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Combo demonstrates activity in CLL/SLL and FL
LUGANO, SWITZERLAND—Results of a phase 1 study suggest a 2-drug combination may be safe and effective in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and follicular lymphoma (FL).
The ongoing study is a test of the BTK inhibitor BGB-3111 and the anti-CD20 antibody obinutuzumab.
The overall response rate (ORR) with this combination was 81% in the entire study population, 89% in treatment-naïve CLL/SLL patients, 92% in relapsed/refractory CLL/SLL patients, and 73% in relapsed/refractory FL patients.
The rate of serious adverse events (AEs) was 24% in both CLL/SLL and FL patients.
These results were presented at the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by BeiGene, Ltd.
“This clinical trial is supported by preclinical work suggesting that BGB-3111 may combine well with antibodies that rely on antibody-dependent cell-mediated cytotoxicity, such as obinutuzumab, because of less off-target inhibition of interleukin-2-inducible T-cell kinase,” said study investigator Constantine Tam, MD, of St. Vincent’s Hospital in Melbourne, Australia.
“The preliminary clinical results to date suggest that the combination is well tolerated and highly active in patients with CLL or SLL and FL. Complete responses have already been observed in patients with both disease types, including CLL or SLL patients with high-risk features, despite a very short follow-up time.”
The trial consists of a dose-escalation phase and a dose-expansion phase in disease-specific cohorts, which include treatment-naive or relapsed/refractory CLL/SLL and relapsed/refractory FL.
The dose-escalation component is testing BGB-3111 at 320 mg once daily or 160 mg twice daily in 28-day cycles, in combination with obinutuzumab. Obinutuzumab is administered in line with standard CLL dosing (3 loading doses of 1000 mg weekly, followed by 1000 mg on day 1 of cycles 2 to 6).
The ongoing dose-expansion component is testing doses of BGB-3111 at 160 mg twice daily with the same obinutuzumab schedule.
As of the data cutoff (March 31, 2017), 45 patients with CLL/SLL and 17 patients with FL were enrolled in the trial.
Patient characteristics
The median age was 68 (range, 28-82) in the CLL/SLL patients and 56 (range, 41-86) in the FL patients.
ECOG performance status was 0 in 42% of CLL/SLL patients, 1 in 56% of these patients, and 2 in 2%. ECOG performance status was 0 in 82% of FL patients, 1 in 12% of these patients, and 2 in 6%.
Twenty CLL/SLL patients were treatment-naïve, and 25 had relapsed/refractory disease. All 17 FL patients had relapsed/refractory disease.
The median number of prior therapies was 1 (range, 1-4) in the relapsed/refractory CLL/SLL patients and 3 (range, 1-7) in the FL patients.
Safety
At the time of the data cutoff, BGB-3111 was deemed well tolerated in patients with CLL/SLL and FL.
The most frequent AEs of any cause occurring in at least 15% of patients with CLL/SLL were petechiae/purpura/contusion (33%), neutropenia (31%), thrombocytopenia (22%), fatigue (18%), pyrexia (18%), upper respiratory tract infection (18%), and diarrhea (16%).
Most of these events were grade 1/2. The exceptions were grade 3/4 neutropenia (20%) and grade 3/4 thrombocytopenia (4%).
The most frequent AEs in FL patients were petechiae/purpura/contusion (35%), fatigue (29%), cough (18%), diarrhea (18%), dizziness (18%), headache (18%), insomnia (18%), nausea (18%), and upper respiratory tract infection (18%). All of these events were grade 1/2.
Serious AEs occurred in 24% of both the CLL/SLL patients and the FL patients.
Infusion-related reactions occurred in 24% of CLL/SLL patients and 6% of FL patients. Nearly all cases were grade 1/2. The exception was 1 grade 4 case in a CLL/SLL patient.
There were no cases of serious hemorrhage (≥ grade 3 hemorrhage or central nervous system hemorrhage of any grade) or atrial fibrillation.
One patient discontinued treatment due to an AE—squamous cell carcinoma. This patient had a prior history of squamous cell carcinoma.
Efficacy
At the time of the data cutoff, 43 patients with CLL/SLL (18 treatment-naive, 25 relapsed/refractory) and 15 patients with relapsed/refractory FL had greater than 12 weeks of follow-up and were evaluable for efficacy.
In treatment-naive CLL/SLL, after a median follow-up of 7.0 months (range, 2.8–11.8 months), the ORR was 89%. The complete response (CR) rate was 22%, the rate of partial response (PR) was 67%, and the rate of stable disease (SD) was 11%.
In relapsed/refractory CLL/SLL, at a median follow-up of 8.0 months (range, 3.8–14.0 months) the ORR was 92%. The CR rate was 16%, the PR rate was 76%, and 4% of patients had SD.
One patient (4%) with relapsed/refractory CLL/SLL had progressive disease (Richter’s transformation).
In relapsed/refractory FL, at a median follow-up of 6.2 months (range, 1.2–10.7 months), the ORR was 73%. The CR rate was 33%, the PR rate was 40%, and 13% of patients had SD.
Two patients (13%) with relapsed/refractory FL had progressive disease.
On the basis of these data, BeiGene plans to expand its global registrational program for BGB-3111 to include a phase 2 trial of BGB-3111 in combination with obinutuzumab compared to obinutuzumab alone in patients with relapsed/refractory FL.
The company is also planning a phase 3 trial comparing BGB-3111 with bendamustine plus rituximab in patients with treatment-naive CLL. 
LUGANO, SWITZERLAND—Results of a phase 1 study suggest a 2-drug combination may be safe and effective in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and follicular lymphoma (FL).
The ongoing study is a test of the BTK inhibitor BGB-3111 and the anti-CD20 antibody obinutuzumab.
The overall response rate (ORR) with this combination was 81% in the entire study population, 89% in treatment-naïve CLL/SLL patients, 92% in relapsed/refractory CLL/SLL patients, and 73% in relapsed/refractory FL patients.
The rate of serious adverse events (AEs) was 24% in both CLL/SLL and FL patients.
These results were presented at the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by BeiGene, Ltd.
“This clinical trial is supported by preclinical work suggesting that BGB-3111 may combine well with antibodies that rely on antibody-dependent cell-mediated cytotoxicity, such as obinutuzumab, because of less off-target inhibition of interleukin-2-inducible T-cell kinase,” said study investigator Constantine Tam, MD, of St. Vincent’s Hospital in Melbourne, Australia.
“The preliminary clinical results to date suggest that the combination is well tolerated and highly active in patients with CLL or SLL and FL. Complete responses have already been observed in patients with both disease types, including CLL or SLL patients with high-risk features, despite a very short follow-up time.”
The trial consists of a dose-escalation phase and a dose-expansion phase in disease-specific cohorts, which include treatment-naive or relapsed/refractory CLL/SLL and relapsed/refractory FL.
The dose-escalation component is testing BGB-3111 at 320 mg once daily or 160 mg twice daily in 28-day cycles, in combination with obinutuzumab. Obinutuzumab is administered in line with standard CLL dosing (3 loading doses of 1000 mg weekly, followed by 1000 mg on day 1 of cycles 2 to 6).
The ongoing dose-expansion component is testing doses of BGB-3111 at 160 mg twice daily with the same obinutuzumab schedule.
As of the data cutoff (March 31, 2017), 45 patients with CLL/SLL and 17 patients with FL were enrolled in the trial.
Patient characteristics
The median age was 68 (range, 28-82) in the CLL/SLL patients and 56 (range, 41-86) in the FL patients.
ECOG performance status was 0 in 42% of CLL/SLL patients, 1 in 56% of these patients, and 2 in 2%. ECOG performance status was 0 in 82% of FL patients, 1 in 12% of these patients, and 2 in 6%.
Twenty CLL/SLL patients were treatment-naïve, and 25 had relapsed/refractory disease. All 17 FL patients had relapsed/refractory disease.
The median number of prior therapies was 1 (range, 1-4) in the relapsed/refractory CLL/SLL patients and 3 (range, 1-7) in the FL patients.
Safety
At the time of the data cutoff, BGB-3111 was deemed well tolerated in patients with CLL/SLL and FL.
The most frequent AEs of any cause occurring in at least 15% of patients with CLL/SLL were petechiae/purpura/contusion (33%), neutropenia (31%), thrombocytopenia (22%), fatigue (18%), pyrexia (18%), upper respiratory tract infection (18%), and diarrhea (16%).
Most of these events were grade 1/2. The exceptions were grade 3/4 neutropenia (20%) and grade 3/4 thrombocytopenia (4%).
The most frequent AEs in FL patients were petechiae/purpura/contusion (35%), fatigue (29%), cough (18%), diarrhea (18%), dizziness (18%), headache (18%), insomnia (18%), nausea (18%), and upper respiratory tract infection (18%). All of these events were grade 1/2.
Serious AEs occurred in 24% of both the CLL/SLL patients and the FL patients.
Infusion-related reactions occurred in 24% of CLL/SLL patients and 6% of FL patients. Nearly all cases were grade 1/2. The exception was 1 grade 4 case in a CLL/SLL patient.
There were no cases of serious hemorrhage (≥ grade 3 hemorrhage or central nervous system hemorrhage of any grade) or atrial fibrillation.
One patient discontinued treatment due to an AE—squamous cell carcinoma. This patient had a prior history of squamous cell carcinoma.
Efficacy
At the time of the data cutoff, 43 patients with CLL/SLL (18 treatment-naive, 25 relapsed/refractory) and 15 patients with relapsed/refractory FL had greater than 12 weeks of follow-up and were evaluable for efficacy.
In treatment-naive CLL/SLL, after a median follow-up of 7.0 months (range, 2.8–11.8 months), the ORR was 89%. The complete response (CR) rate was 22%, the rate of partial response (PR) was 67%, and the rate of stable disease (SD) was 11%.
In relapsed/refractory CLL/SLL, at a median follow-up of 8.0 months (range, 3.8–14.0 months) the ORR was 92%. The CR rate was 16%, the PR rate was 76%, and 4% of patients had SD.
One patient (4%) with relapsed/refractory CLL/SLL had progressive disease (Richter’s transformation).
In relapsed/refractory FL, at a median follow-up of 6.2 months (range, 1.2–10.7 months), the ORR was 73%. The CR rate was 33%, the PR rate was 40%, and 13% of patients had SD.
Two patients (13%) with relapsed/refractory FL had progressive disease.
On the basis of these data, BeiGene plans to expand its global registrational program for BGB-3111 to include a phase 2 trial of BGB-3111 in combination with obinutuzumab compared to obinutuzumab alone in patients with relapsed/refractory FL.
The company is also planning a phase 3 trial comparing BGB-3111 with bendamustine plus rituximab in patients with treatment-naive CLL.
LUGANO, SWITZERLAND—Results of a phase 1 study suggest a 2-drug combination may be safe and effective in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and follicular lymphoma (FL).
