ATLANTA – Twelve months of daily treatment with the novel oral factor Xa inhibitor edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in patients with cancer, according to late-breaking results from a randomized, open-label, blinded-outcomes trial.

Throughout follow-up, trial arms had nearly identical rates of survival free from recurrent VTE or major bleeding, Gary E. Raskob, PhD, reported during a late-breaking oral presentation at the annual meeting of the American Society of Hematology. “Edoxaban was associated with a lower rate of recurrent VTE, which was offset by a similar increase in risk of major bleeding,” he said. “Therefore, oral edoxaban was noninferior to subcutaneous dalteparin for the [combined] primary outcome.”

Venous thromboembolism affects about one in five patients with active cancer and is difficult to treat because patients face increased risks of recurrence and bleeding. The struggle to balance these risks fuels morbidity and mortality and can hamper cancer treatment, said Dr. Raskob of the University of Oklahoma, Oklahoma City.

Pharmacy and medical oncology societies recommend long-term low-molecular-weight heparin for cancer patients with VTE, but the daily burden of subcutaneous injections leads many to stop after about 2-4 months of treatment, Dr. Raskob said. “Direct oral anticoagulants may be an attractive alternative.”

For the trial, 1,446 adults with cancer and lower limb VTE from 114 clinics in North America, Europe, Australia, and New Zealand received either edoxaban (60 mg daily) or dalteparin (200 IU/kg for 30 days, followed by 150 IU/kg) for up to 12 months. Nearly all patients had active cancer. Tumor types reflected what’s most common in practice, such as malignancies of the lung, colon, and breast. About 50 patients had primary or metastatic brain cancers. Approximately two-thirds had pulmonary embolism with or without deep-vein thrombosis, while the rest had isolated deep-vein thrombosis.

After 12 months of follow-up, 12.8% of edoxaban patients had at least one recurrence of VTE or a major bleed, compared with 13.5% of dalteparin patients (hazard ratio, 0.97; 95% confidence interval, 0.70-1.36; P = .006 for noninferiority). Edoxaban also was noninferior to dalteparin after the first 6 months of treatment and in the per-protocol analysis (HRs, 1.0; P = .02 for noninferiority in each analysis). Thus, differences in efficacy did not only reflect better compliance to oral therapy, Dr. Raskob said.

He also reported on individual outcomes. In all, 10.3% of dalteparin recipients had a VTE recurrence, as did 6.5% of edoxaban recipients, for a risk difference of 3.8% (95% CI, 7.1%-0.4%). More than half of recurrences in each group were symptomatic, and none were fatal. Bleeding caused no deaths in either study arm, and each therapy conferred an identical chance of a grade 3-4 major bleed (2.3%).

Edoxaban was associated, however, with a greater frequency of major bleeds (33 events; 6.3%) than was dalteparin (17 events; 3.2%; risk difference, 3.1%; 95% CI, 0.5%-5.7%). In particular, patients who received edoxaban had a slightly higher rate of upper gastrointestinal bleeds. Most had gastric cancer.

Future studies should evaluate whether these patients should receive a lower dose of edoxaban, said Dr. Raskob. “We don’t yet fully know the minimum effective dose [of edoxaban] in cancer patients.”

He also addressed the idea that heparin has antineoplastic activity, calling it “one we should probably abandon. The concept originates from older trials in which researchers probably did not recognize that heparin was preventing fatal pulmonary embolism, he said.

The investigators soon will begin deeper analyses that should inform patient selection, he said. For now, he recommends discussing these findings with patients to help them make an informed choice between oral anticoagulation, with its ease of use but slightly higher rate of major bleeds, and subcutaneous heparin, with its lower bleeding rate and treatment burden.

Daiichi Sankyo provided funding. Dr. Raskob disclosed consulting relationships and honoraria from Daiichi Sankyo, Eli Lilly, Janssen, and several other pharmaceutical companies.

SOURCE: Raskob G et al. ASH Abstract LBA-6.

ATLANTA – Twelve months of daily treatment with the novel oral factor Xa inhibitor edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in patients with cancer, according to late-breaking results from a randomized, open-label, blinded-outcomes trial.

Throughout follow-up, trial arms had nearly identical rates of survival free from recurrent VTE or major bleeding, Gary E. Raskob, PhD, reported during a late-breaking oral presentation at the annual meeting of the American Society of Hematology. “Edoxaban was associated with a lower rate of recurrent VTE, which was offset by a similar increase in risk of major bleeding,” he said. “Therefore, oral edoxaban was noninferior to subcutaneous dalteparin for the [combined] primary outcome.”

Venous thromboembolism affects about one in five patients with active cancer and is difficult to treat because patients face increased risks of recurrence and bleeding. The struggle to balance these risks fuels morbidity and mortality and can hamper cancer treatment, said Dr. Raskob of the University of Oklahoma, Oklahoma City.

Pharmacy and medical oncology societies recommend long-term low-molecular-weight heparin for cancer patients with VTE, but the daily burden of subcutaneous injections leads many to stop after about 2-4 months of treatment, Dr. Raskob said. “Direct oral anticoagulants may be an attractive alternative.”

For the trial, 1,446 adults with cancer and lower limb VTE from 114 clinics in North America, Europe, Australia, and New Zealand received either edoxaban (60 mg daily) or dalteparin (200 IU/kg for 30 days, followed by 150 IU/kg) for up to 12 months. Nearly all patients had active cancer. Tumor types reflected what’s most common in practice, such as malignancies of the lung, colon, and breast. About 50 patients had primary or metastatic brain cancers. Approximately two-thirds had pulmonary embolism with or without deep-vein thrombosis, while the rest had isolated deep-vein thrombosis.

After 12 months of follow-up, 12.8% of edoxaban patients had at least one recurrence of VTE or a major bleed, compared with 13.5% of dalteparin patients (hazard ratio, 0.97; 95% confidence interval, 0.70-1.36; P = .006 for noninferiority). Edoxaban also was noninferior to dalteparin after the first 6 months of treatment and in the per-protocol analysis (HRs, 1.0; P = .02 for noninferiority in each analysis). Thus, differences in efficacy did not only reflect better compliance to oral therapy, Dr. Raskob said.

He also reported on individual outcomes. In all, 10.3% of dalteparin recipients had a VTE recurrence, as did 6.5% of edoxaban recipients, for a risk difference of 3.8% (95% CI, 7.1%-0.4%). More than half of recurrences in each group were symptomatic, and none were fatal. Bleeding caused no deaths in either study arm, and each therapy conferred an identical chance of a grade 3-4 major bleed (2.3%).

Edoxaban was associated, however, with a greater frequency of major bleeds (33 events; 6.3%) than was dalteparin (17 events; 3.2%; risk difference, 3.1%; 95% CI, 0.5%-5.7%). In particular, patients who received edoxaban had a slightly higher rate of upper gastrointestinal bleeds. Most had gastric cancer.

Future studies should evaluate whether these patients should receive a lower dose of edoxaban, said Dr. Raskob. “We don’t yet fully know the minimum effective dose [of edoxaban] in cancer patients.”

He also addressed the idea that heparin has antineoplastic activity, calling it “one we should probably abandon. The concept originates from older trials in which researchers probably did not recognize that heparin was preventing fatal pulmonary embolism, he said.

The investigators soon will begin deeper analyses that should inform patient selection, he said. For now, he recommends discussing these findings with patients to help them make an informed choice between oral anticoagulation, with its ease of use but slightly higher rate of major bleeds, and subcutaneous heparin, with its lower bleeding rate and treatment burden.

Daiichi Sankyo provided funding. Dr. Raskob disclosed consulting relationships and honoraria from Daiichi Sankyo, Eli Lilly, Janssen, and several other pharmaceutical companies.

SOURCE: Raskob G et al. ASH Abstract LBA-6.

ATLANTA – Twelve months of daily treatment with the novel oral factor Xa inhibitor edoxaban was noninferior to standard subcutaneous therapy with dalteparin for treatment of venous thromboembolism in patients with cancer, according to late-breaking results from a randomized, open-label, blinded-outcomes trial.

Throughout follow-up, trial arms had nearly identical rates of survival free from recurrent VTE or major bleeding, Gary E. Raskob, PhD, reported during a late-breaking oral presentation at the annual meeting of the American Society of Hematology. “Edoxaban was associated with a lower rate of recurrent VTE, which was offset by a similar increase in risk of major bleeding,” he said. “Therefore, oral edoxaban was noninferior to subcutaneous dalteparin for the [combined] primary outcome.”

