© Phil McCarten 2017

ATLANTA—The chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; KTE-C19) is showing consistent, ongoing responses more than a year after infusion.

An updated analysis of the phase 1/2 ZUMA-1 trial showed that 42% of patients who received axi-cel maintained an objective response at a median follow-up of 15.4 months.

Forty percent of patients have maintained a complete response (CR).

This compares with a 44% objective response rate and a 39% CR rate in the primary analysis of phase 2 ZUMA-1 data, when the median follow-up was 8.7 months.

Sattva S. Neelapu, MD, of MD Anderson Cancer Center in Houston, Texas, reported the long-term results from ZUMA-1 at the 2017 ASH Annual Meeting (abstract 578). The findings were published simultaneously in NEJM.

The primary phase 2 analysis was previously presented at the AACR Annual Meeting 2017.

At ASH 2017, Dr Neelapu disclosed that he has received research funding and served as a consultant for Kite Pharma, the developer of axi-cel. Kite Pharma and the Leukemia & Lymphoma Society Therapy Acceleration Program supported ZUMA-1.

Study schema and patient characteristics

Phase 1 of ZUMA-1 enrolled 7 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL).

In phase 2, 101 patients were grouped into 2 cohorts—77 with refractory DLBCL and 24 with refractory PMBCL/TFL.

A total of 108 patients were treated in phases 1 and 2 and were included in the long-term pooled analysis.

Patients received a conditioning regimen of cyclophosphamide and fludarabine and, 2 days later, a fixed dose of axi-cel at 2 x 10⁶ CAR T cells/kg.

“Importantly, the product could be manufactured for 99% of enrolled patients,” Dr Neelapu said. “Moreover, 91% of the enrolled patients were dosed with axi-cel, and there were no patients lost to follow-up.”

Patients in the pooled analysis were a median age of 58 (range, 23–76), and 27 (25%) were 65 or older.

Seventy-three patients (68%) were male, 62 (57%) had an ECOG status of 1, 90 (83%) had stage III or IV disease, and 48 (44%) had an IPI score of 3 to 4.

Seventy-six patients (70%) had received 3 or more prior therapies.

Eighty patients (74%) were refractory to their second or later line of therapy, and 70 (65%) had progressive disease as their best response to their last prior therapy. Twenty-five patients (23%) had relapsed after autologous stem cell transplant.

Response

The data cutoff for the long-term analysis was August 11, 2017.

In addition to the ongoing responses mentioned above, the best objective response was 82% in both the phase 2 primary analysis and the long-term analysis for phases 1 and 2.

CR as the best objective response increased from 54% in the primary analysis to 58% at the longer follow-up.

“We did observe deepening of the responses over time,” Dr Neelapu said. “At the time of the first tumor assessment, 60 patients had either partial remission or stable disease. But 23 of those 60 eventually achieved a complete remission up to 15 months post-infusion without any additional therapy.”

The median time to conversion from partial response to CR was 64 days (range, 49–242).

“The durability of these responses was observed consistently across key covariates,” Dr Neelapu added, “including the refractory subgroups, the disease stage groups, IPI risk groups. The CD19 status at baseline did not matter, nor did the cell of origin, or the CD4/CD8 ratio of the product.”

Furthermore, the investigators observed no differences in patients who received tocilizumab or corticosteroids.

The median duration of response for all patients was 11.1 months. For those who achieved CR, the median duration of response has not yet been reached.

Three of the 7 patients (43%) in the phase 1 part of the trial had an ongoing CR at 24 months.

At the median follow-up of 15.4 months, 42% of patients were progression-free, and 56% were alive.

The median overall survival has not been reached. Investigators estimated the 18-month overall survival to be 52%.

Safety

Adverse events (AEs) of grade 3 or higher occurred in 97% of patients, and serious AEs of grade 3 or higher occurred in 46% of patients in the updated analysis.

No new axi-cel-related AEs of cytokine release syndrome, neurologic events, or grade 5 AEs have arisen since the primary analysis.

There were four grade 5 events, 2 of which were related to axi-cel.

“All these four grade 5 events were previously reported—three in the phase 2 and one in the phase 1 trial,” Dr Neelapu said.

Most patients experienced hypogammaglobulinemia and B-cell aplasia. Eight percent of patients had IVIG support during the study.

Infections, such as pneumonia, influenza, and viral infection, were the most common new-onset treatment-emergent serious AEs occurring after 6 months in 10 patients. All were manageable and resolved prior to the data cut-off.

Persistence and resistance

“We observed long-term persistence of the CAR T cells,” Dr Neelapu said.

CAR T cells persisted in 71% of patients still responding at 1 year. And durable responses were observed in patients with and without detectable CAR T cells.

A central review committee analyzed biopsies of 21 evaluable patients at progression to try to determine the mechanism of resistance.

Fourteen of 21 (67%) biopsies were CD19-positive. Of these, 9 were PD-L1-positive, 4 were PD-L1-negative, and 1 was not evaluable.

Seven patients (33%) were CD19-negative compared to baseline. Of these, 4 were PD-L1-positive, 2 were PD-L1-negative, and 1 was not evaluable.

“This PD-L1 expression was observed in both CD19-positive relapses and CD19-negative relapses,” Dr Neelapu emphasized.

Of the 21 patients, 62% were PD-L1-positive.

Investigators hypothesize that 2 potential mechanisms could contribute to relapse: loss of CD19 and expression of PD-L1.

Axi-cel (Yescarta™) was approved by the US Food and Drug Administration in October for the treatment of adults with relapsed or refractory large B-cell lymphoma.

© Phil McCarten 2017

ATLANTA—The chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; KTE-C19) is showing consistent, ongoing responses more than a year after infusion.

An updated analysis of the phase 1/2 ZUMA-1 trial showed that 42% of patients who received axi-cel maintained an objective response at a median follow-up of 15.4 months.

Forty percent of patients have maintained a complete response (CR).

This compares with a 44% objective response rate and a 39% CR rate in the primary analysis of phase 2 ZUMA-1 data, when the median follow-up was 8.7 months.

Sattva S. Neelapu, MD, of MD Anderson Cancer Center in Houston, Texas, reported the long-term results from ZUMA-1 at the 2017 ASH Annual Meeting (abstract 578). The findings were published simultaneously in NEJM.

The primary phase 2 analysis was previously presented at the AACR Annual Meeting 2017.

At ASH 2017, Dr Neelapu disclosed that he has received research funding and served as a consultant for Kite Pharma, the developer of axi-cel. Kite Pharma and the Leukemia & Lymphoma Society Therapy Acceleration Program supported ZUMA-1.

Study schema and patient characteristics

Phase 1 of ZUMA-1 enrolled 7 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL).

In phase 2, 101 patients were grouped into 2 cohorts—77 with refractory DLBCL and 24 with refractory PMBCL/TFL.

A total of 108 patients were treated in phases 1 and 2 and were included in the long-term pooled analysis.

Patients received a conditioning regimen of cyclophosphamide and fludarabine and, 2 days later, a fixed dose of axi-cel at 2 x 10⁶ CAR T cells/kg.

“Importantly, the product could be manufactured for 99% of enrolled patients,” Dr Neelapu said. “Moreover, 91% of the enrolled patients were dosed with axi-cel, and there were no patients lost to follow-up.”

Patients in the pooled analysis were a median age of 58 (range, 23–76), and 27 (25%) were 65 or older.

Seventy-three patients (68%) were male, 62 (57%) had an ECOG status of 1, 90 (83%) had stage III or IV disease, and 48 (44%) had an IPI score of 3 to 4.

Seventy-six patients (70%) had received 3 or more prior therapies.

Eighty patients (74%) were refractory to their second or later line of therapy, and 70 (65%) had progressive disease as their best response to their last prior therapy. Twenty-five patients (23%) had relapsed after autologous stem cell transplant.

Response

The data cutoff for the long-term analysis was August 11, 2017.

In addition to the ongoing responses mentioned above, the best objective response was 82% in both the phase 2 primary analysis and the long-term analysis for phases 1 and 2.

CR as the best objective response increased from 54% in the primary analysis to 58% at the longer follow-up.

“We did observe deepening of the responses over time,” Dr Neelapu said. “At the time of the first tumor assessment, 60 patients had either partial remission or stable disease. But 23 of those 60 eventually achieved a complete remission up to 15 months post-infusion without any additional therapy.”

The median time to conversion from partial response to CR was 64 days (range, 49–242).

“The durability of these responses was observed consistently across key covariates,” Dr Neelapu added, “including the refractory subgroups, the disease stage groups, IPI risk groups. The CD19 status at baseline did not matter, nor did the cell of origin, or the CD4/CD8 ratio of the product.”