The ongoing study is a test of the BTK inhibitor BGB-3111 and the anti-CD20 antibody obinutuzumab.
The overall response rate (ORR) with this combination was 81% in the entire study population, 89% in treatment-naïve CLL/SLL patients, 92% in relapsed/refractory CLL/SLL patients, and 73% in relapsed/refractory FL patients.
The rate of serious adverse events (AEs) was 24% in both CLL/SLL and FL patients.
These results were presented at the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by BeiGene, Ltd.
“This clinical trial is supported by preclinical work suggesting that BGB-3111 may combine well with antibodies that rely on antibody-dependent cell-mediated cytotoxicity, such as obinutuzumab, because of less off-target inhibition of interleukin-2-inducible T-cell kinase,” said study investigator Constantine Tam, MD, of St. Vincent’s Hospital in Melbourne, Australia.
“The preliminary clinical results to date suggest that the combination is well tolerated and highly active in patients with CLL or SLL and FL. Complete responses have already been observed in patients with both disease types, including CLL or SLL patients with high-risk features, despite a very short follow-up time.”
The trial consists of a dose-escalation phase and a dose-expansion phase in disease-specific cohorts, which include treatment-naive or relapsed/refractory CLL/SLL and relapsed/refractory FL.
The dose-escalation component is testing BGB-3111 at 320 mg once daily or 160 mg twice daily in 28-day cycles, in combination with obinutuzumab. Obinutuzumab is administered in line with standard CLL dosing (3 loading doses of 1000 mg weekly, followed by 1000 mg on day 1 of cycles 2 to 6).
The ongoing dose-expansion component is testing doses of BGB-3111 at 160 mg twice daily with the same obinutuzumab schedule.
As of the data cutoff (March 31, 2017), 45 patients with CLL/SLL and 17 patients with FL were enrolled in the trial.
Patient characteristics
The median age was 68 (range, 28-82) in the CLL/SLL patients and 56 (range, 41-86) in the FL patients.
ECOG performance status was 0 in 42% of CLL/SLL patients, 1 in 56% of these patients, and 2 in 2%. ECOG performance status was 0 in 82% of FL patients, 1 in 12% of these patients, and 2 in 6%.
Twenty CLL/SLL patients were treatment-naïve, and 25 had relapsed/refractory disease. All 17 FL patients had relapsed/refractory disease.
The median number of prior therapies was 1 (range, 1-4) in the relapsed/refractory CLL/SLL patients and 3 (range, 1-7) in the FL patients.
Safety
At the time of the data cutoff, BGB-3111 was deemed well tolerated in patients with CLL/SLL and FL.
The most frequent AEs of any cause occurring in at least 15% of patients with CLL/SLL were petechiae/purpura/contusion (33%), neutropenia (31%), thrombocytopenia (22%), fatigue (18%), pyrexia (18%), upper respiratory tract infection (18%), and diarrhea (16%).
Most of these events were grade 1/2. The exceptions were grade 3/4 neutropenia (20%) and grade 3/4 thrombocytopenia (4%).
The most frequent AEs in FL patients were petechiae/purpura/contusion (35%), fatigue (29%), cough (18%), diarrhea (18%), dizziness (18%), headache (18%), insomnia (18%), nausea (18%), and upper respiratory tract infection (18%). All of these events were grade 1/2.
Serious AEs occurred in 24% of both the CLL/SLL patients and the FL patients.
Infusion-related reactions occurred in 24% of CLL/SLL patients and 6% of FL patients. Nearly all cases were grade 1/2. The exception was 1 grade 4 case in a CLL/SLL patient.
There were no cases of serious hemorrhage (≥ grade 3 hemorrhage or central nervous system hemorrhage of any grade) or atrial fibrillation.
One patient discontinued treatment due to an AE—squamous cell carcinoma. This patient had a prior history of squamous cell carcinoma.
Efficacy
At the time of the data cutoff, 43 patients with CLL/SLL (18 treatment-naive, 25 relapsed/refractory) and 15 patients with relapsed/refractory FL had greater than 12 weeks of follow-up and were evaluable for efficacy.
In treatment-naive CLL/SLL, after a median follow-up of 7.0 months (range, 2.8–11.8 months), the ORR was 89%. The complete response (CR) rate was 22%, the rate of partial response (PR) was 67%, and the rate of stable disease (SD) was 11%.
In relapsed/refractory CLL/SLL, at a median follow-up of 8.0 months (range, 3.8–14.0 months) the ORR was 92%. The CR rate was 16%, the PR rate was 76%, and 4% of patients had SD.
One patient (4%) with relapsed/refractory CLL/SLL had progressive disease (Richter’s transformation).
In relapsed/refractory FL, at a median follow-up of 6.2 months (range, 1.2–10.7 months), the ORR was 73%. The CR rate was 33%, the PR rate was 40%, and 13% of patients had SD.
Two patients (13%) with relapsed/refractory FL had progressive disease.
On the basis of these data, BeiGene plans to expand its global registrational program for BGB-3111 to include a phase 2 trial of BGB-3111 in combination with obinutuzumab compared to obinutuzumab alone in patients with relapsed/refractory FL.
The company is also planning a phase 3 trial comparing BGB-3111 with bendamustine plus rituximab in patients with treatment-naive CLL.
Vaccine granted orphan designation for MDS
The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).
DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.
DSP-7888 is being developed by Boston Biomedical, Inc.
The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.
Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.
DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.
There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.
There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.
Eight patients had stable disease, 2 with hematological improvements.
Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).
DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.
DSP-7888 is being developed by Boston Biomedical, Inc.
The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.
Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.
DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.
There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.
There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.
Eight patients had stable disease, 2 with hematological improvements.
Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
The US Food and Drug Administration (FDA) has granted orphan drug designation to DSP-7888, an investigational cancer peptide vaccine, for the treatment of myelodysplastic syndromes (MDS).
DSP-7888 contains peptides to induce Wilms’ tumor gene 1 (WT1)-specific cytotoxic T lymphocytes and helper T cells, which attack WT1-expressing cancerous cells found in various hematologic and solid tumor malignancies.
DSP-7888 is being developed by Boston Biomedical, Inc.
The first clinical data for DSP-7888, from a phase 1/2 study in patients with MDS who progressed on or after first-line azacitidine treatment, were presented at the 2016 ASH Annual Meeting.
Results were reported in 12 patients—7 with higher-risk MDS and 5 with lower-risk disease.
DSP-7888 was given at doses of 3.5 mg/body (n=6) or 10.5 mg/body (n=6) by intradermal injections every 2 to 4 weeks.
There were no dose-limiting toxicities. The most common adverse event was injection site reactions. Six patients had grade 3 injection site reactions.
There were 5 serious adverse events—3 injection site reactions, 1 case of pyrexia, and 1 case of myocarditis.
Eight patients had stable disease, 2 with hematological improvements.
Cytotoxic T lymphocyte induction was observed in 6 patients, and delayed type hypersensitivity response was observed in 10 patients.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
One-year cost of preeclampsia tops $2 billion
The cost of medical care for preeclampsia is estimated to be $2.18 billion for the first year surrounding delivery, split almost evenly between care for mothers and infants, according to a new report.
Preeclampsia is increasing at a more rapid rate than diabetes, ischemic heart failure, Alzheimer’s disease, obesity, and chronic kidney disease – disorders for which substantially more funding has been allocated for research and treatment, said Warren Stevens, PhD, of Precision Health Economics, Los Angeles, and his associates. Precision Health Economics provides consulting and other research services to pharmaceutical, device, government, and nongovernmental groups.
Compared with a healthy pregnancy, preeclampsia increased the probability that a mother would have at least one adverse outcome from 4.6% to 10.1%, and it increased the probability that an infant would have at least one adverse outcome from 7.9% to 14.2%. For mothers, preeclampsia was estimated to raise costs by $6,583 per birth, which translates to an increase of $1.03 billion for U.S. mothers during a single year (2012). For infants, the disorder raised costs by $1.15 billion during that year.
Infant costs varied according to the gestational age at delivery, ranging from $1,311 per birth at 36 weeks’ gestation to $150,000 per birth at 26 weeks’ gestation, Dr. Stevens and his associates reported (Am J Obstet Gynecol. 2017 Jul 11. doi: 10.1016/j.ajog.2017.04.032).
This study could not take into account longer-term adverse outcomes associated with preeclampsia. Women with a history of the disorder are at double the risk of developing ischemic heart disease or cerebrovascular disease compared with women without such a history, and at three times the risk of developing hypertension. Infants are at increased risk of developing stroke, metabolic syndrome, and chronic heart disease, the investigators noted.
The study was supported by rEVO Biologics. Five of the study authors are employees of rEVO Biologics and one author is a steering committee member for a clinical trial supported by the company; another study author is a consultant at Precision Health Economics.
Quantifying the total cost of a health problem helps to show the public, payers, and health care administrators the magnitude of the problem on a population level. By underscoring the economic burden of preeclampsia, Stevens et al. provided important information about the high costs of this condition.
However, we need to go beyond health burden and cost-of-illness studies when considering the value of interventions to prevent and better manage preeclampsia and its adverse outcomes. Cost of the intervention and the cost savings associated with preventing one case of the condition are important parameters that can be used to calculate the potential savings of interventions. In fact, if the lifetimes costs of caring for children with adverse outcomes of preeclampsia are included, the potential cost savings from effective interventions may be even greater.
Rui Li, PhD, and William M. Callaghan, MD, are in the division of reproductive health at the Centers for Disease Control and Prevention, Atlanta. Eleni Tsigas is with the Preeclampsia Foundation in Melbourne, Fla. They reported having no relevant financial disclosures. These remarks are adapted from an editorial (Am J Obstet Gynecol. 2017 Jul 11. doi: 10.1016/j.ajog.2017.06.011).
Quantifying the total cost of a health problem helps to show the public, payers, and health care administrators the magnitude of the problem on a population level. By underscoring the economic burden of preeclampsia, Stevens et al. provided important information about the high costs of this condition.
However, we need to go beyond health burden and cost-of-illness studies when considering the value of interventions to prevent and better manage preeclampsia and its adverse outcomes. Cost of the intervention and the cost savings associated with preventing one case of the condition are important parameters that can be used to calculate the potential savings of interventions. In fact, if the lifetimes costs of caring for children with adverse outcomes of preeclampsia are included, the potential cost savings from effective interventions may be even greater.
Rui Li, PhD, and William M. Callaghan, MD, are in the division of reproductive health at the Centers for Disease Control and Prevention, Atlanta. Eleni Tsigas is with the Preeclampsia Foundation in Melbourne, Fla. They reported having no relevant financial disclosures. These remarks are adapted from an editorial (Am J Obstet Gynecol. 2017 Jul 11. doi: 10.1016/j.ajog.2017.06.011).
