The biosimilar ABP 501 is equally as effective and safe as adalimumab for the treatment of moderate to severe rheumatoid arthritis, according to results of a phase III clinical trial.

In a randomized, double-blind equivalence study across 100 medical centers in 12 countries, 526 patients with moderate to severe RA and inadequate response to methotrexate received either ABP 501 or adalimumab. Of the 526, 494 completed the study. Just over 80% of patients were women, and 95.1% were white, with a mean age of 55.9 years. Patients received either 40-mg ABP 501 or adalimumab subcutaneously on day 1 and every 2 weeks until week 22, with primary endpoint assessments conducted after 24 weeks, according to Dr. Stanley Cohen and his associates (Ann Rheum Dis. 2017 Jun 5. doi: 10.1136/annrheumdis-2016-210459).

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[email protected]

The biosimilar ABP 501 is equally as effective and safe as adalimumab for the treatment of moderate to severe rheumatoid arthritis, according to results of a phase III clinical trial.

In a randomized, double-blind equivalence study across 100 medical centers in 12 countries, 526 patients with moderate to severe RA and inadequate response to methotrexate received either ABP 501 or adalimumab. Of the 526, 494 completed the study. Just over 80% of patients were women, and 95.1% were white, with a mean age of 55.9 years. Patients received either 40-mg ABP 501 or adalimumab subcutaneously on day 1 and every 2 weeks until week 22, with primary endpoint assessments conducted after 24 weeks, according to Dr. Stanley Cohen and his associates (Ann Rheum Dis. 2017 Jun 5. doi: 10.1136/annrheumdis-2016-210459).

copyright kgtoh/Thinkstock

[email protected]

The biosimilar ABP 501 is equally as effective and safe as adalimumab for the treatment of moderate to severe rheumatoid arthritis, according to results of a phase III clinical trial.

In a randomized, double-blind equivalence study across 100 medical centers in 12 countries, 526 patients with moderate to severe RA and inadequate response to methotrexate received either ABP 501 or adalimumab. Of the 526, 494 completed the study. Just over 80% of patients were women, and 95.1% were white, with a mean age of 55.9 years. Patients received either 40-mg ABP 501 or adalimumab subcutaneously on day 1 and every 2 weeks until week 22, with primary endpoint assessments conducted after 24 weeks, according to Dr. Stanley Cohen and his associates (Ann Rheum Dis. 2017 Jun 5. doi: 10.1136/annrheumdis-2016-210459).

copyright kgtoh/Thinkstock

[email protected]

VANCOUVER – A panel of 11 microRNA biomarkers was effective in predicting endometriosis in a small validation study conducted at a Belgium hospital, showing the progress researchers are making toward a noninvasive test.

The research team at Leuven University Hospital developed the model using a population of 120 women, 82 of whom had endometriosis. After extensive analysis, they identified 11 microRNAs, which varied significantly between endometriosis patients and healthy controls and could be used as part of a panel to detect endometriosis. The panel performed well in their validation sample of 60 women with endometriosis and 30 controls, with a sensitivity of 92% and a specificity of 96%.

That validation is good news, but it is still far from being clinically useful. First, the model needs to be tested further in their own predominantly Caucasian population. Then, it needs to be validated by outside researchers, and the model will almost certainly have to be altered to account for different genetic backgrounds, lifestyle habits, and other factors, Arne Vanhie, MD, of Leuven University Hospital said at the World Congress on Endometriosis.

“We may have to tweak it a bit,” he said.

Unfortunately, that tweaking is likely to be time consuming. That’s because RNA extraction and sequencing is labor intensive and expensive, though it could be readily automated if it becomes commercialized.

It’s also technically challenging because microRNA is present in very low concentrations in plasma so researchers must spot a rare signal surrounded by a sea of noise, and that can mean a lot of technical refinement along the way. “We did a lot of testing and trial and error to see what was the best protocol,” Dr. Vanhie said.

The news isn’t all bad. With a well-funded, intensive effort, development could be swift. “There’s no intervention. You just need a tube of blood, so you could go forward with this to make it clinically relevant very easily,” Dr. Vanhie said.

The study was sponsored by the Belgian government. Dr. Vanhie reported having no financial disclosures.

VANCOUVER – A panel of 11 microRNA biomarkers was effective in predicting endometriosis in a small validation study conducted at a Belgium hospital, showing the progress researchers are making toward a noninvasive test.

The research team at Leuven University Hospital developed the model using a population of 120 women, 82 of whom had endometriosis. After extensive analysis, they identified 11 microRNAs, which varied significantly between endometriosis patients and healthy controls and could be used as part of a panel to detect endometriosis. The panel performed well in their validation sample of 60 women with endometriosis and 30 controls, with a sensitivity of 92% and a specificity of 96%.

That validation is good news, but it is still far from being clinically useful. First, the model needs to be tested further in their own predominantly Caucasian population. Then, it needs to be validated by outside researchers, and the model will almost certainly have to be altered to account for different genetic backgrounds, lifestyle habits, and other factors, Arne Vanhie, MD, of Leuven University Hospital said at the World Congress on Endometriosis.

“We may have to tweak it a bit,” he said.

Unfortunately, that tweaking is likely to be time consuming. That’s because RNA extraction and sequencing is labor intensive and expensive, though it could be readily automated if it becomes commercialized.

It’s also technically challenging because microRNA is present in very low concentrations in plasma so researchers must spot a rare signal surrounded by a sea of noise, and that can mean a lot of technical refinement along the way. “We did a lot of testing and trial and error to see what was the best protocol,” Dr. Vanhie said.

The news isn’t all bad. With a well-funded, intensive effort, development could be swift. “There’s no intervention. You just need a tube of blood, so you could go forward with this to make it clinically relevant very easily,” Dr. Vanhie said.

The study was sponsored by the Belgian government. Dr. Vanhie reported having no financial disclosures.

VANCOUVER – A panel of 11 microRNA biomarkers was effective in predicting endometriosis in a small validation study conducted at a Belgium hospital, showing the progress researchers are making toward a noninvasive test.

The research team at Leuven University Hospital developed the model using a population of 120 women, 82 of whom had endometriosis. After extensive analysis, they identified 11 microRNAs, which varied significantly between endometriosis patients and healthy controls and could be used as part of a panel to detect endometriosis. The panel performed well in their validation sample of 60 women with endometriosis and 30 controls, with a sensitivity of 92% and a specificity of 96%.

That validation is good news, but it is still far from being clinically useful. First, the model needs to be tested further in their own predominantly Caucasian population. Then, it needs to be validated by outside researchers, and the model will almost certainly have to be altered to account for different genetic backgrounds, lifestyle habits, and other factors, Arne Vanhie, MD, of Leuven University Hospital said at the World Congress on Endometriosis.

“We may have to tweak it a bit,” he said.

Unfortunately, that tweaking is likely to be time consuming. That’s because RNA extraction and sequencing is labor intensive and expensive, though it could be readily automated if it becomes commercialized.

It’s also technically challenging because microRNA is present in very low concentrations in plasma so researchers must spot a rare signal surrounded by a sea of noise, and that can mean a lot of technical refinement along the way. “We did a lot of testing and trial and error to see what was the best protocol,” Dr. Vanhie said.

The news isn’t all bad. With a well-funded, intensive effort, development could be swift. “There’s no intervention. You just need a tube of blood, so you could go forward with this to make it clinically relevant very easily,” Dr. Vanhie said.

The study was sponsored by the Belgian government. Dr. Vanhie reported having no financial disclosures.

Demand for primary care services will rise by 18% between 2013 and 2023 under current law conditions, according to a report from Congressional Budget Office.

“That increase is caused primarily by growth in the size of the population,” CBO analysts said in the report. “Larger gains in health insurance coverage and more rapid aging of the population explain why the increase is expected to be larger than the 15.5% rise of the previous decade.”

While the report assumes continuation of Affordable Care Act programs, insurance coverage is the smallest component of the 18% rise, according to the CBO.

Drivers of the increase include:

• Population growth (8.7%).
• Growth in volume of care and intensity of care (4%).
• Population aging (3.2%).
• Gains in health insurance coverage (2.1%).

The analysis echoes modeling of primary care demand done by the American Academy of Family Physicians.

Alexander Raths/Fotolia.com

[email protected]

Demand for primary care services will rise by 18% between 2013 and 2023 under current law conditions, according to a report from Congressional Budget Office.

“That increase is caused primarily by growth in the size of the population,” CBO analysts said in the report. “Larger gains in health insurance coverage and more rapid aging of the population explain why the increase is expected to be larger than the 15.5% rise of the previous decade.”

While the report assumes continuation of Affordable Care Act programs, insurance coverage is the smallest component of the 18% rise, according to the CBO.

Drivers of the increase include:

• Population growth (8.7%).
• Growth in volume of care and intensity of care (4%).
• Population aging (3.2%).
• Gains in health insurance coverage (2.1%).

The analysis echoes modeling of primary care demand done by the American Academy of Family Physicians.

Alexander Raths/Fotolia.com

[email protected]

Demand for primary care services will rise by 18% between 2013 and 2023 under current law conditions, according to a report from Congressional Budget Office.

“That increase is caused primarily by growth in the size of the population,” CBO analysts said in the report. “Larger gains in health insurance coverage and more rapid aging of the population explain why the increase is expected to be larger than the 15.5% rise of the previous decade.”

While the report assumes continuation of Affordable Care Act programs, insurance coverage is the smallest component of the 18% rise, according to the CBO.

Drivers of the increase include:

• Population growth (8.7%).
• Growth in volume of care and intensity of care (4%).
• Population aging (3.2%).
• Gains in health insurance coverage (2.1%).

The analysis echoes modeling of primary care demand done by the American Academy of Family Physicians.

