Key clinical point: Patients with relapse-remitting multiple sclerosis (RRMS) have a high prevalence of alexithymia.

Major finding: Alexithymia was observed in about 29.55% of patients and borderline alexithymia was observed in 31.15% of patients; alexithymia positively correlated with anxiety and depression in patients with RRMS (P less than .01). 

Study details: The data come from a cross-sectional study that included 106 consecutively assessed adult patients with RRMS (74 female and 32 male patients). 

Disclosures: The authors declared no conflicts of interest.

Citation: Stojanov J et al. J Postgrad Med. 2020 Jan 13. doi: 10.4103/jpgm.JPGM_499_19.

Key clinical point: Patients with relapse-remitting multiple sclerosis (RRMS) have a high prevalence of alexithymia.

Major finding: Alexithymia was observed in about 29.55% of patients and borderline alexithymia was observed in 31.15% of patients; alexithymia positively correlated with anxiety and depression in patients with RRMS (P less than .01). 

Study details: The data come from a cross-sectional study that included 106 consecutively assessed adult patients with RRMS (74 female and 32 male patients). 

Disclosures: The authors declared no conflicts of interest.

Citation: Stojanov J et al. J Postgrad Med. 2020 Jan 13. doi: 10.4103/jpgm.JPGM_499_19.

Key clinical point: Patients with relapse-remitting multiple sclerosis (RRMS) have a high prevalence of alexithymia.

Major finding: Alexithymia was observed in about 29.55% of patients and borderline alexithymia was observed in 31.15% of patients; alexithymia positively correlated with anxiety and depression in patients with RRMS (P less than .01). 

Study details: The data come from a cross-sectional study that included 106 consecutively assessed adult patients with RRMS (74 female and 32 male patients). 

Disclosures: The authors declared no conflicts of interest.

Citation: Stojanov J et al. J Postgrad Med. 2020 Jan 13. doi: 10.4103/jpgm.JPGM_499_19.

Key clinical point: Patients with multiple sclerosis (MS) have a high prevalence of lower urinary tract symptoms (LUTS).

Major finding: The prevalence of LUTS among patients with MS was 87.7%. The likelihood of urinary problems was higher in patients with a high Expanded Disability Status Scale score (adjusted odds ratio, 0.677; 95% CI, 0.507-0.903; P = .008).

Study details: The data come from a cross-sectional study that included 602 patients with MS. 

Disclosures: The authors declared no conflicts of interest.

Citation: Nazari F et al. BMC Neurol. 2020 Jan 17. doi: 10.1186/s12883-019-1582-1. 

Key clinical point: Patients with multiple sclerosis (MS) have a high prevalence of lower urinary tract symptoms (LUTS).

Major finding: The prevalence of LUTS among patients with MS was 87.7%. The likelihood of urinary problems was higher in patients with a high Expanded Disability Status Scale score (adjusted odds ratio, 0.677; 95% CI, 0.507-0.903; P = .008).

Study details: The data come from a cross-sectional study that included 602 patients with MS. 

Disclosures: The authors declared no conflicts of interest.

Citation: Nazari F et al. BMC Neurol. 2020 Jan 17. doi: 10.1186/s12883-019-1582-1. 

Key clinical point: Patients with multiple sclerosis (MS) have a high prevalence of lower urinary tract symptoms (LUTS).

Major finding: The prevalence of LUTS among patients with MS was 87.7%. The likelihood of urinary problems was higher in patients with a high Expanded Disability Status Scale score (adjusted odds ratio, 0.677; 95% CI, 0.507-0.903; P = .008).

Study details: The data come from a cross-sectional study that included 602 patients with MS. 

Disclosures: The authors declared no conflicts of interest.

Citation: Nazari F et al. BMC Neurol. 2020 Jan 17. doi: 10.1186/s12883-019-1582-1. 

An analysis of four commonly performed surgical procedures for stress urinary incontinence found that they all improved sexual dysfunction to a similar degree over the course of 24 months.

Juanmonino/E+/Getty Images

“There is a growing body of literature concerning female sexual function after treatment for urinary incontinence,” Stephanie M. Glass Clark, MD, of the University of Pittsburgh, and colleagues wrote in a study published in Obstetrics & Gynecology. “Pelvic floor muscle therapy has been shown to improve sexual function as well as urinary incontinence symptoms. Surgical treatment, on the other hand, has had unclear effects on sexual function.”

Dr. Glass Clark and colleagues conducted a combined secondary analysis of the SISTEr (Stress Incontinence Surgical Treatment Efficacy Trial) and TOMUS (Trial of Mid-Urethral Slings) studies. Women in the original trials were randomized to receive surgical treatment for stress urinary incontinence with an autologous fascial sling or Burch colposuspension (SISTEr), or a retropubic or transobturator midurethral sling (TOMUS). Sexual function as assessed by the short version of the Pelvic Organ Prolapse/ Urinary Incontinence Sexual Questionnaire (PISQ-12) was compared between groups at baseline, 12 months, and 24 months.

Of the 924 women included, 249 (27%) had an autologous fascial sling, 239 (26%) underwent Burch colposuspension, 216 (23%) had a retropubic midurethral sling placed, and 220 (24%) had a transobturator midurethral sling placed. The researchers observed no significant differences in mean PISQ-12 scores between the four treatment groups at the time of baseline (P = .07) or at the 12- and 24-month visits (P = .42 and P = .50, respectively). Patients in the two studies showed an overall improvement in sexual function over the 24-month study period.

Specifically, PISQ-12 scores at baseline were 32.6 in the transobturator sling group, 33.1 in the retropubic sling group, 31.9 in the Burch procedure group, and 31.4 in the fascial sling group. At 12 months, the PISQ-12 scores rose to 37.7 in the transobturator sling group, 37.8 in the retropubic sling group, 36.9 in the Burch procedure group, and 37.1 in the fascial sling group. These scores were generally maintained at 24 months (37.7 in the transobturator sling group, 37.1 in the retropubic sling group, 36.7 in the Burch procedure group, and 37.4 in the fascial sling group), and were not statistically different than the scores tabulated at the 12-month follow-up visit (P = .97).

“This study and others demonstrate that sexual function improves with surgical improvement of stress incontinence which may suggest a possible association of urinary incontinence and sexual dysfunction,” Dr. Glass Clark and colleagues concluded. “As we continue to explore the complex and multifaceted problem of sexual dysfunction, further evaluation of the effect of pelvic floor disorders – and their treatments – will be important and necessary research.”

The researchers acknowledged certain limitations of the study, including the fact that there was a low degree of diversity among women in the studied trials, which limits the generalizability of the findings. They also pointed out that the PISQ-12 does not address sexual stimulation or nonpenetrative vaginal intercourse. “Additionally, it limits partner-related problems to erectile dysfunction and premature ejaculation; some eligible participants may be excluded secondary to sexual preferences given the assumptions inherent to the questionnaire that the partner is male,” they wrote.

This secondary analysis had no outside sources of funding. Dr. Glass Clark reported that she received a travel stipend from the Society of Gynecologic Surgeons, sponsored by OB-STATS. Her coauthors reported having no financial conflicts.

[email protected]

SOURCE: Glass Clark SM et al. Obstet Gynecol 2020;135(2):352-60.

An analysis of four commonly performed surgical procedures for stress urinary incontinence found that they all improved sexual dysfunction to a similar degree over the course of 24 months.

Juanmonino/E+/Getty Images

“There is a growing body of literature concerning female sexual function after treatment for urinary incontinence,” Stephanie M. Glass Clark, MD, of the University of Pittsburgh, and colleagues wrote in a study published in Obstetrics & Gynecology. “Pelvic floor muscle therapy has been shown to improve sexual function as well as urinary incontinence symptoms. Surgical treatment, on the other hand, has had unclear effects on sexual function.”

Dr. Glass Clark and colleagues conducted a combined secondary analysis of the SISTEr (Stress Incontinence Surgical Treatment Efficacy Trial) and TOMUS (Trial of Mid-Urethral Slings) studies. Women in the original trials were randomized to receive surgical treatment for stress urinary incontinence with an autologous fascial sling or Burch colposuspension (SISTEr), or a retropubic or transobturator midurethral sling (TOMUS). Sexual function as assessed by the short version of the Pelvic Organ Prolapse/ Urinary Incontinence Sexual Questionnaire (PISQ-12) was compared between groups at baseline, 12 months, and 24 months.

Of the 924 women included, 249 (27%) had an autologous fascial sling, 239 (26%) underwent Burch colposuspension, 216 (23%) had a retropubic midurethral sling placed, and 220 (24%) had a transobturator midurethral sling placed. The researchers observed no significant differences in mean PISQ-12 scores between the four treatment groups at the time of baseline (P = .07) or at the 12- and 24-month visits (P = .42 and P = .50, respectively). Patients in the two studies showed an overall improvement in sexual function over the 24-month study period.

Specifically, PISQ-12 scores at baseline were 32.6 in the transobturator sling group, 33.1 in the retropubic sling group, 31.9 in the Burch procedure group, and 31.4 in the fascial sling group. At 12 months, the PISQ-12 scores rose to 37.7 in the transobturator sling group, 37.8 in the retropubic sling group, 36.9 in the Burch procedure group, and 37.1 in the fascial sling group. These scores were generally maintained at 24 months (37.7 in the transobturator sling group, 37.1 in the retropubic sling group, 36.7 in the Burch procedure group, and 37.4 in the fascial sling group), and were not statistically different than the scores tabulated at the 12-month follow-up visit (P = .97).