Furthermore, the investigators observed no differences in patients who received tocilizumab or corticosteroids.

The median duration of response for all patients was 11.1 months. For those who achieved CR, the median duration of response has not yet been reached.

Three of the 7 patients (43%) in the phase 1 part of the trial had an ongoing CR at 24 months.

At the median follow-up of 15.4 months, 42% of patients were progression-free, and 56% were alive.

The median overall survival has not been reached. Investigators estimated the 18-month overall survival to be 52%.

Safety

Adverse events (AEs) of grade 3 or higher occurred in 97% of patients, and serious AEs of grade 3 or higher occurred in 46% of patients in the updated analysis.

No new axi-cel-related AEs of cytokine release syndrome, neurologic events, or grade 5 AEs have arisen since the primary analysis.

There were four grade 5 events, 2 of which were related to axi-cel.

“All these four grade 5 events were previously reported—three in the phase 2 and one in the phase 1 trial,” Dr Neelapu said.

Most patients experienced hypogammaglobulinemia and B-cell aplasia. Eight percent of patients had IVIG support during the study.

Infections, such as pneumonia, influenza, and viral infection, were the most common new-onset treatment-emergent serious AEs occurring after 6 months in 10 patients. All were manageable and resolved prior to the data cut-off.

Persistence and resistance

“We observed long-term persistence of the CAR T cells,” Dr Neelapu said.

CAR T cells persisted in 71% of patients still responding at 1 year. And durable responses were observed in patients with and without detectable CAR T cells.

A central review committee analyzed biopsies of 21 evaluable patients at progression to try to determine the mechanism of resistance.

Fourteen of 21 (67%) biopsies were CD19-positive. Of these, 9 were PD-L1-positive, 4 were PD-L1-negative, and 1 was not evaluable.

Seven patients (33%) were CD19-negative compared to baseline. Of these, 4 were PD-L1-positive, 2 were PD-L1-negative, and 1 was not evaluable.

“This PD-L1 expression was observed in both CD19-positive relapses and CD19-negative relapses,” Dr Neelapu emphasized.

Of the 21 patients, 62% were PD-L1-positive.

Investigators hypothesize that 2 potential mechanisms could contribute to relapse: loss of CD19 and expression of PD-L1.

Axi-cel (Yescarta™) was approved by the US Food and Drug Administration in October for the treatment of adults with relapsed or refractory large B-cell lymphoma.

© Phil McCarten 2017

ATLANTA—The chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel; KTE-C19) is showing consistent, ongoing responses more than a year after infusion.

An updated analysis of the phase 1/2 ZUMA-1 trial showed that 42% of patients who received axi-cel maintained an objective response at a median follow-up of 15.4 months.

Forty percent of patients have maintained a complete response (CR).

This compares with a 44% objective response rate and a 39% CR rate in the primary analysis of phase 2 ZUMA-1 data, when the median follow-up was 8.7 months.

Sattva S. Neelapu, MD, of MD Anderson Cancer Center in Houston, Texas, reported the long-term results from ZUMA-1 at the 2017 ASH Annual Meeting (abstract 578). The findings were published simultaneously in NEJM.

The primary phase 2 analysis was previously presented at the AACR Annual Meeting 2017.

At ASH 2017, Dr Neelapu disclosed that he has received research funding and served as a consultant for Kite Pharma, the developer of axi-cel. Kite Pharma and the Leukemia & Lymphoma Society Therapy Acceleration Program supported ZUMA-1.

Study schema and patient characteristics

Phase 1 of ZUMA-1 enrolled 7 patients with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), or transformed follicular lymphoma (TFL).

In phase 2, 101 patients were grouped into 2 cohorts—77 with refractory DLBCL and 24 with refractory PMBCL/TFL.

A total of 108 patients were treated in phases 1 and 2 and were included in the long-term pooled analysis.

Patients received a conditioning regimen of cyclophosphamide and fludarabine and, 2 days later, a fixed dose of axi-cel at 2 x 10⁶ CAR T cells/kg.

“Importantly, the product could be manufactured for 99% of enrolled patients,” Dr Neelapu said. “Moreover, 91% of the enrolled patients were dosed with axi-cel, and there were no patients lost to follow-up.”

Patients in the pooled analysis were a median age of 58 (range, 23–76), and 27 (25%) were 65 or older.

Seventy-three patients (68%) were male, 62 (57%) had an ECOG status of 1, 90 (83%) had stage III or IV disease, and 48 (44%) had an IPI score of 3 to 4.

Seventy-six patients (70%) had received 3 or more prior therapies.

Eighty patients (74%) were refractory to their second or later line of therapy, and 70 (65%) had progressive disease as their best response to their last prior therapy. Twenty-five patients (23%) had relapsed after autologous stem cell transplant.

Response

The data cutoff for the long-term analysis was August 11, 2017.

In addition to the ongoing responses mentioned above, the best objective response was 82% in both the phase 2 primary analysis and the long-term analysis for phases 1 and 2.

CR as the best objective response increased from 54% in the primary analysis to 58% at the longer follow-up.

“We did observe deepening of the responses over time,” Dr Neelapu said. “At the time of the first tumor assessment, 60 patients had either partial remission or stable disease. But 23 of those 60 eventually achieved a complete remission up to 15 months post-infusion without any additional therapy.”

The median time to conversion from partial response to CR was 64 days (range, 49–242).

“The durability of these responses was observed consistently across key covariates,” Dr Neelapu added, “including the refractory subgroups, the disease stage groups, IPI risk groups. The CD19 status at baseline did not matter, nor did the cell of origin, or the CD4/CD8 ratio of the product.”

Furthermore, the investigators observed no differences in patients who received tocilizumab or corticosteroids.

The median duration of response for all patients was 11.1 months. For those who achieved CR, the median duration of response has not yet been reached.

Three of the 7 patients (43%) in the phase 1 part of the trial had an ongoing CR at 24 months.

At the median follow-up of 15.4 months, 42% of patients were progression-free, and 56% were alive.

The median overall survival has not been reached. Investigators estimated the 18-month overall survival to be 52%.

Safety

Adverse events (AEs) of grade 3 or higher occurred in 97% of patients, and serious AEs of grade 3 or higher occurred in 46% of patients in the updated analysis.

No new axi-cel-related AEs of cytokine release syndrome, neurologic events, or grade 5 AEs have arisen since the primary analysis.

There were four grade 5 events, 2 of which were related to axi-cel.

“All these four grade 5 events were previously reported—three in the phase 2 and one in the phase 1 trial,” Dr Neelapu said.

Most patients experienced hypogammaglobulinemia and B-cell aplasia. Eight percent of patients had IVIG support during the study.

Infections, such as pneumonia, influenza, and viral infection, were the most common new-onset treatment-emergent serious AEs occurring after 6 months in 10 patients. All were manageable and resolved prior to the data cut-off.

Persistence and resistance

“We observed long-term persistence of the CAR T cells,” Dr Neelapu said.

CAR T cells persisted in 71% of patients still responding at 1 year. And durable responses were observed in patients with and without detectable CAR T cells.

A central review committee analyzed biopsies of 21 evaluable patients at progression to try to determine the mechanism of resistance.

Fourteen of 21 (67%) biopsies were CD19-positive. Of these, 9 were PD-L1-positive, 4 were PD-L1-negative, and 1 was not evaluable.

Seven patients (33%) were CD19-negative compared to baseline. Of these, 4 were PD-L1-positive, 2 were PD-L1-negative, and 1 was not evaluable.

“This PD-L1 expression was observed in both CD19-positive relapses and CD19-negative relapses,” Dr Neelapu emphasized.

Of the 21 patients, 62% were PD-L1-positive.

Investigators hypothesize that 2 potential mechanisms could contribute to relapse: loss of CD19 and expression of PD-L1.

Axi-cel (Yescarta™) was approved by the US Food and Drug Administration in October for the treatment of adults with relapsed or refractory large B-cell lymphoma.

The American Academy of Pediatrics Committee on Infectious Diseases has added information on peramivir, a recently approved antiviral medication, to its Recommendations for Prevention and Control of Influenza in Children for 2017-2018.

Peramivir (Rapivab) was approved by the Food and Drug Administration in September 2017, as an intravenous treatment for acute, uncomplicated influenza in nonhospitalized children aged 2 years and older who have been symptomatic for no more than 2 days, according to the update.

Peramivir is given to 2-12 year olds as a single infusion at 12 mg/kg, with a maximum dose of 600 mg, according to the guideline update (Pediatrics. 2017 Oct;140[4]:e20172550). Patients 13 years and older should receive the 600-mg dose.

