LONDON – Disrupting how microorganisms communicate with each other could be a way to overcome antibiotic resistance and to help heal chronic wounds in patients with epidermolysis bullosa (EB), according to presenters at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

The majority of chronic wounds in patients with EB are colonized with microorganisms, with a predominance of Staphylococcus species, said Erik Gerner, an industrial PhD student at Mölnlycke Health Care in Gothenburg, Sweden, and Gothenburg University.

Because of the growing problem of antibiotic resistance, alternative treatments are needed, and one possible alternative for treating infected wounds could be interfering with quorum sensing, the cell-to-cell communication used by bacteria, he said. He is hoping to explore this possibility as a novel treatment strategy for infected wounds.

“Quorum sensing is defined as the ability to detect and respond to population density,” Mr. Gerner said, noting that, when there is a sufficient density of bacteria, “they start to communicate with each other.” This enables them to act as a community and perform actions that they could not do as individual cells. Such actions include forming biofilms, which helps protect bacteria from their environment, such as the immune system. Other actions include collectively switching on the production of virulence factors and becoming resistant to treatments.

“Bacteria use quorum sensing to act collectively,” Mr. Gerner said. “If we could shut down this quorum sensing system, it would be very beneficial … and increase the chances to heal the wound.”

The quorum sensing system is based on the production of signaling molecules called AHL (N-acyl homoserine lactones), which are constantly produced at a low rate. This isn’t a problem until the level of bacteria increases and the level of quorum sensing breaches a threshold, he explained.

There are several benefits of inhibiting bacterial communication through disrupting quorum sensing, namely, “a low risk of resistance,” Mr. Gerner said. There is also potentially less toxin production by bacteria, and this could help the immune system in killing the invading bacteria.

One approach to disrupting quorum testing that Mr. Gerner has been investigating is the use of sodium salicylate (NaSa). So far, preclinical work shows that NaSa can reduce toxin production but not the growth rate of bacteria. The advantage of using NaSa is that it is nontoxic to human dermal fibroblasts, with similar results seen in human keratinocytes and immune cells. His work to date has shown that NaSa reduced activity of NF-kB (a proinflammatory signaling pathway) in differentiated and lipopolysaccharide-stimulated monocytes; NF-kB activated production of proinflammatory cytokines (such as interleukin-1 beta and IL-6) are elevated in EB wounds. “My studies support the bodies of evidence that bacteria use quorum sensing to coordinate … and to produce a large number of toxic factors,” Mr. Gerner concluded. Future studies will look at the potential of NaSa to disrupt this activity.
 

Skin microbiome of EB wounds

Understanding what bacteria most commonly colonize wounds in patients with EB was the subject of two unrelated presentations at the EB World Congress. Liat Samuelov, MD, of the department of molecular dermatology at Tel Aviv (Israel) Sourasky Medical Center, presented data on skin microbiome characteristics in eight patients with recessive dystrophic EB (RDEB). This showed that there was reduced bacterial diversity in wounds, and a “progressive development of dysbiosis across different stages of DEB wound formation.”

The skin microbiome has been implicated in several skin diseases, Dr. Samuelov and associates observed in a poster presentation. That includes the autoimmune blistering disease bullous pemphigoid (Exp Dermatol. 2017 Dec;26[12]:1221-7). “Colonization of DEB chronic wounds may lead to systemic infections, result in delayed healing, and possibly be involved in the development of squamous cell carcinoma,” they noted in the poster, “thus accurate delineation of the dysbiotic profile … may point to corrective measures of great therapeutic potential.”

The aim was to see what microorganisms were present in the chronic wounds of the patients. To be included in the study, patients must not have had any antibiotic treatment – oral or topical – in the past 6 months. Samples were taken from an untreated wound, around the wound, and from uninvolved skin, which were compared with samples taken from similar areas in age-matched controls.

Reduced bacterial diversity was observed in RDEB wounds, compared with uninvolved or perilesional areas and the skin of control subjects, Dr. Samuelov said in an oral presentation of the study results. There was increased abundance of Staphylococcus epidermidis and decreased Cutibacterium acnes, which she noted was in contrast to other studies where S. aureus was the most common colonizer in RDEB wounds.

Bacterial composition in each group was calculated using the beta-diversity score, while control samples showed similar microbial composition, the DEB samples had no microbial similarities among different samples. These data “suggest the need to ascertain the potential therapeutic benefit of interventions aimed at restoring normal microbiome composition in DEB,” Dr. Samuelov concluded.

Wound colonization and squamous cell carcinoma

Other research on wound microbiology was presented by Laura E. Levin, MD, a dermatologist at New York–Presbyterian, and associates. “Given the potential role of bacteria-induced inflammation in the development of wound-associated SCC [squamous cell carcinoma] in a subset of patients, we sought to improve our understanding of what microbes colonize and infect the wounds of patients with epidermolysis bullosa,” they explained in their poster.

The researchers, from New York–Presbyterian Morgan Stanley Children’s Hospital and Columbia University Irvine Medical Center, New York, presented data from a retrospective analysis of 739 wound cultures taken between 2001 and 2017 from 158 patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database. In the analysis, just under 70% of patients had DEB, of which 90% were of the RDEB subtype; 13% had EB simplex, 14% had junctional EB, and 3% had an unknown EB subtype.

At least one organism grew in 87% of cultures, with the most common microorganism isolated being Staphylococcus aureus (84% of cultures). Other commonly isolated microbes were Pseudomonas aeruginosa in 35% of cultures, Streptococcus group A in 34% of cultures (of which 22% were Streptococcus pyogenes), Corynebacterium species in 31% of cultures, and Proteus species in 18% of cultures.

“Improved understanding of what microbes are colonizing the wounds of our patients may help improve antibiotic stewardship,” the researchers stated.

Looking at the antibiotic susceptibilities, Dr. Levin and associates found that 68% of 115 cultures were sensitive to methicillin and 60% of 15 cultures were sensitive to mupirocin. “Resistance to many systemic and topical antibiotic agents in EB patients supports surveillance cultures with routine testing for mupirocin susceptibility,” they suggested.

A total of 23 patients developed SCC of whom 10 had cultures that grew S. aureus (90%) and P. aeruginosa (50%), and Proteus species (20%). Among the patients who did not develop SCC, the respective cultures positive for each of those microorganisms were 83%, 34%, and 11%. Perhaps “gram-negative and flagellated organisms may be more common in wounds of patients at risk for SCC,” they observed, adding that further studies were needed to determine if “wound microbiome interventions inhibit the risk of development of SCC and improve outcomes.”

Mr. Gerner’s research is supported by Mölnlycke Health Care. Dr. Samuelov had no disclosures. The work by Dr. Levin and associates is supported by the Pediatric Dermatology Research Alliance, EB Research Partnership, and the Epidermolysis Bullosa Medical Research Foundation.

LONDON – Disrupting how microorganisms communicate with each other could be a way to overcome antibiotic resistance and to help heal chronic wounds in patients with epidermolysis bullosa (EB), according to presenters at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

The majority of chronic wounds in patients with EB are colonized with microorganisms, with a predominance of Staphylococcus species, said Erik Gerner, an industrial PhD student at Mölnlycke Health Care in Gothenburg, Sweden, and Gothenburg University.

Because of the growing problem of antibiotic resistance, alternative treatments are needed, and one possible alternative for treating infected wounds could be interfering with quorum sensing, the cell-to-cell communication used by bacteria, he said. He is hoping to explore this possibility as a novel treatment strategy for infected wounds.

“Quorum sensing is defined as the ability to detect and respond to population density,” Mr. Gerner said, noting that, when there is a sufficient density of bacteria, “they start to communicate with each other.” This enables them to act as a community and perform actions that they could not do as individual cells. Such actions include forming biofilms, which helps protect bacteria from their environment, such as the immune system. Other actions include collectively switching on the production of virulence factors and becoming resistant to treatments.

“Bacteria use quorum sensing to act collectively,” Mr. Gerner said. “If we could shut down this quorum sensing system, it would be very beneficial … and increase the chances to heal the wound.”

The quorum sensing system is based on the production of signaling molecules called AHL (N-acyl homoserine lactones), which are constantly produced at a low rate. This isn’t a problem until the level of bacteria increases and the level of quorum sensing breaches a threshold, he explained.

There are several benefits of inhibiting bacterial communication through disrupting quorum sensing, namely, “a low risk of resistance,” Mr. Gerner said. There is also potentially less toxin production by bacteria, and this could help the immune system in killing the invading bacteria.

One approach to disrupting quorum testing that Mr. Gerner has been investigating is the use of sodium salicylate (NaSa). So far, preclinical work shows that NaSa can reduce toxin production but not the growth rate of bacteria. The advantage of using NaSa is that it is nontoxic to human dermal fibroblasts, with similar results seen in human keratinocytes and immune cells. His work to date has shown that NaSa reduced activity of NF-kB (a proinflammatory signaling pathway) in differentiated and lipopolysaccharide-stimulated monocytes; NF-kB activated production of proinflammatory cytokines (such as interleukin-1 beta and IL-6) are elevated in EB wounds. “My studies support the bodies of evidence that bacteria use quorum sensing to coordinate … and to produce a large number of toxic factors,” Mr. Gerner concluded. Future studies will look at the potential of NaSa to disrupt this activity.
 

Skin microbiome of EB wounds

Understanding what bacteria most commonly colonize wounds in patients with EB was the subject of two unrelated presentations at the EB World Congress. Liat Samuelov, MD, of the department of molecular dermatology at Tel Aviv (Israel) Sourasky Medical Center, presented data on skin microbiome characteristics in eight patients with recessive dystrophic EB (RDEB). This showed that there was reduced bacterial diversity in wounds, and a “progressive development of dysbiosis across different stages of DEB wound formation.”

The skin microbiome has been implicated in several skin diseases, Dr. Samuelov and associates observed in a poster presentation. That includes the autoimmune blistering disease bullous pemphigoid (Exp Dermatol. 2017 Dec;26[12]:1221-7). “Colonization of DEB chronic wounds may lead to systemic infections, result in delayed healing, and possibly be involved in the development of squamous cell carcinoma,” they noted in the poster, “thus accurate delineation of the dysbiotic profile … may point to corrective measures of great therapeutic potential.”

The aim was to see what microorganisms were present in the chronic wounds of the patients. To be included in the study, patients must not have had any antibiotic treatment – oral or topical – in the past 6 months. Samples were taken from an untreated wound, around the wound, and from uninvolved skin, which were compared with samples taken from similar areas in age-matched controls.

Reduced bacterial diversity was observed in RDEB wounds, compared with uninvolved or perilesional areas and the skin of control subjects, Dr. Samuelov said in an oral presentation of the study results. There was increased abundance of Staphylococcus epidermidis and decreased Cutibacterium acnes, which she noted was in contrast to other studies where S. aureus was the most common colonizer in RDEB wounds.

Bacterial composition in each group was calculated using the beta-diversity score, while control samples showed similar microbial composition, the DEB samples had no microbial similarities among different samples. These data “suggest the need to ascertain the potential therapeutic benefit of interventions aimed at restoring normal microbiome composition in DEB,” Dr. Samuelov concluded.

