To the Editor:

Nevus of Ota, also known as oculodermal melanocytosis or nevus fuscoceruleus ophthalmomaxillaris, is a hamartoma of dermal melanocytes that is characterized by a unilateral or bilateral blue-brown, speckled patch usually involving the malar, periorbital, temple, and/or forehead regions of the face.¹ It also may affect the sclera, conjunctiva, retinas, corneas, ocular muscles, periosteum, and retrobulbar fat corresponding to the distribution of the ophthalmic (V1) and maxillary (V2) divisions of the trigeminal nerve.

Examination of the oral cavity in the setting of nevus of Ota is imperative, as it can present as a developmental lesion of the oral mucosa.² Involvement of the hard palate is rare but has been observed.^3-5 We present a case of blue-pigmented macules in the upper right periorbital region with involvement of the hard palate that were diagnosed as nevus of Ota.

A 34-year-old Indian man presented with progressive, asymptomatic, ashy blue macules in the upper right periorbital region that had been present since birth. The pigmented macules had gradually increased to cover the infraorbital, maxillary, and temporal regions of the right side of the face with involvement of the conjunctiva and sclera (Figure 1).

Examination of the mucous membrane of the hard palate revealed several blue-pigmented macules with ill-defined borders merging into the surrounding mucosa (Figure 2). Ocular tension was normal and slit-lamp examination of the right eye did not reveal any abnormalities. Hematoxylin and eosin–stained sections prepared from a biopsy of the oral mucosa on the hard palate showed numerous elongated, fusiform, dendritic melanocytes in small aggregates scattered widely between the bundles of collagen in the papillary to midreticular dermis (Figure 3). On histology, the melanocytes stained positive for S100 protein (Figure 4) and human melanoma black 45. No evidence indicative of malignancy was found. The stratified squamous epithelium was unremarkable except for the presence of mild perivascular lymphocytic infiltrate in the subepithelial tissue. A diagnosis of nevus of Ota with involvement of the hard palate was made.

Cutaneous macules may enlarge slowly, become deeper in color, and persist throughout the patient’s life. Its pathogenesis is not known, but it is speculated that nevus of Ota is caused by faulty migration of melanoblasts from the neural crest to the skin. Nevus of Ito also is a dermal melanocytic aberration that exclusively affects the shoulders and often occurs in association with nevus of Ota.¹

Ashy or slate-blue pigmentation in individuals with skin of color (eg, Fitzpatrick skin type V) is uncommon, as this discoloration usually is seen in fair-skinned individuals (eg, Fitzpatrick skin type II).⁶ Occasionally, blue-pigmented lesions of the oral mucosa may be seen in nevus of Ota (as in our patient) and are considered developmental; therefore, examination of the oral cavity is suggested when patients present with blue-pigmented lesions in the facial region. Although this finding is rare, several other cases of blue-pigmented macules on the palatal mucosa have been reported.^3-5

The diagnosis of nevus of Ota should be confirmed by histopathology and can be classified into 5 types according to the distribution of melanocytes, including (1) superficial, (2) superficial dominant, (3) diffuse, (4) deep dominant, and (5) deep.⁷ The diagnosis of nevus of Ota can be made based on its characteristic morphology; however, nevus of 
Ito, Mongolian spots, melanoma, fixed drug eruptions,⁸ and lichen planus pigmantosus should also 
be ruled out.⁹

Nevus of Ota is a well-established entity that should be considered when ashy or slate-blue pigmentation is noted along the branches of the ophthalmic and maxillary divisions of the trigeminal nerve. Diagnosis is largely clinical, but should be confirmed on histopathology and immunohistochemistry. Possible concomitant involvement of the buccal mucosa and/or the hard palate warrants a thorough examination of the oral cavity in the setting of nevus of Ota to identify oral mucosal lesions. Histopathology is essential to confirm its status as well as to exclude melanoma.

To the Editor:

Nevus of Ota, also known as oculodermal melanocytosis or nevus fuscoceruleus ophthalmomaxillaris, is a hamartoma of dermal melanocytes that is characterized by a unilateral or bilateral blue-brown, speckled patch usually involving the malar, periorbital, temple, and/or forehead regions of the face.¹ It also may affect the sclera, conjunctiva, retinas, corneas, ocular muscles, periosteum, and retrobulbar fat corresponding to the distribution of the ophthalmic (V1) and maxillary (V2) divisions of the trigeminal nerve.

Examination of the oral cavity in the setting of nevus of Ota is imperative, as it can present as a developmental lesion of the oral mucosa.² Involvement of the hard palate is rare but has been observed.^3-5 We present a case of blue-pigmented macules in the upper right periorbital region with involvement of the hard palate that were diagnosed as nevus of Ota.

A 34-year-old Indian man presented with progressive, asymptomatic, ashy blue macules in the upper right periorbital region that had been present since birth. The pigmented macules had gradually increased to cover the infraorbital, maxillary, and temporal regions of the right side of the face with involvement of the conjunctiva and sclera (Figure 1).

Examination of the mucous membrane of the hard palate revealed several blue-pigmented macules with ill-defined borders merging into the surrounding mucosa (Figure 2). Ocular tension was normal and slit-lamp examination of the right eye did not reveal any abnormalities. Hematoxylin and eosin–stained sections prepared from a biopsy of the oral mucosa on the hard palate showed numerous elongated, fusiform, dendritic melanocytes in small aggregates scattered widely between the bundles of collagen in the papillary to midreticular dermis (Figure 3). On histology, the melanocytes stained positive for S100 protein (Figure 4) and human melanoma black 45. No evidence indicative of malignancy was found. The stratified squamous epithelium was unremarkable except for the presence of mild perivascular lymphocytic infiltrate in the subepithelial tissue. A diagnosis of nevus of Ota with involvement of the hard palate was made.

Cutaneous macules may enlarge slowly, become deeper in color, and persist throughout the patient’s life. Its pathogenesis is not known, but it is speculated that nevus of Ota is caused by faulty migration of melanoblasts from the neural crest to the skin. Nevus of Ito also is a dermal melanocytic aberration that exclusively affects the shoulders and often occurs in association with nevus of Ota.¹

Ashy or slate-blue pigmentation in individuals with skin of color (eg, Fitzpatrick skin type V) is uncommon, as this discoloration usually is seen in fair-skinned individuals (eg, Fitzpatrick skin type II).⁶ Occasionally, blue-pigmented lesions of the oral mucosa may be seen in nevus of Ota (as in our patient) and are considered developmental; therefore, examination of the oral cavity is suggested when patients present with blue-pigmented lesions in the facial region. Although this finding is rare, several other cases of blue-pigmented macules on the palatal mucosa have been reported.^3-5

The diagnosis of nevus of Ota should be confirmed by histopathology and can be classified into 5 types according to the distribution of melanocytes, including (1) superficial, (2) superficial dominant, (3) diffuse, (4) deep dominant, and (5) deep.⁷ The diagnosis of nevus of Ota can be made based on its characteristic morphology; however, nevus of 
Ito, Mongolian spots, melanoma, fixed drug eruptions,⁸ and lichen planus pigmantosus should also 
be ruled out.⁹

Nevus of Ota is a well-established entity that should be considered when ashy or slate-blue pigmentation is noted along the branches of the ophthalmic and maxillary divisions of the trigeminal nerve. Diagnosis is largely clinical, but should be confirmed on histopathology and immunohistochemistry. Possible concomitant involvement of the buccal mucosa and/or the hard palate warrants a thorough examination of the oral cavity in the setting of nevus of Ota to identify oral mucosal lesions. Histopathology is essential to confirm its status as well as to exclude melanoma.

To the Editor:

Nevus of Ota, also known as oculodermal melanocytosis or nevus fuscoceruleus ophthalmomaxillaris, is a hamartoma of dermal melanocytes that is characterized by a unilateral or bilateral blue-brown, speckled patch usually involving the malar, periorbital, temple, and/or forehead regions of the face.¹ It also may affect the sclera, conjunctiva, retinas, corneas, ocular muscles, periosteum, and retrobulbar fat corresponding to the distribution of the ophthalmic (V1) and maxillary (V2) divisions of the trigeminal nerve.

Examination of the oral cavity in the setting of nevus of Ota is imperative, as it can present as a developmental lesion of the oral mucosa.² Involvement of the hard palate is rare but has been observed.^3-5 We present a case of blue-pigmented macules in the upper right periorbital region with involvement of the hard palate that were diagnosed as nevus of Ota.

A 34-year-old Indian man presented with progressive, asymptomatic, ashy blue macules in the upper right periorbital region that had been present since birth. The pigmented macules had gradually increased to cover the infraorbital, maxillary, and temporal regions of the right side of the face with involvement of the conjunctiva and sclera (Figure 1).

Examination of the mucous membrane of the hard palate revealed several blue-pigmented macules with ill-defined borders merging into the surrounding mucosa (Figure 2). Ocular tension was normal and slit-lamp examination of the right eye did not reveal any abnormalities. Hematoxylin and eosin–stained sections prepared from a biopsy of the oral mucosa on the hard palate showed numerous elongated, fusiform, dendritic melanocytes in small aggregates scattered widely between the bundles of collagen in the papillary to midreticular dermis (Figure 3). On histology, the melanocytes stained positive for S100 protein (Figure 4) and human melanoma black 45. No evidence indicative of malignancy was found. The stratified squamous epithelium was unremarkable except for the presence of mild perivascular lymphocytic infiltrate in the subepithelial tissue. A diagnosis of nevus of Ota with involvement of the hard palate was made.

Cutaneous macules may enlarge slowly, become deeper in color, and persist throughout the patient’s life. Its pathogenesis is not known, but it is speculated that nevus of Ota is caused by faulty migration of melanoblasts from the neural crest to the skin. Nevus of Ito also is a dermal melanocytic aberration that exclusively affects the shoulders and often occurs in association with nevus of Ota.¹

Ashy or slate-blue pigmentation in individuals with skin of color (eg, Fitzpatrick skin type V) is uncommon, as this discoloration usually is seen in fair-skinned individuals (eg, Fitzpatrick skin type II).⁶ Occasionally, blue-pigmented lesions of the oral mucosa may be seen in nevus of Ota (as in our patient) and are considered developmental; therefore, examination of the oral cavity is suggested when patients present with blue-pigmented lesions in the facial region. Although this finding is rare, several other cases of blue-pigmented macules on the palatal mucosa have been reported.^3-5

The diagnosis of nevus of Ota should be confirmed by histopathology and can be classified into 5 types according to the distribution of melanocytes, including (1) superficial, (2) superficial dominant, (3) diffuse, (4) deep dominant, and (5) deep.⁷ The diagnosis of nevus of Ota can be made based on its characteristic morphology; however, nevus of 
Ito, Mongolian spots, melanoma, fixed drug eruptions,⁸ and lichen planus pigmantosus should also 
be ruled out.⁹

Nevus of Ota is a well-established entity that should be considered when ashy or slate-blue pigmentation is noted along the branches of the ophthalmic and maxillary divisions of the trigeminal nerve. Diagnosis is largely clinical, but should be confirmed on histopathology and immunohistochemistry. Possible concomitant involvement of the buccal mucosa and/or the hard palate warrants a thorough examination of the oral cavity in the setting of nevus of Ota to identify oral mucosal lesions. Histopathology is essential to confirm its status as well as to exclude melanoma.

Clinicians treating vasomotor and genitourinary symptoms of menopause should consider estrogen therapy for healthy women with moderate to severe symptoms and no contraindications to hormone therapy, according to a new clinical practice guideline issued by the Endocrine Society.

The guideline, developed by an international panel, is designed to be a comprehensive document that emphasizes individualized clinical recommendations and generally takes a conservative approach to balancing risks and benefits, said Dr. Cynthia Stuenkel, chair of the task force that developed the guideline and professor of medicine at the University of California, San Diego.

