Carfilzomib, a selective second-generation proteasome inhibitor, has performed well in clinical trials. So because other “triplets”—combinations of alkylator, proteasome inhibitor, and steroid—had shown “encouraging” response rates, researchers from the Center for Cancer and Blood Disorders in Bethesda, Maryland, and others, conducted a multicenter study to evaluate the safety and tolerability of twice-weekly carfilzomib combined with cyclophosphamide and dexamethasone (KCyd) for patients newly diagnosed with multiple myeloma (MM).

The researchers tested 3 doses of carfilzomib: 36 mg/m², 45 mg/m², and 56 mg/m². Of the 22 enrolled patients, 16 were treated with the maximum dose.

Fourteen patients completed all 8 cycles of treatment; 10 in the maximum-dose group completed all 8. At 56 mg/m², the overall response rate was 87.5%. Among the 14 patients whose disease responded to therapy, the median time to response was 1 month.

Five patients discontinued treatment because of adverse effects (AEs), but the researchers found no dose-limiting toxicities at any of the dose levels. The most common AEs were nausea, diarrhea, and anemia.

The researchers concluded that based on previous research, KCyd with 36 mg/m² is safe and effective in patients aged ≥ 65 years with newly diagnosed MM. However, their findings suggest that twice-weekly carfilzomib 56 mg/m² in combination with cyclophosphamide and dexamethasone also is effective with “manageable toxicity.”

Source:
Boccia RV, Bessudo A, Agajanian R, et al. Clin Lymphoma Myeloma Leuk. In press.
doi: 10.1016/j.clml.2017.05.009.

Carfilzomib, a selective second-generation proteasome inhibitor, has performed well in clinical trials. So because other “triplets”—combinations of alkylator, proteasome inhibitor, and steroid—had shown “encouraging” response rates, researchers from the Center for Cancer and Blood Disorders in Bethesda, Maryland, and others, conducted a multicenter study to evaluate the safety and tolerability of twice-weekly carfilzomib combined with cyclophosphamide and dexamethasone (KCyd) for patients newly diagnosed with multiple myeloma (MM).

The researchers tested 3 doses of carfilzomib: 36 mg/m², 45 mg/m², and 56 mg/m². Of the 22 enrolled patients, 16 were treated with the maximum dose.

Fourteen patients completed all 8 cycles of treatment; 10 in the maximum-dose group completed all 8. At 56 mg/m², the overall response rate was 87.5%. Among the 14 patients whose disease responded to therapy, the median time to response was 1 month.

Five patients discontinued treatment because of adverse effects (AEs), but the researchers found no dose-limiting toxicities at any of the dose levels. The most common AEs were nausea, diarrhea, and anemia.

The researchers concluded that based on previous research, KCyd with 36 mg/m² is safe and effective in patients aged ≥ 65 years with newly diagnosed MM. However, their findings suggest that twice-weekly carfilzomib 56 mg/m² in combination with cyclophosphamide and dexamethasone also is effective with “manageable toxicity.”

Source:
Boccia RV, Bessudo A, Agajanian R, et al. Clin Lymphoma Myeloma Leuk. In press.
doi: 10.1016/j.clml.2017.05.009.

Carfilzomib, a selective second-generation proteasome inhibitor, has performed well in clinical trials. So because other “triplets”—combinations of alkylator, proteasome inhibitor, and steroid—had shown “encouraging” response rates, researchers from the Center for Cancer and Blood Disorders in Bethesda, Maryland, and others, conducted a multicenter study to evaluate the safety and tolerability of twice-weekly carfilzomib combined with cyclophosphamide and dexamethasone (KCyd) for patients newly diagnosed with multiple myeloma (MM).

The researchers tested 3 doses of carfilzomib: 36 mg/m², 45 mg/m², and 56 mg/m². Of the 22 enrolled patients, 16 were treated with the maximum dose.

Fourteen patients completed all 8 cycles of treatment; 10 in the maximum-dose group completed all 8. At 56 mg/m², the overall response rate was 87.5%. Among the 14 patients whose disease responded to therapy, the median time to response was 1 month.

Five patients discontinued treatment because of adverse effects (AEs), but the researchers found no dose-limiting toxicities at any of the dose levels. The most common AEs were nausea, diarrhea, and anemia.

The researchers concluded that based on previous research, KCyd with 36 mg/m² is safe and effective in patients aged ≥ 65 years with newly diagnosed MM. However, their findings suggest that twice-weekly carfilzomib 56 mg/m² in combination with cyclophosphamide and dexamethasone also is effective with “manageable toxicity.”

Source:
Boccia RV, Bessudo A, Agajanian R, et al. Clin Lymphoma Myeloma Leuk. In press.
doi: 10.1016/j.clml.2017.05.009.

Image by AJ Cann

BERLIN—Researchers have reported positive results from an ongoing phase 2 trial of fitusiran in patients with hemophilia A or B, with or without inhibitors.

Once-monthly treatment with fitusiran reduced the median annualized bleeding rate (ABR) from 20 to 1 in all patients. In patients with inhibitors, the median ABR fell from 38 to 0.

Most adverse events (AEs) were mild or moderate in severity, with the most common AEs being alanine aminotransferase (ALT) increases and injection-site reactions.

These results were presented* at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress.

The research was sponsored by Alnylam Pharmaceuticals, Inc., the company developing fitusiran in collaboration with Sanofi Genzyme.

Fitusiran is an RNAi therapeutic targeting antithrombin for the treatment of patients with hemophilia A and B. Fitusiran is designed to lower levels of antithrombin and promote sufficient thrombin generation upon activation of the clotting cascade to restore hemostasis and prevent bleeding.

John Pasi, PhD, of Barts and the London School of Medicine and Dentistry in London, UK, and his colleagues tested fitusiran in 33 patients, ages 19 to 61, with hemophilia A (n=27) or hemophilia B (n=6), with inhibitors (n=14) or without (n=19).

Fitusiran was administered as a monthly, subcutaneous, fixed dose of 50 mg (n=13) or 80 mg (n=20).

Patients were treated for up to 20 months, with a median of 11 months on study. Five patients discontinued treatment—4 due to withdrawn consent and 1 due to an AE.

Safety

The incidence of AEs was 70%. Most were mild or moderate in severity and unrelated to fitusiran.

Non-laboratory AEs included injection site reactions (18%, n=6), abdominal pain (9%, n=3), diarrhea (9%, n=3), and headache (9%, n=3).

Eleven patients had asymptomatic ALT increases greater than 3 times the upper limit of normal, without concurrent elevations in bilirubin greater than 2 times the upper limit of normal. All of these patients were hepatitis C antibody-positive.

At last follow-up, all ALT elevations were resolved (n=10) or resolving (n=1).

There were serious AEs in 6 patients, and 2 of these events were considered possibly related to fitusiran. One event was seizure with confusion in a patient with a prior history of seizure disorder.

The other serious AE was an asymptomatic ALT elevation in a patient with chronic hepatitis C virus infection. This patient discontinued treatment due to the event.

There were no thromboembolic events, no laboratory evidence for pathological clot formation, and no instances of anti-drug antibody formation.

Efficacy

Fitusiran resulted in approximately 80% lowering of antithrombin, with corresponding increases in thrombin generation.

In all patients, fitusiran reduced the median ABR from 20 (interquartile range [IQR]: 4-36) to 1 (IQR: 0-3).

In patients with inhibitors, fitusiran reduced the median ABR from 38 (IQR: 20-48) to 0 (IQR: 0-3).

Forty-eight percent of all patients (n=16) remained bleed-free during the observation period, and 67% (n=22) did not experience any spontaneous bleeds.

All breakthrough bleeds were successfully managed with replacement factor (recombinant factor VIII or recombinant factor IX) or bypassing agents (recombinant factor VIIa or activated prothrombin complex concentrate).

Based on these results, Sanofi and Alnylam initiated the ATLAS phase 3 program for fitusiran in patients with hemophilia A and B, with or without inhibitors.

*Data in the abstract differ from data presented at the meeting.

Image by AJ Cann

BERLIN—Researchers have reported positive results from an ongoing phase 2 trial of fitusiran in patients with hemophilia A or B, with or without inhibitors.

Once-monthly treatment with fitusiran reduced the median annualized bleeding rate (ABR) from 20 to 1 in all patients. In patients with inhibitors, the median ABR fell from 38 to 0.

Most adverse events (AEs) were mild or moderate in severity, with the most common AEs being alanine aminotransferase (ALT) increases and injection-site reactions.

These results were presented* at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress.

The research was sponsored by Alnylam Pharmaceuticals, Inc., the company developing fitusiran in collaboration with Sanofi Genzyme.

Fitusiran is an RNAi therapeutic targeting antithrombin for the treatment of patients with hemophilia A and B. Fitusiran is designed to lower levels of antithrombin and promote sufficient thrombin generation upon activation of the clotting cascade to restore hemostasis and prevent bleeding.