Wound colonization and squamous cell carcinoma

Other research on wound microbiology was presented by Laura E. Levin, MD, a dermatologist at New York–Presbyterian, and associates. “Given the potential role of bacteria-induced inflammation in the development of wound-associated SCC [squamous cell carcinoma] in a subset of patients, we sought to improve our understanding of what microbes colonize and infect the wounds of patients with epidermolysis bullosa,” they explained in their poster.

The researchers, from New York–Presbyterian Morgan Stanley Children’s Hospital and Columbia University Irvine Medical Center, New York, presented data from a retrospective analysis of 739 wound cultures taken between 2001 and 2017 from 158 patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database. In the analysis, just under 70% of patients had DEB, of which 90% were of the RDEB subtype; 13% had EB simplex, 14% had junctional EB, and 3% had an unknown EB subtype.

At least one organism grew in 87% of cultures, with the most common microorganism isolated being Staphylococcus aureus (84% of cultures). Other commonly isolated microbes were Pseudomonas aeruginosa in 35% of cultures, Streptococcus group A in 34% of cultures (of which 22% were Streptococcus pyogenes), Corynebacterium species in 31% of cultures, and Proteus species in 18% of cultures.

“Improved understanding of what microbes are colonizing the wounds of our patients may help improve antibiotic stewardship,” the researchers stated.

Looking at the antibiotic susceptibilities, Dr. Levin and associates found that 68% of 115 cultures were sensitive to methicillin and 60% of 15 cultures were sensitive to mupirocin. “Resistance to many systemic and topical antibiotic agents in EB patients supports surveillance cultures with routine testing for mupirocin susceptibility,” they suggested.

A total of 23 patients developed SCC of whom 10 had cultures that grew S. aureus (90%) and P. aeruginosa (50%), and Proteus species (20%). Among the patients who did not develop SCC, the respective cultures positive for each of those microorganisms were 83%, 34%, and 11%. Perhaps “gram-negative and flagellated organisms may be more common in wounds of patients at risk for SCC,” they observed, adding that further studies were needed to determine if “wound microbiome interventions inhibit the risk of development of SCC and improve outcomes.”

Mr. Gerner’s research is supported by Mölnlycke Health Care. Dr. Samuelov had no disclosures. The work by Dr. Levin and associates is supported by the Pediatric Dermatology Research Alliance, EB Research Partnership, and the Epidermolysis Bullosa Medical Research Foundation.

LONDON – Disrupting how microorganisms communicate with each other could be a way to overcome antibiotic resistance and to help heal chronic wounds in patients with epidermolysis bullosa (EB), according to presenters at the EB World Congress, organized by the Dystrophic Epidermolysis Bullosa Association (DEBRA).

The majority of chronic wounds in patients with EB are colonized with microorganisms, with a predominance of Staphylococcus species, said Erik Gerner, an industrial PhD student at Mölnlycke Health Care in Gothenburg, Sweden, and Gothenburg University.

Because of the growing problem of antibiotic resistance, alternative treatments are needed, and one possible alternative for treating infected wounds could be interfering with quorum sensing, the cell-to-cell communication used by bacteria, he said. He is hoping to explore this possibility as a novel treatment strategy for infected wounds.

“Quorum sensing is defined as the ability to detect and respond to population density,” Mr. Gerner said, noting that, when there is a sufficient density of bacteria, “they start to communicate with each other.” This enables them to act as a community and perform actions that they could not do as individual cells. Such actions include forming biofilms, which helps protect bacteria from their environment, such as the immune system. Other actions include collectively switching on the production of virulence factors and becoming resistant to treatments.

“Bacteria use quorum sensing to act collectively,” Mr. Gerner said. “If we could shut down this quorum sensing system, it would be very beneficial … and increase the chances to heal the wound.”

The quorum sensing system is based on the production of signaling molecules called AHL (N-acyl homoserine lactones), which are constantly produced at a low rate. This isn’t a problem until the level of bacteria increases and the level of quorum sensing breaches a threshold, he explained.

There are several benefits of inhibiting bacterial communication through disrupting quorum sensing, namely, “a low risk of resistance,” Mr. Gerner said. There is also potentially less toxin production by bacteria, and this could help the immune system in killing the invading bacteria.

One approach to disrupting quorum testing that Mr. Gerner has been investigating is the use of sodium salicylate (NaSa). So far, preclinical work shows that NaSa can reduce toxin production but not the growth rate of bacteria. The advantage of using NaSa is that it is nontoxic to human dermal fibroblasts, with similar results seen in human keratinocytes and immune cells. His work to date has shown that NaSa reduced activity of NF-kB (a proinflammatory signaling pathway) in differentiated and lipopolysaccharide-stimulated monocytes; NF-kB activated production of proinflammatory cytokines (such as interleukin-1 beta and IL-6) are elevated in EB wounds. “My studies support the bodies of evidence that bacteria use quorum sensing to coordinate … and to produce a large number of toxic factors,” Mr. Gerner concluded. Future studies will look at the potential of NaSa to disrupt this activity.
 

Skin microbiome of EB wounds

Understanding what bacteria most commonly colonize wounds in patients with EB was the subject of two unrelated presentations at the EB World Congress. Liat Samuelov, MD, of the department of molecular dermatology at Tel Aviv (Israel) Sourasky Medical Center, presented data on skin microbiome characteristics in eight patients with recessive dystrophic EB (RDEB). This showed that there was reduced bacterial diversity in wounds, and a “progressive development of dysbiosis across different stages of DEB wound formation.”

The skin microbiome has been implicated in several skin diseases, Dr. Samuelov and associates observed in a poster presentation. That includes the autoimmune blistering disease bullous pemphigoid (Exp Dermatol. 2017 Dec;26[12]:1221-7). “Colonization of DEB chronic wounds may lead to systemic infections, result in delayed healing, and possibly be involved in the development of squamous cell carcinoma,” they noted in the poster, “thus accurate delineation of the dysbiotic profile … may point to corrective measures of great therapeutic potential.”

The aim was to see what microorganisms were present in the chronic wounds of the patients. To be included in the study, patients must not have had any antibiotic treatment – oral or topical – in the past 6 months. Samples were taken from an untreated wound, around the wound, and from uninvolved skin, which were compared with samples taken from similar areas in age-matched controls.

Reduced bacterial diversity was observed in RDEB wounds, compared with uninvolved or perilesional areas and the skin of control subjects, Dr. Samuelov said in an oral presentation of the study results. There was increased abundance of Staphylococcus epidermidis and decreased Cutibacterium acnes, which she noted was in contrast to other studies where S. aureus was the most common colonizer in RDEB wounds.

Bacterial composition in each group was calculated using the beta-diversity score, while control samples showed similar microbial composition, the DEB samples had no microbial similarities among different samples. These data “suggest the need to ascertain the potential therapeutic benefit of interventions aimed at restoring normal microbiome composition in DEB,” Dr. Samuelov concluded.

Wound colonization and squamous cell carcinoma

Other research on wound microbiology was presented by Laura E. Levin, MD, a dermatologist at New York–Presbyterian, and associates. “Given the potential role of bacteria-induced inflammation in the development of wound-associated SCC [squamous cell carcinoma] in a subset of patients, we sought to improve our understanding of what microbes colonize and infect the wounds of patients with epidermolysis bullosa,” they explained in their poster.

The researchers, from New York–Presbyterian Morgan Stanley Children’s Hospital and Columbia University Irvine Medical Center, New York, presented data from a retrospective analysis of 739 wound cultures taken between 2001 and 2017 from 158 patients enrolled in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database. In the analysis, just under 70% of patients had DEB, of which 90% were of the RDEB subtype; 13% had EB simplex, 14% had junctional EB, and 3% had an unknown EB subtype.

At least one organism grew in 87% of cultures, with the most common microorganism isolated being Staphylococcus aureus (84% of cultures). Other commonly isolated microbes were Pseudomonas aeruginosa in 35% of cultures, Streptococcus group A in 34% of cultures (of which 22% were Streptococcus pyogenes), Corynebacterium species in 31% of cultures, and Proteus species in 18% of cultures.

“Improved understanding of what microbes are colonizing the wounds of our patients may help improve antibiotic stewardship,” the researchers stated.

Looking at the antibiotic susceptibilities, Dr. Levin and associates found that 68% of 115 cultures were sensitive to methicillin and 60% of 15 cultures were sensitive to mupirocin. “Resistance to many systemic and topical antibiotic agents in EB patients supports surveillance cultures with routine testing for mupirocin susceptibility,” they suggested.

A total of 23 patients developed SCC of whom 10 had cultures that grew S. aureus (90%) and P. aeruginosa (50%), and Proteus species (20%). Among the patients who did not develop SCC, the respective cultures positive for each of those microorganisms were 83%, 34%, and 11%. Perhaps “gram-negative and flagellated organisms may be more common in wounds of patients at risk for SCC,” they observed, adding that further studies were needed to determine if “wound microbiome interventions inhibit the risk of development of SCC and improve outcomes.”

Mr. Gerner’s research is supported by Mölnlycke Health Care. Dr. Samuelov had no disclosures. The work by Dr. Levin and associates is supported by the Pediatric Dermatology Research Alliance, EB Research Partnership, and the Epidermolysis Bullosa Medical Research Foundation.

ORLANDO – Biotin is the most popular consumer supplement for alopecia and highly popular online, but should patients be taking it?

Patients may want something “natural” to treat their hair loss, but “natural is not always good,” Amy McMichael, MD, professor and chair of the department of dermatology at Wake Forest Baptist Health, Winston-Salem, N.C., said at the ODAC Dermatology, Aesthetic, & Surgical Conference.

Dosages of commercially available biotin supplements can vary significantly, with some doses as high as 10,000 mcg, making supraphysiological dosing possible. Dr. McMichael said that, not only is biotin unlikely to help with a patient’s alopecia, but a high intake of biotin can interfere with certain assays that use streptavidin-biotin capture techniques (Clin Chem Lab Med. 2017 May 1;55[6]:817-25). This could present a problem for a patient who experiences an MI or has a thyroid disorder where a high level of biotin could affect lab results, she noted.

Dr. McMichael advises patients that there is a low likelihood that biotin will help their hair loss, and suggests that they stop taking the supplements, noting that all hair supplements contain biotin.

Questioning side effects of 5-alpha reductase inhibitors

Research in the early 2010s associated the 5-alpha reductase inhibitor finasteride with persistent sexual side effects and depression. But a later meta-analysis of the Prostate Cancer Prevention Trial and other trials did not find evidence of persistent sexual side effects or depression in men on finasteride, and the authors said that double-blind, placebo-controlled studies were needed (J Clin Aesthet Dermatol. 2014 Dec;7[12]:51-5).

However, two meta-analyses of 34 clinical trials published in 2015 found that none of the clinical trials evaluating finasteride treatment in patients with androgenic alopecia had accurate safety reporting (JAMA Dermatol. 2015 Jun;151[6]:600-6). Another study published by the same group in 2017 found that 0.8% of men aged 16-42 years to exposed to a 5-alpha reductase inhibitor developed persistent erectile dysfunction after a longer duration of exposure (median, 1,534 days). compared with a shorter duration of exposure (PeerJ. 2017 Mar 9;5:e3020).