“We need to be very mindful of the individual health concerns of our patient – is the individual therapy that we choose safe for her?” noted Dr. Stuenkel during a web-hosted press conference announcing the publication of the guideline.

For women under 60 years of age or fewer than 10 years past menopause who have bothersome vasomotor symptoms (VMS) and are without contraindications, the guideline suggests initiating estrogen therapy, supplemented by a progestogen for those women who have a uterus (J Clin Endocrinol Metab. 2015. doi: 10.1210/jc.2015-2236).

The discussion regarding treatment options should be grounded by a obtaining a baseline history of and assessing risk for cardiovascular disease (CVD) and breast cancer. “Menopause is a portal to the second half of life,” so clinicians should address bone health, smoking cessation, alcohol use, and cardiovascular and cancer risks and screening in their discussion, said Dr. Stuenkel.

The panel makes specific recommendations to tailor treatment depending on risk. For example, women at intermediate to high risk of breast cancer should be steered toward nonhormonal therapies to relieve VMS. Those at moderate risk of CVD can consider transdermal estradiol, while nonhormonal therapies are recommended for the high–CVD risk group.

The genitourinary symptoms of menopause (GSM) can include not just vulvovaginal atrophy but also urinary frequency and recurrent urinary tract infections, said Dr. Stuenkel, so the panel used the broader terminology to address estrogen’s effect on both organ systems.

An initial trial of vaginal moisturizers, used at least twice weekly, supplemented by lubricants as needed before sexual activity, should be the first-line treatment for GSM. For women with persistent symptoms and no history of estrogen-dependent cancers, low-dose vaginal estrogen therapy is a logical next step and does not require accompanying progestogen treatment, according to the guideline.

For women with symptomatic GSM who have had breast or endometrial cancer whose symptoms are not sufficiently treated by nonhormonal methods, low-dose vaginal estrogen is a consideration. This option should be considered with a shared decision-making approach that involves the patient’s oncologist.

Conjugated equine estrogens plus bazedoxefine, a novel selective estrogen receptor modulator (Duavee) can treat VMS and provide protection against bone loss, said the task force. The guideline recommends against the use of custom-compounded hormonal therapy and recommends the use of Food and Drug Administration–approved formulations. Ospemifene can be considered in women with significant dyspareunia and without contraindications, which include a history of breast cancer.

In conclusion, the guideline calls for ongoing rigorous study of the optimal agents and dosing for treatment of symptoms, how best to balance symptom relief with chronic disease prevention, and the merits of long-term hormone therapy beyond the period when symptomatic relief of VMS is needed. “International registries and clinical trials are overdue to address the long-reaching implications of these important issues,” said Dr. Stuenkel and coauthors of the guideline.

Dr. Stuenkel reported no relevant financial disclosures. Three task force members, Dr. Susan Davis, Dr. JoAnn Pinkerton, and Dr. Richard Santen, reported financial ties to pharmaceutical companies. Cosponsoring organizations included the Australasian Menopause Society, the British Menopause Society, European Menopause and Andropause Society, the European Society of Endocrinology, and the International Menopause Society.

[email protected]

On Twitter @karioakes

Clinicians treating vasomotor and genitourinary symptoms of menopause should consider estrogen therapy for healthy women with moderate to severe symptoms and no contraindications to hormone therapy, according to a new clinical practice guideline issued by the Endocrine Society.

The guideline, developed by an international panel, is designed to be a comprehensive document that emphasizes individualized clinical recommendations and generally takes a conservative approach to balancing risks and benefits, said Dr. Cynthia Stuenkel, chair of the task force that developed the guideline and professor of medicine at the University of California, San Diego.

“We need to be very mindful of the individual health concerns of our patient – is the individual therapy that we choose safe for her?” noted Dr. Stuenkel during a web-hosted press conference announcing the publication of the guideline.

For women under 60 years of age or fewer than 10 years past menopause who have bothersome vasomotor symptoms (VMS) and are without contraindications, the guideline suggests initiating estrogen therapy, supplemented by a progestogen for those women who have a uterus (J Clin Endocrinol Metab. 2015. doi: 10.1210/jc.2015-2236).

The discussion regarding treatment options should be grounded by a obtaining a baseline history of and assessing risk for cardiovascular disease (CVD) and breast cancer. “Menopause is a portal to the second half of life,” so clinicians should address bone health, smoking cessation, alcohol use, and cardiovascular and cancer risks and screening in their discussion, said Dr. Stuenkel.

The panel makes specific recommendations to tailor treatment depending on risk. For example, women at intermediate to high risk of breast cancer should be steered toward nonhormonal therapies to relieve VMS. Those at moderate risk of CVD can consider transdermal estradiol, while nonhormonal therapies are recommended for the high–CVD risk group.

The genitourinary symptoms of menopause (GSM) can include not just vulvovaginal atrophy but also urinary frequency and recurrent urinary tract infections, said Dr. Stuenkel, so the panel used the broader terminology to address estrogen’s effect on both organ systems.

An initial trial of vaginal moisturizers, used at least twice weekly, supplemented by lubricants as needed before sexual activity, should be the first-line treatment for GSM. For women with persistent symptoms and no history of estrogen-dependent cancers, low-dose vaginal estrogen therapy is a logical next step and does not require accompanying progestogen treatment, according to the guideline.

For women with symptomatic GSM who have had breast or endometrial cancer whose symptoms are not sufficiently treated by nonhormonal methods, low-dose vaginal estrogen is a consideration. This option should be considered with a shared decision-making approach that involves the patient’s oncologist.

Conjugated equine estrogens plus bazedoxefine, a novel selective estrogen receptor modulator (Duavee) can treat VMS and provide protection against bone loss, said the task force. The guideline recommends against the use of custom-compounded hormonal therapy and recommends the use of Food and Drug Administration–approved formulations. Ospemifene can be considered in women with significant dyspareunia and without contraindications, which include a history of breast cancer.

In conclusion, the guideline calls for ongoing rigorous study of the optimal agents and dosing for treatment of symptoms, how best to balance symptom relief with chronic disease prevention, and the merits of long-term hormone therapy beyond the period when symptomatic relief of VMS is needed. “International registries and clinical trials are overdue to address the long-reaching implications of these important issues,” said Dr. Stuenkel and coauthors of the guideline.

Dr. Stuenkel reported no relevant financial disclosures. Three task force members, Dr. Susan Davis, Dr. JoAnn Pinkerton, and Dr. Richard Santen, reported financial ties to pharmaceutical companies. Cosponsoring organizations included the Australasian Menopause Society, the British Menopause Society, European Menopause and Andropause Society, the European Society of Endocrinology, and the International Menopause Society.

[email protected]

On Twitter @karioakes

Clinicians treating vasomotor and genitourinary symptoms of menopause should consider estrogen therapy for healthy women with moderate to severe symptoms and no contraindications to hormone therapy, according to a new clinical practice guideline issued by the Endocrine Society.

The guideline, developed by an international panel, is designed to be a comprehensive document that emphasizes individualized clinical recommendations and generally takes a conservative approach to balancing risks and benefits, said Dr. Cynthia Stuenkel, chair of the task force that developed the guideline and professor of medicine at the University of California, San Diego.

“We need to be very mindful of the individual health concerns of our patient – is the individual therapy that we choose safe for her?” noted Dr. Stuenkel during a web-hosted press conference announcing the publication of the guideline.

For women under 60 years of age or fewer than 10 years past menopause who have bothersome vasomotor symptoms (VMS) and are without contraindications, the guideline suggests initiating estrogen therapy, supplemented by a progestogen for those women who have a uterus (J Clin Endocrinol Metab. 2015. doi: 10.1210/jc.2015-2236).

The discussion regarding treatment options should be grounded by a obtaining a baseline history of and assessing risk for cardiovascular disease (CVD) and breast cancer. “Menopause is a portal to the second half of life,” so clinicians should address bone health, smoking cessation, alcohol use, and cardiovascular and cancer risks and screening in their discussion, said Dr. Stuenkel.

The panel makes specific recommendations to tailor treatment depending on risk. For example, women at intermediate to high risk of breast cancer should be steered toward nonhormonal therapies to relieve VMS. Those at moderate risk of CVD can consider transdermal estradiol, while nonhormonal therapies are recommended for the high–CVD risk group.

The genitourinary symptoms of menopause (GSM) can include not just vulvovaginal atrophy but also urinary frequency and recurrent urinary tract infections, said Dr. Stuenkel, so the panel used the broader terminology to address estrogen’s effect on both organ systems.

An initial trial of vaginal moisturizers, used at least twice weekly, supplemented by lubricants as needed before sexual activity, should be the first-line treatment for GSM. For women with persistent symptoms and no history of estrogen-dependent cancers, low-dose vaginal estrogen therapy is a logical next step and does not require accompanying progestogen treatment, according to the guideline.

For women with symptomatic GSM who have had breast or endometrial cancer whose symptoms are not sufficiently treated by nonhormonal methods, low-dose vaginal estrogen is a consideration. This option should be considered with a shared decision-making approach that involves the patient’s oncologist.

Conjugated equine estrogens plus bazedoxefine, a novel selective estrogen receptor modulator (Duavee) can treat VMS and provide protection against bone loss, said the task force. The guideline recommends against the use of custom-compounded hormonal therapy and recommends the use of Food and Drug Administration–approved formulations. Ospemifene can be considered in women with significant dyspareunia and without contraindications, which include a history of breast cancer.

In conclusion, the guideline calls for ongoing rigorous study of the optimal agents and dosing for treatment of symptoms, how best to balance symptom relief with chronic disease prevention, and the merits of long-term hormone therapy beyond the period when symptomatic relief of VMS is needed. “International registries and clinical trials are overdue to address the long-reaching implications of these important issues,” said Dr. Stuenkel and coauthors of the guideline.

Dr. Stuenkel reported no relevant financial disclosures. Three task force members, Dr. Susan Davis, Dr. JoAnn Pinkerton, and Dr. Richard Santen, reported financial ties to pharmaceutical companies. Cosponsoring organizations included the Australasian Menopause Society, the British Menopause Society, European Menopause and Andropause Society, the European Society of Endocrinology, and the International Menopause Society.

[email protected]

On Twitter @karioakes

LAS VEGAS – Physicians looking for more options for alleviating dyspareunia in postmenopausal women should consider vaginal dilators, specialized vibrators, and pelvic floor physical therapy, according to Susan Kellogg Spadt, Ph.D.

These approaches can prevent or overcome some of the changes in the pelvic anatomy that can occur with menopause or with prolonged periods without sexual activity, Dr. Kellogg Spadt, a certified sexual counselor and professor of obstetrics and gynecology at Drexel University, Philadelphia, said at the NAMS 2015 Annual Meeting.

Along with the topical atrophy that can occur with the low estrogen state of menopause, hypertonus and foreshortening of the pelvic floor muscles can occur in some postmenopausal women. Multiparous women may experience significant muscle laxity. Some women, especially those who may have gone without intercourse for prolonged periods, may also have vaginal stenosis. These can all present barriers to sexual health for women in midlife, she said.

Pelvic floor physical therapy, said Dr. Kellogg Spadt, is critical to help with all of these physical changes. Clinicians can find physical therapists certified in women’s health through the website of the American Physical Therapy Association (www.apta.org).

With the guidance of a physical therapist, women can learn about home use of a series of graduated vaginal dilators. Beginning with a smaller size, patients typically insert a dilator several times a week (up to daily) for 5-10 minutes, changing size every 2-3 weeks. During the changeover week, patients can start with the smaller size for 5 minutes and then change to the larger dilator for the second half of the session. This consistent, but gradual, approach is well tolerated and produces good results, she said.

