Ideally, chemicals that are toxic to human health are identified and removed from use. Many such chemicals, known as persistent organic pollutants (POPs), have been studied individually for their ill effects in humans. DDT, for instance, once a widely used insecticide, is now classified as a probable human carcinogen and has not been used in the United States since the early 1970s.¹ Other insecticides have similarly been banned but have long half-lives and can persist in the environment for decades. Humans are exposed to POPs mainly through diet, say Ouidir and colleagues, with exposure “nearly ubiquitous.”²



The association between POP exposure during pregnancy and birth weight has not been established, as results from previous studies have been inconsistent, according to researchers.² In addition, birth weight does not distinguish growth-restricted fetuses from those that are constitutionally small. Therefore, Ouidir and colleagues analyzed maternal plasma levels of POPs and measures of fetal growth. Their research was published in JAMA Pediatrics.²



The investigators examined chemical class mixtures of organochlorine pesticides (OCPs), dioxin-like polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), among other groups of POPs, as well as individual chemicals, in 2,284 nonobese low-risk pregnant women before 14 weeks of gestation. They measured 14 fetal growth biometrics using ultrasonography throughout the women’s pregnancies, with researchers focusing their main findings on head and abdominal circumference and femur length measurements.



The researchers found that the OCP mixture was negatively associated with most fetal growth measures, with a reduction of 4.7 mm (95% confidence interval [CI], -6.7 to -2.8 mm) in head circumference, 3.5 mm (95% CI, -4.7 to -2.2) in abdominal circumference, and 0.6 mm (95% CI, -1.1 to -0.2 mm) in femur length. In addition, exposure to the PCB and PBDE mixtures were associated with reduced abdominal circumference.



OCPs have been associated with adverse effects on the endocrine system, lipid metabolism, and embryonic development. They also can result in hematologic and hepatic alterations.³



The JAMA Pediatrics study authors point out that their findings may not take into account the risk pregnant women with occupational exposure to POPs, or other higher exposure situations, may have, as the POP concentrations in their sample were low compared with levels in a nationally representative sample of pregnant women. They say that their findings provide insight into the “implications of POPs for fetal growth when exposures are low and suggest that, even if exposures could be successfully minimized, these associations may persist.”²
 

Ideally, chemicals that are toxic to human health are identified and removed from use. Many such chemicals, known as persistent organic pollutants (POPs), have been studied individually for their ill effects in humans. DDT, for instance, once a widely used insecticide, is now classified as a probable human carcinogen and has not been used in the United States since the early 1970s.¹ Other insecticides have similarly been banned but have long half-lives and can persist in the environment for decades. Humans are exposed to POPs mainly through diet, say Ouidir and colleagues, with exposure “nearly ubiquitous.”²



The association between POP exposure during pregnancy and birth weight has not been established, as results from previous studies have been inconsistent, according to researchers.² In addition, birth weight does not distinguish growth-restricted fetuses from those that are constitutionally small. Therefore, Ouidir and colleagues analyzed maternal plasma levels of POPs and measures of fetal growth. Their research was published in JAMA Pediatrics.²



The investigators examined chemical class mixtures of organochlorine pesticides (OCPs), dioxin-like polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), among other groups of POPs, as well as individual chemicals, in 2,284 nonobese low-risk pregnant women before 14 weeks of gestation. They measured 14 fetal growth biometrics using ultrasonography throughout the women’s pregnancies, with researchers focusing their main findings on head and abdominal circumference and femur length measurements.



The researchers found that the OCP mixture was negatively associated with most fetal growth measures, with a reduction of 4.7 mm (95% confidence interval [CI], -6.7 to -2.8 mm) in head circumference, 3.5 mm (95% CI, -4.7 to -2.2) in abdominal circumference, and 0.6 mm (95% CI, -1.1 to -0.2 mm) in femur length. In addition, exposure to the PCB and PBDE mixtures were associated with reduced abdominal circumference.



OCPs have been associated with adverse effects on the endocrine system, lipid metabolism, and embryonic development. They also can result in hematologic and hepatic alterations.³



The JAMA Pediatrics study authors point out that their findings may not take into account the risk pregnant women with occupational exposure to POPs, or other higher exposure situations, may have, as the POP concentrations in their sample were low compared with levels in a nationally representative sample of pregnant women. They say that their findings provide insight into the “implications of POPs for fetal growth when exposures are low and suggest that, even if exposures could be successfully minimized, these associations may persist.”²
 

Ideally, chemicals that are toxic to human health are identified and removed from use. Many such chemicals, known as persistent organic pollutants (POPs), have been studied individually for their ill effects in humans. DDT, for instance, once a widely used insecticide, is now classified as a probable human carcinogen and has not been used in the United States since the early 1970s.¹ Other insecticides have similarly been banned but have long half-lives and can persist in the environment for decades. Humans are exposed to POPs mainly through diet, say Ouidir and colleagues, with exposure “nearly ubiquitous.”²



The association between POP exposure during pregnancy and birth weight has not been established, as results from previous studies have been inconsistent, according to researchers.² In addition, birth weight does not distinguish growth-restricted fetuses from those that are constitutionally small. Therefore, Ouidir and colleagues analyzed maternal plasma levels of POPs and measures of fetal growth. Their research was published in JAMA Pediatrics.²



The investigators examined chemical class mixtures of organochlorine pesticides (OCPs), dioxin-like polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs), among other groups of POPs, as well as individual chemicals, in 2,284 nonobese low-risk pregnant women before 14 weeks of gestation. They measured 14 fetal growth biometrics using ultrasonography throughout the women’s pregnancies, with researchers focusing their main findings on head and abdominal circumference and femur length measurements.



The researchers found that the OCP mixture was negatively associated with most fetal growth measures, with a reduction of 4.7 mm (95% confidence interval [CI], -6.7 to -2.8 mm) in head circumference, 3.5 mm (95% CI, -4.7 to -2.2) in abdominal circumference, and 0.6 mm (95% CI, -1.1 to -0.2 mm) in femur length. In addition, exposure to the PCB and PBDE mixtures were associated with reduced abdominal circumference.



OCPs have been associated with adverse effects on the endocrine system, lipid metabolism, and embryonic development. They also can result in hematologic and hepatic alterations.³



The JAMA Pediatrics study authors point out that their findings may not take into account the risk pregnant women with occupational exposure to POPs, or other higher exposure situations, may have, as the POP concentrations in their sample were low compared with levels in a nationally representative sample of pregnant women. They say that their findings provide insight into the “implications of POPs for fetal growth when exposures are low and suggest that, even if exposures could be successfully minimized, these associations may persist.”²
 

Given the constellation of non-scarring alopecia on the patient’s posterior scalp (with no scale, papules, or plaques), the physician diagnosed alopecia areata (AA) with associated nail pitting in this patient. Although a scalp biopsy could have confirmed the diagnosis, it was not needed because the clinical picture was sufficient.

Nail pitting is commonly associated with psoriasis (although it is often less dense in presentation), but it can occur with alopecia areata. It may occur concurrently or separately from active alopecia. Pitting of the nails may occur in one or multiple fingernails and occurs in up to a third of patients with AA.

The patient’s scalp was treated with intralesional triamcinolone diluted with normal saline to a concentration of 5 mg/mL (0.5%) and injected in dermal blebs over every square centimeter of involvement. Not every 10-year-old can tolerate this modality, and many families prefer observation or topical steroids. Other topical treatments for AA of the scalp include anthralin, minoxidil, and immunotherapy with squaric acid dibutyl ester or diphencyprone. None of these therapies are approved by the Food and Drug Administration for the treatment of nail disease. There are case reports of systemic tofacitinib clearing significant AA associated nail pitting in adults.

The physician counseled the family to observe the nails and not pursue any antifungal therapies for the nails.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Given the constellation of non-scarring alopecia on the patient’s posterior scalp (with no scale, papules, or plaques), the physician diagnosed alopecia areata (AA) with associated nail pitting in this patient. Although a scalp biopsy could have confirmed the diagnosis, it was not needed because the clinical picture was sufficient.

Nail pitting is commonly associated with psoriasis (although it is often less dense in presentation), but it can occur with alopecia areata. It may occur concurrently or separately from active alopecia. Pitting of the nails may occur in one or multiple fingernails and occurs in up to a third of patients with AA.

The patient’s scalp was treated with intralesional triamcinolone diluted with normal saline to a concentration of 5 mg/mL (0.5%) and injected in dermal blebs over every square centimeter of involvement. Not every 10-year-old can tolerate this modality, and many families prefer observation or topical steroids. Other topical treatments for AA of the scalp include anthralin, minoxidil, and immunotherapy with squaric acid dibutyl ester or diphencyprone. None of these therapies are approved by the Food and Drug Administration for the treatment of nail disease. There are case reports of systemic tofacitinib clearing significant AA associated nail pitting in adults.

The physician counseled the family to observe the nails and not pursue any antifungal therapies for the nails.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

Given the constellation of non-scarring alopecia on the patient’s posterior scalp (with no scale, papules, or plaques), the physician diagnosed alopecia areata (AA) with associated nail pitting in this patient. Although a scalp biopsy could have confirmed the diagnosis, it was not needed because the clinical picture was sufficient.

Nail pitting is commonly associated with psoriasis (although it is often less dense in presentation), but it can occur with alopecia areata. It may occur concurrently or separately from active alopecia. Pitting of the nails may occur in one or multiple fingernails and occurs in up to a third of patients with AA.

The patient’s scalp was treated with intralesional triamcinolone diluted with normal saline to a concentration of 5 mg/mL (0.5%) and injected in dermal blebs over every square centimeter of involvement. Not every 10-year-old can tolerate this modality, and many families prefer observation or topical steroids. Other topical treatments for AA of the scalp include anthralin, minoxidil, and immunotherapy with squaric acid dibutyl ester or diphencyprone. None of these therapies are approved by the Food and Drug Administration for the treatment of nail disease. There are case reports of systemic tofacitinib clearing significant AA associated nail pitting in adults.

The physician counseled the family to observe the nails and not pursue any antifungal therapies for the nails.

‌

Photos and text for Photo Rounds Friday courtesy of Jonathan Karnes, MD (copyright retained). Dr. Karnes is the medical director of MDFMR Dermatology Services, Augusta, ME.

ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.

Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.

The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.

After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.

The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.

However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.

JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.

“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.

Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.

Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m² of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.

Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.

Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.

Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.

Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.

At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.

Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.

MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.

“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.

The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.

Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.

This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.

sworcester@mdedge.com

SOURCE: Sugiura I et al. ASH 2019. Abstract 743.

ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.

Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.

The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.

After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.

The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.

However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.

JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.

“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.

Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.

Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m² of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.

Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.

Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.

Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.

Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.

At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.

Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.

MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.

“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.

The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.

Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.

This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.

sworcester@mdedge.com

SOURCE: Sugiura I et al. ASH 2019. Abstract 743.

ORLANDO – A dasatinib-based two-step treatment regimen before allogeneic hematopoietic cell transplantation (alloHCT) for Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ALL) reduces relapse and toxicity and improves survival versus an imatinib-based approach, according to findings from the phase 2 Ph+ALL213 study.

Of 78 evaluable patients aged 15-64 years with newly diagnosed BCR/ABL1-positive ALL in the single-arm, multicenter study conducted by the Japanese Adult Leukemia Study Group (JALSG), all but one experienced complete remission (CR or CRi) after dasatinib induction (step 1), and 56% achieved molecular complete response (MCR) after intensive consolidation (IC; step 2), Isamu Sugiura, MD, PhD, reported at the annual meeting of the American Society of Hematology.

The MCR rate increased to 66.2% after the first cycle of consolidation, which included high-dose methotrexate/cytarabine followed by 21 days of 100-mg dasatinib (C1), said Dr. Sugiura of the division of hematology and oncology, Toyohashi Municipal Hospital, Japan.

After all cycles of treatment, the MCR rates before and at 30 and 100 days after transplant were 75.9%, 92.7%, and 93.6%, respectively, he added.

The current standard of care of Ph+ALL is tyrosine kinase inhibitor (TKI)-based chemotherapy followed by alloHCT in the first CR, he said noting that deeper MCR at the time of transplant is associated with the best prognosis.

However, early therapy-related mortality, relapse, and non-relapse mortality remain problematic, he said.

JALSG previously reported results from the Ph+ALL202 and Ph+ALL208 studies, which successfully introduced the TKI imatinib into IC followed by alloHCT for newly diagnosed PH+ALL, establishing the standard of care in Japan, Dr. Sugiura said.

“As the next step, Ph+ALL213 was started to evaluate the introduction of dasatinib and two-step chemotherapy,” he said, explaining that 30%-40% of patients in the prior studies were unable to undergo alloHCT at the first CR because of older age, early relapse, or therapy-related death; benefits in Ph+ALL202, for example, were largely seen in patients younger than age 55 years.

Ph+ALL213 was designed to assess to ability of dasatinib to improve efficacy and reduce toxicity in those settings.

Patients with Eastern Cooperative Oncology Group performance status scores of 0-3 and sufficient organ function were enrolled and underwent step 1 (induction), which targeted hematologic complete response (HCR) by day 28 of dasatinib at a dose of 140 mg daily and day 14 of 60 mg/m² of prednisone, followed by step 2 (IC), which targeted MCR by day 28 of 100-mg dasatinib in combination with CALGB BFM-like intensive chemotherapy, Dr. Sugiura said.

Consolidation included four cycles alternating between the C1 methotrexate/cytarabine/dasatinib regimen and a CHOP-like regimen using vincristine/cyclophosphamide/daunorubicin followed by 21 days of 100-mg dasatinib (C2). Maintenance therapy included 12 cycles of 24 days of 100 mg DA with vincristine/prednisone.

Patients who achieved HCR and had an appropriate donor proceeded to alloHCT after the first cycle of C1 (C1-1), and in those who were minimal residual disease (MRD)–positive just before transplantation, 100 mg dasatinib was given for 10 cycles after alloHCT, whereas MRD-negative patients underwent observation.

Toxicities associated with dasatinib included liver dysfunction in 11 patients (14.1%), and pneumonitis with severe allergic reaction in 1 patient, Dr. Sugiura said, adding that no therapy-related mortality was reported.

Overall, 74.4% of patients underwent transplant, which was significantly greater than the 59.6% who did so in the JALSG Ph+ALL202 trial. Other significant differences between the Ph+ALL213 and 202 trials included the rates of related donor transplants (29.3% vs. 50.8%) and use of reduced-intensity conditioning (31.0% vs. 10.2%), respectively, he said.

At a median follow-up of 48.1 months, 3-year event-free survival in the current trial was 66.2%, and overall survival (OS) was 80.5%, and in the 58 patients who underwent transplant at the first CR, the rates, respectively, were 74.1% and 84.5%. In those with MCR they were 79.5% and 90.9%.

Of note, the presence of additional cytogenetic abnormalities at presentation was associated with worse OS (P = .0346), and the effect was greatest when derivative 22 syndrome was present (P = .00174), Dr. Sugiura said.

MRD state at the time of transplant in first CR also was associated with outcomes; 3-year event-free survival was 79.5% in 44 MRD-negative patients, compared with 57.1% in 14 MRD-positive patients, and 3-year overall survival was 90.9% vs. 64.3%, respectively.

“Survival curves for MRD-positive patients were inferior to those for MRD-negative patients not because of hematological relapse, but because of transplant-related mortality caused by therapy-related complications and gastrointestinal acute [graft-versus-host] disease,” he said.

The findings demonstrate that dasatinib-based two-step induction was highly effective and safe as pretransplant therapy, he said, noting that transplant was “maximally used,” and although 16% of patients relapsed, both relapse- and non-relapse-related mortality were minimized, with rates of 8.6% and 10.3%, respectively, after transplant.

Longer observation and a larger study are required to confirm these findings, Dr. Sugiura said, noting that the phase 2 JALSG Ph+ALL219 study will look at the potential for further improving outcomes with the addition of the multitargeted TKI ponatinib in patients who are MRD-positive after IC.

This study was funded by the Ministry of Health, Labor and Welfare of Japan. Dr. Sugiura reported having no disclosures.

sworcester@mdedge.com

SOURCE: Sugiura I et al. ASH 2019. Abstract 743.

Patients with moderate psoriatic arthritis disease activity are more likely to achieve remission or low disease activity with apremilast therapy than are those with high disease activity at baseline, new research suggests.

A paper published in Arthritis Care & Research presents a pooled analysis of the PALACE 1-3 studies that included a total of 1,493 patients with active psoriatic arthritis whose disease had resisted treatment with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs. Participants were randomized either to the oral phosphodiesterase 4 inhibitor apremilast (Otezla) 30 mg twice daily, 20 mg twice daily, or placebo for 24 weeks, after which all patients on placebo were rerandomized to one of the two apremilast doses until 52 weeks.

The analysis focused on 494 patients who were randomized to apremilast 30 mg twice daily at baseline.

At week 16, 40% patients with low disease activity at baseline had achieved remission on their clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score, compared with 7% of patients with moderate disease activity and 2.1% of patients with high disease activity. The cDAPSA score is calculated as a composite score including swollen and tender joint counts, patient’s assessment of pain, and patient’s global assessment of disease activity, with possible scores from 0 to 154. Based on patients’ cDAPSA score, the researchers defined remission as a score of 4 or less, low disease activity as more than 4 and up to 13, moderate disease activity as more than 13 and up to 27, and high disease activity as greater than 27.

Among patients with moderate disease activity, 29.8% achieved low disease activity by week 16; among patients with high disease activity at baseline, 11.5% achieved low disease activity, and 38.1% achieved moderate disease activity.

The study found that patients who had moderate disease activity at baseline and achieved either low disease activity or remission by week 16 had a 58.9%-88.5% probability of remaining at those treatment targets by week 52. Patients with high disease activity at baseline who achieved low disease activity or remission by week 16 had a 64.3%-77.4% probability of achieving treatment targets by week 52.

Overall, nearly twice as many patients who had moderate disease activity at baseline achieved their treatment targets when compared with those who began with high disease activity (46.9% vs. 24.9%).

Any patient who achieved at least a 30% improvement in cDAPSA score by week 16 had a 63% probability of achieving treatment targets by week 52.

First author Philip J. Mease, MD, from the Swedish Medical Center and the University of Washington, Seattle, and coauthors noted that the absence of treatment response by week 16 should point to the need for a treatment adjustment. “Taken together, these findings provide a framework of reference for the selection and monitoring of patients with the highest likelihood of achieving optimal treatment responses with apremilast in clinical practice,” they wrote.

The authors also commented that their study provided support for the use of clinical Disease Activity Index for Psoriatic Arthritis score to monitor patients treated with apremilast.

The study was sponsored by Celgene. Three authors were employees of Celgene at the time of the study, and nine authors declared a range of consultancies, grants, research, and other support from the pharmaceutical sector, including from Celgene.

SOURCE: Mease P et al. Arthritis Care Res. 2019 Jan 7. doi: 10.1002/acr.24134

Patients with moderate psoriatic arthritis disease activity are more likely to achieve remission or low disease activity with apremilast therapy than are those with high disease activity at baseline, new research suggests.

A paper published in Arthritis Care & Research presents a pooled analysis of the PALACE 1-3 studies that included a total of 1,493 patients with active psoriatic arthritis whose disease had resisted treatment with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs. Participants were randomized either to the oral phosphodiesterase 4 inhibitor apremilast (Otezla) 30 mg twice daily, 20 mg twice daily, or placebo for 24 weeks, after which all patients on placebo were rerandomized to one of the two apremilast doses until 52 weeks.

The analysis focused on 494 patients who were randomized to apremilast 30 mg twice daily at baseline.

At week 16, 40% patients with low disease activity at baseline had achieved remission on their clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score, compared with 7% of patients with moderate disease activity and 2.1% of patients with high disease activity. The cDAPSA score is calculated as a composite score including swollen and tender joint counts, patient’s assessment of pain, and patient’s global assessment of disease activity, with possible scores from 0 to 154. Based on patients’ cDAPSA score, the researchers defined remission as a score of 4 or less, low disease activity as more than 4 and up to 13, moderate disease activity as more than 13 and up to 27, and high disease activity as greater than 27.

Among patients with moderate disease activity, 29.8% achieved low disease activity by week 16; among patients with high disease activity at baseline, 11.5% achieved low disease activity, and 38.1% achieved moderate disease activity.

The study found that patients who had moderate disease activity at baseline and achieved either low disease activity or remission by week 16 had a 58.9%-88.5% probability of remaining at those treatment targets by week 52. Patients with high disease activity at baseline who achieved low disease activity or remission by week 16 had a 64.3%-77.4% probability of achieving treatment targets by week 52.

Overall, nearly twice as many patients who had moderate disease activity at baseline achieved their treatment targets when compared with those who began with high disease activity (46.9% vs. 24.9%).

Any patient who achieved at least a 30% improvement in cDAPSA score by week 16 had a 63% probability of achieving treatment targets by week 52.

First author Philip J. Mease, MD, from the Swedish Medical Center and the University of Washington, Seattle, and coauthors noted that the absence of treatment response by week 16 should point to the need for a treatment adjustment. “Taken together, these findings provide a framework of reference for the selection and monitoring of patients with the highest likelihood of achieving optimal treatment responses with apremilast in clinical practice,” they wrote.