“This study and others demonstrate that sexual function improves with surgical improvement of stress incontinence which may suggest a possible association of urinary incontinence and sexual dysfunction,” Dr. Glass Clark and colleagues concluded. “As we continue to explore the complex and multifaceted problem of sexual dysfunction, further evaluation of the effect of pelvic floor disorders – and their treatments – will be important and necessary research.”

The researchers acknowledged certain limitations of the study, including the fact that there was a low degree of diversity among women in the studied trials, which limits the generalizability of the findings. They also pointed out that the PISQ-12 does not address sexual stimulation or nonpenetrative vaginal intercourse. “Additionally, it limits partner-related problems to erectile dysfunction and premature ejaculation; some eligible participants may be excluded secondary to sexual preferences given the assumptions inherent to the questionnaire that the partner is male,” they wrote.

This secondary analysis had no outside sources of funding. Dr. Glass Clark reported that she received a travel stipend from the Society of Gynecologic Surgeons, sponsored by OB-STATS. Her coauthors reported having no financial conflicts.

[email protected]

SOURCE: Glass Clark SM et al. Obstet Gynecol 2020;135(2):352-60.

An analysis of four commonly performed surgical procedures for stress urinary incontinence found that they all improved sexual dysfunction to a similar degree over the course of 24 months.

Juanmonino/E+/Getty Images

“There is a growing body of literature concerning female sexual function after treatment for urinary incontinence,” Stephanie M. Glass Clark, MD, of the University of Pittsburgh, and colleagues wrote in a study published in Obstetrics & Gynecology. “Pelvic floor muscle therapy has been shown to improve sexual function as well as urinary incontinence symptoms. Surgical treatment, on the other hand, has had unclear effects on sexual function.”

Dr. Glass Clark and colleagues conducted a combined secondary analysis of the SISTEr (Stress Incontinence Surgical Treatment Efficacy Trial) and TOMUS (Trial of Mid-Urethral Slings) studies. Women in the original trials were randomized to receive surgical treatment for stress urinary incontinence with an autologous fascial sling or Burch colposuspension (SISTEr), or a retropubic or transobturator midurethral sling (TOMUS). Sexual function as assessed by the short version of the Pelvic Organ Prolapse/ Urinary Incontinence Sexual Questionnaire (PISQ-12) was compared between groups at baseline, 12 months, and 24 months.

Of the 924 women included, 249 (27%) had an autologous fascial sling, 239 (26%) underwent Burch colposuspension, 216 (23%) had a retropubic midurethral sling placed, and 220 (24%) had a transobturator midurethral sling placed. The researchers observed no significant differences in mean PISQ-12 scores between the four treatment groups at the time of baseline (P = .07) or at the 12- and 24-month visits (P = .42 and P = .50, respectively). Patients in the two studies showed an overall improvement in sexual function over the 24-month study period.

Specifically, PISQ-12 scores at baseline were 32.6 in the transobturator sling group, 33.1 in the retropubic sling group, 31.9 in the Burch procedure group, and 31.4 in the fascial sling group. At 12 months, the PISQ-12 scores rose to 37.7 in the transobturator sling group, 37.8 in the retropubic sling group, 36.9 in the Burch procedure group, and 37.1 in the fascial sling group. These scores were generally maintained at 24 months (37.7 in the transobturator sling group, 37.1 in the retropubic sling group, 36.7 in the Burch procedure group, and 37.4 in the fascial sling group), and were not statistically different than the scores tabulated at the 12-month follow-up visit (P = .97).

“This study and others demonstrate that sexual function improves with surgical improvement of stress incontinence which may suggest a possible association of urinary incontinence and sexual dysfunction,” Dr. Glass Clark and colleagues concluded. “As we continue to explore the complex and multifaceted problem of sexual dysfunction, further evaluation of the effect of pelvic floor disorders – and their treatments – will be important and necessary research.”

The researchers acknowledged certain limitations of the study, including the fact that there was a low degree of diversity among women in the studied trials, which limits the generalizability of the findings. They also pointed out that the PISQ-12 does not address sexual stimulation or nonpenetrative vaginal intercourse. “Additionally, it limits partner-related problems to erectile dysfunction and premature ejaculation; some eligible participants may be excluded secondary to sexual preferences given the assumptions inherent to the questionnaire that the partner is male,” they wrote.

This secondary analysis had no outside sources of funding. Dr. Glass Clark reported that she received a travel stipend from the Society of Gynecologic Surgeons, sponsored by OB-STATS. Her coauthors reported having no financial conflicts.

[email protected]

SOURCE: Glass Clark SM et al. Obstet Gynecol 2020;135(2):352-60.

The Diagnosis: Epithelioid Angiosarcoma 

Histopathology showed a large soft-tissue neoplasm with extensive hemorrhage (Figure 1). The epithelioid angiosarcoma (EA) consisted mostly of irregular slit-shaped vessels lined by sheets of atypical endothelial cells (Figure 2). At higher-power magnification, the cellular atypia was prominent and diffuse (Figure 3). Immunostaining of the tumor cells showed positive uptake for CD31, confirming vascular origin (Figure 4). Other vascular markers, including CD34 and factor VIII, as well as nuclear positivity for the erythroblast transformation-specific transcription factor gene, ERG, can be demonstrated by EA. Irregular, smooth muscle actin-positive spindle cells are distributed around some of the vessels. The human herpesvirus 8 stain is negative.  

Compared to classic angiosarcomas, EAs have a predilection for the extremities rather than the head and scalp. Histopathologically, the cells are epithelioid and are strongly positive for vimentin and CD31, in addition to factor VIII, friend leukemia integration 1 transcription factor, and CD34.^1,2 In contrast, epithelioid sarcomas more typically are seen in younger adults and less likely to be CD31 positive.³ An epithelioid hemangioendothelioma is more focal in cellular atypia and forms small nests and trabeculae rather than sheets of atypical cells. Melanoma cells stain positive for human melanoma black 45, Melan-A, and S-100 but not for CD31.³ Glomangiosarcomas typically stain positive for smooth muscle actin and muscle-specific actin.⁴ 

Epithelioid angiosarcomas are rare and aggressive malignancies of endothelial origin.³ They are more prevalent in men and have a peak incidence in the seventh decade of life. They most commonly occur in the deep soft tissues of the extremities but have been reported to form in a variety of primary sites, including the skin, bones, thyroid, and adrenal glands.³  

Tumors tend to be highly aggressive and demonstrate early nodal and solid organ metastases.³ Our case demonstrated the aggressive nature of this high-grade malignancy by showing neoplastic invasion through a vascular wall. Within 2 to 3 years of diagnosis, 50% of patients die of the disease, and the 5-year survival rate is estimated to be 12% to 20%.^3,5 The etiology remains unknown, but EA has been linked to prior exposure to toxic chemicals, irradiation, or Thorotrast contrast media, and it may arise in the setting of arteriovenous fistulae and chronic lymphedema.⁶ 

Although radiation therapy often is utilized, surgery is the primary treatment modality.⁵ Even with wide excision, local recurrence is common. Tumor size is one of the most important prognostic features, with a worse prognosis for tumors larger than 5 cm. Evidence suggests that paclitaxel-based chemotherapeutic regimens may improve survival, and a combination of paclitaxel and sorafenib has been reported to induce remission in metastatic angiosarcoma of parietal EA.⁵ Currently, no standardized treatment regimen for this condition exists.  

Acknowledgment
The authors thank Amanda Marsch, MD (Chicago, Illinois), for obtaining outside pathology consultation.  

The Diagnosis: Epithelioid Angiosarcoma 

Histopathology showed a large soft-tissue neoplasm with extensive hemorrhage (Figure 1). The epithelioid angiosarcoma (EA) consisted mostly of irregular slit-shaped vessels lined by sheets of atypical endothelial cells (Figure 2). At higher-power magnification, the cellular atypia was prominent and diffuse (Figure 3). Immunostaining of the tumor cells showed positive uptake for CD31, confirming vascular origin (Figure 4). Other vascular markers, including CD34 and factor VIII, as well as nuclear positivity for the erythroblast transformation-specific transcription factor gene, ERG, can be demonstrated by EA. Irregular, smooth muscle actin-positive spindle cells are distributed around some of the vessels. The human herpesvirus 8 stain is negative.  

Compared to classic angiosarcomas, EAs have a predilection for the extremities rather than the head and scalp. Histopathologically, the cells are epithelioid and are strongly positive for vimentin and CD31, in addition to factor VIII, friend leukemia integration 1 transcription factor, and CD34.^1,2 In contrast, epithelioid sarcomas more typically are seen in younger adults and less likely to be CD31 positive.³ An epithelioid hemangioendothelioma is more focal in cellular atypia and forms small nests and trabeculae rather than sheets of atypical cells. Melanoma cells stain positive for human melanoma black 45, Melan-A, and S-100 but not for CD31.³ Glomangiosarcomas typically stain positive for smooth muscle actin and muscle-specific actin.⁴ 

Epithelioid angiosarcomas are rare and aggressive malignancies of endothelial origin.³ They are more prevalent in men and have a peak incidence in the seventh decade of life. They most commonly occur in the deep soft tissues of the extremities but have been reported to form in a variety of primary sites, including the skin, bones, thyroid, and adrenal glands.³  

Tumors tend to be highly aggressive and demonstrate early nodal and solid organ metastases.³ Our case demonstrated the aggressive nature of this high-grade malignancy by showing neoplastic invasion through a vascular wall. Within 2 to 3 years of diagnosis, 50% of patients die of the disease, and the 5-year survival rate is estimated to be 12% to 20%.^3,5 The etiology remains unknown, but EA has been linked to prior exposure to toxic chemicals, irradiation, or Thorotrast contrast media, and it may arise in the setting of arteriovenous fistulae and chronic lymphedema.⁶ 

Although radiation therapy often is utilized, surgery is the primary treatment modality.⁵ Even with wide excision, local recurrence is common. Tumor size is one of the most important prognostic features, with a worse prognosis for tumors larger than 5 cm. Evidence suggests that paclitaxel-based chemotherapeutic regimens may improve survival, and a combination of paclitaxel and sorafenib has been reported to induce remission in metastatic angiosarcoma of parietal EA.⁵ Currently, no standardized treatment regimen for this condition exists.  