Quantifying the total cost of a health problem helps to show the public, payers, and health care administrators the magnitude of the problem on a population level. By underscoring the economic burden of preeclampsia, Stevens et al. provided important information about the high costs of this condition.
However, we need to go beyond health burden and cost-of-illness studies when considering the value of interventions to prevent and better manage preeclampsia and its adverse outcomes. Cost of the intervention and the cost savings associated with preventing one case of the condition are important parameters that can be used to calculate the potential savings of interventions. In fact, if the lifetimes costs of caring for children with adverse outcomes of preeclampsia are included, the potential cost savings from effective interventions may be even greater.
Rui Li, PhD, and William M. Callaghan, MD, are in the division of reproductive health at the Centers for Disease Control and Prevention, Atlanta. Eleni Tsigas is with the Preeclampsia Foundation in Melbourne, Fla. They reported having no relevant financial disclosures. These remarks are adapted from an editorial (Am J Obstet Gynecol. 2017 Jul 11. doi: 10.1016/j.ajog.2017.06.011).
The cost of medical care for preeclampsia is estimated to be $2.18 billion for the first year surrounding delivery, split almost evenly between care for mothers and infants, according to a new report.
Preeclampsia is increasing at a more rapid rate than diabetes, ischemic heart failure, Alzheimer’s disease, obesity, and chronic kidney disease – disorders for which substantially more funding has been allocated for research and treatment, said Warren Stevens, PhD, of Precision Health Economics, Los Angeles, and his associates. Precision Health Economics provides consulting and other research services to pharmaceutical, device, government, and nongovernmental groups.
Compared with a healthy pregnancy, preeclampsia increased the probability that a mother would have at least one adverse outcome from 4.6% to 10.1%, and it increased the probability that an infant would have at least one adverse outcome from 7.9% to 14.2%. For mothers, preeclampsia was estimated to raise costs by $6,583 per birth, which translates to an increase of $1.03 billion for U.S. mothers during a single year (2012). For infants, the disorder raised costs by $1.15 billion during that year.
Infant costs varied according to the gestational age at delivery, ranging from $1,311 per birth at 36 weeks’ gestation to $150,000 per birth at 26 weeks’ gestation, Dr. Stevens and his associates reported (Am J Obstet Gynecol. 2017 Jul 11. doi: 10.1016/j.ajog.2017.04.032).
This study could not take into account longer-term adverse outcomes associated with preeclampsia. Women with a history of the disorder are at double the risk of developing ischemic heart disease or cerebrovascular disease compared with women without such a history, and at three times the risk of developing hypertension. Infants are at increased risk of developing stroke, metabolic syndrome, and chronic heart disease, the investigators noted.
The study was supported by rEVO Biologics. Five of the study authors are employees of rEVO Biologics and one author is a steering committee member for a clinical trial supported by the company; another study author is a consultant at Precision Health Economics.
The cost of medical care for preeclampsia is estimated to be $2.18 billion for the first year surrounding delivery, split almost evenly between care for mothers and infants, according to a new report.
Preeclampsia is increasing at a more rapid rate than diabetes, ischemic heart failure, Alzheimer’s disease, obesity, and chronic kidney disease – disorders for which substantially more funding has been allocated for research and treatment, said Warren Stevens, PhD, of Precision Health Economics, Los Angeles, and his associates. Precision Health Economics provides consulting and other research services to pharmaceutical, device, government, and nongovernmental groups.
Compared with a healthy pregnancy, preeclampsia increased the probability that a mother would have at least one adverse outcome from 4.6% to 10.1%, and it increased the probability that an infant would have at least one adverse outcome from 7.9% to 14.2%. For mothers, preeclampsia was estimated to raise costs by $6,583 per birth, which translates to an increase of $1.03 billion for U.S. mothers during a single year (2012). For infants, the disorder raised costs by $1.15 billion during that year.
Infant costs varied according to the gestational age at delivery, ranging from $1,311 per birth at 36 weeks’ gestation to $150,000 per birth at 26 weeks’ gestation, Dr. Stevens and his associates reported (Am J Obstet Gynecol. 2017 Jul 11. doi: 10.1016/j.ajog.2017.04.032).
This study could not take into account longer-term adverse outcomes associated with preeclampsia. Women with a history of the disorder are at double the risk of developing ischemic heart disease or cerebrovascular disease compared with women without such a history, and at three times the risk of developing hypertension. Infants are at increased risk of developing stroke, metabolic syndrome, and chronic heart disease, the investigators noted.
The study was supported by rEVO Biologics. Five of the study authors are employees of rEVO Biologics and one author is a steering committee member for a clinical trial supported by the company; another study author is a consultant at Precision Health Economics.
FROM THE AMERICAN JOURNAL OF OBSTETRICS & GYNECOLOGY
Key clinical point:
Major finding: Compared with healthy pregnancy, preeclampsia increased the probability that a mother would have at least one adverse outcome from 4.6% to 10.1%, and it increased the probability that an infant would have at least one adverse outcome from 7.9% to 14.2%.
Data source: A retrospective cohort study using secondary analysis of numerous data sets and extrapolating from approximately 2 million births in 2012 (1,918,498 births without preeclampsia and 69,193 with preeclampsia).
Disclosures: The study was supported by rEVO Biologics. Five of the study authors are employees of Precision Health Economics and one author is a consultant there; another author is on the steering committee for a clinical trial supported by rEVO Biologics.
Bariatric Surgery for CKD
Q) I know that diabetes can be controlled with bariatric surgery. Is there any proof that it also helps with kidney disease?
With obesity reaching epidemic proportions in the United States, the number of patients undergoing bariatric surgery has increased in recent years. The procedure has been identified as the most effective intervention for the morbidly obese (BMI > 35).1, 2
Obesity is an independent risk factor for the development and progression of chronic kidney disease (CKD).3 It causes changes in the kidney, including hyperfiltration, proteinuria, albuminuria, and reduced glomerular filtration rate (GFR); however, the underlying mechanisms are still poorly understood.4 Research has demonstrated bariatric surgery’s positive effect on morbidly obese patients with CKD, as well as its benefit for patients with diabetes and hypertension—the two major causes of CKD.1,2
Several studies have found that weight loss resulting from bariatric surgery improves proteinuria, albuminuria, and GFR.2,3,5-9 Findings related to serum creatinine (SCr) have been somewhat conflicting. In severely obese patients, the surgery was associated with a reduction in SCr. This association persisted in those with and without baseline CKD, hypertension, and/or diabetes.5 However, other studies found that the procedure lowered SCr in patients with mild renal impairment (SCr 1.3-1.6 mg/dL) but increased levels in those with moderate renal impairment (SCr > 1.6 mg/dL).10 Because the effects of bariatric surgery on kidney function appear to differ based on CKD stage, further research is needed.
Overall, we can conclude that bariatric surgery has merit as an option to prevent and/or slow progression of early-stage CKD in severely obese patients. Larger, long-term studies are needed to analyze the duration of these effects on kidney outcomes, including the development of end-stage kidney disease. And additional research is needed to determine the risks and benefits associated with bariatric surgery in this population. —ZK-K
Zorica Kauric-Klein, APRN-BC, PhD
Assistant Clinical Professor, College of Nursing, Wayne State University, Detroit
1. Schauer PR, Bhatt DL, Kirwan JP, et al; STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. N Engl J Med. 2017;376(7):641-651.
2. Ricci C, Gaeta M, Rausa E, et al. Early impact of bariatric surgery on type II diabetes, hypertension, and hyperlipidemia: a systematic review, meta-analysis and meta-regression on 6,587 patients. Obes Surg. 2014;24(4):522-528.
3. Bolignano D, Zoccali C. Effects of weight loss on renal function in obese CKD patients: a systematic review. Nephrol Dial Transplant. 2013;28(suppl 4):82-98.
4. Hall ME, do Carmo JM, da Silva AA, et al. Obesity, hypertension, and chronic kidney disease. Int J Nephrol Renovasc Dis. 2014;7:75-88.
5. Chang AR, Chen Y, Still C, et al. Bariatric surgery is associated with improvement in kidney outcomes. Kidney Int. 2016;90(1):164-171.
6. Ruiz-Tovar J, Giner L, Sarro-Sobrin F, et al. Laparoscopic sleeve gastrectomy prevents the deterioration of renal function in morbidly obese patients over 40 years. Obes Surg. 2015;25(5):796-799.
7. Neff KJ, Baud G, Raverdy V, et al. Renal function and remission of hypertension after bariatric surgery: a 5-year prospective cohort study. Obes Surg. 2017;27(3):613-619.
8. Nehus EJ, Khoury JC, Inge TH, et al. Kidney outcomes three years after bariatric surgery in severely obese adolescents. Kidney Int. 2017;91(2):451-458.
9. Carlsson LMS, Romeo S, Jacobson P, et al. The incidence of albuminuria after bariatric surgery and usual care in Swedish obese subjects (SOS): a prospective controlled intervention trial. Int J Obes (Lond). 2015;39(1):169-175.
10. Schuster DP, Teodorescu M, Mikami D, et al. Effect of bariatric surgery on normal and abnormal renal function. Surg Obes Relat Dis. 2011;7(4):459-464.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month’s responses were authored by Zorica Kauric-Klein, APRN-BC, PhD, who is an Assistant Clinical Professor in the College of Nursing at Wayne State University in Detroit, and Rebecca Clawson, MAT, PA-C, who is an Instructor in the PA Program at LSU Health Shreveport in Louisiana.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month’s responses were authored by Zorica Kauric-Klein, APRN-BC, PhD, who is an Assistant Clinical Professor in the College of Nursing at Wayne State University in Detroit, and Rebecca Clawson, MAT, PA-C, who is an Instructor in the PA Program at LSU Health Shreveport in Louisiana.
Clinician Reviews in partnership with
Renal Consult is edited by Jane S. Davis, CRNP, DNP, a member of the Clinician Reviews editorial board, who is a nurse practitioner in the Division of Nephrology at the University of Alabama at Birmingham and is the communications chairperson for the National Kidney Foundation’s Council of Advanced Practitioners (NKF-CAP); and Kim Zuber, PA-C, MSPS, DFAAPA, a semi-retired PA who works with the American Academy of Nephrology PAs and is a past chair of the NKF-CAP. This month’s responses were authored by Zorica Kauric-Klein, APRN-BC, PhD, who is an Assistant Clinical Professor in the College of Nursing at Wayne State University in Detroit, and Rebecca Clawson, MAT, PA-C, who is an Instructor in the PA Program at LSU Health Shreveport in Louisiana.
Q) I know that diabetes can be controlled with bariatric surgery. Is there any proof that it also helps with kidney disease?
