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Blood pressure changes and persistent hypertension elevate dementia risk
BALTIMORE – The impact of blood pressure on the risk of dementia in late life follows a U-shaped curve in which elevated mid-life and late-life blood pressure, as well as late-life decline in blood pressure, all independently raise the risk of dementia, according to findings from a longitudinal study of the Framingham Offspring cohort of the Framingham Heart Study.
The findings highlight the benefits of establishing and maintaining lower blood pressure in midlife in preventing or lowering the risk of dementia, Emer McGrath, MD, said at the annual meeting of the American Neurological Association.
The researchers explored the issue using data from the Framingham Offspring cohort of the Framingham Heart Study. The cohort comprises 5,124 children, and spouses of children, of the original Framingham cohort. They have been examined clinically at regular intervals since 1971. The present study focused on 1,440 individuals who had five consecutive examinations during a 15-year period anytime between 1983 and 2001 and who had not been diagnosed with dementia at the time of the final blood pressure determination.
The 1,440 participants had a mean age of 69 years at their fifth examination. Just over half were female, 20% had been diagnosed with cardiovascular disease, and slightly less than 20% had been diagnosed with diabetes. Half were using antihypertensive medications.
During a mean 8-year follow-up period, 107 individuals developed dementia. Dementia was independently associated with midlife hypertension (140/90 mm Hg or higher), with a stronger association for systolic hypertension (hazard ratio, 1.57; 95% confidence interval, 1.05-2.35). Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96; 95% CI, 1.25-3.09), was another independent risk factor for dementia.
Among individuals who did not have hypertension at midlife, a decline in systolic blood pressure to less than 100/70 mm Hg in the ensuing years increased the risk of dementia (HR, 1.63; 95% CI, 1.08-2.46).
According to the researchers, the findings support the hypothesis of the U-shaped relationship between blood pressure and dementia. “Our data also highlight the potential sustained cognitive benefits of lower midlife blood pressure,” Dr. McGrath said.
The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke. Dr. McGrath had no disclosures.
BALTIMORE – The impact of blood pressure on the risk of dementia in late life follows a U-shaped curve in which elevated mid-life and late-life blood pressure, as well as late-life decline in blood pressure, all independently raise the risk of dementia, according to findings from a longitudinal study of the Framingham Offspring cohort of the Framingham Heart Study.
The findings highlight the benefits of establishing and maintaining lower blood pressure in midlife in preventing or lowering the risk of dementia, Emer McGrath, MD, said at the annual meeting of the American Neurological Association.
The researchers explored the issue using data from the Framingham Offspring cohort of the Framingham Heart Study. The cohort comprises 5,124 children, and spouses of children, of the original Framingham cohort. They have been examined clinically at regular intervals since 1971. The present study focused on 1,440 individuals who had five consecutive examinations during a 15-year period anytime between 1983 and 2001 and who had not been diagnosed with dementia at the time of the final blood pressure determination.
The 1,440 participants had a mean age of 69 years at their fifth examination. Just over half were female, 20% had been diagnosed with cardiovascular disease, and slightly less than 20% had been diagnosed with diabetes. Half were using antihypertensive medications.
During a mean 8-year follow-up period, 107 individuals developed dementia. Dementia was independently associated with midlife hypertension (140/90 mm Hg or higher), with a stronger association for systolic hypertension (hazard ratio, 1.57; 95% confidence interval, 1.05-2.35). Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96; 95% CI, 1.25-3.09), was another independent risk factor for dementia.
Among individuals who did not have hypertension at midlife, a decline in systolic blood pressure to less than 100/70 mm Hg in the ensuing years increased the risk of dementia (HR, 1.63; 95% CI, 1.08-2.46).
According to the researchers, the findings support the hypothesis of the U-shaped relationship between blood pressure and dementia. “Our data also highlight the potential sustained cognitive benefits of lower midlife blood pressure,” Dr. McGrath said.
The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke. Dr. McGrath had no disclosures.
BALTIMORE – The impact of blood pressure on the risk of dementia in late life follows a U-shaped curve in which elevated mid-life and late-life blood pressure, as well as late-life decline in blood pressure, all independently raise the risk of dementia, according to findings from a longitudinal study of the Framingham Offspring cohort of the Framingham Heart Study.
The findings highlight the benefits of establishing and maintaining lower blood pressure in midlife in preventing or lowering the risk of dementia, Emer McGrath, MD, said at the annual meeting of the American Neurological Association.
The researchers explored the issue using data from the Framingham Offspring cohort of the Framingham Heart Study. The cohort comprises 5,124 children, and spouses of children, of the original Framingham cohort. They have been examined clinically at regular intervals since 1971. The present study focused on 1,440 individuals who had five consecutive examinations during a 15-year period anytime between 1983 and 2001 and who had not been diagnosed with dementia at the time of the final blood pressure determination.
The 1,440 participants had a mean age of 69 years at their fifth examination. Just over half were female, 20% had been diagnosed with cardiovascular disease, and slightly less than 20% had been diagnosed with diabetes. Half were using antihypertensive medications.
During a mean 8-year follow-up period, 107 individuals developed dementia. Dementia was independently associated with midlife hypertension (140/90 mm Hg or higher), with a stronger association for systolic hypertension (hazard ratio, 1.57; 95% confidence interval, 1.05-2.35). Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96; 95% CI, 1.25-3.09), was another independent risk factor for dementia.
Among individuals who did not have hypertension at midlife, a decline in systolic blood pressure to less than 100/70 mm Hg in the ensuing years increased the risk of dementia (HR, 1.63; 95% CI, 1.08-2.46).
According to the researchers, the findings support the hypothesis of the U-shaped relationship between blood pressure and dementia. “Our data also highlight the potential sustained cognitive benefits of lower midlife blood pressure,” Dr. McGrath said.
The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke. Dr. McGrath had no disclosures.
AT ANA 2016
Key clinical point:
Major finding: Persistence of hypertension into late life, particularly systolic hypertension (HR, 1.96; 95% CI, 1.25-3.09), was another independent risk factor for dementia.
Data source: Offspring cohort of the Framingham Heart Study.
Disclosures: The study was funded by the Framingham Heart Study, the National Institute on Aging, and the National Institute for Neurological Diseases and Stroke. Dr. McGrath had no disclosures.
Pediatric Dermatology Consult - November 2016
BY JUSLEEN AHLUWALIA, MD, AND LAWRENCE F. EICHENFIELD, MD
The presence of an initial tense bulla on the vertex scalp suggests a diagnosis of aplasia cutis congenita. Given the palpable quality of the lesion, magnetic resonance imaging and angiogram (MRI/MRA) of the head with gadolinium enhancement was performed, revealing a 1.5-cm mass underlying the scalp defect, without calvarial deformations. The mass was excised with advancement flap closure. Histologic evaluation of the excised specimen revealed polypoid tissue with unremarkable epidermis and hypocellular dermis with loose connective tissue, lacking adnexal structures. Neural and glial tissue were not identified.
Aplasia cutis congenita (ACC) is a term used to describe congenital absence or defects of the skin.
According to its developmental stage in utero, scalp ACC may present at birth as a deep ulceration, superficial erosion, or a healed, alopecic scar.2 Rarely, some defects may have a cystic or bullous component that may transform into a smooth, atrophic scar with an overlying translucent membrane. This clinical subtype has been described as the “bullous” or “membranous” variant, depending on the stage of bulla maturation.4-8 Our patient displays features demonstrative of the membranous variant. Most commonly, membranous aplasia cutis is an isolated defect and, if there is no palpable component, does not require imaging.2 These usually heal spontaneously, including those with small bone defects. Larger lesions of AC (greater than 3 cm) with large bone defects require urgent imaging.2 Papules or nodules around aplasia cutis may be associated with more significant neural tube anomalies, including congenital ectopic meningeal tissue, also termed atretic or rudimentary meningoceles.7 These may be associated with defects of the skull or tracts with intracranial connections.7 Hair collars, a collarette of coarser hair surrounding bullous or membranous variant of AC, may be indicative of defective neural tube closure.4-8 MRI of the head is recommended in cases of bullous or membranous scalp ACC with a palpable nodule to evaluate for intracranial connection and ectopic neural tissue, as performed in our patient.2 Because imaging of our patient was concerning for ectopic neural tissue within the defect, excision was recommended with histologic examination for neural or glial tissue.
Small scalp ACC lesions can heal by secondary intention with supportive wound care, whereas larger defects may require bone or skin grafting.2 Cautious monitoring of the defect will help prevent the serious sequelae rarely associated with large scalp ACC, including hemorrhage, infection, sagittal sinus thrombosis, and hydrocephalus.2 Generally, most defects heal well within months and the resultant scars become relatively unnoticeable. Those that are apparent can be surgically reconstructed.2
Although most infants with ACC are otherwise healthy, several anomalies have been noted to be associated with the presence of ACC, and thus a multisystem evaluation is recommended during the initial visit. These anomalies include limb abnormalities, epidermal nevi, epidermolysis bullosa, chromosomal abnormalities, such as trisomy 13, ectodermal dysplasias, or other malformation syndromes, including Adams-Oliver syndrome.2,8 Around 30 years ago, Frieden et al. stratified ACC into nine different groups based on the location and presence of these associations.9
Differentiation of scalp ACC from other conditions may be necessary. HSV usually appears as grouped vesicles that can evolve to appear punched out.2 Iatrogenic trauma can produce erosions at the site of scalp electrode placement or forceps use, but is less likely to occur over the vertex scalp.2 Congenital triangular alopecia usually presents as an alopecic, lancet-shaped pattern on the frontal temporal scalp without evidence of scarring. Nevus sebaceous characteristically presents as a solitary yellow-orange, mammilated plaque, but may mimic an erosion given its slightly pink appearance in the neonate.2
References
1. Developmental abnormalities, in “Neonatal and infant dermatology,” 3rd ed. (Philadelphia: Saunders, 2015).
2. Dermatol Ther. 2013 Nov-Dec;26(6):439-44.
3. Br J Plast Surg. 2002 Sep;55(6):530-2.
4. J Am Acad Dermatol. 2003 May;48(5 Suppl):S95-8.
5. J Ultrasound Med. 2009 Oct;28(10):1393-6.
6. Arch Dermatol. 1995 Dec;131(12):1427-31.
7. Pediatr Dermatol. 2015 Mar-Apr;32(2):161-70.
8. Indian J Dermatol. 2011 May;56(3):337-8.
9. J Am Acad Dermatol. 1986 Apr;14(4):646-60.
Dr. Ahluwalia is with the division of pediatric and adolescent dermatology, Rady Children’s Hospital, San Diego. Dr. Eichenfield is in the departments of dermatology and pediatrics, University of California, San Diego.
BY JUSLEEN AHLUWALIA, MD, AND LAWRENCE F. EICHENFIELD, MD
The presence of an initial tense bulla on the vertex scalp suggests a diagnosis of aplasia cutis congenita. Given the palpable quality of the lesion, magnetic resonance imaging and angiogram (MRI/MRA) of the head with gadolinium enhancement was performed, revealing a 1.5-cm mass underlying the scalp defect, without calvarial deformations. The mass was excised with advancement flap closure. Histologic evaluation of the excised specimen revealed polypoid tissue with unremarkable epidermis and hypocellular dermis with loose connective tissue, lacking adnexal structures. Neural and glial tissue were not identified.
Aplasia cutis congenita (ACC) is a term used to describe congenital absence or defects of the skin.
According to its developmental stage in utero, scalp ACC may present at birth as a deep ulceration, superficial erosion, or a healed, alopecic scar.2 Rarely, some defects may have a cystic or bullous component that may transform into a smooth, atrophic scar with an overlying translucent membrane. This clinical subtype has been described as the “bullous” or “membranous” variant, depending on the stage of bulla maturation.4-8 Our patient displays features demonstrative of the membranous variant. Most commonly, membranous aplasia cutis is an isolated defect and, if there is no palpable component, does not require imaging.2 These usually heal spontaneously, including those with small bone defects. Larger lesions of AC (greater than 3 cm) with large bone defects require urgent imaging.2 Papules or nodules around aplasia cutis may be associated with more significant neural tube anomalies, including congenital ectopic meningeal tissue, also termed atretic or rudimentary meningoceles.7 These may be associated with defects of the skull or tracts with intracranial connections.7 Hair collars, a collarette of coarser hair surrounding bullous or membranous variant of AC, may be indicative of defective neural tube closure.4-8 MRI of the head is recommended in cases of bullous or membranous scalp ACC with a palpable nodule to evaluate for intracranial connection and ectopic neural tissue, as performed in our patient.2 Because imaging of our patient was concerning for ectopic neural tissue within the defect, excision was recommended with histologic examination for neural or glial tissue.
Small scalp ACC lesions can heal by secondary intention with supportive wound care, whereas larger defects may require bone or skin grafting.2 Cautious monitoring of the defect will help prevent the serious sequelae rarely associated with large scalp ACC, including hemorrhage, infection, sagittal sinus thrombosis, and hydrocephalus.2 Generally, most defects heal well within months and the resultant scars become relatively unnoticeable. Those that are apparent can be surgically reconstructed.2
Although most infants with ACC are otherwise healthy, several anomalies have been noted to be associated with the presence of ACC, and thus a multisystem evaluation is recommended during the initial visit. These anomalies include limb abnormalities, epidermal nevi, epidermolysis bullosa, chromosomal abnormalities, such as trisomy 13, ectodermal dysplasias, or other malformation syndromes, including Adams-Oliver syndrome.2,8 Around 30 years ago, Frieden et al. stratified ACC into nine different groups based on the location and presence of these associations.9
Differentiation of scalp ACC from other conditions may be necessary. HSV usually appears as grouped vesicles that can evolve to appear punched out.2 Iatrogenic trauma can produce erosions at the site of scalp electrode placement or forceps use, but is less likely to occur over the vertex scalp.2 Congenital triangular alopecia usually presents as an alopecic, lancet-shaped pattern on the frontal temporal scalp without evidence of scarring. Nevus sebaceous characteristically presents as a solitary yellow-orange, mammilated plaque, but may mimic an erosion given its slightly pink appearance in the neonate.2
References
1. Developmental abnormalities, in “Neonatal and infant dermatology,” 3rd ed. (Philadelphia: Saunders, 2015).
2. Dermatol Ther. 2013 Nov-Dec;26(6):439-44.
3. Br J Plast Surg. 2002 Sep;55(6):530-2.
4. J Am Acad Dermatol. 2003 May;48(5 Suppl):S95-8.
5. J Ultrasound Med. 2009 Oct;28(10):1393-6.
6. Arch Dermatol. 1995 Dec;131(12):1427-31.
7. Pediatr Dermatol. 2015 Mar-Apr;32(2):161-70.
8. Indian J Dermatol. 2011 May;56(3):337-8.
9. J Am Acad Dermatol. 1986 Apr;14(4):646-60.
Dr. Ahluwalia is with the division of pediatric and adolescent dermatology, Rady Children’s Hospital, San Diego. Dr. Eichenfield is in the departments of dermatology and pediatrics, University of California, San Diego.
BY JUSLEEN AHLUWALIA, MD, AND LAWRENCE F. EICHENFIELD, MD
The presence of an initial tense bulla on the vertex scalp suggests a diagnosis of aplasia cutis congenita. Given the palpable quality of the lesion, magnetic resonance imaging and angiogram (MRI/MRA) of the head with gadolinium enhancement was performed, revealing a 1.5-cm mass underlying the scalp defect, without calvarial deformations. The mass was excised with advancement flap closure. Histologic evaluation of the excised specimen revealed polypoid tissue with unremarkable epidermis and hypocellular dermis with loose connective tissue, lacking adnexal structures. Neural and glial tissue were not identified.
Aplasia cutis congenita (ACC) is a term used to describe congenital absence or defects of the skin.
According to its developmental stage in utero, scalp ACC may present at birth as a deep ulceration, superficial erosion, or a healed, alopecic scar.2 Rarely, some defects may have a cystic or bullous component that may transform into a smooth, atrophic scar with an overlying translucent membrane. This clinical subtype has been described as the “bullous” or “membranous” variant, depending on the stage of bulla maturation.4-8 Our patient displays features demonstrative of the membranous variant. Most commonly, membranous aplasia cutis is an isolated defect and, if there is no palpable component, does not require imaging.2 These usually heal spontaneously, including those with small bone defects. Larger lesions of AC (greater than 3 cm) with large bone defects require urgent imaging.2 Papules or nodules around aplasia cutis may be associated with more significant neural tube anomalies, including congenital ectopic meningeal tissue, also termed atretic or rudimentary meningoceles.7 These may be associated with defects of the skull or tracts with intracranial connections.7 Hair collars, a collarette of coarser hair surrounding bullous or membranous variant of AC, may be indicative of defective neural tube closure.4-8 MRI of the head is recommended in cases of bullous or membranous scalp ACC with a palpable nodule to evaluate for intracranial connection and ectopic neural tissue, as performed in our patient.2 Because imaging of our patient was concerning for ectopic neural tissue within the defect, excision was recommended with histologic examination for neural or glial tissue.
