View news from the 2021 SABCS, including session summaries, poster write-ups, and interviews with key opinion leaders.

Coverage of the 2021 San Antonio Breast Cancer Symposium

View news from the 2021 ACAAI Annual Scientific Meeting, including session summaries, poster write-ups, and interviews with key opinion leaders.

Coverage of 2021 ACAAI Annual Scientific Meeting

If 2020 was dominated by the news of how COVID-19 spread across the globe, then 2021 has so far been focused on ending the pandemic through vaccine distribution.

A Timeline of COVID-19 Vaccine Developments in 2021

This AJMC® Profiles in Care provides an in-depth look into the results of the outcomes-based agreement between Boehringer Ingelheim and Highmark Inc.

AJMC® Profiles in Care Launches

The rise of disease modifying agents has led to an overall decline in mortality for patients with rheumatoid arthritis (RA), but not everyone has benefited equally. Mortality rates have not budged for those with RA and interstitial lung disease (ILD), according to a study and editorial appearing in this month’s 

First, authors led by Niranjan Jeganathan, MD, of Loma Linda University analyzed data from the CDC Multiple Case Database, segmented out both overall RA mortality rates and trends from 2005 to 2018 as well as those for patients with RA-ILD, using International Classification of Disease, 10th edition codes. They found the following:

RA- and RA-ILD related morality rates were higher in women and older patients.

Despite the first finding, prevalence of ILD was higher in men who died with RA compared with women who with the disease, (13.3% vs 8.7%).

RA-related mortality rates were highest among Native American individuals followed by White individuals. Compared with White patients, Hispanic patients had lower RA-related mortality rates but higher RA-ILD related morality rates.

Overall RA-related morality rates per 1 million population decreased from 30.6 in 2005 to 22.2 in 2018 and declined across all demographic groups. But RA-ILD mortality rates remained stable in both sexes, all races, and all age groups except for those aged 65 to 84 years of age, in which rates declined.

In their accompanying editorial, Pankti Reid, MD, MPH, of the University of Chicago, and Sabina A. Guler, MD, MHSc, of the University of Bern in Switzerland, note that age- and sex-matched data from Denmark that show a 5-year mortality of 36% for RA patients with ILD, compared with 18% for RA patients without this comorbidity. ILD is caused by inflammation that leads to scarring of the lungs; it causes shortness of breath, dry cough, and fatigue; data show it doubles mortality risk in RA.

The RA-ILD combination is not rare. Some level of ILD is present in 60% of RA cases; it’s 

 in at least 10% and is a leading cause of death in these patients, according to the 

Why is ILD such a problem? According to Reid and Guler, the mortality discrepancy “can only partially be explained by more frequent comorbidities (e.g., heart disease and diabetes) affecting patients with RA-ILD.”

They explain that most treatment recommendations for RA-ILD rely on extrapolation from other connective tissue diseases and observational studies or small uncontrolled studies; there are no large, randomized controlled trials specifically in RA-ILD to inform therapeutic decisions.

“Antifibrotic medications show promise for patients with connective tissue disease–associated ILD; however, their efficacy in RA-ILD is still largely unknown,” Reid and Guler write.

Falling RA mortality rates “is not a novel finding,” the editorial notes; this trend was first tracked by the World Health Organization. However, Jeganathan et al, do find discrepancies in some populations within the data set, and say the findings for RA-ILD should be “of particular concern for pulmonologists and rheumatologists because RA or ILD was the underlying cause of death in 77% of the RA-ILD population and mortality from other causes (cancer, heart, or cerebrovascular disease) was less frequent than that in the overall RA population.”

They state, “the interaction between smoking and race in the context of RA mortality remains to be determined.”

The editorial calls for better strategies for RA-ILD management, and states that “We should focus our attention to particularly vulnerable RA subpopulations by ensuring adequate representation in future clinical trials and equal access to health care for all.”

Jeganathan N, Nguyen E, Sathananthan M. Rheumatoid arthritis and associated interstitial lung disease: mortality rates and trends. 2021;18(12):1970-1977. doi: 10.1513/AnnalsATS.202102-115OC.

Reid P, Guler SA. Mortality trends in rheumatoid arthritis: zooming in on interstitial lung disease. 2021;18(12): 

https://doi.org/10.1513/AnnalsATS.202108-899ED

Articles

ILD is caused by inflammation that leads to scarring of the lungs; it causes shortness of breath, dry cough, and fatigue; data show it doubles mortality risk in RA.










Long-term Mortality Decline in RA Skips Those Who Also Have Interstitial Lung Disease

 (NAFLD) are at an increased risk of incident heart failure (HF), according to a study published recently in the 

Journal of the American Heart Association

Results showed further found that there was a higher risk of developing HF with preserved ejection fraction (HFpEF) versus HF with reduced ejection fraction (HFrEF).

