Between 20% and 40% of patients with multiple myeloma (MM) have renal impairment and also may take drugs that raise the risk of venous thromboembolism (VTE). Do those factors contribute to a higher risk of arterial thrombosis in this patient group? Researchers from the University of Arkansas and Ohio State University conducted a large, retrospective, comparative case control study to find out.

Related:  Treating Patients With Multiple Myeloma in the VA

Patients were enrolled in Total Therapy protocols (TT2, TT3a, and TT3b), which tested varying combinations of thalidomide, bortezomib, lenalidomide, and dexamethasone. Of 1,148 patients, 46 (4%) had strokes, usually ischemic stroke (33 patients, or 72%). Hypercoagulability, atrial fibrillation and small-vessel occlusion were common mechanisms. Whereas other research has found a higher risk of arterial thrombosis from activated prothrombotic factors, especially during the early period of chemotherapy, in this study vascular events occurred months later.

Seven patients died in the hospital (15% compared with a national average of 5%). Although 6 of those deaths were stroke related, 36 patients  were discharged home or to a rehabilitation facility; 2 were discharged to a long-term nursing facility. During a median follow-up of 10 years, 6 patients had another stroke. The cumulative risk of recurrent stroke was 15% compared with 5% for the general population.

Related:  Link Found Between Agent Orange Exposure and Multiple Myeloma

Stage I and II cancers and renal insufficiency independently predicted stroke. Also noteworthy, according to the researchers: Patients with MM who developed renal insufficiency had worse clinical outcomes despite improvement in their renal function or lack of significant difference in their baseline renal functions between various treatment protocols. Thus, the increased risk of stroke, recurrent stroke, and mortality could partly be due to renal disease, which may or may not have resulted from myeloma.

Use of combination chemotherapy has “markedly improved” clinical outcomes for MM patients, the researchers say, but those drugs have also been associated with an increased risk of VTE, especially during the first months of chemotherapy. Thalidomide alone did not increase the risk of VTE, nor did lenalinomide on its own. However, thalidomide combined with multiagent chemotherapy increased VTE risk as much as 34% in newly diagnosed patients, and lenalinomide with dexamethasone boosted risk as high as 75%.

The researchers found no significant relationship between mortality and use of thalidomide. Median survival was 103 months for a thalidomide-based regimen and 78 months for a regimen without thalidomide.

Related: Multiple Myeloma: Updates on Diagnosis and Management

The researchers noted that the patients developed strokes despite a trend toward coagulopathy, to the extent that half were ineligible for immediate use of antiplatelet agents. The study findings “heightened our awareness,” the researchers say, that aggressive preventive measures can help reduce the incidence of stroke in patients with renal insufficiency.

Source:
Hinduja A, Limaye K, Ravilla R, et al. PLoS One. 2016;11(11): e0166627.
doi: 10.1371/journal.pone.0166627.

Between 20% and 40% of patients with multiple myeloma (MM) have renal impairment and also may take drugs that raise the risk of venous thromboembolism (VTE). Do those factors contribute to a higher risk of arterial thrombosis in this patient group? Researchers from the University of Arkansas and Ohio State University conducted a large, retrospective, comparative case control study to find out.

Related:  Treating Patients With Multiple Myeloma in the VA

Patients were enrolled in Total Therapy protocols (TT2, TT3a, and TT3b), which tested varying combinations of thalidomide, bortezomib, lenalidomide, and dexamethasone. Of 1,148 patients, 46 (4%) had strokes, usually ischemic stroke (33 patients, or 72%). Hypercoagulability, atrial fibrillation and small-vessel occlusion were common mechanisms. Whereas other research has found a higher risk of arterial thrombosis from activated prothrombotic factors, especially during the early period of chemotherapy, in this study vascular events occurred months later.

Seven patients died in the hospital (15% compared with a national average of 5%). Although 6 of those deaths were stroke related, 36 patients  were discharged home or to a rehabilitation facility; 2 were discharged to a long-term nursing facility. During a median follow-up of 10 years, 6 patients had another stroke. The cumulative risk of recurrent stroke was 15% compared with 5% for the general population.

Related:  Link Found Between Agent Orange Exposure and Multiple Myeloma

Stage I and II cancers and renal insufficiency independently predicted stroke. Also noteworthy, according to the researchers: Patients with MM who developed renal insufficiency had worse clinical outcomes despite improvement in their renal function or lack of significant difference in their baseline renal functions between various treatment protocols. Thus, the increased risk of stroke, recurrent stroke, and mortality could partly be due to renal disease, which may or may not have resulted from myeloma.

Use of combination chemotherapy has “markedly improved” clinical outcomes for MM patients, the researchers say, but those drugs have also been associated with an increased risk of VTE, especially during the first months of chemotherapy. Thalidomide alone did not increase the risk of VTE, nor did lenalinomide on its own. However, thalidomide combined with multiagent chemotherapy increased VTE risk as much as 34% in newly diagnosed patients, and lenalinomide with dexamethasone boosted risk as high as 75%.

The researchers found no significant relationship between mortality and use of thalidomide. Median survival was 103 months for a thalidomide-based regimen and 78 months for a regimen without thalidomide.

Related: Multiple Myeloma: Updates on Diagnosis and Management

The researchers noted that the patients developed strokes despite a trend toward coagulopathy, to the extent that half were ineligible for immediate use of antiplatelet agents. The study findings “heightened our awareness,” the researchers say, that aggressive preventive measures can help reduce the incidence of stroke in patients with renal insufficiency.

Source:
Hinduja A, Limaye K, Ravilla R, et al. PLoS One. 2016;11(11): e0166627.
doi: 10.1371/journal.pone.0166627.

Between 20% and 40% of patients with multiple myeloma (MM) have renal impairment and also may take drugs that raise the risk of venous thromboembolism (VTE). Do those factors contribute to a higher risk of arterial thrombosis in this patient group? Researchers from the University of Arkansas and Ohio State University conducted a large, retrospective, comparative case control study to find out.

