Ob.Gyn. News

Eli Lilly announced it will halt its ACTIV-3 trial evaluating the antibody bamlanivimab in combination with remdesivir for people hospitalized with COVID-19, after new evidence regarding efficacy emerged.

The new data from the National Institutes of Health suggest that the experimental neutralizing antibody therapy does not offer significant clinical benefit for people with more advanced COVID-19 illness, according to a company statement.

Eli Lilly also announced it plans to continue its other trials evaluating the antibody, including those assessing a potential role in treating people in the earlier stages of COVID-19.

“While there was insufficient evidence that bamlanivimab improved clinical outcomes when added to other treatments in hospitalized patients with COVID-19, we remain confident based on data from Lilly’s BLAZE-1 study that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19,” the statement reads.

The ACTIV-3 trial was paused on October 13 after a data and safety monitoring board cited safety concerns.

The most recent data update that triggered an end to the trial did not reveal any significant differences in safety, though.  
 

This article first appeared on Medscape.com.

Eli Lilly announced it will halt its ACTIV-3 trial evaluating the antibody bamlanivimab in combination with remdesivir for people hospitalized with COVID-19, after new evidence regarding efficacy emerged.

The new data from the National Institutes of Health suggest that the experimental neutralizing antibody therapy does not offer significant clinical benefit for people with more advanced COVID-19 illness, according to a company statement.

Eli Lilly also announced it plans to continue its other trials evaluating the antibody, including those assessing a potential role in treating people in the earlier stages of COVID-19.

“While there was insufficient evidence that bamlanivimab improved clinical outcomes when added to other treatments in hospitalized patients with COVID-19, we remain confident based on data from Lilly’s BLAZE-1 study that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19,” the statement reads.

The ACTIV-3 trial was paused on October 13 after a data and safety monitoring board cited safety concerns.

The most recent data update that triggered an end to the trial did not reveal any significant differences in safety, though.  
 

This article first appeared on Medscape.com.

Eli Lilly announced it will halt its ACTIV-3 trial evaluating the antibody bamlanivimab in combination with remdesivir for people hospitalized with COVID-19, after new evidence regarding efficacy emerged.

The new data from the National Institutes of Health suggest that the experimental neutralizing antibody therapy does not offer significant clinical benefit for people with more advanced COVID-19 illness, according to a company statement.

Eli Lilly also announced it plans to continue its other trials evaluating the antibody, including those assessing a potential role in treating people in the earlier stages of COVID-19.

“While there was insufficient evidence that bamlanivimab improved clinical outcomes when added to other treatments in hospitalized patients with COVID-19, we remain confident based on data from Lilly’s BLAZE-1 study that bamlanivimab monotherapy may prevent progression of disease for those earlier in the course of COVID-19,” the statement reads.

The ACTIV-3 trial was paused on October 13 after a data and safety monitoring board cited safety concerns.

The most recent data update that triggered an end to the trial did not reveal any significant differences in safety, though.  
 

This article first appeared on Medscape.com.

When there is an abnormality in the pituitary gland, many potential areas could be affected because of the extent and range of hormones produced by the “master gland,” Ashlyn Smith, PA-C, of Endocrinology Associates, Scottsdale, Ariz., said in a presentation at the at the virtual meeting of the annual Metabolic and Endocrine Disease Summit held by Global Academy for Medical Education.

The most common demographic for pituitary disorders is women in their 30s and 40s, Ms. Smith said. Early red flags for pituitary problems include patients presenting with headaches and/or blurred or double vision, which could signal bitemporal hemianopsia, she said.

Roughly two-thirds of pituitary adenomas are functional, meaning that they secrete pituitary hormones and cause clinical syndromes, Ms. Smith said. The most common reason for hypersecretion is hyperprolactinemia, she said.

Hyperprolactinemia, like most pituitary conditions, is more common in women than men, Ms. Smith noted. However, symptoms may include not only galactorrhea, but also gynecomastia, and hypogonadism, which may be red flags in men, she noted.

“Prolactin inhibits the gonadal pathway, so we see low gonadal hormones. For example, if men present with atypical hypogonadism for their age, or women present with changes in the menstrual cycle, check the prolactin levels,” she said.

The etiologies of hyperprolactinemia include physiologic reasons such as breastfeeding and pregnancy, as well as intercourse and breast manipulation, stress, and sleep issues. Pathologic reasons for prolactin elevation include prolactinoma, gonad-hormone secreting tumor, hypothyroidism, and renal insufficiency, Ms. Smith said.

Evaluation of patients with suspected hyperprolactinemia includes screening for physiologic causes, renal function and thyroid function tests, and a thyroid-specific MRI. Ordering a dedicated MRI of the pituitary gland is important to help identify compression of the optic nerve, noted Ms. Smith.

A medication review also is essential in evaluating hyperprolactinemia, and especially in the setting of the COVID-19 pandemic, because patients may have made changes to psychiatric medications, said Ms. Smith. Neuroleptics and antipsychotics including risperidone, haloperidol, chlorpromazine, and thiothixene can be associated with hyperprolactinemia, as can benzodiazepines and various analgesics and antidepressants, she said.

Treatment in cases of medication-induced hyperprolactinemia can be challenging if the patients are unable to change a medication, said Ms. Smith. However, patients with hypogonadism or low bone mineral density who can’t change medications may benefit from exogenous gonadal hormones, she said.

Some patients with hyperprolactinemia benefit from treatment with dopamine agonists, which may ease symptoms and reduce the size of the prolactinoma, she explained. However, patients on dopamine agonists should be alert to side effects including constipation and orthostasis. Ms. Smith said she recommends that patients on dopamine agonists for hyperprolactinemia take the medication at night so they are lying down if orthostasis occurs.

Monitor prolactin levels at 1 month, and taper or discontinue if the prolactin returns to normal and the adenoma resolves, which can take approximately 2 years, she said. Ms. Smith then advised follow-up every 3 months for 1 year, then annual prolactin checks.

The risk of recurrence ranges from 26% to 69%, Ms. Smith said, and is higher in patients with higher prolactin levels and larger adenomas, she noted. Recurrence is most likely within a year of withdrawal from treatment, she said.

Ms. Smith disclosed serving as an adviser and speaker for Abbott Nutrition, a speaker for Xeris Pharmaceuticals, and an adviser for Sanofi and Radius.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SOURCE: Smith A. MEDS 2020.

When there is an abnormality in the pituitary gland, many potential areas could be affected because of the extent and range of hormones produced by the “master gland,” Ashlyn Smith, PA-C, of Endocrinology Associates, Scottsdale, Ariz., said in a presentation at the at the virtual meeting of the annual Metabolic and Endocrine Disease Summit held by Global Academy for Medical Education.

The most common demographic for pituitary disorders is women in their 30s and 40s, Ms. Smith said. Early red flags for pituitary problems include patients presenting with headaches and/or blurred or double vision, which could signal bitemporal hemianopsia, she said.

Roughly two-thirds of pituitary adenomas are functional, meaning that they secrete pituitary hormones and cause clinical syndromes, Ms. Smith said. The most common reason for hypersecretion is hyperprolactinemia, she said.

Hyperprolactinemia, like most pituitary conditions, is more common in women than men, Ms. Smith noted. However, symptoms may include not only galactorrhea, but also gynecomastia, and hypogonadism, which may be red flags in men, she noted.

“Prolactin inhibits the gonadal pathway, so we see low gonadal hormones. For example, if men present with atypical hypogonadism for their age, or women present with changes in the menstrual cycle, check the prolactin levels,” she said.

The etiologies of hyperprolactinemia include physiologic reasons such as breastfeeding and pregnancy, as well as intercourse and breast manipulation, stress, and sleep issues. Pathologic reasons for prolactin elevation include prolactinoma, gonad-hormone secreting tumor, hypothyroidism, and renal insufficiency, Ms. Smith said.

Evaluation of patients with suspected hyperprolactinemia includes screening for physiologic causes, renal function and thyroid function tests, and a thyroid-specific MRI. Ordering a dedicated MRI of the pituitary gland is important to help identify compression of the optic nerve, noted Ms. Smith.

A medication review also is essential in evaluating hyperprolactinemia, and especially in the setting of the COVID-19 pandemic, because patients may have made changes to psychiatric medications, said Ms. Smith. Neuroleptics and antipsychotics including risperidone, haloperidol, chlorpromazine, and thiothixene can be associated with hyperprolactinemia, as can benzodiazepines and various analgesics and antidepressants, she said.

Treatment in cases of medication-induced hyperprolactinemia can be challenging if the patients are unable to change a medication, said Ms. Smith. However, patients with hypogonadism or low bone mineral density who can’t change medications may benefit from exogenous gonadal hormones, she said.

Some patients with hyperprolactinemia benefit from treatment with dopamine agonists, which may ease symptoms and reduce the size of the prolactinoma, she explained. However, patients on dopamine agonists should be alert to side effects including constipation and orthostasis. Ms. Smith said she recommends that patients on dopamine agonists for hyperprolactinemia take the medication at night so they are lying down if orthostasis occurs.