Physical therapists may also use a pelvic wand, such as the Therawand, for women who have hypertonus of the pelvic musculature. This S-shaped acrylic wand is inserted into the vagina and provides direct internal pressure on the pubococcygeus and puborectalis muscles, facilitating trigger point release. Pelvic wands can be used in physical therapy sessions, but patients can also learn how to use the devices at home, Dr. Kellogg Spadt said.

Vibrators are another tool in addressing dyspareunia. The Intensity exerciser/vibrator is intended for therapeutic use as well as sexual pleasure. The device is powered by four AA batteries and is known to produce very intense orgasms with powerful pelvic muscle contractions. This might be deleterious and even painful for patients with an already tight pelvic floor, but it can be helpful for women with muscle laxity, Dr. Kellogg Spadt said. It can also be an important part of sex therapy for some women, “bringing orgasms to the orgasmless,” she said.

Another device option is Fiera, a small hands-free device that provides a low level of vibration to the clitoris and anterior vulva. It’s not designed to produce an orgasm, but to assist with arousal, so tissues are lubricated and engorged by the time the woman is ready to engage in partner sex play, she said.

Dr. Kellogg Stadt reported being a consultant to or on the advisory board of Neogyn and Nuelle, which markets Fiera. She is also on the speakers bureau of Novo Nordisk and Shionogi.

[email protected]

On Twitter @karioakes

LAS VEGAS – Physicians looking for more options for alleviating dyspareunia in postmenopausal women should consider vaginal dilators, specialized vibrators, and pelvic floor physical therapy, according to Susan Kellogg Spadt, Ph.D.

These approaches can prevent or overcome some of the changes in the pelvic anatomy that can occur with menopause or with prolonged periods without sexual activity, Dr. Kellogg Spadt, a certified sexual counselor and professor of obstetrics and gynecology at Drexel University, Philadelphia, said at the NAMS 2015 Annual Meeting.

Along with the topical atrophy that can occur with the low estrogen state of menopause, hypertonus and foreshortening of the pelvic floor muscles can occur in some postmenopausal women. Multiparous women may experience significant muscle laxity. Some women, especially those who may have gone without intercourse for prolonged periods, may also have vaginal stenosis. These can all present barriers to sexual health for women in midlife, she said.

Pelvic floor physical therapy, said Dr. Kellogg Spadt, is critical to help with all of these physical changes. Clinicians can find physical therapists certified in women’s health through the website of the American Physical Therapy Association (www.apta.org).

With the guidance of a physical therapist, women can learn about home use of a series of graduated vaginal dilators. Beginning with a smaller size, patients typically insert a dilator several times a week (up to daily) for 5-10 minutes, changing size every 2-3 weeks. During the changeover week, patients can start with the smaller size for 5 minutes and then change to the larger dilator for the second half of the session. This consistent, but gradual, approach is well tolerated and produces good results, she said.

Physical therapists may also use a pelvic wand, such as the Therawand, for women who have hypertonus of the pelvic musculature. This S-shaped acrylic wand is inserted into the vagina and provides direct internal pressure on the pubococcygeus and puborectalis muscles, facilitating trigger point release. Pelvic wands can be used in physical therapy sessions, but patients can also learn how to use the devices at home, Dr. Kellogg Spadt said.

Vibrators are another tool in addressing dyspareunia. The Intensity exerciser/vibrator is intended for therapeutic use as well as sexual pleasure. The device is powered by four AA batteries and is known to produce very intense orgasms with powerful pelvic muscle contractions. This might be deleterious and even painful for patients with an already tight pelvic floor, but it can be helpful for women with muscle laxity, Dr. Kellogg Spadt said. It can also be an important part of sex therapy for some women, “bringing orgasms to the orgasmless,” she said.

Another device option is Fiera, a small hands-free device that provides a low level of vibration to the clitoris and anterior vulva. It’s not designed to produce an orgasm, but to assist with arousal, so tissues are lubricated and engorged by the time the woman is ready to engage in partner sex play, she said.

Dr. Kellogg Stadt reported being a consultant to or on the advisory board of Neogyn and Nuelle, which markets Fiera. She is also on the speakers bureau of Novo Nordisk and Shionogi.

[email protected]

On Twitter @karioakes

LAS VEGAS – Physicians looking for more options for alleviating dyspareunia in postmenopausal women should consider vaginal dilators, specialized vibrators, and pelvic floor physical therapy, according to Susan Kellogg Spadt, Ph.D.

These approaches can prevent or overcome some of the changes in the pelvic anatomy that can occur with menopause or with prolonged periods without sexual activity, Dr. Kellogg Spadt, a certified sexual counselor and professor of obstetrics and gynecology at Drexel University, Philadelphia, said at the NAMS 2015 Annual Meeting.

Along with the topical atrophy that can occur with the low estrogen state of menopause, hypertonus and foreshortening of the pelvic floor muscles can occur in some postmenopausal women. Multiparous women may experience significant muscle laxity. Some women, especially those who may have gone without intercourse for prolonged periods, may also have vaginal stenosis. These can all present barriers to sexual health for women in midlife, she said.

Pelvic floor physical therapy, said Dr. Kellogg Spadt, is critical to help with all of these physical changes. Clinicians can find physical therapists certified in women’s health through the website of the American Physical Therapy Association (www.apta.org).

With the guidance of a physical therapist, women can learn about home use of a series of graduated vaginal dilators. Beginning with a smaller size, patients typically insert a dilator several times a week (up to daily) for 5-10 minutes, changing size every 2-3 weeks. During the changeover week, patients can start with the smaller size for 5 minutes and then change to the larger dilator for the second half of the session. This consistent, but gradual, approach is well tolerated and produces good results, she said.

Physical therapists may also use a pelvic wand, such as the Therawand, for women who have hypertonus of the pelvic musculature. This S-shaped acrylic wand is inserted into the vagina and provides direct internal pressure on the pubococcygeus and puborectalis muscles, facilitating trigger point release. Pelvic wands can be used in physical therapy sessions, but patients can also learn how to use the devices at home, Dr. Kellogg Spadt said.

Vibrators are another tool in addressing dyspareunia. The Intensity exerciser/vibrator is intended for therapeutic use as well as sexual pleasure. The device is powered by four AA batteries and is known to produce very intense orgasms with powerful pelvic muscle contractions. This might be deleterious and even painful for patients with an already tight pelvic floor, but it can be helpful for women with muscle laxity, Dr. Kellogg Spadt said. It can also be an important part of sex therapy for some women, “bringing orgasms to the orgasmless,” she said.

Another device option is Fiera, a small hands-free device that provides a low level of vibration to the clitoris and anterior vulva. It’s not designed to produce an orgasm, but to assist with arousal, so tissues are lubricated and engorged by the time the woman is ready to engage in partner sex play, she said.

Dr. Kellogg Stadt reported being a consultant to or on the advisory board of Neogyn and Nuelle, which markets Fiera. She is also on the speakers bureau of Novo Nordisk and Shionogi.

[email protected]

On Twitter @karioakes

Groupings of coexisting MRI lesions of the tibiofemoral and patellofemoral joints were linked to the risk of subsequent radiographic osteoarthritis, investigators reported. Their analysis of data from the prospective, observational MOST study was published online Sept. 28 in Arthritis and Rheumatism.

“The magnitude of lesions such as cartilage damage and coexisting meniscal damage appear to be the main distinction between the subgroups,” said Dr. Jingbo Niu of Boston University and her associates. Several studies have linked individual MRI lesions with incident knee OA, but patterns of coexisting lesions more accurately reflect real-world injuries, such as anterior cruciate ligament tears, which tend to affect more than one knee structure, the investigators noted.

Because directly comparing lesions in a multivariate model does not account for chronology, the investigators used latent class analysis to identify subgroups of coexisting MRI lesions of the tibiofemoral and patellofemoral joints, such as cartilage damage, meniscal tear, meniscal extrusion, synovitis, and effusion. Then they modeled associations between these subgroups and incident OA of the knee (Arthritis Rheum. 2015 Sep 28. doi: 10.1002/art.3943).

Among 885 knees from the MOST study, 203 developed radiographic tibiofemoral OA and 64 developed patellofemoral OA after up to 84 months of follow-up, the researchers reported. Latent class analysis identified four groups of MRI lesions for each knee joint, which exhibited sequentially increasing baseline severity for all MRI features except meniscal damage, the investigators added.

For the patellofemoral joint, the odds of incident knee OA rose sequentially with increasing MRI severity, ranging from 1.0 for minimal lesions to 13.7 for severe lesions (95% confidence interval, 5.0-37.0), according to the study. In contrast, the odds of incident knee radiographic OA (ROA) of the tibiofemoral joint were highest for the “mild” and “severe” groups, which had the most meniscal damage and the most extensive history of knee injury and surgery. Odds ratios for these two groups were 5.6 (95% CI, 3.4-9.4) and 5.0 (95% CI, 2.8-9.0), respectively, said the researchers. “Meniscal damage might play a prominent role in the development of incident ROA in the tibiofemoral joint but not the patellofemoral joint,” they added.

Patients in the MOST study had a high risk of knee OA at baseline, which could limit the generalizability of the findings, Dr. Niu and her associates noted.

The National Institute on Aging and National Institute of Arthritis and Musculoskeletal and Skin Disease, both a part of the National Institutes of Health, supported the study. The investigators did not report conflicts of interest.

Groupings of coexisting MRI lesions of the tibiofemoral and patellofemoral joints were linked to the risk of subsequent radiographic osteoarthritis, investigators reported. Their analysis of data from the prospective, observational MOST study was published online Sept. 28 in Arthritis and Rheumatism.

“The magnitude of lesions such as cartilage damage and coexisting meniscal damage appear to be the main distinction between the subgroups,” said Dr. Jingbo Niu of Boston University and her associates. Several studies have linked individual MRI lesions with incident knee OA, but patterns of coexisting lesions more accurately reflect real-world injuries, such as anterior cruciate ligament tears, which tend to affect more than one knee structure, the investigators noted.

Because directly comparing lesions in a multivariate model does not account for chronology, the investigators used latent class analysis to identify subgroups of coexisting MRI lesions of the tibiofemoral and patellofemoral joints, such as cartilage damage, meniscal tear, meniscal extrusion, synovitis, and effusion. Then they modeled associations between these subgroups and incident OA of the knee (Arthritis Rheum. 2015 Sep 28. doi: 10.1002/art.3943).

Among 885 knees from the MOST study, 203 developed radiographic tibiofemoral OA and 64 developed patellofemoral OA after up to 84 months of follow-up, the researchers reported. Latent class analysis identified four groups of MRI lesions for each knee joint, which exhibited sequentially increasing baseline severity for all MRI features except meniscal damage, the investigators added.

For the patellofemoral joint, the odds of incident knee OA rose sequentially with increasing MRI severity, ranging from 1.0 for minimal lesions to 13.7 for severe lesions (95% confidence interval, 5.0-37.0), according to the study. In contrast, the odds of incident knee radiographic OA (ROA) of the tibiofemoral joint were highest for the “mild” and “severe” groups, which had the most meniscal damage and the most extensive history of knee injury and surgery. Odds ratios for these two groups were 5.6 (95% CI, 3.4-9.4) and 5.0 (95% CI, 2.8-9.0), respectively, said the researchers. “Meniscal damage might play a prominent role in the development of incident ROA in the tibiofemoral joint but not the patellofemoral joint,” they added.

Patients in the MOST study had a high risk of knee OA at baseline, which could limit the generalizability of the findings, Dr. Niu and her associates noted.

The National Institute on Aging and National Institute of Arthritis and Musculoskeletal and Skin Disease, both a part of the National Institutes of Health, supported the study. The investigators did not report conflicts of interest.