“Rapivab is a great addition to our armamentarium of antiviral agents to combat influenza,” John A. Vanchiere, MD, PhD, chief of the section of pediatric infectious diseases at LSU Health Sciences Center, Shreveport. said in a press release from the drug’s manufacturer, BioCryst Pharmaceuticals. “It will be especially helpful for patients who cannot tolerate oral medications. In addition, the long half-life allows for one-time dosing, which will improve compliance.”

Dr. Vanchiere is the lead author in a study of peramivir’s effectiveness against pediatric influenza that was presented as a poster at ID Week 2017.

The phase 3, randomized, control trial included 122 patients, ranging in age from newborns to 18-year-olds, with acute uncomplicated influenza symptoms.

Investigators gave 92 patients peramivir, while the remaining 23 received oral oseltamivir (Tamiflu).

Nearly all (93%) of the patients were white; 61% had an influenza A strain infection, and there were comparable numbers of male and female study subjects.

Vomiting, fever, and tympanic membrane erythema were the most common adverse effects specifically reported in the study, which was funded by BioCryst.

Peramivir is the third neuraminidase inhibitor (NAI) to be approved; other approved NAIs include oral oseltamivir and inhaled zanamivir.

A fourth NAI, intravenous zanamivir, is still investigational in the United States.

Peramivir, like other antiviral drugs, may interfere with a live attenuated influenza vaccine and should not be used within 2 weeks after or 48 hours before the use of an LAIV.

While the AAP’s recommendations highlight the antiviral’s effectiveness in controlling influenza, the Academy warns that antivirals are not a substitute for influenza vaccination.

[email protected]

The American Academy of Pediatrics Committee on Infectious Diseases has added information on peramivir, a recently approved antiviral medication, to its Recommendations for Prevention and Control of Influenza in Children for 2017-2018.

Peramivir (Rapivab) was approved by the Food and Drug Administration in September 2017, as an intravenous treatment for acute, uncomplicated influenza in nonhospitalized children aged 2 years and older who have been symptomatic for no more than 2 days, according to the update.

Peramivir is given to 2-12 year olds as a single infusion at 12 mg/kg, with a maximum dose of 600 mg, according to the guideline update (Pediatrics. 2017 Oct;140[4]:e20172550). Patients 13 years and older should receive the 600-mg dose.

“Rapivab is a great addition to our armamentarium of antiviral agents to combat influenza,” John A. Vanchiere, MD, PhD, chief of the section of pediatric infectious diseases at LSU Health Sciences Center, Shreveport. said in a press release from the drug’s manufacturer, BioCryst Pharmaceuticals. “It will be especially helpful for patients who cannot tolerate oral medications. In addition, the long half-life allows for one-time dosing, which will improve compliance.”

Dr. Vanchiere is the lead author in a study of peramivir’s effectiveness against pediatric influenza that was presented as a poster at ID Week 2017.

The phase 3, randomized, control trial included 122 patients, ranging in age from newborns to 18-year-olds, with acute uncomplicated influenza symptoms.

Investigators gave 92 patients peramivir, while the remaining 23 received oral oseltamivir (Tamiflu).

Nearly all (93%) of the patients were white; 61% had an influenza A strain infection, and there were comparable numbers of male and female study subjects.

Vomiting, fever, and tympanic membrane erythema were the most common adverse effects specifically reported in the study, which was funded by BioCryst.

Peramivir is the third neuraminidase inhibitor (NAI) to be approved; other approved NAIs include oral oseltamivir and inhaled zanamivir.

A fourth NAI, intravenous zanamivir, is still investigational in the United States.

Peramivir, like other antiviral drugs, may interfere with a live attenuated influenza vaccine and should not be used within 2 weeks after or 48 hours before the use of an LAIV.

While the AAP’s recommendations highlight the antiviral’s effectiveness in controlling influenza, the Academy warns that antivirals are not a substitute for influenza vaccination.

[email protected]

The American Academy of Pediatrics Committee on Infectious Diseases has added information on peramivir, a recently approved antiviral medication, to its Recommendations for Prevention and Control of Influenza in Children for 2017-2018.

Peramivir (Rapivab) was approved by the Food and Drug Administration in September 2017, as an intravenous treatment for acute, uncomplicated influenza in nonhospitalized children aged 2 years and older who have been symptomatic for no more than 2 days, according to the update.

Peramivir is given to 2-12 year olds as a single infusion at 12 mg/kg, with a maximum dose of 600 mg, according to the guideline update (Pediatrics. 2017 Oct;140[4]:e20172550). Patients 13 years and older should receive the 600-mg dose.

“Rapivab is a great addition to our armamentarium of antiviral agents to combat influenza,” John A. Vanchiere, MD, PhD, chief of the section of pediatric infectious diseases at LSU Health Sciences Center, Shreveport. said in a press release from the drug’s manufacturer, BioCryst Pharmaceuticals. “It will be especially helpful for patients who cannot tolerate oral medications. In addition, the long half-life allows for one-time dosing, which will improve compliance.”

Dr. Vanchiere is the lead author in a study of peramivir’s effectiveness against pediatric influenza that was presented as a poster at ID Week 2017.

The phase 3, randomized, control trial included 122 patients, ranging in age from newborns to 18-year-olds, with acute uncomplicated influenza symptoms.

Investigators gave 92 patients peramivir, while the remaining 23 received oral oseltamivir (Tamiflu).

Nearly all (93%) of the patients were white; 61% had an influenza A strain infection, and there were comparable numbers of male and female study subjects.

Vomiting, fever, and tympanic membrane erythema were the most common adverse effects specifically reported in the study, which was funded by BioCryst.

Peramivir is the third neuraminidase inhibitor (NAI) to be approved; other approved NAIs include oral oseltamivir and inhaled zanamivir.

A fourth NAI, intravenous zanamivir, is still investigational in the United States.

Peramivir, like other antiviral drugs, may interfere with a live attenuated influenza vaccine and should not be used within 2 weeks after or 48 hours before the use of an LAIV.

While the AAP’s recommendations highlight the antiviral’s effectiveness in controlling influenza, the Academy warns that antivirals are not a substitute for influenza vaccination.

[email protected]

Vidyard Video

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Additional videos from SGS are available here, including these recent offerings:

• Technique for apical suspension at the time of total laparoscopic hysterectomy
• Strategies to overcome the loss of port placement triangulation
• Advances in ablative and non-ablative lasers in gynecology: A clinician’s guide

Vidyard Video

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Additional videos from SGS are available here, including these recent offerings:

• Technique for apical suspension at the time of total laparoscopic hysterectomy
• Strategies to overcome the loss of port placement triangulation
• Advances in ablative and non-ablative lasers in gynecology: A clinician’s guide

Vidyard Video

Visit the Society of Gynecologic Surgeons online: sgsonline.org

Additional videos from SGS are available here, including these recent offerings:

• Technique for apical suspension at the time of total laparoscopic hysterectomy
• Strategies to overcome the loss of port placement triangulation
• Advances in ablative and non-ablative lasers in gynecology: A clinician’s guide

It might be prudent to monitor N-terminal pro–B-type natriuretic peptide (NT-proBNP) and skip natriuretic peptide measures in heart failure patients on sacubitril/valsartan (Entresto), according to a new expert consensus document from the American College of Cardiology on managing heart failure with reduced ejection fraction.

“While rising natriuretic peptide concentrations are correlated with adverse outcomes, this relationship can be confounded with the use of sacubitril/valsartan. Due to neprilysin inhibition, concentrations of BNP rise in patients treated with sacubitril/valsartan and tend not to return to baseline despite chronic therapy. In contrast, NT-proBNP concentrations typically decrease, as NT-proBNP is not a substrate for neprilysin,” explained authors led by heart failure pathway writing committee chairman Clyde W. Yancy, MD, chief of cardiology at Northwestern University in Chicago (J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025).

[email protected]

SOURCE: Yancy C et. al. J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025

It might be prudent to monitor N-terminal pro–B-type natriuretic peptide (NT-proBNP) and skip natriuretic peptide measures in heart failure patients on sacubitril/valsartan (Entresto), according to a new expert consensus document from the American College of Cardiology on managing heart failure with reduced ejection fraction.

“While rising natriuretic peptide concentrations are correlated with adverse outcomes, this relationship can be confounded with the use of sacubitril/valsartan. Due to neprilysin inhibition, concentrations of BNP rise in patients treated with sacubitril/valsartan and tend not to return to baseline despite chronic therapy. In contrast, NT-proBNP concentrations typically decrease, as NT-proBNP is not a substrate for neprilysin,” explained authors led by heart failure pathway writing committee chairman Clyde W. Yancy, MD, chief of cardiology at Northwestern University in Chicago (J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025).