Alexander Raths/Fotolia.com

[email protected]

The Diagnosis: Langerhans Cell Histiocytosis 

Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of Langerhans cells that can affect any organ, most commonly the skin and bones. It typically develops in children aged 1 to 3 years, with a male to female ratio of 2 to 1.¹ Skin manifestations include purpuric papules, pustules, vesicles, erosions, and fissuring distributed predominantly on the scalp and flexural sites. Mucosal sites, particularly the oral mucosa, may be involved and usually present as erosions associated with underlying bone lesions.¹ Langerhans cell histiocytosis should be considered in the differential diagnosis of recalcitrant diaper dermatitis in an infant, especially when there is purpura and erosions, as seen in our patient. Common conditions in infants such as cutaneous candidiasis (intense erythema with superficial erosions, peripheral scale and satellite pustules on flexural areas, potassium hydroxide microscopy revealing yeast forms and pseudohyphae) and seborrheic dermatitis (well-defined pink to red, moist, and often scaly patches favoring the folds) may be distinguished clinically from Hailey-Hailey disease (malodorous plaques with fissures and erosions favoring the folds), which is rare in infancy, and acrodermatitis enteropathica (erythema and erosions with scale-crust and desquamation on periorificial, acral, and intertriginous skin).

Histopathologic evaluation is instrumental in diagnosing the skin lesions of LCH. Further evaluation for systemic involvement is necessary once the diagnosis is made. Skin biopsy of the scalp and right inguinal fold revealed a wedge-shaped infiltrate of histiocytes with slightly folded nuclear contours in our patient (Figure 1). CD1a (Figure 2) and S-100 stains were markedly positive, which is characteristic of LCH. Complete blood cell count, renal function, liver function, urinalysis, and flow cytometry results were within reference range. A skeletal survey and echocardiogram were unremarkable; however, mild hepatosplenomegaly was noted on abdominal ultrasonography.

Treatment of LCH varies based on the extent of organ involvement. For isolated cutaneous disease, topical steroids, topical nitrogen mustard, phototherapy, and thalidomide may be employed.² Multisystem disease requires chemotherapeutic agents including vinblastine and prednisone.^2,3 Because more than half of patients with LCH have oncogenic BRAF V600E mutations,⁴ vemurafenib may have a therapeutic role in treatment. Rare case reports have documented disease response in patients with LCH and Erdheim-Chester disease.^5,6 

Prognosis varies based on age and extent of systemic involvement. Children younger than 2 years with multiorgan involvement have a poor prognosis (35%-55% mortality rate) compared to older children without hematopoietic, hepatosplenic, or lung involvement (100% survival rate). Additionally, response to treatment affects prognosis, as there is a 66% mortality rate in those who do not respond to treatment after 6 weeks.³ Long-term sequelae of LCH include endocrine dysfunction (ie, diabetes insipidus, growth hormone deficiencies), hearing impairment, orthopedic impairment, and neuropsychological disease; thus, multidisciplinary care often is neccessary.⁷

Given the multisystem involvement in our patient, he was treated with vinblastine, 6-mercaptopurine, and prednisolone with only partial and transient disease response. He was then treated with clofarabine with dramatic resolution of the mediastinal mass on follow-up positron emission tomography. The cutaneous lesions persisted and were managed with topical corticosteroids.

The Diagnosis: Langerhans Cell Histiocytosis 

Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of Langerhans cells that can affect any organ, most commonly the skin and bones. It typically develops in children aged 1 to 3 years, with a male to female ratio of 2 to 1.¹ Skin manifestations include purpuric papules, pustules, vesicles, erosions, and fissuring distributed predominantly on the scalp and flexural sites. Mucosal sites, particularly the oral mucosa, may be involved and usually present as erosions associated with underlying bone lesions.¹ Langerhans cell histiocytosis should be considered in the differential diagnosis of recalcitrant diaper dermatitis in an infant, especially when there is purpura and erosions, as seen in our patient. Common conditions in infants such as cutaneous candidiasis (intense erythema with superficial erosions, peripheral scale and satellite pustules on flexural areas, potassium hydroxide microscopy revealing yeast forms and pseudohyphae) and seborrheic dermatitis (well-defined pink to red, moist, and often scaly patches favoring the folds) may be distinguished clinically from Hailey-Hailey disease (malodorous plaques with fissures and erosions favoring the folds), which is rare in infancy, and acrodermatitis enteropathica (erythema and erosions with scale-crust and desquamation on periorificial, acral, and intertriginous skin).

Histopathologic evaluation is instrumental in diagnosing the skin lesions of LCH. Further evaluation for systemic involvement is necessary once the diagnosis is made. Skin biopsy of the scalp and right inguinal fold revealed a wedge-shaped infiltrate of histiocytes with slightly folded nuclear contours in our patient (Figure 1). CD1a (Figure 2) and S-100 stains were markedly positive, which is characteristic of LCH. Complete blood cell count, renal function, liver function, urinalysis, and flow cytometry results were within reference range. A skeletal survey and echocardiogram were unremarkable; however, mild hepatosplenomegaly was noted on abdominal ultrasonography.

Treatment of LCH varies based on the extent of organ involvement. For isolated cutaneous disease, topical steroids, topical nitrogen mustard, phototherapy, and thalidomide may be employed.² Multisystem disease requires chemotherapeutic agents including vinblastine and prednisone.^2,3 Because more than half of patients with LCH have oncogenic BRAF V600E mutations,⁴ vemurafenib may have a therapeutic role in treatment. Rare case reports have documented disease response in patients with LCH and Erdheim-Chester disease.^5,6 

Prognosis varies based on age and extent of systemic involvement. Children younger than 2 years with multiorgan involvement have a poor prognosis (35%-55% mortality rate) compared to older children without hematopoietic, hepatosplenic, or lung involvement (100% survival rate). Additionally, response to treatment affects prognosis, as there is a 66% mortality rate in those who do not respond to treatment after 6 weeks.³ Long-term sequelae of LCH include endocrine dysfunction (ie, diabetes insipidus, growth hormone deficiencies), hearing impairment, orthopedic impairment, and neuropsychological disease; thus, multidisciplinary care often is neccessary.⁷

Given the multisystem involvement in our patient, he was treated with vinblastine, 6-mercaptopurine, and prednisolone with only partial and transient disease response. He was then treated with clofarabine with dramatic resolution of the mediastinal mass on follow-up positron emission tomography. The cutaneous lesions persisted and were managed with topical corticosteroids.

The Diagnosis: Langerhans Cell Histiocytosis 

Langerhans cell histiocytosis (LCH) is a clonal proliferative disorder of Langerhans cells that can affect any organ, most commonly the skin and bones. It typically develops in children aged 1 to 3 years, with a male to female ratio of 2 to 1.¹ Skin manifestations include purpuric papules, pustules, vesicles, erosions, and fissuring distributed predominantly on the scalp and flexural sites. Mucosal sites, particularly the oral mucosa, may be involved and usually present as erosions associated with underlying bone lesions.¹ Langerhans cell histiocytosis should be considered in the differential diagnosis of recalcitrant diaper dermatitis in an infant, especially when there is purpura and erosions, as seen in our patient. Common conditions in infants such as cutaneous candidiasis (intense erythema with superficial erosions, peripheral scale and satellite pustules on flexural areas, potassium hydroxide microscopy revealing yeast forms and pseudohyphae) and seborrheic dermatitis (well-defined pink to red, moist, and often scaly patches favoring the folds) may be distinguished clinically from Hailey-Hailey disease (malodorous plaques with fissures and erosions favoring the folds), which is rare in infancy, and acrodermatitis enteropathica (erythema and erosions with scale-crust and desquamation on periorificial, acral, and intertriginous skin).

Histopathologic evaluation is instrumental in diagnosing the skin lesions of LCH. Further evaluation for systemic involvement is necessary once the diagnosis is made. Skin biopsy of the scalp and right inguinal fold revealed a wedge-shaped infiltrate of histiocytes with slightly folded nuclear contours in our patient (Figure 1). CD1a (Figure 2) and S-100 stains were markedly positive, which is characteristic of LCH. Complete blood cell count, renal function, liver function, urinalysis, and flow cytometry results were within reference range. A skeletal survey and echocardiogram were unremarkable; however, mild hepatosplenomegaly was noted on abdominal ultrasonography.

Treatment of LCH varies based on the extent of organ involvement. For isolated cutaneous disease, topical steroids, topical nitrogen mustard, phototherapy, and thalidomide may be employed.² Multisystem disease requires chemotherapeutic agents including vinblastine and prednisone.^2,3 Because more than half of patients with LCH have oncogenic BRAF V600E mutations,⁴ vemurafenib may have a therapeutic role in treatment. Rare case reports have documented disease response in patients with LCH and Erdheim-Chester disease.^5,6 

Prognosis varies based on age and extent of systemic involvement. Children younger than 2 years with multiorgan involvement have a poor prognosis (35%-55% mortality rate) compared to older children without hematopoietic, hepatosplenic, or lung involvement (100% survival rate). Additionally, response to treatment affects prognosis, as there is a 66% mortality rate in those who do not respond to treatment after 6 weeks.³ Long-term sequelae of LCH include endocrine dysfunction (ie, diabetes insipidus, growth hormone deficiencies), hearing impairment, orthopedic impairment, and neuropsychological disease; thus, multidisciplinary care often is neccessary.⁷

Given the multisystem involvement in our patient, he was treated with vinblastine, 6-mercaptopurine, and prednisolone with only partial and transient disease response. He was then treated with clofarabine with dramatic resolution of the mediastinal mass on follow-up positron emission tomography. The cutaneous lesions persisted and were managed with topical corticosteroids.

CHICAGO – Early data from a phase II trial of immune checkpoint inhibitors to treat relapsed mesothelioma give hope that immunotherapy may be an effective therapeutic option for the rapidly progressive, currently incurable cancer.

Reporting on 12 weeks of data from the randomized multicenter trial, Arnaud Scherpereel, MD, the study’s first author, said in a video interview, “We were very pleased to see that we were able to increase ... the disease control rate to 44% with nivolumab, and 50% with nivolumab plus ipilimumab. This was translated into a overall survival gain for these patients.” The best previous disease control rate seen with other therapies was less than 30%, said Dr. Scherpereel at the annual meeting of the American Society of Clinical Oncology.

Discussing the early results in a video interview, Dr. Scherpereel, head of the pulmonary and thoracic oncology department at the University Hospital of Lille, France noted that the median overall survival for the nivolumab patients was 10.4 months, and has not yet been reached for the nivolumab plus ipilimumab patients. Further, he said in a press briefing, “Tumors shrunk in 18% of patients treated with nivolumab and 26% of those treated with nivolumab plus ipilimumab.”