Both NAFLD and HF are increasing in prevalence. NAFLD incidence has risen 5‐fold over the past 2 decades in the United States and while it is typically silent and underdiagnosed, it is assumed to affect 10% to 30% of the population. Studies have suggested the NAFLD is a risk factor for cardiovascular disease, which is also the leading cause of death.

The study was conducted because while a link between NAFLD and HFpEF has been proposed due to shared disease characteristics, researchers sough additional epidemiological evidence about the independent association between NAFLD and the risk of HF as well the risk of the 2 specific subtypes of HF.

Data for the retrospective, cohort study came from a subset of the national 5% sample of all fee‐for‐service Medicare beneficiaries with no prior diagnosis of HF and included both inpatient and outpatient visits. Follow-up occurred between October 2015 to December 2016.

International Classification of Diseases, Tenth Revision (ICD‐10)

 codes for HFpEF and HFrEF. Beneficiaries with prevalent HF were identified by presence of any HF claims over a 2‐year look‐back period from October 2015 and excluded from the present analysis.

Among 870,535 Medicare patients, 3.2% (N = 27,919) had a clinical diagnosis of NAFLD; these patients were more likely to be women, were less commonly Black patients, and had additional comorbidities, such as diabetes, obesity, and kidney disease.

Compared with patients without NAFLD, follow‐up showed that patients with baseline NAFLD had a significantly higher risk of new‐onset HF in unadjusted (6.4% versus 5.0%; 

<.001) and adjusted hazard ratio [aHR] 1.23; 95% CI, 1.18–1.29) analyses.

Among HF subtypes, the association of NAFLD with later risk of HF was stronger for HFpEF (aHR, 1.24; 95% CI, 1.14–1.34) compared with HFrEF (aHR, 1.09; 95% CI, 0.98–1.2).

“The persistence of an increased risk after adjustment for clinical and demographic factors suggests an epidemiological link between NAFLD and HF beyond the basis of shared risk factors that requires further investigation,” the authors concluded.

Fudim M, Zhong L, Patel KV, et al. Nonalcoholic fatty liver disease and risk of heart failure among Medicare beneficiaries. 

Published online November 10, 2021. 10:e021654

Specifically, patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of developing heart failure (HF) with preserved ejection fraction, according to new research.


Patients With NAFLD Have Higher Risk of HF, Study Finds

Laura is the editorial director of 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

's parent company, MJH Life Sciences™, since 2011. She has an MA in business and economic reporting from New York University.

While earlier palliative care (PC) is associated with an improvement in hospice use and intensive care unit (ICU) utilization, it was not significantly associated with an improvement in end-of-life (EOL) outcomes for patients with acute myeloid leukemia (AML), according to a study 

While PC is an “integral component” of quality cancer care, more research is needed to understand the relationship between early PC and EOL outcomes, the authors wrote.

“Data regarding PC for patients with hematologic malignancies (HMs) generally, as well as earlier PC integration into routine care of these patients, are less mature,” they explained. “The role of early PC in HMs has only recently been studied in the clinical setting.”

The study included retrospective data from the Rhode Island Hospital, which embedded a PC service into inpatient malignant hematology service January 2017. Data was obtained from chart reviews and electronic health records between 2015 and 2019 on patients diagnosed with AML.

A total of 139 patients were included in the final analysis. Cohort A included 46 patients prior to the initiation of the embedded PC service and Cohort B included 93 patients after the service was embedded. In Cohort A, 34 patients died compared with 47 in Cohort B.

In general, PC consultation was associated with a significant increase in hospice use and fewer ICU admissions, as well as a trend toward fewer inpatient deaths. Cohort B had significantly higher use of PC consultation (75%) compared with Cohort A (43%; 

 = .0006). Only 11% of patients in Cohort A had early PC consultation, which increased significantly to 52% in Cohort B.

However, there was no significant improvement EOL quality outcomes between the cohorts or even among patients who received early PC consultation.

“While there was a slight numerical increase in Cohort B in hospice use, a decrease in ICU admission in the last 30 days of life, and a decrease in chemotherapy use in the last 14 days of life, these did not reach statistical significance,” the authors wrote.

They noted that the study might not have identified a benefit for patients receiving early PC consultation because of the limited number of patients who received it and died by the time of the analysis. In addition, they noted that it took time for the cultural shift to occur once the PC service was embedded. During the time of the analysis, not all patients with a new AML diagnosis received a PC consultation.