Related:  Treating Patients With Multiple Myeloma in the VA

Patients were enrolled in Total Therapy protocols (TT2, TT3a, and TT3b), which tested varying combinations of thalidomide, bortezomib, lenalidomide, and dexamethasone. Of 1,148 patients, 46 (4%) had strokes, usually ischemic stroke (33 patients, or 72%). Hypercoagulability, atrial fibrillation and small-vessel occlusion were common mechanisms. Whereas other research has found a higher risk of arterial thrombosis from activated prothrombotic factors, especially during the early period of chemotherapy, in this study vascular events occurred months later.

Seven patients died in the hospital (15% compared with a national average of 5%). Although 6 of those deaths were stroke related, 36 patients  were discharged home or to a rehabilitation facility; 2 were discharged to a long-term nursing facility. During a median follow-up of 10 years, 6 patients had another stroke. The cumulative risk of recurrent stroke was 15% compared with 5% for the general population.

Related:  Link Found Between Agent Orange Exposure and Multiple Myeloma

Stage I and II cancers and renal insufficiency independently predicted stroke. Also noteworthy, according to the researchers: Patients with MM who developed renal insufficiency had worse clinical outcomes despite improvement in their renal function or lack of significant difference in their baseline renal functions between various treatment protocols. Thus, the increased risk of stroke, recurrent stroke, and mortality could partly be due to renal disease, which may or may not have resulted from myeloma.

Use of combination chemotherapy has “markedly improved” clinical outcomes for MM patients, the researchers say, but those drugs have also been associated with an increased risk of VTE, especially during the first months of chemotherapy. Thalidomide alone did not increase the risk of VTE, nor did lenalinomide on its own. However, thalidomide combined with multiagent chemotherapy increased VTE risk as much as 34% in newly diagnosed patients, and lenalinomide with dexamethasone boosted risk as high as 75%.

The researchers found no significant relationship between mortality and use of thalidomide. Median survival was 103 months for a thalidomide-based regimen and 78 months for a regimen without thalidomide.

Related: Multiple Myeloma: Updates on Diagnosis and Management

The researchers noted that the patients developed strokes despite a trend toward coagulopathy, to the extent that half were ineligible for immediate use of antiplatelet agents. The study findings “heightened our awareness,” the researchers say, that aggressive preventive measures can help reduce the incidence of stroke in patients with renal insufficiency.

Source:
Hinduja A, Limaye K, Ravilla R, et al. PLoS One. 2016;11(11): e0166627.
doi: 10.1371/journal.pone.0166627.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics 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.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics 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.

Micrograph showing CLL

The US Food and Drug Administration (FDA) has granted orphan drug designation for the combination of TG-1101 (ublituximab) and TGR-1202 for the treatment of patients with chronic lymphocytic leukemia (CLL).

Ublituximab is a glycoengineered anti-CD20 monoclonal antibody, and TGR-1202 is a next-generation PI3K delta inhibitor. Both drugs are being developed by TG Therapeutics, Inc.

Researchers have evaluated ublituximab and TGR-1202 in combination in a phase 1 trial of patients with relapsed or refractory CLL/small lymphocytic lymphoma (SLL) and non-Hodgkin lymphomas (NHLs).

Results were presented at the 2015 ASH Annual Meeting.

There was a 3+3 dose-escalation portion of the study and a dose-expansion phase. The patients received  TGR-1202 at doses ranging from 400 mg to 1200 mg and 2 different doses of ublituximab—900 mg for patients with NHL and 600 mg or 900 mg for patients with CLL/SLL.

As of ASH, there were 58 patients evaluable for efficacy and 71 evaluable for safety.

There were 10 CLL/SLL patients exposed to higher doses of TGR-1202. Among these patients, the overall response rate was 80%. Seven patients achieved a partial response, 1 achieved a complete response, and the remaining 2 patients had stable disease.

For the entire safety population, the most common adverse events were nausea (46%), diarrhea (44%), fatigue (41%), neutropenia (30%), and infusion-related reactions (25%).

Grade 3/4 adverse events included neutropenia (25%), diarrhea (3%), fatigue (3%), dyspnea (3%), pyrexia (3%), nausea (1%), infusion-related reactions (1%), sinusitis (1%), anemia (1%), hypophosphatemia (1%), and peripheral edema (1%). 

Now, the combination of ublituximab and TGR-1202 is being evaluated in the UNITY-CLL phase 3 trial for patients with previously treated or untreated CLL.

“[W]ith enrollment into our UNITY-CLL phase 3 trial currently exceeding our expectations, we expect to be able to commence a regulatory filing for the combination in 2018, and having orphan drug designation will provide certain cost-saving advantages for us during the regulatory approval process,” said Michael S. Weiss, executive chairman and chief executive officer of TG Therapeutics. 

The FDA grants orphan designation to drugs and biologics 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.

Micrograph showing TTP
Image by Erhabor Osaro

SAN DIEGO—The US Thrombotic Microangiopathies (USTMA) Consortium is planning a longitudinal study to identify biomarkers of relapse and neurocognitive dysfunction in acquired thrombotic thrombocytopenic purpura (TTP).

Earlier studies suggested that ADAMTS13 activity during remission has

limited utility in estimating relapse risk, and cognitive dysfunction

observed in TTP appears to be progressive and independent of relapses.

However, these studies were small with minimal longitudinal data.

Now, the USTMA Consortium, with 13 large referral centers for thrombotic microangiopathies (TMAs) in the US, is providing “the infrastructure for larger US studies in TTP with the goal of improving outcomes in TMAs,” said Marshall A. Mazepa, MD, of the University of Minnesota in Minneapolis.

He described the efforts of the consortium and its plans to conduct a long-term study at the first TTP-TMA Workshop, which took place immediately before the 2016 ASH Annual Meeting.

Dr Mazepa said the objective of the study is to identify biomarkers that

predict the danger period for neurocognitive dysfunction and relapse.

“Hematologists usually do not realize the

neurocognitive dysfunction among patients with TTP, and it is important

that they [hematologists] talk to neurologists,” said Spero Cataland, MD, an organizer of the TTP-TMA Workshop from The Ohio State University in

Columbus.

