 95% CI, 1.000-1.002; 

 = 1.85E-03), and large artery stroke (OR, 1.11; 95% CI, 1.05-1.18; 

Notably, susceptibility to psoriasis was found to not be associated with a higher risk of ischemic stroke (OR, 1.03; 95% CI, 0.98-1.07; 

 = .27) or small vessel stroke (OR, 1.00; 95% CI, 0.95-1.07; 

The sensitivity analysis found weak evidence of horizontal diversity and heterogeneity, ensuring the stability of the results.

Overall, these findings provide evidence for a potential causal relationship between psoriasis and CVD.

The exact mechanism by which psoriasis increases the risk of CVD, if it increases the risk at all, has been debated in previous research. Studies on the relationship between psoriasis and CVD did not adjust for confounding factors, the authors of the present investigation noted, preventing the establishment of a causal relationship.

A strength of this study is that it explores this causal relationship between psoriasis and a series of CVDs. The authors assert that their results are unlikely to be influenced by confounders. Additionally, multiple analytical tools used produced consistent results, while the sensitivity analysis indicated the study results were reliable.

However, the study also faced limitations. The authors acknowledge that the OR value is relatively low, necessitating careful interpretation when generalizing results.

The researchers encourage more in-depth research on the relationship between psoriasis and CVD with a broader population beyond Europe. They also recommend early cardiovascular risk assessment and prevention in patients with psoriasis to facilitate the introduction of individual-specific treatments as soon as possible.

Gao N, Kong M, Li X, et al. The association between psoriasis and risk of cardiovascular disease: a Mendelian randomization analysis. 

 Published online June 29, 2022. doi:10.3389/fimmu.2022.918224

The findings add to previous research on similar outcomes between psoriasis and cardiovascular disease, using a Mendelian randomization study.

Study Suggests Causal Link Between Psoriasis, Cardiovascular Disease

Julia is an associate editor of The American Journal of Managed Care

since 2022 after receiving her Bachelor's degree at Rutgers University–New Brunswick in English and Creative Writing.

Sarah Wells Kocsis, MBA, director of the Center for Public Health at the Milken Institute, talks about the key findings of her recently authored 

, “Chronic Kidney Disease: Finding a Path to Prevention, Earlier Detection, and Management.”

What are the biggest takeaways of your research?

Chronic kidney disease [CKD] is a huge public health problem. It's intricately tied to health equity and social determinants of health. So tackling CKD is going to require a major shift in our mindset and the approach. Roughly 1 in 7 adults have chronic kidney disease, and 9 out of 10 of them don't even know that they have it, so we really need to listen to what the research is telling us. And what it's telling us is that we really need to focus right now on root causes, and these causes are structural, social, and health related. That's going to require practical, scalable, equitable solutions aimed at both detecting and managing the condition upstream at earlier stages and focusing on reducing the burden of this debilitating disease.

Videos

Sarah Wells Kocsis, MBA, is co-author of the Milken Institute report, “Chronic Kidney Disease: Finding a Path to Prevention, Earlier Detection, and Management.” She spoke to The American Journal of Managed Care® about the findings of the report and how they can be incorporated into care for patients with chronic kidney disease (CKD).

Milken Institute's Sarah Wells Kocsis Highlights Key Findings of Her Research on CKD

As the scientific community continues to explore whether 

 (CAR)-based therapy could improve breast cancer survival rates, researchers have outlined the latest research in the disease in a new paper 

Journal of Cellular and Molecular Medicine

Despite advances and improvements made in the disease, the researchers of the study note that breast cancer still remains one of the top causes of cancer death in women around the world.

“There is an unmet therapeutic necessity to develop effective therapies for breast cancer patients with a high risk of recurrence and metastasis and a low survival rate,” wrote the researchers. “Immunotherapeutic techniques based on CAR-redirected immune cells have evolved, with the potential to redirect immune cells such as T and NK [natural killer] cells to suppress malignancies, with various conducted or ongoing clinical trials.”

A variety of preclinical studies have assessed the potential of CAR T-cell therapy in breast cancer, including those that target MUC1, HER2, EGFR, GD2, and TEM8 antigens. Building on the promise demonstrated in preclinical studies, several first-in-human studies have begun, including a phase 1 study assessing the safety and optimal dose of 

-targeted CAR T cells in patients with HER2-positive cancers that have brain and/or leptomeningeal metastases.