Venous thromboembolism affects about one in five patients with active cancer and is difficult to treat because patients face increased risks of recurrence and bleeding. The struggle to balance these risks fuels morbidity and mortality and can hamper cancer treatment, said Dr. Raskob of the University of Oklahoma, Oklahoma City.

Pharmacy and medical oncology societies recommend long-term low-molecular-weight heparin for cancer patients with VTE, but the daily burden of subcutaneous injections leads many to stop after about 2-4 months of treatment, Dr. Raskob said. “Direct oral anticoagulants may be an attractive alternative.”

For the trial, 1,446 adults with cancer and lower limb VTE from 114 clinics in North America, Europe, Australia, and New Zealand received either edoxaban (60 mg daily) or dalteparin (200 IU/kg for 30 days, followed by 150 IU/kg) for up to 12 months. Nearly all patients had active cancer. Tumor types reflected what’s most common in practice, such as malignancies of the lung, colon, and breast. About 50 patients had primary or metastatic brain cancers. Approximately two-thirds had pulmonary embolism with or without deep-vein thrombosis, while the rest had isolated deep-vein thrombosis.

After 12 months of follow-up, 12.8% of edoxaban patients had at least one recurrence of VTE or a major bleed, compared with 13.5% of dalteparin patients (hazard ratio, 0.97; 95% confidence interval, 0.70-1.36; P = .006 for noninferiority). Edoxaban also was noninferior to dalteparin after the first 6 months of treatment and in the per-protocol analysis (HRs, 1.0; P = .02 for noninferiority in each analysis). Thus, differences in efficacy did not only reflect better compliance to oral therapy, Dr. Raskob said.

He also reported on individual outcomes. In all, 10.3% of dalteparin recipients had a VTE recurrence, as did 6.5% of edoxaban recipients, for a risk difference of 3.8% (95% CI, 7.1%-0.4%). More than half of recurrences in each group were symptomatic, and none were fatal. Bleeding caused no deaths in either study arm, and each therapy conferred an identical chance of a grade 3-4 major bleed (2.3%).

Edoxaban was associated, however, with a greater frequency of major bleeds (33 events; 6.3%) than was dalteparin (17 events; 3.2%; risk difference, 3.1%; 95% CI, 0.5%-5.7%). In particular, patients who received edoxaban had a slightly higher rate of upper gastrointestinal bleeds. Most had gastric cancer.

Future studies should evaluate whether these patients should receive a lower dose of edoxaban, said Dr. Raskob. “We don’t yet fully know the minimum effective dose [of edoxaban] in cancer patients.”

He also addressed the idea that heparin has antineoplastic activity, calling it “one we should probably abandon. The concept originates from older trials in which researchers probably did not recognize that heparin was preventing fatal pulmonary embolism, he said.

The investigators soon will begin deeper analyses that should inform patient selection, he said. For now, he recommends discussing these findings with patients to help them make an informed choice between oral anticoagulation, with its ease of use but slightly higher rate of major bleeds, and subcutaneous heparin, with its lower bleeding rate and treatment burden.

Daiichi Sankyo provided funding. Dr. Raskob disclosed consulting relationships and honoraria from Daiichi Sankyo, Eli Lilly, Janssen, and several other pharmaceutical companies.

SOURCE: Raskob G et al. ASH Abstract LBA-6.

BERLIN – Teens who reported psychotic symptoms – especially hallucinations – on a baseline mental health screening were twice as likely to develop persistent psychiatric symptoms over the next year as were those without such experiences.

Hallucinations in particular predicted a persistent course, nearly tripling the risk (odds ratio, 2.74), Saliha El-Bouhaddani said at the meeting of the World Psychiatric Association.

“This is quite informative and quite clinically relevant,” said Ms. El-Bouhaddani, a doctoral student in psychology at the Parnassia Group, Rotterdam, the Netherlands. Because mental health symptoms in young people may be self-limiting, it’s not easy to identify which teens are at high risk for developing persistent problems that can predispose them to a full-blown mental disorder. “But we can see here that psychotic experiences may be very useful in detecting which adolescents may have persistency of symptoms. I believe that screening tools for teenagers should involve questions about psychotic symptoms, because the answer may help us discriminate who will have a self-limiting course and who will have a persistent course.”

Ms. El-Bouhaddani described MasterMind, a longitudinal cohort study of adolescents drawn from the general population. Each teen completed self-report questionnaires on psychotic experiences and psychosocial problems at two time points over a 2-year period. The study was divided into two phases: a 1-year observational period, followed by an intervention for those at risk, and then a 1-year treatment and follow-up period. She reported only the results of the observational phase.

The study enrolled 1,827 young people, who completed four questionnaires: the Strengths & Difficulties Questionnaire, and questionnaires about psychotic experiences, trauma, and self-esteem. One year later, 1,521 of the participants returned and completed the same surveys.

Ms. El-Bouhaddani constructed four potential pathways from baseline to follow-up: no psychiatric symptoms, remitting symptoms (baseline psychosocial symptoms that remitted by 1 year), incident symptoms (symptoms that appeared only at 1 year), and persistent symptoms (symptoms at both baseline and 1 year). Her goal was to identify any baseline characteristics that might predict a persistent course.

At the 1-year point, the cohort was a mean of 13.5 years old. Most subjects (1,134) had no symptoms at either time point. Incident symptoms were present in 151, remitting symptoms in 181, and persistent symptoms in 46.

Several baseline characteristics significantly separated the group with remitting symptoms from all other groups: They were significantly more likely to have a low education level (61%), to have divorced parents (38%), to report frequent household moves (22%), to have repeated a grade (31%), to report low self-esteem (15%), and to have somatic symptoms (3%). Teens with persistent symptoms also reported more somatic symptoms (3%), but they were significantly more likely than any of the other groups to report having had at least one traumatic event (45%).

At follow-up, psychotic incidents were significantly more common in the remitting and persistent groups (40% and 62%, respectively) than in the nonsymptomatic and incident groups (10% and 11%).

Ms. El-Bouhaddani then broke psychotic experiences down into hallucinations and delusions, and examined their relationships to symptom course. Hallucinations were significantly more common than delusions among those with a persistent course (58% vs. 42%).

She conducted a logistic regression analysis, which determined that any psychotic experience nearly doubled the risk of a persistent course of psychiatric symptoms (OR, 1.92). Hallucinations nearly tripled the risk (OR, 2.74), as did traumatic experiences (OR, 3.0). Delusions increased the risk by close to 60% (OR, 1.59).

The SDQ does not contain questions about psychotic experiences or trauma – the two most powerful predictors of persistent symptoms. It’s time to change this, Ms. El-Bouhaddani said.

“From these results it seems as though we should be asking adolescents about psychotic experiences and trauma. Perhaps it’s time for a new version of the SDQ.”

She had no relevant financial disclosures.

msullivan@frontlinemedcom.comw

On Twitter @alz_gal

SOURCE: El-Bouhaddani S et al. WPA 2017 Abstract S-023 002.

BERLIN – Teens who reported psychotic symptoms – especially hallucinations – on a baseline mental health screening were twice as likely to develop persistent psychiatric symptoms over the next year as were those without such experiences.

Hallucinations in particular predicted a persistent course, nearly tripling the risk (odds ratio, 2.74), Saliha El-Bouhaddani said at the meeting of the World Psychiatric Association.

“This is quite informative and quite clinically relevant,” said Ms. El-Bouhaddani, a doctoral student in psychology at the Parnassia Group, Rotterdam, the Netherlands. Because mental health symptoms in young people may be self-limiting, it’s not easy to identify which teens are at high risk for developing persistent problems that can predispose them to a full-blown mental disorder. “But we can see here that psychotic experiences may be very useful in detecting which adolescents may have persistency of symptoms. I believe that screening tools for teenagers should involve questions about psychotic symptoms, because the answer may help us discriminate who will have a self-limiting course and who will have a persistent course.”

Ms. El-Bouhaddani described MasterMind, a longitudinal cohort study of adolescents drawn from the general population. Each teen completed self-report questionnaires on psychotic experiences and psychosocial problems at two time points over a 2-year period. The study was divided into two phases: a 1-year observational period, followed by an intervention for those at risk, and then a 1-year treatment and follow-up period. She reported only the results of the observational phase.

The study enrolled 1,827 young people, who completed four questionnaires: the Strengths & Difficulties Questionnaire, and questionnaires about psychotic experiences, trauma, and self-esteem. One year later, 1,521 of the participants returned and completed the same surveys.