Monitor prolactin levels at 1 month, and taper or discontinue if the prolactin returns to normal and the adenoma resolves, which can take approximately 2 years, she said. Ms. Smith then advised follow-up every 3 months for 1 year, then annual prolactin checks.

The risk of recurrence ranges from 26% to 69%, Ms. Smith said, and is higher in patients with higher prolactin levels and larger adenomas, she noted. Recurrence is most likely within a year of withdrawal from treatment, she said.

Ms. Smith disclosed serving as an adviser and speaker for Abbott Nutrition, a speaker for Xeris Pharmaceuticals, and an adviser for Sanofi and Radius.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SOURCE: Smith A. MEDS 2020.

When there is an abnormality in the pituitary gland, many potential areas could be affected because of the extent and range of hormones produced by the “master gland,” Ashlyn Smith, PA-C, of Endocrinology Associates, Scottsdale, Ariz., said in a presentation at the at the virtual meeting of the annual Metabolic and Endocrine Disease Summit held by Global Academy for Medical Education.

The most common demographic for pituitary disorders is women in their 30s and 40s, Ms. Smith said. Early red flags for pituitary problems include patients presenting with headaches and/or blurred or double vision, which could signal bitemporal hemianopsia, she said.

Roughly two-thirds of pituitary adenomas are functional, meaning that they secrete pituitary hormones and cause clinical syndromes, Ms. Smith said. The most common reason for hypersecretion is hyperprolactinemia, she said.

Hyperprolactinemia, like most pituitary conditions, is more common in women than men, Ms. Smith noted. However, symptoms may include not only galactorrhea, but also gynecomastia, and hypogonadism, which may be red flags in men, she noted.

“Prolactin inhibits the gonadal pathway, so we see low gonadal hormones. For example, if men present with atypical hypogonadism for their age, or women present with changes in the menstrual cycle, check the prolactin levels,” she said.

The etiologies of hyperprolactinemia include physiologic reasons such as breastfeeding and pregnancy, as well as intercourse and breast manipulation, stress, and sleep issues. Pathologic reasons for prolactin elevation include prolactinoma, gonad-hormone secreting tumor, hypothyroidism, and renal insufficiency, Ms. Smith said.

Evaluation of patients with suspected hyperprolactinemia includes screening for physiologic causes, renal function and thyroid function tests, and a thyroid-specific MRI. Ordering a dedicated MRI of the pituitary gland is important to help identify compression of the optic nerve, noted Ms. Smith.

A medication review also is essential in evaluating hyperprolactinemia, and especially in the setting of the COVID-19 pandemic, because patients may have made changes to psychiatric medications, said Ms. Smith. Neuroleptics and antipsychotics including risperidone, haloperidol, chlorpromazine, and thiothixene can be associated with hyperprolactinemia, as can benzodiazepines and various analgesics and antidepressants, she said.

Treatment in cases of medication-induced hyperprolactinemia can be challenging if the patients are unable to change a medication, said Ms. Smith. However, patients with hypogonadism or low bone mineral density who can’t change medications may benefit from exogenous gonadal hormones, she said.

Some patients with hyperprolactinemia benefit from treatment with dopamine agonists, which may ease symptoms and reduce the size of the prolactinoma, she explained. However, patients on dopamine agonists should be alert to side effects including constipation and orthostasis. Ms. Smith said she recommends that patients on dopamine agonists for hyperprolactinemia take the medication at night so they are lying down if orthostasis occurs.

Monitor prolactin levels at 1 month, and taper or discontinue if the prolactin returns to normal and the adenoma resolves, which can take approximately 2 years, she said. Ms. Smith then advised follow-up every 3 months for 1 year, then annual prolactin checks.

The risk of recurrence ranges from 26% to 69%, Ms. Smith said, and is higher in patients with higher prolactin levels and larger adenomas, she noted. Recurrence is most likely within a year of withdrawal from treatment, she said.

Ms. Smith disclosed serving as an adviser and speaker for Abbott Nutrition, a speaker for Xeris Pharmaceuticals, and an adviser for Sanofi and Radius.

Global Academy for Medical Education and this news organization are owned by the same parent company.

SOURCE: Smith A. MEDS 2020.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at [email protected].

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at [email protected].

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Over the past 4 decades there has been increasing use of minimally invasive surgery (MIS) for gynecologic cancer, particularly endometrial and cervical cancers. Uterine manipulators are a device inserted into the uterine cavity during MIS approaches to aid in directing the uterus within the pelvis, facilitating access to the uterine blood supply, defining the cardinal ligaments, lateralizing the ureters, and delineating the cervicovaginal junction. However, concerns have been raised regarding whether these devices are safe to use when the uterine corpus or cervix contains cancer.

In 2018, the LACC trial was published and demonstrated decreased survival for patients with cervical cancer who had undergone radical hysterectomy via a minimally invasive route.¹ Several hypotheses were proposed to explain this finding including possible tumor disruption from use of a uterine manipulator. Regrettably, this study did not document manipulator use, and therefore its influence on outcomes could not be measured. However, since that time there has been honed interest into the potential negative influence of uterine manipulators on endometrial and cervical cancer surgery.

Uterine manipulators typically are inserted through the uterine cervix and reside in the endometrial cavity. It is often an inflated balloon which stabilizes the device within the cavity. Hypotheses for how they may contribute to the spread of malignancy include the massage of endometrial tumor from the pressure of the inflated balloon, facilitation of tumor dissemination through cervical lymphatics or vasculature as the manipulator traverses or punctures a cervical cancer, and possibly perforation of the uterine cavity during placement of the manipulator, and in doing so, contaminating the peritoneal cavity with endometrial or cervical cancer cells that have been dragged through with the device.

Interestingly, uterine manipulator placement is not the only time during which endometrial or cervical cancers may be disturbed prior to resection. Many diagnostic procedures such as cervical excisional procedures (loop electrosurgical excision procedure and conizations) or hysteroscopic resections cause significant intentional disruption of tumor. In the case of hysteroscopy for endometrial cancer, endometrial cancer cells have been detected in the peritoneal washings of endometrial cancer patients who have undergone this procedure, however, no worse outcomes have been associated when hysteroscopy was included as part of the diagnostic work-up, suggesting that more than simply efflux into the peritoneal cavity is necessary for those tumor cells to have metastatic potential.²

Indeed the data is mixed regarding oncologic outcomes with uterine manipulator use, especially for endometrial cancer. In one recent study the outcomes of 951 patients with endometrial cancer from seven Italian centers were evaluated.³ There was no difference in recurrence rates or disease-specific survival between the 579 patients in whom manipulators were used and the 372 patients in which surgery was performed without manipulators. More recently a Spanish study reported retrospectively on 2,661 patients at 15 centers and determined that use of a uterine manipulator (two-thirds of the cohort) was associated with a hazard ratio of 1.74 (95% confidence interval, 1.07-2.83) for risk of death.⁴ Unfortunately, in this study there were substantial differences between sites that used manipulators and those that did not. Additionally, while one would expect different patterns of recurrence if the manipulator was introducing a unique mechanism for metastasis, this was not observed between the manipulator and nonmanipulator arms. Finally, the groups were intrinsically different with respect to important risk factors such as lymphovascular space invasion, which might have contributed to the observed outcomes. It is important to recognize that, in both the LAP-2 and LACE trials, minimally invasive hysterectomy for endometrial cancer had been shown to have noninferior survival outcomes, compared with open hysterectomy.^5,6 While these large randomized, controlled trials did not capture uterine manipulator usage, presumably it was utilized in at least some or most cases, and without apparent significant negative effect.

In cervical cancer, there is more competing data raising concern regarding manipulator use. The SUCCOR study was completed in 2020 and included a retrospective evaluation of 1,272 patients who had undergone open or MIS radical hysterectomy for early stage cervical cancer across 126 European centers during 2013-2014.⁷ They were able to evaluate for variables, such as uterine manipulator use. While they found that recurrence was higher for patients who had MIS hysterectomy, the HR (2.07) was similar to the HR for recurrence (2.76) among those who had uterine manipulator use. Conversely, the hazard ratio for recurrence following MIS radical hysterectomy without a manipulator was comparable with the superior rates seen with open surgery. This study was retrospective and therefore is largely hypothesis generating, however it does raise the question of whether the technique of MIS radical hysterectomy can be performed safely if particular steps, such as avoidance of a uterine manipulator, are followed. We await definitive results from prospective trials to determine this.

As mentioned earlier, the uterine manipulator is an important safety and feasibility tool for MIS hysterectomy. When not utilized, surgeons may need to add additional ports and instrumentation to maneuver the uterus and may have difficulty completing hysterectomy via a MIS approach for obese patients. There are additional urologic safety concerns when uterine elevation and cervicovaginal delineation is missing. Therefore, surgeons should consider use of the uterine manipulator on a case-by-case basis, potentially avoiding its use when it is not felt to be of benefit. While the wealth of prospective data suggests that manipulators are most likely safe in hysterectomy for endometrial cancer, they should be avoided if a minimally invasive approach to cervical cancer is employed.

Dr. Rossi is assistant professor in the division of gynecologic oncology at the University of North Carolina at Chapel Hill. She has no conflicts of interest to report. Email her at [email protected].