With obesity reaching epidemic proportions in the United States, the number of patients undergoing bariatric surgery has increased in recent years. The procedure has been identified as the most effective intervention for the morbidly obese (BMI > 35).1, 2
Obesity is an independent risk factor for the development and progression of chronic kidney disease (CKD).3 It causes changes in the kidney, including hyperfiltration, proteinuria, albuminuria, and reduced glomerular filtration rate (GFR); however, the underlying mechanisms are still poorly understood.4 Research has demonstrated bariatric surgery’s positive effect on morbidly obese patients with CKD, as well as its benefit for patients with diabetes and hypertension—the two major causes of CKD.1,2
Several studies have found that weight loss resulting from bariatric surgery improves proteinuria, albuminuria, and GFR.2,3,5-9 Findings related to serum creatinine (SCr) have been somewhat conflicting. In severely obese patients, the surgery was associated with a reduction in SCr. This association persisted in those with and without baseline CKD, hypertension, and/or diabetes.5 However, other studies found that the procedure lowered SCr in patients with mild renal impairment (SCr 1.3-1.6 mg/dL) but increased levels in those with moderate renal impairment (SCr > 1.6 mg/dL).10 Because the effects of bariatric surgery on kidney function appear to differ based on CKD stage, further research is needed.
Overall, we can conclude that bariatric surgery has merit as an option to prevent and/or slow progression of early-stage CKD in severely obese patients. Larger, long-term studies are needed to analyze the duration of these effects on kidney outcomes, including the development of end-stage kidney disease. And additional research is needed to determine the risks and benefits associated with bariatric surgery in this population. —ZK-K
Zorica Kauric-Klein, APRN-BC, PhD
Assistant Clinical Professor, College of Nursing, Wayne State University, Detroit
Q) I know that diabetes can be controlled with bariatric surgery. Is there any proof that it also helps with kidney disease?
With obesity reaching epidemic proportions in the United States, the number of patients undergoing bariatric surgery has increased in recent years. The procedure has been identified as the most effective intervention for the morbidly obese (BMI > 35).1, 2
Obesity is an independent risk factor for the development and progression of chronic kidney disease (CKD).3 It causes changes in the kidney, including hyperfiltration, proteinuria, albuminuria, and reduced glomerular filtration rate (GFR); however, the underlying mechanisms are still poorly understood.4 Research has demonstrated bariatric surgery’s positive effect on morbidly obese patients with CKD, as well as its benefit for patients with diabetes and hypertension—the two major causes of CKD.1,2
Several studies have found that weight loss resulting from bariatric surgery improves proteinuria, albuminuria, and GFR.2,3,5-9 Findings related to serum creatinine (SCr) have been somewhat conflicting. In severely obese patients, the surgery was associated with a reduction in SCr. This association persisted in those with and without baseline CKD, hypertension, and/or diabetes.5 However, other studies found that the procedure lowered SCr in patients with mild renal impairment (SCr 1.3-1.6 mg/dL) but increased levels in those with moderate renal impairment (SCr > 1.6 mg/dL).10 Because the effects of bariatric surgery on kidney function appear to differ based on CKD stage, further research is needed.
Overall, we can conclude that bariatric surgery has merit as an option to prevent and/or slow progression of early-stage CKD in severely obese patients. Larger, long-term studies are needed to analyze the duration of these effects on kidney outcomes, including the development of end-stage kidney disease. And additional research is needed to determine the risks and benefits associated with bariatric surgery in this population. —ZK-K
Zorica Kauric-Klein, APRN-BC, PhD
Assistant Clinical Professor, College of Nursing, Wayne State University, Detroit
1. Schauer PR, Bhatt DL, Kirwan JP, et al; STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. N Engl J Med. 2017;376(7):641-651.
2. Ricci C, Gaeta M, Rausa E, et al. Early impact of bariatric surgery on type II diabetes, hypertension, and hyperlipidemia: a systematic review, meta-analysis and meta-regression on 6,587 patients. Obes Surg. 2014;24(4):522-528.
3. Bolignano D, Zoccali C. Effects of weight loss on renal function in obese CKD patients: a systematic review. Nephrol Dial Transplant. 2013;28(suppl 4):82-98.
4. Hall ME, do Carmo JM, da Silva AA, et al. Obesity, hypertension, and chronic kidney disease. Int J Nephrol Renovasc Dis. 2014;7:75-88.
5. Chang AR, Chen Y, Still C, et al. Bariatric surgery is associated with improvement in kidney outcomes. Kidney Int. 2016;90(1):164-171.
6. Ruiz-Tovar J, Giner L, Sarro-Sobrin F, et al. Laparoscopic sleeve gastrectomy prevents the deterioration of renal function in morbidly obese patients over 40 years. Obes Surg. 2015;25(5):796-799.
7. Neff KJ, Baud G, Raverdy V, et al. Renal function and remission of hypertension after bariatric surgery: a 5-year prospective cohort study. Obes Surg. 2017;27(3):613-619.
8. Nehus EJ, Khoury JC, Inge TH, et al. Kidney outcomes three years after bariatric surgery in severely obese adolescents. Kidney Int. 2017;91(2):451-458.
9. Carlsson LMS, Romeo S, Jacobson P, et al. The incidence of albuminuria after bariatric surgery and usual care in Swedish obese subjects (SOS): a prospective controlled intervention trial. Int J Obes (Lond). 2015;39(1):169-175.
10. Schuster DP, Teodorescu M, Mikami D, et al. Effect of bariatric surgery on normal and abnormal renal function. Surg Obes Relat Dis. 2011;7(4):459-464.
1. Schauer PR, Bhatt DL, Kirwan JP, et al; STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes—5-year outcomes. N Engl J Med. 2017;376(7):641-651.
2. Ricci C, Gaeta M, Rausa E, et al. Early impact of bariatric surgery on type II diabetes, hypertension, and hyperlipidemia: a systematic review, meta-analysis and meta-regression on 6,587 patients. Obes Surg. 2014;24(4):522-528.
3. Bolignano D, Zoccali C. Effects of weight loss on renal function in obese CKD patients: a systematic review. Nephrol Dial Transplant. 2013;28(suppl 4):82-98.
4. Hall ME, do Carmo JM, da Silva AA, et al. Obesity, hypertension, and chronic kidney disease. Int J Nephrol Renovasc Dis. 2014;7:75-88.
5. Chang AR, Chen Y, Still C, et al. Bariatric surgery is associated with improvement in kidney outcomes. Kidney Int. 2016;90(1):164-171.
6. Ruiz-Tovar J, Giner L, Sarro-Sobrin F, et al. Laparoscopic sleeve gastrectomy prevents the deterioration of renal function in morbidly obese patients over 40 years. Obes Surg. 2015;25(5):796-799.
7. Neff KJ, Baud G, Raverdy V, et al. Renal function and remission of hypertension after bariatric surgery: a 5-year prospective cohort study. Obes Surg. 2017;27(3):613-619.
8. Nehus EJ, Khoury JC, Inge TH, et al. Kidney outcomes three years after bariatric surgery in severely obese adolescents. Kidney Int. 2017;91(2):451-458.
9. Carlsson LMS, Romeo S, Jacobson P, et al. The incidence of albuminuria after bariatric surgery and usual care in Swedish obese subjects (SOS): a prospective controlled intervention trial. Int J Obes (Lond). 2015;39(1):169-175.
10. Schuster DP, Teodorescu M, Mikami D, et al. Effect of bariatric surgery on normal and abnormal renal function. Surg Obes Relat Dis. 2011;7(4):459-464.
OMV meningococcal vaccine also protected against gonorrhea
A group B meningococcal outer-membrane-vesicle (OMV) vaccine used during a meningitis outbreak in New Zealand also protected against gonorrhea, according to a report published online July 10 in the Lancet.
Even though Neisseria meningitidis and Neisseria gonorrhoeae cause distinctly different diseases, the bacteria are closely related and are genetically and antigenically very similar. Most of the virulence factors present in one pathogen have an equivalent in the other, “providing at least one biologically plausible mechanism for cross-protection,” said Helen Petousis-Harris, PhD, of the department of general practice and primary health care, University of Auckland (New Zealand), and her associates. 
Approximately 1 million people – 81% of the New Zealand population younger than 20 years – received almost 3 million doses of the OMV meningococcal B vaccine (MeNZB) in a 2-year mass immunization program during the outbreak, allowing the investigators to compare the rate of gonorrhea between vaccinated and unvaccinated people. They performed a retrospective case-control study involving 14,730 participants, using information from a national health care database, a national immunization registry, and 11 sexual health clinics covering diverse geographic regions. This included 1,241 cases of gonorrhea (cases), 12,487 cases of chlamydia (controls), and 1,002 cases of gonorrhea plus chlamydia coinfection (categorized as controls or cases in separate analyses).
“The adjusted estimate for vaccine effectiveness of the MeNZB against confirmed cases of gonorrhea” was 31% (95% confidence interval, 21-39; P less than .0001), a finding that remained robust across several sensitivity analyses, Dr. Petousis-Harris and her associates said (Lancet. 2017 July 10. doi: 10.1016/S0140-6736(17)31449-6).
“To our knowledge, ours is the first study to show an association between a vaccine and a reduction in the risk of gonorrhea,” they noted. “The potential ability of an OMV group B meningococcal vaccine to provide even modest protection against gonorrhea would have substantial public health benefits in view of the prevalence of gonorrhea. Modeling suggests that a vaccine with 30% efficacy could decrease the prevalence of gonorrhea by more than 30% within 15 years, if immunity is maintained.”
These findings also are important in view of the organism’s increasing resistance to existing antibiotics. Moreover, if further study confirms that the MeNZB vaccine offers some degree of cross-protection against gonorrhea, these data can inform the development of a gonorrhea vaccine, the investigators added.
This study was funded by GlaxoSmithKline Vaccines and Auckland UniServices. Dr. Petousis-Harris reported serving as a consultant for GSK, Merck, and Pfizer, and one of her associates reported ties to Novartis Vaccines, GSK, Protein Sciences, and Merck.
Over decades of research, all of the attempts to create a vaccine against gonorrhea have failed, largely because of the variable nature of Neisseria gonorrhoeae antigens and the failure of the bacteria to induce a protective immune response, so the findings of Dr. Petousis-Harris and her associates are “a step in the right direction” and should reinvigorate interest and investment in this endeavor.
Although MeNZB is no longer available, another meningococcal vaccine (4CMenB, Bexsero) contains the same outer-membrane-vesicle antigen and three of the same recombinant proteins. As the authors pointed out, immunizing adolescents with this vaccine could reduce the rate of gonorrhea substantially, even if it has only moderate efficacy and duration of effect. In particular, reducing the pool of asymptomatic carriers would decrease both transmission and the severe sequelae that develop when the infection goes undetected.
Kate L. Seib, PhD, is a microbiologist at the Institute for Glycomics at Griffith University in Southport, Australia. She reported support by a career development fellowship from the Australian National Health and Medical Research Council. Dr. Seib made these remarks in an accompanying editorial comment (Lancet. 2017 July 10. doi: 10.1016/S0140-6736(17)31605-7).