Ms. El-Bouhaddani constructed four potential pathways from baseline to follow-up: no psychiatric symptoms, remitting symptoms (baseline psychosocial symptoms that remitted by 1 year), incident symptoms (symptoms that appeared only at 1 year), and persistent symptoms (symptoms at both baseline and 1 year). Her goal was to identify any baseline characteristics that might predict a persistent course.

At the 1-year point, the cohort was a mean of 13.5 years old. Most subjects (1,134) had no symptoms at either time point. Incident symptoms were present in 151, remitting symptoms in 181, and persistent symptoms in 46.

Several baseline characteristics significantly separated the group with remitting symptoms from all other groups: They were significantly more likely to have a low education level (61%), to have divorced parents (38%), to report frequent household moves (22%), to have repeated a grade (31%), to report low self-esteem (15%), and to have somatic symptoms (3%). Teens with persistent symptoms also reported more somatic symptoms (3%), but they were significantly more likely than any of the other groups to report having had at least one traumatic event (45%).

At follow-up, psychotic incidents were significantly more common in the remitting and persistent groups (40% and 62%, respectively) than in the nonsymptomatic and incident groups (10% and 11%).

Ms. El-Bouhaddani then broke psychotic experiences down into hallucinations and delusions, and examined their relationships to symptom course. Hallucinations were significantly more common than delusions among those with a persistent course (58% vs. 42%).

She conducted a logistic regression analysis, which determined that any psychotic experience nearly doubled the risk of a persistent course of psychiatric symptoms (OR, 1.92). Hallucinations nearly tripled the risk (OR, 2.74), as did traumatic experiences (OR, 3.0). Delusions increased the risk by close to 60% (OR, 1.59).

The SDQ does not contain questions about psychotic experiences or trauma – the two most powerful predictors of persistent symptoms. It’s time to change this, Ms. El-Bouhaddani said.

“From these results it seems as though we should be asking adolescents about psychotic experiences and trauma. Perhaps it’s time for a new version of the SDQ.”

She had no relevant financial disclosures.

msullivan@frontlinemedcom.comw

On Twitter @alz_gal

SOURCE: El-Bouhaddani S et al. WPA 2017 Abstract S-023 002.

BERLIN – Teens who reported psychotic symptoms – especially hallucinations – on a baseline mental health screening were twice as likely to develop persistent psychiatric symptoms over the next year as were those without such experiences.

Hallucinations in particular predicted a persistent course, nearly tripling the risk (odds ratio, 2.74), Saliha El-Bouhaddani said at the meeting of the World Psychiatric Association.

“This is quite informative and quite clinically relevant,” said Ms. El-Bouhaddani, a doctoral student in psychology at the Parnassia Group, Rotterdam, the Netherlands. Because mental health symptoms in young people may be self-limiting, it’s not easy to identify which teens are at high risk for developing persistent problems that can predispose them to a full-blown mental disorder. “But we can see here that psychotic experiences may be very useful in detecting which adolescents may have persistency of symptoms. I believe that screening tools for teenagers should involve questions about psychotic symptoms, because the answer may help us discriminate who will have a self-limiting course and who will have a persistent course.”

Ms. El-Bouhaddani described MasterMind, a longitudinal cohort study of adolescents drawn from the general population. Each teen completed self-report questionnaires on psychotic experiences and psychosocial problems at two time points over a 2-year period. The study was divided into two phases: a 1-year observational period, followed by an intervention for those at risk, and then a 1-year treatment and follow-up period. She reported only the results of the observational phase.

The study enrolled 1,827 young people, who completed four questionnaires: the Strengths & Difficulties Questionnaire, and questionnaires about psychotic experiences, trauma, and self-esteem. One year later, 1,521 of the participants returned and completed the same surveys.

Ms. El-Bouhaddani constructed four potential pathways from baseline to follow-up: no psychiatric symptoms, remitting symptoms (baseline psychosocial symptoms that remitted by 1 year), incident symptoms (symptoms that appeared only at 1 year), and persistent symptoms (symptoms at both baseline and 1 year). Her goal was to identify any baseline characteristics that might predict a persistent course.

At the 1-year point, the cohort was a mean of 13.5 years old. Most subjects (1,134) had no symptoms at either time point. Incident symptoms were present in 151, remitting symptoms in 181, and persistent symptoms in 46.

Several baseline characteristics significantly separated the group with remitting symptoms from all other groups: They were significantly more likely to have a low education level (61%), to have divorced parents (38%), to report frequent household moves (22%), to have repeated a grade (31%), to report low self-esteem (15%), and to have somatic symptoms (3%). Teens with persistent symptoms also reported more somatic symptoms (3%), but they were significantly more likely than any of the other groups to report having had at least one traumatic event (45%).

At follow-up, psychotic incidents were significantly more common in the remitting and persistent groups (40% and 62%, respectively) than in the nonsymptomatic and incident groups (10% and 11%).

Ms. El-Bouhaddani then broke psychotic experiences down into hallucinations and delusions, and examined their relationships to symptom course. Hallucinations were significantly more common than delusions among those with a persistent course (58% vs. 42%).

She conducted a logistic regression analysis, which determined that any psychotic experience nearly doubled the risk of a persistent course of psychiatric symptoms (OR, 1.92). Hallucinations nearly tripled the risk (OR, 2.74), as did traumatic experiences (OR, 3.0). Delusions increased the risk by close to 60% (OR, 1.59).

The SDQ does not contain questions about psychotic experiences or trauma – the two most powerful predictors of persistent symptoms. It’s time to change this, Ms. El-Bouhaddani said.

“From these results it seems as though we should be asking adolescents about psychotic experiences and trauma. Perhaps it’s time for a new version of the SDQ.”

She had no relevant financial disclosures.

msullivan@frontlinemedcom.comw

On Twitter @alz_gal

SOURCE: El-Bouhaddani S et al. WPA 2017 Abstract S-023 002.

It is important for dermatologists to recognize patients at an increased risk of skin aging early enough to initiate countermeasures. “Wrinkle-prone” skin types can be identified easily through use of the Baumann Skin Type Indicator Questionnaire.¹ The wrinkle-prone Baumann skin type is associated with age or with lifestyle factors that increase the risk for promoting skin aging.² Prevention and treatment of numerous signs of cutaneous aging can be achieved through consistent daily use of oral and topical products suited to the identified specifically wrinkle-prone Baumann skin type.

bonchan/Thinkstock

Skin aging

The numerous causes of skin aging can be divided into two broad categories: intrinsic and extrinsic. Intrinsic aging results from cellular processes that occur over time and is influenced by genetics. Such aging is characterized by decreased function of keratinocytes and fibroblasts, intra- and extracellular accumulation of by-products, reduced function of sirtuins (proteins that regulate cell metabolism and aging), mitochondrial damage, and loss of telomeres.

Extrinsic aging results from environmental exposures that engender cell damage, including UV light, infrared and radiation exposure, air pollution, smoking, tanning beds, alcohol and drug usage, stress, and poor diet. Extrinsic aging occurs as a result of intersecting processes caused by free radicals, DNA damage, glycation, inflammation, and other actions by the immune system. Generally, these factors can be partially mitigated through behavioral change. As much as 80% of facial aging can be ascribed to sun exposure.⁴ Several mechanisms through which sun exposure promotes aging have been well characterized. DNA damage results when UV light induces covalent bonds between nucleic acid base pairs and forms thymine dimers, which can alter tumor suppressor gene p53 function, thereby increasing the risk of cutaneous cancers and aging.⁵ UV exposure also yields free radicals that create damaging oxidative stress,⁶ which can activate the arachidonic acid pathway resulting in inflammation.⁷ Other skin aging mechanisms are not as well understood.
 

The cellular role in aging: Keratinocytes and fibroblasts

Keratinocyte cells found in layers that resemble the brick-and-mortar structure of a brick wall compose the epidermis. Each epidermal layer exhibits specific functional roles and characteristics. The top layer of the epidermis, known as the stratum corneum, is notable because it forms the skin barrier. This protective barrier contains cross-linked proteins for strength, antioxidants to protect the cells from free radicals, a bilayer lipid membrane layer to prevent water evaporation from the cells surface, immune cells, antimicrobial peptides, and a natural microbiome. Damage to any layer of the epidermis can unleash a cascade of events that can lead to increased cutaneous aging.