Acknowledgment
The authors thank Amanda Marsch, MD (Chicago, Illinois), for obtaining outside pathology consultation.  

The Diagnosis: Epithelioid Angiosarcoma 

Histopathology showed a large soft-tissue neoplasm with extensive hemorrhage (Figure 1). The epithelioid angiosarcoma (EA) consisted mostly of irregular slit-shaped vessels lined by sheets of atypical endothelial cells (Figure 2). At higher-power magnification, the cellular atypia was prominent and diffuse (Figure 3). Immunostaining of the tumor cells showed positive uptake for CD31, confirming vascular origin (Figure 4). Other vascular markers, including CD34 and factor VIII, as well as nuclear positivity for the erythroblast transformation-specific transcription factor gene, ERG, can be demonstrated by EA. Irregular, smooth muscle actin-positive spindle cells are distributed around some of the vessels. The human herpesvirus 8 stain is negative.  

Compared to classic angiosarcomas, EAs have a predilection for the extremities rather than the head and scalp. Histopathologically, the cells are epithelioid and are strongly positive for vimentin and CD31, in addition to factor VIII, friend leukemia integration 1 transcription factor, and CD34.^1,2 In contrast, epithelioid sarcomas more typically are seen in younger adults and less likely to be CD31 positive.³ An epithelioid hemangioendothelioma is more focal in cellular atypia and forms small nests and trabeculae rather than sheets of atypical cells. Melanoma cells stain positive for human melanoma black 45, Melan-A, and S-100 but not for CD31.³ Glomangiosarcomas typically stain positive for smooth muscle actin and muscle-specific actin.⁴ 

Epithelioid angiosarcomas are rare and aggressive malignancies of endothelial origin.³ They are more prevalent in men and have a peak incidence in the seventh decade of life. They most commonly occur in the deep soft tissues of the extremities but have been reported to form in a variety of primary sites, including the skin, bones, thyroid, and adrenal glands.³  

Tumors tend to be highly aggressive and demonstrate early nodal and solid organ metastases.³ Our case demonstrated the aggressive nature of this high-grade malignancy by showing neoplastic invasion through a vascular wall. Within 2 to 3 years of diagnosis, 50% of patients die of the disease, and the 5-year survival rate is estimated to be 12% to 20%.^3,5 The etiology remains unknown, but EA has been linked to prior exposure to toxic chemicals, irradiation, or Thorotrast contrast media, and it may arise in the setting of arteriovenous fistulae and chronic lymphedema.⁶ 

Although radiation therapy often is utilized, surgery is the primary treatment modality.⁵ Even with wide excision, local recurrence is common. Tumor size is one of the most important prognostic features, with a worse prognosis for tumors larger than 5 cm. Evidence suggests that paclitaxel-based chemotherapeutic regimens may improve survival, and a combination of paclitaxel and sorafenib has been reported to induce remission in metastatic angiosarcoma of parietal EA.⁵ Currently, no standardized treatment regimen for this condition exists.  

Acknowledgment
The authors thank Amanda Marsch, MD (Chicago, Illinois), for obtaining outside pathology consultation.  

The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.

The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”

The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.

About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.

In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.

“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”

Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:

• COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
• In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
• Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
• Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
• It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
• It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
• Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
• For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
• COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.

The full clinical update is available here.

This article first appeared on Medscape.com.

The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.

The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”

The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.

About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.

In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.

“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”

Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:

• COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
• In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
• Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
• Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
• It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
• It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
• Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
• For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
• COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.

The full clinical update is available here.

This article first appeared on Medscape.com.

The American College of Cardiology on Feb. 13, 2020, released a clinical bulletin that aims to address cardiac implications of the current epidemic of the novel coronavirus, now known as COVID-19.

The bulletin, reviewed and approved by the college’s Science and Quality Oversight Committee, “provides background on the epidemic, which was first reported in late December 2019, and looks at early cardiac implications from case reports,” the ACC noted in a press release. “It also provides information on the potential cardiac implications from analog viral respiratory pandemics and offers early clinical guidance given current COVID-19 uncertainty.”

The document looks at some early cardiac implications of the infection. For example, early case reports suggest patients with underlying conditions are at higher risk of complications or mortality from the virus, with up to 50% of hospitalized patients having a chronic medical illness, the authors wrote.

About 40% of hospitalized patients confirmed to have the virus have cardiovascular or cerebrovascular disease, they noted.

In a recent case report on 138 hospitalized COVID-19 patients, they noted, 19.6% developed acute respiratory distress syndrome, 16.7% developed arrhythmia, 8.7% developed shock, 7.2% developed acute cardiac injury, and 3.6% developed acute kidney injury. “Rates of complication were universally higher for ICU patients,” they wrote.

“The first reported death was a 61-year-old male, with a long history of smoking, who succumbed to acute respiratory distress, heart failure, and cardiac arrest,” the document noted. “Early, unpublished first-hand reports suggest at least some patients develop myocarditis.”

Stressing the current uncertainty about the virus, the bulletin provides the following clinical guidance:

• COVID-19 is spread through droplets and can live for substantial periods outside the body; containment and prevention using standard public health and personal strategies for preventing the spread of communicable disease remains the priority.
• In geographies with active COVID-19 transmission (mainly China), it is reasonable to advise patients with underlying cardiovascular disease of the potential increased risk and to encourage additional, reasonable precautions.
• Older adults are less likely to present with fever, thus close assessment for other symptoms such as cough or shortness of breath is warranted.
• Some experts have suggested that the rigorous use of guideline-directed, plaque-stabilizing agents could offer additional protection to cardiovascular disease (CVD) patients during a widespread outbreak (statins, beta-blockers, ACE inhibitors, acetylsalicylic acid); however, such therapies should be tailored to individual patients.
• It is important for patients with CVD to remain current with vaccinations, including the pneumococcal vaccine, given the increased risk of secondary bacterial infection; it would also be prudent to receive vaccination to prevent another source of fever which could be initially confused with coronavirus infection.
• It may be reasonable to triage COVID-19 patients according to the presence of underlying cardiovascular, respiratory, renal, and other chronic diseases for prioritized treatment.
• Providers are cautioned that classic symptoms and presentation of acute MI may be overshadowed in the context of coronavirus, resulting in underdiagnosis.
• For CVD patients in geographies without widespread COVID-19, emphasis should remain on the threat from influenza, the importance of vaccination and frequent handwashing, and continued adherence to all guideline-directed therapy for underlying chronic conditions.
• COVID-19 is a fast-moving epidemic with an uncertain clinical profile; providers should be prepared for guidance to shift as more information becomes available.

The full clinical update is available here.

This article first appeared on Medscape.com.

In the ever-changing world of health care, one thing is for sure: If you’re not paying attention, you’re falling behind. In this column, I will discuss how you may utilize the Society of Hospital Medicine (SHM) State of Hospital Medicine Report (SoHM) to evaluate your current compensation structure and strengthen your business plan for change. For purposes of this exercise, I will focus on data referenced as Internal Medicine only, hospital-owned Hospital Medicine Groups (HMG).

Issues with retention, recruitment, or burnout may be among the first factors that lead you to reevaluate your compensation plan. The SoHM Report can help you to take a dive into feedback for these areas. Look for any indications that compensation may be affecting your turnover, inability to hire, or leaving your current team frustrated with their current pay structure. Feedback surrounding each of these factors may drive you to evaluate your comp plan but remain mindful that money is not always the answer.

You may complete your evaluation and find the data could suggest you are in fact well paid for the work you do. Even though this may be the case, the evaluation and transparency to your provider team may help flush out the real reason you are struggling with recruitment, retention, or burnout. However, if you do find you have an opportunity to improve your compensation structure, remember that you will need a compelling, data-driven case, to present to your C-suite.

Let us start by understanding how the market has changed over time using data from the 2014, 2016, and 2018 SoHM Reports. Of note, each report is based on data from the prior year. Since 2013, hospital owned HMGs have seen a 16% increase in total compensation while experiencing only a 9% increase in collections. Meanwhile RVU productivity has remained relatively stable over time. From this, we see hospitalists are earning more for similar productivity. The hospital reimbursement for professional fees has not grown at the same rate as compensation. Also, the collection per RVU has remained relatively flat over time.

It’s simple: Hospitalists are earning more and professional revenues are not making up the difference. This market change is driving hospitals to invest more money to maintain their HMGs. If your hospital hasn’t been responding to these data, you will need a strong business plan to get buy in from your hospital administration.

Now that you have evaluated the market change, it is time to put some optics on where your compensation falls in the current market. When you combine your total compensation with your total RVU productivity, you can use the SoHM Report to evaluate the current reported benchmarks for Compensation per RVU. Plotting these benchmarks against your own compensation and any proposed changes can help your administration really begin to see whether a change should be considered. Providing that clear picture in relevance to the SoHM benchmark is important, as a chart or graph can simplify your C-suite’s understanding of your proposal.

By simplifying your example using Compensation per RVU, you are making the conversation easier to follow. Your hospital leaders can clearly see the cost for every RVU generated and understand the impact. This is not to say that you should base your compensation around productivity. It is merely a way to roll in all compensation factors, whether quality related, performance based, or productivity driven, and tie them to a metric that is clear and easy for administration to understand.