Over decades of research, all of the attempts to create a vaccine against gonorrhea have failed, largely because of the variable nature of Neisseria gonorrhoeae antigens and the failure of the bacteria to induce a protective immune response, so the findings of Dr. Petousis-Harris and her associates are “a step in the right direction” and should reinvigorate interest and investment in this endeavor.
Although MeNZB is no longer available, another meningococcal vaccine (4CMenB, Bexsero) contains the same outer-membrane-vesicle antigen and three of the same recombinant proteins. As the authors pointed out, immunizing adolescents with this vaccine could reduce the rate of gonorrhea substantially, even if it has only moderate efficacy and duration of effect. In particular, reducing the pool of asymptomatic carriers would decrease both transmission and the severe sequelae that develop when the infection goes undetected.
Kate L. Seib, PhD, is a microbiologist at the Institute for Glycomics at Griffith University in Southport, Australia. She reported support by a career development fellowship from the Australian National Health and Medical Research Council. Dr. Seib made these remarks in an accompanying editorial comment (Lancet. 2017 July 10. doi: 10.1016/S0140-6736(17)31605-7).
Over decades of research, all of the attempts to create a vaccine against gonorrhea have failed, largely because of the variable nature of Neisseria gonorrhoeae antigens and the failure of the bacteria to induce a protective immune response, so the findings of Dr. Petousis-Harris and her associates are “a step in the right direction” and should reinvigorate interest and investment in this endeavor.
Although MeNZB is no longer available, another meningococcal vaccine (4CMenB, Bexsero) contains the same outer-membrane-vesicle antigen and three of the same recombinant proteins. As the authors pointed out, immunizing adolescents with this vaccine could reduce the rate of gonorrhea substantially, even if it has only moderate efficacy and duration of effect. In particular, reducing the pool of asymptomatic carriers would decrease both transmission and the severe sequelae that develop when the infection goes undetected.
Kate L. Seib, PhD, is a microbiologist at the Institute for Glycomics at Griffith University in Southport, Australia. She reported support by a career development fellowship from the Australian National Health and Medical Research Council. Dr. Seib made these remarks in an accompanying editorial comment (Lancet. 2017 July 10. doi: 10.1016/S0140-6736(17)31605-7).
A group B meningococcal outer-membrane-vesicle (OMV) vaccine used during a meningitis outbreak in New Zealand also protected against gonorrhea, according to a report published online July 10 in the Lancet.
Even though Neisseria meningitidis and Neisseria gonorrhoeae cause distinctly different diseases, the bacteria are closely related and are genetically and antigenically very similar. Most of the virulence factors present in one pathogen have an equivalent in the other, “providing at least one biologically plausible mechanism for cross-protection,” said Helen Petousis-Harris, PhD, of the department of general practice and primary health care, University of Auckland (New Zealand), and her associates.
Approximately 1 million people – 81% of the New Zealand population younger than 20 years – received almost 3 million doses of the OMV meningococcal B vaccine (MeNZB) in a 2-year mass immunization program during the outbreak, allowing the investigators to compare the rate of gonorrhea between vaccinated and unvaccinated people. They performed a retrospective case-control study involving 14,730 participants, using information from a national health care database, a national immunization registry, and 11 sexual health clinics covering diverse geographic regions. This included 1,241 cases of gonorrhea (cases), 12,487 cases of chlamydia (controls), and 1,002 cases of gonorrhea plus chlamydia coinfection (categorized as controls or cases in separate analyses).
“The adjusted estimate for vaccine effectiveness of the MeNZB against confirmed cases of gonorrhea” was 31% (95% confidence interval, 21-39; P less than .0001), a finding that remained robust across several sensitivity analyses, Dr. Petousis-Harris and her associates said (Lancet. 2017 July 10. doi: 10.1016/S0140-6736(17)31449-6).
“To our knowledge, ours is the first study to show an association between a vaccine and a reduction in the risk of gonorrhea,” they noted. “The potential ability of an OMV group B meningococcal vaccine to provide even modest protection against gonorrhea would have substantial public health benefits in view of the prevalence of gonorrhea. Modeling suggests that a vaccine with 30% efficacy could decrease the prevalence of gonorrhea by more than 30% within 15 years, if immunity is maintained.”
These findings also are important in view of the organism’s increasing resistance to existing antibiotics. Moreover, if further study confirms that the MeNZB vaccine offers some degree of cross-protection against gonorrhea, these data can inform the development of a gonorrhea vaccine, the investigators added.
This study was funded by GlaxoSmithKline Vaccines and Auckland UniServices. Dr. Petousis-Harris reported serving as a consultant for GSK, Merck, and Pfizer, and one of her associates reported ties to Novartis Vaccines, GSK, Protein Sciences, and Merck.
A group B meningococcal outer-membrane-vesicle (OMV) vaccine used during a meningitis outbreak in New Zealand also protected against gonorrhea, according to a report published online July 10 in the Lancet.
Even though Neisseria meningitidis and Neisseria gonorrhoeae cause distinctly different diseases, the bacteria are closely related and are genetically and antigenically very similar. Most of the virulence factors present in one pathogen have an equivalent in the other, “providing at least one biologically plausible mechanism for cross-protection,” said Helen Petousis-Harris, PhD, of the department of general practice and primary health care, University of Auckland (New Zealand), and her associates.
Approximately 1 million people – 81% of the New Zealand population younger than 20 years – received almost 3 million doses of the OMV meningococcal B vaccine (MeNZB) in a 2-year mass immunization program during the outbreak, allowing the investigators to compare the rate of gonorrhea between vaccinated and unvaccinated people. They performed a retrospective case-control study involving 14,730 participants, using information from a national health care database, a national immunization registry, and 11 sexual health clinics covering diverse geographic regions. This included 1,241 cases of gonorrhea (cases), 12,487 cases of chlamydia (controls), and 1,002 cases of gonorrhea plus chlamydia coinfection (categorized as controls or cases in separate analyses).
“The adjusted estimate for vaccine effectiveness of the MeNZB against confirmed cases of gonorrhea” was 31% (95% confidence interval, 21-39; P less than .0001), a finding that remained robust across several sensitivity analyses, Dr. Petousis-Harris and her associates said (Lancet. 2017 July 10. doi: 10.1016/S0140-6736(17)31449-6).
“To our knowledge, ours is the first study to show an association between a vaccine and a reduction in the risk of gonorrhea,” they noted. “The potential ability of an OMV group B meningococcal vaccine to provide even modest protection against gonorrhea would have substantial public health benefits in view of the prevalence of gonorrhea. Modeling suggests that a vaccine with 30% efficacy could decrease the prevalence of gonorrhea by more than 30% within 15 years, if immunity is maintained.”
These findings also are important in view of the organism’s increasing resistance to existing antibiotics. Moreover, if further study confirms that the MeNZB vaccine offers some degree of cross-protection against gonorrhea, these data can inform the development of a gonorrhea vaccine, the investigators added.
This study was funded by GlaxoSmithKline Vaccines and Auckland UniServices. Dr. Petousis-Harris reported serving as a consultant for GSK, Merck, and Pfizer, and one of her associates reported ties to Novartis Vaccines, GSK, Protein Sciences, and Merck.
FROM THE LANCET
Key clinical point:
Major finding: The adjusted estimate for the effectiveness of the MeNZB vaccine against cases of gonorrhea was 31%.
Data source: A retrospective case-control study involving 14,730 patients at 11 sexual health clinics across New Zealand.
Disclosures: This study was funded by GlaxoSmithKline Vaccines and Auckland UniServices. Dr. Petousis-Harris reported serving as a consultant for GSK, Merck, and Pfizer, and one of her associates reported ties to Novartis Vaccines, GSK, Protein Sciences, and Merck.
ABS offers a new path to board certification
The American Board of Surgery announced a revised and reformulated path for surgeons to board certification that will replace the current Maintenance of Certification process now in place.
The new program will offer surgeons greater flexibility and more practice-relevant options to achieve lifelong learning in their field and continuous board certification. The ABS based the program on feedback from diplomates (ABS-certified surgeons) including the findings from a 2016 survey sent to 5,000 diplomates.
Effective immediately, diplomates will be asked to report their professional standing, CME activities, and practice assessment participation every 5 years, rather than every 3 years. All diplomates will have their current reporting cycle extended by 2 years. The self-assessment CME requirement has been has been reduced by half. For 2018, more options for recertification will be offered with a greater focus on ongoing, high-value, and practice-relevant learning. The current 10-year interval recertification examination will continue to be offered for those who choose it. Input from diplomates will be sought in the coming months to provide input on the new program.
Find the full statement at http://www.absurgery.org/default.jsp?news_mocchange0717.
The American Board of Surgery announced a revised and reformulated path for surgeons to board certification that will replace the current Maintenance of Certification process now in place.
The new program will offer surgeons greater flexibility and more practice-relevant options to achieve lifelong learning in their field and continuous board certification. The ABS based the program on feedback from diplomates (ABS-certified surgeons) including the findings from a 2016 survey sent to 5,000 diplomates.
Effective immediately, diplomates will be asked to report their professional standing, CME activities, and practice assessment participation every 5 years, rather than every 3 years. All diplomates will have their current reporting cycle extended by 2 years. The self-assessment CME requirement has been has been reduced by half. For 2018, more options for recertification will be offered with a greater focus on ongoing, high-value, and practice-relevant learning. The current 10-year interval recertification examination will continue to be offered for those who choose it. Input from diplomates will be sought in the coming months to provide input on the new program.
Find the full statement at http://www.absurgery.org/default.jsp?news_mocchange0717.
The American Board of Surgery announced a revised and reformulated path for surgeons to board certification that will replace the current Maintenance of Certification process now in place.
The new program will offer surgeons greater flexibility and more practice-relevant options to achieve lifelong learning in their field and continuous board certification. The ABS based the program on feedback from diplomates (ABS-certified surgeons) including the findings from a 2016 survey sent to 5,000 diplomates.
Effective immediately, diplomates will be asked to report their professional standing, CME activities, and practice assessment participation every 5 years, rather than every 3 years. All diplomates will have their current reporting cycle extended by 2 years. The self-assessment CME requirement has been has been reduced by half. For 2018, more options for recertification will be offered with a greater focus on ongoing, high-value, and practice-relevant learning. The current 10-year interval recertification examination will continue to be offered for those who choose it. Input from diplomates will be sought in the coming months to provide input on the new program.
Find the full statement at http://www.absurgery.org/default.jsp?news_mocchange0717.
Algorithm for identifying IPF has low PPV
ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.
“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.
The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).
Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.
The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.
“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.
To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.
Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.
“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.
The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.
“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.
