To the Editor:

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by bilateral, symmetrical, proximal muscle weakness and classic cutaneous manifestations.¹ Patients with antibodies directed against melanoma differentiation–associated gene 5, MDA5, have a distinct presentation due to vasculopathy with more severe cutaneous ulcerations, palmar papules, alopecia, and an elevated risk of rapidly progressive interstitial lung disease.² A ferritin level greater than 1600 ng/mL portends an increased risk for pulmonary disease and therefore can be of prognostic value.³ Further, patients with anti-MDA5 DM are at a lower risk of malignancy and are more likely to test negative for antinuclear antibodies in comparison to other patients with DM.^2,4

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a potentially lethal condition whereby uncontrolled activation of histiocytes in the reticuloendothelial system causes hemophagocytosis and a hyperinflammatory state. Patients present with fever, splenomegaly, cytopenia, and hyperferritinemia.⁵ Autoimmune‐associated hemophagocytic syndrome (AAHS) describes HLH that develops in association with autoimmune conditions, most commonly systemic lupus erythematosus and adult-onset Still disease. Cases reported in association with DM exist but are few in number, and there is no standard-of-care treatment.⁶ We report a case of a woman with anti-MDA5 DM complicated by HLH and DM-associated liver injury.

A 50-year-old woman presented as a direct admit from the rheumatology clinic for diffuse muscle weakness of 8 months’ duration, 40-pound unintentional weight loss, pruritic rash, bilateral joint pains, dry eyes, dry mouth, and altered mental status. Four months prior, she presented to an outside hospital and was given a diagnosis of probable Sjögren syndrome and autoimmune hepatitis vs drug-induced liver injury. At that time, a workup was notable for antibodies against Sjögren syndrome–related antigen A, anti–smooth muscle antibodies, and transaminitis. Ultrasonography of the right upper quadrant revealed hepatic steatosis. The patient was started on oral prednisone and pilocarpine but had been off all medications for 1 month when she presented to our hospital.

On hospital admission, physical examination revealed a violaceous heliotrope rash; a v-sign on the chest; shawl sign; palmar papules with pits at the fingertips; and periungual erythema and ulcerations along the metacarpophalangeal joints, elbows, lateral feet, and upper eyelids (Figure 1). Laboratory workup showed the following results: white blood cell count, 4100/μL (reference range, 4000–11,000/μL); hemoglobin, 11.6 g/dL (reference range, 12–16 g/dL); platelet count, 100,000/μL (reference range, 150,000–450,000/μL); lactate dehydrogenase, 510 U/L (reference range, 80–225 U/L); alkaline phosphatase (ALP), 766 U/L (reference range, 30–120 U/L); alanine aminotransferase (ALT), 88 U/L (reference range, 10–40 U/L); aspartate aminotransferase (AST), 544 U/L (reference range, 10–40 U/L); total bilirubin, 4.2 mg/dL (reference range, 0.3–1.0 mg/dL); direct bilirubin, 3.7 mg/dL (reference range, 0.1–0.3 mg/dL); aldolase, 20.2 U/L (reference range, 1–7.5 U/L), creatine kinase, 180 U/L (reference range, 30–135 U/L); γ-glutamyltransferase (GGT), 2743 U/L (reference range, 8–40 U/L); high sensitivity C-reactive protein, 122.9 mg/L (low-risk reference range, <1.0 mg/L); triglycerides, 534 mg/dL (reference range, <150 mg/dL); ferritin, 3784 ng/mL (reference range, 24–307 ng/mL); antinuclear antibody, negative titer; antimitochondrial antibody, negative titer; soluble IL-2 receptor (CD25), 7000 U/mL (reference range, 189–846 U/mL); anti-Sjögren syndrome–related antigen A antibody, positive.

To the Editor:

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by bilateral, symmetrical, proximal muscle weakness and classic cutaneous manifestations.¹ Patients with antibodies directed against melanoma differentiation–associated gene 5, MDA5, have a distinct presentation due to vasculopathy with more severe cutaneous ulcerations, palmar papules, alopecia, and an elevated risk of rapidly progressive interstitial lung disease.² A ferritin level greater than 1600 ng/mL portends an increased risk for pulmonary disease and therefore can be of prognostic value.³ Further, patients with anti-MDA5 DM are at a lower risk of malignancy and are more likely to test negative for antinuclear antibodies in comparison to other patients with DM.^2,4

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a potentially lethal condition whereby uncontrolled activation of histiocytes in the reticuloendothelial system causes hemophagocytosis and a hyperinflammatory state. Patients present with fever, splenomegaly, cytopenia, and hyperferritinemia.⁵ Autoimmune‐associated hemophagocytic syndrome (AAHS) describes HLH that develops in association with autoimmune conditions, most commonly systemic lupus erythematosus and adult-onset Still disease. Cases reported in association with DM exist but are few in number, and there is no standard-of-care treatment.⁶ We report a case of a woman with anti-MDA5 DM complicated by HLH and DM-associated liver injury.

A 50-year-old woman presented as a direct admit from the rheumatology clinic for diffuse muscle weakness of 8 months’ duration, 40-pound unintentional weight loss, pruritic rash, bilateral joint pains, dry eyes, dry mouth, and altered mental status. Four months prior, she presented to an outside hospital and was given a diagnosis of probable Sjögren syndrome and autoimmune hepatitis vs drug-induced liver injury. At that time, a workup was notable for antibodies against Sjögren syndrome–related antigen A, anti–smooth muscle antibodies, and transaminitis. Ultrasonography of the right upper quadrant revealed hepatic steatosis. The patient was started on oral prednisone and pilocarpine but had been off all medications for 1 month when she presented to our hospital.

On hospital admission, physical examination revealed a violaceous heliotrope rash; a v-sign on the chest; shawl sign; palmar papules with pits at the fingertips; and periungual erythema and ulcerations along the metacarpophalangeal joints, elbows, lateral feet, and upper eyelids (Figure 1). Laboratory workup showed the following results: white blood cell count, 4100/μL (reference range, 4000–11,000/μL); hemoglobin, 11.6 g/dL (reference range, 12–16 g/dL); platelet count, 100,000/μL (reference range, 150,000–450,000/μL); lactate dehydrogenase, 510 U/L (reference range, 80–225 U/L); alkaline phosphatase (ALP), 766 U/L (reference range, 30–120 U/L); alanine aminotransferase (ALT), 88 U/L (reference range, 10–40 U/L); aspartate aminotransferase (AST), 544 U/L (reference range, 10–40 U/L); total bilirubin, 4.2 mg/dL (reference range, 0.3–1.0 mg/dL); direct bilirubin, 3.7 mg/dL (reference range, 0.1–0.3 mg/dL); aldolase, 20.2 U/L (reference range, 1–7.5 U/L), creatine kinase, 180 U/L (reference range, 30–135 U/L); γ-glutamyltransferase (GGT), 2743 U/L (reference range, 8–40 U/L); high sensitivity C-reactive protein, 122.9 mg/L (low-risk reference range, <1.0 mg/L); triglycerides, 534 mg/dL (reference range, <150 mg/dL); ferritin, 3784 ng/mL (reference range, 24–307 ng/mL); antinuclear antibody, negative titer; antimitochondrial antibody, negative titer; soluble IL-2 receptor (CD25), 7000 U/mL (reference range, 189–846 U/mL); anti-Sjögren syndrome–related antigen A antibody, positive.

To the Editor:

Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by bilateral, symmetrical, proximal muscle weakness and classic cutaneous manifestations.¹ Patients with antibodies directed against melanoma differentiation–associated gene 5, MDA5, have a distinct presentation due to vasculopathy with more severe cutaneous ulcerations, palmar papules, alopecia, and an elevated risk of rapidly progressive interstitial lung disease.² A ferritin level greater than 1600 ng/mL portends an increased risk for pulmonary disease and therefore can be of prognostic value.³ Further, patients with anti-MDA5 DM are at a lower risk of malignancy and are more likely to test negative for antinuclear antibodies in comparison to other patients with DM.^2,4

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a potentially lethal condition whereby uncontrolled activation of histiocytes in the reticuloendothelial system causes hemophagocytosis and a hyperinflammatory state. Patients present with fever, splenomegaly, cytopenia, and hyperferritinemia.⁵ Autoimmune‐associated hemophagocytic syndrome (AAHS) describes HLH that develops in association with autoimmune conditions, most commonly systemic lupus erythematosus and adult-onset Still disease. Cases reported in association with DM exist but are few in number, and there is no standard-of-care treatment.⁶ We report a case of a woman with anti-MDA5 DM complicated by HLH and DM-associated liver injury.

A 50-year-old woman presented as a direct admit from the rheumatology clinic for diffuse muscle weakness of 8 months’ duration, 40-pound unintentional weight loss, pruritic rash, bilateral joint pains, dry eyes, dry mouth, and altered mental status. Four months prior, she presented to an outside hospital and was given a diagnosis of probable Sjögren syndrome and autoimmune hepatitis vs drug-induced liver injury. At that time, a workup was notable for antibodies against Sjögren syndrome–related antigen A, anti–smooth muscle antibodies, and transaminitis. Ultrasonography of the right upper quadrant revealed hepatic steatosis. The patient was started on oral prednisone and pilocarpine but had been off all medications for 1 month when she presented to our hospital.

On hospital admission, physical examination revealed a violaceous heliotrope rash; a v-sign on the chest; shawl sign; palmar papules with pits at the fingertips; and periungual erythema and ulcerations along the metacarpophalangeal joints, elbows, lateral feet, and upper eyelids (Figure 1). Laboratory workup showed the following results: white blood cell count, 4100/μL (reference range, 4000–11,000/μL); hemoglobin, 11.6 g/dL (reference range, 12–16 g/dL); platelet count, 100,000/μL (reference range, 150,000–450,000/μL); lactate dehydrogenase, 510 U/L (reference range, 80–225 U/L); alkaline phosphatase (ALP), 766 U/L (reference range, 30–120 U/L); alanine aminotransferase (ALT), 88 U/L (reference range, 10–40 U/L); aspartate aminotransferase (AST), 544 U/L (reference range, 10–40 U/L); total bilirubin, 4.2 mg/dL (reference range, 0.3–1.0 mg/dL); direct bilirubin, 3.7 mg/dL (reference range, 0.1–0.3 mg/dL); aldolase, 20.2 U/L (reference range, 1–7.5 U/L), creatine kinase, 180 U/L (reference range, 30–135 U/L); γ-glutamyltransferase (GGT), 2743 U/L (reference range, 8–40 U/L); high sensitivity C-reactive protein, 122.9 mg/L (low-risk reference range, <1.0 mg/L); triglycerides, 534 mg/dL (reference range, <150 mg/dL); ferritin, 3784 ng/mL (reference range, 24–307 ng/mL); antinuclear antibody, negative titer; antimitochondrial antibody, negative titer; soluble IL-2 receptor (CD25), 7000 U/mL (reference range, 189–846 U/mL); anti-Sjögren syndrome–related antigen A antibody, positive.

As compared with White individuals, minorities often face higher barriers to cancer care. Racial and ethnic disparities in patients with solid tumors, particularly those of the prostate and breast, have been well documented. Hematologic malignancies are less common, but an increasing number of studies have documented disparities within this subgroup of cancer, particularly among Black and non-White Hispanics. An increasing armamentarium of therapeutics, including novel chemotherapy agents and targeted molecular, cellular, and immunologic therapies, has highlighted the need for understanding and exploring the differences in care as well as biology, which may lead to disparate outcomes.

Courtesy NIAID

Overall, an estimated 186,400 people living in the United States are expected to be diagnosed with leukemia, lymphoma, or myeloma in 2021, and new cases of hematologic malignancies are expected to account for 9.8% of the estimated 1,898,160 new cancer cases diagnosed this year.¹

The underlying reasons for disparities are highly complex and multifactorial, and clinicians must consider how the biologic, clinical, demographic, and socioeconomic characteristics of their patients interact. All of these factors can play a role in prognosis and/or access to care.

Disparities in leukemia

Leukemia is a heterogeneous group of diseases affecting both children and adults, but during the past few decades survival rates have steadily improved, particularly among children. Response to therapy and prognosis do vary among leukemia types, but one large analysis reported that there were overall improvements in survival seen across racial/ethnic groups, most age groups, and genders during a 40-year period.²

From 1973 through 2014, survival trends were assessed across four leukemia types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphoid leukemia (CLL). After stratifying survival for each leukemia type by race/ethnicity, improvement rates were not uniform among all groups.

For example, there were substantial improvements of leukemia-specific survival in 2010-2014 among Black (81.0%) and Asian (80.0%) patients with CML, as well as younger patients (20-49 years) with CLL (96.0%). But in contrast, Black patients, those with AML, and individuals over the age of 75 years experienced the lowest improvement in survival.

Studies have found that Hispanics have increased rates of ALL and acute promyelocytic leukemia (APL), but lower rates of AML, as compared to Whites. They also tend to be diagnosed at a younger age and have poorer overall survival.³

Demographics may also play a role, as Hispanics born outside the United States had a higher incidence rate of APL versus U.S.-born Hispanics (incidence rate ratio, 1.79; 1.11-2.94). Thus, the higher incidence rates of increased B-cell ALL may be due to heritable genetic factors, while APL may also be attributable to environmental exposures.⁴

Hispanics living on the Texas-Mexico border were also found to have a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) as compared with Hispanics living elsewhere in Texas⁵ AML and CML were more likely to be observed in patients who resided in this border region, and those with ALL, AML, and CML had worse outcomes compared with Hispanics living elsewhere in Texas. In addition, both Hispanic and non-Hispanic patients along the border have a worse prognosis for ALL than patients in other areas of Texas.

“We don’t yet understand if the differences are due to nonbiologic factors, or if biology plays a role because of the more aggressive disease that we’re seeing,” said study author Anna Eiring, PhD, an assistant professor at Texas Tech University, El Paso. “This is a medically underserved region, and even though we are a safety net hospital, many of the Hispanic patients don’t have health insurance.”

They also tend to have worse socioeconomic status compared with non-Hispanic populations, and there may also be lifestyle and environmental factors. “Exposure to environmental toxins may also play a role, as many work in jobs that could put them at risk,” she said. “Lifestyle factors may also play a role.”

AML is a hematopoietic disorder that is characterized by numerous cytogenetic and molecular aberrations, with poor overall survival. Researchers found that Black patients had shorter survival than White patients, based on an analysis of Surveillance Epidemiology and End Results (SEER) Program data, and performing and performed mutational profiling of 1,339 patients with AML treated on frontline Alliance for Clinical Trials in Oncology (Alliance) protocols.⁶ The disparity was especially pronounced in Black patients under 60 years old, after adjustment for socioeconomic (SEER) and molecular (Alliance) factors. Black race was an independent prognosticator of poor survival.

“Based on our analyses in Black and White AML patients under the age of 60 years, we believe that a differential impact of molecular aberrations, specifically AML-associated gene mutations, contribute to the observed survival disparities,” said study author Ann-Kathrin Eisfeld, MD, an assistant professor in the division of hematology at the Ohio State University, Columbus, and a member of the leukemia research program at the university’s comprehensive cancer center, the James. “For example, NPM1 mutations seem to lack the known positive prognostic impact we are used to seeing in previous studies with White AML patients.”

HRaun/E+

Disparities in lymphoma

Similar to leukemia, lymphomas are a heterogenous and diverse group of malignancies that range from indolent to highly aggressive. The two main types are listed below:

Non-Hodgkin lymphoma (NHL), the most common subtype, with about 80,000 new cases a year in the United States. There are more than 90 types of NHL, the most common being B-cell lymphomas, which include diffuse large B cell, primary mediastinal B cell, follicular, small lymphocytic lymphoma, and chronic lymphocytic leukemia; marginal zone, mantle zone, and Burkitt lymphomas; and Waldenström macroglobulinemia.

Hodgkin lymphoma (HL), less common than NHL, with about 9,000 people diagnosed every year. There are five types of HL, and it is primarily seen in children and young adults.

Disparities in incidence, age at diagnosis, and overall survival have been observed in lymphoma, which, aside from marginal zone and follicular lymphoma, are more common among men. The incidence of most lymphoma subtypes is generally lower in racial and ethnic minority groups, although Black and Hispanic patients tend to be diagnosed at a younger age, and in Black patients, at a more advanced stage and the lymphomas have higher risk features at initial presentation.⁷

One study that looked at racial disparities in Hodgkin lymphoma found that HL was significantly more common in Hispanics versus Whites under the age of 65 years. The 5-, 10-, and 15-year overall survival rates were also inferior for Blacks and Hispanics compared with Whites (P less than 0.005 and P less than 0.001, respectively).⁸

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in the United States, comprising approximately one-third of lymphomas diagnosed in adults (Lee et al. 2020). In one study that examined ancestry and tumor genomics, recurrent somatic mutations in established driver genes, such as ATM, MGA, SETD2, TET2, DNMT3A, and MLL3, were observed more frequently in patients with African ancestry versus those of European ancestry.⁹ Other data suggest a variety of disparities in receipt of treatment. For example, patients with localized disease who were Black, uninsured/Medicaid insured, or of lower socioeconomic status were less likely to receive any form of chemotherapy (all P less than 0.0001), and Black race was also associated with being less likely to receive chemoimmunotherapy.

Leveling the field of disparities is complex and requires a multifaceted approach. But one facility found that they could help minority patients overcome some of the hurdles related to nonbiologic factors by the support of a nurse navigator in addition to therapy.¹⁰ Their study included 204 patients with DLBCL (47 minority patients and 157 White patients) and following the initiation of the nurse navigator program, virtually all patients received frontline chemotherapy (98% versus 96%). The incidence of relapsed/refractory disease was similar (40% versus 38%) and in the relapsed/refractory population, similar proportions of patients underwent hematopoietic stem cell transplantation (32% versus 29%) or received chimeric antigen receptor T-cell therapy (16% versus 19%). The 2-year overall survival rates were 81% and 76% for minorities and Whites, respectively, and 2-year progression-free survival rates were 62% and 65%, respectively.

“We found that the minority patients often needed more help to get care, and they utilized the nurse navigator more intensively,” said study author Bei Hu, MD, who is with the department of hematologic oncology and blood disorders, Levine Cancer Institute/Atrium Health, Charlotte, N.C. “The nurse navigator was able to help them with things like finances, transportation, and insurance.”

Minorities tended to face more barriers than White patients. “Even something as simple as needing money for gas to get to the clinic can be a barrier to care,” said Dr. Hu. “And many of the patients are often uncomfortable discussing these things with their physician – plus a lot is covered in our appointments and we focus on the cancer. So, they may be more comfortable discussing these issues with the nurse.”

Disparities in multiple myeloma

Multiple myeloma is the malignant clonal proliferation of plasma B cells in the bone marrow and, despite the advent of new therapies, remains incurable and generally fatal. It progresses from the more common but often subclinical precursor states of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to overt and symptomatic multiple myeloma. Racial disparities have been observed in all stages of the disease, and as compared with Whites, individuals who are Black have a higher risk of MGUS and myeloma and a higher mortality rate.¹¹ They have not experienced the same survival gains seen in White patients.

Some research suggests that these disparities may be more related to socioeconomic status as opposed to race. One analysis of 562 patients found that those with higher socioeconomic status had a median overall survival of 62.8 months compared with 53.7 and 48.6 months for middle and low socioeconomic status (P = 0.015).¹²

After controlling for confounders including race, patients with low socioeconomic status had a 54% increase in mortality rate relative to those with high status. The authors then performed a similar analysis of 45,505 patients with multiple myeloma from the Surveillance, Epidemiology and End Results-18 database to support their analysis, and that also showed low socioeconomic status to be independently associated with poorer overall survival.

“In some homogeneous health systems, such as the VA, we are seeing that Black patients do as well or better than White patients,” said Catherine Marinac, PhD, an assistant professor of medicine, Harvard Medical School, Boston. “Survival is equal or better, as long as treatment is not delayed and they receive the standard of care.”

Black patients generally have a more indolent disease subtype and may experience less aggressive disease, but they have not experienced the same magnitude in survival as White patients following the introduction of new therapeutics. This disparity lends support to the influence of socioeconomic factors, such as unequal access to novel therapies and/or differences in treatment response, and lower rates of autologous stem cell transplantation.¹³

However, there are racial/ethnic differences in risk for both myeloma and its premalignant conditions, as well as incidence. Blacks have a twofold increased risk of myeloma compared with White individuals and are diagnosed at younger ages. Differences in myeloma incidence is less marked in other racial/ethnic groups, such as Hispanics, where it is only slightly higher than in Whites at 6.7 per 100,00.¹¹ In contrast, the incidence of myeloma is markedly lower in Asians as compared with non-Hispanic Whites (incidence rate of 3.8 versus 6.2 per 100,000). Black persons also have a markedly higher prevalence of MGUS, and these differences suggest that biology, and clinical characteristics, differ by race or ancestry.

“Mortality among Black patients is also higher,” said Dr. Marinac, who is also on the faculty in the division of population sciences at the Dana Farber Cancer Institute, also in Boston. “The higher mortality rate is driven by the higher incidence.”

There are also differences in the prevalence of immunoglobulin isotypes observed across racial/ethnic groups of MGUS patients, Dr. Marinac explained, which is consistent with the hypothesis that there is a biological basis for disparities arising in precursor lesions.

“What we are looking at now is cancer prevention and early intervention,” she said. “There are well-defined precursors to myeloma, and Blacks are three times more likely to have a precursor condition.”

Early detection of precursors followed by preventing progression to full-blown multiple myeloma is one way of addressing disparities, but right now, there are no real screening guidelines. “Most patients now are diagnosed incidentally, and then the only intervention is to monitor them,” Dr. Marinac said. “At Dana Farber, we are now looking to see if we can refine screening, and then see who may need additional monitoring.”

The Promise study, being conducted at Dana Farber, is recruiting participants to examine the molecular changes that occur when precursor conditions develop into full-blown multiple myeloma and is open to individuals considered to be at high risk: Black race and/or have a first-degree relative with multiple myeloma or one of its precursor conditions.

Dr. Marinac also pointed out that there are ongoing clinical trials that are looking at low-risk early interventions in patients with precursor conditions. “We are now looking at lifestyle and metformin,” she said. “The thought is that if we treat them now, we can prevent myeloma from developing.”

Lessening barriers to care

When trying to tease out the strongest/most prominent reasons for the disparities that have been observed in the care of patients with blood cancers, Stephanie Lee, M.D., M.P.H, professor and associate director of the clinical research division at Fred Hutchinson Cancer Research Center, Seattle, thinks that the problem is truly multifactorial.

“Access has been cited many times because some studies show that if access is equitable, sometimes racial/ethnic minorities do the same as non-Hispanic Whites,” she said. “Same thing with quality of care – if all people are treated on clinical trials, sometimes the outcomes are the same.”

That said, many things have to go right to get the best outcomes, and if one factor isn’t optimal, then treatment may never achieve the success that is possible, she noted.

Considering how complex the issue of disparities is, addressing it can seem daunting. Dr. Lee points out that the place to begin is with clinical trials. “I would like to see more studies that test interventions to correct disparities,” said Dr. Lee. “But I have actually seen in my own work that racial and ethnic minorities are less likely to participate in studies, even survey and observational studies where physical risks are low or nonexistent.”

People are studying how to increase minority participation in clinical trials, but thus far, there isn’t one solution. “As with routine care, there are probably a lot of logistical barriers to trial participation that disproportionately affect minority populations,” she noted. “There is also greater distrust of studies.”

But for now, there are some steps that clinicians can take to start to improve these disparities. “I think we can start inquiring about and documenting barriers to care and clinical trial participation, just like we document other aspects of the social history,” Dr. Lee explained. “Truly understanding the problem is the first step toward trying to solve it.”

