Sexual dysfunction is challenging for patients and clinicians. Just as sexual function is multidimensional—with physical and psychosocial elements—sexual dysfunction can likewise have multiple contributing factors, and is often divided into dysfunction of desire, arousal, orgasm, and sex-related pain. Addressing each of these dimensions of sexual dysfunction in relationship to pelvic reconstructive surgery is beyond the scope of this article. Here, we focus on aspects of sexual dysfunction most likely to be reported by patients after surgery for pelvic organ prolapse (POP) or urinary incontinence, or for both. We discuss what is known about why sexual dysfunction develops after these procedures; how to assess symptoms when sexual dysfunction occurs; and how best to treat these difficult problems.

CASE Postoperative sexual concerns

Your 62-year-old patient presents 2 weeks after vaginal hysterectomy, uterosacral vault suspension, anterior and posterior colporrhaphy, and retropubic midurethral polypropylene sling placement. She reports feeling tired but otherwise doing well.

The patient returns 8 weeks postoperatively, having just resumed her customary exercise routine, and reports that she is feeling well. Upon questioning, she says that she has not yet attempted to have sexual intercourse with her 70-year-old husband.

The patient returns 6 months later and reports that, although she is doing well overall, she is unable to have sexual intercourse.

How can you help this patient? What next steps in evaluation are indicated? Then, with an understanding of her problem in hand, what treatment options can you offer to her?

Surgery for pelvic-floor disorders and sexual function

The impact of surgery on sexual function is important to discuss with patients preoperatively and postoperatively. Because patients with POP and urinary incontinence have a higher rate of sexual dysfunction at baseline, it is important to know how surgery to correct these conditions can affect sexual function.¹ Regrettably, many studies of surgical procedures for POP and urinary incontinence either do not include sexual function outcomes or are not powered to detect differences in these outcomes.

Native-tissue repair. A 2015 systematic review looked at studies of women undergoing native-tissue repair for POP without mesh placement of any kind, including a midurethral sling.² Based on 9 studies that reported validated sexual function questionnaire scores, investigators determined that sexual function scores generally improved following surgery. Collectively, for studies included in this review that specifically reported the rate of dyspareunia before and after surgery, 47% of women reported improvement in dyspareunia; 39% reported no change; 18% reported deterioration in dyspareunia; and only 4% had de novo dyspareunia.

Colporrhaphy. Posterior colporrhaphy, commonly performed to correct posterior vaginal prolapse, can narrow vaginal caliber and the introitus, potentially causing dyspareunia. Early description of posterior colporrhaphy technique included plication of the levator ani muscles, which was associated with significant risk of dyspareunia postoperatively.³ However, posterior colporrhaphy that involves standard plication of the rectovaginal muscularis or site-specific repair has been reported to have a dyspareunia rate from 7% to 20%.^4,5 It is generally recommended, therefore, that levator muscle plication during colporrhaphy be avoided in sexually active women.

Continue to: Vaginal mesh...

Vaginal mesh. Mesh has been used in various surgical procedures to correct pelvic floor disorders. Numerous randomized trials have comparatively evaluated the use of transvaginal polypropylene mesh and native tissue for POP repair, and many of these studies have assessed postoperative sexual function. In a 2013 systematic review on sexual function after POP repair, the authors found no significant difference in postoperative sexual function scores or the dyspareunia rate after vaginal mesh repair (14%) and after native-tissue repair (12%).⁶

Studies of postsurgical sexual function are lacking

Important aspects of sexual function—orgasm, arousal, desire, lubrication, sexual satisfaction, effects on the partner—lack studies. A study of 71 sexually active couples assessed sexual function with questionnaires before and after vaginal native-tissue repair and found that, except for orgasm, all domains improved in female questionnaires. In male partners, interest, sexual drive, and overall satisfaction improved, whereas erection, ejaculation, and orgasm remained unchanged.⁷

Urinary incontinence during sexual intercourse affects approximately 30% of women with overactive bladder or stress incontinence.⁸ Several reviews have analyzed data on overall sexual function following urinary incontinence surgery:

• After stress incontinence surgery, the rate of coital incontinence was found to be significantly lower (odds ratio, 0.11).⁹ In this review, 18 studies, comprising more than 1,500 women, were analyzed, with most participants having undergone insertion of a midurethral mesh sling. Most women (55%) reported no change in overall sexual function, based on validated sexual questionnaire scores; 32% reported improvement; and 13% had deterioration in sexual function.
• As for type of midurethral sling, 2 reviews concluded that there is no difference in sexual function outcomes between retropubic and trans‑obturator sling routes.^9,10

Although most studies that have looked at POP and incontinence surgeries show either improvement or no change in sexual function, we stress that sexual function is a secondary outcome in most of those studies, which might not be appropriately powered to detect differences in outcomes. Furthermore, although studies describe dyspareunia and overall sexual function in validated questionnaire scores, most do not evaluate other specific domains of sexual function. It remains unclear, therefore, how POP and incontinence surgeries affect orgasm, desire, arousal, satisfaction, and partner sexual domains; more studies are needed to focus on these areas of female sexual function.

How do we assess these patients?

We do know that sexual function is important to women undergoing gynecologic surgery: In a recent qualitative study of women undergoing pelvic reconstruction, patients rated lack of improvement in sexual function following surgery a “very severe” adverse event.¹¹ Unfortunately, however, sexual activity and function is not always measured before gynecologic surgery. Although specific reporting guidelines do not exist for routine gynecologic surgery, a terminology report from the International Urogynecologic Association/International Continence Society (IUGA/ICS) recommends that sexual activity and partner status be evaluated prior to and following surgical treatment as essential outcomes.¹² In addition, the report recommends that sexual pain be assessed prior to and following surgical procedures.¹²

Ascertain sexual health. First, asking your patients simple questions about sexual function, pain, and bother before and after surgery opens the door to dialogue that allows them, and their partner, to express concerns to you in a safe environment. It also allows you to better understand the significant impact of your surgical interventions on their sexual health.

Questionnaires. Objective measures of vaginal blood flow and engorgement exist, but assessment of sexual activity in the clinical setting is largely limited to self-assessment with questionnaires. Incorporating simple questions, such as “Are you sexually active?,” “Do you have any problems with sexual activity?,” and “Do you have pain with activity?” are likely to be as effective as a more detailed interview and can identify women with sexual concerns.¹³ Many clinicians are put at a disadvantage, however, because they are faced with the difficult situation of addressing postoperative sexual problems without knowing whether the patient had such reports prior to surgery.

Continue to: Aside from simple screening tools...

Aside from simple screening tools, a number of sexual function questionnaires have been developed. Some are generic, and others are condition-specific:

• Generic questionnaires are typically designed to address the function of a range of women. For example, the Female Sexual Function Index comprises 19 questions. Domains include orgasm, desire, arousal, lubrication, pain and satisfaction.¹⁴
• Condition-specific questionnaires of sexual function each have been validated in their target population so that they measure nuances in sexual health relevant to that population. The Pelvic Organ Prolapse/Incontinence Sexual Questionnaire—IUGA-Revised includes questions about the domains listed for the generic Index (above) plus questions about the impact of coital incontinence or bulge symptoms on sexual function.¹²

History-taking. If a woman identifies a problem with sexual function, a thorough history helps elicit whether the condition is lifelong or acquired, situational or general, and, most important, whether or not it is bothersome to her.^14,15 It is important not to make assumptions when pursuing this part of the history, and to encourage patients to be candid about how they have sex and with whom.

Physical examination. The patient should undergo a complete physical exam, including 1) a detailed pelvic exam assessing the vulva, vagina, and pelvic-floor musculature, and 2) estrogenization of the tissue.

Partner concerns. For women who have a partner, addressing the concerns of that partner following gynecologic surgery can be useful to the couple: The partner might be concerned about inflicting pain or doing damage during sex after gynecologic surgery.

CASE Informative discussion

While ascertaining her sexual symptoms, your patient reveals to you that she has attempted sexual intercourse on 3 occasions; each time, penetration was too painful to continue. She tells you she did not have this problem before surgery.

The patient says that she has tried water-based lubricants and is using vaginal estrogen 3 times per week, but “nothing helps.” She reports that she is arousable and has been able to achieve orgasm with clitoral stimulation, but would like to have vaginal intercourse. Her husband does have erectile dysfunction, which, she tells you, can make penetration difficult.

On physical examination, you detect mild atrophy. Vaginal length is 9 cm; no narrowing or scarring of the vaginal introitus or canal is seen. No mesh is visible or palpable. The paths of the midurethral sling arms are nontender. However, levator muscles are tender and tense bilaterally.

Given these findings on examination, what steps can you take to relieve your patient’s pain?

What can we offer these patients?

Treating sexual dysfunction after pelvic reconstructive surgery must, as emphasized earlier, be guided by a careful history and physical exam. Doing so is critical to determining the underlying cause. Whenever feasible, offer the least invasive treatment.

The IUGA/ICS terminology report describes several symptoms of postoperative sexual dysfunction¹²:

• de novo sexual dysfunction
• de novo dyspareunia
• shortened vagina
• tight vagina (introital or vaginal narrowing, or both)
• scarred vagina (including mesh-related problems)
• hispareunia (pain experienced by a male partner after intercourse).

Of course, any one or combination of these symptoms can be present in a given patient. Furthermore, de novo sexual dysfunction, de novo dyspareunia, and hispareunia can have various underlying causes—again, underscoring the importance of the history and exam in determining treatment.

Continue to: Nonsurgical treatment...

Nonsurgical treatment

Nonhormonal vaginal lubricants and moisturizers; vaginal estrogen therapy. Although, in older women, vaginal atrophy is often not a new diagnosis postsurgically, the condition might have been untreated preoperatively and might therefore come into play in sexual dysfunction postoperatively. If a patient reports vaginal dryness or pain upon penetration, assess for vaginal atrophy and, if present, treat accordingly.

Vaginal dilation and physical therapy. A shortened, tight, or scarred vagina might be amenable to therapy with vaginal dilators and physical therapy, but might ultimately require surgery.

Pelvic-floor myalgia or spasm can develop after surgery or, as with atrophy, might have existed preoperatively but was left untreated. Pelvic-floor myalgia should be suspected if the patient describes difficult penetration or a feeling of tightness, even though scarring or constriction of the vagina is not seen on examination. Physical therapy with a specialist in pelvic floor treatment is a first-line treatment for pelvic-floor myalgia,¹⁶ and is likely to be a helpful adjunct in many situations, including mesh-related sexual problems.¹⁷

Oral or vaginal medications to relax pelvic-floor muscle spasm are an option, although efficacy data are limited. If pain is of longstanding duration and is thought to have a neuropathic component, successful use of tricyclic antidepressants, neuroleptics, and serotonin–norepinephrine reuptake inhibitors has been reported.¹⁸

Surgery

Data are sparse regarding surgical treatment of female sexual dysfunction after pelvic reconstructive surgery. Again, it is clear, however, that the key is carefully assessing each patient and then individualizing treatment. Patients can have any type of dysfunction that a patient who hasn’t had surgery can—but is also at risk of conditions directly related to surgery.

In any patient who has had mesh placed as part of surgery, thorough examination is necessary to determine whether or not the implant is involved in sexual dysfunction. If the dysfunction is an apparent result of surgery performed by another surgeon, make every effort to review the operative report to determine which material was implanted and how it was placed.

Trigger-point injection can be attempted in a patient who has site-specific tenderness that is not clearly associated with tissue obstruction of the vagina or mesh erosion.^12,19 Even in areas of apparent banding or scarring related to mesh, trigger-point injection can be attempted to alleviate pain. How often trigger-point injections should be performed is understudied.

If, on examination, tenderness that replicates the dyspareunia is elicited when palpating the levator or obturator internus muscle, pelvic-floor muscle trigger-point injection can be offered (although physical therapy is first-line treatment). Trigger-point injection also can be a useful adjunct in women who have another identified cause of pain but also have developed pelvic-floor muscle spasm.

Not addressing concomitant pelvic-floor myalgia could prevent successful treatment of pain. Inclusion of a pudendal block also might help to alleviate pain.

Continue to: Surgical resection...

Surgical resection. If a skin bridge is clearly observed at the introitus, or if the introitus has been overly narrowed by perineorrhaphy but the remainder of the vagina has adequate length and caliber, surgical resection of the skin bridge might relieve symptoms of difficult penetration. In the case of obstructive perineorrhaphy, an attempt at reversal can be made by incising the perineum vertically but then reapproximating the edges transversely—sometimes referred to as reverse perineorrhaphy.

If scar tissue found elsewhere in the vagina might obstruct penetration, this condition might also be amenable to resection. When scarring is annular, relaxing incisions can be made bilaterally to relieve tension on that tissue; alternatively, it might be necessary to perform a Z-plasty. Nearly always, severe scarring is accompanied by levator myalgia, and a combined approach of surgery and physical therapy is necessary.

Neovagina. It is possible to find vaginal stenosis or shortening, to a varying degree, after surgical prolapse repair, with or without mesh or graft. As discussed, vaginal dilation should be offered but, if this is ineffective, the patient might be a candidate for surgical creation of a neovagina. Numerous techniques have been described for patients with congenital vaginal agenesis, with a few reports of similar techniques used to treat iatrogenic vaginal stenosis or obliteration.

The general principle of all neovagina procedures is to create a space between bladder and rectum of adequate caliber and length for desired sexual function. Reported techniques include a thigh or buttock skin graft, use of bowel or peritoneum, and, recently, a buccal mucosa graft.^20,21

Resection or excision of mesh. In patients who develop sexual dysfunction after mesh placement, the problem can be caused by exposure of the mesh in the vagina or erosion into another organ, but can also arise in the absence of exposure or erosion. Patients might have tenderness to palpation at points where the mesh is palpable through the mucosa but not exposed.

Again, complete investigation is necessary to look for mesh involvement in the vagina and, depending on the type of implant, other adjacent organs. Assessing partner symptoms, such as pain and scratches, also can be telling.

If there is palpable tenderness on vaginal examination of the mesh, resection of the vaginal portion might be an option.¹⁷ Complete excision of mesh implants can be morbid, however, and might not provide a better outcome than partial excision. The risk of morbidity from complete mesh excision must be weighed against the likelihood that partial excision will not resolve pain and that the patient will require further excision subsequently.^17,22 Excising fragmented mesh can be difficult; making every attempt to understand the contribution of mesh to sexual dysfunction is therefore critical to determining how, and how much of, the mesh comes out at the first attempt.

Last, for any woman who opts for surgical intervention to treat pain, you should engage in a discussion to emphasize the multidimensional nature of sexual function and the fact that any surgical intervention might not completely resolve her dysfunction.

Continue to: CASE Discussing options...

CASE Discussing options, choosing an intervention

You discuss the examination findings (no shortening or narrowing of the vagina) with the patient. She is relieved but puzzled as to why she cannot have intercourse. You discuss the tension and tenderness of her pelvic floor and that this is likely the cause. You offer her physical therapy (PT). You also discuss muscle relaxing medications and trigger-point injections if physical therapy alone is unsuccessful or if she cannot do PT (as there are barriers, including insurance coverage and scheduling issues, to accessing PT for many patients). You encourage her to continue use of vaginal estrogen and lubricant during intercourse. She agrees to try PT.

