CHICAGO – Bioresorbable scaffolds, new drugs, adjuvant interventions, and stem and progenitor cell therapy will change how vascular surgeons treat peripheral artery disease in the next 5 years, so they must embrace these emerging treatments or run the risk of being displaced by other specialists, according to a presentation at a symposium on vascular surgery sponsored by Northwestern University.

“Vascular surgeons must position their practices to be the nexus for the evaluation and treatment of the patient and proactively engage in the critical trials of these new technologies,” said Patrick J. Geraghty, MD, of Washington University, St. Louis. “If our specialty fails to adapt to new treatment options, we risk getting sidelined as critical limb ischemia (CLI) treatment moves into a multimodality model.”

CHICAGO – Bioresorbable scaffolds, new drugs, adjuvant interventions, and stem and progenitor cell therapy will change how vascular surgeons treat peripheral artery disease in the next 5 years, so they must embrace these emerging treatments or run the risk of being displaced by other specialists, according to a presentation at a symposium on vascular surgery sponsored by Northwestern University.

“Vascular surgeons must position their practices to be the nexus for the evaluation and treatment of the patient and proactively engage in the critical trials of these new technologies,” said Patrick J. Geraghty, MD, of Washington University, St. Louis. “If our specialty fails to adapt to new treatment options, we risk getting sidelined as critical limb ischemia (CLI) treatment moves into a multimodality model.”

CHICAGO – Bioresorbable scaffolds, new drugs, adjuvant interventions, and stem and progenitor cell therapy will change how vascular surgeons treat peripheral artery disease in the next 5 years, so they must embrace these emerging treatments or run the risk of being displaced by other specialists, according to a presentation at a symposium on vascular surgery sponsored by Northwestern University.

“Vascular surgeons must position their practices to be the nexus for the evaluation and treatment of the patient and proactively engage in the critical trials of these new technologies,” said Patrick J. Geraghty, MD, of Washington University, St. Louis. “If our specialty fails to adapt to new treatment options, we risk getting sidelined as critical limb ischemia (CLI) treatment moves into a multimodality model.”

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. The classic presentation of BP is a generalized, pruritic, bullous eruption in elderly patients, which is occasionally preceded by an urticarial prodrome. Immunopathologically, BP is characterized by IgG and sometimes IgE autoantibodies that target basement membrane zone proteins BP180 and BP230 of the epidermis.¹

The diagnosis of BP should be suspected when an elderly patient presents with tense blisters and can be confirmed via diagnostic testing, including tissue histology and direct immunofluorescence (DIF) as the gold standard, as well as indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and most recently biochip technology as supportive tests.² Since its advent, ELISA has gained popularity as a trustworthy diagnostic test for BP. The specificity of ELISA for BP diagnosis is reported to be 98% to 100%, which leads clinicians to believe that a positive ELISA equals certain diagnosis of BP; however, misdiagnosis of BP based on a positive ELISA result can occur.^3-13 The treatment of BP often involves lifelong immunosuppressive therapy. Complications of immunosuppressive therapy contribute to morbidity and mortality in these patients, thus an accurate diagnosis is paramount before introducing therapy.¹⁴

We present the case of a 74-year-old man with a history of a pruritic nonbullous eruption who was diagnosed with BP and treated for 3 years based on positive ELISA results in the absence of confirmatory histology or DIF.

Case Report

A 74-year-old man with diabetes mellitus, hypertension, hyperlipidemia, benign prostatic hypertrophy, and obstructive sleep apnea presented for further evaluation and confirmation of a prior diagnosis of BP by an outside dermatologist. He reported a pruritic rash on the trunk, back, and extremities of 3 years’ duration. He denied occurrence of blisters at any time.

On presentation to an outside dermatologist 3 years ago, a biopsy was performed along with serologic studies due to the patient’s age and the possibility of an urticarial prodrome in BP. The biopsy revealed epidermal acanthosis, subepidermal separation, and a perivascular and interstitial infiltrate of lymphocytes and eosinophils in the papillary dermis. Direct immunofluorescence was nondiagnostic with a weak discontinuous pattern of IgG and IgA linearly along the basement membrane zone as well as few scattered and clumped cytoid bodies of IgM and IgA. Indirect immunofluoresence revealed a positive IgG titer of 1:40 on monkey esophagus substrate and a positive epidermal pattern on human split-skin substrate with a titer of 1:80. An ELISA for IgG autoantibodies against BP180 and BP230 yielded 15 U and 6 U, respectively (cut off value, 9 U). Based on the positive ELISA for IgG against BP180, a diagnosis of BP was made.

Over the following 3 years, the treatment included prednisone, tetracycline, nicotinamide, doxycycline, and dapsone. Therapy was suboptimal due to the patient’s comorbidities and socioeconomic status. Poorly controlled diabetes mellitus precluded consistent use of prednisone as recommended for BP. Tetracycline and nicotinamide were transiently effective in controlling the patient’s symptoms but were discontinued due to changes in his health insurance. Doxycycline and dapsone were ineffective. Throughout this 3-year period, the patient remained blister free, but the pruritic eruption was persistent.

The patient presented to our clinic due to his frustration with the lack of improvement and doubts about the BP diagnosis given the persistent absence of bullous lesions. Physical examination revealed numerous eroded, scaly, crusted papules on erythematous edematous plaques on all extremities, trunk, and back (Figure 1). The head, neck, face, and oral mucosa were spared. His history and clinical findings were atypical for BP and skin biopsies were performed. Histology revealed epidermal erosion with parakeratosis, spongiosis, and superficial perivascular lymphocytic inflammation with rare eosinophils without subepidermal split (Figure 2). Direct immunofluorescence was negative for IgG, IgA, IgM, C3, and C1q. Additionally, further review of the initial histology by another dermatopathologist revealed that the subepidermal separation reported was more likely artifactual clefts. These findings were not consistent with BP.

Given the patient’s clinical history, lack of bullae, and twice-negative DIF, the diagnosis was determined to be more consistent with eczematous spongiotic dermatitis. He refused a referral for phototherapy due to scheduling inconvenience. The patient was started on cyclosporine 0.5 mg/kg twice daily. After 10 days of treatment, he returned for follow-up and reported notable improvement in the pruritus. On physical examination, his dermatitis was improved with decreased erythema and inflammation.

The patient is being continued on extensive dry skin care with thick moisturizers and additional topical corticosteroid application on an as-needed basis.

Comment

Chronic immunosuppression contributes to morbidity and mortality in patients with BP; therefore, accurate diagnosis of BP is of utmost importance.¹⁴ A meta-analysis described ELISA as a test with high sensitivity and specificity (87% and 98%–100%, respectively) for diagnosis of BP.³ Nevertheless, there are opportunities for misdiagnosis using ELISA, as demonstrated in our case. To determine if the reported sensitivity and specificity of ELISA is accurate and reliable for clinical use, individual studies from the meta-analysis were reviewed.^{4,5,7-10,13,15} Issues identified in our review included dissimilar diagnostic procedures and patient populations among individual studies, several reports of positive ELISA in patients without BP, and a lack of explanation for these false-positive results.

There are notable differences in diagnostic procedures and patient populations among reports that establish the sensitivity and specificity of ELISA for BP diagnosis.^3-13 Studies have detected IgG that targets the NC16A domain of the BP180 kD antigen, the C-terminal of the BP180 kD antigen, or the entire ectodomain of the BP180 kD antigen. Study patient populations varied in disease activity, stage, and treatment. Control patients included healthy patients as well as those with many dermatoses, including pemphigus vulgaris, systemic scleroderma, systemic lupus erythematosus, rheumatoid arthritis, lichen planus, and discoid lupus erythematosus.^3-13 Due to these differences between individual studies, we believe the results that determine the overall sensitivity and specificity of ELISA for BP diagnosis must be interpreted with caution. For ELISA statistics to be clinically applicable to a specific patient, he/she should be similar to the patients studied. Therefore, we believe each study must be evaluated individually for applicability, given the differences that exist between them.

Furthermore, there have been several reports of false-positive ELISA results in patients with other dermatologic disorders, specifically in elderly patients with pruritus who do not fulfill clinical criteria for diagnosis with BP.^16-18 In a population of elderly patients with pruritus for which no specific dermatological or systemic cause was identified, Hofmann et al¹⁸ found that 12% (3/25) of patients showed IgG reactivity to BP180 despite having negative DIF results. In another study of elderly patients with pruritic dermatoses, Feliciani et al¹⁷ found that 33% (5/15) of patients had IgG reactivity against BP230 or BP180, though they did not fulfill BP criteria based on clinical presentation and showed negative DIF and IIF results. These findings suggest that IgG reactivity against BP autoantibodies as determined by ELISA is not uncommon in pruritic diseases of the elderly.

Explanations for false-positive ELISA results were rare. A few authors suggested that false-positives could be attributed to an excessively low cutoff value,^7-9 which was consistent with reports that the titer of autoantibodies to BP180 correlates with disease severity, suggesting that the higher titer of antibodies correlates with more severe disease and likely more accurate diagnosis.^10,19,20 It is important to consider that patients who have low titers of BP180 autoantibodies with inconsistent clinical characteristics and DIF results may not truly have BP. Furthermore, to determine the clinical value of ELISA in identifying patients in the initial phase of BP, sera of BP patients should be compared with sera of elderly patients with pruritic skin disorders because they comprise the patient population that often requires diagnosis.¹⁸

Given the issues identified in our review of the literature, the published sensitivity and specificity of ELISA for BP diagnosis are likely overstated. In conclusion, ELISA should not be relied on as a single criterion adequate for diagnosis of BP.^12,21 Rather, the diagnosis of BP can be obtained with a positive predictive value of 95% when a patient meets 3 of 4 clinical criteria (ie, absence of atrophic scars, absence of head and neck involvement, absence of mucosal involvement, and older than 70 years) and demonstrates linear deposits of predominantly IgG and/or C3 along the basement membrane zone of a perilesional biopsy on DIF.¹⁵ The gold standard for diagnosis of BP remains clinical presentation along with DIF, which can be supported by histology, IIF, and ELISA.²²

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. The classic presentation of BP is a generalized, pruritic, bullous eruption in elderly patients, which is occasionally preceded by an urticarial prodrome. Immunopathologically, BP is characterized by IgG and sometimes IgE autoantibodies that target basement membrane zone proteins BP180 and BP230 of the epidermis.¹

The diagnosis of BP should be suspected when an elderly patient presents with tense blisters and can be confirmed via diagnostic testing, including tissue histology and direct immunofluorescence (DIF) as the gold standard, as well as indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and most recently biochip technology as supportive tests.² Since its advent, ELISA has gained popularity as a trustworthy diagnostic test for BP. The specificity of ELISA for BP diagnosis is reported to be 98% to 100%, which leads clinicians to believe that a positive ELISA equals certain diagnosis of BP; however, misdiagnosis of BP based on a positive ELISA result can occur.^3-13 The treatment of BP often involves lifelong immunosuppressive therapy. Complications of immunosuppressive therapy contribute to morbidity and mortality in these patients, thus an accurate diagnosis is paramount before introducing therapy.¹⁴

We present the case of a 74-year-old man with a history of a pruritic nonbullous eruption who was diagnosed with BP and treated for 3 years based on positive ELISA results in the absence of confirmatory histology or DIF.

Case Report

A 74-year-old man with diabetes mellitus, hypertension, hyperlipidemia, benign prostatic hypertrophy, and obstructive sleep apnea presented for further evaluation and confirmation of a prior diagnosis of BP by an outside dermatologist. He reported a pruritic rash on the trunk, back, and extremities of 3 years’ duration. He denied occurrence of blisters at any time.

On presentation to an outside dermatologist 3 years ago, a biopsy was performed along with serologic studies due to the patient’s age and the possibility of an urticarial prodrome in BP. The biopsy revealed epidermal acanthosis, subepidermal separation, and a perivascular and interstitial infiltrate of lymphocytes and eosinophils in the papillary dermis. Direct immunofluorescence was nondiagnostic with a weak discontinuous pattern of IgG and IgA linearly along the basement membrane zone as well as few scattered and clumped cytoid bodies of IgM and IgA. Indirect immunofluoresence revealed a positive IgG titer of 1:40 on monkey esophagus substrate and a positive epidermal pattern on human split-skin substrate with a titer of 1:80. An ELISA for IgG autoantibodies against BP180 and BP230 yielded 15 U and 6 U, respectively (cut off value, 9 U). Based on the positive ELISA for IgG against BP180, a diagnosis of BP was made.

Over the following 3 years, the treatment included prednisone, tetracycline, nicotinamide, doxycycline, and dapsone. Therapy was suboptimal due to the patient’s comorbidities and socioeconomic status. Poorly controlled diabetes mellitus precluded consistent use of prednisone as recommended for BP. Tetracycline and nicotinamide were transiently effective in controlling the patient’s symptoms but were discontinued due to changes in his health insurance. Doxycycline and dapsone were ineffective. Throughout this 3-year period, the patient remained blister free, but the pruritic eruption was persistent.