The bottom line when considering use of 5-alpha reductase inhibitors in men is to discuss the outlier data on persistent sexual dysfunction in the studies, ask patients whether they have a history of sexual dysfunction and depression, and then only treat appropriate patients with no such history, Dr. McMichael said.

Use of 5-alpha reductase inhibitors also appears to be related to an increased risk of type 2 diabetes in men with benign prostatic hyperplasia, according to more recent data. In a study of patients in the U.K. Clinical Practice Research Datalink and Taiwanese National Health Insurance Research Database who received dutasteride, finasteride, or the alpha blocker tamsulosin, there was a slightly increased risk of type 2 diabetes among those who took the two 5-alpha reductase inhibitors, compared with those on tamsulosin (BMJ. 2019;365:l1204). In light of these results, Dr. McMichael advised clinicians to be aware of these risks and to consider screening patients for type 2 diabetes and ask them about their family history, but the results shouldn’t affect patients at risk for type 2 diabetes or metabolic disorder.
 

JAK inhibitors for alopecia areata

Within the past few years, promising results for Janus kinase (JAK) inhibitors like tofacitinib and ruxolitinib for alopecia areata have been reported, but they are currently not a first-line therapy, Dr. McMichael said. Consider methotrexate first in older adolescents and adults with more than 50% hair loss, followed by a JAK inhibitor if there is no improvement or methotrexate is not tolerated well.

Clinicians can consider enrolling their patients in a clinical trial to give them access to JAK inhibitors as a treatment option, she noted, and if a trial is not available, it may be worth appealing to an insurance company using an article titled “Alopecia areata is a medical disease” coauthored by Dr. McMichael and others (Am Acad Dermatol. 2018 Apr;78[4]:832-4). After two denials by insurance, the manufacturer’s patient assistance program (Xelsource) may be helpful in obtaining tofacitinib (Xeljanz) through a letter and references. There are adolescent data on JAK inhibitors for alopecia, but “absolutely no data” in very young children, so prior to adolescence, she would not recommend this treatment. In a study of 13 adolescents with alopecia areata, totalis, or universalis, those treated with tofacitinib for a mean of 6.5 months, 9 had significant hair regrowth with treatment and adverse events were mild (J Am Acad Dermatol. 2017 Jan;76[1]:29-32).

Dr. McMichael reports being an investigator for Allergan, Intendis, Proctor & Gamble, Samumed, Cassiopia, Concert, Aclaris, and Incyte; and is a consultant for Johnson & Johnson, Proctor & Gamble, Allergan, Bayer, Galderma, Incyte, Samumed, Aclaris, Anacor, Pfizer, Nutrafol, Bioniz, and Almirall.

ORLANDO – Biotin is the most popular consumer supplement for alopecia and highly popular online, but should patients be taking it?

Patients may want something “natural” to treat their hair loss, but “natural is not always good,” Amy McMichael, MD, professor and chair of the department of dermatology at Wake Forest Baptist Health, Winston-Salem, N.C., said at the ODAC Dermatology, Aesthetic, & Surgical Conference.

Dosages of commercially available biotin supplements can vary significantly, with some doses as high as 10,000 mcg, making supraphysiological dosing possible. Dr. McMichael said that, not only is biotin unlikely to help with a patient’s alopecia, but a high intake of biotin can interfere with certain assays that use streptavidin-biotin capture techniques (Clin Chem Lab Med. 2017 May 1;55[6]:817-25). This could present a problem for a patient who experiences an MI or has a thyroid disorder where a high level of biotin could affect lab results, she noted.

Dr. McMichael advises patients that there is a low likelihood that biotin will help their hair loss, and suggests that they stop taking the supplements, noting that all hair supplements contain biotin.

Questioning side effects of 5-alpha reductase inhibitors

Research in the early 2010s associated the 5-alpha reductase inhibitor finasteride with persistent sexual side effects and depression. But a later meta-analysis of the Prostate Cancer Prevention Trial and other trials did not find evidence of persistent sexual side effects or depression in men on finasteride, and the authors said that double-blind, placebo-controlled studies were needed (J Clin Aesthet Dermatol. 2014 Dec;7[12]:51-5).

However, two meta-analyses of 34 clinical trials published in 2015 found that none of the clinical trials evaluating finasteride treatment in patients with androgenic alopecia had accurate safety reporting (JAMA Dermatol. 2015 Jun;151[6]:600-6). Another study published by the same group in 2017 found that 0.8% of men aged 16-42 years to exposed to a 5-alpha reductase inhibitor developed persistent erectile dysfunction after a longer duration of exposure (median, 1,534 days). compared with a shorter duration of exposure (PeerJ. 2017 Mar 9;5:e3020).

The bottom line when considering use of 5-alpha reductase inhibitors in men is to discuss the outlier data on persistent sexual dysfunction in the studies, ask patients whether they have a history of sexual dysfunction and depression, and then only treat appropriate patients with no such history, Dr. McMichael said.

Use of 5-alpha reductase inhibitors also appears to be related to an increased risk of type 2 diabetes in men with benign prostatic hyperplasia, according to more recent data. In a study of patients in the U.K. Clinical Practice Research Datalink and Taiwanese National Health Insurance Research Database who received dutasteride, finasteride, or the alpha blocker tamsulosin, there was a slightly increased risk of type 2 diabetes among those who took the two 5-alpha reductase inhibitors, compared with those on tamsulosin (BMJ. 2019;365:l1204). In light of these results, Dr. McMichael advised clinicians to be aware of these risks and to consider screening patients for type 2 diabetes and ask them about their family history, but the results shouldn’t affect patients at risk for type 2 diabetes or metabolic disorder.
 

JAK inhibitors for alopecia areata

Within the past few years, promising results for Janus kinase (JAK) inhibitors like tofacitinib and ruxolitinib for alopecia areata have been reported, but they are currently not a first-line therapy, Dr. McMichael said. Consider methotrexate first in older adolescents and adults with more than 50% hair loss, followed by a JAK inhibitor if there is no improvement or methotrexate is not tolerated well.

Clinicians can consider enrolling their patients in a clinical trial to give them access to JAK inhibitors as a treatment option, she noted, and if a trial is not available, it may be worth appealing to an insurance company using an article titled “Alopecia areata is a medical disease” coauthored by Dr. McMichael and others (Am Acad Dermatol. 2018 Apr;78[4]:832-4). After two denials by insurance, the manufacturer’s patient assistance program (Xelsource) may be helpful in obtaining tofacitinib (Xeljanz) through a letter and references. There are adolescent data on JAK inhibitors for alopecia, but “absolutely no data” in very young children, so prior to adolescence, she would not recommend this treatment. In a study of 13 adolescents with alopecia areata, totalis, or universalis, those treated with tofacitinib for a mean of 6.5 months, 9 had significant hair regrowth with treatment and adverse events were mild (J Am Acad Dermatol. 2017 Jan;76[1]:29-32).

Dr. McMichael reports being an investigator for Allergan, Intendis, Proctor & Gamble, Samumed, Cassiopia, Concert, Aclaris, and Incyte; and is a consultant for Johnson & Johnson, Proctor & Gamble, Allergan, Bayer, Galderma, Incyte, Samumed, Aclaris, Anacor, Pfizer, Nutrafol, Bioniz, and Almirall.

ORLANDO – Biotin is the most popular consumer supplement for alopecia and highly popular online, but should patients be taking it?

Patients may want something “natural” to treat their hair loss, but “natural is not always good,” Amy McMichael, MD, professor and chair of the department of dermatology at Wake Forest Baptist Health, Winston-Salem, N.C., said at the ODAC Dermatology, Aesthetic, & Surgical Conference.

Dosages of commercially available biotin supplements can vary significantly, with some doses as high as 10,000 mcg, making supraphysiological dosing possible. Dr. McMichael said that, not only is biotin unlikely to help with a patient’s alopecia, but a high intake of biotin can interfere with certain assays that use streptavidin-biotin capture techniques (Clin Chem Lab Med. 2017 May 1;55[6]:817-25). This could present a problem for a patient who experiences an MI or has a thyroid disorder where a high level of biotin could affect lab results, she noted.

Dr. McMichael advises patients that there is a low likelihood that biotin will help their hair loss, and suggests that they stop taking the supplements, noting that all hair supplements contain biotin.

Questioning side effects of 5-alpha reductase inhibitors

Research in the early 2010s associated the 5-alpha reductase inhibitor finasteride with persistent sexual side effects and depression. But a later meta-analysis of the Prostate Cancer Prevention Trial and other trials did not find evidence of persistent sexual side effects or depression in men on finasteride, and the authors said that double-blind, placebo-controlled studies were needed (J Clin Aesthet Dermatol. 2014 Dec;7[12]:51-5).

However, two meta-analyses of 34 clinical trials published in 2015 found that none of the clinical trials evaluating finasteride treatment in patients with androgenic alopecia had accurate safety reporting (JAMA Dermatol. 2015 Jun;151[6]:600-6). Another study published by the same group in 2017 found that 0.8% of men aged 16-42 years to exposed to a 5-alpha reductase inhibitor developed persistent erectile dysfunction after a longer duration of exposure (median, 1,534 days). compared with a shorter duration of exposure (PeerJ. 2017 Mar 9;5:e3020).

The bottom line when considering use of 5-alpha reductase inhibitors in men is to discuss the outlier data on persistent sexual dysfunction in the studies, ask patients whether they have a history of sexual dysfunction and depression, and then only treat appropriate patients with no such history, Dr. McMichael said.

Use of 5-alpha reductase inhibitors also appears to be related to an increased risk of type 2 diabetes in men with benign prostatic hyperplasia, according to more recent data. In a study of patients in the U.K. Clinical Practice Research Datalink and Taiwanese National Health Insurance Research Database who received dutasteride, finasteride, or the alpha blocker tamsulosin, there was a slightly increased risk of type 2 diabetes among those who took the two 5-alpha reductase inhibitors, compared with those on tamsulosin (BMJ. 2019;365:l1204). In light of these results, Dr. McMichael advised clinicians to be aware of these risks and to consider screening patients for type 2 diabetes and ask them about their family history, but the results shouldn’t affect patients at risk for type 2 diabetes or metabolic disorder.
 

JAK inhibitors for alopecia areata

Within the past few years, promising results for Janus kinase (JAK) inhibitors like tofacitinib and ruxolitinib for alopecia areata have been reported, but they are currently not a first-line therapy, Dr. McMichael said. Consider methotrexate first in older adolescents and adults with more than 50% hair loss, followed by a JAK inhibitor if there is no improvement or methotrexate is not tolerated well.

Clinicians can consider enrolling their patients in a clinical trial to give them access to JAK inhibitors as a treatment option, she noted, and if a trial is not available, it may be worth appealing to an insurance company using an article titled “Alopecia areata is a medical disease” coauthored by Dr. McMichael and others (Am Acad Dermatol. 2018 Apr;78[4]:832-4). After two denials by insurance, the manufacturer’s patient assistance program (Xelsource) may be helpful in obtaining tofacitinib (Xeljanz) through a letter and references. There are adolescent data on JAK inhibitors for alopecia, but “absolutely no data” in very young children, so prior to adolescence, she would not recommend this treatment. In a study of 13 adolescents with alopecia areata, totalis, or universalis, those treated with tofacitinib for a mean of 6.5 months, 9 had significant hair regrowth with treatment and adverse events were mild (J Am Acad Dermatol. 2017 Jan;76[1]:29-32).