“This study will be crucial in

improving our understanding of this issue.”

The consortium plans to study 100 TTP patients in remission for 3 years.

Every

3 months, patients will complete neuropsychologic testing, and

investigators will evaluate patients’ end-organ ischemic biomarkers,

ADAMTS13 activity, ultra-large von Willebrand factor levels, and

complement activation biomarkers.

In addition to this study, the USTMA Consortium is participating in the phase 3 HERCULES study of caplacizumab for acquired TTP.

Caplacizumab, which is being developed by Ablynx, was previously evaluated for acquired TTP in the phase 2 TITAN study.

The phase 3 study is a double-blind, placebo-controlled trial designed to determine whether neurocognitive function can be preserved with caplacizumab intervention.

Investigators intend to enroll 92 patients at clinical sites in 17 countries. Recruitment is expected to be complete by the end of 2017.

In closing, Dr Mazepa invited interested clinicians to join the USTMA Consortium by contacting him ([email protected]) or Dr Cataland ([email protected]).

Micrograph showing TTP
Image by Erhabor Osaro

SAN DIEGO—The US Thrombotic Microangiopathies (USTMA) Consortium is planning a longitudinal study to identify biomarkers of relapse and neurocognitive dysfunction in acquired thrombotic thrombocytopenic purpura (TTP).

Earlier studies suggested that ADAMTS13 activity during remission has

limited utility in estimating relapse risk, and cognitive dysfunction

observed in TTP appears to be progressive and independent of relapses.

However, these studies were small with minimal longitudinal data.

Now, the USTMA Consortium, with 13 large referral centers for thrombotic microangiopathies (TMAs) in the US, is providing “the infrastructure for larger US studies in TTP with the goal of improving outcomes in TMAs,” said Marshall A. Mazepa, MD, of the University of Minnesota in Minneapolis.

He described the efforts of the consortium and its plans to conduct a long-term study at the first TTP-TMA Workshop, which took place immediately before the 2016 ASH Annual Meeting.

Dr Mazepa said the objective of the study is to identify biomarkers that

predict the danger period for neurocognitive dysfunction and relapse.

“Hematologists usually do not realize the

neurocognitive dysfunction among patients with TTP, and it is important

that they [hematologists] talk to neurologists,” said Spero Cataland, MD, an organizer of the TTP-TMA Workshop from The Ohio State University in

Columbus.

“This study will be crucial in

improving our understanding of this issue.”

The consortium plans to study 100 TTP patients in remission for 3 years.

Every

3 months, patients will complete neuropsychologic testing, and

investigators will evaluate patients’ end-organ ischemic biomarkers,

ADAMTS13 activity, ultra-large von Willebrand factor levels, and

complement activation biomarkers.

In addition to this study, the USTMA Consortium is participating in the phase 3 HERCULES study of caplacizumab for acquired TTP.

Caplacizumab, which is being developed by Ablynx, was previously evaluated for acquired TTP in the phase 2 TITAN study.

The phase 3 study is a double-blind, placebo-controlled trial designed to determine whether neurocognitive function can be preserved with caplacizumab intervention.

Investigators intend to enroll 92 patients at clinical sites in 17 countries. Recruitment is expected to be complete by the end of 2017.

In closing, Dr Mazepa invited interested clinicians to join the USTMA Consortium by contacting him ([email protected]) or Dr Cataland ([email protected]).

Micrograph showing TTP
Image by Erhabor Osaro

SAN DIEGO—The US Thrombotic Microangiopathies (USTMA) Consortium is planning a longitudinal study to identify biomarkers of relapse and neurocognitive dysfunction in acquired thrombotic thrombocytopenic purpura (TTP).

Earlier studies suggested that ADAMTS13 activity during remission has

limited utility in estimating relapse risk, and cognitive dysfunction

observed in TTP appears to be progressive and independent of relapses.

However, these studies were small with minimal longitudinal data.

Now, the USTMA Consortium, with 13 large referral centers for thrombotic microangiopathies (TMAs) in the US, is providing “the infrastructure for larger US studies in TTP with the goal of improving outcomes in TMAs,” said Marshall A. Mazepa, MD, of the University of Minnesota in Minneapolis.

He described the efforts of the consortium and its plans to conduct a long-term study at the first TTP-TMA Workshop, which took place immediately before the 2016 ASH Annual Meeting.

Dr Mazepa said the objective of the study is to identify biomarkers that

predict the danger period for neurocognitive dysfunction and relapse.

“Hematologists usually do not realize the

neurocognitive dysfunction among patients with TTP, and it is important

that they [hematologists] talk to neurologists,” said Spero Cataland, MD, an organizer of the TTP-TMA Workshop from The Ohio State University in

Columbus.

“This study will be crucial in

improving our understanding of this issue.”

The consortium plans to study 100 TTP patients in remission for 3 years.

Every

3 months, patients will complete neuropsychologic testing, and

investigators will evaluate patients’ end-organ ischemic biomarkers,

ADAMTS13 activity, ultra-large von Willebrand factor levels, and

complement activation biomarkers.

In addition to this study, the USTMA Consortium is participating in the phase 3 HERCULES study of caplacizumab for acquired TTP.

Caplacizumab, which is being developed by Ablynx, was previously evaluated for acquired TTP in the phase 2 TITAN study.

The phase 3 study is a double-blind, placebo-controlled trial designed to determine whether neurocognitive function can be preserved with caplacizumab intervention.

Investigators intend to enroll 92 patients at clinical sites in 17 countries. Recruitment is expected to be complete by the end of 2017.

In closing, Dr Mazepa invited interested clinicians to join the USTMA Consortium by contacting him ([email protected]) or Dr Cataland ([email protected]).

Children in The Gambia
Photo by Aurimas Rimsa

New research suggests that, for young children, iron deficiency anemia offers a

greater protective effect against malaria than sickle cell trait.

The

study indicates that iron deficiency anemia can protect children age 2 and

younger from the blood stage of Plasmodium falciparum malaria, and

treating the anemia with iron supplementation removes this protective

effect.