At 3-month follow-up, she reports great improvement. She is able to have intercourse, although she says she still has discomfort sometimes. She continues to work with the pelvic floor physical therapist and feels optimistic. You plan to see her in 6 months but counsel her to call if symptoms are not improving or are worsening.

Sexual function must be part of the conversation

It is difficult to counsel patients about sexual function after pelvic reconstructive surgery because data that could guide identification of problems (and how to treat them) are incomplete. Assessingsexual function preoperatively and having an open conversation about risks and benefits of surgery, with specific mention of its impact on sexual health, are critical (see “Key touchpoints in managing sexual dysfunction after pelvic reconstructive surgery”).

It is also crucial to assess sexual function postoperatively as a matter of routine. Validated questionnaires can be a useful adjunct to a thorough history and physical exam, and can help guide your discussions.

Treatment of postop sexual dysfunction must, first, account for the complex nature of sexual function and, second, be individualized, starting with the least invasive options, when feasible. 

Sexual dysfunction is challenging for patients and clinicians. Just as sexual function is multidimensional—with physical and psychosocial elements—sexual dysfunction can likewise have multiple contributing factors, and is often divided into dysfunction of desire, arousal, orgasm, and sex-related pain. Addressing each of these dimensions of sexual dysfunction in relationship to pelvic reconstructive surgery is beyond the scope of this article. Here, we focus on aspects of sexual dysfunction most likely to be reported by patients after surgery for pelvic organ prolapse (POP) or urinary incontinence, or for both. We discuss what is known about why sexual dysfunction develops after these procedures; how to assess symptoms when sexual dysfunction occurs; and how best to treat these difficult problems.

CASE Postoperative sexual concerns

Your 62-year-old patient presents 2 weeks after vaginal hysterectomy, uterosacral vault suspension, anterior and posterior colporrhaphy, and retropubic midurethral polypropylene sling placement. She reports feeling tired but otherwise doing well.

The patient returns 8 weeks postoperatively, having just resumed her customary exercise routine, and reports that she is feeling well. Upon questioning, she says that she has not yet attempted to have sexual intercourse with her 70-year-old husband.

The patient returns 6 months later and reports that, although she is doing well overall, she is unable to have sexual intercourse.

How can you help this patient? What next steps in evaluation are indicated? Then, with an understanding of her problem in hand, what treatment options can you offer to her?

Surgery for pelvic-floor disorders and sexual function

The impact of surgery on sexual function is important to discuss with patients preoperatively and postoperatively. Because patients with POP and urinary incontinence have a higher rate of sexual dysfunction at baseline, it is important to know how surgery to correct these conditions can affect sexual function.¹ Regrettably, many studies of surgical procedures for POP and urinary incontinence either do not include sexual function outcomes or are not powered to detect differences in these outcomes.

Native-tissue repair. A 2015 systematic review looked at studies of women undergoing native-tissue repair for POP without mesh placement of any kind, including a midurethral sling.² Based on 9 studies that reported validated sexual function questionnaire scores, investigators determined that sexual function scores generally improved following surgery. Collectively, for studies included in this review that specifically reported the rate of dyspareunia before and after surgery, 47% of women reported improvement in dyspareunia; 39% reported no change; 18% reported deterioration in dyspareunia; and only 4% had de novo dyspareunia.

Colporrhaphy. Posterior colporrhaphy, commonly performed to correct posterior vaginal prolapse, can narrow vaginal caliber and the introitus, potentially causing dyspareunia. Early description of posterior colporrhaphy technique included plication of the levator ani muscles, which was associated with significant risk of dyspareunia postoperatively.³ However, posterior colporrhaphy that involves standard plication of the rectovaginal muscularis or site-specific repair has been reported to have a dyspareunia rate from 7% to 20%.^4,5 It is generally recommended, therefore, that levator muscle plication during colporrhaphy be avoided in sexually active women.

Continue to: Vaginal mesh...

Vaginal mesh. Mesh has been used in various surgical procedures to correct pelvic floor disorders. Numerous randomized trials have comparatively evaluated the use of transvaginal polypropylene mesh and native tissue for POP repair, and many of these studies have assessed postoperative sexual function. In a 2013 systematic review on sexual function after POP repair, the authors found no significant difference in postoperative sexual function scores or the dyspareunia rate after vaginal mesh repair (14%) and after native-tissue repair (12%).⁶

Studies of postsurgical sexual function are lacking

Important aspects of sexual function—orgasm, arousal, desire, lubrication, sexual satisfaction, effects on the partner—lack studies. A study of 71 sexually active couples assessed sexual function with questionnaires before and after vaginal native-tissue repair and found that, except for orgasm, all domains improved in female questionnaires. In male partners, interest, sexual drive, and overall satisfaction improved, whereas erection, ejaculation, and orgasm remained unchanged.⁷

Urinary incontinence during sexual intercourse affects approximately 30% of women with overactive bladder or stress incontinence.⁸ Several reviews have analyzed data on overall sexual function following urinary incontinence surgery:

• After stress incontinence surgery, the rate of coital incontinence was found to be significantly lower (odds ratio, 0.11).⁹ In this review, 18 studies, comprising more than 1,500 women, were analyzed, with most participants having undergone insertion of a midurethral mesh sling. Most women (55%) reported no change in overall sexual function, based on validated sexual questionnaire scores; 32% reported improvement; and 13% had deterioration in sexual function.
• As for type of midurethral sling, 2 reviews concluded that there is no difference in sexual function outcomes between retropubic and trans‑obturator sling routes.^9,10

Although most studies that have looked at POP and incontinence surgeries show either improvement or no change in sexual function, we stress that sexual function is a secondary outcome in most of those studies, which might not be appropriately powered to detect differences in outcomes. Furthermore, although studies describe dyspareunia and overall sexual function in validated questionnaire scores, most do not evaluate other specific domains of sexual function. It remains unclear, therefore, how POP and incontinence surgeries affect orgasm, desire, arousal, satisfaction, and partner sexual domains; more studies are needed to focus on these areas of female sexual function.

How do we assess these patients?

We do know that sexual function is important to women undergoing gynecologic surgery: In a recent qualitative study of women undergoing pelvic reconstruction, patients rated lack of improvement in sexual function following surgery a “very severe” adverse event.¹¹ Unfortunately, however, sexual activity and function is not always measured before gynecologic surgery. Although specific reporting guidelines do not exist for routine gynecologic surgery, a terminology report from the International Urogynecologic Association/International Continence Society (IUGA/ICS) recommends that sexual activity and partner status be evaluated prior to and following surgical treatment as essential outcomes.¹² In addition, the report recommends that sexual pain be assessed prior to and following surgical procedures.¹²

Ascertain sexual health. First, asking your patients simple questions about sexual function, pain, and bother before and after surgery opens the door to dialogue that allows them, and their partner, to express concerns to you in a safe environment. It also allows you to better understand the significant impact of your surgical interventions on their sexual health.

Questionnaires. Objective measures of vaginal blood flow and engorgement exist, but assessment of sexual activity in the clinical setting is largely limited to self-assessment with questionnaires. Incorporating simple questions, such as “Are you sexually active?,” “Do you have any problems with sexual activity?,” and “Do you have pain with activity?” are likely to be as effective as a more detailed interview and can identify women with sexual concerns.¹³ Many clinicians are put at a disadvantage, however, because they are faced with the difficult situation of addressing postoperative sexual problems without knowing whether the patient had such reports prior to surgery.

Continue to: Aside from simple screening tools...

Aside from simple screening tools, a number of sexual function questionnaires have been developed. Some are generic, and others are condition-specific:

• Generic questionnaires are typically designed to address the function of a range of women. For example, the Female Sexual Function Index comprises 19 questions. Domains include orgasm, desire, arousal, lubrication, pain and satisfaction.¹⁴
• Condition-specific questionnaires of sexual function each have been validated in their target population so that they measure nuances in sexual health relevant to that population. The Pelvic Organ Prolapse/Incontinence Sexual Questionnaire—IUGA-Revised includes questions about the domains listed for the generic Index (above) plus questions about the impact of coital incontinence or bulge symptoms on sexual function.¹²

History-taking. If a woman identifies a problem with sexual function, a thorough history helps elicit whether the condition is lifelong or acquired, situational or general, and, most important, whether or not it is bothersome to her.^14,15 It is important not to make assumptions when pursuing this part of the history, and to encourage patients to be candid about how they have sex and with whom.

Physical examination. The patient should undergo a complete physical exam, including 1) a detailed pelvic exam assessing the vulva, vagina, and pelvic-floor musculature, and 2) estrogenization of the tissue.

Partner concerns. For women who have a partner, addressing the concerns of that partner following gynecologic surgery can be useful to the couple: The partner might be concerned about inflicting pain or doing damage during sex after gynecologic surgery.

CASE Informative discussion

While ascertaining her sexual symptoms, your patient reveals to you that she has attempted sexual intercourse on 3 occasions; each time, penetration was too painful to continue. She tells you she did not have this problem before surgery.

The patient says that she has tried water-based lubricants and is using vaginal estrogen 3 times per week, but “nothing helps.” She reports that she is arousable and has been able to achieve orgasm with clitoral stimulation, but would like to have vaginal intercourse. Her husband does have erectile dysfunction, which, she tells you, can make penetration difficult.

On physical examination, you detect mild atrophy. Vaginal length is 9 cm; no narrowing or scarring of the vaginal introitus or canal is seen. No mesh is visible or palpable. The paths of the midurethral sling arms are nontender. However, levator muscles are tender and tense bilaterally.

Given these findings on examination, what steps can you take to relieve your patient’s pain?

What can we offer these patients?

Treating sexual dysfunction after pelvic reconstructive surgery must, as emphasized earlier, be guided by a careful history and physical exam. Doing so is critical to determining the underlying cause. Whenever feasible, offer the least invasive treatment.

The IUGA/ICS terminology report describes several symptoms of postoperative sexual dysfunction¹²:

• de novo sexual dysfunction
• de novo dyspareunia
• shortened vagina
• tight vagina (introital or vaginal narrowing, or both)
• scarred vagina (including mesh-related problems)
• hispareunia (pain experienced by a male partner after intercourse).

Of course, any one or combination of these symptoms can be present in a given patient. Furthermore, de novo sexual dysfunction, de novo dyspareunia, and hispareunia can have various underlying causes—again, underscoring the importance of the history and exam in determining treatment.

Continue to: Nonsurgical treatment...

Nonsurgical treatment

Nonhormonal vaginal lubricants and moisturizers; vaginal estrogen therapy. Although, in older women, vaginal atrophy is often not a new diagnosis postsurgically, the condition might have been untreated preoperatively and might therefore come into play in sexual dysfunction postoperatively. If a patient reports vaginal dryness or pain upon penetration, assess for vaginal atrophy and, if present, treat accordingly.

Vaginal dilation and physical therapy. A shortened, tight, or scarred vagina might be amenable to therapy with vaginal dilators and physical therapy, but might ultimately require surgery.

Pelvic-floor myalgia or spasm can develop after surgery or, as with atrophy, might have existed preoperatively but was left untreated. Pelvic-floor myalgia should be suspected if the patient describes difficult penetration or a feeling of tightness, even though scarring or constriction of the vagina is not seen on examination. Physical therapy with a specialist in pelvic floor treatment is a first-line treatment for pelvic-floor myalgia,¹⁶ and is likely to be a helpful adjunct in many situations, including mesh-related sexual problems.¹⁷

Oral or vaginal medications to relax pelvic-floor muscle spasm are an option, although efficacy data are limited. If pain is of longstanding duration and is thought to have a neuropathic component, successful use of tricyclic antidepressants, neuroleptics, and serotonin–norepinephrine reuptake inhibitors has been reported.¹⁸

Surgery

Data are sparse regarding surgical treatment of female sexual dysfunction after pelvic reconstructive surgery. Again, it is clear, however, that the key is carefully assessing each patient and then individualizing treatment. Patients can have any type of dysfunction that a patient who hasn’t had surgery can—but is also at risk of conditions directly related to surgery.

In any patient who has had mesh placed as part of surgery, thorough examination is necessary to determine whether or not the implant is involved in sexual dysfunction. If the dysfunction is an apparent result of surgery performed by another surgeon, make every effort to review the operative report to determine which material was implanted and how it was placed.

Trigger-point injection can be attempted in a patient who has site-specific tenderness that is not clearly associated with tissue obstruction of the vagina or mesh erosion.^12,19 Even in areas of apparent banding or scarring related to mesh, trigger-point injection can be attempted to alleviate pain. How often trigger-point injections should be performed is understudied.

If, on examination, tenderness that replicates the dyspareunia is elicited when palpating the levator or obturator internus muscle, pelvic-floor muscle trigger-point injection can be offered (although physical therapy is first-line treatment). Trigger-point injection also can be a useful adjunct in women who have another identified cause of pain but also have developed pelvic-floor muscle spasm.

Not addressing concomitant pelvic-floor myalgia could prevent successful treatment of pain. Inclusion of a pudendal block also might help to alleviate pain.

Continue to: Surgical resection...

Surgical resection. If a skin bridge is clearly observed at the introitus, or if the introitus has been overly narrowed by perineorrhaphy but the remainder of the vagina has adequate length and caliber, surgical resection of the skin bridge might relieve symptoms of difficult penetration. In the case of obstructive perineorrhaphy, an attempt at reversal can be made by incising the perineum vertically but then reapproximating the edges transversely—sometimes referred to as reverse perineorrhaphy.

If scar tissue found elsewhere in the vagina might obstruct penetration, this condition might also be amenable to resection. When scarring is annular, relaxing incisions can be made bilaterally to relieve tension on that tissue; alternatively, it might be necessary to perform a Z-plasty. Nearly always, severe scarring is accompanied by levator myalgia, and a combined approach of surgery and physical therapy is necessary.

Neovagina. It is possible to find vaginal stenosis or shortening, to a varying degree, after surgical prolapse repair, with or without mesh or graft. As discussed, vaginal dilation should be offered but, if this is ineffective, the patient might be a candidate for surgical creation of a neovagina. Numerous techniques have been described for patients with congenital vaginal agenesis, with a few reports of similar techniques used to treat iatrogenic vaginal stenosis or obliteration.

The general principle of all neovagina procedures is to create a space between bladder and rectum of adequate caliber and length for desired sexual function. Reported techniques include a thigh or buttock skin graft, use of bowel or peritoneum, and, recently, a buccal mucosa graft.^20,21

Resection or excision of mesh. In patients who develop sexual dysfunction after mesh placement, the problem can be caused by exposure of the mesh in the vagina or erosion into another organ, but can also arise in the absence of exposure or erosion. Patients might have tenderness to palpation at points where the mesh is palpable through the mucosa but not exposed.

Again, complete investigation is necessary to look for mesh involvement in the vagina and, depending on the type of implant, other adjacent organs. Assessing partner symptoms, such as pain and scratches, also can be telling.

If there is palpable tenderness on vaginal examination of the mesh, resection of the vaginal portion might be an option.¹⁷ Complete excision of mesh implants can be morbid, however, and might not provide a better outcome than partial excision. The risk of morbidity from complete mesh excision must be weighed against the likelihood that partial excision will not resolve pain and that the patient will require further excision subsequently.^17,22 Excising fragmented mesh can be difficult; making every attempt to understand the contribution of mesh to sexual dysfunction is therefore critical to determining how, and how much of, the mesh comes out at the first attempt.

