Ob.Gyn. News

On April 13, the Centers for Disease Control and Prevention and the Food and Drug Administration issued a joint statement recommending a pause in Johnson & Johnson vaccine administration, pending review of six reported U.S. cases of a rare and severe type of blood clot occurring after receiving the Johnson & Johnson vaccine. To date, more than 6.8 million doses of that vaccine have been given in the United States, so at this point the rate of detected cases of this problem is less than one in a million.

The six cases occurred in women aged 18-48 years, and symptoms occurred 6-13 days after vaccination. In these cases, cerebral venous sinus thrombosis was seen in addition to thrombocytopenia.

Physicians may receive calls from concerned patients who have received a COVID vaccine. However, more than 95% of the vaccine administrations in the United States to date have been the Pfizer and Moderna messenger RNA vaccines. No association between these vaccines and blood clots has been detected. Also, these six cases occurred within 2 weeks of Johnson & Johnson vaccination, so even among those receiving the Johnson & Johnson vaccine, those who are more than 3 weeks out from their vaccination have no need for concern regarding this rare complication.

Physicians should counsel those who have received the Johnson & Johnson vaccine less than 3 weeks ago to watch for easy bruising, gum bleeding, nose bleeds, leg or arm pain or swelling, severe headache or abdominal pain, shortness of breath, or chest pain. If they notice one or more of those symptoms, they should seek medical attention.

The Centers for Disease Control and Prevention will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the six U.S. cases of the Johnson & Johnson vaccine and determine their significance.

Several cases of unusual thromboses and thrombocytopenia have been detected after the Oxford AstraZeneca vaccine, which uses the same adenovirus vector technology as the Johnson & Johnson vaccine, but which is not authorized for use in the United States. The Oxford AstraZeneca vaccine uses a recombinant deficient chimpanzee adenovirus to deliver the message to cells to produce antibody against the SARS-CoV-2 spike protein. The Johnson & Johnson vaccine uses a recombinant deficient human adenovirus to deliver this same message.  

Two recent reports in the New England Journal of Medicine have reported on thrombosis and thrombocytopenia after the Oxford AstraZeneca vaccine in Europe. Both of these reports identified high levels of IgG antibodies to platelet factor 4–polyanion complexes, similar to the mechanism of heparin-induced thrombocytopenia. The term vaccine-induced immune thrombocytopenia was proposed for this phenomenon. Treatment of this condition involves administration of intravenous immunoglobulin and nonheparin anticoagulants. Recent updates from the World Health Organization report that 169 cases of cerebral venous sinus thrombosis and 53 of splanchnic venous thrombosis occurred after 34 million doses of the Oxford AstraZeneca vaccine was administered in the European Union and United Kingdom.

While this pause in Johnson & Johnson vaccination is disappointing news amid increased cases in parts of the country, the Johnson & Johnson vaccines make up less than 5% of the U.S. vaccine doses administered to date. According to the CDC, more than 122 million Americans have received at least one dose and more than 75 million are fully vaccinated.

Dr. Patterson has received an honorarium from Pfizer for an antifungal symposium and is a subinvestigator for the Novavax vaccine. Her spouse served as a consultant for SCYNEXIS, as a speaker for Gilead Sciences and Basilea, and has received a research grant from the National Institutes of Health for the ACTT remdesivir trial.

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

On April 13, the Centers for Disease Control and Prevention and the Food and Drug Administration issued a joint statement recommending a pause in Johnson & Johnson vaccine administration, pending review of six reported U.S. cases of a rare and severe type of blood clot occurring after receiving the Johnson & Johnson vaccine. To date, more than 6.8 million doses of that vaccine have been given in the United States, so at this point the rate of detected cases of this problem is less than one in a million.

The six cases occurred in women aged 18-48 years, and symptoms occurred 6-13 days after vaccination. In these cases, cerebral venous sinus thrombosis was seen in addition to thrombocytopenia.

Physicians may receive calls from concerned patients who have received a COVID vaccine. However, more than 95% of the vaccine administrations in the United States to date have been the Pfizer and Moderna messenger RNA vaccines. No association between these vaccines and blood clots has been detected. Also, these six cases occurred within 2 weeks of Johnson & Johnson vaccination, so even among those receiving the Johnson & Johnson vaccine, those who are more than 3 weeks out from their vaccination have no need for concern regarding this rare complication.

Physicians should counsel those who have received the Johnson & Johnson vaccine less than 3 weeks ago to watch for easy bruising, gum bleeding, nose bleeds, leg or arm pain or swelling, severe headache or abdominal pain, shortness of breath, or chest pain. If they notice one or more of those symptoms, they should seek medical attention.

The Centers for Disease Control and Prevention will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the six U.S. cases of the Johnson & Johnson vaccine and determine their significance.

Several cases of unusual thromboses and thrombocytopenia have been detected after the Oxford AstraZeneca vaccine, which uses the same adenovirus vector technology as the Johnson & Johnson vaccine, but which is not authorized for use in the United States. The Oxford AstraZeneca vaccine uses a recombinant deficient chimpanzee adenovirus to deliver the message to cells to produce antibody against the SARS-CoV-2 spike protein. The Johnson & Johnson vaccine uses a recombinant deficient human adenovirus to deliver this same message.  

Two recent reports in the New England Journal of Medicine have reported on thrombosis and thrombocytopenia after the Oxford AstraZeneca vaccine in Europe. Both of these reports identified high levels of IgG antibodies to platelet factor 4–polyanion complexes, similar to the mechanism of heparin-induced thrombocytopenia. The term vaccine-induced immune thrombocytopenia was proposed for this phenomenon. Treatment of this condition involves administration of intravenous immunoglobulin and nonheparin anticoagulants. Recent updates from the World Health Organization report that 169 cases of cerebral venous sinus thrombosis and 53 of splanchnic venous thrombosis occurred after 34 million doses of the Oxford AstraZeneca vaccine was administered in the European Union and United Kingdom.

While this pause in Johnson & Johnson vaccination is disappointing news amid increased cases in parts of the country, the Johnson & Johnson vaccines make up less than 5% of the U.S. vaccine doses administered to date. According to the CDC, more than 122 million Americans have received at least one dose and more than 75 million are fully vaccinated.

Dr. Patterson has received an honorarium from Pfizer for an antifungal symposium and is a subinvestigator for the Novavax vaccine. Her spouse served as a consultant for SCYNEXIS, as a speaker for Gilead Sciences and Basilea, and has received a research grant from the National Institutes of Health for the ACTT remdesivir trial.

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

On April 13, the Centers for Disease Control and Prevention and the Food and Drug Administration issued a joint statement recommending a pause in Johnson & Johnson vaccine administration, pending review of six reported U.S. cases of a rare and severe type of blood clot occurring after receiving the Johnson & Johnson vaccine. To date, more than 6.8 million doses of that vaccine have been given in the United States, so at this point the rate of detected cases of this problem is less than one in a million.

The six cases occurred in women aged 18-48 years, and symptoms occurred 6-13 days after vaccination. In these cases, cerebral venous sinus thrombosis was seen in addition to thrombocytopenia.

Physicians may receive calls from concerned patients who have received a COVID vaccine. However, more than 95% of the vaccine administrations in the United States to date have been the Pfizer and Moderna messenger RNA vaccines. No association between these vaccines and blood clots has been detected. Also, these six cases occurred within 2 weeks of Johnson & Johnson vaccination, so even among those receiving the Johnson & Johnson vaccine, those who are more than 3 weeks out from their vaccination have no need for concern regarding this rare complication.

Physicians should counsel those who have received the Johnson & Johnson vaccine less than 3 weeks ago to watch for easy bruising, gum bleeding, nose bleeds, leg or arm pain or swelling, severe headache or abdominal pain, shortness of breath, or chest pain. If they notice one or more of those symptoms, they should seek medical attention.

The Centers for Disease Control and Prevention will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the six U.S. cases of the Johnson & Johnson vaccine and determine their significance.

