Women's Health

The Food and Drug Administration has permitted marketing of the Aptima Mycoplasma genitalium assay, the first test for the diagnoses of sexually transmitted infections (STIs) caused by the M. genitalium bacterium, the agency reported in a press release.

Wikimedia Commons/FitzColinGerald/Creative Commons License

M. genitalium is associated with nongonococcal urethritis in men and cervicitis in women, causing 15%-30% of persistent or recurring urethritis cases and 10%-30% of cervicitis cases, according to the Centers for Disease Control and Prevention. It also can lead to pelvic inflammatory disease (PID) in women. The assay is a nucleic acid amplification test, which can detect the bacterium in urine, as well as urethral, penile meatal, endocervical, or vaginal swab samples.

In a clinical study of 11,774 samples, the Aptima assay correctly identified M. genitalium in about 90% of vaginal, male urethral, male urine, and penile samples. It also correctly identified the bacterium in female urine and endocervical samples 78% and 82% of the time, respectively. The test was even more accurate in identifying samples that did not have M. genitalium present, according to an FDA press release

“In the past, it has been hard to diagnose this organism. By being able to detect it more reliably, doctors may be able to more carefully tailor treatment and use medicines most likely to be effective,” FDA Commissioner Scott Gottlieb, MD, said in the press release. “Having accurate and reliable tests to identify the specific bacteria that’s causing an infection can assist doctors in choosing the right treatment for the right infection, which can reduce overuse of antibiotics and help in the fight against antimicrobial resistance.”

Find the full press release on the FDA website.

The Food and Drug Administration has permitted marketing of the Aptima Mycoplasma genitalium assay, the first test for the diagnoses of sexually transmitted infections (STIs) caused by the M. genitalium bacterium, the agency reported in a press release.

Wikimedia Commons/FitzColinGerald/Creative Commons License

M. genitalium is associated with nongonococcal urethritis in men and cervicitis in women, causing 15%-30% of persistent or recurring urethritis cases and 10%-30% of cervicitis cases, according to the Centers for Disease Control and Prevention. It also can lead to pelvic inflammatory disease (PID) in women. The assay is a nucleic acid amplification test, which can detect the bacterium in urine, as well as urethral, penile meatal, endocervical, or vaginal swab samples.

In a clinical study of 11,774 samples, the Aptima assay correctly identified M. genitalium in about 90% of vaginal, male urethral, male urine, and penile samples. It also correctly identified the bacterium in female urine and endocervical samples 78% and 82% of the time, respectively. The test was even more accurate in identifying samples that did not have M. genitalium present, according to an FDA press release

“In the past, it has been hard to diagnose this organism. By being able to detect it more reliably, doctors may be able to more carefully tailor treatment and use medicines most likely to be effective,” FDA Commissioner Scott Gottlieb, MD, said in the press release. “Having accurate and reliable tests to identify the specific bacteria that’s causing an infection can assist doctors in choosing the right treatment for the right infection, which can reduce overuse of antibiotics and help in the fight against antimicrobial resistance.”

Find the full press release on the FDA website.

The Food and Drug Administration has permitted marketing of the Aptima Mycoplasma genitalium assay, the first test for the diagnoses of sexually transmitted infections (STIs) caused by the M. genitalium bacterium, the agency reported in a press release.

Wikimedia Commons/FitzColinGerald/Creative Commons License

M. genitalium is associated with nongonococcal urethritis in men and cervicitis in women, causing 15%-30% of persistent or recurring urethritis cases and 10%-30% of cervicitis cases, according to the Centers for Disease Control and Prevention. It also can lead to pelvic inflammatory disease (PID) in women. The assay is a nucleic acid amplification test, which can detect the bacterium in urine, as well as urethral, penile meatal, endocervical, or vaginal swab samples.

In a clinical study of 11,774 samples, the Aptima assay correctly identified M. genitalium in about 90% of vaginal, male urethral, male urine, and penile samples. It also correctly identified the bacterium in female urine and endocervical samples 78% and 82% of the time, respectively. The test was even more accurate in identifying samples that did not have M. genitalium present, according to an FDA press release

“In the past, it has been hard to diagnose this organism. By being able to detect it more reliably, doctors may be able to more carefully tailor treatment and use medicines most likely to be effective,” FDA Commissioner Scott Gottlieb, MD, said in the press release. “Having accurate and reliable tests to identify the specific bacteria that’s causing an infection can assist doctors in choosing the right treatment for the right infection, which can reduce overuse of antibiotics and help in the fight against antimicrobial resistance.”

Find the full press release on the FDA website.

Migraine is a highly disabling primary headache disorder that affects more than 44 million Americans annually.¹ The disorder causes pain, photophobia, phonophobia, and nausea that can last for hours, even days. Migraine headaches are 2 times more common in women than in men; although migraine is most common in people 30 to 39 years of age, all ages are affected.^2,3 Frequency of migraine headache is variable; chronic migraineurs experience more than 15 headache days a month.

©Cath Riley/Science Source

Recent estimates indicate that the cost of acute and chronic migraine headaches reaches approximately $78 million a year in the United States. ⁴ This high burden of disease has made effective migraine treatment options absolutely essential. Recent advances in our understanding of migraine pathophysiology have led to new therapeutic targets; there are now many novel treatment approaches on the horizon.

In this article, we review the diagnosis and management of migraine in detail. Our emphasis is on evidence-based approaches to acute and prophylactic treatment, including tried-and-true options and newly emerging therapies.

Neuronal dysfunction and a genetic predisposition

Although migraine was once thought to be caused by abnormalities of vasodilation, current research suggests that the disorder has its origins in primary neuronal dysfunction. There appears to be a genetic predisposition toward widespread neuronal hyperexcitability in migraineurs.⁵ In addition, hypothalamic neurons are thought to initiate migraine by responding to changes in brain homeostasis. Increased parasympathetic tone might activate meningeal pain receptors or lower the threshold for transmitting pain signals from the thalamus to the cortex.⁶

Prodromal symptoms and aura appear to originate from multiple areas across the brain, including the hypothalamus, cortex, limbic system, and brainstem. This widespread brain involvement might explain why some headache sufferers concurrently experience a variety of symptoms, including fatigue, depression, muscle pain, and an abnormal sensitivity to light, sound, and smell.^6,7

After taking the initial history (headache onset, location, duration, associated symptoms), focus attention on assessing the risk of intracranial pathology.

Although the exact mechanisms behind each of these symptoms have yet to be defined precisely, waves of neuronal depolarization—known as cortical spreading depression—are suspected to cause migraine aura.^8-10 Cortical spreading depression activates the trigeminal pain pathway and leads to the release of pro-inflammatory markers such as calcitonin gene-related protein (CGRP).⁶ A better understanding of these complex signaling pathways has helped provide potential therapeutic targets for new migraine drugs.

Diagnosis: Close patient inquiry is most helpful

The International Headache Society (IHS) criteria for primary headache disorders serve as the basis for the diagnosis of migraine and its subtypes, which include migraine without aura and migraine with aura. Due to variability of presentation, migraine with aura is further subdivided into migraine with typical aura (with and without headache), migraine with brainstem aura, hemiplegic migraine, and retinal migraine.¹¹

Continue to: How is migraine defined?

How is migraine defined? Simply, migraine is classically defined as a unilateral, pulsating headache of moderate to severe intensity lasting 4 to 72 hours, associated with photophobia and phonophobia or nausea and vomiting, or both.¹¹ Often visual in nature, aura is a set of neurologic symptoms that lasts for minutes and precedes the onset of the headache. The visual aura is often described as a scintillating scotoma that begins near the point of visual fixation and then spreads left or right. Other aura symptoms include tingling or numbness (second most common), speech disturbance (aphasia), motor changes and, in rare cases, a combination of these in succession. By definition, all of these symptoms fully resolve between attacks.¹¹

Validated valuable questionnaires. To help with accurate and timely diagnosis, researchers have developed and validated simplified questionnaires that can be completed independently by patients presenting to primary care (TABLE 1^12,13):

• ID Migraine is a set of 3 questions that scores positive when a patient endorses at least 2 of the 3 symptoms. ¹²
• MS-Q is similar to the ID Migraine but includes 5 items. A score of ≥4 is a positive screen. ¹³

The sensitivity and specificity of MS-Q (0.93 and 0.81, respectively) are slightly higher than those of ID Migraine (0.81 and 0.75).¹³

Remember POUND. This mnemonic device can also be used during history-taking to aid in diagnostic accuracy. Migraine is highly likely (92%) in patients who endorse 4 of the following 5 symptoms and unlikely (17%) in those who endorse ≤2 symptoms¹⁴: Pulsatile quality of headache 4 to 72 hOurs in duration, Unilateral location, Nausea or vomiting, and Disabling intensity.

Differential Dx. Although the differential diagnosis of headache is broad (TABLE 2^14,15), the history alone can often guide clinicians towards the correct assessment. After taking the initial history (headache onset, location, duration, and associated symptoms), focus your attention on assessing the risk of intracranial pathology. This is best accomplished by assessing specific details of the history (TABLE 3¹⁴) and findings on physical examination¹⁵:

• blood pressure measurement (seated, legs uncrossed, feet flat on the floor; having rested for 5 minutes; arm well supported)
• cranial nerve exam
• extremity strength testing
• eye exam (vision, extra-ocular muscles, visual fields, pupillary reactivity, and funduscopic exam)
• gait (tandem walk)
• reflexes.

Continue to: Further testing needed?

Further testing needed? Neuroimaging should be considered only in patients with an abnormal neurologic exam, atypical headache features, or certain risk factors, such as an immune deficiency. There is no role for electroencephalography or other diagnostic testing in migraine.¹⁶

Take a multipronged approach to treatment

As with other complex, chronic conditions, the treatment of migraine should take a multifaceted approach, including management of acute symptoms as well as prevention of future headaches. In 2015, the American Headache Society published a systematic review that specified particular treatment goals for migraine sufferers. ¹⁷ These goals include:

• headache reduction
• headache relief
• decreased disability from headache
• elimination of nausea and vomiting
• elimination of photophobia and phonophobia.

Our review, which follows, of therapeutic options focuses on the management of migraine in adults. Approaches in special populations (older adults, pregnant women, and children) are discussed afterward.

Pharmacotherapy for acute migraine

Acute migraine should be treated with an abortive medication at the onset of headache. The immediate goal is to relieve pain within 2 hours and prevent its recurrence within the subsequent 48 hours (TABLE 4^12,18-20).

Electroencephalography and other diagnostic testing have no role in the workup of migraine.

In the general population, mild, infrequent migraines can be managed with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs).²¹

Continue to: For moderate-to-severe migraine...

For moderate-to-severe migraine, triptans, which target serotonin receptors, are the drug of choice for most patients.²¹ Triptans are superior to placebo in achieving a pain-free state at 2 and 24 hours after administration; eletriptan has the most desirable outcome, with 68% of patients pain free at 2 hours and 54% pain free at 24 hours.²² Triptans are available as sublingual tablets and nasal sprays, as well as subcutaneous injections for patients with significant associated nausea and vomiting. Avoid prescribing triptans for patients with known vascular disease (eg, history of stroke, myocardial infarction, peripheral vascular disease, uncontrolled hypertension, or signs and symptoms of these conditions), as well as for patients with severe hepatic impairment.

Treat migraine with a multifaceted approach, including management of acute symptoms and prevention of future headaches.

Importantly, although triptans all have a similar mechanism of action, patients might respond differently to different drugs within the class. If a patient does not get adequate headache relief from an appropriate dosage of a given triptan during a particular migraine episode, a different triptan can be tried during the next migraine.²² Additionally, if a patient experiences an adverse effect from one triptan, this does not necessarily mean that a trial of another triptan at a later time is contraindicated.

For patients who have an incomplete response to migraine treatment or for those with frequent recurrence, the combination formulation of sumatriptan, 85 mg, and naproxen, 500 mg, showed the highest rate of resolution of headache within 2 hours compared with either drug alone.²³ A similar result might be found by combining a triptan known to be effective for a patient and an NSAID other than naproxen. If migraine persists despite initial treatment of an attack, a different class of medication should be tried during the course of that attack to attain relief of symptoms of that migraine.²¹

When a patient is seen in an acute care setting (eg, emergency department, urgent care center) while suffering a migraine, additional treatment options are available. Intravenous (IV) anti-emetics are useful for relieving the pain of migraine and nausea, and can be used in combination with an IV NSAID (eg, ketorolac).²¹ The most effective anti-emetics are dopamine receptor type-2 blockers, including chlorpromazine, droperidol, metoclopramide, and prochlorperazine, which has the highest level of efficacy.²⁴ Note that these medications do present the risk of a dystonic reaction; diphenhydramine is therefore often used in tandem to mitigate such a response.

Looking ahead. Although triptans are the current first-line therapy for acute migraine, their effectiveness is limited. Only 20% of patients report sustained relief of pain in the 2 to 24 hours after treatment, and the response can vary from episode to episode.²⁵

Continue to: With better understading of the pathophysiology of migraine...

With better understanding of the pathophysiology of migraine, a host of novel anti-migraine drugs are on the horizon.

CGRP receptor antagonists. The neuropeptide CGRP, which mediates central and peripheral nervous system pain signaling, has been noted to be elevated during acute migraine attacks²⁶; clinical trials are therefore underway to evaluate the safety and efficacy of CGRP receptor antagonists.¹⁸ These agents appear to be better tolerated than triptans, have fewer vascular and central nervous system adverse effects, and present less of a risk of medication overuse headache.¹⁸ Liver toxicity has been seen with some medications in this class and remains an important concern in their development.¹⁹

Phase 3 clinical trials for 1 drug in this class, ubrogepant, were completed in late 2017; full analysis of the data is not yet available. Primary outcomes being evaluated include relief of pain at 2 hours and relief from the most bothersome symptoms again at 2 hours.²⁷

Selective serotonin-HT_1f receptor agonists, such as lasmiditan, offer another potential approach. Although the exact mechanism of action of these agents is not entirely clear, clinical trials have supported their efficacy and safety.²⁰ Importantly, ongoing trials are specifically targeting patients with known cardiovascular risk factors because they are most likely to benefit from the nonvasoconstrictive mechanism of action.^28,29 Adverse effects reported primarily include dizziness, fatigue, and vertigo.

Strategies for managing recurrent episodic migraine

Because of the risk of medication overuse headache with acute treatment, daily preventive therapy for migraine is indicated for any patient with ³⁰ :

• ≥6 headache days a month
• ≥4 headache days a month with some impairment
• ≥3 headache days a month with severe impairment.

Continue to: Treatment begins by having patients identify...

Treatment begins by having patients identify, and then avoid, migraine triggers (TABLE 5). This can be accomplished by having patients keep a headache diary, in which they can enter notations about personal and environmental situations that precede a headache.

For the individual patient, some triggers are modifiable; others are not. Helping a patient develop strategies for coping with triggers, rather than aiming for complete avoidance, might help her (him) manage those that are inescapable (eg stress, menstruation, etc).³¹ For many patients, however, this is not an adequate intervention and other approaches must be explored. When considering which therapy might be best for a given patient, evaluate her (his) comorbidities and assess that particular treatment for potential secondary benefits and the possibility of adverse effects. Pay attention to the choice of preventive therapy in women who are considering pregnancy because many available treatments are potentially teratogenic.

Oral medications. Oral agents from several classes of drugs can be used for migraine prophylaxis, including anti-epileptics,antidepressants, and antihypertensives (TABLE 6^{20,29,30,32-41}). Selected anti-epileptics (divalproex sodium, sodium valproate, topiramate) and beta-blockers (metoprolol, propranolol, and timolol) have the strongest evidence to support their use.³² Overall, regular use of prophylactic medications can reduce headache frequency by 50% for approximately 40% to 45% of patients who take them.²⁹ However, adherence may be limited by adverse effects or perceived lack of efficacy, thus reducing their potential for benefit.⁴²

OnabotulinumtoxinA. In patients with chronic migraine (≥15 headache days a month for at least 3 months) who have failed oral medications, the American Academy of Neurology (AAN) recommends the use of onabotulinumtoxinA.³⁰ The treatment regimen comprises 31 injections at various sites on the head, neck, and shoulders every 3 months.³³

A 2010 large randomized controlled trial showed a decrease in the frequency of headache days for patients receiving onabotulinumtoxinA compared to placebo after a 24-week treatment period (7.8 fewer headache days a month, compared to 6.4 fewer in the placebo group).³³ A recent systematic review also noted a reduction of 2 headache days a month compared with placebo; the authors cautioned, however, that data with which to evaluate onabotulinumtoxinA in comparison to other prophylactic agents are limited.⁴³

Continue to: In both studies...

In both studies, the risk of adverse drug events due to onabotulinumtoxinA was high and led to a significant rate of discontinuation.^33,43 Despite this, onabotulinumtoxinA remains the only Food and Drug Administration (FDA)–approved treatment for chronic migraine, making it reasonable to consider for appropriate patients.

Acupuncture. A 2016 Cochrane review found benefit for patients using acupuncture compared with sham acupuncture.³⁴ When acupuncture was compared with prophylactic agents such as beta-blockers, calcium-channel blockers, and anti-epileptics, however, there was no significant difference between the procedure and pharmacotherapy. Patients willing and able to try acupuncture might see a reduction in the overall number of headaches. Acupuncture has few adverse effects; however, long-term data are lacking.³⁴

Exercise is not supported by robust data for its role as a prophylactic treatment. It is generally considered safe in most populations, however, and can be pursued with little out-of-pocket cost.³⁵

Cognitive behavioral therapy (CBT). The AAN recommends CBT, relaxation therapy, and biofeedback therapy. Accessibility of these services remains limited for many patients, and cost can be prohibitive.¹⁶

Supplements used to help prevent migraine include the root of Petasites hybridus (butterbur), magnesium, vitamin B2 (riboflavin), Tanacetum parthenium (feverfew), and coenzyme Q10.¹⁶ Although the strength of evidence for these therapies is limited by small trials, their overall risk of adverse effects is low, and they might be easier for patients to obtain than acupuncture or CBT.

Continue to: Butterbur, in particular...

Butterbur, in particular, has been found to be beneficial for migraine prevention in 2 small placebo-controlled trials. In a randomized controlled study of 245 patients P hybridus, (specifically, the German formulation, Petadolex), 75 mg BID, reduced the frequency of migraine attack by 48% at 4 months, compared to placebo (number needed to treat, 5.3).⁴⁴ No difference was found at lower dosages. The most common reported adverse effect was burping.