Last, for any woman who opts for surgical intervention to treat pain, you should engage in a discussion to emphasize the multidimensional nature of sexual function and the fact that any surgical intervention might not completely resolve her dysfunction.

Continue to: CASE Discussing options...

CASE Discussing options, choosing an intervention

You discuss the examination findings (no shortening or narrowing of the vagina) with the patient. She is relieved but puzzled as to why she cannot have intercourse. You discuss the tension and tenderness of her pelvic floor and that this is likely the cause. You offer her physical therapy (PT). You also discuss muscle relaxing medications and trigger-point injections if physical therapy alone is unsuccessful or if she cannot do PT (as there are barriers, including insurance coverage and scheduling issues, to accessing PT for many patients). You encourage her to continue use of vaginal estrogen and lubricant during intercourse. She agrees to try PT.

At 3-month follow-up, she reports great improvement. She is able to have intercourse, although she says she still has discomfort sometimes. She continues to work with the pelvic floor physical therapist and feels optimistic. You plan to see her in 6 months but counsel her to call if symptoms are not improving or are worsening.

Sexual function must be part of the conversation

It is difficult to counsel patients about sexual function after pelvic reconstructive surgery because data that could guide identification of problems (and how to treat them) are incomplete. Assessingsexual function preoperatively and having an open conversation about risks and benefits of surgery, with specific mention of its impact on sexual health, are critical (see “Key touchpoints in managing sexual dysfunction after pelvic reconstructive surgery”).

It is also crucial to assess sexual function postoperatively as a matter of routine. Validated questionnaires can be a useful adjunct to a thorough history and physical exam, and can help guide your discussions.

Treatment of postop sexual dysfunction must, first, account for the complex nature of sexual function and, second, be individualized, starting with the least invasive options, when feasible. 

Sexual dysfunction is challenging for patients and clinicians. Just as sexual function is multidimensional—with physical and psychosocial elements—sexual dysfunction can likewise have multiple contributing factors, and is often divided into dysfunction of desire, arousal, orgasm, and sex-related pain. Addressing each of these dimensions of sexual dysfunction in relationship to pelvic reconstructive surgery is beyond the scope of this article. Here, we focus on aspects of sexual dysfunction most likely to be reported by patients after surgery for pelvic organ prolapse (POP) or urinary incontinence, or for both. We discuss what is known about why sexual dysfunction develops after these procedures; how to assess symptoms when sexual dysfunction occurs; and how best to treat these difficult problems.

CASE Postoperative sexual concerns

Your 62-year-old patient presents 2 weeks after vaginal hysterectomy, uterosacral vault suspension, anterior and posterior colporrhaphy, and retropubic midurethral polypropylene sling placement. She reports feeling tired but otherwise doing well.

The patient returns 8 weeks postoperatively, having just resumed her customary exercise routine, and reports that she is feeling well. Upon questioning, she says that she has not yet attempted to have sexual intercourse with her 70-year-old husband.

The patient returns 6 months later and reports that, although she is doing well overall, she is unable to have sexual intercourse.

How can you help this patient? What next steps in evaluation are indicated? Then, with an understanding of her problem in hand, what treatment options can you offer to her?

Surgery for pelvic-floor disorders and sexual function

The impact of surgery on sexual function is important to discuss with patients preoperatively and postoperatively. Because patients with POP and urinary incontinence have a higher rate of sexual dysfunction at baseline, it is important to know how surgery to correct these conditions can affect sexual function.¹ Regrettably, many studies of surgical procedures for POP and urinary incontinence either do not include sexual function outcomes or are not powered to detect differences in these outcomes.

Native-tissue repair. A 2015 systematic review looked at studies of women undergoing native-tissue repair for POP without mesh placement of any kind, including a midurethral sling.² Based on 9 studies that reported validated sexual function questionnaire scores, investigators determined that sexual function scores generally improved following surgery. Collectively, for studies included in this review that specifically reported the rate of dyspareunia before and after surgery, 47% of women reported improvement in dyspareunia; 39% reported no change; 18% reported deterioration in dyspareunia; and only 4% had de novo dyspareunia.

Colporrhaphy. Posterior colporrhaphy, commonly performed to correct posterior vaginal prolapse, can narrow vaginal caliber and the introitus, potentially causing dyspareunia. Early description of posterior colporrhaphy technique included plication of the levator ani muscles, which was associated with significant risk of dyspareunia postoperatively.³ However, posterior colporrhaphy that involves standard plication of the rectovaginal muscularis or site-specific repair has been reported to have a dyspareunia rate from 7% to 20%.^4,5 It is generally recommended, therefore, that levator muscle plication during colporrhaphy be avoided in sexually active women.

Continue to: Vaginal mesh...

Vaginal mesh. Mesh has been used in various surgical procedures to correct pelvic floor disorders. Numerous randomized trials have comparatively evaluated the use of transvaginal polypropylene mesh and native tissue for POP repair, and many of these studies have assessed postoperative sexual function. In a 2013 systematic review on sexual function after POP repair, the authors found no significant difference in postoperative sexual function scores or the dyspareunia rate after vaginal mesh repair (14%) and after native-tissue repair (12%).⁶

Studies of postsurgical sexual function are lacking

Important aspects of sexual function—orgasm, arousal, desire, lubrication, sexual satisfaction, effects on the partner—lack studies. A study of 71 sexually active couples assessed sexual function with questionnaires before and after vaginal native-tissue repair and found that, except for orgasm, all domains improved in female questionnaires. In male partners, interest, sexual drive, and overall satisfaction improved, whereas erection, ejaculation, and orgasm remained unchanged.⁷

Urinary incontinence during sexual intercourse affects approximately 30% of women with overactive bladder or stress incontinence.⁸ Several reviews have analyzed data on overall sexual function following urinary incontinence surgery:

• After stress incontinence surgery, the rate of coital incontinence was found to be significantly lower (odds ratio, 0.11).⁹ In this review, 18 studies, comprising more than 1,500 women, were analyzed, with most participants having undergone insertion of a midurethral mesh sling. Most women (55%) reported no change in overall sexual function, based on validated sexual questionnaire scores; 32% reported improvement; and 13% had deterioration in sexual function.
• As for type of midurethral sling, 2 reviews concluded that there is no difference in sexual function outcomes between retropubic and trans‑obturator sling routes.^9,10

Although most studies that have looked at POP and incontinence surgeries show either improvement or no change in sexual function, we stress that sexual function is a secondary outcome in most of those studies, which might not be appropriately powered to detect differences in outcomes. Furthermore, although studies describe dyspareunia and overall sexual function in validated questionnaire scores, most do not evaluate other specific domains of sexual function. It remains unclear, therefore, how POP and incontinence surgeries affect orgasm, desire, arousal, satisfaction, and partner sexual domains; more studies are needed to focus on these areas of female sexual function.

How do we assess these patients?

We do know that sexual function is important to women undergoing gynecologic surgery: In a recent qualitative study of women undergoing pelvic reconstruction, patients rated lack of improvement in sexual function following surgery a “very severe” adverse event.¹¹ Unfortunately, however, sexual activity and function is not always measured before gynecologic surgery. Although specific reporting guidelines do not exist for routine gynecologic surgery, a terminology report from the International Urogynecologic Association/International Continence Society (IUGA/ICS) recommends that sexual activity and partner status be evaluated prior to and following surgical treatment as essential outcomes.¹² In addition, the report recommends that sexual pain be assessed prior to and following surgical procedures.¹²

Ascertain sexual health. First, asking your patients simple questions about sexual function, pain, and bother before and after surgery opens the door to dialogue that allows them, and their partner, to express concerns to you in a safe environment. It also allows you to better understand the significant impact of your surgical interventions on their sexual health.

Questionnaires. Objective measures of vaginal blood flow and engorgement exist, but assessment of sexual activity in the clinical setting is largely limited to self-assessment with questionnaires. Incorporating simple questions, such as “Are you sexually active?,” “Do you have any problems with sexual activity?,” and “Do you have pain with activity?” are likely to be as effective as a more detailed interview and can identify women with sexual concerns.¹³ Many clinicians are put at a disadvantage, however, because they are faced with the difficult situation of addressing postoperative sexual problems without knowing whether the patient had such reports prior to surgery.

Continue to: Aside from simple screening tools...

Aside from simple screening tools, a number of sexual function questionnaires have been developed. Some are generic, and others are condition-specific:

• Generic questionnaires are typically designed to address the function of a range of women. For example, the Female Sexual Function Index comprises 19 questions. Domains include orgasm, desire, arousal, lubrication, pain and satisfaction.¹⁴
• Condition-specific questionnaires of sexual function each have been validated in their target population so that they measure nuances in sexual health relevant to that population. The Pelvic Organ Prolapse/Incontinence Sexual Questionnaire—IUGA-Revised includes questions about the domains listed for the generic Index (above) plus questions about the impact of coital incontinence or bulge symptoms on sexual function.¹²

History-taking. If a woman identifies a problem with sexual function, a thorough history helps elicit whether the condition is lifelong or acquired, situational or general, and, most important, whether or not it is bothersome to her.^14,15 It is important not to make assumptions when pursuing this part of the history, and to encourage patients to be candid about how they have sex and with whom.

Physical examination. The patient should undergo a complete physical exam, including 1) a detailed pelvic exam assessing the vulva, vagina, and pelvic-floor musculature, and 2) estrogenization of the tissue.

Partner concerns. For women who have a partner, addressing the concerns of that partner following gynecologic surgery can be useful to the couple: The partner might be concerned about inflicting pain or doing damage during sex after gynecologic surgery.

CASE Informative discussion

While ascertaining her sexual symptoms, your patient reveals to you that she has attempted sexual intercourse on 3 occasions; each time, penetration was too painful to continue. She tells you she did not have this problem before surgery.

The patient says that she has tried water-based lubricants and is using vaginal estrogen 3 times per week, but “nothing helps.” She reports that she is arousable and has been able to achieve orgasm with clitoral stimulation, but would like to have vaginal intercourse. Her husband does have erectile dysfunction, which, she tells you, can make penetration difficult.

On physical examination, you detect mild atrophy. Vaginal length is 9 cm; no narrowing or scarring of the vaginal introitus or canal is seen. No mesh is visible or palpable. The paths of the midurethral sling arms are nontender. However, levator muscles are tender and tense bilaterally.

Given these findings on examination, what steps can you take to relieve your patient’s pain?

What can we offer these patients?

Treating sexual dysfunction after pelvic reconstructive surgery must, as emphasized earlier, be guided by a careful history and physical exam. Doing so is critical to determining the underlying cause. Whenever feasible, offer the least invasive treatment.

The IUGA/ICS terminology report describes several symptoms of postoperative sexual dysfunction¹²:

• de novo sexual dysfunction
• de novo dyspareunia
• shortened vagina
• tight vagina (introital or vaginal narrowing, or both)
• scarred vagina (including mesh-related problems)
• hispareunia (pain experienced by a male partner after intercourse).

Of course, any one or combination of these symptoms can be present in a given patient. Furthermore, de novo sexual dysfunction, de novo dyspareunia, and hispareunia can have various underlying causes—again, underscoring the importance of the history and exam in determining treatment.

Continue to: Nonsurgical treatment...

Nonsurgical treatment

Nonhormonal vaginal lubricants and moisturizers; vaginal estrogen therapy. Although, in older women, vaginal atrophy is often not a new diagnosis postsurgically, the condition might have been untreated preoperatively and might therefore come into play in sexual dysfunction postoperatively. If a patient reports vaginal dryness or pain upon penetration, assess for vaginal atrophy and, if present, treat accordingly.

Vaginal dilation and physical therapy. A shortened, tight, or scarred vagina might be amenable to therapy with vaginal dilators and physical therapy, but might ultimately require surgery.

Pelvic-floor myalgia or spasm can develop after surgery or, as with atrophy, might have existed preoperatively but was left untreated. Pelvic-floor myalgia should be suspected if the patient describes difficult penetration or a feeling of tightness, even though scarring or constriction of the vagina is not seen on examination. Physical therapy with a specialist in pelvic floor treatment is a first-line treatment for pelvic-floor myalgia,¹⁶ and is likely to be a helpful adjunct in many situations, including mesh-related sexual problems.¹⁷

Oral or vaginal medications to relax pelvic-floor muscle spasm are an option, although efficacy data are limited. If pain is of longstanding duration and is thought to have a neuropathic component, successful use of tricyclic antidepressants, neuroleptics, and serotonin–norepinephrine reuptake inhibitors has been reported.¹⁸

Surgery

Data are sparse regarding surgical treatment of female sexual dysfunction after pelvic reconstructive surgery. Again, it is clear, however, that the key is carefully assessing each patient and then individualizing treatment. Patients can have any type of dysfunction that a patient who hasn’t had surgery can—but is also at risk of conditions directly related to surgery.

In any patient who has had mesh placed as part of surgery, thorough examination is necessary to determine whether or not the implant is involved in sexual dysfunction. If the dysfunction is an apparent result of surgery performed by another surgeon, make every effort to review the operative report to determine which material was implanted and how it was placed.

Trigger-point injection can be attempted in a patient who has site-specific tenderness that is not clearly associated with tissue obstruction of the vagina or mesh erosion.^12,19 Even in areas of apparent banding or scarring related to mesh, trigger-point injection can be attempted to alleviate pain. How often trigger-point injections should be performed is understudied.

If, on examination, tenderness that replicates the dyspareunia is elicited when palpating the levator or obturator internus muscle, pelvic-floor muscle trigger-point injection can be offered (although physical therapy is first-line treatment). Trigger-point injection also can be a useful adjunct in women who have another identified cause of pain but also have developed pelvic-floor muscle spasm.

Not addressing concomitant pelvic-floor myalgia could prevent successful treatment of pain. Inclusion of a pudendal block also might help to alleviate pain.

Continue to: Surgical resection...

Surgical resection. If a skin bridge is clearly observed at the introitus, or if the introitus has been overly narrowed by perineorrhaphy but the remainder of the vagina has adequate length and caliber, surgical resection of the skin bridge might relieve symptoms of difficult penetration. In the case of obstructive perineorrhaphy, an attempt at reversal can be made by incising the perineum vertically but then reapproximating the edges transversely—sometimes referred to as reverse perineorrhaphy.

If scar tissue found elsewhere in the vagina might obstruct penetration, this condition might also be amenable to resection. When scarring is annular, relaxing incisions can be made bilaterally to relieve tension on that tissue; alternatively, it might be necessary to perform a Z-plasty. Nearly always, severe scarring is accompanied by levator myalgia, and a combined approach of surgery and physical therapy is necessary.

Neovagina. It is possible to find vaginal stenosis or shortening, to a varying degree, after surgical prolapse repair, with or without mesh or graft. As discussed, vaginal dilation should be offered but, if this is ineffective, the patient might be a candidate for surgical creation of a neovagina. Numerous techniques have been described for patients with congenital vaginal agenesis, with a few reports of similar techniques used to treat iatrogenic vaginal stenosis or obliteration.