The authors also commented that their study provided support for the use of clinical Disease Activity Index for Psoriatic Arthritis score to monitor patients treated with apremilast.

The study was sponsored by Celgene. Three authors were employees of Celgene at the time of the study, and nine authors declared a range of consultancies, grants, research, and other support from the pharmaceutical sector, including from Celgene.

SOURCE: Mease P et al. Arthritis Care Res. 2019 Jan 7. doi: 10.1002/acr.24134

Patients with moderate psoriatic arthritis disease activity are more likely to achieve remission or low disease activity with apremilast therapy than are those with high disease activity at baseline, new research suggests.

A paper published in Arthritis Care & Research presents a pooled analysis of the PALACE 1-3 studies that included a total of 1,493 patients with active psoriatic arthritis whose disease had resisted treatment with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs. Participants were randomized either to the oral phosphodiesterase 4 inhibitor apremilast (Otezla) 30 mg twice daily, 20 mg twice daily, or placebo for 24 weeks, after which all patients on placebo were rerandomized to one of the two apremilast doses until 52 weeks.

The analysis focused on 494 patients who were randomized to apremilast 30 mg twice daily at baseline.

At week 16, 40% patients with low disease activity at baseline had achieved remission on their clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) score, compared with 7% of patients with moderate disease activity and 2.1% of patients with high disease activity. The cDAPSA score is calculated as a composite score including swollen and tender joint counts, patient’s assessment of pain, and patient’s global assessment of disease activity, with possible scores from 0 to 154. Based on patients’ cDAPSA score, the researchers defined remission as a score of 4 or less, low disease activity as more than 4 and up to 13, moderate disease activity as more than 13 and up to 27, and high disease activity as greater than 27.

Among patients with moderate disease activity, 29.8% achieved low disease activity by week 16; among patients with high disease activity at baseline, 11.5% achieved low disease activity, and 38.1% achieved moderate disease activity.

The study found that patients who had moderate disease activity at baseline and achieved either low disease activity or remission by week 16 had a 58.9%-88.5% probability of remaining at those treatment targets by week 52. Patients with high disease activity at baseline who achieved low disease activity or remission by week 16 had a 64.3%-77.4% probability of achieving treatment targets by week 52.

Overall, nearly twice as many patients who had moderate disease activity at baseline achieved their treatment targets when compared with those who began with high disease activity (46.9% vs. 24.9%).

Any patient who achieved at least a 30% improvement in cDAPSA score by week 16 had a 63% probability of achieving treatment targets by week 52.

First author Philip J. Mease, MD, from the Swedish Medical Center and the University of Washington, Seattle, and coauthors noted that the absence of treatment response by week 16 should point to the need for a treatment adjustment. “Taken together, these findings provide a framework of reference for the selection and monitoring of patients with the highest likelihood of achieving optimal treatment responses with apremilast in clinical practice,” they wrote.

The authors also commented that their study provided support for the use of clinical Disease Activity Index for Psoriatic Arthritis score to monitor patients treated with apremilast.

The study was sponsored by Celgene. Three authors were employees of Celgene at the time of the study, and nine authors declared a range of consultancies, grants, research, and other support from the pharmaceutical sector, including from Celgene.

SOURCE: Mease P et al. Arthritis Care Res. 2019 Jan 7. doi: 10.1002/acr.24134

At every swipe through my social media feeds, I’m greeted with another topic that has advocates clustered at the extremes. People align, and they align quickly in our strangely polarized world in which anyone who might sit in the middle lies low.

It seems we’re divided: On the left you are a CNN fan or you’re one of those soulless monsters who tunes in to Fox News. You’re pro-life or you’re a baby killer, advocating for late-term abortions or even the execution of live infants. When it comes to firearm regulation, one side says you’re a threat to the Constitution, while the other says that those opposed are responsible for the death of every person who was ever the victim of a discharged firearm. And those who feel strongly about a given topic often justify their attacks on those who disagree. Psychiatry is no stranger to this thinking, and we are the only medical specialty with organized “antipsychiatry” groups who oppose our work. I have been a bit surprised, however, that the topic of suicide prevention is one that has us divided within our own specialty.

Amy Barnhorst, MD, is a psychiatrist at the University of California, Davis, and the author of “The empty promise of suicide prevention: Many of the problems that lead people to kill themselves cannot be fixed with a little serotonin,” an op-ed piece that appeared in the New York Times on April 26, 2019. Dr. Barnhorst began her essay with the story of a patient who was hospitalized after a relative realized she was planning her suicide. That story had an ending that psychiatrists relish: A person with previously unrecognized and untreated bipolar disorder received care, including medication, and got better. This suicide was preventable, a life was saved, and this story followed a model we all hope is being replicated over and over.

Dr. Barnhorst went on to say that this was an outlier in her career, that most of the suicidal patients she sees are impoverished, homeless, addicted, and she wrote about how little the treatment setting has to offer: The idea that a pill would fix these problems is almost laughable. She suggests that there is more to suicide prevention than identifying prospective patients and getting them acute psychiatric care.

The decision to stop living is one that people arrive at by different paths, some over months, but many in a matter of minutes. Those people won’t be intercepted by the mental health system. We certainly need more psychiatric services and more research into better, faster-acting treatments for severe depression and suicidal thoughts, but that will never be enough.

We need to address the root causes of our nation’s suicide problem – poverty, homelessness, and the accompanying exposure to trauma, crime, and drugs. That means better alcohol and drug treatment, family counseling, low-income housing resources, job training, and individual therapy. And for those at risk who still slip past all the checkpoints, we need to make sure they don’t have access to guns and lethal medications.

Psychological autopsies done after suicides have indicated that more than 90% of people who die from suicide suffered from a mental illness, yet 54% of those who ended their own lives had never received a psychiatric diagnosis. There is a hopefulness that, if only we had more – more services, more therapy, more medication – then we could prevent suicide. Unfortunately, this line of thinking, with a “Zero Suicide” initiative, points a finger at those who survive: Suicide is preventable, so someone is to blame, if not a family member for missing the warning signs then the clinician who offered treatment that wasn’t good enough.

Along this line, the New York Times printed another opinion piece on Jan. 6 by Richard A. Friedman, MD, titled, “Why are young Americans killing themselves?” Dr. Friedman’s conclusion was more along the psychiatrist party line: “The good news is that we don’t have to wait for all the answers to know what to do. We know that various psychotherapies and medication are highly effective in treating depression. We just need to do a better job of identifying, reaching out to and providing resources for at-risk youths.”

Dr. Friedman goes on to propose universal screening at school, among other measures to identify those at risk. It is no surprise that Dr. Friedman’s article had more than 1,700 comments before commenting was closed by the Times. I have written about the pros and cons of screening adolescents for depression in a primary care setting, so putting the responsibility of identifying suicidal teenagers on school teachers seems like an ominous responsibility to add to a teacher’s obligations.

I did not read Dr. Barnhorst’s earlier op-ed piece as a condemnation of psychiatric care, but rather as a call to action and a reality check on the idea that psychiatry is the only answer to our suicide epidemic. More people than ever get treatment – from psychiatrists, from primary care doctors, from nonphysician prescribing clinicians, and from so many varieties of psychotherapists, and yet our suicide rates continue to rise.

In a post on the Psychology Today website, Sara Gorman, PhD, and Jack M. Gorman, MD, discussed Dr. Barnhorst’s article. “In the process of making her point, Barnhorst also manages to seriously trivialize the role of antidepressant medication in the treatment of depression and to imply that, given societal woes, there isn’t much we can do to try to prevent suicides – aside from limiting access to lethal means,” they wrote.

The Gormans were not alone in their objections; the day after the op-ed appeared in the New York Times, a well-respected psychiatry department chairman took on not just the content of the op-ed, but also the author, in his Twitter feed. He wrote, “@amybarnhorst doesn’t read scientific literature or skipped training. this article is wrong. #suicide is largely preventable, if proper measures taken n Rx provided. @nytimes please vet authors better @APAPsychiatric.” Dr. Barnhorst, also a voice on Twitter, added the wry response, “I skipped training.” When Twitter users responded that initial Twitter comment conveyed a lack of civility toward a colleague, the original Tweeter – I’m withholding his name with the hope that even writing about these interactions won’t put me on anyone’s enemy list – like many others sitting on the poles of these contentious topics, responded with the following, “All for civility except in the case of misinformation that puts lives at risk, especially when purveyed by a professional who wears the patina of credibility.”

If it’s not yet obvious, I don’t believe there is a simple answer to our suicide problem, nor do I think it puts lives at risk to point out that, so far, our treatments have not lowered suicide rates. The issue is complex and we have no perfect explanation as to why countries differ so greatly with regard to suicide. There are impoverished, war-torn countries with remarkably lower suicide rates, and nations with much stricter gun laws that have higher statistics. Honduras, deemed “the murder capital of the world,” has an enviable suicide rate of only 2.9 per 100,000.

If the solution were as simple as making medications more accessible, the answer might be an easy one (or at least worth trying) – make antidepressants available over-the-counter, a move that would both increase access and decrease stigma.

Some people are determined to end their own lives. They aren’t looking to see psychiatrists or to call hotlines, and they may well resort to an alternate method if any given one is not readily available. For these individuals, suicide may not be preventable, and we may be left to say that this tragic phenomena with its diverse causes should also lead us to explore the root causes of human misery and our cultural features that lead some people to end their own lives while others endure.

Clearly, there are those who have untreated psychiatric illnesses and who make impulsive and lethal decisions – access to care and means restrictions certainly save some lives. And while it is obvious to us as psychiatrists that anyone who is depressed or is having suicidal thoughts is deserving of a psychiatric evaluation and intervention, the truth remains that access to treatment in this country is limited by finances, by the availability of mental health professionals, and by stigma and shame. In the end, I don’t believe we have a single easy answer as to why suicide rates are rising or a singular response that will stop this tragic phenomena. The one thing I am certain of is that our efforts to prevent suicide should unite, and not fracture, our profession.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

At every swipe through my social media feeds, I’m greeted with another topic that has advocates clustered at the extremes. People align, and they align quickly in our strangely polarized world in which anyone who might sit in the middle lies low.

It seems we’re divided: On the left you are a CNN fan or you’re one of those soulless monsters who tunes in to Fox News. You’re pro-life or you’re a baby killer, advocating for late-term abortions or even the execution of live infants. When it comes to firearm regulation, one side says you’re a threat to the Constitution, while the other says that those opposed are responsible for the death of every person who was ever the victim of a discharged firearm. And those who feel strongly about a given topic often justify their attacks on those who disagree. Psychiatry is no stranger to this thinking, and we are the only medical specialty with organized “antipsychiatry” groups who oppose our work. I have been a bit surprised, however, that the topic of suicide prevention is one that has us divided within our own specialty.