The French MAPS-2 study has enrolled 125 adult patients with malignant pleural mesothelioma who had measurable disease progression after one or two prior lines of chemotherapy, including pemetrexed/platinum doublet. Patients were randomized 1:1 to receive either nivolumab or nivolumab plus ipilimumab, until disease control or unacceptable toxicity was reached, for a maximum of 2 years. Patients were mostly (80%) male, with a median age of 71.8 years, and most had the epithelioid malignant pleural mesothelioma subtype.

In commentary at the press briefing announcing the findings, ASCO expert Michael Sabel, MD, said, “I need to emphasize that this is amazing, in that we are seeing [the use of] checkpoint inhibitors expanding beyond melanoma, to other cancers that we thought were not amenable to immunotherapy approaches.”

“This is a great example of how basic cancer research in one field can expand across others,” said Dr. Sabel of the departments of surgery and surgical oncology at the University of Michigan, Ann Arbor.

Most side effects were not severe, but there were three potentially drug-related deaths in the nivolumab-ipilimumab combo arm: one patient died of fulminant hepatitis, one from metabolic encephalitis, and one from acute renal failure. “There is no identified factor that is predictive” in terms of which patients will have the more significant known adverse effects of checkpoint inhibitors, said Dr. Scherpereel. Patients, caregivers, and health care professionals all need to be alert to the possibility of adverse events and act promptly if concerning symptoms crop up, he said.

Dr. Scherpereel said that though his study group has not yet reported the quality of life findings from MAPS-2, he sees that his patients who are study participants are doing better. “In my patients, they have a very good tolerance to this treatment compared to chemotherapy. They have less dyspnea, less chest pain. Clearly, we hope to get these drugs into the routine very quickly for them.”

Bristol-Myers Squibb manufactures both nivolumab and ipilimumab and provided the study drugs. Dr. Sabel disclosed a financial relationship with Merck. Dr. Scherpereel has no relevant financial disclosures.

[email protected]

On Twitter @karioakes

CHICAGO – Early data from a phase II trial of immune checkpoint inhibitors to treat relapsed mesothelioma give hope that immunotherapy may be an effective therapeutic option for the rapidly progressive, currently incurable cancer.

Reporting on 12 weeks of data from the randomized multicenter trial, Arnaud Scherpereel, MD, the study’s first author, said in a video interview, “We were very pleased to see that we were able to increase ... the disease control rate to 44% with nivolumab, and 50% with nivolumab plus ipilimumab. This was translated into a overall survival gain for these patients.” The best previous disease control rate seen with other therapies was less than 30%, said Dr. Scherpereel at the annual meeting of the American Society of Clinical Oncology.

Discussing the early results in a video interview, Dr. Scherpereel, head of the pulmonary and thoracic oncology department at the University Hospital of Lille, France noted that the median overall survival for the nivolumab patients was 10.4 months, and has not yet been reached for the nivolumab plus ipilimumab patients. Further, he said in a press briefing, “Tumors shrunk in 18% of patients treated with nivolumab and 26% of those treated with nivolumab plus ipilimumab.”

The French MAPS-2 study has enrolled 125 adult patients with malignant pleural mesothelioma who had measurable disease progression after one or two prior lines of chemotherapy, including pemetrexed/platinum doublet. Patients were randomized 1:1 to receive either nivolumab or nivolumab plus ipilimumab, until disease control or unacceptable toxicity was reached, for a maximum of 2 years. Patients were mostly (80%) male, with a median age of 71.8 years, and most had the epithelioid malignant pleural mesothelioma subtype.

In commentary at the press briefing announcing the findings, ASCO expert Michael Sabel, MD, said, “I need to emphasize that this is amazing, in that we are seeing [the use of] checkpoint inhibitors expanding beyond melanoma, to other cancers that we thought were not amenable to immunotherapy approaches.”

“This is a great example of how basic cancer research in one field can expand across others,” said Dr. Sabel of the departments of surgery and surgical oncology at the University of Michigan, Ann Arbor.

Most side effects were not severe, but there were three potentially drug-related deaths in the nivolumab-ipilimumab combo arm: one patient died of fulminant hepatitis, one from metabolic encephalitis, and one from acute renal failure. “There is no identified factor that is predictive” in terms of which patients will have the more significant known adverse effects of checkpoint inhibitors, said Dr. Scherpereel. Patients, caregivers, and health care professionals all need to be alert to the possibility of adverse events and act promptly if concerning symptoms crop up, he said.

Dr. Scherpereel said that though his study group has not yet reported the quality of life findings from MAPS-2, he sees that his patients who are study participants are doing better. “In my patients, they have a very good tolerance to this treatment compared to chemotherapy. They have less dyspnea, less chest pain. Clearly, we hope to get these drugs into the routine very quickly for them.”

Bristol-Myers Squibb manufactures both nivolumab and ipilimumab and provided the study drugs. Dr. Sabel disclosed a financial relationship with Merck. Dr. Scherpereel has no relevant financial disclosures.

[email protected]

On Twitter @karioakes

CHICAGO – Early data from a phase II trial of immune checkpoint inhibitors to treat relapsed mesothelioma give hope that immunotherapy may be an effective therapeutic option for the rapidly progressive, currently incurable cancer.

Reporting on 12 weeks of data from the randomized multicenter trial, Arnaud Scherpereel, MD, the study’s first author, said in a video interview, “We were very pleased to see that we were able to increase ... the disease control rate to 44% with nivolumab, and 50% with nivolumab plus ipilimumab. This was translated into a overall survival gain for these patients.” The best previous disease control rate seen with other therapies was less than 30%, said Dr. Scherpereel at the annual meeting of the American Society of Clinical Oncology.

Discussing the early results in a video interview, Dr. Scherpereel, head of the pulmonary and thoracic oncology department at the University Hospital of Lille, France noted that the median overall survival for the nivolumab patients was 10.4 months, and has not yet been reached for the nivolumab plus ipilimumab patients. Further, he said in a press briefing, “Tumors shrunk in 18% of patients treated with nivolumab and 26% of those treated with nivolumab plus ipilimumab.”

The French MAPS-2 study has enrolled 125 adult patients with malignant pleural mesothelioma who had measurable disease progression after one or two prior lines of chemotherapy, including pemetrexed/platinum doublet. Patients were randomized 1:1 to receive either nivolumab or nivolumab plus ipilimumab, until disease control or unacceptable toxicity was reached, for a maximum of 2 years. Patients were mostly (80%) male, with a median age of 71.8 years, and most had the epithelioid malignant pleural mesothelioma subtype.

In commentary at the press briefing announcing the findings, ASCO expert Michael Sabel, MD, said, “I need to emphasize that this is amazing, in that we are seeing [the use of] checkpoint inhibitors expanding beyond melanoma, to other cancers that we thought were not amenable to immunotherapy approaches.”

“This is a great example of how basic cancer research in one field can expand across others,” said Dr. Sabel of the departments of surgery and surgical oncology at the University of Michigan, Ann Arbor.

Most side effects were not severe, but there were three potentially drug-related deaths in the nivolumab-ipilimumab combo arm: one patient died of fulminant hepatitis, one from metabolic encephalitis, and one from acute renal failure. “There is no identified factor that is predictive” in terms of which patients will have the more significant known adverse effects of checkpoint inhibitors, said Dr. Scherpereel. Patients, caregivers, and health care professionals all need to be alert to the possibility of adverse events and act promptly if concerning symptoms crop up, he said.

Dr. Scherpereel said that though his study group has not yet reported the quality of life findings from MAPS-2, he sees that his patients who are study participants are doing better. “In my patients, they have a very good tolerance to this treatment compared to chemotherapy. They have less dyspnea, less chest pain. Clearly, we hope to get these drugs into the routine very quickly for them.”

Bristol-Myers Squibb manufactures both nivolumab and ipilimumab and provided the study drugs. Dr. Sabel disclosed a financial relationship with Merck. Dr. Scherpereel has no relevant financial disclosures.

[email protected]

On Twitter @karioakes

Short-term cognitive-behavioral therapy is an effective intervention for geriatric patients with comorbid acute illness and depression, judging from the findings of a trial of 155 patients.

“The results presented here confirm the interaction of depression with cognitive and functional performance in this vulnerable study population,” wrote Jana Hummel, MD. “However, the extent of the effect on almost all levels of health was unexpected.”

CBT previously had not been used as a treatment for older patients with acute physical illness and comorbid depression, according to Dr. Hummel and her associates (JAMDA. 2017;18:341-9).

The authors recruited patients aged 82 years, plus or minus 6 years, from a 170-bed hospital that served as the Center for Geriatric Medicine at the University of Heidelberg, Germany. Patients who had been admitted to the hospital had a Hospital Anxiety and Depression Scale (HADS) score of greater than 7. Those with dementia or a life expectancy of less than 1 year were excluded from the study, reported Dr. Hummel of the Geriatric and Gerontopsychotherapeutic Practice in Mannheim, Germany, and her associates.

After the patients were discharged, the clinicians began the active intervention. The investigators randomized 56 people into the CBT intervention, a 15-session, manualized program designed for elderly patients who were based at home. The program included several group sessions held at the hospital’s day clinic and two individual sessions conducted by psychotherapists with expertise in gerontology.

The control group was made up of 99 people. Patients in both groups received antidepressants and other medication, the authors reported in the Journal of the American Medical Directors Association.

Four months after discharge, the patients’ severity of depression as measured by HADS scores was significantly lower among the patients in the psychotherapy group than in the usual care group (1.56 plus or minus 1.4, compared with 3.13 plus or minus 1; P less than .001). Likewise, patients in the psychotherapy group also scored lower on the Hamilton Rating Scale for Depression than did those in the control group (10.57 plus or minus 6.4, compared with 21.47 plus or minus 6.9; P less than .001).

In order for CBT to be effective for this population, arrangements might need to be made to transport patients to intervention sites, according to Dr. Hummel and her associates. Alternatively, the treatment could be administered in nursing homes. Ultimately, the authors said, “the interventions have to be tailored to the individual needs, severity of depression, and health situation.”

One limitation of the study is that the cognitive function of some elderly patients could prevent them from benefiting from CBT. However, Dr. Hummel and her associates said they are optimistic about such interventions for other geriatric patients.