References

1. Leukemia & Lymphoma Society. 2021. www.lls.org/facts-and-statistics/facts-and-statistics-overview.

2. Utuama O et al. PLoS One. 2019 Aug 19;14(8):e0220864.

3. Pollyea DA et al. J Cancer Prev Curr Res. 2014;1(1):14-19.

4. Bencomo-Alvarez AE et al. Cancer. 2021 Apr 1;127(7):1068-79.

5. Nabhan C et al. Cancer. 2012 Oct 1;118(19):4842-50.

6. Bhatnagar B et al. Blood. 2020;136(Suppl 1):5-7.

7. Shenoy PJ et al. Cancer. 2011;117:2530-40.

8. Evens AM et al. Ann Oncol. 2012 Aug 1;23(8):2128-37.

9. Lee MJ et al. Cancer. 2020;126:3493-3503.

10. Hu B et al. Cancer. 2021 Jul 21. doi: 10.1002/cncr.33779.

11. Marinac CR et al. Blood Cancer J. 2020 Feb 17;10(2):19.

12. Fiala MA et al. Leuk Lymphoma. 2015;56(9):2643-9.

13. Costa LJ et al. Biol Blood Marrow Transplant. 2015 Apr;21(4):701-6.

As compared with White individuals, minorities often face higher barriers to cancer care. Racial and ethnic disparities in patients with solid tumors, particularly those of the prostate and breast, have been well documented. Hematologic malignancies are less common, but an increasing number of studies have documented disparities within this subgroup of cancer, particularly among Black and non-White Hispanics. An increasing armamentarium of therapeutics, including novel chemotherapy agents and targeted molecular, cellular, and immunologic therapies, has highlighted the need for understanding and exploring the differences in care as well as biology, which may lead to disparate outcomes.

Courtesy NIAID

Overall, an estimated 186,400 people living in the United States are expected to be diagnosed with leukemia, lymphoma, or myeloma in 2021, and new cases of hematologic malignancies are expected to account for 9.8% of the estimated 1,898,160 new cancer cases diagnosed this year.¹

The underlying reasons for disparities are highly complex and multifactorial, and clinicians must consider how the biologic, clinical, demographic, and socioeconomic characteristics of their patients interact. All of these factors can play a role in prognosis and/or access to care.

Disparities in leukemia

Leukemia is a heterogeneous group of diseases affecting both children and adults, but during the past few decades survival rates have steadily improved, particularly among children. Response to therapy and prognosis do vary among leukemia types, but one large analysis reported that there were overall improvements in survival seen across racial/ethnic groups, most age groups, and genders during a 40-year period.²

From 1973 through 2014, survival trends were assessed across four leukemia types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphoid leukemia (CLL). After stratifying survival for each leukemia type by race/ethnicity, improvement rates were not uniform among all groups.

For example, there were substantial improvements of leukemia-specific survival in 2010-2014 among Black (81.0%) and Asian (80.0%) patients with CML, as well as younger patients (20-49 years) with CLL (96.0%). But in contrast, Black patients, those with AML, and individuals over the age of 75 years experienced the lowest improvement in survival.

Studies have found that Hispanics have increased rates of ALL and acute promyelocytic leukemia (APL), but lower rates of AML, as compared to Whites. They also tend to be diagnosed at a younger age and have poorer overall survival.³

Demographics may also play a role, as Hispanics born outside the United States had a higher incidence rate of APL versus U.S.-born Hispanics (incidence rate ratio, 1.79; 1.11-2.94). Thus, the higher incidence rates of increased B-cell ALL may be due to heritable genetic factors, while APL may also be attributable to environmental exposures.⁴

Hispanics living on the Texas-Mexico border were also found to have a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) as compared with Hispanics living elsewhere in Texas⁵ AML and CML were more likely to be observed in patients who resided in this border region, and those with ALL, AML, and CML had worse outcomes compared with Hispanics living elsewhere in Texas. In addition, both Hispanic and non-Hispanic patients along the border have a worse prognosis for ALL than patients in other areas of Texas.

“We don’t yet understand if the differences are due to nonbiologic factors, or if biology plays a role because of the more aggressive disease that we’re seeing,” said study author Anna Eiring, PhD, an assistant professor at Texas Tech University, El Paso. “This is a medically underserved region, and even though we are a safety net hospital, many of the Hispanic patients don’t have health insurance.”

They also tend to have worse socioeconomic status compared with non-Hispanic populations, and there may also be lifestyle and environmental factors. “Exposure to environmental toxins may also play a role, as many work in jobs that could put them at risk,” she said. “Lifestyle factors may also play a role.”

AML is a hematopoietic disorder that is characterized by numerous cytogenetic and molecular aberrations, with poor overall survival. Researchers found that Black patients had shorter survival than White patients, based on an analysis of Surveillance Epidemiology and End Results (SEER) Program data, and performing and performed mutational profiling of 1,339 patients with AML treated on frontline Alliance for Clinical Trials in Oncology (Alliance) protocols.⁶ The disparity was especially pronounced in Black patients under 60 years old, after adjustment for socioeconomic (SEER) and molecular (Alliance) factors. Black race was an independent prognosticator of poor survival.

“Based on our analyses in Black and White AML patients under the age of 60 years, we believe that a differential impact of molecular aberrations, specifically AML-associated gene mutations, contribute to the observed survival disparities,” said study author Ann-Kathrin Eisfeld, MD, an assistant professor in the division of hematology at the Ohio State University, Columbus, and a member of the leukemia research program at the university’s comprehensive cancer center, the James. “For example, NPM1 mutations seem to lack the known positive prognostic impact we are used to seeing in previous studies with White AML patients.”

HRaun/E+

Disparities in lymphoma

Similar to leukemia, lymphomas are a heterogenous and diverse group of malignancies that range from indolent to highly aggressive. The two main types are listed below:

Non-Hodgkin lymphoma (NHL), the most common subtype, with about 80,000 new cases a year in the United States. There are more than 90 types of NHL, the most common being B-cell lymphomas, which include diffuse large B cell, primary mediastinal B cell, follicular, small lymphocytic lymphoma, and chronic lymphocytic leukemia; marginal zone, mantle zone, and Burkitt lymphomas; and Waldenström macroglobulinemia.

Hodgkin lymphoma (HL), less common than NHL, with about 9,000 people diagnosed every year. There are five types of HL, and it is primarily seen in children and young adults.

Disparities in incidence, age at diagnosis, and overall survival have been observed in lymphoma, which, aside from marginal zone and follicular lymphoma, are more common among men. The incidence of most lymphoma subtypes is generally lower in racial and ethnic minority groups, although Black and Hispanic patients tend to be diagnosed at a younger age, and in Black patients, at a more advanced stage and the lymphomas have higher risk features at initial presentation.⁷

One study that looked at racial disparities in Hodgkin lymphoma found that HL was significantly more common in Hispanics versus Whites under the age of 65 years. The 5-, 10-, and 15-year overall survival rates were also inferior for Blacks and Hispanics compared with Whites (P less than 0.005 and P less than 0.001, respectively).⁸

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in the United States, comprising approximately one-third of lymphomas diagnosed in adults (Lee et al. 2020). In one study that examined ancestry and tumor genomics, recurrent somatic mutations in established driver genes, such as ATM, MGA, SETD2, TET2, DNMT3A, and MLL3, were observed more frequently in patients with African ancestry versus those of European ancestry.⁹ Other data suggest a variety of disparities in receipt of treatment. For example, patients with localized disease who were Black, uninsured/Medicaid insured, or of lower socioeconomic status were less likely to receive any form of chemotherapy (all P less than 0.0001), and Black race was also associated with being less likely to receive chemoimmunotherapy.

Leveling the field of disparities is complex and requires a multifaceted approach. But one facility found that they could help minority patients overcome some of the hurdles related to nonbiologic factors by the support of a nurse navigator in addition to therapy.¹⁰ Their study included 204 patients with DLBCL (47 minority patients and 157 White patients) and following the initiation of the nurse navigator program, virtually all patients received frontline chemotherapy (98% versus 96%). The incidence of relapsed/refractory disease was similar (40% versus 38%) and in the relapsed/refractory population, similar proportions of patients underwent hematopoietic stem cell transplantation (32% versus 29%) or received chimeric antigen receptor T-cell therapy (16% versus 19%). The 2-year overall survival rates were 81% and 76% for minorities and Whites, respectively, and 2-year progression-free survival rates were 62% and 65%, respectively.

“We found that the minority patients often needed more help to get care, and they utilized the nurse navigator more intensively,” said study author Bei Hu, MD, who is with the department of hematologic oncology and blood disorders, Levine Cancer Institute/Atrium Health, Charlotte, N.C. “The nurse navigator was able to help them with things like finances, transportation, and insurance.”

Minorities tended to face more barriers than White patients. “Even something as simple as needing money for gas to get to the clinic can be a barrier to care,” said Dr. Hu. “And many of the patients are often uncomfortable discussing these things with their physician – plus a lot is covered in our appointments and we focus on the cancer. So, they may be more comfortable discussing these issues with the nurse.”

Disparities in multiple myeloma

Multiple myeloma is the malignant clonal proliferation of plasma B cells in the bone marrow and, despite the advent of new therapies, remains incurable and generally fatal. It progresses from the more common but often subclinical precursor states of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to overt and symptomatic multiple myeloma. Racial disparities have been observed in all stages of the disease, and as compared with Whites, individuals who are Black have a higher risk of MGUS and myeloma and a higher mortality rate.¹¹ They have not experienced the same survival gains seen in White patients.

Some research suggests that these disparities may be more related to socioeconomic status as opposed to race. One analysis of 562 patients found that those with higher socioeconomic status had a median overall survival of 62.8 months compared with 53.7 and 48.6 months for middle and low socioeconomic status (P = 0.015).¹²

After controlling for confounders including race, patients with low socioeconomic status had a 54% increase in mortality rate relative to those with high status. The authors then performed a similar analysis of 45,505 patients with multiple myeloma from the Surveillance, Epidemiology and End Results-18 database to support their analysis, and that also showed low socioeconomic status to be independently associated with poorer overall survival.

“In some homogeneous health systems, such as the VA, we are seeing that Black patients do as well or better than White patients,” said Catherine Marinac, PhD, an assistant professor of medicine, Harvard Medical School, Boston. “Survival is equal or better, as long as treatment is not delayed and they receive the standard of care.”

Black patients generally have a more indolent disease subtype and may experience less aggressive disease, but they have not experienced the same magnitude in survival as White patients following the introduction of new therapeutics. This disparity lends support to the influence of socioeconomic factors, such as unequal access to novel therapies and/or differences in treatment response, and lower rates of autologous stem cell transplantation.¹³

However, there are racial/ethnic differences in risk for both myeloma and its premalignant conditions, as well as incidence. Blacks have a twofold increased risk of myeloma compared with White individuals and are diagnosed at younger ages. Differences in myeloma incidence is less marked in other racial/ethnic groups, such as Hispanics, where it is only slightly higher than in Whites at 6.7 per 100,00.¹¹ In contrast, the incidence of myeloma is markedly lower in Asians as compared with non-Hispanic Whites (incidence rate of 3.8 versus 6.2 per 100,000). Black persons also have a markedly higher prevalence of MGUS, and these differences suggest that biology, and clinical characteristics, differ by race or ancestry.

“Mortality among Black patients is also higher,” said Dr. Marinac, who is also on the faculty in the division of population sciences at the Dana Farber Cancer Institute, also in Boston. “The higher mortality rate is driven by the higher incidence.”

There are also differences in the prevalence of immunoglobulin isotypes observed across racial/ethnic groups of MGUS patients, Dr. Marinac explained, which is consistent with the hypothesis that there is a biological basis for disparities arising in precursor lesions.

“What we are looking at now is cancer prevention and early intervention,” she said. “There are well-defined precursors to myeloma, and Blacks are three times more likely to have a precursor condition.”

Early detection of precursors followed by preventing progression to full-blown multiple myeloma is one way of addressing disparities, but right now, there are no real screening guidelines. “Most patients now are diagnosed incidentally, and then the only intervention is to monitor them,” Dr. Marinac said. “At Dana Farber, we are now looking to see if we can refine screening, and then see who may need additional monitoring.”

The Promise study, being conducted at Dana Farber, is recruiting participants to examine the molecular changes that occur when precursor conditions develop into full-blown multiple myeloma and is open to individuals considered to be at high risk: Black race and/or have a first-degree relative with multiple myeloma or one of its precursor conditions.

Dr. Marinac also pointed out that there are ongoing clinical trials that are looking at low-risk early interventions in patients with precursor conditions. “We are now looking at lifestyle and metformin,” she said. “The thought is that if we treat them now, we can prevent myeloma from developing.”

Lessening barriers to care

When trying to tease out the strongest/most prominent reasons for the disparities that have been observed in the care of patients with blood cancers, Stephanie Lee, M.D., M.P.H, professor and associate director of the clinical research division at Fred Hutchinson Cancer Research Center, Seattle, thinks that the problem is truly multifactorial.

“Access has been cited many times because some studies show that if access is equitable, sometimes racial/ethnic minorities do the same as non-Hispanic Whites,” she said. “Same thing with quality of care – if all people are treated on clinical trials, sometimes the outcomes are the same.”

That said, many things have to go right to get the best outcomes, and if one factor isn’t optimal, then treatment may never achieve the success that is possible, she noted.

Considering how complex the issue of disparities is, addressing it can seem daunting. Dr. Lee points out that the place to begin is with clinical trials. “I would like to see more studies that test interventions to correct disparities,” said Dr. Lee. “But I have actually seen in my own work that racial and ethnic minorities are less likely to participate in studies, even survey and observational studies where physical risks are low or nonexistent.”

People are studying how to increase minority participation in clinical trials, but thus far, there isn’t one solution. “As with routine care, there are probably a lot of logistical barriers to trial participation that disproportionately affect minority populations,” she noted. “There is also greater distrust of studies.”

But for now, there are some steps that clinicians can take to start to improve these disparities. “I think we can start inquiring about and documenting barriers to care and clinical trial participation, just like we document other aspects of the social history,” Dr. Lee explained. “Truly understanding the problem is the first step toward trying to solve it.”

References

1. Leukemia & Lymphoma Society. 2021. www.lls.org/facts-and-statistics/facts-and-statistics-overview.

2. Utuama O et al. PLoS One. 2019 Aug 19;14(8):e0220864.

3. Pollyea DA et al. J Cancer Prev Curr Res. 2014;1(1):14-19.

4. Bencomo-Alvarez AE et al. Cancer. 2021 Apr 1;127(7):1068-79.

5. Nabhan C et al. Cancer. 2012 Oct 1;118(19):4842-50.

6. Bhatnagar B et al. Blood. 2020;136(Suppl 1):5-7.

7. Shenoy PJ et al. Cancer. 2011;117:2530-40.

8. Evens AM et al. Ann Oncol. 2012 Aug 1;23(8):2128-37.

9. Lee MJ et al. Cancer. 2020;126:3493-3503.

10. Hu B et al. Cancer. 2021 Jul 21. doi: 10.1002/cncr.33779.

11. Marinac CR et al. Blood Cancer J. 2020 Feb 17;10(2):19.

12. Fiala MA et al. Leuk Lymphoma. 2015;56(9):2643-9.

13. Costa LJ et al. Biol Blood Marrow Transplant. 2015 Apr;21(4):701-6.

As compared with White individuals, minorities often face higher barriers to cancer care. Racial and ethnic disparities in patients with solid tumors, particularly those of the prostate and breast, have been well documented. Hematologic malignancies are less common, but an increasing number of studies have documented disparities within this subgroup of cancer, particularly among Black and non-White Hispanics. An increasing armamentarium of therapeutics, including novel chemotherapy agents and targeted molecular, cellular, and immunologic therapies, has highlighted the need for understanding and exploring the differences in care as well as biology, which may lead to disparate outcomes.

Courtesy NIAID

Overall, an estimated 186,400 people living in the United States are expected to be diagnosed with leukemia, lymphoma, or myeloma in 2021, and new cases of hematologic malignancies are expected to account for 9.8% of the estimated 1,898,160 new cancer cases diagnosed this year.¹

The underlying reasons for disparities are highly complex and multifactorial, and clinicians must consider how the biologic, clinical, demographic, and socioeconomic characteristics of their patients interact. All of these factors can play a role in prognosis and/or access to care.

Disparities in leukemia

Leukemia is a heterogeneous group of diseases affecting both children and adults, but during the past few decades survival rates have steadily improved, particularly among children. Response to therapy and prognosis do vary among leukemia types, but one large analysis reported that there were overall improvements in survival seen across racial/ethnic groups, most age groups, and genders during a 40-year period.²

From 1973 through 2014, survival trends were assessed across four leukemia types: acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphoid leukemia (CLL). After stratifying survival for each leukemia type by race/ethnicity, improvement rates were not uniform among all groups.

For example, there were substantial improvements of leukemia-specific survival in 2010-2014 among Black (81.0%) and Asian (80.0%) patients with CML, as well as younger patients (20-49 years) with CLL (96.0%). But in contrast, Black patients, those with AML, and individuals over the age of 75 years experienced the lowest improvement in survival.

Studies have found that Hispanics have increased rates of ALL and acute promyelocytic leukemia (APL), but lower rates of AML, as compared to Whites. They also tend to be diagnosed at a younger age and have poorer overall survival.³

Demographics may also play a role, as Hispanics born outside the United States had a higher incidence rate of APL versus U.S.-born Hispanics (incidence rate ratio, 1.79; 1.11-2.94). Thus, the higher incidence rates of increased B-cell ALL may be due to heritable genetic factors, while APL may also be attributable to environmental exposures.⁴

Hispanics living on the Texas-Mexico border were also found to have a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07-1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04-1.33; P = .0009) as compared with Hispanics living elsewhere in Texas⁵ AML and CML were more likely to be observed in patients who resided in this border region, and those with ALL, AML, and CML had worse outcomes compared with Hispanics living elsewhere in Texas. In addition, both Hispanic and non-Hispanic patients along the border have a worse prognosis for ALL than patients in other areas of Texas.

“We don’t yet understand if the differences are due to nonbiologic factors, or if biology plays a role because of the more aggressive disease that we’re seeing,” said study author Anna Eiring, PhD, an assistant professor at Texas Tech University, El Paso. “This is a medically underserved region, and even though we are a safety net hospital, many of the Hispanic patients don’t have health insurance.”

They also tend to have worse socioeconomic status compared with non-Hispanic populations, and there may also be lifestyle and environmental factors. “Exposure to environmental toxins may also play a role, as many work in jobs that could put them at risk,” she said. “Lifestyle factors may also play a role.”

AML is a hematopoietic disorder that is characterized by numerous cytogenetic and molecular aberrations, with poor overall survival. Researchers found that Black patients had shorter survival than White patients, based on an analysis of Surveillance Epidemiology and End Results (SEER) Program data, and performing and performed mutational profiling of 1,339 patients with AML treated on frontline Alliance for Clinical Trials in Oncology (Alliance) protocols.⁶ The disparity was especially pronounced in Black patients under 60 years old, after adjustment for socioeconomic (SEER) and molecular (Alliance) factors. Black race was an independent prognosticator of poor survival.

“Based on our analyses in Black and White AML patients under the age of 60 years, we believe that a differential impact of molecular aberrations, specifically AML-associated gene mutations, contribute to the observed survival disparities,” said study author Ann-Kathrin Eisfeld, MD, an assistant professor in the division of hematology at the Ohio State University, Columbus, and a member of the leukemia research program at the university’s comprehensive cancer center, the James. “For example, NPM1 mutations seem to lack the known positive prognostic impact we are used to seeing in previous studies with White AML patients.”

HRaun/E+

Disparities in lymphoma

Similar to leukemia, lymphomas are a heterogenous and diverse group of malignancies that range from indolent to highly aggressive. The two main types are listed below:

Non-Hodgkin lymphoma (NHL), the most common subtype, with about 80,000 new cases a year in the United States. There are more than 90 types of NHL, the most common being B-cell lymphomas, which include diffuse large B cell, primary mediastinal B cell, follicular, small lymphocytic lymphoma, and chronic lymphocytic leukemia; marginal zone, mantle zone, and Burkitt lymphomas; and Waldenström macroglobulinemia.

Hodgkin lymphoma (HL), less common than NHL, with about 9,000 people diagnosed every year. There are five types of HL, and it is primarily seen in children and young adults.

Disparities in incidence, age at diagnosis, and overall survival have been observed in lymphoma, which, aside from marginal zone and follicular lymphoma, are more common among men. The incidence of most lymphoma subtypes is generally lower in racial and ethnic minority groups, although Black and Hispanic patients tend to be diagnosed at a younger age, and in Black patients, at a more advanced stage and the lymphomas have higher risk features at initial presentation.⁷

One study that looked at racial disparities in Hodgkin lymphoma found that HL was significantly more common in Hispanics versus Whites under the age of 65 years. The 5-, 10-, and 15-year overall survival rates were also inferior for Blacks and Hispanics compared with Whites (P less than 0.005 and P less than 0.001, respectively).⁸

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in the United States, comprising approximately one-third of lymphomas diagnosed in adults (Lee et al. 2020). In one study that examined ancestry and tumor genomics, recurrent somatic mutations in established driver genes, such as ATM, MGA, SETD2, TET2, DNMT3A, and MLL3, were observed more frequently in patients with African ancestry versus those of European ancestry.⁹ Other data suggest a variety of disparities in receipt of treatment. For example, patients with localized disease who were Black, uninsured/Medicaid insured, or of lower socioeconomic status were less likely to receive any form of chemotherapy (all P less than 0.0001), and Black race was also associated with being less likely to receive chemoimmunotherapy.

Leveling the field of disparities is complex and requires a multifaceted approach. But one facility found that they could help minority patients overcome some of the hurdles related to nonbiologic factors by the support of a nurse navigator in addition to therapy.¹⁰ Their study included 204 patients with DLBCL (47 minority patients and 157 White patients) and following the initiation of the nurse navigator program, virtually all patients received frontline chemotherapy (98% versus 96%). The incidence of relapsed/refractory disease was similar (40% versus 38%) and in the relapsed/refractory population, similar proportions of patients underwent hematopoietic stem cell transplantation (32% versus 29%) or received chimeric antigen receptor T-cell therapy (16% versus 19%). The 2-year overall survival rates were 81% and 76% for minorities and Whites, respectively, and 2-year progression-free survival rates were 62% and 65%, respectively.

“We found that the minority patients often needed more help to get care, and they utilized the nurse navigator more intensively,” said study author Bei Hu, MD, who is with the department of hematologic oncology and blood disorders, Levine Cancer Institute/Atrium Health, Charlotte, N.C. “The nurse navigator was able to help them with things like finances, transportation, and insurance.”

Minorities tended to face more barriers than White patients. “Even something as simple as needing money for gas to get to the clinic can be a barrier to care,” said Dr. Hu. “And many of the patients are often uncomfortable discussing these things with their physician – plus a lot is covered in our appointments and we focus on the cancer. So, they may be more comfortable discussing these issues with the nurse.”

Disparities in multiple myeloma

Multiple myeloma is the malignant clonal proliferation of plasma B cells in the bone marrow and, despite the advent of new therapies, remains incurable and generally fatal. It progresses from the more common but often subclinical precursor states of monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) to overt and symptomatic multiple myeloma. Racial disparities have been observed in all stages of the disease, and as compared with Whites, individuals who are Black have a higher risk of MGUS and myeloma and a higher mortality rate.¹¹ They have not experienced the same survival gains seen in White patients.

Some research suggests that these disparities may be more related to socioeconomic status as opposed to race. One analysis of 562 patients found that those with higher socioeconomic status had a median overall survival of 62.8 months compared with 53.7 and 48.6 months for middle and low socioeconomic status (P = 0.015).¹²

After controlling for confounders including race, patients with low socioeconomic status had a 54% increase in mortality rate relative to those with high status. The authors then performed a similar analysis of 45,505 patients with multiple myeloma from the Surveillance, Epidemiology and End Results-18 database to support their analysis, and that also showed low socioeconomic status to be independently associated with poorer overall survival.