Dr. McMichael reports being an investigator for Allergan, Intendis, Proctor & Gamble, Samumed, Cassiopia, Concert, Aclaris, and Incyte; and is a consultant for Johnson & Johnson, Proctor & Gamble, Allergan, Bayer, Galderma, Incyte, Samumed, Aclaris, Anacor, Pfizer, Nutrafol, Bioniz, and Almirall.

The combination of bevacizumab and pembrolizumab demonstrated acceptable safety and activity in patients with metastatic renal cell carcinoma (mRCC) in a phase 1b/2 study, according to researchers.

Grade 3-4 adverse events were seen in 45% of patients, which “compares favorably” with other combinations of immune checkpoint inhibitors and tyrosine kinase inhibitors, according to study author Arkadiusz Z. Dudek, MD, PhD, of HealthPartners Regions Cancer Care Center in St. Paul, Minn. and colleagues. Their report was published in the Journal of Clinical Oncology.

Phase 1b

The phase 1b portion of the study included 13 patients with clear cell mRCC that relapsed after or was refractory to multiple prior lines of therapy. The patients’ median age was 55 years (range, 33-68 years), and most were men (84.6%).

The patients received infusions of pembrolizumab at 200 mg plus bevacizumab at 10 mg/kg or 15 mg/kg every 3 weeks. The primary objective of the phase 1b component was to determine safety and identify the maximum tolerated dose of the combination.

The overall response rate was 41.7%. Five patients had partial responses, six had stable disease, one had progressive disease, and one was not evaluable.

The median progression-free survival was 9.9 months, and the median overall survival was 17.9 months. No dose-limiting toxicities were observed.
 

Phase 2

The phase 2 component included 48 patients with clear cell mRCC, all of whom were treatment naive. Their median age was 61 years (range, 42-84 years), and most were men (68.8%).

Based on the phase 1b data, the phase 2 dose of bevacizumab was 15 mg/kg every 3 weeks.

After a median time on treatment of 298 days, the overall response rate was 60.9%. One patient achieved a complete response, and two patients had complete responses in target lesions. Of the remaining patients, 25 achieved partial responses, 18 had stable disease, and 2 were unevaluable.

The median progression-free survival was 20.7 months, and the median overall survival was not reached at 28.3 months.
 

Safety

In the combined safety analysis, the most frequent treatment-related grade 3 adverse events were hypertension (25%), proteinuria (10%), adrenal insufficiency (6.7%), and pain/headaches (5.0%).

The most common grade 3 immune-related adverse events were adrenal insufficiency (6.7%), pneumonitis (3.3%), hepatitis (1.7%), skin rash (1.7%), gastritis (1.7%), hypothyroidism (1.7%), and oral mucositis (1.7%).

Two grade 4 adverse events (hyponatremia and duodenal ulcer) were reported. There were no treatment-related grade 5 events.

“The combination of 200 mg of pembrolizumab and a 15-mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC,” the authors wrote. “[The combination] could be further tested in patient populations where TKIs [tyrosine kinase inhibitors] are not well tolerated and can cause early treatment discontinuation.”

This study was funded by Merck. The authors disclosed financial affiliations with Merck and other companies.

SOURCE: Dudek AZ et al. J Clin Oncol. 2020 Feb 25. doi: 10.1200/JCO.19.02394.

The combination of bevacizumab and pembrolizumab demonstrated acceptable safety and activity in patients with metastatic renal cell carcinoma (mRCC) in a phase 1b/2 study, according to researchers.

Grade 3-4 adverse events were seen in 45% of patients, which “compares favorably” with other combinations of immune checkpoint inhibitors and tyrosine kinase inhibitors, according to study author Arkadiusz Z. Dudek, MD, PhD, of HealthPartners Regions Cancer Care Center in St. Paul, Minn. and colleagues. Their report was published in the Journal of Clinical Oncology.

Phase 1b

The phase 1b portion of the study included 13 patients with clear cell mRCC that relapsed after or was refractory to multiple prior lines of therapy. The patients’ median age was 55 years (range, 33-68 years), and most were men (84.6%).

The patients received infusions of pembrolizumab at 200 mg plus bevacizumab at 10 mg/kg or 15 mg/kg every 3 weeks. The primary objective of the phase 1b component was to determine safety and identify the maximum tolerated dose of the combination.

The overall response rate was 41.7%. Five patients had partial responses, six had stable disease, one had progressive disease, and one was not evaluable.

The median progression-free survival was 9.9 months, and the median overall survival was 17.9 months. No dose-limiting toxicities were observed.
 

Phase 2

The phase 2 component included 48 patients with clear cell mRCC, all of whom were treatment naive. Their median age was 61 years (range, 42-84 years), and most were men (68.8%).

Based on the phase 1b data, the phase 2 dose of bevacizumab was 15 mg/kg every 3 weeks.

After a median time on treatment of 298 days, the overall response rate was 60.9%. One patient achieved a complete response, and two patients had complete responses in target lesions. Of the remaining patients, 25 achieved partial responses, 18 had stable disease, and 2 were unevaluable.

The median progression-free survival was 20.7 months, and the median overall survival was not reached at 28.3 months.
 

Safety

In the combined safety analysis, the most frequent treatment-related grade 3 adverse events were hypertension (25%), proteinuria (10%), adrenal insufficiency (6.7%), and pain/headaches (5.0%).

The most common grade 3 immune-related adverse events were adrenal insufficiency (6.7%), pneumonitis (3.3%), hepatitis (1.7%), skin rash (1.7%), gastritis (1.7%), hypothyroidism (1.7%), and oral mucositis (1.7%).

Two grade 4 adverse events (hyponatremia and duodenal ulcer) were reported. There were no treatment-related grade 5 events.

“The combination of 200 mg of pembrolizumab and a 15-mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC,” the authors wrote. “[The combination] could be further tested in patient populations where TKIs [tyrosine kinase inhibitors] are not well tolerated and can cause early treatment discontinuation.”

This study was funded by Merck. The authors disclosed financial affiliations with Merck and other companies.

SOURCE: Dudek AZ et al. J Clin Oncol. 2020 Feb 25. doi: 10.1200/JCO.19.02394.

The combination of bevacizumab and pembrolizumab demonstrated acceptable safety and activity in patients with metastatic renal cell carcinoma (mRCC) in a phase 1b/2 study, according to researchers.

Grade 3-4 adverse events were seen in 45% of patients, which “compares favorably” with other combinations of immune checkpoint inhibitors and tyrosine kinase inhibitors, according to study author Arkadiusz Z. Dudek, MD, PhD, of HealthPartners Regions Cancer Care Center in St. Paul, Minn. and colleagues. Their report was published in the Journal of Clinical Oncology.

Phase 1b

The phase 1b portion of the study included 13 patients with clear cell mRCC that relapsed after or was refractory to multiple prior lines of therapy. The patients’ median age was 55 years (range, 33-68 years), and most were men (84.6%).

The patients received infusions of pembrolizumab at 200 mg plus bevacizumab at 10 mg/kg or 15 mg/kg every 3 weeks. The primary objective of the phase 1b component was to determine safety and identify the maximum tolerated dose of the combination.

The overall response rate was 41.7%. Five patients had partial responses, six had stable disease, one had progressive disease, and one was not evaluable.

The median progression-free survival was 9.9 months, and the median overall survival was 17.9 months. No dose-limiting toxicities were observed.
 

Phase 2

The phase 2 component included 48 patients with clear cell mRCC, all of whom were treatment naive. Their median age was 61 years (range, 42-84 years), and most were men (68.8%).

Based on the phase 1b data, the phase 2 dose of bevacizumab was 15 mg/kg every 3 weeks.

After a median time on treatment of 298 days, the overall response rate was 60.9%. One patient achieved a complete response, and two patients had complete responses in target lesions. Of the remaining patients, 25 achieved partial responses, 18 had stable disease, and 2 were unevaluable.

The median progression-free survival was 20.7 months, and the median overall survival was not reached at 28.3 months.
 

Safety

In the combined safety analysis, the most frequent treatment-related grade 3 adverse events were hypertension (25%), proteinuria (10%), adrenal insufficiency (6.7%), and pain/headaches (5.0%).

The most common grade 3 immune-related adverse events were adrenal insufficiency (6.7%), pneumonitis (3.3%), hepatitis (1.7%), skin rash (1.7%), gastritis (1.7%), hypothyroidism (1.7%), and oral mucositis (1.7%).

Two grade 4 adverse events (hyponatremia and duodenal ulcer) were reported. There were no treatment-related grade 5 events.

“The combination of 200 mg of pembrolizumab and a 15-mg/kg dose of bevacizumab given every 3 weeks is safe and active in metastatic RCC,” the authors wrote. “[The combination] could be further tested in patient populations where TKIs [tyrosine kinase inhibitors] are not well tolerated and can cause early treatment discontinuation.”

This study was funded by Merck. The authors disclosed financial affiliations with Merck and other companies.

SOURCE: Dudek AZ et al. J Clin Oncol. 2020 Feb 25. doi: 10.1200/JCO.19.02394.

The American Association of Endocrine Surgeons has issued a first-of-its-kind set of clinical guidelines for the surgical treatment of thyroid disease, offering evidence-based recommendations on the wide-ranging aspects of thyroidectomy and the management of benign, as well as malignant, thyroid nodules and cancer.

Whereas various endocrine and thyroid societies issue guidelines on many aspects of the management of thyroid disease, the new AAES guidelines are the first specifically to address surgical management of thyroid disease in adults.

“These guidelines truly focus on the surgical decision-making and management of thyroid disease. However, there is something for all clinicians who take care of patients with thyroid disease,” lead author Kepal N. Patel, MD, of NYU Langone Health in New York City, said in an interview.

The guidelines, published in the Annals of Surgery, include a total of 66 recommendations from a multidisciplinary panel of 19 experts who reviewed medical literature spanning 1985-2018.

More than 100,000 thyroidectomies are performed each year in the United States alone, and as surgical indications and treatment paradigms evolve, the need for surgical guidance is more important than ever, Dr. Patel said.

“Such transformations have propagated differences in clinical interpretation and management, and as a result, clinical uncertainty, and even controversy, have emerged,” he said. “Recognizing the importance of these changes, the AAES determined that evidence-based clinical guidelines were necessary to enhance the safe and effective surgical treatment of benign and malignant thyroid disease.”

Key areas addressed in the guidelines include the addition of new cytologic and pathologic diagnostic criteria, molecular profiling tests, operative techniques, and adjuncts, as well as the nuances surrounding the sometimes challenging newer concept of “borderline” thyroid tumors, Dr. Patel noted.