Amy Barnhorst, MD, is a psychiatrist at the University of California, Davis, and the author of “The empty promise of suicide prevention: Many of the problems that lead people to kill themselves cannot be fixed with a little serotonin,” an op-ed piece that appeared in the New York Times on April 26, 2019. Dr. Barnhorst began her essay with the story of a patient who was hospitalized after a relative realized she was planning her suicide. That story had an ending that psychiatrists relish: A person with previously unrecognized and untreated bipolar disorder received care, including medication, and got better. This suicide was preventable, a life was saved, and this story followed a model we all hope is being replicated over and over.

Dr. Barnhorst went on to say that this was an outlier in her career, that most of the suicidal patients she sees are impoverished, homeless, addicted, and she wrote about how little the treatment setting has to offer: The idea that a pill would fix these problems is almost laughable. She suggests that there is more to suicide prevention than identifying prospective patients and getting them acute psychiatric care.

The decision to stop living is one that people arrive at by different paths, some over months, but many in a matter of minutes. Those people won’t be intercepted by the mental health system. We certainly need more psychiatric services and more research into better, faster-acting treatments for severe depression and suicidal thoughts, but that will never be enough.

We need to address the root causes of our nation’s suicide problem – poverty, homelessness, and the accompanying exposure to trauma, crime, and drugs. That means better alcohol and drug treatment, family counseling, low-income housing resources, job training, and individual therapy. And for those at risk who still slip past all the checkpoints, we need to make sure they don’t have access to guns and lethal medications.

Psychological autopsies done after suicides have indicated that more than 90% of people who die from suicide suffered from a mental illness, yet 54% of those who ended their own lives had never received a psychiatric diagnosis. There is a hopefulness that, if only we had more – more services, more therapy, more medication – then we could prevent suicide. Unfortunately, this line of thinking, with a “Zero Suicide” initiative, points a finger at those who survive: Suicide is preventable, so someone is to blame, if not a family member for missing the warning signs then the clinician who offered treatment that wasn’t good enough.

Along this line, the New York Times printed another opinion piece on Jan. 6 by Richard A. Friedman, MD, titled, “Why are young Americans killing themselves?” Dr. Friedman’s conclusion was more along the psychiatrist party line: “The good news is that we don’t have to wait for all the answers to know what to do. We know that various psychotherapies and medication are highly effective in treating depression. We just need to do a better job of identifying, reaching out to and providing resources for at-risk youths.”

Dr. Friedman goes on to propose universal screening at school, among other measures to identify those at risk. It is no surprise that Dr. Friedman’s article had more than 1,700 comments before commenting was closed by the Times. I have written about the pros and cons of screening adolescents for depression in a primary care setting, so putting the responsibility of identifying suicidal teenagers on school teachers seems like an ominous responsibility to add to a teacher’s obligations.

I did not read Dr. Barnhorst’s earlier op-ed piece as a condemnation of psychiatric care, but rather as a call to action and a reality check on the idea that psychiatry is the only answer to our suicide epidemic. More people than ever get treatment – from psychiatrists, from primary care doctors, from nonphysician prescribing clinicians, and from so many varieties of psychotherapists, and yet our suicide rates continue to rise.

In a post on the Psychology Today website, Sara Gorman, PhD, and Jack M. Gorman, MD, discussed Dr. Barnhorst’s article. “In the process of making her point, Barnhorst also manages to seriously trivialize the role of antidepressant medication in the treatment of depression and to imply that, given societal woes, there isn’t much we can do to try to prevent suicides – aside from limiting access to lethal means,” they wrote.

The Gormans were not alone in their objections; the day after the op-ed appeared in the New York Times, a well-respected psychiatry department chairman took on not just the content of the op-ed, but also the author, in his Twitter feed. He wrote, “@amybarnhorst doesn’t read scientific literature or skipped training. this article is wrong. #suicide is largely preventable, if proper measures taken n Rx provided. @nytimes please vet authors better @APAPsychiatric.” Dr. Barnhorst, also a voice on Twitter, added the wry response, “I skipped training.” When Twitter users responded that initial Twitter comment conveyed a lack of civility toward a colleague, the original Tweeter – I’m withholding his name with the hope that even writing about these interactions won’t put me on anyone’s enemy list – like many others sitting on the poles of these contentious topics, responded with the following, “All for civility except in the case of misinformation that puts lives at risk, especially when purveyed by a professional who wears the patina of credibility.”

If it’s not yet obvious, I don’t believe there is a simple answer to our suicide problem, nor do I think it puts lives at risk to point out that, so far, our treatments have not lowered suicide rates. The issue is complex and we have no perfect explanation as to why countries differ so greatly with regard to suicide. There are impoverished, war-torn countries with remarkably lower suicide rates, and nations with much stricter gun laws that have higher statistics. Honduras, deemed “the murder capital of the world,” has an enviable suicide rate of only 2.9 per 100,000.

If the solution were as simple as making medications more accessible, the answer might be an easy one (or at least worth trying) – make antidepressants available over-the-counter, a move that would both increase access and decrease stigma.

Some people are determined to end their own lives. They aren’t looking to see psychiatrists or to call hotlines, and they may well resort to an alternate method if any given one is not readily available. For these individuals, suicide may not be preventable, and we may be left to say that this tragic phenomena with its diverse causes should also lead us to explore the root causes of human misery and our cultural features that lead some people to end their own lives while others endure.

Clearly, there are those who have untreated psychiatric illnesses and who make impulsive and lethal decisions – access to care and means restrictions certainly save some lives. And while it is obvious to us as psychiatrists that anyone who is depressed or is having suicidal thoughts is deserving of a psychiatric evaluation and intervention, the truth remains that access to treatment in this country is limited by finances, by the availability of mental health professionals, and by stigma and shame. In the end, I don’t believe we have a single easy answer as to why suicide rates are rising or a singular response that will stop this tragic phenomena. The one thing I am certain of is that our efforts to prevent suicide should unite, and not fracture, our profession.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

At every swipe through my social media feeds, I’m greeted with another topic that has advocates clustered at the extremes. People align, and they align quickly in our strangely polarized world in which anyone who might sit in the middle lies low.

It seems we’re divided: On the left you are a CNN fan or you’re one of those soulless monsters who tunes in to Fox News. You’re pro-life or you’re a baby killer, advocating for late-term abortions or even the execution of live infants. When it comes to firearm regulation, one side says you’re a threat to the Constitution, while the other says that those opposed are responsible for the death of every person who was ever the victim of a discharged firearm. And those who feel strongly about a given topic often justify their attacks on those who disagree. Psychiatry is no stranger to this thinking, and we are the only medical specialty with organized “antipsychiatry” groups who oppose our work. I have been a bit surprised, however, that the topic of suicide prevention is one that has us divided within our own specialty.

Amy Barnhorst, MD, is a psychiatrist at the University of California, Davis, and the author of “The empty promise of suicide prevention: Many of the problems that lead people to kill themselves cannot be fixed with a little serotonin,” an op-ed piece that appeared in the New York Times on April 26, 2019. Dr. Barnhorst began her essay with the story of a patient who was hospitalized after a relative realized she was planning her suicide. That story had an ending that psychiatrists relish: A person with previously unrecognized and untreated bipolar disorder received care, including medication, and got better. This suicide was preventable, a life was saved, and this story followed a model we all hope is being replicated over and over.

Dr. Barnhorst went on to say that this was an outlier in her career, that most of the suicidal patients she sees are impoverished, homeless, addicted, and she wrote about how little the treatment setting has to offer: The idea that a pill would fix these problems is almost laughable. She suggests that there is more to suicide prevention than identifying prospective patients and getting them acute psychiatric care.

The decision to stop living is one that people arrive at by different paths, some over months, but many in a matter of minutes. Those people won’t be intercepted by the mental health system. We certainly need more psychiatric services and more research into better, faster-acting treatments for severe depression and suicidal thoughts, but that will never be enough.

We need to address the root causes of our nation’s suicide problem – poverty, homelessness, and the accompanying exposure to trauma, crime, and drugs. That means better alcohol and drug treatment, family counseling, low-income housing resources, job training, and individual therapy. And for those at risk who still slip past all the checkpoints, we need to make sure they don’t have access to guns and lethal medications.

Psychological autopsies done after suicides have indicated that more than 90% of people who die from suicide suffered from a mental illness, yet 54% of those who ended their own lives had never received a psychiatric diagnosis. There is a hopefulness that, if only we had more – more services, more therapy, more medication – then we could prevent suicide. Unfortunately, this line of thinking, with a “Zero Suicide” initiative, points a finger at those who survive: Suicide is preventable, so someone is to blame, if not a family member for missing the warning signs then the clinician who offered treatment that wasn’t good enough.

Along this line, the New York Times printed another opinion piece on Jan. 6 by Richard A. Friedman, MD, titled, “Why are young Americans killing themselves?” Dr. Friedman’s conclusion was more along the psychiatrist party line: “The good news is that we don’t have to wait for all the answers to know what to do. We know that various psychotherapies and medication are highly effective in treating depression. We just need to do a better job of identifying, reaching out to and providing resources for at-risk youths.”

Dr. Friedman goes on to propose universal screening at school, among other measures to identify those at risk. It is no surprise that Dr. Friedman’s article had more than 1,700 comments before commenting was closed by the Times. I have written about the pros and cons of screening adolescents for depression in a primary care setting, so putting the responsibility of identifying suicidal teenagers on school teachers seems like an ominous responsibility to add to a teacher’s obligations.

I did not read Dr. Barnhorst’s earlier op-ed piece as a condemnation of psychiatric care, but rather as a call to action and a reality check on the idea that psychiatry is the only answer to our suicide epidemic. More people than ever get treatment – from psychiatrists, from primary care doctors, from nonphysician prescribing clinicians, and from so many varieties of psychotherapists, and yet our suicide rates continue to rise.

In a post on the Psychology Today website, Sara Gorman, PhD, and Jack M. Gorman, MD, discussed Dr. Barnhorst’s article. “In the process of making her point, Barnhorst also manages to seriously trivialize the role of antidepressant medication in the treatment of depression and to imply that, given societal woes, there isn’t much we can do to try to prevent suicides – aside from limiting access to lethal means,” they wrote.

The Gormans were not alone in their objections; the day after the op-ed appeared in the New York Times, a well-respected psychiatry department chairman took on not just the content of the op-ed, but also the author, in his Twitter feed. He wrote, “@amybarnhorst doesn’t read scientific literature or skipped training. this article is wrong. #suicide is largely preventable, if proper measures taken n Rx provided. @nytimes please vet authors better @APAPsychiatric.” Dr. Barnhorst, also a voice on Twitter, added the wry response, “I skipped training.” When Twitter users responded that initial Twitter comment conveyed a lack of civility toward a colleague, the original Tweeter – I’m withholding his name with the hope that even writing about these interactions won’t put me on anyone’s enemy list – like many others sitting on the poles of these contentious topics, responded with the following, “All for civility except in the case of misinformation that puts lives at risk, especially when purveyed by a professional who wears the patina of credibility.”