“In some homogeneous health systems, such as the VA, we are seeing that Black patients do as well or better than White patients,” said Catherine Marinac, PhD, an assistant professor of medicine, Harvard Medical School, Boston. “Survival is equal or better, as long as treatment is not delayed and they receive the standard of care.”

Black patients generally have a more indolent disease subtype and may experience less aggressive disease, but they have not experienced the same magnitude in survival as White patients following the introduction of new therapeutics. This disparity lends support to the influence of socioeconomic factors, such as unequal access to novel therapies and/or differences in treatment response, and lower rates of autologous stem cell transplantation.¹³

However, there are racial/ethnic differences in risk for both myeloma and its premalignant conditions, as well as incidence. Blacks have a twofold increased risk of myeloma compared with White individuals and are diagnosed at younger ages. Differences in myeloma incidence is less marked in other racial/ethnic groups, such as Hispanics, where it is only slightly higher than in Whites at 6.7 per 100,00.¹¹ In contrast, the incidence of myeloma is markedly lower in Asians as compared with non-Hispanic Whites (incidence rate of 3.8 versus 6.2 per 100,000). Black persons also have a markedly higher prevalence of MGUS, and these differences suggest that biology, and clinical characteristics, differ by race or ancestry.

“Mortality among Black patients is also higher,” said Dr. Marinac, who is also on the faculty in the division of population sciences at the Dana Farber Cancer Institute, also in Boston. “The higher mortality rate is driven by the higher incidence.”

There are also differences in the prevalence of immunoglobulin isotypes observed across racial/ethnic groups of MGUS patients, Dr. Marinac explained, which is consistent with the hypothesis that there is a biological basis for disparities arising in precursor lesions.

“What we are looking at now is cancer prevention and early intervention,” she said. “There are well-defined precursors to myeloma, and Blacks are three times more likely to have a precursor condition.”

Early detection of precursors followed by preventing progression to full-blown multiple myeloma is one way of addressing disparities, but right now, there are no real screening guidelines. “Most patients now are diagnosed incidentally, and then the only intervention is to monitor them,” Dr. Marinac said. “At Dana Farber, we are now looking to see if we can refine screening, and then see who may need additional monitoring.”

The Promise study, being conducted at Dana Farber, is recruiting participants to examine the molecular changes that occur when precursor conditions develop into full-blown multiple myeloma and is open to individuals considered to be at high risk: Black race and/or have a first-degree relative with multiple myeloma or one of its precursor conditions.

Dr. Marinac also pointed out that there are ongoing clinical trials that are looking at low-risk early interventions in patients with precursor conditions. “We are now looking at lifestyle and metformin,” she said. “The thought is that if we treat them now, we can prevent myeloma from developing.”

Lessening barriers to care

When trying to tease out the strongest/most prominent reasons for the disparities that have been observed in the care of patients with blood cancers, Stephanie Lee, M.D., M.P.H, professor and associate director of the clinical research division at Fred Hutchinson Cancer Research Center, Seattle, thinks that the problem is truly multifactorial.

“Access has been cited many times because some studies show that if access is equitable, sometimes racial/ethnic minorities do the same as non-Hispanic Whites,” she said. “Same thing with quality of care – if all people are treated on clinical trials, sometimes the outcomes are the same.”

That said, many things have to go right to get the best outcomes, and if one factor isn’t optimal, then treatment may never achieve the success that is possible, she noted.

Considering how complex the issue of disparities is, addressing it can seem daunting. Dr. Lee points out that the place to begin is with clinical trials. “I would like to see more studies that test interventions to correct disparities,” said Dr. Lee. “But I have actually seen in my own work that racial and ethnic minorities are less likely to participate in studies, even survey and observational studies where physical risks are low or nonexistent.”

People are studying how to increase minority participation in clinical trials, but thus far, there isn’t one solution. “As with routine care, there are probably a lot of logistical barriers to trial participation that disproportionately affect minority populations,” she noted. “There is also greater distrust of studies.”

But for now, there are some steps that clinicians can take to start to improve these disparities. “I think we can start inquiring about and documenting barriers to care and clinical trial participation, just like we document other aspects of the social history,” Dr. Lee explained. “Truly understanding the problem is the first step toward trying to solve it.”

References

1. Leukemia & Lymphoma Society. 2021. www.lls.org/facts-and-statistics/facts-and-statistics-overview.

2. Utuama O et al. PLoS One. 2019 Aug 19;14(8):e0220864.

3. Pollyea DA et al. J Cancer Prev Curr Res. 2014;1(1):14-19.

4. Bencomo-Alvarez AE et al. Cancer. 2021 Apr 1;127(7):1068-79.

5. Nabhan C et al. Cancer. 2012 Oct 1;118(19):4842-50.

6. Bhatnagar B et al. Blood. 2020;136(Suppl 1):5-7.

7. Shenoy PJ et al. Cancer. 2011;117:2530-40.

8. Evens AM et al. Ann Oncol. 2012 Aug 1;23(8):2128-37.

9. Lee MJ et al. Cancer. 2020;126:3493-3503.

10. Hu B et al. Cancer. 2021 Jul 21. doi: 10.1002/cncr.33779.

11. Marinac CR et al. Blood Cancer J. 2020 Feb 17;10(2):19.

12. Fiala MA et al. Leuk Lymphoma. 2015;56(9):2643-9.

13. Costa LJ et al. Biol Blood Marrow Transplant. 2015 Apr;21(4):701-6.

The season of conception does not affect whether more boys than girls are born, nor do temperatures in the environment, a large study reveals. Similarly, researchers found no connection with a location’s violent crime level, unemployment rate, or major events like Hurricane Katrina.

But certain chemical pollutants were related to fewer boys being born compared to girls when researchers looked at data for more than 3 million newborns over 8 years in the U.S. and another 3 million born over 30 years in Sweden.

“With data on births in 150 million people in the U.S. over 8 years and 9 million Swedes over 9 years, this is almost surely the largest study to date on the question of environmental factors and their influence on sex ratio at birth,” says Shanna Swan, PhD, who was not affiliated with the research

Variations in the annual sex birth ratio (SRB) – the number of boys born compared to the total birth rate – are well-accepted. Less clear is what things drive these changes.

Although not the first study to look for connections between major events or pollutants in the air, water, and land and the SRB, it is the first to mine two very large electronic medical record databases for answers, senior study author Andrey Rzhetsky, PhD, a professor of medicine and human genetics at the University of Chicago, tells this news organization.

The findings were published Dec. 2, 2021, in PLOS Computational Biology.

And even though the SRB did not vary significantly after Hurricane Katrina in 2005, it did after the 2007 shooting at Virginia Tech, Dr. Rzhetsky and colleagues found. The SRB was lower than expected 34 weeks after the mass shooting.
 

Location, location, location

The researchers also found the levels of chemical pollutants “varied remarkably” across different regions of the country. For example, lead in the land was elevated in the Northeast, Southwest, and Mideastern U.S. but not in the South. Also, the highest levels of total mercury in water samples was found mostly in Eastern states, especially in the Northeast.

Dr. Rzhetsky and colleagues mapped these regional differences in many factors, including hydrazine. Hydrazine is a foaming agent used to make pharmaceuticals, agrochemicals, and as a propellant for spacecraft.

“Hydrazine appears to follow capricious, blotch-like shapes in the eastern U.S., each blotch likely centered at a factory emitting this pollutant,” the authors wrote.

To get a more complete picture, the investigators also compared changes in the SRB to data from the U.S. National Oceanic and Atmospheric Administration, U.S. Environmental Protection Agency, Swedish Meteorological and Hydrological Institute, and Statistics Sweden.

They found that aluminium in air, chromium in water, and total mercury levels drove the SRB up. By comparison, lead in soil and areas with a higher renter occupancy were linked to a lower SRB, or a higher proportion of girls being born.

Dr. Rzhetsky and colleagues also add to the evidence for a link between polychlorinated biphenyls (PCBs) and the SRB. Previous findings conflict, the authors noted.

“Since the sample sizes of the studies published thus far were very small, our PCBs result would have substantially larger statistical power,” they said.

Several pollutants had no significant link to SRB in the study, including levels of lead or chromium in the air, arsenic in the soil, and cadmium in the air or water.
 

Consistent findings

That said, the research had limits.

“The magnitude is new in terms of number of births, and the statistical methods are unusually sophisticated, but the conclusions don’t really differ from much of what has been published,” says Dr. Swan, a professor of environmental medicine and public health at the Icahn School of Medicine at Mount Sinai, New York.

“The takeaway message that many examined exposures are associated with lower – and some with higher – SRBs is not new but consistent with other, smaller studies,” says Dr. Swan, who co-authored a Sept. 2021 study evaluating endocrine-disrupting chemicals and lower birth rates in Asia.

The data on environmental exposures “is, however, quite uneven, and only known at the ecologic and not the individual level,” she says. “We learn, for example, that SRB was significantly reduced ... among families living in areas with the highest septile of lead exposure but also in those among the highest septile of percent renter occupancy.”

“Evaluating these as to mechanism and plausibility is difficult,” Dr. Swan says.
 

More research warranted

The mechanism remains unknown, but the investigators suggested that female embryo pregnancies may end early in development, driving the SRB up. Also, male embryo deaths are more common in the late second or third trimester, at which point they would drive the SRB down. A third factor, maternal hormone levels around the time of conception, could also alter the SRB.

The associations between individual factors and SRB changes are just that – associations – not intended to be interpreted as “sex-specific selection mechanisms” causing the differences at this point, the authors noted. Further studies to confirm the associations are needed.

The research is a good stepping off point for future studies to look closer at the contribution of pollutants like arsenic, lead, cadmium, and more, Dr. Rzhetsky says.

A version of this article first appeared on WebMD.com.

The season of conception does not affect whether more boys than girls are born, nor do temperatures in the environment, a large study reveals. Similarly, researchers found no connection with a location’s violent crime level, unemployment rate, or major events like Hurricane Katrina.

But certain chemical pollutants were related to fewer boys being born compared to girls when researchers looked at data for more than 3 million newborns over 8 years in the U.S. and another 3 million born over 30 years in Sweden.

“With data on births in 150 million people in the U.S. over 8 years and 9 million Swedes over 9 years, this is almost surely the largest study to date on the question of environmental factors and their influence on sex ratio at birth,” says Shanna Swan, PhD, who was not affiliated with the research

Variations in the annual sex birth ratio (SRB) – the number of boys born compared to the total birth rate – are well-accepted. Less clear is what things drive these changes.

Although not the first study to look for connections between major events or pollutants in the air, water, and land and the SRB, it is the first to mine two very large electronic medical record databases for answers, senior study author Andrey Rzhetsky, PhD, a professor of medicine and human genetics at the University of Chicago, tells this news organization.

The findings were published Dec. 2, 2021, in PLOS Computational Biology.

And even though the SRB did not vary significantly after Hurricane Katrina in 2005, it did after the 2007 shooting at Virginia Tech, Dr. Rzhetsky and colleagues found. The SRB was lower than expected 34 weeks after the mass shooting.
 

Location, location, location

The researchers also found the levels of chemical pollutants “varied remarkably” across different regions of the country. For example, lead in the land was elevated in the Northeast, Southwest, and Mideastern U.S. but not in the South. Also, the highest levels of total mercury in water samples was found mostly in Eastern states, especially in the Northeast.

Dr. Rzhetsky and colleagues mapped these regional differences in many factors, including hydrazine. Hydrazine is a foaming agent used to make pharmaceuticals, agrochemicals, and as a propellant for spacecraft.

“Hydrazine appears to follow capricious, blotch-like shapes in the eastern U.S., each blotch likely centered at a factory emitting this pollutant,” the authors wrote.

To get a more complete picture, the investigators also compared changes in the SRB to data from the U.S. National Oceanic and Atmospheric Administration, U.S. Environmental Protection Agency, Swedish Meteorological and Hydrological Institute, and Statistics Sweden.

They found that aluminium in air, chromium in water, and total mercury levels drove the SRB up. By comparison, lead in soil and areas with a higher renter occupancy were linked to a lower SRB, or a higher proportion of girls being born.

Dr. Rzhetsky and colleagues also add to the evidence for a link between polychlorinated biphenyls (PCBs) and the SRB. Previous findings conflict, the authors noted.

“Since the sample sizes of the studies published thus far were very small, our PCBs result would have substantially larger statistical power,” they said.

Several pollutants had no significant link to SRB in the study, including levels of lead or chromium in the air, arsenic in the soil, and cadmium in the air or water.
 

Consistent findings

That said, the research had limits.

“The magnitude is new in terms of number of births, and the statistical methods are unusually sophisticated, but the conclusions don’t really differ from much of what has been published,” says Dr. Swan, a professor of environmental medicine and public health at the Icahn School of Medicine at Mount Sinai, New York.

“The takeaway message that many examined exposures are associated with lower – and some with higher – SRBs is not new but consistent with other, smaller studies,” says Dr. Swan, who co-authored a Sept. 2021 study evaluating endocrine-disrupting chemicals and lower birth rates in Asia.

The data on environmental exposures “is, however, quite uneven, and only known at the ecologic and not the individual level,” she says. “We learn, for example, that SRB was significantly reduced ... among families living in areas with the highest septile of lead exposure but also in those among the highest septile of percent renter occupancy.”

“Evaluating these as to mechanism and plausibility is difficult,” Dr. Swan says.
 

More research warranted

The mechanism remains unknown, but the investigators suggested that female embryo pregnancies may end early in development, driving the SRB up. Also, male embryo deaths are more common in the late second or third trimester, at which point they would drive the SRB down. A third factor, maternal hormone levels around the time of conception, could also alter the SRB.

The associations between individual factors and SRB changes are just that – associations – not intended to be interpreted as “sex-specific selection mechanisms” causing the differences at this point, the authors noted. Further studies to confirm the associations are needed.

The research is a good stepping off point for future studies to look closer at the contribution of pollutants like arsenic, lead, cadmium, and more, Dr. Rzhetsky says.

A version of this article first appeared on WebMD.com.

The season of conception does not affect whether more boys than girls are born, nor do temperatures in the environment, a large study reveals. Similarly, researchers found no connection with a location’s violent crime level, unemployment rate, or major events like Hurricane Katrina.

But certain chemical pollutants were related to fewer boys being born compared to girls when researchers looked at data for more than 3 million newborns over 8 years in the U.S. and another 3 million born over 30 years in Sweden.

“With data on births in 150 million people in the U.S. over 8 years and 9 million Swedes over 9 years, this is almost surely the largest study to date on the question of environmental factors and their influence on sex ratio at birth,” says Shanna Swan, PhD, who was not affiliated with the research

Variations in the annual sex birth ratio (SRB) – the number of boys born compared to the total birth rate – are well-accepted. Less clear is what things drive these changes.

Although not the first study to look for connections between major events or pollutants in the air, water, and land and the SRB, it is the first to mine two very large electronic medical record databases for answers, senior study author Andrey Rzhetsky, PhD, a professor of medicine and human genetics at the University of Chicago, tells this news organization.

The findings were published Dec. 2, 2021, in PLOS Computational Biology.

And even though the SRB did not vary significantly after Hurricane Katrina in 2005, it did after the 2007 shooting at Virginia Tech, Dr. Rzhetsky and colleagues found. The SRB was lower than expected 34 weeks after the mass shooting.
 

Location, location, location

The researchers also found the levels of chemical pollutants “varied remarkably” across different regions of the country. For example, lead in the land was elevated in the Northeast, Southwest, and Mideastern U.S. but not in the South. Also, the highest levels of total mercury in water samples was found mostly in Eastern states, especially in the Northeast.

Dr. Rzhetsky and colleagues mapped these regional differences in many factors, including hydrazine. Hydrazine is a foaming agent used to make pharmaceuticals, agrochemicals, and as a propellant for spacecraft.

“Hydrazine appears to follow capricious, blotch-like shapes in the eastern U.S., each blotch likely centered at a factory emitting this pollutant,” the authors wrote.

To get a more complete picture, the investigators also compared changes in the SRB to data from the U.S. National Oceanic and Atmospheric Administration, U.S. Environmental Protection Agency, Swedish Meteorological and Hydrological Institute, and Statistics Sweden.

They found that aluminium in air, chromium in water, and total mercury levels drove the SRB up. By comparison, lead in soil and areas with a higher renter occupancy were linked to a lower SRB, or a higher proportion of girls being born.

Dr. Rzhetsky and colleagues also add to the evidence for a link between polychlorinated biphenyls (PCBs) and the SRB. Previous findings conflict, the authors noted.

“Since the sample sizes of the studies published thus far were very small, our PCBs result would have substantially larger statistical power,” they said.

Several pollutants had no significant link to SRB in the study, including levels of lead or chromium in the air, arsenic in the soil, and cadmium in the air or water.
 

Consistent findings

That said, the research had limits.

“The magnitude is new in terms of number of births, and the statistical methods are unusually sophisticated, but the conclusions don’t really differ from much of what has been published,” says Dr. Swan, a professor of environmental medicine and public health at the Icahn School of Medicine at Mount Sinai, New York.

“The takeaway message that many examined exposures are associated with lower – and some with higher – SRBs is not new but consistent with other, smaller studies,” says Dr. Swan, who co-authored a Sept. 2021 study evaluating endocrine-disrupting chemicals and lower birth rates in Asia.

The data on environmental exposures “is, however, quite uneven, and only known at the ecologic and not the individual level,” she says. “We learn, for example, that SRB was significantly reduced ... among families living in areas with the highest septile of lead exposure but also in those among the highest septile of percent renter occupancy.”

“Evaluating these as to mechanism and plausibility is difficult,” Dr. Swan says.
 

More research warranted

The mechanism remains unknown, but the investigators suggested that female embryo pregnancies may end early in development, driving the SRB up. Also, male embryo deaths are more common in the late second or third trimester, at which point they would drive the SRB down. A third factor, maternal hormone levels around the time of conception, could also alter the SRB.

The associations between individual factors and SRB changes are just that – associations – not intended to be interpreted as “sex-specific selection mechanisms” causing the differences at this point, the authors noted. Further studies to confirm the associations are needed.

The research is a good stepping off point for future studies to look closer at the contribution of pollutants like arsenic, lead, cadmium, and more, Dr. Rzhetsky says.

A version of this article first appeared on WebMD.com.

Azelaic acid is a bit of a forgotten acid, often in the shadows of glycolic acid and trichloroacetic acid (TCA). However, it has many positive qualities, including being gentle enough to use daily and is safe to use in pregnancy. It is antibacterial, comedolytic, keratolytic, and has antioxidant activity. Unfortunately, in the last decade the formulations of azelaic acid have not been changed considerably. The 20% cream, 15% gel, and 15% foam vehicles are often too irritating and drying to be used in the population it is intended for: those with rosacea, or with inflamed or sensitive skin.

Azelaic acid is a dicarboxylic acid produced by Pityrosporum ovale. It inhibits the synthesis of cellular proteins and is bactericidal against Propionibacterium acnes and Staphylococcus epidermidis. Azelaic acid is both keratolytic and comedolytic by decreasing keratohyalin granules and reducing filaggrin in the epidermis. It not only scavenges free oxygen radicals, thereby reducing inflammation, but is also a tyrosinase inhibitor – making it a safe, non–hydroquinone-based alternative to skin lightening.

Azelaic acid has little toxicity, it is ingested regularly as it is found in wheat, barley, and rye. Topical side effects are usually mild and can subside with increased use. The most common side effects include erythema, local stinging, pruritus, scaling, and a burning sensation. It is considered safe in pregnancy and a great alternative to medications for acne in pregnant or nursing patients.

The largest constraint with azelaic acid preparations on the market – and most likely the reason it has not been more widely used for acne, rosacea, antiaging, and hyperpigmentation – is the formulation. The foam and gel preparations are irritating and difficult to use on dry or sensitive skin. The 20% cream preparations are slightly better tolerated; however, in vitro skin-penetration studies have shown that cutaneous penetration of azelaic acid is greater after application of a 15% gel (aqueous-based vehicle) and 15% foam (hydrophilic oil-in-water emulsion) as compared with the 20% cream formulations.

In my clinical experience, azelaic acid can only be used in rosacea patients with oily or nonsensitive skin. The majority of my rosacea patients cannot tolerate the burning sensation, albeit transient and mild. Acne patients who do not have dry skin and pregnant patients with mild acne are a great population for integrating azelaic acid into an acne regimen. I also use azelaic acid as an alternative for mild melasma and lentigines in patients who are tapering off hydroquinone or cannot use hydroquinone. In the future, we need better, creamier, nonirritating formulations to be developed and more studies of higher concentrations of this acid for both prescription/patient at-home use, as well as more elegant in-office localized peel systems using azelaic acid.

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

References

Fitton A and Goa KL. Drugs. 1991 May;41(5):780-98.

Del Rosso JQ. J Clin Aesthet Dermatol. 2017 Mar;10(3):37-40.

Breathnach AC et al. Clin Dermatol. Apr-Jun 1989;7(2):106-19.
 

Azelaic acid is a bit of a forgotten acid, often in the shadows of glycolic acid and trichloroacetic acid (TCA). However, it has many positive qualities, including being gentle enough to use daily and is safe to use in pregnancy. It is antibacterial, comedolytic, keratolytic, and has antioxidant activity. Unfortunately, in the last decade the formulations of azelaic acid have not been changed considerably. The 20% cream, 15% gel, and 15% foam vehicles are often too irritating and drying to be used in the population it is intended for: those with rosacea, or with inflamed or sensitive skin.

Azelaic acid is a dicarboxylic acid produced by Pityrosporum ovale. It inhibits the synthesis of cellular proteins and is bactericidal against Propionibacterium acnes and Staphylococcus epidermidis. Azelaic acid is both keratolytic and comedolytic by decreasing keratohyalin granules and reducing filaggrin in the epidermis. It not only scavenges free oxygen radicals, thereby reducing inflammation, but is also a tyrosinase inhibitor – making it a safe, non–hydroquinone-based alternative to skin lightening.

Azelaic acid has little toxicity, it is ingested regularly as it is found in wheat, barley, and rye. Topical side effects are usually mild and can subside with increased use. The most common side effects include erythema, local stinging, pruritus, scaling, and a burning sensation. It is considered safe in pregnancy and a great alternative to medications for acne in pregnant or nursing patients.

The largest constraint with azelaic acid preparations on the market – and most likely the reason it has not been more widely used for acne, rosacea, antiaging, and hyperpigmentation – is the formulation. The foam and gel preparations are irritating and difficult to use on dry or sensitive skin. The 20% cream preparations are slightly better tolerated; however, in vitro skin-penetration studies have shown that cutaneous penetration of azelaic acid is greater after application of a 15% gel (aqueous-based vehicle) and 15% foam (hydrophilic oil-in-water emulsion) as compared with the 20% cream formulations.

In my clinical experience, azelaic acid can only be used in rosacea patients with oily or nonsensitive skin. The majority of my rosacea patients cannot tolerate the burning sensation, albeit transient and mild. Acne patients who do not have dry skin and pregnant patients with mild acne are a great population for integrating azelaic acid into an acne regimen. I also use azelaic acid as an alternative for mild melasma and lentigines in patients who are tapering off hydroquinone or cannot use hydroquinone. In the future, we need better, creamier, nonirritating formulations to be developed and more studies of higher concentrations of this acid for both prescription/patient at-home use, as well as more elegant in-office localized peel systems using azelaic acid.

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

References

Fitton A and Goa KL. Drugs. 1991 May;41(5):780-98.

Del Rosso JQ. J Clin Aesthet Dermatol. 2017 Mar;10(3):37-40.

Breathnach AC et al. Clin Dermatol. Apr-Jun 1989;7(2):106-19.
 

Azelaic acid is a bit of a forgotten acid, often in the shadows of glycolic acid and trichloroacetic acid (TCA). However, it has many positive qualities, including being gentle enough to use daily and is safe to use in pregnancy. It is antibacterial, comedolytic, keratolytic, and has antioxidant activity. Unfortunately, in the last decade the formulations of azelaic acid have not been changed considerably. The 20% cream, 15% gel, and 15% foam vehicles are often too irritating and drying to be used in the population it is intended for: those with rosacea, or with inflamed or sensitive skin.