Regrettably, unpurified butterbur extract contains pyrrolizidine alkaloids, potentially hepatotoxic and carcinogenic compounds. Because of variations in purification in production facilities in the United States, butterbur supplements might not have all of these compounds removed—and so should be used with caution.⁴¹

Magnesium. Studies evaluating the use of magnesium have demonstrated varied results; differences in methods and dosing have limited broad application of findings. As with most supplements considered for prophylactic treatment, magnesium dosing is poorly understood, and bioavailability varies in its different forms. Oral supplementation can be given as magnesium dicitrate, 600 mg/d.⁴⁵

Recently, products containing various combinations of feverfew, coenzyme Q10, riboflavin, magnesium, and other supplements have shown benefit in early clinical trials.^36,37

Neural stimulation. Over the past few years, a variety of transcutaneous nerve stimulator devices have gained FDA approval for use in migraine prophylaxis. The long-term safety and efficacy of these devices is not yet well understood, but they appear to provide headache relief in the short term and decrease the frequency of headache.³⁸ Use of the noninvasive stimulators is limited today by high cost and poor coverage by US health care insurers.

Continue to: Newly available medical therapy

Newly available medical therapy. The FDA recently approved erenumab, a fully human monoclonal antibody for prevention of migraine in adults. This is the first drug in the CGRP antagonist class to be approved for this indication. Trials of this once-monthly, self-injectable drug show promising results for patients whose migraines have been refractory to other therapies.

A recent large trial evaluated 955 adults with migraine, randomizing them to receive erenumab, 70 mg; erenumab, 140 mg; or placebo over 28 weeks.³⁹ The groups receiving erenumab had a nearly 2-fold higher odds of having their migraine reduced by 50%, compared with placebo (number needed to treat with the 140-mg dose, 4.27). Similar numbers of participants from all groups discontinued the study.³⁹ Phase 3 trials that are not yet formally published have produced similarly beneficial results.^40,46 The FDA has listed injection site reaction and constipation as the most reported adverse effects.⁴⁰

Three other anti-CGRP antibodies are likely to be approved in the near future: fremanezumab, galcanezumab, and eptinezumab.

The approach to migraine in special populations

Management of acute and chronic migraine in children, pregnant women, and older adults requires special attention: Treatment approaches are different than they are for adults 19 to 65 years of age.

Pediatric patients. Migraine is the most common acute and recurrent headache syndrome in children. Headaches differ from those of adult migraine as a result of variations in brain maturation, plasticity, and cognitive development.⁴⁷ Migraine attacks are often of shorter duration in children, lasting 1 to 2 hours, but can still be preceded by visual aura.⁴⁸ Just as with adults, imaging, electroencephalography, lumbar puncture, and routine labs should be considered only if a child has an abnormal neurological exam or other concerning features (TABLE 2^14,15).

Continue to: The general approach to migraine treatment...

The general approach to migraine treatment in the pediatric population includes education of the child and family about symptom management. Acetaminophen, NSAIDs, and triptans are approved for abortive therapy in children and should be used for acute headache relief in the same way that they are used in adults. Oral rizatriptan, the most well studied triptan in the pediatric population, is approved for use in children as young as 6 years⁴⁹; the pediatric dosage is 5 mg/d for patients weighing 20 to 39 kg and 10 mg/d for patients weighing more than 40 kg (same as the adult dosage).

Don’t prescribe triptans for patients with known vascular disease or severe hepatic impairment.

Oral almotriptan and zolmitriptan are also approved for use in children 12 to 17 years of age. Usual dosages are: almotriptan, 12.5 mg at onset, can repeat in 2 hours as needed (maximum dosage, 25 mg/d); and zolmitriptan, 2.5 mg at onset, can repeat in 2 hours as needed (maximum dosage, 10 mg/d).⁵⁰

For children who are unable to swallow pills or who are vomiting, a non-oral route of administration is preferable. Rizatriptan is available as an orally disintegrating tablet. Zolmitriptan is available in a nasal spray at a dose of 5 mg for children 12 years and older. Sumatriptan is not approved for use in patients younger than 18 years; however, recent studies have shown that it might have good efficacy and tolerability.⁵⁰

Daily prophylactic treatment for recurrent migraine in the pediatric population is an evolving subject; published guidelines do not exist. It is reasonable to consider treatment using the same guidelines as those in place for adults.⁵¹ Topiramate, 1 to 2 mg/kg/d, is the only therapy approved by the FDA for episodic migraine preventive therapy in adolescents.⁵⁰

If a patient doesn’t get adequate headache relief from an appropriate dosage of a given triptan, try a different triptan during the next migraine.

Notably, a nonpharmacotherapeutic approach may be more effective for pediatric prevention. In 2017, a large double-blind, placebo-controlled trial investigated the use of amitriptyline, topiramate, and placebo for the treatment of recurrent migraine in children 8 to 17 years of age. An interim analysis of the 328 children enrolled found no significant differences in reduction of headache frequency with treatment compared with placebo over a 24-week period; the trial was stopped early due to futility.⁵²

Continue to: The study did show...

The study did show, however, that reducing migraine triggers provided a high level of benefit to study participants. Stress is one of the most common migraine triggers in children; lack of sleep, exposure to a warm climate, and exposure to video games are also notable triggers.⁵³ CBT may augment the efficacy of standard migraine medications in the pediatric population and may help prevent recurrence of episodes.⁵⁴

Pregnancy. The treatment of migraine is different in pregnant women than it is in nonpregnant adults because of a concern over adverse effects on fetal development. For acute headache treatment, first-line therapies include trigger avoidance and acetaminophen, 1000 mg (maximum dosage, 4000 mg/d).⁵⁵ If this is ineffective, a 10-mg dose of metoclopramide, as often as every 6 hours (not an FDA-approved indication), can be considered. During the second trimester, NSAIDs can be considered second-line therapy.

Triptans—specifically, sumatriptan and rizatriptan—can also be considered if first-line therapies fail.⁵⁶ Triptan-exposed pregnant women with migraine have a rate of congenital malformations, spontaneous abortions, and prematurity that is similar to what is seen in pregnant women with migraine who have not been exposed to triptans. However, when triptan-exposed women are compared with healthy, non-migraine-suffering women, the rate of spontaneous abortion appears to be increased in the triptan-exposed population.⁵⁷

Ergotamine is contraindicated during pregnancy because of its potential to induce uterine contractions and vasospasm, which can be detrimental to the fetus.⁵⁶Nonpharmacotherapeutic interventions such as heat, ice, massage, rest, and avoidance of triggers are as successful in the pregnant population as in the nonpregnant population. For migraine prevention, coenzyme Q10, vitamins B2 and B6 (pyridoxine), and oral magnesium can be considered. Feverfew and butterbur should be avoided because of concerns about fetal malformation and preterm labor.⁵⁸

Older adults. Choosing appropriate migraine therapy for older adults requires special consideration because of changes in drug metabolism and risks associated with drug adverse effects. Additionally, few studies of migraine drugs have included large populations of adults older than 65 years; medications should therefore be prescribed cautiously in this population, with particular attention to drug–drug interactions.

Continue to: Just as for younger adults...

Just as for younger adults, mild symptoms can be managed effectively with acetaminophen. NSAIDs may be used as well, but carry increased risks of gastric bleeding and elevation in blood pressure.⁵⁹ The use of triptans is acceptable for the appropriate patient, but should be avoided in patients with known vascular disease.⁶⁰ Antiemetics present an increased risk of extrapyramidal adverse effects in the elderly and should be used with caution at the lowest effective dosage.⁵⁹ Novel mechanisms of action make some of the newer agents potentially safer for use in older adults when treating acute migraine.

Stress is one of the most common migraine triggers in children.

For migraine prevention in older adults, particular attention should be paid to reducing triggers and minimizing polypharmacy.

More and more, successful treatment is within reach

With many clinical trials evaluating novel drugs underway, and additional studies contributing to our understanding of nonpharmacotherapeutic approaches to migraine treatment, improved headache control may become increasingly common over the next few years.

CORRESPONDENCE
Kathryn McGrath, MD, Department of Family and Community Medicine, Thomas Jefferson University, 1015 Walnut St, Philadelphia PA 19107; [email protected].

Migraine is a highly disabling primary headache disorder that affects more than 44 million Americans annually.¹ The disorder causes pain, photophobia, phonophobia, and nausea that can last for hours, even days. Migraine headaches are 2 times more common in women than in men; although migraine is most common in people 30 to 39 years of age, all ages are affected.^2,3 Frequency of migraine headache is variable; chronic migraineurs experience more than 15 headache days a month.

©Cath Riley/Science Source

Recent estimates indicate that the cost of acute and chronic migraine headaches reaches approximately $78 million a year in the United States. ⁴ This high burden of disease has made effective migraine treatment options absolutely essential. Recent advances in our understanding of migraine pathophysiology have led to new therapeutic targets; there are now many novel treatment approaches on the horizon.

In this article, we review the diagnosis and management of migraine in detail. Our emphasis is on evidence-based approaches to acute and prophylactic treatment, including tried-and-true options and newly emerging therapies.

Neuronal dysfunction and a genetic predisposition

Although migraine was once thought to be caused by abnormalities of vasodilation, current research suggests that the disorder has its origins in primary neuronal dysfunction. There appears to be a genetic predisposition toward widespread neuronal hyperexcitability in migraineurs.⁵ In addition, hypothalamic neurons are thought to initiate migraine by responding to changes in brain homeostasis. Increased parasympathetic tone might activate meningeal pain receptors or lower the threshold for transmitting pain signals from the thalamus to the cortex.⁶

Prodromal symptoms and aura appear to originate from multiple areas across the brain, including the hypothalamus, cortex, limbic system, and brainstem. This widespread brain involvement might explain why some headache sufferers concurrently experience a variety of symptoms, including fatigue, depression, muscle pain, and an abnormal sensitivity to light, sound, and smell.^6,7

After taking the initial history (headache onset, location, duration, associated symptoms), focus attention on assessing the risk of intracranial pathology.

Although the exact mechanisms behind each of these symptoms have yet to be defined precisely, waves of neuronal depolarization—known as cortical spreading depression—are suspected to cause migraine aura.^8-10 Cortical spreading depression activates the trigeminal pain pathway and leads to the release of pro-inflammatory markers such as calcitonin gene-related protein (CGRP).⁶ A better understanding of these complex signaling pathways has helped provide potential therapeutic targets for new migraine drugs.

Diagnosis: Close patient inquiry is most helpful

The International Headache Society (IHS) criteria for primary headache disorders serve as the basis for the diagnosis of migraine and its subtypes, which include migraine without aura and migraine with aura. Due to variability of presentation, migraine with aura is further subdivided into migraine with typical aura (with and without headache), migraine with brainstem aura, hemiplegic migraine, and retinal migraine.¹¹

Continue to: How is migraine defined?

How is migraine defined? Simply, migraine is classically defined as a unilateral, pulsating headache of moderate to severe intensity lasting 4 to 72 hours, associated with photophobia and phonophobia or nausea and vomiting, or both.¹¹ Often visual in nature, aura is a set of neurologic symptoms that lasts for minutes and precedes the onset of the headache. The visual aura is often described as a scintillating scotoma that begins near the point of visual fixation and then spreads left or right. Other aura symptoms include tingling or numbness (second most common), speech disturbance (aphasia), motor changes and, in rare cases, a combination of these in succession. By definition, all of these symptoms fully resolve between attacks.¹¹

Validated valuable questionnaires. To help with accurate and timely diagnosis, researchers have developed and validated simplified questionnaires that can be completed independently by patients presenting to primary care (TABLE 1^12,13):

• ID Migraine is a set of 3 questions that scores positive when a patient endorses at least 2 of the 3 symptoms. ¹²
• MS-Q is similar to the ID Migraine but includes 5 items. A score of ≥4 is a positive screen. ¹³

The sensitivity and specificity of MS-Q (0.93 and 0.81, respectively) are slightly higher than those of ID Migraine (0.81 and 0.75).¹³

Remember POUND. This mnemonic device can also be used during history-taking to aid in diagnostic accuracy. Migraine is highly likely (92%) in patients who endorse 4 of the following 5 symptoms and unlikely (17%) in those who endorse ≤2 symptoms¹⁴: Pulsatile quality of headache 4 to 72 hOurs in duration, Unilateral location, Nausea or vomiting, and Disabling intensity.

Differential Dx. Although the differential diagnosis of headache is broad (TABLE 2^14,15), the history alone can often guide clinicians towards the correct assessment. After taking the initial history (headache onset, location, duration, and associated symptoms), focus your attention on assessing the risk of intracranial pathology. This is best accomplished by assessing specific details of the history (TABLE 3¹⁴) and findings on physical examination¹⁵:

• blood pressure measurement (seated, legs uncrossed, feet flat on the floor; having rested for 5 minutes; arm well supported)
• cranial nerve exam
• extremity strength testing
• eye exam (vision, extra-ocular muscles, visual fields, pupillary reactivity, and funduscopic exam)
• gait (tandem walk)
• reflexes.

Continue to: Further testing needed?

Further testing needed? Neuroimaging should be considered only in patients with an abnormal neurologic exam, atypical headache features, or certain risk factors, such as an immune deficiency. There is no role for electroencephalography or other diagnostic testing in migraine.¹⁶

Take a multipronged approach to treatment

As with other complex, chronic conditions, the treatment of migraine should take a multifaceted approach, including management of acute symptoms as well as prevention of future headaches. In 2015, the American Headache Society published a systematic review that specified particular treatment goals for migraine sufferers. ¹⁷ These goals include:

• headache reduction
• headache relief
• decreased disability from headache
• elimination of nausea and vomiting
• elimination of photophobia and phonophobia.

Our review, which follows, of therapeutic options focuses on the management of migraine in adults. Approaches in special populations (older adults, pregnant women, and children) are discussed afterward.

Pharmacotherapy for acute migraine

Acute migraine should be treated with an abortive medication at the onset of headache. The immediate goal is to relieve pain within 2 hours and prevent its recurrence within the subsequent 48 hours (TABLE 4^12,18-20).

Electroencephalography and other diagnostic testing have no role in the workup of migraine.

In the general population, mild, infrequent migraines can be managed with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs).²¹

Continue to: For moderate-to-severe migraine...

For moderate-to-severe migraine, triptans, which target serotonin receptors, are the drug of choice for most patients.²¹ Triptans are superior to placebo in achieving a pain-free state at 2 and 24 hours after administration; eletriptan has the most desirable outcome, with 68% of patients pain free at 2 hours and 54% pain free at 24 hours.²² Triptans are available as sublingual tablets and nasal sprays, as well as subcutaneous injections for patients with significant associated nausea and vomiting. Avoid prescribing triptans for patients with known vascular disease (eg, history of stroke, myocardial infarction, peripheral vascular disease, uncontrolled hypertension, or signs and symptoms of these conditions), as well as for patients with severe hepatic impairment.

Treat migraine with a multifaceted approach, including management of acute symptoms and prevention of future headaches.

Importantly, although triptans all have a similar mechanism of action, patients might respond differently to different drugs within the class. If a patient does not get adequate headache relief from an appropriate dosage of a given triptan during a particular migraine episode, a different triptan can be tried during the next migraine.²² Additionally, if a patient experiences an adverse effect from one triptan, this does not necessarily mean that a trial of another triptan at a later time is contraindicated.

For patients who have an incomplete response to migraine treatment or for those with frequent recurrence, the combination formulation of sumatriptan, 85 mg, and naproxen, 500 mg, showed the highest rate of resolution of headache within 2 hours compared with either drug alone.²³ A similar result might be found by combining a triptan known to be effective for a patient and an NSAID other than naproxen. If migraine persists despite initial treatment of an attack, a different class of medication should be tried during the course of that attack to attain relief of symptoms of that migraine.²¹

When a patient is seen in an acute care setting (eg, emergency department, urgent care center) while suffering a migraine, additional treatment options are available. Intravenous (IV) anti-emetics are useful for relieving the pain of migraine and nausea, and can be used in combination with an IV NSAID (eg, ketorolac).²¹ The most effective anti-emetics are dopamine receptor type-2 blockers, including chlorpromazine, droperidol, metoclopramide, and prochlorperazine, which has the highest level of efficacy.²⁴ Note that these medications do present the risk of a dystonic reaction; diphenhydramine is therefore often used in tandem to mitigate such a response.

Looking ahead. Although triptans are the current first-line therapy for acute migraine, their effectiveness is limited. Only 20% of patients report sustained relief of pain in the 2 to 24 hours after treatment, and the response can vary from episode to episode.²⁵

Continue to: With better understading of the pathophysiology of migraine...

With better understanding of the pathophysiology of migraine, a host of novel anti-migraine drugs are on the horizon.

CGRP receptor antagonists. The neuropeptide CGRP, which mediates central and peripheral nervous system pain signaling, has been noted to be elevated during acute migraine attacks²⁶; clinical trials are therefore underway to evaluate the safety and efficacy of CGRP receptor antagonists.¹⁸ These agents appear to be better tolerated than triptans, have fewer vascular and central nervous system adverse effects, and present less of a risk of medication overuse headache.¹⁸ Liver toxicity has been seen with some medications in this class and remains an important concern in their development.¹⁹

Phase 3 clinical trials for 1 drug in this class, ubrogepant, were completed in late 2017; full analysis of the data is not yet available. Primary outcomes being evaluated include relief of pain at 2 hours and relief from the most bothersome symptoms again at 2 hours.²⁷

Selective serotonin-HT_1f receptor agonists, such as lasmiditan, offer another potential approach. Although the exact mechanism of action of these agents is not entirely clear, clinical trials have supported their efficacy and safety.²⁰ Importantly, ongoing trials are specifically targeting patients with known cardiovascular risk factors because they are most likely to benefit from the nonvasoconstrictive mechanism of action.^28,29 Adverse effects reported primarily include dizziness, fatigue, and vertigo.

Strategies for managing recurrent episodic migraine

Because of the risk of medication overuse headache with acute treatment, daily preventive therapy for migraine is indicated for any patient with ³⁰ :

• ≥6 headache days a month
• ≥4 headache days a month with some impairment
• ≥3 headache days a month with severe impairment.

Continue to: Treatment begins by having patients identify...

Treatment begins by having patients identify, and then avoid, migraine triggers (TABLE 5). This can be accomplished by having patients keep a headache diary, in which they can enter notations about personal and environmental situations that precede a headache.

For the individual patient, some triggers are modifiable; others are not. Helping a patient develop strategies for coping with triggers, rather than aiming for complete avoidance, might help her (him) manage those that are inescapable (eg stress, menstruation, etc).³¹ For many patients, however, this is not an adequate intervention and other approaches must be explored. When considering which therapy might be best for a given patient, evaluate her (his) comorbidities and assess that particular treatment for potential secondary benefits and the possibility of adverse effects. Pay attention to the choice of preventive therapy in women who are considering pregnancy because many available treatments are potentially teratogenic.