John Pasi, PhD, of Barts and the London School of Medicine and Dentistry in London, UK, and his colleagues tested fitusiran in 33 patients, ages 19 to 61, with hemophilia A (n=27) or hemophilia B (n=6), with inhibitors (n=14) or without (n=19).

Fitusiran was administered as a monthly, subcutaneous, fixed dose of 50 mg (n=13) or 80 mg (n=20).

Patients were treated for up to 20 months, with a median of 11 months on study. Five patients discontinued treatment—4 due to withdrawn consent and 1 due to an AE.

Safety

The incidence of AEs was 70%. Most were mild or moderate in severity and unrelated to fitusiran.

Non-laboratory AEs included injection site reactions (18%, n=6), abdominal pain (9%, n=3), diarrhea (9%, n=3), and headache (9%, n=3).

Eleven patients had asymptomatic ALT increases greater than 3 times the upper limit of normal, without concurrent elevations in bilirubin greater than 2 times the upper limit of normal. All of these patients were hepatitis C antibody-positive.

At last follow-up, all ALT elevations were resolved (n=10) or resolving (n=1).

There were serious AEs in 6 patients, and 2 of these events were considered possibly related to fitusiran. One event was seizure with confusion in a patient with a prior history of seizure disorder.

The other serious AE was an asymptomatic ALT elevation in a patient with chronic hepatitis C virus infection. This patient discontinued treatment due to the event.

There were no thromboembolic events, no laboratory evidence for pathological clot formation, and no instances of anti-drug antibody formation.

Efficacy

Fitusiran resulted in approximately 80% lowering of antithrombin, with corresponding increases in thrombin generation.

In all patients, fitusiran reduced the median ABR from 20 (interquartile range [IQR]: 4-36) to 1 (IQR: 0-3).

In patients with inhibitors, fitusiran reduced the median ABR from 38 (IQR: 20-48) to 0 (IQR: 0-3).

Forty-eight percent of all patients (n=16) remained bleed-free during the observation period, and 67% (n=22) did not experience any spontaneous bleeds.

All breakthrough bleeds were successfully managed with replacement factor (recombinant factor VIII or recombinant factor IX) or bypassing agents (recombinant factor VIIa or activated prothrombin complex concentrate).

Based on these results, Sanofi and Alnylam initiated the ATLAS phase 3 program for fitusiran in patients with hemophilia A and B, with or without inhibitors.

*Data in the abstract differ from data presented at the meeting.

Image by AJ Cann

BERLIN—Researchers have reported positive results from an ongoing phase 2 trial of fitusiran in patients with hemophilia A or B, with or without inhibitors.

Once-monthly treatment with fitusiran reduced the median annualized bleeding rate (ABR) from 20 to 1 in all patients. In patients with inhibitors, the median ABR fell from 38 to 0.

Most adverse events (AEs) were mild or moderate in severity, with the most common AEs being alanine aminotransferase (ALT) increases and injection-site reactions.

These results were presented* at the International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress.

The research was sponsored by Alnylam Pharmaceuticals, Inc., the company developing fitusiran in collaboration with Sanofi Genzyme.

Fitusiran is an RNAi therapeutic targeting antithrombin for the treatment of patients with hemophilia A and B. Fitusiran is designed to lower levels of antithrombin and promote sufficient thrombin generation upon activation of the clotting cascade to restore hemostasis and prevent bleeding.

John Pasi, PhD, of Barts and the London School of Medicine and Dentistry in London, UK, and his colleagues tested fitusiran in 33 patients, ages 19 to 61, with hemophilia A (n=27) or hemophilia B (n=6), with inhibitors (n=14) or without (n=19).

Fitusiran was administered as a monthly, subcutaneous, fixed dose of 50 mg (n=13) or 80 mg (n=20).

Patients were treated for up to 20 months, with a median of 11 months on study. Five patients discontinued treatment—4 due to withdrawn consent and 1 due to an AE.

Safety

The incidence of AEs was 70%. Most were mild or moderate in severity and unrelated to fitusiran.

Non-laboratory AEs included injection site reactions (18%, n=6), abdominal pain (9%, n=3), diarrhea (9%, n=3), and headache (9%, n=3).

Eleven patients had asymptomatic ALT increases greater than 3 times the upper limit of normal, without concurrent elevations in bilirubin greater than 2 times the upper limit of normal. All of these patients were hepatitis C antibody-positive.

At last follow-up, all ALT elevations were resolved (n=10) or resolving (n=1).

There were serious AEs in 6 patients, and 2 of these events were considered possibly related to fitusiran. One event was seizure with confusion in a patient with a prior history of seizure disorder.

The other serious AE was an asymptomatic ALT elevation in a patient with chronic hepatitis C virus infection. This patient discontinued treatment due to the event.

There were no thromboembolic events, no laboratory evidence for pathological clot formation, and no instances of anti-drug antibody formation.

Efficacy

Fitusiran resulted in approximately 80% lowering of antithrombin, with corresponding increases in thrombin generation.

In all patients, fitusiran reduced the median ABR from 20 (interquartile range [IQR]: 4-36) to 1 (IQR: 0-3).

In patients with inhibitors, fitusiran reduced the median ABR from 38 (IQR: 20-48) to 0 (IQR: 0-3).

Forty-eight percent of all patients (n=16) remained bleed-free during the observation period, and 67% (n=22) did not experience any spontaneous bleeds.

All breakthrough bleeds were successfully managed with replacement factor (recombinant factor VIII or recombinant factor IX) or bypassing agents (recombinant factor VIIa or activated prothrombin complex concentrate).

Based on these results, Sanofi and Alnylam initiated the ATLAS phase 3 program for fitusiran in patients with hemophilia A and B, with or without inhibitors.

*Data in the abstract differ from data presented at the meeting.

on Malignant Lymphoma

LUGANO, SWITZERLAND—A 4-drug regimen has demonstrated efficacy in a phase 2 trial of patients with treatment-naïve extranodal natural killer/T-cell lymphoma (ENKTL).

Treatment with gemcitabine, PEG-asparaginase, dexamethasone, and methotrexate (GAD-M) produced a 94% overall response rate (ORR) and an 83% complete response (CR) rate in this trial.

Responses and survival rates were higher in patients with stage I/II disease, who also received radiotherapy, than in patients with stage III/IV disease.

Grade 1/2 toxicities were frequent, but there were few grade 3/4 non-hematologic toxicities. One patient died of treatment-related toxicity.

Zhiming Li, of Sun Yet-sen University Cancer Center in Guangzhou, China, presented these results at the 14th International Conference on Malignant Lymphoma (ICML).

Patients and treatment

The trial enrolled 41 patients with treatment-naïve ENKTL, and 36 of them were evaluable.

The patients’ median age was 45 (range, 18-75), and 30.6% were female. Most patients (86.1%) had stage I/II disease, 13.9% had an ECOG performance status of 2 or greater, and 41.7% had an IPI score of 2 or greater.

The GAD-M regimen consisted of:

• Gemcitabine given at 1000 mg/m² via intravenous drip on days 1 and 8
• PEG-asparaginase given at 2500 U/m² intramuscularly on day 1
• Dexamethasone given at 20 mg via intravenous drip on days 1 to 3
• Methotrexate given at 3000 mg/m² via continuous, 12-hour infusion on day 1.

The regimen was repeated every 3 weeks.

For patients with stage I/II disease, 2 to 4 cycles of the GAD-M regimen was followed by extensive involved-field radiotherapy and an additional 2 to 4 cycles. For patients with stage III/IV disease, GAD-M was repeated for 6 cycles.

Response and survival

The ORR was 94.4%, both after 2 cycles of GAD-M and after 6 cycles. The CR rate was 50% after 2 cycles and 83.3% after 6 cycles.

In patients with stage I/II disease, the ORR was 100% after 2 cycles and 6 cycles. The CR rate was 54.8% after 2 cycles and 90.3% after 6 cycles.

In patients with stage III/IV disease, the ORR was 60% after 2 cycles and 6 cycles. The CR rate was 20% after 2 cycles and 40% after 6 cycles.

At median follow-up of 23.3 months, the estimated 3-year progression-free survival (PFS) was 72.1%, and the overall survival (OS) was 76.3%.

For patients with stage I/II disease, the PFS was 77.3%, and the OS was 79.3%. For patients with stage III/IV disease, the PFS was 40%, and the OS was 60%.

Safety

Hematologic adverse events (AEs) included anemia (97.2% total, 52.8% grade 3/4), leukocytopenia (94.4%, 27.8% grade 3/4), neutropenia (88.9%, 5.6% grade 3), and thrombocytopenia (47.2%, 13.9% grade 3/4).

Non-hematologic AEs included hypoalbuminemia (100%, 5.6% grade 3), increased transaminases (88.9%, 5.6% grade 3), hyperbilirubinemia (52.8%, 11.1% grade 3), decreased fibrinogen (19.4%, 11.1% grade 4), vomiting (13.9%, 2.8% grade 5), increased creatinine (8.3%, 2.8% grade 3), and abdominal pain (5.6% grade 1).