Several cases of unusual thromboses and thrombocytopenia have been detected after the Oxford AstraZeneca vaccine, which uses the same adenovirus vector technology as the Johnson & Johnson vaccine, but which is not authorized for use in the United States. The Oxford AstraZeneca vaccine uses a recombinant deficient chimpanzee adenovirus to deliver the message to cells to produce antibody against the SARS-CoV-2 spike protein. The Johnson & Johnson vaccine uses a recombinant deficient human adenovirus to deliver this same message.  

Two recent reports in the New England Journal of Medicine have reported on thrombosis and thrombocytopenia after the Oxford AstraZeneca vaccine in Europe. Both of these reports identified high levels of IgG antibodies to platelet factor 4–polyanion complexes, similar to the mechanism of heparin-induced thrombocytopenia. The term vaccine-induced immune thrombocytopenia was proposed for this phenomenon. Treatment of this condition involves administration of intravenous immunoglobulin and nonheparin anticoagulants. Recent updates from the World Health Organization report that 169 cases of cerebral venous sinus thrombosis and 53 of splanchnic venous thrombosis occurred after 34 million doses of the Oxford AstraZeneca vaccine was administered in the European Union and United Kingdom.

While this pause in Johnson & Johnson vaccination is disappointing news amid increased cases in parts of the country, the Johnson & Johnson vaccines make up less than 5% of the U.S. vaccine doses administered to date. According to the CDC, more than 122 million Americans have received at least one dose and more than 75 million are fully vaccinated.

Dr. Patterson has received an honorarium from Pfizer for an antifungal symposium and is a subinvestigator for the Novavax vaccine. Her spouse served as a consultant for SCYNEXIS, as a speaker for Gilead Sciences and Basilea, and has received a research grant from the National Institutes of Health for the ACTT remdesivir trial.

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

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

[email protected]

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

[email protected]

Two recent articles in the medical literature provide new information on mucocutaneous manifestations of COVID-19 in children, which may help guide dermatologists in making accurate diagnoses and stratifying children at risk for serious, systemic illness due to the virus.

In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).

“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.

“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”

In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).

Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).

The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.

“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”

Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”

In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).

In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.

The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”

At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.

Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.

The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.

“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.

“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.

“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”

The researchers reported having no financial disclosures.
 

[email protected]

The next 20 years will see a big shift in cancer type rankings, researchers predict.

At the moment, the most common cancers in the United States are breast, lung, prostate, colorectal, and melanoma.

By 2040, melanoma will have become the second most common cancer type, while prostate cancer will drop in incidence all the way to 14, the study authors predicted. Breast cancer will remain the top cancer to be diagnosed, lung cancer will drop from second to third, and colorectal cancer will remain at fourth.

These predicted rankings of cancer types by their total number of annual cases were published online April 7, 2021, in JAMA Network Open.

The authors also rank cancer type by mortality. Currently, most cancer deaths are caused by lung cancer, followed by colorectal, pancreatic, and breast. By 2040, the most notable change in cancer deaths is that liver and intrahepatic bile duct cancer, currently at sixth, will jump up to third.

Two decades from now, the ranking in terms of cancer deaths will be lung, pancreatic, liver and intrahepatic bile duct, and colorectal.

“Our findings reflect the shifting dynamics of cancer screening and treatment,” lead author Lola Rahib, PhD, a pancreatic cancer scientist at Cancer Commons, the advocacy nonprofit, commented in a press statement.

The new analysis used population-growth projections (based on 2010 U.S. Census data) and current population-based cancer incidence and death rates (from Surveillance, Epidemiology, and End Results 2014-2016) to calculate the changes in incidences and deaths to the year 2040.

The projected, estimated numbers are not ironclad, the researchers acknowledged.

“Our projections assume that the observed rates and trends [from recent years] don’t change over time,” Dr. Rahib said in an interview, but she pointed out that change may indeed happen.

“Any long-term projections should be considered with a grain of salt,” said Kim Miller, MPH, a surveillance research scientist at the American Cancer Society, who was approached for comment.

Dr. Miller explained that “cancer trends can sometimes rapidly change within a few years.” Projections just 2-4 years ahead are “extremely difficult” and those 20 years ahead are even more so, she added in an interview.

“We’re encouraged to see the projected decreases in deaths from lung, colorectal, and breast cancer in the coming years,” said coauthor Lynn Matrisian, PhD, MBA, chief science officer at the Pancreatic Cancer Action Network. “It’s time to shift focus to some of the less commonly diagnosed cancers with the lowest survival rates, like pancreatic and liver cancer.”
 

Difference in opinion on prostate cancer

The huge fall in the incidence of prostate cancer that the authors predict will come about as a result of changes in prostate-specific antigen (PSA)–screening recommendations over the last 15 years, they suggested.

“The most recent change in 2018 recommends that men aged 55-69 can make their own decisions regarding screening, but previous changes recommended against PSA screening,” said Dr. Rahib.

“These changes in screening guidelines have influenced the number of diagnoses of prostate cancer in recent years and will continue to do so to 2040,” Dr. Rahib commented.

Dr. Miller casts doubt on this prediction.

Using data through 2017, “we have seen that the patterns in prostate cancer incidence are already shifting from the steep declines we saw in the early 2010s,” she said. “I would use caution when interpreting the overall trends for prostate, because this cancer in particular is dramatically affected by changes in recommendations for screening with the PSA test.”

Screening has also influenced colorectal cancer incidence, the authors pointed out, saying that the uptake of colorectal cancer screening is associated with a decrease in the number of colorectal cancers and deaths out to 2040, as a result of effectiveness of screening.

For breast cancer, the authors highlighted the fact that, although the number of breast cancers will continue to increase, the number of breast cancer deaths will decrease. That ongoing trend is most likely attributable to increased screening and advancements in treatment.

The study was supported by the National Institutes of Health, National Cancer Institute, the Cancer Prevention and Research Institute of Texas, Cancer Commons and the Pancreatic Cancer Action Network. The study authors and Dr. Miller disclosed no relevant financial relationships.

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

The next 20 years will see a big shift in cancer type rankings, researchers predict.

At the moment, the most common cancers in the United States are breast, lung, prostate, colorectal, and melanoma.

By 2040, melanoma will have become the second most common cancer type, while prostate cancer will drop in incidence all the way to 14, the study authors predicted. Breast cancer will remain the top cancer to be diagnosed, lung cancer will drop from second to third, and colorectal cancer will remain at fourth.

These predicted rankings of cancer types by their total number of annual cases were published online April 7, 2021, in JAMA Network Open.

The authors also rank cancer type by mortality. Currently, most cancer deaths are caused by lung cancer, followed by colorectal, pancreatic, and breast. By 2040, the most notable change in cancer deaths is that liver and intrahepatic bile duct cancer, currently at sixth, will jump up to third.

Two decades from now, the ranking in terms of cancer deaths will be lung, pancreatic, liver and intrahepatic bile duct, and colorectal.

“Our findings reflect the shifting dynamics of cancer screening and treatment,” lead author Lola Rahib, PhD, a pancreatic cancer scientist at Cancer Commons, the advocacy nonprofit, commented in a press statement.

The new analysis used population-growth projections (based on 2010 U.S. Census data) and current population-based cancer incidence and death rates (from Surveillance, Epidemiology, and End Results 2014-2016) to calculate the changes in incidences and deaths to the year 2040.

The projected, estimated numbers are not ironclad, the researchers acknowledged.

“Our projections assume that the observed rates and trends [from recent years] don’t change over time,” Dr. Rahib said in an interview, but she pointed out that change may indeed happen.

“Any long-term projections should be considered with a grain of salt,” said Kim Miller, MPH, a surveillance research scientist at the American Cancer Society, who was approached for comment.

Dr. Miller explained that “cancer trends can sometimes rapidly change within a few years.” Projections just 2-4 years ahead are “extremely difficult” and those 20 years ahead are even more so, she added in an interview.

“We’re encouraged to see the projected decreases in deaths from lung, colorectal, and breast cancer in the coming years,” said coauthor Lynn Matrisian, PhD, MBA, chief science officer at the Pancreatic Cancer Action Network. “It’s time to shift focus to some of the less commonly diagnosed cancers with the lowest survival rates, like pancreatic and liver cancer.”
 