Small scalp ACC lesions can heal by secondary intention with supportive wound care, whereas larger defects may require bone or skin grafting.2 Cautious monitoring of the defect will help prevent the serious sequelae rarely associated with large scalp ACC, including hemorrhage, infection, sagittal sinus thrombosis, and hydrocephalus.2 Generally, most defects heal well within months and the resultant scars become relatively unnoticeable. Those that are apparent can be surgically reconstructed.2
Although most infants with ACC are otherwise healthy, several anomalies have been noted to be associated with the presence of ACC, and thus a multisystem evaluation is recommended during the initial visit. These anomalies include limb abnormalities, epidermal nevi, epidermolysis bullosa, chromosomal abnormalities, such as trisomy 13, ectodermal dysplasias, or other malformation syndromes, including Adams-Oliver syndrome.2,8 Around 30 years ago, Frieden et al. stratified ACC into nine different groups based on the location and presence of these associations.9
Differentiation of scalp ACC from other conditions may be necessary. HSV usually appears as grouped vesicles that can evolve to appear punched out.2 Iatrogenic trauma can produce erosions at the site of scalp electrode placement or forceps use, but is less likely to occur over the vertex scalp.2 Congenital triangular alopecia usually presents as an alopecic, lancet-shaped pattern on the frontal temporal scalp without evidence of scarring. Nevus sebaceous characteristically presents as a solitary yellow-orange, mammilated plaque, but may mimic an erosion given its slightly pink appearance in the neonate.2
References
1. Developmental abnormalities, in “Neonatal and infant dermatology,” 3rd ed. (Philadelphia: Saunders, 2015).
2. Dermatol Ther. 2013 Nov-Dec;26(6):439-44.
3. Br J Plast Surg. 2002 Sep;55(6):530-2.
4. J Am Acad Dermatol. 2003 May;48(5 Suppl):S95-8.
5. J Ultrasound Med. 2009 Oct;28(10):1393-6.
6. Arch Dermatol. 1995 Dec;131(12):1427-31.
7. Pediatr Dermatol. 2015 Mar-Apr;32(2):161-70.
8. Indian J Dermatol. 2011 May;56(3):337-8.
9. J Am Acad Dermatol. 1986 Apr;14(4):646-60.
Dr. Ahluwalia is with the division of pediatric and adolescent dermatology, Rady Children’s Hospital, San Diego. Dr. Eichenfield is in the departments of dermatology and pediatrics, University of California, San Diego.
A 9-month-old previously healthy female, born at term, presents to the dermatology clinic for evaluation of a bluish nodule on the posterior vertex of the scalp (Figure 1). Initially at birth, the area was described as a hairless, tense blister that flattened over several weeks. The hairless nodule has persisted without symptoms. The family denies any history of trauma, including the use of forceps or scalp electrodes during labor. Family history was noncontributory. Review of systems was otherwise negative.
On examination, the patient is a well-developed, active female with a 2-cm, bluish nodule with an overlying atrophic, glistening membrane on the posterior parietal scalp, lateral to the midline. The lesion is surrounded by a ring of subtly coarse, terminal hair. There is no evidence of bleeding or ulceration, and no scalp defects were palpable. The lesion was unchanged with crying. The remainder of the physical examination was normal.
The 50-year quest for better pregnancy data
Editor’s note: As Ob.Gyn. News celebrates its 50th anniversary, we wanted to know how far the medical community has come in identifying and mitigating drug risks during pregnancy and in the postpartum period. In this article, our four expert columnists share their experiences trying to find and interpret critical pregnancy data, as well as how they weigh the potential risks and benefits for their patients.
The search for information
The biggest advance in the past 50 years is the availability of information, even though limited, relating to the effects of drugs in pregnancy and lactation. In the first few years of this period, it was a daunting task to obtain this information. I can recall spending hours in the hospital’s medical library going through huge volumes of Index Medicus to obtain references that the library could order for me. The appearance of Thomas H. Shepard’s first edition (Catalog of Teratogenic Agents) in 1973 was a step forward and in 1977, O.P. Heinonen and colleagues’ book (Birth Defects and Drugs in Pregnancy) was helpful.
Although all of the above sources were helpful, any book in an evolving field will not have the newest information. Two important services, TERIS and Reprotox, were started to allow clinicians to contact them for up-to-date data. Nevertheless, the biggest change was the availability of current information from the U.S. National Library of Medicine via Toxnet, PubMed, and LactMed, relating to the effects of drugs in pregnancy and lactation.
My method is to ask three questions. First, are there other drugs with a similar mechanism of action that have some human data? In most cases, the answer to this question is no, but even when there are data, it is typically very limited. Second, does the drug cross the human placenta? The answer is typically based on the molecular weight. Any drug with a molecular weight less than 1,000 daltons probably crosses. In the second half of pregnancy, especially in the third trimester, almost every drug crosses. Third, do the animal pregnancy data predict embryo/fetal risk? It was thought that it could if the dose causing harm was less than or equal to 10 times the human dose based on BSA or AUC and there were no signs of maternal toxicity. However, using data from my 10th edition, I and eight coauthors, all of whom are knowledgeable on the effects of drugs in pregnancy, found that the animal data for 311 drugs raised the possibility of human embryo-fetal harm that current data confirmed in only 75 (24%) of the drugs (Am J Obstet Gynecol. 2015 Dec;213[6]:810-5).
The system needs to be fixed. One method is to give the Food and Drug Administration the authority to require manufacturers of drugs likely to be used in pregnancy to gather and publish data on their use in pregnancy. That sounds reasonable, but will it ever occur?
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.
Learning the lessons of the past
During the last 50 years, two of the most potent known human teratogens, thalidomide and isotretinoin, became available for prescription in the United States. Thanks to the efforts of Frances Kelsey, MD, PhD, at the FDA, the initial application for approval of thalidomide in the United States was denied in the early 1960s. Subsequently, based on evidence from other countries where thalidomide was marketed that the drug can cause a pattern of serious birth defects, a very strict pregnancy prevention program was implemented when the drug was finally approved in the United States in 2006.
Over the last 50 years, we have also seen an important evolution in our ability to conduct pregnancy exposure safety studies. Though we still have limited ability to conduct clinical trials in pregnant women, the need for good quality observational studies has become more widely accepted. The Centers for Disease Control and Prevention’s National Birth Defects Prevention Study (now in its most recent iteration known as BD STEPS) has been one very important source of data on the safety of a wide variety of medications. Using a case-control study design, women who have delivered infants with specific birth defects and comparison women who have delivered non-malformed infants are interviewed about their exposures in pregnancy. These data have been extremely helpful in generating new hypotheses, confirming or refuting findings from other studies, and in testing hypotheses regarding the safety of medications widely used in women of reproductive age. These analyses, for example, have contributed to the large body of literature now available on the safety of antidepressant medications in pregnancy.
At the same time, in the last 30 years, we have seen a tremendous increase in the number of pregnancy registries required or recommended upon approval of a new drug in the United States. These registry studies, while challenging to complete in a timely manner, have steadily improved in terms of rigor, and several disease-based pregnancy exposure studies have been implemented, which have allowed us to better understand the comparative risks or safety of anticonvulsants and antiretroviral drugs, to name a few.
It is important to note that with all these advances in the last 50 years, we still have a huge gap in knowledge about medication safety in pregnancy and lactation. Recent reviews suggest that more than 80% of drugs currently marketed have insufficient or no data available. If we include over-the-counter medications, the knowledge gap grows larger. With the 2014 approval of the long-awaited Pregnancy and Lactation Labeling Rule, clinicians are now beginning to experience the elimination of the old A-B-C-D-X category system for pregnancy safety. In its place, data-driven product labels are required. These are expected to provide the clinician with a clear summary of the relevant studies for a given medication, and to place these in the context of the background risks for the underlying maternal disease being treated, as well as the population risks. However, it is painfully clear that we have a long way to go to generate the needed, high-quality data, to populate those labels.
Dr. Chambers is a professor of pediatrics and director of clinical research at Rady Children’s Hospital, San Diego, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, a past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She has no relevant financial disclosures.
Moving toward personalized medicine
Nowhere is a lack of actionable data more pronounced than in the impact of mental health drugs in pregnancy.
As Dr. Briggs and Dr. Chambers have outlined, the quality of data regarding the reproductive safety of medications across the therapeutic spectrum has historically been fair at best. The methodology and the rigor has been sparse and to a large extent, in psychiatry, we were only able to look for signals of concern. Prior to the late 1980s and early 1990s, there was little to guide clinicians on the safety of even very commonly used psychiatric medications during pregnancy. The health implications for women of reproductive age are extraordinary and yet that urgency was not matched by the level of investigation until more recently.
In psychiatry, we have rapidly improving data informing women about the risk for major congenital malformations. The clinical dilemma of weighing the necessity to stay on a medication to prevent relapse of a psychiatric disorder with the potential risk of malformation in the fetus is a wrenching one for the mother-to-be. Only good information can help patients, together with their physician, make collaborative decisions that make sense for them. Given the same information and the same severity of illness, women will make different decisions, and that’s a good thing. The calculus couples use to make these private decisions is unique to those involved. But they are able to move through the process because they have a platform of high-quality information.
So where do we go in the future? We need to get beyond the question of risk of major malformations and move toward understanding the long-term neurodevelopmental implications of prenatal exposures – whether such exposures confer risk or are even potentially salutary. One needs only look at the vast body of literature regarding fetal exposure to selective serotonin reuptake inhibitors (SSRIs) to observe the realization of this trend. When it comes to SSRIs, a fairly clear picture has emerged that they pose little absolute risk in terms of congenital malformations. What is missing is how SSRIs impact a child’s learning and development at age 3, 5, and 10. There have been a few studies in this area, but not a single, large prospective study that accurately quantifies both exposure to SSRIs and maternal psychiatric illness during pregnancy.
I expect that the future will also bring a greater understanding of the impact of untreated mental illness on the risk for obstetrical, neonatal, and longer-term neurodevelopmental outcomes. Most of the safety concerns have centered around the effect of fetal exposure to medications, but we also need to better understand how untreated psychiatric disorders impact the spectrum of relevant outcomes.
Getting back to the dilemma faced by pregnant women who really need medication to sustain emotional well-being, there simply is no perfect answer. No decision is perfect or risk free. What we can hope is that we’ll have personalized approaches that take into account the best available data and the patient’s individual situation and wishes. We’ve already come a long way toward meeting that goal, and I’m optimistic about where we’re going.
Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.
Perception of risk
Every year, numerous new medicines are approved by the FDA without data in pregnancy. Animal studies may show a problem that doesn’t appear in humans, or as was the case with thalidomide, the problem may not be apparent in animals and show up later in humans. There are many drugs that are safe in pregnancy, but women are understandably afraid of the potential impact on fetal development.
While my colleagues have presented the advances we’ve made in understanding the actual risks of medications during the prenatal period, it’s also important to focus on the perception of risk and to recognize that the reality and the perception can be vastly different.
At the same time, we began to ask women, using a visual analog scale, what would be their trend toward continuing or terminating pregnancy? Over several studies, we found that the likelihood of termination was high, and certainly much higher than was supported by the evidence of actual harm to the fetus. Specifically, if a woman received information about the safety of the drug and she still gave more than a 50% probability of terminating the pregnancy when surveyed, there was a good chance that she would terminate the pregnancy.
When you consider that most of the drugs that women are commonly prescribed in pregnancy – from most painkillers to antidepressants – are not known to cause malformations in pregnancy, you begin to see how problematic an inflated perception of risk can become.
But we see different trends in women with serious and chronic health problems, such as lupus or epilepsy. These women are typically under the care of a subspecialist, who in many cases has developed a significant knowledge base and comfort level around prescribing the drugs in this area and is able to communicate more clearly to patients both the risks to the fetus and the consequences of failure to treat their condition.
So clearly, the role of the physician and the ob.gyn. in particular is critical. It’s no secret that physicians face a negative legal climate that encourages defensive medicine and that they are often hesitant to tell women, without reservation, that it is okay to take a drug. But we must all remember that it is very easy to cause a woman not to take a medication in pregnancy and often that’s not what’s best for her health. Many women now postpone the age of starting a family and more have chronic conditions that require treatment. The idea of not treating certain conditions for the length of a pregnancy is not always a viable option. Yet there are quite a few women who would consider termination “just to be on the safe side.” That must be taken very seriously by the medical profession.
Dr. Koren is a professor of physiology/pharmacology at Western University, London, Ont., and a professor of medicine at Tel Aviv University. He is the founder of the Motherisk Program. He reported being a paid consultant for Duchesnay and Novartis.
Editor’s note: As Ob.Gyn. News celebrates its 50th anniversary, we wanted to know how far the medical community has come in identifying and mitigating drug risks during pregnancy and in the postpartum period. In this article, our four expert columnists share their experiences trying to find and interpret critical pregnancy data, as well as how they weigh the potential risks and benefits for their patients.
The search for information
The biggest advance in the past 50 years is the availability of information, even though limited, relating to the effects of drugs in pregnancy and lactation. In the first few years of this period, it was a daunting task to obtain this information. I can recall spending hours in the hospital’s medical library going through huge volumes of Index Medicus to obtain references that the library could order for me. The appearance of Thomas H. Shepard’s first edition (Catalog of Teratogenic Agents) in 1973 was a step forward and in 1977, O.P. Heinonen and colleagues’ book (Birth Defects and Drugs in Pregnancy) was helpful.
Although all of the above sources were helpful, any book in an evolving field will not have the newest information. Two important services, TERIS and Reprotox, were started to allow clinicians to contact them for up-to-date data. Nevertheless, the biggest change was the availability of current information from the U.S. National Library of Medicine via Toxnet, PubMed, and LactMed, relating to the effects of drugs in pregnancy and lactation.
My method is to ask three questions. First, are there other drugs with a similar mechanism of action that have some human data? In most cases, the answer to this question is no, but even when there are data, it is typically very limited. Second, does the drug cross the human placenta? The answer is typically based on the molecular weight. Any drug with a molecular weight less than 1,000 daltons probably crosses. In the second half of pregnancy, especially in the third trimester, almost every drug crosses. Third, do the animal pregnancy data predict embryo/fetal risk? It was thought that it could if the dose causing harm was less than or equal to 10 times the human dose based on BSA or AUC and there were no signs of maternal toxicity. However, using data from my 10th edition, I and eight coauthors, all of whom are knowledgeable on the effects of drugs in pregnancy, found that the animal data for 311 drugs raised the possibility of human embryo-fetal harm that current data confirmed in only 75 (24%) of the drugs (Am J Obstet Gynecol. 2015 Dec;213[6]:810-5).
The system needs to be fixed. One method is to give the Food and Drug Administration the authority to require manufacturers of drugs likely to be used in pregnancy to gather and publish data on their use in pregnancy. That sounds reasonable, but will it ever occur?
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.
Learning the lessons of the past
During the last 50 years, two of the most potent known human teratogens, thalidomide and isotretinoin, became available for prescription in the United States. Thanks to the efforts of Frances Kelsey, MD, PhD, at the FDA, the initial application for approval of thalidomide in the United States was denied in the early 1960s. Subsequently, based on evidence from other countries where thalidomide was marketed that the drug can cause a pattern of serious birth defects, a very strict pregnancy prevention program was implemented when the drug was finally approved in the United States in 2006.
Over the last 50 years, we have also seen an important evolution in our ability to conduct pregnancy exposure safety studies. Though we still have limited ability to conduct clinical trials in pregnant women, the need for good quality observational studies has become more widely accepted. The Centers for Disease Control and Prevention’s National Birth Defects Prevention Study (now in its most recent iteration known as BD STEPS) has been one very important source of data on the safety of a wide variety of medications. Using a case-control study design, women who have delivered infants with specific birth defects and comparison women who have delivered non-malformed infants are interviewed about their exposures in pregnancy. These data have been extremely helpful in generating new hypotheses, confirming or refuting findings from other studies, and in testing hypotheses regarding the safety of medications widely used in women of reproductive age. These analyses, for example, have contributed to the large body of literature now available on the safety of antidepressant medications in pregnancy.
At the same time, in the last 30 years, we have seen a tremendous increase in the number of pregnancy registries required or recommended upon approval of a new drug in the United States. These registry studies, while challenging to complete in a timely manner, have steadily improved in terms of rigor, and several disease-based pregnancy exposure studies have been implemented, which have allowed us to better understand the comparative risks or safety of anticonvulsants and antiretroviral drugs, to name a few.
It is important to note that with all these advances in the last 50 years, we still have a huge gap in knowledge about medication safety in pregnancy and lactation. Recent reviews suggest that more than 80% of drugs currently marketed have insufficient or no data available. If we include over-the-counter medications, the knowledge gap grows larger. With the 2014 approval of the long-awaited Pregnancy and Lactation Labeling Rule, clinicians are now beginning to experience the elimination of the old A-B-C-D-X category system for pregnancy safety. In its place, data-driven product labels are required. These are expected to provide the clinician with a clear summary of the relevant studies for a given medication, and to place these in the context of the background risks for the underlying maternal disease being treated, as well as the population risks. However, it is painfully clear that we have a long way to go to generate the needed, high-quality data, to populate those labels.
Dr. Chambers is a professor of pediatrics and director of clinical research at Rady Children’s Hospital, San Diego, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, a past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She has no relevant financial disclosures.
Moving toward personalized medicine
Nowhere is a lack of actionable data more pronounced than in the impact of mental health drugs in pregnancy.
As Dr. Briggs and Dr. Chambers have outlined, the quality of data regarding the reproductive safety of medications across the therapeutic spectrum has historically been fair at best. The methodology and the rigor has been sparse and to a large extent, in psychiatry, we were only able to look for signals of concern. Prior to the late 1980s and early 1990s, there was little to guide clinicians on the safety of even very commonly used psychiatric medications during pregnancy. The health implications for women of reproductive age are extraordinary and yet that urgency was not matched by the level of investigation until more recently.