Azelaic acid is a dicarboxylic acid produced by Pityrosporum ovale. It inhibits the synthesis of cellular proteins and is bactericidal against Propionibacterium acnes and Staphylococcus epidermidis. Azelaic acid is both keratolytic and comedolytic by decreasing keratohyalin granules and reducing filaggrin in the epidermis. It not only scavenges free oxygen radicals, thereby reducing inflammation, but is also a tyrosinase inhibitor – making it a safe, non–hydroquinone-based alternative to skin lightening.

Azelaic acid has little toxicity, it is ingested regularly as it is found in wheat, barley, and rye. Topical side effects are usually mild and can subside with increased use. The most common side effects include erythema, local stinging, pruritus, scaling, and a burning sensation. It is considered safe in pregnancy and a great alternative to medications for acne in pregnant or nursing patients.

The largest constraint with azelaic acid preparations on the market – and most likely the reason it has not been more widely used for acne, rosacea, antiaging, and hyperpigmentation – is the formulation. The foam and gel preparations are irritating and difficult to use on dry or sensitive skin. The 20% cream preparations are slightly better tolerated; however, in vitro skin-penetration studies have shown that cutaneous penetration of azelaic acid is greater after application of a 15% gel (aqueous-based vehicle) and 15% foam (hydrophilic oil-in-water emulsion) as compared with the 20% cream formulations.

In my clinical experience, azelaic acid can only be used in rosacea patients with oily or nonsensitive skin. The majority of my rosacea patients cannot tolerate the burning sensation, albeit transient and mild. Acne patients who do not have dry skin and pregnant patients with mild acne are a great population for integrating azelaic acid into an acne regimen. I also use azelaic acid as an alternative for mild melasma and lentigines in patients who are tapering off hydroquinone or cannot use hydroquinone. In the future, we need better, creamier, nonirritating formulations to be developed and more studies of higher concentrations of this acid for both prescription/patient at-home use, as well as more elegant in-office localized peel systems using azelaic acid.

Dr. Talakoub and Dr. Wesley are cocontributors to this column. Dr. Talakoub is in private practice in McLean, Va. Dr. Wesley practices dermatology in Beverly Hills, Calif. This month’s column is by Dr. Talakoub. Write to them at [email protected]. They had no relevant disclosures.

References

Fitton A and Goa KL. Drugs. 1991 May;41(5):780-98.

Del Rosso JQ. J Clin Aesthet Dermatol. 2017 Mar;10(3):37-40.

Breathnach AC et al. Clin Dermatol. Apr-Jun 1989;7(2):106-19.
 

Two distinct gut microbiota subtypes showed an enhanced clinical response to a low FODMAP diet in an analysis of 41 adults with irritable bowel syndrome and household controls.

Irritable bowel syndrome (IBS) has a significant impact on quality of life, and some patients find relief on a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, wrote Kevin Vervier, PhD, of Wellcome Sanger Institute, Hinxton, England, and colleagues. However, the mechanism of action for the success of low FODMAP diets remains unclear, the diet is hard for many patients to follow, and the long-term impact on health is unknown. Therefore, research is needed to identify patients who would derive the most benefit, they said.

In a study published in Gut, the researchers used metagenomics and functional analysis to identify potential biomarkers of response to a low FODMAP diet. They analyzed stool samples from 41 pairs of IBS patients and household contacts. Stool samples were collected at baseline while on usual diets, and again after 4 weeks and 12 weeks on a low FODMAP diet. The patients were divided into two groups based on microbiota clusters; baseline demographics and clinical characteristics were similar between the clusters. In addition, symptom severity was measured using the IBS Severity Scoring System (IBS-SSS).

Cluster 1 was referred to as IBS^P microbiome type because of its pathogenic properties, and cluster 2 as IBS^H microbiome type because of its resemblance to the microbiome of healthy household controls, the researchers wrote.

“We found a significant enrichment of 109 functional pathways and significant depletion of 13 functional pathways in IBS^P microbiomes compared with IBS^H microbiomes,” the researchers said.

More specifically, the IBS^P microbiomes were enriched in Firmicutes and in genes for amino acid and carbohydrate metabolism, at baseline, while the IBS^H microbiomes were similar to healthy controls.

After 4 weeks on the low FODMAP diet, the IBS^P microbiomes normalized, with increased levels of Bacterioides and decreased levels of pathobionts (including Clostridium difficile, Streptococcus parasanguinis, and Paeniclostridium sordellii) to create a microbiome profile resembling the IBSH microbiomes and healthy controls. The taxonomic profile of microbiomes observed in IBS^H and healthy controls did not demonstrate a significant shift.

Although both microbiome groups showed improvement in IBS-SSS scores from baseline on the low FODMAP diet, decreasing from a mean baseline score of 278 to a diet score of 128, the improvement was greater in the IBS^P group than the IBS^H group (delta, 194 vs. 114, respectively; P = .02), the researchers noted. “The shift in the IBS^P microbiota to a healthy profile appeared stable for at least 3 months and correlated with continuing symptomatic well-being,” they wrote.

The distinct responses of the IBS^P and IBS^H microbiomes to the low FODMAP diet suggest a potential mode of action, the researchers said in their discussion. Based on their findings, “it is possible that removal of the eliciting dietary component starves the pathobionts, leading to reduction in their growth and metabolism and a consequent decrease in symptoms, accompanied by an expansion of commensal or symbiotic species leading to a health-associated microbiome,” but more research is needed to prove causality, they said.

The study findings were limited by several factors, including the relatively small sample size, strict inclusion criteria, restriction of medications, and need for participation by household controls, the researchers noted. Other limitations include the inability to control for other factors that could have impacted the gut microbiota, such as the placebo effect and psychological factors, they said.

However, the findings provide a foundation for more research and should be validated in other populations involving different geographical regions and dietary habits, they said. “The identification of a microbial signature ‘biomarker’ that correlates with improved response to a low FODMAP diet may, if validated, allow better stratification and selection of patients likely to benefit from the diet,” they concluded.
 

Setting the stage for focused studies

The low FODMAP diet has demonstrated effectiveness for symptom relief in IBS, although potential risks include exacerbation of disordered eating, nutrition deficiencies, and disrupting gut microbiota, wrote Peter R. Gibson, MD, and Emma P. Halmos, MD, of Monash University and Alfred Health, Melbourne, in an accompanying editorial. However, the current study takes a new step on the journey to identifying patients most likely to respond to a low FODMAP diet, they said.

The editorialists noted three key takeaway points. First, the fecal microbiome may predict response to a low FODMAP diet. Second, the correction of the microbiome through the low FODMAP diet appeared to continue even after the diet was discontinued. “The other intriguing finding was that trehalose metabolic pathways were ‘activated’ in those with dysbiosis,” suggesting that trehalose might be an unrecognized FODMAP, the researchers noted. Trehalose has not been well studied but has been associated with pathogenicity, they said.

Although the study may overemphasize the impact of the low FODMAP diet given the relatively poor assessment of FODMAP intake, “the beauty of Vervier’s work is not in its definitive nature but in that it enables the creation of feasible innovative hypotheses that can be examined by focused studies,” they concluded.

The current study is important because IBS and related disorders of gut-brain interaction are common and greatly impact the quality of life of affected individuals, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview. Although the mechanisms for improvement are unknown, he said, “The low FODMAP diet is widely used to treat IBS, based on the hypothesis that this diet modifies the gut microbiome in a beneficial way.”

The study authors made two important discoveries, said Dr. Roper. “First, they found that they were able to distinguish IBS versus household controls based on their gut microbial signatures as well expression of key metabolic genes,” he said. “Second, they identified a unique microbiota subtype that was associated with a significant clinical response to the low FODMAP diet in IBS patients; IBS patients with a ‘pathogenic’ microbiome consisting of high Firmicutes and low Bacteroidetes responded to a greater degree to the low FODMAP diet compared to IBS patients with a ‘healthy’ microbiome that was similar to controls,” he explained. “Furthermore, after time on the low FODMAP diet, the IBS patients with pathogenic microbiome signatures developed a microbiome with low Firmicutes and high Bacteroidetes, which is thought to be healthy,” he added.

“These findings are exciting because they suggest that a patient’s microbial signature might be used clinically to predict response to the low FODMAP diet,” said Dr. Roper. “The surprising aspect of these results is that the microbial signature alone was able to predict response to a low FODMAP diet, despite the complex effects of the diet on host physiology and metabolism and the multifactorial etiology of IBS,” he noted. 

However, larger clinical studies are needed to confirm the study findings results in larger patient cohorts and to show that standardized clinical assays can be used to prospectively predict response to dietary interventions such as low FODMAP in IBS, Dr. Roper emphasized.

“This paper provides preliminary and provocative findings that suggest that gut microbiota metabolites may play a role in the pathogenesis of IBS,” said Dr. Roper. “Future basic science and translational research is needed to study the mechanisms by which specific bacterial metabolites regulate intestinal function and disorders such as IBS. I hope that this research will eventually lead to metabolite-based therapies for IBS and other gastrointestinal disorders,” he said.

The study received no outside funding. Lead author Dr. Vervier had no financial conflicts to disclose. Dr. Gibson disclosed authoring two educational/recipe books on the low FODMAP diet, and Monash University financially benefits from the sales of a digital application, booklets, and online courses on the low FODMAP diet. Dr. Halmos had no financial conflicts to disclose. Dr. Roper had no financial conflicts to disclose.

Two distinct gut microbiota subtypes showed an enhanced clinical response to a low FODMAP diet in an analysis of 41 adults with irritable bowel syndrome and household controls.

Irritable bowel syndrome (IBS) has a significant impact on quality of life, and some patients find relief on a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, wrote Kevin Vervier, PhD, of Wellcome Sanger Institute, Hinxton, England, and colleagues. However, the mechanism of action for the success of low FODMAP diets remains unclear, the diet is hard for many patients to follow, and the long-term impact on health is unknown. Therefore, research is needed to identify patients who would derive the most benefit, they said.

In a study published in Gut, the researchers used metagenomics and functional analysis to identify potential biomarkers of response to a low FODMAP diet. They analyzed stool samples from 41 pairs of IBS patients and household contacts. Stool samples were collected at baseline while on usual diets, and again after 4 weeks and 12 weeks on a low FODMAP diet. The patients were divided into two groups based on microbiota clusters; baseline demographics and clinical characteristics were similar between the clusters. In addition, symptom severity was measured using the IBS Severity Scoring System (IBS-SSS).

Cluster 1 was referred to as IBS^P microbiome type because of its pathogenic properties, and cluster 2 as IBS^H microbiome type because of its resemblance to the microbiome of healthy household controls, the researchers wrote.

“We found a significant enrichment of 109 functional pathways and significant depletion of 13 functional pathways in IBS^P microbiomes compared with IBS^H microbiomes,” the researchers said.

More specifically, the IBS^P microbiomes were enriched in Firmicutes and in genes for amino acid and carbohydrate metabolism, at baseline, while the IBS^H microbiomes were similar to healthy controls.

After 4 weeks on the low FODMAP diet, the IBS^P microbiomes normalized, with increased levels of Bacterioides and decreased levels of pathobionts (including Clostridium difficile, Streptococcus parasanguinis, and Paeniclostridium sordellii) to create a microbiome profile resembling the IBSH microbiomes and healthy controls. The taxonomic profile of microbiomes observed in IBS^H and healthy controls did not demonstrate a significant shift.

Although both microbiome groups showed improvement in IBS-SSS scores from baseline on the low FODMAP diet, decreasing from a mean baseline score of 278 to a diet score of 128, the improvement was greater in the IBS^P group than the IBS^H group (delta, 194 vs. 114, respectively; P = .02), the researchers noted. “The shift in the IBS^P microbiota to a healthy profile appeared stable for at least 3 months and correlated with continuing symptomatic well-being,” they wrote.

The distinct responses of the IBS^P and IBS^H microbiomes to the low FODMAP diet suggest a potential mode of action, the researchers said in their discussion. Based on their findings, “it is possible that removal of the eliciting dietary component starves the pathobionts, leading to reduction in their growth and metabolism and a consequent decrease in symptoms, accompanied by an expansion of commensal or symbiotic species leading to a health-associated microbiome,” but more research is needed to prove causality, they said.

The study findings were limited by several factors, including the relatively small sample size, strict inclusion criteria, restriction of medications, and need for participation by household controls, the researchers noted. Other limitations include the inability to control for other factors that could have impacted the gut microbiota, such as the placebo effect and psychological factors, they said.

However, the findings provide a foundation for more research and should be validated in other populations involving different geographical regions and dietary habits, they said. “The identification of a microbial signature ‘biomarker’ that correlates with improved response to a low FODMAP diet may, if validated, allow better stratification and selection of patients likely to benefit from the diet,” they concluded.
 

Setting the stage for focused studies

The low FODMAP diet has demonstrated effectiveness for symptom relief in IBS, although potential risks include exacerbation of disordered eating, nutrition deficiencies, and disrupting gut microbiota, wrote Peter R. Gibson, MD, and Emma P. Halmos, MD, of Monash University and Alfred Health, Melbourne, in an accompanying editorial. However, the current study takes a new step on the journey to identifying patients most likely to respond to a low FODMAP diet, they said.

The editorialists noted three key takeaway points. First, the fecal microbiome may predict response to a low FODMAP diet. Second, the correction of the microbiome through the low FODMAP diet appeared to continue even after the diet was discontinued. “The other intriguing finding was that trehalose metabolic pathways were ‘activated’ in those with dysbiosis,” suggesting that trehalose might be an unrecognized FODMAP, the researchers noted. Trehalose has not been well studied but has been associated with pathogenicity, they said.

Although the study may overemphasize the impact of the low FODMAP diet given the relatively poor assessment of FODMAP intake, “the beauty of Vervier’s work is not in its definitive nature but in that it enables the creation of feasible innovative hypotheses that can be examined by focused studies,” they concluded.

The current study is important because IBS and related disorders of gut-brain interaction are common and greatly impact the quality of life of affected individuals, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview. Although the mechanisms for improvement are unknown, he said, “The low FODMAP diet is widely used to treat IBS, based on the hypothesis that this diet modifies the gut microbiome in a beneficial way.”

The study authors made two important discoveries, said Dr. Roper. “First, they found that they were able to distinguish IBS versus household controls based on their gut microbial signatures as well expression of key metabolic genes,” he said. “Second, they identified a unique microbiota subtype that was associated with a significant clinical response to the low FODMAP diet in IBS patients; IBS patients with a ‘pathogenic’ microbiome consisting of high Firmicutes and low Bacteroidetes responded to a greater degree to the low FODMAP diet compared to IBS patients with a ‘healthy’ microbiome that was similar to controls,” he explained. “Furthermore, after time on the low FODMAP diet, the IBS patients with pathogenic microbiome signatures developed a microbiome with low Firmicutes and high Bacteroidetes, which is thought to be healthy,” he added.

“These findings are exciting because they suggest that a patient’s microbial signature might be used clinically to predict response to the low FODMAP diet,” said Dr. Roper. “The surprising aspect of these results is that the microbial signature alone was able to predict response to a low FODMAP diet, despite the complex effects of the diet on host physiology and metabolism and the multifactorial etiology of IBS,” he noted. 

However, larger clinical studies are needed to confirm the study findings results in larger patient cohorts and to show that standardized clinical assays can be used to prospectively predict response to dietary interventions such as low FODMAP in IBS, Dr. Roper emphasized.

“This paper provides preliminary and provocative findings that suggest that gut microbiota metabolites may play a role in the pathogenesis of IBS,” said Dr. Roper. “Future basic science and translational research is needed to study the mechanisms by which specific bacterial metabolites regulate intestinal function and disorders such as IBS. I hope that this research will eventually lead to metabolite-based therapies for IBS and other gastrointestinal disorders,” he said.

The study received no outside funding. Lead author Dr. Vervier had no financial conflicts to disclose. Dr. Gibson disclosed authoring two educational/recipe books on the low FODMAP diet, and Monash University financially benefits from the sales of a digital application, booklets, and online courses on the low FODMAP diet. Dr. Halmos had no financial conflicts to disclose. Dr. Roper had no financial conflicts to disclose.

Two distinct gut microbiota subtypes showed an enhanced clinical response to a low FODMAP diet in an analysis of 41 adults with irritable bowel syndrome and household controls.

Irritable bowel syndrome (IBS) has a significant impact on quality of life, and some patients find relief on a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet, wrote Kevin Vervier, PhD, of Wellcome Sanger Institute, Hinxton, England, and colleagues. However, the mechanism of action for the success of low FODMAP diets remains unclear, the diet is hard for many patients to follow, and the long-term impact on health is unknown. Therefore, research is needed to identify patients who would derive the most benefit, they said.

In a study published in Gut, the researchers used metagenomics and functional analysis to identify potential biomarkers of response to a low FODMAP diet. They analyzed stool samples from 41 pairs of IBS patients and household contacts. Stool samples were collected at baseline while on usual diets, and again after 4 weeks and 12 weeks on a low FODMAP diet. The patients were divided into two groups based on microbiota clusters; baseline demographics and clinical characteristics were similar between the clusters. In addition, symptom severity was measured using the IBS Severity Scoring System (IBS-SSS).

Cluster 1 was referred to as IBS^P microbiome type because of its pathogenic properties, and cluster 2 as IBS^H microbiome type because of its resemblance to the microbiome of healthy household controls, the researchers wrote.

“We found a significant enrichment of 109 functional pathways and significant depletion of 13 functional pathways in IBS^P microbiomes compared with IBS^H microbiomes,” the researchers said.

More specifically, the IBS^P microbiomes were enriched in Firmicutes and in genes for amino acid and carbohydrate metabolism, at baseline, while the IBS^H microbiomes were similar to healthy controls.

After 4 weeks on the low FODMAP diet, the IBS^P microbiomes normalized, with increased levels of Bacterioides and decreased levels of pathobionts (including Clostridium difficile, Streptococcus parasanguinis, and Paeniclostridium sordellii) to create a microbiome profile resembling the IBSH microbiomes and healthy controls. The taxonomic profile of microbiomes observed in IBS^H and healthy controls did not demonstrate a significant shift.

Although both microbiome groups showed improvement in IBS-SSS scores from baseline on the low FODMAP diet, decreasing from a mean baseline score of 278 to a diet score of 128, the improvement was greater in the IBS^P group than the IBS^H group (delta, 194 vs. 114, respectively; P = .02), the researchers noted. “The shift in the IBS^P microbiota to a healthy profile appeared stable for at least 3 months and correlated with continuing symptomatic well-being,” they wrote.

The distinct responses of the IBS^P and IBS^H microbiomes to the low FODMAP diet suggest a potential mode of action, the researchers said in their discussion. Based on their findings, “it is possible that removal of the eliciting dietary component starves the pathobionts, leading to reduction in their growth and metabolism and a consequent decrease in symptoms, accompanied by an expansion of commensal or symbiotic species leading to a health-associated microbiome,” but more research is needed to prove causality, they said.

The study findings were limited by several factors, including the relatively small sample size, strict inclusion criteria, restriction of medications, and need for participation by household controls, the researchers noted. Other limitations include the inability to control for other factors that could have impacted the gut microbiota, such as the placebo effect and psychological factors, they said.

However, the findings provide a foundation for more research and should be validated in other populations involving different geographical regions and dietary habits, they said. “The identification of a microbial signature ‘biomarker’ that correlates with improved response to a low FODMAP diet may, if validated, allow better stratification and selection of patients likely to benefit from the diet,” they concluded.
 

Setting the stage for focused studies

The low FODMAP diet has demonstrated effectiveness for symptom relief in IBS, although potential risks include exacerbation of disordered eating, nutrition deficiencies, and disrupting gut microbiota, wrote Peter R. Gibson, MD, and Emma P. Halmos, MD, of Monash University and Alfred Health, Melbourne, in an accompanying editorial. However, the current study takes a new step on the journey to identifying patients most likely to respond to a low FODMAP diet, they said.

The editorialists noted three key takeaway points. First, the fecal microbiome may predict response to a low FODMAP diet. Second, the correction of the microbiome through the low FODMAP diet appeared to continue even after the diet was discontinued. “The other intriguing finding was that trehalose metabolic pathways were ‘activated’ in those with dysbiosis,” suggesting that trehalose might be an unrecognized FODMAP, the researchers noted. Trehalose has not been well studied but has been associated with pathogenicity, they said.

Although the study may overemphasize the impact of the low FODMAP diet given the relatively poor assessment of FODMAP intake, “the beauty of Vervier’s work is not in its definitive nature but in that it enables the creation of feasible innovative hypotheses that can be examined by focused studies,” they concluded.

The current study is important because IBS and related disorders of gut-brain interaction are common and greatly impact the quality of life of affected individuals, Jatin Roper, MD, of Duke University in Durham, N.C., said in an interview. Although the mechanisms for improvement are unknown, he said, “The low FODMAP diet is widely used to treat IBS, based on the hypothesis that this diet modifies the gut microbiome in a beneficial way.”

The study authors made two important discoveries, said Dr. Roper. “First, they found that they were able to distinguish IBS versus household controls based on their gut microbial signatures as well expression of key metabolic genes,” he said. “Second, they identified a unique microbiota subtype that was associated with a significant clinical response to the low FODMAP diet in IBS patients; IBS patients with a ‘pathogenic’ microbiome consisting of high Firmicutes and low Bacteroidetes responded to a greater degree to the low FODMAP diet compared to IBS patients with a ‘healthy’ microbiome that was similar to controls,” he explained. “Furthermore, after time on the low FODMAP diet, the IBS patients with pathogenic microbiome signatures developed a microbiome with low Firmicutes and high Bacteroidetes, which is thought to be healthy,” he added.

“These findings are exciting because they suggest that a patient’s microbial signature might be used clinically to predict response to the low FODMAP diet,” said Dr. Roper. “The surprising aspect of these results is that the microbial signature alone was able to predict response to a low FODMAP diet, despite the complex effects of the diet on host physiology and metabolism and the multifactorial etiology of IBS,” he noted. 

However, larger clinical studies are needed to confirm the study findings results in larger patient cohorts and to show that standardized clinical assays can be used to prospectively predict response to dietary interventions such as low FODMAP in IBS, Dr. Roper emphasized.

“This paper provides preliminary and provocative findings that suggest that gut microbiota metabolites may play a role in the pathogenesis of IBS,” said Dr. Roper. “Future basic science and translational research is needed to study the mechanisms by which specific bacterial metabolites regulate intestinal function and disorders such as IBS. I hope that this research will eventually lead to metabolite-based therapies for IBS and other gastrointestinal disorders,” he said.

The study received no outside funding. Lead author Dr. Vervier had no financial conflicts to disclose. Dr. Gibson disclosed authoring two educational/recipe books on the low FODMAP diet, and Monash University financially benefits from the sales of a digital application, booklets, and online courses on the low FODMAP diet. Dr. Halmos had no financial conflicts to disclose. Dr. Roper had no financial conflicts to disclose.

In recent weeks, the Centers for Disease Control and Prevention has greatly expanded recommendations for boosters for vaccinations against COVID-19.

These recommendations have been widened because of the continued emergence of new variants of the virus and the wane of protection over time for both vaccinations and previous disease.

The new recommendations take away some of the questions surrounding eligibility for booster vaccinations while potentially leaving some additional questions. All in all, they provide flexibility for individuals to help protect themselves against the COVID-19 virus, as many are considering celebrating the holidays with friends and family.

The first item that has become clear is that all individuals over 18 are now not only eligible for a booster vaccination a certain time after they have completed their series, but have a recommendation for one.¹

But what about a fourth dose?  There is a possibility that some patients should be receiving one.  For those who require a three-dose series due to a condition that makes them immunocompromised, they should receive their booster vaccination six months after completion of the three-dose series.  This distinction  may cause confusion for some, but is important for those immunocompromised.