The researchers reported these findings in EBioMedicine.

“This study is elegant in its simplicity yet remains one of the most

substantial and systematic attempts to unveil the cellular-level

relationship between anemia, iron supplementation, and malaria risk,”

said study author Carla Cerami, MD, PhD, of the Medical Research Council

Unit The Gambia in Banjul, Gambia.

For this study, she and her colleagues analyzed the red blood cells of 135 anemic children who were participating in an iron supplementation trial.

The children ranged in age from 6 months to 24 months and lived in a malaria-endemic region of The Gambia where sickle cell trait was also common.

The children received iron (12 mg/day) through micronutrient powder for 84 days, and the researchers analyzed the children’s red blood cells at baseline, day 49, and day 84.

The team conducted in vitro growth and invasion assays with P falciparum laboratory and field strains. The study’s primary endpoint was in vitro parasite growth in the children’s RBCs.

The researchers found that “anemia substantially reduced the invasion and growth of both laboratory and field strains of P falciparum.” The team noted a roughly 10% growth reduction per standard deviation shift in hemoglobin.

On a population-wide basis, anemia reduced the blood stage of malaria by 15.9%, while the sickle cell trait reduced it by 3.5%.

“Our finding that anemia offers greater natural protection against blood-stage malaria infection than sickle cell trait has led us to formulate the interesting hypothesis that the widespread prevalence of anemia in people of African descent is a genetic signature of malaria,” said study author Morgan Goheen, PhD, of University of North Carolina in Chapel Hill.

The researchers also found that deficits in invasion and growth for blood-stage P falciparum were reversed when anemic children had received 7 weeks of iron supplementation. Parasite growth was 2.4-fold higher after supplementation than it was at baseline (P<0.001).

Prior work by the same research group suggested the increased invasion and growth rates following iron supplementation are caused by the parasites’ strong preference for young red blood cells.

The researchers said these new field results consolidate the evidence that iron supplementation increases the risk of P falciparum malaria and provide support for the use of malaria prophylaxis in

conjunction with iron supplementation, especially during the early

phases of erythroid recovery.

Children in The Gambia
Photo by Aurimas Rimsa

New research suggests that, for young children, iron deficiency anemia offers a

greater protective effect against malaria than sickle cell trait.

The

study indicates that iron deficiency anemia can protect children age 2 and

younger from the blood stage of Plasmodium falciparum malaria, and

treating the anemia with iron supplementation removes this protective

effect.

The researchers reported these findings in EBioMedicine.

“This study is elegant in its simplicity yet remains one of the most

substantial and systematic attempts to unveil the cellular-level

relationship between anemia, iron supplementation, and malaria risk,”

said study author Carla Cerami, MD, PhD, of the Medical Research Council

Unit The Gambia in Banjul, Gambia.

For this study, she and her colleagues analyzed the red blood cells of 135 anemic children who were participating in an iron supplementation trial.

The children ranged in age from 6 months to 24 months and lived in a malaria-endemic region of The Gambia where sickle cell trait was also common.

The children received iron (12 mg/day) through micronutrient powder for 84 days, and the researchers analyzed the children’s red blood cells at baseline, day 49, and day 84.

The team conducted in vitro growth and invasion assays with P falciparum laboratory and field strains. The study’s primary endpoint was in vitro parasite growth in the children’s RBCs.

The researchers found that “anemia substantially reduced the invasion and growth of both laboratory and field strains of P falciparum.” The team noted a roughly 10% growth reduction per standard deviation shift in hemoglobin.

On a population-wide basis, anemia reduced the blood stage of malaria by 15.9%, while the sickle cell trait reduced it by 3.5%.

“Our finding that anemia offers greater natural protection against blood-stage malaria infection than sickle cell trait has led us to formulate the interesting hypothesis that the widespread prevalence of anemia in people of African descent is a genetic signature of malaria,” said study author Morgan Goheen, PhD, of University of North Carolina in Chapel Hill.

The researchers also found that deficits in invasion and growth for blood-stage P falciparum were reversed when anemic children had received 7 weeks of iron supplementation. Parasite growth was 2.4-fold higher after supplementation than it was at baseline (P<0.001).

Prior work by the same research group suggested the increased invasion and growth rates following iron supplementation are caused by the parasites’ strong preference for young red blood cells.

The researchers said these new field results consolidate the evidence that iron supplementation increases the risk of P falciparum malaria and provide support for the use of malaria prophylaxis in

conjunction with iron supplementation, especially during the early

phases of erythroid recovery.

Children in The Gambia
Photo by Aurimas Rimsa

New research suggests that, for young children, iron deficiency anemia offers a

greater protective effect against malaria than sickle cell trait.

The

study indicates that iron deficiency anemia can protect children age 2 and

younger from the blood stage of Plasmodium falciparum malaria, and

treating the anemia with iron supplementation removes this protective

effect.

The researchers reported these findings in EBioMedicine.

“This study is elegant in its simplicity yet remains one of the most

substantial and systematic attempts to unveil the cellular-level

relationship between anemia, iron supplementation, and malaria risk,”

said study author Carla Cerami, MD, PhD, of the Medical Research Council

Unit The Gambia in Banjul, Gambia.

For this study, she and her colleagues analyzed the red blood cells of 135 anemic children who were participating in an iron supplementation trial.

The children ranged in age from 6 months to 24 months and lived in a malaria-endemic region of The Gambia where sickle cell trait was also common.

The children received iron (12 mg/day) through micronutrient powder for 84 days, and the researchers analyzed the children’s red blood cells at baseline, day 49, and day 84.

The team conducted in vitro growth and invasion assays with P falciparum laboratory and field strains. The study’s primary endpoint was in vitro parasite growth in the children’s RBCs.

The researchers found that “anemia substantially reduced the invasion and growth of both laboratory and field strains of P falciparum.” The team noted a roughly 10% growth reduction per standard deviation shift in hemoglobin.

On a population-wide basis, anemia reduced the blood stage of malaria by 15.9%, while the sickle cell trait reduced it by 3.5%.