The general principle of all neovagina procedures is to create a space between bladder and rectum of adequate caliber and length for desired sexual function. Reported techniques include a thigh or buttock skin graft, use of bowel or peritoneum, and, recently, a buccal mucosa graft.^20,21

Resection or excision of mesh. In patients who develop sexual dysfunction after mesh placement, the problem can be caused by exposure of the mesh in the vagina or erosion into another organ, but can also arise in the absence of exposure or erosion. Patients might have tenderness to palpation at points where the mesh is palpable through the mucosa but not exposed.

Again, complete investigation is necessary to look for mesh involvement in the vagina and, depending on the type of implant, other adjacent organs. Assessing partner symptoms, such as pain and scratches, also can be telling.

If there is palpable tenderness on vaginal examination of the mesh, resection of the vaginal portion might be an option.¹⁷ Complete excision of mesh implants can be morbid, however, and might not provide a better outcome than partial excision. The risk of morbidity from complete mesh excision must be weighed against the likelihood that partial excision will not resolve pain and that the patient will require further excision subsequently.^17,22 Excising fragmented mesh can be difficult; making every attempt to understand the contribution of mesh to sexual dysfunction is therefore critical to determining how, and how much of, the mesh comes out at the first attempt.

Last, for any woman who opts for surgical intervention to treat pain, you should engage in a discussion to emphasize the multidimensional nature of sexual function and the fact that any surgical intervention might not completely resolve her dysfunction.

Continue to: CASE Discussing options...

CASE Discussing options, choosing an intervention

You discuss the examination findings (no shortening or narrowing of the vagina) with the patient. She is relieved but puzzled as to why she cannot have intercourse. You discuss the tension and tenderness of her pelvic floor and that this is likely the cause. You offer her physical therapy (PT). You also discuss muscle relaxing medications and trigger-point injections if physical therapy alone is unsuccessful or if she cannot do PT (as there are barriers, including insurance coverage and scheduling issues, to accessing PT for many patients). You encourage her to continue use of vaginal estrogen and lubricant during intercourse. She agrees to try PT.

At 3-month follow-up, she reports great improvement. She is able to have intercourse, although she says she still has discomfort sometimes. She continues to work with the pelvic floor physical therapist and feels optimistic. You plan to see her in 6 months but counsel her to call if symptoms are not improving or are worsening.

Sexual function must be part of the conversation

It is difficult to counsel patients about sexual function after pelvic reconstructive surgery because data that could guide identification of problems (and how to treat them) are incomplete. Assessingsexual function preoperatively and having an open conversation about risks and benefits of surgery, with specific mention of its impact on sexual health, are critical (see “Key touchpoints in managing sexual dysfunction after pelvic reconstructive surgery”).

It is also crucial to assess sexual function postoperatively as a matter of routine. Validated questionnaires can be a useful adjunct to a thorough history and physical exam, and can help guide your discussions.

Treatment of postop sexual dysfunction must, first, account for the complex nature of sexual function and, second, be individualized, starting with the least invasive options, when feasible. 

Quality improvement (QI) is essential to the advancement of medicine. QI differs from research as it focuses on already proven knowledge and aims to make quick, sustainable change in local health care systems. Community hospitals may not have organized quality improvement initiatives and often rely on individual hospitalists to be their champions.

Although there are resources for quality improvement projects, initiating a project can seem daunting to a hospitalist. Our aim is to equip the community hospitalist with basic skills to initiate their own successful project. We present our “Top 10” tips to review.



1. Start small: Many quality improvement ideas include grandiose changes that require a large buy-in or worse, more money. When starting a QI project, you need to consider low-cost, high-impact projects. Even the smallest projects can make considerable change. Focus on ideas that require only one or two improvement cycles to implement. Understand your hospital culture, flow, and processes, and then pick a project that is reasonable.

Projects can be as simple as decreasing the number of daily labs ordered by your hospitalist group. Projects that are small could still improve patient satisfaction and decrease costs. Listen to your colleagues, if they are discussing an issue, turn this into an idea! As you learn the culture of your hospital you will be able to tackle larger projects. Plus, it gets your name out there!

2. Establish buy-in: Surround yourself with champions of your cause. Properly identifying and engaging key players is paramount to a successful QI project. First, start with your hospital administration, and garner their support by aligning your project with the goals and objectives that the administration leaders have identified to be important for your institution. Next, select a motivated multidisciplinary team. When choosing your team, be sure to include a representative from the various stakeholders, that is, the individuals who have a variety of hospital roles likely to be affected by the outcome of the project. Stakeholders ensure the success of the project because they have a fundamental understanding of how the project will influence workflow, can predict issues before they arise, and often become empowered to make changes that directly influence their work.

Lastly, include at least one well-respected and highly influential member on your team. Change is always hard, and this person’s support and endorsement of the project, can often move mountains when challenges arise.

5. Remove waste: When determining QI projects, consider focusing on health care waste. Many of the current processes at our institutions have redundancies that add unhealthy time, effort, and inefficiency to our days that can not only impede patient care but also can lead to burnout. When outlining a project idea, consider mapping the process in your interested area to identify those redundancies and inefficiencies. Consider focusing on these instead of building an entirely new process. Improving inefficiencies also can help with provider buy-in with process changes, especially if this helps in improving their everyday frustrations.

6. Express your values: Create a sense of urgency around the problem you are trying to solve. Educate your colleagues to understand the depth of the QI initiative and its impact on their ability to care for patients and patient safety. Express genuine interest in improving your colleagues’ ability to care for patients and improve their days.

Sharing your passion about your project allows people to understand your vested interest in improving the system. This will inspire team members to lead the way to change and encourage colleagues to adopt the recommended changes.

7. Recognize and reward your team: Involve “champions” in every process change. Identify people who are part of your team and ensure they feel valued. Recognition and acknowledgment will allow people to feel more involved and to gain their buy-in. When it comes to results or progress, consider your group’s dynamics. If they are competitive, consider posting progress results on a publicly displayed run chart. If your group is less likely to be motivated by competition, hold individual meetings to help show progress. This is a crucial dynamic to understand, because creating a competitive environment may alienate some members of your group. Remember, the final result is not to blame those lagging behind but to encourage everyone to find the best pathway to success.

8. Be okay with failure: Celebrate your failures because failure is a chance to learn. Every failure is an educational opportunity to understand what not to do, or a chance to gain insight into a process that did not work.

Be a divergent thinker. Start considering problems as part of the path to solution, rather than a barrier in the way. Be open to change and learn from your mistakes. Don’t just be okay with your failures, own them. This will lead to trust with your team members and show your commitment.

9. Finish: This is key. You must finish your project. Even if you anticipate that the project will fail, you should see the project through to its completion. This proves both you and the process of QI are valid and worthwhile; you have to see results and share them with others.

Completing your project also shows your colleagues that you are resilient, committed, and dedicated. Completing a QI project, even with disappointing results, is a success in and of itself. In the end, it is most important to remember to show progress, not perfection.

10. Create sustainability: When your QI project is finished, you need to decide if the changes are sustainable. Some projects show small change and do not need permanent implementation, rather reminders over time. Other projects may be sustainable with EHR or organizational changes. Once you have successful results, your goal should be to find a way to ensure that the process stays in place over time. This is where all your hard work establishing buy-in comes in handy. Your team is more likely to create sustainable change with the hard work you forged through following these key tips.

These Top 10 tips are a hospitalist’s starting point to begin making changes at their own community hospital. Your motivation and effort in making quality change will not go unnoticed. Small ideas will open doors for larger, more sustainable QI projects. Remember, a failure just means a new idea for the next cycle! Enjoy the process of working collaboratively with your hospital on improving quality. Good luck!

Dr. Astik is a hospitalist and instructor of medicine at Northwestern Memorial Hospital, Chicago. Dr. Corbett is a hospitalist and assistant professor at the University of Oklahoma, Tulsa. Dr. Patel is a hospitalist and assistant professor at the University of Colorado, Denver. Dr. Ronan is a hospitalist and associate professor at Christus St. Vincent Regional Medical Center, Santa Fe, NM.

Quality improvement (QI) is essential to the advancement of medicine. QI differs from research as it focuses on already proven knowledge and aims to make quick, sustainable change in local health care systems. Community hospitals may not have organized quality improvement initiatives and often rely on individual hospitalists to be their champions.

Although there are resources for quality improvement projects, initiating a project can seem daunting to a hospitalist. Our aim is to equip the community hospitalist with basic skills to initiate their own successful project. We present our “Top 10” tips to review.



1. Start small: Many quality improvement ideas include grandiose changes that require a large buy-in or worse, more money. When starting a QI project, you need to consider low-cost, high-impact projects. Even the smallest projects can make considerable change. Focus on ideas that require only one or two improvement cycles to implement. Understand your hospital culture, flow, and processes, and then pick a project that is reasonable.

Projects can be as simple as decreasing the number of daily labs ordered by your hospitalist group. Projects that are small could still improve patient satisfaction and decrease costs. Listen to your colleagues, if they are discussing an issue, turn this into an idea! As you learn the culture of your hospital you will be able to tackle larger projects. Plus, it gets your name out there!

2. Establish buy-in: Surround yourself with champions of your cause. Properly identifying and engaging key players is paramount to a successful QI project. First, start with your hospital administration, and garner their support by aligning your project with the goals and objectives that the administration leaders have identified to be important for your institution. Next, select a motivated multidisciplinary team. When choosing your team, be sure to include a representative from the various stakeholders, that is, the individuals who have a variety of hospital roles likely to be affected by the outcome of the project. Stakeholders ensure the success of the project because they have a fundamental understanding of how the project will influence workflow, can predict issues before they arise, and often become empowered to make changes that directly influence their work.

Lastly, include at least one well-respected and highly influential member on your team. Change is always hard, and this person’s support and endorsement of the project, can often move mountains when challenges arise.

5. Remove waste: When determining QI projects, consider focusing on health care waste. Many of the current processes at our institutions have redundancies that add unhealthy time, effort, and inefficiency to our days that can not only impede patient care but also can lead to burnout. When outlining a project idea, consider mapping the process in your interested area to identify those redundancies and inefficiencies. Consider focusing on these instead of building an entirely new process. Improving inefficiencies also can help with provider buy-in with process changes, especially if this helps in improving their everyday frustrations.

6. Express your values: Create a sense of urgency around the problem you are trying to solve. Educate your colleagues to understand the depth of the QI initiative and its impact on their ability to care for patients and patient safety. Express genuine interest in improving your colleagues’ ability to care for patients and improve their days.

Sharing your passion about your project allows people to understand your vested interest in improving the system. This will inspire team members to lead the way to change and encourage colleagues to adopt the recommended changes.

7. Recognize and reward your team: Involve “champions” in every process change. Identify people who are part of your team and ensure they feel valued. Recognition and acknowledgment will allow people to feel more involved and to gain their buy-in. When it comes to results or progress, consider your group’s dynamics. If they are competitive, consider posting progress results on a publicly displayed run chart. If your group is less likely to be motivated by competition, hold individual meetings to help show progress. This is a crucial dynamic to understand, because creating a competitive environment may alienate some members of your group. Remember, the final result is not to blame those lagging behind but to encourage everyone to find the best pathway to success.

8. Be okay with failure: Celebrate your failures because failure is a chance to learn. Every failure is an educational opportunity to understand what not to do, or a chance to gain insight into a process that did not work.

Be a divergent thinker. Start considering problems as part of the path to solution, rather than a barrier in the way. Be open to change and learn from your mistakes. Don’t just be okay with your failures, own them. This will lead to trust with your team members and show your commitment.

9. Finish: This is key. You must finish your project. Even if you anticipate that the project will fail, you should see the project through to its completion. This proves both you and the process of QI are valid and worthwhile; you have to see results and share them with others.

Completing your project also shows your colleagues that you are resilient, committed, and dedicated. Completing a QI project, even with disappointing results, is a success in and of itself. In the end, it is most important to remember to show progress, not perfection.

10. Create sustainability: When your QI project is finished, you need to decide if the changes are sustainable. Some projects show small change and do not need permanent implementation, rather reminders over time. Other projects may be sustainable with EHR or organizational changes. Once you have successful results, your goal should be to find a way to ensure that the process stays in place over time. This is where all your hard work establishing buy-in comes in handy. Your team is more likely to create sustainable change with the hard work you forged through following these key tips.

These Top 10 tips are a hospitalist’s starting point to begin making changes at their own community hospital. Your motivation and effort in making quality change will not go unnoticed. Small ideas will open doors for larger, more sustainable QI projects. Remember, a failure just means a new idea for the next cycle! Enjoy the process of working collaboratively with your hospital on improving quality. Good luck!

Dr. Astik is a hospitalist and instructor of medicine at Northwestern Memorial Hospital, Chicago. Dr. Corbett is a hospitalist and assistant professor at the University of Oklahoma, Tulsa. Dr. Patel is a hospitalist and assistant professor at the University of Colorado, Denver. Dr. Ronan is a hospitalist and associate professor at Christus St. Vincent Regional Medical Center, Santa Fe, NM.

Quality improvement (QI) is essential to the advancement of medicine. QI differs from research as it focuses on already proven knowledge and aims to make quick, sustainable change in local health care systems. Community hospitals may not have organized quality improvement initiatives and often rely on individual hospitalists to be their champions.

Although there are resources for quality improvement projects, initiating a project can seem daunting to a hospitalist. Our aim is to equip the community hospitalist with basic skills to initiate their own successful project. We present our “Top 10” tips to review.



1. Start small: Many quality improvement ideas include grandiose changes that require a large buy-in or worse, more money. When starting a QI project, you need to consider low-cost, high-impact projects. Even the smallest projects can make considerable change. Focus on ideas that require only one or two improvement cycles to implement. Understand your hospital culture, flow, and processes, and then pick a project that is reasonable.

Projects can be as simple as decreasing the number of daily labs ordered by your hospitalist group. Projects that are small could still improve patient satisfaction and decrease costs. Listen to your colleagues, if they are discussing an issue, turn this into an idea! As you learn the culture of your hospital you will be able to tackle larger projects. Plus, it gets your name out there!

2. Establish buy-in: Surround yourself with champions of your cause. Properly identifying and engaging key players is paramount to a successful QI project. First, start with your hospital administration, and garner their support by aligning your project with the goals and objectives that the administration leaders have identified to be important for your institution. Next, select a motivated multidisciplinary team. When choosing your team, be sure to include a representative from the various stakeholders, that is, the individuals who have a variety of hospital roles likely to be affected by the outcome of the project. Stakeholders ensure the success of the project because they have a fundamental understanding of how the project will influence workflow, can predict issues before they arise, and often become empowered to make changes that directly influence their work.

Lastly, include at least one well-respected and highly influential member on your team. Change is always hard, and this person’s support and endorsement of the project, can often move mountains when challenges arise.

5. Remove waste: When determining QI projects, consider focusing on health care waste. Many of the current processes at our institutions have redundancies that add unhealthy time, effort, and inefficiency to our days that can not only impede patient care but also can lead to burnout. When outlining a project idea, consider mapping the process in your interested area to identify those redundancies and inefficiencies. Consider focusing on these instead of building an entirely new process. Improving inefficiencies also can help with provider buy-in with process changes, especially if this helps in improving their everyday frustrations.

6. Express your values: Create a sense of urgency around the problem you are trying to solve. Educate your colleagues to understand the depth of the QI initiative and its impact on their ability to care for patients and patient safety. Express genuine interest in improving your colleagues’ ability to care for patients and improve their days.