Difference in opinion on prostate cancer

The huge fall in the incidence of prostate cancer that the authors predict will come about as a result of changes in prostate-specific antigen (PSA)–screening recommendations over the last 15 years, they suggested.

“The most recent change in 2018 recommends that men aged 55-69 can make their own decisions regarding screening, but previous changes recommended against PSA screening,” said Dr. Rahib.

“These changes in screening guidelines have influenced the number of diagnoses of prostate cancer in recent years and will continue to do so to 2040,” Dr. Rahib commented.

Dr. Miller casts doubt on this prediction.

Using data through 2017, “we have seen that the patterns in prostate cancer incidence are already shifting from the steep declines we saw in the early 2010s,” she said. “I would use caution when interpreting the overall trends for prostate, because this cancer in particular is dramatically affected by changes in recommendations for screening with the PSA test.”

Screening has also influenced colorectal cancer incidence, the authors pointed out, saying that the uptake of colorectal cancer screening is associated with a decrease in the number of colorectal cancers and deaths out to 2040, as a result of effectiveness of screening.

For breast cancer, the authors highlighted the fact that, although the number of breast cancers will continue to increase, the number of breast cancer deaths will decrease. That ongoing trend is most likely attributable to increased screening and advancements in treatment.

The study was supported by the National Institutes of Health, National Cancer Institute, the Cancer Prevention and Research Institute of Texas, Cancer Commons and the Pancreatic Cancer Action Network. The study authors and Dr. Miller disclosed no relevant financial relationships.

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

The next 20 years will see a big shift in cancer type rankings, researchers predict.

At the moment, the most common cancers in the United States are breast, lung, prostate, colorectal, and melanoma.

By 2040, melanoma will have become the second most common cancer type, while prostate cancer will drop in incidence all the way to 14, the study authors predicted. Breast cancer will remain the top cancer to be diagnosed, lung cancer will drop from second to third, and colorectal cancer will remain at fourth.

These predicted rankings of cancer types by their total number of annual cases were published online April 7, 2021, in JAMA Network Open.

The authors also rank cancer type by mortality. Currently, most cancer deaths are caused by lung cancer, followed by colorectal, pancreatic, and breast. By 2040, the most notable change in cancer deaths is that liver and intrahepatic bile duct cancer, currently at sixth, will jump up to third.

Two decades from now, the ranking in terms of cancer deaths will be lung, pancreatic, liver and intrahepatic bile duct, and colorectal.

“Our findings reflect the shifting dynamics of cancer screening and treatment,” lead author Lola Rahib, PhD, a pancreatic cancer scientist at Cancer Commons, the advocacy nonprofit, commented in a press statement.

The new analysis used population-growth projections (based on 2010 U.S. Census data) and current population-based cancer incidence and death rates (from Surveillance, Epidemiology, and End Results 2014-2016) to calculate the changes in incidences and deaths to the year 2040.

The projected, estimated numbers are not ironclad, the researchers acknowledged.

“Our projections assume that the observed rates and trends [from recent years] don’t change over time,” Dr. Rahib said in an interview, but she pointed out that change may indeed happen.

“Any long-term projections should be considered with a grain of salt,” said Kim Miller, MPH, a surveillance research scientist at the American Cancer Society, who was approached for comment.

Dr. Miller explained that “cancer trends can sometimes rapidly change within a few years.” Projections just 2-4 years ahead are “extremely difficult” and those 20 years ahead are even more so, she added in an interview.

“We’re encouraged to see the projected decreases in deaths from lung, colorectal, and breast cancer in the coming years,” said coauthor Lynn Matrisian, PhD, MBA, chief science officer at the Pancreatic Cancer Action Network. “It’s time to shift focus to some of the less commonly diagnosed cancers with the lowest survival rates, like pancreatic and liver cancer.”
 

Difference in opinion on prostate cancer

The huge fall in the incidence of prostate cancer that the authors predict will come about as a result of changes in prostate-specific antigen (PSA)–screening recommendations over the last 15 years, they suggested.

“The most recent change in 2018 recommends that men aged 55-69 can make their own decisions regarding screening, but previous changes recommended against PSA screening,” said Dr. Rahib.

“These changes in screening guidelines have influenced the number of diagnoses of prostate cancer in recent years and will continue to do so to 2040,” Dr. Rahib commented.

Dr. Miller casts doubt on this prediction.

Using data through 2017, “we have seen that the patterns in prostate cancer incidence are already shifting from the steep declines we saw in the early 2010s,” she said. “I would use caution when interpreting the overall trends for prostate, because this cancer in particular is dramatically affected by changes in recommendations for screening with the PSA test.”

Screening has also influenced colorectal cancer incidence, the authors pointed out, saying that the uptake of colorectal cancer screening is associated with a decrease in the number of colorectal cancers and deaths out to 2040, as a result of effectiveness of screening.

For breast cancer, the authors highlighted the fact that, although the number of breast cancers will continue to increase, the number of breast cancer deaths will decrease. That ongoing trend is most likely attributable to increased screening and advancements in treatment.

The study was supported by the National Institutes of Health, National Cancer Institute, the Cancer Prevention and Research Institute of Texas, Cancer Commons and the Pancreatic Cancer Action Network. The study authors and Dr. Miller disclosed no relevant financial relationships.

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

Seven years after concluding that evidence was insufficient to recommend screening for vitamin D deficiency in the general population, the United States Preventive Services Task Force (USPSTF) has revisited the issue – and come up with the same conclusion.

Overall, “the current evidence is inadequate to determine whether screening for and treatment of asymptomatic low 25(OH)D levels improve clinical outcomes in community dwelling adults,” the task force concluded in its statement, recommending an “I” for insufficient.

The statement was published online April 13 in JAMA.

In the absence of screening recommendations, clinicians may be best advised to instead focus on diet and supplementation for those considered at risk, said Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia.

“Rather than posing the question of screening the general population for vitamin D deficiency, let’s focus on ensuring that everyone consumes the age-based recommended daily allowance of vitamin D instead,” Dr. Cappola, a coauthor of the accompanying editorial, said in an interview.
 

No studies have directly evaluated benefits of screening

The latest USPSTF recommendation is based on a systematic review of the benefits and harms of screening and early treatment for vitamin D deficiency in asymptomatic, community-dwelling nonpregnant adults aged 18 or older in the primary care setting with no signs or symptoms of deficiency.

The review found no studies that directly evaluated the benefits of screening for vitamin D deficiency.

However, 26 randomized clinical trials and one nested case-control study evaluated the effectiveness of treatment of vitamin D deficiency with supplementation.

And while observational studies have linked lower vitamin D levels with a multitude of conditions and risks, evidence of any benefit was inconsistent, with none identified for most major outcomes in asymptomatic adults – the focus of the Task Force recommendation.

“Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events,” the review authors stress.

“The evidence is inconclusive about the effect of treatment on physical functioning and infection.”
 

One in four are vitamin D deficient

In terms of the further question of the potential harms of vitamin D screening of asymptomatic individuals, a key concern is the potential for misclassification and over- or underdiagnosis due to inconsistent cutoffs and variability of different screening assays, the review concluded.

However, with the rare exception of vitamin D toxicity from supplementation well above sufficient levels, treatment with vitamin D supplementation appears relatively safe.

With a lack of consensus even over the basic cutoff for vitamin D deficiency, the National Academy of Medicine determined in 2011 that hydroxyvitamin D (25[OH]D) levels below 20 ng/mL are deficient for bone health, with no evidence of different thresholds for any other health condition.

Based on that cutoff, the National Health and Nutrition Examination Survey (NHANES), reported in 2014 that 25% of the U.S. population over the age of 1 was vitamin D deficient, with 18% of the population having 25(OH)D levels of 12-19 ng/mL and 5% having very low levels (< 12 ng/mL).
 

More work needed to determine groups at risk

While the task force report did not delve into testing or treatment recommendations for symptomatic adults, key established risk factors that may help clinicians identify those who are vitamin D deficient include obesity, receiving little or no UVB light exposure, and older age.