“Our finding that anemia offers greater natural protection against blood-stage malaria infection than sickle cell trait has led us to formulate the interesting hypothesis that the widespread prevalence of anemia in people of African descent is a genetic signature of malaria,” said study author Morgan Goheen, PhD, of University of North Carolina in Chapel Hill.

The researchers also found that deficits in invasion and growth for blood-stage P falciparum were reversed when anemic children had received 7 weeks of iron supplementation. Parasite growth was 2.4-fold higher after supplementation than it was at baseline (P<0.001).

Prior work by the same research group suggested the increased invasion and growth rates following iron supplementation are caused by the parasites’ strong preference for young red blood cells.

The researchers said these new field results consolidate the evidence that iron supplementation increases the risk of P falciparum malaria and provide support for the use of malaria prophylaxis in

conjunction with iron supplementation, especially during the early

phases of erythroid recovery.

Antihemophilic factor

The European Commission has granted marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

Lonoctocog alfa is indicated for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

According to CSL Behring, lonoctocog alfa will be launched in European markets in the coming months, as market access is obtained.

Lonoctocog alfa is also approved for use in the US and Canada.

Regulatory submissions for lonoctocog alfa are based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12. 

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.*

O et al; rVIII-SingleChain, results of the pivotal efficacy data from a

phase III PK, efficacy and safety clinical study in children less than

12 years of age with severe hemophilia A; WFH 2016 World Congress, July

2016.

Antihemophilic factor

The European Commission has granted marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

Lonoctocog alfa is indicated for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

According to CSL Behring, lonoctocog alfa will be launched in European markets in the coming months, as market access is obtained.

Lonoctocog alfa is also approved for use in the US and Canada.

Regulatory submissions for lonoctocog alfa are based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12. 

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.*

O et al; rVIII-SingleChain, results of the pivotal efficacy data from a

phase III PK, efficacy and safety clinical study in children less than

12 years of age with severe hemophilia A; WFH 2016 World Congress, July

2016.

Antihemophilic factor

The European Commission has granted marketing authorization for lonoctocog alfa (Afstyla), a recombinant factor VIII (FVIII) single-chain therapy.

Lonoctocog alfa is indicated for the treatment and prophylaxis of bleeding in hemophilia A patients of all ages.

Lonoctocog alfa is the first and only single-chain recombinant FVIII therapy for hemophilia A specifically designed to provide long-lasting protection from bleeds with 2- to 3-times weekly dosing, according to CSL Behring, the company developing the product.

The company says lonoctocog alfa uses a covalent bond that forms one structural entity—a single polypeptide chain—to improve the stability of FVIII and provide FVIII activity with the option of twice-weekly dosing.

According to CSL Behring, lonoctocog alfa will be launched in European markets in the coming months, as market access is obtained.

Lonoctocog alfa is also approved for use in the US and Canada.

Regulatory submissions for lonoctocog alfa are based on results from the AFFINITY clinical development program, which includes a trial of children (n=84) and a trial of adolescents and adults (n=175).

Among patients who received lonoctocog alfa prophylactically in these trials, the median annualized bleeding rate was 1.14 in the adults/adolescents and 3.69 in children younger than 12. 

In all, there were 1195 bleeding events—848 in the adults/adolescents and 347 in the children.

Ninety-four percent of bleeds in adults/adolescents and 96% of bleeds in pediatric patients were effectively controlled with no more than 2 infusions of lonoctocog alfa weekly.

Eighty-one percent of bleeds in adults/adolescents and 86% of bleeds in pediatric patients were controlled by a single infusion.

Researchers assessed safety in 258 patients from both studies. Adverse reactions occurred in 14 patients and included hypersensitivity (n=4), dizziness (n=2), paresthesia (n=1), rash (n=1), erythema (n=1), pruritus (n=1), pyrexia (n=1), injection-site pain (n=1), chills (n=1), and feeling hot (n=1).

One patient withdrew from treatment due to hypersensitivity.

None of the patients developed neutralizing antibodies to FVIII or antibodies to host cell proteins. There were no reports of anaphylaxis or thrombosis.

Results from the trial of adolescents/adults were published in Blood in August 2016. Results from the trial of children were presented at the World Federation of Hemophilia 2016 World Congress in July 2016.*

O et al; rVIII-SingleChain, results of the pivotal efficacy data from a

phase III PK, efficacy and safety clinical study in children less than

12 years of age with severe hemophilia A; WFH 2016 World Congress, July

2016.

Q)I overheard a conversation at the hospital in which one of the nephrologists told an internist that allopurinol is better than other medications for treating gout because it slows the progression of chronic kidney disease (CKD). What does the data say?

CKD is a growing problem in America; the number of adults with CKD doubled from 2000 to 2008.¹ Gout is considered an independent risk factor for CKD progression.² Some randomized controlled trials (RCTs) have shown an association between allopurinol use and decreased proteinuria.³

A recent large retrospective review of Medicare charts assessed the correlation between use and dose of allopurinol and incidence of renal failure in patients older than 65.¹ The researchers found that, compared with lower doses, allopurinol doses of 200 to 299 mg/d and > 300 mg/d were associated with a significantly lower hazard ratio for kidney failure, in a multivariate-adjusted model. The findings therefore suggest that doses > 199 mg may slow progression to kidney failure in the elderly.

Despite the strengths of this study, it is worth noting that it did not consider stage of kidney disease, nor did it distinguish comorbidities of the patients. The retrospective chart review format did not allow for identification of concurrent medication use (including OTC and herbal products).

The National Institute of Diabetes and Digestive and Kidney Diseases is currently conducting an RCT to investigate the renoprotective effects of allopurinol versus placebo in diabetic patients. (Clinical Trials.gov identifier: NCT02017171). Enrollment was completed in 2014, and results are expected in June 2019.

One important proviso about allopurinol: While it is inexpensive and generally well tolerated, prescribers should be aware of rare sensitivity reactions, particularly Stevens-Johnson syndrome. —MRS

Mary Rogers Sorey, MSN
Division of Nephrology and Hypertension at Vanderbilt University Medical Center, Nashville

Q)I overheard a conversation at the hospital in which one of the nephrologists told an internist that allopurinol is better than other medications for treating gout because it slows the progression of chronic kidney disease (CKD). What does the data say?