Remember, when designing your new compensation plan, you can reference the SoHM Report to see how HMGs around the country are providing incentive and what percentage of compensation is based on incentive. There are sections within the report directly outlining these data points.

Now that we have reviewed market change and how to visualize change between your current and proposed future state, I will leave you with some final thoughts regarding other considerations when building your business plan:

• Focus on only physician-generated RVUs.
• Consider Length of Stay impact on productivity.
• Decide if Case Mix Index changes have impacted your staffing needs.
• Understand your E and M coding practices in reference to industry benchmarks. The SoHM Report provides benchmarks for billing practices across the country.
• Lastly, clearly identify the issues you want to address and set goals with measurable outcomes.

There is still time for your group to be part of the 2020 State of Hospital Medicine Report data by participating in the 2020 Survey. Data are being accepted through Feb. 28, 2020. Submit your data at www.hospitalmedicine.org/2020survey.
 

Mr. Sandroni is director of operations, hospitalists, at Rochester (N.Y.) Regional Health.

In the ever-changing world of health care, one thing is for sure: If you’re not paying attention, you’re falling behind. In this column, I will discuss how you may utilize the Society of Hospital Medicine (SHM) State of Hospital Medicine Report (SoHM) to evaluate your current compensation structure and strengthen your business plan for change. For purposes of this exercise, I will focus on data referenced as Internal Medicine only, hospital-owned Hospital Medicine Groups (HMG).

Issues with retention, recruitment, or burnout may be among the first factors that lead you to reevaluate your compensation plan. The SoHM Report can help you to take a dive into feedback for these areas. Look for any indications that compensation may be affecting your turnover, inability to hire, or leaving your current team frustrated with their current pay structure. Feedback surrounding each of these factors may drive you to evaluate your comp plan but remain mindful that money is not always the answer.

You may complete your evaluation and find the data could suggest you are in fact well paid for the work you do. Even though this may be the case, the evaluation and transparency to your provider team may help flush out the real reason you are struggling with recruitment, retention, or burnout. However, if you do find you have an opportunity to improve your compensation structure, remember that you will need a compelling, data-driven case, to present to your C-suite.

Let us start by understanding how the market has changed over time using data from the 2014, 2016, and 2018 SoHM Reports. Of note, each report is based on data from the prior year. Since 2013, hospital owned HMGs have seen a 16% increase in total compensation while experiencing only a 9% increase in collections. Meanwhile RVU productivity has remained relatively stable over time. From this, we see hospitalists are earning more for similar productivity. The hospital reimbursement for professional fees has not grown at the same rate as compensation. Also, the collection per RVU has remained relatively flat over time.

It’s simple: Hospitalists are earning more and professional revenues are not making up the difference. This market change is driving hospitals to invest more money to maintain their HMGs. If your hospital hasn’t been responding to these data, you will need a strong business plan to get buy in from your hospital administration.

Now that you have evaluated the market change, it is time to put some optics on where your compensation falls in the current market. When you combine your total compensation with your total RVU productivity, you can use the SoHM Report to evaluate the current reported benchmarks for Compensation per RVU. Plotting these benchmarks against your own compensation and any proposed changes can help your administration really begin to see whether a change should be considered. Providing that clear picture in relevance to the SoHM benchmark is important, as a chart or graph can simplify your C-suite’s understanding of your proposal.

By simplifying your example using Compensation per RVU, you are making the conversation easier to follow. Your hospital leaders can clearly see the cost for every RVU generated and understand the impact. This is not to say that you should base your compensation around productivity. It is merely a way to roll in all compensation factors, whether quality related, performance based, or productivity driven, and tie them to a metric that is clear and easy for administration to understand.

Remember, when designing your new compensation plan, you can reference the SoHM Report to see how HMGs around the country are providing incentive and what percentage of compensation is based on incentive. There are sections within the report directly outlining these data points.

Now that we have reviewed market change and how to visualize change between your current and proposed future state, I will leave you with some final thoughts regarding other considerations when building your business plan:

• Focus on only physician-generated RVUs.
• Consider Length of Stay impact on productivity.
• Decide if Case Mix Index changes have impacted your staffing needs.
• Understand your E and M coding practices in reference to industry benchmarks. The SoHM Report provides benchmarks for billing practices across the country.
• Lastly, clearly identify the issues you want to address and set goals with measurable outcomes.

There is still time for your group to be part of the 2020 State of Hospital Medicine Report data by participating in the 2020 Survey. Data are being accepted through Feb. 28, 2020. Submit your data at www.hospitalmedicine.org/2020survey.
 

Mr. Sandroni is director of operations, hospitalists, at Rochester (N.Y.) Regional Health.

In the ever-changing world of health care, one thing is for sure: If you’re not paying attention, you’re falling behind. In this column, I will discuss how you may utilize the Society of Hospital Medicine (SHM) State of Hospital Medicine Report (SoHM) to evaluate your current compensation structure and strengthen your business plan for change. For purposes of this exercise, I will focus on data referenced as Internal Medicine only, hospital-owned Hospital Medicine Groups (HMG).

Issues with retention, recruitment, or burnout may be among the first factors that lead you to reevaluate your compensation plan. The SoHM Report can help you to take a dive into feedback for these areas. Look for any indications that compensation may be affecting your turnover, inability to hire, or leaving your current team frustrated with their current pay structure. Feedback surrounding each of these factors may drive you to evaluate your comp plan but remain mindful that money is not always the answer.

You may complete your evaluation and find the data could suggest you are in fact well paid for the work you do. Even though this may be the case, the evaluation and transparency to your provider team may help flush out the real reason you are struggling with recruitment, retention, or burnout. However, if you do find you have an opportunity to improve your compensation structure, remember that you will need a compelling, data-driven case, to present to your C-suite.

Let us start by understanding how the market has changed over time using data from the 2014, 2016, and 2018 SoHM Reports. Of note, each report is based on data from the prior year. Since 2013, hospital owned HMGs have seen a 16% increase in total compensation while experiencing only a 9% increase in collections. Meanwhile RVU productivity has remained relatively stable over time. From this, we see hospitalists are earning more for similar productivity. The hospital reimbursement for professional fees has not grown at the same rate as compensation. Also, the collection per RVU has remained relatively flat over time.

It’s simple: Hospitalists are earning more and professional revenues are not making up the difference. This market change is driving hospitals to invest more money to maintain their HMGs. If your hospital hasn’t been responding to these data, you will need a strong business plan to get buy in from your hospital administration.

Now that you have evaluated the market change, it is time to put some optics on where your compensation falls in the current market. When you combine your total compensation with your total RVU productivity, you can use the SoHM Report to evaluate the current reported benchmarks for Compensation per RVU. Plotting these benchmarks against your own compensation and any proposed changes can help your administration really begin to see whether a change should be considered. Providing that clear picture in relevance to the SoHM benchmark is important, as a chart or graph can simplify your C-suite’s understanding of your proposal.

By simplifying your example using Compensation per RVU, you are making the conversation easier to follow. Your hospital leaders can clearly see the cost for every RVU generated and understand the impact. This is not to say that you should base your compensation around productivity. It is merely a way to roll in all compensation factors, whether quality related, performance based, or productivity driven, and tie them to a metric that is clear and easy for administration to understand.

Remember, when designing your new compensation plan, you can reference the SoHM Report to see how HMGs around the country are providing incentive and what percentage of compensation is based on incentive. There are sections within the report directly outlining these data points.

Now that we have reviewed market change and how to visualize change between your current and proposed future state, I will leave you with some final thoughts regarding other considerations when building your business plan:

• Focus on only physician-generated RVUs.
• Consider Length of Stay impact on productivity.
• Decide if Case Mix Index changes have impacted your staffing needs.
• Understand your E and M coding practices in reference to industry benchmarks. The SoHM Report provides benchmarks for billing practices across the country.
• Lastly, clearly identify the issues you want to address and set goals with measurable outcomes.

There is still time for your group to be part of the 2020 State of Hospital Medicine Report data by participating in the 2020 Survey. Data are being accepted through Feb. 28, 2020. Submit your data at www.hospitalmedicine.org/2020survey.
 

Mr. Sandroni is director of operations, hospitalists, at Rochester (N.Y.) Regional Health.

Patients with a pulmonary artery pressure/cardiac output slope greater than 3 mm Hg/L/min on cardiopulmonary exercise tests have more than double the risk of cardiovascular hospitalization and all-cause mortality, according to a prospective study of 714 subjects with exertional dyspnea but preserved ejection fractions.

SPL/Science Source

The findings “suggest that across a wide range of individuals with chronic dyspnea, exercise can unmask abnormal pulmonary vascular responses that in turn bear significant clinical implications. These findings, coupled with a growing body of work ... suggest that reintroduction of an exercise based definition of [pulmonary hypertension (PH)] in PH guidelines” – using the pulmonary artery pressure/cardiac output slope – “merits consideration,” wrote Jennifer Ho, MD, a heart failure and transplantation cardiologist at Massachusetts General Hospital, Boston, and colleagues (J Am Coll Cardiol. 2020 Jan 7;75[1]:17-26. doi: 10.1016/j.jacc.2019.10.048).
 

A new definition takes hold

The slope captures the steepness of pulmonary artery pressure increase as cardiac output goes up, giving a measure of overall pulmonary resistance. A value above 3 mm Hg/L/min means that pulmonary artery pressure (PAP) is too high for a given cardiac output (CO). The slope “is preferable to using a single absolute cut point value for exercise PAP” to define exercise pulmonary hypertension.“ Indeed, we confirm that in the absence of elevated PAP/CO, an absolute exercise PAP [above] 30 mm Hg” – the definition of exercise-induced pulmonary hypertension in years past – “does not portend worse outcomes,” Dr. Ho and her team noted.