“With time, this has changed, and it is possible that this analysis would have different results if completed at a later date, with a larger cohort of patients, and a statistical significance between these two groups could be detected,” they wrote.

The single site nature of the analysis was one limitation, as was the lack of standardization of the PC consultation. Some patients in the postanalysis group did not receive the intervention at all.

“The value of early PC in HMs may be better measured using patient-reported outcomes and QOL [quality-of-life] measures rather than established EOL care quality outcomes,” the authors concluded.” Future research is needed to more definitively examine the association between early PC and EOL outcomes in patients with HMs, as well as to directly analyze benefits in patient reported symptoms and QOL metrics.”

Pelcovits A, Olszewski AJ, Decker D, Guyer D, Leblanc TW, Egan P. Impact of early palliative care on end-of-life outcomes in hematologic malignancies. 

. Published online November 25, 2021. doi:10.1089/jpm.2021.0193

Setting up a palliative care consultation program for patients with acute myeloid leukemia (AML) improved some aspects of care.

Can Earlier Use of Palliative Care Improve End-of-Life Outcomes in AML?

 the role of skin-produced antimicrobial peptides (AMPs) in hidradenitis suppurativa (HS), a chronic, inflammatory skin disease in hair follicles.

HS, which is linked with microbial dysbiosis and immune dysregulation, defined by recurrent nodules, tunnels and scarring, primarily in skin folds. Previous work has shown dysregulated levels of AMPs in HS. AMPs are key defense players in innate immunity and help fight microbial invasion, particularly against Gram-positive and Gram-negative bacteria, as well as some fungal and viral agents. They are also strong immunomodulators and have been implicated in several chronic inflammatory conditions in the epithelium of the intestines, airways, 

Researchers screened PubMed, Embase, and the Cochrane Library, ultimately choosing 18 retrospective and prospective studies published between 2009 and 2020.

1 study analyzed isolated outer root sheath (ORS) occipital hair follicle keratinocytes from patients

1 study examined the serum of patients with HS

In addition, 8 studies analyzed both mRNA and protein levels of AMPs; 3 studies only analyzed mRNA levels; 7 studies analyzed protein levels.

For mRNA analysis, most studies used quantitative real-time polymerase chain reactions (qPCR); for protein analysis, most studies used immunohistochemistry (IHC).

Results showed that members of the human β-defensin (hBD) and S100 protein families were the most commonly investigated AMPs. S100 proteins are expressed in the epidermis and regulate of cell proliferation and differentiation.

The studies found a consistent overexpression of hBD-2, S100A7, S100A8 and S100A9 at both the mRNA and protein levels, and a decreased expression of hBD-1. The mechanisms behind the lower levels of hBD-1 in the development of HS remain unclear. Evidence was mixed on the involvement of hBD-3 in HS, with 4 studies reported upregulation of hBD-3 mRNA and protein and 3 studies finding no upregulation of hBD-3 mRNA or protein

Overall, the studies indicate a dysregulation of AMPs in both lesional and nonlesional HS skin.

“Future studies investigating epigenomic, genomic and protein expression are warranted to achieve a more comprehensive view of their potential significance in the pathogenesis of HS,” concluded the authors.

Yao Y, Frew JW, Thomsen SF, Ring HC. Antimicrobial peptides in hidradenitis suppurativa: A systematic review. 

 Published online September 9, 2021. doi: 10.1111/bjd.207

Hidradenitis suppurativa, which is linked with microbial dysbiosis and immune dysregulation, is defined by recurrent nodules, tunnels and scarring, primarily in skin folds; the review found a multitude of antimicrobial peptides expressed in this skin disease. 



Review Examines Role of Antimicrobial Peptides in Hidradenitis Suppurativa

 since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey. 

Results of an observational study revealed that for each additional medication, people aging with 

 have more drug­–drug interactions compared with those without HIV.

also showed that after adjusting for known non–antiretroviral therapy (ART) drug–drug interactions, each additional non-ART medication confers excess risk of hospitalization among those 

—typically defined as the simultaneous use of 5 or more medications—is common among older adults in North America and Europe and is associated with hospital admission and mortality in a dose-response manner, in addition to other adverse events.

 with HIV, polypharmacy poses a host of challenges as these individuals “typically have polypharmacy a decade earlier than uninfected individuals” and “have excess physiological frailty, making them more susceptible to the adverse effects of medications,” the researchers wrote.

The greater the number of medications taken concomitantly, the higher the risk of harmful interactions with other medications and substances. Although ART extends survival, medications must be taken for life and “have an exceptionally large number of drug–drug interactions,” they added.

To better understand the association between hospitalization and all known pairwise drug interactions (KPDIs) in this population, the researchers used data from DrugBank, which contains information on all US FDA-approved drugs and was last updated in 2018.