Groupings of coexisting MRI lesions of the tibiofemoral and patellofemoral joints were linked to the risk of subsequent radiographic osteoarthritis, investigators reported. Their analysis of data from the prospective, observational MOST study was published online Sept. 28 in Arthritis and Rheumatism.

“The magnitude of lesions such as cartilage damage and coexisting meniscal damage appear to be the main distinction between the subgroups,” said Dr. Jingbo Niu of Boston University and her associates. Several studies have linked individual MRI lesions with incident knee OA, but patterns of coexisting lesions more accurately reflect real-world injuries, such as anterior cruciate ligament tears, which tend to affect more than one knee structure, the investigators noted.

Because directly comparing lesions in a multivariate model does not account for chronology, the investigators used latent class analysis to identify subgroups of coexisting MRI lesions of the tibiofemoral and patellofemoral joints, such as cartilage damage, meniscal tear, meniscal extrusion, synovitis, and effusion. Then they modeled associations between these subgroups and incident OA of the knee (Arthritis Rheum. 2015 Sep 28. doi: 10.1002/art.3943).

Among 885 knees from the MOST study, 203 developed radiographic tibiofemoral OA and 64 developed patellofemoral OA after up to 84 months of follow-up, the researchers reported. Latent class analysis identified four groups of MRI lesions for each knee joint, which exhibited sequentially increasing baseline severity for all MRI features except meniscal damage, the investigators added.

For the patellofemoral joint, the odds of incident knee OA rose sequentially with increasing MRI severity, ranging from 1.0 for minimal lesions to 13.7 for severe lesions (95% confidence interval, 5.0-37.0), according to the study. In contrast, the odds of incident knee radiographic OA (ROA) of the tibiofemoral joint were highest for the “mild” and “severe” groups, which had the most meniscal damage and the most extensive history of knee injury and surgery. Odds ratios for these two groups were 5.6 (95% CI, 3.4-9.4) and 5.0 (95% CI, 2.8-9.0), respectively, said the researchers. “Meniscal damage might play a prominent role in the development of incident ROA in the tibiofemoral joint but not the patellofemoral joint,” they added.

Patients in the MOST study had a high risk of knee OA at baseline, which could limit the generalizability of the findings, Dr. Niu and her associates noted.

The National Institute on Aging and National Institute of Arthritis and Musculoskeletal and Skin Disease, both a part of the National Institutes of Health, supported the study. The investigators did not report conflicts of interest.

LAS VEGAS – Management of blunt cerebrovascular injuries using 64-channel computed tomographic angiography screening coupled with digital subtraction angiography for a definitive diagnosis is safe and effective for identifying clinically significant injury and for maintaining a low stroke rate, according to a review of 228 cases.

The computed tomographic angiography (CTA) screening was positive in 189 patients (83%), and digital subtraction angiography (DSA) confirmed injury in 104 (55%) of those. The remaining 39 patients were found to have no injury on DSA, Dr. Charles P. Shahan of the University of Tennessee, Memphis reported at the annual meeting of the American Association for the Surgery of Trauma (AAST).

©windcatcher/Thinkstock.com

Stroke related to blunt cerebrovascular injury (BCVI) occurred in five patients (4.8%); three of those patients were symptomatic at the time of presentation, and two became symptomatic while on therapy for a known lesion. None of the patients who had a negative screening CTA, including three with injuries missed on CTA, had a stroke, Dr. Shahan said.

The current study follows a prior study reported at the 2013 AAST annual meeting that suggested that 64-channel multidetector CTA could be the primary screening tool for BCVI. The previously used 32-channel multidetector CTA was found to be inadequate, with a sensitivity of only 52%. Sensitivity increased to 68% with the 64-channel CTA, but the positive predictive value remained remarkably low at 36%, he said.

That study led to a change in the screening algorithm, replacing DSA with CTA for screening, and reserving DSA for definitive BCVI diagnosis following a positive CTA or unexplained neurologic findings, he explained, noting that the rationale was that most injuries missed were low-grade injuries less likely to result in further injury, and that with CTA alone, about two-thirds of patients would be treated unnecessarily because of the false-positive rate.

The purpose of the current study was to evaluate outcomes in the wake of the algorithm change and to assess the potential for missed, clinically significant BCVI.

Study subjects were patients who underwent DSA over an 18-month period after implementation of the algorithm change. Most (64%) were men with a mean age of 43 years and a mean injury severity score of 22 out of 75, indicating moderate or severe injury.

The stroke rate was statistically unchanged in the second study, compared with the first. The findings demonstrate the safety and efficacy of the current management algorithm for BCVI, as well as the value of using DSA to identify false-positive CTA findings. In fact, definitive diagnosis by DSA led to avoidance of potentially harmful anticoagulation in 45% of CTA-positive patients, with no increase in the incidence of strokes resulting from injuries missed by CTA, Dr. Shahan said.

“Considering there were 85 false-positive CTAs, and also considering that our average length of heparin time is approximately 7 days prior to reevaluation, we’ve extrapolated this to nearly 600 heparin infusion days that were avoided by confirmatory DSA testing,” he said, concluding that “CTA with 64-channel multidetector technology with experienced radiology staff in a high-volume center can be safe and effective for BCVI screening.”

He added, however, that false-positive rates with CTA continue to necessitate DSA confirmation to avoid overtreatment.

“We feel that CTA screening with DSA confirmation has allowed us to maintain an acceptably low stroke rate and prevented a tremendous amount of unnecessary anticoagulation in these patients,” he said.

Dr. Clay Cothren Burlew, who was an invited discussant for Dr. Shahan’s paper, applauded Dr. Shahan and his colleagues for “continuing to question the validity of CTA as our primary diagnostic modality for BCVI,” and said the findings made her “stop and think, should we all be doing confirmatory angiography? … Are CTAs actually overcalling 45% of the injuries that we identify?”

Dr. Burlew of the University of Colorado, Denver, questioned whether the high rate of false positives is a result of radiologists who “overcall” questionable findings knowing that a confirmatory angiogram will quickly follow.

“I think this evaluation should be a model for others. Each institution should critically review their individual rates and methods of BCVI diagnosis,” she said, adding that “for centers with a marked increase in the identification of BCVI following institution of CTA as their screening tool, consideration of confirmatory angiography is recommended due to the potential false-positive rate of up to 45%.”

However, confirmatory angiography may not be warranted at centers whose screen yields remain the same with no missed injuries, she said.

“All programs should evaluate their injuries, appropriateness of diagnosis, and impact of subsequent treatment. Only then will we have optimal outcomes,” she concluded.

Dr. Shahan and Dr. Burlew reported having no relevant financial disclosures.

[email protected]

LAS VEGAS – Management of blunt cerebrovascular injuries using 64-channel computed tomographic angiography screening coupled with digital subtraction angiography for a definitive diagnosis is safe and effective for identifying clinically significant injury and for maintaining a low stroke rate, according to a review of 228 cases.

The computed tomographic angiography (CTA) screening was positive in 189 patients (83%), and digital subtraction angiography (DSA) confirmed injury in 104 (55%) of those. The remaining 39 patients were found to have no injury on DSA, Dr. Charles P. Shahan of the University of Tennessee, Memphis reported at the annual meeting of the American Association for the Surgery of Trauma (AAST).

©windcatcher/Thinkstock.com

Stroke related to blunt cerebrovascular injury (BCVI) occurred in five patients (4.8%); three of those patients were symptomatic at the time of presentation, and two became symptomatic while on therapy for a known lesion. None of the patients who had a negative screening CTA, including three with injuries missed on CTA, had a stroke, Dr. Shahan said.

The current study follows a prior study reported at the 2013 AAST annual meeting that suggested that 64-channel multidetector CTA could be the primary screening tool for BCVI. The previously used 32-channel multidetector CTA was found to be inadequate, with a sensitivity of only 52%. Sensitivity increased to 68% with the 64-channel CTA, but the positive predictive value remained remarkably low at 36%, he said.

That study led to a change in the screening algorithm, replacing DSA with CTA for screening, and reserving DSA for definitive BCVI diagnosis following a positive CTA or unexplained neurologic findings, he explained, noting that the rationale was that most injuries missed were low-grade injuries less likely to result in further injury, and that with CTA alone, about two-thirds of patients would be treated unnecessarily because of the false-positive rate.

The purpose of the current study was to evaluate outcomes in the wake of the algorithm change and to assess the potential for missed, clinically significant BCVI.

Study subjects were patients who underwent DSA over an 18-month period after implementation of the algorithm change. Most (64%) were men with a mean age of 43 years and a mean injury severity score of 22 out of 75, indicating moderate or severe injury.

The stroke rate was statistically unchanged in the second study, compared with the first. The findings demonstrate the safety and efficacy of the current management algorithm for BCVI, as well as the value of using DSA to identify false-positive CTA findings. In fact, definitive diagnosis by DSA led to avoidance of potentially harmful anticoagulation in 45% of CTA-positive patients, with no increase in the incidence of strokes resulting from injuries missed by CTA, Dr. Shahan said.

“Considering there were 85 false-positive CTAs, and also considering that our average length of heparin time is approximately 7 days prior to reevaluation, we’ve extrapolated this to nearly 600 heparin infusion days that were avoided by confirmatory DSA testing,” he said, concluding that “CTA with 64-channel multidetector technology with experienced radiology staff in a high-volume center can be safe and effective for BCVI screening.”

He added, however, that false-positive rates with CTA continue to necessitate DSA confirmation to avoid overtreatment.

“We feel that CTA screening with DSA confirmation has allowed us to maintain an acceptably low stroke rate and prevented a tremendous amount of unnecessary anticoagulation in these patients,” he said.

Dr. Clay Cothren Burlew, who was an invited discussant for Dr. Shahan’s paper, applauded Dr. Shahan and his colleagues for “continuing to question the validity of CTA as our primary diagnostic modality for BCVI,” and said the findings made her “stop and think, should we all be doing confirmatory angiography? … Are CTAs actually overcalling 45% of the injuries that we identify?”

Dr. Burlew of the University of Colorado, Denver, questioned whether the high rate of false positives is a result of radiologists who “overcall” questionable findings knowing that a confirmatory angiogram will quickly follow.

“I think this evaluation should be a model for others. Each institution should critically review their individual rates and methods of BCVI diagnosis,” she said, adding that “for centers with a marked increase in the identification of BCVI following institution of CTA as their screening tool, consideration of confirmatory angiography is recommended due to the potential false-positive rate of up to 45%.”

However, confirmatory angiography may not be warranted at centers whose screen yields remain the same with no missed injuries, she said.

“All programs should evaluate their injuries, appropriateness of diagnosis, and impact of subsequent treatment. Only then will we have optimal outcomes,” she concluded.

Dr. Shahan and Dr. Burlew reported having no relevant financial disclosures.

[email protected]

LAS VEGAS – Management of blunt cerebrovascular injuries using 64-channel computed tomographic angiography screening coupled with digital subtraction angiography for a definitive diagnosis is safe and effective for identifying clinically significant injury and for maintaining a low stroke rate, according to a review of 228 cases.

The computed tomographic angiography (CTA) screening was positive in 189 patients (83%), and digital subtraction angiography (DSA) confirmed injury in 104 (55%) of those. The remaining 39 patients were found to have no injury on DSA, Dr. Charles P. Shahan of the University of Tennessee, Memphis reported at the annual meeting of the American Association for the Surgery of Trauma (AAST).

©windcatcher/Thinkstock.com

Stroke related to blunt cerebrovascular injury (BCVI) occurred in five patients (4.8%); three of those patients were symptomatic at the time of presentation, and two became symptomatic while on therapy for a known lesion. None of the patients who had a negative screening CTA, including three with injuries missed on CTA, had a stroke, Dr. Shahan said.