Oral medications. Oral agents from several classes of drugs can be used for migraine prophylaxis, including anti-epileptics,antidepressants, and antihypertensives (TABLE 6^{20,29,30,32-41}). Selected anti-epileptics (divalproex sodium, sodium valproate, topiramate) and beta-blockers (metoprolol, propranolol, and timolol) have the strongest evidence to support their use.³² Overall, regular use of prophylactic medications can reduce headache frequency by 50% for approximately 40% to 45% of patients who take them.²⁹ However, adherence may be limited by adverse effects or perceived lack of efficacy, thus reducing their potential for benefit.⁴²

OnabotulinumtoxinA. In patients with chronic migraine (≥15 headache days a month for at least 3 months) who have failed oral medications, the American Academy of Neurology (AAN) recommends the use of onabotulinumtoxinA.³⁰ The treatment regimen comprises 31 injections at various sites on the head, neck, and shoulders every 3 months.³³

A 2010 large randomized controlled trial showed a decrease in the frequency of headache days for patients receiving onabotulinumtoxinA compared to placebo after a 24-week treatment period (7.8 fewer headache days a month, compared to 6.4 fewer in the placebo group).³³ A recent systematic review also noted a reduction of 2 headache days a month compared with placebo; the authors cautioned, however, that data with which to evaluate onabotulinumtoxinA in comparison to other prophylactic agents are limited.⁴³

Continue to: In both studies...

In both studies, the risk of adverse drug events due to onabotulinumtoxinA was high and led to a significant rate of discontinuation.^33,43 Despite this, onabotulinumtoxinA remains the only Food and Drug Administration (FDA)–approved treatment for chronic migraine, making it reasonable to consider for appropriate patients.

Acupuncture. A 2016 Cochrane review found benefit for patients using acupuncture compared with sham acupuncture.³⁴ When acupuncture was compared with prophylactic agents such as beta-blockers, calcium-channel blockers, and anti-epileptics, however, there was no significant difference between the procedure and pharmacotherapy. Patients willing and able to try acupuncture might see a reduction in the overall number of headaches. Acupuncture has few adverse effects; however, long-term data are lacking.³⁴

Exercise is not supported by robust data for its role as a prophylactic treatment. It is generally considered safe in most populations, however, and can be pursued with little out-of-pocket cost.³⁵

Cognitive behavioral therapy (CBT). The AAN recommends CBT, relaxation therapy, and biofeedback therapy. Accessibility of these services remains limited for many patients, and cost can be prohibitive.¹⁶

Supplements used to help prevent migraine include the root of Petasites hybridus (butterbur), magnesium, vitamin B2 (riboflavin), Tanacetum parthenium (feverfew), and coenzyme Q10.¹⁶ Although the strength of evidence for these therapies is limited by small trials, their overall risk of adverse effects is low, and they might be easier for patients to obtain than acupuncture or CBT.

Continue to: Butterbur, in particular...

Butterbur, in particular, has been found to be beneficial for migraine prevention in 2 small placebo-controlled trials. In a randomized controlled study of 245 patients P hybridus, (specifically, the German formulation, Petadolex), 75 mg BID, reduced the frequency of migraine attack by 48% at 4 months, compared to placebo (number needed to treat, 5.3).⁴⁴ No difference was found at lower dosages. The most common reported adverse effect was burping.

Regrettably, unpurified butterbur extract contains pyrrolizidine alkaloids, potentially hepatotoxic and carcinogenic compounds. Because of variations in purification in production facilities in the United States, butterbur supplements might not have all of these compounds removed—and so should be used with caution.⁴¹

Magnesium. Studies evaluating the use of magnesium have demonstrated varied results; differences in methods and dosing have limited broad application of findings. As with most supplements considered for prophylactic treatment, magnesium dosing is poorly understood, and bioavailability varies in its different forms. Oral supplementation can be given as magnesium dicitrate, 600 mg/d.⁴⁵

Recently, products containing various combinations of feverfew, coenzyme Q10, riboflavin, magnesium, and other supplements have shown benefit in early clinical trials.^36,37

Neural stimulation. Over the past few years, a variety of transcutaneous nerve stimulator devices have gained FDA approval for use in migraine prophylaxis. The long-term safety and efficacy of these devices is not yet well understood, but they appear to provide headache relief in the short term and decrease the frequency of headache.³⁸ Use of the noninvasive stimulators is limited today by high cost and poor coverage by US health care insurers.

Continue to: Newly available medical therapy

Newly available medical therapy. The FDA recently approved erenumab, a fully human monoclonal antibody for prevention of migraine in adults. This is the first drug in the CGRP antagonist class to be approved for this indication. Trials of this once-monthly, self-injectable drug show promising results for patients whose migraines have been refractory to other therapies.

A recent large trial evaluated 955 adults with migraine, randomizing them to receive erenumab, 70 mg; erenumab, 140 mg; or placebo over 28 weeks.³⁹ The groups receiving erenumab had a nearly 2-fold higher odds of having their migraine reduced by 50%, compared with placebo (number needed to treat with the 140-mg dose, 4.27). Similar numbers of participants from all groups discontinued the study.³⁹ Phase 3 trials that are not yet formally published have produced similarly beneficial results.^40,46 The FDA has listed injection site reaction and constipation as the most reported adverse effects.⁴⁰

Three other anti-CGRP antibodies are likely to be approved in the near future: fremanezumab, galcanezumab, and eptinezumab.

The approach to migraine in special populations

Management of acute and chronic migraine in children, pregnant women, and older adults requires special attention: Treatment approaches are different than they are for adults 19 to 65 years of age.

Pediatric patients. Migraine is the most common acute and recurrent headache syndrome in children. Headaches differ from those of adult migraine as a result of variations in brain maturation, plasticity, and cognitive development.⁴⁷ Migraine attacks are often of shorter duration in children, lasting 1 to 2 hours, but can still be preceded by visual aura.⁴⁸ Just as with adults, imaging, electroencephalography, lumbar puncture, and routine labs should be considered only if a child has an abnormal neurological exam or other concerning features (TABLE 2^14,15).

Continue to: The general approach to migraine treatment...

The general approach to migraine treatment in the pediatric population includes education of the child and family about symptom management. Acetaminophen, NSAIDs, and triptans are approved for abortive therapy in children and should be used for acute headache relief in the same way that they are used in adults. Oral rizatriptan, the most well studied triptan in the pediatric population, is approved for use in children as young as 6 years⁴⁹; the pediatric dosage is 5 mg/d for patients weighing 20 to 39 kg and 10 mg/d for patients weighing more than 40 kg (same as the adult dosage).

Don’t prescribe triptans for patients with known vascular disease or severe hepatic impairment.

Oral almotriptan and zolmitriptan are also approved for use in children 12 to 17 years of age. Usual dosages are: almotriptan, 12.5 mg at onset, can repeat in 2 hours as needed (maximum dosage, 25 mg/d); and zolmitriptan, 2.5 mg at onset, can repeat in 2 hours as needed (maximum dosage, 10 mg/d).⁵⁰

For children who are unable to swallow pills or who are vomiting, a non-oral route of administration is preferable. Rizatriptan is available as an orally disintegrating tablet. Zolmitriptan is available in a nasal spray at a dose of 5 mg for children 12 years and older. Sumatriptan is not approved for use in patients younger than 18 years; however, recent studies have shown that it might have good efficacy and tolerability.⁵⁰

Daily prophylactic treatment for recurrent migraine in the pediatric population is an evolving subject; published guidelines do not exist. It is reasonable to consider treatment using the same guidelines as those in place for adults.⁵¹ Topiramate, 1 to 2 mg/kg/d, is the only therapy approved by the FDA for episodic migraine preventive therapy in adolescents.⁵⁰

If a patient doesn’t get adequate headache relief from an appropriate dosage of a given triptan, try a different triptan during the next migraine.

Notably, a nonpharmacotherapeutic approach may be more effective for pediatric prevention. In 2017, a large double-blind, placebo-controlled trial investigated the use of amitriptyline, topiramate, and placebo for the treatment of recurrent migraine in children 8 to 17 years of age. An interim analysis of the 328 children enrolled found no significant differences in reduction of headache frequency with treatment compared with placebo over a 24-week period; the trial was stopped early due to futility.⁵²

Continue to: The study did show...

The study did show, however, that reducing migraine triggers provided a high level of benefit to study participants. Stress is one of the most common migraine triggers in children; lack of sleep, exposure to a warm climate, and exposure to video games are also notable triggers.⁵³ CBT may augment the efficacy of standard migraine medications in the pediatric population and may help prevent recurrence of episodes.⁵⁴

Pregnancy. The treatment of migraine is different in pregnant women than it is in nonpregnant adults because of a concern over adverse effects on fetal development. For acute headache treatment, first-line therapies include trigger avoidance and acetaminophen, 1000 mg (maximum dosage, 4000 mg/d).⁵⁵ If this is ineffective, a 10-mg dose of metoclopramide, as often as every 6 hours (not an FDA-approved indication), can be considered. During the second trimester, NSAIDs can be considered second-line therapy.

Triptans—specifically, sumatriptan and rizatriptan—can also be considered if first-line therapies fail.⁵⁶ Triptan-exposed pregnant women with migraine have a rate of congenital malformations, spontaneous abortions, and prematurity that is similar to what is seen in pregnant women with migraine who have not been exposed to triptans. However, when triptan-exposed women are compared with healthy, non-migraine-suffering women, the rate of spontaneous abortion appears to be increased in the triptan-exposed population.⁵⁷

Ergotamine is contraindicated during pregnancy because of its potential to induce uterine contractions and vasospasm, which can be detrimental to the fetus.⁵⁶Nonpharmacotherapeutic interventions such as heat, ice, massage, rest, and avoidance of triggers are as successful in the pregnant population as in the nonpregnant population. For migraine prevention, coenzyme Q10, vitamins B2 and B6 (pyridoxine), and oral magnesium can be considered. Feverfew and butterbur should be avoided because of concerns about fetal malformation and preterm labor.⁵⁸

Older adults. Choosing appropriate migraine therapy for older adults requires special consideration because of changes in drug metabolism and risks associated with drug adverse effects. Additionally, few studies of migraine drugs have included large populations of adults older than 65 years; medications should therefore be prescribed cautiously in this population, with particular attention to drug–drug interactions.

Continue to: Just as for younger adults...

Just as for younger adults, mild symptoms can be managed effectively with acetaminophen. NSAIDs may be used as well, but carry increased risks of gastric bleeding and elevation in blood pressure.⁵⁹ The use of triptans is acceptable for the appropriate patient, but should be avoided in patients with known vascular disease.⁶⁰ Antiemetics present an increased risk of extrapyramidal adverse effects in the elderly and should be used with caution at the lowest effective dosage.⁵⁹ Novel mechanisms of action make some of the newer agents potentially safer for use in older adults when treating acute migraine.

Stress is one of the most common migraine triggers in children.

For migraine prevention in older adults, particular attention should be paid to reducing triggers and minimizing polypharmacy.

More and more, successful treatment is within reach

With many clinical trials evaluating novel drugs underway, and additional studies contributing to our understanding of nonpharmacotherapeutic approaches to migraine treatment, improved headache control may become increasingly common over the next few years.

CORRESPONDENCE
Kathryn McGrath, MD, Department of Family and Community Medicine, Thomas Jefferson University, 1015 Walnut St, Philadelphia PA 19107; [email protected].

Migraine is a highly disabling primary headache disorder that affects more than 44 million Americans annually.¹ The disorder causes pain, photophobia, phonophobia, and nausea that can last for hours, even days. Migraine headaches are 2 times more common in women than in men; although migraine is most common in people 30 to 39 years of age, all ages are affected.^2,3 Frequency of migraine headache is variable; chronic migraineurs experience more than 15 headache days a month.

©Cath Riley/Science Source

Recent estimates indicate that the cost of acute and chronic migraine headaches reaches approximately $78 million a year in the United States. ⁴ This high burden of disease has made effective migraine treatment options absolutely essential. Recent advances in our understanding of migraine pathophysiology have led to new therapeutic targets; there are now many novel treatment approaches on the horizon.

In this article, we review the diagnosis and management of migraine in detail. Our emphasis is on evidence-based approaches to acute and prophylactic treatment, including tried-and-true options and newly emerging therapies.

Neuronal dysfunction and a genetic predisposition

Although migraine was once thought to be caused by abnormalities of vasodilation, current research suggests that the disorder has its origins in primary neuronal dysfunction. There appears to be a genetic predisposition toward widespread neuronal hyperexcitability in migraineurs.⁵ In addition, hypothalamic neurons are thought to initiate migraine by responding to changes in brain homeostasis. Increased parasympathetic tone might activate meningeal pain receptors or lower the threshold for transmitting pain signals from the thalamus to the cortex.⁶

Prodromal symptoms and aura appear to originate from multiple areas across the brain, including the hypothalamus, cortex, limbic system, and brainstem. This widespread brain involvement might explain why some headache sufferers concurrently experience a variety of symptoms, including fatigue, depression, muscle pain, and an abnormal sensitivity to light, sound, and smell.^6,7

After taking the initial history (headache onset, location, duration, associated symptoms), focus attention on assessing the risk of intracranial pathology.

Although the exact mechanisms behind each of these symptoms have yet to be defined precisely, waves of neuronal depolarization—known as cortical spreading depression—are suspected to cause migraine aura.^8-10 Cortical spreading depression activates the trigeminal pain pathway and leads to the release of pro-inflammatory markers such as calcitonin gene-related protein (CGRP).⁶ A better understanding of these complex signaling pathways has helped provide potential therapeutic targets for new migraine drugs.

Diagnosis: Close patient inquiry is most helpful

The International Headache Society (IHS) criteria for primary headache disorders serve as the basis for the diagnosis of migraine and its subtypes, which include migraine without aura and migraine with aura. Due to variability of presentation, migraine with aura is further subdivided into migraine with typical aura (with and without headache), migraine with brainstem aura, hemiplegic migraine, and retinal migraine.¹¹

Continue to: How is migraine defined?

How is migraine defined? Simply, migraine is classically defined as a unilateral, pulsating headache of moderate to severe intensity lasting 4 to 72 hours, associated with photophobia and phonophobia or nausea and vomiting, or both.¹¹ Often visual in nature, aura is a set of neurologic symptoms that lasts for minutes and precedes the onset of the headache. The visual aura is often described as a scintillating scotoma that begins near the point of visual fixation and then spreads left or right. Other aura symptoms include tingling or numbness (second most common), speech disturbance (aphasia), motor changes and, in rare cases, a combination of these in succession. By definition, all of these symptoms fully resolve between attacks.¹¹

Validated valuable questionnaires. To help with accurate and timely diagnosis, researchers have developed and validated simplified questionnaires that can be completed independently by patients presenting to primary care (TABLE 1^12,13):

• ID Migraine is a set of 3 questions that scores positive when a patient endorses at least 2 of the 3 symptoms. ¹²
• MS-Q is similar to the ID Migraine but includes 5 items. A score of ≥4 is a positive screen. ¹³

The sensitivity and specificity of MS-Q (0.93 and 0.81, respectively) are slightly higher than those of ID Migraine (0.81 and 0.75).¹³

Remember POUND. This mnemonic device can also be used during history-taking to aid in diagnostic accuracy. Migraine is highly likely (92%) in patients who endorse 4 of the following 5 symptoms and unlikely (17%) in those who endorse ≤2 symptoms¹⁴: Pulsatile quality of headache 4 to 72 hOurs in duration, Unilateral location, Nausea or vomiting, and Disabling intensity.

Differential Dx. Although the differential diagnosis of headache is broad (TABLE 2^14,15), the history alone can often guide clinicians towards the correct assessment. After taking the initial history (headache onset, location, duration, and associated symptoms), focus your attention on assessing the risk of intracranial pathology. This is best accomplished by assessing specific details of the history (TABLE 3¹⁴) and findings on physical examination¹⁵:

• blood pressure measurement (seated, legs uncrossed, feet flat on the floor; having rested for 5 minutes; arm well supported)
• cranial nerve exam
• extremity strength testing
• eye exam (vision, extra-ocular muscles, visual fields, pupillary reactivity, and funduscopic exam)
• gait (tandem walk)
• reflexes.

Continue to: Further testing needed?

Further testing needed? Neuroimaging should be considered only in patients with an abnormal neurologic exam, atypical headache features, or certain risk factors, such as an immune deficiency. There is no role for electroencephalography or other diagnostic testing in migraine.¹⁶

Take a multipronged approach to treatment

As with other complex, chronic conditions, the treatment of migraine should take a multifaceted approach, including management of acute symptoms as well as prevention of future headaches. In 2015, the American Headache Society published a systematic review that specified particular treatment goals for migraine sufferers. ¹⁷ These goals include:

• headache reduction
• headache relief
• decreased disability from headache
• elimination of nausea and vomiting
• elimination of photophobia and phonophobia.

Our review, which follows, of therapeutic options focuses on the management of migraine in adults. Approaches in special populations (older adults, pregnant women, and children) are discussed afterward.

Pharmacotherapy for acute migraine

Acute migraine should be treated with an abortive medication at the onset of headache. The immediate goal is to relieve pain within 2 hours and prevent its recurrence within the subsequent 48 hours (TABLE 4^12,18-20).

Electroencephalography and other diagnostic testing have no role in the workup of migraine.

In the general population, mild, infrequent migraines can be managed with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs).²¹

Continue to: For moderate-to-severe migraine...

For moderate-to-severe migraine, triptans, which target serotonin receptors, are the drug of choice for most patients.²¹ Triptans are superior to placebo in achieving a pain-free state at 2 and 24 hours after administration; eletriptan has the most desirable outcome, with 68% of patients pain free at 2 hours and 54% pain free at 24 hours.²² Triptans are available as sublingual tablets and nasal sprays, as well as subcutaneous injections for patients with significant associated nausea and vomiting. Avoid prescribing triptans for patients with known vascular disease (eg, history of stroke, myocardial infarction, peripheral vascular disease, uncontrolled hypertension, or signs and symptoms of these conditions), as well as for patients with severe hepatic impairment.

Treat migraine with a multifaceted approach, including management of acute symptoms and prevention of future headaches.

Importantly, although triptans all have a similar mechanism of action, patients might respond differently to different drugs within the class. If a patient does not get adequate headache relief from an appropriate dosage of a given triptan during a particular migraine episode, a different triptan can be tried during the next migraine.²² Additionally, if a patient experiences an adverse effect from one triptan, this does not necessarily mean that a trial of another triptan at a later time is contraindicated.