If it’s not yet obvious, I don’t believe there is a simple answer to our suicide problem, nor do I think it puts lives at risk to point out that, so far, our treatments have not lowered suicide rates. The issue is complex and we have no perfect explanation as to why countries differ so greatly with regard to suicide. There are impoverished, war-torn countries with remarkably lower suicide rates, and nations with much stricter gun laws that have higher statistics. Honduras, deemed “the murder capital of the world,” has an enviable suicide rate of only 2.9 per 100,000.

If the solution were as simple as making medications more accessible, the answer might be an easy one (or at least worth trying) – make antidepressants available over-the-counter, a move that would both increase access and decrease stigma.

Some people are determined to end their own lives. They aren’t looking to see psychiatrists or to call hotlines, and they may well resort to an alternate method if any given one is not readily available. For these individuals, suicide may not be preventable, and we may be left to say that this tragic phenomena with its diverse causes should also lead us to explore the root causes of human misery and our cultural features that lead some people to end their own lives while others endure.

Clearly, there are those who have untreated psychiatric illnesses and who make impulsive and lethal decisions – access to care and means restrictions certainly save some lives. And while it is obvious to us as psychiatrists that anyone who is depressed or is having suicidal thoughts is deserving of a psychiatric evaluation and intervention, the truth remains that access to treatment in this country is limited by finances, by the availability of mental health professionals, and by stigma and shame. In the end, I don’t believe we have a single easy answer as to why suicide rates are rising or a singular response that will stop this tragic phenomena. The one thing I am certain of is that our efforts to prevent suicide should unite, and not fracture, our profession.

Dr. Miller is coauthor with Annette Hanson, MD, of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, both in Baltimore.

Among young adults with supratentorial intracerebral hemorrhage (ICH), black race and Hispanic ethnicity are associated with better functional outcomes, compared with white race, researchers reported Jan. 22 in Neurology.

“There has been considerable research on stroke in older people, but there is still much to be learned about stroke in younger people and how it affects people of different races and ethnicities,” study author Daniel Woo, MD, professor of neurology at the University of Cincinnati, said in a news release. “Our study found that, even when you account for factors that affect outcomes, such as how big the stroke is, race and ethnicity were still independent predictors of how well people would recover.”
 

A subset of ERICH participants

To examine predictors of functional outcome in young patients with ICH, researchers analyzed data from a subset of patients in the Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study. ERICH enrolled patients with nontraumatic ICHs at 42 sites in the United States. It included 1,000 non-Hispanic black patients, 1,000 non-Hispanic white patients, and 1,000 Hispanic patients. Participants self-reported race and ethnicity.

Lead author Laura C. Miyares from Yale School of Medicine in New Haven, Conn., and colleagues analyzed data from 418 patients in ERICH who were aged 18-49 years and had supratentorial ICH. The cohort had an average age of 43 years, and 69% were male. In this subset, 41% were black, 12% were white, and 47% were Hispanic.

The primary outcome was modified Rankin Scale (mRS) score 3 months after the ICH, and the investigators defined a poor outcome as a score of 4 or greater. At 3 months, 35% had a poor functional outcome. Approximately 18% were unable to walk without assistance and attend to their bodily needs (mRS 4); 8% were bedridden, incontinent, and required nursing care (mRS 5); and 10% had died (mRS 6).

The percentage of patients with a poor functional outcome was 52% among white patients, 35% among black patients, and 31% among Hispanic patients. In a univariable analysis, black patients had a 51% reduction in odds of a poor outcome, compared with white patients, and Hispanic patients had a 59% reduction.

“The association between race/ethnicity and 3-month post-ICH functional outcome remained significant after adjusting for age, sex, premorbid disability, ICH location, ICH volume, [intraventricular hemorrhage] extension, systolic blood pressure, and [Glasgow Coma Scale] score on admission,” the researchers said. “In multivariable analysis, using white patients as the reference category, black patients had a 58% reduction in the odds of poor functional outcome at 3 months and Hispanic patients had a 66% reduction in the same odds.”

Their analysis identified the importance of other risk factors as well. “The volume of the hematoma, the most powerful predictor of outcome in older patients with ICH, was also found to be the most significant predictor of poor outcome in young patients,” they said.
 

Vascular risks and oral anticoagulants

About 80% of the young adults with ICH had a history of diagnosed hypertension. In nearly half, the condition was untreated. “After hypertension, the most common stroke risk factors in the young were diabetes, high cholesterol, smoking, and alcohol abuse,” the authors said. “In combination, these results indicate that vascular risk factors, especially untreated, could explain a large proportion of cases of ICH in the young.”

“Our results also point to treatment with oral anticoagulants before hospitalization as a potential mediator of the effect of race/ethnicity on short-term functional outcomes,” they said. About 8% of the white patients used oral anticoagulants, compared with 4% of the black patients and 1% of the Hispanic patients. Oral anticoagulant treatment “is a known risk factor for ICH and an established predictor of poor outcome in this condition. However, because only a small proportion of enrolled young patients with ICH were on [oral anticoagulants] prior to presentation, these results should be further validated by future studies.”

The study’s limitations include the broad categorization of racial and ethnic groups, the fact that younger patients with supratentorial ICH were more likely to be black or Hispanic and less likely to be white, and the exclusion of a significant proportion of cases of young white patients with smaller ICH volumes because of missing data, the researchers noted. Although the cohort was large, researchers may need to study more patients to capture differences among racial and ethnic groups, the investigators said.

The association between race/ethnicity and functional outcome could relate to “distinct pathophysiologies of the initial bleed or unique mechanisms of secondary injury,” the researchers suggested. “Future studies are necessary to probe the potential biological and social mediators of these findings to elucidate the role of race/ethnicity in ICH severity and functional recovery, and to develop improved prognostication for a racially varied population.”

ERICH is supported by the National Institute of Neurological Disorders and Stroke. Authors disclosed grants from the government, professional societies, and a university.

jremaly@mdedge.com

SOURCE: Miyares LC et al. Neurology. 2020 Jan 22. doi: 10.1212/WNL.0000000000008930.

Among young adults with supratentorial intracerebral hemorrhage (ICH), black race and Hispanic ethnicity are associated with better functional outcomes, compared with white race, researchers reported Jan. 22 in Neurology.

“There has been considerable research on stroke in older people, but there is still much to be learned about stroke in younger people and how it affects people of different races and ethnicities,” study author Daniel Woo, MD, professor of neurology at the University of Cincinnati, said in a news release. “Our study found that, even when you account for factors that affect outcomes, such as how big the stroke is, race and ethnicity were still independent predictors of how well people would recover.”
 

A subset of ERICH participants

To examine predictors of functional outcome in young patients with ICH, researchers analyzed data from a subset of patients in the Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study. ERICH enrolled patients with nontraumatic ICHs at 42 sites in the United States. It included 1,000 non-Hispanic black patients, 1,000 non-Hispanic white patients, and 1,000 Hispanic patients. Participants self-reported race and ethnicity.

Lead author Laura C. Miyares from Yale School of Medicine in New Haven, Conn., and colleagues analyzed data from 418 patients in ERICH who were aged 18-49 years and had supratentorial ICH. The cohort had an average age of 43 years, and 69% were male. In this subset, 41% were black, 12% were white, and 47% were Hispanic.

The primary outcome was modified Rankin Scale (mRS) score 3 months after the ICH, and the investigators defined a poor outcome as a score of 4 or greater. At 3 months, 35% had a poor functional outcome. Approximately 18% were unable to walk without assistance and attend to their bodily needs (mRS 4); 8% were bedridden, incontinent, and required nursing care (mRS 5); and 10% had died (mRS 6).

The percentage of patients with a poor functional outcome was 52% among white patients, 35% among black patients, and 31% among Hispanic patients. In a univariable analysis, black patients had a 51% reduction in odds of a poor outcome, compared with white patients, and Hispanic patients had a 59% reduction.

“The association between race/ethnicity and 3-month post-ICH functional outcome remained significant after adjusting for age, sex, premorbid disability, ICH location, ICH volume, [intraventricular hemorrhage] extension, systolic blood pressure, and [Glasgow Coma Scale] score on admission,” the researchers said. “In multivariable analysis, using white patients as the reference category, black patients had a 58% reduction in the odds of poor functional outcome at 3 months and Hispanic patients had a 66% reduction in the same odds.”

Their analysis identified the importance of other risk factors as well. “The volume of the hematoma, the most powerful predictor of outcome in older patients with ICH, was also found to be the most significant predictor of poor outcome in young patients,” they said.
 

Vascular risks and oral anticoagulants

About 80% of the young adults with ICH had a history of diagnosed hypertension. In nearly half, the condition was untreated. “After hypertension, the most common stroke risk factors in the young were diabetes, high cholesterol, smoking, and alcohol abuse,” the authors said. “In combination, these results indicate that vascular risk factors, especially untreated, could explain a large proportion of cases of ICH in the young.”

“Our results also point to treatment with oral anticoagulants before hospitalization as a potential mediator of the effect of race/ethnicity on short-term functional outcomes,” they said. About 8% of the white patients used oral anticoagulants, compared with 4% of the black patients and 1% of the Hispanic patients. Oral anticoagulant treatment “is a known risk factor for ICH and an established predictor of poor outcome in this condition. However, because only a small proportion of enrolled young patients with ICH were on [oral anticoagulants] prior to presentation, these results should be further validated by future studies.”

The study’s limitations include the broad categorization of racial and ethnic groups, the fact that younger patients with supratentorial ICH were more likely to be black or Hispanic and less likely to be white, and the exclusion of a significant proportion of cases of young white patients with smaller ICH volumes because of missing data, the researchers noted. Although the cohort was large, researchers may need to study more patients to capture differences among racial and ethnic groups, the investigators said.

The association between race/ethnicity and functional outcome could relate to “distinct pathophysiologies of the initial bleed or unique mechanisms of secondary injury,” the researchers suggested. “Future studies are necessary to probe the potential biological and social mediators of these findings to elucidate the role of race/ethnicity in ICH severity and functional recovery, and to develop improved prognostication for a racially varied population.”

ERICH is supported by the National Institute of Neurological Disorders and Stroke. Authors disclosed grants from the government, professional societies, and a university.

jremaly@mdedge.com

SOURCE: Miyares LC et al. Neurology. 2020 Jan 22. doi: 10.1212/WNL.0000000000008930.