In terms of imaging recommendations, for instance, the guidelines recommend the preoperative use of computed tomography or magnetic resonance imaging, as stated in Recommendation 6: “CT or MRI with intravenous contrast should be used preoperatively as an adjunct to ultrasound in selected patients with clinical suspicion for advanced locoregional thyroid cancer.” The recommendation is cited as being “strong,” with a “low quality of evidence.”

Further diagnostic recommendations cover issues that include voice assessment, the risk for vocal fold dysfunction related to thyroid disease and surgery, and the use of fine-needle aspiration biopsy in evaluating suspicious thyroid nodules and lymph nodes.

The guidelines also address the indications for thyroidectomy, with recommendations regarding the extent and outcomes of surgery spanning different categories of thyroid disease. A key recommendation along those lines, for instance, indicates that, when possible, thyroidectomy should be performed by surgeons who perform a high volume of such procedures.

Approaches for safe and effective perioperative management are also covered, and include measures to prevent complications and the use of thyroid tissue diagnosis during surgery, such as core-needle biopsy of the thyroid and cervical lymph nodes, and incisional biopsy of the thyroid, nodal dissection, and concurrent parathyroidectomy.

Other recommendations address the optimal management of thyroid cancer, with an emphasis on a personalized, evidence-based approach tailored to the patient’s situation and preferences.

The authors underscored that, as technology rapidly evolves, “in the future, this work will certainly and rightly need to be done again.” In the meantime, they wrote, recommendations should be relevant to “the target audience [of] the practicing surgeon in a community hospital, academic center, or training program.”

An AAES press release noted that “the members of the expert panel hope their efforts will meet the need for evidence-based recommendations to ‘define practice, personalize care, stratify risk, reduce health care costs, improve outcomes, and identify rational challenges for future efforts.’ ”

The authors of the guidelines reported no conflicts of interest in regard to the guidelines, although the article lists disclosures for six authors.

This article first appeared on Medscape.com.
 

The American Association of Endocrine Surgeons has issued a first-of-its-kind set of clinical guidelines for the surgical treatment of thyroid disease, offering evidence-based recommendations on the wide-ranging aspects of thyroidectomy and the management of benign, as well as malignant, thyroid nodules and cancer.

Whereas various endocrine and thyroid societies issue guidelines on many aspects of the management of thyroid disease, the new AAES guidelines are the first specifically to address surgical management of thyroid disease in adults.

“These guidelines truly focus on the surgical decision-making and management of thyroid disease. However, there is something for all clinicians who take care of patients with thyroid disease,” lead author Kepal N. Patel, MD, of NYU Langone Health in New York City, said in an interview.

The guidelines, published in the Annals of Surgery, include a total of 66 recommendations from a multidisciplinary panel of 19 experts who reviewed medical literature spanning 1985-2018.

More than 100,000 thyroidectomies are performed each year in the United States alone, and as surgical indications and treatment paradigms evolve, the need for surgical guidance is more important than ever, Dr. Patel said.

“Such transformations have propagated differences in clinical interpretation and management, and as a result, clinical uncertainty, and even controversy, have emerged,” he said. “Recognizing the importance of these changes, the AAES determined that evidence-based clinical guidelines were necessary to enhance the safe and effective surgical treatment of benign and malignant thyroid disease.”

Key areas addressed in the guidelines include the addition of new cytologic and pathologic diagnostic criteria, molecular profiling tests, operative techniques, and adjuncts, as well as the nuances surrounding the sometimes challenging newer concept of “borderline” thyroid tumors, Dr. Patel noted.

In terms of imaging recommendations, for instance, the guidelines recommend the preoperative use of computed tomography or magnetic resonance imaging, as stated in Recommendation 6: “CT or MRI with intravenous contrast should be used preoperatively as an adjunct to ultrasound in selected patients with clinical suspicion for advanced locoregional thyroid cancer.” The recommendation is cited as being “strong,” with a “low quality of evidence.”

Further diagnostic recommendations cover issues that include voice assessment, the risk for vocal fold dysfunction related to thyroid disease and surgery, and the use of fine-needle aspiration biopsy in evaluating suspicious thyroid nodules and lymph nodes.

The guidelines also address the indications for thyroidectomy, with recommendations regarding the extent and outcomes of surgery spanning different categories of thyroid disease. A key recommendation along those lines, for instance, indicates that, when possible, thyroidectomy should be performed by surgeons who perform a high volume of such procedures.

Approaches for safe and effective perioperative management are also covered, and include measures to prevent complications and the use of thyroid tissue diagnosis during surgery, such as core-needle biopsy of the thyroid and cervical lymph nodes, and incisional biopsy of the thyroid, nodal dissection, and concurrent parathyroidectomy.

Other recommendations address the optimal management of thyroid cancer, with an emphasis on a personalized, evidence-based approach tailored to the patient’s situation and preferences.

The authors underscored that, as technology rapidly evolves, “in the future, this work will certainly and rightly need to be done again.” In the meantime, they wrote, recommendations should be relevant to “the target audience [of] the practicing surgeon in a community hospital, academic center, or training program.”

An AAES press release noted that “the members of the expert panel hope their efforts will meet the need for evidence-based recommendations to ‘define practice, personalize care, stratify risk, reduce health care costs, improve outcomes, and identify rational challenges for future efforts.’ ”

The authors of the guidelines reported no conflicts of interest in regard to the guidelines, although the article lists disclosures for six authors.

This article first appeared on Medscape.com.
 

The American Association of Endocrine Surgeons has issued a first-of-its-kind set of clinical guidelines for the surgical treatment of thyroid disease, offering evidence-based recommendations on the wide-ranging aspects of thyroidectomy and the management of benign, as well as malignant, thyroid nodules and cancer.

Whereas various endocrine and thyroid societies issue guidelines on many aspects of the management of thyroid disease, the new AAES guidelines are the first specifically to address surgical management of thyroid disease in adults.

“These guidelines truly focus on the surgical decision-making and management of thyroid disease. However, there is something for all clinicians who take care of patients with thyroid disease,” lead author Kepal N. Patel, MD, of NYU Langone Health in New York City, said in an interview.

The guidelines, published in the Annals of Surgery, include a total of 66 recommendations from a multidisciplinary panel of 19 experts who reviewed medical literature spanning 1985-2018.

More than 100,000 thyroidectomies are performed each year in the United States alone, and as surgical indications and treatment paradigms evolve, the need for surgical guidance is more important than ever, Dr. Patel said.

“Such transformations have propagated differences in clinical interpretation and management, and as a result, clinical uncertainty, and even controversy, have emerged,” he said. “Recognizing the importance of these changes, the AAES determined that evidence-based clinical guidelines were necessary to enhance the safe and effective surgical treatment of benign and malignant thyroid disease.”

Key areas addressed in the guidelines include the addition of new cytologic and pathologic diagnostic criteria, molecular profiling tests, operative techniques, and adjuncts, as well as the nuances surrounding the sometimes challenging newer concept of “borderline” thyroid tumors, Dr. Patel noted.

In terms of imaging recommendations, for instance, the guidelines recommend the preoperative use of computed tomography or magnetic resonance imaging, as stated in Recommendation 6: “CT or MRI with intravenous contrast should be used preoperatively as an adjunct to ultrasound in selected patients with clinical suspicion for advanced locoregional thyroid cancer.” The recommendation is cited as being “strong,” with a “low quality of evidence.”

Further diagnostic recommendations cover issues that include voice assessment, the risk for vocal fold dysfunction related to thyroid disease and surgery, and the use of fine-needle aspiration biopsy in evaluating suspicious thyroid nodules and lymph nodes.

The guidelines also address the indications for thyroidectomy, with recommendations regarding the extent and outcomes of surgery spanning different categories of thyroid disease. A key recommendation along those lines, for instance, indicates that, when possible, thyroidectomy should be performed by surgeons who perform a high volume of such procedures.

Approaches for safe and effective perioperative management are also covered, and include measures to prevent complications and the use of thyroid tissue diagnosis during surgery, such as core-needle biopsy of the thyroid and cervical lymph nodes, and incisional biopsy of the thyroid, nodal dissection, and concurrent parathyroidectomy.

Other recommendations address the optimal management of thyroid cancer, with an emphasis on a personalized, evidence-based approach tailored to the patient’s situation and preferences.

The authors underscored that, as technology rapidly evolves, “in the future, this work will certainly and rightly need to be done again.” In the meantime, they wrote, recommendations should be relevant to “the target audience [of] the practicing surgeon in a community hospital, academic center, or training program.”

An AAES press release noted that “the members of the expert panel hope their efforts will meet the need for evidence-based recommendations to ‘define practice, personalize care, stratify risk, reduce health care costs, improve outcomes, and identify rational challenges for future efforts.’ ”

The authors of the guidelines reported no conflicts of interest in regard to the guidelines, although the article lists disclosures for six authors.

This article first appeared on Medscape.com.
 

Patients with type 2 diabetes who were part of a health care plan and used a computer and/or app on a mobile device to access a portal (website) with tools for managing diabetes were more adherent with prescription refills and had improved hemoglobin A_1c levels, according to findings from a 33-month study published online in JAMA Network Open.

The improvements were greater in patients without prior portal usage, who began accessing the portal via a mobile device (smartphone or tablet) app as well as computer, compared with those who used only a computer.

Moreover, the improvements were greatest in patients with poorly controlled diabetes (HbA_1c greater than 8%) who began accessing the portal by both means.

“Patients with greater clinical need were able to benefit even more from mobile portal access, both in taking their medications more often and in actually improving blood sugar levels,” lead author Ilana Graetz, PhD, an associate professor at the Rollins School of Health Policy and Management, Emory University, Atlanta, observed in a statement from Kaiser Permanente.

The results show that “patients can use technology to better manage their own care, their medications, and their diabetes,” added senior author Mary Reed, DrPH, a research scientist at the Kaiser Permanente Division of Research, Oakland, California. “This is an example of how the health care system, by offering patients access to their own information and the ability to manage their health care online, can improve their health.”

“Offering this in a mobile-friendly way can give even more patients the ability to engage with their health care,” Dr. Reed noted. “It literally puts the access to these tools in the patient’s own pocket wherever they go.”

Checking refills and lab results

Dr. Graetz and colleagues performed a retrospective analysis of data from 111,463 adults with type 2 diabetes who were not receiving insulin but were taking oral diabetes medications and were covered by a health care plan with Kaiser Permanente Northern California from April 1, 2015 to December 31, 2017. The patients were a mean age of 64 years, and 54% were men.

Patients could register online for free access to a portal that allowed them to get general health information and see their laboratory test results, as well as securely send and receive messages to and from their health care providers, make medical appointments, and request prescription refills.

Study outcomes were change in oral diabetes medication adherence and HbA_1c levels at 33 months.

At baseline, 28% of patients had poor medication adherence (monthly days covered, less than 80%), and 20% had poor glycemic control.

After 33 months, the proportion of patients who never accessed the diabetes management portal dropped from 35% to 25%, and the proportion who accessed it from both a computer and an app increased from 34% to 62%.

Among patients with no prior portal access and who began accessing the portal by computer only, medication adherence increased by 1.16% and A_1c dropped by 0.06%.

However, among patients with no prior portal access who began to access it using both a computer and an app, diabetes management improvement was greater: medication adherence increased by 1.67% and HbA_1c levels dropped by 0.13%.