For patients who have an incomplete response to migraine treatment or for those with frequent recurrence, the combination formulation of sumatriptan, 85 mg, and naproxen, 500 mg, showed the highest rate of resolution of headache within 2 hours compared with either drug alone.²³ A similar result might be found by combining a triptan known to be effective for a patient and an NSAID other than naproxen. If migraine persists despite initial treatment of an attack, a different class of medication should be tried during the course of that attack to attain relief of symptoms of that migraine.²¹

When a patient is seen in an acute care setting (eg, emergency department, urgent care center) while suffering a migraine, additional treatment options are available. Intravenous (IV) anti-emetics are useful for relieving the pain of migraine and nausea, and can be used in combination with an IV NSAID (eg, ketorolac).²¹ The most effective anti-emetics are dopamine receptor type-2 blockers, including chlorpromazine, droperidol, metoclopramide, and prochlorperazine, which has the highest level of efficacy.²⁴ Note that these medications do present the risk of a dystonic reaction; diphenhydramine is therefore often used in tandem to mitigate such a response.

Looking ahead. Although triptans are the current first-line therapy for acute migraine, their effectiveness is limited. Only 20% of patients report sustained relief of pain in the 2 to 24 hours after treatment, and the response can vary from episode to episode.²⁵

Continue to: With better understading of the pathophysiology of migraine...

With better understanding of the pathophysiology of migraine, a host of novel anti-migraine drugs are on the horizon.

CGRP receptor antagonists. The neuropeptide CGRP, which mediates central and peripheral nervous system pain signaling, has been noted to be elevated during acute migraine attacks²⁶; clinical trials are therefore underway to evaluate the safety and efficacy of CGRP receptor antagonists.¹⁸ These agents appear to be better tolerated than triptans, have fewer vascular and central nervous system adverse effects, and present less of a risk of medication overuse headache.¹⁸ Liver toxicity has been seen with some medications in this class and remains an important concern in their development.¹⁹

Phase 3 clinical trials for 1 drug in this class, ubrogepant, were completed in late 2017; full analysis of the data is not yet available. Primary outcomes being evaluated include relief of pain at 2 hours and relief from the most bothersome symptoms again at 2 hours.²⁷

Selective serotonin-HT_1f receptor agonists, such as lasmiditan, offer another potential approach. Although the exact mechanism of action of these agents is not entirely clear, clinical trials have supported their efficacy and safety.²⁰ Importantly, ongoing trials are specifically targeting patients with known cardiovascular risk factors because they are most likely to benefit from the nonvasoconstrictive mechanism of action.^28,29 Adverse effects reported primarily include dizziness, fatigue, and vertigo.

Strategies for managing recurrent episodic migraine

Because of the risk of medication overuse headache with acute treatment, daily preventive therapy for migraine is indicated for any patient with ³⁰ :

• ≥6 headache days a month
• ≥4 headache days a month with some impairment
• ≥3 headache days a month with severe impairment.

Continue to: Treatment begins by having patients identify...

Treatment begins by having patients identify, and then avoid, migraine triggers (TABLE 5). This can be accomplished by having patients keep a headache diary, in which they can enter notations about personal and environmental situations that precede a headache.

For the individual patient, some triggers are modifiable; others are not. Helping a patient develop strategies for coping with triggers, rather than aiming for complete avoidance, might help her (him) manage those that are inescapable (eg stress, menstruation, etc).³¹ For many patients, however, this is not an adequate intervention and other approaches must be explored. When considering which therapy might be best for a given patient, evaluate her (his) comorbidities and assess that particular treatment for potential secondary benefits and the possibility of adverse effects. Pay attention to the choice of preventive therapy in women who are considering pregnancy because many available treatments are potentially teratogenic.

Oral medications. Oral agents from several classes of drugs can be used for migraine prophylaxis, including anti-epileptics,antidepressants, and antihypertensives (TABLE 6^{20,29,30,32-41}). Selected anti-epileptics (divalproex sodium, sodium valproate, topiramate) and beta-blockers (metoprolol, propranolol, and timolol) have the strongest evidence to support their use.³² Overall, regular use of prophylactic medications can reduce headache frequency by 50% for approximately 40% to 45% of patients who take them.²⁹ However, adherence may be limited by adverse effects or perceived lack of efficacy, thus reducing their potential for benefit.⁴²

OnabotulinumtoxinA. In patients with chronic migraine (≥15 headache days a month for at least 3 months) who have failed oral medications, the American Academy of Neurology (AAN) recommends the use of onabotulinumtoxinA.³⁰ The treatment regimen comprises 31 injections at various sites on the head, neck, and shoulders every 3 months.³³

A 2010 large randomized controlled trial showed a decrease in the frequency of headache days for patients receiving onabotulinumtoxinA compared to placebo after a 24-week treatment period (7.8 fewer headache days a month, compared to 6.4 fewer in the placebo group).³³ A recent systematic review also noted a reduction of 2 headache days a month compared with placebo; the authors cautioned, however, that data with which to evaluate onabotulinumtoxinA in comparison to other prophylactic agents are limited.⁴³

Continue to: In both studies...

In both studies, the risk of adverse drug events due to onabotulinumtoxinA was high and led to a significant rate of discontinuation.^33,43 Despite this, onabotulinumtoxinA remains the only Food and Drug Administration (FDA)–approved treatment for chronic migraine, making it reasonable to consider for appropriate patients.

Acupuncture. A 2016 Cochrane review found benefit for patients using acupuncture compared with sham acupuncture.³⁴ When acupuncture was compared with prophylactic agents such as beta-blockers, calcium-channel blockers, and anti-epileptics, however, there was no significant difference between the procedure and pharmacotherapy. Patients willing and able to try acupuncture might see a reduction in the overall number of headaches. Acupuncture has few adverse effects; however, long-term data are lacking.³⁴

Exercise is not supported by robust data for its role as a prophylactic treatment. It is generally considered safe in most populations, however, and can be pursued with little out-of-pocket cost.³⁵

Cognitive behavioral therapy (CBT). The AAN recommends CBT, relaxation therapy, and biofeedback therapy. Accessibility of these services remains limited for many patients, and cost can be prohibitive.¹⁶

Supplements used to help prevent migraine include the root of Petasites hybridus (butterbur), magnesium, vitamin B2 (riboflavin), Tanacetum parthenium (feverfew), and coenzyme Q10.¹⁶ Although the strength of evidence for these therapies is limited by small trials, their overall risk of adverse effects is low, and they might be easier for patients to obtain than acupuncture or CBT.

Continue to: Butterbur, in particular...

Butterbur, in particular, has been found to be beneficial for migraine prevention in 2 small placebo-controlled trials. In a randomized controlled study of 245 patients P hybridus, (specifically, the German formulation, Petadolex), 75 mg BID, reduced the frequency of migraine attack by 48% at 4 months, compared to placebo (number needed to treat, 5.3).⁴⁴ No difference was found at lower dosages. The most common reported adverse effect was burping.

Regrettably, unpurified butterbur extract contains pyrrolizidine alkaloids, potentially hepatotoxic and carcinogenic compounds. Because of variations in purification in production facilities in the United States, butterbur supplements might not have all of these compounds removed—and so should be used with caution.⁴¹

Magnesium. Studies evaluating the use of magnesium have demonstrated varied results; differences in methods and dosing have limited broad application of findings. As with most supplements considered for prophylactic treatment, magnesium dosing is poorly understood, and bioavailability varies in its different forms. Oral supplementation can be given as magnesium dicitrate, 600 mg/d.⁴⁵

Recently, products containing various combinations of feverfew, coenzyme Q10, riboflavin, magnesium, and other supplements have shown benefit in early clinical trials.^36,37

Neural stimulation. Over the past few years, a variety of transcutaneous nerve stimulator devices have gained FDA approval for use in migraine prophylaxis. The long-term safety and efficacy of these devices is not yet well understood, but they appear to provide headache relief in the short term and decrease the frequency of headache.³⁸ Use of the noninvasive stimulators is limited today by high cost and poor coverage by US health care insurers.

Continue to: Newly available medical therapy

Newly available medical therapy. The FDA recently approved erenumab, a fully human monoclonal antibody for prevention of migraine in adults. This is the first drug in the CGRP antagonist class to be approved for this indication. Trials of this once-monthly, self-injectable drug show promising results for patients whose migraines have been refractory to other therapies.

A recent large trial evaluated 955 adults with migraine, randomizing them to receive erenumab, 70 mg; erenumab, 140 mg; or placebo over 28 weeks.³⁹ The groups receiving erenumab had a nearly 2-fold higher odds of having their migraine reduced by 50%, compared with placebo (number needed to treat with the 140-mg dose, 4.27). Similar numbers of participants from all groups discontinued the study.³⁹ Phase 3 trials that are not yet formally published have produced similarly beneficial results.^40,46 The FDA has listed injection site reaction and constipation as the most reported adverse effects.⁴⁰

Three other anti-CGRP antibodies are likely to be approved in the near future: fremanezumab, galcanezumab, and eptinezumab.

The approach to migraine in special populations

Management of acute and chronic migraine in children, pregnant women, and older adults requires special attention: Treatment approaches are different than they are for adults 19 to 65 years of age.

Pediatric patients. Migraine is the most common acute and recurrent headache syndrome in children. Headaches differ from those of adult migraine as a result of variations in brain maturation, plasticity, and cognitive development.⁴⁷ Migraine attacks are often of shorter duration in children, lasting 1 to 2 hours, but can still be preceded by visual aura.⁴⁸ Just as with adults, imaging, electroencephalography, lumbar puncture, and routine labs should be considered only if a child has an abnormal neurological exam or other concerning features (TABLE 2^14,15).

Continue to: The general approach to migraine treatment...

The general approach to migraine treatment in the pediatric population includes education of the child and family about symptom management. Acetaminophen, NSAIDs, and triptans are approved for abortive therapy in children and should be used for acute headache relief in the same way that they are used in adults. Oral rizatriptan, the most well studied triptan in the pediatric population, is approved for use in children as young as 6 years⁴⁹; the pediatric dosage is 5 mg/d for patients weighing 20 to 39 kg and 10 mg/d for patients weighing more than 40 kg (same as the adult dosage).

Don’t prescribe triptans for patients with known vascular disease or severe hepatic impairment.

Oral almotriptan and zolmitriptan are also approved for use in children 12 to 17 years of age. Usual dosages are: almotriptan, 12.5 mg at onset, can repeat in 2 hours as needed (maximum dosage, 25 mg/d); and zolmitriptan, 2.5 mg at onset, can repeat in 2 hours as needed (maximum dosage, 10 mg/d).⁵⁰

For children who are unable to swallow pills or who are vomiting, a non-oral route of administration is preferable. Rizatriptan is available as an orally disintegrating tablet. Zolmitriptan is available in a nasal spray at a dose of 5 mg for children 12 years and older. Sumatriptan is not approved for use in patients younger than 18 years; however, recent studies have shown that it might have good efficacy and tolerability.⁵⁰

Daily prophylactic treatment for recurrent migraine in the pediatric population is an evolving subject; published guidelines do not exist. It is reasonable to consider treatment using the same guidelines as those in place for adults.⁵¹ Topiramate, 1 to 2 mg/kg/d, is the only therapy approved by the FDA for episodic migraine preventive therapy in adolescents.⁵⁰

If a patient doesn’t get adequate headache relief from an appropriate dosage of a given triptan, try a different triptan during the next migraine.

Notably, a nonpharmacotherapeutic approach may be more effective for pediatric prevention. In 2017, a large double-blind, placebo-controlled trial investigated the use of amitriptyline, topiramate, and placebo for the treatment of recurrent migraine in children 8 to 17 years of age. An interim analysis of the 328 children enrolled found no significant differences in reduction of headache frequency with treatment compared with placebo over a 24-week period; the trial was stopped early due to futility.⁵²

Continue to: The study did show...

The study did show, however, that reducing migraine triggers provided a high level of benefit to study participants. Stress is one of the most common migraine triggers in children; lack of sleep, exposure to a warm climate, and exposure to video games are also notable triggers.⁵³ CBT may augment the efficacy of standard migraine medications in the pediatric population and may help prevent recurrence of episodes.⁵⁴

Pregnancy. The treatment of migraine is different in pregnant women than it is in nonpregnant adults because of a concern over adverse effects on fetal development. For acute headache treatment, first-line therapies include trigger avoidance and acetaminophen, 1000 mg (maximum dosage, 4000 mg/d).⁵⁵ If this is ineffective, a 10-mg dose of metoclopramide, as often as every 6 hours (not an FDA-approved indication), can be considered. During the second trimester, NSAIDs can be considered second-line therapy.

Triptans—specifically, sumatriptan and rizatriptan—can also be considered if first-line therapies fail.⁵⁶ Triptan-exposed pregnant women with migraine have a rate of congenital malformations, spontaneous abortions, and prematurity that is similar to what is seen in pregnant women with migraine who have not been exposed to triptans. However, when triptan-exposed women are compared with healthy, non-migraine-suffering women, the rate of spontaneous abortion appears to be increased in the triptan-exposed population.⁵⁷

Ergotamine is contraindicated during pregnancy because of its potential to induce uterine contractions and vasospasm, which can be detrimental to the fetus.⁵⁶Nonpharmacotherapeutic interventions such as heat, ice, massage, rest, and avoidance of triggers are as successful in the pregnant population as in the nonpregnant population. For migraine prevention, coenzyme Q10, vitamins B2 and B6 (pyridoxine), and oral magnesium can be considered. Feverfew and butterbur should be avoided because of concerns about fetal malformation and preterm labor.⁵⁸

Older adults. Choosing appropriate migraine therapy for older adults requires special consideration because of changes in drug metabolism and risks associated with drug adverse effects. Additionally, few studies of migraine drugs have included large populations of adults older than 65 years; medications should therefore be prescribed cautiously in this population, with particular attention to drug–drug interactions.

Continue to: Just as for younger adults...

Just as for younger adults, mild symptoms can be managed effectively with acetaminophen. NSAIDs may be used as well, but carry increased risks of gastric bleeding and elevation in blood pressure.⁵⁹ The use of triptans is acceptable for the appropriate patient, but should be avoided in patients with known vascular disease.⁶⁰ Antiemetics present an increased risk of extrapyramidal adverse effects in the elderly and should be used with caution at the lowest effective dosage.⁵⁹ Novel mechanisms of action make some of the newer agents potentially safer for use in older adults when treating acute migraine.

Stress is one of the most common migraine triggers in children.

For migraine prevention in older adults, particular attention should be paid to reducing triggers and minimizing polypharmacy.

More and more, successful treatment is within reach

With many clinical trials evaluating novel drugs underway, and additional studies contributing to our understanding of nonpharmacotherapeutic approaches to migraine treatment, improved headache control may become increasingly common over the next few years.

CORRESPONDENCE
Kathryn McGrath, MD, Department of Family and Community Medicine, Thomas Jefferson University, 1015 Walnut St, Philadelphia PA 19107; [email protected].

Women with rheumatoid arthritis who undergo assisted reproduction treatment have a decreased likelihood of live births versus women without rheumatoid arthritis, according to authors of a recent Denmark-wide cohort study.

The problem might be caused by an impaired chance of embryo implantation, authors of the study reported in the Annals of the Rheumatic Diseases.

Corticosteroids prescribed before embryo transfer might have improved the likelihood of live birth in these women with rheumatoid arthritis, according to the investigators, led by Professor Bente Mertz Nørgård of the center for clinical epidemiology at the Odense (Denmark) University Hospital.

However, findings with regard to that potential effect of corticosteroids were “not unambiguous,” said Prof. Nørgård and her coauthors said in their report.

The cohort study, based on Danish registry data from 1994-2017, included 1,149 embryo transfers in women and rheumatoid arthritis with 198,941 embryo transfers in women without rheumatoid arthritis.

Live births per embryo transfer were less likely in women with rheumatoid arthritis versus those they were in women with no rheumatoid arthritis, with an adjusted odds ratio of 0.78 (95% confidence interval, 0.65-0.92), according to investigators.

Chances of biochemical and clinical pregnancies were also lower in women with rheumatoid arthritis, with odds ratios of 0.81 (95% CI, 0.68-0.95) and 0.82 (95% CI, 0.59-1.15), respectively, the investigators found in an analysis of secondary outcomes in the study.

Corticosteroids prescribed before embryo transfer increased odds of live birth, with an adjusted odds ratio of 1.32 (95% CI, 0.85-2.05), though the underlying reason why corticosteroids were prescribed could not be established in this data set, investigators cautioned.

“The impact of corticosteroid prior to embryo transfer, found in our study, could be due to a suppression of ‘abnormalities in the immune system’ in women with RA, but we have to underline that this is speculative,” Prof. Nørgård and her colleagues said in a discussion of their results.

Future investigations are needed to clarify the role of corticosteroids in women with rheumatoid arthritis undergoing assisted reproduction treatment, they added.

Support for the study came from the Research Foundation of the Region of Southern Denmark and the Free Research Foundation at Odense University Hospital. Dr. Nørgård and her coauthors said they had no competing interests related to the research.

SOURCE: Nørgård BM et al. Ann Rheum Dis. 2019 Jan 12. doi: 10.1136/annrheumdis-2018-214619.

Women with rheumatoid arthritis who undergo assisted reproduction treatment have a decreased likelihood of live births versus women without rheumatoid arthritis, according to authors of a recent Denmark-wide cohort study.

The problem might be caused by an impaired chance of embryo implantation, authors of the study reported in the Annals of the Rheumatic Diseases.

Corticosteroids prescribed before embryo transfer might have improved the likelihood of live birth in these women with rheumatoid arthritis, according to the investigators, led by Professor Bente Mertz Nørgård of the center for clinical epidemiology at the Odense (Denmark) University Hospital.

However, findings with regard to that potential effect of corticosteroids were “not unambiguous,” said Prof. Nørgård and her coauthors said in their report.

The cohort study, based on Danish registry data from 1994-2017, included 1,149 embryo transfers in women and rheumatoid arthritis with 198,941 embryo transfers in women without rheumatoid arthritis.

Live births per embryo transfer were less likely in women with rheumatoid arthritis versus those they were in women with no rheumatoid arthritis, with an adjusted odds ratio of 0.78 (95% confidence interval, 0.65-0.92), according to investigators.

Chances of biochemical and clinical pregnancies were also lower in women with rheumatoid arthritis, with odds ratios of 0.81 (95% CI, 0.68-0.95) and 0.82 (95% CI, 0.59-1.15), respectively, the investigators found in an analysis of secondary outcomes in the study.

Corticosteroids prescribed before embryo transfer increased odds of live birth, with an adjusted odds ratio of 1.32 (95% CI, 0.85-2.05), though the underlying reason why corticosteroids were prescribed could not be established in this data set, investigators cautioned.

“The impact of corticosteroid prior to embryo transfer, found in our study, could be due to a suppression of ‘abnormalities in the immune system’ in women with RA, but we have to underline that this is speculative,” Prof. Nørgård and her colleagues said in a discussion of their results.