Boosters in women who are pregnant

The recommendations also include specific comments about individuals who are pregnant. Although initial studies did not include pregnant individuals, there has been increasing real world data that vaccination against COVID, including booster vaccinations, is safe and recommended. As pregnancy increases the risk of severe disease if infected by COVID-19, both the CDC and the American College of Obstetricians and Gynecologists,² along with other specialty organizations, such as the Royal College of Obstetricians and Gynaecologists, recommend vaccinations for pregnant individuals.

The CDC goes on to describe that there is no evidence of vaccination increasing the risk of infertility. The vaccine protects the pregnant individual and also provides protection to the baby once born. The same is true of breastfeeding individuals.³

I hope that this information allows physicians to feel comfortable recommending vaccinations and boosters to those who are pregnant and breast feeding.
 

Expanded recommendations for those aged 16-17 years

Recently, the CDC also expanded booster recommendations to include those aged 16-17 years, 6 months after completing their vaccine series.

Those under 18 are currently only able to receive the Pfizer-BioNtech vaccine. This new guidance has left some parents wondering if there will also be approval for booster vaccinations soon for those aged 12-16 who are approaching or have reached six months past the initial vaccine.¹

Booster brand for those over 18 years?

Although the recommendation has been simplified for all over age 18 years, there is still a decision to be made about which vaccine to use as the booster.

The recommendations allow individuals to decide which brand of vaccine they would like to have as a booster. They may choose to be vaccinated with the same vaccine they originally received or with a different vaccine. This vaccine flexibility may cause confusion, but ultimately is a good thing as it allows individuals to receive whatever vaccine is available and most convenient. This also allows individuals who have been vaccinated outside of the United States by a different brand of vaccine to also receive a booster vaccination with one of the options available here.
 

Take home message

Overall, the expansion of booster recommendations will help everyone avoid severe disease from COVID-19 infections. Physicians now have more clarity on who should be receiving these vaccines. Along with testing, masking, and appropriate distancing, these recommendations should help prevent severe disease and death from COVID-19.

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program, also in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

References

1. COVID-19 Vaccine Booster Shots. Centers for Disease Control and Prevention. 2021 Dec 9.

2. COVID-19 Vaccines and Pregnancy: Conversation Guide. American College of Obstetricians and Gynecologists. 2021 November.

3. COVID-19 Vaccines While Pregnant or Breastfeeding. Centers for Disease Control and Prevention. 2021 Dec 6.

In recent weeks, the Centers for Disease Control and Prevention has greatly expanded recommendations for boosters for vaccinations against COVID-19.

These recommendations have been widened because of the continued emergence of new variants of the virus and the wane of protection over time for both vaccinations and previous disease.

The new recommendations take away some of the questions surrounding eligibility for booster vaccinations while potentially leaving some additional questions. All in all, they provide flexibility for individuals to help protect themselves against the COVID-19 virus, as many are considering celebrating the holidays with friends and family.

The first item that has become clear is that all individuals over 18 are now not only eligible for a booster vaccination a certain time after they have completed their series, but have a recommendation for one.¹

But what about a fourth dose?  There is a possibility that some patients should be receiving one.  For those who require a three-dose series due to a condition that makes them immunocompromised, they should receive their booster vaccination six months after completion of the three-dose series.  This distinction  may cause confusion for some, but is important for those immunocompromised.

Boosters in women who are pregnant

The recommendations also include specific comments about individuals who are pregnant. Although initial studies did not include pregnant individuals, there has been increasing real world data that vaccination against COVID, including booster vaccinations, is safe and recommended. As pregnancy increases the risk of severe disease if infected by COVID-19, both the CDC and the American College of Obstetricians and Gynecologists,² along with other specialty organizations, such as the Royal College of Obstetricians and Gynaecologists, recommend vaccinations for pregnant individuals.

The CDC goes on to describe that there is no evidence of vaccination increasing the risk of infertility. The vaccine protects the pregnant individual and also provides protection to the baby once born. The same is true of breastfeeding individuals.³

I hope that this information allows physicians to feel comfortable recommending vaccinations and boosters to those who are pregnant and breast feeding.
 

Expanded recommendations for those aged 16-17 years

Recently, the CDC also expanded booster recommendations to include those aged 16-17 years, 6 months after completing their vaccine series.

Those under 18 are currently only able to receive the Pfizer-BioNtech vaccine. This new guidance has left some parents wondering if there will also be approval for booster vaccinations soon for those aged 12-16 who are approaching or have reached six months past the initial vaccine.¹

Booster brand for those over 18 years?

Although the recommendation has been simplified for all over age 18 years, there is still a decision to be made about which vaccine to use as the booster.

The recommendations allow individuals to decide which brand of vaccine they would like to have as a booster. They may choose to be vaccinated with the same vaccine they originally received or with a different vaccine. This vaccine flexibility may cause confusion, but ultimately is a good thing as it allows individuals to receive whatever vaccine is available and most convenient. This also allows individuals who have been vaccinated outside of the United States by a different brand of vaccine to also receive a booster vaccination with one of the options available here.
 

Take home message

Overall, the expansion of booster recommendations will help everyone avoid severe disease from COVID-19 infections. Physicians now have more clarity on who should be receiving these vaccines. Along with testing, masking, and appropriate distancing, these recommendations should help prevent severe disease and death from COVID-19.

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program, also in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

References

1. COVID-19 Vaccine Booster Shots. Centers for Disease Control and Prevention. 2021 Dec 9.

2. COVID-19 Vaccines and Pregnancy: Conversation Guide. American College of Obstetricians and Gynecologists. 2021 November.

3. COVID-19 Vaccines While Pregnant or Breastfeeding. Centers for Disease Control and Prevention. 2021 Dec 6.

In recent weeks, the Centers for Disease Control and Prevention has greatly expanded recommendations for boosters for vaccinations against COVID-19.

These recommendations have been widened because of the continued emergence of new variants of the virus and the wane of protection over time for both vaccinations and previous disease.

The new recommendations take away some of the questions surrounding eligibility for booster vaccinations while potentially leaving some additional questions. All in all, they provide flexibility for individuals to help protect themselves against the COVID-19 virus, as many are considering celebrating the holidays with friends and family.

The first item that has become clear is that all individuals over 18 are now not only eligible for a booster vaccination a certain time after they have completed their series, but have a recommendation for one.¹

But what about a fourth dose?  There is a possibility that some patients should be receiving one.  For those who require a three-dose series due to a condition that makes them immunocompromised, they should receive their booster vaccination six months after completion of the three-dose series.  This distinction  may cause confusion for some, but is important for those immunocompromised.

Boosters in women who are pregnant

The recommendations also include specific comments about individuals who are pregnant. Although initial studies did not include pregnant individuals, there has been increasing real world data that vaccination against COVID, including booster vaccinations, is safe and recommended. As pregnancy increases the risk of severe disease if infected by COVID-19, both the CDC and the American College of Obstetricians and Gynecologists,² along with other specialty organizations, such as the Royal College of Obstetricians and Gynaecologists, recommend vaccinations for pregnant individuals.

The CDC goes on to describe that there is no evidence of vaccination increasing the risk of infertility. The vaccine protects the pregnant individual and also provides protection to the baby once born. The same is true of breastfeeding individuals.³

I hope that this information allows physicians to feel comfortable recommending vaccinations and boosters to those who are pregnant and breast feeding.
 

Expanded recommendations for those aged 16-17 years

Recently, the CDC also expanded booster recommendations to include those aged 16-17 years, 6 months after completing their vaccine series.

Those under 18 are currently only able to receive the Pfizer-BioNtech vaccine. This new guidance has left some parents wondering if there will also be approval for booster vaccinations soon for those aged 12-16 who are approaching or have reached six months past the initial vaccine.¹

Booster brand for those over 18 years?

Although the recommendation has been simplified for all over age 18 years, there is still a decision to be made about which vaccine to use as the booster.

The recommendations allow individuals to decide which brand of vaccine they would like to have as a booster. They may choose to be vaccinated with the same vaccine they originally received or with a different vaccine. This vaccine flexibility may cause confusion, but ultimately is a good thing as it allows individuals to receive whatever vaccine is available and most convenient. This also allows individuals who have been vaccinated outside of the United States by a different brand of vaccine to also receive a booster vaccination with one of the options available here.
 

Take home message

Overall, the expansion of booster recommendations will help everyone avoid severe disease from COVID-19 infections. Physicians now have more clarity on who should be receiving these vaccines. Along with testing, masking, and appropriate distancing, these recommendations should help prevent severe disease and death from COVID-19.

Dr. Wheat is a family physician at Erie Family Health Center in Chicago. She is program director of Northwestern’s McGaw Family Medicine residency program, also in Chicago. Dr. Wheat serves on the editorial advisory board of Family Practice News. You can contact her at [email protected].

References

1. COVID-19 Vaccine Booster Shots. Centers for Disease Control and Prevention. 2021 Dec 9.

2. COVID-19 Vaccines and Pregnancy: Conversation Guide. American College of Obstetricians and Gynecologists. 2021 November.

3. COVID-19 Vaccines While Pregnant or Breastfeeding. Centers for Disease Control and Prevention. 2021 Dec 6.

There are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up.

Does a skin barrier repair moisturizer really repair?

First, let’s briefly review what the skin barrier is. The stratum corneum (SC), the most superficial layer of the epidermis, averages approximately 15-cell layers in thickness.^1,2 The keratinocytes reside there in a pattern resembling a brick wall. The “mortar” is composed of the lipid contents extruded from the lamellar granules. This protective barrier functions to prevent transepidermal water loss (TEWL) and entry of allergens, irritants, and pathogens into deeper layers of the skin. This column will focus briefly on the structure and function of the skin barrier and the barrier repair technologies that use synthetic lipids such as myristoyl-palmitoyl and myristyl/palmityl-oxo-stearamide/arachamide MEA.

Structure of the skin barrier

SC keratinocytes are surrounded by lamella made from lipid bilayers. The lipids have hydrophilic heads and hydrophobic tails; the bilayer arises when the hydrophobic tails face the center and the hydrophilic heads face out of the bilayer. This formation yields a disc-shaped hydrophobic lamellar center. There are actually several of these lamellar layers between keratinocytes.

Dr. Leslie S. Baumann

The naturally occurring primary lipids of the bilayer lamellae are made up of an equal ratio of ceramides, cholesterol, and free fatty acid. Arranged in a 1:1:1 ratio, they fit together like pieces of a puzzle to achieve skin barrier homeostasis. The shape and size of these puzzle pieces is critical. An incorrect shape results in a hole in the skin barrier resulting in dehydration, inflammation, and sensitivity.
 

Ceramides

Ceramides are a complex family of lipids (sphingolipids – a sphingoid base and a fatty acid) involved in cell, as well as barrier, homeostasis and water-holding capacity. In fact, they are known to play a crucial role in cell proliferation, differentiation, and apoptosis.³ There are at least 16 types of naturally occurring ceramides. For years, they have been included in barrier repair moisturizers. They are difficult to work with in moisturizers for several reasons:

• Ceramides are abundant in brain tissue and the ceramides used in moisturizers in the past were derived from bovine brain tissue. Prior to the emergence of bovine spongiform encephalopathy (mad cow disease), many ceramides in skin-care products were animal derived, which made them expensive and undesirable.
• Ceramides in skin care that are made from plant sources are referred to as phyto-derived ceramides. Although they share a similar structure with ceramides that occur in human skin, there are differences in chain length, hydroxylation pattern, and the degree of unsaturation that lead to structural diversity.⁴ The shape of ceramides is critical for a strong skin barrier because the lipids in the skin barrier must fit together like puzzle pieces to form a water-tight barrier. Natural sources of ceramides include rice, wheat, potato, konjac, and maize. Standardization of ceramide shape and structure makes using phyto-derived ceramides in skin care products challenging.
• Ceramides, because of their waxy consistency, require heat during the mixing process of skin care product manufacturing. This heat can make other ingredients inactive in the skin care formulation. (Ceramides are typically added early in the formulation process, and the heat-sensitive ones are added later.)
• Many forms of ceramides are unstable in the product manufacturing and bottling processes.
• Skin penetration of ceramides depends on the shape and size of ceramides.

Synthetic ceramides have been developed to make ceramides safe, affordable, and more easily formulated into moisturizers. These formulations synthesized in the lab are sometimes called pseudoceramides because they are structurally different compounds that mimic the activity of ceramides. They are developed to be less expensive to manufacture, safer than those derived from animals, and easier to formulate, and they can be made into the specific shape of the ceramide puzzle piece.
 

Ceramides in skin care

The naturally occurring intercellular lipids of the SC are composed of approximately equal proportions of ceramides, cholesterol, and fatty acids (referred to in this article as the “three barrier lipids” for simplicity).^5-9 Alterations in any of these three barrier lipids or their regulatory enzymes result in impairments in the function of the epidermal barrier. Therefore, any synthetic ceramide must mimic the shape of natural ceramides, or the three barrier lipids in the moisturizer must mimic the shape of the entire bilayer lamella. Unfortunately, most barrier repair moisturizers do not meet these criteria and are not true barrier repair moisturizers.

How do you know if a moisturizer repairs the skin barrier?

Clinical tests such as measuring transepidermal water loss (TEWL) with a Tewameter are usually done to support the barrier repair claim. However, occlusive ingredients like oils can lower TEWL without affecting the barrier. In fact, we believe that sebum on the skin can make an impaired barrier and result in normal TEWL even when the barrier is impaired. So, just because a product improved TEWL does not necessarily mean that it repairs the barrier.

One way to test the ability of a moisturizer to repair the barrier is to look at a structural analysis of the moisturizer to see if it forms the requisite bilayer lamellar shape. An easy way to do this testing is to look for the cross pattern under a cross polarized microscope. The cross pattern is known as optical anisotropy. ⁸

Dr. Leslie S. Baumann

The best barrier repair creams

Optimal barrier repair creams either feature a 1:1:1 ratio of epidermal lipids or form a cross structure when viewed with a cross-polarized microscope.⁸ There are several categories of barrier repair moisturizers that meet these criteria.

Baumann L Cosmetic Dermatology Ed 3 (McGraw Hill) 2022 in press

Barrier repair creams with a 1:1:1 ratio of lipids:

Peter Elias, MD, holds the patent on barrier repair moisturizer technology that has a 1:1:1 ratio. His well-established technology is used in a prescription barrier repair cream called EpiCeram^® which is approved by the Food and Drug Administration to treat eczema. There are no other moisturizers that I know of that contain this 1:1:1 lipid ratio.

There is a barrier repair cream on the market that contains a 2:4:2 ratio of lipids based on a study that showed that this ratio is effective in older skin with an impaired barrier. It is unknown if this moisturizer forms a cross pattern.
 

Barrier repair creams that demonstrate a cross pattern:

Multilamellar emulsion (MLE) technology: This barrier repair technology, invented in South Korea, contains the synthetic pseudoceramide called myristyl/palmityl-oxo-stearamide/arachamide MEA (C34H67NO3/C36H71NO3/C38H75NO3), or the pseudoceramide myristoyl-palmitoyl-oxostearamide-arachamide MEA.

In a 2019 pilot study by Ye and colleagues, the investigators treated 33 older volunteers twice daily for 30 days with approximately 3 mL of an emollient containing MLE technology. In addition, 30 untreated older subjects and 11 young volunteers served as controls. The investigators found that the topically applied barrier repair emollient significantly improved barrier function, as well as stratum corneum hydration. Circulating levels of the important, age-related plasma cytokines interleukin-1 beta and IL-6 were found to have normalized, while tumor necrosis factor–alpha decreased markedly. The investigators suggested that repair of the skin barrier might diminish circulating proinflammatory cytokine levels (such as amyloid A) in aged humans, potentially mitigating the development of chronic inflammatory conditions.¹⁰

MLE technology has also been shown to improve childhood atopic dermatitis and prevent steroid atrophy.^11,12 The consistent use of MLE technology in moisturizers has been shown to alleviate inflammatory factors in the blood and is believed to lessen systemic inflammation.¹⁰

Physiologic (PSL) lipid repair technology: This technology was invented by one of the South Korean researchers who helped develop MLE technology. It contains pseudoceramides, fatty acids, and cholesterol. The figure of the cross pattern above, as seen under the cross polarized microscope, is an image taken of this PSL lipid repair technology.
 

Conclusion

Do not believe that a moisturizer repairs the barrier just because it says so on the label. Three of the most popular body moisturizes used to treat eczema do not actually have the proper formula to repair the barrier. Unfortunately, there are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up. To restore the skin barrier to a healthy condition, it is imperative that the barrier repair moisturizers that you are recommending for patients have the correct 1:1:1 ratio of epidermal lipids or contain bilayer lamella that mimic the natural multilamellar layers and display the cross pattern under a cross-polarized microscope.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Christophers E and Kligman AM. J Invest Dermatol. 1964;42:407-9.

2. Blair C. Br J Dermatol. 1968;80(7):430-6.

3. Morita O et al. Food Chem Toxicol. 2009 Apr;47(4):681-6.

4. Tessema E N et al. Skin pharmacology and physiology. 2017;30(3):115-38.

5. Coderch L et al. Am J Clin Dermatol. 2003;4(2):107-29.

6. Man MQ et al. Arch Dermatol. 1993;129(6):728-38.

7. Man MQ M et al. J Invest Dermatol. 1996 May;106(5):1096-101.

8. Park BD et al. J Invest Dermatol. 2003;121(4):794-801.

9. Proksch E and Jensen J. Skin as an organ of protection, in “Fitzpatrick’s Dermatology in General Medicine,” 7th ed. New York: McGraw-Hill, 2008, pp. 383-95.

10. Ye L et al. J Eur Acad Dermatol Venereol. 2019;33(11):2197-201.

11. Lee EJ et al. Ann Dermatol. 2003;15(4):133-8.

12. Ahn SK et al. J Dermatol. 2006;33(2):80-90.

There are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up.

Does a skin barrier repair moisturizer really repair?

First, let’s briefly review what the skin barrier is. The stratum corneum (SC), the most superficial layer of the epidermis, averages approximately 15-cell layers in thickness.^1,2 The keratinocytes reside there in a pattern resembling a brick wall. The “mortar” is composed of the lipid contents extruded from the lamellar granules. This protective barrier functions to prevent transepidermal water loss (TEWL) and entry of allergens, irritants, and pathogens into deeper layers of the skin. This column will focus briefly on the structure and function of the skin barrier and the barrier repair technologies that use synthetic lipids such as myristoyl-palmitoyl and myristyl/palmityl-oxo-stearamide/arachamide MEA.

Structure of the skin barrier

SC keratinocytes are surrounded by lamella made from lipid bilayers. The lipids have hydrophilic heads and hydrophobic tails; the bilayer arises when the hydrophobic tails face the center and the hydrophilic heads face out of the bilayer. This formation yields a disc-shaped hydrophobic lamellar center. There are actually several of these lamellar layers between keratinocytes.

Dr. Leslie S. Baumann

The naturally occurring primary lipids of the bilayer lamellae are made up of an equal ratio of ceramides, cholesterol, and free fatty acid. Arranged in a 1:1:1 ratio, they fit together like pieces of a puzzle to achieve skin barrier homeostasis. The shape and size of these puzzle pieces is critical. An incorrect shape results in a hole in the skin barrier resulting in dehydration, inflammation, and sensitivity.
 

Ceramides

Ceramides are a complex family of lipids (sphingolipids – a sphingoid base and a fatty acid) involved in cell, as well as barrier, homeostasis and water-holding capacity. In fact, they are known to play a crucial role in cell proliferation, differentiation, and apoptosis.³ There are at least 16 types of naturally occurring ceramides. For years, they have been included in barrier repair moisturizers. They are difficult to work with in moisturizers for several reasons:

• Ceramides are abundant in brain tissue and the ceramides used in moisturizers in the past were derived from bovine brain tissue. Prior to the emergence of bovine spongiform encephalopathy (mad cow disease), many ceramides in skin-care products were animal derived, which made them expensive and undesirable.
• Ceramides in skin care that are made from plant sources are referred to as phyto-derived ceramides. Although they share a similar structure with ceramides that occur in human skin, there are differences in chain length, hydroxylation pattern, and the degree of unsaturation that lead to structural diversity.⁴ The shape of ceramides is critical for a strong skin barrier because the lipids in the skin barrier must fit together like puzzle pieces to form a water-tight barrier. Natural sources of ceramides include rice, wheat, potato, konjac, and maize. Standardization of ceramide shape and structure makes using phyto-derived ceramides in skin care products challenging.
• Ceramides, because of their waxy consistency, require heat during the mixing process of skin care product manufacturing. This heat can make other ingredients inactive in the skin care formulation. (Ceramides are typically added early in the formulation process, and the heat-sensitive ones are added later.)
• Many forms of ceramides are unstable in the product manufacturing and bottling processes.
• Skin penetration of ceramides depends on the shape and size of ceramides.

Synthetic ceramides have been developed to make ceramides safe, affordable, and more easily formulated into moisturizers. These formulations synthesized in the lab are sometimes called pseudoceramides because they are structurally different compounds that mimic the activity of ceramides. They are developed to be less expensive to manufacture, safer than those derived from animals, and easier to formulate, and they can be made into the specific shape of the ceramide puzzle piece.
 

Ceramides in skin care

The naturally occurring intercellular lipids of the SC are composed of approximately equal proportions of ceramides, cholesterol, and fatty acids (referred to in this article as the “three barrier lipids” for simplicity).^5-9 Alterations in any of these three barrier lipids or their regulatory enzymes result in impairments in the function of the epidermal barrier. Therefore, any synthetic ceramide must mimic the shape of natural ceramides, or the three barrier lipids in the moisturizer must mimic the shape of the entire bilayer lamella. Unfortunately, most barrier repair moisturizers do not meet these criteria and are not true barrier repair moisturizers.

How do you know if a moisturizer repairs the skin barrier?

Clinical tests such as measuring transepidermal water loss (TEWL) with a Tewameter are usually done to support the barrier repair claim. However, occlusive ingredients like oils can lower TEWL without affecting the barrier. In fact, we believe that sebum on the skin can make an impaired barrier and result in normal TEWL even when the barrier is impaired. So, just because a product improved TEWL does not necessarily mean that it repairs the barrier.

One way to test the ability of a moisturizer to repair the barrier is to look at a structural analysis of the moisturizer to see if it forms the requisite bilayer lamellar shape. An easy way to do this testing is to look for the cross pattern under a cross polarized microscope. The cross pattern is known as optical anisotropy. ⁸

Dr. Leslie S. Baumann

The best barrier repair creams

Optimal barrier repair creams either feature a 1:1:1 ratio of epidermal lipids or form a cross structure when viewed with a cross-polarized microscope.⁸ There are several categories of barrier repair moisturizers that meet these criteria.

Baumann L Cosmetic Dermatology Ed 3 (McGraw Hill) 2022 in press

Barrier repair creams with a 1:1:1 ratio of lipids:

Peter Elias, MD, holds the patent on barrier repair moisturizer technology that has a 1:1:1 ratio. His well-established technology is used in a prescription barrier repair cream called EpiCeram^® which is approved by the Food and Drug Administration to treat eczema. There are no other moisturizers that I know of that contain this 1:1:1 lipid ratio.

There is a barrier repair cream on the market that contains a 2:4:2 ratio of lipids based on a study that showed that this ratio is effective in older skin with an impaired barrier. It is unknown if this moisturizer forms a cross pattern.
 

Barrier repair creams that demonstrate a cross pattern:

Multilamellar emulsion (MLE) technology: This barrier repair technology, invented in South Korea, contains the synthetic pseudoceramide called myristyl/palmityl-oxo-stearamide/arachamide MEA (C34H67NO3/C36H71NO3/C38H75NO3), or the pseudoceramide myristoyl-palmitoyl-oxostearamide-arachamide MEA.