And among patients with no prior portal usage who had an initial HbA_1c level of more than 8.0% and began to access the website by both means, medication adherence increased by 5.09%, equivalent to an added 1.5 medication-adherent days per month, and HbA_1c levels fell by 0.19%.

There was also “a more modest, but still statistically significant increase,” of about 0.5 added medication-adherent days per month in patients with lower initial A_1c levels who began accessing the portal both ways.

“Although medication adherence measured by medication dispensed cannot guarantee which medications were actually used by patients,” the authors wrote, “our findings of concurrent improvements in [HbA_1c] levels confirm physiological improvements in diabetes control.”

“Convenient access to portal self-management tools through a mobile device could significantly improve diabetes management,” they conclude.

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with type 2 diabetes who were part of a health care plan and used a computer and/or app on a mobile device to access a portal (website) with tools for managing diabetes were more adherent with prescription refills and had improved hemoglobin A_1c levels, according to findings from a 33-month study published online in JAMA Network Open.

The improvements were greater in patients without prior portal usage, who began accessing the portal via a mobile device (smartphone or tablet) app as well as computer, compared with those who used only a computer.

Moreover, the improvements were greatest in patients with poorly controlled diabetes (HbA_1c greater than 8%) who began accessing the portal by both means.

“Patients with greater clinical need were able to benefit even more from mobile portal access, both in taking their medications more often and in actually improving blood sugar levels,” lead author Ilana Graetz, PhD, an associate professor at the Rollins School of Health Policy and Management, Emory University, Atlanta, observed in a statement from Kaiser Permanente.

The results show that “patients can use technology to better manage their own care, their medications, and their diabetes,” added senior author Mary Reed, DrPH, a research scientist at the Kaiser Permanente Division of Research, Oakland, California. “This is an example of how the health care system, by offering patients access to their own information and the ability to manage their health care online, can improve their health.”

“Offering this in a mobile-friendly way can give even more patients the ability to engage with their health care,” Dr. Reed noted. “It literally puts the access to these tools in the patient’s own pocket wherever they go.”

Checking refills and lab results

Dr. Graetz and colleagues performed a retrospective analysis of data from 111,463 adults with type 2 diabetes who were not receiving insulin but were taking oral diabetes medications and were covered by a health care plan with Kaiser Permanente Northern California from April 1, 2015 to December 31, 2017. The patients were a mean age of 64 years, and 54% were men.

Patients could register online for free access to a portal that allowed them to get general health information and see their laboratory test results, as well as securely send and receive messages to and from their health care providers, make medical appointments, and request prescription refills.

Study outcomes were change in oral diabetes medication adherence and HbA_1c levels at 33 months.

At baseline, 28% of patients had poor medication adherence (monthly days covered, less than 80%), and 20% had poor glycemic control.

After 33 months, the proportion of patients who never accessed the diabetes management portal dropped from 35% to 25%, and the proportion who accessed it from both a computer and an app increased from 34% to 62%.

Among patients with no prior portal access and who began accessing the portal by computer only, medication adherence increased by 1.16% and A_1c dropped by 0.06%.

However, among patients with no prior portal access who began to access it using both a computer and an app, diabetes management improvement was greater: medication adherence increased by 1.67% and HbA_1c levels dropped by 0.13%.

And among patients with no prior portal usage who had an initial HbA_1c level of more than 8.0% and began to access the website by both means, medication adherence increased by 5.09%, equivalent to an added 1.5 medication-adherent days per month, and HbA_1c levels fell by 0.19%.

There was also “a more modest, but still statistically significant increase,” of about 0.5 added medication-adherent days per month in patients with lower initial A_1c levels who began accessing the portal both ways.

“Although medication adherence measured by medication dispensed cannot guarantee which medications were actually used by patients,” the authors wrote, “our findings of concurrent improvements in [HbA_1c] levels confirm physiological improvements in diabetes control.”

“Convenient access to portal self-management tools through a mobile device could significantly improve diabetes management,” they conclude.

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported no relevant financial relationships.

This article first appeared on Medscape.com.

Patients with type 2 diabetes who were part of a health care plan and used a computer and/or app on a mobile device to access a portal (website) with tools for managing diabetes were more adherent with prescription refills and had improved hemoglobin A_1c levels, according to findings from a 33-month study published online in JAMA Network Open.

The improvements were greater in patients without prior portal usage, who began accessing the portal via a mobile device (smartphone or tablet) app as well as computer, compared with those who used only a computer.

Moreover, the improvements were greatest in patients with poorly controlled diabetes (HbA_1c greater than 8%) who began accessing the portal by both means.

“Patients with greater clinical need were able to benefit even more from mobile portal access, both in taking their medications more often and in actually improving blood sugar levels,” lead author Ilana Graetz, PhD, an associate professor at the Rollins School of Health Policy and Management, Emory University, Atlanta, observed in a statement from Kaiser Permanente.

The results show that “patients can use technology to better manage their own care, their medications, and their diabetes,” added senior author Mary Reed, DrPH, a research scientist at the Kaiser Permanente Division of Research, Oakland, California. “This is an example of how the health care system, by offering patients access to their own information and the ability to manage their health care online, can improve their health.”

“Offering this in a mobile-friendly way can give even more patients the ability to engage with their health care,” Dr. Reed noted. “It literally puts the access to these tools in the patient’s own pocket wherever they go.”

Checking refills and lab results

Dr. Graetz and colleagues performed a retrospective analysis of data from 111,463 adults with type 2 diabetes who were not receiving insulin but were taking oral diabetes medications and were covered by a health care plan with Kaiser Permanente Northern California from April 1, 2015 to December 31, 2017. The patients were a mean age of 64 years, and 54% were men.

Patients could register online for free access to a portal that allowed them to get general health information and see their laboratory test results, as well as securely send and receive messages to and from their health care providers, make medical appointments, and request prescription refills.

Study outcomes were change in oral diabetes medication adherence and HbA_1c levels at 33 months.

At baseline, 28% of patients had poor medication adherence (monthly days covered, less than 80%), and 20% had poor glycemic control.

After 33 months, the proportion of patients who never accessed the diabetes management portal dropped from 35% to 25%, and the proportion who accessed it from both a computer and an app increased from 34% to 62%.

Among patients with no prior portal access and who began accessing the portal by computer only, medication adherence increased by 1.16% and A_1c dropped by 0.06%.

However, among patients with no prior portal access who began to access it using both a computer and an app, diabetes management improvement was greater: medication adherence increased by 1.67% and HbA_1c levels dropped by 0.13%.

And among patients with no prior portal usage who had an initial HbA_1c level of more than 8.0% and began to access the website by both means, medication adherence increased by 5.09%, equivalent to an added 1.5 medication-adherent days per month, and HbA_1c levels fell by 0.19%.

There was also “a more modest, but still statistically significant increase,” of about 0.5 added medication-adherent days per month in patients with lower initial A_1c levels who began accessing the portal both ways.

“Although medication adherence measured by medication dispensed cannot guarantee which medications were actually used by patients,” the authors wrote, “our findings of concurrent improvements in [HbA_1c] levels confirm physiological improvements in diabetes control.”

“Convenient access to portal self-management tools through a mobile device could significantly improve diabetes management,” they conclude.

The study was supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases. The authors reported no relevant financial relationships.

This article first appeared on Medscape.com.

The Food and Drug Administration has approved the oral cortisol synthesis inhibitor osilodrostat (Isturisa) for the nonsurgical treatment of adults with Cushing’s disease who either are not good candidates for pituitary gland surgery – the recommended first-line therapy – or in whom the disease persists after surgery.

Cushing’s disease is a rare condition caused when a pituitary tumor releases too much of the hormone adrenocorticotropin, which in turn, triggers the adrenal gland to overproduce cortisol. The condition is associated with serious health complications, including high blood pressure, obesity, type 2 diabetes, and compromised immunity.

Osilodrostat is the first therapy approved by the FDA to tackle the overproduction of cortisol, which it does by blocking the 11-beta-hydroxylase enzyme and thus preventing cortisol synthesis, the agency said in a press release.

In November 2019, the European Medicines Agency recommended the granting of a marketing authorization for osilodrostat, also for treating adults with Cushing’s disease.

The U.S. approval was based on outcomes from a study that evaluated the drug’s safety and efficacy in 137 adults with Cushing’s disease who had undergone pituitary surgery but were not cured, or who were not surgical candidates, according the release. About three-quarters of the patients were women, and the mean age was 41 years.

All of the patients started a 24-week, single-arm, open-label period at a dose of 2 mg of osilodrostat twice daily that could be increased every 2 weeks to 30 mg twice daily.

By week 24, cortisol levels in roughly half the patients were within the normal range, and 71 patients who did not need any more dose increases and who tolerated the drug were randomized to either osilodrostat or placebo for an 8-week withdrawal study. At the end of that time, 86% of the osilodrostat patients maintained their normal-range cortisol levels, compared with 30% of those taking placebo.

Osilodrostat is taken as an oral tablet twice a day, in the morning and evening. Among the common side effects reported in the study were adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema, although hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors, and androgens may also occur, according to the release.

The drug had been given an Orphan Drug Designation in recognition of its intended use in the treatment of a rare disease. The approval was granted to Novartis.

The Food and Drug Administration has approved the oral cortisol synthesis inhibitor osilodrostat (Isturisa) for the nonsurgical treatment of adults with Cushing’s disease who either are not good candidates for pituitary gland surgery – the recommended first-line therapy – or in whom the disease persists after surgery.

Cushing’s disease is a rare condition caused when a pituitary tumor releases too much of the hormone adrenocorticotropin, which in turn, triggers the adrenal gland to overproduce cortisol. The condition is associated with serious health complications, including high blood pressure, obesity, type 2 diabetes, and compromised immunity.

Osilodrostat is the first therapy approved by the FDA to tackle the overproduction of cortisol, which it does by blocking the 11-beta-hydroxylase enzyme and thus preventing cortisol synthesis, the agency said in a press release.

In November 2019, the European Medicines Agency recommended the granting of a marketing authorization for osilodrostat, also for treating adults with Cushing’s disease.

The U.S. approval was based on outcomes from a study that evaluated the drug’s safety and efficacy in 137 adults with Cushing’s disease who had undergone pituitary surgery but were not cured, or who were not surgical candidates, according the release. About three-quarters of the patients were women, and the mean age was 41 years.

All of the patients started a 24-week, single-arm, open-label period at a dose of 2 mg of osilodrostat twice daily that could be increased every 2 weeks to 30 mg twice daily.

By week 24, cortisol levels in roughly half the patients were within the normal range, and 71 patients who did not need any more dose increases and who tolerated the drug were randomized to either osilodrostat or placebo for an 8-week withdrawal study. At the end of that time, 86% of the osilodrostat patients maintained their normal-range cortisol levels, compared with 30% of those taking placebo.

Osilodrostat is taken as an oral tablet twice a day, in the morning and evening. Among the common side effects reported in the study were adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema, although hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors, and androgens may also occur, according to the release.