In an accompanying editorial titled, “Exercise Pulmonary Hypertension Is Back,” Marius Hoeper, MD, a senior physician in the department of respiratory medicine at Hannover (Germany) Medical School, explained that the findings likely signal the revival of exercise pulmonary hypertension as a useful clinical concept (J Am Coll Cardiol. 2020 Jan 7;75[1]:27-8. doi: 10.1016/j.jacc.2019.11.010).

The standalone 30 mm Hg cut point was largely abandoned about a decade ago when it was realized that pressures above that mark were “not necessarily abnormal in certain subjects, for instance in athletes or elderly individuals,” he said.

But it’s become clear in recent years, and now confirmed by Dr. Ho and her team, that what matters is not the stand-alone measurement, but it’s relationship to cardiac output. “There is now sufficient evidence to define exercise PH by an abnormal [mean]PAP/CO slope [above] 3 mm Hg/L/min,” Dr. Hoeper said.
 

Abnormal slopes in over 40%

Each subject in the Massachusetts General study had an average of 10 paired PAP and CO measurements taken by invasive hemodynamic monitoring, including pulmonary artery catheterization via the internal jugular vein, while they road a stationary bicycle. The measurements were used to calculate the PAP/CO slope. A slope greater than 3 mm Hg/L/min was defined as abnormal based on previous research.

Results of the one-time assessment were correlated with the study’s primary outcome – cardiovascular hospitalization or all-cause death – over a mean follow up of 3.7 years. Subjects were 57 years old, on average, and 59% were women; just 2% had a previous diagnosis of pulmonary hypertension. Overall, 41% of the subjects had abnormal PAP/CO slopes, 26% had abnormal slopes without resting pulmonary hypertension, and 208 subjects (29%) met the primary outcome.

After adjustments for age, sex, and cardiopulmonary comorbidities, abnormal slopes more than doubled the risk of the primary outcome (hazard ratio [HR] 2.03; 95% confidence interval [CI]: 1.48-2.78; P less than .001). The risk remained elevated even in the absence of resting pulmonary hypertension (HR 1.75, 95% CI 1.21-2.54, P = .003), and in people with only mildly elevated resting PAPs of 21-29 mm Hg.

Older people were more likely to have abnormally elevated slopes, as well as were those with cardiopulmonary comorbidities, lower exercise tolerance, lower peak oxygen uptake, and more severely impaired right ventricular function. Diabetes, prior heart failure, chronic obstructive pulmonary disease, and interstitial lung disease were more prevalent in the elevated slope group, and their median N-terminal pro–B type natriuretic peptide level was 154 pg/mL, versus 52 pg/mL among people with normal slopes.

A simpler test is needed

In his editorial, Dr. Hoeper noted that diagnosing exercise PH by elevated slope “will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” but for the most part, the new definition “will have little immediate [effect] on clinical practice, as evidence-based treatments for this condition are not yet available.”

Even so, “having a globally accepted gold standard” for exercise PH based on the PAP/CO slope might well spur development of “simpler, noninvasive” ways to measure it so it can be used outside of specialty settings.

Dr. Ho and her team agreed. “These findings should prompt additional work using less invasive measurement modalities such as exercise echocardiography to evaluate” exercise PAP/CO slopes, they said.

The work was funded by the National Institutes of Health, Gilead Sciences, the American Heart Association, and the Massachusetts General Hospital Heart Failure Research Innovation Fund. The investigators had no relevant disclosures. Dr. Hoeper reported lecture and consultation fees from Actelion, Bayer, Merck Sharp and Dohme, and Pfizer.

[email protected]

SOURCE: Ho JE et al., J Am Coll Cardiol. 2020 Jan 7;75(1):17-26. doi: 10.1016/j.jacc.2019.10.048.

Patients with a pulmonary artery pressure/cardiac output slope greater than 3 mm Hg/L/min on cardiopulmonary exercise tests have more than double the risk of cardiovascular hospitalization and all-cause mortality, according to a prospective study of 714 subjects with exertional dyspnea but preserved ejection fractions.

SPL/Science Source

The findings “suggest that across a wide range of individuals with chronic dyspnea, exercise can unmask abnormal pulmonary vascular responses that in turn bear significant clinical implications. These findings, coupled with a growing body of work ... suggest that reintroduction of an exercise based definition of [pulmonary hypertension (PH)] in PH guidelines” – using the pulmonary artery pressure/cardiac output slope – “merits consideration,” wrote Jennifer Ho, MD, a heart failure and transplantation cardiologist at Massachusetts General Hospital, Boston, and colleagues (J Am Coll Cardiol. 2020 Jan 7;75[1]:17-26. doi: 10.1016/j.jacc.2019.10.048).
 

A new definition takes hold

The slope captures the steepness of pulmonary artery pressure increase as cardiac output goes up, giving a measure of overall pulmonary resistance. A value above 3 mm Hg/L/min means that pulmonary artery pressure (PAP) is too high for a given cardiac output (CO). The slope “is preferable to using a single absolute cut point value for exercise PAP” to define exercise pulmonary hypertension.“ Indeed, we confirm that in the absence of elevated PAP/CO, an absolute exercise PAP [above] 30 mm Hg” – the definition of exercise-induced pulmonary hypertension in years past – “does not portend worse outcomes,” Dr. Ho and her team noted.

In an accompanying editorial titled, “Exercise Pulmonary Hypertension Is Back,” Marius Hoeper, MD, a senior physician in the department of respiratory medicine at Hannover (Germany) Medical School, explained that the findings likely signal the revival of exercise pulmonary hypertension as a useful clinical concept (J Am Coll Cardiol. 2020 Jan 7;75[1]:27-8. doi: 10.1016/j.jacc.2019.11.010).

The standalone 30 mm Hg cut point was largely abandoned about a decade ago when it was realized that pressures above that mark were “not necessarily abnormal in certain subjects, for instance in athletes or elderly individuals,” he said.

But it’s become clear in recent years, and now confirmed by Dr. Ho and her team, that what matters is not the stand-alone measurement, but it’s relationship to cardiac output. “There is now sufficient evidence to define exercise PH by an abnormal [mean]PAP/CO slope [above] 3 mm Hg/L/min,” Dr. Hoeper said.
 

Abnormal slopes in over 40%

Each subject in the Massachusetts General study had an average of 10 paired PAP and CO measurements taken by invasive hemodynamic monitoring, including pulmonary artery catheterization via the internal jugular vein, while they road a stationary bicycle. The measurements were used to calculate the PAP/CO slope. A slope greater than 3 mm Hg/L/min was defined as abnormal based on previous research.

Results of the one-time assessment were correlated with the study’s primary outcome – cardiovascular hospitalization or all-cause death – over a mean follow up of 3.7 years. Subjects were 57 years old, on average, and 59% were women; just 2% had a previous diagnosis of pulmonary hypertension. Overall, 41% of the subjects had abnormal PAP/CO slopes, 26% had abnormal slopes without resting pulmonary hypertension, and 208 subjects (29%) met the primary outcome.

After adjustments for age, sex, and cardiopulmonary comorbidities, abnormal slopes more than doubled the risk of the primary outcome (hazard ratio [HR] 2.03; 95% confidence interval [CI]: 1.48-2.78; P less than .001). The risk remained elevated even in the absence of resting pulmonary hypertension (HR 1.75, 95% CI 1.21-2.54, P = .003), and in people with only mildly elevated resting PAPs of 21-29 mm Hg.

Older people were more likely to have abnormally elevated slopes, as well as were those with cardiopulmonary comorbidities, lower exercise tolerance, lower peak oxygen uptake, and more severely impaired right ventricular function. Diabetes, prior heart failure, chronic obstructive pulmonary disease, and interstitial lung disease were more prevalent in the elevated slope group, and their median N-terminal pro–B type natriuretic peptide level was 154 pg/mL, versus 52 pg/mL among people with normal slopes.

A simpler test is needed

In his editorial, Dr. Hoeper noted that diagnosing exercise PH by elevated slope “will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” but for the most part, the new definition “will have little immediate [effect] on clinical practice, as evidence-based treatments for this condition are not yet available.”

Even so, “having a globally accepted gold standard” for exercise PH based on the PAP/CO slope might well spur development of “simpler, noninvasive” ways to measure it so it can be used outside of specialty settings.

Dr. Ho and her team agreed. “These findings should prompt additional work using less invasive measurement modalities such as exercise echocardiography to evaluate” exercise PAP/CO slopes, they said.

The work was funded by the National Institutes of Health, Gilead Sciences, the American Heart Association, and the Massachusetts General Hospital Heart Failure Research Innovation Fund. The investigators had no relevant disclosures. Dr. Hoeper reported lecture and consultation fees from Actelion, Bayer, Merck Sharp and Dohme, and Pfizer.

[email protected]

SOURCE: Ho JE et al., J Am Coll Cardiol. 2020 Jan 7;75(1):17-26. doi: 10.1016/j.jacc.2019.10.048.

Patients with a pulmonary artery pressure/cardiac output slope greater than 3 mm Hg/L/min on cardiopulmonary exercise tests have more than double the risk of cardiovascular hospitalization and all-cause mortality, according to a prospective study of 714 subjects with exertional dyspnea but preserved ejection fractions.

SPL/Science Source

The findings “suggest that across a wide range of individuals with chronic dyspnea, exercise can unmask abnormal pulmonary vascular responses that in turn bear significant clinical implications. These findings, coupled with a growing body of work ... suggest that reintroduction of an exercise based definition of [pulmonary hypertension (PH)] in PH guidelines” – using the pulmonary artery pressure/cardiac output slope – “merits consideration,” wrote Jennifer Ho, MD, a heart failure and transplantation cardiologist at Massachusetts General Hospital, Boston, and colleagues (J Am Coll Cardiol. 2020 Jan 7;75[1]:17-26. doi: 10.1016/j.jacc.2019.10.048).
 