Sharing your passion about your project allows people to understand your vested interest in improving the system. This will inspire team members to lead the way to change and encourage colleagues to adopt the recommended changes.

7. Recognize and reward your team: Involve “champions” in every process change. Identify people who are part of your team and ensure they feel valued. Recognition and acknowledgment will allow people to feel more involved and to gain their buy-in. When it comes to results or progress, consider your group’s dynamics. If they are competitive, consider posting progress results on a publicly displayed run chart. If your group is less likely to be motivated by competition, hold individual meetings to help show progress. This is a crucial dynamic to understand, because creating a competitive environment may alienate some members of your group. Remember, the final result is not to blame those lagging behind but to encourage everyone to find the best pathway to success.

8. Be okay with failure: Celebrate your failures because failure is a chance to learn. Every failure is an educational opportunity to understand what not to do, or a chance to gain insight into a process that did not work.

Be a divergent thinker. Start considering problems as part of the path to solution, rather than a barrier in the way. Be open to change and learn from your mistakes. Don’t just be okay with your failures, own them. This will lead to trust with your team members and show your commitment.

9. Finish: This is key. You must finish your project. Even if you anticipate that the project will fail, you should see the project through to its completion. This proves both you and the process of QI are valid and worthwhile; you have to see results and share them with others.

Completing your project also shows your colleagues that you are resilient, committed, and dedicated. Completing a QI project, even with disappointing results, is a success in and of itself. In the end, it is most important to remember to show progress, not perfection.

10. Create sustainability: When your QI project is finished, you need to decide if the changes are sustainable. Some projects show small change and do not need permanent implementation, rather reminders over time. Other projects may be sustainable with EHR or organizational changes. Once you have successful results, your goal should be to find a way to ensure that the process stays in place over time. This is where all your hard work establishing buy-in comes in handy. Your team is more likely to create sustainable change with the hard work you forged through following these key tips.

These Top 10 tips are a hospitalist’s starting point to begin making changes at their own community hospital. Your motivation and effort in making quality change will not go unnoticed. Small ideas will open doors for larger, more sustainable QI projects. Remember, a failure just means a new idea for the next cycle! Enjoy the process of working collaboratively with your hospital on improving quality. Good luck!

Dr. Astik is a hospitalist and instructor of medicine at Northwestern Memorial Hospital, Chicago. Dr. Corbett is a hospitalist and assistant professor at the University of Oklahoma, Tulsa. Dr. Patel is a hospitalist and assistant professor at the University of Colorado, Denver. Dr. Ronan is a hospitalist and associate professor at Christus St. Vincent Regional Medical Center, Santa Fe, NM.

The Food and Drug Administration has approved Dengvaxia, the first vaccine indicated for the prevention of dengue virus disease caused by all viral serotypes. The vaccine was approved for children aged 9-16 years who live in endemic areas and have previously had laboratory-confirmed dengue disease.

Dengue is endemic in the U.S. territories of American Samoa, Guam, Puerto Rico, and the U.S. Virgin Islands, according to an FDA statement announcing the approval.

While the first infection with dengue virus typically results in either no symptoms or a mild illness that can be mistaken for the flu, a second infection can lead to a more severe form of the disease, including dengue hemorrhagic fever, which can be fatal. About 95% of hospitalized patients with dengue disease have a second dengue virus infection.

FDA approval of Dengvaxia is based on results from three randomized, placebo-controlled studies of 35,000 individuals in dengue-endemic areas. The vaccine was about 76% effective in preventing symptomatic, laboratory-confirmed dengue disease in people aged 9-16 years with a previous dengue diagnosis. The most common adverse events were headache, muscle pain, joint pain, fatigue, injection site pain, and low-grade fever; the frequency of adverse events decreased after each subsequent dose.

“Infection by one type of dengue virus usually provides immunity against that specific serotype, but a subsequent infection by any of the other three serotypes of the virus increases the risk of developing severe dengue disease. ... The FDA’s approval of this vaccine will help protect people previously infected with dengue virus from subsequent development of dengue disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement.

lfranki@mdedge.com

The Food and Drug Administration has approved Dengvaxia, the first vaccine indicated for the prevention of dengue virus disease caused by all viral serotypes. The vaccine was approved for children aged 9-16 years who live in endemic areas and have previously had laboratory-confirmed dengue disease.

Dengue is endemic in the U.S. territories of American Samoa, Guam, Puerto Rico, and the U.S. Virgin Islands, according to an FDA statement announcing the approval.

While the first infection with dengue virus typically results in either no symptoms or a mild illness that can be mistaken for the flu, a second infection can lead to a more severe form of the disease, including dengue hemorrhagic fever, which can be fatal. About 95% of hospitalized patients with dengue disease have a second dengue virus infection.

FDA approval of Dengvaxia is based on results from three randomized, placebo-controlled studies of 35,000 individuals in dengue-endemic areas. The vaccine was about 76% effective in preventing symptomatic, laboratory-confirmed dengue disease in people aged 9-16 years with a previous dengue diagnosis. The most common adverse events were headache, muscle pain, joint pain, fatigue, injection site pain, and low-grade fever; the frequency of adverse events decreased after each subsequent dose.

“Infection by one type of dengue virus usually provides immunity against that specific serotype, but a subsequent infection by any of the other three serotypes of the virus increases the risk of developing severe dengue disease. ... The FDA’s approval of this vaccine will help protect people previously infected with dengue virus from subsequent development of dengue disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement.

lfranki@mdedge.com

The Food and Drug Administration has approved Dengvaxia, the first vaccine indicated for the prevention of dengue virus disease caused by all viral serotypes. The vaccine was approved for children aged 9-16 years who live in endemic areas and have previously had laboratory-confirmed dengue disease.

Dengue is endemic in the U.S. territories of American Samoa, Guam, Puerto Rico, and the U.S. Virgin Islands, according to an FDA statement announcing the approval.

While the first infection with dengue virus typically results in either no symptoms or a mild illness that can be mistaken for the flu, a second infection can lead to a more severe form of the disease, including dengue hemorrhagic fever, which can be fatal. About 95% of hospitalized patients with dengue disease have a second dengue virus infection.

FDA approval of Dengvaxia is based on results from three randomized, placebo-controlled studies of 35,000 individuals in dengue-endemic areas. The vaccine was about 76% effective in preventing symptomatic, laboratory-confirmed dengue disease in people aged 9-16 years with a previous dengue diagnosis. The most common adverse events were headache, muscle pain, joint pain, fatigue, injection site pain, and low-grade fever; the frequency of adverse events decreased after each subsequent dose.

“Infection by one type of dengue virus usually provides immunity against that specific serotype, but a subsequent infection by any of the other three serotypes of the virus increases the risk of developing severe dengue disease. ... The FDA’s approval of this vaccine will help protect people previously infected with dengue virus from subsequent development of dengue disease,” Peter Marks, MD, director of the FDA’s Center for Biologics Evaluation and Research, said in the FDA statement.

lfranki@mdedge.com

The addition of liraglutide to metformin shows significantly improved glycemic control in children and adolescents with type 2 diabetes, compared with metformin alone, according to data presented at the Pediatric Academic Societies annual meeting in Baltimore.

The phase 3 study, which was simultaneously published in the New England Journal of Medicine, involved 134 patients aged 10-17 years with type 2 diabetes who were managing their diabetes with diet and exercise, metformin, or insulin.

Participants were randomized either to subcutaneous liraglutide – dose-escalated up to 1.8 mg/day, depending on efficacy and side effects – or placebo for 52 weeks. The first 26 weeks were double blind and the second 26 weeks were an open-label extension period.

At 26 weeks, mean glycated hemoglobin levels in the liraglutide group had decreased by 0.64 percentage points from baseline, but in the placebo group they had increased by 0.42 percentage points, representing a treatment difference of –1.06 percentage points (P less than .001). By week 52, the treatment difference between the two groups had increased to –1.30 percentage points.

William V. Tamborlane, MD, from the department of pediatrics at Yale University, New Haven, Conn., and his coauthors wrote that metformin is the approved drug of choice for pediatric patients with type 2 diabetes, and that insulin currently is the only approved option for those who do not have an adequate response to metformin monotherapy.

“This discrepancy in available treatments for youth as compared with adults persists because of a lack of successfully completed trials needed for approval of new drugs for the treatment of type 2 diabetes in children since a trial of metformin was completed in 1999,” they wrote.

The study showed that significantly more patients in the liraglutide group (63.7%) achieved glycated hemoglobin levels below 7%, compared with 36.5% of patients in the placebo group. Fasting plasma glucose levels were decreased in the liraglutide group at both 26 and 52 weeks, but had increased in the placebo group.

Although the number of reported adverse events were similar between the two groups, there were significantly more reports of gastrointestinal adverse events – particularly nausea – in patients taking liraglutide, compared with those on placebo.

However, the study did not show a difference between liraglutide and placebo in lowering body mass index, although mean body weight decreases – which were seen in both groups – were maintained at week 52 only in the liraglutide group. The authors suggested this might be owing to the relatively small number of patients enrolled in the study and that some of the children were still growing.

Novo Nordisk, which manufactures liraglutide, supported the study. Twelve authors reported grants or support from Novo Nordisk in relation to the trial. Three authors were employees of Novo Nordisk. Eight authors reported unrelated grants and fees from Novo Nordisk and other pharmaceutical companies.

SOURCE: Tamborlane WV et al. N Engl J Med. 2019 Apr 28. doi: 10.1056/NEJMoa1903822.

The addition of liraglutide to metformin shows significantly improved glycemic control in children and adolescents with type 2 diabetes, compared with metformin alone, according to data presented at the Pediatric Academic Societies annual meeting in Baltimore.

The phase 3 study, which was simultaneously published in the New England Journal of Medicine, involved 134 patients aged 10-17 years with type 2 diabetes who were managing their diabetes with diet and exercise, metformin, or insulin.

Participants were randomized either to subcutaneous liraglutide – dose-escalated up to 1.8 mg/day, depending on efficacy and side effects – or placebo for 52 weeks. The first 26 weeks were double blind and the second 26 weeks were an open-label extension period.

At 26 weeks, mean glycated hemoglobin levels in the liraglutide group had decreased by 0.64 percentage points from baseline, but in the placebo group they had increased by 0.42 percentage points, representing a treatment difference of –1.06 percentage points (P less than .001). By week 52, the treatment difference between the two groups had increased to –1.30 percentage points.

William V. Tamborlane, MD, from the department of pediatrics at Yale University, New Haven, Conn., and his coauthors wrote that metformin is the approved drug of choice for pediatric patients with type 2 diabetes, and that insulin currently is the only approved option for those who do not have an adequate response to metformin monotherapy.

“This discrepancy in available treatments for youth as compared with adults persists because of a lack of successfully completed trials needed for approval of new drugs for the treatment of type 2 diabetes in children since a trial of metformin was completed in 1999,” they wrote.

The study showed that significantly more patients in the liraglutide group (63.7%) achieved glycated hemoglobin levels below 7%, compared with 36.5% of patients in the placebo group. Fasting plasma glucose levels were decreased in the liraglutide group at both 26 and 52 weeks, but had increased in the placebo group.

Although the number of reported adverse events were similar between the two groups, there were significantly more reports of gastrointestinal adverse events – particularly nausea – in patients taking liraglutide, compared with those on placebo.

However, the study did not show a difference between liraglutide and placebo in lowering body mass index, although mean body weight decreases – which were seen in both groups – were maintained at week 52 only in the liraglutide group. The authors suggested this might be owing to the relatively small number of patients enrolled in the study and that some of the children were still growing.

Novo Nordisk, which manufactures liraglutide, supported the study. Twelve authors reported grants or support from Novo Nordisk in relation to the trial. Three authors were employees of Novo Nordisk. Eight authors reported unrelated grants and fees from Novo Nordisk and other pharmaceutical companies.

SOURCE: Tamborlane WV et al. N Engl J Med. 2019 Apr 28. doi: 10.1056/NEJMoa1903822.

The addition of liraglutide to metformin shows significantly improved glycemic control in children and adolescents with type 2 diabetes, compared with metformin alone, according to data presented at the Pediatric Academic Societies annual meeting in Baltimore.

The phase 3 study, which was simultaneously published in the New England Journal of Medicine, involved 134 patients aged 10-17 years with type 2 diabetes who were managing their diabetes with diet and exercise, metformin, or insulin.

Participants were randomized either to subcutaneous liraglutide – dose-escalated up to 1.8 mg/day, depending on efficacy and side effects – or placebo for 52 weeks. The first 26 weeks were double blind and the second 26 weeks were an open-label extension period.

At 26 weeks, mean glycated hemoglobin levels in the liraglutide group had decreased by 0.64 percentage points from baseline, but in the placebo group they had increased by 0.42 percentage points, representing a treatment difference of –1.06 percentage points (P less than .001). By week 52, the treatment difference between the two groups had increased to –1.30 percentage points.

William V. Tamborlane, MD, from the department of pediatrics at Yale University, New Haven, Conn., and his coauthors wrote that metformin is the approved drug of choice for pediatric patients with type 2 diabetes, and that insulin currently is the only approved option for those who do not have an adequate response to metformin monotherapy.

“This discrepancy in available treatments for youth as compared with adults persists because of a lack of successfully completed trials needed for approval of new drugs for the treatment of type 2 diabetes in children since a trial of metformin was completed in 1999,” they wrote.

The study showed that significantly more patients in the liraglutide group (63.7%) achieved glycated hemoglobin levels below 7%, compared with 36.5% of patients in the placebo group. Fasting plasma glucose levels were decreased in the liraglutide group at both 26 and 52 weeks, but had increased in the placebo group.

Although the number of reported adverse events were similar between the two groups, there were significantly more reports of gastrointestinal adverse events – particularly nausea – in patients taking liraglutide, compared with those on placebo.

However, the study did not show a difference between liraglutide and placebo in lowering body mass index, although mean body weight decreases – which were seen in both groups – were maintained at week 52 only in the liraglutide group. The authors suggested this might be owing to the relatively small number of patients enrolled in the study and that some of the children were still growing.

Novo Nordisk, which manufactures liraglutide, supported the study. Twelve authors reported grants or support from Novo Nordisk in relation to the trial. Three authors were employees of Novo Nordisk. Eight authors reported unrelated grants and fees from Novo Nordisk and other pharmaceutical companies.

SOURCE: Tamborlane WV et al. N Engl J Med. 2019 Apr 28. doi: 10.1056/NEJMoa1903822.

Almost 31% of the estimated 54 million adults in the United States with arthritis have severe joint pain, according to the Centers for Disease Control and Prevention.

Nationally, the prevalence of severe joint pain was 30.8% in adults with arthritis in 2017, but state-specific, age-standardized prevalences varied from a low of 20.8% in Colorado to 45.2% in Mississippi. Regionally, prevalences of both severe joint pain and physical inactivity in arthritis patients were highest in the Southeast, noted Dana Guglielmo, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and associates (MMWR 2019 May 3;68(17):381-7).

The prevalence of arthritis itself was lowest in the District of Columbia at 15.7% and highest in West Virginia at 34.6%. Alabama, at 30.4%, was the only other state above 30%. Colorado had the lowest physical inactivity rate (23.2%), while Kentucky had the highest (44.4%), the investigators said.