The drug had been given an Orphan Drug Designation in recognition of its intended use in the treatment of a rare disease. The approval was granted to Novartis.

The Food and Drug Administration has approved the oral cortisol synthesis inhibitor osilodrostat (Isturisa) for the nonsurgical treatment of adults with Cushing’s disease who either are not good candidates for pituitary gland surgery – the recommended first-line therapy – or in whom the disease persists after surgery.

Cushing’s disease is a rare condition caused when a pituitary tumor releases too much of the hormone adrenocorticotropin, which in turn, triggers the adrenal gland to overproduce cortisol. The condition is associated with serious health complications, including high blood pressure, obesity, type 2 diabetes, and compromised immunity.

Osilodrostat is the first therapy approved by the FDA to tackle the overproduction of cortisol, which it does by blocking the 11-beta-hydroxylase enzyme and thus preventing cortisol synthesis, the agency said in a press release.

In November 2019, the European Medicines Agency recommended the granting of a marketing authorization for osilodrostat, also for treating adults with Cushing’s disease.

The U.S. approval was based on outcomes from a study that evaluated the drug’s safety and efficacy in 137 adults with Cushing’s disease who had undergone pituitary surgery but were not cured, or who were not surgical candidates, according the release. About three-quarters of the patients were women, and the mean age was 41 years.

All of the patients started a 24-week, single-arm, open-label period at a dose of 2 mg of osilodrostat twice daily that could be increased every 2 weeks to 30 mg twice daily.

By week 24, cortisol levels in roughly half the patients were within the normal range, and 71 patients who did not need any more dose increases and who tolerated the drug were randomized to either osilodrostat or placebo for an 8-week withdrawal study. At the end of that time, 86% of the osilodrostat patients maintained their normal-range cortisol levels, compared with 30% of those taking placebo.

Osilodrostat is taken as an oral tablet twice a day, in the morning and evening. Among the common side effects reported in the study were adrenal insufficiency, headache, vomiting, nausea, fatigue, and edema, although hypocortisolism, QTc prolongation, and elevations in adrenal hormone precursors, and androgens may also occur, according to the release.

The drug had been given an Orphan Drug Designation in recognition of its intended use in the treatment of a rare disease. The approval was granted to Novartis.

Women who had experienced stillbirth were more than twice as likely to eventually develop end-stage renal disease (ESRD) than were those who had not, and they were also at greater risk for chronic kidney disease (CKD), according to findings published in the American Journal of Obstetrics & Gynecology.

Peter M Barrett, MB, of the University College Cork (Ireland), and colleagues conducted a population-based cohort study using data from the Swedish Medical Birth Register, National Patient Register, and the Swedish Renal Register to identify women who had live births and stillbirths. They then used anonymized unique personal identification numbers to cross-reference the registries.

From a full cohort of nearly 2 million women who gave birth during 1973-2012, and during a median follow-up of 20.7 years, 13,032 women experienced stillbirth, which, until 2008, was defined as fetal death after 28 weeks’ gestation, and after 2008, as occurring after 22 weeks. Women were excluded if they had any diagnosis of renal disease before their first pregnancy, as well as for a history of cardiovascular disease, chronic hypertension, diabetes, and certain other conditions at baseline.

Overall, 18,017 women developed CKD, and 1,283 developed ESRD. The fully adjusted model showed adjusted hazard ratios of 1.26 for CKD (95% confidence interval, 1.09-1.45) and 2.25 for ESRD (95% CI, 1.55-3.25) in women who had experienced stillbirth, compared with those who had not experienced stillbirth.

The researchers reported that associations between stillbirth and renal disease existed independently of underlying medical and obstetric comorbidities, such as congenital malformations, being small for gestational age, and preeclampsia, and that when those comorbidities were excluded, “the associations between stillbirth and maternal renal disease were strengthened (CKD: aHR, 1.33; 95% CI, 1.13-1.57; and ESRD: aHR, 2.95; 95% CI, 1.86-4.68).”

In addition, they noted that there was no significant association between stillbirth and either CKD or ESRD in women who had prepregnancy medical comorbidities (CKD: aHR, 1.13; 95% CI 0.73-1.75; and ESRD: aHR 1.49; 95% CI, 0.78-2.85).

“Further research is required to better understand the underlying pathophysiology of this association and to determine whether affected women would benefit from closer surveillance and follow-up for future hypertension and renal disease,” the authors concluded.

The work was performed within the Irish Clinical Academic Training Programme and was funded by grants from several organizations. The authors reported no conflicts of interest.

[email protected]

SOURCE: Barret PM et al. Am J Obstet Gynecol. 2020 Feb 26. doi: 10.1016/j.ajog.2020.02.031.

Women who had experienced stillbirth were more than twice as likely to eventually develop end-stage renal disease (ESRD) than were those who had not, and they were also at greater risk for chronic kidney disease (CKD), according to findings published in the American Journal of Obstetrics & Gynecology.

Peter M Barrett, MB, of the University College Cork (Ireland), and colleagues conducted a population-based cohort study using data from the Swedish Medical Birth Register, National Patient Register, and the Swedish Renal Register to identify women who had live births and stillbirths. They then used anonymized unique personal identification numbers to cross-reference the registries.

From a full cohort of nearly 2 million women who gave birth during 1973-2012, and during a median follow-up of 20.7 years, 13,032 women experienced stillbirth, which, until 2008, was defined as fetal death after 28 weeks’ gestation, and after 2008, as occurring after 22 weeks. Women were excluded if they had any diagnosis of renal disease before their first pregnancy, as well as for a history of cardiovascular disease, chronic hypertension, diabetes, and certain other conditions at baseline.

Overall, 18,017 women developed CKD, and 1,283 developed ESRD. The fully adjusted model showed adjusted hazard ratios of 1.26 for CKD (95% confidence interval, 1.09-1.45) and 2.25 for ESRD (95% CI, 1.55-3.25) in women who had experienced stillbirth, compared with those who had not experienced stillbirth.

The researchers reported that associations between stillbirth and renal disease existed independently of underlying medical and obstetric comorbidities, such as congenital malformations, being small for gestational age, and preeclampsia, and that when those comorbidities were excluded, “the associations between stillbirth and maternal renal disease were strengthened (CKD: aHR, 1.33; 95% CI, 1.13-1.57; and ESRD: aHR, 2.95; 95% CI, 1.86-4.68).”

In addition, they noted that there was no significant association between stillbirth and either CKD or ESRD in women who had prepregnancy medical comorbidities (CKD: aHR, 1.13; 95% CI 0.73-1.75; and ESRD: aHR 1.49; 95% CI, 0.78-2.85).

“Further research is required to better understand the underlying pathophysiology of this association and to determine whether affected women would benefit from closer surveillance and follow-up for future hypertension and renal disease,” the authors concluded.

The work was performed within the Irish Clinical Academic Training Programme and was funded by grants from several organizations. The authors reported no conflicts of interest.

[email protected]

SOURCE: Barret PM et al. Am J Obstet Gynecol. 2020 Feb 26. doi: 10.1016/j.ajog.2020.02.031.

Women who had experienced stillbirth were more than twice as likely to eventually develop end-stage renal disease (ESRD) than were those who had not, and they were also at greater risk for chronic kidney disease (CKD), according to findings published in the American Journal of Obstetrics & Gynecology.

Peter M Barrett, MB, of the University College Cork (Ireland), and colleagues conducted a population-based cohort study using data from the Swedish Medical Birth Register, National Patient Register, and the Swedish Renal Register to identify women who had live births and stillbirths. They then used anonymized unique personal identification numbers to cross-reference the registries.

From a full cohort of nearly 2 million women who gave birth during 1973-2012, and during a median follow-up of 20.7 years, 13,032 women experienced stillbirth, which, until 2008, was defined as fetal death after 28 weeks’ gestation, and after 2008, as occurring after 22 weeks. Women were excluded if they had any diagnosis of renal disease before their first pregnancy, as well as for a history of cardiovascular disease, chronic hypertension, diabetes, and certain other conditions at baseline.

Overall, 18,017 women developed CKD, and 1,283 developed ESRD. The fully adjusted model showed adjusted hazard ratios of 1.26 for CKD (95% confidence interval, 1.09-1.45) and 2.25 for ESRD (95% CI, 1.55-3.25) in women who had experienced stillbirth, compared with those who had not experienced stillbirth.

The researchers reported that associations between stillbirth and renal disease existed independently of underlying medical and obstetric comorbidities, such as congenital malformations, being small for gestational age, and preeclampsia, and that when those comorbidities were excluded, “the associations between stillbirth and maternal renal disease were strengthened (CKD: aHR, 1.33; 95% CI, 1.13-1.57; and ESRD: aHR, 2.95; 95% CI, 1.86-4.68).”

In addition, they noted that there was no significant association between stillbirth and either CKD or ESRD in women who had prepregnancy medical comorbidities (CKD: aHR, 1.13; 95% CI 0.73-1.75; and ESRD: aHR 1.49; 95% CI, 0.78-2.85).

“Further research is required to better understand the underlying pathophysiology of this association and to determine whether affected women would benefit from closer surveillance and follow-up for future hypertension and renal disease,” the authors concluded.

The work was performed within the Irish Clinical Academic Training Programme and was funded by grants from several organizations. The authors reported no conflicts of interest.

[email protected]

SOURCE: Barret PM et al. Am J Obstet Gynecol. 2020 Feb 26. doi: 10.1016/j.ajog.2020.02.031.

Oral hygiene may be a key factor in diabetes risk, new data from a Korean national health database suggest.

“Frequent tooth brushing may be an attenuating factor for the risk of new-onset diabetes, and the presence of periodontal disease and increased number of missing teeth may be augmenting factors,” wrote Yoonkyung Chang, MD, of the Department of Neurology, Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea, and colleagues.

“Improving oral hygiene may be associated with a decreased risk of occurrence of new-onset diabetes,” they continued in an article published online in Diabetologia.

Periodontal disease involves inflammatory reactions that affect the surrounding tissues of the teeth. Inflammation, in turn, is an important cause of diabetes because it increases insulin resistance and endothelial dysfunction, Dr. Chang and colleagues explained.

They analyzed data gathered during 2003-2006 from 188,013 individuals from the Korean National Health Insurance System – Health Screening Cohort who had complete data and did not have diabetes at baseline. Oral hygiene behaviors, including frequency of tooth brushing, and dental visits or cleanings, were collected by self-report.

Over a median follow-up of 10 years, there were 31,545 new cases of diabetes, with an estimated overall 10-year event rate of 16.1%. The rate was 17.2% for those with periodontal disease at baseline, compared with 15.8% for those without, which was a significant difference even after adjustments for multiple confounders (hazard ratio, 1.09; P less than .001).

Compared with patients who had no missing teeth, the event rate for new-onset diabetes rose from 15.4% for patients with 1 missing tooth (HR, 1.08; P less than .001) to 21.4% for those with 15 or more missing teeth (HR, 1.21; P less than .001).

Professional dental cleaning did not have a significant effect after multivariate analysis. However, the number of daily tooth brushings by the individual did. Compared with brushing 0-1 times/day, those who brushed 3 or more times/day had a significantly lower risk for new-onset diabetes (HR, 0.92; P less than .001).