According to the researchers, most of these clinical trials have been focused on 

-targeted CAR T cells. One open-label phase 1 trial, currently recruiting, is assessing the preliminary efficacy of intravenously administered TnMUC1-CAR T cells among patients with advanced TnMUC1-positive breast cancer.

Preclinical studies of CAR NK cells include those targeting HER2/neu, EGFR, L-ICON1, and EpCAM. Data on HER2/neu has been promising, with one murine study showing that intravenous injection of NK-92-scFv(FRP5)-zeta cells led to a reduction in progressive signals 12 hours and 24 hours after injection. HER2/neu-specific CAR NK cells also demonstrated an ability to successfully lyse HER2-expressing MDA-MB468 breast cancer cell lines in vitro.

Some data suggest that EGFR-specific CAR NK cells may be used in patients with triple-negative breast cancer (TNBC) who have elevated EGFR expression. In one study, researchers found that EGFR-CAR NK cells produce cytotoxic and antitumor effects on HS578T, MDA- MB-468, and MDA-MB-231 TNBC cell lines that express upregulated EGFR. The group also saw indications that these CAR NK cells could inhibit the growth of tumors in vivo.

The group also cited data of CAR NK cells targeting tissue factor (TF)—a new surface antigen expressed in 50% to 85% of patients with TNBC—in which TF-targeting CAR NK cells eliminated TF-positive MDA-MB-231 cells in vitro and significantly inhibited tumor growth in vivo.

“Studies on CAR-NK cells collectively deliver a few vital signs for upcoming development,” explained the researchers. “NK-tailored CAR structure appears to be essential for maximizing NK cell toxicity. Also, optimizing a procedure for the expansion and activation of harvested NK cells is required to attain a homogeneous population of clinically substantial counts of memory-like, unexhausted NK cells. Additionally, the utility of CAR-NK cells in the treatment of breast cancer may need further modifications of the NK cells beyond CAR transduction to increase trafficking and desensitize them to the immunosuppressive tumor microenvironment.”

Nikoo M, Rudiansyah M, Bokov DO, et al. Potential of chimeric antigen receptor (CAR)-redirected immune cells in breast cancer therapies: recent advances. 

2022;26(15):4137-4156. doi:10.1111/jcmm.17465

Despite advances made against the disease, researchers note that breast cancer still remains a top cause of cancer-related mortality in women around the world. 


Targeted Treatment for Breast Cancer Explored in New Study

Plasma prostasin levels had a cross-sectional association with the risk of cancer mortality and the risk of 

, which may help understand the link between diabetes and cancer. 

Plasma prostasin levels act as a biomarker for tumors, mostly demonstrating an association with glucose metabolism and hyperglycemia-associated tumor pathology.

, used the Malmo Diet and Cancer study, which was conducted in Malmo, Sweden. The study sample is made of the participants in the Malmo Diet and Cancer Study Cardiovascular Cohort in particular. Patients with prevalent diabetes were excluded for this study. Smoking habits, alcohol consumption, current medication, leisure-time physical activity, and educational level were obtained from the participants as part of demographic information.

There were 4658 participants, with a mean (SD) age of 57.5 (5.9) years; most were female (60.1%) and 361 (7.75%) had prevalent diabetes.

A cross-sectional analysis revealed an association between prostasin and diabetes, as the multivariable adjusted OR for the highest vs lowest quartile was 1.95 (95% CI, 1.39-2.76). The OR per 1 SD increase in prostasin was 1.32 (95% CI, 1.16-1.50).

A longitudinal analysis that excluded participants with prevalent diabetes (4297 participants with a mean age of 57.3 [5.9] years) found a prostasin concentration of 8.44 (0.44) NPX for men and 8.18 (0.48) for women. This analysis also found that the glomerular filtration rate (eGFR) values decreased as the prostasin levels increased. 

Other risk factors demonstrated an increasing trend from the first to fourth quartiles. Prostasin levels in patients without diabetes had a positive correlation with fasting blood glucose levels, plasma insulin levels, and HOMA2-HR.