The current study follows a prior study reported at the 2013 AAST annual meeting that suggested that 64-channel multidetector CTA could be the primary screening tool for BCVI. The previously used 32-channel multidetector CTA was found to be inadequate, with a sensitivity of only 52%. Sensitivity increased to 68% with the 64-channel CTA, but the positive predictive value remained remarkably low at 36%, he said.

That study led to a change in the screening algorithm, replacing DSA with CTA for screening, and reserving DSA for definitive BCVI diagnosis following a positive CTA or unexplained neurologic findings, he explained, noting that the rationale was that most injuries missed were low-grade injuries less likely to result in further injury, and that with CTA alone, about two-thirds of patients would be treated unnecessarily because of the false-positive rate.

The purpose of the current study was to evaluate outcomes in the wake of the algorithm change and to assess the potential for missed, clinically significant BCVI.

Study subjects were patients who underwent DSA over an 18-month period after implementation of the algorithm change. Most (64%) were men with a mean age of 43 years and a mean injury severity score of 22 out of 75, indicating moderate or severe injury.

The stroke rate was statistically unchanged in the second study, compared with the first. The findings demonstrate the safety and efficacy of the current management algorithm for BCVI, as well as the value of using DSA to identify false-positive CTA findings. In fact, definitive diagnosis by DSA led to avoidance of potentially harmful anticoagulation in 45% of CTA-positive patients, with no increase in the incidence of strokes resulting from injuries missed by CTA, Dr. Shahan said.

“Considering there were 85 false-positive CTAs, and also considering that our average length of heparin time is approximately 7 days prior to reevaluation, we’ve extrapolated this to nearly 600 heparin infusion days that were avoided by confirmatory DSA testing,” he said, concluding that “CTA with 64-channel multidetector technology with experienced radiology staff in a high-volume center can be safe and effective for BCVI screening.”

He added, however, that false-positive rates with CTA continue to necessitate DSA confirmation to avoid overtreatment.

“We feel that CTA screening with DSA confirmation has allowed us to maintain an acceptably low stroke rate and prevented a tremendous amount of unnecessary anticoagulation in these patients,” he said.

Dr. Clay Cothren Burlew, who was an invited discussant for Dr. Shahan’s paper, applauded Dr. Shahan and his colleagues for “continuing to question the validity of CTA as our primary diagnostic modality for BCVI,” and said the findings made her “stop and think, should we all be doing confirmatory angiography? … Are CTAs actually overcalling 45% of the injuries that we identify?”

Dr. Burlew of the University of Colorado, Denver, questioned whether the high rate of false positives is a result of radiologists who “overcall” questionable findings knowing that a confirmatory angiogram will quickly follow.

“I think this evaluation should be a model for others. Each institution should critically review their individual rates and methods of BCVI diagnosis,” she said, adding that “for centers with a marked increase in the identification of BCVI following institution of CTA as their screening tool, consideration of confirmatory angiography is recommended due to the potential false-positive rate of up to 45%.”

However, confirmatory angiography may not be warranted at centers whose screen yields remain the same with no missed injuries, she said.

“All programs should evaluate their injuries, appropriateness of diagnosis, and impact of subsequent treatment. Only then will we have optimal outcomes,” she concluded.

Dr. Shahan and Dr. Burlew reported having no relevant financial disclosures.

[email protected]

Obtain gastric biopsies to check for Helicobacter pylori infection in patients undergoing routine esophagogastroduodenoscopy for dyspepsia, even if their mucosa appears normal and they’re immunocompetent, the American Gastroenterological Association advises in a new guideline for upper gastrointestinal biopsy to evaluate dyspepsia in the adult patient in the absence of visible mucosal lesions, which was published in the October issue of Gastroenterology.

The group suggests taking five biopsy specimens from the gastric body and antrum using the updated Sydney System; placing the samples in the same jar; and relying on routine staining to make the call. “Experienced GI pathologists can determine the anatomic location of biopsy specimens sent from the stomach, which obviates the need for” – and cost of – “separating specimens into multiple jars.” They can also identify “virtually all cases of H. pylori .... Therefore, routine use of ancillary special staining” needlessly adds cost, said the guideline authors, led by Dr. Yu-Xiao Yang of the University of Pennsylvania in Philadelphia (Gastroenterology. 2015 Aug 14. doi: 10.1053/j.gastro.2015.07.039).

©sgame/thinkstockphotos.com

The group also counsels against routine biopsies of normal-appearing esophagus and gastroesophageal junctions in patients undergoing esophagogastroduodenoscopy (EGD) for dyspepsia, regardless of their immune status.

It does recommend biopsies of normal-appearing duodenum in immunocompromised patients to check for opportunistic infections and graft-versus-host disease (GVHD) after bone marrow transplant, but counsels against routine duodenum biopsies in immunocompetent patients undergoing EGD solely for dyspepsia if signs and symptoms of celiac disease are absent. Again, routine use of special staining isn’t necessary. “Studies using [hematoxylin and eosin] counting methods show similar results as those obtained using CD3 [T-cell marker] stains,” the authors wrote.

The purpose of the guideline is to establish evidence-based standards for biopsies of normal-appearing mucosa in the upper gastrointestinal tract. No such standards existed until now, so “there [is] likely wide practice variation in whether or not such biopsies of normal-appearing mucosa are obtained,” they said.

The advice is based on a thorough review of the medical literature, and a grading of its strength. The guideline is meant for adult patients undergoing EGD solely for dyspepsia, and assumes that endoscopic biopsy has negligible complications.

The esophageal biopsy recommendations are strong, meaning that “most individuals should receive the recommended course of action.” The gastric biopsy advice is a mix of both strong and conditional recommendations, while the duodenal biopsy recommendations are conditional. Evidence for each recommendation ranged from very low to moderate.

Regarding gastric biopsy, H. pylori can lurk in normal-looking mucosa, and evidence supports detection and treatment for both symptom relief and cancer risk reduction. In the immunocompromised, gastric biopsies can also help detect cytomegalovirus infection.

The five-biopsy Sydney System gathers specimens from the lesser and greater curve of the gastric antrum, lesser curvature of the corpus, middle portion of the greater curvature of the corpus, and the incisura angularis. The thorough approach probably detects H. pylori missed by a three-biopsy method, with little added cost.

Esophageal biopsies of normal mucosa aren’t necessary, the authors said, because “although a number of microscopic changes in the esophageal mucosa can be seen in patients with” gastroesophageal reflux disease, they aren’t much help in distinguishing it from heartburn or even healthy controls. For immune compromised patients, GVHD is more likely to show up at other sites, such as the duodenum.

Although the group counsels against routine duodenum biopsies in immunocompetent patients, it did note that “if the suspicion of celiac disease is high, biopsies of the normal-appearing duodenum may be of value even if serologies ... are negative.”

Funding source and disclosures for the work are available from AGA.

[email protected]

Obtain gastric biopsies to check for Helicobacter pylori infection in patients undergoing routine esophagogastroduodenoscopy for dyspepsia, even if their mucosa appears normal and they’re immunocompetent, the American Gastroenterological Association advises in a new guideline for upper gastrointestinal biopsy to evaluate dyspepsia in the adult patient in the absence of visible mucosal lesions, which was published in the October issue of Gastroenterology.

The group suggests taking five biopsy specimens from the gastric body and antrum using the updated Sydney System; placing the samples in the same jar; and relying on routine staining to make the call. “Experienced GI pathologists can determine the anatomic location of biopsy specimens sent from the stomach, which obviates the need for” – and cost of – “separating specimens into multiple jars.” They can also identify “virtually all cases of H. pylori .... Therefore, routine use of ancillary special staining” needlessly adds cost, said the guideline authors, led by Dr. Yu-Xiao Yang of the University of Pennsylvania in Philadelphia (Gastroenterology. 2015 Aug 14. doi: 10.1053/j.gastro.2015.07.039).

©sgame/thinkstockphotos.com

The group also counsels against routine biopsies of normal-appearing esophagus and gastroesophageal junctions in patients undergoing esophagogastroduodenoscopy (EGD) for dyspepsia, regardless of their immune status.

It does recommend biopsies of normal-appearing duodenum in immunocompromised patients to check for opportunistic infections and graft-versus-host disease (GVHD) after bone marrow transplant, but counsels against routine duodenum biopsies in immunocompetent patients undergoing EGD solely for dyspepsia if signs and symptoms of celiac disease are absent. Again, routine use of special staining isn’t necessary. “Studies using [hematoxylin and eosin] counting methods show similar results as those obtained using CD3 [T-cell marker] stains,” the authors wrote.

The purpose of the guideline is to establish evidence-based standards for biopsies of normal-appearing mucosa in the upper gastrointestinal tract. No such standards existed until now, so “there [is] likely wide practice variation in whether or not such biopsies of normal-appearing mucosa are obtained,” they said.

The advice is based on a thorough review of the medical literature, and a grading of its strength. The guideline is meant for adult patients undergoing EGD solely for dyspepsia, and assumes that endoscopic biopsy has negligible complications.

The esophageal biopsy recommendations are strong, meaning that “most individuals should receive the recommended course of action.” The gastric biopsy advice is a mix of both strong and conditional recommendations, while the duodenal biopsy recommendations are conditional. Evidence for each recommendation ranged from very low to moderate.

Regarding gastric biopsy, H. pylori can lurk in normal-looking mucosa, and evidence supports detection and treatment for both symptom relief and cancer risk reduction. In the immunocompromised, gastric biopsies can also help detect cytomegalovirus infection.

The five-biopsy Sydney System gathers specimens from the lesser and greater curve of the gastric antrum, lesser curvature of the corpus, middle portion of the greater curvature of the corpus, and the incisura angularis. The thorough approach probably detects H. pylori missed by a three-biopsy method, with little added cost.

Esophageal biopsies of normal mucosa aren’t necessary, the authors said, because “although a number of microscopic changes in the esophageal mucosa can be seen in patients with” gastroesophageal reflux disease, they aren’t much help in distinguishing it from heartburn or even healthy controls. For immune compromised patients, GVHD is more likely to show up at other sites, such as the duodenum.

Although the group counsels against routine duodenum biopsies in immunocompetent patients, it did note that “if the suspicion of celiac disease is high, biopsies of the normal-appearing duodenum may be of value even if serologies ... are negative.”

Funding source and disclosures for the work are available from AGA.

[email protected]

Obtain gastric biopsies to check for Helicobacter pylori infection in patients undergoing routine esophagogastroduodenoscopy for dyspepsia, even if their mucosa appears normal and they’re immunocompetent, the American Gastroenterological Association advises in a new guideline for upper gastrointestinal biopsy to evaluate dyspepsia in the adult patient in the absence of visible mucosal lesions, which was published in the October issue of Gastroenterology.

The group suggests taking five biopsy specimens from the gastric body and antrum using the updated Sydney System; placing the samples in the same jar; and relying on routine staining to make the call. “Experienced GI pathologists can determine the anatomic location of biopsy specimens sent from the stomach, which obviates the need for” – and cost of – “separating specimens into multiple jars.” They can also identify “virtually all cases of H. pylori .... Therefore, routine use of ancillary special staining” needlessly adds cost, said the guideline authors, led by Dr. Yu-Xiao Yang of the University of Pennsylvania in Philadelphia (Gastroenterology. 2015 Aug 14. doi: 10.1053/j.gastro.2015.07.039).

©sgame/thinkstockphotos.com

The group also counsels against routine biopsies of normal-appearing esophagus and gastroesophageal junctions in patients undergoing esophagogastroduodenoscopy (EGD) for dyspepsia, regardless of their immune status.