The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
This study glaringly displays potential problems with using ICD codes for research purposes and calls into question results from a handful of studies that yielded epidemiological estimates for idiopathic pulmonary fibrosis. We are reminded that practitioner-generated diagnostic codes of IPF recorded in the medical record are subject to inaccuracies, which can be illuminated by the “gold standard” – multidisciplinary adjudication.
Moving forward, particularly as longitudinal, nationwide IPF registries come online, patient-level case validation should be employed. As we move into the era of ICD-10, the study should serve as a call to improve IPF case ascertainment accuracy for any investigators choosing to use large data analytic strategies. Doing so will mute the background noise and allow us to better hear the signals of this complex disease.
Evans R. Fernandez Perez, MD, is a pulmonologist at National Jewish Health, Denver. He made his comments in an editorial, and reported speaker’s fees from Boehringer Ingelheim and Genentech (Ann Am Thorac Soc. 2017 Jun;14[6]:829-30).
This study glaringly displays potential problems with using ICD codes for research purposes and calls into question results from a handful of studies that yielded epidemiological estimates for idiopathic pulmonary fibrosis. We are reminded that practitioner-generated diagnostic codes of IPF recorded in the medical record are subject to inaccuracies, which can be illuminated by the “gold standard” – multidisciplinary adjudication.
Moving forward, particularly as longitudinal, nationwide IPF registries come online, patient-level case validation should be employed. As we move into the era of ICD-10, the study should serve as a call to improve IPF case ascertainment accuracy for any investigators choosing to use large data analytic strategies. Doing so will mute the background noise and allow us to better hear the signals of this complex disease.
Evans R. Fernandez Perez, MD, is a pulmonologist at National Jewish Health, Denver. He made his comments in an editorial, and reported speaker’s fees from Boehringer Ingelheim and Genentech (Ann Am Thorac Soc. 2017 Jun;14[6]:829-30).
This study glaringly displays potential problems with using ICD codes for research purposes and calls into question results from a handful of studies that yielded epidemiological estimates for idiopathic pulmonary fibrosis. We are reminded that practitioner-generated diagnostic codes of IPF recorded in the medical record are subject to inaccuracies, which can be illuminated by the “gold standard” – multidisciplinary adjudication.
Moving forward, particularly as longitudinal, nationwide IPF registries come online, patient-level case validation should be employed. As we move into the era of ICD-10, the study should serve as a call to improve IPF case ascertainment accuracy for any investigators choosing to use large data analytic strategies. Doing so will mute the background noise and allow us to better hear the signals of this complex disease.
Evans R. Fernandez Perez, MD, is a pulmonologist at National Jewish Health, Denver. He made his comments in an editorial, and reported speaker’s fees from Boehringer Ingelheim and Genentech (Ann Am Thorac Soc. 2017 Jun;14[6]:829-30).
ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.
“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.
The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).
Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.
The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.
“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.
To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.
Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.
“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.
The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.
“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.
The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
ICD-9 codes were poor at picking out idiopathic pulmonary fibrosis patients from administrative databases for epidemiologic studies, but a new tool could improve diagnostic accuracy, according to Kaiser Permanente and University of California, San Francisco (UCSF), investigators.
“In the age of large administrative databases and electronic medical records, there is rich opportunity to conduct population-based studies” of disease behavior, outcomes, health care use, and other matters, but researchers first need to be able to accurately identify patients with idiopathic pulmonary fibrosis (IPF) in large data sets, said investigators led by Brett Ley, MD, an assistant professor of medicine at UCSF.
The research community has traditionally relied on claims for specific IPF diagnostic codes – ICD-9 code 516.3 or ICD-9-CM code 516.31 – to identify patients, but the approach had never been validated. To see how well it works, the investigators applied it to the nearly 5.4 million adults in the Kaiser Permanente Northern California system during 2000-2014. After patients with interstitial lung disease-associated codes entered on or after the day of the last IPF code were excluded, the algorithm identified 2,608 patients as having IPF (Ann Am Thorac Soc. 2017 Jun;14[6]:880-7).
Next, the investigators randomly selected 150 of those patients and examined their medical records, procedure codes, CTs, and other patient-level data to see how many of them really had IPF. The results weren’t good. The positive predictive value of the IPF code-based algorithm was only 42.2%, with a sensitivity 55.6%.
The widely used code-based IPF algorithm does “not generate accurate estimates of IPF incidence and prevalence. ... Over half of the patients identified as having IPF ... did not have IPF on case review. Alarmingly, whereas half of the misclassified cases had an alternative [interstitial lung disease] diagnosis, the other half had no clinical or radiologic evidence of ILD [interstitial lung disease] at all.” The algorithm also “likely misses a substantial proportion of patients who do have IPF,” Dr. Ley and his colleagues said.
“We can only speculate about the reasons. ... It seems likely to be due to a combination of misdiagnosis at the clinical level and miscoding at the administrative level,” they said.
To try to improve the situation, the team tweaked the algorithm to include only patients 50 years or older who had at least two 516.3 or 516.31 claims 1 month or more apart and a chest CT procedure code beforehand. They again excluded ILD-associated claims on or after the day of the last IPF code.
Although the sensitivity of the modified algorithm was lower than the original, it had a more robust positive predictive value of 70.4% in the derivation cohort and 61.8% in the validation cohort, both derived from the 150 patients used to validate the original algorithm.
“By making a few simple, empirically derived changes to the IPF algorithm,” it’s possible to “more reliably identif[y] patients” with IPF. “We believe the modified IPF algorithm will be useful for population-based studies of IPF ... that require high diagnostic certainty,” the investigators concluded.
The traditional algorithm found an incidence of 6.8 cases per 100,000 person-years, which was on the low end of previous reports, perhaps because of the relative health and youth of the 5.4 million patient pool. As in past studies, IPF incidence increased with older age and was highest in white patients and men.
“Whether the more specific codes provided by the ICD-10 system will allow for improved case classification of IPF requires further study,” the investigators noted.
The work was funded by the National Institutes of Health. Dr. Ley reported speaker’s fees from Genentech, and one of the authors was an employee of the company. The senior author Harold Collard, MD, an associate professor in UCSF’s Division of Pulmonary and Critical Care Medicine, reported personal fees from Takeda, ImmuneWorks, Parexel, Pharma Capital Partners, and others.
FROM THE ANNALS OF THE AMERICAN THORACIC SOCIETY
Key clinical point:
Major finding: The positive predictive value of the traditional IPF code-based algorithm was only 42.2%, with a sensitivity of 55.6%.
Data source: A study including almost 5.4 million patients at Kaiser Permanente Northern California.
Disclosures: The work was funded by the National Institutes of Health. One of the investigators was a Genentech employee. Others reported speaker’s and personal fees from Genentech and other companies.
Allopurinol and ventricular arrhythmias: Is there a link?
MADRID – Newly begun allopurinol treatment of elderly patients was linked with a significantly reduced incidence of ventricular arrhythmias in a review of more than 28,000 Medicare beneficiaries.
The antiarrhythmic effect appeared to strengthen with more prolonged allopurinol treatment, reaching a 28% reduction in ventricular arrhythmia incidence among patients on allopurinol for more than 2 years, compared with patients who never received the uric acid reducer, Jasvinder A. Singh, MD, reported in a poster at the European Congress of Rheumatology.
He and his associates used data collected from more than 3 million U.S. Medicare beneficiaries during 2006-2012 from a random Medicare 5% sample. This group included 28,755 patients who began a prescription for allopurinol after not having filled a prescription for the drug during the prior 365 days. The patients averaged 77 years of age.
The outcome of interest was a new onset ventricular arrhythmia, defined as an arrhythmia episode in a patient with no prior record of arrhythmia during the previous 365 days. Arrhythmia occurred in 2,538 of the patients on new allopurinol treatment (9%).
In a multivariate analysis that compared new allopurinol users with patients without allopurinol exposure and controlled for several demographic and clinical features, allopurinol use was linked with a statistically significant 18% reduced rate of incident ventricular arrhythmias in those who recieved it, compared with similar patients who did not receive allopurinol, Dr. Singh and his associates reported.
An additional analysis looked at the relative risk reduction associated with various lengths of allopurinol use. Compared with patients not on allopurinol, those taking it for more than 2 years had a significant 28% reduced rate of arrhythmias; those on it for 6 months to 2 years had a significant 24% reduction in incident arrhythmias; and those on it for 1-180 days had no significant change in their arrhythmia incidence.
Other individual factors that significantly correlated with increased ventricular arrhythmias included older age, male sex, African American race, presence of comorbidities, and treatment with a beta-blockers. Like allopurinol, treatment with a statin linked with a significantly reduced arrhythmia incidence.
In a second, related report at the meeting, Dr. Singh and his associates used a very similar data set to see if a link existed between new-onset allopurinol treatment and a reduced incidence of peripheral artery disease. This analysis showed that allopurinol use linked with a statistically significant 12% reduction in new onset peripheral artery disease. They again found that the clinical impact of allopurinol treatment grew larger as the duration of allopurinol treatment increased.
Dr. Singh has financial ties to Allergan, Bioiberica, Crealta, Iroko, Merz, Regeneron, Savient, and Takeda.
[email protected]
On Twitter @mitchelzoler
MADRID – Newly begun allopurinol treatment of elderly patients was linked with a significantly reduced incidence of ventricular arrhythmias in a review of more than 28,000 Medicare beneficiaries.
The antiarrhythmic effect appeared to strengthen with more prolonged allopurinol treatment, reaching a 28% reduction in ventricular arrhythmia incidence among patients on allopurinol for more than 2 years, compared with patients who never received the uric acid reducer, Jasvinder A. Singh, MD, reported in a poster at the European Congress of Rheumatology.
He and his associates used data collected from more than 3 million U.S. Medicare beneficiaries during 2006-2012 from a random Medicare 5% sample. This group included 28,755 patients who began a prescription for allopurinol after not having filled a prescription for the drug during the prior 365 days. The patients averaged 77 years of age.
The outcome of interest was a new onset ventricular arrhythmia, defined as an arrhythmia episode in a patient with no prior record of arrhythmia during the previous 365 days. Arrhythmia occurred in 2,538 of the patients on new allopurinol treatment (9%).
In a multivariate analysis that compared new allopurinol users with patients without allopurinol exposure and controlled for several demographic and clinical features, allopurinol use was linked with a statistically significant 18% reduced rate of incident ventricular arrhythmias in those who recieved it, compared with similar patients who did not receive allopurinol, Dr. Singh and his associates reported.
An additional analysis looked at the relative risk reduction associated with various lengths of allopurinol use. Compared with patients not on allopurinol, those taking it for more than 2 years had a significant 28% reduced rate of arrhythmias; those on it for 6 months to 2 years had a significant 24% reduction in incident arrhythmias; and those on it for 1-180 days had no significant change in their arrhythmia incidence.
Other individual factors that significantly correlated with increased ventricular arrhythmias included older age, male sex, African American race, presence of comorbidities, and treatment with a beta-blockers. Like allopurinol, treatment with a statin linked with a significantly reduced arrhythmia incidence.