Future investigations are needed to clarify the role of corticosteroids in women with rheumatoid arthritis undergoing assisted reproduction treatment, they added.

Support for the study came from the Research Foundation of the Region of Southern Denmark and the Free Research Foundation at Odense University Hospital. Dr. Nørgård and her coauthors said they had no competing interests related to the research.

SOURCE: Nørgård BM et al. Ann Rheum Dis. 2019 Jan 12. doi: 10.1136/annrheumdis-2018-214619.

Women with rheumatoid arthritis who undergo assisted reproduction treatment have a decreased likelihood of live births versus women without rheumatoid arthritis, according to authors of a recent Denmark-wide cohort study.

The problem might be caused by an impaired chance of embryo implantation, authors of the study reported in the Annals of the Rheumatic Diseases.

Corticosteroids prescribed before embryo transfer might have improved the likelihood of live birth in these women with rheumatoid arthritis, according to the investigators, led by Professor Bente Mertz Nørgård of the center for clinical epidemiology at the Odense (Denmark) University Hospital.

However, findings with regard to that potential effect of corticosteroids were “not unambiguous,” said Prof. Nørgård and her coauthors said in their report.

The cohort study, based on Danish registry data from 1994-2017, included 1,149 embryo transfers in women and rheumatoid arthritis with 198,941 embryo transfers in women without rheumatoid arthritis.

Live births per embryo transfer were less likely in women with rheumatoid arthritis versus those they were in women with no rheumatoid arthritis, with an adjusted odds ratio of 0.78 (95% confidence interval, 0.65-0.92), according to investigators.

Chances of biochemical and clinical pregnancies were also lower in women with rheumatoid arthritis, with odds ratios of 0.81 (95% CI, 0.68-0.95) and 0.82 (95% CI, 0.59-1.15), respectively, the investigators found in an analysis of secondary outcomes in the study.

Corticosteroids prescribed before embryo transfer increased odds of live birth, with an adjusted odds ratio of 1.32 (95% CI, 0.85-2.05), though the underlying reason why corticosteroids were prescribed could not be established in this data set, investigators cautioned.

“The impact of corticosteroid prior to embryo transfer, found in our study, could be due to a suppression of ‘abnormalities in the immune system’ in women with RA, but we have to underline that this is speculative,” Prof. Nørgård and her colleagues said in a discussion of their results.

Future investigations are needed to clarify the role of corticosteroids in women with rheumatoid arthritis undergoing assisted reproduction treatment, they added.

Support for the study came from the Research Foundation of the Region of Southern Denmark and the Free Research Foundation at Odense University Hospital. Dr. Nørgård and her coauthors said they had no competing interests related to the research.

SOURCE: Nørgård BM et al. Ann Rheum Dis. 2019 Jan 12. doi: 10.1136/annrheumdis-2018-214619.

Point-of-care intrapartum molecular screening of group B Streptococcus reduced the incidence of early-onset disease cases and antibiotic use, according to research published in Obstetrics & Gynecology.

James Gathany/CDC

Najoua El Helali, PharmD, from the Service de Microbiologie Clinique at Groupe Hospitalier Paris Saint-Joseph, and her colleagues measured the rate of early-onset disease group B Streptococcus (GBS) in a single-center study analyzing antenatal culture screening for 4 years prior to implementation (2006-2009) of polymerase chain reaction (PCR) screening (2010-2015). There were 11,226 deliveries (11,818 live births) during the antenatal screening period and 18,835 deliveries (18,980 live births) during the PCR screening period. Overall, 4% of deliveries during the antenatal period and 0.1% of deliveries during the intrapartum period were not screened for GBS (P less than .001).

During 2006-2015, the rate of early-onset disease of GBS decreased to 0.21/1,000 cases from 1.01/1,000 cases (risk ratio, 0.25; 95% confidence interval, 0.14-0.43; P = .026), while the rate of probable early-onset disease GBS decreased to 0.73/1,000 cases from 2.8/1,000 cases (RR, 0.25; (95% CI, 0.14-0.43; P less than .001).

For patients with early-onset GBS, length of stay in hospital decreased by 64%, and antibiotic therapy decreased by 60%, but there was no significant difference in average length of stay or duration of antibiotic therapy during the study period. There was a reduction in annual delivery- and treatment-associated costs of early-onset disease GBS from $41,875 to $11,945, while the estimated extra cost of PCR screening to avoid one additional case of early-onset disease GBS was $5,819 and a cost increase of $49 per newborn.

“The additional PCR costs were offset in part by the reduction in early-onset GBS disease treatment costs,” the investigators said.

“A randomized, controlled multicenter study is probably needed to evaluate the cost-effectiveness of this prevention strategy and demonstrate a better efficacy in populations where poorly followed women are of unknown GBS status at presentation for delivery,” the researchers said. “In term newborns, however, using infection rate as an endpoint is problematic given the sample size needed.”

The researchers said their study was potentially limited by lack of a control group and population selection, and described mothers in their center as “mostly well-informed and well-monitored during their pregnancy.”

The authors reported no relevant conflicts of interest.

SOURCE: El Helali N et al. Obstet Gynecol. 2019. doi: 10.1097/AOG.0000000000003057.

Point-of-care intrapartum molecular screening of group B Streptococcus reduced the incidence of early-onset disease cases and antibiotic use, according to research published in Obstetrics & Gynecology.

James Gathany/CDC

Najoua El Helali, PharmD, from the Service de Microbiologie Clinique at Groupe Hospitalier Paris Saint-Joseph, and her colleagues measured the rate of early-onset disease group B Streptococcus (GBS) in a single-center study analyzing antenatal culture screening for 4 years prior to implementation (2006-2009) of polymerase chain reaction (PCR) screening (2010-2015). There were 11,226 deliveries (11,818 live births) during the antenatal screening period and 18,835 deliveries (18,980 live births) during the PCR screening period. Overall, 4% of deliveries during the antenatal period and 0.1% of deliveries during the intrapartum period were not screened for GBS (P less than .001).

During 2006-2015, the rate of early-onset disease of GBS decreased to 0.21/1,000 cases from 1.01/1,000 cases (risk ratio, 0.25; 95% confidence interval, 0.14-0.43; P = .026), while the rate of probable early-onset disease GBS decreased to 0.73/1,000 cases from 2.8/1,000 cases (RR, 0.25; (95% CI, 0.14-0.43; P less than .001).

For patients with early-onset GBS, length of stay in hospital decreased by 64%, and antibiotic therapy decreased by 60%, but there was no significant difference in average length of stay or duration of antibiotic therapy during the study period. There was a reduction in annual delivery- and treatment-associated costs of early-onset disease GBS from $41,875 to $11,945, while the estimated extra cost of PCR screening to avoid one additional case of early-onset disease GBS was $5,819 and a cost increase of $49 per newborn.

“The additional PCR costs were offset in part by the reduction in early-onset GBS disease treatment costs,” the investigators said.

“A randomized, controlled multicenter study is probably needed to evaluate the cost-effectiveness of this prevention strategy and demonstrate a better efficacy in populations where poorly followed women are of unknown GBS status at presentation for delivery,” the researchers said. “In term newborns, however, using infection rate as an endpoint is problematic given the sample size needed.”

The researchers said their study was potentially limited by lack of a control group and population selection, and described mothers in their center as “mostly well-informed and well-monitored during their pregnancy.”

The authors reported no relevant conflicts of interest.

SOURCE: El Helali N et al. Obstet Gynecol. 2019. doi: 10.1097/AOG.0000000000003057.

Point-of-care intrapartum molecular screening of group B Streptococcus reduced the incidence of early-onset disease cases and antibiotic use, according to research published in Obstetrics & Gynecology.

James Gathany/CDC

Najoua El Helali, PharmD, from the Service de Microbiologie Clinique at Groupe Hospitalier Paris Saint-Joseph, and her colleagues measured the rate of early-onset disease group B Streptococcus (GBS) in a single-center study analyzing antenatal culture screening for 4 years prior to implementation (2006-2009) of polymerase chain reaction (PCR) screening (2010-2015). There were 11,226 deliveries (11,818 live births) during the antenatal screening period and 18,835 deliveries (18,980 live births) during the PCR screening period. Overall, 4% of deliveries during the antenatal period and 0.1% of deliveries during the intrapartum period were not screened for GBS (P less than .001).

During 2006-2015, the rate of early-onset disease of GBS decreased to 0.21/1,000 cases from 1.01/1,000 cases (risk ratio, 0.25; 95% confidence interval, 0.14-0.43; P = .026), while the rate of probable early-onset disease GBS decreased to 0.73/1,000 cases from 2.8/1,000 cases (RR, 0.25; (95% CI, 0.14-0.43; P less than .001).

For patients with early-onset GBS, length of stay in hospital decreased by 64%, and antibiotic therapy decreased by 60%, but there was no significant difference in average length of stay or duration of antibiotic therapy during the study period. There was a reduction in annual delivery- and treatment-associated costs of early-onset disease GBS from $41,875 to $11,945, while the estimated extra cost of PCR screening to avoid one additional case of early-onset disease GBS was $5,819 and a cost increase of $49 per newborn.

“The additional PCR costs were offset in part by the reduction in early-onset GBS disease treatment costs,” the investigators said.

“A randomized, controlled multicenter study is probably needed to evaluate the cost-effectiveness of this prevention strategy and demonstrate a better efficacy in populations where poorly followed women are of unknown GBS status at presentation for delivery,” the researchers said. “In term newborns, however, using infection rate as an endpoint is problematic given the sample size needed.”

The researchers said their study was potentially limited by lack of a control group and population selection, and described mothers in their center as “mostly well-informed and well-monitored during their pregnancy.”

The authors reported no relevant conflicts of interest.

SOURCE: El Helali N et al. Obstet Gynecol. 2019. doi: 10.1097/AOG.0000000000003057.

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

Young women who delay starting contraception when they start sexual activity are at increased risk of unwanted pregnancy, according to data from a cross-sectional study of more than 26,000 women in the United States.

Jupiterimages/thinkstock

Unintended pregnancy in the United States is associated with delayed prenatal care, premature birth, and low birth weight and remains more common among African American and Hispanic women than among white women, and it also is more common among low-income women than among high income women, wrote Mara E. Murray Horwitz, MD, of Harvard Pilgrim Health Care Institute in Boston and her colleagues.

“Reducing unintended pregnancy and the associated socioeconomic disparities is a national public health priority,” they wrote.

In a study published in Pediatrics, the researchers reviewed data from four cycles of the National Survey of Family Growth between 2002 and 2015. They examined self-reported responses from 26,359 women aged 15-44 years with sexual debuts during 1970-2014, including the dates of sexual debut, initiation of contraceptives, and rates of unwanted pregnancy. Timely contraceptive initiation was defined as use within a month of starting sexual activity.

Overall, one in five women reported delayed initiation of contraception. This delay was significantly associated with an increased unwanted pregnancy risk within 3 months of starting sexual activity, compared with timely use of contraception (adjusted risk ratio, 3.7). The average age of sexual debut was 17 years.

When the researchers examined subgroups, they found that one in four respondents who were African American, Hispanic, or low income reported delayed contraceptive initiation.

No association with unwanted pregnancy was found between effective versus less effective contraception methods. Timely contraceptive use increased during the study period from less than 10% in the 1970s to more than 25% in the 2000s, but condoms accounted for most of this increase. Use of other methods including long-acting reversible and short-acting hormonal options was low, especially among African American, Hispanic, and low-income women, Dr. Murray Horwitz and her colleagues noted.

The study was limited by several factors including the use of self-reports, lack of data on the exact start of contraceptive initiation, and the lack of association between contraceptive method and unwanted pregnancy, the researchers noted. However, the findings suggest that clinicians can help by intervening with young patients and educating them about early adoption of pregnancy prevention strategies.

The study was funded by the National Institutes of Health; Dr. Murray Horwitz was supported by an award from the NIH and Harvard Pilgrim Health Care Institute. Another researcher received support from Harvard Pilgrim Health Care Institute to provide mentorship for the study. The remaining researcher had no relevant financial disclosures.

SOURCE: Murray Horwitz M et al. Pediatrics. 2019;143(2):e20182463.

A new consensus statement places renewed focus on maternal interpregnancy care, with a goal of extending care past the postpartum period to provide a wellness-maximizing continuum of care.

The document, developed by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine (SMFM), recognizes that pregnancy is part of the lifelong continuum of health and wellness. Although not all women will go on to have another pregnancy, the concept of interpregnancy care recognizes that ob.gyns. have a vital role that extends past the postpartum period.

“This is a shift in what we used to think was our job. We used to think that our job ended when the baby came out,” said the first author of the obstetric care consensus statement, Judette Marie Louis, MD, an ob.gyn. faculty member at the University of South Florida, Tampa, and a SMFM board member. “For too long, our focus was just the baby; we need to tell women, ‘You’re important too,’ ” she said in an interview.

“The interpregnancy period is an opportunity to address these complications of medical issues that have developed during pregnancy, to assess a woman’s mental and physical well-being, and to optimize her health along her life course,” Dr. Louis and her coauthors wrote in Obstetrics & Gynecology.

Conceptually, the opportunity for interpregnancy care arises after any pregnancy, no matter the outcome, and is part of the continuum of care for women of reproductive age. For women who do not intend a future pregnancy, well-woman care is the focus, while women who currently intend to become pregnant again receive interpregnancy care. Women may move from one arm of the continuum to the other if their intentions change or if they become pregnant, explained Dr. Louis and her coauthors.

Birth spacing

The new consensus document includes an emphasis on long-term health outcomes as well as maternal and neonatal outcomes in future pregnancies. Although the evidence is of no more than moderate quality, women should be advised to have an interpregnancy interval of at least 6 months and offered counseling about family planning before delivery. Risks and benefits of an interpregnancy interval of less than 18 months should be reviewed as well.

Stuart Jenner/Thinkstock

For women with a history of preterm birth and those who have had a prior cesarean delivery and desire a subsequent trial of labor, birth spacing is particularly important, noted Dr. Louis and her colleagues. There is higher-risk evidence for uterine rupture after cesarean delivery if delivery-to-delivery intervals are 18-24 months or less.

Recommendations regarding the length of the interpregnancy interval generally should not be affected by a history of prior infertility.

Other recommendations

High-quality evidence supports breast feeding’s salutary effects on maternal and child health, so women should receive anticipatory support and guidance to enable breastfeeding, according to the document.

In accordance with other guidelines, the document recommends that all women be screened for depression post partum and as part of well-woman care in the interpregnancy interval. Procedures for effective diagnosis, treatment, and follow-up should accompany the screening.

Best practices dictate that women are asked about alcohol, prescription, and nonprescription drug use as a routine matter. High-quality evidence supports offering smoking cessation support to women who smoke and giving specific advice about nutrition and physical activity that’s based on “proven behavioral techniques.”

Evidence is of moderate quality that women should be encouraged to reach their prepregnancy weight by a year after delivery, with the ultimate goal of having a body mass index of 18.5-24.9.

High-quality evidence backs encouragement to engage in safe sex practices, with care providers also advised to facilitate partner screening and treatment for STIs.

Screening for STIs should follow guidance put forward by the Centers for Disease Control and Prevention and should be offered to women at high risk for STIs; those with a history of STI should have a careful history taken to determine risks for current or repeat infections, wrote Dr. Louis and her coauthors. These strong recommendations have high-quality evidence behind them.

The consensus statement recommends screening women for intimate partner violence, with moderate-quality evidence to support the recommendation. Patient navigators, expert medical interpretation, and other health educators can be offered to women with health literacy or language and communication challenges, but the evidence backing the recommendation is of low quality.

A subset of the interpregnancy care recommendations gives additional guidance regarding women with a history of high-risk pregnancy. All women planning pregnancy – or who could become pregnant – should take 500 mcg of folic acid daily beginning 1 month before fertilization and continuing through the 12th week of pregnancy. Folic acid supplementation for women who have had children with neural tube defects should begin at least 3 months before fertilization and continue through 12 weeks of pregnancy, at a dose of 400 mg.

All prescription and nonprescription medications, as well as potential environmental teratogens, should be reviewed before a repeat pregnancy. This, as well as the folic acid recommendations, are strong recommendations backed by high-quality evidence.

When appropriate, genetic counseling should be offered to women who have had prior pregnancies with genetic disorders or congenital anomalies. Asymptomatic genitourinary infections should not be treated in women with a history of preterm birth during the interpregnancy interval. These are strong recommendations, but are backed by low to moderate quality evidence, wrote Dr. Louis and her colleagues.

Another section of the consensus document specifically addresses specific health conditions, including diabetes, gestational diabetes, gestational and chronic hypertension, and preeclampsia, as well as mental health disorders and overweight or obesity.

For each, Dr. Louis and her coauthors recommend counseling that reviews complications and risk for future disease; for example, not only does prior preeclampsia increase risk for that complication in future pregnancies, risk for later cardiovascular disease is also doubled. The document outlines recommended interpregnancy testing, management considerations and medications of concern for health care providers caring for women with these conditions, and condition-specific goals.

Of the association between gestational diabetes, hypertension, and preeclampsia with later disease, Dr. Louis said in the interview, “We don’t know. ... It may be that pregnancy accelerates these diseases. We do know that normal changes in pregnancy stress your body, and that preeclampsia damages your vessels. Pregnancy can give you a warning, but we don’t have enough information to predict the outcome” in later life. “We do know there is some advice we can give: stop smoking and maintain a normal body weight.”

Other conditions such as HIV, renal disease, epilepsy, autoimmune and thyroid disease, and thrombophilias and antiphospholipid antibody syndrome are also addressed in this section of the consensus document.

Specific attention also is given to psychosocial risks, such as socioeconomic disadvantages and being a member of a racial or ethnic minority. Social determinants of health are complex, said Dr. Louis, but socioeconomic and racial stressors can include the added burden of caring for loved ones with constrained resources. Additionally, there can be access issues: Women can get emergent care by presenting to the ED but receiving continued primary and specialty care can be much more of a challenge.

Regarding racism, Dr. Louis said, “We all come into caring for these women with certain ideas.” For example, it’s not enough to say of a patient, “She’s noncompliant. You need to ask why.” When the “why” question is asked, then you may discover, “there’s something you can help the patient with,” she said. “We need to ask why, and then take steps to help our patients.”

Document building

The working group for the consensus document felt it was important to include nonphysicians who care for women, Dr. Louis said, so drafts were reviewed by and input received from the American College of Nurse-Midwives and the National Association of Nurse Practitioners in Women’s Health. Both groups endorsed the document.

The collaborative process of putting drafts together and then reviewing and revising the document was a big part of the reason it took 2 years to produce the interpregnancy care consensus statement. “It was the equivalent of two full gestations with a short interpregnancy interval!” said Dr. Louis, laughing. But seeking input from all stakeholders strengthened the final product.