CKD is a growing problem in America; the number of adults with CKD doubled from 2000 to 2008.¹ Gout is considered an independent risk factor for CKD progression.² Some randomized controlled trials (RCTs) have shown an association between allopurinol use and decreased proteinuria.³

A recent large retrospective review of Medicare charts assessed the correlation between use and dose of allopurinol and incidence of renal failure in patients older than 65.¹ The researchers found that, compared with lower doses, allopurinol doses of 200 to 299 mg/d and > 300 mg/d were associated with a significantly lower hazard ratio for kidney failure, in a multivariate-adjusted model. The findings therefore suggest that doses > 199 mg may slow progression to kidney failure in the elderly.

Despite the strengths of this study, it is worth noting that it did not consider stage of kidney disease, nor did it distinguish comorbidities of the patients. The retrospective chart review format did not allow for identification of concurrent medication use (including OTC and herbal products).

The National Institute of Diabetes and Digestive and Kidney Diseases is currently conducting an RCT to investigate the renoprotective effects of allopurinol versus placebo in diabetic patients. (Clinical Trials.gov identifier: NCT02017171). Enrollment was completed in 2014, and results are expected in June 2019.

One important proviso about allopurinol: While it is inexpensive and generally well tolerated, prescribers should be aware of rare sensitivity reactions, particularly Stevens-Johnson syndrome. —MRS

Mary Rogers Sorey, MSN
Division of Nephrology and Hypertension at Vanderbilt University Medical Center, Nashville

Q)I overheard a conversation at the hospital in which one of the nephrologists told an internist that allopurinol is better than other medications for treating gout because it slows the progression of chronic kidney disease (CKD). What does the data say?

CKD is a growing problem in America; the number of adults with CKD doubled from 2000 to 2008.¹ Gout is considered an independent risk factor for CKD progression.² Some randomized controlled trials (RCTs) have shown an association between allopurinol use and decreased proteinuria.³

A recent large retrospective review of Medicare charts assessed the correlation between use and dose of allopurinol and incidence of renal failure in patients older than 65.¹ The researchers found that, compared with lower doses, allopurinol doses of 200 to 299 mg/d and > 300 mg/d were associated with a significantly lower hazard ratio for kidney failure, in a multivariate-adjusted model. The findings therefore suggest that doses > 199 mg may slow progression to kidney failure in the elderly.

Despite the strengths of this study, it is worth noting that it did not consider stage of kidney disease, nor did it distinguish comorbidities of the patients. The retrospective chart review format did not allow for identification of concurrent medication use (including OTC and herbal products).

The National Institute of Diabetes and Digestive and Kidney Diseases is currently conducting an RCT to investigate the renoprotective effects of allopurinol versus placebo in diabetic patients. (Clinical Trials.gov identifier: NCT02017171). Enrollment was completed in 2014, and results are expected in June 2019.

One important proviso about allopurinol: While it is inexpensive and generally well tolerated, prescribers should be aware of rare sensitivity reactions, particularly Stevens-Johnson syndrome. —MRS

Mary Rogers Sorey, MSN
Division of Nephrology and Hypertension at Vanderbilt University Medical Center, Nashville

Explantation of mesh used in ventral hernia repair occurs in approximately 1 of every 1,000 surgeries, but it’s a “hidden” morbidity because it almost always happens well after the 30- to 90-day window in which postoperative complications are typically reported in most registries and surveillance systems, according to a report in the Journal of the American College of Surgeons.

Mesh explantation usually occurs 1-3 years after implantation and triples the operative costs of the original ventral hernia repair. The rate of 1 per 1,000 surgeries and the massive increase in cost are comparable with those of occult injury of the common bile duct during cholecystectomy that later requires biliary reconstruction. But mesh explantation doesn’t generate the “profound attention” accorded to bile duct injury, perhaps because it develops much later in the postoperative course.

“It is surprising that mesh complications have not yet prompted similar concern,” said Kristy Kummerow Broman, MD, of the department of surgery, Vanderbilt University Medical Center, Nashville, Tenn., and her associates.

Until now, the frequency and cost of mesh explantation after ventral hernia repair in the general population have not been known. To make a reasonable estimate, the investigators constructed a cohort of 619,751 patients using information from inpatient and surgery databases for New York, California, and Florida between 2005 and 2011. Most of these were open procedures (91%), while 9% were laparoscopic.

During a mean follow-up of 3 years, 438 patients (0.7 per 1,000) underwent mesh explantation. This is a clinically significant incidence, and is likely an underestimate because ICD-9 and CPT coding for mesh removal is highly variable, Dr. Broman and her associates said.

This rate, for just three states during 3 years of follow-up, is nearly twice as high as the rate of mesh-related complications voluntarily reported to the FDA in post-marketing surveillance for the entire country during a 7-year period, they noted (J Am Coll Surg. 2017 Jan;224:35-42).

“It is paramount” that surgeons, manufacturers, and regulatory groups advocate mandatory reporting and “extend the surveillance for at least 1-3 years after implantation of a mesh device,” Dr. Broman and her associates said.

In this study, the median time to explantation was approximately 1 year (range, 2 days to 6 years), and 80% of explantations occurred within 2 years.

The median cumulative operative cost – excluding physician fees, nonsurgical medical costs, and the costs of patient disability and lost productivity – were $21,889 for patients requiring mesh explantation, compared with only $6,579 for those who did not. This finding highlights “the profound long-term implications of implantable devices in abdominal wall reconstruction,” they noted.

To put their findings in context, the investigators reviewed the literature regarding major bile duct injury during cholecystectomy. One large study on cases from 2001 to 2011 found that the rate of biliary reconstruction was comparable with that of explantation, at 0.8 to 1.1 per 1,000. Similarly, reoperation for bile duct injury approximately tripled the operative costs ($9,061 for patients who required biliary reconstruction vs $2,689 for those who didn’t). However, the $21,000 for mesh reoperation far exceeds the $9,000 for biliary reoperation.