The dermis is composed of fibroblast cells, which synthesize collagen, elastin, hyaluronic acid, heparan sulfate, and other glycosaminoglycans that keep the skin smooth, strong, and healthy. Collagen confers strength, elastin provides elasticity, and the glycosaminoglycans such as hyaluronic acid, heparan sulfate, and dermatan sulfate bind water, impart volume to the skin, and provide support for important cell-to-cell communication.

When keratinocytes and fibroblasts age, they may no longer respond to cellular signals such as growth factors. The primary aim of any antiaging skin care regimen is to protect and rejuvenate these key skin cells.

Cellular damage that contributes to skin aging

The accumulated damage from intrinsic and extrinsic factors yields keratinocytes and fibroblasts that fail to produce important cellular components as well as they did when they were younger. Cellular factors that age cells include nuclear DNA damage, mitochondrial DNA damage, diminished lysosomal function, structural impairment of proteins, and damage to cell membranes. This harm occurs because of the direct effects of UV radiation, pollution, toxins, free radicals (oxidation), glycation, and inflammation.

Preventing and treating DNA damage

DNA damage presents as thymine-thymine dimers, pyrimidine-pyrimidine dimers, impaired telomeres, or other mutations. Broad-spectrum sunscreens and sun avoidance are important steps in preventing DNA damage induced from exposure to UV radiation. Other cosmeceutical agents have been designed to hinder the effects of UV radiation or to foster DNA repair. Besides sunscreen, the key members of the dermatologic armamentarium against DNA damage are various antioxidants. Data have been gathered over the last few decades that support the protective effects of antioxidants such as polypodium leucotomos,ascorbic acid, and green tea. Other antioxidants are associated with less data, but hypothetically should deliver similar benefits.

Polypodium leucotomos (PL), an oral extract derived from ferns, has been demonstrated to display photoprotective effects at an oral dose of 7.5 mg. PL has consistently exhibited antitumor and skin protective effects.⁸ A 2004 study in humans revealed that two oral doses of PL contributed to a significant reduction in DNA damage after UV exposure,⁹ and a 2017 study showed that PL protected skin DNA from UVB.¹⁰ Although PL has been linked to topical benefits, it is the oral form that is most often used to protect skin.

Ascorbic acid, also known as vitamin C, has been amply demonstrated to confer benefits when given both orally and topically. An acidic environment is necessary for optimal absorption. Topical application of ascorbic acid, along with vitamin E and ferulic acid, has been demonstrated to decrease the formation of thymine dimers.¹¹ Unlike other antioxidants, ascorbic acid also stimulates procollagen genes in fibroblasts to increase collagen synthesis.¹²

Madeleine_Steinbach/Thinkstock

Preventing and treating mitochondrial DNA damage

UV radiation elicits mitochondrial DNA damage known as the “common deletion.”¹⁷ Damaged mitochondria produce harmful free radicals known as reactive oxygen species. Mitochondria damage caused by ROS decreases the mitochondria’s ability to generate ATP energy, which is necessary for DNA repair and other cellular processes.

Free radicals and UV radiation damage mitochondria, as does normal cellular metabolism. The range of damage includes mitochondrial DNA impairment, loss of mitochondrial enzymes, and decreased ATP production. This leads to less energy for DNA repair and other reparative processes. While there is no established way to reduce mitochondrial damage once it has occurred, several research initiatives to achieve this end are underway. Currently, protecting the mitochondria from harm with sunscreens and antioxidants is the best option.

Antioxidants are effective in preventing the damaging effects of free radicals on vulnerable mitochondria. As a component of the mitochondrial respiratory chain and an antioxidant itself, coenzyme Q10 is particularly useful in this role. CoQ10 is available in both oral and topical formulations. Oral forms should be taken only in the morning because of a caffeine-like effect. Topical forms of CoQ10 have a dark yellow color that may be unappealing to patients. Polypodium leucotomos has been shown to lower the number of common deletions found in the mitochondria of irradiated keratinocytes and fibroblasts.¹⁸ The oral form is recommended. Another potent antioxidant, curcumin, is being studied for mitochondrial protective properties.¹⁹ Its strong yellow color and smell render it better suited for oral use although many companies are trying to develop cosmetically elegant topical formulations.
 

Scavenging free radicals

Ultraviolet light, pollution, and other insults engender free radical formation. Even sunscreen use has been linked to increased production of free radicals. Free radicals, also known as reactive oxygen species, harm cells in many ways including mitochondrial damage, DNA mutations, glycation, lysosomal damage, and oxidation of important lipids and other cellular components such as proteins. Antioxidants present various beneficial effects including scavenging free radicals, decreasing activation of mitogen-activated protein kinases, chelation of copper required by tyrosinase, and suppression of inflammatory factors, such as nuclear factor (NF)-kB.^20. Antioxidants are essential in preventing aged skin.

In summary, skin aging has many causes. Although they are not all understood, some of the processes have been elucidated. Next month, this column will focus on the prevention and treatment of inflammation and glycation, as well as reversing the effects of aging on skin cells.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014). She also wrote a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. Baumann, Leslie S. “Cosmeceuticals and cosmetic ingredients” (New York: McGraw-Hill Education / Medical, 2014).

2. Baumann, Leslie S. The Baumann Skin Typing System in “Textbook of Aging Skin” (New York: Springer-Verlag Berlin Heidelberg, 2017). pp. 1579-94.

3. Storm A et al. J Am Acad Dermatol. 2008 Dec;59(6):975-80.

4. Uitto J. N Engl J Med. 1997 Nov 13;337(20):1463-5.

5. Tornaletti S et al. Science. 1994;263(5152):1436-8.

6. Bickers D et al. J. Investig. Dermatol. 2006;126(12):2565-75.

7. Yaar M et al. Br J Dermatol. 2007 Nov;157(5):874-87.

8. Parrado C et al. Int J Mol Sci. 2016 Jun 29;17(7). pii: E1026.

9. Middelkamp-Hup MA et al. J Am Acad Dermatol. 2004 Dec;51(6):910-8.

10. Kohli I et al. J Am Acad Dermatol. 2017 Jul;77(1):33-41.

11. Murray JC et al. J Am Acad Dermatol. 2008;59(3):418-25.

12. Geesin JC et al. J Invest Dermatol. 1988 Apr;90(4):420-4.

13. Thompson BC et al. PLoS One. 2015 Feb 6;10(2):e0117491.

14. Surjana D et al. Carcinogenesis. 2013 May;34(5):1144-9.

15. Meeran SM et al. Cancer Res. 2006 May 15;66(10):5512-20.

16. Elmets CA et al. J Am Acad Dermatol. 2001 Mar;44(3):425-32.

17. Berneburg M et al. J Invest Dermatol. 2004 May;122(5):1277-83.

18. Villa A et al. J Am Acad Dermatol. 2010 Mar;62(3):511-3.

19. Trujillo J et al. Arch Pharm Chem Life Sci. 2014. doi: 10.1002/ardp.2014002662014.

20. Muthusam V et al. Arch Dermatol Res. 2010 Jan;302(1):5-17.

It is important for dermatologists to recognize patients at an increased risk of skin aging early enough to initiate countermeasures. “Wrinkle-prone” skin types can be identified easily through use of the Baumann Skin Type Indicator Questionnaire.¹ The wrinkle-prone Baumann skin type is associated with age or with lifestyle factors that increase the risk for promoting skin aging.² Prevention and treatment of numerous signs of cutaneous aging can be achieved through consistent daily use of oral and topical products suited to the identified specifically wrinkle-prone Baumann skin type.

bonchan/Thinkstock

Skin aging

The numerous causes of skin aging can be divided into two broad categories: intrinsic and extrinsic. Intrinsic aging results from cellular processes that occur over time and is influenced by genetics. Such aging is characterized by decreased function of keratinocytes and fibroblasts, intra- and extracellular accumulation of by-products, reduced function of sirtuins (proteins that regulate cell metabolism and aging), mitochondrial damage, and loss of telomeres.

Extrinsic aging results from environmental exposures that engender cell damage, including UV light, infrared and radiation exposure, air pollution, smoking, tanning beds, alcohol and drug usage, stress, and poor diet. Extrinsic aging occurs as a result of intersecting processes caused by free radicals, DNA damage, glycation, inflammation, and other actions by the immune system. Generally, these factors can be partially mitigated through behavioral change. As much as 80% of facial aging can be ascribed to sun exposure.⁴ Several mechanisms through which sun exposure promotes aging have been well characterized. DNA damage results when UV light induces covalent bonds between nucleic acid base pairs and forms thymine dimers, which can alter tumor suppressor gene p53 function, thereby increasing the risk of cutaneous cancers and aging.⁵ UV exposure also yields free radicals that create damaging oxidative stress,⁶ which can activate the arachidonic acid pathway resulting in inflammation.⁷ Other skin aging mechanisms are not as well understood.
 