References

1. N Engl J Med. 2018 Nov 15. doi: 10.1056/NEJMoa1806395.

2. Fertil Steril. 2011 Oct. doi: 10.1016/j.fertnstert.2011.07.1146.

3. Am J Obstet Gynecol. 2017 Jun. doi: 10.1016/j.ajog.2017.01.027.

4. Am J Obstet Gynecol. 2020 Jul 18. doi: 10.1016/j.ajog.2020.07.025.

5. J Clin Oncol. 2009 Nov 10. doi: 10.1200/JCO.2009.22.3248.

6. JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.2068.

7. Int J Gynecol Cancer. 2020. doi: 10.1136/ijgc-2020-001506.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Antibody response to the SARS-CoV-2 virus wanes over time, latest research has suggested.

An ongoing study led by Imperial College London (ICL) found that the proportion of people testing positive for COVID-19 antibodies dropped by 26.5% over a 3-month period between June and September.

The findings from a non–peer reviewed preprint suggested that infection with SARS-CoV-2 confers only limited protection against reinfection.

Professor Paul Elliott, director of the REACT-2 programme at ICL, said: “Testing positive for antibodies does not mean you are immune to COVID-19.

“It remains unclear what level of immunity antibodies provide, or for how long this immunity lasts.”

Experts said that, while the findings suggested that immunity might fade over time, the severity of illness from further infections could be reduced.
 

Antibody prevalence declined in all adults

Results from cross-sectional studies over the 3-month period involved 365,104 adults who self-administered a lateral flow immunoassay test.

There were 17,576 positive tests over the three rounds.

Antibody prevalence, adjusted for test characteristics and weighted to the adult population of England, declined from 6.0% to 4.4%, a reduction of 26.5% over the 3 months.

The decline was seen in all age groups. However, the lowest prevalence of a positive test, and the largest fall, was seen in those aged 75 years and older.

No change was seen in positive antibody tests in health care workers over the 3 months.

The results suggested that people who did not show symptoms of COVID-19 were more likely to lose detectable antibodies sooner than those who did show symptoms.

Prof Helen Ward, one of the lead authors of the report said that, while it was clear that the proportion of people with antibodies was falling over time, “We don’t yet know whether this will leave these people at risk of reinfection with the virus that causes COVID-19, but it is essential that everyone continues to follow guidance to reduce the risk to themselves and others.”
 

Results ‘weaken argument for herd immunity’

Commenting on the results to the Science Media Centre, Rowland Kao, professor of veterinary epidemiology and data science at the University of Edinburgh, warned that, if the results were correct, “any strategy that relies on ‘herd immunity’ lacks credibility.”

However, he added that, “while the decline is substantial, nevertheless substantial proportions of the population do retain some immune response, over 4 months after the peak of the epidemic”.

Eleanor Riley, professor of immunology and infectious disease, also from the University of Edinburgh, said it was too early to assume that immunity to SARS-CoV-2 did not last because “the study does not look at antibody concentrations, antibody function, or other aspects of immunity such as T-cell immunity and does not look at the trajectory of antibody levels in the same individuals over time”.

However, she said the findings did not mean that a vaccine would be ineffective because vaccines contained adjuvants that could induce durable immune responses, particularly with multiple immunizations.

“What is not clear is how quickly antibody levels would rise again if a person encounters the SARS-CoV-2 virus a second time. It is possible they will still rapidly respond, and either have a milder illness, or remain protected through immune memory,” commented Dr. Alexander Edwards, associate professor in biomedical technology at the University of Reading.

Health Minister Lord Bethell said: “Regardless of the result of an antibody test, everyone must continue to comply with government guidelines including social distancing, self-isolating, and getting a test if you have symptoms, and always remember: hands, face, space.”
 

This article first appeared on Medscape.com.

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Danny Dvir, MD, has a message for physicians who have patients with severe valvular heart disease who are deferring valve replacement or repair until after the COVID-19 pandemic: Urge them not to wait.

Data from the Multicenter International Valve Disease Registry vividly demonstrate that clinical outcomes are poor in patients with uncorrected valve disease who become hospitalized with COVID-19. Indeed, the mortality rate within 30 days after hospital admission in 136 such patients enrolled in the registry from centers in Europe, North America, and Israel was 42%, Dr. Dvir reported at the Transcatheter Cardiovascular Research Therapeutics virtual annual meeting.

“That’s dramatically higher than for an age-matched population infected with COVID-19 without valvular heart disease, which is 10%-15%,” he noted at the meeting sponsored by the Cardiovascular Research Foundation.

The bright spot was that, in the small subgroup of 15 registry participants who underwent transcatheter or, much less frequently, surgical treatment of their failing valve while COVID-19 infected, 30-day mortality was far lower. In fact, it was comparable with the background rate in hospitalized COVID-19 patients without valve disease, according to Dr. Dvir, an interventional cardiologist at Shaare Zedek Medical Center, Hebrew University, Jerusalem.

He personally did several of the transcatheter aortic valve replacements.

“It’s doable. I truly believe that when you get a severe aortic stenosis patient who’s infected with the coronavirus, they get very unstable, but we can treat them. We can treat them even during the infection,” Dr. Dvir said.

The majority of patients in the registry had severe aortic stenosis. In the 42 such patients aged 80 years or more who didn’t undergo transcatheter aortic valve replacement (TAVR) or surgical valve replacement, 30-day mortality was 60%. In contrast, only one of the six patients in this advanced-age category who underwent valve replacement while infected died. Similarly, 30-day mortality was 24% among those younger than age 80 who valve remained untreated, but it dropped to 11% in those who received a prosthetic valve.

“We try our best to protect our patients through social distancing, but we have a treatment that can potentially reduce their mortality risk if they get infected later on. So I say to my patients: ‘Don’t wait at home. Do not wait! If you get infected when you have severe aortic stenosis, the clinical outcome is bad.’ But it seems reasonable that if they get infected when they’ve already been treated for their aortic stenosis or mitral regurgitation, they will do better.”

Dr. Dvir noted that, although the case numbers in the registry series were small and subject to potential bias, the data suggest this treatment approach may be lifesaving.

Session comoderator Timothy D. Henry, MD, commented that this registry study contains a great take-home point: “This is really consistent with what see in a lot of the other areas of COVID, that what we know to be best clinical care, we should do it, with or without the COVID.”

He asked Dr. Dvir about any special measures he takes while doing TAVR in this extreme setting. In the United States, for example, interventionalists are increasingly using transesophageal echocardiography to guide their procedures using conscious sedation, without intubation, noted Dr. Henry, medical director of the Carl and Edyth Lindner Center for Research at the Christ Hospital, Cincinnati.

“We try to minimize the procedure time; that’s one of the important things,” Dr. Dvir replied. “And you need to be protected during the procedure in a very cautious and meticulous way. You need many fans in the room because you sweat a lot.”

Discussant Renu Virmani, MD, president of the CVPath Institute in Gaithersburg, Md., commented: “The main thing I get from this presentation is the need for patients to be educated that if you’ve got valve disease, you’re better off getting it treated before you’ve got COVID. Obviously, try to prevent getting COVID – that’s the best thing you can do – but you can’t always control that.”

Discussant Mamas Mamas, MD, professor of cardiology at Keele University, Staffordshire, England, said deferred treatment of severe valvular heart disease during the pandemic has created a looming public health crisis in the United Kingdom.

“We’ve analyzed the U.K. management of aortic stenosis, and what we’ve found is that during the COVID pandemic there have been 2,500 fewer cases of aortic stenosis that have been treated. We’ve got 2,500 patients on the waiting list, and we’ve got to work out how we’re going to treat them. We estimate with simulations that about 300 of them are going to die before we can get them treated for their aortic stenosis,” according to Dr. Mamas.

Dr. Henry commented that deferral of valve procedures is “really challenging” for a couple of reasons: Not only are patients scared to come into the hospital because they fear getting COVID, but they don’t want to be hospitalized during the pandemic because their family can’t visit them there.

“These patients are mostly over 80 years old. No one wants to come in the hospital when the family won’t be around, especially when you’re 90 years old,” the interventional cardiologist said.

Dr. Dvir reported serving as a consultant to Medtronic, Edwards Lifesciences, Abbott, and Jena.

[email protected]

Fewer than one-third of women hospitalized with influenza receive the recommended flu vaccine, according to a study using data over nine flu seasons.

Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).

Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.

Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.

Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.

She noted that pregnant women are at high risk for influenza-associated hospitalization.

“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview

“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»

FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
 

Vaccine uptake lowest in first two trimesters

Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.

Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).

“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.

Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.

She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.

Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.

Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”

Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”

Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.

“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.

Holstein and Sheffield have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fewer than one-third of women hospitalized with influenza receive the recommended flu vaccine, according to a study using data over nine flu seasons.

Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).

Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.

Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.

Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.

She noted that pregnant women are at high risk for influenza-associated hospitalization.

“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview

“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»

FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
 

Vaccine uptake lowest in first two trimesters

Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.

Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).

“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.

Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.

She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.

Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.

Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”

Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”

Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.

“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.