Dr. Louis reported no conflicts of interest and no outside sources of funding were reported.

[email protected]

SOURCE: Louis JM et al. Obstet Gynecol. 2019;133:e51-72.

A new consensus statement places renewed focus on maternal interpregnancy care, with a goal of extending care past the postpartum period to provide a wellness-maximizing continuum of care.

The document, developed by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine (SMFM), recognizes that pregnancy is part of the lifelong continuum of health and wellness. Although not all women will go on to have another pregnancy, the concept of interpregnancy care recognizes that ob.gyns. have a vital role that extends past the postpartum period.

“This is a shift in what we used to think was our job. We used to think that our job ended when the baby came out,” said the first author of the obstetric care consensus statement, Judette Marie Louis, MD, an ob.gyn. faculty member at the University of South Florida, Tampa, and a SMFM board member. “For too long, our focus was just the baby; we need to tell women, ‘You’re important too,’ ” she said in an interview.

“The interpregnancy period is an opportunity to address these complications of medical issues that have developed during pregnancy, to assess a woman’s mental and physical well-being, and to optimize her health along her life course,” Dr. Louis and her coauthors wrote in Obstetrics & Gynecology.

Conceptually, the opportunity for interpregnancy care arises after any pregnancy, no matter the outcome, and is part of the continuum of care for women of reproductive age. For women who do not intend a future pregnancy, well-woman care is the focus, while women who currently intend to become pregnant again receive interpregnancy care. Women may move from one arm of the continuum to the other if their intentions change or if they become pregnant, explained Dr. Louis and her coauthors.

Birth spacing

The new consensus document includes an emphasis on long-term health outcomes as well as maternal and neonatal outcomes in future pregnancies. Although the evidence is of no more than moderate quality, women should be advised to have an interpregnancy interval of at least 6 months and offered counseling about family planning before delivery. Risks and benefits of an interpregnancy interval of less than 18 months should be reviewed as well.

Stuart Jenner/Thinkstock

For women with a history of preterm birth and those who have had a prior cesarean delivery and desire a subsequent trial of labor, birth spacing is particularly important, noted Dr. Louis and her colleagues. There is higher-risk evidence for uterine rupture after cesarean delivery if delivery-to-delivery intervals are 18-24 months or less.

Recommendations regarding the length of the interpregnancy interval generally should not be affected by a history of prior infertility.

Other recommendations

High-quality evidence supports breast feeding’s salutary effects on maternal and child health, so women should receive anticipatory support and guidance to enable breastfeeding, according to the document.

In accordance with other guidelines, the document recommends that all women be screened for depression post partum and as part of well-woman care in the interpregnancy interval. Procedures for effective diagnosis, treatment, and follow-up should accompany the screening.

Best practices dictate that women are asked about alcohol, prescription, and nonprescription drug use as a routine matter. High-quality evidence supports offering smoking cessation support to women who smoke and giving specific advice about nutrition and physical activity that’s based on “proven behavioral techniques.”

Evidence is of moderate quality that women should be encouraged to reach their prepregnancy weight by a year after delivery, with the ultimate goal of having a body mass index of 18.5-24.9.

High-quality evidence backs encouragement to engage in safe sex practices, with care providers also advised to facilitate partner screening and treatment for STIs.

Screening for STIs should follow guidance put forward by the Centers for Disease Control and Prevention and should be offered to women at high risk for STIs; those with a history of STI should have a careful history taken to determine risks for current or repeat infections, wrote Dr. Louis and her coauthors. These strong recommendations have high-quality evidence behind them.

The consensus statement recommends screening women for intimate partner violence, with moderate-quality evidence to support the recommendation. Patient navigators, expert medical interpretation, and other health educators can be offered to women with health literacy or language and communication challenges, but the evidence backing the recommendation is of low quality.

A subset of the interpregnancy care recommendations gives additional guidance regarding women with a history of high-risk pregnancy. All women planning pregnancy – or who could become pregnant – should take 500 mcg of folic acid daily beginning 1 month before fertilization and continuing through the 12th week of pregnancy. Folic acid supplementation for women who have had children with neural tube defects should begin at least 3 months before fertilization and continue through 12 weeks of pregnancy, at a dose of 400 mg.

All prescription and nonprescription medications, as well as potential environmental teratogens, should be reviewed before a repeat pregnancy. This, as well as the folic acid recommendations, are strong recommendations backed by high-quality evidence.

When appropriate, genetic counseling should be offered to women who have had prior pregnancies with genetic disorders or congenital anomalies. Asymptomatic genitourinary infections should not be treated in women with a history of preterm birth during the interpregnancy interval. These are strong recommendations, but are backed by low to moderate quality evidence, wrote Dr. Louis and her colleagues.

Another section of the consensus document specifically addresses specific health conditions, including diabetes, gestational diabetes, gestational and chronic hypertension, and preeclampsia, as well as mental health disorders and overweight or obesity.

For each, Dr. Louis and her coauthors recommend counseling that reviews complications and risk for future disease; for example, not only does prior preeclampsia increase risk for that complication in future pregnancies, risk for later cardiovascular disease is also doubled. The document outlines recommended interpregnancy testing, management considerations and medications of concern for health care providers caring for women with these conditions, and condition-specific goals.

Of the association between gestational diabetes, hypertension, and preeclampsia with later disease, Dr. Louis said in the interview, “We don’t know. ... It may be that pregnancy accelerates these diseases. We do know that normal changes in pregnancy stress your body, and that preeclampsia damages your vessels. Pregnancy can give you a warning, but we don’t have enough information to predict the outcome” in later life. “We do know there is some advice we can give: stop smoking and maintain a normal body weight.”

Other conditions such as HIV, renal disease, epilepsy, autoimmune and thyroid disease, and thrombophilias and antiphospholipid antibody syndrome are also addressed in this section of the consensus document.

Specific attention also is given to psychosocial risks, such as socioeconomic disadvantages and being a member of a racial or ethnic minority. Social determinants of health are complex, said Dr. Louis, but socioeconomic and racial stressors can include the added burden of caring for loved ones with constrained resources. Additionally, there can be access issues: Women can get emergent care by presenting to the ED but receiving continued primary and specialty care can be much more of a challenge.

Regarding racism, Dr. Louis said, “We all come into caring for these women with certain ideas.” For example, it’s not enough to say of a patient, “She’s noncompliant. You need to ask why.” When the “why” question is asked, then you may discover, “there’s something you can help the patient with,” she said. “We need to ask why, and then take steps to help our patients.”

Document building

The working group for the consensus document felt it was important to include nonphysicians who care for women, Dr. Louis said, so drafts were reviewed by and input received from the American College of Nurse-Midwives and the National Association of Nurse Practitioners in Women’s Health. Both groups endorsed the document.

The collaborative process of putting drafts together and then reviewing and revising the document was a big part of the reason it took 2 years to produce the interpregnancy care consensus statement. “It was the equivalent of two full gestations with a short interpregnancy interval!” said Dr. Louis, laughing. But seeking input from all stakeholders strengthened the final product.

Dr. Louis reported no conflicts of interest and no outside sources of funding were reported.

[email protected]

SOURCE: Louis JM et al. Obstet Gynecol. 2019;133:e51-72.

A new consensus statement places renewed focus on maternal interpregnancy care, with a goal of extending care past the postpartum period to provide a wellness-maximizing continuum of care.

The document, developed by the American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine (SMFM), recognizes that pregnancy is part of the lifelong continuum of health and wellness. Although not all women will go on to have another pregnancy, the concept of interpregnancy care recognizes that ob.gyns. have a vital role that extends past the postpartum period.

“This is a shift in what we used to think was our job. We used to think that our job ended when the baby came out,” said the first author of the obstetric care consensus statement, Judette Marie Louis, MD, an ob.gyn. faculty member at the University of South Florida, Tampa, and a SMFM board member. “For too long, our focus was just the baby; we need to tell women, ‘You’re important too,’ ” she said in an interview.

“The interpregnancy period is an opportunity to address these complications of medical issues that have developed during pregnancy, to assess a woman’s mental and physical well-being, and to optimize her health along her life course,” Dr. Louis and her coauthors wrote in Obstetrics & Gynecology.

Conceptually, the opportunity for interpregnancy care arises after any pregnancy, no matter the outcome, and is part of the continuum of care for women of reproductive age. For women who do not intend a future pregnancy, well-woman care is the focus, while women who currently intend to become pregnant again receive interpregnancy care. Women may move from one arm of the continuum to the other if their intentions change or if they become pregnant, explained Dr. Louis and her coauthors.

Birth spacing

The new consensus document includes an emphasis on long-term health outcomes as well as maternal and neonatal outcomes in future pregnancies. Although the evidence is of no more than moderate quality, women should be advised to have an interpregnancy interval of at least 6 months and offered counseling about family planning before delivery. Risks and benefits of an interpregnancy interval of less than 18 months should be reviewed as well.

Stuart Jenner/Thinkstock

For women with a history of preterm birth and those who have had a prior cesarean delivery and desire a subsequent trial of labor, birth spacing is particularly important, noted Dr. Louis and her colleagues. There is higher-risk evidence for uterine rupture after cesarean delivery if delivery-to-delivery intervals are 18-24 months or less.

Recommendations regarding the length of the interpregnancy interval generally should not be affected by a history of prior infertility.

Other recommendations

High-quality evidence supports breast feeding’s salutary effects on maternal and child health, so women should receive anticipatory support and guidance to enable breastfeeding, according to the document.

In accordance with other guidelines, the document recommends that all women be screened for depression post partum and as part of well-woman care in the interpregnancy interval. Procedures for effective diagnosis, treatment, and follow-up should accompany the screening.

Best practices dictate that women are asked about alcohol, prescription, and nonprescription drug use as a routine matter. High-quality evidence supports offering smoking cessation support to women who smoke and giving specific advice about nutrition and physical activity that’s based on “proven behavioral techniques.”

Evidence is of moderate quality that women should be encouraged to reach their prepregnancy weight by a year after delivery, with the ultimate goal of having a body mass index of 18.5-24.9.

High-quality evidence backs encouragement to engage in safe sex practices, with care providers also advised to facilitate partner screening and treatment for STIs.

Screening for STIs should follow guidance put forward by the Centers for Disease Control and Prevention and should be offered to women at high risk for STIs; those with a history of STI should have a careful history taken to determine risks for current or repeat infections, wrote Dr. Louis and her coauthors. These strong recommendations have high-quality evidence behind them.

The consensus statement recommends screening women for intimate partner violence, with moderate-quality evidence to support the recommendation. Patient navigators, expert medical interpretation, and other health educators can be offered to women with health literacy or language and communication challenges, but the evidence backing the recommendation is of low quality.

A subset of the interpregnancy care recommendations gives additional guidance regarding women with a history of high-risk pregnancy. All women planning pregnancy – or who could become pregnant – should take 500 mcg of folic acid daily beginning 1 month before fertilization and continuing through the 12th week of pregnancy. Folic acid supplementation for women who have had children with neural tube defects should begin at least 3 months before fertilization and continue through 12 weeks of pregnancy, at a dose of 400 mg.

All prescription and nonprescription medications, as well as potential environmental teratogens, should be reviewed before a repeat pregnancy. This, as well as the folic acid recommendations, are strong recommendations backed by high-quality evidence.

When appropriate, genetic counseling should be offered to women who have had prior pregnancies with genetic disorders or congenital anomalies. Asymptomatic genitourinary infections should not be treated in women with a history of preterm birth during the interpregnancy interval. These are strong recommendations, but are backed by low to moderate quality evidence, wrote Dr. Louis and her colleagues.

Another section of the consensus document specifically addresses specific health conditions, including diabetes, gestational diabetes, gestational and chronic hypertension, and preeclampsia, as well as mental health disorders and overweight or obesity.

For each, Dr. Louis and her coauthors recommend counseling that reviews complications and risk for future disease; for example, not only does prior preeclampsia increase risk for that complication in future pregnancies, risk for later cardiovascular disease is also doubled. The document outlines recommended interpregnancy testing, management considerations and medications of concern for health care providers caring for women with these conditions, and condition-specific goals.

Of the association between gestational diabetes, hypertension, and preeclampsia with later disease, Dr. Louis said in the interview, “We don’t know. ... It may be that pregnancy accelerates these diseases. We do know that normal changes in pregnancy stress your body, and that preeclampsia damages your vessels. Pregnancy can give you a warning, but we don’t have enough information to predict the outcome” in later life. “We do know there is some advice we can give: stop smoking and maintain a normal body weight.”

Other conditions such as HIV, renal disease, epilepsy, autoimmune and thyroid disease, and thrombophilias and antiphospholipid antibody syndrome are also addressed in this section of the consensus document.

Specific attention also is given to psychosocial risks, such as socioeconomic disadvantages and being a member of a racial or ethnic minority. Social determinants of health are complex, said Dr. Louis, but socioeconomic and racial stressors can include the added burden of caring for loved ones with constrained resources. Additionally, there can be access issues: Women can get emergent care by presenting to the ED but receiving continued primary and specialty care can be much more of a challenge.

Regarding racism, Dr. Louis said, “We all come into caring for these women with certain ideas.” For example, it’s not enough to say of a patient, “She’s noncompliant. You need to ask why.” When the “why” question is asked, then you may discover, “there’s something you can help the patient with,” she said. “We need to ask why, and then take steps to help our patients.”

Document building

The working group for the consensus document felt it was important to include nonphysicians who care for women, Dr. Louis said, so drafts were reviewed by and input received from the American College of Nurse-Midwives and the National Association of Nurse Practitioners in Women’s Health. Both groups endorsed the document.

The collaborative process of putting drafts together and then reviewing and revising the document was a big part of the reason it took 2 years to produce the interpregnancy care consensus statement. “It was the equivalent of two full gestations with a short interpregnancy interval!” said Dr. Louis, laughing. But seeking input from all stakeholders strengthened the final product.

Dr. Louis reported no conflicts of interest and no outside sources of funding were reported.

[email protected]

SOURCE: Louis JM et al. Obstet Gynecol. 2019;133:e51-72.

Incidence of late-onset disease for group B streptococcus is higher than early-onset disease for infants under 90 days old in the United States, according to a multistate study of invasive group B streptococcal disease published in JAMA Pediatrics.

Janice Haney Carr/CDC

Using data from the Active Bacterial Core surveillance (ABCs) program, Srinivas Acharya Nanduri, MD, MPH, at the Centers for Disease Control and Prevention, and colleagues performed an analysis of early-onset disease (EOD) and late-onset disease (LOD) cases of group B Streptococcus (GBS) in infants from 10 different states between 2006 and 2015, and whether mothers of infants with EOD received intrapartum antibiotic prophylaxis (IAP). EOD was defined as between 0 and 6 days old, while LOD occurred between 7 days and 89 days old.

They found 1,277 cases of EOD and 1,387 cases of LOD in total, with a decrease in incidence of EOD from 0.37 per 1,000 live births in 2006 to 0.23 per 1,000 live births in 2015 (P less than .001); LOD incidence remained stable at a mean 0.31 per 1,000 live births during the same time period.

In 2015, the national burden for EOD and LOD was estimated at 840 and 1,265 cases, respectively. Mothers of infants with EOD did not have indications for and did not receive IAP in 617 cases (48%) and did not receive IAP despite indications in 278 (22%) cases.

“While the current culture-based screening strategy has been highly successful in reducing EOD burden, our data show that almost half of remaining infants with EOD were born to mothers with no indication for receiving IAP,” Dr. Nanduri and colleagues wrote.

Because there currently is no effective prevention strategy against LOS GBS, the investigators wrote that a maternal vaccine against the most common serotypes “holds promise to prevent a substantial portion of this remaining burden,” and noted several GBS candidate vaccines were in advanced stages of development.

The researchers also looked at GBS serotype data in 1,743 patients from seven different centers. The most commonly found serotype isolates of 887 EOD cases were Ia (242 cases, 27%) and III (242 cases, 27%) overall. Serotype III was most common for LOD cases (481 cases, 56%) and increased in incidence from 0.12 per 1,000 live births to 0.20 per 1,000 live births during the study period (P less than .001), while serotype IV was responsible for 53 cases (6%) of both EOD and LOD.

Dr. Nanduri and associates wrote that over 99% of the serotyped EOD (881 cases) and serotyped LOD (853 cases) cases were caused by serotypes Ia, Ib, II, III, IV, and V. With regard to antimicrobial resistance, there were no cases of beta-lactam resistance, but there was constitutive clindamycin resistance in 359 isolate test results (21%).

The researchers noted that they were limited in the study by 1 year of whole-genome sequencing data, the ABCs capturing only 10% of live birth data in the United States, and conclusions on EOD prevention restricted to data from labor and delivery records.

This study was funded in part by the CDC. Paula S. Vagnone received grants from the CDC, while William S. Schaffner, MD, received grants from the CDC and personal fees from Pfizer, Merck, SutroVax, Shionogi, Dynavax, and Seqirus outside of the study. The other authors reported no relevant disclosures.

SOURCE: Nanduri SA et al. JAMA Pediatr. 2019 Jan 14. doi: 10.1001/jamapediatrics.2018.4826.

Incidence of late-onset disease for group B streptococcus is higher than early-onset disease for infants under 90 days old in the United States, according to a multistate study of invasive group B streptococcal disease published in JAMA Pediatrics.

Janice Haney Carr/CDC

Using data from the Active Bacterial Core surveillance (ABCs) program, Srinivas Acharya Nanduri, MD, MPH, at the Centers for Disease Control and Prevention, and colleagues performed an analysis of early-onset disease (EOD) and late-onset disease (LOD) cases of group B Streptococcus (GBS) in infants from 10 different states between 2006 and 2015, and whether mothers of infants with EOD received intrapartum antibiotic prophylaxis (IAP). EOD was defined as between 0 and 6 days old, while LOD occurred between 7 days and 89 days old.

They found 1,277 cases of EOD and 1,387 cases of LOD in total, with a decrease in incidence of EOD from 0.37 per 1,000 live births in 2006 to 0.23 per 1,000 live births in 2015 (P less than .001); LOD incidence remained stable at a mean 0.31 per 1,000 live births during the same time period.

In 2015, the national burden for EOD and LOD was estimated at 840 and 1,265 cases, respectively. Mothers of infants with EOD did not have indications for and did not receive IAP in 617 cases (48%) and did not receive IAP despite indications in 278 (22%) cases.

“While the current culture-based screening strategy has been highly successful in reducing EOD burden, our data show that almost half of remaining infants with EOD were born to mothers with no indication for receiving IAP,” Dr. Nanduri and colleagues wrote.