The cellular role in aging: Keratinocytes and fibroblasts

Keratinocyte cells found in layers that resemble the brick-and-mortar structure of a brick wall compose the epidermis. Each epidermal layer exhibits specific functional roles and characteristics. The top layer of the epidermis, known as the stratum corneum, is notable because it forms the skin barrier. This protective barrier contains cross-linked proteins for strength, antioxidants to protect the cells from free radicals, a bilayer lipid membrane layer to prevent water evaporation from the cells surface, immune cells, antimicrobial peptides, and a natural microbiome. Damage to any layer of the epidermis can unleash a cascade of events that can lead to increased cutaneous aging.

The dermis is composed of fibroblast cells, which synthesize collagen, elastin, hyaluronic acid, heparan sulfate, and other glycosaminoglycans that keep the skin smooth, strong, and healthy. Collagen confers strength, elastin provides elasticity, and the glycosaminoglycans such as hyaluronic acid, heparan sulfate, and dermatan sulfate bind water, impart volume to the skin, and provide support for important cell-to-cell communication.

When keratinocytes and fibroblasts age, they may no longer respond to cellular signals such as growth factors. The primary aim of any antiaging skin care regimen is to protect and rejuvenate these key skin cells.

Cellular damage that contributes to skin aging

The accumulated damage from intrinsic and extrinsic factors yields keratinocytes and fibroblasts that fail to produce important cellular components as well as they did when they were younger. Cellular factors that age cells include nuclear DNA damage, mitochondrial DNA damage, diminished lysosomal function, structural impairment of proteins, and damage to cell membranes. This harm occurs because of the direct effects of UV radiation, pollution, toxins, free radicals (oxidation), glycation, and inflammation.

Preventing and treating DNA damage

DNA damage presents as thymine-thymine dimers, pyrimidine-pyrimidine dimers, impaired telomeres, or other mutations. Broad-spectrum sunscreens and sun avoidance are important steps in preventing DNA damage induced from exposure to UV radiation. Other cosmeceutical agents have been designed to hinder the effects of UV radiation or to foster DNA repair. Besides sunscreen, the key members of the dermatologic armamentarium against DNA damage are various antioxidants. Data have been gathered over the last few decades that support the protective effects of antioxidants such as polypodium leucotomos,ascorbic acid, and green tea. Other antioxidants are associated with less data, but hypothetically should deliver similar benefits.

Polypodium leucotomos (PL), an oral extract derived from ferns, has been demonstrated to display photoprotective effects at an oral dose of 7.5 mg. PL has consistently exhibited antitumor and skin protective effects.⁸ A 2004 study in humans revealed that two oral doses of PL contributed to a significant reduction in DNA damage after UV exposure,⁹ and a 2017 study showed that PL protected skin DNA from UVB.¹⁰ Although PL has been linked to topical benefits, it is the oral form that is most often used to protect skin.

Ascorbic acid, also known as vitamin C, has been amply demonstrated to confer benefits when given both orally and topically. An acidic environment is necessary for optimal absorption. Topical application of ascorbic acid, along with vitamin E and ferulic acid, has been demonstrated to decrease the formation of thymine dimers.¹¹ Unlike other antioxidants, ascorbic acid also stimulates procollagen genes in fibroblasts to increase collagen synthesis.¹²

Madeleine_Steinbach/Thinkstock

Preventing and treating mitochondrial DNA damage

UV radiation elicits mitochondrial DNA damage known as the “common deletion.”¹⁷ Damaged mitochondria produce harmful free radicals known as reactive oxygen species. Mitochondria damage caused by ROS decreases the mitochondria’s ability to generate ATP energy, which is necessary for DNA repair and other cellular processes.

Free radicals and UV radiation damage mitochondria, as does normal cellular metabolism. The range of damage includes mitochondrial DNA impairment, loss of mitochondrial enzymes, and decreased ATP production. This leads to less energy for DNA repair and other reparative processes. While there is no established way to reduce mitochondrial damage once it has occurred, several research initiatives to achieve this end are underway. Currently, protecting the mitochondria from harm with sunscreens and antioxidants is the best option.

Antioxidants are effective in preventing the damaging effects of free radicals on vulnerable mitochondria. As a component of the mitochondrial respiratory chain and an antioxidant itself, coenzyme Q10 is particularly useful in this role. CoQ10 is available in both oral and topical formulations. Oral forms should be taken only in the morning because of a caffeine-like effect. Topical forms of CoQ10 have a dark yellow color that may be unappealing to patients. Polypodium leucotomos has been shown to lower the number of common deletions found in the mitochondria of irradiated keratinocytes and fibroblasts.¹⁸ The oral form is recommended. Another potent antioxidant, curcumin, is being studied for mitochondrial protective properties.¹⁹ Its strong yellow color and smell render it better suited for oral use although many companies are trying to develop cosmetically elegant topical formulations.
 

Scavenging free radicals

Ultraviolet light, pollution, and other insults engender free radical formation. Even sunscreen use has been linked to increased production of free radicals. Free radicals, also known as reactive oxygen species, harm cells in many ways including mitochondrial damage, DNA mutations, glycation, lysosomal damage, and oxidation of important lipids and other cellular components such as proteins. Antioxidants present various beneficial effects including scavenging free radicals, decreasing activation of mitogen-activated protein kinases, chelation of copper required by tyrosinase, and suppression of inflammatory factors, such as nuclear factor (NF)-kB.^20. Antioxidants are essential in preventing aged skin.

In summary, skin aging has many causes. Although they are not all understood, some of the processes have been elucidated. Next month, this column will focus on the prevention and treatment of inflammation and glycation, as well as reversing the effects of aging on skin cells.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014). She also wrote a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. Baumann, Leslie S. “Cosmeceuticals and cosmetic ingredients” (New York: McGraw-Hill Education / Medical, 2014).

2. Baumann, Leslie S. The Baumann Skin Typing System in “Textbook of Aging Skin” (New York: Springer-Verlag Berlin Heidelberg, 2017). pp. 1579-94.

3. Storm A et al. J Am Acad Dermatol. 2008 Dec;59(6):975-80.

4. Uitto J. N Engl J Med. 1997 Nov 13;337(20):1463-5.

5. Tornaletti S et al. Science. 1994;263(5152):1436-8.

6. Bickers D et al. J. Investig. Dermatol. 2006;126(12):2565-75.

7. Yaar M et al. Br J Dermatol. 2007 Nov;157(5):874-87.

8. Parrado C et al. Int J Mol Sci. 2016 Jun 29;17(7). pii: E1026.

9. Middelkamp-Hup MA et al. J Am Acad Dermatol. 2004 Dec;51(6):910-8.

10. Kohli I et al. J Am Acad Dermatol. 2017 Jul;77(1):33-41.

11. Murray JC et al. J Am Acad Dermatol. 2008;59(3):418-25.

12. Geesin JC et al. J Invest Dermatol. 1988 Apr;90(4):420-4.

13. Thompson BC et al. PLoS One. 2015 Feb 6;10(2):e0117491.

14. Surjana D et al. Carcinogenesis. 2013 May;34(5):1144-9.

15. Meeran SM et al. Cancer Res. 2006 May 15;66(10):5512-20.

16. Elmets CA et al. J Am Acad Dermatol. 2001 Mar;44(3):425-32.

17. Berneburg M et al. J Invest Dermatol. 2004 May;122(5):1277-83.

18. Villa A et al. J Am Acad Dermatol. 2010 Mar;62(3):511-3.

19. Trujillo J et al. Arch Pharm Chem Life Sci. 2014. doi: 10.1002/ardp.2014002662014.

20. Muthusam V et al. Arch Dermatol Res. 2010 Jan;302(1):5-17.

It is important for dermatologists to recognize patients at an increased risk of skin aging early enough to initiate countermeasures. “Wrinkle-prone” skin types can be identified easily through use of the Baumann Skin Type Indicator Questionnaire.¹ The wrinkle-prone Baumann skin type is associated with age or with lifestyle factors that increase the risk for promoting skin aging.² Prevention and treatment of numerous signs of cutaneous aging can be achieved through consistent daily use of oral and topical products suited to the identified specifically wrinkle-prone Baumann skin type.

bonchan/Thinkstock

Skin aging

The numerous causes of skin aging can be divided into two broad categories: intrinsic and extrinsic. Intrinsic aging results from cellular processes that occur over time and is influenced by genetics. Such aging is characterized by decreased function of keratinocytes and fibroblasts, intra- and extracellular accumulation of by-products, reduced function of sirtuins (proteins that regulate cell metabolism and aging), mitochondrial damage, and loss of telomeres.