Holstein and Sheffield have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Fewer than one-third of women hospitalized with influenza receive the recommended flu vaccine, according to a study using data over nine flu seasons.

Researchers analyzed data from 9,652 women ages 15-44 who were hospitalized with laboratory-confirmed influenza from October through April during the 2010-2019 influenza seasons. Data were pulled from the U.S. Influenza Hospitalization Surveillance Network (FluSurv-NET).

Of those women, 2,697 (28%) were pregnant. Median age was 28 and median gestational age was 32 weeks. Those studied included 36% who were non-Hispanic White; 29% non-Hispanic Black; and 20% Hispanic women.

Some 89% of the women, pregnant and nonpregnant, received antivirals while in the hospital but only 31% reported they had received the flu vaccine in the current season, despite guideline recommendations citing clear evidence that vaccination is safe for mother and baby.

Rachel Holstein, MPH, an epidemiology and information science fellow at the Centers for Disease Control and Prevention, who presented her team’s work as part of IDWeek 2020, explained that the mother’s vaccination can help protect the baby from flu infection for several months after birth, before the baby can be vaccinated.

She noted that pregnant women are at high risk for influenza-associated hospitalization.

“Changes in the immune system, heart, and lungs during pregnancy make pregnant women, and women up to 2 weeks post partum, more prone to severe illness from flu, including illness resulting in hospitalization,” she said in an interview

“Vaccination has been shown to reduce the risk of flu-associated acute respiratory infection in pregnant women by up to one-half,” she said. “A 2018 study showed that getting a flu shot reduced a pregnant woman’s risk of being hospitalized with flu by an average of 40%.»

FluSurv-NET data show hospitalizations were more common in the third trimester of pregnancy compared with the first and second, Holstein said. The most common underlying conditions among these women were asthma (23%) and obesity (10%), and 12% were current tobacco smokers. Overall, 5% of pregnant women with flu required ICU admission, 2% needed mechanical ventilation, and 6% developed pneumonia.
 

Vaccine uptake lowest in first two trimesters

Holstein said vaccine coverage was lowest among women in their first or second trimesters for all 9 seasons, and overall vaccination coverage increased significantly over time.

Uptake also differed by age. The data showed coverage was lower among women aged 15-34 years, compared with women 35 years and older (34% vs. 50%).

“It was as low as 15% among pregnant women aged 15-34 years in the 2011-12 season,” she added.

Jeanne Sheffield, MD, director of the division of maternal-fetal medicine at Johns Hopkins Medicine, Baltimore, said in an interview the low uptake of vaccine shown in this study is both familiar and frustrating.

She said education from health care providers has improved, but women are nonetheless frequently fearful. She pointed out the widespread phenomenon of vaccine hesitancy in the general population.

Coverage was 45.3% among adults in the 2018-2019 flu season, 8.2 percentage points higher than coverage during the 2017-18 season (37.1%) according to CDC estimates.

Added to that, she said, is further hesitancy when women believe vaccination could harm the unborn baby, despite “very good data that flu vaccine is safe in pregnancy, acceptable in pregnancy in all trimesters, and is optimal standard of care.”

Holstein added, “We know from past research that a range of factors – including negative attitudes and beliefs about vaccines, less knowledge about and access to vaccines, and a lack of trust in healthcare providers and vaccines – can contribute to lower vaccination rates.”

Healthcare providers play a key role in increasing flu vaccinations among pregnant women, she said.

“A provider recommendation, combined with an offer to administer a flu vaccine at the time of visit, remains one of the best ways to accomplish this,” Holstein said.

Holstein and Sheffield have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Women who experience irregular and long menstrual cycles in adolescence and adulthood are more likely to die before the age of 70 years than women with regular or short cycles, reported Yi-Xin Wang, PhD, of Harvard TH Chan School of Public Health, Boston, and associates. This is particularly true in the presence of cardiovascular disease and a history of smoking.

In a peer-reviewed observational study of 79,505 premenopausal women enrolled in the Nurses’ Health Study II, the researchers sought to determine whether a life-long history of irregular or long menstrual cycles was associated with premature death. Patients averaged a mean age of 37.7 years and had no history of cardiovascular disease, cancer, or diabetes at enrollment.

Although irregular and long menstrual cycles are common and frequently linked with an increased risk of major chronic diseases – such as ovarian cancer, coronary heart disease, type 2 diabetes, and mental health problems – in women of reproductive age, actual evidence linking irregular or long menstrual cycles with mortality is scant, the researchers noted in the BMJ.

During the study, participants checked in at ages 14-17 years, 18-22 years, and 29-46 years to report the usual length and regularity of their menstrual cycles. Over 24 years of follow-up, a total of 1,975 premature deaths were noted, including 894 from cancer and 172 from cardiovascular disease.
 

Irregular cycles appear to bring risks

After considering other possible factors of influence, including age, weight, lifestyle, and family medical history, Dr. Wang and associates noted higher rates of mortality among those consistently reporting irregular cycles than women in the same age ranges with very regular cycles. Specifically, women aged 18-22 years and 29-46 years with cycles of 40 days or more were at greater risk of dying prematurely than were those in the same age ranges with cycles of 26-31 days.

Cardiovascular disease was a stronger predictor of death than cancer or other causes. Also included in the higher-risk group were those who currently smoked.

Among women reporting very regular cycles and women reporting always irregular cycles, mortality rates per 1,000 person-years were 1.05 and 1.23 at ages 14-17 years, 1.00 and 1.37 at ages 18-22 years, and 1.00 and 1.68 at ages 29-46 years, respectively.

The study also found that women reporting irregular cycles or no periods had a higher body mass indexes (28.2 vs. 25.0 kg/m²); were more likely to have conditions including hypertension (13.2% vs. 6.2%), high blood cholesterol levels (23.9% vs. 14.9%), hirsutism (8.4%

vs. 1.8%), or endometriosis (5.9% vs. 4.5%); and uterine fibroids (10.0% vs. 7.8%); and a higher prevalence of family history of diabetes (19.4% vs. 15.8%).

Dr. Wang and associates also observed – using multivariable Cox models – a greater risk of premature death across all categories and all age ranges in women with decreasing menstrual cycle regularity. In models that were fully adjusted, cycle lengths that were 40 days or more or too irregular to estimate from ages 18-22 and 29-46 expressed hazard ratios for premature death at the time of follow-up of 1.34 and 1.40, compared with women in the same age ranges reporting cycle lengths of 26-31 days.

Of note, Dr. Wang and colleagues unexpectedly discovered an increased risk of premature death in women who had used contraceptives between 14-17 years. They suggested that a greater number of women self-reporting contraceptive use in adolescence may have been using contraceptives to manage symptoms of polycystic ovary syndrome (PCOS) and other conditions such as endometriosis.

Relying on the potential inaccuracy inherent in patient recall of their menstrual cycle characteristics, and the likelihood for other unmeasured factors, may have affected study results. Study strengths included the significant number of participants who had a high follow-up rate over many years, and the availability of menstrual cycle data at three different points across the reproductive lifespan.

Because the mechanisms underlying these associations are likely related to the disrupted hormonal environment, the study results “emphasize the need for primary care providers to include menstrual cycle characteristics throughout the reproductive life span as additional vital signs in assessing women’s general health status,” Dr. Wang and colleagues cautioned.
 

Expert suggests a probable underlying link

“Irregular menstrual cycles in women have long been known to be associated with significant morbidities, including the leading causes of mortality worldwide such as cardiovascular disease and cancer,” Reshef Tal, MD, PhD, assistant professor of obstetrics, gynecology & reproductive sciences at Yale University, New Haven, Conn., said in an interview. “The findings of this large study that irregular menstrual cycles are associated with premature death, most strongly from cardiovascular causes, are therefore not surprising.”

Dr. Tal acknowledged that one probable underlying link is PCOS, which is recognized as the most common hormonal disorder affecting women of reproductive age. The irregular periods that characterize PCOS are tied to a number of metabolic risk factors, including obesity, insulin resistance, dyslipidemia, and hypertension, which increase the long-term risk of cardiovascular disease and cancer of the uterus.

“The study did not have information on patients’ pelvic ultrasound findings and male hormone levels, which would have helped to establish PCOS diagnosis. However, women in this study who had irregular cycles tended to have more hirsutism, high cholesterol, hypertension as well as higher BMI, suggesting that PCOS is at least partly responsible for the observed association with cardiovascular disease. Interestingly, the association between irregular cycles and early mortality was independent of BMI, indicating that mechanisms other than metabolic factors may also play a role,” observed Dr. Tal, who was asked to comment on the study.

“Irregular periods are a symptom and not a disease, so it is important to identify underlying metabolic risk factors. Furthermore, physicians are advised to counsel patients experiencing menstrual irregularity, [to advise them to] maintain a healthy lifestyle and be alert to health changes,” Dr. Tal suggested.

The study was funded by the National Institutes of Health. The investigators had no relevant financial disclosures. Dr. Tal said he had no relevant financial disclosures.

SOURCE: Chavarro J et al. BMJ. 2020. doi: 10.1136/bmj.m3464.