There were 702 patients who developed diabetes in a follow-up period of 21.9 (7.0) years. Participants with higher prostasin levels had a higher risk of diabetes, as the HR for diabetes in the highest and lowest quartile of prostasin was 1.76 (95% CI, 1.41-2.19) and a per 1 SD increase in prostasin had an HR of 1.23 (95% CI, 1.13-1.34). The association was reduced after adjusting for fasting blood levels or HOMA2-IR but was still significant.

Age, fasting blood glucose, and eGFR were significant factors in relation to the risk of diabetes, which was more evident in younger participants, those without impaired fasting blood glucose levels, and in participants with impaired renal function. The relationship between prostasin and diabetes was linear and not time dependent.

There were 651 participants who died from cancer in a mean follow-up period of 23.5 (6.1) years; prostasin was found to have a significant association with cancer mortality. A multivariable adjustment found that the HR was 1.43 (95% CI, 1.14-1.80) when comparing the highest vs lowest quartile of prostasin and per 1 SD increase in prostasin was 1.13 (95% CI, 1.04-1.23). These results remained the same after excluding cancer at baseline.

There was also an interaction found between prostasin and fasting blood glucose for risk of cancer mortality, where the HR for cancer mortality was 1.52 (95% CI, 1.07-2.16) and 1.11 (95% CI, 1.01-1.21) per 1 SD increase in prostasin in participants with and without impaired fasting blood glucose levels at baseline.

Predictive ability of prostasin for cancer mortality and diabetes did not significantly improve.

There were some limitations to this study. Prostasin levels were measure in arbitrary units and couldn’t be compared with absolute values. Bonferroni adjustments for biomarkers were not made. Prostasin levels measurements were made with blood samples that were frozen for over a decade, which makes the stability of the storage unclear. Serial measurements of prostasin and risk factors over time were not in this study. Diabetes type was also not determined.

The researchers concluded that plasma prostasin is a potential risk marker for development of diabetes and for cancer mortality risk in those with high blood glucose levels.

Bao X, Xu B, Muhammad IF, Nilsson PM, Nilsson J, Engstrom G. Plasma prostasin: a novel risk marker for incidence of diabetes and cancer mortality. 

. Published online August 4, 2022. doi:10.1007/s00125-022-05771-w

A cross-sectional association was found between plasma prostasin level and risk of diabetes and cancer mortality in patients with high blood glucose levels.

Biomarker Linked With Risk of Diabetes, Cancer Deaths

Matthew is an associate editor of The American Journal of Managed Care® (AJMC®). He has been working on AJMC® since 2019 after receiving his Bachelor's degree at Rutgers University–New Brunswick in journalism and economics.

More consideration is needed from insurance companies in prioritizing the clinical judgement of physicians caring for patients with 

 (HS) to avoid unnecessary treatments and reduce the time to effective management, said Brindley Brooks, who founded HS Connect (HSconnect.org), a patient advocacy group for those affected with the disease.

What do you want insurance companies to know about HS?

There are a lot of hurdles for people with HS to get appropriate treatment. There’s currently only one FDA-approved treatment for HS. All of the precursors that we are required by most insurances to try, including metformin in some cases, spironolactone—those are all good options for HS. However, none of them are FDA approved for the treatment of HS. So, it's difficult because there are a lot of hoops to jump through as an HS patient in order to sometimes get to the next step where you need to go.

So, when people enter treatment, they may be past the point where some of those prior medications will work, and need to kind of go straight to something like a Humira [adalimumab] based on what stage they're at and the progression of their disease. But unfortunately, without doing all of those prior medications, a lot of times insurance companies won't approve those medications like Humira until later and when they've gone through the whole gamut. That's a really frustrating situation for a patient with HS.

Each of those medications, we’re told to give sometimes up to 6 months to work. Six months is a really long time when you're dealing with this chronic condition. So, it feels like it's an endless cycle of jumping through hoops to get to where you need to be, and where your physician thinks you need to be. So, I think that one of the difficult things about dealing with insurance for us is the amount of time that it takes to jump through all those hoops when the medical provider who is an expert potentially in this area is saying: this is futile to try these but we have to for insurance.


It is a really depressing thing to deal with, because you know that you're just prolonging your disease process and potential help for your disease. And dealing with it on a daily basis is very painful. For us, 3 to 6 months is a really long time—so, I wish there was more consideration given to the doctors and the physicians who are prescribing as far as their clinical judgment and that insurance would take that more into consideration.