In psychiatry, we have rapidly improving data informing women about the risk for major congenital malformations. The clinical dilemma of weighing the necessity to stay on a medication to prevent relapse of a psychiatric disorder with the potential risk of malformation in the fetus is a wrenching one for the mother-to-be. Only good information can help patients, together with their physician, make collaborative decisions that make sense for them. Given the same information and the same severity of illness, women will make different decisions, and that’s a good thing. The calculus couples use to make these private decisions is unique to those involved. But they are able to move through the process because they have a platform of high-quality information.
So where do we go in the future? We need to get beyond the question of risk of major malformations and move toward understanding the long-term neurodevelopmental implications of prenatal exposures – whether such exposures confer risk or are even potentially salutary. One needs only look at the vast body of literature regarding fetal exposure to selective serotonin reuptake inhibitors (SSRIs) to observe the realization of this trend. When it comes to SSRIs, a fairly clear picture has emerged that they pose little absolute risk in terms of congenital malformations. What is missing is how SSRIs impact a child’s learning and development at age 3, 5, and 10. There have been a few studies in this area, but not a single, large prospective study that accurately quantifies both exposure to SSRIs and maternal psychiatric illness during pregnancy.
I expect that the future will also bring a greater understanding of the impact of untreated mental illness on the risk for obstetrical, neonatal, and longer-term neurodevelopmental outcomes. Most of the safety concerns have centered around the effect of fetal exposure to medications, but we also need to better understand how untreated psychiatric disorders impact the spectrum of relevant outcomes.
Getting back to the dilemma faced by pregnant women who really need medication to sustain emotional well-being, there simply is no perfect answer. No decision is perfect or risk free. What we can hope is that we’ll have personalized approaches that take into account the best available data and the patient’s individual situation and wishes. We’ve already come a long way toward meeting that goal, and I’m optimistic about where we’re going.
Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.
Perception of risk
Every year, numerous new medicines are approved by the FDA without data in pregnancy. Animal studies may show a problem that doesn’t appear in humans, or as was the case with thalidomide, the problem may not be apparent in animals and show up later in humans. There are many drugs that are safe in pregnancy, but women are understandably afraid of the potential impact on fetal development.
While my colleagues have presented the advances we’ve made in understanding the actual risks of medications during the prenatal period, it’s also important to focus on the perception of risk and to recognize that the reality and the perception can be vastly different.
At the same time, we began to ask women, using a visual analog scale, what would be their trend toward continuing or terminating pregnancy? Over several studies, we found that the likelihood of termination was high, and certainly much higher than was supported by the evidence of actual harm to the fetus. Specifically, if a woman received information about the safety of the drug and she still gave more than a 50% probability of terminating the pregnancy when surveyed, there was a good chance that she would terminate the pregnancy.
When you consider that most of the drugs that women are commonly prescribed in pregnancy – from most painkillers to antidepressants – are not known to cause malformations in pregnancy, you begin to see how problematic an inflated perception of risk can become.
But we see different trends in women with serious and chronic health problems, such as lupus or epilepsy. These women are typically under the care of a subspecialist, who in many cases has developed a significant knowledge base and comfort level around prescribing the drugs in this area and is able to communicate more clearly to patients both the risks to the fetus and the consequences of failure to treat their condition.
So clearly, the role of the physician and the ob.gyn. in particular is critical. It’s no secret that physicians face a negative legal climate that encourages defensive medicine and that they are often hesitant to tell women, without reservation, that it is okay to take a drug. But we must all remember that it is very easy to cause a woman not to take a medication in pregnancy and often that’s not what’s best for her health. Many women now postpone the age of starting a family and more have chronic conditions that require treatment. The idea of not treating certain conditions for the length of a pregnancy is not always a viable option. Yet there are quite a few women who would consider termination “just to be on the safe side.” That must be taken very seriously by the medical profession.
Dr. Koren is a professor of physiology/pharmacology at Western University, London, Ont., and a professor of medicine at Tel Aviv University. He is the founder of the Motherisk Program. He reported being a paid consultant for Duchesnay and Novartis.
Editor’s note: As Ob.Gyn. News celebrates its 50th anniversary, we wanted to know how far the medical community has come in identifying and mitigating drug risks during pregnancy and in the postpartum period. In this article, our four expert columnists share their experiences trying to find and interpret critical pregnancy data, as well as how they weigh the potential risks and benefits for their patients.
The search for information
The biggest advance in the past 50 years is the availability of information, even though limited, relating to the effects of drugs in pregnancy and lactation. In the first few years of this period, it was a daunting task to obtain this information. I can recall spending hours in the hospital’s medical library going through huge volumes of Index Medicus to obtain references that the library could order for me. The appearance of Thomas H. Shepard’s first edition (Catalog of Teratogenic Agents) in 1973 was a step forward and in 1977, O.P. Heinonen and colleagues’ book (Birth Defects and Drugs in Pregnancy) was helpful.
Although all of the above sources were helpful, any book in an evolving field will not have the newest information. Two important services, TERIS and Reprotox, were started to allow clinicians to contact them for up-to-date data. Nevertheless, the biggest change was the availability of current information from the U.S. National Library of Medicine via Toxnet, PubMed, and LactMed, relating to the effects of drugs in pregnancy and lactation.
My method is to ask three questions. First, are there other drugs with a similar mechanism of action that have some human data? In most cases, the answer to this question is no, but even when there are data, it is typically very limited. Second, does the drug cross the human placenta? The answer is typically based on the molecular weight. Any drug with a molecular weight less than 1,000 daltons probably crosses. In the second half of pregnancy, especially in the third trimester, almost every drug crosses. Third, do the animal pregnancy data predict embryo/fetal risk? It was thought that it could if the dose causing harm was less than or equal to 10 times the human dose based on BSA or AUC and there were no signs of maternal toxicity. However, using data from my 10th edition, I and eight coauthors, all of whom are knowledgeable on the effects of drugs in pregnancy, found that the animal data for 311 drugs raised the possibility of human embryo-fetal harm that current data confirmed in only 75 (24%) of the drugs (Am J Obstet Gynecol. 2015 Dec;213[6]:810-5).
The system needs to be fixed. One method is to give the Food and Drug Administration the authority to require manufacturers of drugs likely to be used in pregnancy to gather and publish data on their use in pregnancy. That sounds reasonable, but will it ever occur?
Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, and Washington State University, Spokane. He is coauthor of “Drugs in Pregnancy and Lactation,” and coeditor of “Diseases, Complications, and Drug Therapy in Obstetrics.” He has no relevant financial disclosures.
Learning the lessons of the past
During the last 50 years, two of the most potent known human teratogens, thalidomide and isotretinoin, became available for prescription in the United States. Thanks to the efforts of Frances Kelsey, MD, PhD, at the FDA, the initial application for approval of thalidomide in the United States was denied in the early 1960s. Subsequently, based on evidence from other countries where thalidomide was marketed that the drug can cause a pattern of serious birth defects, a very strict pregnancy prevention program was implemented when the drug was finally approved in the United States in 2006.
Over the last 50 years, we have also seen an important evolution in our ability to conduct pregnancy exposure safety studies. Though we still have limited ability to conduct clinical trials in pregnant women, the need for good quality observational studies has become more widely accepted. The Centers for Disease Control and Prevention’s National Birth Defects Prevention Study (now in its most recent iteration known as BD STEPS) has been one very important source of data on the safety of a wide variety of medications. Using a case-control study design, women who have delivered infants with specific birth defects and comparison women who have delivered non-malformed infants are interviewed about their exposures in pregnancy. These data have been extremely helpful in generating new hypotheses, confirming or refuting findings from other studies, and in testing hypotheses regarding the safety of medications widely used in women of reproductive age. These analyses, for example, have contributed to the large body of literature now available on the safety of antidepressant medications in pregnancy.
At the same time, in the last 30 years, we have seen a tremendous increase in the number of pregnancy registries required or recommended upon approval of a new drug in the United States. These registry studies, while challenging to complete in a timely manner, have steadily improved in terms of rigor, and several disease-based pregnancy exposure studies have been implemented, which have allowed us to better understand the comparative risks or safety of anticonvulsants and antiretroviral drugs, to name a few.
It is important to note that with all these advances in the last 50 years, we still have a huge gap in knowledge about medication safety in pregnancy and lactation. Recent reviews suggest that more than 80% of drugs currently marketed have insufficient or no data available. If we include over-the-counter medications, the knowledge gap grows larger. With the 2014 approval of the long-awaited Pregnancy and Lactation Labeling Rule, clinicians are now beginning to experience the elimination of the old A-B-C-D-X category system for pregnancy safety. In its place, data-driven product labels are required. These are expected to provide the clinician with a clear summary of the relevant studies for a given medication, and to place these in the context of the background risks for the underlying maternal disease being treated, as well as the population risks. However, it is painfully clear that we have a long way to go to generate the needed, high-quality data, to populate those labels.
Dr. Chambers is a professor of pediatrics and director of clinical research at Rady Children’s Hospital, San Diego, and associate director of the Clinical and Translational Research Institute at the University of California, San Diego. She is director of MotherToBaby California, a past president of the Organization of Teratology Information Specialists, and past president of the Teratology Society. She has no relevant financial disclosures.
Moving toward personalized medicine
Nowhere is a lack of actionable data more pronounced than in the impact of mental health drugs in pregnancy.
As Dr. Briggs and Dr. Chambers have outlined, the quality of data regarding the reproductive safety of medications across the therapeutic spectrum has historically been fair at best. The methodology and the rigor has been sparse and to a large extent, in psychiatry, we were only able to look for signals of concern. Prior to the late 1980s and early 1990s, there was little to guide clinicians on the safety of even very commonly used psychiatric medications during pregnancy. The health implications for women of reproductive age are extraordinary and yet that urgency was not matched by the level of investigation until more recently.
In psychiatry, we have rapidly improving data informing women about the risk for major congenital malformations. The clinical dilemma of weighing the necessity to stay on a medication to prevent relapse of a psychiatric disorder with the potential risk of malformation in the fetus is a wrenching one for the mother-to-be. Only good information can help patients, together with their physician, make collaborative decisions that make sense for them. Given the same information and the same severity of illness, women will make different decisions, and that’s a good thing. The calculus couples use to make these private decisions is unique to those involved. But they are able to move through the process because they have a platform of high-quality information.
So where do we go in the future? We need to get beyond the question of risk of major malformations and move toward understanding the long-term neurodevelopmental implications of prenatal exposures – whether such exposures confer risk or are even potentially salutary. One needs only look at the vast body of literature regarding fetal exposure to selective serotonin reuptake inhibitors (SSRIs) to observe the realization of this trend. When it comes to SSRIs, a fairly clear picture has emerged that they pose little absolute risk in terms of congenital malformations. What is missing is how SSRIs impact a child’s learning and development at age 3, 5, and 10. There have been a few studies in this area, but not a single, large prospective study that accurately quantifies both exposure to SSRIs and maternal psychiatric illness during pregnancy.
I expect that the future will also bring a greater understanding of the impact of untreated mental illness on the risk for obstetrical, neonatal, and longer-term neurodevelopmental outcomes. Most of the safety concerns have centered around the effect of fetal exposure to medications, but we also need to better understand how untreated psychiatric disorders impact the spectrum of relevant outcomes.
Getting back to the dilemma faced by pregnant women who really need medication to sustain emotional well-being, there simply is no perfect answer. No decision is perfect or risk free. What we can hope is that we’ll have personalized approaches that take into account the best available data and the patient’s individual situation and wishes. We’ve already come a long way toward meeting that goal, and I’m optimistic about where we’re going.
Dr. Cohen is the director of the Center for Women’s Mental Health at Massachusetts General Hospital in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications.
Perception of risk
Every year, numerous new medicines are approved by the FDA without data in pregnancy. Animal studies may show a problem that doesn’t appear in humans, or as was the case with thalidomide, the problem may not be apparent in animals and show up later in humans. There are many drugs that are safe in pregnancy, but women are understandably afraid of the potential impact on fetal development.
While my colleagues have presented the advances we’ve made in understanding the actual risks of medications during the prenatal period, it’s also important to focus on the perception of risk and to recognize that the reality and the perception can be vastly different.
At the same time, we began to ask women, using a visual analog scale, what would be their trend toward continuing or terminating pregnancy? Over several studies, we found that the likelihood of termination was high, and certainly much higher than was supported by the evidence of actual harm to the fetus. Specifically, if a woman received information about the safety of the drug and she still gave more than a 50% probability of terminating the pregnancy when surveyed, there was a good chance that she would terminate the pregnancy.
When you consider that most of the drugs that women are commonly prescribed in pregnancy – from most painkillers to antidepressants – are not known to cause malformations in pregnancy, you begin to see how problematic an inflated perception of risk can become.
But we see different trends in women with serious and chronic health problems, such as lupus or epilepsy. These women are typically under the care of a subspecialist, who in many cases has developed a significant knowledge base and comfort level around prescribing the drugs in this area and is able to communicate more clearly to patients both the risks to the fetus and the consequences of failure to treat their condition.
So clearly, the role of the physician and the ob.gyn. in particular is critical. It’s no secret that physicians face a negative legal climate that encourages defensive medicine and that they are often hesitant to tell women, without reservation, that it is okay to take a drug. But we must all remember that it is very easy to cause a woman not to take a medication in pregnancy and often that’s not what’s best for her health. Many women now postpone the age of starting a family and more have chronic conditions that require treatment. The idea of not treating certain conditions for the length of a pregnancy is not always a viable option. Yet there are quite a few women who would consider termination “just to be on the safe side.” That must be taken very seriously by the medical profession.
Dr. Koren is a professor of physiology/pharmacology at Western University, London, Ont., and a professor of medicine at Tel Aviv University. He is the founder of the Motherisk Program. He reported being a paid consultant for Duchesnay and Novartis.
VIDEO: The surgical treatment of pelvic congestion
BY CHARLES E. MILLER, MD
Chronic pelvic pain is described as the presence of lower abdominal or pelvic pain for longer than 6 months. It is believed to affect approximately one in six women and 12%-15% of women of reproductive age. The diagnosis and treatment of chronic pelvic pain adds as much as a $2 billion burden to our health system annually.
It was first described clinically in the literature in 1857, while the existence of pelvic varicosities wasn’t documented for nearly another 100 years. Pelvic congestion syndrome (PCS) accounts for 30%-70% of cases presenting with chronic pelvic pain. PCS can be due to pelvic venous insufficiency, characterized by reflux into pelvic veins leading to pelvic varicosities or alternative venous pathways secondary to varicose veins of the leg.
Other etiologies of PCS include nutcracker syndrome (left renal vein compressed between the aorta and the superior mesenteric artery), May-Thurner syndrome (compression of the left common iliac vein by the right common iliac artery) or, less likely, tumor thrombosis of the inferior vena cava, portal vein thrombosis, renal cell carcinoma, left renal thrombosis, or left kidney arterial-venous fistula.
While there appears to be significant literature indicating a long-term success rate of greater than 80% in patients treated by percutaneous endovascular procedures (embolization, stenting), there is far less information on the postsurgical success of blocking the varicose gonadal vein. Nevertheless, our long-term results with gonadal vein clipping is virtually the same as that of our radiological colleagues.
It is a pleasure to welcome Courtney Steller, DO, to this edition of the Master Class in Gynecologic Surgery to discuss the diagnosis and treatment of PCS, with an emphasis on surgical correction.
Dr. Steller is a recent graduate of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill. She is currently in private practice and is an associate at the Family Health Centers of San Diego, Calif.
Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported having no financial disclosures relevant to this column. Email him at [email protected].
Pelvic congestion syndrome: A treatable cause of pain
BY COURTNEY STELLER, DO
Pelvic congestion syndrome is a poorly understood and underdiagnosed disease. Yet, over the last decade, the syndrome has become less controversial as the etiology has become better understood and as the diagnostic approach has become more specific. Through these advances, treatments have also become increasingly more successful.
This is an important shift, because the chronic pelvic pain experienced by patients with pelvic congestion significantly impacts their quality of life and well-being. As the pain persists, it can become exceedingly difficult to manage. Many patients we have ultimately treated for pelvic congestion syndrome have had years of various work-ups, significant diagnostic investigations, and trials of different treatments without having any cause of their pain identified or achieving any lasting symptom relief. 
The pelvic pain in patients with pelvic congestion syndrome (PCS) can be noncyclical or cyclical. It is present most of the time but tends to get worse at the end of the day and after long periods of standing and/or sitting. The pain also may worsen with intercourse, largely afterward. The syndrome tends to occur in premenopausal and multiparous women, but it’s important to appreciate that this is not always the case; we have diagnosed and treated PCS in several young, nulliparous patients as well.
Features and diagnosis
PCS is a disorder of pelvic venous circulation that predominantly affects the ovarian veins. It is sometimes referred to as pelvic vein incompetence or pelvic vascular dysfunction. Just as veins in the legs can enlarge and become varicose, the ovarian veins – and sometimes the internal iliac veins – can become incompetent and unable to effectively return blood back to the heart.
Pregnancy may predispose patients to developing the abnormally dilated and refluxing veins that characterize PCS, as the increase in pelvic vein capacity and uterine compression can lead to significant stasis of blood in the pelvis and subsequent damage to the veins and the venous valves. There also is believed to be an estrogen component to the development of PCS, because estrogen is known to act as a vasodilator. Moreover, a congenital absence and incompetence of venous valves in some cases has been reported.