Women who experience irregular and long menstrual cycles in adolescence and adulthood are more likely to die before the age of 70 years than women with regular or short cycles, reported Yi-Xin Wang, PhD, of Harvard TH Chan School of Public Health, Boston, and associates. This is particularly true in the presence of cardiovascular disease and a history of smoking.

In a peer-reviewed observational study of 79,505 premenopausal women enrolled in the Nurses’ Health Study II, the researchers sought to determine whether a life-long history of irregular or long menstrual cycles was associated with premature death. Patients averaged a mean age of 37.7 years and had no history of cardiovascular disease, cancer, or diabetes at enrollment.

Although irregular and long menstrual cycles are common and frequently linked with an increased risk of major chronic diseases – such as ovarian cancer, coronary heart disease, type 2 diabetes, and mental health problems – in women of reproductive age, actual evidence linking irregular or long menstrual cycles with mortality is scant, the researchers noted in the BMJ.

During the study, participants checked in at ages 14-17 years, 18-22 years, and 29-46 years to report the usual length and regularity of their menstrual cycles. Over 24 years of follow-up, a total of 1,975 premature deaths were noted, including 894 from cancer and 172 from cardiovascular disease.
 

Irregular cycles appear to bring risks

After considering other possible factors of influence, including age, weight, lifestyle, and family medical history, Dr. Wang and associates noted higher rates of mortality among those consistently reporting irregular cycles than women in the same age ranges with very regular cycles. Specifically, women aged 18-22 years and 29-46 years with cycles of 40 days or more were at greater risk of dying prematurely than were those in the same age ranges with cycles of 26-31 days.

Cardiovascular disease was a stronger predictor of death than cancer or other causes. Also included in the higher-risk group were those who currently smoked.

Among women reporting very regular cycles and women reporting always irregular cycles, mortality rates per 1,000 person-years were 1.05 and 1.23 at ages 14-17 years, 1.00 and 1.37 at ages 18-22 years, and 1.00 and 1.68 at ages 29-46 years, respectively.

The study also found that women reporting irregular cycles or no periods had a higher body mass indexes (28.2 vs. 25.0 kg/m²); were more likely to have conditions including hypertension (13.2% vs. 6.2%), high blood cholesterol levels (23.9% vs. 14.9%), hirsutism (8.4%

vs. 1.8%), or endometriosis (5.9% vs. 4.5%); and uterine fibroids (10.0% vs. 7.8%); and a higher prevalence of family history of diabetes (19.4% vs. 15.8%).

Dr. Wang and associates also observed – using multivariable Cox models – a greater risk of premature death across all categories and all age ranges in women with decreasing menstrual cycle regularity. In models that were fully adjusted, cycle lengths that were 40 days or more or too irregular to estimate from ages 18-22 and 29-46 expressed hazard ratios for premature death at the time of follow-up of 1.34 and 1.40, compared with women in the same age ranges reporting cycle lengths of 26-31 days.

Of note, Dr. Wang and colleagues unexpectedly discovered an increased risk of premature death in women who had used contraceptives between 14-17 years. They suggested that a greater number of women self-reporting contraceptive use in adolescence may have been using contraceptives to manage symptoms of polycystic ovary syndrome (PCOS) and other conditions such as endometriosis.

Relying on the potential inaccuracy inherent in patient recall of their menstrual cycle characteristics, and the likelihood for other unmeasured factors, may have affected study results. Study strengths included the significant number of participants who had a high follow-up rate over many years, and the availability of menstrual cycle data at three different points across the reproductive lifespan.

Because the mechanisms underlying these associations are likely related to the disrupted hormonal environment, the study results “emphasize the need for primary care providers to include menstrual cycle characteristics throughout the reproductive life span as additional vital signs in assessing women’s general health status,” Dr. Wang and colleagues cautioned.
 

Expert suggests a probable underlying link

“Irregular menstrual cycles in women have long been known to be associated with significant morbidities, including the leading causes of mortality worldwide such as cardiovascular disease and cancer,” Reshef Tal, MD, PhD, assistant professor of obstetrics, gynecology & reproductive sciences at Yale University, New Haven, Conn., said in an interview. “The findings of this large study that irregular menstrual cycles are associated with premature death, most strongly from cardiovascular causes, are therefore not surprising.”

Dr. Tal acknowledged that one probable underlying link is PCOS, which is recognized as the most common hormonal disorder affecting women of reproductive age. The irregular periods that characterize PCOS are tied to a number of metabolic risk factors, including obesity, insulin resistance, dyslipidemia, and hypertension, which increase the long-term risk of cardiovascular disease and cancer of the uterus.

“The study did not have information on patients’ pelvic ultrasound findings and male hormone levels, which would have helped to establish PCOS diagnosis. However, women in this study who had irregular cycles tended to have more hirsutism, high cholesterol, hypertension as well as higher BMI, suggesting that PCOS is at least partly responsible for the observed association with cardiovascular disease. Interestingly, the association between irregular cycles and early mortality was independent of BMI, indicating that mechanisms other than metabolic factors may also play a role,” observed Dr. Tal, who was asked to comment on the study.

“Irregular periods are a symptom and not a disease, so it is important to identify underlying metabolic risk factors. Furthermore, physicians are advised to counsel patients experiencing menstrual irregularity, [to advise them to] maintain a healthy lifestyle and be alert to health changes,” Dr. Tal suggested.

The study was funded by the National Institutes of Health. The investigators had no relevant financial disclosures. Dr. Tal said he had no relevant financial disclosures.

SOURCE: Chavarro J et al. BMJ. 2020. doi: 10.1136/bmj.m3464.

Women who experience irregular and long menstrual cycles in adolescence and adulthood are more likely to die before the age of 70 years than women with regular or short cycles, reported Yi-Xin Wang, PhD, of Harvard TH Chan School of Public Health, Boston, and associates. This is particularly true in the presence of cardiovascular disease and a history of smoking.

In a peer-reviewed observational study of 79,505 premenopausal women enrolled in the Nurses’ Health Study II, the researchers sought to determine whether a life-long history of irregular or long menstrual cycles was associated with premature death. Patients averaged a mean age of 37.7 years and had no history of cardiovascular disease, cancer, or diabetes at enrollment.

Although irregular and long menstrual cycles are common and frequently linked with an increased risk of major chronic diseases – such as ovarian cancer, coronary heart disease, type 2 diabetes, and mental health problems – in women of reproductive age, actual evidence linking irregular or long menstrual cycles with mortality is scant, the researchers noted in the BMJ.

During the study, participants checked in at ages 14-17 years, 18-22 years, and 29-46 years to report the usual length and regularity of their menstrual cycles. Over 24 years of follow-up, a total of 1,975 premature deaths were noted, including 894 from cancer and 172 from cardiovascular disease.
 

Irregular cycles appear to bring risks

After considering other possible factors of influence, including age, weight, lifestyle, and family medical history, Dr. Wang and associates noted higher rates of mortality among those consistently reporting irregular cycles than women in the same age ranges with very regular cycles. Specifically, women aged 18-22 years and 29-46 years with cycles of 40 days or more were at greater risk of dying prematurely than were those in the same age ranges with cycles of 26-31 days.

Cardiovascular disease was a stronger predictor of death than cancer or other causes. Also included in the higher-risk group were those who currently smoked.

Among women reporting very regular cycles and women reporting always irregular cycles, mortality rates per 1,000 person-years were 1.05 and 1.23 at ages 14-17 years, 1.00 and 1.37 at ages 18-22 years, and 1.00 and 1.68 at ages 29-46 years, respectively.

The study also found that women reporting irregular cycles or no periods had a higher body mass indexes (28.2 vs. 25.0 kg/m²); were more likely to have conditions including hypertension (13.2% vs. 6.2%), high blood cholesterol levels (23.9% vs. 14.9%), hirsutism (8.4%

vs. 1.8%), or endometriosis (5.9% vs. 4.5%); and uterine fibroids (10.0% vs. 7.8%); and a higher prevalence of family history of diabetes (19.4% vs. 15.8%).

Dr. Wang and associates also observed – using multivariable Cox models – a greater risk of premature death across all categories and all age ranges in women with decreasing menstrual cycle regularity. In models that were fully adjusted, cycle lengths that were 40 days or more or too irregular to estimate from ages 18-22 and 29-46 expressed hazard ratios for premature death at the time of follow-up of 1.34 and 1.40, compared with women in the same age ranges reporting cycle lengths of 26-31 days.

Of note, Dr. Wang and colleagues unexpectedly discovered an increased risk of premature death in women who had used contraceptives between 14-17 years. They suggested that a greater number of women self-reporting contraceptive use in adolescence may have been using contraceptives to manage symptoms of polycystic ovary syndrome (PCOS) and other conditions such as endometriosis.

Relying on the potential inaccuracy inherent in patient recall of their menstrual cycle characteristics, and the likelihood for other unmeasured factors, may have affected study results. Study strengths included the significant number of participants who had a high follow-up rate over many years, and the availability of menstrual cycle data at three different points across the reproductive lifespan.