The grade 5 treatment-related AE occurred in a 61-year-old man. He died of electrolyte disorders caused by severe vomiting.

on Malignant Lymphoma

LUGANO, SWITZERLAND—A 4-drug regimen has demonstrated efficacy in a phase 2 trial of patients with treatment-naïve extranodal natural killer/T-cell lymphoma (ENKTL).

Treatment with gemcitabine, PEG-asparaginase, dexamethasone, and methotrexate (GAD-M) produced a 94% overall response rate (ORR) and an 83% complete response (CR) rate in this trial.

Responses and survival rates were higher in patients with stage I/II disease, who also received radiotherapy, than in patients with stage III/IV disease.

Grade 1/2 toxicities were frequent, but there were few grade 3/4 non-hematologic toxicities. One patient died of treatment-related toxicity.

Zhiming Li, of Sun Yet-sen University Cancer Center in Guangzhou, China, presented these results at the 14th International Conference on Malignant Lymphoma (ICML).

Patients and treatment

The trial enrolled 41 patients with treatment-naïve ENKTL, and 36 of them were evaluable.

The patients’ median age was 45 (range, 18-75), and 30.6% were female. Most patients (86.1%) had stage I/II disease, 13.9% had an ECOG performance status of 2 or greater, and 41.7% had an IPI score of 2 or greater.

The GAD-M regimen consisted of:

• Gemcitabine given at 1000 mg/m² via intravenous drip on days 1 and 8
• PEG-asparaginase given at 2500 U/m² intramuscularly on day 1
• Dexamethasone given at 20 mg via intravenous drip on days 1 to 3
• Methotrexate given at 3000 mg/m² via continuous, 12-hour infusion on day 1.

The regimen was repeated every 3 weeks.

For patients with stage I/II disease, 2 to 4 cycles of the GAD-M regimen was followed by extensive involved-field radiotherapy and an additional 2 to 4 cycles. For patients with stage III/IV disease, GAD-M was repeated for 6 cycles.

Response and survival

The ORR was 94.4%, both after 2 cycles of GAD-M and after 6 cycles. The CR rate was 50% after 2 cycles and 83.3% after 6 cycles.

In patients with stage I/II disease, the ORR was 100% after 2 cycles and 6 cycles. The CR rate was 54.8% after 2 cycles and 90.3% after 6 cycles.

In patients with stage III/IV disease, the ORR was 60% after 2 cycles and 6 cycles. The CR rate was 20% after 2 cycles and 40% after 6 cycles.

At median follow-up of 23.3 months, the estimated 3-year progression-free survival (PFS) was 72.1%, and the overall survival (OS) was 76.3%.

For patients with stage I/II disease, the PFS was 77.3%, and the OS was 79.3%. For patients with stage III/IV disease, the PFS was 40%, and the OS was 60%.

Safety

Hematologic adverse events (AEs) included anemia (97.2% total, 52.8% grade 3/4), leukocytopenia (94.4%, 27.8% grade 3/4), neutropenia (88.9%, 5.6% grade 3), and thrombocytopenia (47.2%, 13.9% grade 3/4).

Non-hematologic AEs included hypoalbuminemia (100%, 5.6% grade 3), increased transaminases (88.9%, 5.6% grade 3), hyperbilirubinemia (52.8%, 11.1% grade 3), decreased fibrinogen (19.4%, 11.1% grade 4), vomiting (13.9%, 2.8% grade 5), increased creatinine (8.3%, 2.8% grade 3), and abdominal pain (5.6% grade 1).

The grade 5 treatment-related AE occurred in a 61-year-old man. He died of electrolyte disorders caused by severe vomiting.

on Malignant Lymphoma

LUGANO, SWITZERLAND—A 4-drug regimen has demonstrated efficacy in a phase 2 trial of patients with treatment-naïve extranodal natural killer/T-cell lymphoma (ENKTL).

Treatment with gemcitabine, PEG-asparaginase, dexamethasone, and methotrexate (GAD-M) produced a 94% overall response rate (ORR) and an 83% complete response (CR) rate in this trial.

Responses and survival rates were higher in patients with stage I/II disease, who also received radiotherapy, than in patients with stage III/IV disease.

Grade 1/2 toxicities were frequent, but there were few grade 3/4 non-hematologic toxicities. One patient died of treatment-related toxicity.

Zhiming Li, of Sun Yet-sen University Cancer Center in Guangzhou, China, presented these results at the 14th International Conference on Malignant Lymphoma (ICML).

Patients and treatment

The trial enrolled 41 patients with treatment-naïve ENKTL, and 36 of them were evaluable.

The patients’ median age was 45 (range, 18-75), and 30.6% were female. Most patients (86.1%) had stage I/II disease, 13.9% had an ECOG performance status of 2 or greater, and 41.7% had an IPI score of 2 or greater.

The GAD-M regimen consisted of:

• Gemcitabine given at 1000 mg/m² via intravenous drip on days 1 and 8
• PEG-asparaginase given at 2500 U/m² intramuscularly on day 1
• Dexamethasone given at 20 mg via intravenous drip on days 1 to 3
• Methotrexate given at 3000 mg/m² via continuous, 12-hour infusion on day 1.

The regimen was repeated every 3 weeks.

For patients with stage I/II disease, 2 to 4 cycles of the GAD-M regimen was followed by extensive involved-field radiotherapy and an additional 2 to 4 cycles. For patients with stage III/IV disease, GAD-M was repeated for 6 cycles.

Response and survival

The ORR was 94.4%, both after 2 cycles of GAD-M and after 6 cycles. The CR rate was 50% after 2 cycles and 83.3% after 6 cycles.

In patients with stage I/II disease, the ORR was 100% after 2 cycles and 6 cycles. The CR rate was 54.8% after 2 cycles and 90.3% after 6 cycles.

In patients with stage III/IV disease, the ORR was 60% after 2 cycles and 6 cycles. The CR rate was 20% after 2 cycles and 40% after 6 cycles.

At median follow-up of 23.3 months, the estimated 3-year progression-free survival (PFS) was 72.1%, and the overall survival (OS) was 76.3%.

For patients with stage I/II disease, the PFS was 77.3%, and the OS was 79.3%. For patients with stage III/IV disease, the PFS was 40%, and the OS was 60%.

Safety

Hematologic adverse events (AEs) included anemia (97.2% total, 52.8% grade 3/4), leukocytopenia (94.4%, 27.8% grade 3/4), neutropenia (88.9%, 5.6% grade 3), and thrombocytopenia (47.2%, 13.9% grade 3/4).

Non-hematologic AEs included hypoalbuminemia (100%, 5.6% grade 3), increased transaminases (88.9%, 5.6% grade 3), hyperbilirubinemia (52.8%, 11.1% grade 3), decreased fibrinogen (19.4%, 11.1% grade 4), vomiting (13.9%, 2.8% grade 5), increased creatinine (8.3%, 2.8% grade 3), and abdominal pain (5.6% grade 1).

The grade 5 treatment-related AE occurred in a 61-year-old man. He died of electrolyte disorders caused by severe vomiting.

la Santa Creu i Sant Pau

New research suggests that mutations in the RFWD3 gene cause Fanconi anemia (FA).

Investigators detected mutations in the RFWD3 gene in a child with FA and confirmed the relationship between the mutations and the disorder via functional studies in cell and animal models.

The team described this research in The Journal of Clinical Oncology.

Previously, there was knowledge of 21 genes involved in FA.

“The discovery of new genes is essential not only for genetic diagnosis and advice, but also for the development of new therapies,” said study author Jordi Surrallés, PhD, of the Hospital de la Santa Creu i Sant Pau and Universitat Autonoma de Barcelona in Spain.

“The RFWD3 protein is one of the few deficient proteins in patients with Fanconi anemia in which we can see a clear enzymatic activity (ubiquitin ligase), which opens the door to massive drug screenings. In this sense, my group has already worked on several screenings of thousands of therapeutic molecules with the aim of repositioning a drug for this disease.” 

la Santa Creu i Sant Pau

New research suggests that mutations in the RFWD3 gene cause Fanconi anemia (FA).

Investigators detected mutations in the RFWD3 gene in a child with FA and confirmed the relationship between the mutations and the disorder via functional studies in cell and animal models.

The team described this research in The Journal of Clinical Oncology.

Previously, there was knowledge of 21 genes involved in FA.

“The discovery of new genes is essential not only for genetic diagnosis and advice, but also for the development of new therapies,” said study author Jordi Surrallés, PhD, of the Hospital de la Santa Creu i Sant Pau and Universitat Autonoma de Barcelona in Spain.

“The RFWD3 protein is one of the few deficient proteins in patients with Fanconi anemia in which we can see a clear enzymatic activity (ubiquitin ligase), which opens the door to massive drug screenings. In this sense, my group has already worked on several screenings of thousands of therapeutic molecules with the aim of repositioning a drug for this disease.” 

la Santa Creu i Sant Pau

New research suggests that mutations in the RFWD3 gene cause Fanconi anemia (FA).