The current analysis is an extension of a previous study and includes those “

 with HIV receiving ART who had suppressed HIV-1 RNA and people without HIV who were receiving at least 1 prescription medication from the US Veterans Affairs Healthcare System (

) in the fiscal year of 2009 (Oct 1, 2008, to Sept 30, 2009).”

Individuals were followed up with until March 2019 for hospitalization and all-cause mortality, while analyses were restricted to medications filled on a chronic basis (at least 90 consecutive days allowing for a 30-day refill window). The researchers utilized the Veterans Aging Cohort Study (VACS) Index 2.0 to adjust for frailty (scored 0 to 100) with higher scores indicating a greater risk of mortality due to physiological injury.

A total of 9186 people living with HIV and 37,930 individuals without HIV were included in the final study; the majority of patients were male and aged 50 to 64 years.

Compared with a random sample of medications, real-world pattern of medication counts and combinations were associated with 5 to 6 times more KPDIs (eg, for a combination of 6 medications, the KPDI count was 1.09 in the random sample, 5.49 in the HIV-negative population, and 7.13 in those living with HIV)

Among people aging with HIV, the median (interquartile range) CD4 count was 511 (346-720) cells/mm

Non-ART medication counts were lower for people aging with HIV than those without HIV (mean [SD] count, 3 [3] vs 4 [3])

People aging with HIV had higher VACS Index 2.0 scores, suggesting greater physiological frailty than those without HIV (mean score, 50 [15] vs 33 [11])

For each additional observed medication, people aging with HIV had approximately 2.94 additional KPDIs and comparators had approximately 2.67 additional KPDIs

Adjustment for demographics, physiological frailty, and KPDI Index reduced the association between medication count and risk of hospitalization for people aging with HIV (HR, 1.08; 95% CI, 1.07-1.09 reduced to HR, 1.06; 95% CI, 1.05-1.07) and those without HIV (HR, 1.08; 95% CI, 1.07-1.08 reduced to, HR 1.04; 95% CI, 1.03-1.05)

People living with HIV also had higher rates of hospitalization and mortality. Overall, findings suggest “people aging with HIV might be more susceptible to harm from polypharmacy than those without HIV, both due to KPDIs and other mechanisms of injury,” the authors said. 

Furthermore, they found that “when an individual was on a large number of medications, the harmful effects of polypharmacy appeared to outweigh benefit.”

As individuals with HIV were taking a lower number of non-HIV medications than those without ART, the authors hypothesized HIV-care providers are already concerned about polypharmacy.

Measures of medication count reflected in the analysis were conservative, as they only included those dispensed within the VA, marking a limitation to the study. The nature of drug interactions is also highly variable and investigators were not able to evaluate interactions between alcohol or other substances. Unadjusted confounding may have also affected the results.

Future analyses including more women patients should be carried out in health care systems to yield more generalizable findings, the researchers said.

“Sophisticated informatics tools are needed to better guide drug selection and deprescribing to avoid excess hospitalizations and mortality due to polypharmacy,” they concluded.

Justice AC, Gordon KS, Romero J, et al. Polypharmacy-associated risk of hospitalization among people ageing with and without HIV: an observational study. 

 Published online October 1, 2021. doi:10.1016/S2666-7568(21)00206-3

People aging with HIV have more drug–drug interactions compared with those without HIV, according to results of an observational study. 

High Rates of Polypharmacy-Associated Adverse Events Seen in Those Aging With HIV 

Active vitamin D therapy was found to significantly increase the risk of hypercalcemia among patients with nondialysis 

 (ND-CKD) and secondary hyperparathyroidism (SHPT) compared with placebo, according to a recent meta-analysis.

The systematic literature review and meta-analysis, published in 

, used published randomized, placebo-controlled clinical trials of active vitamin D to clarify the relationship between active vitamin D and SHPT in patients with ND-CKD. SHPT is a common complication in patients with CKD and is characterized by the excessive secretion of parathyroid hormone (PTH), which can lead to worsened kidney function. The condition affects 40% to 82% of patients with stage 3 and stage 4 CKD.

“These observations highlight the urgent need for new treatments for SHPT in patients with ND-CKD that effectively reduce PTH levels, while avoiding undesired elevations in serum calcium,” wrote the investigators.

SHPT is also heavily associated with CKD-mineral bone disorder and if elevations in serum PTH are not addressed, patients can experience bone disease and vascular and valvular calcification, which can lead to increased risks of bone fractures, cardiovascular disease, and mortality.

The pathogenesis of SHPT involves several factors, including presence of hypocalcemia, phosphate retention, and associated increases in serum fibroblast growth factor 23 and insufficient levels of vitamin D. Patients with CKD frequently have low levels of vitamin D, which contributes heavily to the development of SHPT.