Because there currently is no effective prevention strategy against LOS GBS, the investigators wrote that a maternal vaccine against the most common serotypes “holds promise to prevent a substantial portion of this remaining burden,” and noted several GBS candidate vaccines were in advanced stages of development.

The researchers also looked at GBS serotype data in 1,743 patients from seven different centers. The most commonly found serotype isolates of 887 EOD cases were Ia (242 cases, 27%) and III (242 cases, 27%) overall. Serotype III was most common for LOD cases (481 cases, 56%) and increased in incidence from 0.12 per 1,000 live births to 0.20 per 1,000 live births during the study period (P less than .001), while serotype IV was responsible for 53 cases (6%) of both EOD and LOD.

Dr. Nanduri and associates wrote that over 99% of the serotyped EOD (881 cases) and serotyped LOD (853 cases) cases were caused by serotypes Ia, Ib, II, III, IV, and V. With regard to antimicrobial resistance, there were no cases of beta-lactam resistance, but there was constitutive clindamycin resistance in 359 isolate test results (21%).

The researchers noted that they were limited in the study by 1 year of whole-genome sequencing data, the ABCs capturing only 10% of live birth data in the United States, and conclusions on EOD prevention restricted to data from labor and delivery records.

This study was funded in part by the CDC. Paula S. Vagnone received grants from the CDC, while William S. Schaffner, MD, received grants from the CDC and personal fees from Pfizer, Merck, SutroVax, Shionogi, Dynavax, and Seqirus outside of the study. The other authors reported no relevant disclosures.

SOURCE: Nanduri SA et al. JAMA Pediatr. 2019 Jan 14. doi: 10.1001/jamapediatrics.2018.4826.

Incidence of late-onset disease for group B streptococcus is higher than early-onset disease for infants under 90 days old in the United States, according to a multistate study of invasive group B streptococcal disease published in JAMA Pediatrics.

Janice Haney Carr/CDC

Using data from the Active Bacterial Core surveillance (ABCs) program, Srinivas Acharya Nanduri, MD, MPH, at the Centers for Disease Control and Prevention, and colleagues performed an analysis of early-onset disease (EOD) and late-onset disease (LOD) cases of group B Streptococcus (GBS) in infants from 10 different states between 2006 and 2015, and whether mothers of infants with EOD received intrapartum antibiotic prophylaxis (IAP). EOD was defined as between 0 and 6 days old, while LOD occurred between 7 days and 89 days old.

They found 1,277 cases of EOD and 1,387 cases of LOD in total, with a decrease in incidence of EOD from 0.37 per 1,000 live births in 2006 to 0.23 per 1,000 live births in 2015 (P less than .001); LOD incidence remained stable at a mean 0.31 per 1,000 live births during the same time period.

In 2015, the national burden for EOD and LOD was estimated at 840 and 1,265 cases, respectively. Mothers of infants with EOD did not have indications for and did not receive IAP in 617 cases (48%) and did not receive IAP despite indications in 278 (22%) cases.

“While the current culture-based screening strategy has been highly successful in reducing EOD burden, our data show that almost half of remaining infants with EOD were born to mothers with no indication for receiving IAP,” Dr. Nanduri and colleagues wrote.

Because there currently is no effective prevention strategy against LOS GBS, the investigators wrote that a maternal vaccine against the most common serotypes “holds promise to prevent a substantial portion of this remaining burden,” and noted several GBS candidate vaccines were in advanced stages of development.

The researchers also looked at GBS serotype data in 1,743 patients from seven different centers. The most commonly found serotype isolates of 887 EOD cases were Ia (242 cases, 27%) and III (242 cases, 27%) overall. Serotype III was most common for LOD cases (481 cases, 56%) and increased in incidence from 0.12 per 1,000 live births to 0.20 per 1,000 live births during the study period (P less than .001), while serotype IV was responsible for 53 cases (6%) of both EOD and LOD.

Dr. Nanduri and associates wrote that over 99% of the serotyped EOD (881 cases) and serotyped LOD (853 cases) cases were caused by serotypes Ia, Ib, II, III, IV, and V. With regard to antimicrobial resistance, there were no cases of beta-lactam resistance, but there was constitutive clindamycin resistance in 359 isolate test results (21%).

The researchers noted that they were limited in the study by 1 year of whole-genome sequencing data, the ABCs capturing only 10% of live birth data in the United States, and conclusions on EOD prevention restricted to data from labor and delivery records.

This study was funded in part by the CDC. Paula S. Vagnone received grants from the CDC, while William S. Schaffner, MD, received grants from the CDC and personal fees from Pfizer, Merck, SutroVax, Shionogi, Dynavax, and Seqirus outside of the study. The other authors reported no relevant disclosures.

SOURCE: Nanduri SA et al. JAMA Pediatr. 2019 Jan 14. doi: 10.1001/jamapediatrics.2018.4826.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

[email protected]

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

[email protected]

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

[email protected]

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

Females are the fastest growing population to seek care at the Veterans Health Administration (VHA).¹ Based on a 2014 study examining prevalence of military sexual trauma (MST), it is estimated that about one-third of females in the military screen positive for MST, and the rates are higher for younger veterans.² Military sexual trauma includes both rape and any sexual activity that occurred without consent; offensive sexual remarks or advances can also represent MST. The issue of MST, therefore, is an important one to address adequately, especially for female veterans who are screened through the VHA system.

Since 1992, the VHA has been required to provide services for MST, defined as “sexual harassment that is threatening in character or physical assault of a sexual nature that occurred while the victim was in the military.”³ Despite this mandate, it has taken many years for all VHA hospitals to adopt recommended screening tools to identify survivors of MST and give them proper resources. Only half of VHA hospitals adopted screening 6 years after the policy change.⁴ In addition, the environment in which the survivors receive MST care may trigger posttraumatic stress symptoms as many of the other patients seeking care at the VHA hospital resemble the perpetrators.⁵ Thus, up to half of females who report a history of MST do not receive care for their MST through the VHA.⁶

Having a history of MST significantly increases the risks of developing mental health disorders, including posttraumatic stress disorder (PTSD), major depressive disorder, generalized anxiety disorder, and suicidal ideation.² This group also has overall decreased quality of life (QOL). Female veterans have increased sexual dysfunction and dissatisfaction, which is heightened with a history of MST.⁷ Addressing MST requires treatment of all aspects of life affected by MST, such as mental health, sexual function, and QOL. The quality of treatment for MST through VHA hospitals deserves attention and likely still requires improvement with better incorporation of the patient’s perspective.

Qualitative research allows for incorporation of the patient’s perspective and is useful for exploring new ideas and themes.⁸ Current qualitative research using individual interviews of MST survivors focuses more on mental health treatment modalities through the VHA system and how resources are used within the system.^9,10 While it is important to understand the quantity of these resources, their quality also should be explored. Research has identified unique gender-specific concerns such as female-only mental health groups.¹⁰ However, there has been less focus on how to improve current therapies and the treatment modalities (regardless of whether it is a community service or at the VHA system) females find most helpful. There is a gap in understanding the patient’s perspective and assessment of current MST treatments as well as the unmet needs both within and outside of the VHA system. Therefore, the purpose of this study is 2-fold: (1) examine the utilization of VHA services for MST, as well as outside services, through focusgroup sessions; and (2) to offer specific recommendations for improving MST treatment for female veterans from the patient’s perspective.

Methods

After obtaining institutional review board approval (16-H192), females who screened positive for a history of MST, using the validated MST screening questionnaire, were recruited from the Women’s Continuity Clinic, Urology clinic, and via a research flyer placed within key locations at the New Mexico Veterans Affairs (VA) Health Care System (NMVAHCS).¹¹ Inclusion criteria were veterans aged > 18 years who could speak and understand English. Those who agreed to participate attended any 1 of 5 focus groups. Prior to initiation of the focus groups, the investigators generated a focus-group script, including specific questions or probes to explore treatment, unmet needs (such as other health conditions the veteran associated with MST that were not being addressed), and recommendations for care improvement.

Subjects granted consent privately prior to conduction of the focus group. Each participant completed a basic demographic (age, race, ethnicity) and clinical history (including pain conditions and therapy received for MST). These characteristics were evaluated with descriptive statistics, including means and frequencies.

The focus groups took place on the NM VAHCS Raymond G. Murphy VA Medical Center campus in a private conference room and were moderated by nonmedical research personnel experienced in focus-group moderation. Focus groups were recorded and transcribed. An iterative process was used with revisions to the script and probe questions as needed. Focus groups were planned for 2 hours but were allowed to continue at the participants’ discretion.

The de-identified transcripts were uploaded to the web-based qualitative engine Dedoose 6.2.21 software (Los Angeles, CA) and coded. Using grounded theory, the codes were grouped into themes and subsequently organized into emergent concepts.^8,12 Following constant comparative methodology, ideas were compared and combined between each focus group.^8,13 After completion of the focus groups, the generated ideas were organized and refined to create a conceptual framework that represented the collective ideas from the focus groups.

Results

Between January and June 2017, 5 focus groups with 17 participants were conducted; each session lasted about 3 hours. The average age was 52 ± 8.3 years, and were from a diverse racial and ethnic background. Most reported that > 20 years had passed since the first MST, and care-seeking for the first time was > 11 years after the trauma, although symptoms related to the MST most frequently began within 1 year of the trauma (Table 1). 

Preliminary Themes

The Trauma

Focus-group participants noted improved therapies offered by the VA but challenges obtaining health care:

“…because I’m really trying to deal with it and just be happy and get my joy back and deal with the isolation.”

“Another way that the memories affected me was barricading myself in my own house, starting from the front door.”

Male-Dominated VA

Participants also noted that, along with screening improving the system, dedicated female staff and service connection are important:

“The Womens Clinic is nice, and it’s nice to know that I can go there and I’m not having to discuss everything with men all over the place.”

“The other thing... that would be really good for survivors of MST, is help with disability.”

While the focus-group participants found dedicated women’s clinics helpful and providing improved care, the overall VA environment remains male-dominated:

“Because it’s really hard to relax and be vulnerable and be in your body and in your emotions if there‘s a bunch of penises around. When I saw these guys on the floor I’m like, I ain’t going in there.”

This male-dominated sense also incorporated a feeling of being misunderstood by a system that has traditionally cared for male veterans:

“People don‘t understand. They think, oh, you‘re overreacting, but they don’t know what it feels like to be inside.”

“I wouldn’t say they treat you like a second citizen, but it’s like almost every appointment I go to that’s not in the Women’s Clinic, the secretaries or whatever will be like ‘Oh, are you looking for somebody, or...’

Assumption Females Are Not Veterans

“There was an older gentleman behind me, they were like ‘Are you checking him in?’ I said, ‘I’m sure he’ll check himself in, but I’m checking myself in.’”

Participants also reported that there is an assumption that you’re not a veteran when you’re female:

“All of the care should be geared to be the same. And we know we need to recognize that men have their issues, and women will have their issues. But we don’t need to just say ‘all women have this issue, throw them over there.’”

Self-Doubt

“The world doesn’t validate rape, you asked for it, it was what you were wearing, it was what you said.”

Ongoing efforts to have female-only spaces, therapy groups, and support networks were encouraged by all 5 focus groups. These themes, provided the foundation for emergent concepts regarding patients’ perceptions of their treatment for MST: (1) Improvement has been slow but measurable; (2) VA cares more about male veterans; (3) The isolation from MST is pervasive; (4) It’s hard to navigate the VA system or any health care when you’re traumatized; and (5) Sexual assault leaves lasting self-doubt that providers need to address.

Isolation

Because there are barriers to seeking care the overarching method for coping with the effects of MST was isolation.

Overcoming the isolation was essential to seeking any care. Participants reported years of living alone, avoiding social situations and contexts, and difficulty with basic tasks because of the isolation.

“That the coping skills, that the isolation is a coping skill and all these things, and that I had to do that to survive.”

Lack of family and provider support and the VHA’s perceived focus on male veterans perpetuated this sense of isolation. Additionally, feeding the isolation were other maladaptive behaviors, such as alcoholism, weight gain, and anger.

“I was always an athlete until my MST, and I still find myself drinking whisky and wanting to smoke pot. It’s not that I want to, I guess it gives me a sense of relief, because my MST made me an alcoholic.”

Participants reported that successful treatment of MST must include treatment of other maladaptive behaviors and specific provider-behavior changes.

At times, providers contribute to female MST survivors’ feeling undervalued:

“I had an hour session and she kept looking at her watch and blowing me off, and I finally said, okay, I’m done, good-bye, after 45 minutes.”

Validation

Participants’ suggestions to improve MST treatment, including goal sharing, validation, knowledge, and support:

“They should have staff awareness groups, or focus groups to teach them the same thing that the patients are receiving as far as how to handle yourself, how to interact with others. Don’t bring your sh** from home into your job. You’re an employee, don’t take it personal.” (

Therapies for MST

A variety of modalities was recommended as helpful in coping with symptoms associated with MST. One female noted her therapy dog allowed her to get her first Papanicolaou (Pap) smear in years:

“Pelvic exams are like the seventh circle of hell. Like, God, you’d think I was being abducted by aliens or something. Last time, up here, they let me bring my little dog, which was extraordinarily helpful for me.”

For others, more traditional therapy such as prolonged exposure therapy or cognitive behavioral therapy, was helpful.

“After my prolonged exposure therapy; it saved my life. I’m not suicidal, and the only thing that’s really, really affected is sometimes I still have to sleep with a night light. Over 80% of the symptoms that I had and the problems that I had were alleviated with the therapy.”

Other veterans noted alternative therapies as beneficial for overcoming trauma:

“Yoga has really helped me with dealing with chronic pain and letting go of things that no longer serve me, and remembering about the inhale, the exhale, there’s a pause between the exhale and an inhale, where that’s where I make my choices, my thoughts, catch it, check it, change it, challenge my thoughts, that’s really, really helped me.”

From these concepts, and the specific suggestions female veterans provided for improvement in care, we developed a pictorial conceptual framework of the results. 

Discussion

This qualitative study of the quality of MST treatment with specific suggestions for improvement shows that the underlying force impacting health care in female survivors of MST is isolation. In turn, that isolation is perpetuated by personal beliefs, mental health, lack of support, and the VHA culture. While there was improvement in VHA care noted, female veterans offered many specific suggestions—simple ones that could be rapidly implemented—to enhance care. Many of these suggestions were targeted at provider-level behaviors such as validation, goal setting, knowledge (both about the military and about MST), and support.

Previous work showed that tangible (ie, words, being present) support rather than broad social support only generally helps reduces posttraumatic stress symptoms.¹⁵ These researchers found that tangible support moderated the relationship between number of lifetime traumas and PTSD. Schumm and colleagues also found that high social support predicted lower PTSD severity for inner-city women who experienced both child abuse and adult rape.¹⁶ A prior meta-analysis found social support was the strongest correlate of PTSD (effect size = 0.4).¹⁷

Our finding that female MST survivors desire verbal support from physicians may point to the inherent sense that validation helps healing, demonstrated by this meta-analysis. Importantly, the focus group participants did not specify the type of physician (psychiatrist, primary care provider, gynecologist, surgeon, etc) who needed to provide this support. Thus, we believe this suggestion is applicable to all physician interactions when the history of MST comes up. Physicians may be unaware of their profound impact in helping women recover from MST. This validation may also apply to survivors of other types of sexual trauma.

A second simple suggestion that arose from the focus groups was the need for broader options for MST therapy. Current data on the locations female veterans are treated for MST include specialty MST clinics, specialty PTSD clinics, psychosocial rehabilitation, and substance use disorder clinics, showing a wide range of settings.¹⁸ But female veterans are also asking for more services, including animal therapy, art therapy, yoga, and tai chi. While it may not be possible to offer every resource at every VHA facility, partnering with community services may help fulfill this veteran need. The advent of telehealth may also help address female veterans’ concerns about being surrounded by male patients and should be further explored.

The focus groups’ third suggestion for improvement in MST was better treatment for the health problems associated with sexual trauma, such as chronic pelvic pain, sexual dysfunction, and weight gain. It is important to note that the female veterans provided this list of associated health conditions from the broader facilitator question “What health problems do you think you have because of MST?” Females correctly identified common sequelae of sexual abuse, including pelvic pain and sexual dysfunction.^14,19 Weight gain and obesity have been associated with childhood sexual trauma and abuse, but they are not well studied in MST and may be worth further exploration.^20,21

Limitations

There are several inherent weaknesses in this study. The female veterans who agreed to participate in the focus group may not be representative of the entire population, particularly as survivors may be reluctant to talk about their MST experience. The participants in our focus groups were most commonly 2 decades past the MST and their experience with therapy may differ from that of women more recently traumatized and engaged in therapy. However, the fact that many of these females were still receiving some form of therapy 20 years after the traumatic event deserves attention.

Recall bias may have affected how female veterans described their experiences with MST treatment. We did not inquire about the timing of therapy and whether they sought VA care first, followed by community care, or vice versa. Finally, although the data were analyzed separately by 3 investigators, biases in data analysis may arise with qualitative methods.

Strengths of the study included the inherent patient-centered approach and ability to analyze data not readily extracted from patient records or validated questionnaires. Additionally, this qualitative approach allows for the discovery of patient-driven ideas and concerns. Our focus groups also contained a majority of minority females (including Hispanic and American Indian) populations that are frequently underrepresented in research.

Conclusion

Our data show there is still substantial room for improvement in the therapies and in the physician-level care for MST. While each treatment experience was unique, the collective agreement was that multimodal therapy was beneficial. However, the isolation that often comes from MST makes accessing care and treatment challenging. A crucial component to combating this isolation is provider validation and support for the female’s experience with MST. The simple act of hearing “I believe you” from the provider can make a huge impact on continuing to seek care and overcoming the consequences of MST.

Females are the fastest growing population to seek care at the Veterans Health Administration (VHA).¹ Based on a 2014 study examining prevalence of military sexual trauma (MST), it is estimated that about one-third of females in the military screen positive for MST, and the rates are higher for younger veterans.² Military sexual trauma includes both rape and any sexual activity that occurred without consent; offensive sexual remarks or advances can also represent MST. The issue of MST, therefore, is an important one to address adequately, especially for female veterans who are screened through the VHA system.

Since 1992, the VHA has been required to provide services for MST, defined as “sexual harassment that is threatening in character or physical assault of a sexual nature that occurred while the victim was in the military.”³ Despite this mandate, it has taken many years for all VHA hospitals to adopt recommended screening tools to identify survivors of MST and give them proper resources. Only half of VHA hospitals adopted screening 6 years after the policy change.⁴ In addition, the environment in which the survivors receive MST care may trigger posttraumatic stress symptoms as many of the other patients seeking care at the VHA hospital resemble the perpetrators.⁵ Thus, up to half of females who report a history of MST do not receive care for their MST through the VHA.⁶

Having a history of MST significantly increases the risks of developing mental health disorders, including posttraumatic stress disorder (PTSD), major depressive disorder, generalized anxiety disorder, and suicidal ideation.² This group also has overall decreased quality of life (QOL). Female veterans have increased sexual dysfunction and dissatisfaction, which is heightened with a history of MST.⁷ Addressing MST requires treatment of all aspects of life affected by MST, such as mental health, sexual function, and QOL. The quality of treatment for MST through VHA hospitals deserves attention and likely still requires improvement with better incorporation of the patient’s perspective.