In a 2019 pilot study by Ye and colleagues, the investigators treated 33 older volunteers twice daily for 30 days with approximately 3 mL of an emollient containing MLE technology. In addition, 30 untreated older subjects and 11 young volunteers served as controls. The investigators found that the topically applied barrier repair emollient significantly improved barrier function, as well as stratum corneum hydration. Circulating levels of the important, age-related plasma cytokines interleukin-1 beta and IL-6 were found to have normalized, while tumor necrosis factor–alpha decreased markedly. The investigators suggested that repair of the skin barrier might diminish circulating proinflammatory cytokine levels (such as amyloid A) in aged humans, potentially mitigating the development of chronic inflammatory conditions.¹⁰

MLE technology has also been shown to improve childhood atopic dermatitis and prevent steroid atrophy.^11,12 The consistent use of MLE technology in moisturizers has been shown to alleviate inflammatory factors in the blood and is believed to lessen systemic inflammation.¹⁰

Physiologic (PSL) lipid repair technology: This technology was invented by one of the South Korean researchers who helped develop MLE technology. It contains pseudoceramides, fatty acids, and cholesterol. The figure of the cross pattern above, as seen under the cross polarized microscope, is an image taken of this PSL lipid repair technology.
 

Conclusion

Do not believe that a moisturizer repairs the barrier just because it says so on the label. Three of the most popular body moisturizes used to treat eczema do not actually have the proper formula to repair the barrier. Unfortunately, there are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up. To restore the skin barrier to a healthy condition, it is imperative that the barrier repair moisturizers that you are recommending for patients have the correct 1:1:1 ratio of epidermal lipids or contain bilayer lamella that mimic the natural multilamellar layers and display the cross pattern under a cross-polarized microscope.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Christophers E and Kligman AM. J Invest Dermatol. 1964;42:407-9.

2. Blair C. Br J Dermatol. 1968;80(7):430-6.

3. Morita O et al. Food Chem Toxicol. 2009 Apr;47(4):681-6.

4. Tessema E N et al. Skin pharmacology and physiology. 2017;30(3):115-38.

5. Coderch L et al. Am J Clin Dermatol. 2003;4(2):107-29.

6. Man MQ et al. Arch Dermatol. 1993;129(6):728-38.

7. Man MQ M et al. J Invest Dermatol. 1996 May;106(5):1096-101.

8. Park BD et al. J Invest Dermatol. 2003;121(4):794-801.

9. Proksch E and Jensen J. Skin as an organ of protection, in “Fitzpatrick’s Dermatology in General Medicine,” 7th ed. New York: McGraw-Hill, 2008, pp. 383-95.

10. Ye L et al. J Eur Acad Dermatol Venereol. 2019;33(11):2197-201.

11. Lee EJ et al. Ann Dermatol. 2003;15(4):133-8.

12. Ahn SK et al. J Dermatol. 2006;33(2):80-90.

There are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up.

Does a skin barrier repair moisturizer really repair?

First, let’s briefly review what the skin barrier is. The stratum corneum (SC), the most superficial layer of the epidermis, averages approximately 15-cell layers in thickness.^1,2 The keratinocytes reside there in a pattern resembling a brick wall. The “mortar” is composed of the lipid contents extruded from the lamellar granules. This protective barrier functions to prevent transepidermal water loss (TEWL) and entry of allergens, irritants, and pathogens into deeper layers of the skin. This column will focus briefly on the structure and function of the skin barrier and the barrier repair technologies that use synthetic lipids such as myristoyl-palmitoyl and myristyl/palmityl-oxo-stearamide/arachamide MEA.

Structure of the skin barrier

SC keratinocytes are surrounded by lamella made from lipid bilayers. The lipids have hydrophilic heads and hydrophobic tails; the bilayer arises when the hydrophobic tails face the center and the hydrophilic heads face out of the bilayer. This formation yields a disc-shaped hydrophobic lamellar center. There are actually several of these lamellar layers between keratinocytes.

Dr. Leslie S. Baumann

The naturally occurring primary lipids of the bilayer lamellae are made up of an equal ratio of ceramides, cholesterol, and free fatty acid. Arranged in a 1:1:1 ratio, they fit together like pieces of a puzzle to achieve skin barrier homeostasis. The shape and size of these puzzle pieces is critical. An incorrect shape results in a hole in the skin barrier resulting in dehydration, inflammation, and sensitivity.
 

Ceramides

Ceramides are a complex family of lipids (sphingolipids – a sphingoid base and a fatty acid) involved in cell, as well as barrier, homeostasis and water-holding capacity. In fact, they are known to play a crucial role in cell proliferation, differentiation, and apoptosis.³ There are at least 16 types of naturally occurring ceramides. For years, they have been included in barrier repair moisturizers. They are difficult to work with in moisturizers for several reasons:

• Ceramides are abundant in brain tissue and the ceramides used in moisturizers in the past were derived from bovine brain tissue. Prior to the emergence of bovine spongiform encephalopathy (mad cow disease), many ceramides in skin-care products were animal derived, which made them expensive and undesirable.
• Ceramides in skin care that are made from plant sources are referred to as phyto-derived ceramides. Although they share a similar structure with ceramides that occur in human skin, there are differences in chain length, hydroxylation pattern, and the degree of unsaturation that lead to structural diversity.⁴ The shape of ceramides is critical for a strong skin barrier because the lipids in the skin barrier must fit together like puzzle pieces to form a water-tight barrier. Natural sources of ceramides include rice, wheat, potato, konjac, and maize. Standardization of ceramide shape and structure makes using phyto-derived ceramides in skin care products challenging.
• Ceramides, because of their waxy consistency, require heat during the mixing process of skin care product manufacturing. This heat can make other ingredients inactive in the skin care formulation. (Ceramides are typically added early in the formulation process, and the heat-sensitive ones are added later.)
• Many forms of ceramides are unstable in the product manufacturing and bottling processes.
• Skin penetration of ceramides depends on the shape and size of ceramides.

Synthetic ceramides have been developed to make ceramides safe, affordable, and more easily formulated into moisturizers. These formulations synthesized in the lab are sometimes called pseudoceramides because they are structurally different compounds that mimic the activity of ceramides. They are developed to be less expensive to manufacture, safer than those derived from animals, and easier to formulate, and they can be made into the specific shape of the ceramide puzzle piece.
 

Ceramides in skin care

The naturally occurring intercellular lipids of the SC are composed of approximately equal proportions of ceramides, cholesterol, and fatty acids (referred to in this article as the “three barrier lipids” for simplicity).^5-9 Alterations in any of these three barrier lipids or their regulatory enzymes result in impairments in the function of the epidermal barrier. Therefore, any synthetic ceramide must mimic the shape of natural ceramides, or the three barrier lipids in the moisturizer must mimic the shape of the entire bilayer lamella. Unfortunately, most barrier repair moisturizers do not meet these criteria and are not true barrier repair moisturizers.

How do you know if a moisturizer repairs the skin barrier?

Clinical tests such as measuring transepidermal water loss (TEWL) with a Tewameter are usually done to support the barrier repair claim. However, occlusive ingredients like oils can lower TEWL without affecting the barrier. In fact, we believe that sebum on the skin can make an impaired barrier and result in normal TEWL even when the barrier is impaired. So, just because a product improved TEWL does not necessarily mean that it repairs the barrier.

One way to test the ability of a moisturizer to repair the barrier is to look at a structural analysis of the moisturizer to see if it forms the requisite bilayer lamellar shape. An easy way to do this testing is to look for the cross pattern under a cross polarized microscope. The cross pattern is known as optical anisotropy. ⁸

Dr. Leslie S. Baumann

The best barrier repair creams

Optimal barrier repair creams either feature a 1:1:1 ratio of epidermal lipids or form a cross structure when viewed with a cross-polarized microscope.⁸ There are several categories of barrier repair moisturizers that meet these criteria.

Baumann L Cosmetic Dermatology Ed 3 (McGraw Hill) 2022 in press

Barrier repair creams with a 1:1:1 ratio of lipids:

Peter Elias, MD, holds the patent on barrier repair moisturizer technology that has a 1:1:1 ratio. His well-established technology is used in a prescription barrier repair cream called EpiCeram^® which is approved by the Food and Drug Administration to treat eczema. There are no other moisturizers that I know of that contain this 1:1:1 lipid ratio.

There is a barrier repair cream on the market that contains a 2:4:2 ratio of lipids based on a study that showed that this ratio is effective in older skin with an impaired barrier. It is unknown if this moisturizer forms a cross pattern.
 

Barrier repair creams that demonstrate a cross pattern:

Multilamellar emulsion (MLE) technology: This barrier repair technology, invented in South Korea, contains the synthetic pseudoceramide called myristyl/palmityl-oxo-stearamide/arachamide MEA (C34H67NO3/C36H71NO3/C38H75NO3), or the pseudoceramide myristoyl-palmitoyl-oxostearamide-arachamide MEA.

In a 2019 pilot study by Ye and colleagues, the investigators treated 33 older volunteers twice daily for 30 days with approximately 3 mL of an emollient containing MLE technology. In addition, 30 untreated older subjects and 11 young volunteers served as controls. The investigators found that the topically applied barrier repair emollient significantly improved barrier function, as well as stratum corneum hydration. Circulating levels of the important, age-related plasma cytokines interleukin-1 beta and IL-6 were found to have normalized, while tumor necrosis factor–alpha decreased markedly. The investigators suggested that repair of the skin barrier might diminish circulating proinflammatory cytokine levels (such as amyloid A) in aged humans, potentially mitigating the development of chronic inflammatory conditions.¹⁰

MLE technology has also been shown to improve childhood atopic dermatitis and prevent steroid atrophy.^11,12 The consistent use of MLE technology in moisturizers has been shown to alleviate inflammatory factors in the blood and is believed to lessen systemic inflammation.¹⁰

Physiologic (PSL) lipid repair technology: This technology was invented by one of the South Korean researchers who helped develop MLE technology. It contains pseudoceramides, fatty acids, and cholesterol. The figure of the cross pattern above, as seen under the cross polarized microscope, is an image taken of this PSL lipid repair technology.
 

Conclusion

Do not believe that a moisturizer repairs the barrier just because it says so on the label. Three of the most popular body moisturizes used to treat eczema do not actually have the proper formula to repair the barrier. Unfortunately, there are dozens of skin care products that claim to repair the barrier that do not have the science or ingredient content to back them up. To restore the skin barrier to a healthy condition, it is imperative that the barrier repair moisturizers that you are recommending for patients have the correct 1:1:1 ratio of epidermal lipids or contain bilayer lamella that mimic the natural multilamellar layers and display the cross pattern under a cross-polarized microscope.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions, a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Christophers E and Kligman AM. J Invest Dermatol. 1964;42:407-9.

2. Blair C. Br J Dermatol. 1968;80(7):430-6.

3. Morita O et al. Food Chem Toxicol. 2009 Apr;47(4):681-6.

4. Tessema E N et al. Skin pharmacology and physiology. 2017;30(3):115-38.

5. Coderch L et al. Am J Clin Dermatol. 2003;4(2):107-29.

6. Man MQ et al. Arch Dermatol. 1993;129(6):728-38.

7. Man MQ M et al. J Invest Dermatol. 1996 May;106(5):1096-101.

8. Park BD et al. J Invest Dermatol. 2003;121(4):794-801.

9. Proksch E and Jensen J. Skin as an organ of protection, in “Fitzpatrick’s Dermatology in General Medicine,” 7th ed. New York: McGraw-Hill, 2008, pp. 383-95.

10. Ye L et al. J Eur Acad Dermatol Venereol. 2019;33(11):2197-201.

11. Lee EJ et al. Ann Dermatol. 2003;15(4):133-8.

12. Ahn SK et al. J Dermatol. 2006;33(2):80-90.

Chilblain lupus erythematosus, described by Jonathan Hutchinson, is an uncommon form of cutaneous lupus that affects women more frequently than men. Clinically, distal extremities such as toes, fingertips and heels, as well as the rims of the ears or nose develop erythematous to purple plaques. Lesions may be painful or pruritic. Over time, lesions may develop atrophy and resemble those of discoid lupus. While the pathogenesis is unknown, exposure to cold or wet environments can precipitate lesions.

Histopathology reveals a deep and superficial lymphocytic infiltrate with perieccrine involvement and fibrin deposition in vessels. Dermal edema is often present. Direct immunofluorescence shows an interface dermatitis positive for IgM, IgA, and C3.

The Mayo Clinic developed diagnostic criteria for diagnosing chilblains lupus. Two major criteria are acral skin lesions induced by cold exposure and evidence of lupus erythematosus in skin lesions (histopathologically or by direct immunofluorescence). Three minor criteria are the coexistence of systemic lupus erythematosus or discoid lupus erythematosus, response to antilupus treatment, and negative cryoglobulin and cold agglutinin studies.

Chilblains, or perniosis, has a similar clinical presentation to chilblain lupus erythematosus. However, serologic evidence of lupus, such as a positive antinuclear antibody (ANA), will be absent. Lupus pernio (Besnier-Tenneson syndrome) is a form of sarcoidosis that tends to favor the nose. These lesions are not precipitated by cold. It can be differentiated on histology. “COVID toes” is an entity described during the coronavirus pandemic, during which dermatologists noted pernio-like lesions in patients testing positive for coronavirus.

The patient’s labs revealed a positive ANA at 1:320 in a nucleolar speckled pattern, elevated double-stranded DNA, low C3 and C4 levels, elevated cardiolipin IgM Ab, and elevated sedimentation rate. COVID-19 antigen testing and COVID-19 antibodies were negative. A serum protein electrophoresis was negative. Cryoglobulins were negative.

Treatment includes protection from cold. Smoking cessation should be discussed. Topical steroids and topical calcineurin inhibitors are first-line treatments for mild disease. Antimalarials, such as hydroxychloroquine can be helpful. Systemic calcium channel blockers, systemic steroids, mycophenolate mofetil, and tacrolimus have all been reported as treatments. This patient responded well to hydroxychloroquine and topical steroids with full resolution of lesions.

This case was submitted by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Su WP et al. Cutis. 1994 Dec;54(6):395-9.

Werth V and Newman S. Chilblain lupus (SLE pernio). Dermatology Advisor. 2017.

Chilblain lupus erythematosus, described by Jonathan Hutchinson, is an uncommon form of cutaneous lupus that affects women more frequently than men. Clinically, distal extremities such as toes, fingertips and heels, as well as the rims of the ears or nose develop erythematous to purple plaques. Lesions may be painful or pruritic. Over time, lesions may develop atrophy and resemble those of discoid lupus. While the pathogenesis is unknown, exposure to cold or wet environments can precipitate lesions.

Histopathology reveals a deep and superficial lymphocytic infiltrate with perieccrine involvement and fibrin deposition in vessels. Dermal edema is often present. Direct immunofluorescence shows an interface dermatitis positive for IgM, IgA, and C3.

The Mayo Clinic developed diagnostic criteria for diagnosing chilblains lupus. Two major criteria are acral skin lesions induced by cold exposure and evidence of lupus erythematosus in skin lesions (histopathologically or by direct immunofluorescence). Three minor criteria are the coexistence of systemic lupus erythematosus or discoid lupus erythematosus, response to antilupus treatment, and negative cryoglobulin and cold agglutinin studies.

Chilblains, or perniosis, has a similar clinical presentation to chilblain lupus erythematosus. However, serologic evidence of lupus, such as a positive antinuclear antibody (ANA), will be absent. Lupus pernio (Besnier-Tenneson syndrome) is a form of sarcoidosis that tends to favor the nose. These lesions are not precipitated by cold. It can be differentiated on histology. “COVID toes” is an entity described during the coronavirus pandemic, during which dermatologists noted pernio-like lesions in patients testing positive for coronavirus.

The patient’s labs revealed a positive ANA at 1:320 in a nucleolar speckled pattern, elevated double-stranded DNA, low C3 and C4 levels, elevated cardiolipin IgM Ab, and elevated sedimentation rate. COVID-19 antigen testing and COVID-19 antibodies were negative. A serum protein electrophoresis was negative. Cryoglobulins were negative.

Treatment includes protection from cold. Smoking cessation should be discussed. Topical steroids and topical calcineurin inhibitors are first-line treatments for mild disease. Antimalarials, such as hydroxychloroquine can be helpful. Systemic calcium channel blockers, systemic steroids, mycophenolate mofetil, and tacrolimus have all been reported as treatments. This patient responded well to hydroxychloroquine and topical steroids with full resolution of lesions.

This case was submitted by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Su WP et al. Cutis. 1994 Dec;54(6):395-9.

Werth V and Newman S. Chilblain lupus (SLE pernio). Dermatology Advisor. 2017.

Chilblain lupus erythematosus, described by Jonathan Hutchinson, is an uncommon form of cutaneous lupus that affects women more frequently than men. Clinically, distal extremities such as toes, fingertips and heels, as well as the rims of the ears or nose develop erythematous to purple plaques. Lesions may be painful or pruritic. Over time, lesions may develop atrophy and resemble those of discoid lupus. While the pathogenesis is unknown, exposure to cold or wet environments can precipitate lesions.

Histopathology reveals a deep and superficial lymphocytic infiltrate with perieccrine involvement and fibrin deposition in vessels. Dermal edema is often present. Direct immunofluorescence shows an interface dermatitis positive for IgM, IgA, and C3.

The Mayo Clinic developed diagnostic criteria for diagnosing chilblains lupus. Two major criteria are acral skin lesions induced by cold exposure and evidence of lupus erythematosus in skin lesions (histopathologically or by direct immunofluorescence). Three minor criteria are the coexistence of systemic lupus erythematosus or discoid lupus erythematosus, response to antilupus treatment, and negative cryoglobulin and cold agglutinin studies.

Chilblains, or perniosis, has a similar clinical presentation to chilblain lupus erythematosus. However, serologic evidence of lupus, such as a positive antinuclear antibody (ANA), will be absent. Lupus pernio (Besnier-Tenneson syndrome) is a form of sarcoidosis that tends to favor the nose. These lesions are not precipitated by cold. It can be differentiated on histology. “COVID toes” is an entity described during the coronavirus pandemic, during which dermatologists noted pernio-like lesions in patients testing positive for coronavirus.

The patient’s labs revealed a positive ANA at 1:320 in a nucleolar speckled pattern, elevated double-stranded DNA, low C3 and C4 levels, elevated cardiolipin IgM Ab, and elevated sedimentation rate. COVID-19 antigen testing and COVID-19 antibodies were negative. A serum protein electrophoresis was negative. Cryoglobulins were negative.

Treatment includes protection from cold. Smoking cessation should be discussed. Topical steroids and topical calcineurin inhibitors are first-line treatments for mild disease. Antimalarials, such as hydroxychloroquine can be helpful. Systemic calcium channel blockers, systemic steroids, mycophenolate mofetil, and tacrolimus have all been reported as treatments. This patient responded well to hydroxychloroquine and topical steroids with full resolution of lesions.

This case was submitted by Dr. Bilu Martin.

Dr. Bilu Martin is a board-certified dermatologist in private practice at Premier Dermatology, MD, in Aventura, Fla. More diagnostic cases are available at mdedge.com/dermatology. To submit a case for possible publication, send an email to [email protected].

References

Su WP et al. Cutis. 1994 Dec;54(6):395-9.

Werth V and Newman S. Chilblain lupus (SLE pernio). Dermatology Advisor. 2017.

A recent study published in the Journal of Hospital Medicine examined patient discharges from hospitals in Ontario, Canada, to determine if morning discharges were associated with positive outcomes. Some hospitalist programs have embraced discharge before noon (DBN) initiatives like those studied in the article.¹ Unfortunately, the researchers concluded that the Canadian DBNs did not positively impact hospital length of stay, readmissions, or mortality rates.

DBN has been a quality improvement target for hospitals hoping to improve throughput and free up scarce beds, while promoting patient safety by encouraging discharge as soon as patients are ready to leave. Yet other researchers have questioned its actual impact on quality metrics. One author called DBN’s purported impact an “urban legend,”² while a JHM editorial accompanying the Ontario study noted, “Hospitals are delicate organisms; a singular focus on one metric will undoubtedly impact others.”³

Might DBN be an artificial target that doesn’t actually enhance throughput, but leads instead to unintended consequences, such as patients being held over for an additional night in the hospital, rather than being discharged when they are ready to go on the afternoon before, in order to boost DBN rates? A perennial debate in hospital medicine is likely to be reignited by the new findings.
 

‘No significant overall association’

Quality improvement initiatives targeting morning discharges have included stakeholder meetings, incentives programs, discharge-centered breakfast programs, and creation of deadlines for discharge orders, the new study’s authors noted. Although these initiatives have gained support, critics have suggested that their supporting evidence is not robust.

The Canadian researchers retrospectively reviewed all patient admissions to general internal medicine services (GIMs) – largely similar to hospital medicine services in the United States – at seven hospitals in Toronto and Mississauga over a 7-year period ending Oct. 31, 2017, counting all of these patients who were discharged alive between 8 a.m. and noon. DBN averaged 19% of total live discharges across the diverse hospitals, with their diverse discharge practices.

But they found no significant overall association between morning discharge and hospital or emergency department length of stay. “Our findings suggest that increasing the number of morning discharges alone is unlikely to substantially improve patient throughput in GIM, but further research is needed to determine the effectiveness of specific interventions,” they concluded.

“We used a very narrow lens, looking specifically at throughput for the hospitals and emergency departments and whether DBN makes it more efficient,” said corresponding author Amol Verma, MD, MPhil, FRCPC, clinician-scientist at St. Michael’s Hospital, University of Toronto, in a recent interview. “What we found was that, on days when more patients are discharged in the morning, patients do not flow more quickly through the hospital. That suggests that increasing morning discharges is unlikely to make a difference.”
 

What does DBN really mean?

The semantics of DBN deserve further exploration. Is DBN about the actual hour of discharge, or the time when the hospitalist signs a discharge order – which may be well before the patient actually gets a wheelchair ride down to the hospital’s front doors? And if DBN is an organized program promoting morning discharges, how is it incentivized or otherwise rewarded?

Other factors, such as arrival of medications from the pharmacy or results from clinical tests, access to an ambulance if needed, transport to the front door, and bed cleaning will impact how quickly a doctor’s discharge orders get acted upon – and how quickly the newly emptied bed is available for the next occupant.

The clinician’s views on discharge practices may diverge from hospital administrator or health system perspectives, with its imperatives for efficient throughput in order to bring in more patients, Dr. Verma said. The hospitalist is also concerned about whether the patient feels ready to go home. “We can all agree that patients should leave the hospital as soon as they are medically able to do so,” he said. Longer hospital stays are associated with increased rates of hospital-acquired infections and other iatrogenic complications.

But there is not agreement on the components of a safe discharge – or on the other dimensions of effective patient flow and transitions of care. How do we optimize treatments initiated in the hospital? Does the patient need one more CAT scan? And what about the concerns of patient-centered care? Does the patient have a caregiver able to help them when they get home? There is a lot of uncertainty, Dr. Verma said. “These kinds of decisions have to get made many times every day by hospitalists,” he noted.

“We find ourselves trying to mirror the ebbs and flows of the emergency department with what’s happening in the hospital,” said Venkat Gundareddy, MBBS, MPH, associate director of the division of hospital medicine at Johns Hopkins Medicine in Baltimore. “The majority of hospital discharges happen during business hours, but the emergency department doesn’t stop admitting overnight, thus creating a throughput challenge.” Discharges are also based on clinical outcomes and on patients transferring to other facilities that prefer patients to arrive earlier in the day.

“Hospitalists may not fully appreciate these dynamics, because we’re siloed on our units,” Dr. Gundareddy said. “There is a subset of patients who would fit the bill for early discharge, but other patients come into the hospital with greater complexities, and a need for more coordination. Their discharges are harder to predict, although it gets clearer as their care progresses.”

The hospitals included in the Ontario study are at 90% -100% capacity, so their flexibility is constrained and throughput is a critical issue, Dr. Verma said. “But if you start with the target of more efficient throughput, there is no logical or practical reason to assume that discharge before noon would help. If we believe someone is ready for discharge based on physiologic changes, their response to treatment, and the conclusion of medical investigations, none of these conform to the clock. It’s equally likely the patient achieves them in the afternoon or evening.”