Investigators detected mutations in the RFWD3 gene in a child with FA and confirmed the relationship between the mutations and the disorder via functional studies in cell and animal models.

The team described this research in The Journal of Clinical Oncology.

Previously, there was knowledge of 21 genes involved in FA.

“The discovery of new genes is essential not only for genetic diagnosis and advice, but also for the development of new therapies,” said study author Jordi Surrallés, PhD, of the Hospital de la Santa Creu i Sant Pau and Universitat Autonoma de Barcelona in Spain.

“The RFWD3 protein is one of the few deficient proteins in patients with Fanconi anemia in which we can see a clear enzymatic activity (ubiquitin ligase), which opens the door to massive drug screenings. In this sense, my group has already worked on several screenings of thousands of therapeutic molecules with the aim of repositioning a drug for this disease.” 

MADRID – Fatigue is an important symptom in patients with psoriatic arthritis but often goes unaddressed when treatment only involves disease modifying drugs.

A survey of more than 1,000 patients with psoriatic arthritis (PsA) in Denmark found that more than half had moderate or severe levels of fatigue, and a principal component analysis of the sources of fatigue found three factors responsible for the majority of reported patient fatigue: chronic inflammation, chronic pain, and chronification of the PsA, Tanja S. Jørgensen, PhD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler
 

MADRID – Fatigue is an important symptom in patients with psoriatic arthritis but often goes unaddressed when treatment only involves disease modifying drugs.

A survey of more than 1,000 patients with psoriatic arthritis (PsA) in Denmark found that more than half had moderate or severe levels of fatigue, and a principal component analysis of the sources of fatigue found three factors responsible for the majority of reported patient fatigue: chronic inflammation, chronic pain, and chronification of the PsA, Tanja S. Jørgensen, PhD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler
 

MADRID – Fatigue is an important symptom in patients with psoriatic arthritis but often goes unaddressed when treatment only involves disease modifying drugs.

A survey of more than 1,000 patients with psoriatic arthritis (PsA) in Denmark found that more than half had moderate or severe levels of fatigue, and a principal component analysis of the sources of fatigue found three factors responsible for the majority of reported patient fatigue: chronic inflammation, chronic pain, and chronification of the PsA, Tanja S. Jørgensen, PhD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler
 

CHICAGO – With growing pressure to deliver higher-quality care at reduced costs, more physicians and practices are looking to join a clinically integrated network. But establishing and successfully operating such a network is sometimes easier said than done.

A clinically integrated network is defined as a collection of health providers, such as physicians, hospitals, and post-acute specialists that join together to improve care and reduce costs. Such networks generally share record systems, track data, and rely on evidence-based guidelines to provide high-quality care across participating providers.

If a group meets Federal Trade Commission compliance requirements to be considered a clinically integrated network, the government will provide a safe harbor from antitrust scrutiny. The four components that networks must meet to be considered clinically integrated include: physician leadership and commitment, development and implementation of clinical practice guidelines to improve performance, development of infrastructure and technology, and financial incentives for achieving goals.

An accountable care organization (ACO) that participates in the Medicare Shared Savings Program is deemed “clinically integrated.” The clinical integration network (CIN) is the actual legal entity/network that the physicians join. Unlike physician hospital organizations (PHOs), clinically integrated networks can jointly negotiate contractual fees as long as the primary purpose of the negotiation is to achieve care improvement, according to a summary by the Medical Group Management Association.

Clinically integrated networks can also support ACOs or patient centered medical homes as part of the clinically integrated network by serving as a mechanism for sharing infrastructure and development costs.

“For doctors, participating in a clinically integrated network is an opportunity to work as part of a group, without giving up their independence,” George Mayzell, MD, chief clinical officer for Vizient Southeast, said during a recent American Bar Association meeting. Participation in such a network also may potentially support some of the alternative payment models under the Medicare Access and CHIP Reauthorization Act (MACRA), he said.

From financial challenges to lack of collaboration to data woes, physicians can face unexpected barriers as their clinically integrated network gets off the ground. Below, experts discuss the top five roadblocks to clinically integrated networks and how doctors and hospitals can overcome them.
 

1. Contribution reluctance

Although there is no hard-and-fast level, investments of time, energy, and financial resources by all participating providers are necessary to create and maintain a clinically integrated network, according to the Federal Trade Commission. However, physicians can sometimes be wary of contributing substantially to a new network, said April E. Schweitzer, a Chicago-based health law attorney who specializes in clinical integration networks and accountable care organizations.

Some doctors feel comfortable contributing only nominal amounts or believe that the system should bear the burden of costs, Ms. Schweitzer said at an American Bar Association meeting.

2. Savings expectations

Network members often have high hopes when it comes to the savings and reimbursement bonuses they expect to see once the network launches. The reality can be disappointing, said Dr. Mayzell.

“Creating savings takes time and a high level of patience/commitment,” Dr. Mayzell said in an interview. “Even when the savings are realized early on, financial awards are often low, and if they’re spread out between all of the primary care physicians and the specialists, they are not very motivating. This must be taken into account.”

It helps to set reasonable expectations early on about reimbursement, Ms. Schweitzer said. The same goes for managing payer contract expectations.

“You want to manage expectations at the outset,” she said during the meeting. “And you really do want to be honest about what the payers in your market are looking for and are expecting.”

3. Balancing leadership

Sophisticated clinically integrated networks require significant infrastructure and IT costs, thus most are funded by a hospital or health system, Ms. Schweitzer said. As a result, the hospital or health system is likely to be the sole corporate member of the legal entity serving as the network. But because success within the network requires physicians to potentially change their practice patterns, it is important to have true physician leadership on the governing board of the clinically integrated network.

Class voting is one way to balance the need for a physician-led network with appropriate governance of a clinically integrated network, Ms. Schweitzer said in an interview. Class voting allows “physicians to comprise a majority of the governing board of a clinically integrated network [while allowing the corporate member] to retain decision-making power because the physician class gets one vote and the hospital or health system class gets one vote.”

In addition, she advised giving the hospital or health system certain reserved powers to protect the health system’s tax-exempt status. This includes:

• Ensuring that the CIN serves community and charitable purposes.
• Protecting and promoting the community benefits served by the corporate member and ensuring that the assets and income of the corporate member and the CIN are used to serve community objectives.
• Protecting the assets and income of the corporate member and the CIN by ensuring that the CIN complies with all applicable laws and regulatory requirements.

4. EHR interoperability

For a successful network, quality data must be aggregated from all providers. This can prove challenging when independent physicians each have separate electronic health record systems, Dr. Mayzell said.

“You can try to aggregate this data manually, but that is extremely challenging,” he said in an interview. “To aggregate [EHR] level data, you generally need to use additional software and organizations that connect electronically with each of their systems. This is often very expensive and cumbersome, with each system requiring a different interface and often each version of each system requiring a different interface.”

In the beginning stages of the network, survey all participating providers about the most widely used EHR systems to narrow interfacing to a manageable number, Ms. Schweitzer advised.

“This is what a lot of our clients are doing during the steering committee phase,” she said. “That’s when you’re bringing the health system and the doctors together to make decisions about how this entity will run.”

Additionally, consider alternative methods for data downloads, such as flat fees, payer downloads, or manual entries. Incorporate a long-term strategy about how many record systems the network will be using in future years, added Dr. Mayzell.

5. Resistance to data download

When it comes to data, many physicians feel that patient data are “their” data, and they are uneasy about giving access to that data when participating in a clinically integrated network, Ms. Schweitzer said. Patient privacy is also a top concern.

While these are valid concerns, networks need as much data as possible in their data warehouse to show payers that their participating physicians are providing quality care, while reducing cost, she said.

A full data download is beneficial for the network because overinclusion allows for more accurate assessment and better extrapolation in quality improvement, she said. This means each participating physician submits all their patient data, regardless of payer. Remind members that from an IT perspective, data from one doctor are merely grains of sand in a beach of data. Explain to uneasy members that the data are scrubbed of all patient identifiers and that it is the aggregate data that are most valuable to the network.

“If you’re going through one of these processes, I would encourage you to push the lawyers hard because there are answers to these questions about data privacy and you should understand that 99% of the time, the data that are going to be seen, are going to be scrubbed,” she said. “I urge you to ask tough questions if you’re in the room and discussing that particular issue.”

agallegos@frontlinemedcom.com

On Twitter @legal_med

CHICAGO – With growing pressure to deliver higher-quality care at reduced costs, more physicians and practices are looking to join a clinically integrated network. But establishing and successfully operating such a network is sometimes easier said than done.

A clinically integrated network is defined as a collection of health providers, such as physicians, hospitals, and post-acute specialists that join together to improve care and reduce costs. Such networks generally share record systems, track data, and rely on evidence-based guidelines to provide high-quality care across participating providers.