A new definition takes hold

The slope captures the steepness of pulmonary artery pressure increase as cardiac output goes up, giving a measure of overall pulmonary resistance. A value above 3 mm Hg/L/min means that pulmonary artery pressure (PAP) is too high for a given cardiac output (CO). The slope “is preferable to using a single absolute cut point value for exercise PAP” to define exercise pulmonary hypertension.“ Indeed, we confirm that in the absence of elevated PAP/CO, an absolute exercise PAP [above] 30 mm Hg” – the definition of exercise-induced pulmonary hypertension in years past – “does not portend worse outcomes,” Dr. Ho and her team noted.

In an accompanying editorial titled, “Exercise Pulmonary Hypertension Is Back,” Marius Hoeper, MD, a senior physician in the department of respiratory medicine at Hannover (Germany) Medical School, explained that the findings likely signal the revival of exercise pulmonary hypertension as a useful clinical concept (J Am Coll Cardiol. 2020 Jan 7;75[1]:27-8. doi: 10.1016/j.jacc.2019.11.010).

The standalone 30 mm Hg cut point was largely abandoned about a decade ago when it was realized that pressures above that mark were “not necessarily abnormal in certain subjects, for instance in athletes or elderly individuals,” he said.

But it’s become clear in recent years, and now confirmed by Dr. Ho and her team, that what matters is not the stand-alone measurement, but it’s relationship to cardiac output. “There is now sufficient evidence to define exercise PH by an abnormal [mean]PAP/CO slope [above] 3 mm Hg/L/min,” Dr. Hoeper said.
 

Abnormal slopes in over 40%

Each subject in the Massachusetts General study had an average of 10 paired PAP and CO measurements taken by invasive hemodynamic monitoring, including pulmonary artery catheterization via the internal jugular vein, while they road a stationary bicycle. The measurements were used to calculate the PAP/CO slope. A slope greater than 3 mm Hg/L/min was defined as abnormal based on previous research.

Results of the one-time assessment were correlated with the study’s primary outcome – cardiovascular hospitalization or all-cause death – over a mean follow up of 3.7 years. Subjects were 57 years old, on average, and 59% were women; just 2% had a previous diagnosis of pulmonary hypertension. Overall, 41% of the subjects had abnormal PAP/CO slopes, 26% had abnormal slopes without resting pulmonary hypertension, and 208 subjects (29%) met the primary outcome.

After adjustments for age, sex, and cardiopulmonary comorbidities, abnormal slopes more than doubled the risk of the primary outcome (hazard ratio [HR] 2.03; 95% confidence interval [CI]: 1.48-2.78; P less than .001). The risk remained elevated even in the absence of resting pulmonary hypertension (HR 1.75, 95% CI 1.21-2.54, P = .003), and in people with only mildly elevated resting PAPs of 21-29 mm Hg.

Older people were more likely to have abnormally elevated slopes, as well as were those with cardiopulmonary comorbidities, lower exercise tolerance, lower peak oxygen uptake, and more severely impaired right ventricular function. Diabetes, prior heart failure, chronic obstructive pulmonary disease, and interstitial lung disease were more prevalent in the elevated slope group, and their median N-terminal pro–B type natriuretic peptide level was 154 pg/mL, versus 52 pg/mL among people with normal slopes.

A simpler test is needed

In his editorial, Dr. Hoeper noted that diagnosing exercise PH by elevated slope “will occasionally help physicians and patients to better understand exertional dyspnea and to detect early pulmonary vascular disease in patients at risk,” but for the most part, the new definition “will have little immediate [effect] on clinical practice, as evidence-based treatments for this condition are not yet available.”

Even so, “having a globally accepted gold standard” for exercise PH based on the PAP/CO slope might well spur development of “simpler, noninvasive” ways to measure it so it can be used outside of specialty settings.

Dr. Ho and her team agreed. “These findings should prompt additional work using less invasive measurement modalities such as exercise echocardiography to evaluate” exercise PAP/CO slopes, they said.

The work was funded by the National Institutes of Health, Gilead Sciences, the American Heart Association, and the Massachusetts General Hospital Heart Failure Research Innovation Fund. The investigators had no relevant disclosures. Dr. Hoeper reported lecture and consultation fees from Actelion, Bayer, Merck Sharp and Dohme, and Pfizer.

[email protected]

SOURCE: Ho JE et al., J Am Coll Cardiol. 2020 Jan 7;75(1):17-26. doi: 10.1016/j.jacc.2019.10.048.

When it comes to physician happiness both in and outside the workplace, oncologists are about average, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

Oncologists landed in the middle of the pack among all physicians surveyed for happiness. Rheumatologists were most likely to report being very or extremely happy outside of work (60%) and neurologists were least likely to do so (44%), but about half of oncologists (51%) reported being very/extremely happy outside of work. For happiness at work, dermatologists topped the list (41%), neurologists came in last (18%), and oncologists remained in the middle (29%).

Oncologists were average when it came to burnout as well, matching the rate of overall physicians. Specifically, 32% of oncologists were burned out, 4% were depressed, and 9% were both burned out and depressed.

The most commonly reported factors contributing to burnout among oncologists were an overabundance of bureaucratic tasks (74%), spending too many hours at work (42%), and a lack of respect from colleagues in the workplace (36%).

Exercise was the most commonly reported way oncologists dealt with burnout (51%), followed by talking with family and friends (49%), and isolating themselves from others (38%). In addition, 57% of oncologists took 3-4 weeks’ vacation, compared with 44% of physicians overall; 29% of oncologists took less than 3 weeks’ vacation.

About 18% of oncologists said they had contemplated suicide, and 1% said they’d attempted it; 72% said they’d never had thoughts of suicide. Just under one-quarter of oncologists said they were currently seeking professional help or were planning to seek help for symptoms of depression and/or burnout.

“The survey results are concerning on several levels,” Maurie Markman, MD, of Cancer Treatment Centers of America, Philadelphia, said in an interview.

“First, the data suggest a considerable number of oncologists are simply burned out from the day-to-day bureaucracy (paperwork, etc.) of medical practice, which has absolutely nothing to do with the actual care delivered. This likely impacts the willingness to continue in this role. Second, one must be concerned for the future recruitment of physicians to become clinical oncologists. And finally, one must wonder about the impact of these concerning figures on the quality of care being provided to cancer patients.”

This survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians. Oncologists made up 1% of the survey pool.

[email protected]

When it comes to physician happiness both in and outside the workplace, oncologists are about average, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

Oncologists landed in the middle of the pack among all physicians surveyed for happiness. Rheumatologists were most likely to report being very or extremely happy outside of work (60%) and neurologists were least likely to do so (44%), but about half of oncologists (51%) reported being very/extremely happy outside of work. For happiness at work, dermatologists topped the list (41%), neurologists came in last (18%), and oncologists remained in the middle (29%).

Oncologists were average when it came to burnout as well, matching the rate of overall physicians. Specifically, 32% of oncologists were burned out, 4% were depressed, and 9% were both burned out and depressed.

The most commonly reported factors contributing to burnout among oncologists were an overabundance of bureaucratic tasks (74%), spending too many hours at work (42%), and a lack of respect from colleagues in the workplace (36%).

Exercise was the most commonly reported way oncologists dealt with burnout (51%), followed by talking with family and friends (49%), and isolating themselves from others (38%). In addition, 57% of oncologists took 3-4 weeks’ vacation, compared with 44% of physicians overall; 29% of oncologists took less than 3 weeks’ vacation.

About 18% of oncologists said they had contemplated suicide, and 1% said they’d attempted it; 72% said they’d never had thoughts of suicide. Just under one-quarter of oncologists said they were currently seeking professional help or were planning to seek help for symptoms of depression and/or burnout.

“The survey results are concerning on several levels,” Maurie Markman, MD, of Cancer Treatment Centers of America, Philadelphia, said in an interview.

“First, the data suggest a considerable number of oncologists are simply burned out from the day-to-day bureaucracy (paperwork, etc.) of medical practice, which has absolutely nothing to do with the actual care delivered. This likely impacts the willingness to continue in this role. Second, one must be concerned for the future recruitment of physicians to become clinical oncologists. And finally, one must wonder about the impact of these concerning figures on the quality of care being provided to cancer patients.”

This survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians. Oncologists made up 1% of the survey pool.

[email protected]

When it comes to physician happiness both in and outside the workplace, oncologists are about average, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

Oncologists landed in the middle of the pack among all physicians surveyed for happiness. Rheumatologists were most likely to report being very or extremely happy outside of work (60%) and neurologists were least likely to do so (44%), but about half of oncologists (51%) reported being very/extremely happy outside of work. For happiness at work, dermatologists topped the list (41%), neurologists came in last (18%), and oncologists remained in the middle (29%).

Oncologists were average when it came to burnout as well, matching the rate of overall physicians. Specifically, 32% of oncologists were burned out, 4% were depressed, and 9% were both burned out and depressed.

The most commonly reported factors contributing to burnout among oncologists were an overabundance of bureaucratic tasks (74%), spending too many hours at work (42%), and a lack of respect from colleagues in the workplace (36%).

Exercise was the most commonly reported way oncologists dealt with burnout (51%), followed by talking with family and friends (49%), and isolating themselves from others (38%). In addition, 57% of oncologists took 3-4 weeks’ vacation, compared with 44% of physicians overall; 29% of oncologists took less than 3 weeks’ vacation.