[email protected]

SOURCE: Yancy C et. al. J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025

It might be prudent to monitor N-terminal pro–B-type natriuretic peptide (NT-proBNP) and skip natriuretic peptide measures in heart failure patients on sacubitril/valsartan (Entresto), according to a new expert consensus document from the American College of Cardiology on managing heart failure with reduced ejection fraction.

“While rising natriuretic peptide concentrations are correlated with adverse outcomes, this relationship can be confounded with the use of sacubitril/valsartan. Due to neprilysin inhibition, concentrations of BNP rise in patients treated with sacubitril/valsartan and tend not to return to baseline despite chronic therapy. In contrast, NT-proBNP concentrations typically decrease, as NT-proBNP is not a substrate for neprilysin,” explained authors led by heart failure pathway writing committee chairman Clyde W. Yancy, MD, chief of cardiology at Northwestern University in Chicago (J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025).

[email protected]

SOURCE: Yancy C et. al. J Am Coll Cardiol. 2017 Dec 22. doi: 10.1016/j.jacc.2017.11.025

MONTREAL – The risk for unplanned cesarean delivery is increased when maternal gestational weight gain exceeds the recommended amount – as it does in almost half of pregnancies in the United States.

In a new analysis of data from the Infant Feeding Practices Study II (IFPS II), women with excessive gestational weight gain (GWG) were found to have an adjusted odds ratio of 1.61 for unplanned cesarean delivery, compared with women with adequate GWG (95% confidence interval, 1.11-2.33; P = .013).

Kari Oakes/Frontline Medical News

[email protected]

SOURCE: Francescon J. NAPCRG 2017 Abstract P495.

MONTREAL – The risk for unplanned cesarean delivery is increased when maternal gestational weight gain exceeds the recommended amount – as it does in almost half of pregnancies in the United States.

In a new analysis of data from the Infant Feeding Practices Study II (IFPS II), women with excessive gestational weight gain (GWG) were found to have an adjusted odds ratio of 1.61 for unplanned cesarean delivery, compared with women with adequate GWG (95% confidence interval, 1.11-2.33; P = .013).

Kari Oakes/Frontline Medical News

[email protected]

SOURCE: Francescon J. NAPCRG 2017 Abstract P495.

MONTREAL – The risk for unplanned cesarean delivery is increased when maternal gestational weight gain exceeds the recommended amount – as it does in almost half of pregnancies in the United States.

In a new analysis of data from the Infant Feeding Practices Study II (IFPS II), women with excessive gestational weight gain (GWG) were found to have an adjusted odds ratio of 1.61 for unplanned cesarean delivery, compared with women with adequate GWG (95% confidence interval, 1.11-2.33; P = .013).

Kari Oakes/Frontline Medical News

[email protected]

SOURCE: Francescon J. NAPCRG 2017 Abstract P495.

Pemphigus patients may be more likely to develop chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma, based on the findings of a retrospective study conducted at the Rambam Health Care Campus, Haifa, Israel.

Although the findings are preliminary, the possible associations should be considered when treating pemphigus patients, the investigators reported in the Journal of the American Academy of Dermatology.

Khalaf Kridin, MD, of the Rambam Health Care Campus department of dermatology and his fellow investigators conducted a cross-sectional, retrospective, controlled study of 11,859 patients gathered from the Clait Health Services computerized database. A total of 1,985 pemphigus patients and 9,874 control patients were included. Patients were 72 years old on average, and most were female (60%) and Jewish (90%).

Dr. Kridin and his colleagues measured the prevalence of acute and chronic leukemia, Hodgkin and non-Hodgkin lymphoma, multiple myeloma, and polycythemia vera.

The pemphigus patients, compared with the control group, had a significantly higher prevalence of chronic leukemia (0.9% vs 0.4% [P = .007]), multiple myeloma (0.8% vs 0.4% [P = .009]), and non-Hodgkin lymphoma (1.8% vs 1.2% [P = .040]).

In a sensitivity analysis, patients with pemphigus were twice as likely to have chronic leukemia (odds ratio = 2.1; 95% confidence interval, 1.2-3.6) and multiple myeloma (OR = 2.2; 95% CI, 1.2-3.9) and were one and a half times as likely to have non-Hodgkin lymphoma (OR = 1.5; 95% CI, 1.0-2.2).

Dr. Kridin and his fellow investigators hypothesized that the risks may be related to some pemphigus treatments.

“Certain immunosuppressive treatments for pemphigus, such as azathioprine, could increase the risk of developing hematologic malignancies,” they wrote. “Controlling for immunosuppressive agents attenuated the association of pemphigus with non-Hodgkin lymphoma and multiple myeloma, hinting that they play a role in the higher prevalence.”

Chronic immune stimulation also may be influencing a higher prevalence of hematologic cancers in pemphigus patients “by randomly introducing pro-oncogenic mutations in rapidly dividing cells,” they said.

Investigators were limited by a lack of data on patients’ immunopathological subtype, clinical features, severity of pemphigus, and precise histological type of leukemia and lymphoma.

Dr. Kridin and his fellow investigators reported no relevant financial disclosures.

[email protected]

SOURCE: Kridin K et al. J Am Acad Dermatol. 2017 Dec 2. doi:10.1016/j.jaad.2017.11.039.

Pemphigus patients may be more likely to develop chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma, based on the findings of a retrospective study conducted at the Rambam Health Care Campus, Haifa, Israel.

Although the findings are preliminary, the possible associations should be considered when treating pemphigus patients, the investigators reported in the Journal of the American Academy of Dermatology.

Khalaf Kridin, MD, of the Rambam Health Care Campus department of dermatology and his fellow investigators conducted a cross-sectional, retrospective, controlled study of 11,859 patients gathered from the Clait Health Services computerized database. A total of 1,985 pemphigus patients and 9,874 control patients were included. Patients were 72 years old on average, and most were female (60%) and Jewish (90%).

Dr. Kridin and his colleagues measured the prevalence of acute and chronic leukemia, Hodgkin and non-Hodgkin lymphoma, multiple myeloma, and polycythemia vera.

The pemphigus patients, compared with the control group, had a significantly higher prevalence of chronic leukemia (0.9% vs 0.4% [P = .007]), multiple myeloma (0.8% vs 0.4% [P = .009]), and non-Hodgkin lymphoma (1.8% vs 1.2% [P = .040]).

In a sensitivity analysis, patients with pemphigus were twice as likely to have chronic leukemia (odds ratio = 2.1; 95% confidence interval, 1.2-3.6) and multiple myeloma (OR = 2.2; 95% CI, 1.2-3.9) and were one and a half times as likely to have non-Hodgkin lymphoma (OR = 1.5; 95% CI, 1.0-2.2).

Dr. Kridin and his fellow investigators hypothesized that the risks may be related to some pemphigus treatments.

“Certain immunosuppressive treatments for pemphigus, such as azathioprine, could increase the risk of developing hematologic malignancies,” they wrote. “Controlling for immunosuppressive agents attenuated the association of pemphigus with non-Hodgkin lymphoma and multiple myeloma, hinting that they play a role in the higher prevalence.”

Chronic immune stimulation also may be influencing a higher prevalence of hematologic cancers in pemphigus patients “by randomly introducing pro-oncogenic mutations in rapidly dividing cells,” they said.

Investigators were limited by a lack of data on patients’ immunopathological subtype, clinical features, severity of pemphigus, and precise histological type of leukemia and lymphoma.

Dr. Kridin and his fellow investigators reported no relevant financial disclosures.

[email protected]

SOURCE: Kridin K et al. J Am Acad Dermatol. 2017 Dec 2. doi:10.1016/j.jaad.2017.11.039.

Pemphigus patients may be more likely to develop chronic leukemia, multiple myeloma, and non-Hodgkin lymphoma, based on the findings of a retrospective study conducted at the Rambam Health Care Campus, Haifa, Israel.

Although the findings are preliminary, the possible associations should be considered when treating pemphigus patients, the investigators reported in the Journal of the American Academy of Dermatology.

Khalaf Kridin, MD, of the Rambam Health Care Campus department of dermatology and his fellow investigators conducted a cross-sectional, retrospective, controlled study of 11,859 patients gathered from the Clait Health Services computerized database. A total of 1,985 pemphigus patients and 9,874 control patients were included. Patients were 72 years old on average, and most were female (60%) and Jewish (90%).

Dr. Kridin and his colleagues measured the prevalence of acute and chronic leukemia, Hodgkin and non-Hodgkin lymphoma, multiple myeloma, and polycythemia vera.

The pemphigus patients, compared with the control group, had a significantly higher prevalence of chronic leukemia (0.9% vs 0.4% [P = .007]), multiple myeloma (0.8% vs 0.4% [P = .009]), and non-Hodgkin lymphoma (1.8% vs 1.2% [P = .040]).