If a group meets Federal Trade Commission compliance requirements to be considered a clinically integrated network, the government will provide a safe harbor from antitrust scrutiny. The four components that networks must meet to be considered clinically integrated include: physician leadership and commitment, development and implementation of clinical practice guidelines to improve performance, development of infrastructure and technology, and financial incentives for achieving goals.

An accountable care organization (ACO) that participates in the Medicare Shared Savings Program is deemed “clinically integrated.” The clinical integration network (CIN) is the actual legal entity/network that the physicians join. Unlike physician hospital organizations (PHOs), clinically integrated networks can jointly negotiate contractual fees as long as the primary purpose of the negotiation is to achieve care improvement, according to a summary by the Medical Group Management Association.

Clinically integrated networks can also support ACOs or patient centered medical homes as part of the clinically integrated network by serving as a mechanism for sharing infrastructure and development costs.

“For doctors, participating in a clinically integrated network is an opportunity to work as part of a group, without giving up their independence,” George Mayzell, MD, chief clinical officer for Vizient Southeast, said during a recent American Bar Association meeting. Participation in such a network also may potentially support some of the alternative payment models under the Medicare Access and CHIP Reauthorization Act (MACRA), he said.

From financial challenges to lack of collaboration to data woes, physicians can face unexpected barriers as their clinically integrated network gets off the ground. Below, experts discuss the top five roadblocks to clinically integrated networks and how doctors and hospitals can overcome them.
 

1. Contribution reluctance

Although there is no hard-and-fast level, investments of time, energy, and financial resources by all participating providers are necessary to create and maintain a clinically integrated network, according to the Federal Trade Commission. However, physicians can sometimes be wary of contributing substantially to a new network, said April E. Schweitzer, a Chicago-based health law attorney who specializes in clinical integration networks and accountable care organizations.

Some doctors feel comfortable contributing only nominal amounts or believe that the system should bear the burden of costs, Ms. Schweitzer said at an American Bar Association meeting.

2. Savings expectations

Network members often have high hopes when it comes to the savings and reimbursement bonuses they expect to see once the network launches. The reality can be disappointing, said Dr. Mayzell.

“Creating savings takes time and a high level of patience/commitment,” Dr. Mayzell said in an interview. “Even when the savings are realized early on, financial awards are often low, and if they’re spread out between all of the primary care physicians and the specialists, they are not very motivating. This must be taken into account.”

It helps to set reasonable expectations early on about reimbursement, Ms. Schweitzer said. The same goes for managing payer contract expectations.

“You want to manage expectations at the outset,” she said during the meeting. “And you really do want to be honest about what the payers in your market are looking for and are expecting.”

3. Balancing leadership

Sophisticated clinically integrated networks require significant infrastructure and IT costs, thus most are funded by a hospital or health system, Ms. Schweitzer said. As a result, the hospital or health system is likely to be the sole corporate member of the legal entity serving as the network. But because success within the network requires physicians to potentially change their practice patterns, it is important to have true physician leadership on the governing board of the clinically integrated network.

Class voting is one way to balance the need for a physician-led network with appropriate governance of a clinically integrated network, Ms. Schweitzer said in an interview. Class voting allows “physicians to comprise a majority of the governing board of a clinically integrated network [while allowing the corporate member] to retain decision-making power because the physician class gets one vote and the hospital or health system class gets one vote.”

In addition, she advised giving the hospital or health system certain reserved powers to protect the health system’s tax-exempt status. This includes:

• Ensuring that the CIN serves community and charitable purposes.
• Protecting and promoting the community benefits served by the corporate member and ensuring that the assets and income of the corporate member and the CIN are used to serve community objectives.
• Protecting the assets and income of the corporate member and the CIN by ensuring that the CIN complies with all applicable laws and regulatory requirements.

4. EHR interoperability

For a successful network, quality data must be aggregated from all providers. This can prove challenging when independent physicians each have separate electronic health record systems, Dr. Mayzell said.

“You can try to aggregate this data manually, but that is extremely challenging,” he said in an interview. “To aggregate [EHR] level data, you generally need to use additional software and organizations that connect electronically with each of their systems. This is often very expensive and cumbersome, with each system requiring a different interface and often each version of each system requiring a different interface.”

In the beginning stages of the network, survey all participating providers about the most widely used EHR systems to narrow interfacing to a manageable number, Ms. Schweitzer advised.

“This is what a lot of our clients are doing during the steering committee phase,” she said. “That’s when you’re bringing the health system and the doctors together to make decisions about how this entity will run.”

Additionally, consider alternative methods for data downloads, such as flat fees, payer downloads, or manual entries. Incorporate a long-term strategy about how many record systems the network will be using in future years, added Dr. Mayzell.

5. Resistance to data download

When it comes to data, many physicians feel that patient data are “their” data, and they are uneasy about giving access to that data when participating in a clinically integrated network, Ms. Schweitzer said. Patient privacy is also a top concern.

While these are valid concerns, networks need as much data as possible in their data warehouse to show payers that their participating physicians are providing quality care, while reducing cost, she said.

A full data download is beneficial for the network because overinclusion allows for more accurate assessment and better extrapolation in quality improvement, she said. This means each participating physician submits all their patient data, regardless of payer. Remind members that from an IT perspective, data from one doctor are merely grains of sand in a beach of data. Explain to uneasy members that the data are scrubbed of all patient identifiers and that it is the aggregate data that are most valuable to the network.

“If you’re going through one of these processes, I would encourage you to push the lawyers hard because there are answers to these questions about data privacy and you should understand that 99% of the time, the data that are going to be seen, are going to be scrubbed,” she said. “I urge you to ask tough questions if you’re in the room and discussing that particular issue.”

agallegos@frontlinemedcom.com

On Twitter @legal_med

CHICAGO – With growing pressure to deliver higher-quality care at reduced costs, more physicians and practices are looking to join a clinically integrated network. But establishing and successfully operating such a network is sometimes easier said than done.

A clinically integrated network is defined as a collection of health providers, such as physicians, hospitals, and post-acute specialists that join together to improve care and reduce costs. Such networks generally share record systems, track data, and rely on evidence-based guidelines to provide high-quality care across participating providers.

If a group meets Federal Trade Commission compliance requirements to be considered a clinically integrated network, the government will provide a safe harbor from antitrust scrutiny. The four components that networks must meet to be considered clinically integrated include: physician leadership and commitment, development and implementation of clinical practice guidelines to improve performance, development of infrastructure and technology, and financial incentives for achieving goals.

An accountable care organization (ACO) that participates in the Medicare Shared Savings Program is deemed “clinically integrated.” The clinical integration network (CIN) is the actual legal entity/network that the physicians join. Unlike physician hospital organizations (PHOs), clinically integrated networks can jointly negotiate contractual fees as long as the primary purpose of the negotiation is to achieve care improvement, according to a summary by the Medical Group Management Association.

Clinically integrated networks can also support ACOs or patient centered medical homes as part of the clinically integrated network by serving as a mechanism for sharing infrastructure and development costs.

“For doctors, participating in a clinically integrated network is an opportunity to work as part of a group, without giving up their independence,” George Mayzell, MD, chief clinical officer for Vizient Southeast, said during a recent American Bar Association meeting. Participation in such a network also may potentially support some of the alternative payment models under the Medicare Access and CHIP Reauthorization Act (MACRA), he said.

From financial challenges to lack of collaboration to data woes, physicians can face unexpected barriers as their clinically integrated network gets off the ground. Below, experts discuss the top five roadblocks to clinically integrated networks and how doctors and hospitals can overcome them.
 

1. Contribution reluctance

Although there is no hard-and-fast level, investments of time, energy, and financial resources by all participating providers are necessary to create and maintain a clinically integrated network, according to the Federal Trade Commission. However, physicians can sometimes be wary of contributing substantially to a new network, said April E. Schweitzer, a Chicago-based health law attorney who specializes in clinical integration networks and accountable care organizations.

Some doctors feel comfortable contributing only nominal amounts or believe that the system should bear the burden of costs, Ms. Schweitzer said at an American Bar Association meeting.

2. Savings expectations

Network members often have high hopes when it comes to the savings and reimbursement bonuses they expect to see once the network launches. The reality can be disappointing, said Dr. Mayzell.

“Creating savings takes time and a high level of patience/commitment,” Dr. Mayzell said in an interview. “Even when the savings are realized early on, financial awards are often low, and if they’re spread out between all of the primary care physicians and the specialists, they are not very motivating. This must be taken into account.”

It helps to set reasonable expectations early on about reimbursement, Ms. Schweitzer said. The same goes for managing payer contract expectations.

“You want to manage expectations at the outset,” she said during the meeting. “And you really do want to be honest about what the payers in your market are looking for and are expecting.”

3. Balancing leadership

Sophisticated clinically integrated networks require significant infrastructure and IT costs, thus most are funded by a hospital or health system, Ms. Schweitzer said. As a result, the hospital or health system is likely to be the sole corporate member of the legal entity serving as the network. But because success within the network requires physicians to potentially change their practice patterns, it is important to have true physician leadership on the governing board of the clinically integrated network.