Other views on morning discharge

An alternative perspective comes from New York University’s Langone Medical Center, which has published positive results, including earlier subsequent arrivals to the inpatient unit from the emergency department, from increasing its hospital’s DBN rate.⁴

The hospital has continued to encourage morning discharges, which have consistently run 35%-40% or more of total discharges on two acute inpatient units at Langone’s Tisch Hospital. A previous study described the multidisciplinary intervention that resulted in a statistically significant increase in DBN – from 11% to 38% in the first 13 months – while significantly reducing high-frequency admission peaks.⁵

“We’ve been doing DBN for a number of years,” said Benjamin Wertheimer, MD, a hospitalist at Langone Medical Center and one of the studies’ authors. It is an achievable – and sustainable – goal. “Many hospitals around the country have problems with the flow of patients. Many hospitals are full – even before accounting for the COVID pandemic.” There is good evidence that, for a patient who no longer requires hospitalization, getting them out as early as possible, with a safe plan for their discharge, is a good thing, he said. “We see DBN as an important operational metric.”

If the necessary work is done correctly on the afternoon before the discharge, then a DBN approach can push communication, coordination, and advance planning, Dr Wertheimer said. Otherwise, essential discharge tasks may lag until the last minute. “We try to put the pieces in place the day before through a better planned process. But it should never be that DBN takes precedence over when the patient is safely ready to go,” he said.

“Our true measure of success would be how well we are preparing, communicating, putting safe plans into place,” he added. “DBN does not in and of itself answer all the safety and quality concerns. We set priorities around specific quality targets. DBN is just one of our operational and safety measures.”

The DBN intervention at Langone started with a multidisciplinary kickoff event in which all team members received education on its importance, a clear description of roles in the DBN process, and a corresponding checklist of daily responsibilities. The checklist was utilized at newly implemented afternoon interdisciplinary rounds, scripted to identify next-day DBNs, and make sure everything is in place for them, he explained.

“We provide daily feedback to floor staff on the DBN percentage, celebrate success, and offer real-time opportunities for case review,” Dr. Wertheimer said. “We have been careful about how we message this goal. Quality and safety come first, and we want to be prepared for discharge in advance of when the patient is ready.”
 

A boost for discharges

Mark Williams, MD, MHM, recently appointed chief of hospital medicine at Washington University School of Medicine in St. Louis, and a principal investigator for Project BOOST (Better Outcomes by Optimizing Safe Transitions), SHM’s quality improvement mentoring initiative aimed at helping hospitals improve care transitions, said that debates about DBN have gone on for a long time in hospital medicine.

“Around 2002, consultants told the CEO of a community hospital affiliated with Emory Healthcare that if our hospitalists could discharge patients before noon it would improve throughput,” he recalled. The consultants came from the hospitality industry, where DBN is easier to achieve.

But in hospital medicine, he said, “We use the whole day of the discharge in delivering care. I said to the CEO, ‘I can get you 100% discharge before noon – I’ll just hold the patients overnight,’” he explained. “In our initial experience, we pushed DBN up to about 10% -15%, and it opened up a few beds, which rapidly filled.”

Project BOOST encouraged the goal of getting patients ready to go out as soon as they were clinically ready, but did not advocate specifically for DBN, Dr. Williams said. “The problem is that hospital throughput starts to gum up when occupancy goes over 80% or 90%, and many academic medical centers regularly reach occupancy rates greater than 100%, particularly in the afternoon.” The deluge of patients includes transfers from other hospitals, postsurgical patients, and admissions from the emergency department.

“Boarding in the ED is a real issue,” he said. “Right now, it’s a crisis of overoccupancy, and the problem is that the pipeline is pouring patients into the system faster than they can be discharged.”

Dr. Williams believes there needs to be bigger thinking about these issues. Could hospitals, health systems, and hospitalists practice more preventive medicine so that some of these patients don’t need to come to the hospital? “Can you better address high blood pressure to prevent strokes and make sure patients with heart disease risk factors are enrolled in exercise and nutrition programs? What about access to healthy foods and the other social determinants of health? What if we provided adequate, consistent housing and transportation to medical visits?” he wondered.

Hospital at home programs may also offer some relief, he said. “If suddenly there weren’t so many emergency room visits by patients who need to get admitted, we’d have enough beds in the hospital.”
 

A more holistic view

John Nelson, MD, MHM, hospital medicine pioneer and management consultant, has been studying hospital throughput and policies to improve it for a long time. His 2010 column in The Hospitalist, “The Earlier the Better,” said attaching a financial incentive for hospitalists to discharge patients by a preset hour has produced mixed results.⁶ But Dr. Nelson offered some easy steps hospitalists can take to maximize earlier discharges, including to write “probable discharge tomorrow” as an order in the patient’s medical record.

The afternoon before a planned discharge, the hospitalist could talk to a patient’s family members about the discharge plan and order any outstanding tests to be done that evening to be ready for morning rounds – which he suggested should start by 7:00 a.m. The hospitalist could dictate the discharge summary the afternoon before. Even if a discharge can’t proceed as planned, the time isn’t necessarily wasted.

In a recent interview, Dr. Nelson noted that the movement to reduce average length of stay in the hospital has complicated the discharge picture by reducing a hospital’s flexibility. But he added that it’s still worth tracking and collecting data on discharge times, and to keep the conversation going. “Just don’t lose sight of the real goal, which is not DBN but optimal length-of-stay management,” he said.

Dr. Gundareddy said that, as his group has dealt with these issues, some steps have emerged to help manage discharges and throughput. “We didn’t have case management and social work services over the weekend, but when we added that support, it changed how our Mondays went.”

He encourages hospitalists to focus on the actual processes that create bottlenecks preventing throughput. “A good example of effective restructuring is lab testing. It’s amazing to think that you could have lab test results available for 7:00 a.m. rounds. There are areas that deserve more attention and more research regarding DBN. What is the impact of discharge before noon programs on the patients who aren’t being planned for discharge that day? Do they get neglected? I feel that happens sometimes.”

The COVID pandemic has further complicated these questions, Dr. Gundareddy said. “Early on in the pandemic, we were unsure how things were going with discharges, since all of the focus was on the COVID crisis. A lot of outpatient and surgical services came to a standstill, and there weren’t enough of the right kinds of beds for COVID patients. It was hard to align staff appropriately with the new clinical goals and to train them during the crisis.” Now, patients who delayed care during the pandemic are turning up at the hospital with greater acuity.

As with all incentives, DBN can have unintended consequences – especially if you monetize the practice, Dr. Verma said. “Most hospitalists are already working so hard – making so many decisions every day. These incentives could push decisions that aren’t in anybody’s best interests.”

Various groups have created comprehensive packages of protocols for improving transitions of care, he said. Organized programs to maximize efficiency of transitions and patient flow, including Project BOOST and Project RED (Re-Engineered Discharge) at Boston University Medical Center, are important sources of tools and resources. “But we should stop flogging hospitalists to discharge patients before noon,” Dr. Verma said, “Discharge is more complex than that. Instead, we should work to improve discharges in more holistic ways.”
 

References

1. Kirubarajan A et al. Morning discharges and patient length of stay in inpatient general internal medicine. J Hosp Med. 2021 Jun;16(6):333-8. doi: 10.12788/jhm.3605.

2. Shine D. Discharge before noon: An urban legend. Am J Med. 2015 May;128(5):445-6. doi:10.1016/j.amjmed.2014.12.011.

3. Zorian A et al. Discharge by noon: Toward a better understanding of benefits and costs. J Hosp Med. 2021 Jun;16(6):384. doi: 10.12788/jhm.3613.

4. Wertheimer B et al. Discharge before noon: Effect on throughput and sustainability. J Hosp Med. 2015 Oct;10(10):664-9. doi: 10.1002/jhm.2412.

5. Wertheimer B et al. Discharge before noon: an achievable hospital goal. J Hosp Med. 2014 Apr;9(4):210-4. doi: 10.1002/jhm.2154.

6. Nelson J. The earlier, the better. The Hospitalist. 2010 May.

A recent study published in the Journal of Hospital Medicine examined patient discharges from hospitals in Ontario, Canada, to determine if morning discharges were associated with positive outcomes. Some hospitalist programs have embraced discharge before noon (DBN) initiatives like those studied in the article.¹ Unfortunately, the researchers concluded that the Canadian DBNs did not positively impact hospital length of stay, readmissions, or mortality rates.

DBN has been a quality improvement target for hospitals hoping to improve throughput and free up scarce beds, while promoting patient safety by encouraging discharge as soon as patients are ready to leave. Yet other researchers have questioned its actual impact on quality metrics. One author called DBN’s purported impact an “urban legend,”² while a JHM editorial accompanying the Ontario study noted, “Hospitals are delicate organisms; a singular focus on one metric will undoubtedly impact others.”³

Might DBN be an artificial target that doesn’t actually enhance throughput, but leads instead to unintended consequences, such as patients being held over for an additional night in the hospital, rather than being discharged when they are ready to go on the afternoon before, in order to boost DBN rates? A perennial debate in hospital medicine is likely to be reignited by the new findings.
 

‘No significant overall association’

Quality improvement initiatives targeting morning discharges have included stakeholder meetings, incentives programs, discharge-centered breakfast programs, and creation of deadlines for discharge orders, the new study’s authors noted. Although these initiatives have gained support, critics have suggested that their supporting evidence is not robust.

The Canadian researchers retrospectively reviewed all patient admissions to general internal medicine services (GIMs) – largely similar to hospital medicine services in the United States – at seven hospitals in Toronto and Mississauga over a 7-year period ending Oct. 31, 2017, counting all of these patients who were discharged alive between 8 a.m. and noon. DBN averaged 19% of total live discharges across the diverse hospitals, with their diverse discharge practices.

But they found no significant overall association between morning discharge and hospital or emergency department length of stay. “Our findings suggest that increasing the number of morning discharges alone is unlikely to substantially improve patient throughput in GIM, but further research is needed to determine the effectiveness of specific interventions,” they concluded.

“We used a very narrow lens, looking specifically at throughput for the hospitals and emergency departments and whether DBN makes it more efficient,” said corresponding author Amol Verma, MD, MPhil, FRCPC, clinician-scientist at St. Michael’s Hospital, University of Toronto, in a recent interview. “What we found was that, on days when more patients are discharged in the morning, patients do not flow more quickly through the hospital. That suggests that increasing morning discharges is unlikely to make a difference.”
 

What does DBN really mean?

The semantics of DBN deserve further exploration. Is DBN about the actual hour of discharge, or the time when the hospitalist signs a discharge order – which may be well before the patient actually gets a wheelchair ride down to the hospital’s front doors? And if DBN is an organized program promoting morning discharges, how is it incentivized or otherwise rewarded?

Other factors, such as arrival of medications from the pharmacy or results from clinical tests, access to an ambulance if needed, transport to the front door, and bed cleaning will impact how quickly a doctor’s discharge orders get acted upon – and how quickly the newly emptied bed is available for the next occupant.

The clinician’s views on discharge practices may diverge from hospital administrator or health system perspectives, with its imperatives for efficient throughput in order to bring in more patients, Dr. Verma said. The hospitalist is also concerned about whether the patient feels ready to go home. “We can all agree that patients should leave the hospital as soon as they are medically able to do so,” he said. Longer hospital stays are associated with increased rates of hospital-acquired infections and other iatrogenic complications.

But there is not agreement on the components of a safe discharge – or on the other dimensions of effective patient flow and transitions of care. How do we optimize treatments initiated in the hospital? Does the patient need one more CAT scan? And what about the concerns of patient-centered care? Does the patient have a caregiver able to help them when they get home? There is a lot of uncertainty, Dr. Verma said. “These kinds of decisions have to get made many times every day by hospitalists,” he noted.

“We find ourselves trying to mirror the ebbs and flows of the emergency department with what’s happening in the hospital,” said Venkat Gundareddy, MBBS, MPH, associate director of the division of hospital medicine at Johns Hopkins Medicine in Baltimore. “The majority of hospital discharges happen during business hours, but the emergency department doesn’t stop admitting overnight, thus creating a throughput challenge.” Discharges are also based on clinical outcomes and on patients transferring to other facilities that prefer patients to arrive earlier in the day.

“Hospitalists may not fully appreciate these dynamics, because we’re siloed on our units,” Dr. Gundareddy said. “There is a subset of patients who would fit the bill for early discharge, but other patients come into the hospital with greater complexities, and a need for more coordination. Their discharges are harder to predict, although it gets clearer as their care progresses.”

The hospitals included in the Ontario study are at 90% -100% capacity, so their flexibility is constrained and throughput is a critical issue, Dr. Verma said. “But if you start with the target of more efficient throughput, there is no logical or practical reason to assume that discharge before noon would help. If we believe someone is ready for discharge based on physiologic changes, their response to treatment, and the conclusion of medical investigations, none of these conform to the clock. It’s equally likely the patient achieves them in the afternoon or evening.”

Other views on morning discharge

An alternative perspective comes from New York University’s Langone Medical Center, which has published positive results, including earlier subsequent arrivals to the inpatient unit from the emergency department, from increasing its hospital’s DBN rate.⁴

The hospital has continued to encourage morning discharges, which have consistently run 35%-40% or more of total discharges on two acute inpatient units at Langone’s Tisch Hospital. A previous study described the multidisciplinary intervention that resulted in a statistically significant increase in DBN – from 11% to 38% in the first 13 months – while significantly reducing high-frequency admission peaks.⁵

“We’ve been doing DBN for a number of years,” said Benjamin Wertheimer, MD, a hospitalist at Langone Medical Center and one of the studies’ authors. It is an achievable – and sustainable – goal. “Many hospitals around the country have problems with the flow of patients. Many hospitals are full – even before accounting for the COVID pandemic.” There is good evidence that, for a patient who no longer requires hospitalization, getting them out as early as possible, with a safe plan for their discharge, is a good thing, he said. “We see DBN as an important operational metric.”

If the necessary work is done correctly on the afternoon before the discharge, then a DBN approach can push communication, coordination, and advance planning, Dr Wertheimer said. Otherwise, essential discharge tasks may lag until the last minute. “We try to put the pieces in place the day before through a better planned process. But it should never be that DBN takes precedence over when the patient is safely ready to go,” he said.

“Our true measure of success would be how well we are preparing, communicating, putting safe plans into place,” he added. “DBN does not in and of itself answer all the safety and quality concerns. We set priorities around specific quality targets. DBN is just one of our operational and safety measures.”

The DBN intervention at Langone started with a multidisciplinary kickoff event in which all team members received education on its importance, a clear description of roles in the DBN process, and a corresponding checklist of daily responsibilities. The checklist was utilized at newly implemented afternoon interdisciplinary rounds, scripted to identify next-day DBNs, and make sure everything is in place for them, he explained.

“We provide daily feedback to floor staff on the DBN percentage, celebrate success, and offer real-time opportunities for case review,” Dr. Wertheimer said. “We have been careful about how we message this goal. Quality and safety come first, and we want to be prepared for discharge in advance of when the patient is ready.”
 

A boost for discharges

Mark Williams, MD, MHM, recently appointed chief of hospital medicine at Washington University School of Medicine in St. Louis, and a principal investigator for Project BOOST (Better Outcomes by Optimizing Safe Transitions), SHM’s quality improvement mentoring initiative aimed at helping hospitals improve care transitions, said that debates about DBN have gone on for a long time in hospital medicine.

“Around 2002, consultants told the CEO of a community hospital affiliated with Emory Healthcare that if our hospitalists could discharge patients before noon it would improve throughput,” he recalled. The consultants came from the hospitality industry, where DBN is easier to achieve.

But in hospital medicine, he said, “We use the whole day of the discharge in delivering care. I said to the CEO, ‘I can get you 100% discharge before noon – I’ll just hold the patients overnight,’” he explained. “In our initial experience, we pushed DBN up to about 10% -15%, and it opened up a few beds, which rapidly filled.”

Project BOOST encouraged the goal of getting patients ready to go out as soon as they were clinically ready, but did not advocate specifically for DBN, Dr. Williams said. “The problem is that hospital throughput starts to gum up when occupancy goes over 80% or 90%, and many academic medical centers regularly reach occupancy rates greater than 100%, particularly in the afternoon.” The deluge of patients includes transfers from other hospitals, postsurgical patients, and admissions from the emergency department.

“Boarding in the ED is a real issue,” he said. “Right now, it’s a crisis of overoccupancy, and the problem is that the pipeline is pouring patients into the system faster than they can be discharged.”

Dr. Williams believes there needs to be bigger thinking about these issues. Could hospitals, health systems, and hospitalists practice more preventive medicine so that some of these patients don’t need to come to the hospital? “Can you better address high blood pressure to prevent strokes and make sure patients with heart disease risk factors are enrolled in exercise and nutrition programs? What about access to healthy foods and the other social determinants of health? What if we provided adequate, consistent housing and transportation to medical visits?” he wondered.

Hospital at home programs may also offer some relief, he said. “If suddenly there weren’t so many emergency room visits by patients who need to get admitted, we’d have enough beds in the hospital.”
 

A more holistic view

John Nelson, MD, MHM, hospital medicine pioneer and management consultant, has been studying hospital throughput and policies to improve it for a long time. His 2010 column in The Hospitalist, “The Earlier the Better,” said attaching a financial incentive for hospitalists to discharge patients by a preset hour has produced mixed results.⁶ But Dr. Nelson offered some easy steps hospitalists can take to maximize earlier discharges, including to write “probable discharge tomorrow” as an order in the patient’s medical record.

The afternoon before a planned discharge, the hospitalist could talk to a patient’s family members about the discharge plan and order any outstanding tests to be done that evening to be ready for morning rounds – which he suggested should start by 7:00 a.m. The hospitalist could dictate the discharge summary the afternoon before. Even if a discharge can’t proceed as planned, the time isn’t necessarily wasted.

In a recent interview, Dr. Nelson noted that the movement to reduce average length of stay in the hospital has complicated the discharge picture by reducing a hospital’s flexibility. But he added that it’s still worth tracking and collecting data on discharge times, and to keep the conversation going. “Just don’t lose sight of the real goal, which is not DBN but optimal length-of-stay management,” he said.

Dr. Gundareddy said that, as his group has dealt with these issues, some steps have emerged to help manage discharges and throughput. “We didn’t have case management and social work services over the weekend, but when we added that support, it changed how our Mondays went.”

He encourages hospitalists to focus on the actual processes that create bottlenecks preventing throughput. “A good example of effective restructuring is lab testing. It’s amazing to think that you could have lab test results available for 7:00 a.m. rounds. There are areas that deserve more attention and more research regarding DBN. What is the impact of discharge before noon programs on the patients who aren’t being planned for discharge that day? Do they get neglected? I feel that happens sometimes.”

The COVID pandemic has further complicated these questions, Dr. Gundareddy said. “Early on in the pandemic, we were unsure how things were going with discharges, since all of the focus was on the COVID crisis. A lot of outpatient and surgical services came to a standstill, and there weren’t enough of the right kinds of beds for COVID patients. It was hard to align staff appropriately with the new clinical goals and to train them during the crisis.” Now, patients who delayed care during the pandemic are turning up at the hospital with greater acuity.

As with all incentives, DBN can have unintended consequences – especially if you monetize the practice, Dr. Verma said. “Most hospitalists are already working so hard – making so many decisions every day. These incentives could push decisions that aren’t in anybody’s best interests.”

Various groups have created comprehensive packages of protocols for improving transitions of care, he said. Organized programs to maximize efficiency of transitions and patient flow, including Project BOOST and Project RED (Re-Engineered Discharge) at Boston University Medical Center, are important sources of tools and resources. “But we should stop flogging hospitalists to discharge patients before noon,” Dr. Verma said, “Discharge is more complex than that. Instead, we should work to improve discharges in more holistic ways.”
 

References

1. Kirubarajan A et al. Morning discharges and patient length of stay in inpatient general internal medicine. J Hosp Med. 2021 Jun;16(6):333-8. doi: 10.12788/jhm.3605.

2. Shine D. Discharge before noon: An urban legend. Am J Med. 2015 May;128(5):445-6. doi:10.1016/j.amjmed.2014.12.011.

3. Zorian A et al. Discharge by noon: Toward a better understanding of benefits and costs. J Hosp Med. 2021 Jun;16(6):384. doi: 10.12788/jhm.3613.

4. Wertheimer B et al. Discharge before noon: Effect on throughput and sustainability. J Hosp Med. 2015 Oct;10(10):664-9. doi: 10.1002/jhm.2412.

5. Wertheimer B et al. Discharge before noon: an achievable hospital goal. J Hosp Med. 2014 Apr;9(4):210-4. doi: 10.1002/jhm.2154.

6. Nelson J. The earlier, the better. The Hospitalist. 2010 May.

A recent study published in the Journal of Hospital Medicine examined patient discharges from hospitals in Ontario, Canada, to determine if morning discharges were associated with positive outcomes. Some hospitalist programs have embraced discharge before noon (DBN) initiatives like those studied in the article.¹ Unfortunately, the researchers concluded that the Canadian DBNs did not positively impact hospital length of stay, readmissions, or mortality rates.

DBN has been a quality improvement target for hospitals hoping to improve throughput and free up scarce beds, while promoting patient safety by encouraging discharge as soon as patients are ready to leave. Yet other researchers have questioned its actual impact on quality metrics. One author called DBN’s purported impact an “urban legend,”² while a JHM editorial accompanying the Ontario study noted, “Hospitals are delicate organisms; a singular focus on one metric will undoubtedly impact others.”³

Might DBN be an artificial target that doesn’t actually enhance throughput, but leads instead to unintended consequences, such as patients being held over for an additional night in the hospital, rather than being discharged when they are ready to go on the afternoon before, in order to boost DBN rates? A perennial debate in hospital medicine is likely to be reignited by the new findings.
 

‘No significant overall association’

Quality improvement initiatives targeting morning discharges have included stakeholder meetings, incentives programs, discharge-centered breakfast programs, and creation of deadlines for discharge orders, the new study’s authors noted. Although these initiatives have gained support, critics have suggested that their supporting evidence is not robust.

The Canadian researchers retrospectively reviewed all patient admissions to general internal medicine services (GIMs) – largely similar to hospital medicine services in the United States – at seven hospitals in Toronto and Mississauga over a 7-year period ending Oct. 31, 2017, counting all of these patients who were discharged alive between 8 a.m. and noon. DBN averaged 19% of total live discharges across the diverse hospitals, with their diverse discharge practices.

But they found no significant overall association between morning discharge and hospital or emergency department length of stay. “Our findings suggest that increasing the number of morning discharges alone is unlikely to substantially improve patient throughput in GIM, but further research is needed to determine the effectiveness of specific interventions,” they concluded.

“We used a very narrow lens, looking specifically at throughput for the hospitals and emergency departments and whether DBN makes it more efficient,” said corresponding author Amol Verma, MD, MPhil, FRCPC, clinician-scientist at St. Michael’s Hospital, University of Toronto, in a recent interview. “What we found was that, on days when more patients are discharged in the morning, patients do not flow more quickly through the hospital. That suggests that increasing morning discharges is unlikely to make a difference.”
 

What does DBN really mean?

The semantics of DBN deserve further exploration. Is DBN about the actual hour of discharge, or the time when the hospitalist signs a discharge order – which may be well before the patient actually gets a wheelchair ride down to the hospital’s front doors? And if DBN is an organized program promoting morning discharges, how is it incentivized or otherwise rewarded?

Other factors, such as arrival of medications from the pharmacy or results from clinical tests, access to an ambulance if needed, transport to the front door, and bed cleaning will impact how quickly a doctor’s discharge orders get acted upon – and how quickly the newly emptied bed is available for the next occupant.