About 18% of oncologists said they had contemplated suicide, and 1% said they’d attempted it; 72% said they’d never had thoughts of suicide. Just under one-quarter of oncologists said they were currently seeking professional help or were planning to seek help for symptoms of depression and/or burnout.

“The survey results are concerning on several levels,” Maurie Markman, MD, of Cancer Treatment Centers of America, Philadelphia, said in an interview.

“First, the data suggest a considerable number of oncologists are simply burned out from the day-to-day bureaucracy (paperwork, etc.) of medical practice, which has absolutely nothing to do with the actual care delivered. This likely impacts the willingness to continue in this role. Second, one must be concerned for the future recruitment of physicians to become clinical oncologists. And finally, one must wonder about the impact of these concerning figures on the quality of care being provided to cancer patients.”

This survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians. Oncologists made up 1% of the survey pool.

[email protected]

More research suggests that a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
 

In a pilot study of 40 participants, those who were randomly assigned to receive intravenous ketamine plus outpatient motivational enhancement therapy (MET) showed greater abstinence rates, longer time to relapse, and fewer heavy drinking days than did those who received MET plus midazolam.

The findings support a U.K. study published late last year showing that a single dose of intravenous ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone (Nat Commun. 2019 Nov 26;10[1]:5187).

“I think the take-home message is that behavioral treatment can be helpful, but there are vulnerabilities that can get in the way,” current study investigator Elias Dakwar, MD, of the New York State Psychiatric Institute, Columbia University, New York, said in an interview.

“It’s an important area of research to understand in order to make behavioral treatments more effective, and ketamine appears to have the properties to address those vulnerabilities,” Dr. Dakwar said.

The study was published in the American Journal of Psychiatry (2019 Dec 2. doi: 10.1176/appi.ajp.2019.19070684).
 

Real-world approach

Pathologic alcohol use is responsible for an estimated 3.8% of all deaths globally, yet current interventions for alcohol use disorder have limited efficacy, the researchers noted.

New treatments with innovative mechanisms would be valuable, they added.

Ketamine is a high-affinity N-methyl-d-aspartate receptor (NMDAR) antagonist.

Previously, research offered “promising results” with the use of ketamine for cocaine use disorder, including increased motivation to quit and decreased craving, Dr. Dakwar noted.

“Those results led us to think about how ketamine might be helpful for other substance use disorders, especially given the overlap in clinical vulnerabilities and epidemiology,” he said.

The study from the U.K. researchers was conducted in 90 patients with harmful drinking behavior but who had not been diagnosed with alcohol use disorder.

Dr. Dakwar noted that this was “a nontreatment study. None of the people there had alcohol use disorder; they were heavy drinkers. Also, the effects there were fairly modest.

“My interest was how to integrate ketamine into a clinical, real-world framework that could be helpful for people,” he added.

The study included 40 participants (52.5% women; 70.3% white; mean age, 53 years) with alcohol dependence whose average consumption was five drinks per day.

All entered a 5-week outpatient program of MET, which involved engaging in strategies to promote motivation and self-directed change.

During the program’s second week, the participants were randomly assigned to received a 52-minute IV infusion of ketamine 0.71 mg/kg (n = 17) or the benzodiazepine midazolam 0.025 mg/kg (n = 23).

This ketamine dose was selected “because it was the highest dose tolerated by participants in preliminary studies,” the researchers reported.

“Midazolam was chosen as the active control because it alters consciousness without any known persistent ... effect on alcohol dependence,” they added.

The “timeline follow back method” was used to assess alcohol use after treatment. Abstinence was confirmed by measuring urine ethyl glucuronide levels with urine toxicology tests.

Other measures included use of a visual analogue scale, the Clinical Institute Withdrawal Assessment, and the modified Perceived Stress Scale.

Primary outcome met

Results showed that 47.1% of the ketamine group and 59.1% of the midazolam group used alcohol during the 21 days after treatment infusion; 17.6% and 40.9%, respectively, had a heavy drinking day.

For the primary outcome measure of alcohol abstinence, the “quadratic effect of time was significant” (P = .004), as was time-by-treatment interaction (P less than .001).

Although the model-estimated proportions of alcohol abstinence remained stable for the ketamine group for 21 days post infusion, the proportions decreased significantly for the control group.

The odds of having a heavy drinking day did not change significantly after treatment for the ketamine group (odds ratio, 0.98; P = .74) but increased significantly with each postinfusion day for the midazolam group (OR, 1.19; P less than .001).

For the ketamine group, time to relapse was also significantly longer (P = .04).

No significant differences were found between the groups in rates of withdrawal, craving, or stress sensitivity.

A new direction?

The most common adverse events after treatment were sedation, seen in 12 members of the midazolam group and in 8 members of the ketamine group, and headache, seen in four and six members, respectively.

Although two ketamine-group members experienced mild agitation for up to 1 hour post infusion, no incidents of persistent psychoactive effects were reported in either group.

No participants who received ketamine dropped out during the study period; among those who received midazolam, six dropped out.

“These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder,” the investigators wrote.

However, a larger patient population will be needed in future research in order to “replicate these promising results,” they added.

Dr. Dakwar noted that the time to first drink after treatment was comparable between the groups.

“But what was different in the ketamine group was that they didn’t continue drinking after that first drink. They didn’t initiate heavy drinking, they didn’t relapse, they were able to bounce back and stay with the program,” he said.

“It was surprising but still consistent with the central hypothesis that ketamine provides this opportunity for setting the foundation for the requisite commitment so that, once things become difficult, they’re still able to maintain recovery,” Dr. Dakwar said.

‘Provocative findings’

In an accompanying editorial, Sanjay J. Mathew, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine in Houston, and Rebecca B. Price, PhD, of the department of psychiatry at the University of Pittsburgh, noted that ketamine’s effects on abstinence “were robust” in this trial.

“It is also noteworthy that, in spite of recruiting from a population of patients with active and significant substance use history (a group that has routinely been excluded from ketamine trials in depression), no participant showed evidence of new drug-seeking behaviors,” Dr. Mathew and Dr. Price wrote.

“Overall, these findings are provocative and hypothesis generating but certainly not definitive because of the small sample size,” they add.

Other limitations cited include the short follow-up period and the fact that only half of the participants were available for a 6-month follow-up telephone interview. In addition, generalizability was limited because the population did not have additional medical or psychiatric illnesses or additional substance use disorders, the editorialists wrote.

Because of the limitations, the investigators “are appropriately circumspect about the immediate clinical implications of this small pilot study.”

Still, the results “affirm the potential of rational combinatorial approaches for a vexing medical and public health problem,” Dr. Mathew and Dr. Price concluded.

The study was funded by grants from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the New York State Psychiatric Institute. The study authors and Dr. Price reported no relevant financial relationships. Dr Mathew reported serving as a consultant to or having received research support from several companies, including Alkermes, Allergan, Clexio Biosciences, and Janssen. The original article includes a full list of his disclosures.
 

A version of this article first appeared on Medscape.com.

More research suggests that a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
 

In a pilot study of 40 participants, those who were randomly assigned to receive intravenous ketamine plus outpatient motivational enhancement therapy (MET) showed greater abstinence rates, longer time to relapse, and fewer heavy drinking days than did those who received MET plus midazolam.

The findings support a U.K. study published late last year showing that a single dose of intravenous ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone (Nat Commun. 2019 Nov 26;10[1]:5187).

“I think the take-home message is that behavioral treatment can be helpful, but there are vulnerabilities that can get in the way,” current study investigator Elias Dakwar, MD, of the New York State Psychiatric Institute, Columbia University, New York, said in an interview.

“It’s an important area of research to understand in order to make behavioral treatments more effective, and ketamine appears to have the properties to address those vulnerabilities,” Dr. Dakwar said.

The study was published in the American Journal of Psychiatry (2019 Dec 2. doi: 10.1176/appi.ajp.2019.19070684).
 

Real-world approach

Pathologic alcohol use is responsible for an estimated 3.8% of all deaths globally, yet current interventions for alcohol use disorder have limited efficacy, the researchers noted.

New treatments with innovative mechanisms would be valuable, they added.

Ketamine is a high-affinity N-methyl-d-aspartate receptor (NMDAR) antagonist.

Previously, research offered “promising results” with the use of ketamine for cocaine use disorder, including increased motivation to quit and decreased craving, Dr. Dakwar noted.

“Those results led us to think about how ketamine might be helpful for other substance use disorders, especially given the overlap in clinical vulnerabilities and epidemiology,” he said.

The study from the U.K. researchers was conducted in 90 patients with harmful drinking behavior but who had not been diagnosed with alcohol use disorder.

Dr. Dakwar noted that this was “a nontreatment study. None of the people there had alcohol use disorder; they were heavy drinkers. Also, the effects there were fairly modest.

“My interest was how to integrate ketamine into a clinical, real-world framework that could be helpful for people,” he added.

The study included 40 participants (52.5% women; 70.3% white; mean age, 53 years) with alcohol dependence whose average consumption was five drinks per day.

All entered a 5-week outpatient program of MET, which involved engaging in strategies to promote motivation and self-directed change.

During the program’s second week, the participants were randomly assigned to received a 52-minute IV infusion of ketamine 0.71 mg/kg (n = 17) or the benzodiazepine midazolam 0.025 mg/kg (n = 23).

This ketamine dose was selected “because it was the highest dose tolerated by participants in preliminary studies,” the researchers reported.

“Midazolam was chosen as the active control because it alters consciousness without any known persistent ... effect on alcohol dependence,” they added.

The “timeline follow back method” was used to assess alcohol use after treatment. Abstinence was confirmed by measuring urine ethyl glucuronide levels with urine toxicology tests.

Other measures included use of a visual analogue scale, the Clinical Institute Withdrawal Assessment, and the modified Perceived Stress Scale.