Class voting is one way to balance the need for a physician-led network with appropriate governance of a clinically integrated network, Ms. Schweitzer said in an interview. Class voting allows “physicians to comprise a majority of the governing board of a clinically integrated network [while allowing the corporate member] to retain decision-making power because the physician class gets one vote and the hospital or health system class gets one vote.”

In addition, she advised giving the hospital or health system certain reserved powers to protect the health system’s tax-exempt status. This includes:

• Ensuring that the CIN serves community and charitable purposes.
• Protecting and promoting the community benefits served by the corporate member and ensuring that the assets and income of the corporate member and the CIN are used to serve community objectives.
• Protecting the assets and income of the corporate member and the CIN by ensuring that the CIN complies with all applicable laws and regulatory requirements.

4. EHR interoperability

For a successful network, quality data must be aggregated from all providers. This can prove challenging when independent physicians each have separate electronic health record systems, Dr. Mayzell said.

“You can try to aggregate this data manually, but that is extremely challenging,” he said in an interview. “To aggregate [EHR] level data, you generally need to use additional software and organizations that connect electronically with each of their systems. This is often very expensive and cumbersome, with each system requiring a different interface and often each version of each system requiring a different interface.”

In the beginning stages of the network, survey all participating providers about the most widely used EHR systems to narrow interfacing to a manageable number, Ms. Schweitzer advised.

“This is what a lot of our clients are doing during the steering committee phase,” she said. “That’s when you’re bringing the health system and the doctors together to make decisions about how this entity will run.”

Additionally, consider alternative methods for data downloads, such as flat fees, payer downloads, or manual entries. Incorporate a long-term strategy about how many record systems the network will be using in future years, added Dr. Mayzell.

5. Resistance to data download

When it comes to data, many physicians feel that patient data are “their” data, and they are uneasy about giving access to that data when participating in a clinically integrated network, Ms. Schweitzer said. Patient privacy is also a top concern.

While these are valid concerns, networks need as much data as possible in their data warehouse to show payers that their participating physicians are providing quality care, while reducing cost, she said.

A full data download is beneficial for the network because overinclusion allows for more accurate assessment and better extrapolation in quality improvement, she said. This means each participating physician submits all their patient data, regardless of payer. Remind members that from an IT perspective, data from one doctor are merely grains of sand in a beach of data. Explain to uneasy members that the data are scrubbed of all patient identifiers and that it is the aggregate data that are most valuable to the network.

“If you’re going through one of these processes, I would encourage you to push the lawyers hard because there are answers to these questions about data privacy and you should understand that 99% of the time, the data that are going to be seen, are going to be scrubbed,” she said. “I urge you to ask tough questions if you’re in the room and discussing that particular issue.”

agallegos@frontlinemedcom.com

On Twitter @legal_med

A blood test has been found to be effective for detecting early pancreatic cancer in those at high risk, with the potential to find the deadly cancer at a time when it is more likely to be treatable with surgery, according to phase 2b findings recently published in Science Translational Medicine.

In a 337-person study, researchers found that a blood panel for the protein thrombospondin-2 (THBS2) and cancer antigen 19-9 (CA19-9), measured with a standard ELISA test, together detected pancreatic ductal adenocarcinoma (PDAC) with a specificity of 98% and a sensitivity of 87%. The test was effective at distinguishing patients with PDAC from controls and those with benign pancreatic disease across all stages of the cancer, wrote Kenneth Zaret, PhD, at the University of Pennsylvania, Philadelphia.

©Martynasfoto/Thinkstock

A blood test has been found to be effective for detecting early pancreatic cancer in those at high risk, with the potential to find the deadly cancer at a time when it is more likely to be treatable with surgery, according to phase 2b findings recently published in Science Translational Medicine.

In a 337-person study, researchers found that a blood panel for the protein thrombospondin-2 (THBS2) and cancer antigen 19-9 (CA19-9), measured with a standard ELISA test, together detected pancreatic ductal adenocarcinoma (PDAC) with a specificity of 98% and a sensitivity of 87%. The test was effective at distinguishing patients with PDAC from controls and those with benign pancreatic disease across all stages of the cancer, wrote Kenneth Zaret, PhD, at the University of Pennsylvania, Philadelphia.

©Martynasfoto/Thinkstock

A blood test has been found to be effective for detecting early pancreatic cancer in those at high risk, with the potential to find the deadly cancer at a time when it is more likely to be treatable with surgery, according to phase 2b findings recently published in Science Translational Medicine.

In a 337-person study, researchers found that a blood panel for the protein thrombospondin-2 (THBS2) and cancer antigen 19-9 (CA19-9), measured with a standard ELISA test, together detected pancreatic ductal adenocarcinoma (PDAC) with a specificity of 98% and a sensitivity of 87%. The test was effective at distinguishing patients with PDAC from controls and those with benign pancreatic disease across all stages of the cancer, wrote Kenneth Zaret, PhD, at the University of Pennsylvania, Philadelphia.

©Martynasfoto/Thinkstock

DENVER – An antiviral drug that is a key player in the recent revolution in the treatment of hepatitis C infection also blocks Zika virus replication both in vitro and in a mouse model, Alysson R. Muotri, PhD, said at the annual meeting of the Teratology Society.

Rattikankeawpun/Thinkstock

bjancin@frontlinemedcom.com


 

DENVER – An antiviral drug that is a key player in the recent revolution in the treatment of hepatitis C infection also blocks Zika virus replication both in vitro and in a mouse model, Alysson R. Muotri, PhD, said at the annual meeting of the Teratology Society.

Rattikankeawpun/Thinkstock

bjancin@frontlinemedcom.com


 

DENVER – An antiviral drug that is a key player in the recent revolution in the treatment of hepatitis C infection also blocks Zika virus replication both in vitro and in a mouse model, Alysson R. Muotri, PhD, said at the annual meeting of the Teratology Society.

Rattikankeawpun/Thinkstock

bjancin@frontlinemedcom.com


 

Last month’s column on good hiring practices, which stressed the importance of replacing marginal employees with excellent ones, triggered an interesting round of discussion. “Isn’t it true,” asked one contributor, “that most physicians tolerate marginal employees because it’s less painful than firing them?”

Indeed it is. Firing someone is never easy, and it is particularly tough on physicians. Sometimes, however, it is unavoidable if you want to preserve the efficiency and morale of your other employees, as well as your own.

Before you do it, however, be sure that you have legitimate grounds, and assemble as much documentation as you can. Record all terminatable transgressions in the employee’s permanent record, and document all verbal and written warnings. This is essential. You must be prepared to prove that your reasons for termination were legal.

Former employees will sometimes charge that any of a number of their civil rights was violated. For example, federal law prohibits you from firing anyone because of race, gender, national origin, disability, religion, or age (if the employee is over 40). You cannot fire a woman because she is pregnant or recently gave birth. Other illegal reasons include assertion of antidiscrimination rights, refusal to take a lie detector test, and report of OSHA violations.

You also can’t terminate someone for refusing to commit an illegal act, such as filing false insurance claims, or for exercising a legal right, such as voting or participating in a political demonstration. You cannot fire an alcohol abuser unless he or she is caught drinking at work, but many forms of illegal drug use are legitimate cause for termination. Other laws may apply, depending on where you live. When in doubt, contact your state labor department or fair employment office.

If a fired employee alleges that he or she was fired for any of these illegal reasons and you do not have convincing documentation to counter the charge, you may find yourself defending your actions in court. If you anticipate such problems, you can ask the employee to sign a waver of future litigation in exchange for a concession from you – such as extra severance pay or a promise not to contest an unemployment application. Also, consider adding employment practices liability insurance (EPLI) to your umbrella policy, since lawsuits are always a possibility despite all efforts to prevent them.

Once you have all your legal ducks in a row, don’t procrastinate. Get it over with first thing on Monday morning. If you wait until Friday afternoon (as many do), you will worry about the dreaded task all week long, and the fired employee will stew about it all weekend.

Explain the performance you have expected, the steps you have taken to help correct the problems you have seen, and the fact that the problems persist. Try to limit the conversation to a minute or two, have the final paycheck ready, and make it clear that the decision has already been made, so begging and pleading will not change anything.

I’ve been asked to share exactly what I say, so, for what it’s worth: “I have called you in to discuss a difficult issue. You know that we have not been happy with your performance. We are still not happy with it, despite all the discussions we have had, and we feel that you can do better elsewhere. So, today, we will part company, and I wish you the best of luck in your future endeavors. Here is your severance check. I hope there are no hard feelings.”

There will, of course, be hard feelings, but that cannot be helped. The point is to be quick, firm, and decisive. Get it over with and allow everyone to move on.

Be sure to get all your office keys back – or change the locks if you cannot. Back up all important computer files, and change all your passwords. Most employees know more of them than you would ever suspect.

Finally, call the staff together and explain what you have done. They should hear the real story from you, not some distorted version via the rumor mill. You don’t have to explain your reasoning or divulge every detail, but do explain how the termination will affect everyone else. Responsibilities will need to be shifted until a replacement can be hired, and all employees should understand that.