In a recent study looking at pelvic vein incompetence and symptoms of chronic pelvic pain, these women were reported to have a distinctive symptom profile, with the “most notable” features being the presence of dull pelvic pain that radiates to the upper thighs and is aggravated by prolonged standing and walking – symptoms that are similar to the leg symptoms experienced by patients with severe varicose veins (Eur J Obstet Gynecol Reprod Biol. 2016 Jan;196:21-5).
Other investigators have similarly described the pelvic pain related to PCS as a dull ache or heaviness sensation that is most severe at the end of the day and that is lessened with supine positioning (though not necessarily immediately) and often exacerbated with sexual intercourse, especially post coitus. These descriptions are in line with my experience with PCS. There is usually exquisite tenderness on pelvic exam, especially localized to the adnexa. Patients will often have varicose veins on their upper legs or labia.
Interestingly, it has been repeatedly shown that many women have dilated and incompetent pelvic veins without also having such pathognomonic pain. We therefore cannot treat women based solely on the finding of abnormal veins.
On the other hand we must determine which patients with chronic pelvic pain have PCS. The differential diagnosis for PCS includes endometriosis, adenomyosis chronic pelvic inflammatory disease, adhesive disease, adnexal masses, adnexal torsion, and several nongynecologic diseases including interstitial cystitis and irritable bowel syndrome.
Venography has become the gold standard for diagnosing pelvic congestion. The procedure involves catheterization of the ovarian veins through a femoral or jugular approach. In our experience, the common femoral vein is the more frequently used access point. Using a contrast injection, the interventional radiologist can assess the degree of venous dilation and reflux in the pelvis.
There currently is no consensus on a cutoff for vein diameter or on any validated measures for congestion. According to one report on PCS authored by interventional radiologists, the diagnosis of PCS is confirmed with the venographic findings of ovarian vein diameter greater than 6 mm, retrograde ovarian or pelvic venous flow, presence of several tortuous collateral pelvic venous pathways, and delayed or stagnant clearance on contrast (Semin Intervent Radiol. 2008 Dec;25[4]:361-8).
The criteria vary, however. A recent literature review on pelvic congestion syndrome by Chiara Borghi, MD, and Lucio Dell’Atti, MD, states that incompetent pelvic veins are defined as more than 5-10 mm in diameter (Arch Gynecol Obstet. 2016 Feb;293[2]:291-301).
To more accurately diagnose PCS, our patients undergo tilt-table venography. The patient is placed into a reverse-Trendelenburg upright or semi-upright position to potentially exacerbate any venous reflux or dilation.
Other methods of identifying and diagnosing pelvic congestion have included transabdominal and transvaginal ultrasound, CT, and MRI. While CT and MRI both offer an overview of the pelvic vasculature and are helpful for ruling out other causes of chronic pelvic pain, they have low specificity for pelvic varices, according to the Italian review.
Sonography performed in the supine position, on the other hand, appears to be increasingly viewed as an acceptable screening tool for determining which patients may ultimately benefit from venography. It is also important in evaluation to rule out other pathologies not yet excluded. However, it should not be used for diagnosis of PCS.
Treating PCS
There are two main approaches to treating PCS: venous ligation (a gynecologic surgical approach) and percutaneous transcatheter embolization (performed by interventional radiologists).
The literature and evidence base is still in its infancy, but is growing. In our experience, both approaches lead to good resolution of symptoms over time in the majority of patients, and appear superior to the medical therapies that have been proposed for treating PCS, such as progestins and gonadotropin-releasing hormone agonists. Success rates with medical therapy are more variable and appear to be more short lived.
A review published this year on the effectiveness of embolization of pelvic veins for reducing chronic pelvic pain showed that 75% of women undergoing embolization had symptomatic relief that generally increased over time and was sustained. The authors concluded that embolization appears to be effective for the majority of women, and is safe, although they also noted that the quality of the evidence is low (J Vasc Interv Radiol. 2016 Oct;27[10]:1478-86.e8). Their review was based almost entirely on prospective case series.
Dr. Borghi and Dr. Dell’Atti offered a similar assessment of embolization for PCS, stating in their review article that clinical success has been reported in 70%-85% of patients. They also report nearly equivalent success rates of up to 75% with treatment via surgical ligation of ovarian and/or pelvic vasculature. These findings are from mostly observational data and case series.
Decisions about which approach to take should be individualized. If there are no differences with respect to insurance coverage for the patient, then embolization may be the preferred approach because it is the most minimally invasive technique and can potentially be performed at the time of diagnostic venography, negating the need for a second procedure. A skilled interventional radiologist familiar with the disease and the treatment is necessary. Various embolic agents are utilized, including coils, glues, foams, and other agents that cause sclerosis of the abnormal veins.
In other cases, venous ligation is preferred, especially when an additional gynecologic surgery, such as a cystectomy or myomectomy, is required.
Surgical ligation of ovarian veins was initially performed via laparotomy using a traditional retroperitoneal approach. The surgical goal is to isolate the ovarian vein significantly above the pelvic brim and before the vein becomes substantially dilated. Laparotomy therefore requires a vertical mid-line incision to provide adequate access to the appropriate portion of the ovarian vessels, leading to potentially high morbidity and poor cosmesis.
More recently, gynecologic surgeons skilled in laparoscopy have successfully managed PCS transperitoneally. A few small series of bilateral laparoscopic transperitoneal ligation of ovarian veins have been reported, including one by Tigellio Gargiulo, MD, who clipped both veins in their upper third, near their distal ends at the inferior vena cava (right) and the renal vein (left) (J Am Assoc Gynecol Laparosc. 2003 Nov;10[4]:501-4).
We prefer a robot-assisted laparoscopic approach for most of our patients. Not only does the improved dexterity help while working with sensitive vasculature, but more importantly we are able to use Firefly fluorescence.
The procedure generally is as follows. The uterine adnexa on the affected side is grasped and placed on tension so that the infundibulopelvic (IP) ligament can be visualized as it courses up and above the pelvic brim. The peritoneum immediately over the IP ligament is gently grasped and tented upward, and a small incision is made into the peritoneum, providing access into the retroperitoneum. The ureter should be visualized medial to this dissection.
The peritoneal tissue is then gently dissected off the ovarian vessels. Once the vessels are freed from the peritoneal tissue, the dilated ovarian vein is often clearly visualized. It is important to note that if no venous dilation is seen during laparoscopy, the procedure should not be aborted. Due to the Trendelenburg position that is utilized in gynecologic – and especially laparoscopic – surgery, the venous system sometimes appears falsely “normal” at this time.
Once the ovarian vessels have been isolated, the arteries must be separated from the veins. The adventitial tissue is dissected until the vessels are separated. Great care should be taken to ensure that all movements run parallel to the vessels and not perpendicular, therefore decreasing the risk of bleeding.
This process can be challenging. The surgeon is working with delicate vasculature. Often there are several branches from the vein that have formed due to the abnormal venous system. The best way to approach it is to identify planes and separate those planes in order to isolate individual vessels. If difficulties are still encountered, the surgeon should restart the dissection higher.
Once the dilated ovarian vein is isolated, one to two clips are placed.
Usually the artery is clearly distinct from the vein as it is smaller, more elastic, and can be seen pulsing. However, occasionally it is difficult to distinguish. In these cases, assistance with the da Vinci surgical system is useful: Indocyanine green (ICG) dye can be injected intravenously and visualized with a near-infrared light on the da Vinci platform. The dye is then seen glowing green as it first courses through the artery and then the vein.
For patients who have been found on venography to have bilateral disease, we perform the ligation procedure bilaterally. Once ligation is complete, the more competent collateral veins in the pelvis will assume more of the venous circulation.
In our experience, patients have ultimately noted substantial pain relief after these procedures, both with the endoscopic embolization and the surgical ligation. Patients are counseled that it can take several months to notice a relief in the pain.
In rare cases, pelvic congestion is related to extrinsic compression. For instance, the left renal vein can become compressed between the aorta and the superior mesenteric artery (the nutcracker syndrome), or the left common iliac vein can be compressed between the overlying right internal iliac artery and the underlying vertebral body (May-Thurner syndrome). Both of these conditions can lead to secondary PCS.
Such complex conditions are usually treated by vascular surgeons. May-Thurner syndrome is treated via stenting, while nutcracker syndrome can be treated with stenting or transposition of the renal vein to the distal vena cava.
Dr. Steller is an associate at the Family Health Centers of San Diego. She reported having no relevant financial disclosures.
BY CHARLES E. MILLER, MD
Chronic pelvic pain is described as the presence of lower abdominal or pelvic pain for longer than 6 months. It is believed to affect approximately one in six women and 12%-15% of women of reproductive age. The diagnosis and treatment of chronic pelvic pain adds as much as a $2 billion burden to our health system annually.
It was first described clinically in the literature in 1857, while the existence of pelvic varicosities wasn’t documented for nearly another 100 years. Pelvic congestion syndrome (PCS) accounts for 30%-70% of cases presenting with chronic pelvic pain. PCS can be due to pelvic venous insufficiency, characterized by reflux into pelvic veins leading to pelvic varicosities or alternative venous pathways secondary to varicose veins of the leg.
Other etiologies of PCS include nutcracker syndrome (left renal vein compressed between the aorta and the superior mesenteric artery), May-Thurner syndrome (compression of the left common iliac vein by the right common iliac artery) or, less likely, tumor thrombosis of the inferior vena cava, portal vein thrombosis, renal cell carcinoma, left renal thrombosis, or left kidney arterial-venous fistula.
While there appears to be significant literature indicating a long-term success rate of greater than 80% in patients treated by percutaneous endovascular procedures (embolization, stenting), there is far less information on the postsurgical success of blocking the varicose gonadal vein. Nevertheless, our long-term results with gonadal vein clipping is virtually the same as that of our radiological colleagues.
It is a pleasure to welcome Courtney Steller, DO, to this edition of the Master Class in Gynecologic Surgery to discuss the diagnosis and treatment of PCS, with an emphasis on surgical correction.
Dr. Steller is a recent graduate of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill. She is currently in private practice and is an associate at the Family Health Centers of San Diego, Calif.
Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported having no financial disclosures relevant to this column. Email him at [email protected].
Pelvic congestion syndrome: A treatable cause of pain
BY COURTNEY STELLER, DO
Pelvic congestion syndrome is a poorly understood and underdiagnosed disease. Yet, over the last decade, the syndrome has become less controversial as the etiology has become better understood and as the diagnostic approach has become more specific. Through these advances, treatments have also become increasingly more successful.
This is an important shift, because the chronic pelvic pain experienced by patients with pelvic congestion significantly impacts their quality of life and well-being. As the pain persists, it can become exceedingly difficult to manage. Many patients we have ultimately treated for pelvic congestion syndrome have had years of various work-ups, significant diagnostic investigations, and trials of different treatments without having any cause of their pain identified or achieving any lasting symptom relief.
The pelvic pain in patients with pelvic congestion syndrome (PCS) can be noncyclical or cyclical. It is present most of the time but tends to get worse at the end of the day and after long periods of standing and/or sitting. The pain also may worsen with intercourse, largely afterward. The syndrome tends to occur in premenopausal and multiparous women, but it’s important to appreciate that this is not always the case; we have diagnosed and treated PCS in several young, nulliparous patients as well.
Features and diagnosis
PCS is a disorder of pelvic venous circulation that predominantly affects the ovarian veins. It is sometimes referred to as pelvic vein incompetence or pelvic vascular dysfunction. Just as veins in the legs can enlarge and become varicose, the ovarian veins – and sometimes the internal iliac veins – can become incompetent and unable to effectively return blood back to the heart.
Pregnancy may predispose patients to developing the abnormally dilated and refluxing veins that characterize PCS, as the increase in pelvic vein capacity and uterine compression can lead to significant stasis of blood in the pelvis and subsequent damage to the veins and the venous valves. There also is believed to be an estrogen component to the development of PCS, because estrogen is known to act as a vasodilator. Moreover, a congenital absence and incompetence of venous valves in some cases has been reported.
In a recent study looking at pelvic vein incompetence and symptoms of chronic pelvic pain, these women were reported to have a distinctive symptom profile, with the “most notable” features being the presence of dull pelvic pain that radiates to the upper thighs and is aggravated by prolonged standing and walking – symptoms that are similar to the leg symptoms experienced by patients with severe varicose veins (Eur J Obstet Gynecol Reprod Biol. 2016 Jan;196:21-5).
Other investigators have similarly described the pelvic pain related to PCS as a dull ache or heaviness sensation that is most severe at the end of the day and that is lessened with supine positioning (though not necessarily immediately) and often exacerbated with sexual intercourse, especially post coitus. These descriptions are in line with my experience with PCS. There is usually exquisite tenderness on pelvic exam, especially localized to the adnexa. Patients will often have varicose veins on their upper legs or labia.
Interestingly, it has been repeatedly shown that many women have dilated and incompetent pelvic veins without also having such pathognomonic pain. We therefore cannot treat women based solely on the finding of abnormal veins.
On the other hand we must determine which patients with chronic pelvic pain have PCS. The differential diagnosis for PCS includes endometriosis, adenomyosis chronic pelvic inflammatory disease, adhesive disease, adnexal masses, adnexal torsion, and several nongynecologic diseases including interstitial cystitis and irritable bowel syndrome.
Venography has become the gold standard for diagnosing pelvic congestion. The procedure involves catheterization of the ovarian veins through a femoral or jugular approach. In our experience, the common femoral vein is the more frequently used access point. Using a contrast injection, the interventional radiologist can assess the degree of venous dilation and reflux in the pelvis.
There currently is no consensus on a cutoff for vein diameter or on any validated measures for congestion. According to one report on PCS authored by interventional radiologists, the diagnosis of PCS is confirmed with the venographic findings of ovarian vein diameter greater than 6 mm, retrograde ovarian or pelvic venous flow, presence of several tortuous collateral pelvic venous pathways, and delayed or stagnant clearance on contrast (Semin Intervent Radiol. 2008 Dec;25[4]:361-8).
The criteria vary, however. A recent literature review on pelvic congestion syndrome by Chiara Borghi, MD, and Lucio Dell’Atti, MD, states that incompetent pelvic veins are defined as more than 5-10 mm in diameter (Arch Gynecol Obstet. 2016 Feb;293[2]:291-301).
To more accurately diagnose PCS, our patients undergo tilt-table venography. The patient is placed into a reverse-Trendelenburg upright or semi-upright position to potentially exacerbate any venous reflux or dilation.
Other methods of identifying and diagnosing pelvic congestion have included transabdominal and transvaginal ultrasound, CT, and MRI. While CT and MRI both offer an overview of the pelvic vasculature and are helpful for ruling out other causes of chronic pelvic pain, they have low specificity for pelvic varices, according to the Italian review.
Sonography performed in the supine position, on the other hand, appears to be increasingly viewed as an acceptable screening tool for determining which patients may ultimately benefit from venography. It is also important in evaluation to rule out other pathologies not yet excluded. However, it should not be used for diagnosis of PCS.
Treating PCS
There are two main approaches to treating PCS: venous ligation (a gynecologic surgical approach) and percutaneous transcatheter embolization (performed by interventional radiologists).
The literature and evidence base is still in its infancy, but is growing. In our experience, both approaches lead to good resolution of symptoms over time in the majority of patients, and appear superior to the medical therapies that have been proposed for treating PCS, such as progestins and gonadotropin-releasing hormone agonists. Success rates with medical therapy are more variable and appear to be more short lived.
A review published this year on the effectiveness of embolization of pelvic veins for reducing chronic pelvic pain showed that 75% of women undergoing embolization had symptomatic relief that generally increased over time and was sustained. The authors concluded that embolization appears to be effective for the majority of women, and is safe, although they also noted that the quality of the evidence is low (J Vasc Interv Radiol. 2016 Oct;27[10]:1478-86.e8). Their review was based almost entirely on prospective case series.
Dr. Borghi and Dr. Dell’Atti offered a similar assessment of embolization for PCS, stating in their review article that clinical success has been reported in 70%-85% of patients. They also report nearly equivalent success rates of up to 75% with treatment via surgical ligation of ovarian and/or pelvic vasculature. These findings are from mostly observational data and case series.
Decisions about which approach to take should be individualized. If there are no differences with respect to insurance coverage for the patient, then embolization may be the preferred approach because it is the most minimally invasive technique and can potentially be performed at the time of diagnostic venography, negating the need for a second procedure. A skilled interventional radiologist familiar with the disease and the treatment is necessary. Various embolic agents are utilized, including coils, glues, foams, and other agents that cause sclerosis of the abnormal veins.
In other cases, venous ligation is preferred, especially when an additional gynecologic surgery, such as a cystectomy or myomectomy, is required.
Surgical ligation of ovarian veins was initially performed via laparotomy using a traditional retroperitoneal approach. The surgical goal is to isolate the ovarian vein significantly above the pelvic brim and before the vein becomes substantially dilated. Laparotomy therefore requires a vertical mid-line incision to provide adequate access to the appropriate portion of the ovarian vessels, leading to potentially high morbidity and poor cosmesis.
More recently, gynecologic surgeons skilled in laparoscopy have successfully managed PCS transperitoneally. A few small series of bilateral laparoscopic transperitoneal ligation of ovarian veins have been reported, including one by Tigellio Gargiulo, MD, who clipped both veins in their upper third, near their distal ends at the inferior vena cava (right) and the renal vein (left) (J Am Assoc Gynecol Laparosc. 2003 Nov;10[4]:501-4).