In a second, related report at the meeting, Dr. Singh and his associates used a very similar data set to see if a link existed between new-onset allopurinol treatment and a reduced incidence of peripheral artery disease. This analysis showed that allopurinol use linked with a statistically significant 12% reduction in new onset peripheral artery disease. They again found that the clinical impact of allopurinol treatment grew larger as the duration of allopurinol treatment increased.
Dr. Singh has financial ties to Allergan, Bioiberica, Crealta, Iroko, Merz, Regeneron, Savient, and Takeda.
[email protected]
On Twitter @mitchelzoler
MADRID – Newly begun allopurinol treatment of elderly patients was linked with a significantly reduced incidence of ventricular arrhythmias in a review of more than 28,000 Medicare beneficiaries.
The antiarrhythmic effect appeared to strengthen with more prolonged allopurinol treatment, reaching a 28% reduction in ventricular arrhythmia incidence among patients on allopurinol for more than 2 years, compared with patients who never received the uric acid reducer, Jasvinder A. Singh, MD, reported in a poster at the European Congress of Rheumatology.
He and his associates used data collected from more than 3 million U.S. Medicare beneficiaries during 2006-2012 from a random Medicare 5% sample. This group included 28,755 patients who began a prescription for allopurinol after not having filled a prescription for the drug during the prior 365 days. The patients averaged 77 years of age.
The outcome of interest was a new onset ventricular arrhythmia, defined as an arrhythmia episode in a patient with no prior record of arrhythmia during the previous 365 days. Arrhythmia occurred in 2,538 of the patients on new allopurinol treatment (9%).
In a multivariate analysis that compared new allopurinol users with patients without allopurinol exposure and controlled for several demographic and clinical features, allopurinol use was linked with a statistically significant 18% reduced rate of incident ventricular arrhythmias in those who recieved it, compared with similar patients who did not receive allopurinol, Dr. Singh and his associates reported.
An additional analysis looked at the relative risk reduction associated with various lengths of allopurinol use. Compared with patients not on allopurinol, those taking it for more than 2 years had a significant 28% reduced rate of arrhythmias; those on it for 6 months to 2 years had a significant 24% reduction in incident arrhythmias; and those on it for 1-180 days had no significant change in their arrhythmia incidence.
Other individual factors that significantly correlated with increased ventricular arrhythmias included older age, male sex, African American race, presence of comorbidities, and treatment with a beta-blockers. Like allopurinol, treatment with a statin linked with a significantly reduced arrhythmia incidence.
In a second, related report at the meeting, Dr. Singh and his associates used a very similar data set to see if a link existed between new-onset allopurinol treatment and a reduced incidence of peripheral artery disease. This analysis showed that allopurinol use linked with a statistically significant 12% reduction in new onset peripheral artery disease. They again found that the clinical impact of allopurinol treatment grew larger as the duration of allopurinol treatment increased.
Dr. Singh has financial ties to Allergan, Bioiberica, Crealta, Iroko, Merz, Regeneron, Savient, and Takeda.
[email protected]
On Twitter @mitchelzoler
AT THE EULAR 2017 CONGRESS
Key clinical point:
Major finding: Patients on allopurinol for more than 2 years had a 28% reduced rate of ventricular arrhythmias, compared with those not on allopurinol treatment.
Data source: A 5% random sample of Medicare beneficiaries during 2006-2012.
Disclosures: Dr. Singh has been a consultant to Allergan, Bioiberica, Crealta, Iroko, Merz, Regeneron, Savient, and Takeda and has received research support from Savient and Takeda.
Optimal age for cardiovascular disease screening remains elusive
SAN FRANCISCO – In the United States, deaths from cardiovascular disease fell by about 50% in men and women between 1980 and 2000, and fell an additional 31% between 2000 and 2010, according to Robert Baron, MD.
That’s the good news, driven largely by the introduction of statin therapy and by risk-factor modifications. The not-so-great news? The optimal screening age for CVD risk remains elusive.
“We’ve been arguing about this for at least 30 years,” he said at the UCSF Annual Advances in Internal Medicine.
The 2013 American College of Cardiology/American Heart Association Guideline on the Assessment of Cardiovascular Risk recommends screening at age 21 years to identify those with an LDL cholesterol level greater than 190 mg/dL, while a more recent draft recommendation statement from the United States Preventive Services Task Force (USPSTF) recommends screening at age 35 in men and 45 in women for most cases, or at age 20 in people deemed to be at increased risk. Both sets of guidelines recommend the use of statins in patients with atherosclerotic cardiovascular disease, and LDL of 190 mg/dL or greater, and/or diabetes.
“In essence, the USPSTF guidelines are saying definitely use statins for primary prevention in high-risk people; they’re just creating a little more gray area as to what exactly constitutes high risk,” said Dr. Baron, an internist who is associate dean at UCSF Medical Center, San Francisco. “The question is, how do you draw the line? I would argue that depends on the patient preference.”
In a recently published analysis, researchers set out to determine how the USPSTF guidelines compare with the ACC/AHA guidelines in terms of the proportion of U.S. adults potentially treated (JAMA. 2017 Apr 18; 317[15]:1563-7). After using estimates based on data from 3,416 participants in the 2009-2014 National Health and Nutrition Examination Survey, the researchers found that USPSTF recommendations would be associated with statin initiation in 16% of U.S. adults aged 40-75 years without prior CVD, compared with 24% according to the ACC/AHA guidelines.
Among those adults for whom therapy would no longer be recommended under the USPSTF recommendations, 55% are aged 40-59 years with a mean 30-year cardiovascular risk exceeding 30%, and 28% have diabetes. According to Dr. Baron, the comparison “reinforces the primary prevention message. It gives the patient a bit more flexibility.”
After starting patients on a statin, the best available evidence recommends monitoring adherence but not treating to a specific LDL goal, he said. Statins should not be used in patients older than age 75 unless they have existing ASCVD. The addition of other lipid-modifying drugs is generally not recommended, but it may be needed in patients who demonstrate intolerance to statins. Patients should also avoid using NSAIDS, which raise CVD risk, and instead use medications that lower it, such as aspirin, he said.
Dr. Baron reported having no relevant financial disclosures.
SAN FRANCISCO – In the United States, deaths from cardiovascular disease fell by about 50% in men and women between 1980 and 2000, and fell an additional 31% between 2000 and 2010, according to Robert Baron, MD.
That’s the good news, driven largely by the introduction of statin therapy and by risk-factor modifications. The not-so-great news? The optimal screening age for CVD risk remains elusive.
“We’ve been arguing about this for at least 30 years,” he said at the UCSF Annual Advances in Internal Medicine.
The 2013 American College of Cardiology/American Heart Association Guideline on the Assessment of Cardiovascular Risk recommends screening at age 21 years to identify those with an LDL cholesterol level greater than 190 mg/dL, while a more recent draft recommendation statement from the United States Preventive Services Task Force (USPSTF) recommends screening at age 35 in men and 45 in women for most cases, or at age 20 in people deemed to be at increased risk. Both sets of guidelines recommend the use of statins in patients with atherosclerotic cardiovascular disease, and LDL of 190 mg/dL or greater, and/or diabetes.
“In essence, the USPSTF guidelines are saying definitely use statins for primary prevention in high-risk people; they’re just creating a little more gray area as to what exactly constitutes high risk,” said Dr. Baron, an internist who is associate dean at UCSF Medical Center, San Francisco. “The question is, how do you draw the line? I would argue that depends on the patient preference.”
In a recently published analysis, researchers set out to determine how the USPSTF guidelines compare with the ACC/AHA guidelines in terms of the proportion of U.S. adults potentially treated (JAMA. 2017 Apr 18; 317[15]:1563-7). After using estimates based on data from 3,416 participants in the 2009-2014 National Health and Nutrition Examination Survey, the researchers found that USPSTF recommendations would be associated with statin initiation in 16% of U.S. adults aged 40-75 years without prior CVD, compared with 24% according to the ACC/AHA guidelines.
Among those adults for whom therapy would no longer be recommended under the USPSTF recommendations, 55% are aged 40-59 years with a mean 30-year cardiovascular risk exceeding 30%, and 28% have diabetes. According to Dr. Baron, the comparison “reinforces the primary prevention message. It gives the patient a bit more flexibility.”
After starting patients on a statin, the best available evidence recommends monitoring adherence but not treating to a specific LDL goal, he said. Statins should not be used in patients older than age 75 unless they have existing ASCVD. The addition of other lipid-modifying drugs is generally not recommended, but it may be needed in patients who demonstrate intolerance to statins. Patients should also avoid using NSAIDS, which raise CVD risk, and instead use medications that lower it, such as aspirin, he said.
Dr. Baron reported having no relevant financial disclosures.
SAN FRANCISCO – In the United States, deaths from cardiovascular disease fell by about 50% in men and women between 1980 and 2000, and fell an additional 31% between 2000 and 2010, according to Robert Baron, MD.
That’s the good news, driven largely by the introduction of statin therapy and by risk-factor modifications. The not-so-great news? The optimal screening age for CVD risk remains elusive.
“We’ve been arguing about this for at least 30 years,” he said at the UCSF Annual Advances in Internal Medicine.
The 2013 American College of Cardiology/American Heart Association Guideline on the Assessment of Cardiovascular Risk recommends screening at age 21 years to identify those with an LDL cholesterol level greater than 190 mg/dL, while a more recent draft recommendation statement from the United States Preventive Services Task Force (USPSTF) recommends screening at age 35 in men and 45 in women for most cases, or at age 20 in people deemed to be at increased risk. Both sets of guidelines recommend the use of statins in patients with atherosclerotic cardiovascular disease, and LDL of 190 mg/dL or greater, and/or diabetes.
“In essence, the USPSTF guidelines are saying definitely use statins for primary prevention in high-risk people; they’re just creating a little more gray area as to what exactly constitutes high risk,” said Dr. Baron, an internist who is associate dean at UCSF Medical Center, San Francisco. “The question is, how do you draw the line? I would argue that depends on the patient preference.”
In a recently published analysis, researchers set out to determine how the USPSTF guidelines compare with the ACC/AHA guidelines in terms of the proportion of U.S. adults potentially treated (JAMA. 2017 Apr 18; 317[15]:1563-7). After using estimates based on data from 3,416 participants in the 2009-2014 National Health and Nutrition Examination Survey, the researchers found that USPSTF recommendations would be associated with statin initiation in 16% of U.S. adults aged 40-75 years without prior CVD, compared with 24% according to the ACC/AHA guidelines.
Among those adults for whom therapy would no longer be recommended under the USPSTF recommendations, 55% are aged 40-59 years with a mean 30-year cardiovascular risk exceeding 30%, and 28% have diabetes. According to Dr. Baron, the comparison “reinforces the primary prevention message. It gives the patient a bit more flexibility.”