The investigators searched 3 literature databases, and their data cutoff was May 14, 2020. For inclusion, the studies had to be randomized, double-blind, placebo-controlled trials of adults with ND-CKD and SHPT, evaluating single-agent active vitamin D. The studies also had to involve at least 30 participants per treatment arm and have a study period of at least 6 weeks.

Overall, 1704 articles were identified, of which 6 studies covering 799 patients were eligible for the analysis. The duration of the studies ranged between 16 weeks and 2 years. Five of the studies evaluated the use of paricalcitol and 1 evaluated alfacalcidol. Across the studies, hypercalcemia was reported in 1.1% to  43.3% of patients treated with active vitamin D therapy, which was considerably higher than patients treated with a placebo (range, 0.0%-3.4%).

During the primary meta-analysis on all 6 studies, the investigators observed that patients with ND-CKD and SHPT treated with active vitamin D therapy experienced a 6.6-fold increased risk of hypercalcemia compared with those treated with placebo (odds ratio [OR], 6.63; 95% CI, 2.37-18.55; 

Two sensitivity analyses were performed to assess the robustness of the results from the primary analysis. One sensitivity analysis involved the exclusion of a study that was identified to have a high risk of bias and found that active vitamin D therapy was associated with a 6.2-fold greater probability of hypercalcemia vs placebo (OR, 7.22; 95% CI, 2.21-23.60; 

 = .001). The other analysis excluded 2 studies that accounted for a large proportion of the observed hypercalcemia episodes, finding that active vitamin D therapy was associated with a 2.0-fold greater risk of hypercalcemia vs placebo (OR, 3.03; 95% CI, 1.06-8.71; 

The meta-analysis and review had several limitations, including the small the number of studies, heterogeneity of the study designs, and lack of control for confounding factors.

“Future analyses of real-world data may help overcome a number of these limitations because this could enable a larger and broader population to be evaluated,” noted the investigators.

Cozzolino M, Bernard L, Csomor PA. Active vitamin D increases the risk of hypercalcaemia in non-dialysis chronic kidney disease patients with secondary hyperparathyroidism: A systematic review and meta-analysis. 

. November 29, 2021;14(10):2437-2443. doi: 10.1093/ckj/sfab091

Patients with chronic kidney disease (CKD) and elevated levels of parathyroid hormone who are treated with active vitamin D therapy experienced significantly higher risks of hypercalcemia, investigators concluded in a meta-analysis.

Potential Link Found Between Vitamin D Therapy, Higher Hypercalcemia Risk in CKD 

There are currently no approved disease-modifying therapies for acid sphingomyelinase deficiency (ASMD), also known as Niemann-Pick disease (NPD), an inherited lysosomal storage disorder. Enzyme replacement therapy with olipudase alfa has been a promising option in clinical trials, and a 

 showed significant improvements along with a tolerable safety profile in children with chronic ASMD without central nervous system (CNS) manifestations.

ASMD is a rare disorder caused by sequence variants in the 

gene, which encodes the lysosomal enzyme acid sphingomyelinase (ASM). The resulting buildup of sphingomyelin leads to a variety of manifestations, including hepatosplenomegaly, thrombocytopenia, hyperlipidemia, interstitial lung disease (ILD), liver dysfunction and fibrosis, and CNS damage in severe cases. ASMD phenotypes include type A, which is characterized by severe infantile onset with neurovisceral manifestations and fatality; type A/B, which has neurovisceral manifestations but is chronic; and type B, which is chronic and does not typically involve neurological symptoms.

The single-arm, phase 1/2, open-label ASCEND-Peds study (

) included 20 pediatric patients with confirmed ASMD stratified into 3 cohorts: infants/early children (less than 6 years of age), children (6 to 11 years old), and adolescents (12 to 17 years old). Patients with low platelet counts (<60 × 109/L), levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above 250 IU/L, bilirubinabove 25.7 µmol/L were excluded from the study, as were those with rapidly progression neurovisceral manifestations. Patients with genotypes associated with ASMD type A were also excluded.

Participants received olipudase alfa infusions once every 2 weeks and were monitored as inpatients for minimum 24 hours post-infusion as the doses were escalated. The doses were as follows:

All 20 patients reached the maintenance dose. A total of 7 patients, all in the children or early children cohorts, had at least 1 dose reduction or repeat dose at some point before reaching the final maintenance dose.