“CBT provides psychological benefit to older patients with depressive symptoms, and it also can reverse some of the functional and cognitive decline associated with depression, they wrote. “It may prove to be an important tool in the treatment of depression in old age and multimorbidity.”

The study was funded with grants from the Robert Bosch Foundation and the Dietmar Hopp Foundation. Dr, Hummel and her associates declared no conflicts of interest.

[email protected]

On Twitter @ginalhenderson
 

Short-term cognitive-behavioral therapy is an effective intervention for geriatric patients with comorbid acute illness and depression, judging from the findings of a trial of 155 patients.

“The results presented here confirm the interaction of depression with cognitive and functional performance in this vulnerable study population,” wrote Jana Hummel, MD. “However, the extent of the effect on almost all levels of health was unexpected.”

CBT previously had not been used as a treatment for older patients with acute physical illness and comorbid depression, according to Dr. Hummel and her associates (JAMDA. 2017;18:341-9).

The authors recruited patients aged 82 years, plus or minus 6 years, from a 170-bed hospital that served as the Center for Geriatric Medicine at the University of Heidelberg, Germany. Patients who had been admitted to the hospital had a Hospital Anxiety and Depression Scale (HADS) score of greater than 7. Those with dementia or a life expectancy of less than 1 year were excluded from the study, reported Dr. Hummel of the Geriatric and Gerontopsychotherapeutic Practice in Mannheim, Germany, and her associates.

After the patients were discharged, the clinicians began the active intervention. The investigators randomized 56 people into the CBT intervention, a 15-session, manualized program designed for elderly patients who were based at home. The program included several group sessions held at the hospital’s day clinic and two individual sessions conducted by psychotherapists with expertise in gerontology.

The control group was made up of 99 people. Patients in both groups received antidepressants and other medication, the authors reported in the Journal of the American Medical Directors Association.

Four months after discharge, the patients’ severity of depression as measured by HADS scores was significantly lower among the patients in the psychotherapy group than in the usual care group (1.56 plus or minus 1.4, compared with 3.13 plus or minus 1; P less than .001). Likewise, patients in the psychotherapy group also scored lower on the Hamilton Rating Scale for Depression than did those in the control group (10.57 plus or minus 6.4, compared with 21.47 plus or minus 6.9; P less than .001).

In order for CBT to be effective for this population, arrangements might need to be made to transport patients to intervention sites, according to Dr. Hummel and her associates. Alternatively, the treatment could be administered in nursing homes. Ultimately, the authors said, “the interventions have to be tailored to the individual needs, severity of depression, and health situation.”

One limitation of the study is that the cognitive function of some elderly patients could prevent them from benefiting from CBT. However, Dr. Hummel and her associates said they are optimistic about such interventions for other geriatric patients.

“CBT provides psychological benefit to older patients with depressive symptoms, and it also can reverse some of the functional and cognitive decline associated with depression, they wrote. “It may prove to be an important tool in the treatment of depression in old age and multimorbidity.”

The study was funded with grants from the Robert Bosch Foundation and the Dietmar Hopp Foundation. Dr, Hummel and her associates declared no conflicts of interest.

[email protected]

On Twitter @ginalhenderson
 

Short-term cognitive-behavioral therapy is an effective intervention for geriatric patients with comorbid acute illness and depression, judging from the findings of a trial of 155 patients.

“The results presented here confirm the interaction of depression with cognitive and functional performance in this vulnerable study population,” wrote Jana Hummel, MD. “However, the extent of the effect on almost all levels of health was unexpected.”

CBT previously had not been used as a treatment for older patients with acute physical illness and comorbid depression, according to Dr. Hummel and her associates (JAMDA. 2017;18:341-9).

The authors recruited patients aged 82 years, plus or minus 6 years, from a 170-bed hospital that served as the Center for Geriatric Medicine at the University of Heidelberg, Germany. Patients who had been admitted to the hospital had a Hospital Anxiety and Depression Scale (HADS) score of greater than 7. Those with dementia or a life expectancy of less than 1 year were excluded from the study, reported Dr. Hummel of the Geriatric and Gerontopsychotherapeutic Practice in Mannheim, Germany, and her associates.

After the patients were discharged, the clinicians began the active intervention. The investigators randomized 56 people into the CBT intervention, a 15-session, manualized program designed for elderly patients who were based at home. The program included several group sessions held at the hospital’s day clinic and two individual sessions conducted by psychotherapists with expertise in gerontology.

The control group was made up of 99 people. Patients in both groups received antidepressants and other medication, the authors reported in the Journal of the American Medical Directors Association.

Four months after discharge, the patients’ severity of depression as measured by HADS scores was significantly lower among the patients in the psychotherapy group than in the usual care group (1.56 plus or minus 1.4, compared with 3.13 plus or minus 1; P less than .001). Likewise, patients in the psychotherapy group also scored lower on the Hamilton Rating Scale for Depression than did those in the control group (10.57 plus or minus 6.4, compared with 21.47 plus or minus 6.9; P less than .001).

In order for CBT to be effective for this population, arrangements might need to be made to transport patients to intervention sites, according to Dr. Hummel and her associates. Alternatively, the treatment could be administered in nursing homes. Ultimately, the authors said, “the interventions have to be tailored to the individual needs, severity of depression, and health situation.”

One limitation of the study is that the cognitive function of some elderly patients could prevent them from benefiting from CBT. However, Dr. Hummel and her associates said they are optimistic about such interventions for other geriatric patients.

“CBT provides psychological benefit to older patients with depressive symptoms, and it also can reverse some of the functional and cognitive decline associated with depression, they wrote. “It may prove to be an important tool in the treatment of depression in old age and multimorbidity.”

The study was funded with grants from the Robert Bosch Foundation and the Dietmar Hopp Foundation. Dr, Hummel and her associates declared no conflicts of interest.

[email protected]

On Twitter @ginalhenderson
 

Both high and low gestational weight gain, compared with the recommended weight gain, are associated with increased risks of adverse perinatal outcomes, according to a systematic review and meta-analysis.

Researchers reviewed 302 studies that categorized women by their prepregnancy body mass index and followed them for gestational weight gain, as well as maternal and neonatal outcomes. They included in their meta-analysis 23 cohort studies involving 1,309,136 pregnancies in 10 countries. Only studies assessing singleton pregnancies in women aged 18 years and older were included.

Stephanie Horrocks/iStockphoto

Both high and low gestational weight gain, compared with the recommended weight gain, are associated with increased risks of adverse perinatal outcomes, according to a systematic review and meta-analysis.

Researchers reviewed 302 studies that categorized women by their prepregnancy body mass index and followed them for gestational weight gain, as well as maternal and neonatal outcomes. They included in their meta-analysis 23 cohort studies involving 1,309,136 pregnancies in 10 countries. Only studies assessing singleton pregnancies in women aged 18 years and older were included.

Stephanie Horrocks/iStockphoto

Both high and low gestational weight gain, compared with the recommended weight gain, are associated with increased risks of adverse perinatal outcomes, according to a systematic review and meta-analysis.

Researchers reviewed 302 studies that categorized women by their prepregnancy body mass index and followed them for gestational weight gain, as well as maternal and neonatal outcomes. They included in their meta-analysis 23 cohort studies involving 1,309,136 pregnancies in 10 countries. Only studies assessing singleton pregnancies in women aged 18 years and older were included.

Stephanie Horrocks/iStockphoto

Take-Home Points

• The prevalence of preoperative pneumonia is 1.2% among hip fracture patients aged >65 years.
• Preoperative pneumonia is an independent risk factor for mortality and adverse events including renal failure, prolonged ventilator dependence, and prolonged altered mental status after geriatric hip fracture surgery.
• Underweight BMI (<18.5 kg/m²) was associated with higher mortality within 30 days among hip fracture patients admitted with pneumonia.
• The mortality rate normalized to that of patients without pneumonia within 2 weeks of hip fracture surgery.
• Time from admission to surgery was not associated with adverse events or mortality among hip fracture patients admitted with pneumonia.

Preoperative pneumonia remains relatively unexplored as a risk factor for adverse outcomes in geriatric hip fracture surgery. Dated studies report a 0.3% to 3.2% prevalence of “recent pneumonia” in patients presenting with hip fracture but provide neither a definition of pneumonia based on clinical criteria nor a subset analysis of outcomes in the pneumonia group.^1-3 Although active pneumonia has been identified as a preoperative optimization target in the management guidelines for geriatric hip fracture,⁴ we are unaware of any studies that have reported on differences in demographics, comorbidities, delay to surgery, or adverse outcomes between hip fracture patients with and without preoperative pneumonia.

This paucity of information on the effect of preoperative pneumonia in the hip fracture population may be related to low prevalence of preoperative pneumonia and a cadre of variable definitions, which limit identification of a cohort of patients with preoperative pneumonia large enough from which to draw meaningful results. Database studies, especially those using surgical registries rather than administrative or reimbursement data, offer particular advantages for investigation of such rare clinical entities.⁵Medical care of patients with pneumonia alone is known to be facilitated by assessments of mortality risk from clinical and laboratory data. The modified British Thoracic Society rule/CURB-65 (confusion, urea, respiratory rate, blood pressure) score is strongly predictive of mortality in hospitalized adults with pneumonia (odds ratio [OR], 4.59; 95% confidence interval [CI], 1.42-14.85; P = .011) and may guide antibiotic therapy, laboratory investigations, and the decision to intubate in a patient with pneumonia.^6-8 This score is predictive of adverse events (AEs), hospital length of stay, and use of intensive care services.^6,7,9-13 We hypothesized that preoperative clinical indicators assessed by pneumonia severity scores as well as patient demographics and baseline comorbidities may also have prognostic value for risk of AEs in a cohort of geriatric hip fracture surgery patients with preoperative pneumonia.

In this article, we first describe the prevalence of preoperative pneumonia in geriatric hip fracture surgery patients as well as demographic and operative differences between patients with and without the disease. We then ask 3 questions: Is preoperative pneumonia an independent risk factor for mortality and adverse outcomes in geriatric hip fracture surgery? Is there a postoperative interval during which the unadjusted mortality rate is higher among patients with preoperative pneumonia? In patients with preoperative pneumonia, what are the predictors of morbidity and mortality?