Because the mechanisms underlying these associations are likely related to the disrupted hormonal environment, the study results “emphasize the need for primary care providers to include menstrual cycle characteristics throughout the reproductive life span as additional vital signs in assessing women’s general health status,” Dr. Wang and colleagues cautioned.
 

Expert suggests a probable underlying link

“Irregular menstrual cycles in women have long been known to be associated with significant morbidities, including the leading causes of mortality worldwide such as cardiovascular disease and cancer,” Reshef Tal, MD, PhD, assistant professor of obstetrics, gynecology & reproductive sciences at Yale University, New Haven, Conn., said in an interview. “The findings of this large study that irregular menstrual cycles are associated with premature death, most strongly from cardiovascular causes, are therefore not surprising.”

Dr. Tal acknowledged that one probable underlying link is PCOS, which is recognized as the most common hormonal disorder affecting women of reproductive age. The irregular periods that characterize PCOS are tied to a number of metabolic risk factors, including obesity, insulin resistance, dyslipidemia, and hypertension, which increase the long-term risk of cardiovascular disease and cancer of the uterus.

“The study did not have information on patients’ pelvic ultrasound findings and male hormone levels, which would have helped to establish PCOS diagnosis. However, women in this study who had irregular cycles tended to have more hirsutism, high cholesterol, hypertension as well as higher BMI, suggesting that PCOS is at least partly responsible for the observed association with cardiovascular disease. Interestingly, the association between irregular cycles and early mortality was independent of BMI, indicating that mechanisms other than metabolic factors may also play a role,” observed Dr. Tal, who was asked to comment on the study.

“Irregular periods are a symptom and not a disease, so it is important to identify underlying metabolic risk factors. Furthermore, physicians are advised to counsel patients experiencing menstrual irregularity, [to advise them to] maintain a healthy lifestyle and be alert to health changes,” Dr. Tal suggested.

The study was funded by the National Institutes of Health. The investigators had no relevant financial disclosures. Dr. Tal said he had no relevant financial disclosures.

SOURCE: Chavarro J et al. BMJ. 2020. doi: 10.1136/bmj.m3464.

Sexual activity and function improve or at least are maintained following pelvic organ prolapse surgery, Danielle D. Antosh, MD, of the Houston Methodist Hospital and colleagues reported in a systematic review of prospective comparative studies on pelvic organ prolapse surgery, which was published in Obstetrics & Gynecology.

In a preliminary search of 3,124 citations, Dr. Antosh and her colleagues, who are members of the Society of Gynecologic Surgeons Systematic Review Group responsible for the study, identified and accepted 74 articles representing 67 original studies. Ten of these were ancillary studies with different reported outcomes or follow-up times, and 44 were randomized control trials. They compared the pre- and postoperative effects of pelvic organ prolapse (POP) surgery on sexual function for changes in sexual activity and function across eight different prolapse surgery categories: mixed native tissue repairs, anterior repair, posterior repair, uterosacral ligament suspension, sacrospinous ligament suspension, transvaginal mesh, biologic grafts, and sacrocolpopexy. In only three categories – posterior repair, transvaginal mesh, and biological grafts – postoperative changes in sexual function scores were similar or remained unchanged. In all other categories, total sexual function scores improved. Dyspareunia was lower after surgery for all prolapse surgery types.

“Although sexual function improves in the majority of women, it is important to note that a small proportion of women can develop de novo (new onset) dyspareunia after surgery. The rate of this ranges from 0%-9% for prolapse surgeries. However, there is limited data on posterior repairs,” Dr. Antosh said in a later interview.* 
 

POP surgeries positively impact sexual function, dyspareunia outcomes

The researchers determined that there is “moderate to high quality data” supporting the influence of POP on sexual activity and function. They also observed a lower prevalence of dyspareunia postoperatively across all surgery types, compared with baseline. Additionally, no decrease in sexual function was reported across surgical categories; in fact, sexual activity and function improved or stayed the same after POP surgery in this review.

Across most POP surgery groups, Dr. Antosh and colleagues found that with the exception of the sacrospinous ligament suspension, transvaginal mesh, and sacrocolpopexy groups, the rate of postoperative sexual activity was modestly higher. Several studies attributed this finding to a lack of partner or partner-related issues. Another 16 studies (7.7%) cited pain as the primary factor for postoperative sexual inactivity.

Few studies included in the review “reported both preoperative and postoperative rates of sexual activity and dyspareunia, and no study reported patient-level changes in sexual activity or dyspareunia (except occasionally, for de novo activity or dyspareunia),” Dr. Antosh and associates clarified. As a result, they concluded that their findings are based primarily on qualitative comparisons of events reported pre- and postoperatively from different but overlapping sets of studies.

The finding that the prevalence of dyspareunia decreased following all types of POP surgery is consistent with previous reviews. Because the studies did not account for minimally important differences in sexual function scores, it is important to consider this when interpreting results of the review. Dr. Antosh and colleagues also noted that some studies did not define dyspareunia, and those that did frequently used measures that were not validated. They also were unable to identify the persistence of dyspareunia following surgery as this was not recorded in the literature.
 

Menopausal status and other considerations

Also worth noting, the mean age of women in the studies were postmenopausal, yet the “studies did not stratify sexual function outcomes based on premenopause compared with postmenopause status.”

The researchers advised that future studies using validated definitions of sexual activity, function, and dyspareunia, as well as reporting both their preoperative and postoperative measures would do much to improve the quality of research reported.

It is widely recognized that women with pelvic floor disorders experience a high rate of sexual dysfunction, so the need to achieve optimum outcomes that at least maintain if not improve sexual function postoperatively should be of key concern when planning POP surgery for patients, they cautioned. Previous studies have observed that women experiencing POP rated the need for improved sexual function second only to resolved bulge symptoms and improvement in overall function. The women also classified sexual dysfunction in the same category of adversity as having chronic pain or having to be admitted to an intensive care unit.
 

Study provides preoperative counseling help

David M. Jaspan, DO, chairman of the department of obstetrics and gynecology and Natasha Abdullah, MD, obstetrics and gynecology resident, both of Einstein Medical Center, Philadelphia, collaboratively commented on the study findings: “This review provides physicians with data to add to the preoperative counseling for patients undergoing pelvic organ prolapse surgery.”

In particular, they noted that, while the article “is a review of previous literature, Table 1 provides an opportunity for physicians to share with their patients the important answers to their concerns surrounding postoperative sexual activity, dyspareunia, and total changes in sexual function scores based on the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire 12 (PISQ-12).” 

Noting the clinical usefulness of the questionnaire, they added: “The PISQ-12 is a validated and reliable short form that evaluates sexual function in women with urinary incontinence and/or pelvic organ prolapse and predicts PISQ-31 scores. It was developed from the data of 99 of 182 women surveyed to create the long form (PISQ-31); 46 patients were recruited for further validation. Test-retest reliability was checked with a subset of 20 patients. All subsets regression analysis with R greater than 0.92 identified 12 items that predicted PISQ-31 scores. The PISQ-12 covers three domains of function: Behavioral/Emotive, Physical, and Partner-Related.”

Because ob.gyns. are trained to recognize the “multifactorial reasons (age, partner relationship, other health conditions etc.) that surround sexual activity,” Dr. Jaspan and Dr. Abdullah cautioned against prematurely concluding that the lower sexual activity score is directly related to POP surgery. 

“Because sexual function is such an important postsurgical outcome for patients, this article provides significant preoperative counseling data for patients on all POP repair options,” they observed. “No surgical option worsens sexual function. The article concludes that individually validated definitions of sexual activity, function, and dyspareunia in a measuring instrument would improve the quality of data for future studies.”

The study authors reported no relevant financial disclosures. Although no direct funding was provided by the Society of Gynecologic Surgeons, they did provide meeting space, oversight, stipends for expert and statistical support, and aid in disseminating findings. Dr. Abdullah and Dr. Jaspan had no relevant financial disclosures.
 

SOURCE: Antosh DD et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000004125.

*This article was updated on 10/28.

Sexual activity and function improve or at least are maintained following pelvic organ prolapse surgery, Danielle D. Antosh, MD, of the Houston Methodist Hospital and colleagues reported in a systematic review of prospective comparative studies on pelvic organ prolapse surgery, which was published in Obstetrics & Gynecology.

In a preliminary search of 3,124 citations, Dr. Antosh and her colleagues, who are members of the Society of Gynecologic Surgeons Systematic Review Group responsible for the study, identified and accepted 74 articles representing 67 original studies. Ten of these were ancillary studies with different reported outcomes or follow-up times, and 44 were randomized control trials. They compared the pre- and postoperative effects of pelvic organ prolapse (POP) surgery on sexual function for changes in sexual activity and function across eight different prolapse surgery categories: mixed native tissue repairs, anterior repair, posterior repair, uterosacral ligament suspension, sacrospinous ligament suspension, transvaginal mesh, biologic grafts, and sacrocolpopexy. In only three categories – posterior repair, transvaginal mesh, and biological grafts – postoperative changes in sexual function scores were similar or remained unchanged. In all other categories, total sexual function scores improved. Dyspareunia was lower after surgery for all prolapse surgery types.