In general, obesity is associated with a 1.3- to 2-fold risk of being vitamin D deficient based on the criteria used, while non-Hispanic Blacks are 2-10 times more likely to be deficient compared with non-Hispanic White patients, the task force noted.

However, the implications of vitamin D deficiency in certain populations can vary. For instance, non-Hispanic Black people, despite having a higher prevalence of lower vitamin D levels compared with White people, in fact, have lower reported rates of fractures.

To address the various issues and gain a better understanding of the complexities of vitamin D deficiency, the task force calls for further research in key areas.

“More research is needed to determine whether total serum 25(OH)D levels are the best measure of vitamin D deficiency and whether the best measure of vitamin D deficiency varies by subgroups defined by race, ethnicity, or sex,” the authors indicated.

Furthermore, “more research is needed to determine the cutoff that defines vitamin D deficiency and whether that cutoff varies by specific clinical outcome or by subgroups defined by race, ethnicity, or sex.”
 

No support for population-based screening in guidelines

With the lack of conclusive evidence, no organizations currently recommend population-based screening for vitamin D deficiency in asymptomatic patients, and the American Society for Clinical Pathology endorses this stance.

The Endocrine Society and the American Association of Clinical Endocrinologists meanwhile do recommend screening for vitamin D deficiency in patients considered at risk.

Data show there was as much as an 80-fold increase in Medicare reimbursement volumes for vitamin D testing among clinicians from 2000 to 2010; however, that rate may have leveled off after the National Academy of Medicine reported on set deficiency levels, said Sherri-Ann M. Burnett-Bowie, MD, MPH, Dr. Cappola’s editorial coauthor.

Dr. Burnett-Bowie noted that she regularly tests her patients’ vitamin D levels, however most of her patients have osteoporosis or fractures.

“I do screen them for vitamin D deficiency since optimizing their vitamin D will improve calcium absorption, which is important for treating their osteoporosis,” Dr. Burnett-Bowie, of the endocrine division, department of medicine, Massachusetts General Hospital, Boston, said in an interview.

In terms of broader testing of asymptomatic patients in the general population, however, any changes in screening will likely be contingent on developments in the effects of treatment, she said.

“Given the challenge in finding benefits of vitamin D supplementation in those who are deficient, it will likely be more challenging to find benefits from wider screening,” she concluded.

The USPSTF and editorialists reported having no relevant financial relationships.

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

Seven years after concluding that evidence was insufficient to recommend screening for vitamin D deficiency in the general population, the United States Preventive Services Task Force (USPSTF) has revisited the issue – and come up with the same conclusion.

Overall, “the current evidence is inadequate to determine whether screening for and treatment of asymptomatic low 25(OH)D levels improve clinical outcomes in community dwelling adults,” the task force concluded in its statement, recommending an “I” for insufficient.

The statement was published online April 13 in JAMA.

In the absence of screening recommendations, clinicians may be best advised to instead focus on diet and supplementation for those considered at risk, said Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia.

“Rather than posing the question of screening the general population for vitamin D deficiency, let’s focus on ensuring that everyone consumes the age-based recommended daily allowance of vitamin D instead,” Dr. Cappola, a coauthor of the accompanying editorial, said in an interview.
 

No studies have directly evaluated benefits of screening

The latest USPSTF recommendation is based on a systematic review of the benefits and harms of screening and early treatment for vitamin D deficiency in asymptomatic, community-dwelling nonpregnant adults aged 18 or older in the primary care setting with no signs or symptoms of deficiency.

The review found no studies that directly evaluated the benefits of screening for vitamin D deficiency.

However, 26 randomized clinical trials and one nested case-control study evaluated the effectiveness of treatment of vitamin D deficiency with supplementation.

And while observational studies have linked lower vitamin D levels with a multitude of conditions and risks, evidence of any benefit was inconsistent, with none identified for most major outcomes in asymptomatic adults – the focus of the Task Force recommendation.

“Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events,” the review authors stress.

“The evidence is inconclusive about the effect of treatment on physical functioning and infection.”
 

One in four are vitamin D deficient

In terms of the further question of the potential harms of vitamin D screening of asymptomatic individuals, a key concern is the potential for misclassification and over- or underdiagnosis due to inconsistent cutoffs and variability of different screening assays, the review concluded.

However, with the rare exception of vitamin D toxicity from supplementation well above sufficient levels, treatment with vitamin D supplementation appears relatively safe.

With a lack of consensus even over the basic cutoff for vitamin D deficiency, the National Academy of Medicine determined in 2011 that hydroxyvitamin D (25[OH]D) levels below 20 ng/mL are deficient for bone health, with no evidence of different thresholds for any other health condition.

Based on that cutoff, the National Health and Nutrition Examination Survey (NHANES), reported in 2014 that 25% of the U.S. population over the age of 1 was vitamin D deficient, with 18% of the population having 25(OH)D levels of 12-19 ng/mL and 5% having very low levels (< 12 ng/mL).
 

More work needed to determine groups at risk

While the task force report did not delve into testing or treatment recommendations for symptomatic adults, key established risk factors that may help clinicians identify those who are vitamin D deficient include obesity, receiving little or no UVB light exposure, and older age.

In general, obesity is associated with a 1.3- to 2-fold risk of being vitamin D deficient based on the criteria used, while non-Hispanic Blacks are 2-10 times more likely to be deficient compared with non-Hispanic White patients, the task force noted.

However, the implications of vitamin D deficiency in certain populations can vary. For instance, non-Hispanic Black people, despite having a higher prevalence of lower vitamin D levels compared with White people, in fact, have lower reported rates of fractures.

To address the various issues and gain a better understanding of the complexities of vitamin D deficiency, the task force calls for further research in key areas.

“More research is needed to determine whether total serum 25(OH)D levels are the best measure of vitamin D deficiency and whether the best measure of vitamin D deficiency varies by subgroups defined by race, ethnicity, or sex,” the authors indicated.

Furthermore, “more research is needed to determine the cutoff that defines vitamin D deficiency and whether that cutoff varies by specific clinical outcome or by subgroups defined by race, ethnicity, or sex.”
 

No support for population-based screening in guidelines

With the lack of conclusive evidence, no organizations currently recommend population-based screening for vitamin D deficiency in asymptomatic patients, and the American Society for Clinical Pathology endorses this stance.

The Endocrine Society and the American Association of Clinical Endocrinologists meanwhile do recommend screening for vitamin D deficiency in patients considered at risk.

Data show there was as much as an 80-fold increase in Medicare reimbursement volumes for vitamin D testing among clinicians from 2000 to 2010; however, that rate may have leveled off after the National Academy of Medicine reported on set deficiency levels, said Sherri-Ann M. Burnett-Bowie, MD, MPH, Dr. Cappola’s editorial coauthor.

Dr. Burnett-Bowie noted that she regularly tests her patients’ vitamin D levels, however most of her patients have osteoporosis or fractures.

“I do screen them for vitamin D deficiency since optimizing their vitamin D will improve calcium absorption, which is important for treating their osteoporosis,” Dr. Burnett-Bowie, of the endocrine division, department of medicine, Massachusetts General Hospital, Boston, said in an interview.

In terms of broader testing of asymptomatic patients in the general population, however, any changes in screening will likely be contingent on developments in the effects of treatment, she said.

“Given the challenge in finding benefits of vitamin D supplementation in those who are deficient, it will likely be more challenging to find benefits from wider screening,” she concluded.

The USPSTF and editorialists reported having no relevant financial relationships.

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

Seven years after concluding that evidence was insufficient to recommend screening for vitamin D deficiency in the general population, the United States Preventive Services Task Force (USPSTF) has revisited the issue – and come up with the same conclusion.

Overall, “the current evidence is inadequate to determine whether screening for and treatment of asymptomatic low 25(OH)D levels improve clinical outcomes in community dwelling adults,” the task force concluded in its statement, recommending an “I” for insufficient.

The statement was published online April 13 in JAMA.

In the absence of screening recommendations, clinicians may be best advised to instead focus on diet and supplementation for those considered at risk, said Anne R. Cappola, MD, of the University of Pennsylvania, Philadelphia.