In a sensitivity analysis, patients with pemphigus were twice as likely to have chronic leukemia (odds ratio = 2.1; 95% confidence interval, 1.2-3.6) and multiple myeloma (OR = 2.2; 95% CI, 1.2-3.9) and were one and a half times as likely to have non-Hodgkin lymphoma (OR = 1.5; 95% CI, 1.0-2.2).

Dr. Kridin and his fellow investigators hypothesized that the risks may be related to some pemphigus treatments.

“Certain immunosuppressive treatments for pemphigus, such as azathioprine, could increase the risk of developing hematologic malignancies,” they wrote. “Controlling for immunosuppressive agents attenuated the association of pemphigus with non-Hodgkin lymphoma and multiple myeloma, hinting that they play a role in the higher prevalence.”

Chronic immune stimulation also may be influencing a higher prevalence of hematologic cancers in pemphigus patients “by randomly introducing pro-oncogenic mutations in rapidly dividing cells,” they said.

Investigators were limited by a lack of data on patients’ immunopathological subtype, clinical features, severity of pemphigus, and precise histological type of leukemia and lymphoma.

Dr. Kridin and his fellow investigators reported no relevant financial disclosures.

[email protected]

SOURCE: Kridin K et al. J Am Acad Dermatol. 2017 Dec 2. doi:10.1016/j.jaad.2017.11.039.

As psychiatrists, we understand that behavior is complex and determined by multiple factors. However, despite our understanding that behavior is cultural, sociological, psychological, and biological, we often lose sight of the biological perspective because the brain is such a complex organ and because we are inundated with psychological theories of behavior. As I have said before, we cannot abdicate our role of being biologists in the reflection of mental health and wellness.

Accordingly, I feel it is my duty to bring our attention to a biologic etiology of suicidal behavior. I came across an article on the life expectancy of individuals afflicted with fetal alcohol syndrome in the Journal of Population Therapeutics and Clinical Pharmacology (2016;23[1]:e53-9). The findings were astonishing. As it turns out, the life expectancy of people with fetal alcohol syndrome is 34 years of age on average, and the leading causes of death were “external causes,” which accounted for 44% of the deaths. Suicide was responsible for 15% of those deaths, accidents for 14%, poisoning by illegal drugs or alcohol for 7%, and other external causes for another 7%, according to the article.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital Family Medicine Clinic in Chicago; clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago; former president/CEO of Community Mental Health Council; and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.

As psychiatrists, we understand that behavior is complex and determined by multiple factors. However, despite our understanding that behavior is cultural, sociological, psychological, and biological, we often lose sight of the biological perspective because the brain is such a complex organ and because we are inundated with psychological theories of behavior. As I have said before, we cannot abdicate our role of being biologists in the reflection of mental health and wellness.

Accordingly, I feel it is my duty to bring our attention to a biologic etiology of suicidal behavior. I came across an article on the life expectancy of individuals afflicted with fetal alcohol syndrome in the Journal of Population Therapeutics and Clinical Pharmacology (2016;23[1]:e53-9). The findings were astonishing. As it turns out, the life expectancy of people with fetal alcohol syndrome is 34 years of age on average, and the leading causes of death were “external causes,” which accounted for 44% of the deaths. Suicide was responsible for 15% of those deaths, accidents for 14%, poisoning by illegal drugs or alcohol for 7%, and other external causes for another 7%, according to the article.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital Family Medicine Clinic in Chicago; clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago; former president/CEO of Community Mental Health Council; and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.

As psychiatrists, we understand that behavior is complex and determined by multiple factors. However, despite our understanding that behavior is cultural, sociological, psychological, and biological, we often lose sight of the biological perspective because the brain is such a complex organ and because we are inundated with psychological theories of behavior. As I have said before, we cannot abdicate our role of being biologists in the reflection of mental health and wellness.

Accordingly, I feel it is my duty to bring our attention to a biologic etiology of suicidal behavior. I came across an article on the life expectancy of individuals afflicted with fetal alcohol syndrome in the Journal of Population Therapeutics and Clinical Pharmacology (2016;23[1]:e53-9). The findings were astonishing. As it turns out, the life expectancy of people with fetal alcohol syndrome is 34 years of age on average, and the leading causes of death were “external causes,” which accounted for 44% of the deaths. Suicide was responsible for 15% of those deaths, accidents for 14%, poisoning by illegal drugs or alcohol for 7%, and other external causes for another 7%, according to the article.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital Family Medicine Clinic in Chicago; clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago; former president/CEO of Community Mental Health Council; and former director of the Institute for Juvenile Research (birthplace of child psychiatry), also in Chicago.

Pertuzumab has been approved for the treatment of human epidermal growth factor receptor (HER) 2–positive breast cancer patients at high risk of recurrence, according to the Food and Drug Administration.

The approval was based on results from the APHINITY trial, which included 4,804 patients who had HER2-positive early breast cancers that were excised prior to the study. After a median follow-up period of 45.4 months, an invasive disease event occurred in 7.1% of all patients who received pertuzumab (Perjeta) and in 8.7% of patients who received placebo. In patients with hormone receptor–negative disease, invasive events occurred in 8.2% of the pertuzumab group and in 10.6% of the placebo group. In patients with node-positive disease, the invasive event rate was 9.2% in the pertuzumab group and 12.1% in the placebo group.

The most common adverse events associated with pertuzumab were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting; the most common severe adverse events were neutropenia, febrile neutropenia, diarrhea, decreased neutrophil count, anemia, decreased white blood cell count, leukopenia, fatigue, nausea, and stomatitis.

“The initial pertuzumab dose is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by 420 mg administered as a 30- to 60-minute intravenous infusion,” the FDA said in the statement.

Find the full statement on the FDA website.

[email protected]

Pertuzumab has been approved for the treatment of human epidermal growth factor receptor (HER) 2–positive breast cancer patients at high risk of recurrence, according to the Food and Drug Administration.

The approval was based on results from the APHINITY trial, which included 4,804 patients who had HER2-positive early breast cancers that were excised prior to the study. After a median follow-up period of 45.4 months, an invasive disease event occurred in 7.1% of all patients who received pertuzumab (Perjeta) and in 8.7% of patients who received placebo. In patients with hormone receptor–negative disease, invasive events occurred in 8.2% of the pertuzumab group and in 10.6% of the placebo group. In patients with node-positive disease, the invasive event rate was 9.2% in the pertuzumab group and 12.1% in the placebo group.

The most common adverse events associated with pertuzumab were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting; the most common severe adverse events were neutropenia, febrile neutropenia, diarrhea, decreased neutrophil count, anemia, decreased white blood cell count, leukopenia, fatigue, nausea, and stomatitis.

“The initial pertuzumab dose is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by 420 mg administered as a 30- to 60-minute intravenous infusion,” the FDA said in the statement.

Find the full statement on the FDA website.

[email protected]

Pertuzumab has been approved for the treatment of human epidermal growth factor receptor (HER) 2–positive breast cancer patients at high risk of recurrence, according to the Food and Drug Administration.

The approval was based on results from the APHINITY trial, which included 4,804 patients who had HER2-positive early breast cancers that were excised prior to the study. After a median follow-up period of 45.4 months, an invasive disease event occurred in 7.1% of all patients who received pertuzumab (Perjeta) and in 8.7% of patients who received placebo. In patients with hormone receptor–negative disease, invasive events occurred in 8.2% of the pertuzumab group and in 10.6% of the placebo group. In patients with node-positive disease, the invasive event rate was 9.2% in the pertuzumab group and 12.1% in the placebo group.

The most common adverse events associated with pertuzumab were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting; the most common severe adverse events were neutropenia, febrile neutropenia, diarrhea, decreased neutrophil count, anemia, decreased white blood cell count, leukopenia, fatigue, nausea, and stomatitis.

“The initial pertuzumab dose is 840 mg administered as a 60-minute intravenous infusion, followed every 3 weeks thereafter by 420 mg administered as a 30- to 60-minute intravenous infusion,” the FDA said in the statement.

Find the full statement on the FDA website.

[email protected]

Take-Home Points

• An increasing number of THAs and HAs were performed over time for FNF.
• HA patients tended to be older.
• Hospitalization and blood transfusion rates were higher for THA.
• Hospital size affected the rate of HAs, while hospital location affected the rate of THAs.
• A larger proportion of THA patients had private insurance.

Femoral neck fractures (FNFs) are a common source of morbidity and mortality worldwide. The increasing number of FNFs in the United States is attributed to increases in number of US residents >65 years old, the average life span, and the incidence of osteoporosis.¹ Three hundred forty thousand hip fractures occurred in the United States in 1996, and the number is expected to double by 2050.² By that year, an estimated 6.3 million hip fractures will occur worldwide.³ Given the 1-year mortality rate of 14% to 36%, optimizing the management of these fractures is an important public health issue that must be addressed.⁴

Treatment is based on preoperative ambulatory status, cognitive function, comorbidities, fracture type and displacement, and other factors. In physiologically elderly patients with displaced fractures, surgical treatment usually involves either hemiarthroplasty (HA) or total hip arthroplasty (THA). There is controversy regarding which modality is the preferred treatment.