After starting patients on a statin, the best available evidence recommends monitoring adherence but not treating to a specific LDL goal, he said. Statins should not be used in patients older than age 75 unless they have existing ASCVD. The addition of other lipid-modifying drugs is generally not recommended, but it may be needed in patients who demonstrate intolerance to statins. Patients should also avoid using NSAIDS, which raise CVD risk, and instead use medications that lower it, such as aspirin, he said.
Dr. Baron reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM THE ANNUAL ADVANCES IN INTERNAL MEDICINE
Higher ADHD risk seen in children with migraine
BOSTON – Children aged 5-12 years with signs of migraine headache were as much as seven times as likely as other children to also appear to have attention-deficit/hyperactivity disorder (ADHD), but those with tension-type headaches didn’t face a higher risk of ADHD, a Brazilian study showed.
It’s not clear why the apparent link between migraines and ADHD exists. However, lead study author Marco Antônio Arruda, MD, PhD, a pediatric neurologist in São Paulo (Brazil) University, said in an interview that other research has linked migraine to mental health problems.
The study, presented at the annual meeting of the American Academy of Neurology and published online in the Journal of Attention Disorders (2017. doi: 10.1177/1087054717710767), was launched to better understand the connection between migraine and ADHD, which are thought to each affect as many as 1 in 10 children.
The study analyzes data from mothers and teachers of 5,671 children aged 5-12 years who answered questions as part of a Brazil-wide epidemiologic study called the Attention Brazil Project. Just over half of the participants were boys, and about half were from the Brazilian middle class.
Based on answers from mothers and teachers, the researchers estimated that 9% of the children had episodic migraine and 0.6% had chronic migraine. The level of episodic tension-type headache was estimated at 12.8%, with a lower rate in the two poorest vs. the two richest quintiles (8.6% vs. 14.4%, respectively; relative risk, 0.6; 95% confidence interval, 0.5-0.8).
The researchers estimated that 5.3% of the children overall showed signs of ADHD (7.5% in boys vs. 3.1% in girls; RR, 2.4; 95% CI, 1.9-3.1).
There was no sign that children with tension-type headaches had a significantly higher risk of ADHD than other children. However, compared with controls, those with various types of migraine headaches did have a higher risk of ADHD. Nearly 11% of those with migraine overall showed signs of ADHD, compared with 2.6% of the control group (RR, 4.1; 95% CI, 2.7-6.2). The numbers for episodic migraine were nearly identical to those for migraine overall: 10.2% vs. 2.6% (RR, 3.8; 95% CI, 2.5-5.9).
Just over 19% of kids in a third migraine group – those with chronic migraine, defined as headaches appearing more than 14 days per month for the last 3 months – showed signs of ADHD, compared with just 2.6% of the control group (RR = 7.3; 95% CI, 3.5-15.5).
“A number of risk factors to the association were identified, including male gender, prenatal exposure to tobacco, high headache frequency, and below average school performance,” Dr. Arruda said. “However, we did not find a significant influence of age, race, city density, national region where a child lives, income class, and prenatal exposure to alcohol in the comorbidity of ADHD and migraine in this sample. These results help us to identify risk groups allowing early interventions.”
Regarding an explanation for the links between migraines and ADHD, Dr. Arruda pointed to genetic and epigenetic factors that affect brain neurotransmitters and said he believes that stress and other stimuli could be influencing dopamine and noradrenergic processes.
Dr. Arruda said his next step is to examine whether stimulant drugs – the class used to treat ADHD – may help reduce headaches too.
“My clinical experience strongly indicates that psychostimulants have a highly positive effect on migraine prophylaxis, although headache occurs in the very beginning of the treatment,” Dr. Arruda said. “So, we are looking for financial support to conduct a randomized, double-blind, placebo control study to check this hypothesis.”
The study received no specific funding, and Dr. Arruda reported no relevant financial disclosures.
BOSTON – Children aged 5-12 years with signs of migraine headache were as much as seven times as likely as other children to also appear to have attention-deficit/hyperactivity disorder (ADHD), but those with tension-type headaches didn’t face a higher risk of ADHD, a Brazilian study showed.
It’s not clear why the apparent link between migraines and ADHD exists. However, lead study author Marco Antônio Arruda, MD, PhD, a pediatric neurologist in São Paulo (Brazil) University, said in an interview that other research has linked migraine to mental health problems.
The study, presented at the annual meeting of the American Academy of Neurology and published online in the Journal of Attention Disorders (2017. doi: 10.1177/1087054717710767), was launched to better understand the connection between migraine and ADHD, which are thought to each affect as many as 1 in 10 children.
The study analyzes data from mothers and teachers of 5,671 children aged 5-12 years who answered questions as part of a Brazil-wide epidemiologic study called the Attention Brazil Project. Just over half of the participants were boys, and about half were from the Brazilian middle class.
Based on answers from mothers and teachers, the researchers estimated that 9% of the children had episodic migraine and 0.6% had chronic migraine. The level of episodic tension-type headache was estimated at 12.8%, with a lower rate in the two poorest vs. the two richest quintiles (8.6% vs. 14.4%, respectively; relative risk, 0.6; 95% confidence interval, 0.5-0.8).
The researchers estimated that 5.3% of the children overall showed signs of ADHD (7.5% in boys vs. 3.1% in girls; RR, 2.4; 95% CI, 1.9-3.1).
There was no sign that children with tension-type headaches had a significantly higher risk of ADHD than other children. However, compared with controls, those with various types of migraine headaches did have a higher risk of ADHD. Nearly 11% of those with migraine overall showed signs of ADHD, compared with 2.6% of the control group (RR, 4.1; 95% CI, 2.7-6.2). The numbers for episodic migraine were nearly identical to those for migraine overall: 10.2% vs. 2.6% (RR, 3.8; 95% CI, 2.5-5.9).
Just over 19% of kids in a third migraine group – those with chronic migraine, defined as headaches appearing more than 14 days per month for the last 3 months – showed signs of ADHD, compared with just 2.6% of the control group (RR = 7.3; 95% CI, 3.5-15.5).
“A number of risk factors to the association were identified, including male gender, prenatal exposure to tobacco, high headache frequency, and below average school performance,” Dr. Arruda said. “However, we did not find a significant influence of age, race, city density, national region where a child lives, income class, and prenatal exposure to alcohol in the comorbidity of ADHD and migraine in this sample. These results help us to identify risk groups allowing early interventions.”
Regarding an explanation for the links between migraines and ADHD, Dr. Arruda pointed to genetic and epigenetic factors that affect brain neurotransmitters and said he believes that stress and other stimuli could be influencing dopamine and noradrenergic processes.
Dr. Arruda said his next step is to examine whether stimulant drugs – the class used to treat ADHD – may help reduce headaches too.
“My clinical experience strongly indicates that psychostimulants have a highly positive effect on migraine prophylaxis, although headache occurs in the very beginning of the treatment,” Dr. Arruda said. “So, we are looking for financial support to conduct a randomized, double-blind, placebo control study to check this hypothesis.”
The study received no specific funding, and Dr. Arruda reported no relevant financial disclosures.
BOSTON – Children aged 5-12 years with signs of migraine headache were as much as seven times as likely as other children to also appear to have attention-deficit/hyperactivity disorder (ADHD), but those with tension-type headaches didn’t face a higher risk of ADHD, a Brazilian study showed.
It’s not clear why the apparent link between migraines and ADHD exists. However, lead study author Marco Antônio Arruda, MD, PhD, a pediatric neurologist in São Paulo (Brazil) University, said in an interview that other research has linked migraine to mental health problems.
The study, presented at the annual meeting of the American Academy of Neurology and published online in the Journal of Attention Disorders (2017. doi: 10.1177/1087054717710767), was launched to better understand the connection between migraine and ADHD, which are thought to each affect as many as 1 in 10 children.
The study analyzes data from mothers and teachers of 5,671 children aged 5-12 years who answered questions as part of a Brazil-wide epidemiologic study called the Attention Brazil Project. Just over half of the participants were boys, and about half were from the Brazilian middle class.
Based on answers from mothers and teachers, the researchers estimated that 9% of the children had episodic migraine and 0.6% had chronic migraine. The level of episodic tension-type headache was estimated at 12.8%, with a lower rate in the two poorest vs. the two richest quintiles (8.6% vs. 14.4%, respectively; relative risk, 0.6; 95% confidence interval, 0.5-0.8).
The researchers estimated that 5.3% of the children overall showed signs of ADHD (7.5% in boys vs. 3.1% in girls; RR, 2.4; 95% CI, 1.9-3.1).
There was no sign that children with tension-type headaches had a significantly higher risk of ADHD than other children. However, compared with controls, those with various types of migraine headaches did have a higher risk of ADHD. Nearly 11% of those with migraine overall showed signs of ADHD, compared with 2.6% of the control group (RR, 4.1; 95% CI, 2.7-6.2). The numbers for episodic migraine were nearly identical to those for migraine overall: 10.2% vs. 2.6% (RR, 3.8; 95% CI, 2.5-5.9).
Just over 19% of kids in a third migraine group – those with chronic migraine, defined as headaches appearing more than 14 days per month for the last 3 months – showed signs of ADHD, compared with just 2.6% of the control group (RR = 7.3; 95% CI, 3.5-15.5).
“A number of risk factors to the association were identified, including male gender, prenatal exposure to tobacco, high headache frequency, and below average school performance,” Dr. Arruda said. “However, we did not find a significant influence of age, race, city density, national region where a child lives, income class, and prenatal exposure to alcohol in the comorbidity of ADHD and migraine in this sample. These results help us to identify risk groups allowing early interventions.”
Regarding an explanation for the links between migraines and ADHD, Dr. Arruda pointed to genetic and epigenetic factors that affect brain neurotransmitters and said he believes that stress and other stimuli could be influencing dopamine and noradrenergic processes.
Dr. Arruda said his next step is to examine whether stimulant drugs – the class used to treat ADHD – may help reduce headaches too.
“My clinical experience strongly indicates that psychostimulants have a highly positive effect on migraine prophylaxis, although headache occurs in the very beginning of the treatment,” Dr. Arruda said. “So, we are looking for financial support to conduct a randomized, double-blind, placebo control study to check this hypothesis.”
The study received no specific funding, and Dr. Arruda reported no relevant financial disclosures.
AT AAN 2017
Key clinical point: , but there’s no excess risk in children with tension-type headaches.
Major finding: Of children with chronic migraine, 19.4% (0.6% of the total) showed signs of ADHD, vs. 2.6% of the control group (RR, 7.3; 95% CI, 3.5-15.5).
Data source: Surveys of mothers and teachers of 5,671 Brazilian children aged 5-12 years.
Disclosures: The study received no specific funding, and Dr. Arruda reported no relevant financial disclosures.