All patients experienced at least 1 adverse event (AE) during the study, 17% of which were considered infusion-associated reactions (IARs). Overall, 88% of IARs were categorized as mild. Pyrexia, cough, vomiting, nasopharyngitis, diarrhea, headache, nausea, rhinitis, oropharyngeal pain, ear pain, and rhinorrhea were all common AEs. A total of 5 patients experienced serious AEs, all of which were resolved. One severe anaphylactic reaction was reported, and that patient was able to continue therapy after a desensitization regimen. There were 10 total dose-limiting toxicity events in 6 patients, all of which resolved after dose reduction or repeat dosing.

Efficacy was considered exploratory in this trial, but patients experienced improvements in moderate or severe splenomegaly and hepatomegaly by an assessment at week 26 of the trial. Eleven of 12 patients with severe splenomegaly at baseline and all 10 patients with severe hepatomegaly at baseline improved to moderate levels by week 52. Overall decreases in spleen and liver volume were similar across all 3 age groups.

Five of 6 patients who showed severe ILD at baseline showed improvements to mild or moderate, and ILD was absent in 1 by week 52. Mean lipid levels were within normal limits by week 52—an improvement over baseline, when mean levels of total cholesterol, low-density lipoprotein, and triglycerides were above normal limits and high-density lipoprotein levels were abnormally low.

Although the study lacked a placebo group and included a small sample size, these findings suggest olipudase alfa is well-tolerated and may lead to clinically meaningful improvements after 6 months that are maintained through 12 months of treatment in pediatric patients with chronic ASMD.

Diaz GA, Jones SA, Scarpa M, et al. One-year results of a clinical trial of olipudase alfa enzyme replacement therapy in pediatric patients with acid sphingomyelinase deficiency. 

 2021;23(8):1543-1550. doi:10.1038/s41436-021-01156-3

Findings from the single-arm, open-label ASCEND-Peds trial suggest olipudase alfa is well-tolerated and may lead to clinically meaningful improvements in patients with acid sphingomyelinase deficiency (ASMD) who do not have neurovisceral manifestations.

Pediatric Patients With ASMD Show Significant Improvement in Olipudase Alfa Trial

Advances in technology to manage diabetes offer opportunities for precision in insulin delivery that were unimaginable a generation ago. But barriers to automated insulin delivery (AID) remain, according to authors of a recent review article appearing in 

Although some patients with type 2 diabetes (T2D) use insulin, those with type 1 diabetes (T1D) cannot survive with either multiple daily injections or delivery through a pump; which route patients choose and why is a highly personal choice, and patients with T1D have advocated for the right to have options to fit personal needs.

However, as the authors from the Barbara Davis Center for Diabetes at the University of Colorado note, the goal of administering insulin to people with diabetes is not simply to keep them alive but also to reduce both the micro- and macrovascular complications the disease can cause; these are more likely if a patient experiences chronic swings in glucose levels and multiple episodes a day of hyper- and hypoglycemia.

While the old measure of health for a person with T1D was limited to the periodic glycated hemoglobin (A1C) test, more recently, the time-in-range (TIR) measure has gained recognition. As the Colorado authors write, today, the major treatment goal is to keep the glucose range between 70 mg/dL and 180mg/dL for 70% of the time, while maintaining an A1C of 7% or less to minimizing hypoglycemia exposure. Multiple studies show that AID systems offer superior TIR and are a game-changer for parents who seek peace of mind as they send children with T1D to school or hope to ease them into sports or activities.

The authors cite multiple factors for why some patients have not embraced AID technology, which under FDA guidelines have 3 distinct components: a continuous glucose monitor (CGM), which reads blood glucose levels; a pump to deliver insulin; and an algorithm that uses data collected from the CGM to send commands to the pump.

Although AID technology has become increasingly smaller, more discrete, and less burdensome, it still must be worn on the body. The authors identified cosmetic impact and the potential for skin injury as 2 factors that limit AID uptake. Other factors include the possibility that the device may limit physical activity. The authors also list “lack of access related to incomplete coverage and high cost,” along with racial and ethnic disparities, which could be tied to provider or patient biases about device use. Finally, the authors list “psychosocial barriers.”

Patients and some parents of children with T1D have expressed caution about a having device attached to the body in some studies, although youth with T1D are among the most common users of AID systems. Over time, as children with T1D reach their teenage years, concern over the look of the device and being different from others emerges, especially among females, according to the authors. They cited studies that found skin irritations were common; this was reported by nearly 90% of those using continuous subcutaneous insulin infusion and nearly 80% using CGM.

Successive upgrades in automated systems have lightened the load on people with diabetes or their parents, but there remains a requirement on the part of the users to understand how to navigate the system. “This causes concern for some that the technology may be too complicated for them to confidently utilize and is often noted as a barrier to uptake of these devices,” the authors wrote. “Parents of children with T1D sometimes describe concern regarding malfunction and risk of hypoglycemia associated with pump use, despite research suggesting pump use is associated with reduction in hypoglycemia.” For some, studies suggest, using AID technology may initially increase the sense of burden, although this will decrease over time.