It does recommend biopsies of normal-appearing duodenum in immunocompromised patients to check for opportunistic infections and graft-versus-host disease (GVHD) after bone marrow transplant, but counsels against routine duodenum biopsies in immunocompetent patients undergoing EGD solely for dyspepsia if signs and symptoms of celiac disease are absent. Again, routine use of special staining isn’t necessary. “Studies using [hematoxylin and eosin] counting methods show similar results as those obtained using CD3 [T-cell marker] stains,” the authors wrote.

The purpose of the guideline is to establish evidence-based standards for biopsies of normal-appearing mucosa in the upper gastrointestinal tract. No such standards existed until now, so “there [is] likely wide practice variation in whether or not such biopsies of normal-appearing mucosa are obtained,” they said.

The advice is based on a thorough review of the medical literature, and a grading of its strength. The guideline is meant for adult patients undergoing EGD solely for dyspepsia, and assumes that endoscopic biopsy has negligible complications.

The esophageal biopsy recommendations are strong, meaning that “most individuals should receive the recommended course of action.” The gastric biopsy advice is a mix of both strong and conditional recommendations, while the duodenal biopsy recommendations are conditional. Evidence for each recommendation ranged from very low to moderate.

Regarding gastric biopsy, H. pylori can lurk in normal-looking mucosa, and evidence supports detection and treatment for both symptom relief and cancer risk reduction. In the immunocompromised, gastric biopsies can also help detect cytomegalovirus infection.

The five-biopsy Sydney System gathers specimens from the lesser and greater curve of the gastric antrum, lesser curvature of the corpus, middle portion of the greater curvature of the corpus, and the incisura angularis. The thorough approach probably detects H. pylori missed by a three-biopsy method, with little added cost.

Esophageal biopsies of normal mucosa aren’t necessary, the authors said, because “although a number of microscopic changes in the esophageal mucosa can be seen in patients with” gastroesophageal reflux disease, they aren’t much help in distinguishing it from heartburn or even healthy controls. For immune compromised patients, GVHD is more likely to show up at other sites, such as the duodenum.

Although the group counsels against routine duodenum biopsies in immunocompetent patients, it did note that “if the suspicion of celiac disease is high, biopsies of the normal-appearing duodenum may be of value even if serologies ... are negative.”

Funding source and disclosures for the work are available from AGA.

[email protected]

The tyrosine kinase inhibitor ponatinib produced a high degree of complete cytogenetic responses when used in first-line treatment of patients with chronic myeloid leukemia in chronic phase. But the drug’s toxicities, especially its propensity for causing thromboembolic events, mitigate against its upfront use, investigators say.

In a small phase II study, 90% of evaluable patients with chronic-phase chronic myeloid leukemia (CML) treated with the tyrosine kinase inhibitor (TKI) had a complete cytogenetic response (CCyR) after 3 months, and 94% had a CCyR after 6 months, but that efficacy came at the cost of significant adverse events requiring dose reductions, treatment interruptions, and early termination of the trial for safety reasons at the recommendation of the Food and Drug Administration, reported Dr. Preetesh Jain of MD Anderson Cancer Center in Houston, Tex., and colleagues.

“[O]ur study shows that ponatinib is a very potent TKI with high clinical activity in the first-line treatment of patients with chronic-phase CML. However, at the doses currently used in other settings, the safety profile might not be appropriate for treatment of this patient population who have other treatment options with high efficacy,” the investigators wrote (Lancet Haematol. 2015;2[9]:e376-e383).

Ponatinib (Iclusig) is a third-generation TKI with action against malignancies with mutations in the ABL kinase domain that make the cancers resistant to first- and second-generation TKIs such as imatinib (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna).

Ponatinib is approved in the United States for treatment of adult patients with CML positive for the T3151 mutation in chronic phase, accelerated phase, or blast phase, or T3151-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL). It is also approved for treatment of adults with chronic phase, accelerated phase, or blast phase CML or Ph+ALL for whom no other TKI is indicated.

The drug labeling carries a boxed warning about increased risk for vascular occlusion, heart failure, and hepatotoxicity. The warning notes that “[a]rterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig-treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures.”

In a single-arm, open label trial, the investigators enrolled 51 patients with recently diagnosed CML in chronic phase, starting them on doses of oral ponatinib 45 mg daily. The protocol was later amended to a starting dose of 30 mg daily because of the high frequency of dose reductions required among patients started at 45 mg. Following a warning from the FDA about vascular complications with the drug, patients were started on daily low-dose aspirin (81 mg), and all drug doses were reduced to either 30 mg or 15 mg daily.

One of the patients discontinued therapy prior to assessment because of the FDA warning, leaving 50 for assessment at 6 months.

Of 46 patients evaluable for the primary outcome of CCyR by 6 months, 43 (94%) achieved it. Major molecular responses, defined as a BCR-ABL to ABL transcript ratio of 0.1% or lower, occurred in 40 of 50 patients (80%) evaluable for this secondary endpoint, and deep molecular response (MR4.5), defined as a ratio less than 0.0032% or lower, occurred in 28 of 50 (55%).

Cardiovascular events, primarily hypertension, occurred in 25 patients (49%), 15 (29%) had grade 3-4 myelosuppression, and 5 patients (10%) developed cerebrovascular or vaso-occlusive disease.

In all, 43 patients (85%) needed treatment interruptions at some time and 45 (88%) needed dose reductions. The study was terminated in June 2014, a little more than a year after recruitment began.

The study was sponsored by MD Anderson Cancer Center with partial support from Ariad Pharmaceuticals. Coauthors Hagop Kantarjian, Elias Jabbour, and Jorge Cortes report receiving grants, research support, or serving as consultants to Ariad.

The tyrosine kinase inhibitor ponatinib produced a high degree of complete cytogenetic responses when used in first-line treatment of patients with chronic myeloid leukemia in chronic phase. But the drug’s toxicities, especially its propensity for causing thromboembolic events, mitigate against its upfront use, investigators say.

In a small phase II study, 90% of evaluable patients with chronic-phase chronic myeloid leukemia (CML) treated with the tyrosine kinase inhibitor (TKI) had a complete cytogenetic response (CCyR) after 3 months, and 94% had a CCyR after 6 months, but that efficacy came at the cost of significant adverse events requiring dose reductions, treatment interruptions, and early termination of the trial for safety reasons at the recommendation of the Food and Drug Administration, reported Dr. Preetesh Jain of MD Anderson Cancer Center in Houston, Tex., and colleagues.

“[O]ur study shows that ponatinib is a very potent TKI with high clinical activity in the first-line treatment of patients with chronic-phase CML. However, at the doses currently used in other settings, the safety profile might not be appropriate for treatment of this patient population who have other treatment options with high efficacy,” the investigators wrote (Lancet Haematol. 2015;2[9]:e376-e383).

Ponatinib (Iclusig) is a third-generation TKI with action against malignancies with mutations in the ABL kinase domain that make the cancers resistant to first- and second-generation TKIs such as imatinib (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna).

Ponatinib is approved in the United States for treatment of adult patients with CML positive for the T3151 mutation in chronic phase, accelerated phase, or blast phase, or T3151-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL). It is also approved for treatment of adults with chronic phase, accelerated phase, or blast phase CML or Ph+ALL for whom no other TKI is indicated.

The drug labeling carries a boxed warning about increased risk for vascular occlusion, heart failure, and hepatotoxicity. The warning notes that “[a]rterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig-treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures.”

In a single-arm, open label trial, the investigators enrolled 51 patients with recently diagnosed CML in chronic phase, starting them on doses of oral ponatinib 45 mg daily. The protocol was later amended to a starting dose of 30 mg daily because of the high frequency of dose reductions required among patients started at 45 mg. Following a warning from the FDA about vascular complications with the drug, patients were started on daily low-dose aspirin (81 mg), and all drug doses were reduced to either 30 mg or 15 mg daily.

One of the patients discontinued therapy prior to assessment because of the FDA warning, leaving 50 for assessment at 6 months.

Of 46 patients evaluable for the primary outcome of CCyR by 6 months, 43 (94%) achieved it. Major molecular responses, defined as a BCR-ABL to ABL transcript ratio of 0.1% or lower, occurred in 40 of 50 patients (80%) evaluable for this secondary endpoint, and deep molecular response (MR4.5), defined as a ratio less than 0.0032% or lower, occurred in 28 of 50 (55%).

Cardiovascular events, primarily hypertension, occurred in 25 patients (49%), 15 (29%) had grade 3-4 myelosuppression, and 5 patients (10%) developed cerebrovascular or vaso-occlusive disease.

In all, 43 patients (85%) needed treatment interruptions at some time and 45 (88%) needed dose reductions. The study was terminated in June 2014, a little more than a year after recruitment began.

The study was sponsored by MD Anderson Cancer Center with partial support from Ariad Pharmaceuticals. Coauthors Hagop Kantarjian, Elias Jabbour, and Jorge Cortes report receiving grants, research support, or serving as consultants to Ariad.

The tyrosine kinase inhibitor ponatinib produced a high degree of complete cytogenetic responses when used in first-line treatment of patients with chronic myeloid leukemia in chronic phase. But the drug’s toxicities, especially its propensity for causing thromboembolic events, mitigate against its upfront use, investigators say.

In a small phase II study, 90% of evaluable patients with chronic-phase chronic myeloid leukemia (CML) treated with the tyrosine kinase inhibitor (TKI) had a complete cytogenetic response (CCyR) after 3 months, and 94% had a CCyR after 6 months, but that efficacy came at the cost of significant adverse events requiring dose reductions, treatment interruptions, and early termination of the trial for safety reasons at the recommendation of the Food and Drug Administration, reported Dr. Preetesh Jain of MD Anderson Cancer Center in Houston, Tex., and colleagues.

“[O]ur study shows that ponatinib is a very potent TKI with high clinical activity in the first-line treatment of patients with chronic-phase CML. However, at the doses currently used in other settings, the safety profile might not be appropriate for treatment of this patient population who have other treatment options with high efficacy,” the investigators wrote (Lancet Haematol. 2015;2[9]:e376-e383).

Ponatinib (Iclusig) is a third-generation TKI with action against malignancies with mutations in the ABL kinase domain that make the cancers resistant to first- and second-generation TKIs such as imatinib (Gleevec), dasatinib (Sprycel), and nilotinib (Tasigna).

Ponatinib is approved in the United States for treatment of adult patients with CML positive for the T3151 mutation in chronic phase, accelerated phase, or blast phase, or T3151-positive Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL). It is also approved for treatment of adults with chronic phase, accelerated phase, or blast phase CML or Ph+ALL for whom no other TKI is indicated.

The drug labeling carries a boxed warning about increased risk for vascular occlusion, heart failure, and hepatotoxicity. The warning notes that “[a]rterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig-treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures.”

In a single-arm, open label trial, the investigators enrolled 51 patients with recently diagnosed CML in chronic phase, starting them on doses of oral ponatinib 45 mg daily. The protocol was later amended to a starting dose of 30 mg daily because of the high frequency of dose reductions required among patients started at 45 mg. Following a warning from the FDA about vascular complications with the drug, patients were started on daily low-dose aspirin (81 mg), and all drug doses were reduced to either 30 mg or 15 mg daily.

One of the patients discontinued therapy prior to assessment because of the FDA warning, leaving 50 for assessment at 6 months.

Of 46 patients evaluable for the primary outcome of CCyR by 6 months, 43 (94%) achieved it. Major molecular responses, defined as a BCR-ABL to ABL transcript ratio of 0.1% or lower, occurred in 40 of 50 patients (80%) evaluable for this secondary endpoint, and deep molecular response (MR4.5), defined as a ratio less than 0.0032% or lower, occurred in 28 of 50 (55%).