It's not a one-size fits all disease. Sometimes it's a combination of multiple things in order to get a patient to resolution—not even resolution, because that's a rarity—but to be in a better situation with their HS, and to be under better control. So, I really do wish that insurance companies would take more into consideration the providers opinion and their expertise on the disease.

Brindley Brooks, who founded HS Connect (HSconnect.org), a patient advocacy group for those affected with hidradenitis suppurativa (HS), discussed step edits and other barriers to treatment caused by insurance requirements in the management of HS.

Advocate Speaks on Prior Authorization, Insurance-related Barriers for HS Treatment

Allison Fortier is a PharmD candidate in the class of 2022 at Midwestern University College of Pharmacy.

Milena Murray, PharmD, MSc, BCIDP, AAHIVP, is an associate professor of pharmacy practice at Midwestern University Chicago College of Pharmacy and an HIV/ID clinical pharmacist at the Northwestern ID Center.

Approximately 37.9 million people living with HIV are at risk of infection with SARS-CoV-2, the virus that causes COVID-19.

 However, the COVID-19 pandemic created setbacks for individual and public health HIV treatment goals. These delays in care had many adverse effects.

People were told to stay home, and many appointments and procedures were canceled.

 Further, those who may have received their diagnosis in the hospital could not follow up for care and receive treatment, and access to antiretroviral therapy (ART) was restricted during the pandemic, which led to decreased adherence. This, in turn, affected the HIV care continuum.

A 2022 respective cohort study reported that overall HIV testing between 2019 and 2020 dropped 35.4%.

 Notably, populations with the highest risk for transmission had an overall decrease in testing of up to 58.7%. Routine HIV appointments have also been hindered by the COVID-19 pandemic, with many people with HIV being lost to follow-up.

While the number of telemedicine visits has increased, gaps in care remain. The most severely impacted countries were those in Latin America, with a reported 24.3% reduction in HIV consultations.

 In September 2021, the World Health Organization (WHO) released guidance on maintaining health services, including safe delivery of HIV services, noting that in the sub-Saharan African region, a 6-month interruption of ART would result in over 500,000 adult deaths from HIV and an up to a 2-fold increase in perinatal transmission of HIV.

Accessibility to HIV treatment has advanced in the last few decades, but all barriers have not been eliminated. Obstacles, including cost and social pressures, are still present, and COVID-19 has further decreased the availability of ARTs. A 2020 survey conducted by UNAIDS and the BaiHuaLin alliance of people with HIV, with support of the Chinese National Center for AIDS/STD Control and Prevention, showed that 32.6% of people in China living with HIV were at risk for ART discontinuation and 48.6% were unsure how they could get ART in the future.

 These numbers were reported before the COVID-19 pandemic and have likely increased due to the pandemic. Mitigation strategies include multimonth medication dispenses, extended clinic hours, mobile clinics, and televisits.

Along with HIV care, many other health processes were disrupted, including routine vaccinations. According to insurance claim statistics pulled from a health care firm, adults 19 and older have missed almost 27 million vaccinations since January 2020.

Fortunately, the decreases in testing, positive tests, and numbers of people starting ART in the early months of the pandemic eventually started to reverse.

 Multimonth ART prescriptions became more mainstream, increasing access to medication. An abstract presented at the Conference on Retroviruses and Opportunistic Infections (CROI) in March 2021 stated, “[People] with HIV, who are virally suppressed and stable, do not need to be coming in every month to collect their medication.”

 Tiffany Harris, PhD, MS, Columbia University Mailman School of Public Health, presented data at CROI from 1059 facilities in 11 countries, reporting that 51% of patients received 3 months’ medication at one time from October to December 2019, which rose to 80% from June to September 2020.

 The WHO also supports allowing ART dispensing for up to 6 months at a time, which would limit disruption of ART and decrease client volumes in health facilities.

The impact of the COVID-19 pandemic reverberated worldwide, and people with HIV experienced ART discontinuation and loss of follow-up. Resuming efforts to achieve HIV treatment targets should be prioritized, and keeping up with wellness visits will become the focus for many people with chronic diseases.

1. Jiang H, Zhou Y, Tang W. Maintaining HIV care during the COVID-19 pandemic. 

. 2020;7(5):e308-e309. doi:10.1016/S2352-3018(20)30105-3

2. Rick F, Odoke W, van den Hombergh J, Benzaken AS, Avelino-Silva VI. Impact of coronavirus disease (COVID-19) on HIV testing and care provision across four continents. 