This study was supported by the Department of Veterans Affairs, the VA Tennessee Valley Healthcare System, and the Americas Hernia Society Quality Collaborative. Dr. Broman reported having no relevant financial disclosures; her associates reported ties to Intuitive Surgical Solutions, Bard Davol, Ariste Medical, and Pfizer.

Explantation of mesh used in ventral hernia repair occurs in approximately 1 of every 1,000 surgeries, but it’s a “hidden” morbidity because it almost always happens well after the 30- to 90-day window in which postoperative complications are typically reported in most registries and surveillance systems, according to a report in the Journal of the American College of Surgeons.

Mesh explantation usually occurs 1-3 years after implantation and triples the operative costs of the original ventral hernia repair. The rate of 1 per 1,000 surgeries and the massive increase in cost are comparable with those of occult injury of the common bile duct during cholecystectomy that later requires biliary reconstruction. But mesh explantation doesn’t generate the “profound attention” accorded to bile duct injury, perhaps because it develops much later in the postoperative course.

“It is surprising that mesh complications have not yet prompted similar concern,” said Kristy Kummerow Broman, MD, of the department of surgery, Vanderbilt University Medical Center, Nashville, Tenn., and her associates.

Until now, the frequency and cost of mesh explantation after ventral hernia repair in the general population have not been known. To make a reasonable estimate, the investigators constructed a cohort of 619,751 patients using information from inpatient and surgery databases for New York, California, and Florida between 2005 and 2011. Most of these were open procedures (91%), while 9% were laparoscopic.

During a mean follow-up of 3 years, 438 patients (0.7 per 1,000) underwent mesh explantation. This is a clinically significant incidence, and is likely an underestimate because ICD-9 and CPT coding for mesh removal is highly variable, Dr. Broman and her associates said.

This rate, for just three states during 3 years of follow-up, is nearly twice as high as the rate of mesh-related complications voluntarily reported to the FDA in post-marketing surveillance for the entire country during a 7-year period, they noted (J Am Coll Surg. 2017 Jan;224:35-42).

“It is paramount” that surgeons, manufacturers, and regulatory groups advocate mandatory reporting and “extend the surveillance for at least 1-3 years after implantation of a mesh device,” Dr. Broman and her associates said.

In this study, the median time to explantation was approximately 1 year (range, 2 days to 6 years), and 80% of explantations occurred within 2 years.

The median cumulative operative cost – excluding physician fees, nonsurgical medical costs, and the costs of patient disability and lost productivity – were $21,889 for patients requiring mesh explantation, compared with only $6,579 for those who did not. This finding highlights “the profound long-term implications of implantable devices in abdominal wall reconstruction,” they noted.

To put their findings in context, the investigators reviewed the literature regarding major bile duct injury during cholecystectomy. One large study on cases from 2001 to 2011 found that the rate of biliary reconstruction was comparable with that of explantation, at 0.8 to 1.1 per 1,000. Similarly, reoperation for bile duct injury approximately tripled the operative costs ($9,061 for patients who required biliary reconstruction vs $2,689 for those who didn’t). However, the $21,000 for mesh reoperation far exceeds the $9,000 for biliary reoperation.

This study was supported by the Department of Veterans Affairs, the VA Tennessee Valley Healthcare System, and the Americas Hernia Society Quality Collaborative. Dr. Broman reported having no relevant financial disclosures; her associates reported ties to Intuitive Surgical Solutions, Bard Davol, Ariste Medical, and Pfizer.

Explantation of mesh used in ventral hernia repair occurs in approximately 1 of every 1,000 surgeries, but it’s a “hidden” morbidity because it almost always happens well after the 30- to 90-day window in which postoperative complications are typically reported in most registries and surveillance systems, according to a report in the Journal of the American College of Surgeons.

Mesh explantation usually occurs 1-3 years after implantation and triples the operative costs of the original ventral hernia repair. The rate of 1 per 1,000 surgeries and the massive increase in cost are comparable with those of occult injury of the common bile duct during cholecystectomy that later requires biliary reconstruction. But mesh explantation doesn’t generate the “profound attention” accorded to bile duct injury, perhaps because it develops much later in the postoperative course.

“It is surprising that mesh complications have not yet prompted similar concern,” said Kristy Kummerow Broman, MD, of the department of surgery, Vanderbilt University Medical Center, Nashville, Tenn., and her associates.

Until now, the frequency and cost of mesh explantation after ventral hernia repair in the general population have not been known. To make a reasonable estimate, the investigators constructed a cohort of 619,751 patients using information from inpatient and surgery databases for New York, California, and Florida between 2005 and 2011. Most of these were open procedures (91%), while 9% were laparoscopic.

During a mean follow-up of 3 years, 438 patients (0.7 per 1,000) underwent mesh explantation. This is a clinically significant incidence, and is likely an underestimate because ICD-9 and CPT coding for mesh removal is highly variable, Dr. Broman and her associates said.

This rate, for just three states during 3 years of follow-up, is nearly twice as high as the rate of mesh-related complications voluntarily reported to the FDA in post-marketing surveillance for the entire country during a 7-year period, they noted (J Am Coll Surg. 2017 Jan;224:35-42).

“It is paramount” that surgeons, manufacturers, and regulatory groups advocate mandatory reporting and “extend the surveillance for at least 1-3 years after implantation of a mesh device,” Dr. Broman and her associates said.

In this study, the median time to explantation was approximately 1 year (range, 2 days to 6 years), and 80% of explantations occurred within 2 years.

The median cumulative operative cost – excluding physician fees, nonsurgical medical costs, and the costs of patient disability and lost productivity – were $21,889 for patients requiring mesh explantation, compared with only $6,579 for those who did not. This finding highlights “the profound long-term implications of implantable devices in abdominal wall reconstruction,” they noted.