Cardiovascular events, primarily hypertension, occurred in 25 patients (49%), 15 (29%) had grade 3-4 myelosuppression, and 5 patients (10%) developed cerebrovascular or vaso-occlusive disease.

In all, 43 patients (85%) needed treatment interruptions at some time and 45 (88%) needed dose reductions. The study was terminated in June 2014, a little more than a year after recruitment began.

The study was sponsored by MD Anderson Cancer Center with partial support from Ariad Pharmaceuticals. Coauthors Hagop Kantarjian, Elias Jabbour, and Jorge Cortes report receiving grants, research support, or serving as consultants to Ariad.

Among adults with hand osteoarthritis, ultrasonographic evidence of persistent joint-level inflammation increased the odds of subsequent erosions by as much as 11 times, said authors of a 2-year prospective study.

“These observations implicate a role for inflammation in the pathogenesis of erosive osteoarthritis and might render new therapeutic options that can halt erosive development,” said Dr. Marion C. Kortekaas and her associates at Leiden (the Netherlands) University Medical Center. The findings appeared online in Arthritis & Rheumatology.

©Astrid Gast/thinkstockphotos.com

The pathogenesis of erosive hand OA remains poorly understood, despite its high clinical burden, the researchers noted. To assess potential risk factors for erosive development, they used standard ultrasonographic methods to examine the interphalangeal joints of 56 consecutive patients who presented to a rheumatology outpatient clinic with hand OA based on American College of Rheumatology criteria. They also scored radiographs for osteophytes or joint-space narrowing with the OARSI method and used the Verbruggen-Veys method to identify and exclude joints that were already eroded (E phase) or remodeled (R phase) at baseline (Arthritis Rheum. 2015 Sep 28. doi: 10.1002/art.39438). At baseline, 18 patients had ultrasonographic evidence of erosions in a total of 51 interphalangeal joints, the investigators said. At the 2.3-year follow-up, a total of 38 interphalangeal joints from 26 patients showed erosive development.

After accounting for age, gender, body mass index, and baseline cartilage and bone abnormalities, all ultrasonographic features of inflammation that were at least grade 1 at baseline and follow-up predicted erosive development. Persistent power Doppler signal was the strongest risk factor, yielding an odds ratio of 11.4 in the adjusted model (95% confidence interval, 2.7-49.1). Other significant risk factors included moderate to severe baseline synovial thickening (OR, 8.8; 95% CI, 2.4-32.3) and power Doppler signal (OR, 7.1; 95% CI, 1.9-26.9).

“The present study confirms that inflammatory US features found at baseline are associated with erosive development on the joint level in hand OA,” the investigators wrote. “These associations are already found after 2 years of follow-up, which is important for future prospective trials.”

The researchers reported having no funding sources or conflicts of interest.

Among adults with hand osteoarthritis, ultrasonographic evidence of persistent joint-level inflammation increased the odds of subsequent erosions by as much as 11 times, said authors of a 2-year prospective study.

“These observations implicate a role for inflammation in the pathogenesis of erosive osteoarthritis and might render new therapeutic options that can halt erosive development,” said Dr. Marion C. Kortekaas and her associates at Leiden (the Netherlands) University Medical Center. The findings appeared online in Arthritis & Rheumatology.

©Astrid Gast/thinkstockphotos.com

The pathogenesis of erosive hand OA remains poorly understood, despite its high clinical burden, the researchers noted. To assess potential risk factors for erosive development, they used standard ultrasonographic methods to examine the interphalangeal joints of 56 consecutive patients who presented to a rheumatology outpatient clinic with hand OA based on American College of Rheumatology criteria. They also scored radiographs for osteophytes or joint-space narrowing with the OARSI method and used the Verbruggen-Veys method to identify and exclude joints that were already eroded (E phase) or remodeled (R phase) at baseline (Arthritis Rheum. 2015 Sep 28. doi: 10.1002/art.39438). At baseline, 18 patients had ultrasonographic evidence of erosions in a total of 51 interphalangeal joints, the investigators said. At the 2.3-year follow-up, a total of 38 interphalangeal joints from 26 patients showed erosive development.

After accounting for age, gender, body mass index, and baseline cartilage and bone abnormalities, all ultrasonographic features of inflammation that were at least grade 1 at baseline and follow-up predicted erosive development. Persistent power Doppler signal was the strongest risk factor, yielding an odds ratio of 11.4 in the adjusted model (95% confidence interval, 2.7-49.1). Other significant risk factors included moderate to severe baseline synovial thickening (OR, 8.8; 95% CI, 2.4-32.3) and power Doppler signal (OR, 7.1; 95% CI, 1.9-26.9).

“The present study confirms that inflammatory US features found at baseline are associated with erosive development on the joint level in hand OA,” the investigators wrote. “These associations are already found after 2 years of follow-up, which is important for future prospective trials.”

The researchers reported having no funding sources or conflicts of interest.

Among adults with hand osteoarthritis, ultrasonographic evidence of persistent joint-level inflammation increased the odds of subsequent erosions by as much as 11 times, said authors of a 2-year prospective study.

“These observations implicate a role for inflammation in the pathogenesis of erosive osteoarthritis and might render new therapeutic options that can halt erosive development,” said Dr. Marion C. Kortekaas and her associates at Leiden (the Netherlands) University Medical Center. The findings appeared online in Arthritis & Rheumatology.

©Astrid Gast/thinkstockphotos.com

The pathogenesis of erosive hand OA remains poorly understood, despite its high clinical burden, the researchers noted. To assess potential risk factors for erosive development, they used standard ultrasonographic methods to examine the interphalangeal joints of 56 consecutive patients who presented to a rheumatology outpatient clinic with hand OA based on American College of Rheumatology criteria. They also scored radiographs for osteophytes or joint-space narrowing with the OARSI method and used the Verbruggen-Veys method to identify and exclude joints that were already eroded (E phase) or remodeled (R phase) at baseline (Arthritis Rheum. 2015 Sep 28. doi: 10.1002/art.39438). At baseline, 18 patients had ultrasonographic evidence of erosions in a total of 51 interphalangeal joints, the investigators said. At the 2.3-year follow-up, a total of 38 interphalangeal joints from 26 patients showed erosive development.

After accounting for age, gender, body mass index, and baseline cartilage and bone abnormalities, all ultrasonographic features of inflammation that were at least grade 1 at baseline and follow-up predicted erosive development. Persistent power Doppler signal was the strongest risk factor, yielding an odds ratio of 11.4 in the adjusted model (95% confidence interval, 2.7-49.1). Other significant risk factors included moderate to severe baseline synovial thickening (OR, 8.8; 95% CI, 2.4-32.3) and power Doppler signal (OR, 7.1; 95% CI, 1.9-26.9).

“The present study confirms that inflammatory US features found at baseline are associated with erosive development on the joint level in hand OA,” the investigators wrote. “These associations are already found after 2 years of follow-up, which is important for future prospective trials.”

The researchers reported having no funding sources or conflicts of interest.

Drug production

Photo courtesy of the FDA

Using the words “breakthrough” and “promising” to describe new drugs affects the public’s perception of the drugs’ effectiveness, according to a study published in JAMA Internal Medicine.

Investigators noted that, in everyday usage, the term “breakthrough” represents a highly significant or definitive advance.

However, the US Food and Drug Administration’s (FDA’s) “breakthrough therapy designation” has a different meaning.

Since the Safety and Innovation Act became law in 2012, the FDA can assign breakthrough designation to a drug that “treats a serious or life-threatening condition” and “may demonstrate a substantial improvement . . . over available therapies” based on preliminary evidence.

And since the creation of the Safety and Innovation Act, all FDA press releases announcing the approval of breakthrough-designated drugs have used the term “breakthrough,” while about half have used the term “promising.”

“Today, patients and their families can easily find FDA press releases on the Internet, or they often hear about them in the news,” said study author Steven Woloshin, MD, of The Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire.

“But the reality is that unless patients fully understand how the FDA is using the term ‘breakthrough,’ they may have unwarranted confidence in the evidence supporting drug claims. So we thought it was important to test how these terms affect the judgement of people without medical training.”

Survey details

The investigators conducted an online survey of 597 Americans. Participants were randomly given 1 of 5 short descriptions of a recently approved drug.

The descriptions were based on an FDA press release for a metastatic lung cancer breakthrough-designated drug that was conditionally approved based on the surrogate outcome of tumor shrinkage.

The first, “facts-only” description described the drug as meeting the criteria for breakthrough designation but did not actually use the term “breakthrough.”

A second and a third description included the facts and added the terms “breakthrough” and “promising,” respectively.

The fourth, “tentative” description included the facts, used the word “breakthrough,” and used the following FDA-required language for professional labeling:

The FDA pointed out that the drug was approved based on tumor shrinkage but that an improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

The fifth, “definitive” description included the same information as the tentative description, but “may be contingent” was changed to “is contingent.”

Participants were then asked to judge the drug’s benefit, harm, and strength of evidence.

Results

The investigators found that adding either “breakthrough” or “promising” in the description significantly increased the percentage of participants who rated the drug as “very” or “completely” effective compared with the facts-only description—23% and 25% vs 11%.

Adding “breakthrough” or “promising” to the description also significantly increased the number of people who reported believing that evidence supporting the drug is “strong” or “extremely strong”—59% and 63% vs 43%.

At the same time, adding either the tentative or definitive explanations significantly reduced the percentage of participants who believed (incorrectly) that the drug had been “proven to save lives”—16% tentative and 10% definitive vs 31% breakthrough.

Finally, when participants were asked which of 2 drugs—one described as “breakthrough,” the other as meeting the breakthrough criteria—they would take for a potentially deadly condition, 92% chose the “breakthrough” drug.

“Our findings clearly indicate that words like ‘breakthrough’ and ‘promising’ increase people’s beliefs in a drug’s effectiveness,” said Lisa Schwartz, MD, of The Dartmouth Institute for Health Policy and Clinical Practice.

“In light of [the findings], press releases with neutral terms and that clearly explain the limited evidence supporting what breakthrough designation and accelerated approval mean might help consumers make more accurate judgements about these drugs.”

Drug production

Photo courtesy of the FDA

Using the words “breakthrough” and “promising” to describe new drugs affects the public’s perception of the drugs’ effectiveness, according to a study published in JAMA Internal Medicine.

Investigators noted that, in everyday usage, the term “breakthrough” represents a highly significant or definitive advance.

However, the US Food and Drug Administration’s (FDA’s) “breakthrough therapy designation” has a different meaning.

Since the Safety and Innovation Act became law in 2012, the FDA can assign breakthrough designation to a drug that “treats a serious or life-threatening condition” and “may demonstrate a substantial improvement . . . over available therapies” based on preliminary evidence.

And since the creation of the Safety and Innovation Act, all FDA press releases announcing the approval of breakthrough-designated drugs have used the term “breakthrough,” while about half have used the term “promising.”

“Today, patients and their families can easily find FDA press releases on the Internet, or they often hear about them in the news,” said study author Steven Woloshin, MD, of The Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire.

“But the reality is that unless patients fully understand how the FDA is using the term ‘breakthrough,’ they may have unwarranted confidence in the evidence supporting drug claims. So we thought it was important to test how these terms affect the judgement of people without medical training.”

Survey details

The investigators conducted an online survey of 597 Americans. Participants were randomly given 1 of 5 short descriptions of a recently approved drug.

The descriptions were based on an FDA press release for a metastatic lung cancer breakthrough-designated drug that was conditionally approved based on the surrogate outcome of tumor shrinkage.

The first, “facts-only” description described the drug as meeting the criteria for breakthrough designation but did not actually use the term “breakthrough.”