The patient presented to our clinic due to his frustration with the lack of improvement and doubts about the BP diagnosis given the persistent absence of bullous lesions. Physical examination revealed numerous eroded, scaly, crusted papules on erythematous edematous plaques on all extremities, trunk, and back (Figure 1). The head, neck, face, and oral mucosa were spared. His history and clinical findings were atypical for BP and skin biopsies were performed. Histology revealed epidermal erosion with parakeratosis, spongiosis, and superficial perivascular lymphocytic inflammation with rare eosinophils without subepidermal split (Figure 2). Direct immunofluorescence was negative for IgG, IgA, IgM, C3, and C1q. Additionally, further review of the initial histology by another dermatopathologist revealed that the subepidermal separation reported was more likely artifactual clefts. These findings were not consistent with BP.

Given the patient’s clinical history, lack of bullae, and twice-negative DIF, the diagnosis was determined to be more consistent with eczematous spongiotic dermatitis. He refused a referral for phototherapy due to scheduling inconvenience. The patient was started on cyclosporine 0.5 mg/kg twice daily. After 10 days of treatment, he returned for follow-up and reported notable improvement in the pruritus. On physical examination, his dermatitis was improved with decreased erythema and inflammation.

The patient is being continued on extensive dry skin care with thick moisturizers and additional topical corticosteroid application on an as-needed basis.

Comment

Chronic immunosuppression contributes to morbidity and mortality in patients with BP; therefore, accurate diagnosis of BP is of utmost importance.¹⁴ A meta-analysis described ELISA as a test with high sensitivity and specificity (87% and 98%–100%, respectively) for diagnosis of BP.³ Nevertheless, there are opportunities for misdiagnosis using ELISA, as demonstrated in our case. To determine if the reported sensitivity and specificity of ELISA is accurate and reliable for clinical use, individual studies from the meta-analysis were reviewed.^{4,5,7-10,13,15} Issues identified in our review included dissimilar diagnostic procedures and patient populations among individual studies, several reports of positive ELISA in patients without BP, and a lack of explanation for these false-positive results.

There are notable differences in diagnostic procedures and patient populations among reports that establish the sensitivity and specificity of ELISA for BP diagnosis.^3-13 Studies have detected IgG that targets the NC16A domain of the BP180 kD antigen, the C-terminal of the BP180 kD antigen, or the entire ectodomain of the BP180 kD antigen. Study patient populations varied in disease activity, stage, and treatment. Control patients included healthy patients as well as those with many dermatoses, including pemphigus vulgaris, systemic scleroderma, systemic lupus erythematosus, rheumatoid arthritis, lichen planus, and discoid lupus erythematosus.^3-13 Due to these differences between individual studies, we believe the results that determine the overall sensitivity and specificity of ELISA for BP diagnosis must be interpreted with caution. For ELISA statistics to be clinically applicable to a specific patient, he/she should be similar to the patients studied. Therefore, we believe each study must be evaluated individually for applicability, given the differences that exist between them.

Furthermore, there have been several reports of false-positive ELISA results in patients with other dermatologic disorders, specifically in elderly patients with pruritus who do not fulfill clinical criteria for diagnosis with BP.^16-18 In a population of elderly patients with pruritus for which no specific dermatological or systemic cause was identified, Hofmann et al¹⁸ found that 12% (3/25) of patients showed IgG reactivity to BP180 despite having negative DIF results. In another study of elderly patients with pruritic dermatoses, Feliciani et al¹⁷ found that 33% (5/15) of patients had IgG reactivity against BP230 or BP180, though they did not fulfill BP criteria based on clinical presentation and showed negative DIF and IIF results. These findings suggest that IgG reactivity against BP autoantibodies as determined by ELISA is not uncommon in pruritic diseases of the elderly.

Explanations for false-positive ELISA results were rare. A few authors suggested that false-positives could be attributed to an excessively low cutoff value,^7-9 which was consistent with reports that the titer of autoantibodies to BP180 correlates with disease severity, suggesting that the higher titer of antibodies correlates with more severe disease and likely more accurate diagnosis.^10,19,20 It is important to consider that patients who have low titers of BP180 autoantibodies with inconsistent clinical characteristics and DIF results may not truly have BP. Furthermore, to determine the clinical value of ELISA in identifying patients in the initial phase of BP, sera of BP patients should be compared with sera of elderly patients with pruritic skin disorders because they comprise the patient population that often requires diagnosis.¹⁸

Given the issues identified in our review of the literature, the published sensitivity and specificity of ELISA for BP diagnosis are likely overstated. In conclusion, ELISA should not be relied on as a single criterion adequate for diagnosis of BP.^12,21 Rather, the diagnosis of BP can be obtained with a positive predictive value of 95% when a patient meets 3 of 4 clinical criteria (ie, absence of atrophic scars, absence of head and neck involvement, absence of mucosal involvement, and older than 70 years) and demonstrates linear deposits of predominantly IgG and/or C3 along the basement membrane zone of a perilesional biopsy on DIF.¹⁵ The gold standard for diagnosis of BP remains clinical presentation along with DIF, which can be supported by histology, IIF, and ELISA.²²

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. The classic presentation of BP is a generalized, pruritic, bullous eruption in elderly patients, which is occasionally preceded by an urticarial prodrome. Immunopathologically, BP is characterized by IgG and sometimes IgE autoantibodies that target basement membrane zone proteins BP180 and BP230 of the epidermis.¹

The diagnosis of BP should be suspected when an elderly patient presents with tense blisters and can be confirmed via diagnostic testing, including tissue histology and direct immunofluorescence (DIF) as the gold standard, as well as indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and most recently biochip technology as supportive tests.² Since its advent, ELISA has gained popularity as a trustworthy diagnostic test for BP. The specificity of ELISA for BP diagnosis is reported to be 98% to 100%, which leads clinicians to believe that a positive ELISA equals certain diagnosis of BP; however, misdiagnosis of BP based on a positive ELISA result can occur.^3-13 The treatment of BP often involves lifelong immunosuppressive therapy. Complications of immunosuppressive therapy contribute to morbidity and mortality in these patients, thus an accurate diagnosis is paramount before introducing therapy.¹⁴

We present the case of a 74-year-old man with a history of a pruritic nonbullous eruption who was diagnosed with BP and treated for 3 years based on positive ELISA results in the absence of confirmatory histology or DIF.

Case Report

A 74-year-old man with diabetes mellitus, hypertension, hyperlipidemia, benign prostatic hypertrophy, and obstructive sleep apnea presented for further evaluation and confirmation of a prior diagnosis of BP by an outside dermatologist. He reported a pruritic rash on the trunk, back, and extremities of 3 years’ duration. He denied occurrence of blisters at any time.

On presentation to an outside dermatologist 3 years ago, a biopsy was performed along with serologic studies due to the patient’s age and the possibility of an urticarial prodrome in BP. The biopsy revealed epidermal acanthosis, subepidermal separation, and a perivascular and interstitial infiltrate of lymphocytes and eosinophils in the papillary dermis. Direct immunofluorescence was nondiagnostic with a weak discontinuous pattern of IgG and IgA linearly along the basement membrane zone as well as few scattered and clumped cytoid bodies of IgM and IgA. Indirect immunofluoresence revealed a positive IgG titer of 1:40 on monkey esophagus substrate and a positive epidermal pattern on human split-skin substrate with a titer of 1:80. An ELISA for IgG autoantibodies against BP180 and BP230 yielded 15 U and 6 U, respectively (cut off value, 9 U). Based on the positive ELISA for IgG against BP180, a diagnosis of BP was made.

Over the following 3 years, the treatment included prednisone, tetracycline, nicotinamide, doxycycline, and dapsone. Therapy was suboptimal due to the patient’s comorbidities and socioeconomic status. Poorly controlled diabetes mellitus precluded consistent use of prednisone as recommended for BP. Tetracycline and nicotinamide were transiently effective in controlling the patient’s symptoms but were discontinued due to changes in his health insurance. Doxycycline and dapsone were ineffective. Throughout this 3-year period, the patient remained blister free, but the pruritic eruption was persistent.

The patient presented to our clinic due to his frustration with the lack of improvement and doubts about the BP diagnosis given the persistent absence of bullous lesions. Physical examination revealed numerous eroded, scaly, crusted papules on erythematous edematous plaques on all extremities, trunk, and back (Figure 1). The head, neck, face, and oral mucosa were spared. His history and clinical findings were atypical for BP and skin biopsies were performed. Histology revealed epidermal erosion with parakeratosis, spongiosis, and superficial perivascular lymphocytic inflammation with rare eosinophils without subepidermal split (Figure 2). Direct immunofluorescence was negative for IgG, IgA, IgM, C3, and C1q. Additionally, further review of the initial histology by another dermatopathologist revealed that the subepidermal separation reported was more likely artifactual clefts. These findings were not consistent with BP.

Given the patient’s clinical history, lack of bullae, and twice-negative DIF, the diagnosis was determined to be more consistent with eczematous spongiotic dermatitis. He refused a referral for phototherapy due to scheduling inconvenience. The patient was started on cyclosporine 0.5 mg/kg twice daily. After 10 days of treatment, he returned for follow-up and reported notable improvement in the pruritus. On physical examination, his dermatitis was improved with decreased erythema and inflammation.

The patient is being continued on extensive dry skin care with thick moisturizers and additional topical corticosteroid application on an as-needed basis.

Comment

Chronic immunosuppression contributes to morbidity and mortality in patients with BP; therefore, accurate diagnosis of BP is of utmost importance.¹⁴ A meta-analysis described ELISA as a test with high sensitivity and specificity (87% and 98%–100%, respectively) for diagnosis of BP.³ Nevertheless, there are opportunities for misdiagnosis using ELISA, as demonstrated in our case. To determine if the reported sensitivity and specificity of ELISA is accurate and reliable for clinical use, individual studies from the meta-analysis were reviewed.^{4,5,7-10,13,15} Issues identified in our review included dissimilar diagnostic procedures and patient populations among individual studies, several reports of positive ELISA in patients without BP, and a lack of explanation for these false-positive results.

There are notable differences in diagnostic procedures and patient populations among reports that establish the sensitivity and specificity of ELISA for BP diagnosis.^3-13 Studies have detected IgG that targets the NC16A domain of the BP180 kD antigen, the C-terminal of the BP180 kD antigen, or the entire ectodomain of the BP180 kD antigen. Study patient populations varied in disease activity, stage, and treatment. Control patients included healthy patients as well as those with many dermatoses, including pemphigus vulgaris, systemic scleroderma, systemic lupus erythematosus, rheumatoid arthritis, lichen planus, and discoid lupus erythematosus.^3-13 Due to these differences between individual studies, we believe the results that determine the overall sensitivity and specificity of ELISA for BP diagnosis must be interpreted with caution. For ELISA statistics to be clinically applicable to a specific patient, he/she should be similar to the patients studied. Therefore, we believe each study must be evaluated individually for applicability, given the differences that exist between them.

Furthermore, there have been several reports of false-positive ELISA results in patients with other dermatologic disorders, specifically in elderly patients with pruritus who do not fulfill clinical criteria for diagnosis with BP.^16-18 In a population of elderly patients with pruritus for which no specific dermatological or systemic cause was identified, Hofmann et al¹⁸ found that 12% (3/25) of patients showed IgG reactivity to BP180 despite having negative DIF results. In another study of elderly patients with pruritic dermatoses, Feliciani et al¹⁷ found that 33% (5/15) of patients had IgG reactivity against BP230 or BP180, though they did not fulfill BP criteria based on clinical presentation and showed negative DIF and IIF results. These findings suggest that IgG reactivity against BP autoantibodies as determined by ELISA is not uncommon in pruritic diseases of the elderly.

Explanations for false-positive ELISA results were rare. A few authors suggested that false-positives could be attributed to an excessively low cutoff value,^7-9 which was consistent with reports that the titer of autoantibodies to BP180 correlates with disease severity, suggesting that the higher titer of antibodies correlates with more severe disease and likely more accurate diagnosis.^10,19,20 It is important to consider that patients who have low titers of BP180 autoantibodies with inconsistent clinical characteristics and DIF results may not truly have BP. Furthermore, to determine the clinical value of ELISA in identifying patients in the initial phase of BP, sera of BP patients should be compared with sera of elderly patients with pruritic skin disorders because they comprise the patient population that often requires diagnosis.¹⁸

Given the issues identified in our review of the literature, the published sensitivity and specificity of ELISA for BP diagnosis are likely overstated. In conclusion, ELISA should not be relied on as a single criterion adequate for diagnosis of BP.^12,21 Rather, the diagnosis of BP can be obtained with a positive predictive value of 95% when a patient meets 3 of 4 clinical criteria (ie, absence of atrophic scars, absence of head and neck involvement, absence of mucosal involvement, and older than 70 years) and demonstrates linear deposits of predominantly IgG and/or C3 along the basement membrane zone of a perilesional biopsy on DIF.¹⁵ The gold standard for diagnosis of BP remains clinical presentation along with DIF, which can be supported by histology, IIF, and ELISA.²²

HOLLYWOOD, FLA. – Incompatible Type A plasma appears to be a safe and effective part of an initial resuscitation protocol for trauma patients who need a massive transfusion.