Proponents of HA point to a higher rate of dislocation for FNFs treated with THAs,^5,6 attributed to increased range of motion.⁷ Proponents of THA point to superior short-term clinical results and fewer complications, especially in mobile, independent patients.⁸

We conducted a study to assess recent US national trends in performing THA and HA for FNFs and to evaluate perioperative outcomes for each treatment group. 

Materials and Methods

Data for this study were obtained from the National Center for Health Statistics (NCHS) National Hospital Discharge Survey (NHDS) and were imported into Microsoft Office Excel 2010.⁹ The NHDS examines patient discharges from various hospitals across the US, including federal, military, and Veterans Administration hospitals.⁹ Only short-stay hospitals (mean stay, <30 days) and hospitals with a general specialty are included in the survey. Each year, about 1% of all hospital admissions from across the US are abstracted and weighted to provide nationwide estimates. The information collected from each hospital record includes age, sex, race, marital status, discharge month, discharge status, days of care, hospital location, hospital size (number of beds), hospital type (proprietary or for-profit, government, nonprofit/church), and up to 15 discharge diagnoses and 8 procedures performed during admission.⁹

International Classification of Diseases, Ninth Revision (ICD-9) procedure codes were used to search the NHDS for patients admitted after FNF for each year from 2001 through 2010. These codes were then used to identify patients within this group who underwent THA or HA. We also collected data on patient demographics, hospitalization duration, discharge disposition, in-hospital adverse events (deep vein thrombosis [DVT], pulmonary embolism [PE], blood transfusion, mortality), form of primary medical insurance, number of hospital beds (0-99, 100-199, 200-299, 300-499, ≥500), hospital type (proprietary, government, nonprofit/church), and hospital region (Northeast, Midwest, South, West). 

Trends were evaluated by linear regression with the Pearson correlation coefficient (r). Statistical comparisons were made using the Student t test for continuous data, and both the Fisher exact test and the χ² test for categorical variables. Significance level was set at P < .05. All analyses were performed with IBM SPSS Statistics 22. 

Results

Hospital stay was longer (P < .01) for THA patients (7.7 days; range, 1-312 days) than for HA patients (6.7 days; range, 1-118 days), and blood transfusion rate was higher (P = .02) for THA patients (30.4%) than for HA patients (25.7%), but the groups did not differ in their rates of DVT (THA, 1.2%; HA, 0.80%, P = .50), PE (THA, 0.52%; HA, 0.72%, P = .52), or mortality (THA, 1.8%; HA, 2.9%; P = .16). Discharge disposition varied with surgical status (P < .01): 23.2% of THA patients and 11.6% of HA patients were discharged directly home after their inpatient stay, and 76.8% of THA patients and 88.4% of HA patients were discharged or transferred to a short- or long-term care facility.

Private medical insurance provided coverage for 14.3% of THAs and 9.1% of HAs, and Medicare provided coverage for 80.9% of THAs and 86.0% of HAs (P < .01).

 

 

Discussion

The NHDS data showed a preference for HA over THA in the treatment of FNFs and suggested THA was favored for younger, healthier patients while HA was reserved for older patients with more comorbidities. Despite being younger and healthier, the THA group had higher transfusion rates and longer hospitalizations, possibly because of the increased complexity of THA procedures, which generally involve more operative time and increased blood loss. The resultant higher transfusion rate for THAs likely contributed to longer hospitalizations for FNFs. However, the THA and HA groups did not differ in their rates of DVT, PE, or mortality.

Multiple studies have noted no differences in mortality, infection, or general complications between THA and HA for FNF.^8,10,11 THA patients have better functional outcomes, including Harris and Oxford hip scores and walking distance, but higher dislocation rates,^8,10-12 and HA patients are at higher risk for reoperation because of progressive acetabular erosion.^8,10,11

We noted an increase in use of both THA and HA for FNF over the study period (2001-2010). In a review of operative treatment for FNF by surgeons applying for the American Board of Orthopaedic Surgery certification between 1999 and 2011, Miller and colleagues¹³ found a similar increase in the THA rate over time, but decreases in the HA and internal fixation rates, with candidates in the “adult reconstruction” subspecialty showing a particularly strong trend toward THA use.

These findings reflect a general propensity toward femoral head replacement rather than preservation through open reduction and internal fixation (ORIF). Recent studies have found that ORIF carries a 39% to 43% rate of fixation failure and need for secondary revision, as well as risks of avascular necrosis, malunion, and nonunion.^1,14-16 This need for secondary surgery makes ORIF ultimately less cost-effective than either THA or HA.16,17 Most authors would recommend arthroplasty for FNF in elderly patients with normal mental function^1,16,18 and would reserve ORIF for young patients with good bone stock, joint space preservation, and reducible noncomminuted fractures.^1,19

Our study results suggest that smaller hospitals (<100 beds) tend to have lower rates of HA (P < .01, significant) and THA (P = .10, not significant; Table), possibly because FNF patients who present to these hospitals may be referred elsewhere because of regional differences in the availability of orthopedic traumatologists and arthroplasty subspecialists. Surgeon volume affects postoperative outcomes and may play a role in referral patterns.²⁰ Ames and colleagues²⁰ found that HA performed for FNF by surgeons with high-volume THA experience (vs non-hip-arthroplasty surgeons) had lower rates of dislocation, superficial infection, and mortality.

Regional differences were significant for THA alone, with the highest THA rates in the South (5.2%) and the lowest in the West (3.3%; Figure 5). There were no clear regional trends for HA. Possible explanations include a propensity toward a more aggressive approach in these regions, increased regional prevalence of acetabular disease, regional surgeon preferences, and regional differences in patient characteristics (eg, increased prevalence of obesity in the South).²¹

HA rates were highest for nonprofit/church hospitals and lowest for proprietary hospitals, whereas THA rates did not differ by hospital type. Possible explanations include an older, less mobile nonprofit/church patient cohort that is more amenable to HA, and surgeon preference. 

THA patients were more likely to be covered by private medical insurance than by Medicare—a finding in agreement with Hochfelder and colleagues,²² who found that, compared with federal insurance and self-pay patients, private insurance patients were 41% more likely to undergo THA than HA or internal fixation for FNF. We think that the age difference between our THA and HA groups contributed to the insurance variability in our study.

Our study had several limitations. It was conducted to examine the rates of THA and HA after FNF, not to survey treatment types, including ORIF and nonoperative management. The NHDS database does not provide information on HA implant type (unipolar, bipolar), use or nonuse of cement with HA, or surgical approach. Surgical approach could influence the rate of postoperative dislocation, an outcome measure that was not examined in this study. Last, the NHDS database tracks admissions and discharges, not patients. When a patient is discharged, collection of information on the patient’s postoperative course stops; a patient who returns even only 1 day later is recorded as a new or unique patient. Therefore, intermediate or long-term outcome information is unavailable, which likely led to an underrepresentation of DVT, PE, and mortality after these THA and HA procedures.

There was a trend toward femoral head replacement rather than ORIF in the treatment of FNF. Cognitively functional and independent elderly patients, and patients with osteoarthritis or rheumatoid arthritis, may benefit from THA, whereas HA may be better suited to cognitively dysfunctional patients.^23,24 The NHDS reflects an increasing trend toward arthroplasty over ORIF, but the exact treatment choice is affected by hospital type, size,  location and surgeon preference, training, and subspecialization.

Take-Home Points

• An increasing number of THAs and HAs were performed over time for FNF.
• HA patients tended to be older.
• Hospitalization and blood transfusion rates were higher for THA.
• Hospital size affected the rate of HAs, while hospital location affected the rate of THAs.
• A larger proportion of THA patients had private insurance.

Femoral neck fractures (FNFs) are a common source of morbidity and mortality worldwide. The increasing number of FNFs in the United States is attributed to increases in number of US residents >65 years old, the average life span, and the incidence of osteoporosis.¹ Three hundred forty thousand hip fractures occurred in the United States in 1996, and the number is expected to double by 2050.² By that year, an estimated 6.3 million hip fractures will occur worldwide.³ Given the 1-year mortality rate of 14% to 36%, optimizing the management of these fractures is an important public health issue that must be addressed.⁴

Treatment is based on preoperative ambulatory status, cognitive function, comorbidities, fracture type and displacement, and other factors. In physiologically elderly patients with displaced fractures, surgical treatment usually involves either hemiarthroplasty (HA) or total hip arthroplasty (THA). There is controversy regarding which modality is the preferred treatment.