The differences among arthritis patients were demographic as well as geographic in 2017. The prevalence of severe joint pain was 33.0% among those aged 18-44 years and 35.6% in those 45-64 but only 25.1% in those aged 65 and older. Whites had a 27.4% prevalence of severe joint pain, compared with 42.0% for Hispanics and 50.9% for blacks. For arthritis patients with a college degree, the age-standardized prevalence of severe joint pain was 15.1%, compared with 35.5% for high school graduates and 54.1% for those with less than a high school degree, based on data from the Behavioral Risk Factor Surveillance System.

“Although persons with arthritis report that pain, or fear of causing or worsening it, is a substantial barrier to exercising, physical activity is an inexpensive intervention that can reduce pain, prevent or delay disability and limitations, and improve mental health, physical functioning, and quality of life with few adverse effects,” wrote Ms. Guglielmo and associates. Adults with severe joint pain “should engage in regular physical activity according to their abilities and avoid physical inactivity [since] even small amounts of physical activity can improve physical functioning in adults with joint conditions.”

rfranki@mdedge.com

SOURCE: Guglielmo D et al. MMWR 2019 May 3;68(17):381-7.

Almost 31% of the estimated 54 million adults in the United States with arthritis have severe joint pain, according to the Centers for Disease Control and Prevention.

Nationally, the prevalence of severe joint pain was 30.8% in adults with arthritis in 2017, but state-specific, age-standardized prevalences varied from a low of 20.8% in Colorado to 45.2% in Mississippi. Regionally, prevalences of both severe joint pain and physical inactivity in arthritis patients were highest in the Southeast, noted Dana Guglielmo, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and associates (MMWR 2019 May 3;68(17):381-7).

The prevalence of arthritis itself was lowest in the District of Columbia at 15.7% and highest in West Virginia at 34.6%. Alabama, at 30.4%, was the only other state above 30%. Colorado had the lowest physical inactivity rate (23.2%), while Kentucky had the highest (44.4%), the investigators said.

The differences among arthritis patients were demographic as well as geographic in 2017. The prevalence of severe joint pain was 33.0% among those aged 18-44 years and 35.6% in those 45-64 but only 25.1% in those aged 65 and older. Whites had a 27.4% prevalence of severe joint pain, compared with 42.0% for Hispanics and 50.9% for blacks. For arthritis patients with a college degree, the age-standardized prevalence of severe joint pain was 15.1%, compared with 35.5% for high school graduates and 54.1% for those with less than a high school degree, based on data from the Behavioral Risk Factor Surveillance System.

“Although persons with arthritis report that pain, or fear of causing or worsening it, is a substantial barrier to exercising, physical activity is an inexpensive intervention that can reduce pain, prevent or delay disability and limitations, and improve mental health, physical functioning, and quality of life with few adverse effects,” wrote Ms. Guglielmo and associates. Adults with severe joint pain “should engage in regular physical activity according to their abilities and avoid physical inactivity [since] even small amounts of physical activity can improve physical functioning in adults with joint conditions.”

rfranki@mdedge.com

SOURCE: Guglielmo D et al. MMWR 2019 May 3;68(17):381-7.

Almost 31% of the estimated 54 million adults in the United States with arthritis have severe joint pain, according to the Centers for Disease Control and Prevention.

Nationally, the prevalence of severe joint pain was 30.8% in adults with arthritis in 2017, but state-specific, age-standardized prevalences varied from a low of 20.8% in Colorado to 45.2% in Mississippi. Regionally, prevalences of both severe joint pain and physical inactivity in arthritis patients were highest in the Southeast, noted Dana Guglielmo, MPH, of the CDC’s National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and associates (MMWR 2019 May 3;68(17):381-7).

The prevalence of arthritis itself was lowest in the District of Columbia at 15.7% and highest in West Virginia at 34.6%. Alabama, at 30.4%, was the only other state above 30%. Colorado had the lowest physical inactivity rate (23.2%), while Kentucky had the highest (44.4%), the investigators said.

The differences among arthritis patients were demographic as well as geographic in 2017. The prevalence of severe joint pain was 33.0% among those aged 18-44 years and 35.6% in those 45-64 but only 25.1% in those aged 65 and older. Whites had a 27.4% prevalence of severe joint pain, compared with 42.0% for Hispanics and 50.9% for blacks. For arthritis patients with a college degree, the age-standardized prevalence of severe joint pain was 15.1%, compared with 35.5% for high school graduates and 54.1% for those with less than a high school degree, based on data from the Behavioral Risk Factor Surveillance System.

“Although persons with arthritis report that pain, or fear of causing or worsening it, is a substantial barrier to exercising, physical activity is an inexpensive intervention that can reduce pain, prevent or delay disability and limitations, and improve mental health, physical functioning, and quality of life with few adverse effects,” wrote Ms. Guglielmo and associates. Adults with severe joint pain “should engage in regular physical activity according to their abilities and avoid physical inactivity [since] even small amounts of physical activity can improve physical functioning in adults with joint conditions.”

rfranki@mdedge.com

SOURCE: Guglielmo D et al. MMWR 2019 May 3;68(17):381-7.

NEWPORT BEACH, CALIF. – Researchers say they’ve found an association between the percentage of cytogenetically abnormal cells at allogeneic stem cell transplant (ASCT) and posttransplant outcomes in patients with myelodysplastic syndromes (MDS).

Patients who had more than 60% cytogenetically abnormal cells at ASCT had significantly inferior overall survival (OS) and relapse-free survival (RFS), compared to patients with fewer abnormal cells.

Dipenkumar Modi, MD, of Barbara Ann Karmanos Cancer Institute at Wayne State University in Detroit, and his colleagues conducted this research and presented the results at the Acute Leukemia Forum of Hemedicus.

The researchers studied 109 adult MDS patients who underwent ASCT from January 2000 through December 2016. The patients were divided into three groups based on the percentage of cytogenetically abnormal cells at ASCT:

• Group 1 had less than 30% (n = 22)
• Group 2 had 30%-60% (n = 23)
• Group 3 had greater than 60% (n = 64).

Baseline characteristics were largely similar between the groups. However, patients in group 3 were significantly more likely than those in groups 1 and 2 to have del(5q) and monosomy 5+7 (P = .048).

Patients in group 1 had a significantly higher percentage of bone marrow transplants (as opposed to peripheral blood stem cell transplants) than patients in groups 2 and 3 (P = .039). And patients in group 1 had significantly fewer blasts at ASCT than patients in groups 2 and 3 (P = .011).

The researchers found no significant between-group differences in relapse and nonrelapse mortality, but there were significant differences in OS and RFS.

Patients in group 3 had inferior RFS compared to patients in group 1, which was the reference group. The hazard ratio (HR) was 2.503 (P = .013) in a univariable analysis and 2.196 (P = .049) in a multivariable analysis.

Group 3 also had inferior OS compared to group 1. The hazard ratio was 2.589 (P = .021) in a univariable analysis and 2.478 (P = .040) in a multivariable analysis.

There was no significant difference in RFS or OS between groups 1 and 2. The HR for RFS in group 2 was 1.879 (P = .148) in a univariable analysis and 1.365 (P = .506) in a multivariable analysis. The HR for OS was 1.997 (P = .155) and 1.413 (P = .511), respectively.

Dr. Modi said these results suggest patients with greater than 60% cytogenetically abnormal cells at ASCT should be monitored more closely after transplant, and their immunosuppressive medication should be tapered as soon as possible.

Dr. Modi and his colleagues reported having no conflicts of interest relevant to this research.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

jensmith@mdedge.com

NEWPORT BEACH, CALIF. – Researchers say they’ve found an association between the percentage of cytogenetically abnormal cells at allogeneic stem cell transplant (ASCT) and posttransplant outcomes in patients with myelodysplastic syndromes (MDS).

Patients who had more than 60% cytogenetically abnormal cells at ASCT had significantly inferior overall survival (OS) and relapse-free survival (RFS), compared to patients with fewer abnormal cells.

Dipenkumar Modi, MD, of Barbara Ann Karmanos Cancer Institute at Wayne State University in Detroit, and his colleagues conducted this research and presented the results at the Acute Leukemia Forum of Hemedicus.

The researchers studied 109 adult MDS patients who underwent ASCT from January 2000 through December 2016. The patients were divided into three groups based on the percentage of cytogenetically abnormal cells at ASCT:

• Group 1 had less than 30% (n = 22)
• Group 2 had 30%-60% (n = 23)
• Group 3 had greater than 60% (n = 64).

Baseline characteristics were largely similar between the groups. However, patients in group 3 were significantly more likely than those in groups 1 and 2 to have del(5q) and monosomy 5+7 (P = .048).

Patients in group 1 had a significantly higher percentage of bone marrow transplants (as opposed to peripheral blood stem cell transplants) than patients in groups 2 and 3 (P = .039). And patients in group 1 had significantly fewer blasts at ASCT than patients in groups 2 and 3 (P = .011).

The researchers found no significant between-group differences in relapse and nonrelapse mortality, but there were significant differences in OS and RFS.

Patients in group 3 had inferior RFS compared to patients in group 1, which was the reference group. The hazard ratio (HR) was 2.503 (P = .013) in a univariable analysis and 2.196 (P = .049) in a multivariable analysis.

Group 3 also had inferior OS compared to group 1. The hazard ratio was 2.589 (P = .021) in a univariable analysis and 2.478 (P = .040) in a multivariable analysis.

There was no significant difference in RFS or OS between groups 1 and 2. The HR for RFS in group 2 was 1.879 (P = .148) in a univariable analysis and 1.365 (P = .506) in a multivariable analysis. The HR for OS was 1.997 (P = .155) and 1.413 (P = .511), respectively.

Dr. Modi said these results suggest patients with greater than 60% cytogenetically abnormal cells at ASCT should be monitored more closely after transplant, and their immunosuppressive medication should be tapered as soon as possible.

Dr. Modi and his colleagues reported having no conflicts of interest relevant to this research.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

jensmith@mdedge.com

NEWPORT BEACH, CALIF. – Researchers say they’ve found an association between the percentage of cytogenetically abnormal cells at allogeneic stem cell transplant (ASCT) and posttransplant outcomes in patients with myelodysplastic syndromes (MDS).

Patients who had more than 60% cytogenetically abnormal cells at ASCT had significantly inferior overall survival (OS) and relapse-free survival (RFS), compared to patients with fewer abnormal cells.

Dipenkumar Modi, MD, of Barbara Ann Karmanos Cancer Institute at Wayne State University in Detroit, and his colleagues conducted this research and presented the results at the Acute Leukemia Forum of Hemedicus.

The researchers studied 109 adult MDS patients who underwent ASCT from January 2000 through December 2016. The patients were divided into three groups based on the percentage of cytogenetically abnormal cells at ASCT:

• Group 1 had less than 30% (n = 22)
• Group 2 had 30%-60% (n = 23)
• Group 3 had greater than 60% (n = 64).

Baseline characteristics were largely similar between the groups. However, patients in group 3 were significantly more likely than those in groups 1 and 2 to have del(5q) and monosomy 5+7 (P = .048).

Patients in group 1 had a significantly higher percentage of bone marrow transplants (as opposed to peripheral blood stem cell transplants) than patients in groups 2 and 3 (P = .039). And patients in group 1 had significantly fewer blasts at ASCT than patients in groups 2 and 3 (P = .011).

The researchers found no significant between-group differences in relapse and nonrelapse mortality, but there were significant differences in OS and RFS.

Patients in group 3 had inferior RFS compared to patients in group 1, which was the reference group. The hazard ratio (HR) was 2.503 (P = .013) in a univariable analysis and 2.196 (P = .049) in a multivariable analysis.

Group 3 also had inferior OS compared to group 1. The hazard ratio was 2.589 (P = .021) in a univariable analysis and 2.478 (P = .040) in a multivariable analysis.

There was no significant difference in RFS or OS between groups 1 and 2. The HR for RFS in group 2 was 1.879 (P = .148) in a univariable analysis and 1.365 (P = .506) in a multivariable analysis. The HR for OS was 1.997 (P = .155) and 1.413 (P = .511), respectively.

Dr. Modi said these results suggest patients with greater than 60% cytogenetically abnormal cells at ASCT should be monitored more closely after transplant, and their immunosuppressive medication should be tapered as soon as possible.

Dr. Modi and his colleagues reported having no conflicts of interest relevant to this research.

The Acute Leukemia Forum is held by Hemedicus, which is owned by the same company as this news organization.

jensmith@mdedge.com

A migraine preventive with improved efficacy and adverse event profile and a favorable mode of administration would be valuable to patients with migraine, according to the results of a study published in Headache. When offered hypothetical preventive migraine medicines with a wide array of attributes, patients leaned toward those with a reduction in migraine days and an avoidance of weight gain, according to an analysis of responses to a discrete-choice experiment survey.

“We found that respondents had a significant willingness to pay for medicines with higher efficacy and less-severe adverse events,” wrote Carol Mansfield, PhD, of RTI Health Solutions in North Carolina, and coauthors.

To evaluate patient preferences for theoretical migraine medicine, the researchers conducted a discrete-choice experiment via a web-based survey. Respondents met eligibility criteria if they were adults aged 18 years or older who self-reported 6 or more migraine days per month and completed the survey in full. They were asked to choose between options defined by six attributes: reduction in headache days per month, frequency of limitations with physical activities, cognition problems, weight gain, how the medicine is taken, and monthly out-of-pocket cost.

Of the 300 respondents included in the analysis, 72% indicated that migraines make physical activities difficult all or most of the time, and 81% had taken a prescription migraine preventive in the last 6 months. Respondents reported, on average, approximately 16 headache days per month. Among noncost attributes, respondents valued a change from a 10% reduction in migraine days to a 50% reduction more highly than avoiding the worst levels of adverse events – defined as memory problems and 10% weight gain – but were willing to trade off efficacy for less-severe adverse events. Avoiding memory problems was more important than avoiding thinking problems. Avoiding a 10% weight gain was more important than avoiding thinking and memory problems. Respondents preferred a once-monthly injection or daily pill to twice-monthly injections. Respondents, on average, were willing to pay $116 per month for an improvement from 10% to 50% in reduced headache days (95% confidence interval [CI], $91-$141) and $43 for an improvement from 10% to 25% (95% CI, $34-$53). They were also willing to pay $84 per month to avoid a 10% weight gain (95% CI, $64-$103), $59 per month to avoid memory problems (95% CI, $42-$76), and $32 per month to avoid thinking problems (95% CI, $18-$46).

The coauthors acknowledged their study’s limitations, including all migraine diagnoses being self-reported and the study sample not necessarily being representative of patients with migraine overall. In addition, though the potential medicinal attributes used were prominent in clinical literature and focus groups, they could choose only a limited amount and so their analysis “did not address other attributes that may be important to patients.”

Given their findings, the researchers recommended that “clinicians should work with patients to select treatments that meet each patient’s needs.”

Amgen and Novartis funded the study. The authors reported numerous conflicts of interest, including receiving grants, consulting fees, and royalties from pharmaceutical companies and organizations. During the study, three of the authors were employed at RTI Health Solutions, a non-for-profit organization that conducts research with pharmaceutical companies such as the study’s sponsor.

SOURCE: Mansfield C et al. Headache. 2019 May;59(5):715-26. doi: 10.1111/head.13498.