We prefer a robot-assisted laparoscopic approach for most of our patients. Not only does the improved dexterity help while working with sensitive vasculature, but more importantly we are able to use Firefly fluorescence.
The procedure generally is as follows. The uterine adnexa on the affected side is grasped and placed on tension so that the infundibulopelvic (IP) ligament can be visualized as it courses up and above the pelvic brim. The peritoneum immediately over the IP ligament is gently grasped and tented upward, and a small incision is made into the peritoneum, providing access into the retroperitoneum. The ureter should be visualized medial to this dissection.
The peritoneal tissue is then gently dissected off the ovarian vessels. Once the vessels are freed from the peritoneal tissue, the dilated ovarian vein is often clearly visualized. It is important to note that if no venous dilation is seen during laparoscopy, the procedure should not be aborted. Due to the Trendelenburg position that is utilized in gynecologic – and especially laparoscopic – surgery, the venous system sometimes appears falsely “normal” at this time.
Once the ovarian vessels have been isolated, the arteries must be separated from the veins. The adventitial tissue is dissected until the vessels are separated. Great care should be taken to ensure that all movements run parallel to the vessels and not perpendicular, therefore decreasing the risk of bleeding.
This process can be challenging. The surgeon is working with delicate vasculature. Often there are several branches from the vein that have formed due to the abnormal venous system. The best way to approach it is to identify planes and separate those planes in order to isolate individual vessels. If difficulties are still encountered, the surgeon should restart the dissection higher.
Once the dilated ovarian vein is isolated, one to two clips are placed.
Usually the artery is clearly distinct from the vein as it is smaller, more elastic, and can be seen pulsing. However, occasionally it is difficult to distinguish. In these cases, assistance with the da Vinci surgical system is useful: Indocyanine green (ICG) dye can be injected intravenously and visualized with a near-infrared light on the da Vinci platform. The dye is then seen glowing green as it first courses through the artery and then the vein.
For patients who have been found on venography to have bilateral disease, we perform the ligation procedure bilaterally. Once ligation is complete, the more competent collateral veins in the pelvis will assume more of the venous circulation.
In our experience, patients have ultimately noted substantial pain relief after these procedures, both with the endoscopic embolization and the surgical ligation. Patients are counseled that it can take several months to notice a relief in the pain.
In rare cases, pelvic congestion is related to extrinsic compression. For instance, the left renal vein can become compressed between the aorta and the superior mesenteric artery (the nutcracker syndrome), or the left common iliac vein can be compressed between the overlying right internal iliac artery and the underlying vertebral body (May-Thurner syndrome). Both of these conditions can lead to secondary PCS.
Such complex conditions are usually treated by vascular surgeons. May-Thurner syndrome is treated via stenting, while nutcracker syndrome can be treated with stenting or transposition of the renal vein to the distal vena cava.
Dr. Steller is an associate at the Family Health Centers of San Diego. She reported having no relevant financial disclosures.
BY CHARLES E. MILLER, MD
Chronic pelvic pain is described as the presence of lower abdominal or pelvic pain for longer than 6 months. It is believed to affect approximately one in six women and 12%-15% of women of reproductive age. The diagnosis and treatment of chronic pelvic pain adds as much as a $2 billion burden to our health system annually.
It was first described clinically in the literature in 1857, while the existence of pelvic varicosities wasn’t documented for nearly another 100 years. Pelvic congestion syndrome (PCS) accounts for 30%-70% of cases presenting with chronic pelvic pain. PCS can be due to pelvic venous insufficiency, characterized by reflux into pelvic veins leading to pelvic varicosities or alternative venous pathways secondary to varicose veins of the leg.
Other etiologies of PCS include nutcracker syndrome (left renal vein compressed between the aorta and the superior mesenteric artery), May-Thurner syndrome (compression of the left common iliac vein by the right common iliac artery) or, less likely, tumor thrombosis of the inferior vena cava, portal vein thrombosis, renal cell carcinoma, left renal thrombosis, or left kidney arterial-venous fistula.
While there appears to be significant literature indicating a long-term success rate of greater than 80% in patients treated by percutaneous endovascular procedures (embolization, stenting), there is far less information on the postsurgical success of blocking the varicose gonadal vein. Nevertheless, our long-term results with gonadal vein clipping is virtually the same as that of our radiological colleagues.
It is a pleasure to welcome Courtney Steller, DO, to this edition of the Master Class in Gynecologic Surgery to discuss the diagnosis and treatment of PCS, with an emphasis on surgical correction.
Dr. Steller is a recent graduate of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill. She is currently in private practice and is an associate at the Family Health Centers of San Diego, Calif.
Dr. Miller is clinical associate professor at the University of Illinois at Chicago, and past president of the AAGL and the International Society for Gynecologic Endoscopy. He is a reproductive endocrinologist and minimally invasive gynecologic surgeon in private practice in Naperville and Schaumburg, Ill.; director of minimally invasive gynecologic surgery and the director of the AAGL/SRS Fellowship in Minimally Invasive Gynecologic Surgery at Advocate Lutheran General Hospital, Park Ridge, Ill.; and the medical editor of this column, Master Class. He reported having no financial disclosures relevant to this column. Email him at [email protected].
Pelvic congestion syndrome: A treatable cause of pain
BY COURTNEY STELLER, DO
Pelvic congestion syndrome is a poorly understood and underdiagnosed disease. Yet, over the last decade, the syndrome has become less controversial as the etiology has become better understood and as the diagnostic approach has become more specific. Through these advances, treatments have also become increasingly more successful.
This is an important shift, because the chronic pelvic pain experienced by patients with pelvic congestion significantly impacts their quality of life and well-being. As the pain persists, it can become exceedingly difficult to manage. Many patients we have ultimately treated for pelvic congestion syndrome have had years of various work-ups, significant diagnostic investigations, and trials of different treatments without having any cause of their pain identified or achieving any lasting symptom relief.
The pelvic pain in patients with pelvic congestion syndrome (PCS) can be noncyclical or cyclical. It is present most of the time but tends to get worse at the end of the day and after long periods of standing and/or sitting. The pain also may worsen with intercourse, largely afterward. The syndrome tends to occur in premenopausal and multiparous women, but it’s important to appreciate that this is not always the case; we have diagnosed and treated PCS in several young, nulliparous patients as well.
Features and diagnosis
PCS is a disorder of pelvic venous circulation that predominantly affects the ovarian veins. It is sometimes referred to as pelvic vein incompetence or pelvic vascular dysfunction. Just as veins in the legs can enlarge and become varicose, the ovarian veins – and sometimes the internal iliac veins – can become incompetent and unable to effectively return blood back to the heart.
Pregnancy may predispose patients to developing the abnormally dilated and refluxing veins that characterize PCS, as the increase in pelvic vein capacity and uterine compression can lead to significant stasis of blood in the pelvis and subsequent damage to the veins and the venous valves. There also is believed to be an estrogen component to the development of PCS, because estrogen is known to act as a vasodilator. Moreover, a congenital absence and incompetence of venous valves in some cases has been reported.
In a recent study looking at pelvic vein incompetence and symptoms of chronic pelvic pain, these women were reported to have a distinctive symptom profile, with the “most notable” features being the presence of dull pelvic pain that radiates to the upper thighs and is aggravated by prolonged standing and walking – symptoms that are similar to the leg symptoms experienced by patients with severe varicose veins (Eur J Obstet Gynecol Reprod Biol. 2016 Jan;196:21-5).
Other investigators have similarly described the pelvic pain related to PCS as a dull ache or heaviness sensation that is most severe at the end of the day and that is lessened with supine positioning (though not necessarily immediately) and often exacerbated with sexual intercourse, especially post coitus. These descriptions are in line with my experience with PCS. There is usually exquisite tenderness on pelvic exam, especially localized to the adnexa. Patients will often have varicose veins on their upper legs or labia.
Interestingly, it has been repeatedly shown that many women have dilated and incompetent pelvic veins without also having such pathognomonic pain. We therefore cannot treat women based solely on the finding of abnormal veins.
On the other hand we must determine which patients with chronic pelvic pain have PCS. The differential diagnosis for PCS includes endometriosis, adenomyosis chronic pelvic inflammatory disease, adhesive disease, adnexal masses, adnexal torsion, and several nongynecologic diseases including interstitial cystitis and irritable bowel syndrome.
Venography has become the gold standard for diagnosing pelvic congestion. The procedure involves catheterization of the ovarian veins through a femoral or jugular approach. In our experience, the common femoral vein is the more frequently used access point. Using a contrast injection, the interventional radiologist can assess the degree of venous dilation and reflux in the pelvis.
There currently is no consensus on a cutoff for vein diameter or on any validated measures for congestion. According to one report on PCS authored by interventional radiologists, the diagnosis of PCS is confirmed with the venographic findings of ovarian vein diameter greater than 6 mm, retrograde ovarian or pelvic venous flow, presence of several tortuous collateral pelvic venous pathways, and delayed or stagnant clearance on contrast (Semin Intervent Radiol. 2008 Dec;25[4]:361-8).
The criteria vary, however. A recent literature review on pelvic congestion syndrome by Chiara Borghi, MD, and Lucio Dell’Atti, MD, states that incompetent pelvic veins are defined as more than 5-10 mm in diameter (Arch Gynecol Obstet. 2016 Feb;293[2]:291-301).
To more accurately diagnose PCS, our patients undergo tilt-table venography. The patient is placed into a reverse-Trendelenburg upright or semi-upright position to potentially exacerbate any venous reflux or dilation.
Other methods of identifying and diagnosing pelvic congestion have included transabdominal and transvaginal ultrasound, CT, and MRI. While CT and MRI both offer an overview of the pelvic vasculature and are helpful for ruling out other causes of chronic pelvic pain, they have low specificity for pelvic varices, according to the Italian review.
Sonography performed in the supine position, on the other hand, appears to be increasingly viewed as an acceptable screening tool for determining which patients may ultimately benefit from venography. It is also important in evaluation to rule out other pathologies not yet excluded. However, it should not be used for diagnosis of PCS.
Treating PCS
There are two main approaches to treating PCS: venous ligation (a gynecologic surgical approach) and percutaneous transcatheter embolization (performed by interventional radiologists).
The literature and evidence base is still in its infancy, but is growing. In our experience, both approaches lead to good resolution of symptoms over time in the majority of patients, and appear superior to the medical therapies that have been proposed for treating PCS, such as progestins and gonadotropin-releasing hormone agonists. Success rates with medical therapy are more variable and appear to be more short lived.
A review published this year on the effectiveness of embolization of pelvic veins for reducing chronic pelvic pain showed that 75% of women undergoing embolization had symptomatic relief that generally increased over time and was sustained. The authors concluded that embolization appears to be effective for the majority of women, and is safe, although they also noted that the quality of the evidence is low (J Vasc Interv Radiol. 2016 Oct;27[10]:1478-86.e8). Their review was based almost entirely on prospective case series.
Dr. Borghi and Dr. Dell’Atti offered a similar assessment of embolization for PCS, stating in their review article that clinical success has been reported in 70%-85% of patients. They also report nearly equivalent success rates of up to 75% with treatment via surgical ligation of ovarian and/or pelvic vasculature. These findings are from mostly observational data and case series.
Decisions about which approach to take should be individualized. If there are no differences with respect to insurance coverage for the patient, then embolization may be the preferred approach because it is the most minimally invasive technique and can potentially be performed at the time of diagnostic venography, negating the need for a second procedure. A skilled interventional radiologist familiar with the disease and the treatment is necessary. Various embolic agents are utilized, including coils, glues, foams, and other agents that cause sclerosis of the abnormal veins.
In other cases, venous ligation is preferred, especially when an additional gynecologic surgery, such as a cystectomy or myomectomy, is required.
Surgical ligation of ovarian veins was initially performed via laparotomy using a traditional retroperitoneal approach. The surgical goal is to isolate the ovarian vein significantly above the pelvic brim and before the vein becomes substantially dilated. Laparotomy therefore requires a vertical mid-line incision to provide adequate access to the appropriate portion of the ovarian vessels, leading to potentially high morbidity and poor cosmesis.
More recently, gynecologic surgeons skilled in laparoscopy have successfully managed PCS transperitoneally. A few small series of bilateral laparoscopic transperitoneal ligation of ovarian veins have been reported, including one by Tigellio Gargiulo, MD, who clipped both veins in their upper third, near their distal ends at the inferior vena cava (right) and the renal vein (left) (J Am Assoc Gynecol Laparosc. 2003 Nov;10[4]:501-4).
We prefer a robot-assisted laparoscopic approach for most of our patients. Not only does the improved dexterity help while working with sensitive vasculature, but more importantly we are able to use Firefly fluorescence.
The procedure generally is as follows. The uterine adnexa on the affected side is grasped and placed on tension so that the infundibulopelvic (IP) ligament can be visualized as it courses up and above the pelvic brim. The peritoneum immediately over the IP ligament is gently grasped and tented upward, and a small incision is made into the peritoneum, providing access into the retroperitoneum. The ureter should be visualized medial to this dissection.
The peritoneal tissue is then gently dissected off the ovarian vessels. Once the vessels are freed from the peritoneal tissue, the dilated ovarian vein is often clearly visualized. It is important to note that if no venous dilation is seen during laparoscopy, the procedure should not be aborted. Due to the Trendelenburg position that is utilized in gynecologic – and especially laparoscopic – surgery, the venous system sometimes appears falsely “normal” at this time.
Once the ovarian vessels have been isolated, the arteries must be separated from the veins. The adventitial tissue is dissected until the vessels are separated. Great care should be taken to ensure that all movements run parallel to the vessels and not perpendicular, therefore decreasing the risk of bleeding.
This process can be challenging. The surgeon is working with delicate vasculature. Often there are several branches from the vein that have formed due to the abnormal venous system. The best way to approach it is to identify planes and separate those planes in order to isolate individual vessels. If difficulties are still encountered, the surgeon should restart the dissection higher.
Once the dilated ovarian vein is isolated, one to two clips are placed.
Usually the artery is clearly distinct from the vein as it is smaller, more elastic, and can be seen pulsing. However, occasionally it is difficult to distinguish. In these cases, assistance with the da Vinci surgical system is useful: Indocyanine green (ICG) dye can be injected intravenously and visualized with a near-infrared light on the da Vinci platform. The dye is then seen glowing green as it first courses through the artery and then the vein.
For patients who have been found on venography to have bilateral disease, we perform the ligation procedure bilaterally. Once ligation is complete, the more competent collateral veins in the pelvis will assume more of the venous circulation.
In our experience, patients have ultimately noted substantial pain relief after these procedures, both with the endoscopic embolization and the surgical ligation. Patients are counseled that it can take several months to notice a relief in the pain.
In rare cases, pelvic congestion is related to extrinsic compression. For instance, the left renal vein can become compressed between the aorta and the superior mesenteric artery (the nutcracker syndrome), or the left common iliac vein can be compressed between the overlying right internal iliac artery and the underlying vertebral body (May-Thurner syndrome). Both of these conditions can lead to secondary PCS.
Such complex conditions are usually treated by vascular surgeons. May-Thurner syndrome is treated via stenting, while nutcracker syndrome can be treated with stenting or transposition of the renal vein to the distal vena cava.
Dr. Steller is an associate at the Family Health Centers of San Diego. She reported having no relevant financial disclosures.
Some Patients With Diabetes Aren’t Getting Needed Weight Advice
About two-thirds of overweight and obese patients are not getting the advice they need from their health care providers (HCPs) about weight management, according to a study by Arizona State researchers, reported in the CDC’s Preventing Chronic Disease.
The researchers conducted a phone survey of 1,109 overweight or obese adults, asking whether a HCP had in the previous 12 months given them advice about their weight. A “concerning” finding, the researchers say: Only 35% of the respondents reported getting advice.
Related: Confronting the Diabetes Epidemic
As body mass index (BMI) increased, so did the likelihood of receiving weight-loss advice: 22% of those with a BMI of 25.0 to 29.9 received advice vs 63% of those with a BMI of 40.0 or higher. Hispanics were the most likely of the 3 racial/ethnic groups to report receiving advice from a HCP. The researchers say other studies have suggested that a higher prevalence of weight problems among African Americans and Hispanics draws more attention from HCPs for counseling.
High-risk patients, such as the extremely obese or those with comorbidities, are most likely to receive weight-loss advice, the researchers say. But demographic factors also come into play: People with high levels of education are more likely than those with low levels to receive advice, and middle-aged people are more likely to get advice than are younger or older patients.
Related: Diabetes Report: The News Isn’t Good
Patients in the lowest-income groups had significantly lower odds of receiving weight-loss advice compared with those in higher income groups. Adjusting for health insurance did not change the results. That finding is “problematic,” the researchers say, because people with the lowest incomes tend to have poorer health outcomes than that of those with higher incomes.
About two-thirds of overweight and obese patients are not getting the advice they need from their health care providers (HCPs) about weight management, according to a study by Arizona State researchers, reported in the CDC’s Preventing Chronic Disease.
The researchers conducted a phone survey of 1,109 overweight or obese adults, asking whether a HCP had in the previous 12 months given them advice about their weight. A “concerning” finding, the researchers say: Only 35% of the respondents reported getting advice.
Related: Confronting the Diabetes Epidemic
As body mass index (BMI) increased, so did the likelihood of receiving weight-loss advice: 22% of those with a BMI of 25.0 to 29.9 received advice vs 63% of those with a BMI of 40.0 or higher. Hispanics were the most likely of the 3 racial/ethnic groups to report receiving advice from a HCP. The researchers say other studies have suggested that a higher prevalence of weight problems among African Americans and Hispanics draws more attention from HCPs for counseling.