Proponents of HA point to a higher rate of dislocation for FNFs treated with THAs,^5,6 attributed to increased range of motion.⁷ Proponents of THA point to superior short-term clinical results and fewer complications, especially in mobile, independent patients.⁸

We conducted a study to assess recent US national trends in performing THA and HA for FNFs and to evaluate perioperative outcomes for each treatment group. 

Materials and Methods

Data for this study were obtained from the National Center for Health Statistics (NCHS) National Hospital Discharge Survey (NHDS) and were imported into Microsoft Office Excel 2010.⁹ The NHDS examines patient discharges from various hospitals across the US, including federal, military, and Veterans Administration hospitals.⁹ Only short-stay hospitals (mean stay, <30 days) and hospitals with a general specialty are included in the survey. Each year, about 1% of all hospital admissions from across the US are abstracted and weighted to provide nationwide estimates. The information collected from each hospital record includes age, sex, race, marital status, discharge month, discharge status, days of care, hospital location, hospital size (number of beds), hospital type (proprietary or for-profit, government, nonprofit/church), and up to 15 discharge diagnoses and 8 procedures performed during admission.⁹

International Classification of Diseases, Ninth Revision (ICD-9) procedure codes were used to search the NHDS for patients admitted after FNF for each year from 2001 through 2010. These codes were then used to identify patients within this group who underwent THA or HA. We also collected data on patient demographics, hospitalization duration, discharge disposition, in-hospital adverse events (deep vein thrombosis [DVT], pulmonary embolism [PE], blood transfusion, mortality), form of primary medical insurance, number of hospital beds (0-99, 100-199, 200-299, 300-499, ≥500), hospital type (proprietary, government, nonprofit/church), and hospital region (Northeast, Midwest, South, West). 

Trends were evaluated by linear regression with the Pearson correlation coefficient (r). Statistical comparisons were made using the Student t test for continuous data, and both the Fisher exact test and the χ² test for categorical variables. Significance level was set at P < .05. All analyses were performed with IBM SPSS Statistics 22. 

Results

Hospital stay was longer (P < .01) for THA patients (7.7 days; range, 1-312 days) than for HA patients (6.7 days; range, 1-118 days), and blood transfusion rate was higher (P = .02) for THA patients (30.4%) than for HA patients (25.7%), but the groups did not differ in their rates of DVT (THA, 1.2%; HA, 0.80%, P = .50), PE (THA, 0.52%; HA, 0.72%, P = .52), or mortality (THA, 1.8%; HA, 2.9%; P = .16). Discharge disposition varied with surgical status (P < .01): 23.2% of THA patients and 11.6% of HA patients were discharged directly home after their inpatient stay, and 76.8% of THA patients and 88.4% of HA patients were discharged or transferred to a short- or long-term care facility.

Private medical insurance provided coverage for 14.3% of THAs and 9.1% of HAs, and Medicare provided coverage for 80.9% of THAs and 86.0% of HAs (P < .01).

 

 

Discussion

The NHDS data showed a preference for HA over THA in the treatment of FNFs and suggested THA was favored for younger, healthier patients while HA was reserved for older patients with more comorbidities. Despite being younger and healthier, the THA group had higher transfusion rates and longer hospitalizations, possibly because of the increased complexity of THA procedures, which generally involve more operative time and increased blood loss. The resultant higher transfusion rate for THAs likely contributed to longer hospitalizations for FNFs. However, the THA and HA groups did not differ in their rates of DVT, PE, or mortality.

Multiple studies have noted no differences in mortality, infection, or general complications between THA and HA for FNF.^8,10,11 THA patients have better functional outcomes, including Harris and Oxford hip scores and walking distance, but higher dislocation rates,^8,10-12 and HA patients are at higher risk for reoperation because of progressive acetabular erosion.^8,10,11

We noted an increase in use of both THA and HA for FNF over the study period (2001-2010). In a review of operative treatment for FNF by surgeons applying for the American Board of Orthopaedic Surgery certification between 1999 and 2011, Miller and colleagues¹³ found a similar increase in the THA rate over time, but decreases in the HA and internal fixation rates, with candidates in the “adult reconstruction” subspecialty showing a particularly strong trend toward THA use.

These findings reflect a general propensity toward femoral head replacement rather than preservation through open reduction and internal fixation (ORIF). Recent studies have found that ORIF carries a 39% to 43% rate of fixation failure and need for secondary revision, as well as risks of avascular necrosis, malunion, and nonunion.^1,14-16 This need for secondary surgery makes ORIF ultimately less cost-effective than either THA or HA.16,17 Most authors would recommend arthroplasty for FNF in elderly patients with normal mental function^1,16,18 and would reserve ORIF for young patients with good bone stock, joint space preservation, and reducible noncomminuted fractures.^1,19

Our study results suggest that smaller hospitals (<100 beds) tend to have lower rates of HA (P < .01, significant) and THA (P = .10, not significant; Table), possibly because FNF patients who present to these hospitals may be referred elsewhere because of regional differences in the availability of orthopedic traumatologists and arthroplasty subspecialists. Surgeon volume affects postoperative outcomes and may play a role in referral patterns.²⁰ Ames and colleagues²⁰ found that HA performed for FNF by surgeons with high-volume THA experience (vs non-hip-arthroplasty surgeons) had lower rates of dislocation, superficial infection, and mortality.

Regional differences were significant for THA alone, with the highest THA rates in the South (5.2%) and the lowest in the West (3.3%; Figure 5). There were no clear regional trends for HA. Possible explanations include a propensity toward a more aggressive approach in these regions, increased regional prevalence of acetabular disease, regional surgeon preferences, and regional differences in patient characteristics (eg, increased prevalence of obesity in the South).²¹

HA rates were highest for nonprofit/church hospitals and lowest for proprietary hospitals, whereas THA rates did not differ by hospital type. Possible explanations include an older, less mobile nonprofit/church patient cohort that is more amenable to HA, and surgeon preference. 

THA patients were more likely to be covered by private medical insurance than by Medicare—a finding in agreement with Hochfelder and colleagues,²² who found that, compared with federal insurance and self-pay patients, private insurance patients were 41% more likely to undergo THA than HA or internal fixation for FNF. We think that the age difference between our THA and HA groups contributed to the insurance variability in our study.

Our study had several limitations. It was conducted to examine the rates of THA and HA after FNF, not to survey treatment types, including ORIF and nonoperative management. The NHDS database does not provide information on HA implant type (unipolar, bipolar), use or nonuse of cement with HA, or surgical approach. Surgical approach could influence the rate of postoperative dislocation, an outcome measure that was not examined in this study. Last, the NHDS database tracks admissions and discharges, not patients. When a patient is discharged, collection of information on the patient’s postoperative course stops; a patient who returns even only 1 day later is recorded as a new or unique patient. Therefore, intermediate or long-term outcome information is unavailable, which likely led to an underrepresentation of DVT, PE, and mortality after these THA and HA procedures.

There was a trend toward femoral head replacement rather than ORIF in the treatment of FNF. Cognitively functional and independent elderly patients, and patients with osteoarthritis or rheumatoid arthritis, may benefit from THA, whereas HA may be better suited to cognitively dysfunctional patients.^23,24 The NHDS reflects an increasing trend toward arthroplasty over ORIF, but the exact treatment choice is affected by hospital type, size,  location and surgeon preference, training, and subspecialization.

Take-Home Points

• An increasing number of THAs and HAs were performed over time for FNF.
• HA patients tended to be older.
• Hospitalization and blood transfusion rates were higher for THA.
• Hospital size affected the rate of HAs, while hospital location affected the rate of THAs.
• A larger proportion of THA patients had private insurance.

Femoral neck fractures (FNFs) are a common source of morbidity and mortality worldwide. The increasing number of FNFs in the United States is attributed to increases in number of US residents >65 years old, the average life span, and the incidence of osteoporosis.¹ Three hundred forty thousand hip fractures occurred in the United States in 1996, and the number is expected to double by 2050.² By that year, an estimated 6.3 million hip fractures will occur worldwide.³ Given the 1-year mortality rate of 14% to 36%, optimizing the management of these fractures is an important public health issue that must be addressed.⁴

Treatment is based on preoperative ambulatory status, cognitive function, comorbidities, fracture type and displacement, and other factors. In physiologically elderly patients with displaced fractures, surgical treatment usually involves either hemiarthroplasty (HA) or total hip arthroplasty (THA). There is controversy regarding which modality is the preferred treatment.