There were no increases in morbidity, mortality, or transfusion-related acute lung injury among 120 patients who received Type A plasma, compared with those who got compatible plasma, Bryan C. Morse, MD, said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Type AB blood products are preferred for initial transfusions for trauma patients with unknown blood type. While type AB blood products are universally acceptable to patients, they are also in short supply. In an attempt to mitigate this shortage, some trauma centers are relying on anecdotal data, much drawn from real-life combat experience dating from World War II to present times, suggesting that Type A plasma is safe for initial resuscitation protocols. But the body of data from well-constructed trials is small, said Dr. Morse of Emory University, Atlanta. Thus, EAST sponsored this retrospective registry study, which examined outcomes in 1,536 trauma patients who received plasma transfusions as part of a massive transfusion protocol from 2012 to 2016.

The primary endpoints were overall morbidity, and mortality at four time points: 6 and 24 hours, and 7 and 28 days. Eight trauma centers contributed data to the study.

The group was largely male (75%) with a mean age of 37 years. Patients were seriously injured, with a mean Injury Severity Score (ISS) of 25. About 60% suffered from blunt-force trauma. Among the entire group, 120 (8%) received incompatible type A plasma.

About 28% of patients (434) experienced an adverse event. These were numerically but not significantly more common among the incompatible A plasma group (35% vs. 28%; P = .14). Events included acute respiratory distress syndrome (6% vs. 7.6%), thromboembolism (9% vs. 7%), pneumonia (19% vs. 15%), and acute kidney injury (8% each).

There were two cases of transfusion-related acute lung injury, both of which occurred in the compatible type A group.

Mortality was similar at every time point: 6 hours (16% vs. 15%), 24 hours (25% vs. 22%), 7 days (35% vs. 32%), and 28 days (38% vs. 35%).

A multivariate regression model controlled for treatment center, ISS, units of packed red cells given by 4 hours, mechanism of injury, Type A plasma incompatibility, and age.

In the morbidity analysis, only ISS and units of red blood cells at 4 hours were associated with a significant increase in risk (odd ratio 1.02). Incompatible Type A plasma did not significantly increase the risk of morbidity.

In the mortality analysis, units of red cells, ISS, and age were significantly associated with increased risk. Again, incompatible Type A plasma did not significantly increase the risk of death.

Dr. Morse had no financial declaration.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

HOLLYWOOD, FLA. – Incompatible Type A plasma appears to be a safe and effective part of an initial resuscitation protocol for trauma patients who need a massive transfusion.

There were no increases in morbidity, mortality, or transfusion-related acute lung injury among 120 patients who received Type A plasma, compared with those who got compatible plasma, Bryan C. Morse, MD, said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Type AB blood products are preferred for initial transfusions for trauma patients with unknown blood type. While type AB blood products are universally acceptable to patients, they are also in short supply. In an attempt to mitigate this shortage, some trauma centers are relying on anecdotal data, much drawn from real-life combat experience dating from World War II to present times, suggesting that Type A plasma is safe for initial resuscitation protocols. But the body of data from well-constructed trials is small, said Dr. Morse of Emory University, Atlanta. Thus, EAST sponsored this retrospective registry study, which examined outcomes in 1,536 trauma patients who received plasma transfusions as part of a massive transfusion protocol from 2012 to 2016.

The primary endpoints were overall morbidity, and mortality at four time points: 6 and 24 hours, and 7 and 28 days. Eight trauma centers contributed data to the study.

The group was largely male (75%) with a mean age of 37 years. Patients were seriously injured, with a mean Injury Severity Score (ISS) of 25. About 60% suffered from blunt-force trauma. Among the entire group, 120 (8%) received incompatible type A plasma.

About 28% of patients (434) experienced an adverse event. These were numerically but not significantly more common among the incompatible A plasma group (35% vs. 28%; P = .14). Events included acute respiratory distress syndrome (6% vs. 7.6%), thromboembolism (9% vs. 7%), pneumonia (19% vs. 15%), and acute kidney injury (8% each).

There were two cases of transfusion-related acute lung injury, both of which occurred in the compatible type A group.

Mortality was similar at every time point: 6 hours (16% vs. 15%), 24 hours (25% vs. 22%), 7 days (35% vs. 32%), and 28 days (38% vs. 35%).

A multivariate regression model controlled for treatment center, ISS, units of packed red cells given by 4 hours, mechanism of injury, Type A plasma incompatibility, and age.

In the morbidity analysis, only ISS and units of red blood cells at 4 hours were associated with a significant increase in risk (odd ratio 1.02). Incompatible Type A plasma did not significantly increase the risk of morbidity.

In the mortality analysis, units of red cells, ISS, and age were significantly associated with increased risk. Again, incompatible Type A plasma did not significantly increase the risk of death.

Dr. Morse had no financial declaration.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

HOLLYWOOD, FLA. – Incompatible Type A plasma appears to be a safe and effective part of an initial resuscitation protocol for trauma patients who need a massive transfusion.

There were no increases in morbidity, mortality, or transfusion-related acute lung injury among 120 patients who received Type A plasma, compared with those who got compatible plasma, Bryan C. Morse, MD, said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Type AB blood products are preferred for initial transfusions for trauma patients with unknown blood type. While type AB blood products are universally acceptable to patients, they are also in short supply. In an attempt to mitigate this shortage, some trauma centers are relying on anecdotal data, much drawn from real-life combat experience dating from World War II to present times, suggesting that Type A plasma is safe for initial resuscitation protocols. But the body of data from well-constructed trials is small, said Dr. Morse of Emory University, Atlanta. Thus, EAST sponsored this retrospective registry study, which examined outcomes in 1,536 trauma patients who received plasma transfusions as part of a massive transfusion protocol from 2012 to 2016.

The primary endpoints were overall morbidity, and mortality at four time points: 6 and 24 hours, and 7 and 28 days. Eight trauma centers contributed data to the study.

The group was largely male (75%) with a mean age of 37 years. Patients were seriously injured, with a mean Injury Severity Score (ISS) of 25. About 60% suffered from blunt-force trauma. Among the entire group, 120 (8%) received incompatible type A plasma.

About 28% of patients (434) experienced an adverse event. These were numerically but not significantly more common among the incompatible A plasma group (35% vs. 28%; P = .14). Events included acute respiratory distress syndrome (6% vs. 7.6%), thromboembolism (9% vs. 7%), pneumonia (19% vs. 15%), and acute kidney injury (8% each).

There were two cases of transfusion-related acute lung injury, both of which occurred in the compatible type A group.

Mortality was similar at every time point: 6 hours (16% vs. 15%), 24 hours (25% vs. 22%), 7 days (35% vs. 32%), and 28 days (38% vs. 35%).

A multivariate regression model controlled for treatment center, ISS, units of packed red cells given by 4 hours, mechanism of injury, Type A plasma incompatibility, and age.

In the morbidity analysis, only ISS and units of red blood cells at 4 hours were associated with a significant increase in risk (odd ratio 1.02). Incompatible Type A plasma did not significantly increase the risk of morbidity.

In the mortality analysis, units of red cells, ISS, and age were significantly associated with increased risk. Again, incompatible Type A plasma did not significantly increase the risk of death.

Dr. Morse had no financial declaration.

msullivan@frontlinemedcom.com

On Twitter @Alz_Gal

As pediatric and adolescent gynecologists, we are seeing an increasing number of adolescents with gender identity issues and have come to believe that all obstetrician-gynecologists need to have an understanding of varying gender identities, as well as their role in managing these patients’ care.

We had the honor to assist the American College of Obstetricians and Gynecologists’ (ACOG) Committee on Adolescent Health Care in the development of a new Committee Opinion to guide ob.gyns. in caring for transgender adolescents (Obstet Gynecol 2017;129:e11-6). As our culture grows more aware of the nuances and spectrum of gender identity, our health care practices must grow as well. Ob.gyns. are often uniquely positioned as being among the first people transgender adolescents present to – whether it’s signaling disassociation with their gender when answering routine medical questions or directly addressing gender with them as a trusted and private resource. Even when seeing a patient too young to consider hormone therapy, an ob.gyn. can offer vital early behavioral health support, educational and community resources, and specialist referrals.

Transgender adolescent patients have likely faced negative stereotypes and stigmas in social settings or through media that make them cautious and protective of their identity. They are also more likely to face social ostracism such as bullying and/or dissent and rejection from their parents, deepening the vulnerability of their situation. As a result, transgender adolescents can have increased instances of anxiety, depression, sexual harassment, homelessness, and risk-taking behavior. Medical practices can signal to transgender patients that they are safe and welcoming from the start by offering gender neutral forms, brochures, and information for LGBT patients in the waiting room, and having sensitive employees at every step – from the front desk onward.

As we’ve just outlined, transgender adolescent patients face unique challenges, including increased rates of social and mental health risks. In response, ob.gyns. must be prepared to have a comprehensive conversation about health and well-being beyond sexual and reproductive health. They must also be equipped to address the psychosocial issues associated with transgender adolescents. This includes knowledge of what to look for and offering patients resources, education, and referrals to guarantee their health and safety.

It is important that ob.gyns. are aware that transgender men have female reproductive organs and can present with common gynecological problems such as abnormal bleeding, ovarian cysts, and torsion, as well as pregnancy and pregnancy complications. Finally, ob.gyns. can serve a unique role in counseling about fertility and fertility preservation. Thus, not only do we provide essential health care, including ongoing primary care, but we can position ourselves as part of the support network for these adolescents and their families.

Most importantly, when addressing an adolescent transgender patient, we must understand there is no uniform transgender experience. Expressing gender, sexual identity, and behavior patterns will vary from patient to patient. There are a wide range of treatment options available for transgender patients, from hormone to surgical therapies. An ob.gyn.’s responsibility is to help each individual make an informed decision, and help that patient think ahead to the future.

While this all may seem like a lot, it’s important to remember the essential components of our role as health care providers do not change because an adolescent patient is transgender. Care should always include education about their bodies, safe sex, deliberate and thoughtful assessment of symptoms or concerns, and preventive care services such as STI screenings and contraception. We are simply adding more nuanced cultural and medical understanding to those practices.
 

Dr. Gomez-Lobo is director of pediatric and adolescent obstetrics and gynecology, Medstar Washington Hospital Center/Children’s National Health System, Washington, D.C. Dr. Sokkary is associate professor of ob.gyn. at Navicent Health Center/Mercer School of Medicine in Macon, Ga. They are members of the ACOG Committee on Adolescent Health Care. They reported having no relevant financial disclosures.

As pediatric and adolescent gynecologists, we are seeing an increasing number of adolescents with gender identity issues and have come to believe that all obstetrician-gynecologists need to have an understanding of varying gender identities, as well as their role in managing these patients’ care.

We had the honor to assist the American College of Obstetricians and Gynecologists’ (ACOG) Committee on Adolescent Health Care in the development of a new Committee Opinion to guide ob.gyns. in caring for transgender adolescents (Obstet Gynecol 2017;129:e11-6). As our culture grows more aware of the nuances and spectrum of gender identity, our health care practices must grow as well. Ob.gyns. are often uniquely positioned as being among the first people transgender adolescents present to – whether it’s signaling disassociation with their gender when answering routine medical questions or directly addressing gender with them as a trusted and private resource. Even when seeing a patient too young to consider hormone therapy, an ob.gyn. can offer vital early behavioral health support, educational and community resources, and specialist referrals.

Transgender adolescent patients have likely faced negative stereotypes and stigmas in social settings or through media that make them cautious and protective of their identity. They are also more likely to face social ostracism such as bullying and/or dissent and rejection from their parents, deepening the vulnerability of their situation. As a result, transgender adolescents can have increased instances of anxiety, depression, sexual harassment, homelessness, and risk-taking behavior. Medical practices can signal to transgender patients that they are safe and welcoming from the start by offering gender neutral forms, brochures, and information for LGBT patients in the waiting room, and having sensitive employees at every step – from the front desk onward.

As we’ve just outlined, transgender adolescent patients face unique challenges, including increased rates of social and mental health risks. In response, ob.gyns. must be prepared to have a comprehensive conversation about health and well-being beyond sexual and reproductive health. They must also be equipped to address the psychosocial issues associated with transgender adolescents. This includes knowledge of what to look for and offering patients resources, education, and referrals to guarantee their health and safety.

It is important that ob.gyns. are aware that transgender men have female reproductive organs and can present with common gynecological problems such as abnormal bleeding, ovarian cysts, and torsion, as well as pregnancy and pregnancy complications. Finally, ob.gyns. can serve a unique role in counseling about fertility and fertility preservation. Thus, not only do we provide essential health care, including ongoing primary care, but we can position ourselves as part of the support network for these adolescents and their families.

Most importantly, when addressing an adolescent transgender patient, we must understand there is no uniform transgender experience. Expressing gender, sexual identity, and behavior patterns will vary from patient to patient. There are a wide range of treatment options available for transgender patients, from hormone to surgical therapies. An ob.gyn.’s responsibility is to help each individual make an informed decision, and help that patient think ahead to the future.

While this all may seem like a lot, it’s important to remember the essential components of our role as health care providers do not change because an adolescent patient is transgender. Care should always include education about their bodies, safe sex, deliberate and thoughtful assessment of symptoms or concerns, and preventive care services such as STI screenings and contraception. We are simply adding more nuanced cultural and medical understanding to those practices.
 