In subgroup analyses, periodontal disease was more strongly associated with new-onset diabetes in adults aged 51 years and younger (HR, 1.14), compared with those who were 52 years or older (HR, 1.06).

The study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. The authors reported no relevant financial relationships.
 

This article first appeared on Medscape.com.

Oral hygiene may be a key factor in diabetes risk, new data from a Korean national health database suggest.

“Frequent tooth brushing may be an attenuating factor for the risk of new-onset diabetes, and the presence of periodontal disease and increased number of missing teeth may be augmenting factors,” wrote Yoonkyung Chang, MD, of the Department of Neurology, Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea, and colleagues.

“Improving oral hygiene may be associated with a decreased risk of occurrence of new-onset diabetes,” they continued in an article published online in Diabetologia.

Periodontal disease involves inflammatory reactions that affect the surrounding tissues of the teeth. Inflammation, in turn, is an important cause of diabetes because it increases insulin resistance and endothelial dysfunction, Dr. Chang and colleagues explained.

They analyzed data gathered during 2003-2006 from 188,013 individuals from the Korean National Health Insurance System – Health Screening Cohort who had complete data and did not have diabetes at baseline. Oral hygiene behaviors, including frequency of tooth brushing, and dental visits or cleanings, were collected by self-report.

Over a median follow-up of 10 years, there were 31,545 new cases of diabetes, with an estimated overall 10-year event rate of 16.1%. The rate was 17.2% for those with periodontal disease at baseline, compared with 15.8% for those without, which was a significant difference even after adjustments for multiple confounders (hazard ratio, 1.09; P less than .001).

Compared with patients who had no missing teeth, the event rate for new-onset diabetes rose from 15.4% for patients with 1 missing tooth (HR, 1.08; P less than .001) to 21.4% for those with 15 or more missing teeth (HR, 1.21; P less than .001).

Professional dental cleaning did not have a significant effect after multivariate analysis. However, the number of daily tooth brushings by the individual did. Compared with brushing 0-1 times/day, those who brushed 3 or more times/day had a significantly lower risk for new-onset diabetes (HR, 0.92; P less than .001).

In subgroup analyses, periodontal disease was more strongly associated with new-onset diabetes in adults aged 51 years and younger (HR, 1.14), compared with those who were 52 years or older (HR, 1.06).

The study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. The authors reported no relevant financial relationships.
 

This article first appeared on Medscape.com.

Oral hygiene may be a key factor in diabetes risk, new data from a Korean national health database suggest.

“Frequent tooth brushing may be an attenuating factor for the risk of new-onset diabetes, and the presence of periodontal disease and increased number of missing teeth may be augmenting factors,” wrote Yoonkyung Chang, MD, of the Department of Neurology, Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, South Korea, and colleagues.

“Improving oral hygiene may be associated with a decreased risk of occurrence of new-onset diabetes,” they continued in an article published online in Diabetologia.

Periodontal disease involves inflammatory reactions that affect the surrounding tissues of the teeth. Inflammation, in turn, is an important cause of diabetes because it increases insulin resistance and endothelial dysfunction, Dr. Chang and colleagues explained.

They analyzed data gathered during 2003-2006 from 188,013 individuals from the Korean National Health Insurance System – Health Screening Cohort who had complete data and did not have diabetes at baseline. Oral hygiene behaviors, including frequency of tooth brushing, and dental visits or cleanings, were collected by self-report.

Over a median follow-up of 10 years, there were 31,545 new cases of diabetes, with an estimated overall 10-year event rate of 16.1%. The rate was 17.2% for those with periodontal disease at baseline, compared with 15.8% for those without, which was a significant difference even after adjustments for multiple confounders (hazard ratio, 1.09; P less than .001).

Compared with patients who had no missing teeth, the event rate for new-onset diabetes rose from 15.4% for patients with 1 missing tooth (HR, 1.08; P less than .001) to 21.4% for those with 15 or more missing teeth (HR, 1.21; P less than .001).

Professional dental cleaning did not have a significant effect after multivariate analysis. However, the number of daily tooth brushings by the individual did. Compared with brushing 0-1 times/day, those who brushed 3 or more times/day had a significantly lower risk for new-onset diabetes (HR, 0.92; P less than .001).

In subgroup analyses, periodontal disease was more strongly associated with new-onset diabetes in adults aged 51 years and younger (HR, 1.14), compared with those who were 52 years or older (HR, 1.06).

The study was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education. The authors reported no relevant financial relationships.
 

This article first appeared on Medscape.com.

Nationwide influenza activity declined for the third consecutive week, but the 2019-2020 season is on pace to be the longest in more than a decade.

Outpatient visits to health care providers for influenza-like illness dropped from 5.5% the previous week to 5.3% of all visits for the week ending Feb. 29, the Centers for Disease Control and Prevention said on March 6.

The national baseline rate of 2.4% was first reached during the week of Nov. 9, 2019 – marking the start of flu season – and has remained at or above that level for 17 consecutive weeks. Last year’s season, which also was the longest in a decade, lasted 21 consecutive weeks but started 2 weeks later than the current season and had a lower outpatient-visit rate (4.5%) for the last week of February, CDC data show.

This season’s earlier start could mean that even a somewhat steep decline in visits to below the baseline rate – marking the end of the season – might take 5 or 6 weeks and would make 2019-2020 even longer than 2018-2019.

The activity situation on the state level reflects the small national decline. For the week ending Feb. 29, there were 33 states at level 10 on the CDC’s 1-10 activity scale, compared with 37 the week before, and a total of 40 in the “high” range of 8-10, compared with 43 the week before, the CDC’s influenza division reported.

The other main measure of influenza activity, percentage of respiratory specimens testing positive, also declined for the third week in a row and is now at 24.3% after reaching a high of 30.3% during the week of Feb. 2-8, the influenza division said.

The overall cumulative hospitalization rate continues to remain at a fairly typical 57.9 per 100,000 population, but rates for school-aged children (84.9 per 100,000) and young adults (31.2 per 100,000) are among the highest ever recorded at this point in the season. Mortality among children – now at 136 for 2019-2020 – is higher than for any season since reporting began in 2004, with the exception of the 2009 pandemic, the CDC said.
 

[email protected]

Nationwide influenza activity declined for the third consecutive week, but the 2019-2020 season is on pace to be the longest in more than a decade.

Outpatient visits to health care providers for influenza-like illness dropped from 5.5% the previous week to 5.3% of all visits for the week ending Feb. 29, the Centers for Disease Control and Prevention said on March 6.

The national baseline rate of 2.4% was first reached during the week of Nov. 9, 2019 – marking the start of flu season – and has remained at or above that level for 17 consecutive weeks. Last year’s season, which also was the longest in a decade, lasted 21 consecutive weeks but started 2 weeks later than the current season and had a lower outpatient-visit rate (4.5%) for the last week of February, CDC data show.

This season’s earlier start could mean that even a somewhat steep decline in visits to below the baseline rate – marking the end of the season – might take 5 or 6 weeks and would make 2019-2020 even longer than 2018-2019.

The activity situation on the state level reflects the small national decline. For the week ending Feb. 29, there were 33 states at level 10 on the CDC’s 1-10 activity scale, compared with 37 the week before, and a total of 40 in the “high” range of 8-10, compared with 43 the week before, the CDC’s influenza division reported.

The other main measure of influenza activity, percentage of respiratory specimens testing positive, also declined for the third week in a row and is now at 24.3% after reaching a high of 30.3% during the week of Feb. 2-8, the influenza division said.

The overall cumulative hospitalization rate continues to remain at a fairly typical 57.9 per 100,000 population, but rates for school-aged children (84.9 per 100,000) and young adults (31.2 per 100,000) are among the highest ever recorded at this point in the season. Mortality among children – now at 136 for 2019-2020 – is higher than for any season since reporting began in 2004, with the exception of the 2009 pandemic, the CDC said.
 

[email protected]

Nationwide influenza activity declined for the third consecutive week, but the 2019-2020 season is on pace to be the longest in more than a decade.

Outpatient visits to health care providers for influenza-like illness dropped from 5.5% the previous week to 5.3% of all visits for the week ending Feb. 29, the Centers for Disease Control and Prevention said on March 6.

The national baseline rate of 2.4% was first reached during the week of Nov. 9, 2019 – marking the start of flu season – and has remained at or above that level for 17 consecutive weeks. Last year’s season, which also was the longest in a decade, lasted 21 consecutive weeks but started 2 weeks later than the current season and had a lower outpatient-visit rate (4.5%) for the last week of February, CDC data show.

This season’s earlier start could mean that even a somewhat steep decline in visits to below the baseline rate – marking the end of the season – might take 5 or 6 weeks and would make 2019-2020 even longer than 2018-2019.

The activity situation on the state level reflects the small national decline. For the week ending Feb. 29, there were 33 states at level 10 on the CDC’s 1-10 activity scale, compared with 37 the week before, and a total of 40 in the “high” range of 8-10, compared with 43 the week before, the CDC’s influenza division reported.

The other main measure of influenza activity, percentage of respiratory specimens testing positive, also declined for the third week in a row and is now at 24.3% after reaching a high of 30.3% during the week of Feb. 2-8, the influenza division said.

The overall cumulative hospitalization rate continues to remain at a fairly typical 57.9 per 100,000 population, but rates for school-aged children (84.9 per 100,000) and young adults (31.2 per 100,000) are among the highest ever recorded at this point in the season. Mortality among children – now at 136 for 2019-2020 – is higher than for any season since reporting began in 2004, with the exception of the 2009 pandemic, the CDC said.
 

[email protected]

Infant rice cereal contains lower levels of arsenic than it did in 2014, according to test results released by the Food and Drug Administration.

In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.

Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.

The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.

“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.

“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.

[email protected]

Infant rice cereal contains lower levels of arsenic than it did in 2014, according to test results released by the Food and Drug Administration.

In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.

Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.

The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.

“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.

“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.

[email protected]

Infant rice cereal contains lower levels of arsenic than it did in 2014, according to test results released by the Food and Drug Administration.

In April 2016, the FDA issued draft guidance calling for manufacturers of the product to reduce the level of arsenic in their cereals by establishing an action level of arsenic of 100 mcg/kg or 100 parts per billion.

Seventy-six percent of samples of infant rice cereal tested in 2018 had levels of arsenic at or below 100 parts per billion versus 47% of samples tested in 2014, according to a statement from the FDA. In 2011-2013, an even lower percentage of samples tested contained amounts of inorganic arsenic at or below the FDA’s current action level for this element, whose consumption has been associated with cancer, skin lesions, cardiovascular diseases, and diabetes.

The 2018 data is based on the testing of 149 samples of infant white and brown rice cereal samples.

“Results from our tests show that manufacturers have made significant progress in ensuring lower levels of inorganic arsenic in infant rice cereal,” Susan Mayne, PhD, director of the Center for Food Safety and Applied Nutrition, said in the FDA statement.

“Both white rice and brown rice cereals showed improvement in meeting the FDA’s 100 ppb proposed action level, but the improvement was greatest for white rice cereals, which tend to have lower levels of inorganic arsenic overall,” according to the statement.

[email protected]