Among young adults with supratentorial intracerebral hemorrhage (ICH), black race and Hispanic ethnicity are associated with better functional outcomes, compared with white race, researchers reported Jan. 22 in Neurology.

“There has been considerable research on stroke in older people, but there is still much to be learned about stroke in younger people and how it affects people of different races and ethnicities,” study author Daniel Woo, MD, professor of neurology at the University of Cincinnati, said in a news release. “Our study found that, even when you account for factors that affect outcomes, such as how big the stroke is, race and ethnicity were still independent predictors of how well people would recover.”
 

A subset of ERICH participants

To examine predictors of functional outcome in young patients with ICH, researchers analyzed data from a subset of patients in the Ethnic/Racial Variations in Intracerebral Hemorrhage (ERICH) study. ERICH enrolled patients with nontraumatic ICHs at 42 sites in the United States. It included 1,000 non-Hispanic black patients, 1,000 non-Hispanic white patients, and 1,000 Hispanic patients. Participants self-reported race and ethnicity.

Lead author Laura C. Miyares from Yale School of Medicine in New Haven, Conn., and colleagues analyzed data from 418 patients in ERICH who were aged 18-49 years and had supratentorial ICH. The cohort had an average age of 43 years, and 69% were male. In this subset, 41% were black, 12% were white, and 47% were Hispanic.

The primary outcome was modified Rankin Scale (mRS) score 3 months after the ICH, and the investigators defined a poor outcome as a score of 4 or greater. At 3 months, 35% had a poor functional outcome. Approximately 18% were unable to walk without assistance and attend to their bodily needs (mRS 4); 8% were bedridden, incontinent, and required nursing care (mRS 5); and 10% had died (mRS 6).

The percentage of patients with a poor functional outcome was 52% among white patients, 35% among black patients, and 31% among Hispanic patients. In a univariable analysis, black patients had a 51% reduction in odds of a poor outcome, compared with white patients, and Hispanic patients had a 59% reduction.

“The association between race/ethnicity and 3-month post-ICH functional outcome remained significant after adjusting for age, sex, premorbid disability, ICH location, ICH volume, [intraventricular hemorrhage] extension, systolic blood pressure, and [Glasgow Coma Scale] score on admission,” the researchers said. “In multivariable analysis, using white patients as the reference category, black patients had a 58% reduction in the odds of poor functional outcome at 3 months and Hispanic patients had a 66% reduction in the same odds.”

Their analysis identified the importance of other risk factors as well. “The volume of the hematoma, the most powerful predictor of outcome in older patients with ICH, was also found to be the most significant predictor of poor outcome in young patients,” they said.
 

Vascular risks and oral anticoagulants

About 80% of the young adults with ICH had a history of diagnosed hypertension. In nearly half, the condition was untreated. “After hypertension, the most common stroke risk factors in the young were diabetes, high cholesterol, smoking, and alcohol abuse,” the authors said. “In combination, these results indicate that vascular risk factors, especially untreated, could explain a large proportion of cases of ICH in the young.”

“Our results also point to treatment with oral anticoagulants before hospitalization as a potential mediator of the effect of race/ethnicity on short-term functional outcomes,” they said. About 8% of the white patients used oral anticoagulants, compared with 4% of the black patients and 1% of the Hispanic patients. Oral anticoagulant treatment “is a known risk factor for ICH and an established predictor of poor outcome in this condition. However, because only a small proportion of enrolled young patients with ICH were on [oral anticoagulants] prior to presentation, these results should be further validated by future studies.”

The study’s limitations include the broad categorization of racial and ethnic groups, the fact that younger patients with supratentorial ICH were more likely to be black or Hispanic and less likely to be white, and the exclusion of a significant proportion of cases of young white patients with smaller ICH volumes because of missing data, the researchers noted. Although the cohort was large, researchers may need to study more patients to capture differences among racial and ethnic groups, the investigators said.

The association between race/ethnicity and functional outcome could relate to “distinct pathophysiologies of the initial bleed or unique mechanisms of secondary injury,” the researchers suggested. “Future studies are necessary to probe the potential biological and social mediators of these findings to elucidate the role of race/ethnicity in ICH severity and functional recovery, and to develop improved prognostication for a racially varied population.”

ERICH is supported by the National Institute of Neurological Disorders and Stroke. Authors disclosed grants from the government, professional societies, and a university.

jremaly@mdedge.com

SOURCE: Miyares LC et al. Neurology. 2020 Jan 22. doi: 10.1212/WNL.0000000000008930.

SAN ANTONIO – In the current era of high-definition colonoscopy, patients with three or more nonadvanced small tubular adenomas are no longer at high risk for metachronous advanced neoplasia compared with individuals with one or two such adenomas, Carol Rouphael, MD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

She presented a retrospective study of 3,377 patients who had their first colonoscopies at age 50 or older in 2006 or later, when high-definition colonscopes took over.

The clinical implications of the study are clear: “Our findings suggest the colonoscopy interval for individuals with three or more nonadvanced adenomas should be similar to low-risk adenoma patients; that is, 5-10 years,” said Dr. Rouphael, a gastroenterology fellow at the Cleveland Clinic.

Studies conducted in the early 2000s using standard-definition colonoscopes showed that the risk of metachronous advanced neoplasia (MAN) – that is, colorectal cancer or a pathologically advanced adenoma – was twice as great in patients with three or more small tubular adenomas compared with patients with just one or two of them. Thus, guidelines called for such patients to undergo repeat colonoscopy at a shorter time interval post polypectomy, typically 3 years. But with contemporary colonoscopy using high-definition optics, gastroenterologists are detecting a lot more small adenomas. Dr. Rouphael and coworkers wondered if the definition of high risk established more than a decade ago, prior to the use of high-definition colonoscopes, still held true. They concluded that the answer is no.

Eleven percent of patients in their study had features indicative of high-risk adenoma on the initial colonoscopy. Twenty-four percent of these patients had an adenoma with advanced pathology, meaning villous features or high-grade dysplasia; 51% had an adenoma 10 mm or more in size without advanced pathology; and the remaining 25% of patients were classified as having high-risk adenoma on the basis of having three or more small tubular adenomas.

Follow-up colonoscopy was performed a median of 42 months later in the high-risk adenoma group, 54 months later in the low-risk adenoma patients with one or two small tubular adenomas, and at 61 months in those with no adenomas. At follow-up, MAN was discovered in 3.8% of patients with no adenomas at baseline, 4.6% of the low-risk adenoma group, and 9.3% of the overall high-risk adenoma group. However, within the high-risk adenoma group the risk of MAN varied widely: 6.3% in patients with three or more nonadvanced adenomas, 6.1% in those with three or four nonadvanced adenomas, 7.7% in patients with five or more nonadvanced adenomas, 8.3% in those with a 10-mm or larger adenoma without advanced pathology, and 14.6% in patients with an adenoma with advanced pathology at baseline.

In a multivariate analysis adjusted for age, sex, ethnicity, and time between first and follow-up colonoscopy, the risk of MAN did not differ significantly between patients with three or four nonadvanced adenomas and those with one or two, nor between patients with five or more versus one or two. In addition, there was no significant difference in MAN risk between patients with no adenomas at baseline and those with one or two low-risk, nonadvanced adenomas. In contrast, patients with a 10-mm or larger adenoma without advanced pathology at baseline were 1.9-fold more likely to have MAN at follow-up colonoscopy than were patients with one or two small tubular adenomas. And patients having an adenoma with advanced pathology at baseline were at 3.7-fold greater risk of developing MAN than were those with baseline low-risk adenoma, according to Dr. Rouphael.

She reported having no financial conflicts regarding her study, which won the Fellows-in-Training Award at the annual meeting.

bjancin@mdedge.com

SOURCE: Rouphael C. ACG 2019 Abstract 9.

SAN ANTONIO – In the current era of high-definition colonoscopy, patients with three or more nonadvanced small tubular adenomas are no longer at high risk for metachronous advanced neoplasia compared with individuals with one or two such adenomas, Carol Rouphael, MD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

She presented a retrospective study of 3,377 patients who had their first colonoscopies at age 50 or older in 2006 or later, when high-definition colonscopes took over.

The clinical implications of the study are clear: “Our findings suggest the colonoscopy interval for individuals with three or more nonadvanced adenomas should be similar to low-risk adenoma patients; that is, 5-10 years,” said Dr. Rouphael, a gastroenterology fellow at the Cleveland Clinic.

Studies conducted in the early 2000s using standard-definition colonoscopes showed that the risk of metachronous advanced neoplasia (MAN) – that is, colorectal cancer or a pathologically advanced adenoma – was twice as great in patients with three or more small tubular adenomas compared with patients with just one or two of them. Thus, guidelines called for such patients to undergo repeat colonoscopy at a shorter time interval post polypectomy, typically 3 years. But with contemporary colonoscopy using high-definition optics, gastroenterologists are detecting a lot more small adenomas. Dr. Rouphael and coworkers wondered if the definition of high risk established more than a decade ago, prior to the use of high-definition colonoscopes, still held true. They concluded that the answer is no.

Eleven percent of patients in their study had features indicative of high-risk adenoma on the initial colonoscopy. Twenty-four percent of these patients had an adenoma with advanced pathology, meaning villous features or high-grade dysplasia; 51% had an adenoma 10 mm or more in size without advanced pathology; and the remaining 25% of patients were classified as having high-risk adenoma on the basis of having three or more small tubular adenomas.

Follow-up colonoscopy was performed a median of 42 months later in the high-risk adenoma group, 54 months later in the low-risk adenoma patients with one or two small tubular adenomas, and at 61 months in those with no adenomas. At follow-up, MAN was discovered in 3.8% of patients with no adenomas at baseline, 4.6% of the low-risk adenoma group, and 9.3% of the overall high-risk adenoma group. However, within the high-risk adenoma group the risk of MAN varied widely: 6.3% in patients with three or more nonadvanced adenomas, 6.1% in those with three or four nonadvanced adenomas, 7.7% in patients with five or more nonadvanced adenomas, 8.3% in those with a 10-mm or larger adenoma without advanced pathology, and 14.6% in patients with an adenoma with advanced pathology at baseline.

In a multivariate analysis adjusted for age, sex, ethnicity, and time between first and follow-up colonoscopy, the risk of MAN did not differ significantly between patients with three or four nonadvanced adenomas and those with one or two, nor between patients with five or more versus one or two. In addition, there was no significant difference in MAN risk between patients with no adenomas at baseline and those with one or two low-risk, nonadvanced adenomas. In contrast, patients with a 10-mm or larger adenoma without advanced pathology at baseline were 1.9-fold more likely to have MAN at follow-up colonoscopy than were patients with one or two small tubular adenomas. And patients having an adenoma with advanced pathology at baseline were at 3.7-fold greater risk of developing MAN than were those with baseline low-risk adenoma, according to Dr. Rouphael.