“Rather than posing the question of screening the general population for vitamin D deficiency, let’s focus on ensuring that everyone consumes the age-based recommended daily allowance of vitamin D instead,” Dr. Cappola, a coauthor of the accompanying editorial, said in an interview.
 

No studies have directly evaluated benefits of screening

The latest USPSTF recommendation is based on a systematic review of the benefits and harms of screening and early treatment for vitamin D deficiency in asymptomatic, community-dwelling nonpregnant adults aged 18 or older in the primary care setting with no signs or symptoms of deficiency.

The review found no studies that directly evaluated the benefits of screening for vitamin D deficiency.

However, 26 randomized clinical trials and one nested case-control study evaluated the effectiveness of treatment of vitamin D deficiency with supplementation.

And while observational studies have linked lower vitamin D levels with a multitude of conditions and risks, evidence of any benefit was inconsistent, with none identified for most major outcomes in asymptomatic adults – the focus of the Task Force recommendation.

“Among asymptomatic, community-dwelling populations with low vitamin D levels, the evidence suggests that treatment with vitamin D has no effect on mortality or the incidence of fractures, falls, depression, diabetes, cardiovascular disease, cancer, or adverse events,” the review authors stress.

“The evidence is inconclusive about the effect of treatment on physical functioning and infection.”
 

One in four are vitamin D deficient

In terms of the further question of the potential harms of vitamin D screening of asymptomatic individuals, a key concern is the potential for misclassification and over- or underdiagnosis due to inconsistent cutoffs and variability of different screening assays, the review concluded.

However, with the rare exception of vitamin D toxicity from supplementation well above sufficient levels, treatment with vitamin D supplementation appears relatively safe.

With a lack of consensus even over the basic cutoff for vitamin D deficiency, the National Academy of Medicine determined in 2011 that hydroxyvitamin D (25[OH]D) levels below 20 ng/mL are deficient for bone health, with no evidence of different thresholds for any other health condition.

Based on that cutoff, the National Health and Nutrition Examination Survey (NHANES), reported in 2014 that 25% of the U.S. population over the age of 1 was vitamin D deficient, with 18% of the population having 25(OH)D levels of 12-19 ng/mL and 5% having very low levels (< 12 ng/mL).
 

More work needed to determine groups at risk

While the task force report did not delve into testing or treatment recommendations for symptomatic adults, key established risk factors that may help clinicians identify those who are vitamin D deficient include obesity, receiving little or no UVB light exposure, and older age.

In general, obesity is associated with a 1.3- to 2-fold risk of being vitamin D deficient based on the criteria used, while non-Hispanic Blacks are 2-10 times more likely to be deficient compared with non-Hispanic White patients, the task force noted.

However, the implications of vitamin D deficiency in certain populations can vary. For instance, non-Hispanic Black people, despite having a higher prevalence of lower vitamin D levels compared with White people, in fact, have lower reported rates of fractures.

To address the various issues and gain a better understanding of the complexities of vitamin D deficiency, the task force calls for further research in key areas.

“More research is needed to determine whether total serum 25(OH)D levels are the best measure of vitamin D deficiency and whether the best measure of vitamin D deficiency varies by subgroups defined by race, ethnicity, or sex,” the authors indicated.

Furthermore, “more research is needed to determine the cutoff that defines vitamin D deficiency and whether that cutoff varies by specific clinical outcome or by subgroups defined by race, ethnicity, or sex.”
 

No support for population-based screening in guidelines

With the lack of conclusive evidence, no organizations currently recommend population-based screening for vitamin D deficiency in asymptomatic patients, and the American Society for Clinical Pathology endorses this stance.

The Endocrine Society and the American Association of Clinical Endocrinologists meanwhile do recommend screening for vitamin D deficiency in patients considered at risk.

Data show there was as much as an 80-fold increase in Medicare reimbursement volumes for vitamin D testing among clinicians from 2000 to 2010; however, that rate may have leveled off after the National Academy of Medicine reported on set deficiency levels, said Sherri-Ann M. Burnett-Bowie, MD, MPH, Dr. Cappola’s editorial coauthor.

Dr. Burnett-Bowie noted that she regularly tests her patients’ vitamin D levels, however most of her patients have osteoporosis or fractures.

“I do screen them for vitamin D deficiency since optimizing their vitamin D will improve calcium absorption, which is important for treating their osteoporosis,” Dr. Burnett-Bowie, of the endocrine division, department of medicine, Massachusetts General Hospital, Boston, said in an interview.

In terms of broader testing of asymptomatic patients in the general population, however, any changes in screening will likely be contingent on developments in the effects of treatment, she said.

“Given the challenge in finding benefits of vitamin D supplementation in those who are deficient, it will likely be more challenging to find benefits from wider screening,” she concluded.

The USPSTF and editorialists reported having no relevant financial relationships.

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

The Food and Drug Administration has lifted in-person dispensing requirements for mifepristone when used for medical termination of early pregnancy.  
In an April 12, 2021, letter to the American College of Obstetricians and Gynecologists and the Society of Maternal-Fetal Medicine, acting commissioner of food and drugs Janet Woodcock stated that the FDA would exercise discretion to permit the dispensing of mifepristone through the mail when done by or under the supervision of a certified prescriber; or through a mail-order pharmacy under the supervision of a certified prescriber.  
The decision follows a trial period of suspension of the in-person dispensing requirement in response to safety concerns for patients as well as providers associated with in-person clinic visits during the COVID-19 pandemic. The Center for Drug Evaluation and Research reviewed safety and clinical outcomes data on mifepristone use when prescriptions were handled by mail or mail-order pharmacy and found that "the small number of adverse events reported to FDA during the COVID-19 public health emergency [PHE] provide no indication that any program deviation or noncompliance with the mifepristone [Risk Evaluation and Mitigation Strategy] program contributed to the reported adverse events," according to the letter. The analysis covers Mifeprex and the approved generic, mifepristone tablets, both 200-mg doses. 
As long as other mifepristone REMS criteria are met, the FDA will continue to permit mail and mail-order prescriptions, according to the letter. 
"By halting enforcement of the in-person dispensing requirement during the COVID-19 pandemic, the FDA is recognizing and responding to the available evidence - which has clearly and definitively demonstrated that the in-person dispensing requirement for mifepristone is unnecessary and restrictive," Maureen G. Phipps, MD, MPH, CEO of ACOG, said in a statement in response to the FDA decision.  
ACOG petitioned the FDA to suspend the in-person requirement to reduce the risk of transmission in the wake of the COVID-19 pandemic, given safety concerns and the potential impact on hard-hit communities, particularly communities of color, Dr. Phipps emphasized. Data from a review period with a suspension of the in-person requirement yielded no additional safety concerns with mifepristone use, and contributed to the FDA decision to lift the requirement. 
"Thanks to the FDA's intent to exercise discretion in enforcing the in-person dispensing requirement, those in need of an abortion or miscarriage management will be able to do so safety and effectively by acquiring mifepristone though the mail - just as they would any other medication with a similarly strong safety profile," said Dr. Phipps. "We are pleased to see mifepristone regulated on the basis of the scientific evidence during the pandemic, rather than political bias against comprehensive reproductive health care, and we look forward to working with policy makers to ensure this principle governs postpandemic care."  
CDER is communicating the decision to all approved application holders subject to the mifepristone REMS program, according to the letter.  
[email protected]