. 2022;23(2):169-177. doi:10.1111/hiv.13180

3. Ford N, Vitoria M, Doherty M. World Health Organization guidance to support human immunodeficiency virus care models during the coronavirus disease 2019 era. 

 2022;74(9):1708-1710. doi:10.1093/cid/ciab855

4. UNAIDS and China working together during the COVID-19 outbreak to ensure that people living with HIV continue to get treatment. News release. UNAIDS. February 19, 2020. https://www.unaids.org/en/resources/presscentre/pressreleaseandstatementarchive/2020/february/20200218_china_covid19

5. Declines in routine adult and teen vaccinations continued in 2021. Avalere Health. January 10, 2022. https://avalere.com/insights/declines-in-routine-adult-and-teen-vaccinations-continued-in-2021

 2021;21(6):774-775. doi:10.1016/S1473-3099(21)00279-6

7. Peabody R, Harris T. “Resilient” HIV programmes in African countries have maintained viral suppression during the COVID-19 pandemic. Aidsmap.com. March 17, 2021. https://www.aidsmap.com/news/mar-2021/resilient-hiv-programmes-african-countries-have-maintained-viral-suppression-during

Not all barriers to HIV-related care and services have been eliminated, and these gaps in care were exacerbated by treatment disruptions brought on by the COVIDC-19 pandemic.

Contributor: It’s Important to Prioritize HIV Care During the COVID-19 Pandemic

Investigators are calling for a reexamination and refinement of the process in which second opinions for 

 are delivered by dermatopathologists, after their study findings 

 showed that prior results likely influenced incorrect interpretation of study cases.

“Medical second opinions are common, although little is known about the best processes for obtaining them,” the study authors wrote, adding that they wanted “to measure the extent to which dermatopathologists’ diagnoses are influenced by prior diagnostic information from another dermatopathologist.”

The study cohort comprised 149 dermatopathologists (68%, male; median age, 47 [range, 34-76] years; 41%, Southern United States; 99%, board certified in dermatapathology) randomly assigned in 2 phases to interpret slide sets of melanocytic skin biopsy specimens from the Melanoma Pathology Study; these slides were organized by class, ranging from class 1 (benign/mildly dysplastic nevi) to class V (malignant invasive melanoma). 

Phase 1 did not include prior diagnostic information from another dermatopathologist. Phase 2 involved reexamining the same 5 slide sets (90 cases) but with prior diagnostic information that indicated a less or more severe diagnosis compared with what each clinician produced in phase 1. All prior diagnostic information “were actually diagnoses from board-certified and or fellowship-trained dermatopathologists.”

Overall, when handing down their second opinion, the dermatopathologists were 52% more likely (relative risk [RR], 1.52; 95% CI, 1.34-1.73) to give a more severe diagnosis following their phase 2 slide review vs their phase 1 diagnosis—when prior diagnostic information was not provided—and if the prior diagnosis provided in phase 2 indicated more severe disease. In addition, although a slightly lower finding, they were also more likely, at 38% (RR, 1.38; 95% CI, 1.19-1.59), to hand down a second opinion of a less severe case of disease if their phase 2–provided diagnostic information indicated less severe disease.

There were 5322 overall interpretations, and most physicians had been interpreting melanocyte skin lesions for 5 to 9 years (26%) or 10 to 19 years (42%). Forty-eight percent spent 10% to 24% of their caseload performing these interpretations.

The study authors also noted trends of influenced opinions even among those who claimed not to be swayed by another diagnosis. Thirty-one percent of dermatopathologists who originally indicated their diagnostic ability was not affected by a prior diagnosis showed evidence of influence in this regard, according to a baseline survey. In addition, study findings showed that of those who consulted on cases, 21% were swayed when giving a decision and 47% handed down an incorrect phase 2 diagnosis even when their phase 1 diagnosis was correct.

“While medical practice has long incorporated second opinions, the potential influence of antecedent diagnostic information has never been systematically studied to our knowledge,” the authors wrote. “A lack of research on second opinions may reflect the challenges in studying the topic.”

They added that their results may actually be an underestimation of influence, however, because notes saved from phase 1 slide observations may have led the dermatopathologists to ignore the initial diagnostic information in phase 2. The possibility of being less influenced in a testing situation and training (board certification and fellowship) were both cited as potential reasons for this.