She reported having no financial conflicts regarding her study, which won the Fellows-in-Training Award at the annual meeting.

bjancin@mdedge.com

SOURCE: Rouphael C. ACG 2019 Abstract 9.

SAN ANTONIO – In the current era of high-definition colonoscopy, patients with three or more nonadvanced small tubular adenomas are no longer at high risk for metachronous advanced neoplasia compared with individuals with one or two such adenomas, Carol Rouphael, MD, reported at the annual meeting of the American College of Gastroenterology.

Bruce Jancin/MDedge News

She presented a retrospective study of 3,377 patients who had their first colonoscopies at age 50 or older in 2006 or later, when high-definition colonscopes took over.

The clinical implications of the study are clear: “Our findings suggest the colonoscopy interval for individuals with three or more nonadvanced adenomas should be similar to low-risk adenoma patients; that is, 5-10 years,” said Dr. Rouphael, a gastroenterology fellow at the Cleveland Clinic.

Studies conducted in the early 2000s using standard-definition colonoscopes showed that the risk of metachronous advanced neoplasia (MAN) – that is, colorectal cancer or a pathologically advanced adenoma – was twice as great in patients with three or more small tubular adenomas compared with patients with just one or two of them. Thus, guidelines called for such patients to undergo repeat colonoscopy at a shorter time interval post polypectomy, typically 3 years. But with contemporary colonoscopy using high-definition optics, gastroenterologists are detecting a lot more small adenomas. Dr. Rouphael and coworkers wondered if the definition of high risk established more than a decade ago, prior to the use of high-definition colonoscopes, still held true. They concluded that the answer is no.

Eleven percent of patients in their study had features indicative of high-risk adenoma on the initial colonoscopy. Twenty-four percent of these patients had an adenoma with advanced pathology, meaning villous features or high-grade dysplasia; 51% had an adenoma 10 mm or more in size without advanced pathology; and the remaining 25% of patients were classified as having high-risk adenoma on the basis of having three or more small tubular adenomas.

Follow-up colonoscopy was performed a median of 42 months later in the high-risk adenoma group, 54 months later in the low-risk adenoma patients with one or two small tubular adenomas, and at 61 months in those with no adenomas. At follow-up, MAN was discovered in 3.8% of patients with no adenomas at baseline, 4.6% of the low-risk adenoma group, and 9.3% of the overall high-risk adenoma group. However, within the high-risk adenoma group the risk of MAN varied widely: 6.3% in patients with three or more nonadvanced adenomas, 6.1% in those with three or four nonadvanced adenomas, 7.7% in patients with five or more nonadvanced adenomas, 8.3% in those with a 10-mm or larger adenoma without advanced pathology, and 14.6% in patients with an adenoma with advanced pathology at baseline.

In a multivariate analysis adjusted for age, sex, ethnicity, and time between first and follow-up colonoscopy, the risk of MAN did not differ significantly between patients with three or four nonadvanced adenomas and those with one or two, nor between patients with five or more versus one or two. In addition, there was no significant difference in MAN risk between patients with no adenomas at baseline and those with one or two low-risk, nonadvanced adenomas. In contrast, patients with a 10-mm or larger adenoma without advanced pathology at baseline were 1.9-fold more likely to have MAN at follow-up colonoscopy than were patients with one or two small tubular adenomas. And patients having an adenoma with advanced pathology at baseline were at 3.7-fold greater risk of developing MAN than were those with baseline low-risk adenoma, according to Dr. Rouphael.

She reported having no financial conflicts regarding her study, which won the Fellows-in-Training Award at the annual meeting.

bjancin@mdedge.com

SOURCE: Rouphael C. ACG 2019 Abstract 9.

Subacute cutaneous lupus erythematosus

Subacute cutaneous lupus erythematosus (SCLE) is a type of cutaneous lupus erythematosus that may occur independently of or in combination with systemic lupus erythematosus. About 10%-15% of patients with SCLE will develop systemic lupus erythematosus. White females are more typically affected.

SCLE lesions often present as scaly, annular, or polycyclic scaly patches and plaques with central clearing. They may appear psoriasiform. They heal without atrophy or scarring but may leave dyspigmentation. Follicular plugging is absent. Lesions generally occur on sun exposed areas such as the neck, V of the chest, and upper extremities. Up to 75% of patients may exhibit associated symptoms such as photosensitivity, oral ulcers, and arthritis. Less than 20% of patients will develop internal disease, including nephritis and pulmonary disease. Symptoms of Sjögren’s syndrome and SCLE may overlap in some patients, and will portend higher risk for internal disease.

The differential diagnosis includes eczema, psoriasis, dermatophytosis, granuloma annulare, and erythema annulare centrifugum. Histology reveals epidermal atrophy and keratinocyte apoptosis, with a superficial and perivascular lymphohistiocytic infiltrate in the upper dermis. Interface changes at the dermal-epidermal junction can be seen. Direct immunofluorescence of lesional skin is positive in one-third of cases, often revealing granular deposits of IgG and IgM at the dermal-epidermal junction and around hair follicles (called the lupus-band test). Serology in SCLE may reveal a positive antinuclear antigen test, as well as positive Ro/SSA antigen. Other lupus serologies such as La/SSB, dsDNA, antihistone, and Sm antibodies may be positive, but are less commonly seen.

Several drugs may cause SCLE, such as hydrochlorothiazide, terbinafine, ACE inhibitors, NSAIDs, calcium-channel blockers, interferons, anticonvulsants, griseofulvin, penicillamine, spironolactone, tumor necrosis factor–alpha inhibitors, and statins. Discontinuing the offending medications may clear the lesions, but not always.

Treatment includes sunscreen and avoidance of sun exposure. Potent topical corticosteroids are helpful. If systemic treatment is indicated, antimalarials are first line.

This case and photo were submitted by Dr. Bilu Martin.

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

Subacute cutaneous lupus erythematosus

Subacute cutaneous lupus erythematosus (SCLE) is a type of cutaneous lupus erythematosus that may occur independently of or in combination with systemic lupus erythematosus. About 10%-15% of patients with SCLE will develop systemic lupus erythematosus. White females are more typically affected.

SCLE lesions often present as scaly, annular, or polycyclic scaly patches and plaques with central clearing. They may appear psoriasiform. They heal without atrophy or scarring but may leave dyspigmentation. Follicular plugging is absent. Lesions generally occur on sun exposed areas such as the neck, V of the chest, and upper extremities. Up to 75% of patients may exhibit associated symptoms such as photosensitivity, oral ulcers, and arthritis. Less than 20% of patients will develop internal disease, including nephritis and pulmonary disease. Symptoms of Sjögren’s syndrome and SCLE may overlap in some patients, and will portend higher risk for internal disease.

The differential diagnosis includes eczema, psoriasis, dermatophytosis, granuloma annulare, and erythema annulare centrifugum. Histology reveals epidermal atrophy and keratinocyte apoptosis, with a superficial and perivascular lymphohistiocytic infiltrate in the upper dermis. Interface changes at the dermal-epidermal junction can be seen. Direct immunofluorescence of lesional skin is positive in one-third of cases, often revealing granular deposits of IgG and IgM at the dermal-epidermal junction and around hair follicles (called the lupus-band test). Serology in SCLE may reveal a positive antinuclear antigen test, as well as positive Ro/SSA antigen. Other lupus serologies such as La/SSB, dsDNA, antihistone, and Sm antibodies may be positive, but are less commonly seen.

Several drugs may cause SCLE, such as hydrochlorothiazide, terbinafine, ACE inhibitors, NSAIDs, calcium-channel blockers, interferons, anticonvulsants, griseofulvin, penicillamine, spironolactone, tumor necrosis factor–alpha inhibitors, and statins. Discontinuing the offending medications may clear the lesions, but not always.

Treatment includes sunscreen and avoidance of sun exposure. Potent topical corticosteroids are helpful. If systemic treatment is indicated, antimalarials are first line.

This case and photo were submitted by Dr. Bilu Martin.

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

Subacute cutaneous lupus erythematosus

Subacute cutaneous lupus erythematosus (SCLE) is a type of cutaneous lupus erythematosus that may occur independently of or in combination with systemic lupus erythematosus. About 10%-15% of patients with SCLE will develop systemic lupus erythematosus. White females are more typically affected.

SCLE lesions often present as scaly, annular, or polycyclic scaly patches and plaques with central clearing. They may appear psoriasiform. They heal without atrophy or scarring but may leave dyspigmentation. Follicular plugging is absent. Lesions generally occur on sun exposed areas such as the neck, V of the chest, and upper extremities. Up to 75% of patients may exhibit associated symptoms such as photosensitivity, oral ulcers, and arthritis. Less than 20% of patients will develop internal disease, including nephritis and pulmonary disease. Symptoms of Sjögren’s syndrome and SCLE may overlap in some patients, and will portend higher risk for internal disease.

The differential diagnosis includes eczema, psoriasis, dermatophytosis, granuloma annulare, and erythema annulare centrifugum. Histology reveals epidermal atrophy and keratinocyte apoptosis, with a superficial and perivascular lymphohistiocytic infiltrate in the upper dermis. Interface changes at the dermal-epidermal junction can be seen. Direct immunofluorescence of lesional skin is positive in one-third of cases, often revealing granular deposits of IgG and IgM at the dermal-epidermal junction and around hair follicles (called the lupus-band test). Serology in SCLE may reveal a positive antinuclear antigen test, as well as positive Ro/SSA antigen. Other lupus serologies such as La/SSB, dsDNA, antihistone, and Sm antibodies may be positive, but are less commonly seen.

Several drugs may cause SCLE, such as hydrochlorothiazide, terbinafine, ACE inhibitors, NSAIDs, calcium-channel blockers, interferons, anticonvulsants, griseofulvin, penicillamine, spironolactone, tumor necrosis factor–alpha inhibitors, and statins. Discontinuing the offending medications may clear the lesions, but not always.

Treatment includes sunscreen and avoidance of sun exposure. Potent topical corticosteroids are helpful. If systemic treatment is indicated, antimalarials are first line.

This case and photo were submitted by Dr. Bilu Martin.

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

This column should arrive just in time. By now, you may have already failed some or all of your New Year’s resolutions. By this time in February, eighty percent of us will abort what we resolved to do this year. If this was you, it could be considered a catastrophic failure because not only is it a new year, it is a new decade. That’s right, the opportunity to fix the 10-year-imperfect you won’t come again until 2030!

marekuliasz/iStock/Getty Images

I’m among you. I intended to read fiction daily (starting with “The Great Gatsby,” not “Moby Dick” – I thought I would give myself a fighting chance, but alas ...), to workout at least 5 days every week (I tore my left triangular fibrocartilage complex, so there’s that), to write at least 500 words daily (I’m typing this one-handed: I’m lucky to get 500 letters a day). So I’m out.