High-risk patients, such as the extremely obese or those with comorbidities, are most likely to receive weight-loss advice, the researchers say. But demographic factors also come into play: People with high levels of education are more likely than those with low levels to receive advice, and middle-aged people are more likely to get advice than are younger or older patients.
Related: Diabetes Report: The News Isn’t Good
Patients in the lowest-income groups had significantly lower odds of receiving weight-loss advice compared with those in higher income groups. Adjusting for health insurance did not change the results. That finding is “problematic,” the researchers say, because people with the lowest incomes tend to have poorer health outcomes than that of those with higher incomes.
About two-thirds of overweight and obese patients are not getting the advice they need from their health care providers (HCPs) about weight management, according to a study by Arizona State researchers, reported in the CDC’s Preventing Chronic Disease.
The researchers conducted a phone survey of 1,109 overweight or obese adults, asking whether a HCP had in the previous 12 months given them advice about their weight. A “concerning” finding, the researchers say: Only 35% of the respondents reported getting advice.
Related: Confronting the Diabetes Epidemic
As body mass index (BMI) increased, so did the likelihood of receiving weight-loss advice: 22% of those with a BMI of 25.0 to 29.9 received advice vs 63% of those with a BMI of 40.0 or higher. Hispanics were the most likely of the 3 racial/ethnic groups to report receiving advice from a HCP. The researchers say other studies have suggested that a higher prevalence of weight problems among African Americans and Hispanics draws more attention from HCPs for counseling.
High-risk patients, such as the extremely obese or those with comorbidities, are most likely to receive weight-loss advice, the researchers say. But demographic factors also come into play: People with high levels of education are more likely than those with low levels to receive advice, and middle-aged people are more likely to get advice than are younger or older patients.
Related: Diabetes Report: The News Isn’t Good
Patients in the lowest-income groups had significantly lower odds of receiving weight-loss advice compared with those in higher income groups. Adjusting for health insurance did not change the results. That finding is “problematic,” the researchers say, because people with the lowest incomes tend to have poorer health outcomes than that of those with higher incomes.
Use Whiteboards to Enhance Patient-Provider Communication
Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”
View a chart outlining key communication tactics
What I Say and Do
With my team, I use whiteboards as a tool to enhance communication: 1) I introduce myself and my team members, then write our names on the whiteboard paired with an explanation of my role as the attending physician for the hospital medicine service; 2) on a daily basis, I ask the patient and family/support what their primary concerns and goals are and write those on the whiteboard; and 3) I invite the patient and family/support to use the whiteboard to write additional concerns or questions as they arise.
Why I Do It
Hospitals are confusing places. One of our key roles as hospitalists is to coordinate and clarify all of the moving pieces and to communicate clearly to patients and their family that there is someone doing that work on their behalf. The whiteboard can help to accomplish that and to visually indicate “reflective listening.” If I ask patients what their concerns and goals are on a daily basis, I can better address them, and writing those on the whiteboard is a way to visually let patients know I have heard them—and heard them accurately. Finally, as we know from experience at our institution, when patients are invited to write on the whiteboard, they are likely to do so and will often write important information that hasn’t come up during routine rounding.
How I Do It
The key to effectiveness is to build whiteboard use into the clinical workflow and patient conversation rather than create an extra task to complete. I have developed a routine using the whiteboard that is more or less the same for every patient.
Also, whiteboard design can influence the use of the whiteboard as a communication tool. I favor designs that have few prescriptive boxes and more space for writing. I have found whiteboards labeled with a “What are your goals?” section to be helpful.
Patrick Kneeland, MD, is medical director for patient and provider experience and director of the Excellence in Communication Curriculum, University of Colorado Hospital and Clinics.
Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”
View a chart outlining key communication tactics
What I Say and Do
With my team, I use whiteboards as a tool to enhance communication: 1) I introduce myself and my team members, then write our names on the whiteboard paired with an explanation of my role as the attending physician for the hospital medicine service; 2) on a daily basis, I ask the patient and family/support what their primary concerns and goals are and write those on the whiteboard; and 3) I invite the patient and family/support to use the whiteboard to write additional concerns or questions as they arise.
Why I Do It
Hospitals are confusing places. One of our key roles as hospitalists is to coordinate and clarify all of the moving pieces and to communicate clearly to patients and their family that there is someone doing that work on their behalf. The whiteboard can help to accomplish that and to visually indicate “reflective listening.” If I ask patients what their concerns and goals are on a daily basis, I can better address them, and writing those on the whiteboard is a way to visually let patients know I have heard them—and heard them accurately. Finally, as we know from experience at our institution, when patients are invited to write on the whiteboard, they are likely to do so and will often write important information that hasn’t come up during routine rounding.
How I Do It
The key to effectiveness is to build whiteboard use into the clinical workflow and patient conversation rather than create an extra task to complete. I have developed a routine using the whiteboard that is more or less the same for every patient.
Also, whiteboard design can influence the use of the whiteboard as a communication tool. I favor designs that have few prescriptive boxes and more space for writing. I have found whiteboards labeled with a “What are your goals?” section to be helpful.
Patrick Kneeland, MD, is medical director for patient and provider experience and director of the Excellence in Communication Curriculum, University of Colorado Hospital and Clinics.
Editor’s note: “Everything We Say and Do” is an informational series developed by SHM’s Patient Experience Committee to provide readers with thoughtful and actionable communication tactics that have great potential to positively impact patients’ experience of care. Each article will focus on how the contributor applies one or more of the “key communication” tactics in practice to maintain provider accountability for “everything we say and do that affects our patients’ thoughts, feelings, and well-being.”
View a chart outlining key communication tactics
What I Say and Do
With my team, I use whiteboards as a tool to enhance communication: 1) I introduce myself and my team members, then write our names on the whiteboard paired with an explanation of my role as the attending physician for the hospital medicine service; 2) on a daily basis, I ask the patient and family/support what their primary concerns and goals are and write those on the whiteboard; and 3) I invite the patient and family/support to use the whiteboard to write additional concerns or questions as they arise.
Why I Do It
Hospitals are confusing places. One of our key roles as hospitalists is to coordinate and clarify all of the moving pieces and to communicate clearly to patients and their family that there is someone doing that work on their behalf. The whiteboard can help to accomplish that and to visually indicate “reflective listening.” If I ask patients what their concerns and goals are on a daily basis, I can better address them, and writing those on the whiteboard is a way to visually let patients know I have heard them—and heard them accurately. Finally, as we know from experience at our institution, when patients are invited to write on the whiteboard, they are likely to do so and will often write important information that hasn’t come up during routine rounding.
How I Do It
The key to effectiveness is to build whiteboard use into the clinical workflow and patient conversation rather than create an extra task to complete. I have developed a routine using the whiteboard that is more or less the same for every patient.
Also, whiteboard design can influence the use of the whiteboard as a communication tool. I favor designs that have few prescriptive boxes and more space for writing. I have found whiteboards labeled with a “What are your goals?” section to be helpful.
Patrick Kneeland, MD, is medical director for patient and provider experience and director of the Excellence in Communication Curriculum, University of Colorado Hospital and Clinics.
New SHM Members – November 2016
F. W. Erdman, Alabama
S. Baquai, MD, California
J. Bullock, California
A. Chong, MD, California
J. Decolongon, California
J. Do, MD, California
T. Farmer, ACNP, California
T. Holden, MD, California
M. Khare, California
P. Lally, MD, California
B. Lee, MD, California
J. Lee, MD, California
A. Mannan, MD, California
N. Pandher, California
E. Park, CaliforniaB. Patel, USA, California
N. Patel, California
S. Singh, MD, California
M. Vakili, California
A. Zandpour, AHIP, California
L. Chong, MD, FACP, Connecticut
G. Cudjoe, MBBS, Connecticut
S. Gazi, MD, Connecticut
S. Pattisapu, Connecticut
M. Rai, Connecticut
S. Roshan, MD, Connecticut
A. Seye, MD, Connecticut
L. Zheng, Connecticut
S. Raghavan, MD, PhD, Colorado
M. Altieri, MHSc, PA-C, Florida
M. Bishai, DO, Florida
B. Burns, Florida
A. Chan, MD, Florida
M. Cuk, Florida
S. Epps, DO, Florida
N. Fedotova, PhD, Florida
A. Lee, MD, Florida
M. Ruiz, Florida
D. Britt, Georgia
W. Futch, Georgia
B. Kruszewski, Georgia
I. Lowell, MD, MBA, Georgia
Y. Patel, MD, Georgia
G. Polk-Seldon, FNP, Georgia
T. Truong, MD, Georgia
J. Walker, DO, Georgia
S. Wang, MBA, Georgia
S. Del Mundo, Hawaii
T. Hiura, MD, Hawaii
D. Orchard, Idaho
S. Pontickio, MD, Idaho
R. Antoine, MD, Illinois
A. Baid, Illinois
C. Boyle, MD, Illinois
M. Delibasic, MD, Illinois
J. Gemson, Illinois
J. Mechurova, MD, Illinois
T. Morales, Illinois
H. Omar, Illinois
B. Pathak, MD, Illinois
S. Rao, MD, Illinois
Z. Ritchey, Illinois
A. Veerabahu, Illinois
T. Barley, MD, Indiana
M. Meyer, ACNP, MSN, Indiana
D. Ross, MA, Indiana
K. Sorg, MD, Indiana
A. Evans, Iowa
R. Miller, MD, Louisiana
D. Pollet, MD, Louisiana
J. Goldberg, MD, Maine
S. Gutierrez, MD, Maine
K. Osborne, FNP, Maine
V. Pramanik, MD, Maine
C. Sherpa, Maine
H. Abinader, Maryland
I. Pena, Maryland
D. Press, MD, Maryland
D. Soffer, Maryland
J. Bennett, FAAP, Massachusetts
N. Howe, ACNP, Massachusetts
J. Hudspeth, MD, Massachusetts
I. Ismail, MD, Massachusetts
B. Lall, MD, Massachusetts
M. Lawler, MD, Massachusetts
E. O’Fallon, MD, Massachusetts
J. Ringwala, Massachusetts
M. Soe, MD, Massachusetts
E. Sweatt, MD, Massachusetts
M. Trivedi, Massachusetts
E. Chappe, MD, Michigan
A. Goyal, MD, Michigan
E. Hunter, DO, Michigan
S. Malewskim ACNP, MSN, RN, Michigan
W. Ladner, Minnesota
J. Purdy, Minnesota
T. VanLith, PA-C, Minnesota
P. Acharya, MBBS, Mississippi
A. Ladd, CNP, Mississippi
S. Morris, DO, MBA, Mississippi
R. Walters, DO, Mississippi
R. Allen, DO, Missouri
L. Andrea, MissouriA. Arnaud, Missouri
M. Board, Missouri
S. Njagi, MD, FAAFP, MBchB, Missouri
J. Patel, Missouri
A. Roman, MD, Missouri
R. Singh, Missouri
F. Wang, Missouri
S. Byington, MD, Montana
T. Lloyd, Montana
B. Bulian, MD, Nebraska
S. Adagi, New Jersey
C. Cristescu, MeD, New Jersey
A. Malhotra, MD, New Jersey
K. Patel, DO, New Jersey
S. Terner, MD, New Jersey
H. Alqam, New Mexico
A. Attreya, DO, New Mexico
K. Avila, New Mexico
K. Chan, New Mexico
S. Montano, New Mexico
C. Morales, New Mexico
A. Stecker, New Mexico
D. Varela, New Mexico
M. Ahmed, MD, New York
G. Apergis, MD, New York
J. Dekhtyar, MD, New York
J. Dillon, New York
N. Jaglall, MD, New YorkL. Kruzhkov, New York
R. Malhan, MD, New York
J. Mathew, New YorkV. Miro, New York
B. Gautam, North Carolina
K. Gold, MD, North Carolina P. Greene, MD, North Carolina
S. Grotzke, North Carolina
S. Hester, MD, North Carolina
P. Le, MD, North Carolina
J. McClung, MD, North Carolina
J. Ramsey, MD, North Carolina
J. Sullivan, DO, North Carolina
C. Chadwell, Ohio
R. Dash, MD, Ohio
E. Ofungwu, USAR, Ohio
R. Raj, MD, Ohio
I. Rawal, Ohio
N. Beach, DO, Oregon
M. Christensen, ACNP, Oregon
K. Haugen, MD, Oregon
J. Luty, MD, Oregon
K. Andersen, Pennsylvania
O. Ball, MD, Pennsylvania
S. Harris, DO, Pennsylvania
R. Koubek, Pennsylvania
B. Krug, MHA, Pennsylvania
A. Levin, MD, Pennsylvania
A. Marwah, Pennsylvania
D. McAllister, FNP, Pennsylvania
C. Sakosky, FNP, Pennsylvania
J. Steffl, PA-C, Pennsylvania
A. Sukits, MS, PA-C, Pennsylvania
S. Clemens, Rhode Island
C. Drasny, MD, South Carolina
J. Harris, MD, South Carolina
D. Head, MD, South Carolina
S. Johnson, South Carolina
A. Evjen, MD, South Dakota
P. Pate, Tennessee
J. Patterson, ACNP-BC, MSN, Tennessee
A. Seth, MD, Tennessee
P. Boeckmann, FACHE, Texas
M. Gupta, Texas
J. Jain, MD, Texas
K. Roberts, Texas
C. Romero, MD, PhD, Texas
D. Buzanoski, MD, Utah
N. Whitaker, FACP, Utah
E. Greenberger, MD, Vermont
R. McEntee, MD, Vermont
C. Rickman, FACP, Vermont
W. Austin, MSHA, Virginia
E. Orshansky, MD, Virginia
G. Psarros, MD, Virginia
N. Trivedi, Virginia
E. Addison, Washington
J. Gifford, PA-C, Washington
V. Johnson, ARNP, CFNP, MHSc, Washington
C. Wang, MD, Washington
M. Brown, West Virginia
V. Raina, MD, Wisconsin
F. Germa, MD, CCP(EM), FCEP (C), Canada
J. Podavin, Canada
K. Slatkovsky, Canada
M. Kitamura, Japan
M. Rafei, Oman
F. W. Erdman, Alabama
S. Baquai, MD, California
J. Bullock, California
A. Chong, MD, California
J. Decolongon, California
J. Do, MD, California
T. Farmer, ACNP, California
T. Holden, MD, California
M. Khare, California
P. Lally, MD, California
B. Lee, MD, California
J. Lee, MD, California
A. Mannan, MD, California
N. Pandher, California
E. Park, CaliforniaB. Patel, USA, California
N. Patel, California
S. Singh, MD, California
M. Vakili, California
A. Zandpour, AHIP, California
L. Chong, MD, FACP, Connecticut
G. Cudjoe, MBBS, Connecticut
S. Gazi, MD, Connecticut
S. Pattisapu, Connecticut
M. Rai, Connecticut
S. Roshan, MD, Connecticut
A. Seye, MD, Connecticut
L. Zheng, Connecticut
S. Raghavan, MD, PhD, Colorado
M. Altieri, MHSc, PA-C, Florida
M. Bishai, DO, Florida
B. Burns, Florida
A. Chan, MD, Florida
M. Cuk, Florida
S. Epps, DO, Florida
N. Fedotova, PhD, Florida
A. Lee, MD, Florida
M. Ruiz, Florida
D. Britt, Georgia
W. Futch, Georgia
B. Kruszewski, Georgia
I. Lowell, MD, MBA, Georgia
Y. Patel, MD, Georgia
G. Polk-Seldon, FNP, Georgia
T. Truong, MD, Georgia
J. Walker, DO, Georgia
S. Wang, MBA, Georgia
S. Del Mundo, Hawaii
T. Hiura, MD, Hawaii
D. Orchard, Idaho
S. Pontickio, MD, Idaho
R. Antoine, MD, Illinois
A. Baid, Illinois
C. Boyle, MD, Illinois
M. Delibasic, MD, Illinois
J. Gemson, Illinois
J. Mechurova, MD, Illinois
T. Morales, Illinois
H. Omar, Illinois
B. Pathak, MD, Illinois
S. Rao, MD, Illinois
Z. Ritchey, Illinois
A. Veerabahu, Illinois
T. Barley, MD, Indiana
M. Meyer, ACNP, MSN, Indiana
D. Ross, MA, Indiana
K. Sorg, MD, Indiana
A. Evans, Iowa
R. Miller, MD, Louisiana
D. Pollet, MD, Louisiana
J. Goldberg, MD, Maine
S. Gutierrez, MD, Maine