“The adage ‘2 heads are better than 1’ should be carefully considered in the context of medical decision-making,” the authors concluded. “We need to consider and refine the methods of how these 2 heads come together.”

Elmore JG, Eguchi MM, Barnhill RL, et al. Effect of prior diagnoses on dermatopathologists’ interpretations of melanocytic lesions: a randomized controlled trial. 

Published online August 10, 2022. doi:10.1001/jamadermatol.2022.2932

This study investigated how an initial diagnosis influences delivery of second opinions concerning skin cancers, including the possibility of an incorrect diagnosis.



Second Opinions Likely Influenced by Initial Dermatopathology Diagnosis

A new report has found that serum fibrinogen to albumin ratio (FAR) is a predictor of active disease, severe active disease, and poor prognosis in patients with 

, found the ratio was a better predictor than either of the factors alone.

One problem in treating SLE is that the disease can affect a wide variety of organs, and the disease course varies significantly among patients, explained the authors. They said it is not clear why and how the disease progresses, although it is believed to be related to genetics, autoimmune system abnormalities, and endocrine hormone disorders, among other factors.

“Many studies have proved that the type and dose of hormones used in the treatment of SLE are closely related to disease activity; hence, timely and effective evaluation of activity indexes is very important,” the authors wrote.

Significant effort has already been put into the task of identifying biomarkers of disease activity. Albumin has already been linked with lupus nephritis (LN) and a poor prognosis, the authors said, and albumin to globulin ratio has been shown to be predictive of developing LN.

“The FAR as a new inflammatory marker has been proven to have good predictive value in the diagnosis and prognosis of diabetes nephropathy, acute renal injury, rheumatoid disease, and so on,” they wrote. Yet, little research shows whether FAR can predict activity and prognosis in SLE and how well such predictions might stack up to either fibrinogen or albumin alone.

The investigators enrolled 168 people with SLE from Funan County People’s Hospital in China into their retrospective analysis, which included clinical data, laboratory reports, and disease prognosis. They found links between triglycerides, FAR, erythrocyte sedimentation rate, and anti–double-stranded DNA and disease activity, and found that complement 3 had protective value.

FAR and fibrinogen positively correlated with SLE disease activity index scores, but albumin was negatively correlated, the authors said.

“The receiver operating curve analysis showed that the predictive values of FAR for active, severe active, and poor prognosis SLE were 0.769, 0.769, and 0.734, respectively, and were significant higher than fibrinogen and albumin (

The investigators said their study was limited because they did not analyze certain other factors that might be linked with a poor prognosis, such as inflammatory factors or other thrombus markers. They also did not include organ damage in their diagnosis.

The authors said larger, broader studies could help better isolate the optimal way to predict disease activity and prognosis. For now, though, they said their data suggest that FAR is a potentially important influencer of disease severity and prognosis, but also had predictive value.

“In other words, FAR might be a potential effective biomarker to judge the severity and prognosis of SLE and have a wide range of clinical applications,” they concluded.

Dai L-L, Chen C, Wu J, Cheng J-F, He F. The predictive value of fibrinogen-to-albumin ratio in the active, severe active, and poor prognosis of systemic lupus erythematosus: a single-center retrospective study. 

. Published online July 23, 2022. doi:10.1002/jcla.24621

This ratio could be used to better predict disease activity and poor prognosis.


Fibrinogen to Albumin Ratio Shows Promise as SLE Predictive Biomarker

Laura is the vice president of content for The American Journal of Managed Care

) and all its brands, including The American Journal of Accountable Care

, Evidence-Based Oncology™, and The Center for Biosimilars

, since 2011. She also oversees Managed Healthcare Executive

She has an MA in business and economic reporting from New York University. You can reach her at 

Psychological interventions can positively impact patient outcomes, but do not significantly effect patient confidence in 

Although biosimilars reduce costs and expand access to high-quality treatments, patients may have negative perceptions because of a lack of knowledge. “There is a need to educate patients on biosimilars’ clinical equivalence to bio-originators, and specific interventions have not yet been extensively tested,” wrote the authors from Wake Forest School of Medicine.