Methods

Yale University’s Human Investigations Committee approved this retrospective cohort study, which used the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database for the period 2005 to 2012. ACS-NSQIP is a prospective, multi-institutional outcomes program that collects data on preoperative comorbidities, intraoperative variables, and 30-day postoperative outcomes for patients undergoing surgical procedures in inpatient and outpatient settings.¹⁴

Unlike administrative databases, which are based on reimbursement data, ACS-NSQIP data are collected by trained surgical clinical reviewers for the purposes of quality improvement and clinical research, and data quality is ensured with routine auditing.¹⁵ The program has gained a high degree of respect as a powerful and valid data source in both general¹⁶ and orthopedic¹⁷ surgery literature. The database offers a particular advantage with respect to the study of preoperative pneumonia: Only patients with new or recently diagnosed pneumonia on antibiotic therapy who meet strict criteria for characteristic findings on chest radiography, clinical signs and symptoms of respiratory illness, and positive cultures are coded as having actively treated pneumonia at time of surgery.¹⁵

To identify hip fracture patients over the age of 65 years who underwent operative fixation of a hip fracture, we used Current Procedural Terminology (CPT) hip fracture codes, including 27235 (percutaneous screw fixation), 27236 or 27244 (plate-and-screw fixation), and 27245 (intramedullary device), as well as 27125 (hemiarthroplasty) and 27130 (arthroplasty) for patients with a postoperative International Classification of Disease, Ninth Revision (ICD-9) diagnosis code (820.x, 820.2x, or 820.8) consistent with acute hip fracture.^18,19 Procedure type, anesthesia type, and delay from admission to surgery were captured for all procedures.

Preoperative demographics included age, sex, transfer origin, functional status, and body mass index (BMI) category. Binary comorbidities were classified as preoperative anemia (hematocrit, <0.41 for men, <0.36 for women), confusion, dyspnea at rest, uremia (blood urea nitrogen, >6.8 mmol/L), history of cardiovascular disease (congestive heart failure, myocardial infarction, percutaneous coronary intervention, angina pectoris, medically treated hypertension, peripheral vascular disease, or resting claudication), chronic obstructive pulmonary disease, diabetes, renal disease (renal failure or dialysis), and cigarette use in preceding 12 months.^20,21 Although preoperative hypotension and respiratory rate are often considered in patients with pneumonia, these variables were not available from the ACS-NSQIP data.^6,22Pearson χ² test for categorical variables was used to compare baseline demographics and operative characteristics between patients with and without pneumonia, and Student t test was used to compare intervals from hospital admission to hip fracture surgery, surgery start to surgery stop, and surgery to discharge between patients with and without preoperative pneumonia.

Binary outcome measures were compared between patients with and without preoperative pneumonia. “Any AE” included any serious AE (SAE) or any minor AE. SAEs included death, acute renal failure, ventilator use >48 hours, unplanned intubation, septic shock, sepsis, return to operating room, coma >24 hours, cardiac arrest requiring cardiopulmonary resuscitation, myocardial infarction, thromboembolic event (deep vein thrombosis or pulmonary embolism), and stroke/cerebrovascular accident. Minor AEs included progressive renal insufficiency, urinary tract infection, organ/space infection, superficial surgical-site infection, deep surgical-site infection, and wound dehiscence. Other binary outcome measures included discharge destination and unplanned readmission within 30 days after hip fracture surgery.²³Poisson regression with robust error variance as described by Zou²⁴ was used to compare the rates of any, minor, and individual AEs, and any SAEs, between patients with and without pneumonia. Multivariate analysis accounted for the baseline variables in Table 1. AEs that occurred more than once in each group were included in the analyses.

Results

Of the 7128 geriatric hip fracture patients in this study, 82 (1.2%) had active pneumonia at time of surgery (Table 1). Age, BMI, preoperative uremia, history of cardiovascular disease, diabetes, renal disease, and smoking were similar between groups. In addition, there was no difference in anesthesia type or fixation procedure between the pneumonia and no-pneumonia groups. Patients with preoperative pneumonia differed significantly with respect to sex, transfer from facility, preoperative functional dependence, anemia, confusion, dyspnea at rest, and history of chronic obstructive pulmonary disease (Table 1).

Interval from admission to surgery was longer (P < .001) for geriatric hip fracture patients with preoperative pneumonia (mean, 6.8 days; 95% CI, 2.5-11.1 days) than for those without pneumonia (mean, 1.5 days; CI, 1.4-1.5 days). There was no difference (P = .124) in operative time between the pneumonia group (mean, 72.8 min; CI, 64.0-81.5 min) and the no-pneumonia group (mean, 66.1 min; CI, 61.2-67.0 min). Interval from surgery to discharge was longer (P < .001) for patients with preoperative pneumonia (mean, 10.1 days; CI, 6.9-13.4 days) than for those without pneumonia (mean, 6.3 days; CI, 6.1-6.4 days).

Adverse outcomes of geriatric hip fracture surgery are listed in Table 2. In the multivariate analysis, preoperative pneumonia was significantly associated with any AE (relative risk [RR]) = 1.44) and any SAE (RR = 1.79).

Discussion

In the general US population, pneumonia accounts for 1.4% of deaths in people 65 years to 74 years old, 2.1% in people 75 years to 84 years, and 3.1% in people 85 years or older. In total, 3.4% of hospital inpatient deaths are attributed to pneumonia.²⁵ In hospitalized general orthopedic surgical patients as well as hip fracture patients, pneumonia is strongly associated with increased mortality.^26,27

We identified a preoperative pneumonia prevalence of 1.2%, which is comparable to the rates reported in the literature (0.3%-3.2%).^1-3 To our knowledge, our study represents the largest series of patients with preoperative pneumonia at time of hip fracture repair, and the first to independently associate preoperative pneumonia with increased incidence of AEs, including death.

This study had its limitations. First, the ACS-NSQIP morbidity and mortality data, which are limited to the first 30 postoperative days, may be skewed because AEs that occurred after that interval are not captured. Second, coding of pneumonia in ACS-NSQIP does not convey specific information about the disease and its severity—infectious organism(s) responsible; acquisition setting (healthcare or community); treatment given, including antibiotic(s) selection, steroid use, dosing, and duration; and measures of treatment efficacy—limiting interpretation of the difference in delay to surgery. We cannot say whether the longer interval in patients with pneumonia reflects medical optimization, or whether the delay itself or any interventions during that time positively or negatively affected outcomes. In addition, despite using a large national database, we obtained a relatively small sample of patients (82) who had pneumonia before surgical hip fracture repair.

Multivariate analysis controlling for baseline demographics and comorbidities revealed that multiple SAEs were independently associated with preoperative pneumonia (overall SAE, RR = 1.79). Postoperative use of ventilator support for longer than 48 hours (RR = 6.48) and coma longer than 24 hours (RR = 7.31) are expected given the severity of pulmonary compromise in the study cohort.^28,29 Acute renal failure (RR = 14.61) can occur in both hip fracture patients and community-acquired pneumonia patients and may be a multifactorial complication of the pulmonary infection, of the anesthesia, or of the surgical intervention in this cohort.^30-32Unadjusted mortality in hip fracture takes months to a year to normalize to that of age-matched controls.^32-34 In our series, the unadjusted death rate in the pneumonia cohort (Figure) was transiently elevated during the first weeks after surgery but then drew nearer the rate in the nondiseased hip fracture cohort by the end of the first month. Early death in the pneumonia group likely was multifactorial, potentially influenced by the increased burden of comorbidities in the pneumonia group at baseline, and the longer delay to surgery,^35-38 as well as by the natural history of treated pneumonia in hospital patients, who, compared with age-matched hospitalized controls, also exhibit higher mortality during only the first 2 to 4 months of hospitalization for pneumonia.³⁹ We regret that quality improvement strategies in the treatment of geriatric hip fracture surgery with pneumonia cannot be extrapolated from these results.

Similarly, the utility of BMI <18.5 kg/m² as an actionable preoperative finding cannot be assessed from these results. However, we propose that underweight geriatric hip fracture patients with pneumonia may benefit from more aggressive preoperative optimization that does not delay surgery. Higher acuity of postoperative care, including more intensive nursing care and early coordination of care with respiratory therapists and medical comanagement teams, may also be beneficial.

Anesthesia type did not differ between patients with and without preoperative pneumonia and was not associated with AEs in patients with preoperative pneumonia. Consistent with our findings, multiple studies have reported no significant differences in short-term outcomes of hip fracture repair between general and spinal anesthesia, though no other study has compared the benefits of general and spinal anesthesia for patients with preoperative pneumonia.^40-44 Although spinal anesthesia (relative to general anesthesia) has been reported to have benefits in hip and knee arthroplasty, these benefits appear not to translate to hip fracture repair.^45-50 The results of the present study suggest that general and spinal anesthesia may be equivalent in terms of risk for the geriatric hip fracture patient with preoperative pneumonia.^43,44Our attempt to evaluate the CURB-65 pneumonia severity score as a prognosticator of AEs was thwarted by the absence of required variables in the ACS-NSQIP dataset (confusion, uremia, dyspnea, and age were available; hypotension and blood pressure were not). In our analysis, we did include, individually, variables previously found to predict AEs in the medical pneumonia population (confusion, uremia, dyspnea at rest, anemia).^9-11,32 However, these clinical findings are nonspecific in hip fracture patients, who may become anemic, confused, dyspneic, or uremic from a multitude of factors related to their injury and unrelated to pneumonia, including but not limited to hemorrhage, muscle damage, renal injury, and pulmonary embolism. It is not surprising that confusion, uremia, dyspnea at rest, and anemia were not individually predictive of AEs or death within 30 days after surgery in the cohort of geriatric hip fracture patients with pneumonia.

There is no literature that argues for or against delaying hip fracture surgery in geriatric hip fracture patients with pneumonia. The surgical delay observed in this population is ostensibly related to medical optimization of the pneumonia and/or underlying comorbidities. However, we did not find a morbidity or mortality detriment or benefit in delaying surgery by 1 to 4 days in this population. Delay of surgery is a poor covariate, given extensive confounding by medical management and preoperative optimizing of comorbid conditions (reflected in our independent variable and covariates) as well as institutional and surgeon variations in policy and behavior and other unaccounted influences. Although some authors have found no difference in mortality or major AEs between hip fracture patients who had a surgical delay and those who did not,^31,51-53 other series and meta-analyses have suggested a mortality detriment in a surgical delay of more than 2 days^36,54 or 4 days⁵⁵ from admission. Given our data, we cannot recommend against immediate hip fracture repair in the subpopulation of geriatric hip fracture patients with pneumonia.