If you are asked in the future to give a reference or write a letter of recommendation for the terminated employee, be sure that everything you say is truthful and well documented.

Last month’s column on good hiring practices, which stressed the importance of replacing marginal employees with excellent ones, triggered an interesting round of discussion. “Isn’t it true,” asked one contributor, “that most physicians tolerate marginal employees because it’s less painful than firing them?”

Indeed it is. Firing someone is never easy, and it is particularly tough on physicians. Sometimes, however, it is unavoidable if you want to preserve the efficiency and morale of your other employees, as well as your own.

Before you do it, however, be sure that you have legitimate grounds, and assemble as much documentation as you can. Record all terminatable transgressions in the employee’s permanent record, and document all verbal and written warnings. This is essential. You must be prepared to prove that your reasons for termination were legal.

Former employees will sometimes charge that any of a number of their civil rights was violated. For example, federal law prohibits you from firing anyone because of race, gender, national origin, disability, religion, or age (if the employee is over 40). You cannot fire a woman because she is pregnant or recently gave birth. Other illegal reasons include assertion of antidiscrimination rights, refusal to take a lie detector test, and report of OSHA violations.

You also can’t terminate someone for refusing to commit an illegal act, such as filing false insurance claims, or for exercising a legal right, such as voting or participating in a political demonstration. You cannot fire an alcohol abuser unless he or she is caught drinking at work, but many forms of illegal drug use are legitimate cause for termination. Other laws may apply, depending on where you live. When in doubt, contact your state labor department or fair employment office.

If a fired employee alleges that he or she was fired for any of these illegal reasons and you do not have convincing documentation to counter the charge, you may find yourself defending your actions in court. If you anticipate such problems, you can ask the employee to sign a waver of future litigation in exchange for a concession from you – such as extra severance pay or a promise not to contest an unemployment application. Also, consider adding employment practices liability insurance (EPLI) to your umbrella policy, since lawsuits are always a possibility despite all efforts to prevent them.

Once you have all your legal ducks in a row, don’t procrastinate. Get it over with first thing on Monday morning. If you wait until Friday afternoon (as many do), you will worry about the dreaded task all week long, and the fired employee will stew about it all weekend.

Explain the performance you have expected, the steps you have taken to help correct the problems you have seen, and the fact that the problems persist. Try to limit the conversation to a minute or two, have the final paycheck ready, and make it clear that the decision has already been made, so begging and pleading will not change anything.

I’ve been asked to share exactly what I say, so, for what it’s worth: “I have called you in to discuss a difficult issue. You know that we have not been happy with your performance. We are still not happy with it, despite all the discussions we have had, and we feel that you can do better elsewhere. So, today, we will part company, and I wish you the best of luck in your future endeavors. Here is your severance check. I hope there are no hard feelings.”

There will, of course, be hard feelings, but that cannot be helped. The point is to be quick, firm, and decisive. Get it over with and allow everyone to move on.

Be sure to get all your office keys back – or change the locks if you cannot. Back up all important computer files, and change all your passwords. Most employees know more of them than you would ever suspect.

Finally, call the staff together and explain what you have done. They should hear the real story from you, not some distorted version via the rumor mill. You don’t have to explain your reasoning or divulge every detail, but do explain how the termination will affect everyone else. Responsibilities will need to be shifted until a replacement can be hired, and all employees should understand that.

If you are asked in the future to give a reference or write a letter of recommendation for the terminated employee, be sure that everything you say is truthful and well documented.

Last month’s column on good hiring practices, which stressed the importance of replacing marginal employees with excellent ones, triggered an interesting round of discussion. “Isn’t it true,” asked one contributor, “that most physicians tolerate marginal employees because it’s less painful than firing them?”

Indeed it is. Firing someone is never easy, and it is particularly tough on physicians. Sometimes, however, it is unavoidable if you want to preserve the efficiency and morale of your other employees, as well as your own.

Before you do it, however, be sure that you have legitimate grounds, and assemble as much documentation as you can. Record all terminatable transgressions in the employee’s permanent record, and document all verbal and written warnings. This is essential. You must be prepared to prove that your reasons for termination were legal.

Former employees will sometimes charge that any of a number of their civil rights was violated. For example, federal law prohibits you from firing anyone because of race, gender, national origin, disability, religion, or age (if the employee is over 40). You cannot fire a woman because she is pregnant or recently gave birth. Other illegal reasons include assertion of antidiscrimination rights, refusal to take a lie detector test, and report of OSHA violations.

You also can’t terminate someone for refusing to commit an illegal act, such as filing false insurance claims, or for exercising a legal right, such as voting or participating in a political demonstration. You cannot fire an alcohol abuser unless he or she is caught drinking at work, but many forms of illegal drug use are legitimate cause for termination. Other laws may apply, depending on where you live. When in doubt, contact your state labor department or fair employment office.

If a fired employee alleges that he or she was fired for any of these illegal reasons and you do not have convincing documentation to counter the charge, you may find yourself defending your actions in court. If you anticipate such problems, you can ask the employee to sign a waver of future litigation in exchange for a concession from you – such as extra severance pay or a promise not to contest an unemployment application. Also, consider adding employment practices liability insurance (EPLI) to your umbrella policy, since lawsuits are always a possibility despite all efforts to prevent them.

Once you have all your legal ducks in a row, don’t procrastinate. Get it over with first thing on Monday morning. If you wait until Friday afternoon (as many do), you will worry about the dreaded task all week long, and the fired employee will stew about it all weekend.

Explain the performance you have expected, the steps you have taken to help correct the problems you have seen, and the fact that the problems persist. Try to limit the conversation to a minute or two, have the final paycheck ready, and make it clear that the decision has already been made, so begging and pleading will not change anything.

I’ve been asked to share exactly what I say, so, for what it’s worth: “I have called you in to discuss a difficult issue. You know that we have not been happy with your performance. We are still not happy with it, despite all the discussions we have had, and we feel that you can do better elsewhere. So, today, we will part company, and I wish you the best of luck in your future endeavors. Here is your severance check. I hope there are no hard feelings.”

There will, of course, be hard feelings, but that cannot be helped. The point is to be quick, firm, and decisive. Get it over with and allow everyone to move on.

Be sure to get all your office keys back – or change the locks if you cannot. Back up all important computer files, and change all your passwords. Most employees know more of them than you would ever suspect.

Finally, call the staff together and explain what you have done. They should hear the real story from you, not some distorted version via the rumor mill. You don’t have to explain your reasoning or divulge every detail, but do explain how the termination will affect everyone else. Responsibilities will need to be shifted until a replacement can be hired, and all employees should understand that.

If you are asked in the future to give a reference or write a letter of recommendation for the terminated employee, be sure that everything you say is truthful and well documented.

An appeals court has struck down Wisconsin’s medical malpractice cap for noneconomic damages, ruling that the $750,000 limit is unconstitutional.

In a July opinion, a panel of the First District Court of Appeals wrote that the medical liability cap denies equal protection for the most severely injured patients who are awarded damages exceeding the limit. The decision reinstates a $16.5 million noneconomic damages verdict awarded to a Wisconsin women who lost her limbs after a delayed sepsis diagnosis, according to court documents.

The Wisconsin Medical Society expressed its disappointment at the decision, warning that the ruling could destabilize Wisconsin’s medical liability environment and endanger patients’ access to high-quality, affordable care.

“This decision endangers the long-term solvency of the Injured Patients and Families Compensation Fund and its ability to adequately compensate patients and incentivizes attorneys to file questionable cases in hopes of astronomical jury awards seen in other states without caps,” Noel Deep, MD, president of the Wisconsin Medical Society, said in a statement. “We look forward to further opportunities to explain the importance of the cap to the stability of Wisconsin’s medical liability environment and its benefits for all Wisconsin patients as this case progresses.”

The Wisconsin Association for Justice, an association for the plaintiffs’ bar, praised the cap’s elimination.

“The Court of Appeals, in a concise and well-reasoned opinion, took a brave step toward ensuring that injured patients in Wisconsin can achieve justice by utilizing their constitutional right to a civil jury trial,” Association President Benjamin S. Wagner said in a statement. “The data the court relied upon speaks for itself. The imposition of damage caps against a person like Ascaris Mayo has no rational relationship to controlling medical costs, nor does the verdict impose a financial hardship on the Injured Patients and Families Compensation Fund. To the contrary, the court’s decision ensures that the fund meets its dual statutory obligations to provide excess insurance to medical professionals and provide compensation to injured patients and families.”

The ruling results from a medical malpractice lawsuit filed by patient Ascaris Mayo and her family against Infinity Health Care in Milwaukee, an emergency physician, a physician assistant, ProAssurance Wisconsin Insurance, and the Wisconsin Injured Patients and Families Compensation Fund. The suit claimed that, during a visit to the emergency department at Columbia St. Mary’s Hospital in Milwaukee for abdominal pain and a high fever, health providers failed to diagnosis and treat Ms. Mayo for sepsis. The sepsis led to organ failure, dry gangrene, and, eventually, amputation of her extremities, according to court documents.