Dr. Gomez-Lobo is director of pediatric and adolescent obstetrics and gynecology, Medstar Washington Hospital Center/Children’s National Health System, Washington, D.C. Dr. Sokkary is associate professor of ob.gyn. at Navicent Health Center/Mercer School of Medicine in Macon, Ga. They are members of the ACOG Committee on Adolescent Health Care. They reported having no relevant financial disclosures.

As pediatric and adolescent gynecologists, we are seeing an increasing number of adolescents with gender identity issues and have come to believe that all obstetrician-gynecologists need to have an understanding of varying gender identities, as well as their role in managing these patients’ care.

We had the honor to assist the American College of Obstetricians and Gynecologists’ (ACOG) Committee on Adolescent Health Care in the development of a new Committee Opinion to guide ob.gyns. in caring for transgender adolescents (Obstet Gynecol 2017;129:e11-6). As our culture grows more aware of the nuances and spectrum of gender identity, our health care practices must grow as well. Ob.gyns. are often uniquely positioned as being among the first people transgender adolescents present to – whether it’s signaling disassociation with their gender when answering routine medical questions or directly addressing gender with them as a trusted and private resource. Even when seeing a patient too young to consider hormone therapy, an ob.gyn. can offer vital early behavioral health support, educational and community resources, and specialist referrals.

Transgender adolescent patients have likely faced negative stereotypes and stigmas in social settings or through media that make them cautious and protective of their identity. They are also more likely to face social ostracism such as bullying and/or dissent and rejection from their parents, deepening the vulnerability of their situation. As a result, transgender adolescents can have increased instances of anxiety, depression, sexual harassment, homelessness, and risk-taking behavior. Medical practices can signal to transgender patients that they are safe and welcoming from the start by offering gender neutral forms, brochures, and information for LGBT patients in the waiting room, and having sensitive employees at every step – from the front desk onward.

As we’ve just outlined, transgender adolescent patients face unique challenges, including increased rates of social and mental health risks. In response, ob.gyns. must be prepared to have a comprehensive conversation about health and well-being beyond sexual and reproductive health. They must also be equipped to address the psychosocial issues associated with transgender adolescents. This includes knowledge of what to look for and offering patients resources, education, and referrals to guarantee their health and safety.

It is important that ob.gyns. are aware that transgender men have female reproductive organs and can present with common gynecological problems such as abnormal bleeding, ovarian cysts, and torsion, as well as pregnancy and pregnancy complications. Finally, ob.gyns. can serve a unique role in counseling about fertility and fertility preservation. Thus, not only do we provide essential health care, including ongoing primary care, but we can position ourselves as part of the support network for these adolescents and their families.

Most importantly, when addressing an adolescent transgender patient, we must understand there is no uniform transgender experience. Expressing gender, sexual identity, and behavior patterns will vary from patient to patient. There are a wide range of treatment options available for transgender patients, from hormone to surgical therapies. An ob.gyn.’s responsibility is to help each individual make an informed decision, and help that patient think ahead to the future.

While this all may seem like a lot, it’s important to remember the essential components of our role as health care providers do not change because an adolescent patient is transgender. Care should always include education about their bodies, safe sex, deliberate and thoughtful assessment of symptoms or concerns, and preventive care services such as STI screenings and contraception. We are simply adding more nuanced cultural and medical understanding to those practices.
 

Dr. Gomez-Lobo is director of pediatric and adolescent obstetrics and gynecology, Medstar Washington Hospital Center/Children’s National Health System, Washington, D.C. Dr. Sokkary is associate professor of ob.gyn. at Navicent Health Center/Mercer School of Medicine in Macon, Ga. They are members of the ACOG Committee on Adolescent Health Care. They reported having no relevant financial disclosures.

Clostridium difficile (C difficile) infection (CDI) is a leading cause of infectious diarrhea among hospitalized patients and, increasingly, in ambulatory patients.^1,2 The high prevalence of CDI and the high recurrence rates (15%-30%) led the CDC to categorize C difficile as an "urgent" threat (the highest category) in its 2013 Antimicrobial Resistance Threat Report.^3-5 The Infectious Diseases Society of America guideline recommended treatment for CDI is vancomycin or metronidazole; more recent studies also support fidaxomicin use.^4,6,7  

Patients experiencing recurrent CDI are at risk for further recurrences, such that after the third CDI episode, the risk of subsequent recurrences exceeds 50%.⁸ This recurrence rate has stimulated research into other treatments, including fecal microbiota transplantation (FMT). A recent systematic  review of FMT reports that 85% of patients have resolution of symptoms without recurrence after FMT, although this is based on data from case series and 2 small randomized clinical trials.⁹

A commonly cited barrier to FMT is patient acceptance. In response to this concern, a previous survey demonstrated that 81% of respondents would opt for FMT to treat a hypothetical case of recurrent CDI.¹⁰ However, the surveyed population did not have CDI, and the 48% response rate is concerning, since those with a favorable opinion of FMT might be more willing to complete a survey than would other patients. Accordingly, the authors systematically surveyed hospitalized veterans with active CDI to assess their knowledge, attitudes, and opinions about FMT as a treatment for CDI.

Methods

In-person patient interviews were conducted by one of the study authors at the Minneapolis VA Health Care System (MVAHCS), consisting of 13 to 18 questions. Questions addressed any prior CDI episodes and knowledge of the following: CDI, recurrence risk, and FMT; preferred route and location of FMT administration; concerns regarding FMT; likelihood of agreeing to undergo FMT (if available); and likelihood of enrollment in a hypothetical study comparing FMT to standard antibiotic treatment. The survey was developed internally and was not validated. Questions used the Likert-scale (Survey).

Patients with CDI were identified by monitoring for positive C difficile polymerase chain reaction (PCR) stool tests and then screened for inclusion by medical record review. Inclusion criteria were (1) MVAHCS hospitalization; and (2) written informed consent. Exclusion criteria were the inability to communicate or participate in an interview. Patient responses regarding their likelihood of agreeing to FMT for CDI treatment under different circumstances were compared using Wilcoxon rank sum test. These circumstances included FMT for their current episode of CDI, FMT for a subsequent episode, and FMT if recommended by their physician. Possible concerns regarding FMT also were solicited, including infection risk, effectiveness, and procedural aesthetics. The MVAHCS institutional review board approved the study.

Results

Stool PCR tests for CDI were monitored for 158 days from 2013 to 2014 (based on availability of study staff), yielding 106 positive results. Of those, 31 (29%) were from outpatients and not addressed further. Of the 75 positive CDI tests from 66 hospitalized patients (9 patients had duplicate tests), 18 of 66 (27%) were not able to provide consent and were excluded, leaving 48 eligible patients. Six (13%) were missed for logistic reasons (patient at a test or procedure, discharged before approached, etc), leaving 42 patients who were approached for participation. Among these, 34 (81%) consented to participate in the survey. Two subjects (6%) found the topic so unappealing that they terminated the interview.

The majority of enrolled subjects were men (32/34, 94%), with a mean age of 65.3 years (range, 31-89). Eleven subjects (32%) reported a prior CDI episode, with 10 reporting 1 such episode, and the other 2 episodes. Those with prior CDI reported the effect of CDI on their overall quality of life as 5.1 (1 = no limitation, 10 = severe limitation). Respondents were fairly accurate regarding the risk of recurrence after an initial episode of CDI, with the average expectedrecurrence rate estimated at 33%. In contrast, their estimation of the risk of recurrence after a second CDI episode was lower (28%), although the risk of recurrent episodes increases with each CDI recurrence.

Regarding FMT, 5 subjects indicated awareness of the procedure: 2 learning of it from a news source, 1 from family, 1 from a health care provider, and 1 was unsure of the source. After subjects received a description of FMT, their opinions regarding the procedure were elicited. When asked which route of delivery they would prefer if they were to undergo FMT, the 33 subjects who provided a response indicated a strong preference for either enema (15, 45%) or colonoscopy (10, 30%), compared with just 4 (12%) indicating no preference, 2 (6%) choosing nasogastric tube administration, and 2 (6%) indicating that they would not undergo FMT by any route (P < .001).

Regarding the location of FMT administration (hospital setting vs self-administered at home), 31 of 33 respondents (94%) indicated they would prefer FMT to occur in the hospital vs 2 (6%) preferring self-administration at home (P < .001). The preferred source of donor stool was more evenly distributed, with 14 of 32 respondents (44%) indicating a preference for an anonymous donor, 11 preferring a family member (34%), and 7 (21%) with no preference (P = .21).

Subjects were asked about concerns regarding FMT, and asked to rate each on a 5-point Likert scale (1 = not at all concerning; 5 = overwhelming concern). Concerns regarding risk of infection and effectiveness received an average score of 2.74 and 2.72, respectively, whereas concern regarding the aesthetics, or "yuck factor" was slightly lower (2.1: P = NS for all comparisons). Subjects also were asked to rate the likelihood of undergoing FMT, if it were available, for their current episode of CDI, a subsequent episode of CDI, or if their physician recommended undergoing FMT (10 point scale: 1 = not at all likely; 10 = certainly agree to FMT). The mean scores (SD) for agreeing to FMT for the current or a subsequent episode were 4.8 (SD 2.7) and 5.6 (SD 3.0); P = .12, but increased to 7.1 (SD 3.23) if FMT were recommended by their physician (P < .001 for FMT if physician recommended vs FMT for current episode; P = .001 for FMT if physician recommended vs FMT for a subsequent episode). Finally, subjects were asked about the likelihood of enrolling in a study comparing FMT to standard antimicrobial treatment, with answers ranging from 1 (almost certainly would not enroll) to 5 (almost certainly would enroll). Among the 32 respondents to this question, 17 (53%) answered either "probably would enroll" or "almost certainly would enroll," with a mean score of 3.2.  

Discussion

Overall, VA patients with a current episode of CDI were not aware of FMT, with just 15% knowing about the procedure. However, after learning about FMT, patients expressed clear opinions regarding the route and setting of FMT administration, with enema or colonoscopy being the preferred routes, and a hospital the preferred setting. In contrast, subjects expressed ambivalence with regard to the source of donor stool, with no clear preference for stool from an anonymous donor vs from a family member.

When asked about concerns regarding FMT, none of the presented options (risk of infection, uncertain effectiveness, or procedural aesthetics) emerged as significantly more important than did others, although the oft-cited concern regarding FMT aesthetics engendered the lowest overall level of concern. In terms of FMT acceptance, 4 subjects (12%) were opposed to the procedure, indicating that they were not at all likely to agree to FMT for all scenarios (defined as a score of 1 or 2 on the 10-point Likert scale) or by terminating the survey because of the questions. However, 15 (44%) indicated that they would certainly agree to FMT (defined as a score of 9 or 10 on the 10-point Likert scale) if their physician recommended it. Physician recommendation for FMT resulted in the highest overall likelihood of agreeing to FMT, a finding in agreement with a previous survey of FMT for CDI.¹⁰ Most subjects indicated likely enrollment in a potential study comparing FMT with standard antimicrobial therapy.

Strengths/Limitations

Study strengths included surveying patients with current CDI, such that patients had personal experience with the disease in question. Use of in-person interviews also resulted in a robust response rate of 81% and allowed subjects to clarify any unclear questions with study personnel. Weaknesses included a relatively small sample size, underrepresentation of women, and lack of detail regarding respondent characteristics. Additionally, capsule delivery of FMT was not assessed since this method of delivery had not been published at the time of survey administration.

Conclusion

This survey of VA patients with CDI suggests that aesthetic concerns are not a critical deterrent for this population, and interest in FMT for the treatment of recurrent CDI exists. Physician recommendation to undergo FMT seems to be the most influential factor affecting the likelihood of agreeing to undergo FMT. These results support the feasibility of conducting clinical trials of FMT in the VA system.

Clostridium difficile (C difficile) infection (CDI) is a leading cause of infectious diarrhea among hospitalized patients and, increasingly, in ambulatory patients.^1,2 The high prevalence of CDI and the high recurrence rates (15%-30%) led the CDC to categorize C difficile as an "urgent" threat (the highest category) in its 2013 Antimicrobial Resistance Threat Report.^3-5 The Infectious Diseases Society of America guideline recommended treatment for CDI is vancomycin or metronidazole; more recent studies also support fidaxomicin use.^4,6,7  

Patients experiencing recurrent CDI are at risk for further recurrences, such that after the third CDI episode, the risk of subsequent recurrences exceeds 50%.⁸ This recurrence rate has stimulated research into other treatments, including fecal microbiota transplantation (FMT). A recent systematic  review of FMT reports that 85% of patients have resolution of symptoms without recurrence after FMT, although this is based on data from case series and 2 small randomized clinical trials.⁹

A commonly cited barrier to FMT is patient acceptance. In response to this concern, a previous survey demonstrated that 81% of respondents would opt for FMT to treat a hypothetical case of recurrent CDI.¹⁰ However, the surveyed population did not have CDI, and the 48% response rate is concerning, since those with a favorable opinion of FMT might be more willing to complete a survey than would other patients. Accordingly, the authors systematically surveyed hospitalized veterans with active CDI to assess their knowledge, attitudes, and opinions about FMT as a treatment for CDI.