Extrinsic aging results from environmental exposures that engender cell damage, including UV light, infrared and radiation exposure, air pollution, smoking, tanning beds, alcohol and drug usage, stress, and poor diet. Extrinsic aging occurs as a result of intersecting processes caused by free radicals, DNA damage, glycation, inflammation, and other actions by the immune system. Generally, these factors can be partially mitigated through behavioral change. As much as 80% of facial aging can be ascribed to sun exposure.⁴ Several mechanisms through which sun exposure promotes aging have been well characterized. DNA damage results when UV light induces covalent bonds between nucleic acid base pairs and forms thymine dimers, which can alter tumor suppressor gene p53 function, thereby increasing the risk of cutaneous cancers and aging.⁵ UV exposure also yields free radicals that create damaging oxidative stress,⁶ which can activate the arachidonic acid pathway resulting in inflammation.⁷ Other skin aging mechanisms are not as well understood.
 

The cellular role in aging: Keratinocytes and fibroblasts

Keratinocyte cells found in layers that resemble the brick-and-mortar structure of a brick wall compose the epidermis. Each epidermal layer exhibits specific functional roles and characteristics. The top layer of the epidermis, known as the stratum corneum, is notable because it forms the skin barrier. This protective barrier contains cross-linked proteins for strength, antioxidants to protect the cells from free radicals, a bilayer lipid membrane layer to prevent water evaporation from the cells surface, immune cells, antimicrobial peptides, and a natural microbiome. Damage to any layer of the epidermis can unleash a cascade of events that can lead to increased cutaneous aging.

The dermis is composed of fibroblast cells, which synthesize collagen, elastin, hyaluronic acid, heparan sulfate, and other glycosaminoglycans that keep the skin smooth, strong, and healthy. Collagen confers strength, elastin provides elasticity, and the glycosaminoglycans such as hyaluronic acid, heparan sulfate, and dermatan sulfate bind water, impart volume to the skin, and provide support for important cell-to-cell communication.

When keratinocytes and fibroblasts age, they may no longer respond to cellular signals such as growth factors. The primary aim of any antiaging skin care regimen is to protect and rejuvenate these key skin cells.

Cellular damage that contributes to skin aging

The accumulated damage from intrinsic and extrinsic factors yields keratinocytes and fibroblasts that fail to produce important cellular components as well as they did when they were younger. Cellular factors that age cells include nuclear DNA damage, mitochondrial DNA damage, diminished lysosomal function, structural impairment of proteins, and damage to cell membranes. This harm occurs because of the direct effects of UV radiation, pollution, toxins, free radicals (oxidation), glycation, and inflammation.

Preventing and treating DNA damage

DNA damage presents as thymine-thymine dimers, pyrimidine-pyrimidine dimers, impaired telomeres, or other mutations. Broad-spectrum sunscreens and sun avoidance are important steps in preventing DNA damage induced from exposure to UV radiation. Other cosmeceutical agents have been designed to hinder the effects of UV radiation or to foster DNA repair. Besides sunscreen, the key members of the dermatologic armamentarium against DNA damage are various antioxidants. Data have been gathered over the last few decades that support the protective effects of antioxidants such as polypodium leucotomos,ascorbic acid, and green tea. Other antioxidants are associated with less data, but hypothetically should deliver similar benefits.

Polypodium leucotomos (PL), an oral extract derived from ferns, has been demonstrated to display photoprotective effects at an oral dose of 7.5 mg. PL has consistently exhibited antitumor and skin protective effects.⁸ A 2004 study in humans revealed that two oral doses of PL contributed to a significant reduction in DNA damage after UV exposure,⁹ and a 2017 study showed that PL protected skin DNA from UVB.¹⁰ Although PL has been linked to topical benefits, it is the oral form that is most often used to protect skin.

Ascorbic acid, also known as vitamin C, has been amply demonstrated to confer benefits when given both orally and topically. An acidic environment is necessary for optimal absorption. Topical application of ascorbic acid, along with vitamin E and ferulic acid, has been demonstrated to decrease the formation of thymine dimers.¹¹ Unlike other antioxidants, ascorbic acid also stimulates procollagen genes in fibroblasts to increase collagen synthesis.¹²

Madeleine_Steinbach/Thinkstock

Preventing and treating mitochondrial DNA damage

UV radiation elicits mitochondrial DNA damage known as the “common deletion.”¹⁷ Damaged mitochondria produce harmful free radicals known as reactive oxygen species. Mitochondria damage caused by ROS decreases the mitochondria’s ability to generate ATP energy, which is necessary for DNA repair and other cellular processes.

Free radicals and UV radiation damage mitochondria, as does normal cellular metabolism. The range of damage includes mitochondrial DNA impairment, loss of mitochondrial enzymes, and decreased ATP production. This leads to less energy for DNA repair and other reparative processes. While there is no established way to reduce mitochondrial damage once it has occurred, several research initiatives to achieve this end are underway. Currently, protecting the mitochondria from harm with sunscreens and antioxidants is the best option.

Antioxidants are effective in preventing the damaging effects of free radicals on vulnerable mitochondria. As a component of the mitochondrial respiratory chain and an antioxidant itself, coenzyme Q10 is particularly useful in this role. CoQ10 is available in both oral and topical formulations. Oral forms should be taken only in the morning because of a caffeine-like effect. Topical forms of CoQ10 have a dark yellow color that may be unappealing to patients. Polypodium leucotomos has been shown to lower the number of common deletions found in the mitochondria of irradiated keratinocytes and fibroblasts.¹⁸ The oral form is recommended. Another potent antioxidant, curcumin, is being studied for mitochondrial protective properties.¹⁹ Its strong yellow color and smell render it better suited for oral use although many companies are trying to develop cosmetically elegant topical formulations.
 

Scavenging free radicals

Ultraviolet light, pollution, and other insults engender free radical formation. Even sunscreen use has been linked to increased production of free radicals. Free radicals, also known as reactive oxygen species, harm cells in many ways including mitochondrial damage, DNA mutations, glycation, lysosomal damage, and oxidation of important lipids and other cellular components such as proteins. Antioxidants present various beneficial effects including scavenging free radicals, decreasing activation of mitogen-activated protein kinases, chelation of copper required by tyrosinase, and suppression of inflammatory factors, such as nuclear factor (NF)-kB.^20. Antioxidants are essential in preventing aged skin.

In summary, skin aging has many causes. Although they are not all understood, some of the processes have been elucidated. Next month, this column will focus on the prevention and treatment of inflammation and glycation, as well as reversing the effects of aging on skin cells.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann wrote two textbooks: “Cosmetic Dermatology: Principles and Practice” (New York: McGraw-Hill, 2002) and “Cosmeceuticals and Cosmetic Ingredients” (New York: McGraw-Hill, 2014). She also wrote a New York Times Best Sellers book for consumers, “The Skin Type Solution” (New York: Bantam Dell, 2006). Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC.

References

1. Baumann, Leslie S. “Cosmeceuticals and cosmetic ingredients” (New York: McGraw-Hill Education / Medical, 2014).

2. Baumann, Leslie S. The Baumann Skin Typing System in “Textbook of Aging Skin” (New York: Springer-Verlag Berlin Heidelberg, 2017). pp. 1579-94.

3. Storm A et al. J Am Acad Dermatol. 2008 Dec;59(6):975-80.

4. Uitto J. N Engl J Med. 1997 Nov 13;337(20):1463-5.

5. Tornaletti S et al. Science. 1994;263(5152):1436-8.

6. Bickers D et al. J. Investig. Dermatol. 2006;126(12):2565-75.

7. Yaar M et al. Br J Dermatol. 2007 Nov;157(5):874-87.

8. Parrado C et al. Int J Mol Sci. 2016 Jun 29;17(7). pii: E1026.

9. Middelkamp-Hup MA et al. J Am Acad Dermatol. 2004 Dec;51(6):910-8.

10. Kohli I et al. J Am Acad Dermatol. 2017 Jul;77(1):33-41.

11. Murray JC et al. J Am Acad Dermatol. 2008;59(3):418-25.

12. Geesin JC et al. J Invest Dermatol. 1988 Apr;90(4):420-4.

13. Thompson BC et al. PLoS One. 2015 Feb 6;10(2):e0117491.

14. Surjana D et al. Carcinogenesis. 2013 May;34(5):1144-9.

15. Meeran SM et al. Cancer Res. 2006 May 15;66(10):5512-20.

16. Elmets CA et al. J Am Acad Dermatol. 2001 Mar;44(3):425-32.

17. Berneburg M et al. J Invest Dermatol. 2004 May;122(5):1277-83.

18. Villa A et al. J Am Acad Dermatol. 2010 Mar;62(3):511-3.

19. Trujillo J et al. Arch Pharm Chem Life Sci. 2014. doi: 10.1002/ardp.2014002662014.

20. Muthusam V et al. Arch Dermatol Res. 2010 Jan;302(1):5-17.

LOS ANGELES – The relationship between elevated C-reactive protein concentrations and increased all-cause mortality risk varies by gender and by race/ethnicity, an analysis of national data showed.