Patients with self-reported psoriasis were recruited to complete a survey between May 17, 2020, and January 25, 2021. A total of 1253 patients completed the survey. The mean age of the participants was 36 years, and a slight majority (53%) were female. A majority were White (65%), had at least a bachelor’s degree (67%), and had annual household incomes over $50,000 (53%).

The respondents were randomized into 10 groups:

Group A had a hypothetical scenario where they were stepping up to a biosimilar from a topical corticosteroid cream (biosimilar control group)

Group B had a hypothetical scenario where they were stepping up to a biologic from a topical corticosteroid cream

Groups C through J were given a hypothetical scenario in which they had achieved great results on a biologic for 2 years and were being asked to switch to a biosimilar

Group D was informed of evidence of comparable clinical effectiveness

Group E was presented with an illustration depicting comparable effectiveness

Group F was given anecdotes of treatment success in other patients with psoriasis

Group G received anecdotes of treatment success in another patient with psoriasis who was a lot like them

Group H was explained the rigorous evaluation biosimilars go through to gain approval

Group I received an explanation of biologics and biosimilars and were asked to explain it to another patient with multiple choice options

Group J received an explanation of biologics and biosimilars and were asked to explain it to another patient with a free response format

Group D was the only intervention that did not produce slightly higher treatment confidence compared with the biosimilar switch control group. Group E, which received an illustration on comparability for biosimilars and biologics, and Group H, which received an explanation on the evaluation biosimilars go through for FDA approval, had the highest confidence scores. 

Of the 2 groups receiving anecdotes of patients with psoriasis, the group receiving anecdotes of a patient a lot like them had slightly greater increases in confidence. Of the patients who were asked to explain biologics and biosimilars to another patient, the free response format was slightly more effective at improving confidence.

“Although the reassurance interventions generally produced small trends in the expected direction, no statistically significant differences were detected,” the authors noted.

They added that these psychologic interventions are easily implementable techniques that clinicians can use to improve outcomes, and that improving confidence in biosimilars is an important aspect of expanding access to medications. However, the interventions studied did not improve confidence in biosimilars by much, the researchers wrote.

“Reiterating the rigorous evaluation process that biosimilars undergo to gain FDA approval and/or providing patients with illustrations depicting biosimilars’ comparability to bio-originators appear to produce small improvements in biosimilar confidence and may be interventions to focus on for future development,” they concluded.

Hrin ML, Bray JK, Feldman SR. Reassurance techniques do not significantly impact confidence in biosimilars for psoriasis: a survey of a convenience sample of individuals with self-identified psoriasis. 

. Published online July 28, 2022. doi:10.1007/s13555-022-00781-3

A number of psychologic interventions were assessed to see if they could have an effect on patient confidence in biosimilars to treat psoriasis.

Can Reassurance Techniques Improve Patient Confidence in Biosimilars for Psoriasis?

More research on intertriginous disease in 

 is needed to better understand patient needs and gaps in care, as well as build awareness among dermatologists on the subtype, said Patrick Burnett, MD, PhD, FAAD, chief medical officer of Arcutis Biotherapeutics.

What are some next investigative steps following the 

 shown in the Skin Insights: Uncovering Psoriasis Survey?

I think a survey like the one that we did, I think one of the advantages of that survey was that it was very robust. We're talking about over 500 patients and focused on a specific group, which is those patients who are currently being treated with topical therapy. That kind of research allows you to learn something new about this population that you maybe didn't [know] before.

I guess I'll take a step back and look at a previous example of this in psoriasis. There's a publication that 

, and others did looking at itch in psoriasis. And when I was training as a dermatologist, 

 was the disease that itched—psoriasis could itch, but we said it was a relatively small fraction of patients. So, if somebody came in and you weren't sure if they had psoriasis or atopic dermatitis, if it itched, you would just say they must have atopic dermatitis.

I think what this publication by Dr. Lebwohl and others showed is that from a patient perspective, first of all, itch is very common, but also itch is the No. 1 driver for their perception of severity. Whereas when you ask the doctors what makes a patient have severe disease, the No. 1 factor that they identified was body surface area, because that's what a doctor can see. Unless you ask with a specific patient-related outcome assessment measure how much itch a patient is having, it's not visible to you when they walk into the office.

Patrick Burnett, MD, PhD, FAAD, chief medical officer of Arcutis Biotherapeutics, discusses the need for increased research and awareness on intertriginous disease in psoriasis.