To put their findings in context, the investigators reviewed the literature regarding major bile duct injury during cholecystectomy. One large study on cases from 2001 to 2011 found that the rate of biliary reconstruction was comparable with that of explantation, at 0.8 to 1.1 per 1,000. Similarly, reoperation for bile duct injury approximately tripled the operative costs ($9,061 for patients who required biliary reconstruction vs $2,689 for those who didn’t). However, the $21,000 for mesh reoperation far exceeds the $9,000 for biliary reoperation.

This study was supported by the Department of Veterans Affairs, the VA Tennessee Valley Healthcare System, and the Americas Hernia Society Quality Collaborative. Dr. Broman reported having no relevant financial disclosures; her associates reported ties to Intuitive Surgical Solutions, Bard Davol, Ariste Medical, and Pfizer.

Compared with midweight mesh, lightweight mesh was associated with more surgical site infection and longer hospital stay following open ventral hernia repair, according to a report published in the American Journal of Surgery.

In addition, lightweight mesh was associated with greater pain, more limitation of movement, and poorer quality of life for up to 2 years after the procedure, compared with midweight mesh.

Compared with midweight mesh, lightweight mesh was associated with more surgical site infection and longer hospital stay following open ventral hernia repair, according to a report published in the American Journal of Surgery.

In addition, lightweight mesh was associated with greater pain, more limitation of movement, and poorer quality of life for up to 2 years after the procedure, compared with midweight mesh.

Compared with midweight mesh, lightweight mesh was associated with more surgical site infection and longer hospital stay following open ventral hernia repair, according to a report published in the American Journal of Surgery.

In addition, lightweight mesh was associated with greater pain, more limitation of movement, and poorer quality of life for up to 2 years after the procedure, compared with midweight mesh.

The 2016-2017 flu season shifted into high gear at the end of calendar year 2016, as four states were reported to be at the highest level of flu activity and six others were close behind, according to the Centers for Disease Control and Prevention.

For the week ending Dec. 31, 2016, Georgia, New Jersey, Oklahoma, and Oregon were at level 10 on the CDC’s 1-10 scale of influenza-like illness (ILI). Others in the “high” range were New York at level 9 and Alabama, Louisiana, Missouri, South Carolina, and Utah at level 8. Puerto Rico was also at level 8, after being at level 10 for the previous few weeks. An additional 10 states were in the “moderate” range (6-7), the CDC reported.

[email protected]

The 2016-2017 flu season shifted into high gear at the end of calendar year 2016, as four states were reported to be at the highest level of flu activity and six others were close behind, according to the Centers for Disease Control and Prevention.

For the week ending Dec. 31, 2016, Georgia, New Jersey, Oklahoma, and Oregon were at level 10 on the CDC’s 1-10 scale of influenza-like illness (ILI). Others in the “high” range were New York at level 9 and Alabama, Louisiana, Missouri, South Carolina, and Utah at level 8. Puerto Rico was also at level 8, after being at level 10 for the previous few weeks. An additional 10 states were in the “moderate” range (6-7), the CDC reported.

[email protected]

The 2016-2017 flu season shifted into high gear at the end of calendar year 2016, as four states were reported to be at the highest level of flu activity and six others were close behind, according to the Centers for Disease Control and Prevention.

For the week ending Dec. 31, 2016, Georgia, New Jersey, Oklahoma, and Oregon were at level 10 on the CDC’s 1-10 scale of influenza-like illness (ILI). Others in the “high” range were New York at level 9 and Alabama, Louisiana, Missouri, South Carolina, and Utah at level 8. Puerto Rico was also at level 8, after being at level 10 for the previous few weeks. An additional 10 states were in the “moderate” range (6-7), the CDC reported.

[email protected]

Annual hospitalization rates in the United States for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were shown to be higher in adolescents, boys, and black children, in a cross-sectional analysis of discharge records from more than 4,100 hospitals.

Using relevant ICD-9 codes, researchers at Harvard University identified 1,571 patients hospitalized for SJS, TEN, or both in 2009 and 2012, as listed in the Kids Inpatient Database from the Agency for Healthcare Research and Quality. The highest hospitalization rates per 100,000 in each year were for adolescents between 15 and 19 years (P = .01), boys (P = .03), and black children (P = .82). The overall risk of death from these conditions was 1.5% in 2009 and 0.3% in 2012. The data were published online in a brief report (Pediatr Dermatol. 2016 Dec 19. doi: 10.1111/pde.13050).

Madhero88/Wikimedia Commons/CC-ASA 3.0

[email protected]

On Twitter @whitneymcknight

Annual hospitalization rates in the United States for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were shown to be higher in adolescents, boys, and black children, in a cross-sectional analysis of discharge records from more than 4,100 hospitals.

Using relevant ICD-9 codes, researchers at Harvard University identified 1,571 patients hospitalized for SJS, TEN, or both in 2009 and 2012, as listed in the Kids Inpatient Database from the Agency for Healthcare Research and Quality. The highest hospitalization rates per 100,000 in each year were for adolescents between 15 and 19 years (P = .01), boys (P = .03), and black children (P = .82). The overall risk of death from these conditions was 1.5% in 2009 and 0.3% in 2012. The data were published online in a brief report (Pediatr Dermatol. 2016 Dec 19. doi: 10.1111/pde.13050).

Madhero88/Wikimedia Commons/CC-ASA 3.0

[email protected]

On Twitter @whitneymcknight

Annual hospitalization rates in the United States for Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were shown to be higher in adolescents, boys, and black children, in a cross-sectional analysis of discharge records from more than 4,100 hospitals.

Using relevant ICD-9 codes, researchers at Harvard University identified 1,571 patients hospitalized for SJS, TEN, or both in 2009 and 2012, as listed in the Kids Inpatient Database from the Agency for Healthcare Research and Quality. The highest hospitalization rates per 100,000 in each year were for adolescents between 15 and 19 years (P = .01), boys (P = .03), and black children (P = .82). The overall risk of death from these conditions was 1.5% in 2009 and 0.3% in 2012. The data were published online in a brief report (Pediatr Dermatol. 2016 Dec 19. doi: 10.1111/pde.13050).

Madhero88/Wikimedia Commons/CC-ASA 3.0

[email protected]

On Twitter @whitneymcknight