The Food and Drug Administration has lifted in-person dispensing requirements for mifepristone when used for medical termination of early pregnancy.  
In an April 12, 2021, letter to the American College of Obstetricians and Gynecologists and the Society of Maternal-Fetal Medicine, acting commissioner of food and drugs Janet Woodcock stated that the FDA would exercise discretion to permit the dispensing of mifepristone through the mail when done by or under the supervision of a certified prescriber; or through a mail-order pharmacy under the supervision of a certified prescriber.  
The decision follows a trial period of suspension of the in-person dispensing requirement in response to safety concerns for patients as well as providers associated with in-person clinic visits during the COVID-19 pandemic. The Center for Drug Evaluation and Research reviewed safety and clinical outcomes data on mifepristone use when prescriptions were handled by mail or mail-order pharmacy and found that "the small number of adverse events reported to FDA during the COVID-19 public health emergency [PHE] provide no indication that any program deviation or noncompliance with the mifepristone [Risk Evaluation and Mitigation Strategy] program contributed to the reported adverse events," according to the letter. The analysis covers Mifeprex and the approved generic, mifepristone tablets, both 200-mg doses. 
As long as other mifepristone REMS criteria are met, the FDA will continue to permit mail and mail-order prescriptions, according to the letter. 
"By halting enforcement of the in-person dispensing requirement during the COVID-19 pandemic, the FDA is recognizing and responding to the available evidence - which has clearly and definitively demonstrated that the in-person dispensing requirement for mifepristone is unnecessary and restrictive," Maureen G. Phipps, MD, MPH, CEO of ACOG, said in a statement in response to the FDA decision.  
ACOG petitioned the FDA to suspend the in-person requirement to reduce the risk of transmission in the wake of the COVID-19 pandemic, given safety concerns and the potential impact on hard-hit communities, particularly communities of color, Dr. Phipps emphasized. Data from a review period with a suspension of the in-person requirement yielded no additional safety concerns with mifepristone use, and contributed to the FDA decision to lift the requirement. 
"Thanks to the FDA's intent to exercise discretion in enforcing the in-person dispensing requirement, those in need of an abortion or miscarriage management will be able to do so safety and effectively by acquiring mifepristone though the mail - just as they would any other medication with a similarly strong safety profile," said Dr. Phipps. "We are pleased to see mifepristone regulated on the basis of the scientific evidence during the pandemic, rather than political bias against comprehensive reproductive health care, and we look forward to working with policy makers to ensure this principle governs postpandemic care."  
CDER is communicating the decision to all approved application holders subject to the mifepristone REMS program, according to the letter.  
[email protected]

The Food and Drug Administration has lifted in-person dispensing requirements for mifepristone when used for medical termination of early pregnancy.  
In an April 12, 2021, letter to the American College of Obstetricians and Gynecologists and the Society of Maternal-Fetal Medicine, acting commissioner of food and drugs Janet Woodcock stated that the FDA would exercise discretion to permit the dispensing of mifepristone through the mail when done by or under the supervision of a certified prescriber; or through a mail-order pharmacy under the supervision of a certified prescriber.  
The decision follows a trial period of suspension of the in-person dispensing requirement in response to safety concerns for patients as well as providers associated with in-person clinic visits during the COVID-19 pandemic. The Center for Drug Evaluation and Research reviewed safety and clinical outcomes data on mifepristone use when prescriptions were handled by mail or mail-order pharmacy and found that "the small number of adverse events reported to FDA during the COVID-19 public health emergency [PHE] provide no indication that any program deviation or noncompliance with the mifepristone [Risk Evaluation and Mitigation Strategy] program contributed to the reported adverse events," according to the letter. The analysis covers Mifeprex and the approved generic, mifepristone tablets, both 200-mg doses. 
As long as other mifepristone REMS criteria are met, the FDA will continue to permit mail and mail-order prescriptions, according to the letter. 
"By halting enforcement of the in-person dispensing requirement during the COVID-19 pandemic, the FDA is recognizing and responding to the available evidence - which has clearly and definitively demonstrated that the in-person dispensing requirement for mifepristone is unnecessary and restrictive," Maureen G. Phipps, MD, MPH, CEO of ACOG, said in a statement in response to the FDA decision.  
ACOG petitioned the FDA to suspend the in-person requirement to reduce the risk of transmission in the wake of the COVID-19 pandemic, given safety concerns and the potential impact on hard-hit communities, particularly communities of color, Dr. Phipps emphasized. Data from a review period with a suspension of the in-person requirement yielded no additional safety concerns with mifepristone use, and contributed to the FDA decision to lift the requirement. 
"Thanks to the FDA's intent to exercise discretion in enforcing the in-person dispensing requirement, those in need of an abortion or miscarriage management will be able to do so safety and effectively by acquiring mifepristone though the mail - just as they would any other medication with a similarly strong safety profile," said Dr. Phipps. "We are pleased to see mifepristone regulated on the basis of the scientific evidence during the pandemic, rather than political bias against comprehensive reproductive health care, and we look forward to working with policy makers to ensure this principle governs postpandemic care."  
CDER is communicating the decision to all approved application holders subject to the mifepristone REMS program, according to the letter.  
[email protected]

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

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

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

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

It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.

Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.

“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.

But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.

With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.

Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
 

Decreased infections

If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.

The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”

B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.

In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.

Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.

The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
 

Human factors

Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.

By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.

In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.

Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.

However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
 

Double surge

Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.

He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.

Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.

Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.

In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.

Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.

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

A novel therapy combining platelet-rich plasma (PRP) with follicle-stimulating hormone that is injected directly into the ovaries has the potential to restore ovarian function for women who experience early menopause, possibly allowing for pregnancy without the need for donor eggs.

“The resumption of ovarian function in our participants means women with early menopause could have the opportunity to pursue pregnancy through IVF [in vitro fertilization] using their own eggs,” the authors of the groundbreaking pilot study report.

In the small study, published online March 29 in Menopause, menstruation resumed within a mean of about 5 weeks for 11 of 12 patients with early menopause who were treated with the technique. One patient achieved a clinical pregnancy.

In commenting on the study, Stephanie S. Faubion, MD, medical director of the North American Menopause Society, was cautious in her interpretation, noting the need for more research in larger samples.

“Any pregnancy that results from a regenerative therapy is novel,” she told this news organization. “Still, we are a long way away from this being a standard therapy for women with premature ovarian insufficiency.”
 

Pilot study: Platelet-rich plasma combination with FSH

Early menopause is the cessation of ovarian function at or before the age of 45 years. It is estimated that 12.2% of women experience early menopause. For these women, currently, the only chance of becoming pregnant is with donor eggs.

PRP, an autologous plasma preparation containing more than 10 times the concentration of growth factors and active metabolites than normal plasma, has recently been shown to have the potential to restore the menstrual cycles in perimenopausal women, allowing IVF. It has also been shown to benefit women with premature ovarian insufficiency (POI). However, there have been few reports of pregnancies or live births.

Chao Chin Hsu, MD, PhD, of the National Taiwan University Hospital, Taipei, and colleagues investigated whether the combination of the activated PRP treatment with gondatrophins such as FSH could provide a more robust effect so as to sufficiently stimulate follicles. They used the intraovarian injection of the combination to treat a 38-year-old woman with POI.

The effort was successful, and the woman gave birth to healthy twins.

To further evaluate the approach, the authors conducted a pilot study involving 12 women with early menopause (mean age, 44.4 years) between November 2018 and November 2019.

The women received intraovarian injection with PRP prepared from 40 mL of autologous peripheral blood combined with recombinant FSH.

Following the treatment, 11 of the 12 women experienced resumption of menstruation within a mean of 37 days. For seven patients, menstruation resumed within a month; for three, it resumed within about 2 months; and for one, it resumed after approximately 3 months.

Of note, the menstrual cycles were mostly irregular, with an interval of about 45.6 days.

The women’s average serum FSH level dropped significantly from 70.5 IU/L at baseline to 26.2 IU/L within days of treatment, as did the average luteinizing hormone level (34.8 before and 14.3 IU/L after treatment), indicative of improved ovary function.

For six participants, 10 oocyte retrieval procedures were performed after a mean of about 2 months. Thirteen mature eggs were retrieved, and fertilization via intracytoplasmic sperm injection was attempted, resulting in 10 fertilized oocytes.

Cleavage-stage embryos were transferred into two of the participants. One achieved a clinical pregnancy, defined as a pregnancy that was confirmed by ultrasound and by the presence of a fetal heartbeat. The pregnancy ended in miscarriage at 7 weeks’ gestation.

The length of controlled ovarian stimulation necessary for follicle growth ranged from 8 to 14 days, which the authors note is similar to that seen with women of normal reproductive age.

“Although the use of PRP in reproductive medicine is considered experimental, we demonstrated the restoration of ovarian function in early menopausal women who adopted whole dimension subcortical ovarian injection of PRP/gonadotropin,” the authors write.