Methods

In-person patient interviews were conducted by one of the study authors at the Minneapolis VA Health Care System (MVAHCS), consisting of 13 to 18 questions. Questions addressed any prior CDI episodes and knowledge of the following: CDI, recurrence risk, and FMT; preferred route and location of FMT administration; concerns regarding FMT; likelihood of agreeing to undergo FMT (if available); and likelihood of enrollment in a hypothetical study comparing FMT to standard antibiotic treatment. The survey was developed internally and was not validated. Questions used the Likert-scale (Survey).

Patients with CDI were identified by monitoring for positive C difficile polymerase chain reaction (PCR) stool tests and then screened for inclusion by medical record review. Inclusion criteria were (1) MVAHCS hospitalization; and (2) written informed consent. Exclusion criteria were the inability to communicate or participate in an interview. Patient responses regarding their likelihood of agreeing to FMT for CDI treatment under different circumstances were compared using Wilcoxon rank sum test. These circumstances included FMT for their current episode of CDI, FMT for a subsequent episode, and FMT if recommended by their physician. Possible concerns regarding FMT also were solicited, including infection risk, effectiveness, and procedural aesthetics. The MVAHCS institutional review board approved the study.

Results

Stool PCR tests for CDI were monitored for 158 days from 2013 to 2014 (based on availability of study staff), yielding 106 positive results. Of those, 31 (29%) were from outpatients and not addressed further. Of the 75 positive CDI tests from 66 hospitalized patients (9 patients had duplicate tests), 18 of 66 (27%) were not able to provide consent and were excluded, leaving 48 eligible patients. Six (13%) were missed for logistic reasons (patient at a test or procedure, discharged before approached, etc), leaving 42 patients who were approached for participation. Among these, 34 (81%) consented to participate in the survey. Two subjects (6%) found the topic so unappealing that they terminated the interview.

The majority of enrolled subjects were men (32/34, 94%), with a mean age of 65.3 years (range, 31-89). Eleven subjects (32%) reported a prior CDI episode, with 10 reporting 1 such episode, and the other 2 episodes. Those with prior CDI reported the effect of CDI on their overall quality of life as 5.1 (1 = no limitation, 10 = severe limitation). Respondents were fairly accurate regarding the risk of recurrence after an initial episode of CDI, with the average expectedrecurrence rate estimated at 33%. In contrast, their estimation of the risk of recurrence after a second CDI episode was lower (28%), although the risk of recurrent episodes increases with each CDI recurrence.

Regarding FMT, 5 subjects indicated awareness of the procedure: 2 learning of it from a news source, 1 from family, 1 from a health care provider, and 1 was unsure of the source. After subjects received a description of FMT, their opinions regarding the procedure were elicited. When asked which route of delivery they would prefer if they were to undergo FMT, the 33 subjects who provided a response indicated a strong preference for either enema (15, 45%) or colonoscopy (10, 30%), compared with just 4 (12%) indicating no preference, 2 (6%) choosing nasogastric tube administration, and 2 (6%) indicating that they would not undergo FMT by any route (P < .001).

Regarding the location of FMT administration (hospital setting vs self-administered at home), 31 of 33 respondents (94%) indicated they would prefer FMT to occur in the hospital vs 2 (6%) preferring self-administration at home (P < .001). The preferred source of donor stool was more evenly distributed, with 14 of 32 respondents (44%) indicating a preference for an anonymous donor, 11 preferring a family member (34%), and 7 (21%) with no preference (P = .21).

Subjects were asked about concerns regarding FMT, and asked to rate each on a 5-point Likert scale (1 = not at all concerning; 5 = overwhelming concern). Concerns regarding risk of infection and effectiveness received an average score of 2.74 and 2.72, respectively, whereas concern regarding the aesthetics, or "yuck factor" was slightly lower (2.1: P = NS for all comparisons). Subjects also were asked to rate the likelihood of undergoing FMT, if it were available, for their current episode of CDI, a subsequent episode of CDI, or if their physician recommended undergoing FMT (10 point scale: 1 = not at all likely; 10 = certainly agree to FMT). The mean scores (SD) for agreeing to FMT for the current or a subsequent episode were 4.8 (SD 2.7) and 5.6 (SD 3.0); P = .12, but increased to 7.1 (SD 3.23) if FMT were recommended by their physician (P < .001 for FMT if physician recommended vs FMT for current episode; P = .001 for FMT if physician recommended vs FMT for a subsequent episode). Finally, subjects were asked about the likelihood of enrolling in a study comparing FMT to standard antimicrobial treatment, with answers ranging from 1 (almost certainly would not enroll) to 5 (almost certainly would enroll). Among the 32 respondents to this question, 17 (53%) answered either "probably would enroll" or "almost certainly would enroll," with a mean score of 3.2.  

Discussion

Overall, VA patients with a current episode of CDI were not aware of FMT, with just 15% knowing about the procedure. However, after learning about FMT, patients expressed clear opinions regarding the route and setting of FMT administration, with enema or colonoscopy being the preferred routes, and a hospital the preferred setting. In contrast, subjects expressed ambivalence with regard to the source of donor stool, with no clear preference for stool from an anonymous donor vs from a family member.

When asked about concerns regarding FMT, none of the presented options (risk of infection, uncertain effectiveness, or procedural aesthetics) emerged as significantly more important than did others, although the oft-cited concern regarding FMT aesthetics engendered the lowest overall level of concern. In terms of FMT acceptance, 4 subjects (12%) were opposed to the procedure, indicating that they were not at all likely to agree to FMT for all scenarios (defined as a score of 1 or 2 on the 10-point Likert scale) or by terminating the survey because of the questions. However, 15 (44%) indicated that they would certainly agree to FMT (defined as a score of 9 or 10 on the 10-point Likert scale) if their physician recommended it. Physician recommendation for FMT resulted in the highest overall likelihood of agreeing to FMT, a finding in agreement with a previous survey of FMT for CDI.¹⁰ Most subjects indicated likely enrollment in a potential study comparing FMT with standard antimicrobial therapy.

Strengths/Limitations

Study strengths included surveying patients with current CDI, such that patients had personal experience with the disease in question. Use of in-person interviews also resulted in a robust response rate of 81% and allowed subjects to clarify any unclear questions with study personnel. Weaknesses included a relatively small sample size, underrepresentation of women, and lack of detail regarding respondent characteristics. Additionally, capsule delivery of FMT was not assessed since this method of delivery had not been published at the time of survey administration.

Conclusion

This survey of VA patients with CDI suggests that aesthetic concerns are not a critical deterrent for this population, and interest in FMT for the treatment of recurrent CDI exists. Physician recommendation to undergo FMT seems to be the most influential factor affecting the likelihood of agreeing to undergo FMT. These results support the feasibility of conducting clinical trials of FMT in the VA system.

Clostridium difficile (C difficile) infection (CDI) is a leading cause of infectious diarrhea among hospitalized patients and, increasingly, in ambulatory patients.^1,2 The high prevalence of CDI and the high recurrence rates (15%-30%) led the CDC to categorize C difficile as an "urgent" threat (the highest category) in its 2013 Antimicrobial Resistance Threat Report.^3-5 The Infectious Diseases Society of America guideline recommended treatment for CDI is vancomycin or metronidazole; more recent studies also support fidaxomicin use.^4,6,7  

Patients experiencing recurrent CDI are at risk for further recurrences, such that after the third CDI episode, the risk of subsequent recurrences exceeds 50%.⁸ This recurrence rate has stimulated research into other treatments, including fecal microbiota transplantation (FMT). A recent systematic  review of FMT reports that 85% of patients have resolution of symptoms without recurrence after FMT, although this is based on data from case series and 2 small randomized clinical trials.⁹

A commonly cited barrier to FMT is patient acceptance. In response to this concern, a previous survey demonstrated that 81% of respondents would opt for FMT to treat a hypothetical case of recurrent CDI.¹⁰ However, the surveyed population did not have CDI, and the 48% response rate is concerning, since those with a favorable opinion of FMT might be more willing to complete a survey than would other patients. Accordingly, the authors systematically surveyed hospitalized veterans with active CDI to assess their knowledge, attitudes, and opinions about FMT as a treatment for CDI.

Methods

In-person patient interviews were conducted by one of the study authors at the Minneapolis VA Health Care System (MVAHCS), consisting of 13 to 18 questions. Questions addressed any prior CDI episodes and knowledge of the following: CDI, recurrence risk, and FMT; preferred route and location of FMT administration; concerns regarding FMT; likelihood of agreeing to undergo FMT (if available); and likelihood of enrollment in a hypothetical study comparing FMT to standard antibiotic treatment. The survey was developed internally and was not validated. Questions used the Likert-scale (Survey).

Patients with CDI were identified by monitoring for positive C difficile polymerase chain reaction (PCR) stool tests and then screened for inclusion by medical record review. Inclusion criteria were (1) MVAHCS hospitalization; and (2) written informed consent. Exclusion criteria were the inability to communicate or participate in an interview. Patient responses regarding their likelihood of agreeing to FMT for CDI treatment under different circumstances were compared using Wilcoxon rank sum test. These circumstances included FMT for their current episode of CDI, FMT for a subsequent episode, and FMT if recommended by their physician. Possible concerns regarding FMT also were solicited, including infection risk, effectiveness, and procedural aesthetics. The MVAHCS institutional review board approved the study.

Results

Stool PCR tests for CDI were monitored for 158 days from 2013 to 2014 (based on availability of study staff), yielding 106 positive results. Of those, 31 (29%) were from outpatients and not addressed further. Of the 75 positive CDI tests from 66 hospitalized patients (9 patients had duplicate tests), 18 of 66 (27%) were not able to provide consent and were excluded, leaving 48 eligible patients. Six (13%) were missed for logistic reasons (patient at a test or procedure, discharged before approached, etc), leaving 42 patients who were approached for participation. Among these, 34 (81%) consented to participate in the survey. Two subjects (6%) found the topic so unappealing that they terminated the interview.

The majority of enrolled subjects were men (32/34, 94%), with a mean age of 65.3 years (range, 31-89). Eleven subjects (32%) reported a prior CDI episode, with 10 reporting 1 such episode, and the other 2 episodes. Those with prior CDI reported the effect of CDI on their overall quality of life as 5.1 (1 = no limitation, 10 = severe limitation). Respondents were fairly accurate regarding the risk of recurrence after an initial episode of CDI, with the average expectedrecurrence rate estimated at 33%. In contrast, their estimation of the risk of recurrence after a second CDI episode was lower (28%), although the risk of recurrent episodes increases with each CDI recurrence.

Regarding FMT, 5 subjects indicated awareness of the procedure: 2 learning of it from a news source, 1 from family, 1 from a health care provider, and 1 was unsure of the source. After subjects received a description of FMT, their opinions regarding the procedure were elicited. When asked which route of delivery they would prefer if they were to undergo FMT, the 33 subjects who provided a response indicated a strong preference for either enema (15, 45%) or colonoscopy (10, 30%), compared with just 4 (12%) indicating no preference, 2 (6%) choosing nasogastric tube administration, and 2 (6%) indicating that they would not undergo FMT by any route (P < .001).

Regarding the location of FMT administration (hospital setting vs self-administered at home), 31 of 33 respondents (94%) indicated they would prefer FMT to occur in the hospital vs 2 (6%) preferring self-administration at home (P < .001). The preferred source of donor stool was more evenly distributed, with 14 of 32 respondents (44%) indicating a preference for an anonymous donor, 11 preferring a family member (34%), and 7 (21%) with no preference (P = .21).

Subjects were asked about concerns regarding FMT, and asked to rate each on a 5-point Likert scale (1 = not at all concerning; 5 = overwhelming concern). Concerns regarding risk of infection and effectiveness received an average score of 2.74 and 2.72, respectively, whereas concern regarding the aesthetics, or "yuck factor" was slightly lower (2.1: P = NS for all comparisons). Subjects also were asked to rate the likelihood of undergoing FMT, if it were available, for their current episode of CDI, a subsequent episode of CDI, or if their physician recommended undergoing FMT (10 point scale: 1 = not at all likely; 10 = certainly agree to FMT). The mean scores (SD) for agreeing to FMT for the current or a subsequent episode were 4.8 (SD 2.7) and 5.6 (SD 3.0); P = .12, but increased to 7.1 (SD 3.23) if FMT were recommended by their physician (P < .001 for FMT if physician recommended vs FMT for current episode; P = .001 for FMT if physician recommended vs FMT for a subsequent episode). Finally, subjects were asked about the likelihood of enrolling in a study comparing FMT to standard antimicrobial treatment, with answers ranging from 1 (almost certainly would not enroll) to 5 (almost certainly would enroll). Among the 32 respondents to this question, 17 (53%) answered either "probably would enroll" or "almost certainly would enroll," with a mean score of 3.2.  

Discussion

Overall, VA patients with a current episode of CDI were not aware of FMT, with just 15% knowing about the procedure. However, after learning about FMT, patients expressed clear opinions regarding the route and setting of FMT administration, with enema or colonoscopy being the preferred routes, and a hospital the preferred setting. In contrast, subjects expressed ambivalence with regard to the source of donor stool, with no clear preference for stool from an anonymous donor vs from a family member.