A migraine preventive with improved efficacy and adverse event profile and a favorable mode of administration would be valuable to patients with migraine, according to the results of a study published in Headache. When offered hypothetical preventive migraine medicines with a wide array of attributes, patients leaned toward those with a reduction in migraine days and an avoidance of weight gain, according to an analysis of responses to a discrete-choice experiment survey.

“We found that respondents had a significant willingness to pay for medicines with higher efficacy and less-severe adverse events,” wrote Carol Mansfield, PhD, of RTI Health Solutions in North Carolina, and coauthors.

To evaluate patient preferences for theoretical migraine medicine, the researchers conducted a discrete-choice experiment via a web-based survey. Respondents met eligibility criteria if they were adults aged 18 years or older who self-reported 6 or more migraine days per month and completed the survey in full. They were asked to choose between options defined by six attributes: reduction in headache days per month, frequency of limitations with physical activities, cognition problems, weight gain, how the medicine is taken, and monthly out-of-pocket cost.

Of the 300 respondents included in the analysis, 72% indicated that migraines make physical activities difficult all or most of the time, and 81% had taken a prescription migraine preventive in the last 6 months. Respondents reported, on average, approximately 16 headache days per month. Among noncost attributes, respondents valued a change from a 10% reduction in migraine days to a 50% reduction more highly than avoiding the worst levels of adverse events – defined as memory problems and 10% weight gain – but were willing to trade off efficacy for less-severe adverse events. Avoiding memory problems was more important than avoiding thinking problems. Avoiding a 10% weight gain was more important than avoiding thinking and memory problems. Respondents preferred a once-monthly injection or daily pill to twice-monthly injections. Respondents, on average, were willing to pay $116 per month for an improvement from 10% to 50% in reduced headache days (95% confidence interval [CI], $91-$141) and $43 for an improvement from 10% to 25% (95% CI, $34-$53). They were also willing to pay $84 per month to avoid a 10% weight gain (95% CI, $64-$103), $59 per month to avoid memory problems (95% CI, $42-$76), and $32 per month to avoid thinking problems (95% CI, $18-$46).

The coauthors acknowledged their study’s limitations, including all migraine diagnoses being self-reported and the study sample not necessarily being representative of patients with migraine overall. In addition, though the potential medicinal attributes used were prominent in clinical literature and focus groups, they could choose only a limited amount and so their analysis “did not address other attributes that may be important to patients.”

Given their findings, the researchers recommended that “clinicians should work with patients to select treatments that meet each patient’s needs.”

Amgen and Novartis funded the study. The authors reported numerous conflicts of interest, including receiving grants, consulting fees, and royalties from pharmaceutical companies and organizations. During the study, three of the authors were employed at RTI Health Solutions, a non-for-profit organization that conducts research with pharmaceutical companies such as the study’s sponsor.

SOURCE: Mansfield C et al. Headache. 2019 May;59(5):715-26. doi: 10.1111/head.13498.

A migraine preventive with improved efficacy and adverse event profile and a favorable mode of administration would be valuable to patients with migraine, according to the results of a study published in Headache. When offered hypothetical preventive migraine medicines with a wide array of attributes, patients leaned toward those with a reduction in migraine days and an avoidance of weight gain, according to an analysis of responses to a discrete-choice experiment survey.

“We found that respondents had a significant willingness to pay for medicines with higher efficacy and less-severe adverse events,” wrote Carol Mansfield, PhD, of RTI Health Solutions in North Carolina, and coauthors.

To evaluate patient preferences for theoretical migraine medicine, the researchers conducted a discrete-choice experiment via a web-based survey. Respondents met eligibility criteria if they were adults aged 18 years or older who self-reported 6 or more migraine days per month and completed the survey in full. They were asked to choose between options defined by six attributes: reduction in headache days per month, frequency of limitations with physical activities, cognition problems, weight gain, how the medicine is taken, and monthly out-of-pocket cost.

Of the 300 respondents included in the analysis, 72% indicated that migraines make physical activities difficult all or most of the time, and 81% had taken a prescription migraine preventive in the last 6 months. Respondents reported, on average, approximately 16 headache days per month. Among noncost attributes, respondents valued a change from a 10% reduction in migraine days to a 50% reduction more highly than avoiding the worst levels of adverse events – defined as memory problems and 10% weight gain – but were willing to trade off efficacy for less-severe adverse events. Avoiding memory problems was more important than avoiding thinking problems. Avoiding a 10% weight gain was more important than avoiding thinking and memory problems. Respondents preferred a once-monthly injection or daily pill to twice-monthly injections. Respondents, on average, were willing to pay $116 per month for an improvement from 10% to 50% in reduced headache days (95% confidence interval [CI], $91-$141) and $43 for an improvement from 10% to 25% (95% CI, $34-$53). They were also willing to pay $84 per month to avoid a 10% weight gain (95% CI, $64-$103), $59 per month to avoid memory problems (95% CI, $42-$76), and $32 per month to avoid thinking problems (95% CI, $18-$46).

The coauthors acknowledged their study’s limitations, including all migraine diagnoses being self-reported and the study sample not necessarily being representative of patients with migraine overall. In addition, though the potential medicinal attributes used were prominent in clinical literature and focus groups, they could choose only a limited amount and so their analysis “did not address other attributes that may be important to patients.”

Given their findings, the researchers recommended that “clinicians should work with patients to select treatments that meet each patient’s needs.”

Amgen and Novartis funded the study. The authors reported numerous conflicts of interest, including receiving grants, consulting fees, and royalties from pharmaceutical companies and organizations. During the study, three of the authors were employed at RTI Health Solutions, a non-for-profit organization that conducts research with pharmaceutical companies such as the study’s sponsor.

SOURCE: Mansfield C et al. Headache. 2019 May;59(5):715-26. doi: 10.1111/head.13498.

The Food and Drug Administration has approved ivosidenib (Tibsovo) for newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation in patients who are at least 75 years old or have comorbidities preventing the use of intensive induction chemotherapy.

Wikimedia Commons/FitzColinGerald/Creative Commons License

In July 2018, the FDA approved ivosidenib for adults with relapsed or refractory AML with a susceptible IDH1 mutation.

The latest approval was based on results from an open-label, single-arm, multicenter trial of patients with newly diagnosed AML with an IDH1 mutation. Patients were treated with 500 mg ivosidenib daily until disease progression, development of unacceptable toxicity, or hematopoietic stem cell transplantation; the median age of the 28 patients treated with ivosidenib was 77 years.

Of the 28 patients treated, 12 achieved complete remission or complete remission with partial hematologic recovery; 7 of the 17 transfusion-dependent patients achieved transfusion independence for at least 8 weeks.

The most common adverse events were diarrhea, fatigue, edema, decreased appetite, leukocytosis, nausea, arthralgia, abdominal pain, dyspnea, differentiation syndrome, and myalgia. The drug’s prescribing information includes a boxed warning on the risk of differentiation syndrome.

“The recommended ivosidenib dose is 500 mg orally once daily with or without food until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treatment is recommended for a minimum of 6 months to allow time for clinical response,” the FDA noted.

Find the full press release on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has approved ivosidenib (Tibsovo) for newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation in patients who are at least 75 years old or have comorbidities preventing the use of intensive induction chemotherapy.

Wikimedia Commons/FitzColinGerald/Creative Commons License

In July 2018, the FDA approved ivosidenib for adults with relapsed or refractory AML with a susceptible IDH1 mutation.

The latest approval was based on results from an open-label, single-arm, multicenter trial of patients with newly diagnosed AML with an IDH1 mutation. Patients were treated with 500 mg ivosidenib daily until disease progression, development of unacceptable toxicity, or hematopoietic stem cell transplantation; the median age of the 28 patients treated with ivosidenib was 77 years.

Of the 28 patients treated, 12 achieved complete remission or complete remission with partial hematologic recovery; 7 of the 17 transfusion-dependent patients achieved transfusion independence for at least 8 weeks.

The most common adverse events were diarrhea, fatigue, edema, decreased appetite, leukocytosis, nausea, arthralgia, abdominal pain, dyspnea, differentiation syndrome, and myalgia. The drug’s prescribing information includes a boxed warning on the risk of differentiation syndrome.

“The recommended ivosidenib dose is 500 mg orally once daily with or without food until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treatment is recommended for a minimum of 6 months to allow time for clinical response,” the FDA noted.

Find the full press release on the FDA website.

lfranki@mdedge.com

The Food and Drug Administration has approved ivosidenib (Tibsovo) for newly diagnosed acute myeloid leukemia (AML) with a susceptible IDH1 mutation in patients who are at least 75 years old or have comorbidities preventing the use of intensive induction chemotherapy.

Wikimedia Commons/FitzColinGerald/Creative Commons License

In July 2018, the FDA approved ivosidenib for adults with relapsed or refractory AML with a susceptible IDH1 mutation.

The latest approval was based on results from an open-label, single-arm, multicenter trial of patients with newly diagnosed AML with an IDH1 mutation. Patients were treated with 500 mg ivosidenib daily until disease progression, development of unacceptable toxicity, or hematopoietic stem cell transplantation; the median age of the 28 patients treated with ivosidenib was 77 years.

Of the 28 patients treated, 12 achieved complete remission or complete remission with partial hematologic recovery; 7 of the 17 transfusion-dependent patients achieved transfusion independence for at least 8 weeks.

The most common adverse events were diarrhea, fatigue, edema, decreased appetite, leukocytosis, nausea, arthralgia, abdominal pain, dyspnea, differentiation syndrome, and myalgia. The drug’s prescribing information includes a boxed warning on the risk of differentiation syndrome.

“The recommended ivosidenib dose is 500 mg orally once daily with or without food until disease progression or unacceptable toxicity. For patients without disease progression or unacceptable toxicity, treatment is recommended for a minimum of 6 months to allow time for clinical response,” the FDA noted.

Find the full press release on the FDA website.

lfranki@mdedge.com

NEW ORLEANS – The gene therapy LentiGlobin can reduce transfusion dependence in children and young adults with non-beta⁰/beta⁰ thalassemia, according to two trials.

Jennifer Smith/MDedge News

In a phase 1/2 trial, 8 of 10 of patients achieved transfusion independence at a median follow-up of 36.0 months. In a phase 3 trial, transfusion independence was achieved by 2 of 3 patients with follow-up of at least 12 months.

Timothy S. Olson, MD, PhD, of Children’s Hospital of Philadelphia, presented results from the phase 1/2 HGB-204 trial and the phase 3 HGB-207 trial at the annual meeting of the American Society of Pediatric Hematology/Oncology.
 

Treatment

In both trials, patients received granulocyte colony-stimulating factor and plerixafor for hematopoietic stem cell mobilization. Their cells were collected via apheresis and transduced with the betibeglogene darolentivec (BB305) lentiviral vector. The patients received busulfan (for an average of 4 days) as conditioning and were infused with the transduced cells.

The manufacturing process for LentiGlobin was refined in the HGB-207 trial, which translated to a product with a higher vector copy number and higher proportion of CD34+ cells transduced, Dr. Olson said.

The median vector copy number was 3.1 in the HGB-207 trial and 0.7 in the HGB-204 trial. The median proportion of CD34+ cells transfused was 81% and 29%, respectively. The median cell dose was 7.7 x 10⁶ CD34+ cells/kg and 7.1 x 10⁶ CD34+ cells/kg, respectively.

HGB-204 patients and efficacy

The HGB-204 trial included 10 patients with non-beta⁰/beta⁰ genotypes – 6 with beta^E/beta⁰, 1 with beta⁺/beta⁰, 2 with beta⁺/beta⁺, and 1 with an “other” genotype.

The patients’ median age at consent was 19.5 years (range, 16-34). The annualized median prestudy red blood cell (RBC) transfusion volume was 151 mL/kg per year.


At a median follow-up of 36 months, 8 of the 10 patients achieved transfusion independence. The median duration of transfusion independence was 38 months. The median weighted average hemoglobin during transfusion independence was 10.2 g/dL.

“Two patients did not achieve transfusion independence, and both patients were on the lower end of the spectrum both in terms of vector copy number per cell and the percentage of CD34+ cells that were successfully transduced,” Dr. Olson said. “Both patients actually experienced a reduction in the annualized transfusion volume requirements of between 43% and 77%.”

HGB-207 patients and efficacy

The HGB-207 trial included 16 patients with non-beta⁰/beta⁰ genotypes – 6 with beta^E/beta⁰, 7 with beta⁺/beta⁰, and 3 with the beta⁺/beta⁺ genotype.

The patients’ median age at consent was 19 years . The annualized median prestudy RBC transfusion volume was 192 mL/kg per year.

The median follow-up in this trial is 9.3 months. Ten of 11 patients with at least 3 months of follow-up are transfusion-free with hemoglobin levels greater than 11 g/dL.

Two patients have achieved transfusion independence according to the protocol definition, which is weighted average hemoglobin of 9 g/dL or greater without any RBC transfusions for at least 12 months.

“In the one patient in this study who did not achieve transfusion independence, the vector-derived hemoglobin was quite low, and this correlated with a very low vector copy number seen in circulating peripheral blood mononuclear cells,” Dr. Olson said.

It isn’t clear why this occurred, however, as the vector copy number wasn’t especially low in the LentiGlobin product the patient received. Therefore, the researchers are still investigating why this patient failed to achieve transfusion independence.

Safety in both trials

“Very importantly, there were no deaths, there were no engraftment failures, there was no evidence of vector-mediated replication-competent lentivirus, and integration site analysis revealed no evidence of clonal dominance,” Dr. Olson said.

He added that most of the grade 3 or greater adverse events seen in both trials were directly attributable to busulfan-based myeloablative conditioning, including four episodes of veno-occlusive disease.

Nonhematologic grade 3 or higher adverse events in HGB-204 included stomatitis (n = 8), febrile neutropenia (n = 6), irregular menstruation (n = 3), pharyngeal inflammation (n = 2), and veno-occlusive liver disease (n = 1).

Nonhematologic grade 3 or higher adverse events in HGB-207 included stomatitis (n = 9), febrile neutropenia (n = 4), pharyngeal inflammation (n = 2), epistaxis (n = 3), pyrexia (n = 3), veno-occlusive liver disease (n = 3), ALT increase (n = 2), bilirubin increase (n = 2), and hypoxia (n = 2).

One patient in HGB-207 had grade 3 thrombocytopenia considered possibly related to LentiGlobin.

Dr. Olson reported advisory board engagement with bluebird bio, which sponsored both trials.

jensmith@mdedge.com

SOURCE: Olson TS et al. ASPHO 2019. Abstract 2002.

NEW ORLEANS – The gene therapy LentiGlobin can reduce transfusion dependence in children and young adults with non-beta⁰/beta⁰ thalassemia, according to two trials.

Jennifer Smith/MDedge News

In a phase 1/2 trial, 8 of 10 of patients achieved transfusion independence at a median follow-up of 36.0 months. In a phase 3 trial, transfusion independence was achieved by 2 of 3 patients with follow-up of at least 12 months.

Timothy S. Olson, MD, PhD, of Children’s Hospital of Philadelphia, presented results from the phase 1/2 HGB-204 trial and the phase 3 HGB-207 trial at the annual meeting of the American Society of Pediatric Hematology/Oncology.
 