A second and a third description included the facts and added the terms “breakthrough” and “promising,” respectively.

The fourth, “tentative” description included the facts, used the word “breakthrough,” and used the following FDA-required language for professional labeling:

The FDA pointed out that the drug was approved based on tumor shrinkage but that an improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

The fifth, “definitive” description included the same information as the tentative description, but “may be contingent” was changed to “is contingent.”

Participants were then asked to judge the drug’s benefit, harm, and strength of evidence.

Results

The investigators found that adding either “breakthrough” or “promising” in the description significantly increased the percentage of participants who rated the drug as “very” or “completely” effective compared with the facts-only description—23% and 25% vs 11%.

Adding “breakthrough” or “promising” to the description also significantly increased the number of people who reported believing that evidence supporting the drug is “strong” or “extremely strong”—59% and 63% vs 43%.

At the same time, adding either the tentative or definitive explanations significantly reduced the percentage of participants who believed (incorrectly) that the drug had been “proven to save lives”—16% tentative and 10% definitive vs 31% breakthrough.

Finally, when participants were asked which of 2 drugs—one described as “breakthrough,” the other as meeting the breakthrough criteria—they would take for a potentially deadly condition, 92% chose the “breakthrough” drug.

“Our findings clearly indicate that words like ‘breakthrough’ and ‘promising’ increase people’s beliefs in a drug’s effectiveness,” said Lisa Schwartz, MD, of The Dartmouth Institute for Health Policy and Clinical Practice.

“In light of [the findings], press releases with neutral terms and that clearly explain the limited evidence supporting what breakthrough designation and accelerated approval mean might help consumers make more accurate judgements about these drugs.”

Drug production

Photo courtesy of the FDA

Using the words “breakthrough” and “promising” to describe new drugs affects the public’s perception of the drugs’ effectiveness, according to a study published in JAMA Internal Medicine.

Investigators noted that, in everyday usage, the term “breakthrough” represents a highly significant or definitive advance.

However, the US Food and Drug Administration’s (FDA’s) “breakthrough therapy designation” has a different meaning.

Since the Safety and Innovation Act became law in 2012, the FDA can assign breakthrough designation to a drug that “treats a serious or life-threatening condition” and “may demonstrate a substantial improvement . . . over available therapies” based on preliminary evidence.

And since the creation of the Safety and Innovation Act, all FDA press releases announcing the approval of breakthrough-designated drugs have used the term “breakthrough,” while about half have used the term “promising.”

“Today, patients and their families can easily find FDA press releases on the Internet, or they often hear about them in the news,” said study author Steven Woloshin, MD, of The Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire.

“But the reality is that unless patients fully understand how the FDA is using the term ‘breakthrough,’ they may have unwarranted confidence in the evidence supporting drug claims. So we thought it was important to test how these terms affect the judgement of people without medical training.”

Survey details

The investigators conducted an online survey of 597 Americans. Participants were randomly given 1 of 5 short descriptions of a recently approved drug.

The descriptions were based on an FDA press release for a metastatic lung cancer breakthrough-designated drug that was conditionally approved based on the surrogate outcome of tumor shrinkage.

The first, “facts-only” description described the drug as meeting the criteria for breakthrough designation but did not actually use the term “breakthrough.”

A second and a third description included the facts and added the terms “breakthrough” and “promising,” respectively.

The fourth, “tentative” description included the facts, used the word “breakthrough,” and used the following FDA-required language for professional labeling:

The FDA pointed out that the drug was approved based on tumor shrinkage but that an improvement in survival or disease-related symptoms has not been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

The fifth, “definitive” description included the same information as the tentative description, but “may be contingent” was changed to “is contingent.”

Participants were then asked to judge the drug’s benefit, harm, and strength of evidence.

Results

The investigators found that adding either “breakthrough” or “promising” in the description significantly increased the percentage of participants who rated the drug as “very” or “completely” effective compared with the facts-only description—23% and 25% vs 11%.

Adding “breakthrough” or “promising” to the description also significantly increased the number of people who reported believing that evidence supporting the drug is “strong” or “extremely strong”—59% and 63% vs 43%.

At the same time, adding either the tentative or definitive explanations significantly reduced the percentage of participants who believed (incorrectly) that the drug had been “proven to save lives”—16% tentative and 10% definitive vs 31% breakthrough.

Finally, when participants were asked which of 2 drugs—one described as “breakthrough,” the other as meeting the breakthrough criteria—they would take for a potentially deadly condition, 92% chose the “breakthrough” drug.

“Our findings clearly indicate that words like ‘breakthrough’ and ‘promising’ increase people’s beliefs in a drug’s effectiveness,” said Lisa Schwartz, MD, of The Dartmouth Institute for Health Policy and Clinical Practice.

“In light of [the findings], press releases with neutral terms and that clearly explain the limited evidence supporting what breakthrough designation and accelerated approval mean might help consumers make more accurate judgements about these drugs.”

Vial of heparin

Researchers believe they have identified a therapeutic target for heparin-induced thrombocytopenia (HIT).

The team noted that HIT is caused by antibodies to complexes that form between platelet factor 4 (PF4), which is released from activated platelets, and heparin or cellular glycosaminoglycans.

The researchers elucidated the crystal structure of 3 PF4 complexes and found evidence suggesting that tetramerization of PF4 is targetable.

Zheng Cai, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues described this work in Nature Communications.

Previously, the researchers identified KKO, a murine monoclonal antibody to PF4/heparin complexes that causes HIT in a murine model. The team said human HIT antibodies compete with KKO for binding to PF4/heparin, and KKO augments the formation of pathogenic immune complexes.

The researchers also identified RTO, an isotype-matched, anti-PF4 antibody that binds to PF4 but does not generate pathogenic complexes.

For the current study, the team described and compared the crystal structures of PF4 in complex with Fabs derived from KKO and RTO to the structure of PF4 in complex with fondaparinux.

The researchers noted that PF4 molecules can exist singly as monomers, doubly as dimers, and as a 4-part complex called a tetramer, which have an “open” end and a “closed” end.

The crystal structure of PF4 in complex with fondaparinux showed that fondaparinux binds to the “closed” end of the PF4 tetramer, which stabilizes the tetramer.

The crystal structure of PF4 in complex with KKO showed that KKO binds to the “open” end of the stabilized tetramer, making contact with 3 of 4 monomers in the tetramer.

The researchers said this helps explain the requirement for heparin as a backbone for the complex. They also said this finding provides new insight into how a normal host protein such as PF4 can be converted into a target of the host immune system, which leads to an autoimmune disorder.

The crystal structure of PF4 in complex with RTO showed that RTO binds to PF4 monomers rather than tetramers. And RTO binds to the monomers in a way that prevents them from combining into tetramers.

Via cell experiments, the researchers confirmed that RTO prevents the formation of antigenic complexes, as well as the activation of platelets by KKO and human HIT antibodies. RTO also prevented clot formation caused by KKO in a mouse model of HIT.

These results suggest that binding of RTO to PF4 monomers prevents the formation of pathogenic complexes that are central to the pathology of HIT. So the researchers believe RTO can provide the basis for new diagnostics and may pave the way for a therapy to stop HIT early in its progression.

Vial of heparin

Researchers believe they have identified a therapeutic target for heparin-induced thrombocytopenia (HIT).

The team noted that HIT is caused by antibodies to complexes that form between platelet factor 4 (PF4), which is released from activated platelets, and heparin or cellular glycosaminoglycans.

The researchers elucidated the crystal structure of 3 PF4 complexes and found evidence suggesting that tetramerization of PF4 is targetable.

Zheng Cai, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues described this work in Nature Communications.

Previously, the researchers identified KKO, a murine monoclonal antibody to PF4/heparin complexes that causes HIT in a murine model. The team said human HIT antibodies compete with KKO for binding to PF4/heparin, and KKO augments the formation of pathogenic immune complexes.

The researchers also identified RTO, an isotype-matched, anti-PF4 antibody that binds to PF4 but does not generate pathogenic complexes.

For the current study, the team described and compared the crystal structures of PF4 in complex with Fabs derived from KKO and RTO to the structure of PF4 in complex with fondaparinux.

The researchers noted that PF4 molecules can exist singly as monomers, doubly as dimers, and as a 4-part complex called a tetramer, which have an “open” end and a “closed” end.

The crystal structure of PF4 in complex with fondaparinux showed that fondaparinux binds to the “closed” end of the PF4 tetramer, which stabilizes the tetramer.

The crystal structure of PF4 in complex with KKO showed that KKO binds to the “open” end of the stabilized tetramer, making contact with 3 of 4 monomers in the tetramer.

The researchers said this helps explain the requirement for heparin as a backbone for the complex. They also said this finding provides new insight into how a normal host protein such as PF4 can be converted into a target of the host immune system, which leads to an autoimmune disorder.

The crystal structure of PF4 in complex with RTO showed that RTO binds to PF4 monomers rather than tetramers. And RTO binds to the monomers in a way that prevents them from combining into tetramers.

Via cell experiments, the researchers confirmed that RTO prevents the formation of antigenic complexes, as well as the activation of platelets by KKO and human HIT antibodies. RTO also prevented clot formation caused by KKO in a mouse model of HIT.

These results suggest that binding of RTO to PF4 monomers prevents the formation of pathogenic complexes that are central to the pathology of HIT. So the researchers believe RTO can provide the basis for new diagnostics and may pave the way for a therapy to stop HIT early in its progression.

Vial of heparin

Researchers believe they have identified a therapeutic target for heparin-induced thrombocytopenia (HIT).

The team noted that HIT is caused by antibodies to complexes that form between platelet factor 4 (PF4), which is released from activated platelets, and heparin or cellular glycosaminoglycans.

The researchers elucidated the crystal structure of 3 PF4 complexes and found evidence suggesting that tetramerization of PF4 is targetable.

Zheng Cai, PhD, of the University of Pennsylvania in Philadelphia, and his colleagues described this work in Nature Communications.

Previously, the researchers identified KKO, a murine monoclonal antibody to PF4/heparin complexes that causes HIT in a murine model. The team said human HIT antibodies compete with KKO for binding to PF4/heparin, and KKO augments the formation of pathogenic immune complexes.

The researchers also identified RTO, an isotype-matched, anti-PF4 antibody that binds to PF4 but does not generate pathogenic complexes.

For the current study, the team described and compared the crystal structures of PF4 in complex with Fabs derived from KKO and RTO to the structure of PF4 in complex with fondaparinux.

The researchers noted that PF4 molecules can exist singly as monomers, doubly as dimers, and as a 4-part complex called a tetramer, which have an “open” end and a “closed” end.

The crystal structure of PF4 in complex with fondaparinux showed that fondaparinux binds to the “closed” end of the PF4 tetramer, which stabilizes the tetramer.

The crystal structure of PF4 in complex with KKO showed that KKO binds to the “open” end of the stabilized tetramer, making contact with 3 of 4 monomers in the tetramer.

The researchers said this helps explain the requirement for heparin as a backbone for the complex. They also said this finding provides new insight into how a normal host protein such as PF4 can be converted into a target of the host immune system, which leads to an autoimmune disorder.

The crystal structure of PF4 in complex with RTO showed that RTO binds to PF4 monomers rather than tetramers. And RTO binds to the monomers in a way that prevents them from combining into tetramers.

Via cell experiments, the researchers confirmed that RTO prevents the formation of antigenic complexes, as well as the activation of platelets by KKO and human HIT antibodies. RTO also prevented clot formation caused by KKO in a mouse model of HIT.

These results suggest that binding of RTO to PF4 monomers prevents the formation of pathogenic complexes that are central to the pathology of HIT. So the researchers believe RTO can provide the basis for new diagnostics and may pave the way for a therapy to stop HIT early in its progression.