A jury awarded Ms. Mayo and her husband $9 million in economic damages and $16.5 million in noneconomic damages. After the verdict, representatives for the Wisconsin Injured Patients and Families Compensation Fund moved to reduce the noneconomic damages award to $750,000 per the state’s cap. The Mayos challenged the reduction, arguing that the cap violated their constitutional rights. A circuit court concluded that the cap was not facially unconstitutional and that it was unconstitutional as applied to the Mayos because it violated the Mayos’ rights to equal protection and due process. Both the Mayos and representatives for the compensation fund appealed.

In their decision, the appeals panel shot down the reasoning used by Wisconsin’s Legislature to enact the noneconomic damages cap, raising doubts that the limit reduces defensive medicine by physicians and prevents a doctor shortage in the state.

“The record before us does not support a finding that the legislative objectives articulated in [the statute] are promoted in any way because the amount of the noneconomic damages cap is $750,000,” the judges wrote. “Data demonstrate that many states with no caps on noneconomic damages actually have higher physician retention rates than Wisconsin. [In addition,] the record before us shows that the ability to accurately measure the financial impact of ‘defensive medicine’ practices has not improved. ... Indeed, data suggest that the existence of noneconomic damages caps may actually increase the risk to patient safety.”

The case is expected to be appealed to the Wisconsin Supreme Court.

agallegos@frontlinemedcom.com

On Twitter @legal_med

An appeals court has struck down Wisconsin’s medical malpractice cap for noneconomic damages, ruling that the $750,000 limit is unconstitutional.

In a July opinion, a panel of the First District Court of Appeals wrote that the medical liability cap denies equal protection for the most severely injured patients who are awarded damages exceeding the limit. The decision reinstates a $16.5 million noneconomic damages verdict awarded to a Wisconsin women who lost her limbs after a delayed sepsis diagnosis, according to court documents.

The Wisconsin Medical Society expressed its disappointment at the decision, warning that the ruling could destabilize Wisconsin’s medical liability environment and endanger patients’ access to high-quality, affordable care.

“This decision endangers the long-term solvency of the Injured Patients and Families Compensation Fund and its ability to adequately compensate patients and incentivizes attorneys to file questionable cases in hopes of astronomical jury awards seen in other states without caps,” Noel Deep, MD, president of the Wisconsin Medical Society, said in a statement. “We look forward to further opportunities to explain the importance of the cap to the stability of Wisconsin’s medical liability environment and its benefits for all Wisconsin patients as this case progresses.”

The Wisconsin Association for Justice, an association for the plaintiffs’ bar, praised the cap’s elimination.

“The Court of Appeals, in a concise and well-reasoned opinion, took a brave step toward ensuring that injured patients in Wisconsin can achieve justice by utilizing their constitutional right to a civil jury trial,” Association President Benjamin S. Wagner said in a statement. “The data the court relied upon speaks for itself. The imposition of damage caps against a person like Ascaris Mayo has no rational relationship to controlling medical costs, nor does the verdict impose a financial hardship on the Injured Patients and Families Compensation Fund. To the contrary, the court’s decision ensures that the fund meets its dual statutory obligations to provide excess insurance to medical professionals and provide compensation to injured patients and families.”

The ruling results from a medical malpractice lawsuit filed by patient Ascaris Mayo and her family against Infinity Health Care in Milwaukee, an emergency physician, a physician assistant, ProAssurance Wisconsin Insurance, and the Wisconsin Injured Patients and Families Compensation Fund. The suit claimed that, during a visit to the emergency department at Columbia St. Mary’s Hospital in Milwaukee for abdominal pain and a high fever, health providers failed to diagnosis and treat Ms. Mayo for sepsis. The sepsis led to organ failure, dry gangrene, and, eventually, amputation of her extremities, according to court documents.

A jury awarded Ms. Mayo and her husband $9 million in economic damages and $16.5 million in noneconomic damages. After the verdict, representatives for the Wisconsin Injured Patients and Families Compensation Fund moved to reduce the noneconomic damages award to $750,000 per the state’s cap. The Mayos challenged the reduction, arguing that the cap violated their constitutional rights. A circuit court concluded that the cap was not facially unconstitutional and that it was unconstitutional as applied to the Mayos because it violated the Mayos’ rights to equal protection and due process. Both the Mayos and representatives for the compensation fund appealed.

In their decision, the appeals panel shot down the reasoning used by Wisconsin’s Legislature to enact the noneconomic damages cap, raising doubts that the limit reduces defensive medicine by physicians and prevents a doctor shortage in the state.

“The record before us does not support a finding that the legislative objectives articulated in [the statute] are promoted in any way because the amount of the noneconomic damages cap is $750,000,” the judges wrote. “Data demonstrate that many states with no caps on noneconomic damages actually have higher physician retention rates than Wisconsin. [In addition,] the record before us shows that the ability to accurately measure the financial impact of ‘defensive medicine’ practices has not improved. ... Indeed, data suggest that the existence of noneconomic damages caps may actually increase the risk to patient safety.”

The case is expected to be appealed to the Wisconsin Supreme Court.

agallegos@frontlinemedcom.com

On Twitter @legal_med

An appeals court has struck down Wisconsin’s medical malpractice cap for noneconomic damages, ruling that the $750,000 limit is unconstitutional.

In a July opinion, a panel of the First District Court of Appeals wrote that the medical liability cap denies equal protection for the most severely injured patients who are awarded damages exceeding the limit. The decision reinstates a $16.5 million noneconomic damages verdict awarded to a Wisconsin women who lost her limbs after a delayed sepsis diagnosis, according to court documents.

The Wisconsin Medical Society expressed its disappointment at the decision, warning that the ruling could destabilize Wisconsin’s medical liability environment and endanger patients’ access to high-quality, affordable care.

“This decision endangers the long-term solvency of the Injured Patients and Families Compensation Fund and its ability to adequately compensate patients and incentivizes attorneys to file questionable cases in hopes of astronomical jury awards seen in other states without caps,” Noel Deep, MD, president of the Wisconsin Medical Society, said in a statement. “We look forward to further opportunities to explain the importance of the cap to the stability of Wisconsin’s medical liability environment and its benefits for all Wisconsin patients as this case progresses.”

The Wisconsin Association for Justice, an association for the plaintiffs’ bar, praised the cap’s elimination.

“The Court of Appeals, in a concise and well-reasoned opinion, took a brave step toward ensuring that injured patients in Wisconsin can achieve justice by utilizing their constitutional right to a civil jury trial,” Association President Benjamin S. Wagner said in a statement. “The data the court relied upon speaks for itself. The imposition of damage caps against a person like Ascaris Mayo has no rational relationship to controlling medical costs, nor does the verdict impose a financial hardship on the Injured Patients and Families Compensation Fund. To the contrary, the court’s decision ensures that the fund meets its dual statutory obligations to provide excess insurance to medical professionals and provide compensation to injured patients and families.”

The ruling results from a medical malpractice lawsuit filed by patient Ascaris Mayo and her family against Infinity Health Care in Milwaukee, an emergency physician, a physician assistant, ProAssurance Wisconsin Insurance, and the Wisconsin Injured Patients and Families Compensation Fund. The suit claimed that, during a visit to the emergency department at Columbia St. Mary’s Hospital in Milwaukee for abdominal pain and a high fever, health providers failed to diagnosis and treat Ms. Mayo for sepsis. The sepsis led to organ failure, dry gangrene, and, eventually, amputation of her extremities, according to court documents.

A jury awarded Ms. Mayo and her husband $9 million in economic damages and $16.5 million in noneconomic damages. After the verdict, representatives for the Wisconsin Injured Patients and Families Compensation Fund moved to reduce the noneconomic damages award to $750,000 per the state’s cap. The Mayos challenged the reduction, arguing that the cap violated their constitutional rights. A circuit court concluded that the cap was not facially unconstitutional and that it was unconstitutional as applied to the Mayos because it violated the Mayos’ rights to equal protection and due process. Both the Mayos and representatives for the compensation fund appealed.

In their decision, the appeals panel shot down the reasoning used by Wisconsin’s Legislature to enact the noneconomic damages cap, raising doubts that the limit reduces defensive medicine by physicians and prevents a doctor shortage in the state.

“The record before us does not support a finding that the legislative objectives articulated in [the statute] are promoted in any way because the amount of the noneconomic damages cap is $750,000,” the judges wrote. “Data demonstrate that many states with no caps on noneconomic damages actually have higher physician retention rates than Wisconsin. [In addition,] the record before us shows that the ability to accurately measure the financial impact of ‘defensive medicine’ practices has not improved. ... Indeed, data suggest that the existence of noneconomic damages caps may actually increase the risk to patient safety.”

The case is expected to be appealed to the Wisconsin Supreme Court.

agallegos@frontlinemedcom.com

On Twitter @legal_med