Our study findings suggest that preoperative pneumonia is a rare independent risk factor for AEs after hip fracture surgery in geriatric patients. Underweight BMI is predictive of death in geriatric hip fracture surgery patients who present with pneumonia, whereas early surgical repair appears not to be associated with adverse outcomes. Further investigation is warranted to determine if such patients benefit from specific preoperative and postoperative strategies for optimizing medical and surgical care based on these findings.

Am J Orthop. 2017;46(3):E177-E185. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• The prevalence of preoperative pneumonia is 1.2% among hip fracture patients aged >65 years.
• Preoperative pneumonia is an independent risk factor for mortality and adverse events including renal failure, prolonged ventilator dependence, and prolonged altered mental status after geriatric hip fracture surgery.
• Underweight BMI (<18.5 kg/m²) was associated with higher mortality within 30 days among hip fracture patients admitted with pneumonia.
• The mortality rate normalized to that of patients without pneumonia within 2 weeks of hip fracture surgery.
• Time from admission to surgery was not associated with adverse events or mortality among hip fracture patients admitted with pneumonia.

Preoperative pneumonia remains relatively unexplored as a risk factor for adverse outcomes in geriatric hip fracture surgery. Dated studies report a 0.3% to 3.2% prevalence of “recent pneumonia” in patients presenting with hip fracture but provide neither a definition of pneumonia based on clinical criteria nor a subset analysis of outcomes in the pneumonia group.^1-3 Although active pneumonia has been identified as a preoperative optimization target in the management guidelines for geriatric hip fracture,⁴ we are unaware of any studies that have reported on differences in demographics, comorbidities, delay to surgery, or adverse outcomes between hip fracture patients with and without preoperative pneumonia.

This paucity of information on the effect of preoperative pneumonia in the hip fracture population may be related to low prevalence of preoperative pneumonia and a cadre of variable definitions, which limit identification of a cohort of patients with preoperative pneumonia large enough from which to draw meaningful results. Database studies, especially those using surgical registries rather than administrative or reimbursement data, offer particular advantages for investigation of such rare clinical entities.⁵Medical care of patients with pneumonia alone is known to be facilitated by assessments of mortality risk from clinical and laboratory data. The modified British Thoracic Society rule/CURB-65 (confusion, urea, respiratory rate, blood pressure) score is strongly predictive of mortality in hospitalized adults with pneumonia (odds ratio [OR], 4.59; 95% confidence interval [CI], 1.42-14.85; P = .011) and may guide antibiotic therapy, laboratory investigations, and the decision to intubate in a patient with pneumonia.^6-8 This score is predictive of adverse events (AEs), hospital length of stay, and use of intensive care services.^6,7,9-13 We hypothesized that preoperative clinical indicators assessed by pneumonia severity scores as well as patient demographics and baseline comorbidities may also have prognostic value for risk of AEs in a cohort of geriatric hip fracture surgery patients with preoperative pneumonia.

In this article, we first describe the prevalence of preoperative pneumonia in geriatric hip fracture surgery patients as well as demographic and operative differences between patients with and without the disease. We then ask 3 questions: Is preoperative pneumonia an independent risk factor for mortality and adverse outcomes in geriatric hip fracture surgery? Is there a postoperative interval during which the unadjusted mortality rate is higher among patients with preoperative pneumonia? In patients with preoperative pneumonia, what are the predictors of morbidity and mortality?

Methods

Yale University’s Human Investigations Committee approved this retrospective cohort study, which used the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database for the period 2005 to 2012. ACS-NSQIP is a prospective, multi-institutional outcomes program that collects data on preoperative comorbidities, intraoperative variables, and 30-day postoperative outcomes for patients undergoing surgical procedures in inpatient and outpatient settings.¹⁴

Unlike administrative databases, which are based on reimbursement data, ACS-NSQIP data are collected by trained surgical clinical reviewers for the purposes of quality improvement and clinical research, and data quality is ensured with routine auditing.¹⁵ The program has gained a high degree of respect as a powerful and valid data source in both general¹⁶ and orthopedic¹⁷ surgery literature. The database offers a particular advantage with respect to the study of preoperative pneumonia: Only patients with new or recently diagnosed pneumonia on antibiotic therapy who meet strict criteria for characteristic findings on chest radiography, clinical signs and symptoms of respiratory illness, and positive cultures are coded as having actively treated pneumonia at time of surgery.¹⁵

To identify hip fracture patients over the age of 65 years who underwent operative fixation of a hip fracture, we used Current Procedural Terminology (CPT) hip fracture codes, including 27235 (percutaneous screw fixation), 27236 or 27244 (plate-and-screw fixation), and 27245 (intramedullary device), as well as 27125 (hemiarthroplasty) and 27130 (arthroplasty) for patients with a postoperative International Classification of Disease, Ninth Revision (ICD-9) diagnosis code (820.x, 820.2x, or 820.8) consistent with acute hip fracture.^18,19 Procedure type, anesthesia type, and delay from admission to surgery were captured for all procedures.

Preoperative demographics included age, sex, transfer origin, functional status, and body mass index (BMI) category. Binary comorbidities were classified as preoperative anemia (hematocrit, <0.41 for men, <0.36 for women), confusion, dyspnea at rest, uremia (blood urea nitrogen, >6.8 mmol/L), history of cardiovascular disease (congestive heart failure, myocardial infarction, percutaneous coronary intervention, angina pectoris, medically treated hypertension, peripheral vascular disease, or resting claudication), chronic obstructive pulmonary disease, diabetes, renal disease (renal failure or dialysis), and cigarette use in preceding 12 months.^20,21 Although preoperative hypotension and respiratory rate are often considered in patients with pneumonia, these variables were not available from the ACS-NSQIP data.^6,22Pearson χ² test for categorical variables was used to compare baseline demographics and operative characteristics between patients with and without pneumonia, and Student t test was used to compare intervals from hospital admission to hip fracture surgery, surgery start to surgery stop, and surgery to discharge between patients with and without preoperative pneumonia.

Binary outcome measures were compared between patients with and without preoperative pneumonia. “Any AE” included any serious AE (SAE) or any minor AE. SAEs included death, acute renal failure, ventilator use >48 hours, unplanned intubation, septic shock, sepsis, return to operating room, coma >24 hours, cardiac arrest requiring cardiopulmonary resuscitation, myocardial infarction, thromboembolic event (deep vein thrombosis or pulmonary embolism), and stroke/cerebrovascular accident. Minor AEs included progressive renal insufficiency, urinary tract infection, organ/space infection, superficial surgical-site infection, deep surgical-site infection, and wound dehiscence. Other binary outcome measures included discharge destination and unplanned readmission within 30 days after hip fracture surgery.²³Poisson regression with robust error variance as described by Zou²⁴ was used to compare the rates of any, minor, and individual AEs, and any SAEs, between patients with and without pneumonia. Multivariate analysis accounted for the baseline variables in Table 1. AEs that occurred more than once in each group were included in the analyses.

Results

Of the 7128 geriatric hip fracture patients in this study, 82 (1.2%) had active pneumonia at time of surgery (Table 1). Age, BMI, preoperative uremia, history of cardiovascular disease, diabetes, renal disease, and smoking were similar between groups. In addition, there was no difference in anesthesia type or fixation procedure between the pneumonia and no-pneumonia groups. Patients with preoperative pneumonia differed significantly with respect to sex, transfer from facility, preoperative functional dependence, anemia, confusion, dyspnea at rest, and history of chronic obstructive pulmonary disease (Table 1).

Interval from admission to surgery was longer (P < .001) for geriatric hip fracture patients with preoperative pneumonia (mean, 6.8 days; 95% CI, 2.5-11.1 days) than for those without pneumonia (mean, 1.5 days; CI, 1.4-1.5 days). There was no difference (P = .124) in operative time between the pneumonia group (mean, 72.8 min; CI, 64.0-81.5 min) and the no-pneumonia group (mean, 66.1 min; CI, 61.2-67.0 min). Interval from surgery to discharge was longer (P < .001) for patients with preoperative pneumonia (mean, 10.1 days; CI, 6.9-13.4 days) than for those without pneumonia (mean, 6.3 days; CI, 6.1-6.4 days).

Adverse outcomes of geriatric hip fracture surgery are listed in Table 2. In the multivariate analysis, preoperative pneumonia was significantly associated with any AE (relative risk [RR]) = 1.44) and any SAE (RR = 1.79).

Discussion

In the general US population, pneumonia accounts for 1.4% of deaths in people 65 years to 74 years old, 2.1% in people 75 years to 84 years, and 3.1% in people 85 years or older. In total, 3.4% of hospital inpatient deaths are attributed to pneumonia.²⁵ In hospitalized general orthopedic surgical patients as well as hip fracture patients, pneumonia is strongly associated with increased mortality.^26,27

We identified a preoperative pneumonia prevalence of 1.2%, which is comparable to the rates reported in the literature (0.3%-3.2%).^1-3 To our knowledge, our study represents the largest series of patients with preoperative pneumonia at time of hip fracture repair, and the first to independently associate preoperative pneumonia with increased incidence of AEs, including death.

This study had its limitations. First, the ACS-NSQIP morbidity and mortality data, which are limited to the first 30 postoperative days, may be skewed because AEs that occurred after that interval are not captured. Second, coding of pneumonia in ACS-NSQIP does not convey specific information about the disease and its severity—infectious organism(s) responsible; acquisition setting (healthcare or community); treatment given, including antibiotic(s) selection, steroid use, dosing, and duration; and measures of treatment efficacy—limiting interpretation of the difference in delay to surgery. We cannot say whether the longer interval in patients with pneumonia reflects medical optimization, or whether the delay itself or any interventions during that time positively or negatively affected outcomes. In addition, despite using a large national database, we obtained a relatively small sample of patients (82) who had pneumonia before surgical hip fracture repair.