Proponents of HA point to a higher rate of dislocation for FNFs treated with THAs,^5,6 attributed to increased range of motion.⁷ Proponents of THA point to superior short-term clinical results and fewer complications, especially in mobile, independent patients.⁸

We conducted a study to assess recent US national trends in performing THA and HA for FNFs and to evaluate perioperative outcomes for each treatment group. 

Materials and Methods

Data for this study were obtained from the National Center for Health Statistics (NCHS) National Hospital Discharge Survey (NHDS) and were imported into Microsoft Office Excel 2010.⁹ The NHDS examines patient discharges from various hospitals across the US, including federal, military, and Veterans Administration hospitals.⁹ Only short-stay hospitals (mean stay, <30 days) and hospitals with a general specialty are included in the survey. Each year, about 1% of all hospital admissions from across the US are abstracted and weighted to provide nationwide estimates. The information collected from each hospital record includes age, sex, race, marital status, discharge month, discharge status, days of care, hospital location, hospital size (number of beds), hospital type (proprietary or for-profit, government, nonprofit/church), and up to 15 discharge diagnoses and 8 procedures performed during admission.⁹

International Classification of Diseases, Ninth Revision (ICD-9) procedure codes were used to search the NHDS for patients admitted after FNF for each year from 2001 through 2010. These codes were then used to identify patients within this group who underwent THA or HA. We also collected data on patient demographics, hospitalization duration, discharge disposition, in-hospital adverse events (deep vein thrombosis [DVT], pulmonary embolism [PE], blood transfusion, mortality), form of primary medical insurance, number of hospital beds (0-99, 100-199, 200-299, 300-499, ≥500), hospital type (proprietary, government, nonprofit/church), and hospital region (Northeast, Midwest, South, West). 

Trends were evaluated by linear regression with the Pearson correlation coefficient (r). Statistical comparisons were made using the Student t test for continuous data, and both the Fisher exact test and the χ² test for categorical variables. Significance level was set at P < .05. All analyses were performed with IBM SPSS Statistics 22. 

Results

Hospital stay was longer (P < .01) for THA patients (7.7 days; range, 1-312 days) than for HA patients (6.7 days; range, 1-118 days), and blood transfusion rate was higher (P = .02) for THA patients (30.4%) than for HA patients (25.7%), but the groups did not differ in their rates of DVT (THA, 1.2%; HA, 0.80%, P = .50), PE (THA, 0.52%; HA, 0.72%, P = .52), or mortality (THA, 1.8%; HA, 2.9%; P = .16). Discharge disposition varied with surgical status (P < .01): 23.2% of THA patients and 11.6% of HA patients were discharged directly home after their inpatient stay, and 76.8% of THA patients and 88.4% of HA patients were discharged or transferred to a short- or long-term care facility.

Private medical insurance provided coverage for 14.3% of THAs and 9.1% of HAs, and Medicare provided coverage for 80.9% of THAs and 86.0% of HAs (P < .01).

 

 

Discussion

The NHDS data showed a preference for HA over THA in the treatment of FNFs and suggested THA was favored for younger, healthier patients while HA was reserved for older patients with more comorbidities. Despite being younger and healthier, the THA group had higher transfusion rates and longer hospitalizations, possibly because of the increased complexity of THA procedures, which generally involve more operative time and increased blood loss. The resultant higher transfusion rate for THAs likely contributed to longer hospitalizations for FNFs. However, the THA and HA groups did not differ in their rates of DVT, PE, or mortality.

Multiple studies have noted no differences in mortality, infection, or general complications between THA and HA for FNF.^8,10,11 THA patients have better functional outcomes, including Harris and Oxford hip scores and walking distance, but higher dislocation rates,^8,10-12 and HA patients are at higher risk for reoperation because of progressive acetabular erosion.^8,10,11

We noted an increase in use of both THA and HA for FNF over the study period (2001-2010). In a review of operative treatment for FNF by surgeons applying for the American Board of Orthopaedic Surgery certification between 1999 and 2011, Miller and colleagues¹³ found a similar increase in the THA rate over time, but decreases in the HA and internal fixation rates, with candidates in the “adult reconstruction” subspecialty showing a particularly strong trend toward THA use.

These findings reflect a general propensity toward femoral head replacement rather than preservation through open reduction and internal fixation (ORIF). Recent studies have found that ORIF carries a 39% to 43% rate of fixation failure and need for secondary revision, as well as risks of avascular necrosis, malunion, and nonunion.^1,14-16 This need for secondary surgery makes ORIF ultimately less cost-effective than either THA or HA.16,17 Most authors would recommend arthroplasty for FNF in elderly patients with normal mental function^1,16,18 and would reserve ORIF for young patients with good bone stock, joint space preservation, and reducible noncomminuted fractures.^1,19

Our study results suggest that smaller hospitals (<100 beds) tend to have lower rates of HA (P < .01, significant) and THA (P = .10, not significant; Table), possibly because FNF patients who present to these hospitals may be referred elsewhere because of regional differences in the availability of orthopedic traumatologists and arthroplasty subspecialists. Surgeon volume affects postoperative outcomes and may play a role in referral patterns.²⁰ Ames and colleagues²⁰ found that HA performed for FNF by surgeons with high-volume THA experience (vs non-hip-arthroplasty surgeons) had lower rates of dislocation, superficial infection, and mortality.

Regional differences were significant for THA alone, with the highest THA rates in the South (5.2%) and the lowest in the West (3.3%; Figure 5). There were no clear regional trends for HA. Possible explanations include a propensity toward a more aggressive approach in these regions, increased regional prevalence of acetabular disease, regional surgeon preferences, and regional differences in patient characteristics (eg, increased prevalence of obesity in the South).²¹

HA rates were highest for nonprofit/church hospitals and lowest for proprietary hospitals, whereas THA rates did not differ by hospital type. Possible explanations include an older, less mobile nonprofit/church patient cohort that is more amenable to HA, and surgeon preference. 

THA patients were more likely to be covered by private medical insurance than by Medicare—a finding in agreement with Hochfelder and colleagues,²² who found that, compared with federal insurance and self-pay patients, private insurance patients were 41% more likely to undergo THA than HA or internal fixation for FNF. We think that the age difference between our THA and HA groups contributed to the insurance variability in our study.

Our study had several limitations. It was conducted to examine the rates of THA and HA after FNF, not to survey treatment types, including ORIF and nonoperative management. The NHDS database does not provide information on HA implant type (unipolar, bipolar), use or nonuse of cement with HA, or surgical approach. Surgical approach could influence the rate of postoperative dislocation, an outcome measure that was not examined in this study. Last, the NHDS database tracks admissions and discharges, not patients. When a patient is discharged, collection of information on the patient’s postoperative course stops; a patient who returns even only 1 day later is recorded as a new or unique patient. Therefore, intermediate or long-term outcome information is unavailable, which likely led to an underrepresentation of DVT, PE, and mortality after these THA and HA procedures.

There was a trend toward femoral head replacement rather than ORIF in the treatment of FNF. Cognitively functional and independent elderly patients, and patients with osteoarthritis or rheumatoid arthritis, may benefit from THA, whereas HA may be better suited to cognitively dysfunctional patients.^23,24 The NHDS reflects an increasing trend toward arthroplasty over ORIF, but the exact treatment choice is affected by hospital type, size,  location and surgeon preference, training, and subspecialization.

Angiotensin II has been approved for use in intravenous infusions to increase blood pressure in adults with septic or other distributive shock, the Food and Drug Administration announced.

Shock-related drops in blood pressure can restrict blood flow to vital organs and can result in organ failure and death. “There is a need for treatment options for critically ill hypotensive patients who do not adequately respond to available therapies,” Norman Stockbridge, MD, PhD, director of the division of cardiovascular and renal products in the FDA’s Center for Drug Evaluation and Research, said in a written statement.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

Angiotensin II has been approved for use in intravenous infusions to increase blood pressure in adults with septic or other distributive shock, the Food and Drug Administration announced.

Shock-related drops in blood pressure can restrict blood flow to vital organs and can result in organ failure and death. “There is a need for treatment options for critically ill hypotensive patients who do not adequately respond to available therapies,” Norman Stockbridge, MD, PhD, director of the division of cardiovascular and renal products in the FDA’s Center for Drug Evaluation and Research, said in a written statement.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]

Angiotensin II has been approved for use in intravenous infusions to increase blood pressure in adults with septic or other distributive shock, the Food and Drug Administration announced.

Shock-related drops in blood pressure can restrict blood flow to vital organs and can result in organ failure and death. “There is a need for treatment options for critically ill hypotensive patients who do not adequately respond to available therapies,” Norman Stockbridge, MD, PhD, director of the division of cardiovascular and renal products in the FDA’s Center for Drug Evaluation and Research, said in a written statement.

Wikimedia Commons/FitzColinGerald/Creative Commons License

[email protected]