When asked about concerns regarding FMT, none of the presented options (risk of infection, uncertain effectiveness, or procedural aesthetics) emerged as significantly more important than did others, although the oft-cited concern regarding FMT aesthetics engendered the lowest overall level of concern. In terms of FMT acceptance, 4 subjects (12%) were opposed to the procedure, indicating that they were not at all likely to agree to FMT for all scenarios (defined as a score of 1 or 2 on the 10-point Likert scale) or by terminating the survey because of the questions. However, 15 (44%) indicated that they would certainly agree to FMT (defined as a score of 9 or 10 on the 10-point Likert scale) if their physician recommended it. Physician recommendation for FMT resulted in the highest overall likelihood of agreeing to FMT, a finding in agreement with a previous survey of FMT for CDI.¹⁰ Most subjects indicated likely enrollment in a potential study comparing FMT with standard antimicrobial therapy.

Strengths/Limitations

Study strengths included surveying patients with current CDI, such that patients had personal experience with the disease in question. Use of in-person interviews also resulted in a robust response rate of 81% and allowed subjects to clarify any unclear questions with study personnel. Weaknesses included a relatively small sample size, underrepresentation of women, and lack of detail regarding respondent characteristics. Additionally, capsule delivery of FMT was not assessed since this method of delivery had not been published at the time of survey administration.

Conclusion

This survey of VA patients with CDI suggests that aesthetic concerns are not a critical deterrent for this population, and interest in FMT for the treatment of recurrent CDI exists. Physician recommendation to undergo FMT seems to be the most influential factor affecting the likelihood of agreeing to undergo FMT. These results support the feasibility of conducting clinical trials of FMT in the VA system.

Cases of the most commonly reported STDs reached an “unprecedented” high in the US in 2015, with > 1.5 million chlamydia cases, nearly 400,000 gonorrhea cases, and nearly 24,000 cases of primary and secondary syphilis.

According to the CDC’s annual Sexually Transmitted Disease Surveillance Report, between 2014 and 2015, the number of syphilis cases rose by 19%, followed by gonorrhea (12.8%) and chlamydia (5.9%). Young people aged 15 to 24 accounted for nearly two thirds of chlamydia diagnoses and half of gonorrhea diagnoses. Men who have sex with men accounted for most new gonorrhea and syphilis cases. The report also notes that antibiotic-resistant gonorrhea may be higher in this group.

Syphilis diagnoses in women jumped by > 27% in 1 year, which presents  a serious risk for infants. For example, reported congenital syphilis (transmitted from a pregnant woman to the baby) rose by 6%.

But all 3 of those STDs are not only treatable, they’re curable with antibiotics. Widespread access to screening and treatment would reduce the spread. Undiagnosed and untreated, these diseases pose severe and often irreversible health consequences, including infertility, chronic pain, and a greater risk of acquiring HIV. The CDC also estimates a ”substantial economic burden” of nearly $16 billion a year.

In recent years, > 50% of state and local STD programs have had their budgets cut, the report notes, and  > 20 health department STD clinics closed their doors in 1 year alone. “STD prevention resources across the nation are stretched thin,” said Dr. Jonathan Mermin, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.

The CDC says an effective national response to the epidemic requires engagement from many players. One suggestion: making screening a standard part of medical care, especially for pregnant women, and integrating STD prevention and treatment into prenatal care and other routine visits.

Cases of the most commonly reported STDs reached an “unprecedented” high in the US in 2015, with > 1.5 million chlamydia cases, nearly 400,000 gonorrhea cases, and nearly 24,000 cases of primary and secondary syphilis.

According to the CDC’s annual Sexually Transmitted Disease Surveillance Report, between 2014 and 2015, the number of syphilis cases rose by 19%, followed by gonorrhea (12.8%) and chlamydia (5.9%). Young people aged 15 to 24 accounted for nearly two thirds of chlamydia diagnoses and half of gonorrhea diagnoses. Men who have sex with men accounted for most new gonorrhea and syphilis cases. The report also notes that antibiotic-resistant gonorrhea may be higher in this group.

Syphilis diagnoses in women jumped by > 27% in 1 year, which presents  a serious risk for infants. For example, reported congenital syphilis (transmitted from a pregnant woman to the baby) rose by 6%.

But all 3 of those STDs are not only treatable, they’re curable with antibiotics. Widespread access to screening and treatment would reduce the spread. Undiagnosed and untreated, these diseases pose severe and often irreversible health consequences, including infertility, chronic pain, and a greater risk of acquiring HIV. The CDC also estimates a ”substantial economic burden” of nearly $16 billion a year.

In recent years, > 50% of state and local STD programs have had their budgets cut, the report notes, and  > 20 health department STD clinics closed their doors in 1 year alone. “STD prevention resources across the nation are stretched thin,” said Dr. Jonathan Mermin, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.

The CDC says an effective national response to the epidemic requires engagement from many players. One suggestion: making screening a standard part of medical care, especially for pregnant women, and integrating STD prevention and treatment into prenatal care and other routine visits.

Cases of the most commonly reported STDs reached an “unprecedented” high in the US in 2015, with > 1.5 million chlamydia cases, nearly 400,000 gonorrhea cases, and nearly 24,000 cases of primary and secondary syphilis.

According to the CDC’s annual Sexually Transmitted Disease Surveillance Report, between 2014 and 2015, the number of syphilis cases rose by 19%, followed by gonorrhea (12.8%) and chlamydia (5.9%). Young people aged 15 to 24 accounted for nearly two thirds of chlamydia diagnoses and half of gonorrhea diagnoses. Men who have sex with men accounted for most new gonorrhea and syphilis cases. The report also notes that antibiotic-resistant gonorrhea may be higher in this group.

Syphilis diagnoses in women jumped by > 27% in 1 year, which presents  a serious risk for infants. For example, reported congenital syphilis (transmitted from a pregnant woman to the baby) rose by 6%.

But all 3 of those STDs are not only treatable, they’re curable with antibiotics. Widespread access to screening and treatment would reduce the spread. Undiagnosed and untreated, these diseases pose severe and often irreversible health consequences, including infertility, chronic pain, and a greater risk of acquiring HIV. The CDC also estimates a ”substantial economic burden” of nearly $16 billion a year.

In recent years, > 50% of state and local STD programs have had their budgets cut, the report notes, and  > 20 health department STD clinics closed their doors in 1 year alone. “STD prevention resources across the nation are stretched thin,” said Dr. Jonathan Mermin, director of CDC’s National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention.

The CDC says an effective national response to the epidemic requires engagement from many players. One suggestion: making screening a standard part of medical care, especially for pregnant women, and integrating STD prevention and treatment into prenatal care and other routine visits.

Vial of heparin

Many surgical patients may be receiving anticoagulants they don’t need, according to research published in Annals of Surgery.

The study challenges standard of care guidelines, which recommend that all general surgery patients receive treatment to prevent venous thromboembolism (VTE).

The new findings suggest that anticoagulants may be unnecessary for most surgical patients and could even be harmful to some.

“A ‘one-size-fits-all approach’ doesn’t always make sense,” said study author Christopher Pannucci, MD, of the University of Utah in Salt Lake City.

“A healthy 35-year-old is very different from someone who is 85 and has a history of clots. Our research indicates that there could be a substantial number of people who are being over-treated.”

Dr Pannucci and his colleagues reviewed data from 13 studies to determine which surgical patients were most likely, and least likely, to benefit from anticoagulants. There was data on VTE events in 11 studies (n=14,776) and data on clinically relevant bleeding in 8 studies (n=7590).

In most of the studies, patients received mechanical VTE prophylaxis, which meant elastic compression and/or sequential compression devices.

Some studies compared mechanical prophylaxis to anticoagulants, including heparin, low-molecular-weight heparin, direct factor Xa inhibitors, direct thrombin inhibitors, warfarin, dextran, and aspirin.

The studies included a broad range of surgical patients, from individuals with few VTE risk factors to those with multiple risk factors, such as obesity, advanced age, and personal or family history of VTE.

The patients were divided into 1 of 5 categories indicating overall VTE risk. Assessment was based on the Caprini score.

VTE risk without anticoagulant treatment

There were 11 studies in which some patients did not receive anticoagulants (n=6085).

Among these patients, those who were classified as having the highest risk of VTE were 14 times more likely to develop VTE than patients in the low-risk category—10.7% vs 0.7%.

These findings were independent of surgery type.

“It was eye-opening to see that there is this huge variability in risk among the overall group of patients that walk into your office,” Dr Pannucci said. “Unless you consider a patient’s risk based on their individual factors, you would never know.”

VTE outcomes by risk score

When given, anticoagulants did significantly reduce the risk of VTE for the overall study population and for high-risk patients.

The odds ratios (ORs) were 0.66 (P=0.001) for the overall population, 0.60 (P=0.04) for patients with Caprini scores of 7 to 8, and 0.41 (P=0.0002) for patients with scores higher than 8.

Unfortunately, anticoagulants did not make a significant difference in VTE rates for mid- or low-risk patients.

The ORs were 0.45 (P=0.31) for patients with Caprini scores of 0 to 2, 1.31 (P=0.57) for patients with scores of 3 to 4, and 0.96 (P=0.85) for patients with scores of 5 to 6.

Risk of bleeding

Anticoagulants significantly increased clinically relevant bleeding for the overall population. The OR was 1.69 (P=0.006).

Patients who received anticoagulants were not significantly more likely to have clinically relevant bleeding if they had risk scores of 0 to 2 (OR=2.47, P=0.61), 3 to 4 (OR=1.05, P=0.87), 5 to 6 (OR=2.10, P=0.06), 7 to 8 (OR=3.15, P=0.16), or >8 (OR=2.31, P=0.16).

“For the first time, we have data that prophylaxis for the highest-risk groups is beneficial, and data that suggests that lower-risk patients may need no prophylaxis,” said study author Peter Henke, MD, of the University of Michigan in Ann Arbor.

He and his colleagues noted, however, that prospective studies are needed to confirm these findings.

Vial of heparin

Many surgical patients may be receiving anticoagulants they don’t need, according to research published in Annals of Surgery.

The study challenges standard of care guidelines, which recommend that all general surgery patients receive treatment to prevent venous thromboembolism (VTE).

The new findings suggest that anticoagulants may be unnecessary for most surgical patients and could even be harmful to some.

“A ‘one-size-fits-all approach’ doesn’t always make sense,” said study author Christopher Pannucci, MD, of the University of Utah in Salt Lake City.

“A healthy 35-year-old is very different from someone who is 85 and has a history of clots. Our research indicates that there could be a substantial number of people who are being over-treated.”

Dr Pannucci and his colleagues reviewed data from 13 studies to determine which surgical patients were most likely, and least likely, to benefit from anticoagulants. There was data on VTE events in 11 studies (n=14,776) and data on clinically relevant bleeding in 8 studies (n=7590).

In most of the studies, patients received mechanical VTE prophylaxis, which meant elastic compression and/or sequential compression devices.

Some studies compared mechanical prophylaxis to anticoagulants, including heparin, low-molecular-weight heparin, direct factor Xa inhibitors, direct thrombin inhibitors, warfarin, dextran, and aspirin.

The studies included a broad range of surgical patients, from individuals with few VTE risk factors to those with multiple risk factors, such as obesity, advanced age, and personal or family history of VTE.

The patients were divided into 1 of 5 categories indicating overall VTE risk. Assessment was based on the Caprini score.

VTE risk without anticoagulant treatment

There were 11 studies in which some patients did not receive anticoagulants (n=6085).

Among these patients, those who were classified as having the highest risk of VTE were 14 times more likely to develop VTE than patients in the low-risk category—10.7% vs 0.7%.

These findings were independent of surgery type.

“It was eye-opening to see that there is this huge variability in risk among the overall group of patients that walk into your office,” Dr Pannucci said. “Unless you consider a patient’s risk based on their individual factors, you would never know.”

VTE outcomes by risk score

When given, anticoagulants did significantly reduce the risk of VTE for the overall study population and for high-risk patients.

The odds ratios (ORs) were 0.66 (P=0.001) for the overall population, 0.60 (P=0.04) for patients with Caprini scores of 7 to 8, and 0.41 (P=0.0002) for patients with scores higher than 8.

Unfortunately, anticoagulants did not make a significant difference in VTE rates for mid- or low-risk patients.

The ORs were 0.45 (P=0.31) for patients with Caprini scores of 0 to 2, 1.31 (P=0.57) for patients with scores of 3 to 4, and 0.96 (P=0.85) for patients with scores of 5 to 6.

Risk of bleeding

Anticoagulants significantly increased clinically relevant bleeding for the overall population. The OR was 1.69 (P=0.006).

Patients who received anticoagulants were not significantly more likely to have clinically relevant bleeding if they had risk scores of 0 to 2 (OR=2.47, P=0.61), 3 to 4 (OR=1.05, P=0.87), 5 to 6 (OR=2.10, P=0.06), 7 to 8 (OR=3.15, P=0.16), or >8 (OR=2.31, P=0.16).

“For the first time, we have data that prophylaxis for the highest-risk groups is beneficial, and data that suggests that lower-risk patients may need no prophylaxis,” said study author Peter Henke, MD, of the University of Michigan in Ann Arbor.

He and his colleagues noted, however, that prospective studies are needed to confirm these findings.

Vial of heparin

Many surgical patients may be receiving anticoagulants they don’t need, according to research published in Annals of Surgery.