The clinician’s views on discharge practices may diverge from hospital administrator or health system perspectives, with its imperatives for efficient throughput in order to bring in more patients, Dr. Verma said. The hospitalist is also concerned about whether the patient feels ready to go home. “We can all agree that patients should leave the hospital as soon as they are medically able to do so,” he said. Longer hospital stays are associated with increased rates of hospital-acquired infections and other iatrogenic complications.

But there is not agreement on the components of a safe discharge – or on the other dimensions of effective patient flow and transitions of care. How do we optimize treatments initiated in the hospital? Does the patient need one more CAT scan? And what about the concerns of patient-centered care? Does the patient have a caregiver able to help them when they get home? There is a lot of uncertainty, Dr. Verma said. “These kinds of decisions have to get made many times every day by hospitalists,” he noted.

“We find ourselves trying to mirror the ebbs and flows of the emergency department with what’s happening in the hospital,” said Venkat Gundareddy, MBBS, MPH, associate director of the division of hospital medicine at Johns Hopkins Medicine in Baltimore. “The majority of hospital discharges happen during business hours, but the emergency department doesn’t stop admitting overnight, thus creating a throughput challenge.” Discharges are also based on clinical outcomes and on patients transferring to other facilities that prefer patients to arrive earlier in the day.

“Hospitalists may not fully appreciate these dynamics, because we’re siloed on our units,” Dr. Gundareddy said. “There is a subset of patients who would fit the bill for early discharge, but other patients come into the hospital with greater complexities, and a need for more coordination. Their discharges are harder to predict, although it gets clearer as their care progresses.”

The hospitals included in the Ontario study are at 90% -100% capacity, so their flexibility is constrained and throughput is a critical issue, Dr. Verma said. “But if you start with the target of more efficient throughput, there is no logical or practical reason to assume that discharge before noon would help. If we believe someone is ready for discharge based on physiologic changes, their response to treatment, and the conclusion of medical investigations, none of these conform to the clock. It’s equally likely the patient achieves them in the afternoon or evening.”

Other views on morning discharge

An alternative perspective comes from New York University’s Langone Medical Center, which has published positive results, including earlier subsequent arrivals to the inpatient unit from the emergency department, from increasing its hospital’s DBN rate.⁴

The hospital has continued to encourage morning discharges, which have consistently run 35%-40% or more of total discharges on two acute inpatient units at Langone’s Tisch Hospital. A previous study described the multidisciplinary intervention that resulted in a statistically significant increase in DBN – from 11% to 38% in the first 13 months – while significantly reducing high-frequency admission peaks.⁵

“We’ve been doing DBN for a number of years,” said Benjamin Wertheimer, MD, a hospitalist at Langone Medical Center and one of the studies’ authors. It is an achievable – and sustainable – goal. “Many hospitals around the country have problems with the flow of patients. Many hospitals are full – even before accounting for the COVID pandemic.” There is good evidence that, for a patient who no longer requires hospitalization, getting them out as early as possible, with a safe plan for their discharge, is a good thing, he said. “We see DBN as an important operational metric.”

If the necessary work is done correctly on the afternoon before the discharge, then a DBN approach can push communication, coordination, and advance planning, Dr Wertheimer said. Otherwise, essential discharge tasks may lag until the last minute. “We try to put the pieces in place the day before through a better planned process. But it should never be that DBN takes precedence over when the patient is safely ready to go,” he said.

“Our true measure of success would be how well we are preparing, communicating, putting safe plans into place,” he added. “DBN does not in and of itself answer all the safety and quality concerns. We set priorities around specific quality targets. DBN is just one of our operational and safety measures.”

The DBN intervention at Langone started with a multidisciplinary kickoff event in which all team members received education on its importance, a clear description of roles in the DBN process, and a corresponding checklist of daily responsibilities. The checklist was utilized at newly implemented afternoon interdisciplinary rounds, scripted to identify next-day DBNs, and make sure everything is in place for them, he explained.

“We provide daily feedback to floor staff on the DBN percentage, celebrate success, and offer real-time opportunities for case review,” Dr. Wertheimer said. “We have been careful about how we message this goal. Quality and safety come first, and we want to be prepared for discharge in advance of when the patient is ready.”
 

A boost for discharges

Mark Williams, MD, MHM, recently appointed chief of hospital medicine at Washington University School of Medicine in St. Louis, and a principal investigator for Project BOOST (Better Outcomes by Optimizing Safe Transitions), SHM’s quality improvement mentoring initiative aimed at helping hospitals improve care transitions, said that debates about DBN have gone on for a long time in hospital medicine.

“Around 2002, consultants told the CEO of a community hospital affiliated with Emory Healthcare that if our hospitalists could discharge patients before noon it would improve throughput,” he recalled. The consultants came from the hospitality industry, where DBN is easier to achieve.

But in hospital medicine, he said, “We use the whole day of the discharge in delivering care. I said to the CEO, ‘I can get you 100% discharge before noon – I’ll just hold the patients overnight,’” he explained. “In our initial experience, we pushed DBN up to about 10% -15%, and it opened up a few beds, which rapidly filled.”

Project BOOST encouraged the goal of getting patients ready to go out as soon as they were clinically ready, but did not advocate specifically for DBN, Dr. Williams said. “The problem is that hospital throughput starts to gum up when occupancy goes over 80% or 90%, and many academic medical centers regularly reach occupancy rates greater than 100%, particularly in the afternoon.” The deluge of patients includes transfers from other hospitals, postsurgical patients, and admissions from the emergency department.

“Boarding in the ED is a real issue,” he said. “Right now, it’s a crisis of overoccupancy, and the problem is that the pipeline is pouring patients into the system faster than they can be discharged.”

Dr. Williams believes there needs to be bigger thinking about these issues. Could hospitals, health systems, and hospitalists practice more preventive medicine so that some of these patients don’t need to come to the hospital? “Can you better address high blood pressure to prevent strokes and make sure patients with heart disease risk factors are enrolled in exercise and nutrition programs? What about access to healthy foods and the other social determinants of health? What if we provided adequate, consistent housing and transportation to medical visits?” he wondered.

Hospital at home programs may also offer some relief, he said. “If suddenly there weren’t so many emergency room visits by patients who need to get admitted, we’d have enough beds in the hospital.”
 

A more holistic view

John Nelson, MD, MHM, hospital medicine pioneer and management consultant, has been studying hospital throughput and policies to improve it for a long time. His 2010 column in The Hospitalist, “The Earlier the Better,” said attaching a financial incentive for hospitalists to discharge patients by a preset hour has produced mixed results.⁶ But Dr. Nelson offered some easy steps hospitalists can take to maximize earlier discharges, including to write “probable discharge tomorrow” as an order in the patient’s medical record.

The afternoon before a planned discharge, the hospitalist could talk to a patient’s family members about the discharge plan and order any outstanding tests to be done that evening to be ready for morning rounds – which he suggested should start by 7:00 a.m. The hospitalist could dictate the discharge summary the afternoon before. Even if a discharge can’t proceed as planned, the time isn’t necessarily wasted.

In a recent interview, Dr. Nelson noted that the movement to reduce average length of stay in the hospital has complicated the discharge picture by reducing a hospital’s flexibility. But he added that it’s still worth tracking and collecting data on discharge times, and to keep the conversation going. “Just don’t lose sight of the real goal, which is not DBN but optimal length-of-stay management,” he said.

Dr. Gundareddy said that, as his group has dealt with these issues, some steps have emerged to help manage discharges and throughput. “We didn’t have case management and social work services over the weekend, but when we added that support, it changed how our Mondays went.”

He encourages hospitalists to focus on the actual processes that create bottlenecks preventing throughput. “A good example of effective restructuring is lab testing. It’s amazing to think that you could have lab test results available for 7:00 a.m. rounds. There are areas that deserve more attention and more research regarding DBN. What is the impact of discharge before noon programs on the patients who aren’t being planned for discharge that day? Do they get neglected? I feel that happens sometimes.”

The COVID pandemic has further complicated these questions, Dr. Gundareddy said. “Early on in the pandemic, we were unsure how things were going with discharges, since all of the focus was on the COVID crisis. A lot of outpatient and surgical services came to a standstill, and there weren’t enough of the right kinds of beds for COVID patients. It was hard to align staff appropriately with the new clinical goals and to train them during the crisis.” Now, patients who delayed care during the pandemic are turning up at the hospital with greater acuity.

As with all incentives, DBN can have unintended consequences – especially if you monetize the practice, Dr. Verma said. “Most hospitalists are already working so hard – making so many decisions every day. These incentives could push decisions that aren’t in anybody’s best interests.”

Various groups have created comprehensive packages of protocols for improving transitions of care, he said. Organized programs to maximize efficiency of transitions and patient flow, including Project BOOST and Project RED (Re-Engineered Discharge) at Boston University Medical Center, are important sources of tools and resources. “But we should stop flogging hospitalists to discharge patients before noon,” Dr. Verma said, “Discharge is more complex than that. Instead, we should work to improve discharges in more holistic ways.”
 

References

1. Kirubarajan A et al. Morning discharges and patient length of stay in inpatient general internal medicine. J Hosp Med. 2021 Jun;16(6):333-8. doi: 10.12788/jhm.3605.

2. Shine D. Discharge before noon: An urban legend. Am J Med. 2015 May;128(5):445-6. doi:10.1016/j.amjmed.2014.12.011.

3. Zorian A et al. Discharge by noon: Toward a better understanding of benefits and costs. J Hosp Med. 2021 Jun;16(6):384. doi: 10.12788/jhm.3613.

4. Wertheimer B et al. Discharge before noon: Effect on throughput and sustainability. J Hosp Med. 2015 Oct;10(10):664-9. doi: 10.1002/jhm.2412.

5. Wertheimer B et al. Discharge before noon: an achievable hospital goal. J Hosp Med. 2014 Apr;9(4):210-4. doi: 10.1002/jhm.2154.

6. Nelson J. The earlier, the better. The Hospitalist. 2010 May.

Only 12 state medical boards have taken action against physicians who have spread false or misleading information about COVID-19, according to a new survey from the Federation of State Medical Boards (FSMB).

The FSMB reports that in its 2021 annual survey two-thirds of its 71 member boards (which includes the United States, its territories, and Washington, DC) reported an increase in complaints about doctors spreading false or misleading information.

“The staggering number of state medical boards that have seen an increase in COVID-19 disinformation complaints is a sign of how widespread the issue has become,” said Humayun J. Chaudhry, DO, MACP, president and CEO of the FSMB, in a statement.

The FSMB board of directors warned physicians in July that they risked disciplinary action if they spread COVID-19 vaccine misinformation or disinformation.

The organization said 15 state boards have now adopted similar statements.

Dr. Chaudhry said the FSMB was “encouraged by the number of boards that have already taken action to combat COVID-19 disinformation by disciplining physicians who engage in that behavior and by reminding all physicians that their words and actions matter, and they should think twice before spreading disinformation that may harm patients.”

This news organization asked the FSMB for further comment on why more physicians have not been disciplined, but did not receive a response before publication.

Misinformation policies a new battleground

The FSMB and member board policies on COVID-19 around the country have become a new front in the war against mandates and restrictions.

The Tennessee Board of Medical Examiners voted just recently to remove its statement of policy against the spread of misinformation from its website after a Republican lawmaker allegedly threatened to dissolve the board.

The vote came just a few months after the board had approved the policy. The board did not rescind the policy, however, according to a report by the Associated Press.

In California, the president of the state’s medical board tweeted on December 8 about what she said was an incident of harassment by a group that has promoted “fake COVID-19 treatments.”Ms. Kristina Lawson said she observed four men sitting in front of her house in a truck. They flew a drone over her residence, and then followed her to work, parking nose-to-nose with her vehicle.

Ms. Lawson claimed that when she went to drive home the four men ambushed her in what was by then a dark parking garage. She said her “concern turned to terror” as they jumped out, cameras and recording equipment in hand.

The men told law enforcement called to the scene that they were just trying to interview her, according to a statement emailed by Ms. Lawson.

They had not made such a request to the California Medical Board.

Ms. Lawson tweeted that she would continue to volunteer for the board. “That means protecting Californians from bad doctors, and ensuring disinformation and misinformation do not detract from our work to protect patients and consumers,” she wrote.

The men who ambushed Ms. Larson allegedly identified themselves and were wearing clothing emblazoned with the logo of “America’s Frontline Doctors,” an organization that has trafficked in COVID-19 conspiracy theories and promoted unproven treatments like hydroxychloroquine and ivermectin, according to Time. It is led by Simone Gold, MD, who was arrested for breaching the U.S. Capitol on January 6.

Despite her activities, on November 30, the California Medical Board renewed Ms. Gold’s 2-year license to practice.

Who’s being disciplined, who’s not

Dr. Gold is not alone. An investigation by NPRin September found that 15 of 16 physicians who have spread false information in a high-profile manner have medical licenses in good standing.

Sherri Tenpenny, DO, who has claimed that COVID-19 vaccines magnetize people and “interface” with 5G cell phone towers, was able to renew her license with the Ohio State Medical Board on October 1, according to the Cincinnati Enquirer.

Some boards have acted. The Oregon Medical Board revoked the license of Steven LaTulippe, MD, and fined him $10,000 for spreading misinformation about masks and overprescribing opioids.

In August, Rhode Island’s Board of Medical Licensure suspended Mark Brody’s license for 5 years after finding that the doctor spread falsehoods about COVID-19 vaccines, according to board documents.

Maine physician Paul Gosselin, DO, is on temporary suspension until a February hearing, while the osteopathic board investigates his issuance of vaccine exemption letters and the promotion of unproven COVID-19 therapies.

The board found that Gosselin had “engaged in conduct that constitutes fraud or deceit,” according to official documents.

The Washington State Medical Board has opened an investigation into Ryan N. Cole, MD, a physician who has claimed that COVID vaccines are “fake,” and was appointed to a regional health board in Idaho in September, according to the Washington Post.

The Idaho Capital Sun reported that Dr. Cole claims he is licensed in 11 states, including Washington. The Idaho Medical Association has also filed a complaint about Dr. Cole with the Idaho Board of Medicine, according to the paper.

New FSMB guidance coming

The FSMB said it expects more disciplinary actions as investigations continue to unfold.

The organization is drafting a new policy document that will include further guidelines and recommendations for state medical boards “to help address the spread of disinformation,” it said. The final document would be released in April 2022.

In the meantime, some states, like Tennessee and others, are trying to find ways to counter the current policy — a development the FSMB called “troubling.”

“The FSMB strongly opposes any effort to restrict a board’s authority to evaluate the standard of care and assess risk for patient harm,” the organization said in its statement.

A version of this article was first published on Medscape.com.

Only 12 state medical boards have taken action against physicians who have spread false or misleading information about COVID-19, according to a new survey from the Federation of State Medical Boards (FSMB).

The FSMB reports that in its 2021 annual survey two-thirds of its 71 member boards (which includes the United States, its territories, and Washington, DC) reported an increase in complaints about doctors spreading false or misleading information.

“The staggering number of state medical boards that have seen an increase in COVID-19 disinformation complaints is a sign of how widespread the issue has become,” said Humayun J. Chaudhry, DO, MACP, president and CEO of the FSMB, in a statement.

The FSMB board of directors warned physicians in July that they risked disciplinary action if they spread COVID-19 vaccine misinformation or disinformation.

The organization said 15 state boards have now adopted similar statements.

Dr. Chaudhry said the FSMB was “encouraged by the number of boards that have already taken action to combat COVID-19 disinformation by disciplining physicians who engage in that behavior and by reminding all physicians that their words and actions matter, and they should think twice before spreading disinformation that may harm patients.”

This news organization asked the FSMB for further comment on why more physicians have not been disciplined, but did not receive a response before publication.

Misinformation policies a new battleground

The FSMB and member board policies on COVID-19 around the country have become a new front in the war against mandates and restrictions.

The Tennessee Board of Medical Examiners voted just recently to remove its statement of policy against the spread of misinformation from its website after a Republican lawmaker allegedly threatened to dissolve the board.

The vote came just a few months after the board had approved the policy. The board did not rescind the policy, however, according to a report by the Associated Press.

In California, the president of the state’s medical board tweeted on December 8 about what she said was an incident of harassment by a group that has promoted “fake COVID-19 treatments.”Ms. Kristina Lawson said she observed four men sitting in front of her house in a truck. They flew a drone over her residence, and then followed her to work, parking nose-to-nose with her vehicle.

Ms. Lawson claimed that when she went to drive home the four men ambushed her in what was by then a dark parking garage. She said her “concern turned to terror” as they jumped out, cameras and recording equipment in hand.

The men told law enforcement called to the scene that they were just trying to interview her, according to a statement emailed by Ms. Lawson.

They had not made such a request to the California Medical Board.

Ms. Lawson tweeted that she would continue to volunteer for the board. “That means protecting Californians from bad doctors, and ensuring disinformation and misinformation do not detract from our work to protect patients and consumers,” she wrote.

The men who ambushed Ms. Larson allegedly identified themselves and were wearing clothing emblazoned with the logo of “America’s Frontline Doctors,” an organization that has trafficked in COVID-19 conspiracy theories and promoted unproven treatments like hydroxychloroquine and ivermectin, according to Time. It is led by Simone Gold, MD, who was arrested for breaching the U.S. Capitol on January 6.

Despite her activities, on November 30, the California Medical Board renewed Ms. Gold’s 2-year license to practice.

Who’s being disciplined, who’s not

Dr. Gold is not alone. An investigation by NPRin September found that 15 of 16 physicians who have spread false information in a high-profile manner have medical licenses in good standing.

Sherri Tenpenny, DO, who has claimed that COVID-19 vaccines magnetize people and “interface” with 5G cell phone towers, was able to renew her license with the Ohio State Medical Board on October 1, according to the Cincinnati Enquirer.

Some boards have acted. The Oregon Medical Board revoked the license of Steven LaTulippe, MD, and fined him $10,000 for spreading misinformation about masks and overprescribing opioids.

In August, Rhode Island’s Board of Medical Licensure suspended Mark Brody’s license for 5 years after finding that the doctor spread falsehoods about COVID-19 vaccines, according to board documents.

Maine physician Paul Gosselin, DO, is on temporary suspension until a February hearing, while the osteopathic board investigates his issuance of vaccine exemption letters and the promotion of unproven COVID-19 therapies.

The board found that Gosselin had “engaged in conduct that constitutes fraud or deceit,” according to official documents.

The Washington State Medical Board has opened an investigation into Ryan N. Cole, MD, a physician who has claimed that COVID vaccines are “fake,” and was appointed to a regional health board in Idaho in September, according to the Washington Post.

The Idaho Capital Sun reported that Dr. Cole claims he is licensed in 11 states, including Washington. The Idaho Medical Association has also filed a complaint about Dr. Cole with the Idaho Board of Medicine, according to the paper.

New FSMB guidance coming

The FSMB said it expects more disciplinary actions as investigations continue to unfold.

The organization is drafting a new policy document that will include further guidelines and recommendations for state medical boards “to help address the spread of disinformation,” it said. The final document would be released in April 2022.

In the meantime, some states, like Tennessee and others, are trying to find ways to counter the current policy — a development the FSMB called “troubling.”

“The FSMB strongly opposes any effort to restrict a board’s authority to evaluate the standard of care and assess risk for patient harm,” the organization said in its statement.

A version of this article was first published on Medscape.com.

Only 12 state medical boards have taken action against physicians who have spread false or misleading information about COVID-19, according to a new survey from the Federation of State Medical Boards (FSMB).

The FSMB reports that in its 2021 annual survey two-thirds of its 71 member boards (which includes the United States, its territories, and Washington, DC) reported an increase in complaints about doctors spreading false or misleading information.

“The staggering number of state medical boards that have seen an increase in COVID-19 disinformation complaints is a sign of how widespread the issue has become,” said Humayun J. Chaudhry, DO, MACP, president and CEO of the FSMB, in a statement.

The FSMB board of directors warned physicians in July that they risked disciplinary action if they spread COVID-19 vaccine misinformation or disinformation.

The organization said 15 state boards have now adopted similar statements.

Dr. Chaudhry said the FSMB was “encouraged by the number of boards that have already taken action to combat COVID-19 disinformation by disciplining physicians who engage in that behavior and by reminding all physicians that their words and actions matter, and they should think twice before spreading disinformation that may harm patients.”

This news organization asked the FSMB for further comment on why more physicians have not been disciplined, but did not receive a response before publication.

Misinformation policies a new battleground

The FSMB and member board policies on COVID-19 around the country have become a new front in the war against mandates and restrictions.

The Tennessee Board of Medical Examiners voted just recently to remove its statement of policy against the spread of misinformation from its website after a Republican lawmaker allegedly threatened to dissolve the board.

The vote came just a few months after the board had approved the policy. The board did not rescind the policy, however, according to a report by the Associated Press.

In California, the president of the state’s medical board tweeted on December 8 about what she said was an incident of harassment by a group that has promoted “fake COVID-19 treatments.”Ms. Kristina Lawson said she observed four men sitting in front of her house in a truck. They flew a drone over her residence, and then followed her to work, parking nose-to-nose with her vehicle.

Ms. Lawson claimed that when she went to drive home the four men ambushed her in what was by then a dark parking garage. She said her “concern turned to terror” as they jumped out, cameras and recording equipment in hand.

The men told law enforcement called to the scene that they were just trying to interview her, according to a statement emailed by Ms. Lawson.

They had not made such a request to the California Medical Board.

Ms. Lawson tweeted that she would continue to volunteer for the board. “That means protecting Californians from bad doctors, and ensuring disinformation and misinformation do not detract from our work to protect patients and consumers,” she wrote.

The men who ambushed Ms. Larson allegedly identified themselves and were wearing clothing emblazoned with the logo of “America’s Frontline Doctors,” an organization that has trafficked in COVID-19 conspiracy theories and promoted unproven treatments like hydroxychloroquine and ivermectin, according to Time. It is led by Simone Gold, MD, who was arrested for breaching the U.S. Capitol on January 6.

Despite her activities, on November 30, the California Medical Board renewed Ms. Gold’s 2-year license to practice.

Who’s being disciplined, who’s not

Dr. Gold is not alone. An investigation by NPRin September found that 15 of 16 physicians who have spread false information in a high-profile manner have medical licenses in good standing.

Sherri Tenpenny, DO, who has claimed that COVID-19 vaccines magnetize people and “interface” with 5G cell phone towers, was able to renew her license with the Ohio State Medical Board on October 1, according to the Cincinnati Enquirer.

Some boards have acted. The Oregon Medical Board revoked the license of Steven LaTulippe, MD, and fined him $10,000 for spreading misinformation about masks and overprescribing opioids.

In August, Rhode Island’s Board of Medical Licensure suspended Mark Brody’s license for 5 years after finding that the doctor spread falsehoods about COVID-19 vaccines, according to board documents.

Maine physician Paul Gosselin, DO, is on temporary suspension until a February hearing, while the osteopathic board investigates his issuance of vaccine exemption letters and the promotion of unproven COVID-19 therapies.

The board found that Gosselin had “engaged in conduct that constitutes fraud or deceit,” according to official documents.

The Washington State Medical Board has opened an investigation into Ryan N. Cole, MD, a physician who has claimed that COVID vaccines are “fake,” and was appointed to a regional health board in Idaho in September, according to the Washington Post.

The Idaho Capital Sun reported that Dr. Cole claims he is licensed in 11 states, including Washington. The Idaho Medical Association has also filed a complaint about Dr. Cole with the Idaho Board of Medicine, according to the paper.

New FSMB guidance coming

The FSMB said it expects more disciplinary actions as investigations continue to unfold.

The organization is drafting a new policy document that will include further guidelines and recommendations for state medical boards “to help address the spread of disinformation,” it said. The final document would be released in April 2022.

In the meantime, some states, like Tennessee and others, are trying to find ways to counter the current policy — a development the FSMB called “troubling.”

“The FSMB strongly opposes any effort to restrict a board’s authority to evaluate the standard of care and assess risk for patient harm,” the organization said in its statement.

A version of this article was first published on Medscape.com.