Primary outcome met

Results showed that 47.1% of the ketamine group and 59.1% of the midazolam group used alcohol during the 21 days after treatment infusion; 17.6% and 40.9%, respectively, had a heavy drinking day.

For the primary outcome measure of alcohol abstinence, the “quadratic effect of time was significant” (P = .004), as was time-by-treatment interaction (P less than .001).

Although the model-estimated proportions of alcohol abstinence remained stable for the ketamine group for 21 days post infusion, the proportions decreased significantly for the control group.

The odds of having a heavy drinking day did not change significantly after treatment for the ketamine group (odds ratio, 0.98; P = .74) but increased significantly with each postinfusion day for the midazolam group (OR, 1.19; P less than .001).

For the ketamine group, time to relapse was also significantly longer (P = .04).

No significant differences were found between the groups in rates of withdrawal, craving, or stress sensitivity.

A new direction?

The most common adverse events after treatment were sedation, seen in 12 members of the midazolam group and in 8 members of the ketamine group, and headache, seen in four and six members, respectively.

Although two ketamine-group members experienced mild agitation for up to 1 hour post infusion, no incidents of persistent psychoactive effects were reported in either group.

No participants who received ketamine dropped out during the study period; among those who received midazolam, six dropped out.

“These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder,” the investigators wrote.

However, a larger patient population will be needed in future research in order to “replicate these promising results,” they added.

Dr. Dakwar noted that the time to first drink after treatment was comparable between the groups.

“But what was different in the ketamine group was that they didn’t continue drinking after that first drink. They didn’t initiate heavy drinking, they didn’t relapse, they were able to bounce back and stay with the program,” he said.

“It was surprising but still consistent with the central hypothesis that ketamine provides this opportunity for setting the foundation for the requisite commitment so that, once things become difficult, they’re still able to maintain recovery,” Dr. Dakwar said.

‘Provocative findings’

In an accompanying editorial, Sanjay J. Mathew, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine in Houston, and Rebecca B. Price, PhD, of the department of psychiatry at the University of Pittsburgh, noted that ketamine’s effects on abstinence “were robust” in this trial.

“It is also noteworthy that, in spite of recruiting from a population of patients with active and significant substance use history (a group that has routinely been excluded from ketamine trials in depression), no participant showed evidence of new drug-seeking behaviors,” Dr. Mathew and Dr. Price wrote.

“Overall, these findings are provocative and hypothesis generating but certainly not definitive because of the small sample size,” they add.

Other limitations cited include the short follow-up period and the fact that only half of the participants were available for a 6-month follow-up telephone interview. In addition, generalizability was limited because the population did not have additional medical or psychiatric illnesses or additional substance use disorders, the editorialists wrote.

Because of the limitations, the investigators “are appropriately circumspect about the immediate clinical implications of this small pilot study.”

Still, the results “affirm the potential of rational combinatorial approaches for a vexing medical and public health problem,” Dr. Mathew and Dr. Price concluded.

The study was funded by grants from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the New York State Psychiatric Institute. The study authors and Dr. Price reported no relevant financial relationships. Dr Mathew reported serving as a consultant to or having received research support from several companies, including Alkermes, Allergan, Clexio Biosciences, and Janssen. The original article includes a full list of his disclosures.
 

A version of this article first appeared on Medscape.com.

More research suggests that a single infusion of ketamine combined with counseling may help alcohol-dependent patients curb their drinking.
 

In a pilot study of 40 participants, those who were randomly assigned to receive intravenous ketamine plus outpatient motivational enhancement therapy (MET) showed greater abstinence rates, longer time to relapse, and fewer heavy drinking days than did those who received MET plus midazolam.

The findings support a U.K. study published late last year showing that a single dose of intravenous ketamine plus therapy that focused on reactivating drinking-related “maladaptive reward memories” reduced drinking urges and alcohol intake more than just ketamine or a placebo infusion alone (Nat Commun. 2019 Nov 26;10[1]:5187).

“I think the take-home message is that behavioral treatment can be helpful, but there are vulnerabilities that can get in the way,” current study investigator Elias Dakwar, MD, of the New York State Psychiatric Institute, Columbia University, New York, said in an interview.

“It’s an important area of research to understand in order to make behavioral treatments more effective, and ketamine appears to have the properties to address those vulnerabilities,” Dr. Dakwar said.

The study was published in the American Journal of Psychiatry (2019 Dec 2. doi: 10.1176/appi.ajp.2019.19070684).
 

Real-world approach

Pathologic alcohol use is responsible for an estimated 3.8% of all deaths globally, yet current interventions for alcohol use disorder have limited efficacy, the researchers noted.

New treatments with innovative mechanisms would be valuable, they added.

Ketamine is a high-affinity N-methyl-d-aspartate receptor (NMDAR) antagonist.

Previously, research offered “promising results” with the use of ketamine for cocaine use disorder, including increased motivation to quit and decreased craving, Dr. Dakwar noted.

“Those results led us to think about how ketamine might be helpful for other substance use disorders, especially given the overlap in clinical vulnerabilities and epidemiology,” he said.

The study from the U.K. researchers was conducted in 90 patients with harmful drinking behavior but who had not been diagnosed with alcohol use disorder.

Dr. Dakwar noted that this was “a nontreatment study. None of the people there had alcohol use disorder; they were heavy drinkers. Also, the effects there were fairly modest.

“My interest was how to integrate ketamine into a clinical, real-world framework that could be helpful for people,” he added.

The study included 40 participants (52.5% women; 70.3% white; mean age, 53 years) with alcohol dependence whose average consumption was five drinks per day.

All entered a 5-week outpatient program of MET, which involved engaging in strategies to promote motivation and self-directed change.

During the program’s second week, the participants were randomly assigned to received a 52-minute IV infusion of ketamine 0.71 mg/kg (n = 17) or the benzodiazepine midazolam 0.025 mg/kg (n = 23).

This ketamine dose was selected “because it was the highest dose tolerated by participants in preliminary studies,” the researchers reported.

“Midazolam was chosen as the active control because it alters consciousness without any known persistent ... effect on alcohol dependence,” they added.

The “timeline follow back method” was used to assess alcohol use after treatment. Abstinence was confirmed by measuring urine ethyl glucuronide levels with urine toxicology tests.

Other measures included use of a visual analogue scale, the Clinical Institute Withdrawal Assessment, and the modified Perceived Stress Scale.

Primary outcome met

Results showed that 47.1% of the ketamine group and 59.1% of the midazolam group used alcohol during the 21 days after treatment infusion; 17.6% and 40.9%, respectively, had a heavy drinking day.

For the primary outcome measure of alcohol abstinence, the “quadratic effect of time was significant” (P = .004), as was time-by-treatment interaction (P less than .001).

Although the model-estimated proportions of alcohol abstinence remained stable for the ketamine group for 21 days post infusion, the proportions decreased significantly for the control group.

The odds of having a heavy drinking day did not change significantly after treatment for the ketamine group (odds ratio, 0.98; P = .74) but increased significantly with each postinfusion day for the midazolam group (OR, 1.19; P less than .001).

For the ketamine group, time to relapse was also significantly longer (P = .04).

No significant differences were found between the groups in rates of withdrawal, craving, or stress sensitivity.

A new direction?

The most common adverse events after treatment were sedation, seen in 12 members of the midazolam group and in 8 members of the ketamine group, and headache, seen in four and six members, respectively.

Although two ketamine-group members experienced mild agitation for up to 1 hour post infusion, no incidents of persistent psychoactive effects were reported in either group.

No participants who received ketamine dropped out during the study period; among those who received midazolam, six dropped out.

“These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder,” the investigators wrote.

However, a larger patient population will be needed in future research in order to “replicate these promising results,” they added.

Dr. Dakwar noted that the time to first drink after treatment was comparable between the groups.

“But what was different in the ketamine group was that they didn’t continue drinking after that first drink. They didn’t initiate heavy drinking, they didn’t relapse, they were able to bounce back and stay with the program,” he said.

“It was surprising but still consistent with the central hypothesis that ketamine provides this opportunity for setting the foundation for the requisite commitment so that, once things become difficult, they’re still able to maintain recovery,” Dr. Dakwar said.

‘Provocative findings’

In an accompanying editorial, Sanjay J. Mathew, MD, of the department of psychiatry and behavioral sciences at Baylor College of Medicine in Houston, and Rebecca B. Price, PhD, of the department of psychiatry at the University of Pittsburgh, noted that ketamine’s effects on abstinence “were robust” in this trial.

“It is also noteworthy that, in spite of recruiting from a population of patients with active and significant substance use history (a group that has routinely been excluded from ketamine trials in depression), no participant showed evidence of new drug-seeking behaviors,” Dr. Mathew and Dr. Price wrote.

“Overall, these findings are provocative and hypothesis generating but certainly not definitive because of the small sample size,” they add.

Other limitations cited include the short follow-up period and the fact that only half of the participants were available for a 6-month follow-up telephone interview. In addition, generalizability was limited because the population did not have additional medical or psychiatric illnesses or additional substance use disorders, the editorialists wrote.

Because of the limitations, the investigators “are appropriately circumspect about the immediate clinical implications of this small pilot study.”

Still, the results “affirm the potential of rational combinatorial approaches for a vexing medical and public health problem,” Dr. Mathew and Dr. Price concluded.

The study was funded by grants from the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the New York State Psychiatric Institute. The study authors and Dr. Price reported no relevant financial relationships. Dr Mathew reported serving as a consultant to or having received research support from several companies, including Alkermes, Allergan, Clexio Biosciences, and Janssen. The original article includes a full list of his disclosures.
 

A version of this article first appeared on Medscape.com.