The study challenges standard of care guidelines, which recommend that all general surgery patients receive treatment to prevent venous thromboembolism (VTE).

The new findings suggest that anticoagulants may be unnecessary for most surgical patients and could even be harmful to some.

“A ‘one-size-fits-all approach’ doesn’t always make sense,” said study author Christopher Pannucci, MD, of the University of Utah in Salt Lake City.

“A healthy 35-year-old is very different from someone who is 85 and has a history of clots. Our research indicates that there could be a substantial number of people who are being over-treated.”

Dr Pannucci and his colleagues reviewed data from 13 studies to determine which surgical patients were most likely, and least likely, to benefit from anticoagulants. There was data on VTE events in 11 studies (n=14,776) and data on clinically relevant bleeding in 8 studies (n=7590).

In most of the studies, patients received mechanical VTE prophylaxis, which meant elastic compression and/or sequential compression devices.

Some studies compared mechanical prophylaxis to anticoagulants, including heparin, low-molecular-weight heparin, direct factor Xa inhibitors, direct thrombin inhibitors, warfarin, dextran, and aspirin.

The studies included a broad range of surgical patients, from individuals with few VTE risk factors to those with multiple risk factors, such as obesity, advanced age, and personal or family history of VTE.

The patients were divided into 1 of 5 categories indicating overall VTE risk. Assessment was based on the Caprini score.

VTE risk without anticoagulant treatment

There were 11 studies in which some patients did not receive anticoagulants (n=6085).

Among these patients, those who were classified as having the highest risk of VTE were 14 times more likely to develop VTE than patients in the low-risk category—10.7% vs 0.7%.

These findings were independent of surgery type.

“It was eye-opening to see that there is this huge variability in risk among the overall group of patients that walk into your office,” Dr Pannucci said. “Unless you consider a patient’s risk based on their individual factors, you would never know.”

VTE outcomes by risk score

When given, anticoagulants did significantly reduce the risk of VTE for the overall study population and for high-risk patients.

The odds ratios (ORs) were 0.66 (P=0.001) for the overall population, 0.60 (P=0.04) for patients with Caprini scores of 7 to 8, and 0.41 (P=0.0002) for patients with scores higher than 8.

Unfortunately, anticoagulants did not make a significant difference in VTE rates for mid- or low-risk patients.

The ORs were 0.45 (P=0.31) for patients with Caprini scores of 0 to 2, 1.31 (P=0.57) for patients with scores of 3 to 4, and 0.96 (P=0.85) for patients with scores of 5 to 6.

Risk of bleeding

Anticoagulants significantly increased clinically relevant bleeding for the overall population. The OR was 1.69 (P=0.006).

Patients who received anticoagulants were not significantly more likely to have clinically relevant bleeding if they had risk scores of 0 to 2 (OR=2.47, P=0.61), 3 to 4 (OR=1.05, P=0.87), 5 to 6 (OR=2.10, P=0.06), 7 to 8 (OR=3.15, P=0.16), or >8 (OR=2.31, P=0.16).

“For the first time, we have data that prophylaxis for the highest-risk groups is beneficial, and data that suggests that lower-risk patients may need no prophylaxis,” said study author Peter Henke, MD, of the University of Michigan in Ann Arbor.

He and his colleagues noted, however, that prospective studies are needed to confirm these findings.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

A new study shows that 5-year survival rates for US patients with hematologic malignancies have increased greatly since the 1950s, but there is still room for improvement, particularly for patients with acute myeloid leukemia (AML).

Researchers found the absolute difference in improvement for 5-year survival from 1950-1954 to 2008-2013 ranged from 38.2% for non-Hodgkin lymphoma (NHL) to 56.6% for Hodgkin lymphoma.

And although the 5-year survival rate for Hodgkin lymphoma patients reached 86.6% for 2008-2013, the 5-year survival rate for patients with AML only reached 27.4%.

This study also revealed large disparities in overall cancer mortality rates between different counties across the country.

Ali H. Mokdad, PhD, of the Institute for Health Metrics and Evaluation in Seattle, Washington, and his colleagues reported these findings in JAMA.

Overall cancer deaths

The researchers found there were 19,511,910 cancer deaths recorded in the US between 1980 and 2014. Cancer mortality decreased by 20.1% between 1980 and 2014, from 240.2 deaths per 100,000 people to 192.0 deaths per 100,000 people.

In 1980, cancer mortality ranged from 130.6 per 100,000 in Summit County, Colorado, to 386.9 per 100,000 in North Slope Borough, Alaska.

In 2014, cancer mortality ranged from 70.7 per 100,000 in Summit County, Colorado, to 503.1 per 100,000 in Union County, Florida.

“Such significant disparities among US counties is unacceptable,” Dr Mokdad said. “Every person should have access to early screenings for cancer, as well as adequate treatment.”

Mortality rates for hematologic malignancies

In 2014, the mortality rates, per 100,000 people, for hematologic malignancies were:

• 0.4 for Hodgkin lymphoma (rank out of all cancers, 27)
• 8.3 for NHL (rank, 7)
• 3.9 for multiple myeloma (rank, 16)
• 9.0 for all leukemias (rank, 6)
• 0.7 for acute lymphoid leukemia (ALL)
• 2.6 for chronic lymphoid leukemia (CLL)
• 5.1 for AML
• 0.6 for chronic myeloid leukemia (CML).

The leukemia subtypes were not assigned a rank.

5-year survival rates for hematologic malignancies

Hodgkin lymphoma

• 30% for 1950-54
• 68.6% for 1973-77
• 72.1% for 1978-82
• 86.6% for 2008-2013
• Absolute difference (between the first and latest year of data), 56.6%.

NHL

• 33% for 1950-54
• 45.3% for 1973-77
• 48.7% for 1978-82
• 71.2% for 2008-2013
• Absolute difference, 38.2%.

Multiple myeloma

• 6% for 1950-54
• 23.4% for 1973-77
• 26.6% for 1978-82
• 49.8% for 2008-2013
• Absolute difference, 43.8%.

Leukemia

• 10% for 1950-54
• 34% for 1973-77
• 36.3% for 1978-82
• 60.1% for 2008-2013
• Absolute difference, 50.1%.

ALL

• 39.2% for 1973-77
• 50.5% for 1978-82
• 68.1% for 2008-2013
• Absolute difference, 28.9%.

CLL

• 67% for 1973-77
• 66.3% for 1978-82
• 82.5% for 2008-2013
• Absolute difference, 15.5%.

AML

• 6.2% for 1973-77
• 7.9% for 1978-82
• 27.4% for 2008-2013
• Absolute difference, 21.2%.

CML

• 21.1% for 1973-77
• 25.8% for 1978-82
• 66.4% for 2008-2013
• Absolute difference, 45.3%.

For the leukemia subtypes, there was no data for 1950 to 1954.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

A new study shows that 5-year survival rates for US patients with hematologic malignancies have increased greatly since the 1950s, but there is still room for improvement, particularly for patients with acute myeloid leukemia (AML).

Researchers found the absolute difference in improvement for 5-year survival from 1950-1954 to 2008-2013 ranged from 38.2% for non-Hodgkin lymphoma (NHL) to 56.6% for Hodgkin lymphoma.

And although the 5-year survival rate for Hodgkin lymphoma patients reached 86.6% for 2008-2013, the 5-year survival rate for patients with AML only reached 27.4%.

This study also revealed large disparities in overall cancer mortality rates between different counties across the country.

Ali H. Mokdad, PhD, of the Institute for Health Metrics and Evaluation in Seattle, Washington, and his colleagues reported these findings in JAMA.

Overall cancer deaths

The researchers found there were 19,511,910 cancer deaths recorded in the US between 1980 and 2014. Cancer mortality decreased by 20.1% between 1980 and 2014, from 240.2 deaths per 100,000 people to 192.0 deaths per 100,000 people.

In 1980, cancer mortality ranged from 130.6 per 100,000 in Summit County, Colorado, to 386.9 per 100,000 in North Slope Borough, Alaska.

In 2014, cancer mortality ranged from 70.7 per 100,000 in Summit County, Colorado, to 503.1 per 100,000 in Union County, Florida.

“Such significant disparities among US counties is unacceptable,” Dr Mokdad said. “Every person should have access to early screenings for cancer, as well as adequate treatment.”

Mortality rates for hematologic malignancies

In 2014, the mortality rates, per 100,000 people, for hematologic malignancies were:

• 0.4 for Hodgkin lymphoma (rank out of all cancers, 27)
• 8.3 for NHL (rank, 7)
• 3.9 for multiple myeloma (rank, 16)
• 9.0 for all leukemias (rank, 6)
• 0.7 for acute lymphoid leukemia (ALL)
• 2.6 for chronic lymphoid leukemia (CLL)
• 5.1 for AML
• 0.6 for chronic myeloid leukemia (CML).

The leukemia subtypes were not assigned a rank.

5-year survival rates for hematologic malignancies

Hodgkin lymphoma

• 30% for 1950-54
• 68.6% for 1973-77
• 72.1% for 1978-82
• 86.6% for 2008-2013
• Absolute difference (between the first and latest year of data), 56.6%.

NHL

• 33% for 1950-54
• 45.3% for 1973-77
• 48.7% for 1978-82
• 71.2% for 2008-2013
• Absolute difference, 38.2%.

Multiple myeloma

• 6% for 1950-54
• 23.4% for 1973-77
• 26.6% for 1978-82
• 49.8% for 2008-2013
• Absolute difference, 43.8%.

Leukemia

• 10% for 1950-54
• 34% for 1973-77
• 36.3% for 1978-82
• 60.1% for 2008-2013
• Absolute difference, 50.1%.

ALL

• 39.2% for 1973-77
• 50.5% for 1978-82
• 68.1% for 2008-2013
• Absolute difference, 28.9%.

CLL

• 67% for 1973-77
• 66.3% for 1978-82
• 82.5% for 2008-2013
• Absolute difference, 15.5%.

AML

• 6.2% for 1973-77
• 7.9% for 1978-82
• 27.4% for 2008-2013
• Absolute difference, 21.2%.

CML

• 21.1% for 1973-77
• 25.8% for 1978-82
• 66.4% for 2008-2013
• Absolute difference, 45.3%.

For the leukemia subtypes, there was no data for 1950 to 1954.

Cancer patient receiving
chemotherapy
Photo by Rhoda Baer

A new study shows that 5-year survival rates for US patients with hematologic malignancies have increased greatly since the 1950s, but there is still room for improvement, particularly for patients with acute myeloid leukemia (AML).

Researchers found the absolute difference in improvement for 5-year survival from 1950-1954 to 2008-2013 ranged from 38.2% for non-Hodgkin lymphoma (NHL) to 56.6% for Hodgkin lymphoma.

And although the 5-year survival rate for Hodgkin lymphoma patients reached 86.6% for 2008-2013, the 5-year survival rate for patients with AML only reached 27.4%.

This study also revealed large disparities in overall cancer mortality rates between different counties across the country.

Ali H. Mokdad, PhD, of the Institute for Health Metrics and Evaluation in Seattle, Washington, and his colleagues reported these findings in JAMA.

Overall cancer deaths

The researchers found there were 19,511,910 cancer deaths recorded in the US between 1980 and 2014. Cancer mortality decreased by 20.1% between 1980 and 2014, from 240.2 deaths per 100,000 people to 192.0 deaths per 100,000 people.

In 1980, cancer mortality ranged from 130.6 per 100,000 in Summit County, Colorado, to 386.9 per 100,000 in North Slope Borough, Alaska.

In 2014, cancer mortality ranged from 70.7 per 100,000 in Summit County, Colorado, to 503.1 per 100,000 in Union County, Florida.

“Such significant disparities among US counties is unacceptable,” Dr Mokdad said. “Every person should have access to early screenings for cancer, as well as adequate treatment.”

Mortality rates for hematologic malignancies

In 2014, the mortality rates, per 100,000 people, for hematologic malignancies were:

• 0.4 for Hodgkin lymphoma (rank out of all cancers, 27)
• 8.3 for NHL (rank, 7)
• 3.9 for multiple myeloma (rank, 16)
• 9.0 for all leukemias (rank, 6)
• 0.7 for acute lymphoid leukemia (ALL)
• 2.6 for chronic lymphoid leukemia (CLL)
• 5.1 for AML
• 0.6 for chronic myeloid leukemia (CML).

The leukemia subtypes were not assigned a rank.

5-year survival rates for hematologic malignancies

Hodgkin lymphoma

• 30% for 1950-54
• 68.6% for 1973-77
• 72.1% for 1978-82
• 86.6% for 2008-2013
• Absolute difference (between the first and latest year of data), 56.6%.

NHL

• 33% for 1950-54
• 45.3% for 1973-77
• 48.7% for 1978-82
• 71.2% for 2008-2013
• Absolute difference, 38.2%.

Multiple myeloma

• 6% for 1950-54
• 23.4% for 1973-77
• 26.6% for 1978-82
• 49.8% for 2008-2013
• Absolute difference, 43.8%.

Leukemia

• 10% for 1950-54
• 34% for 1973-77
• 36.3% for 1978-82
• 60.1% for 2008-2013
• Absolute difference, 50.1%.

ALL

• 39.2% for 1973-77
• 50.5% for 1978-82
• 68.1% for 2008-2013
• Absolute difference, 28.9%.