Treatment

In both trials, patients received granulocyte colony-stimulating factor and plerixafor for hematopoietic stem cell mobilization. Their cells were collected via apheresis and transduced with the betibeglogene darolentivec (BB305) lentiviral vector. The patients received busulfan (for an average of 4 days) as conditioning and were infused with the transduced cells.

The manufacturing process for LentiGlobin was refined in the HGB-207 trial, which translated to a product with a higher vector copy number and higher proportion of CD34+ cells transduced, Dr. Olson said.

The median vector copy number was 3.1 in the HGB-207 trial and 0.7 in the HGB-204 trial. The median proportion of CD34+ cells transfused was 81% and 29%, respectively. The median cell dose was 7.7 x 10⁶ CD34+ cells/kg and 7.1 x 10⁶ CD34+ cells/kg, respectively.

HGB-204 patients and efficacy

The HGB-204 trial included 10 patients with non-beta⁰/beta⁰ genotypes – 6 with beta^E/beta⁰, 1 with beta⁺/beta⁰, 2 with beta⁺/beta⁺, and 1 with an “other” genotype.

The patients’ median age at consent was 19.5 years (range, 16-34). The annualized median prestudy red blood cell (RBC) transfusion volume was 151 mL/kg per year.


At a median follow-up of 36 months, 8 of the 10 patients achieved transfusion independence. The median duration of transfusion independence was 38 months. The median weighted average hemoglobin during transfusion independence was 10.2 g/dL.

“Two patients did not achieve transfusion independence, and both patients were on the lower end of the spectrum both in terms of vector copy number per cell and the percentage of CD34+ cells that were successfully transduced,” Dr. Olson said. “Both patients actually experienced a reduction in the annualized transfusion volume requirements of between 43% and 77%.”

HGB-207 patients and efficacy

The HGB-207 trial included 16 patients with non-beta⁰/beta⁰ genotypes – 6 with beta^E/beta⁰, 7 with beta⁺/beta⁰, and 3 with the beta⁺/beta⁺ genotype.

The patients’ median age at consent was 19 years . The annualized median prestudy RBC transfusion volume was 192 mL/kg per year.

The median follow-up in this trial is 9.3 months. Ten of 11 patients with at least 3 months of follow-up are transfusion-free with hemoglobin levels greater than 11 g/dL.

Two patients have achieved transfusion independence according to the protocol definition, which is weighted average hemoglobin of 9 g/dL or greater without any RBC transfusions for at least 12 months.

“In the one patient in this study who did not achieve transfusion independence, the vector-derived hemoglobin was quite low, and this correlated with a very low vector copy number seen in circulating peripheral blood mononuclear cells,” Dr. Olson said.

It isn’t clear why this occurred, however, as the vector copy number wasn’t especially low in the LentiGlobin product the patient received. Therefore, the researchers are still investigating why this patient failed to achieve transfusion independence.

Safety in both trials

“Very importantly, there were no deaths, there were no engraftment failures, there was no evidence of vector-mediated replication-competent lentivirus, and integration site analysis revealed no evidence of clonal dominance,” Dr. Olson said.

He added that most of the grade 3 or greater adverse events seen in both trials were directly attributable to busulfan-based myeloablative conditioning, including four episodes of veno-occlusive disease.

Nonhematologic grade 3 or higher adverse events in HGB-204 included stomatitis (n = 8), febrile neutropenia (n = 6), irregular menstruation (n = 3), pharyngeal inflammation (n = 2), and veno-occlusive liver disease (n = 1).

Nonhematologic grade 3 or higher adverse events in HGB-207 included stomatitis (n = 9), febrile neutropenia (n = 4), pharyngeal inflammation (n = 2), epistaxis (n = 3), pyrexia (n = 3), veno-occlusive liver disease (n = 3), ALT increase (n = 2), bilirubin increase (n = 2), and hypoxia (n = 2).

One patient in HGB-207 had grade 3 thrombocytopenia considered possibly related to LentiGlobin.

Dr. Olson reported advisory board engagement with bluebird bio, which sponsored both trials.

jensmith@mdedge.com

SOURCE: Olson TS et al. ASPHO 2019. Abstract 2002.

NEW ORLEANS – The gene therapy LentiGlobin can reduce transfusion dependence in children and young adults with non-beta⁰/beta⁰ thalassemia, according to two trials.

Jennifer Smith/MDedge News

In a phase 1/2 trial, 8 of 10 of patients achieved transfusion independence at a median follow-up of 36.0 months. In a phase 3 trial, transfusion independence was achieved by 2 of 3 patients with follow-up of at least 12 months.

Timothy S. Olson, MD, PhD, of Children’s Hospital of Philadelphia, presented results from the phase 1/2 HGB-204 trial and the phase 3 HGB-207 trial at the annual meeting of the American Society of Pediatric Hematology/Oncology.
 

Treatment

In both trials, patients received granulocyte colony-stimulating factor and plerixafor for hematopoietic stem cell mobilization. Their cells were collected via apheresis and transduced with the betibeglogene darolentivec (BB305) lentiviral vector. The patients received busulfan (for an average of 4 days) as conditioning and were infused with the transduced cells.

The manufacturing process for LentiGlobin was refined in the HGB-207 trial, which translated to a product with a higher vector copy number and higher proportion of CD34+ cells transduced, Dr. Olson said.

The median vector copy number was 3.1 in the HGB-207 trial and 0.7 in the HGB-204 trial. The median proportion of CD34+ cells transfused was 81% and 29%, respectively. The median cell dose was 7.7 x 10⁶ CD34+ cells/kg and 7.1 x 10⁶ CD34+ cells/kg, respectively.

HGB-204 patients and efficacy

The HGB-204 trial included 10 patients with non-beta⁰/beta⁰ genotypes – 6 with beta^E/beta⁰, 1 with beta⁺/beta⁰, 2 with beta⁺/beta⁺, and 1 with an “other” genotype.

The patients’ median age at consent was 19.5 years (range, 16-34). The annualized median prestudy red blood cell (RBC) transfusion volume was 151 mL/kg per year.


At a median follow-up of 36 months, 8 of the 10 patients achieved transfusion independence. The median duration of transfusion independence was 38 months. The median weighted average hemoglobin during transfusion independence was 10.2 g/dL.

“Two patients did not achieve transfusion independence, and both patients were on the lower end of the spectrum both in terms of vector copy number per cell and the percentage of CD34+ cells that were successfully transduced,” Dr. Olson said. “Both patients actually experienced a reduction in the annualized transfusion volume requirements of between 43% and 77%.”

HGB-207 patients and efficacy

The HGB-207 trial included 16 patients with non-beta⁰/beta⁰ genotypes – 6 with beta^E/beta⁰, 7 with beta⁺/beta⁰, and 3 with the beta⁺/beta⁺ genotype.

The patients’ median age at consent was 19 years . The annualized median prestudy RBC transfusion volume was 192 mL/kg per year.

The median follow-up in this trial is 9.3 months. Ten of 11 patients with at least 3 months of follow-up are transfusion-free with hemoglobin levels greater than 11 g/dL.

Two patients have achieved transfusion independence according to the protocol definition, which is weighted average hemoglobin of 9 g/dL or greater without any RBC transfusions for at least 12 months.

“In the one patient in this study who did not achieve transfusion independence, the vector-derived hemoglobin was quite low, and this correlated with a very low vector copy number seen in circulating peripheral blood mononuclear cells,” Dr. Olson said.

It isn’t clear why this occurred, however, as the vector copy number wasn’t especially low in the LentiGlobin product the patient received. Therefore, the researchers are still investigating why this patient failed to achieve transfusion independence.

Safety in both trials

“Very importantly, there were no deaths, there were no engraftment failures, there was no evidence of vector-mediated replication-competent lentivirus, and integration site analysis revealed no evidence of clonal dominance,” Dr. Olson said.

He added that most of the grade 3 or greater adverse events seen in both trials were directly attributable to busulfan-based myeloablative conditioning, including four episodes of veno-occlusive disease.

Nonhematologic grade 3 or higher adverse events in HGB-204 included stomatitis (n = 8), febrile neutropenia (n = 6), irregular menstruation (n = 3), pharyngeal inflammation (n = 2), and veno-occlusive liver disease (n = 1).

Nonhematologic grade 3 or higher adverse events in HGB-207 included stomatitis (n = 9), febrile neutropenia (n = 4), pharyngeal inflammation (n = 2), epistaxis (n = 3), pyrexia (n = 3), veno-occlusive liver disease (n = 3), ALT increase (n = 2), bilirubin increase (n = 2), and hypoxia (n = 2).

One patient in HGB-207 had grade 3 thrombocytopenia considered possibly related to LentiGlobin.

Dr. Olson reported advisory board engagement with bluebird bio, which sponsored both trials.

jensmith@mdedge.com

SOURCE: Olson TS et al. ASPHO 2019. Abstract 2002.

Isolated limb perfusion (ILP) for the adjuvant treatment of melanoma involves isolating the blood flow of a limb from the rest of the body to allow for high concentrations of chemotherapeutic agents locally. Chemotherapy with nitrogen mustard is the preferred chemotherapeutic agent in ILP for the adjuvant treatment of locally advanced melanoma.¹ Systemic exposure to nitrogen mustard has shown to be carcinogenic, and its topical application has been associated with the development of actinic keratosis, basal cell carcinoma (BCC), and squamous cell carcinoma.^2,3 However, the long-term effects of ILP with nitrogen mustard are not well defined. In 1998, one of the authors (R.L.M.) described a patient with melanoma of the left leg that was treated with ILP with nitrogen mustard who subsequently developed numerous BCCs on the same leg.⁴ This same patient has since been successfully managed with only topical chemotherapeutic agents for the last 21 years.

An 86-year-old man with a history of melanoma underwent wide resection, lymph node dissection, and adjuvant ILP with nitrogen mustard for the treatment of melanoma of the medial left thigh approximately 50 years ago. He denied any prior radiation treatment. He subsequently presented years later to our dermatology clinic with many biopsy-proven superficial and nodular BCCs of the left leg over the course of the last 30 years. On physical examination, the patient had several pink papules and macules on the left lower leg (Figure). The patient had previously undergone multiple invasive excisions with grafting for the treatment of BCCs by a plastic surgeon prior to presentation to our clinic but has since had many years of control under our care with only topical chemotherapeutic agents. His current medication regimen consists of 5-fluorouracil twice daily, which he tolerates without serious side effects. He also has used imiquimod in the past.

Treatment modalities for NMSC include surgical excision with defined margins, Mohs micrographic surgery, radiotherapy, electrodesiccation and curettage, cryotherapy, photodynamic therapy, and topical therapy. Our patient experienced such a high volume of superficial BCCs that the decision was made to avoid frequent surgical procedures and to treat with topical chemotherapeutic agents. He had an excellent response to topical 5-fluorouracil, and the treatment has been well tolerated. This case is valuable for clinicians, as it demonstrates that topical chemotherapy can be a well-tolerated option for patients who present with frequent superficial BCCs to prevent numerous invasive surgical treatments.

Isolated limb perfusion (ILP) for the adjuvant treatment of melanoma involves isolating the blood flow of a limb from the rest of the body to allow for high concentrations of chemotherapeutic agents locally. Chemotherapy with nitrogen mustard is the preferred chemotherapeutic agent in ILP for the adjuvant treatment of locally advanced melanoma.¹ Systemic exposure to nitrogen mustard has shown to be carcinogenic, and its topical application has been associated with the development of actinic keratosis, basal cell carcinoma (BCC), and squamous cell carcinoma.^2,3 However, the long-term effects of ILP with nitrogen mustard are not well defined. In 1998, one of the authors (R.L.M.) described a patient with melanoma of the left leg that was treated with ILP with nitrogen mustard who subsequently developed numerous BCCs on the same leg.⁴ This same patient has since been successfully managed with only topical chemotherapeutic agents for the last 21 years.

An 86-year-old man with a history of melanoma underwent wide resection, lymph node dissection, and adjuvant ILP with nitrogen mustard for the treatment of melanoma of the medial left thigh approximately 50 years ago. He denied any prior radiation treatment. He subsequently presented years later to our dermatology clinic with many biopsy-proven superficial and nodular BCCs of the left leg over the course of the last 30 years. On physical examination, the patient had several pink papules and macules on the left lower leg (Figure). The patient had previously undergone multiple invasive excisions with grafting for the treatment of BCCs by a plastic surgeon prior to presentation to our clinic but has since had many years of control under our care with only topical chemotherapeutic agents. His current medication regimen consists of 5-fluorouracil twice daily, which he tolerates without serious side effects. He also has used imiquimod in the past.

Treatment modalities for NMSC include surgical excision with defined margins, Mohs micrographic surgery, radiotherapy, electrodesiccation and curettage, cryotherapy, photodynamic therapy, and topical therapy. Our patient experienced such a high volume of superficial BCCs that the decision was made to avoid frequent surgical procedures and to treat with topical chemotherapeutic agents. He had an excellent response to topical 5-fluorouracil, and the treatment has been well tolerated. This case is valuable for clinicians, as it demonstrates that topical chemotherapy can be a well-tolerated option for patients who present with frequent superficial BCCs to prevent numerous invasive surgical treatments.

Isolated limb perfusion (ILP) for the adjuvant treatment of melanoma involves isolating the blood flow of a limb from the rest of the body to allow for high concentrations of chemotherapeutic agents locally. Chemotherapy with nitrogen mustard is the preferred chemotherapeutic agent in ILP for the adjuvant treatment of locally advanced melanoma.¹ Systemic exposure to nitrogen mustard has shown to be carcinogenic, and its topical application has been associated with the development of actinic keratosis, basal cell carcinoma (BCC), and squamous cell carcinoma.^2,3 However, the long-term effects of ILP with nitrogen mustard are not well defined. In 1998, one of the authors (R.L.M.) described a patient with melanoma of the left leg that was treated with ILP with nitrogen mustard who subsequently developed numerous BCCs on the same leg.⁴ This same patient has since been successfully managed with only topical chemotherapeutic agents for the last 21 years.

An 86-year-old man with a history of melanoma underwent wide resection, lymph node dissection, and adjuvant ILP with nitrogen mustard for the treatment of melanoma of the medial left thigh approximately 50 years ago. He denied any prior radiation treatment. He subsequently presented years later to our dermatology clinic with many biopsy-proven superficial and nodular BCCs of the left leg over the course of the last 30 years. On physical examination, the patient had several pink papules and macules on the left lower leg (Figure). The patient had previously undergone multiple invasive excisions with grafting for the treatment of BCCs by a plastic surgeon prior to presentation to our clinic but has since had many years of control under our care with only topical chemotherapeutic agents. His current medication regimen consists of 5-fluorouracil twice daily, which he tolerates without serious side effects. He also has used imiquimod in the past.

Treatment modalities for NMSC include surgical excision with defined margins, Mohs micrographic surgery, radiotherapy, electrodesiccation and curettage, cryotherapy, photodynamic therapy, and topical therapy. Our patient experienced such a high volume of superficial BCCs that the decision was made to avoid frequent surgical procedures and to treat with topical chemotherapeutic agents. He had an excellent response to topical 5-fluorouracil, and the treatment has been well tolerated. This case is valuable for clinicians, as it demonstrates that topical chemotherapy can be a well-tolerated option for patients who present with frequent superficial BCCs to prevent numerous invasive surgical treatments.