“Although sexual function improves in the majority of women, it is important to note that a small proportion of women can develop de novo (new onset) dyspareunia after surgery. The rate of this ranges from 0%-9% for prolapse surgeries. However, there is limited data on posterior repairs,” Dr. Antosh said in a later interview.* 
 

POP surgeries positively impact sexual function, dyspareunia outcomes

The researchers determined that there is “moderate to high quality data” supporting the influence of POP on sexual activity and function. They also observed a lower prevalence of dyspareunia postoperatively across all surgery types, compared with baseline. Additionally, no decrease in sexual function was reported across surgical categories; in fact, sexual activity and function improved or stayed the same after POP surgery in this review.

Across most POP surgery groups, Dr. Antosh and colleagues found that with the exception of the sacrospinous ligament suspension, transvaginal mesh, and sacrocolpopexy groups, the rate of postoperative sexual activity was modestly higher. Several studies attributed this finding to a lack of partner or partner-related issues. Another 16 studies (7.7%) cited pain as the primary factor for postoperative sexual inactivity.

Few studies included in the review “reported both preoperative and postoperative rates of sexual activity and dyspareunia, and no study reported patient-level changes in sexual activity or dyspareunia (except occasionally, for de novo activity or dyspareunia),” Dr. Antosh and associates clarified. As a result, they concluded that their findings are based primarily on qualitative comparisons of events reported pre- and postoperatively from different but overlapping sets of studies.

The finding that the prevalence of dyspareunia decreased following all types of POP surgery is consistent with previous reviews. Because the studies did not account for minimally important differences in sexual function scores, it is important to consider this when interpreting results of the review. Dr. Antosh and colleagues also noted that some studies did not define dyspareunia, and those that did frequently used measures that were not validated. They also were unable to identify the persistence of dyspareunia following surgery as this was not recorded in the literature.
 

Menopausal status and other considerations

Also worth noting, the mean age of women in the studies were postmenopausal, yet the “studies did not stratify sexual function outcomes based on premenopause compared with postmenopause status.”

The researchers advised that future studies using validated definitions of sexual activity, function, and dyspareunia, as well as reporting both their preoperative and postoperative measures would do much to improve the quality of research reported.

It is widely recognized that women with pelvic floor disorders experience a high rate of sexual dysfunction, so the need to achieve optimum outcomes that at least maintain if not improve sexual function postoperatively should be of key concern when planning POP surgery for patients, they cautioned. Previous studies have observed that women experiencing POP rated the need for improved sexual function second only to resolved bulge symptoms and improvement in overall function. The women also classified sexual dysfunction in the same category of adversity as having chronic pain or having to be admitted to an intensive care unit.
 

Study provides preoperative counseling help

David M. Jaspan, DO, chairman of the department of obstetrics and gynecology and Natasha Abdullah, MD, obstetrics and gynecology resident, both of Einstein Medical Center, Philadelphia, collaboratively commented on the study findings: “This review provides physicians with data to add to the preoperative counseling for patients undergoing pelvic organ prolapse surgery.”

In particular, they noted that, while the article “is a review of previous literature, Table 1 provides an opportunity for physicians to share with their patients the important answers to their concerns surrounding postoperative sexual activity, dyspareunia, and total changes in sexual function scores based on the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire 12 (PISQ-12).” 

Noting the clinical usefulness of the questionnaire, they added: “The PISQ-12 is a validated and reliable short form that evaluates sexual function in women with urinary incontinence and/or pelvic organ prolapse and predicts PISQ-31 scores. It was developed from the data of 99 of 182 women surveyed to create the long form (PISQ-31); 46 patients were recruited for further validation. Test-retest reliability was checked with a subset of 20 patients. All subsets regression analysis with R greater than 0.92 identified 12 items that predicted PISQ-31 scores. The PISQ-12 covers three domains of function: Behavioral/Emotive, Physical, and Partner-Related.”

Because ob.gyns. are trained to recognize the “multifactorial reasons (age, partner relationship, other health conditions etc.) that surround sexual activity,” Dr. Jaspan and Dr. Abdullah cautioned against prematurely concluding that the lower sexual activity score is directly related to POP surgery. 

“Because sexual function is such an important postsurgical outcome for patients, this article provides significant preoperative counseling data for patients on all POP repair options,” they observed. “No surgical option worsens sexual function. The article concludes that individually validated definitions of sexual activity, function, and dyspareunia in a measuring instrument would improve the quality of data for future studies.”

The study authors reported no relevant financial disclosures. Although no direct funding was provided by the Society of Gynecologic Surgeons, they did provide meeting space, oversight, stipends for expert and statistical support, and aid in disseminating findings. Dr. Abdullah and Dr. Jaspan had no relevant financial disclosures.
 

SOURCE: Antosh DD et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000004125.

*This article was updated on 10/28.

Sexual activity and function improve or at least are maintained following pelvic organ prolapse surgery, Danielle D. Antosh, MD, of the Houston Methodist Hospital and colleagues reported in a systematic review of prospective comparative studies on pelvic organ prolapse surgery, which was published in Obstetrics & Gynecology.

In a preliminary search of 3,124 citations, Dr. Antosh and her colleagues, who are members of the Society of Gynecologic Surgeons Systematic Review Group responsible for the study, identified and accepted 74 articles representing 67 original studies. Ten of these were ancillary studies with different reported outcomes or follow-up times, and 44 were randomized control trials. They compared the pre- and postoperative effects of pelvic organ prolapse (POP) surgery on sexual function for changes in sexual activity and function across eight different prolapse surgery categories: mixed native tissue repairs, anterior repair, posterior repair, uterosacral ligament suspension, sacrospinous ligament suspension, transvaginal mesh, biologic grafts, and sacrocolpopexy. In only three categories – posterior repair, transvaginal mesh, and biological grafts – postoperative changes in sexual function scores were similar or remained unchanged. In all other categories, total sexual function scores improved. Dyspareunia was lower after surgery for all prolapse surgery types.

“Although sexual function improves in the majority of women, it is important to note that a small proportion of women can develop de novo (new onset) dyspareunia after surgery. The rate of this ranges from 0%-9% for prolapse surgeries. However, there is limited data on posterior repairs,” Dr. Antosh said in a later interview.* 
 

POP surgeries positively impact sexual function, dyspareunia outcomes

The researchers determined that there is “moderate to high quality data” supporting the influence of POP on sexual activity and function. They also observed a lower prevalence of dyspareunia postoperatively across all surgery types, compared with baseline. Additionally, no decrease in sexual function was reported across surgical categories; in fact, sexual activity and function improved or stayed the same after POP surgery in this review.

Across most POP surgery groups, Dr. Antosh and colleagues found that with the exception of the sacrospinous ligament suspension, transvaginal mesh, and sacrocolpopexy groups, the rate of postoperative sexual activity was modestly higher. Several studies attributed this finding to a lack of partner or partner-related issues. Another 16 studies (7.7%) cited pain as the primary factor for postoperative sexual inactivity.

Few studies included in the review “reported both preoperative and postoperative rates of sexual activity and dyspareunia, and no study reported patient-level changes in sexual activity or dyspareunia (except occasionally, for de novo activity or dyspareunia),” Dr. Antosh and associates clarified. As a result, they concluded that their findings are based primarily on qualitative comparisons of events reported pre- and postoperatively from different but overlapping sets of studies.

The finding that the prevalence of dyspareunia decreased following all types of POP surgery is consistent with previous reviews. Because the studies did not account for minimally important differences in sexual function scores, it is important to consider this when interpreting results of the review. Dr. Antosh and colleagues also noted that some studies did not define dyspareunia, and those that did frequently used measures that were not validated. They also were unable to identify the persistence of dyspareunia following surgery as this was not recorded in the literature.
 

Menopausal status and other considerations

Also worth noting, the mean age of women in the studies were postmenopausal, yet the “studies did not stratify sexual function outcomes based on premenopause compared with postmenopause status.”

The researchers advised that future studies using validated definitions of sexual activity, function, and dyspareunia, as well as reporting both their preoperative and postoperative measures would do much to improve the quality of research reported.

It is widely recognized that women with pelvic floor disorders experience a high rate of sexual dysfunction, so the need to achieve optimum outcomes that at least maintain if not improve sexual function postoperatively should be of key concern when planning POP surgery for patients, they cautioned. Previous studies have observed that women experiencing POP rated the need for improved sexual function second only to resolved bulge symptoms and improvement in overall function. The women also classified sexual dysfunction in the same category of adversity as having chronic pain or having to be admitted to an intensive care unit.
 

Study provides preoperative counseling help

David M. Jaspan, DO, chairman of the department of obstetrics and gynecology and Natasha Abdullah, MD, obstetrics and gynecology resident, both of Einstein Medical Center, Philadelphia, collaboratively commented on the study findings: “This review provides physicians with data to add to the preoperative counseling for patients undergoing pelvic organ prolapse surgery.”

In particular, they noted that, while the article “is a review of previous literature, Table 1 provides an opportunity for physicians to share with their patients the important answers to their concerns surrounding postoperative sexual activity, dyspareunia, and total changes in sexual function scores based on the Pelvic Organ Prolapse/Incontinence Sexual Questionnaire 12 (PISQ-12).” 