Multivariate analysis controlling for baseline demographics and comorbidities revealed that multiple SAEs were independently associated with preoperative pneumonia (overall SAE, RR = 1.79). Postoperative use of ventilator support for longer than 48 hours (RR = 6.48) and coma longer than 24 hours (RR = 7.31) are expected given the severity of pulmonary compromise in the study cohort.^28,29 Acute renal failure (RR = 14.61) can occur in both hip fracture patients and community-acquired pneumonia patients and may be a multifactorial complication of the pulmonary infection, of the anesthesia, or of the surgical intervention in this cohort.^30-32Unadjusted mortality in hip fracture takes months to a year to normalize to that of age-matched controls.^32-34 In our series, the unadjusted death rate in the pneumonia cohort (Figure) was transiently elevated during the first weeks after surgery but then drew nearer the rate in the nondiseased hip fracture cohort by the end of the first month. Early death in the pneumonia group likely was multifactorial, potentially influenced by the increased burden of comorbidities in the pneumonia group at baseline, and the longer delay to surgery,^35-38 as well as by the natural history of treated pneumonia in hospital patients, who, compared with age-matched hospitalized controls, also exhibit higher mortality during only the first 2 to 4 months of hospitalization for pneumonia.³⁹ We regret that quality improvement strategies in the treatment of geriatric hip fracture surgery with pneumonia cannot be extrapolated from these results.

Similarly, the utility of BMI <18.5 kg/m² as an actionable preoperative finding cannot be assessed from these results. However, we propose that underweight geriatric hip fracture patients with pneumonia may benefit from more aggressive preoperative optimization that does not delay surgery. Higher acuity of postoperative care, including more intensive nursing care and early coordination of care with respiratory therapists and medical comanagement teams, may also be beneficial.

Anesthesia type did not differ between patients with and without preoperative pneumonia and was not associated with AEs in patients with preoperative pneumonia. Consistent with our findings, multiple studies have reported no significant differences in short-term outcomes of hip fracture repair between general and spinal anesthesia, though no other study has compared the benefits of general and spinal anesthesia for patients with preoperative pneumonia.^40-44 Although spinal anesthesia (relative to general anesthesia) has been reported to have benefits in hip and knee arthroplasty, these benefits appear not to translate to hip fracture repair.^45-50 The results of the present study suggest that general and spinal anesthesia may be equivalent in terms of risk for the geriatric hip fracture patient with preoperative pneumonia.^43,44Our attempt to evaluate the CURB-65 pneumonia severity score as a prognosticator of AEs was thwarted by the absence of required variables in the ACS-NSQIP dataset (confusion, uremia, dyspnea, and age were available; hypotension and blood pressure were not). In our analysis, we did include, individually, variables previously found to predict AEs in the medical pneumonia population (confusion, uremia, dyspnea at rest, anemia).^9-11,32 However, these clinical findings are nonspecific in hip fracture patients, who may become anemic, confused, dyspneic, or uremic from a multitude of factors related to their injury and unrelated to pneumonia, including but not limited to hemorrhage, muscle damage, renal injury, and pulmonary embolism. It is not surprising that confusion, uremia, dyspnea at rest, and anemia were not individually predictive of AEs or death within 30 days after surgery in the cohort of geriatric hip fracture patients with pneumonia.

There is no literature that argues for or against delaying hip fracture surgery in geriatric hip fracture patients with pneumonia. The surgical delay observed in this population is ostensibly related to medical optimization of the pneumonia and/or underlying comorbidities. However, we did not find a morbidity or mortality detriment or benefit in delaying surgery by 1 to 4 days in this population. Delay of surgery is a poor covariate, given extensive confounding by medical management and preoperative optimizing of comorbid conditions (reflected in our independent variable and covariates) as well as institutional and surgeon variations in policy and behavior and other unaccounted influences. Although some authors have found no difference in mortality or major AEs between hip fracture patients who had a surgical delay and those who did not,^31,51-53 other series and meta-analyses have suggested a mortality detriment in a surgical delay of more than 2 days^36,54 or 4 days⁵⁵ from admission. Given our data, we cannot recommend against immediate hip fracture repair in the subpopulation of geriatric hip fracture patients with pneumonia.

Our study findings suggest that preoperative pneumonia is a rare independent risk factor for AEs after hip fracture surgery in geriatric patients. Underweight BMI is predictive of death in geriatric hip fracture surgery patients who present with pneumonia, whereas early surgical repair appears not to be associated with adverse outcomes. Further investigation is warranted to determine if such patients benefit from specific preoperative and postoperative strategies for optimizing medical and surgical care based on these findings.

Am J Orthop. 2017;46(3):E177-E185. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• The prevalence of preoperative pneumonia is 1.2% among hip fracture patients aged >65 years.
• Preoperative pneumonia is an independent risk factor for mortality and adverse events including renal failure, prolonged ventilator dependence, and prolonged altered mental status after geriatric hip fracture surgery.
• Underweight BMI (<18.5 kg/m²) was associated with higher mortality within 30 days among hip fracture patients admitted with pneumonia.
• The mortality rate normalized to that of patients without pneumonia within 2 weeks of hip fracture surgery.
• Time from admission to surgery was not associated with adverse events or mortality among hip fracture patients admitted with pneumonia.

Preoperative pneumonia remains relatively unexplored as a risk factor for adverse outcomes in geriatric hip fracture surgery. Dated studies report a 0.3% to 3.2% prevalence of “recent pneumonia” in patients presenting with hip fracture but provide neither a definition of pneumonia based on clinical criteria nor a subset analysis of outcomes in the pneumonia group.^1-3 Although active pneumonia has been identified as a preoperative optimization target in the management guidelines for geriatric hip fracture,⁴ we are unaware of any studies that have reported on differences in demographics, comorbidities, delay to surgery, or adverse outcomes between hip fracture patients with and without preoperative pneumonia.

This paucity of information on the effect of preoperative pneumonia in the hip fracture population may be related to low prevalence of preoperative pneumonia and a cadre of variable definitions, which limit identification of a cohort of patients with preoperative pneumonia large enough from which to draw meaningful results. Database studies, especially those using surgical registries rather than administrative or reimbursement data, offer particular advantages for investigation of such rare clinical entities.⁵Medical care of patients with pneumonia alone is known to be facilitated by assessments of mortality risk from clinical and laboratory data. The modified British Thoracic Society rule/CURB-65 (confusion, urea, respiratory rate, blood pressure) score is strongly predictive of mortality in hospitalized adults with pneumonia (odds ratio [OR], 4.59; 95% confidence interval [CI], 1.42-14.85; P = .011) and may guide antibiotic therapy, laboratory investigations, and the decision to intubate in a patient with pneumonia.^6-8 This score is predictive of adverse events (AEs), hospital length of stay, and use of intensive care services.^6,7,9-13 We hypothesized that preoperative clinical indicators assessed by pneumonia severity scores as well as patient demographics and baseline comorbidities may also have prognostic value for risk of AEs in a cohort of geriatric hip fracture surgery patients with preoperative pneumonia.

In this article, we first describe the prevalence of preoperative pneumonia in geriatric hip fracture surgery patients as well as demographic and operative differences between patients with and without the disease. We then ask 3 questions: Is preoperative pneumonia an independent risk factor for mortality and adverse outcomes in geriatric hip fracture surgery? Is there a postoperative interval during which the unadjusted mortality rate is higher among patients with preoperative pneumonia? In patients with preoperative pneumonia, what are the predictors of morbidity and mortality?

Methods

Yale University’s Human Investigations Committee approved this retrospective cohort study, which used the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database for the period 2005 to 2012. ACS-NSQIP is a prospective, multi-institutional outcomes program that collects data on preoperative comorbidities, intraoperative variables, and 30-day postoperative outcomes for patients undergoing surgical procedures in inpatient and outpatient settings.¹⁴

Unlike administrative databases, which are based on reimbursement data, ACS-NSQIP data are collected by trained surgical clinical reviewers for the purposes of quality improvement and clinical research, and data quality is ensured with routine auditing.¹⁵ The program has gained a high degree of respect as a powerful and valid data source in both general¹⁶ and orthopedic¹⁷ surgery literature. The database offers a particular advantage with respect to the study of preoperative pneumonia: Only patients with new or recently diagnosed pneumonia on antibiotic therapy who meet strict criteria for characteristic findings on chest radiography, clinical signs and symptoms of respiratory illness, and positive cultures are coded as having actively treated pneumonia at time of surgery.¹⁵

To identify hip fracture patients over the age of 65 years who underwent operative fixation of a hip fracture, we used Current Procedural Terminology (CPT) hip fracture codes, including 27235 (percutaneous screw fixation), 27236 or 27244 (plate-and-screw fixation), and 27245 (intramedullary device), as well as 27125 (hemiarthroplasty) and 27130 (arthroplasty) for patients with a postoperative International Classification of Disease, Ninth Revision (ICD-9) diagnosis code (820.x, 820.2x, or 820.8) consistent with acute hip fracture.^18,19 Procedure type, anesthesia type, and delay from admission to surgery were captured for all procedures.

Preoperative demographics included age, sex, transfer origin, functional status, and body mass index (BMI) category. Binary comorbidities were classified as preoperative anemia (hematocrit, <0.41 for men, <0.36 for women), confusion, dyspnea at rest, uremia (blood urea nitrogen, >6.8 mmol/L), history of cardiovascular disease (congestive heart failure, myocardial infarction, percutaneous coronary intervention, angina pectoris, medically treated hypertension, peripheral vascular disease, or resting claudication), chronic obstructive pulmonary disease, diabetes, renal disease (renal failure or dialysis), and cigarette use in preceding 12 months.^20,21 Although preoperative hypotension and respiratory rate are often considered in patients with pneumonia, these variables were not available from the ACS-NSQIP data.^6,22Pearson χ² test for categorical variables was used to compare baseline demographics and operative characteristics between patients with and without pneumonia, and Student t test was used to compare intervals from hospital admission to hip fracture surgery, surgery start to surgery stop, and surgery to discharge between patients with and without preoperative pneumonia.