“Most remarkably, an early menopausal woman achieved pregnancy after the treatment followed by IVF with her mature ovulating follicle,” they report.
 

Mechanisms, caveats

The mechanisms thought to underlie the success of the approach include increases in ovarian vascularization and stromal cell proliferation and reductions in oxidative stress and cell death in ovaries, the authors explain.

Key caveats with the treatment include the fact that anesthesia and laparoscopy are required, and precise administration is required at 15 injection sites in 1-2 mm of the ovarian subcortical area, which can be difficult to achieve, Dr. Hsu said in an interview.

“If a new instrument could be developed in which physicians can carry out this treatment through a vaginal approach, like the transvaginal retrieval of eggs in IVF treatments,” the approach could become more acceptable, Dr. Hsu added.

The authors call for studies with larger sample sizes and say it will also be interesting to determine effects in different groups: For example, women with cancer who have undergone chemotherapy.

Dr. Faubion, who is director of the Mayo Clinic Women’s Health, Rochester, Minn., says the causes of early menopause could be important in determining the treatment’s efficacy.

“[The therapy’s] success may depend on the reason the woman experienced early menopause: For instance, due to chemotherapy, radiation, virus, autoimmune disease, genetic mutation, or other cause,” she said.

She also noted that cost could be an important factor.

“I don’t see a cost estimate, but it will be substantial,” she said. “So, even if the success rate improves as this technique is further studied, cost and the invasive nature of the treatment may prove to be substantial barriers to this therapy becoming mainstream,” she said.

The authors and Dr. Faubion have disclosed no relevant financial relationships.

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

A novel therapy combining platelet-rich plasma (PRP) with follicle-stimulating hormone that is injected directly into the ovaries has the potential to restore ovarian function for women who experience early menopause, possibly allowing for pregnancy without the need for donor eggs.

“The resumption of ovarian function in our participants means women with early menopause could have the opportunity to pursue pregnancy through IVF [in vitro fertilization] using their own eggs,” the authors of the groundbreaking pilot study report.

In the small study, published online March 29 in Menopause, menstruation resumed within a mean of about 5 weeks for 11 of 12 patients with early menopause who were treated with the technique. One patient achieved a clinical pregnancy.

In commenting on the study, Stephanie S. Faubion, MD, medical director of the North American Menopause Society, was cautious in her interpretation, noting the need for more research in larger samples.

“Any pregnancy that results from a regenerative therapy is novel,” she told this news organization. “Still, we are a long way away from this being a standard therapy for women with premature ovarian insufficiency.”
 

Pilot study: Platelet-rich plasma combination with FSH

Early menopause is the cessation of ovarian function at or before the age of 45 years. It is estimated that 12.2% of women experience early menopause. For these women, currently, the only chance of becoming pregnant is with donor eggs.

PRP, an autologous plasma preparation containing more than 10 times the concentration of growth factors and active metabolites than normal plasma, has recently been shown to have the potential to restore the menstrual cycles in perimenopausal women, allowing IVF. It has also been shown to benefit women with premature ovarian insufficiency (POI). However, there have been few reports of pregnancies or live births.

Chao Chin Hsu, MD, PhD, of the National Taiwan University Hospital, Taipei, and colleagues investigated whether the combination of the activated PRP treatment with gondatrophins such as FSH could provide a more robust effect so as to sufficiently stimulate follicles. They used the intraovarian injection of the combination to treat a 38-year-old woman with POI.

The effort was successful, and the woman gave birth to healthy twins.

To further evaluate the approach, the authors conducted a pilot study involving 12 women with early menopause (mean age, 44.4 years) between November 2018 and November 2019.

The women received intraovarian injection with PRP prepared from 40 mL of autologous peripheral blood combined with recombinant FSH.

Following the treatment, 11 of the 12 women experienced resumption of menstruation within a mean of 37 days. For seven patients, menstruation resumed within a month; for three, it resumed within about 2 months; and for one, it resumed after approximately 3 months.

Of note, the menstrual cycles were mostly irregular, with an interval of about 45.6 days.

The women’s average serum FSH level dropped significantly from 70.5 IU/L at baseline to 26.2 IU/L within days of treatment, as did the average luteinizing hormone level (34.8 before and 14.3 IU/L after treatment), indicative of improved ovary function.

For six participants, 10 oocyte retrieval procedures were performed after a mean of about 2 months. Thirteen mature eggs were retrieved, and fertilization via intracytoplasmic sperm injection was attempted, resulting in 10 fertilized oocytes.

Cleavage-stage embryos were transferred into two of the participants. One achieved a clinical pregnancy, defined as a pregnancy that was confirmed by ultrasound and by the presence of a fetal heartbeat. The pregnancy ended in miscarriage at 7 weeks’ gestation.

The length of controlled ovarian stimulation necessary for follicle growth ranged from 8 to 14 days, which the authors note is similar to that seen with women of normal reproductive age.

“Although the use of PRP in reproductive medicine is considered experimental, we demonstrated the restoration of ovarian function in early menopausal women who adopted whole dimension subcortical ovarian injection of PRP/gonadotropin,” the authors write.

“Most remarkably, an early menopausal woman achieved pregnancy after the treatment followed by IVF with her mature ovulating follicle,” they report.
 

Mechanisms, caveats

The mechanisms thought to underlie the success of the approach include increases in ovarian vascularization and stromal cell proliferation and reductions in oxidative stress and cell death in ovaries, the authors explain.

Key caveats with the treatment include the fact that anesthesia and laparoscopy are required, and precise administration is required at 15 injection sites in 1-2 mm of the ovarian subcortical area, which can be difficult to achieve, Dr. Hsu said in an interview.

“If a new instrument could be developed in which physicians can carry out this treatment through a vaginal approach, like the transvaginal retrieval of eggs in IVF treatments,” the approach could become more acceptable, Dr. Hsu added.

The authors call for studies with larger sample sizes and say it will also be interesting to determine effects in different groups: For example, women with cancer who have undergone chemotherapy.

Dr. Faubion, who is director of the Mayo Clinic Women’s Health, Rochester, Minn., says the causes of early menopause could be important in determining the treatment’s efficacy.

“[The therapy’s] success may depend on the reason the woman experienced early menopause: For instance, due to chemotherapy, radiation, virus, autoimmune disease, genetic mutation, or other cause,” she said.

She also noted that cost could be an important factor.

“I don’t see a cost estimate, but it will be substantial,” she said. “So, even if the success rate improves as this technique is further studied, cost and the invasive nature of the treatment may prove to be substantial barriers to this therapy becoming mainstream,” she said.

The authors and Dr. Faubion have disclosed no relevant financial relationships.

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

A novel therapy combining platelet-rich plasma (PRP) with follicle-stimulating hormone that is injected directly into the ovaries has the potential to restore ovarian function for women who experience early menopause, possibly allowing for pregnancy without the need for donor eggs.

“The resumption of ovarian function in our participants means women with early menopause could have the opportunity to pursue pregnancy through IVF [in vitro fertilization] using their own eggs,” the authors of the groundbreaking pilot study report.

In the small study, published online March 29 in Menopause, menstruation resumed within a mean of about 5 weeks for 11 of 12 patients with early menopause who were treated with the technique. One patient achieved a clinical pregnancy.

In commenting on the study, Stephanie S. Faubion, MD, medical director of the North American Menopause Society, was cautious in her interpretation, noting the need for more research in larger samples.

“Any pregnancy that results from a regenerative therapy is novel,” she told this news organization. “Still, we are a long way away from this being a standard therapy for women with premature ovarian insufficiency.”
 

Pilot study: Platelet-rich plasma combination with FSH

Early menopause is the cessation of ovarian function at or before the age of 45 years. It is estimated that 12.2% of women experience early menopause. For these women, currently, the only chance of becoming pregnant is with donor eggs.

PRP, an autologous plasma preparation containing more than 10 times the concentration of growth factors and active metabolites than normal plasma, has recently been shown to have the potential to restore the menstrual cycles in perimenopausal women, allowing IVF. It has also been shown to benefit women with premature ovarian insufficiency (POI). However, there have been few reports of pregnancies or live births.