K. Osborne, FNP, Maine
V. Pramanik, MD, Maine
C. Sherpa, Maine
H. Abinader, Maryland
I. Pena, Maryland
D. Press, MD, Maryland
D. Soffer, Maryland
J. Bennett, FAAP, Massachusetts
N. Howe, ACNP, Massachusetts
J. Hudspeth, MD, Massachusetts
I. Ismail, MD, Massachusetts
B. Lall, MD, Massachusetts
M. Lawler, MD, Massachusetts
E. O’Fallon, MD, Massachusetts
J. Ringwala, Massachusetts
M. Soe, MD, Massachusetts
E. Sweatt, MD, Massachusetts
M. Trivedi, Massachusetts
E. Chappe, MD, Michigan
A. Goyal, MD, Michigan
E. Hunter, DO, Michigan
S. Malewskim ACNP, MSN, RN, Michigan
W. Ladner, Minnesota
J. Purdy, Minnesota
T. VanLith, PA-C, Minnesota
P. Acharya, MBBS, Mississippi
A. Ladd, CNP, Mississippi
S. Morris, DO, MBA, Mississippi
R. Walters, DO, Mississippi
R. Allen, DO, Missouri
L. Andrea, MissouriA. Arnaud, Missouri
M. Board, Missouri
S. Njagi, MD, FAAFP, MBchB, Missouri
J. Patel, Missouri
A. Roman, MD, Missouri
R. Singh, Missouri
F. Wang, Missouri
S. Byington, MD, Montana
T. Lloyd, Montana
B. Bulian, MD, Nebraska
S. Adagi, New Jersey
C. Cristescu, MeD, New Jersey
A. Malhotra, MD, New Jersey
K. Patel, DO, New Jersey
S. Terner, MD, New Jersey
H. Alqam, New Mexico
A. Attreya, DO, New Mexico
K. Avila, New Mexico
K. Chan, New Mexico
S. Montano, New Mexico
C. Morales, New Mexico
A. Stecker, New Mexico
D. Varela, New Mexico
M. Ahmed, MD, New York
G. Apergis, MD, New York
J. Dekhtyar, MD, New York
J. Dillon, New York
N. Jaglall, MD, New YorkL. Kruzhkov, New York
R. Malhan, MD, New York
J. Mathew, New YorkV. Miro, New York
B. Gautam, North Carolina
K. Gold, MD, North Carolina P. Greene, MD, North Carolina
S. Grotzke, North Carolina
S. Hester, MD, North Carolina
P. Le, MD, North Carolina
J. McClung, MD, North Carolina
J. Ramsey, MD, North Carolina
J. Sullivan, DO, North Carolina
C. Chadwell, Ohio
R. Dash, MD, Ohio
E. Ofungwu, USAR, Ohio
R. Raj, MD, Ohio
I. Rawal, Ohio
N. Beach, DO, Oregon
M. Christensen, ACNP, Oregon
K. Haugen, MD, Oregon
J. Luty, MD, Oregon
K. Andersen, Pennsylvania
O. Ball, MD, Pennsylvania
S. Harris, DO, Pennsylvania
R. Koubek, Pennsylvania
B. Krug, MHA, Pennsylvania
A. Levin, MD, Pennsylvania
A. Marwah, Pennsylvania
D. McAllister, FNP, Pennsylvania
C. Sakosky, FNP, Pennsylvania
J. Steffl, PA-C, Pennsylvania
A. Sukits, MS, PA-C, Pennsylvania
S. Clemens, Rhode Island
C. Drasny, MD, South Carolina
J. Harris, MD, South Carolina
D. Head, MD, South Carolina
S. Johnson, South Carolina
A. Evjen, MD, South Dakota
P. Pate, Tennessee
J. Patterson, ACNP-BC, MSN, Tennessee
A. Seth, MD, Tennessee
P. Boeckmann, FACHE, Texas
M. Gupta, Texas
J. Jain, MD, Texas
K. Roberts, Texas
C. Romero, MD, PhD, Texas
D. Buzanoski, MD, Utah
N. Whitaker, FACP, Utah
E. Greenberger, MD, Vermont
R. McEntee, MD, Vermont
C. Rickman, FACP, Vermont
W. Austin, MSHA, Virginia
E. Orshansky, MD, Virginia
G. Psarros, MD, Virginia
N. Trivedi, Virginia
E. Addison, Washington
J. Gifford, PA-C, Washington
V. Johnson, ARNP, CFNP, MHSc, Washington
C. Wang, MD, Washington
M. Brown, West Virginia
V. Raina, MD, Wisconsin
F. Germa, MD, CCP(EM), FCEP (C), Canada
J. Podavin, Canada
K. Slatkovsky, Canada
M. Kitamura, Japan
M. Rafei, Oman
F. W. Erdman, Alabama
S. Baquai, MD, California
J. Bullock, California
A. Chong, MD, California
J. Decolongon, California
J. Do, MD, California
T. Farmer, ACNP, California
T. Holden, MD, California
M. Khare, California
P. Lally, MD, California
B. Lee, MD, California
J. Lee, MD, California
A. Mannan, MD, California
N. Pandher, California
E. Park, CaliforniaB. Patel, USA, California
N. Patel, California
S. Singh, MD, California
M. Vakili, California
A. Zandpour, AHIP, California
L. Chong, MD, FACP, Connecticut
G. Cudjoe, MBBS, Connecticut
S. Gazi, MD, Connecticut
S. Pattisapu, Connecticut
M. Rai, Connecticut
S. Roshan, MD, Connecticut
A. Seye, MD, Connecticut
L. Zheng, Connecticut
S. Raghavan, MD, PhD, Colorado
M. Altieri, MHSc, PA-C, Florida
M. Bishai, DO, Florida
B. Burns, Florida
A. Chan, MD, Florida
M. Cuk, Florida
S. Epps, DO, Florida
N. Fedotova, PhD, Florida
A. Lee, MD, Florida
M. Ruiz, Florida
D. Britt, Georgia
W. Futch, Georgia
B. Kruszewski, Georgia
I. Lowell, MD, MBA, Georgia
Y. Patel, MD, Georgia
G. Polk-Seldon, FNP, Georgia
T. Truong, MD, Georgia
J. Walker, DO, Georgia
S. Wang, MBA, Georgia
S. Del Mundo, Hawaii
T. Hiura, MD, Hawaii
D. Orchard, Idaho
S. Pontickio, MD, Idaho
R. Antoine, MD, Illinois
A. Baid, Illinois
C. Boyle, MD, Illinois
M. Delibasic, MD, Illinois
J. Gemson, Illinois
J. Mechurova, MD, Illinois
T. Morales, Illinois
H. Omar, Illinois
B. Pathak, MD, Illinois
S. Rao, MD, Illinois
Z. Ritchey, Illinois
A. Veerabahu, Illinois
T. Barley, MD, Indiana
M. Meyer, ACNP, MSN, Indiana
D. Ross, MA, Indiana
K. Sorg, MD, Indiana
A. Evans, Iowa
R. Miller, MD, Louisiana
D. Pollet, MD, Louisiana
J. Goldberg, MD, Maine
S. Gutierrez, MD, Maine
K. Osborne, FNP, Maine
V. Pramanik, MD, Maine
C. Sherpa, Maine
H. Abinader, Maryland
I. Pena, Maryland
D. Press, MD, Maryland
D. Soffer, Maryland
J. Bennett, FAAP, Massachusetts
N. Howe, ACNP, Massachusetts
J. Hudspeth, MD, Massachusetts
I. Ismail, MD, Massachusetts
B. Lall, MD, Massachusetts
M. Lawler, MD, Massachusetts
E. O’Fallon, MD, Massachusetts
J. Ringwala, Massachusetts
M. Soe, MD, Massachusetts
E. Sweatt, MD, Massachusetts
M. Trivedi, Massachusetts
E. Chappe, MD, Michigan
A. Goyal, MD, Michigan
E. Hunter, DO, Michigan
S. Malewskim ACNP, MSN, RN, Michigan
W. Ladner, Minnesota
J. Purdy, Minnesota
T. VanLith, PA-C, Minnesota
P. Acharya, MBBS, Mississippi
A. Ladd, CNP, Mississippi
S. Morris, DO, MBA, Mississippi
R. Walters, DO, Mississippi
R. Allen, DO, Missouri
L. Andrea, MissouriA. Arnaud, Missouri
M. Board, Missouri
S. Njagi, MD, FAAFP, MBchB, Missouri
J. Patel, Missouri
A. Roman, MD, Missouri
R. Singh, Missouri
F. Wang, Missouri
S. Byington, MD, Montana
T. Lloyd, Montana
B. Bulian, MD, Nebraska
S. Adagi, New Jersey
C. Cristescu, MeD, New Jersey
A. Malhotra, MD, New Jersey
K. Patel, DO, New Jersey
S. Terner, MD, New Jersey
H. Alqam, New Mexico
A. Attreya, DO, New Mexico
K. Avila, New Mexico
K. Chan, New Mexico
S. Montano, New Mexico
C. Morales, New Mexico
A. Stecker, New Mexico
D. Varela, New Mexico
M. Ahmed, MD, New York
G. Apergis, MD, New York
J. Dekhtyar, MD, New York
J. Dillon, New York
N. Jaglall, MD, New YorkL. Kruzhkov, New York
R. Malhan, MD, New York
J. Mathew, New YorkV. Miro, New York
B. Gautam, North Carolina
K. Gold, MD, North Carolina P. Greene, MD, North Carolina
S. Grotzke, North Carolina
S. Hester, MD, North Carolina
P. Le, MD, North Carolina
J. McClung, MD, North Carolina
J. Ramsey, MD, North Carolina
J. Sullivan, DO, North Carolina
C. Chadwell, Ohio
R. Dash, MD, Ohio
E. Ofungwu, USAR, Ohio
R. Raj, MD, Ohio
I. Rawal, Ohio
N. Beach, DO, Oregon
M. Christensen, ACNP, Oregon
K. Haugen, MD, Oregon
J. Luty, MD, Oregon
K. Andersen, Pennsylvania
O. Ball, MD, Pennsylvania
S. Harris, DO, Pennsylvania
R. Koubek, Pennsylvania
B. Krug, MHA, Pennsylvania
A. Levin, MD, Pennsylvania
A. Marwah, Pennsylvania
D. McAllister, FNP, Pennsylvania
C. Sakosky, FNP, Pennsylvania
J. Steffl, PA-C, Pennsylvania
A. Sukits, MS, PA-C, Pennsylvania
S. Clemens, Rhode Island
C. Drasny, MD, South Carolina
J. Harris, MD, South Carolina
D. Head, MD, South Carolina
S. Johnson, South Carolina
A. Evjen, MD, South Dakota
P. Pate, Tennessee
J. Patterson, ACNP-BC, MSN, Tennessee
A. Seth, MD, Tennessee
P. Boeckmann, FACHE, Texas
M. Gupta, Texas
J. Jain, MD, Texas
K. Roberts, Texas
C. Romero, MD, PhD, Texas
D. Buzanoski, MD, Utah
N. Whitaker, FACP, Utah
E. Greenberger, MD, Vermont
R. McEntee, MD, Vermont
C. Rickman, FACP, Vermont
W. Austin, MSHA, Virginia
E. Orshansky, MD, Virginia
G. Psarros, MD, Virginia
N. Trivedi, Virginia
E. Addison, Washington
J. Gifford, PA-C, Washington
V. Johnson, ARNP, CFNP, MHSc, Washington
C. Wang, MD, Washington
M. Brown, West Virginia
V. Raina, MD, Wisconsin
F. Germa, MD, CCP(EM), FCEP (C), Canada
J. Podavin, Canada
K. Slatkovsky, Canada
M. Kitamura, Japan
M. Rafei, Oman
Preventive Treatment for Posttraumatic Stress Disorder
Identifying people who might be at risk for posttraumatic stress disorder (PTSD) before the trauma—and teaching them preventive coping skills—could reduce or prevent long-term effects, according to University of Oxford in Oxford, United Kingdom, and King’s College London, United Kingdom, researchers.
They assessed 453 newly recruited paramedics every 4 months for 2 years. Of those, 386 paramedics participated in follow-up interviews.
Related: Let’s Dance: A Holistic Approach to Treating Veterans With Posttraumatic Stress Disorder
Over the 2 years, 32 participants (8.3%) had an episode of PTSD, and 41 participants had (10.6%) an episode of major depression (MD). Most of the episodes were moderate and short lived. In most cases, the participant had recovered by the next 4-month assessment. However, at 2 years, those who had experienced episodes of PTSD or MD during the follow-up period reported more days off work, poorer sleep, poorer quality of life, and greater burn out as well as weight gain (mean gain, 6.9 kg) for those with P
Ten participants who developed PTSD received treatment during follow-up, as did 12 participants who developed MD. Five of 9 participants who had recurrent P
Related: Telehealth for Native Americans With PTSD
The researchers tested a number of possible pretrauma predictors of PTSD and MD. They correlated several: cognitive style (eg, suppression, rumination, intentional numbing), coping style (eg, avoidant styles, such as wishful thinking), and psychological traits (eg, neuroticism). However, they found rumination about memories of stressful events uniquely predicted an episode of PTSD. Perceived resilience uniquely predicted an episode of MD.
Interestingly, about 42% of the study participants had a psychiatric history before training—more than the general population. That might be a factor that draws them to emergency work, the researchers suggest.
Some predictors, such as psychiatric history, are fixed, the researchers note. But others, such as cognitive styles, can be modified or taught. Studies have shown that rumination can be redirected through training in concrete thinking, for instance, and psychoeducation and cognitive behavioral techniques (eg, modifying interpretations of stressful events) have been used to strengthen resilience. The predictors they identified in their study could serve as targets, the researchers suggest, for modifying future resilience programs.
Source:
Wild J, Smith KV, Thompson E, Béar F, Lommen MJ, Ehlers A. Psychol Med. 2016;46(12):2571-2582. doi: 10.1017/S0033291716000532.
Identifying people who might be at risk for posttraumatic stress disorder (PTSD) before the trauma—and teaching them preventive coping skills—could reduce or prevent long-term effects, according to University of Oxford in Oxford, United Kingdom, and King’s College London, United Kingdom, researchers.
They assessed 453 newly recruited paramedics every 4 months for 2 years. Of those, 386 paramedics participated in follow-up interviews.
Related: Let’s Dance: A Holistic Approach to Treating Veterans With Posttraumatic Stress Disorder
Over the 2 years, 32 participants (8.3%) had an episode of PTSD, and 41 participants had (10.6%) an episode of major depression (MD). Most of the episodes were moderate and short lived. In most cases, the participant had recovered by the next 4-month assessment. However, at 2 years, those who had experienced episodes of PTSD or MD during the follow-up period reported more days off work, poorer sleep, poorer quality of life, and greater burn out as well as weight gain (mean gain, 6.9 kg) for those with P
Ten participants who developed PTSD received treatment during follow-up, as did 12 participants who developed MD. Five of 9 participants who had recurrent P
Related: Telehealth for Native Americans With PTSD
The researchers tested a number of possible pretrauma predictors of PTSD and MD. They correlated several: cognitive style (eg, suppression, rumination, intentional numbing), coping style (eg, avoidant styles, such as wishful thinking), and psychological traits (eg, neuroticism). However, they found rumination about memories of stressful events uniquely predicted an episode of PTSD. Perceived resilience uniquely predicted an episode of MD.
Interestingly, about 42% of the study participants had a psychiatric history before training—more than the general population. That might be a factor that draws them to emergency work, the researchers suggest.
Some predictors, such as psychiatric history, are fixed, the researchers note. But others, such as cognitive styles, can be modified or taught. Studies have shown that rumination can be redirected through training in concrete thinking, for instance, and psychoeducation and cognitive behavioral techniques (eg, modifying interpretations of stressful events) have been used to strengthen resilience. The predictors they identified in their study could serve as targets, the researchers suggest, for modifying future resilience programs.
Source:
Wild J, Smith KV, Thompson E, Béar F, Lommen MJ, Ehlers A. Psychol Med. 2016;46(12):2571-2582. doi: 10.1017/S0033291716000532.
Identifying people who might be at risk for posttraumatic stress disorder (PTSD) before the trauma—and teaching them preventive coping skills—could reduce or prevent long-term effects, according to University of Oxford in Oxford, United Kingdom, and King’s College London, United Kingdom, researchers.
They assessed 453 newly recruited paramedics every 4 months for 2 years. Of those, 386 paramedics participated in follow-up interviews.
Related: Let’s Dance: A Holistic Approach to Treating Veterans With Posttraumatic Stress Disorder
Over the 2 years, 32 participants (8.3%) had an episode of PTSD, and 41 participants had (10.6%) an episode of major depression (MD). Most of the episodes were moderate and short lived. In most cases, the participant had recovered by the next 4-month assessment. However, at 2 years, those who had experienced episodes of PTSD or MD during the follow-up period reported more days off work, poorer sleep, poorer quality of life, and greater burn out as well as weight gain (mean gain, 6.9 kg) for those with P
Ten participants who developed PTSD received treatment during follow-up, as did 12 participants who developed MD. Five of 9 participants who had recurrent P
Related: Telehealth for Native Americans With PTSD
The researchers tested a number of possible pretrauma predictors of PTSD and MD. They correlated several: cognitive style (eg, suppression, rumination, intentional numbing), coping style (eg, avoidant styles, such as wishful thinking), and psychological traits (eg, neuroticism). However, they found rumination about memories of stressful events uniquely predicted an episode of PTSD. Perceived resilience uniquely predicted an episode of MD.
Interestingly, about 42% of the study participants had a psychiatric history before training—more than the general population. That might be a factor that draws them to emergency work, the researchers suggest.
Some predictors, such as psychiatric history, are fixed, the researchers note. But others, such as cognitive styles, can be modified or taught. Studies have shown that rumination can be redirected through training in concrete thinking, for instance, and psychoeducation and cognitive behavioral techniques (eg, modifying interpretations of stressful events) have been used to strengthen resilience. The predictors they identified in their study could serve as targets, the researchers suggest, for modifying future resilience programs.
Source:
Wild J, Smith KV, Thompson E, Béar F, Lommen MJ, Ehlers A. Psychol Med. 2016;46(12):2571-2582. doi: 10.1017/S0033291716000532.
Improving cognitive function in cancer survivors
chemotherapy
Photo by Rhoda Baer
A new study suggests a computer program known as InsightTM may help improve cognitive function and overall well-being in cancer survivors.