Binary outcome measures were compared between patients with and without preoperative pneumonia. “Any AE” included any serious AE (SAE) or any minor AE. SAEs included death, acute renal failure, ventilator use >48 hours, unplanned intubation, septic shock, sepsis, return to operating room, coma >24 hours, cardiac arrest requiring cardiopulmonary resuscitation, myocardial infarction, thromboembolic event (deep vein thrombosis or pulmonary embolism), and stroke/cerebrovascular accident. Minor AEs included progressive renal insufficiency, urinary tract infection, organ/space infection, superficial surgical-site infection, deep surgical-site infection, and wound dehiscence. Other binary outcome measures included discharge destination and unplanned readmission within 30 days after hip fracture surgery.²³Poisson regression with robust error variance as described by Zou²⁴ was used to compare the rates of any, minor, and individual AEs, and any SAEs, between patients with and without pneumonia. Multivariate analysis accounted for the baseline variables in Table 1. AEs that occurred more than once in each group were included in the analyses.

Results

Of the 7128 geriatric hip fracture patients in this study, 82 (1.2%) had active pneumonia at time of surgery (Table 1). Age, BMI, preoperative uremia, history of cardiovascular disease, diabetes, renal disease, and smoking were similar between groups. In addition, there was no difference in anesthesia type or fixation procedure between the pneumonia and no-pneumonia groups. Patients with preoperative pneumonia differed significantly with respect to sex, transfer from facility, preoperative functional dependence, anemia, confusion, dyspnea at rest, and history of chronic obstructive pulmonary disease (Table 1).

Interval from admission to surgery was longer (P < .001) for geriatric hip fracture patients with preoperative pneumonia (mean, 6.8 days; 95% CI, 2.5-11.1 days) than for those without pneumonia (mean, 1.5 days; CI, 1.4-1.5 days). There was no difference (P = .124) in operative time between the pneumonia group (mean, 72.8 min; CI, 64.0-81.5 min) and the no-pneumonia group (mean, 66.1 min; CI, 61.2-67.0 min). Interval from surgery to discharge was longer (P < .001) for patients with preoperative pneumonia (mean, 10.1 days; CI, 6.9-13.4 days) than for those without pneumonia (mean, 6.3 days; CI, 6.1-6.4 days).

Adverse outcomes of geriatric hip fracture surgery are listed in Table 2. In the multivariate analysis, preoperative pneumonia was significantly associated with any AE (relative risk [RR]) = 1.44) and any SAE (RR = 1.79).

Discussion

In the general US population, pneumonia accounts for 1.4% of deaths in people 65 years to 74 years old, 2.1% in people 75 years to 84 years, and 3.1% in people 85 years or older. In total, 3.4% of hospital inpatient deaths are attributed to pneumonia.²⁵ In hospitalized general orthopedic surgical patients as well as hip fracture patients, pneumonia is strongly associated with increased mortality.^26,27

We identified a preoperative pneumonia prevalence of 1.2%, which is comparable to the rates reported in the literature (0.3%-3.2%).^1-3 To our knowledge, our study represents the largest series of patients with preoperative pneumonia at time of hip fracture repair, and the first to independently associate preoperative pneumonia with increased incidence of AEs, including death.

This study had its limitations. First, the ACS-NSQIP morbidity and mortality data, which are limited to the first 30 postoperative days, may be skewed because AEs that occurred after that interval are not captured. Second, coding of pneumonia in ACS-NSQIP does not convey specific information about the disease and its severity—infectious organism(s) responsible; acquisition setting (healthcare or community); treatment given, including antibiotic(s) selection, steroid use, dosing, and duration; and measures of treatment efficacy—limiting interpretation of the difference in delay to surgery. We cannot say whether the longer interval in patients with pneumonia reflects medical optimization, or whether the delay itself or any interventions during that time positively or negatively affected outcomes. In addition, despite using a large national database, we obtained a relatively small sample of patients (82) who had pneumonia before surgical hip fracture repair.

Multivariate analysis controlling for baseline demographics and comorbidities revealed that multiple SAEs were independently associated with preoperative pneumonia (overall SAE, RR = 1.79). Postoperative use of ventilator support for longer than 48 hours (RR = 6.48) and coma longer than 24 hours (RR = 7.31) are expected given the severity of pulmonary compromise in the study cohort.^28,29 Acute renal failure (RR = 14.61) can occur in both hip fracture patients and community-acquired pneumonia patients and may be a multifactorial complication of the pulmonary infection, of the anesthesia, or of the surgical intervention in this cohort.^30-32Unadjusted mortality in hip fracture takes months to a year to normalize to that of age-matched controls.^32-34 In our series, the unadjusted death rate in the pneumonia cohort (Figure) was transiently elevated during the first weeks after surgery but then drew nearer the rate in the nondiseased hip fracture cohort by the end of the first month. Early death in the pneumonia group likely was multifactorial, potentially influenced by the increased burden of comorbidities in the pneumonia group at baseline, and the longer delay to surgery,^35-38 as well as by the natural history of treated pneumonia in hospital patients, who, compared with age-matched hospitalized controls, also exhibit higher mortality during only the first 2 to 4 months of hospitalization for pneumonia.³⁹ We regret that quality improvement strategies in the treatment of geriatric hip fracture surgery with pneumonia cannot be extrapolated from these results.

Similarly, the utility of BMI <18.5 kg/m² as an actionable preoperative finding cannot be assessed from these results. However, we propose that underweight geriatric hip fracture patients with pneumonia may benefit from more aggressive preoperative optimization that does not delay surgery. Higher acuity of postoperative care, including more intensive nursing care and early coordination of care with respiratory therapists and medical comanagement teams, may also be beneficial.

Anesthesia type did not differ between patients with and without preoperative pneumonia and was not associated with AEs in patients with preoperative pneumonia. Consistent with our findings, multiple studies have reported no significant differences in short-term outcomes of hip fracture repair between general and spinal anesthesia, though no other study has compared the benefits of general and spinal anesthesia for patients with preoperative pneumonia.^40-44 Although spinal anesthesia (relative to general anesthesia) has been reported to have benefits in hip and knee arthroplasty, these benefits appear not to translate to hip fracture repair.^45-50 The results of the present study suggest that general and spinal anesthesia may be equivalent in terms of risk for the geriatric hip fracture patient with preoperative pneumonia.^43,44Our attempt to evaluate the CURB-65 pneumonia severity score as a prognosticator of AEs was thwarted by the absence of required variables in the ACS-NSQIP dataset (confusion, uremia, dyspnea, and age were available; hypotension and blood pressure were not). In our analysis, we did include, individually, variables previously found to predict AEs in the medical pneumonia population (confusion, uremia, dyspnea at rest, anemia).^9-11,32 However, these clinical findings are nonspecific in hip fracture patients, who may become anemic, confused, dyspneic, or uremic from a multitude of factors related to their injury and unrelated to pneumonia, including but not limited to hemorrhage, muscle damage, renal injury, and pulmonary embolism. It is not surprising that confusion, uremia, dyspnea at rest, and anemia were not individually predictive of AEs or death within 30 days after surgery in the cohort of geriatric hip fracture patients with pneumonia.

There is no literature that argues for or against delaying hip fracture surgery in geriatric hip fracture patients with pneumonia. The surgical delay observed in this population is ostensibly related to medical optimization of the pneumonia and/or underlying comorbidities. However, we did not find a morbidity or mortality detriment or benefit in delaying surgery by 1 to 4 days in this population. Delay of surgery is a poor covariate, given extensive confounding by medical management and preoperative optimizing of comorbid conditions (reflected in our independent variable and covariates) as well as institutional and surgeon variations in policy and behavior and other unaccounted influences. Although some authors have found no difference in mortality or major AEs between hip fracture patients who had a surgical delay and those who did not,^31,51-53 other series and meta-analyses have suggested a mortality detriment in a surgical delay of more than 2 days^36,54 or 4 days⁵⁵ from admission. Given our data, we cannot recommend against immediate hip fracture repair in the subpopulation of geriatric hip fracture patients with pneumonia.

Our study findings suggest that preoperative pneumonia is a rare independent risk factor for AEs after hip fracture surgery in geriatric patients. Underweight BMI is predictive of death in geriatric hip fracture surgery patients who present with pneumonia, whereas early surgical repair appears not to be associated with adverse outcomes. Further investigation is warranted to determine if such patients benefit from specific preoperative and postoperative strategies for optimizing medical and surgical care based on these findings.

Am J Orthop. 2017;46(3):E177-E185. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

CHICAGO – The standard of care for patients with non–small cell lung cancer positive for the anaplastic lymphoma kinase (ALK) is the ALK inhibitor crizotinib (Xalkori). However, many patients on crizotinib will have disease progression within the first year of therapy, and many will go on to have central nervous system (CNS) metastases.

The multicenter international ALEX trial compared crizotinib with the second-generation ALK inhibitor alectinib (Alecensa). The investigators found that alectinib reduced the risk of progression by 53% and the time to CNS progression by 84%.

In this video interview at the annual meeting of the American Society of Clinical Oncology, Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston, outlines the ALEX trial results, which are being hailed as “practice changing.”

CHICAGO – The standard of care for patients with non–small cell lung cancer positive for the anaplastic lymphoma kinase (ALK) is the ALK inhibitor crizotinib (Xalkori). However, many patients on crizotinib will have disease progression within the first year of therapy, and many will go on to have central nervous system (CNS) metastases.

The multicenter international ALEX trial compared crizotinib with the second-generation ALK inhibitor alectinib (Alecensa). The investigators found that alectinib reduced the risk of progression by 53% and the time to CNS progression by 84%.

In this video interview at the annual meeting of the American Society of Clinical Oncology, Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston, outlines the ALEX trial results, which are being hailed as “practice changing.”

CHICAGO – The standard of care for patients with non–small cell lung cancer positive for the anaplastic lymphoma kinase (ALK) is the ALK inhibitor crizotinib (Xalkori). However, many patients on crizotinib will have disease progression within the first year of therapy, and many will go on to have central nervous system (CNS) metastases.

The multicenter international ALEX trial compared crizotinib with the second-generation ALK inhibitor alectinib (Alecensa). The investigators found that alectinib reduced the risk of progression by 53% and the time to CNS progression by 84%.

In this video interview at the annual meeting of the American Society of Clinical Oncology, Alice T. Shaw, MD, PhD, of Massachusetts General Hospital Cancer Center in Boston, outlines the ALEX trial results, which are being hailed as “practice changing.”