Chao Chin Hsu, MD, PhD, of the National Taiwan University Hospital, Taipei, and colleagues investigated whether the combination of the activated PRP treatment with gondatrophins such as FSH could provide a more robust effect so as to sufficiently stimulate follicles. They used the intraovarian injection of the combination to treat a 38-year-old woman with POI.

The effort was successful, and the woman gave birth to healthy twins.

To further evaluate the approach, the authors conducted a pilot study involving 12 women with early menopause (mean age, 44.4 years) between November 2018 and November 2019.

The women received intraovarian injection with PRP prepared from 40 mL of autologous peripheral blood combined with recombinant FSH.

Following the treatment, 11 of the 12 women experienced resumption of menstruation within a mean of 37 days. For seven patients, menstruation resumed within a month; for three, it resumed within about 2 months; and for one, it resumed after approximately 3 months.

Of note, the menstrual cycles were mostly irregular, with an interval of about 45.6 days.

The women’s average serum FSH level dropped significantly from 70.5 IU/L at baseline to 26.2 IU/L within days of treatment, as did the average luteinizing hormone level (34.8 before and 14.3 IU/L after treatment), indicative of improved ovary function.

For six participants, 10 oocyte retrieval procedures were performed after a mean of about 2 months. Thirteen mature eggs were retrieved, and fertilization via intracytoplasmic sperm injection was attempted, resulting in 10 fertilized oocytes.

Cleavage-stage embryos were transferred into two of the participants. One achieved a clinical pregnancy, defined as a pregnancy that was confirmed by ultrasound and by the presence of a fetal heartbeat. The pregnancy ended in miscarriage at 7 weeks’ gestation.

The length of controlled ovarian stimulation necessary for follicle growth ranged from 8 to 14 days, which the authors note is similar to that seen with women of normal reproductive age.

“Although the use of PRP in reproductive medicine is considered experimental, we demonstrated the restoration of ovarian function in early menopausal women who adopted whole dimension subcortical ovarian injection of PRP/gonadotropin,” the authors write.

“Most remarkably, an early menopausal woman achieved pregnancy after the treatment followed by IVF with her mature ovulating follicle,” they report.
 

Mechanisms, caveats

The mechanisms thought to underlie the success of the approach include increases in ovarian vascularization and stromal cell proliferation and reductions in oxidative stress and cell death in ovaries, the authors explain.

Key caveats with the treatment include the fact that anesthesia and laparoscopy are required, and precise administration is required at 15 injection sites in 1-2 mm of the ovarian subcortical area, which can be difficult to achieve, Dr. Hsu said in an interview.

“If a new instrument could be developed in which physicians can carry out this treatment through a vaginal approach, like the transvaginal retrieval of eggs in IVF treatments,” the approach could become more acceptable, Dr. Hsu added.

The authors call for studies with larger sample sizes and say it will also be interesting to determine effects in different groups: For example, women with cancer who have undergone chemotherapy.

Dr. Faubion, who is director of the Mayo Clinic Women’s Health, Rochester, Minn., says the causes of early menopause could be important in determining the treatment’s efficacy.

“[The therapy’s] success may depend on the reason the woman experienced early menopause: For instance, due to chemotherapy, radiation, virus, autoimmune disease, genetic mutation, or other cause,” she said.

She also noted that cost could be an important factor.

“I don’t see a cost estimate, but it will be substantial,” she said. “So, even if the success rate improves as this technique is further studied, cost and the invasive nature of the treatment may prove to be substantial barriers to this therapy becoming mainstream,” she said.

The authors and Dr. Faubion have disclosed no relevant financial relationships.

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

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

This article was updated 4/13/21.

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

This article was updated 4/13/21.

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

This article was updated 4/13/21.

A shorter period between eating and going to sleep increased the risk of GERD during pregnancy by approximately 12%, according to data from 400 women.

Antonio_Diaz/iStock/via Getty Images

Gastroesophageal reflux disease (GERD) is a common condition in pregnancy because of changes in gastrointestinal motility caused by hormonal changes, and a short meal-to-bed time (MTBT) also has been associated with increased GERD symptoms, but data on the impact of MTBT on GERD in pregnant women in particular are lacking, wrote Duc T. Quach, MD, of the University of Medicine and Pharmacy in Ho Chi Minh City, Vietnam, and colleagues.

In a cross-sectional study published in the Journal of Clinical Gastroenterology, the researchers identified 400 pregnant women aged 18 years and older in various stages of pregnancy who were seen at a single hospital in Vietnam. A short MTBT was defined as going to bed 2 hours or less after eating. Primary outcomes were GERD, defined as troublesome heartburn and/or regurgitation at least once a week, and reflux-related insomnia, defined as trouble initiating or maintaining nighttime sleep. Participants also reported the number of days of troublesome reflux symptoms and frequency of reflux-related insomnia over the last 7 days.

A total of 154 participants had a diagnosis of GERD, for an overall prevalence of 38.5%, similar to that seen in GERD studies of GERD and pregnancy, the researchers noted, and of those with GERD, 20 participants (13.0%) reported reflux-related insomnia.

The overall prevalence of heartburn, regurgitation, nausea with or without vomiting, and epigastric pain were 11.8%, 35.8%, 30.0%, and 5.5%, respectively. A total of 139 women reported reflux symptoms on at least 2 of the past 7 days, and 40 women reported both daytime and nighttime reflux symptoms.
 

Short meal-to-bed time shows strongest association

A short MTBT was the strongest predictor of GERD in multivariate analysis (odds ratio, 12.73; 95% confidence interval, 2.92-55.45; P = .001); previous history of reflux symptoms (OR, 9.05; 95% CI, 5.29-15.50; P < 001) and being in the third trimester versus first or second of pregnancy (OR, 1.66, 95% CI, 1.03-2.69; P = .039) also remained significant predictors in a multivariate analysis. In addition, nighttime short MTBT (but not daytime short MTBT) was the strongest risk factor for reflux-related insomnia (OR, 4.60), although alcohol consumption and a history of reflux-related symptoms also remained significant in multivariate analysis.

“Interestingly, the number of days during which reflux symptoms were experienced during the last 7 days sequentially increased across subgroups of participants with no short MTBT, either daytime or nighttime short MTBT, and with both daytime and nighttime MTBT,” the researchers wrote. At 4-7 days, none of the patients with no short MTBT reported reflux symptoms, compared with 7.5% of those with either daytime or nighttime MTBT and 20.9% of those with both daytime and nighttime MTBT.

The study findings were limited by several factors, including the inability to accurately record participants’ diets and the potential for overestimating the odds ratio of risk factors in patients with reflux-related insomnia because of the small numbers. However, the results support findings from previous studies and suggest that dietary modifications could provide a nonpharmacological treatment target for managing GERD in pregnant women, they concluded.
 

Behavioral intervention may benefit pregnant women

The study is important because heartburn and regurgitation are common challenges during pregnancy, Ziad F. Gellad, MD, of Duke University, Durham, N.C., said in an interview. “Understanding risk factors for these conditions can be helpful in designing behavioral and pharmaceutical therapeutic interventions.”

The link between short MTBT and increased risk for GERD is well-known, said Dr. Gellad. “Lengthening the time to laying supine after a meal is a common recommendation given to patients with GERD and is included in published GERD guidelines.” Although pregnant woman may have been excluded from trials on which the guidelines and recommendations are based, “it is reasonable to expect that findings would translate to this population that is generally higher risk for reflux,” he noted.

Dr. Gellad was interested to see the dose response between MTBT and reflux, with those patients having both daytime and nighttime short MTBT experiencing reflux more often than those with short MTBT in only one of those time periods (4-7 days vs. 1-3 days).

The key message for clinicians is that, for all individuals, pregnant or not, “avoiding late night meals and short meal-to-bed time is an appropriate behavioral intervention to recommend for patients with troublesome heartburn or regurgitation,” Dr. Gellad emphasized. However, more research is needed in some areas, “implementation studies would be helpful to understand how best to educate patients on behavioral modifications known to decrease reflux symptoms.”

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Gellad had no relevant financial disclosures, but serves as a member of the GI & Hepatology News board of editors.