Burdens related to the health care team. 

The authors cited 3 issues: providers who resisted using new technology, providers who acted as “gatekeepers” to technology if people with diabetes did not have a history of checking blood glucose at least 4 times a day, and those providers who did not offer telehealth support to patients who uploaded their CGM data, a feature for all AID systems.

The authors cited multiple studies that found cost was a major barrier to AID uptake among those with low incomes, and a reason why those who started CGM stopped using it. Lack of insurance coverage, inadequate coverage, or the burden of having to spend hours on the phone with insurers were also cited. However, the perceived benefit of AID was often very personal, the authors found. “Most participants discussed weighing cost against benefit of devices, and some anticipated the cost to be too great to consider uptake of the devices, while others felt the benefits outweighed the costs, with one participant stating, ‘I would sell my house … I would do whatever I had to do.’”

Issues with cost and type of coverage are tied to the disparities in who uses AID. Data show that non-Hispanic White and female youth are more likely to use insulin pumps than other groups, the authors found. Being from a high-income family and having private health coverage also increased the odds, especially in the pediatric population, and the gap in technology use between high-income and low-income groups is growing wider, the authors said.

A major benefit of AID use is increased sleep among parents of children with T1D, studies show. While the use of these systems is known to decrease the chance of hypoglycemia, which would seem to ease depression and anxiety, the authors cited studies that found for a subset of patients, fear of device malfunctioning has the opposite effect.

The authors state that while cost and coverage remain concerns, in the United States, Medicare coverage is improving, and recent actions that link coverage to “modern device use profile and evidence-based requirements” are encouraging.

Pauley ME, Berget C, Messer LH, Forlenza GP. Barriers to uptake of insulin technologies and novel solutions. 

. 2021;14:339-354. doi:10.2147/MDER.S312858.

Authors from the University of Colorado say factors from skin irritations, to cost, to lack of insurance coverage, to physician barriers have limited uptake of automated insulin delivery systems.

Exploring the Barriers to Uptake of Automated Insulin Delivery

 treatment (GHT) and multidisciplinary care (GHMDC) has been shown in a new study to result in significantly better health outcomes among adults with Prader-Willi syndrome (PWS) who received this care combination throughout childhood. As a result, such a treatment regimen should be continued once individuals with PWS reach adult age, according to 

There is a high mortality rate among children and adults with PWS, with their hypothalamic dysfunction also often associated with hyperphagia, pituitary hormone deficiencies, abnormal temperature regulation, and inadequate pain registration. Additional somatic and psychosocial factors associated with PWS include musculoskeletal problems, low basal metabolic rate, behavioral challenges, biochemical anomalies, and cardiovascular risk factors (eg, obesity, hypertension, 

 [T2D]). GHT has been shown to improve many of these, the authors of this investigation noted.

“GHMDC has greatly improved the health of children with PWS,” the authors wrote. “However, little is known about the effects of childhood GHMDC on health outcomes in adulthood.”

The 109 patients (n = 53, male; 56, female; median age, 28 [range, 18-72] years; median body mass index [BMI], 29 kg/m

) included in the final study analysis received outpatient care at the Dutch Centre of Reference for Prader-Willi Syndrome in Rotterdam, The Netherlands, between January 2015 and January 2021, and they were divided into 3 groups for this analysis:

Received GHMDC from childhood to adulthood (GHMDC+ group; n = 39)

Never received GHMDC (GHMDC– group; n = 63)

Received GHMDC during childhood, but it was discontinued before adulthood (GHMDC

Overall, patient screening showed a 74-percentage-point difference in those who reported at least 1 undetected health problem between the GHMDC+ (10%) and GHMDC– (84%) groups. In addition, any health problems in the GHMDC+ group developed between the final pediatric and first adult-care visits and did not require medical intervention, and no one in the GHMDC+ group reported at least 2 or 3 or more undetected health problems vs 41% and 14% in the GHMDC– group.

Significant differences were also seen in median BMI and prevalence of T2D in the GHMDC+ group compared with the GHMDC– group, even after accounting for age:

T2D incidence: 0% vs 27% (75% of whom were treated)

Meanwhile, overall rates of hypertension, hypercholesterolemia, and vitamin D deficiency were at least 21 percentage points lower in the GHMDC+ vs the GHMDC– group.

The authors highlighted that because obesity and T2D are important cardiovascular disease risk factors, their finding of their effects on outcomes among those in the GHMDC– group is especially important. Because of this, patient vulnerability to both needs to be reduced.