The study included subjects who reported persistent problems with concentration and/or memory after receiving chemotherapy.
Using the Insight program significantly improved the subjects’ self-reported cognitive function and lowered their levels of anxiety, depression, fatigue, and stress.
However, there was no significant difference in the results of objective neuropsychological function tests between subjects who used the Insight program and subjects who received standard care.
These results were published in the Journal of Clinical Oncology.
“To the best of our knowledge, this is the largest cognitive intervention study that has shown a benefit for patients who are reporting persistent cognitive symptoms following chemotherapy,” said study author Victoria J. Bray, MD, of the University of Sydney in Australia.
About the study
Dr Bray and her colleagues enrolled 242 adult cancer survivors in Australia who had completed at least 3 cycles of chemotherapy in the prior 6 months to 60 months and reported persistent cognitive symptoms.
The subjects’ median age was 53 (range, 23 to 74). Nearly all were women (95%), and 89% had survived breast cancer.
At the beginning of the study, all subjects received a personalized, 30-minute telephone consultation that provided tips and strategies for coping with cognitive problems in daily life.
Subjects were then randomized to Insight (used at home) or standard oncology care per their treating physician.
The primary outcome of the study was self-reported cognitive function, which was assessed using a validated questionnaire known as FACT-COG. It evaluates perceived cognitive impairments, perceived cognitive abilities, and the impact of perceived cognitive impairment on quality of life.
Separate measures were used to evaluate objective neuropsychological function, anxiety/depression, fatigue, and stress.
About the intervention
Dr Bray and her colleagues described Insight as a neurocognitive learning program that uses exercises intended to improve cognition through speed and accuracy of information processing.
The program targets visual precision, divided attention, working memory, field of view, and visual processing speed, which are frequently affected in patients with cancer.
Subjects received the Insight program in disc form and were advised to use the program for 40 minutes 4 times a week for 15 weeks (40 hours total). The program had a built-in measure that could determine subjects’ compliance.
Key findings
Self-reported cognitive function was significantly better in the Insight group than the standard care group, both at the end of the 15-week program and 6 months later.
In addition, Insight participants had significantly lower levels of anxiety, depression, and fatigue immediately after the intervention, significant improvements in quality of life at 6 months, and significant improvements in stress at both time points.
Results of objective neuropsychological function tests were not significantly different between the Insight group and the standard care group, either immediately after the intervention or at 6 months.
Next steps
The researchers said longer follow-up is needed to determine if the effects of the Insight program are long-lasting. And there are still a number of other unanswered questions to be addressed in future research.
For one, it is unclear which method of delivering cognitive rehabilitation is better. A self-directed program such as this one may be suitable for some cancer survivors, while a group-based program may work better for others. It’s also unclear what the ideal duration and “dose” of cognitive training should be.
“If we could identify patients who are at risk of cognitive impairment, we could intervene earlier and possibly achieve even better results,” Dr Bray said. “We would also like to explore whether there is added benefit from combining cognitive training with physical exercise.” 
chemotherapy
Photo by Rhoda Baer
A new study suggests a computer program known as InsightTM may help improve cognitive function and overall well-being in cancer survivors.
The study included subjects who reported persistent problems with concentration and/or memory after receiving chemotherapy.
Using the Insight program significantly improved the subjects’ self-reported cognitive function and lowered their levels of anxiety, depression, fatigue, and stress.
However, there was no significant difference in the results of objective neuropsychological function tests between subjects who used the Insight program and subjects who received standard care.
These results were published in the Journal of Clinical Oncology.
“To the best of our knowledge, this is the largest cognitive intervention study that has shown a benefit for patients who are reporting persistent cognitive symptoms following chemotherapy,” said study author Victoria J. Bray, MD, of the University of Sydney in Australia.
About the study
Dr Bray and her colleagues enrolled 242 adult cancer survivors in Australia who had completed at least 3 cycles of chemotherapy in the prior 6 months to 60 months and reported persistent cognitive symptoms.
The subjects’ median age was 53 (range, 23 to 74). Nearly all were women (95%), and 89% had survived breast cancer.
At the beginning of the study, all subjects received a personalized, 30-minute telephone consultation that provided tips and strategies for coping with cognitive problems in daily life.
Subjects were then randomized to Insight (used at home) or standard oncology care per their treating physician.
The primary outcome of the study was self-reported cognitive function, which was assessed using a validated questionnaire known as FACT-COG. It evaluates perceived cognitive impairments, perceived cognitive abilities, and the impact of perceived cognitive impairment on quality of life.
Separate measures were used to evaluate objective neuropsychological function, anxiety/depression, fatigue, and stress.
About the intervention
Dr Bray and her colleagues described Insight as a neurocognitive learning program that uses exercises intended to improve cognition through speed and accuracy of information processing.
The program targets visual precision, divided attention, working memory, field of view, and visual processing speed, which are frequently affected in patients with cancer.
Subjects received the Insight program in disc form and were advised to use the program for 40 minutes 4 times a week for 15 weeks (40 hours total). The program had a built-in measure that could determine subjects’ compliance.
Key findings
Self-reported cognitive function was significantly better in the Insight group than the standard care group, both at the end of the 15-week program and 6 months later.
In addition, Insight participants had significantly lower levels of anxiety, depression, and fatigue immediately after the intervention, significant improvements in quality of life at 6 months, and significant improvements in stress at both time points.
Results of objective neuropsychological function tests were not significantly different between the Insight group and the standard care group, either immediately after the intervention or at 6 months.
Next steps
The researchers said longer follow-up is needed to determine if the effects of the Insight program are long-lasting. And there are still a number of other unanswered questions to be addressed in future research.
For one, it is unclear which method of delivering cognitive rehabilitation is better. A self-directed program such as this one may be suitable for some cancer survivors, while a group-based program may work better for others. It’s also unclear what the ideal duration and “dose” of cognitive training should be.
“If we could identify patients who are at risk of cognitive impairment, we could intervene earlier and possibly achieve even better results,” Dr Bray said. “We would also like to explore whether there is added benefit from combining cognitive training with physical exercise.”
chemotherapy
Photo by Rhoda Baer
A new study suggests a computer program known as InsightTM may help improve cognitive function and overall well-being in cancer survivors.
The study included subjects who reported persistent problems with concentration and/or memory after receiving chemotherapy.
Using the Insight program significantly improved the subjects’ self-reported cognitive function and lowered their levels of anxiety, depression, fatigue, and stress.
However, there was no significant difference in the results of objective neuropsychological function tests between subjects who used the Insight program and subjects who received standard care.
These results were published in the Journal of Clinical Oncology.
“To the best of our knowledge, this is the largest cognitive intervention study that has shown a benefit for patients who are reporting persistent cognitive symptoms following chemotherapy,” said study author Victoria J. Bray, MD, of the University of Sydney in Australia.
About the study
Dr Bray and her colleagues enrolled 242 adult cancer survivors in Australia who had completed at least 3 cycles of chemotherapy in the prior 6 months to 60 months and reported persistent cognitive symptoms.
The subjects’ median age was 53 (range, 23 to 74). Nearly all were women (95%), and 89% had survived breast cancer.
At the beginning of the study, all subjects received a personalized, 30-minute telephone consultation that provided tips and strategies for coping with cognitive problems in daily life.
Subjects were then randomized to Insight (used at home) or standard oncology care per their treating physician.
The primary outcome of the study was self-reported cognitive function, which was assessed using a validated questionnaire known as FACT-COG. It evaluates perceived cognitive impairments, perceived cognitive abilities, and the impact of perceived cognitive impairment on quality of life.
Separate measures were used to evaluate objective neuropsychological function, anxiety/depression, fatigue, and stress.
About the intervention
Dr Bray and her colleagues described Insight as a neurocognitive learning program that uses exercises intended to improve cognition through speed and accuracy of information processing.
The program targets visual precision, divided attention, working memory, field of view, and visual processing speed, which are frequently affected in patients with cancer.
Subjects received the Insight program in disc form and were advised to use the program for 40 minutes 4 times a week for 15 weeks (40 hours total). The program had a built-in measure that could determine subjects’ compliance.
Key findings
Self-reported cognitive function was significantly better in the Insight group than the standard care group, both at the end of the 15-week program and 6 months later.
In addition, Insight participants had significantly lower levels of anxiety, depression, and fatigue immediately after the intervention, significant improvements in quality of life at 6 months, and significant improvements in stress at both time points.
Results of objective neuropsychological function tests were not significantly different between the Insight group and the standard care group, either immediately after the intervention or at 6 months.
Next steps
The researchers said longer follow-up is needed to determine if the effects of the Insight program are long-lasting. And there are still a number of other unanswered questions to be addressed in future research.
For one, it is unclear which method of delivering cognitive rehabilitation is better. A self-directed program such as this one may be suitable for some cancer survivors, while a group-based program may work better for others. It’s also unclear what the ideal duration and “dose” of cognitive training should be.
“If we could identify patients who are at risk of cognitive impairment, we could intervene earlier and possibly achieve even better results,” Dr Bray said. “We would also like to explore whether there is added benefit from combining cognitive training with physical exercise.”
Team maps genomic landscape of CBF-AML
whole-genome sequencing
Photo courtesy of the US
Food and Drug Administration
Whole-genome and whole-exome sequencing has provided new insight into the pathogenesis and development of core-binding factor acute myeloid leukemia (CBF-AML), according to researchers.
The team said their work has revealed “dramatic” differences in the genomic landscape of CBF-AMLs that contribute to the diversity of this disease.
The researchers reported their findings in Nature Genetics.
“We set out to understand the genetic variations that contribute to the development of CBF-AML using whole-exome and whole-genome sequencing,” said study author Jeffery Klco, MD, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“Our goal was to define a detailed mutational landscape to understand better the genetic changes that contribute to disease.”
Dr Klco and his colleagues sequenced samples from 87 children and 78 adults with CBF-AML. Eighty-five of the patients had the RUNX1-RUNX1T1 subtype, and 80 had the CBFB-MYH11 subtype.
Development and relapse
The researchers identified several genes with mutations that may contribute to CBF-AML development, including CCND2, DHX15, ASXL2, ZBTB7A, and MGA.
“Many of the mutations we identified interfered with molecular signaling or epigenetic factors,” said study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.
“Some of the mutations, like ASXL2, are epigenetic regulators that modify the local state of chromatin,” Dr Klco noted. “Others, like ZBTB7A, appear to act like tumor suppressors.”
The researchers also compared mutations present at diagnosis and relapse in an attempt to understand how CBF-AML changes over time.
Their results suggested that KMT2C mutations are associated with relapse. Of the 4 patients in this study who had KMT2C mutations, 3 relapsed in less than 12 months, and the fourth had residual disease after a course of remission-induction therapy.
Similarities and differences
The researchers found a similar mutational landscape in adults and children with CBF-AML but differences between patients with the RUNX1-RUNX1T1 and CBFB-MYH11 subtypes.
NRAS was the most frequently mutated gene in CBF-AMLs, but NRAS mutations were more common in CBFB-MYH11 AML than RUNX1-RUNX1T1 AML. The same was true for mutations in NF1 and WT1.
Patients with both subtypes of CBF-AML had mutations in NRAS, KIT, NF1, WT1, FLT3, KRAS, MGA, TTN, CCND2, KDM6A, PHIP, TET2, HCN1, KMT2C, and SETD2.
But only patients with CBFB-MYH11 AML had mutations in PTPN11.
Only patients with RUNX1-RUNX1T1 AML had mutations in ASXL2, ZBTB7A, EZH2, SMC1A, DHX15, RAD21, CBL, DNM2, CSF3R, GIGYF2, SMC3, and ZNF687.
The researchers said their findings suggest a range of mutations may play roles in CBF-AML, but additional research is needed to confirm their precise function in the disease.
Further studies are already underway to fully evaluate the contributions of the different genes as well as the roles of the newly identified genetic alterations in CBF-AML.
whole-genome sequencing
Photo courtesy of the US
Food and Drug Administration
Whole-genome and whole-exome sequencing has provided new insight into the pathogenesis and development of core-binding factor acute myeloid leukemia (CBF-AML), according to researchers.
The team said their work has revealed “dramatic” differences in the genomic landscape of CBF-AMLs that contribute to the diversity of this disease.
The researchers reported their findings in Nature Genetics.
“We set out to understand the genetic variations that contribute to the development of CBF-AML using whole-exome and whole-genome sequencing,” said study author Jeffery Klco, MD, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“Our goal was to define a detailed mutational landscape to understand better the genetic changes that contribute to disease.”
Dr Klco and his colleagues sequenced samples from 87 children and 78 adults with CBF-AML. Eighty-five of the patients had the RUNX1-RUNX1T1 subtype, and 80 had the CBFB-MYH11 subtype.
Development and relapse
The researchers identified several genes with mutations that may contribute to CBF-AML development, including CCND2, DHX15, ASXL2, ZBTB7A, and MGA.
“Many of the mutations we identified interfered with molecular signaling or epigenetic factors,” said study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.
“Some of the mutations, like ASXL2, are epigenetic regulators that modify the local state of chromatin,” Dr Klco noted. “Others, like ZBTB7A, appear to act like tumor suppressors.”
The researchers also compared mutations present at diagnosis and relapse in an attempt to understand how CBF-AML changes over time.
Their results suggested that KMT2C mutations are associated with relapse. Of the 4 patients in this study who had KMT2C mutations, 3 relapsed in less than 12 months, and the fourth had residual disease after a course of remission-induction therapy.
Similarities and differences
The researchers found a similar mutational landscape in adults and children with CBF-AML but differences between patients with the RUNX1-RUNX1T1 and CBFB-MYH11 subtypes.
NRAS was the most frequently mutated gene in CBF-AMLs, but NRAS mutations were more common in CBFB-MYH11 AML than RUNX1-RUNX1T1 AML. The same was true for mutations in NF1 and WT1.
Patients with both subtypes of CBF-AML had mutations in NRAS, KIT, NF1, WT1, FLT3, KRAS, MGA, TTN, CCND2, KDM6A, PHIP, TET2, HCN1, KMT2C, and SETD2.
But only patients with CBFB-MYH11 AML had mutations in PTPN11.
Only patients with RUNX1-RUNX1T1 AML had mutations in ASXL2, ZBTB7A, EZH2, SMC1A, DHX15, RAD21, CBL, DNM2, CSF3R, GIGYF2, SMC3, and ZNF687.
The researchers said their findings suggest a range of mutations may play roles in CBF-AML, but additional research is needed to confirm their precise function in the disease.
Further studies are already underway to fully evaluate the contributions of the different genes as well as the roles of the newly identified genetic alterations in CBF-AML.
whole-genome sequencing
Photo courtesy of the US
Food and Drug Administration
Whole-genome and whole-exome sequencing has provided new insight into the pathogenesis and development of core-binding factor acute myeloid leukemia (CBF-AML), according to researchers.
The team said their work has revealed “dramatic” differences in the genomic landscape of CBF-AMLs that contribute to the diversity of this disease.
The researchers reported their findings in Nature Genetics.
“We set out to understand the genetic variations that contribute to the development of CBF-AML using whole-exome and whole-genome sequencing,” said study author Jeffery Klco, MD, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.
“Our goal was to define a detailed mutational landscape to understand better the genetic changes that contribute to disease.”
Dr Klco and his colleagues sequenced samples from 87 children and 78 adults with CBF-AML. Eighty-five of the patients had the RUNX1-RUNX1T1 subtype, and 80 had the CBFB-MYH11 subtype.
Development and relapse
The researchers identified several genes with mutations that may contribute to CBF-AML development, including CCND2, DHX15, ASXL2, ZBTB7A, and MGA.
“Many of the mutations we identified interfered with molecular signaling or epigenetic factors,” said study author Jinghui Zhang, PhD, of St. Jude Children’s Research Hospital.
“Some of the mutations, like ASXL2, are epigenetic regulators that modify the local state of chromatin,” Dr Klco noted. “Others, like ZBTB7A, appear to act like tumor suppressors.”
The researchers also compared mutations present at diagnosis and relapse in an attempt to understand how CBF-AML changes over time.
Their results suggested that KMT2C mutations are associated with relapse. Of the 4 patients in this study who had KMT2C mutations, 3 relapsed in less than 12 months, and the fourth had residual disease after a course of remission-induction therapy.
Similarities and differences
The researchers found a similar mutational landscape in adults and children with CBF-AML but differences between patients with the RUNX1-RUNX1T1 and CBFB-MYH11 subtypes.
NRAS was the most frequently mutated gene in CBF-AMLs, but NRAS mutations were more common in CBFB-MYH11 AML than RUNX1-RUNX1T1 AML. The same was true for mutations in NF1 and WT1.
Patients with both subtypes of CBF-AML had mutations in NRAS, KIT, NF1, WT1, FLT3, KRAS, MGA, TTN, CCND2, KDM6A, PHIP, TET2, HCN1, KMT2C, and SETD2.
But only patients with CBFB-MYH11 AML had mutations in PTPN11.
Only patients with RUNX1-RUNX1T1 AML had mutations in ASXL2, ZBTB7A, EZH2, SMC1A, DHX15, RAD21, CBL, DNM2, CSF3R, GIGYF2, SMC3, and ZNF687.
The researchers said their findings suggest a range of mutations may play roles in CBF-AML, but additional research is needed to confirm their precise function in the disease.
Further studies are already underway to fully evaluate the contributions of the different genes as well as the roles of the newly identified genetic alterations in CBF-AML.