“Opportunities exist to discuss the importance of this marker and the relationship with mortality risk,” study author M. Ryan Richardson said in an interview following the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “Although we do not fully understand all of the mechanisms that underlie this harmful relationship, our results add to the limited evidence available to those working within the clinical setting.”

dbrunk@frontlinemedcom.com

SOURCE: M. Ryan Richardson et al.

LOS ANGELES – The relationship between elevated C-reactive protein concentrations and increased all-cause mortality risk varies by gender and by race/ethnicity, an analysis of national data showed.

“Opportunities exist to discuss the importance of this marker and the relationship with mortality risk,” study author M. Ryan Richardson said in an interview following the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “Although we do not fully understand all of the mechanisms that underlie this harmful relationship, our results add to the limited evidence available to those working within the clinical setting.”

dbrunk@frontlinemedcom.com

SOURCE: M. Ryan Richardson et al.

LOS ANGELES – The relationship between elevated C-reactive protein concentrations and increased all-cause mortality risk varies by gender and by race/ethnicity, an analysis of national data showed.

“Opportunities exist to discuss the importance of this marker and the relationship with mortality risk,” study author M. Ryan Richardson said in an interview following the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “Although we do not fully understand all of the mechanisms that underlie this harmful relationship, our results add to the limited evidence available to those working within the clinical setting.”

dbrunk@frontlinemedcom.com

SOURCE: M. Ryan Richardson et al.

ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.

The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.

The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).

aotto@frontlinemedcom.com
 

ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.

The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.

The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).

aotto@frontlinemedcom.com
 

ANAHEIM, CALIF. – Low levels of four phosphatidylcholines – essential components of cell membranes – predict the risk of incident coronary heart disease about as well as body mass index does, according to an analysis presented at the American Heart Association scientific sessions.

The findings come from the BiomarCaRE consortium (Biomarker for Cardiovascular Risk Assessment in Europe), a European Union–funded effort to evaluate the predictive value of new and existing biomarkers for cardiovascular disease.

The new findings “demonstrate the value of metabolomics for biomarker discovery and improved risk stratification,” said lead investigator Tanja Zeller, PhD, of the department of general and interventional cardiology, University Heart Center Hamburg (Germany).

aotto@frontlinemedcom.com
 

The Food and Drug Administration has approved Sanofi’s insulin lispro injections (Admelog) for improved blood sugar control in adults and children aged 3 years and older with type 1 and type 2 diabetes mellitus, according to a news release from the FDA.

Insulin lispro injections are to be administered subcutaneously by injection, infusion via an insulin pump, or intravenously. Doses should be individualized based on route of administration and patients’ individual metabolic needs. All diabetes patients should regularly monitor their blood sugar levels and insulin regimens should be exclusively modified under medical supervision.

“With today’s approval, we are providing an important short-acting insulin option for patients that meets our standards for safety and effectiveness,” Mary T. Thanh Hai, MD, deputy director of the Office of New Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, said in a statement.

Admelog, a biosimilar to Eli Lilly’s Humalog, was approved as a follow-on product based on the prior approval of Humalog. This allowed insulin lispro injections to be passed through the abbreviated approval pathway under the Federal Food, Drug, and Cosmetic Act, formally known as the 505(b)(2) pathway. The makers of insulin lispro found it was scientifically justified to use the previous safety and effectiveness data from the approval of Humalog to support the approval of insulin lispro injections. In addition to the Humalog data, the insulin lispro injection data included findings from two phase 3 clinical trials, each of which comprised about 500 diabetes patients. Using this abbreviated pathway can reduce the costs of drug development significantly, allowing new products to be offered to patients at lower prices.

“One of my key policy efforts is increasing competition in the market for prescription drugs and helping facilitate the entry of lower-cost alternatives. This is particularly important for drugs like insulin that are taken by millions of Americans every day for a patient’s lifetime to manage a chronic disease,” FDA Commissioner Scott Gottlieb, MD, said in a statement “In the coming months, we’ll be taking additional policy steps to help to make sure patients continue to benefit from improved access to lower cost, safe and effective alternatives to brand name drugs approved through the agency’s abbreviated pathways.”

Insulin lispro injections are short-acting insulin products that can help improve blood sugar levels in diabetes patients. This can be useful in controlling blood sugar levels after eating. This contrasts with long-acting insulin products, which are intended to control background insulin levels between meals. The blood sugar control needs of type 1 and type 2 diabetes patients are unique. Type 1 patients require both short- and long-term controls, while some type 2 patients may never need a short-acting insulin product. Because of these differences, providing insulin lispro injections as a blood sugar control method may be particularly useful to type 1 diabetes patients who need to control mealtime blood sugar levels.

ilacy@frontlinemedcom.com

The Food and Drug Administration has approved Sanofi’s insulin lispro injections (Admelog) for improved blood sugar control in adults and children aged 3 years and older with type 1 and type 2 diabetes mellitus, according to a news release from the FDA.

Insulin lispro injections are to be administered subcutaneously by injection, infusion via an insulin pump, or intravenously. Doses should be individualized based on route of administration and patients’ individual metabolic needs. All diabetes patients should regularly monitor their blood sugar levels and insulin regimens should be exclusively modified under medical supervision.

“With today’s approval, we are providing an important short-acting insulin option for patients that meets our standards for safety and effectiveness,” Mary T. Thanh Hai, MD, deputy director of the Office of New Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, said in a statement.

Admelog, a biosimilar to Eli Lilly’s Humalog, was approved as a follow-on product based on the prior approval of Humalog. This allowed insulin lispro injections to be passed through the abbreviated approval pathway under the Federal Food, Drug, and Cosmetic Act, formally known as the 505(b)(2) pathway. The makers of insulin lispro found it was scientifically justified to use the previous safety and effectiveness data from the approval of Humalog to support the approval of insulin lispro injections. In addition to the Humalog data, the insulin lispro injection data included findings from two phase 3 clinical trials, each of which comprised about 500 diabetes patients. Using this abbreviated pathway can reduce the costs of drug development significantly, allowing new products to be offered to patients at lower prices.

“One of my key policy efforts is increasing competition in the market for prescription drugs and helping facilitate the entry of lower-cost alternatives. This is particularly important for drugs like insulin that are taken by millions of Americans every day for a patient’s lifetime to manage a chronic disease,” FDA Commissioner Scott Gottlieb, MD, said in a statement “In the coming months, we’ll be taking additional policy steps to help to make sure patients continue to benefit from improved access to lower cost, safe and effective alternatives to brand name drugs approved through the agency’s abbreviated pathways.”

Insulin lispro injections are short-acting insulin products that can help improve blood sugar levels in diabetes patients. This can be useful in controlling blood sugar levels after eating. This contrasts with long-acting insulin products, which are intended to control background insulin levels between meals. The blood sugar control needs of type 1 and type 2 diabetes patients are unique. Type 1 patients require both short- and long-term controls, while some type 2 patients may never need a short-acting insulin product. Because of these differences, providing insulin lispro injections as a blood sugar control method may be particularly useful to type 1 diabetes patients who need to control mealtime blood sugar levels.

ilacy@frontlinemedcom.com

The Food and Drug Administration has approved Sanofi’s insulin lispro injections (Admelog) for improved blood sugar control in adults and children aged 3 years and older with type 1 and type 2 diabetes mellitus, according to a news release from the FDA.

Insulin lispro injections are to be administered subcutaneously by injection, infusion via an insulin pump, or intravenously. Doses should be individualized based on route of administration and patients’ individual metabolic needs. All diabetes patients should regularly monitor their blood sugar levels and insulin regimens should be exclusively modified under medical supervision.