Noting the clinical usefulness of the questionnaire, they added: “The PISQ-12 is a validated and reliable short form that evaluates sexual function in women with urinary incontinence and/or pelvic organ prolapse and predicts PISQ-31 scores. It was developed from the data of 99 of 182 women surveyed to create the long form (PISQ-31); 46 patients were recruited for further validation. Test-retest reliability was checked with a subset of 20 patients. All subsets regression analysis with R greater than 0.92 identified 12 items that predicted PISQ-31 scores. The PISQ-12 covers three domains of function: Behavioral/Emotive, Physical, and Partner-Related.”

Because ob.gyns. are trained to recognize the “multifactorial reasons (age, partner relationship, other health conditions etc.) that surround sexual activity,” Dr. Jaspan and Dr. Abdullah cautioned against prematurely concluding that the lower sexual activity score is directly related to POP surgery. 

“Because sexual function is such an important postsurgical outcome for patients, this article provides significant preoperative counseling data for patients on all POP repair options,” they observed. “No surgical option worsens sexual function. The article concludes that individually validated definitions of sexual activity, function, and dyspareunia in a measuring instrument would improve the quality of data for future studies.”

The study authors reported no relevant financial disclosures. Although no direct funding was provided by the Society of Gynecologic Surgeons, they did provide meeting space, oversight, stipends for expert and statistical support, and aid in disseminating findings. Dr. Abdullah and Dr. Jaspan had no relevant financial disclosures.
 

SOURCE: Antosh DD et al. Obstet Gynecol. 2020. doi: 10.1097/AOG.0000000000004125.

*This article was updated on 10/28.

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.
 

Rates similar to other very sick patients

The study showed that while thromboembolic complications were high, they were not as high as seen in some of the earlier studies from Asia and Europe, Dr. Piazza noted.

“The numbers we were seeing in early reports were so high we couldn’t figure out how that was possible,” he said. “Our study suggests that, in a U.S. population receiving thromboprophylaxis, the rate of thromboembolic complications [are] more in line with what we would expect to see in other very sick patients who end up in ICU.”

He suggested that the very high rates of thromboembolic complications in the early studies from Asia may have been because of the lack of thromboprophylaxis, which is not routine in hospitalized patients there. “Some of the earlier studies also used routine ultrasound and so picked up asymptomatic thrombotic events, which was not the case in our study. So our results are more representative of the U.S. population.”

Dr. Piazza attributed the high rate of thromboembolic complications being reported with COVID-19 to the sheer number of very sick patients being admitted to the hospital.

“We are accustomed to seeing a rare case of thrombosis despite prophylaxis in hospitalized patients, but we are seeing more in COVID patients. This is probably just because we have more critically ill patients,” he said.

“We are seeing an incredible influx of patients to the ICU that we have never experienced before, so the increase in thromboembolic complications is more obvious. In prior years we probably haven’t had enough critically ill patients at any one time to raise the flag about thromboprophylaxis,” he commented.

The study also found a high rate of cardiovascular complications. They are seeing an increase in the risk of MI, which is to be expected in such sick patients, but they also see quite a bit of new atrial fibrillation, myocarditis, and heart failure in patients who don’t always have underlying cardiovascular disease, he said.

“So this virus does appear to have a predilection to causing cardiovascular complications, but this is probably because it is making patients so sick,” Dr. Piazza said. “If flu was this virulent and resulted in such high rates of acute respiratory distress syndrome (ARDS), we would probably see similar cardiovascular complication rates.”

For the current report, the researchers analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through the Mass General Brigham integrated health network. Of these, 170 had been admitted to the ICU, 229 had been hospitalized but not treated in ICU, and 715 were outpatients. In terms of ethnicity, 22% were Hispanic/Latino and 44% were non-White. 

Cardiovascular risk factors were common, with 36% of patients having hypertension, 29% hyperlipidemia, and 18% diabetes. Prophylactic anticoagulation was prescribed in 89% of patients with COVID-19 in the intensive care cohort and 85% of those in the hospitalized non–intensive care setting.

Results showed that major arterial or venous thromboembolism (VTE) occurred in 35% of the intensive care cohort, 2.6% of those hospitalized but not treated in ICU, and 0% of outpatients.

Major adverse cardiovascular events occurred in 46% of the intensive care cohort, 6.1% of those hospitalized but non-ICU, and 0% of outpatients.

Symptomatic VTE occurred in 27% of those admitted to ICU, 2.2% of those hospitalized but non-ICU, and 0% of outpatients.

“We found that outpatients had a very low rate of thromboembolic complications, with the vast majority of the risk being in hospitalized patients, especially those in ICU,” Dr. Piazza said.

“These results suggest that we don’t need routine thromboprophylaxis for all outpatients with COVID-19, but there will probably be some patients who need it – those with risk factors for thromboembolism.”

Catheter- and device-associated deep vein thrombosis accounted for 76.9% of the DVTs observed in the study.

“Our finding of high frequency of catheter-associated DVT supports the judicious use of central venous catheters that have been widely implemented, especially in the ICU, to minimize recurrent health care team exposure and facilitate monitoring,” the researchers wrote.
 

ARDS biggest risk factor

Of all the markers of disease severity, the presence of ARDS had the strongest association with adverse outcomes, including major arterial or VTE, major adverse cardiovascular events, symptomatic VTE, and death.

“The severe inflammatory state associated with ARDS and other complications of COVID-19 and its resultant hypercoagulability may explain, at least in part, the high frequency of thromboembolic events. Improved risk stratification, utilizing biochemical markers of inflammation and activated coagulation as well as clinical indicators, such as ARDS, may play an important role in the early identification of patients with an increased likelihood of developing symptomatic VTE or arterial thrombosis,” the researchers wrote. “They may benefit from full- or intermediate-intensity antithrombotic therapy rather than prophylactic anticoagulation.”

They point out that this study provides a cross-sectional view of the cardiovascular complications of COVID-19 in a large health care network, consisting of two academic medical centers serving the greater Boston area, several community hospitals, and numerous outpatient care sites.

“The study incorporates a wide scope of clinically meaningful cardiovascular endpoints and utilizes a rigorous process of event adjudication. Although data on patients with COVID-19 in the ICU have been the subject of most reports, our study provides insights into the broad spectrum of all hospitalized and outpatient populations,” the authors noted.

“The high frequency of arterial or venous thromboembolism in hospitalized patients despite routine thromboprophylaxis suggests the need for improved risk stratification and enhanced preventive efforts,” they concluded.

The study is continuing, and the researchers expect to have data on 10,000 patients by the end of winter.
 

Wait for randomized trials

In an accompanying editorial, Robert McBane, MD, Mayo Clinic, Rochester, Minn., said that these data provide important real-world arterial and venous thrombotic event rates across a large, integrated health care network and an experienced roster of clinician-scientists devoted to thrombosis research.

Noting that whether to interpret these results as alarming or reassuring requires a comparison of expected thromboembolic event rates separate from the pandemic, he pointed out that, while the overall VTE rate among ICU patients was high, the vast majority of these events were attributable to central venous lines, and apart from these, the event rates do not appear inflated relative to prior published incidence rates from the pre–COVID-19 era.

“It is therefore important to resist the urge to overprevent or overtreat patients and expose them to the serious risks of major bleeding,” Dr. McBane wrote, adding that “the systematized approach to delivery of guideline-driven VTE prophylaxis across this large, integrated health network likely contributed to the relatively low rates of serious thrombotic outcomes reported.”

He further noted that, as the majority of VTE events were related to central venous lines in ICU patients, “this underscores the importance of a bundled care approach to central venous line management with daily assessment of the continued necessity of central access.

“A number of important clinical trials aimed at optimizing thromboprophylaxis during hospitalization, following hospital dismissal, and in ambulatory settings are underway. Until available, the lessons of thoughtful anticoagulant prophylaxis and treatment guidelines harvested from years of clinical research appear to apply,” he concluded.

This study was funded, in part, by a research grant from Janssen Pharmaceuticals. Dr. Piazza has received research grant support from EKOS Corporation, Bayer, Bristol-Myers Squibb/Pfizer, Portola Pharmaceuticals, and Janssen Pharmaceuticals; and has received consulting fees from Amgen, Pfizer, Boston Scientific, Agile, and Thrombolex. Dr. McBane reported no relevant disclosures.

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

Major thromboembolic complications and adverse cardiovascular events occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high use of thromboprophylaxis, in a new large observational U.S. study.

“Despite very high rate of antithrombotic prophylaxis there were a high rate of thromboembolic events suggesting that we are probably not providing enough thromboprophylaxis,” lead author Gregory Piazza, MD, Brigham and Women’s Hospital, Boston, said in an interview. 

“Standard prophylaxis as recommended in the guidelines is a low dose of low-molecular-weight heparin once daily, but these results suggest [patients] probably need higher doses,” he added.

However, Dr. Piazza cautioned that this is an observational study and randomized trials are needed to make changes in treatment strategies. Several such trials are currently underway.

The current study was published online ahead of print in the Nov. 3 issue of the Journal of the American College of Cardiology.