If you resolved to do something this year, chances are it was to make a better you: a self-improvement goal such as losing weight, saving more money, or exercising more. According to a Marist Poll, these were the most popular resolutions for 2020. At the bottom of the most-likely-resolutions list were things like “worry less” or “be kinder to others.” These are important goals we’d agree, but we don’t deem them resolution-worthy. Why?

And why do we have New Year’s resolutions in the first place? When I looked into this further, I was surprised by some of the history I discovered.

As far back as the Babylonians, once a year, we’ve tried our best to get better. At the feast of Akitu, the Babylonian new year festival (about March on our modern calendar), people resolved to do a better job of paying debts and returning favors – spin had not been invented, and yoga hadn’t caught on in the Middle East yet. This fundamental desire to be a better human seems hardwired, and long before Bullet Journals we seem to have loved “fresh start” days on the calendar. Yet, we’re doomed to fail, over and over, at least for the last 5,000 or so attempts.

We know so much more now. Put your Nike Renue Fusion shoes next to your bed so you get up and run first thing. Set SMART goals. Sign up for automatic retirement contribution and for automatic, plant-based meal delivery from Blue Apron. (I’ve no conflict of interest in these products).

Good ideas all, but I’m suggesting a different approach: Resolve to do something else this year.

Rather than try the same things we’ve attempted, how about selecting something from the bottom of the Marist Poll list – such as resolving to be more humble. Admit when you don’t know something or don’t understand what’s being discussed. Recognize and acknowledge when you’ve screwed up. Or resolve to be more selfless. Add on someone else’s patient, an extra call without expecting a favor in return, or do what you can to help a curbside consult, even if there is no reward or even a small risk to you. Repay the debt you owe your friends, family, colleagues, staff, and patients.

These things are a little trickier to track, but you can find a way to keep yourself accountable. Add a box to your weekly planner that says “Be humble and kind” and check it off for the next 42 weeks. Good news, March 1 falls on a Sunday this year – let’s call it the feast of Akitu.

Happy New Year! And good luck!
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

This column should arrive just in time. By now, you may have already failed some or all of your New Year’s resolutions. By this time in February, eighty percent of us will abort what we resolved to do this year. If this was you, it could be considered a catastrophic failure because not only is it a new year, it is a new decade. That’s right, the opportunity to fix the 10-year-imperfect you won’t come again until 2030!

marekuliasz/iStock/Getty Images

I’m among you. I intended to read fiction daily (starting with “The Great Gatsby,” not “Moby Dick” – I thought I would give myself a fighting chance, but alas ...), to workout at least 5 days every week (I tore my left triangular fibrocartilage complex, so there’s that), to write at least 500 words daily (I’m typing this one-handed: I’m lucky to get 500 letters a day). So I’m out.

If you resolved to do something this year, chances are it was to make a better you: a self-improvement goal such as losing weight, saving more money, or exercising more. According to a Marist Poll, these were the most popular resolutions for 2020. At the bottom of the most-likely-resolutions list were things like “worry less” or “be kinder to others.” These are important goals we’d agree, but we don’t deem them resolution-worthy. Why?

And why do we have New Year’s resolutions in the first place? When I looked into this further, I was surprised by some of the history I discovered.

As far back as the Babylonians, once a year, we’ve tried our best to get better. At the feast of Akitu, the Babylonian new year festival (about March on our modern calendar), people resolved to do a better job of paying debts and returning favors – spin had not been invented, and yoga hadn’t caught on in the Middle East yet. This fundamental desire to be a better human seems hardwired, and long before Bullet Journals we seem to have loved “fresh start” days on the calendar. Yet, we’re doomed to fail, over and over, at least for the last 5,000 or so attempts.

We know so much more now. Put your Nike Renue Fusion shoes next to your bed so you get up and run first thing. Set SMART goals. Sign up for automatic retirement contribution and for automatic, plant-based meal delivery from Blue Apron. (I’ve no conflict of interest in these products).

Good ideas all, but I’m suggesting a different approach: Resolve to do something else this year.

Rather than try the same things we’ve attempted, how about selecting something from the bottom of the Marist Poll list – such as resolving to be more humble. Admit when you don’t know something or don’t understand what’s being discussed. Recognize and acknowledge when you’ve screwed up. Or resolve to be more selfless. Add on someone else’s patient, an extra call without expecting a favor in return, or do what you can to help a curbside consult, even if there is no reward or even a small risk to you. Repay the debt you owe your friends, family, colleagues, staff, and patients.

These things are a little trickier to track, but you can find a way to keep yourself accountable. Add a box to your weekly planner that says “Be humble and kind” and check it off for the next 42 weeks. Good news, March 1 falls on a Sunday this year – let’s call it the feast of Akitu.

Happy New Year! And good luck!
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

This column should arrive just in time. By now, you may have already failed some or all of your New Year’s resolutions. By this time in February, eighty percent of us will abort what we resolved to do this year. If this was you, it could be considered a catastrophic failure because not only is it a new year, it is a new decade. That’s right, the opportunity to fix the 10-year-imperfect you won’t come again until 2030!

marekuliasz/iStock/Getty Images

I’m among you. I intended to read fiction daily (starting with “The Great Gatsby,” not “Moby Dick” – I thought I would give myself a fighting chance, but alas ...), to workout at least 5 days every week (I tore my left triangular fibrocartilage complex, so there’s that), to write at least 500 words daily (I’m typing this one-handed: I’m lucky to get 500 letters a day). So I’m out.

If you resolved to do something this year, chances are it was to make a better you: a self-improvement goal such as losing weight, saving more money, or exercising more. According to a Marist Poll, these were the most popular resolutions for 2020. At the bottom of the most-likely-resolutions list were things like “worry less” or “be kinder to others.” These are important goals we’d agree, but we don’t deem them resolution-worthy. Why?

And why do we have New Year’s resolutions in the first place? When I looked into this further, I was surprised by some of the history I discovered.

As far back as the Babylonians, once a year, we’ve tried our best to get better. At the feast of Akitu, the Babylonian new year festival (about March on our modern calendar), people resolved to do a better job of paying debts and returning favors – spin had not been invented, and yoga hadn’t caught on in the Middle East yet. This fundamental desire to be a better human seems hardwired, and long before Bullet Journals we seem to have loved “fresh start” days on the calendar. Yet, we’re doomed to fail, over and over, at least for the last 5,000 or so attempts.

We know so much more now. Put your Nike Renue Fusion shoes next to your bed so you get up and run first thing. Set SMART goals. Sign up for automatic retirement contribution and for automatic, plant-based meal delivery from Blue Apron. (I’ve no conflict of interest in these products).

Good ideas all, but I’m suggesting a different approach: Resolve to do something else this year.

Rather than try the same things we’ve attempted, how about selecting something from the bottom of the Marist Poll list – such as resolving to be more humble. Admit when you don’t know something or don’t understand what’s being discussed. Recognize and acknowledge when you’ve screwed up. Or resolve to be more selfless. Add on someone else’s patient, an extra call without expecting a favor in return, or do what you can to help a curbside consult, even if there is no reward or even a small risk to you. Repay the debt you owe your friends, family, colleagues, staff, and patients.

These things are a little trickier to track, but you can find a way to keep yourself accountable. Add a box to your weekly planner that says “Be humble and kind” and check it off for the next 42 weeks. Good news, March 1 falls on a Sunday this year – let’s call it the feast of Akitu.

Happy New Year! And good luck!
 

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com.

Hepatitis C virus (HCV) is known to be a common sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). To examine this relationship in HIV-negative MSM, researchers in the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative evaluated HCV-incidence and its risk-factors in this population, who were using pre-exposure prophylaxis (PrEP).

Participants in the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. During the period, participants used daily or event-driven PrEP and could switch regimens during follow-up, according to the report by published in the Journal of Hepatology. 
HIV-negative MSM on PrEP are at risk for incident HCV-infection, while identified risk-factors are similar to those in HIV-positive MSM. 

Among 350 participants, they detected 15 HCV infections in 14 participants, finding 8 primary infections and 7 reinfections. The researchers found that the factors associated with incident HCV-infection were higher number of receptive condomless anal sex acts with casual partners, anal STI, injecting drug use, and sharing straws when snorting drugs. These are similar risk-factors  to those found among in HIV-positive MSM.

They concluded that, because HIV-negative MSM on PrEP are at risk for incident HCV-infection, regular HCV-testing was needed, especially for those with a previous HCV-infection.

Hepatitis C virus (HCV) is known to be a common sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). To examine this relationship in HIV-negative MSM, researchers in the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative evaluated HCV-incidence and its risk-factors in this population, who were using pre-exposure prophylaxis (PrEP).

Participants in the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. During the period, participants used daily or event-driven PrEP and could switch regimens during follow-up, according to the report by published in the Journal of Hepatology. 
HIV-negative MSM on PrEP are at risk for incident HCV-infection, while identified risk-factors are similar to those in HIV-positive MSM. 

Among 350 participants, they detected 15 HCV infections in 14 participants, finding 8 primary infections and 7 reinfections. The researchers found that the factors associated with incident HCV-infection were higher number of receptive condomless anal sex acts with casual partners, anal STI, injecting drug use, and sharing straws when snorting drugs. These are similar risk-factors  to those found among in HIV-positive MSM.

They concluded that, because HIV-negative MSM on PrEP are at risk for incident HCV-infection, regular HCV-testing was needed, especially for those with a previous HCV-infection.

Hepatitis C virus (HCV) is known to be a common sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). To examine this relationship in HIV-negative MSM, researchers in the Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative evaluated HCV-incidence and its risk-factors in this population, who were using pre-exposure prophylaxis (PrEP).

Participants in the Amsterdam PrEP project were tested for HCV antibodies or HCV-RNA every 6 months. During the period, participants used daily or event-driven PrEP and could switch regimens during follow-up, according to the report by published in the Journal of Hepatology. 
HIV-negative MSM on PrEP are at risk for incident HCV-infection, while identified risk-factors are similar to those in HIV-positive MSM. 

Among 350 participants, they detected 15 HCV infections in 14 participants, finding 8 primary infections and 7 reinfections. The researchers found that the factors associated with incident HCV-infection were higher number of receptive condomless anal sex acts with casual partners, anal STI, injecting drug use, and sharing straws when snorting drugs. These are similar risk-factors  to those found among in HIV-positive MSM.

They concluded that, because HIV-negative MSM on PrEP are at risk for incident HCV-infection, regular HCV-testing was needed, especially for those with a previous HCV-infection.