“With today’s approval, we are providing an important short-acting insulin option for patients that meets our standards for safety and effectiveness,” Mary T. Thanh Hai, MD, deputy director of the Office of New Drug Evaluation II in the FDA’s Center for Drug Evaluation and Research, said in a statement.

Admelog, a biosimilar to Eli Lilly’s Humalog, was approved as a follow-on product based on the prior approval of Humalog. This allowed insulin lispro injections to be passed through the abbreviated approval pathway under the Federal Food, Drug, and Cosmetic Act, formally known as the 505(b)(2) pathway. The makers of insulin lispro found it was scientifically justified to use the previous safety and effectiveness data from the approval of Humalog to support the approval of insulin lispro injections. In addition to the Humalog data, the insulin lispro injection data included findings from two phase 3 clinical trials, each of which comprised about 500 diabetes patients. Using this abbreviated pathway can reduce the costs of drug development significantly, allowing new products to be offered to patients at lower prices.

“One of my key policy efforts is increasing competition in the market for prescription drugs and helping facilitate the entry of lower-cost alternatives. This is particularly important for drugs like insulin that are taken by millions of Americans every day for a patient’s lifetime to manage a chronic disease,” FDA Commissioner Scott Gottlieb, MD, said in a statement “In the coming months, we’ll be taking additional policy steps to help to make sure patients continue to benefit from improved access to lower cost, safe and effective alternatives to brand name drugs approved through the agency’s abbreviated pathways.”

Insulin lispro injections are short-acting insulin products that can help improve blood sugar levels in diabetes patients. This can be useful in controlling blood sugar levels after eating. This contrasts with long-acting insulin products, which are intended to control background insulin levels between meals. The blood sugar control needs of type 1 and type 2 diabetes patients are unique. Type 1 patients require both short- and long-term controls, while some type 2 patients may never need a short-acting insulin product. Because of these differences, providing insulin lispro injections as a blood sugar control method may be particularly useful to type 1 diabetes patients who need to control mealtime blood sugar levels.

ilacy@frontlinemedcom.com

The Role of the Robotic Platform in Inguinal Hernia Repair Surgery is an interventional trial currently recruiting patients who require inguinal hernia repair surgery.

The trial will compare postoperative pain in patients undergoing laparoscopic inguinal hernia surgery repair or robotic inguinal hernia repair surgery. The laparoscopic approach has been used frequently and has several advantages. However, it has several disadvantages that the robotic approach may address. As such, the study investigators have hypothesized that the robotic approach will result in less postoperative pain than the laparoscopic approach.

SOURCE: Clinicaltrials.gov. NCT02816658.

lfranki@frontlinemedcom.com

The Role of the Robotic Platform in Inguinal Hernia Repair Surgery is an interventional trial currently recruiting patients who require inguinal hernia repair surgery.

The trial will compare postoperative pain in patients undergoing laparoscopic inguinal hernia surgery repair or robotic inguinal hernia repair surgery. The laparoscopic approach has been used frequently and has several advantages. However, it has several disadvantages that the robotic approach may address. As such, the study investigators have hypothesized that the robotic approach will result in less postoperative pain than the laparoscopic approach.

SOURCE: Clinicaltrials.gov. NCT02816658.

lfranki@frontlinemedcom.com

The Role of the Robotic Platform in Inguinal Hernia Repair Surgery is an interventional trial currently recruiting patients who require inguinal hernia repair surgery.

The trial will compare postoperative pain in patients undergoing laparoscopic inguinal hernia surgery repair or robotic inguinal hernia repair surgery. The laparoscopic approach has been used frequently and has several advantages. However, it has several disadvantages that the robotic approach may address. As such, the study investigators have hypothesized that the robotic approach will result in less postoperative pain than the laparoscopic approach.

SOURCE: Clinicaltrials.gov. NCT02816658.

lfranki@frontlinemedcom.com

A survey of 305 inpatients showed that patients who reported that at least one provider sat down while caring for them were more likely to feel that their provider spent appropriate time with them and that their provider kept them well informed. The authors concluded that sitting down at a patient’s bedside improves some aspects of patients’ and families’ experience of their hospital care, and should be included in hospital efforts to improve the patient experience.

Reference

1. Adebusuyi OA et al. Does sitting enhance patient satisfaction in the hospital? [abstract]. J Hosp Med. 2017; 12 (suppl 2). Accessed Aug. 7, 2017.

A survey of 305 inpatients showed that patients who reported that at least one provider sat down while caring for them were more likely to feel that their provider spent appropriate time with them and that their provider kept them well informed. The authors concluded that sitting down at a patient’s bedside improves some aspects of patients’ and families’ experience of their hospital care, and should be included in hospital efforts to improve the patient experience.

Reference

1. Adebusuyi OA et al. Does sitting enhance patient satisfaction in the hospital? [abstract]. J Hosp Med. 2017; 12 (suppl 2). Accessed Aug. 7, 2017.

A survey of 305 inpatients showed that patients who reported that at least one provider sat down while caring for them were more likely to feel that their provider spent appropriate time with them and that their provider kept them well informed. The authors concluded that sitting down at a patient’s bedside improves some aspects of patients’ and families’ experience of their hospital care, and should be included in hospital efforts to improve the patient experience.

Reference

1. Adebusuyi OA et al. Does sitting enhance patient satisfaction in the hospital? [abstract]. J Hosp Med. 2017; 12 (suppl 2). Accessed Aug. 7, 2017.

ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.

The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.

In a video interview at the annual meeting of the American Society of Hematology, John F. Seymour, MBBS, PhD, discussed results from a planned interim analysis of the phase 3 MURANO study comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.

Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.

The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.

ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.

The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.

In a video interview at the annual meeting of the American Society of Hematology, John F. Seymour, MBBS, PhD, discussed results from a planned interim analysis of the phase 3 MURANO study comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.

Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.

The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.

ATLANTA – Relapsed or refractory chronic lymphocytic leukemia (CLL) often has a suboptimal response to conventional chemotherapy, because of adverse biological features that can accumulate in cells.

The combination of bendamustine (Treanda) and rituximab has been associated with about 60% overall responses rates, median progression-free survival of approximately 15 months, and overall survival of nearly 3 years in patients with CLL, and there is now evidence that substituting venetoclax (Venclexta) for bendamustine could improve outcomes even further.

In a video interview at the annual meeting of the American Society of Hematology, John F. Seymour, MBBS, PhD, discussed results from a planned interim analysis of the phase 3 MURANO study comparing bendamustine plus rituximab with venetoclax plus rituximab in patients with relapsed/refractory CLL.

Venetoclax/rituximab was superior to bendamustine/rituximab for prolonging progression-free survival, with effects consistent across subgroups, regardless of mutation status, and for having a clinically meaningful improvement in overall survival.

The MURANO trial was funded by AbbVie. Dr. Seymour reported honoraria, research funding, and advisory committee and speakers bureau participation for AbbVie and other companies.

Hormone therapy should not be used to prevent chronic conditions in postmenopausal women, according to updated recommendations from the U.S. Preventive Services Task Force. The recommendations were published online Dec. 12 in JAMA.

In the latest recommendation statement, the USPSTF issued D recommendations against using combination estrogen and progestin to prevent chronic conditions in postmenopausal women and against using estrogen only to prevent chronic conditions in postmenopausal women who have undergone hysterectomies (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.18261). A grade D recommendation is defined as “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”

Judith Flacke/Thinkstock

obnews@frontlinemedcom.com

Hormone therapy should not be used to prevent chronic conditions in postmenopausal women, according to updated recommendations from the U.S. Preventive Services Task Force. The recommendations were published online Dec. 12 in JAMA.

In the latest recommendation statement, the USPSTF issued D recommendations against using combination estrogen and progestin to prevent chronic conditions in postmenopausal women and against using estrogen only to prevent chronic conditions in postmenopausal women who have undergone hysterectomies (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.18261). A grade D recommendation is defined as “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”

Judith Flacke/Thinkstock

obnews@frontlinemedcom.com

Hormone therapy should not be used to prevent chronic conditions in postmenopausal women, according to updated recommendations from the U.S. Preventive Services Task Force. The recommendations were published online Dec. 12 in JAMA.

In the latest recommendation statement, the USPSTF issued D recommendations against using combination estrogen and progestin to prevent chronic conditions in postmenopausal women and against using estrogen only to prevent chronic conditions in postmenopausal women who have undergone hysterectomies (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.18261). A grade D recommendation is defined as “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”

Judith Flacke/Thinkstock

obnews@frontlinemedcom.com