CLL

• 67% for 1973-77
• 66.3% for 1978-82
• 82.5% for 2008-2013
• Absolute difference, 15.5%.

AML

• 6.2% for 1973-77
• 7.9% for 1978-82
• 27.4% for 2008-2013
• Absolute difference, 21.2%.

CML

• 21.1% for 1973-77
• 25.8% for 1978-82
• 66.4% for 2008-2013
• Absolute difference, 45.3%.

For the leukemia subtypes, there was no data for 1950 to 1954.

Lenalidomide (Revlimid®)
Photo courtesy of Celgene

Health Canada has expanded the approved indication for lenalidomide (Revlimid®) to include the treatment of patients with multiple myeloma (MM).

Lenalidomide is now approved for use in combination with dexamethasone to treat patients newly diagnosed with MM who are not eligible for stem cell transplant.

Lenalidomide was previously approved in Canada for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality, with or without additional cytogenetic abnormalities.

Lenalidomide is a product of Celgene Corporation.

“The expanded indication of Revlimid® provides [MM] patients with a treatment much earlier in their disease and offers this patient population an all-oral, melphalan-free option for a disease that continues to be difficult to treat,” said Donna Reece, MD, of Princess Margaret Hospital in Toronto, Ontario, Canada.

The expanded approval of lenalidomide is based on safety and efficacy results from the phase 3 FIRST trial. Updated results from this study were published in the Journal of Clinical Oncology last November.

The trial included 1623 patients with newly diagnosed MM who were not eligible for stem cell transplant.

Patients were randomized to receive:

• Lenalidomide and low-dose dexamethasone (Rd) in 28-day cycles until disease progression (n=535)
• 18 cycles of Rd (Rd18) for 72 weeks (n=541)
• Melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

In the intent-to-treat population, the overall response rate was 81% for the continuous Rd group, 79% for the Rd18 group, and 67% in the MPT group. The complete response rates were 21%, 20%, and 12%, respectively.

The median progression-free survival (PFS) was 26.0 months in the continuous Rd group, 21.0 months in the Rd18 group, and 21.9 months in the MPT group. At 4 years, the PFS rates were 33%, 14%, and 13%, respectively.

The median overall survival (OS) was 58.9 months in the continuous Rd group, 56.7 months in the Rd18 group, and 48.5 months in the MPT group. At 4 years, the OS rates were 60%, 57%, and 51%, respectively.

The most frequent grade 3/4 hematologic treatment-emergent adverse events were neutropenia and anemia. The rate of grade 3/4 neutropenia was higher in the MPT group than the continuous Rd or Rd18 groups.

Infections were the most common grade 3/4 non-hematologic treatment-emergent adverse events. The rate of grade 3/4 infections was higher in the Rd groups than the MPT group.

“With this new clinical evidence, we know that keeping newly diagnosed multiple myeloma patients on Revlimid® may help delay disease progression and reduce the risk of death,” Dr Reece said. “As such, we are looking forward to having Revlimid® as a key option in the first-line setting for the appropriate patients.”

Lenalidomide (Revlimid®)
Photo courtesy of Celgene

Health Canada has expanded the approved indication for lenalidomide (Revlimid®) to include the treatment of patients with multiple myeloma (MM).

Lenalidomide is now approved for use in combination with dexamethasone to treat patients newly diagnosed with MM who are not eligible for stem cell transplant.

Lenalidomide was previously approved in Canada for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality, with or without additional cytogenetic abnormalities.

Lenalidomide is a product of Celgene Corporation.

“The expanded indication of Revlimid® provides [MM] patients with a treatment much earlier in their disease and offers this patient population an all-oral, melphalan-free option for a disease that continues to be difficult to treat,” said Donna Reece, MD, of Princess Margaret Hospital in Toronto, Ontario, Canada.

The expanded approval of lenalidomide is based on safety and efficacy results from the phase 3 FIRST trial. Updated results from this study were published in the Journal of Clinical Oncology last November.

The trial included 1623 patients with newly diagnosed MM who were not eligible for stem cell transplant.

Patients were randomized to receive:

• Lenalidomide and low-dose dexamethasone (Rd) in 28-day cycles until disease progression (n=535)
• 18 cycles of Rd (Rd18) for 72 weeks (n=541)
• Melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

In the intent-to-treat population, the overall response rate was 81% for the continuous Rd group, 79% for the Rd18 group, and 67% in the MPT group. The complete response rates were 21%, 20%, and 12%, respectively.

The median progression-free survival (PFS) was 26.0 months in the continuous Rd group, 21.0 months in the Rd18 group, and 21.9 months in the MPT group. At 4 years, the PFS rates were 33%, 14%, and 13%, respectively.

The median overall survival (OS) was 58.9 months in the continuous Rd group, 56.7 months in the Rd18 group, and 48.5 months in the MPT group. At 4 years, the OS rates were 60%, 57%, and 51%, respectively.

The most frequent grade 3/4 hematologic treatment-emergent adverse events were neutropenia and anemia. The rate of grade 3/4 neutropenia was higher in the MPT group than the continuous Rd or Rd18 groups.

Infections were the most common grade 3/4 non-hematologic treatment-emergent adverse events. The rate of grade 3/4 infections was higher in the Rd groups than the MPT group.

“With this new clinical evidence, we know that keeping newly diagnosed multiple myeloma patients on Revlimid® may help delay disease progression and reduce the risk of death,” Dr Reece said. “As such, we are looking forward to having Revlimid® as a key option in the first-line setting for the appropriate patients.”

Lenalidomide (Revlimid®)
Photo courtesy of Celgene

Health Canada has expanded the approved indication for lenalidomide (Revlimid®) to include the treatment of patients with multiple myeloma (MM).

Lenalidomide is now approved for use in combination with dexamethasone to treat patients newly diagnosed with MM who are not eligible for stem cell transplant.

Lenalidomide was previously approved in Canada for the treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality, with or without additional cytogenetic abnormalities.

Lenalidomide is a product of Celgene Corporation.

“The expanded indication of Revlimid® provides [MM] patients with a treatment much earlier in their disease and offers this patient population an all-oral, melphalan-free option for a disease that continues to be difficult to treat,” said Donna Reece, MD, of Princess Margaret Hospital in Toronto, Ontario, Canada.

The expanded approval of lenalidomide is based on safety and efficacy results from the phase 3 FIRST trial. Updated results from this study were published in the Journal of Clinical Oncology last November.

The trial included 1623 patients with newly diagnosed MM who were not eligible for stem cell transplant.

Patients were randomized to receive:

• Lenalidomide and low-dose dexamethasone (Rd) in 28-day cycles until disease progression (n=535)
• 18 cycles of Rd (Rd18) for 72 weeks (n=541)
• Melphalan, prednisone, and thalidomide (MPT) for 72 weeks (n=547).

In the intent-to-treat population, the overall response rate was 81% for the continuous Rd group, 79% for the Rd18 group, and 67% in the MPT group. The complete response rates were 21%, 20%, and 12%, respectively.

The median progression-free survival (PFS) was 26.0 months in the continuous Rd group, 21.0 months in the Rd18 group, and 21.9 months in the MPT group. At 4 years, the PFS rates were 33%, 14%, and 13%, respectively.

The median overall survival (OS) was 58.9 months in the continuous Rd group, 56.7 months in the Rd18 group, and 48.5 months in the MPT group. At 4 years, the OS rates were 60%, 57%, and 51%, respectively.

The most frequent grade 3/4 hematologic treatment-emergent adverse events were neutropenia and anemia. The rate of grade 3/4 neutropenia was higher in the MPT group than the continuous Rd or Rd18 groups.

Infections were the most common grade 3/4 non-hematologic treatment-emergent adverse events. The rate of grade 3/4 infections was higher in the Rd groups than the MPT group.

“With this new clinical evidence, we know that keeping newly diagnosed multiple myeloma patients on Revlimid® may help delay disease progression and reduce the risk of death,” Dr Reece said. “As such, we are looking forward to having Revlimid® as a key option in the first-line setting for the appropriate patients.”

Clinical question: Does hydrocortisone therapy prevent progression to septic shock in patients with severe sepsis without shock?

Background: Current sepsis management guidelines recommend use of hydrocortisone in patients with septic shock who are unable to restore hemodynamic stability with IV fluids and pressors; current guidelines also recommend against use of corticosteroids without shock. However, these recommendations are based on two RCTs and remain controversial.

Study design: Multicenter, placebo-controlled, double-blind RCT.

Setting: Thirty-four intermediate or intensive care units in German university and community hospitals.

Synopsis: Investigators randomly assigned 380 patients to hydrocortisone or placebo. Patients were included if they had clinical evidence of infection, evidence of SIRS (systemic inflammatory response syndrome), and evidence of organ dysfunction. Patients were excluded if they had any of the following: sepsis-induced hypotension, separate indication for systemic steroid use, or hypersensitivity to steroids. Primary outcome was the occurrence of septic shock within 14 days. Secondary outcomes included time to septic shock or death, death in the ICU or hospital, organ dysfunction, ventilator therapy, renal replacement therapy, and secondary infection.

Study results showed no significant difference in the primary outcome between groups, or in any of the secondary outcomes. In a post-hoc analysis, there was more hyperglycemia and less delirium in the study group.

Study limitations are inclusion of patients only after consent, potentially missing early septic shock, and the fact that many analyses were done post-hoc.

Bottom line: Steroids should be avoided in severe sepsis without shock.

Citation: Keh D, Trips E, Marx G, et al. Effect of hydrocortisone on development of shock among patients with severe sepsis. JAMA. 2016;316(17):1775-85.
 

Dr. Graves is an assistant professor at the University of Utah School of Medicine and associate program director of quality and patient safety for the University of Utah Internal Medicine residency training program.

Clinical question: Does hydrocortisone therapy prevent progression to septic shock in patients with severe sepsis without shock?

Background: Current sepsis management guidelines recommend use of hydrocortisone in patients with septic shock who are unable to restore hemodynamic stability with IV fluids and pressors; current guidelines also recommend against use of corticosteroids without shock. However, these recommendations are based on two RCTs and remain controversial.

Study design: Multicenter, placebo-controlled, double-blind RCT.

Setting: Thirty-four intermediate or intensive care units in German university and community hospitals.

Synopsis: Investigators randomly assigned 380 patients to hydrocortisone or placebo. Patients were included if they had clinical evidence of infection, evidence of SIRS (systemic inflammatory response syndrome), and evidence of organ dysfunction. Patients were excluded if they had any of the following: sepsis-induced hypotension, separate indication for systemic steroid use, or hypersensitivity to steroids. Primary outcome was the occurrence of septic shock within 14 days. Secondary outcomes included time to septic shock or death, death in the ICU or hospital, organ dysfunction, ventilator therapy, renal replacement therapy, and secondary infection.

Study results showed no significant difference in the primary outcome between groups, or in any of the secondary outcomes. In a post-hoc analysis, there was more hyperglycemia and less delirium in the study group.

Study limitations are inclusion of patients only after consent, potentially missing early septic shock, and the fact that many analyses were done post-hoc.

Bottom line: Steroids should be avoided in severe sepsis without shock.

Citation: Keh D, Trips E, Marx G, et al. Effect of hydrocortisone on development of shock among patients with severe sepsis. JAMA. 2016;316(17):1775-85.
 

Dr. Graves is an assistant professor at the University of Utah School of Medicine and associate program director of quality and patient safety for the University of Utah Internal Medicine residency training program.

Clinical question: Does hydrocortisone therapy prevent progression to septic shock in patients with severe sepsis without shock?

Background: Current sepsis management guidelines recommend use of hydrocortisone in patients with septic shock who are unable to restore hemodynamic stability with IV fluids and pressors; current guidelines also recommend against use of corticosteroids without shock. However, these recommendations are based on two RCTs and remain controversial.

Study design: Multicenter, placebo-controlled, double-blind RCT.

Setting: Thirty-four intermediate or intensive care units in German university and community hospitals.

Synopsis: Investigators randomly assigned 380 patients to hydrocortisone or placebo. Patients were included if they had clinical evidence of infection, evidence of SIRS (systemic inflammatory response syndrome), and evidence of organ dysfunction. Patients were excluded if they had any of the following: sepsis-induced hypotension, separate indication for systemic steroid use, or hypersensitivity to steroids. Primary outcome was the occurrence of septic shock within 14 days. Secondary outcomes included time to septic shock or death, death in the ICU or hospital, organ dysfunction, ventilator therapy, renal replacement therapy, and secondary infection.

Study results showed no significant difference in the primary outcome between groups, or in any of the secondary outcomes. In a post-hoc analysis, there was more hyperglycemia and less delirium in the study group.

Study limitations are inclusion of patients only after consent, potentially missing early septic shock, and the fact that many analyses were done post-hoc.

Bottom line: Steroids should be avoided in severe sepsis without shock.

Citation: Keh D, Trips E, Marx G, et al. Effect of hydrocortisone on development of shock among patients with severe sepsis. JAMA. 2016;316(17):1775-85.
 

Dr. Graves is an assistant professor at the University of Utah School of Medicine and associate program director of quality and patient safety for the University of Utah Internal Medicine residency training program.