It’s also possible that GHMDC prevents both in patients who have PWS, as well as can lead to early detection of otherwise undiagnosed problems.

“Our data clearly show that the combination of both has beneficial effects. However, as all patients who received GHT were treated in a multidisciplinary setting, it is unknown which effects are the result of GHT and which are the result of multidisciplinary care,” the authors concluded. “Therefore, we recommend continuing GHMDC after patients with PWS have reached adult age.”

Because not all adults living with PWS have access to hormone treatment, the authors support approval of the treatment for this entire group, as well.

Pellikaan K, Rosenberg AG, Davidse K, et al. Effects of childhood multidisciplinary care and growth hormone treatment on health problems in adults with Prader-Willi syndrome. 

2021;10(15):3250. doi:10.3390/jcm10153250

Multidisciplinary care that includes growth hormone treatment should not cease once patients with Prader-Willi syndrome reach adulthood, according to authors of a study on care outcomes.

Researchers Call for Continued Multidisciplinary Care Through Adulthood in Prader-Willi Syndrome

The prevalence of potential drug-drug interactions (pDDIs) is significant in people living with 

The prevalence of pDDIs also varies according to the drug use pattern considered, with people using multiple drugs, or polydrug users, being at the highest risk.

Antiretroviral therapy (ART) agents pose a high risk for pDDIs. According to the study, ART agents mainly induce, inhibit, or are a substrate of cytochrome P450 enzymes, particularly isozyme CYP3A4, and could lead to pDDIs in PLHIV who both use illicit drugs and are on ART. The study authors also pointed out that not all ART or illicit drugs are associated with higher risk of pDDIs.

“While the prevalence of pDDIs associated with medication used concomitantly with ART because of associated comorbidities has been well described, with reported rates ranging between 34.9% and 89.2%, there is still a dearth of data on pDDIs between ART drugs and illicit drugs,” the authors said.

Part of a larger research project, this study by the Interdisciplinary Spanish AIDS Society  analyzed multiple aspects of illicit drug use by PLHIV across 12 regions in Spain from 36 institutions There was a total sample of 694 PLHIV taking ART and illicit drugs, with drug type, frequency, and mode of consumption during the last year being the 3 variables used to measure illicit drug use.

Overall, the study used 6 main variables:

Use of illicit drugs and other substances

Awareness, beliefs, intentional nonadherence, and communication with health care providers on the use of drugs and potential pDDIs

Health and use-of-health care-system–related variables

After excluding 38 participants due to lack of information, 335 (51.1%) participants exhibited pDDIs between their ART regimen and the illegal drugs they were consuming or had consumed in the previous year. The researchers identified 708 significant or contraindicated pDDIs, with only 1 pDDI being considered a contraindicated combination, and the mean (SD) number of pDDIs per patient was 2.1 (1.7).

Of 656 PLHIV, 220 (33.5%) consumed 1 illicit drug, 128 (19.5%) consumed 2 drugs, 93 (14.2%) consumed 3 drugs, 48 (7.3%) consumed 4 drugs, and 167 (25.5%) consumed 5 or more drugs.

Cannabis, cocaine, nitrates, and MDMA were among the most commonly used illicit drugs, and cannabis, cocaine, MDMA, and GHB/GBL exhibited a higher prevalence of pDDIs. Nitrates were the only drugs to not result in pDDIs.

The results suggest the prevalence of pDDIs is significant in PLHIV who use drugs and that the prevalence differs according to the drug use pattern considered. The results also show that experiencing pDDIs could lead to intentional nonadherence.

“Although we did not find any impact of pDDIs on other health-related variables, longitudinal studies should be undertaken to determine whether pDDIs could have an impact on the long-term health status of PLHIV,” the authors said.

PLHIV people with HIV at the highest risk of pDDIs according to their drug use pattern and monitor their treatment.

“An awareness, recognition, and the correct management of pDDIs are important in optimizing the medical and pharmaceutical care administered to PLHIV and could help to prevent a loss of efficacy of the drugs administered, as well as any adverse events that they may cause,” the authors said. “Therefore, it is essential to provide practitioners responsible for the care of patients with adequate training and the support tools required to easily access validated information.”

Castro-Granell V, Garin N, Jaen A, Cenoz S, Galindo MJ, Fuster-RuizdeApodaca MJ. Prevalence, beliefs and impact of drug-drug interactions between antiretroviral therapy and illicit drugs among people living with HIV in Spain. 

New data show the prevalence of potential drug-drug interactions varies according to the drug use pattern considered, with people living with HIV using multiple illegal drugs being at the highest risk.