Qualitative research allows for incorporation of the patient’s perspective and is useful for exploring new ideas and themes.⁸ Current qualitative research using individual interviews of MST survivors focuses more on mental health treatment modalities through the VHA system and how resources are used within the system.^9,10 While it is important to understand the quantity of these resources, their quality also should be explored. Research has identified unique gender-specific concerns such as female-only mental health groups.¹⁰ However, there has been less focus on how to improve current therapies and the treatment modalities (regardless of whether it is a community service or at the VHA system) females find most helpful. There is a gap in understanding the patient’s perspective and assessment of current MST treatments as well as the unmet needs both within and outside of the VHA system. Therefore, the purpose of this study is 2-fold: (1) examine the utilization of VHA services for MST, as well as outside services, through focusgroup sessions; and (2) to offer specific recommendations for improving MST treatment for female veterans from the patient’s perspective.

Methods

After obtaining institutional review board approval (16-H192), females who screened positive for a history of MST, using the validated MST screening questionnaire, were recruited from the Women’s Continuity Clinic, Urology clinic, and via a research flyer placed within key locations at the New Mexico Veterans Affairs (VA) Health Care System (NMVAHCS).¹¹ Inclusion criteria were veterans aged > 18 years who could speak and understand English. Those who agreed to participate attended any 1 of 5 focus groups. Prior to initiation of the focus groups, the investigators generated a focus-group script, including specific questions or probes to explore treatment, unmet needs (such as other health conditions the veteran associated with MST that were not being addressed), and recommendations for care improvement.

Subjects granted consent privately prior to conduction of the focus group. Each participant completed a basic demographic (age, race, ethnicity) and clinical history (including pain conditions and therapy received for MST). These characteristics were evaluated with descriptive statistics, including means and frequencies.

The focus groups took place on the NM VAHCS Raymond G. Murphy VA Medical Center campus in a private conference room and were moderated by nonmedical research personnel experienced in focus-group moderation. Focus groups were recorded and transcribed. An iterative process was used with revisions to the script and probe questions as needed. Focus groups were planned for 2 hours but were allowed to continue at the participants’ discretion.

The de-identified transcripts were uploaded to the web-based qualitative engine Dedoose 6.2.21 software (Los Angeles, CA) and coded. Using grounded theory, the codes were grouped into themes and subsequently organized into emergent concepts.^8,12 Following constant comparative methodology, ideas were compared and combined between each focus group.^8,13 After completion of the focus groups, the generated ideas were organized and refined to create a conceptual framework that represented the collective ideas from the focus groups.

Results

Between January and June 2017, 5 focus groups with 17 participants were conducted; each session lasted about 3 hours. The average age was 52 ± 8.3 years, and were from a diverse racial and ethnic background. Most reported that > 20 years had passed since the first MST, and care-seeking for the first time was > 11 years after the trauma, although symptoms related to the MST most frequently began within 1 year of the trauma (Table 1). 

Preliminary Themes

The Trauma

Focus-group participants noted improved therapies offered by the VA but challenges obtaining health care:

“…because I’m really trying to deal with it and just be happy and get my joy back and deal with the isolation.”

“Another way that the memories affected me was barricading myself in my own house, starting from the front door.”

Male-Dominated VA

Participants also noted that, along with screening improving the system, dedicated female staff and service connection are important:

“The Womens Clinic is nice, and it’s nice to know that I can go there and I’m not having to discuss everything with men all over the place.”

“The other thing... that would be really good for survivors of MST, is help with disability.”

While the focus-group participants found dedicated women’s clinics helpful and providing improved care, the overall VA environment remains male-dominated:

“Because it’s really hard to relax and be vulnerable and be in your body and in your emotions if there‘s a bunch of penises around. When I saw these guys on the floor I’m like, I ain’t going in there.”

This male-dominated sense also incorporated a feeling of being misunderstood by a system that has traditionally cared for male veterans:

“People don‘t understand. They think, oh, you‘re overreacting, but they don’t know what it feels like to be inside.”

“I wouldn’t say they treat you like a second citizen, but it’s like almost every appointment I go to that’s not in the Women’s Clinic, the secretaries or whatever will be like ‘Oh, are you looking for somebody, or...’

Assumption Females Are Not Veterans

“There was an older gentleman behind me, they were like ‘Are you checking him in?’ I said, ‘I’m sure he’ll check himself in, but I’m checking myself in.’”

Participants also reported that there is an assumption that you’re not a veteran when you’re female:

“All of the care should be geared to be the same. And we know we need to recognize that men have their issues, and women will have their issues. But we don’t need to just say ‘all women have this issue, throw them over there.’”

Self-Doubt

“The world doesn’t validate rape, you asked for it, it was what you were wearing, it was what you said.”

Ongoing efforts to have female-only spaces, therapy groups, and support networks were encouraged by all 5 focus groups. These themes, provided the foundation for emergent concepts regarding patients’ perceptions of their treatment for MST: (1) Improvement has been slow but measurable; (2) VA cares more about male veterans; (3) The isolation from MST is pervasive; (4) It’s hard to navigate the VA system or any health care when you’re traumatized; and (5) Sexual assault leaves lasting self-doubt that providers need to address.

Isolation

Because there are barriers to seeking care the overarching method for coping with the effects of MST was isolation.

Overcoming the isolation was essential to seeking any care. Participants reported years of living alone, avoiding social situations and contexts, and difficulty with basic tasks because of the isolation.

“That the coping skills, that the isolation is a coping skill and all these things, and that I had to do that to survive.”

Lack of family and provider support and the VHA’s perceived focus on male veterans perpetuated this sense of isolation. Additionally, feeding the isolation were other maladaptive behaviors, such as alcoholism, weight gain, and anger.

“I was always an athlete until my MST, and I still find myself drinking whisky and wanting to smoke pot. It’s not that I want to, I guess it gives me a sense of relief, because my MST made me an alcoholic.”

Participants reported that successful treatment of MST must include treatment of other maladaptive behaviors and specific provider-behavior changes.

At times, providers contribute to female MST survivors’ feeling undervalued:

“I had an hour session and she kept looking at her watch and blowing me off, and I finally said, okay, I’m done, good-bye, after 45 minutes.”

Validation

Participants’ suggestions to improve MST treatment, including goal sharing, validation, knowledge, and support:

“They should have staff awareness groups, or focus groups to teach them the same thing that the patients are receiving as far as how to handle yourself, how to interact with others. Don’t bring your sh** from home into your job. You’re an employee, don’t take it personal.” (

Therapies for MST

A variety of modalities was recommended as helpful in coping with symptoms associated with MST. One female noted her therapy dog allowed her to get her first Papanicolaou (Pap) smear in years:

“Pelvic exams are like the seventh circle of hell. Like, God, you’d think I was being abducted by aliens or something. Last time, up here, they let me bring my little dog, which was extraordinarily helpful for me.”

For others, more traditional therapy such as prolonged exposure therapy or cognitive behavioral therapy, was helpful.

“After my prolonged exposure therapy; it saved my life. I’m not suicidal, and the only thing that’s really, really affected is sometimes I still have to sleep with a night light. Over 80% of the symptoms that I had and the problems that I had were alleviated with the therapy.”

Other veterans noted alternative therapies as beneficial for overcoming trauma:

“Yoga has really helped me with dealing with chronic pain and letting go of things that no longer serve me, and remembering about the inhale, the exhale, there’s a pause between the exhale and an inhale, where that’s where I make my choices, my thoughts, catch it, check it, change it, challenge my thoughts, that’s really, really helped me.”

From these concepts, and the specific suggestions female veterans provided for improvement in care, we developed a pictorial conceptual framework of the results. 

Discussion

This qualitative study of the quality of MST treatment with specific suggestions for improvement shows that the underlying force impacting health care in female survivors of MST is isolation. In turn, that isolation is perpetuated by personal beliefs, mental health, lack of support, and the VHA culture. While there was improvement in VHA care noted, female veterans offered many specific suggestions—simple ones that could be rapidly implemented—to enhance care. Many of these suggestions were targeted at provider-level behaviors such as validation, goal setting, knowledge (both about the military and about MST), and support.

Previous work showed that tangible (ie, words, being present) support rather than broad social support only generally helps reduces posttraumatic stress symptoms.¹⁵ These researchers found that tangible support moderated the relationship between number of lifetime traumas and PTSD. Schumm and colleagues also found that high social support predicted lower PTSD severity for inner-city women who experienced both child abuse and adult rape.¹⁶ A prior meta-analysis found social support was the strongest correlate of PTSD (effect size = 0.4).¹⁷

Our finding that female MST survivors desire verbal support from physicians may point to the inherent sense that validation helps healing, demonstrated by this meta-analysis. Importantly, the focus group participants did not specify the type of physician (psychiatrist, primary care provider, gynecologist, surgeon, etc) who needed to provide this support. Thus, we believe this suggestion is applicable to all physician interactions when the history of MST comes up. Physicians may be unaware of their profound impact in helping women recover from MST. This validation may also apply to survivors of other types of sexual trauma.

A second simple suggestion that arose from the focus groups was the need for broader options for MST therapy. Current data on the locations female veterans are treated for MST include specialty MST clinics, specialty PTSD clinics, psychosocial rehabilitation, and substance use disorder clinics, showing a wide range of settings.¹⁸ But female veterans are also asking for more services, including animal therapy, art therapy, yoga, and tai chi. While it may not be possible to offer every resource at every VHA facility, partnering with community services may help fulfill this veteran need. The advent of telehealth may also help address female veterans’ concerns about being surrounded by male patients and should be further explored.

The focus groups’ third suggestion for improvement in MST was better treatment for the health problems associated with sexual trauma, such as chronic pelvic pain, sexual dysfunction, and weight gain. It is important to note that the female veterans provided this list of associated health conditions from the broader facilitator question “What health problems do you think you have because of MST?” Females correctly identified common sequelae of sexual abuse, including pelvic pain and sexual dysfunction.^14,19 Weight gain and obesity have been associated with childhood sexual trauma and abuse, but they are not well studied in MST and may be worth further exploration.^20,21

Limitations

There are several inherent weaknesses in this study. The female veterans who agreed to participate in the focus group may not be representative of the entire population, particularly as survivors may be reluctant to talk about their MST experience. The participants in our focus groups were most commonly 2 decades past the MST and their experience with therapy may differ from that of women more recently traumatized and engaged in therapy. However, the fact that many of these females were still receiving some form of therapy 20 years after the traumatic event deserves attention.

Recall bias may have affected how female veterans described their experiences with MST treatment. We did not inquire about the timing of therapy and whether they sought VA care first, followed by community care, or vice versa. Finally, although the data were analyzed separately by 3 investigators, biases in data analysis may arise with qualitative methods.

Strengths of the study included the inherent patient-centered approach and ability to analyze data not readily extracted from patient records or validated questionnaires. Additionally, this qualitative approach allows for the discovery of patient-driven ideas and concerns. Our focus groups also contained a majority of minority females (including Hispanic and American Indian) populations that are frequently underrepresented in research.

Conclusion

Our data show there is still substantial room for improvement in the therapies and in the physician-level care for MST. While each treatment experience was unique, the collective agreement was that multimodal therapy was beneficial. However, the isolation that often comes from MST makes accessing care and treatment challenging. A crucial component to combating this isolation is provider validation and support for the female’s experience with MST. The simple act of hearing “I believe you” from the provider can make a huge impact on continuing to seek care and overcoming the consequences of MST.

Females are the fastest growing population to seek care at the Veterans Health Administration (VHA).¹ Based on a 2014 study examining prevalence of military sexual trauma (MST), it is estimated that about one-third of females in the military screen positive for MST, and the rates are higher for younger veterans.² Military sexual trauma includes both rape and any sexual activity that occurred without consent; offensive sexual remarks or advances can also represent MST. The issue of MST, therefore, is an important one to address adequately, especially for female veterans who are screened through the VHA system.

Since 1992, the VHA has been required to provide services for MST, defined as “sexual harassment that is threatening in character or physical assault of a sexual nature that occurred while the victim was in the military.”³ Despite this mandate, it has taken many years for all VHA hospitals to adopt recommended screening tools to identify survivors of MST and give them proper resources. Only half of VHA hospitals adopted screening 6 years after the policy change.⁴ In addition, the environment in which the survivors receive MST care may trigger posttraumatic stress symptoms as many of the other patients seeking care at the VHA hospital resemble the perpetrators.⁵ Thus, up to half of females who report a history of MST do not receive care for their MST through the VHA.⁶

Having a history of MST significantly increases the risks of developing mental health disorders, including posttraumatic stress disorder (PTSD), major depressive disorder, generalized anxiety disorder, and suicidal ideation.² This group also has overall decreased quality of life (QOL). Female veterans have increased sexual dysfunction and dissatisfaction, which is heightened with a history of MST.⁷ Addressing MST requires treatment of all aspects of life affected by MST, such as mental health, sexual function, and QOL. The quality of treatment for MST through VHA hospitals deserves attention and likely still requires improvement with better incorporation of the patient’s perspective.

Qualitative research allows for incorporation of the patient’s perspective and is useful for exploring new ideas and themes.⁸ Current qualitative research using individual interviews of MST survivors focuses more on mental health treatment modalities through the VHA system and how resources are used within the system.^9,10 While it is important to understand the quantity of these resources, their quality also should be explored. Research has identified unique gender-specific concerns such as female-only mental health groups.¹⁰ However, there has been less focus on how to improve current therapies and the treatment modalities (regardless of whether it is a community service or at the VHA system) females find most helpful. There is a gap in understanding the patient’s perspective and assessment of current MST treatments as well as the unmet needs both within and outside of the VHA system. Therefore, the purpose of this study is 2-fold: (1) examine the utilization of VHA services for MST, as well as outside services, through focusgroup sessions; and (2) to offer specific recommendations for improving MST treatment for female veterans from the patient’s perspective.

Methods

After obtaining institutional review board approval (16-H192), females who screened positive for a history of MST, using the validated MST screening questionnaire, were recruited from the Women’s Continuity Clinic, Urology clinic, and via a research flyer placed within key locations at the New Mexico Veterans Affairs (VA) Health Care System (NMVAHCS).¹¹ Inclusion criteria were veterans aged > 18 years who could speak and understand English. Those who agreed to participate attended any 1 of 5 focus groups. Prior to initiation of the focus groups, the investigators generated a focus-group script, including specific questions or probes to explore treatment, unmet needs (such as other health conditions the veteran associated with MST that were not being addressed), and recommendations for care improvement.

Subjects granted consent privately prior to conduction of the focus group. Each participant completed a basic demographic (age, race, ethnicity) and clinical history (including pain conditions and therapy received for MST). These characteristics were evaluated with descriptive statistics, including means and frequencies.

The focus groups took place on the NM VAHCS Raymond G. Murphy VA Medical Center campus in a private conference room and were moderated by nonmedical research personnel experienced in focus-group moderation. Focus groups were recorded and transcribed. An iterative process was used with revisions to the script and probe questions as needed. Focus groups were planned for 2 hours but were allowed to continue at the participants’ discretion.

The de-identified transcripts were uploaded to the web-based qualitative engine Dedoose 6.2.21 software (Los Angeles, CA) and coded. Using grounded theory, the codes were grouped into themes and subsequently organized into emergent concepts.^8,12 Following constant comparative methodology, ideas were compared and combined between each focus group.^8,13 After completion of the focus groups, the generated ideas were organized and refined to create a conceptual framework that represented the collective ideas from the focus groups.

Results

Between January and June 2017, 5 focus groups with 17 participants were conducted; each session lasted about 3 hours. The average age was 52 ± 8.3 years, and were from a diverse racial and ethnic background. Most reported that > 20 years had passed since the first MST, and care-seeking for the first time was > 11 years after the trauma, although symptoms related to the MST most frequently began within 1 year of the trauma (Table 1). 

Preliminary Themes

The Trauma

Focus-group participants noted improved therapies offered by the VA but challenges obtaining health care:

“…because I’m really trying to deal with it and just be happy and get my joy back and deal with the isolation.”

“Another way that the memories affected me was barricading myself in my own house, starting from the front door.”

Male-Dominated VA

Participants also noted that, along with screening improving the system, dedicated female staff and service connection are important:

“The Womens Clinic is nice, and it’s nice to know that I can go there and I’m not having to discuss everything with men all over the place.”

“The other thing... that would be really good for survivors of MST, is help with disability.”

While the focus-group participants found dedicated women’s clinics helpful and providing improved care, the overall VA environment remains male-dominated:

“Because it’s really hard to relax and be vulnerable and be in your body and in your emotions if there‘s a bunch of penises around. When I saw these guys on the floor I’m like, I ain’t going in there.”

This male-dominated sense also incorporated a feeling of being misunderstood by a system that has traditionally cared for male veterans:

“People don‘t understand. They think, oh, you‘re overreacting, but they don’t know what it feels like to be inside.”

“I wouldn’t say they treat you like a second citizen, but it’s like almost every appointment I go to that’s not in the Women’s Clinic, the secretaries or whatever will be like ‘Oh, are you looking for somebody, or...’

Assumption Females Are Not Veterans

“There was an older gentleman behind me, they were like ‘Are you checking him in?’ I said, ‘I’m sure he’ll check himself in, but I’m checking myself in.’”

Participants also reported that there is an assumption that you’re not a veteran when you’re female:

“All of the care should be geared to be the same. And we know we need to recognize that men have their issues, and women will have their issues. But we don’t need to just say ‘all women have this issue, throw them over there.’”

Self-Doubt

“The world doesn’t validate rape, you asked for it, it was what you were wearing, it was what you said.”

Ongoing efforts to have female-only spaces, therapy groups, and support networks were encouraged by all 5 focus groups. These themes, provided the foundation for emergent concepts regarding patients’ perceptions of their treatment for MST: (1) Improvement has been slow but measurable; (2) VA cares more about male veterans; (3) The isolation from MST is pervasive; (4) It’s hard to navigate the VA system or any health care when you’re traumatized; and (5) Sexual assault leaves lasting self-doubt that providers need to address.

Isolation

Because there are barriers to seeking care the overarching method for coping with the effects of MST was isolation.

Overcoming the isolation was essential to seeking any care. Participants reported years of living alone, avoiding social situations and contexts, and difficulty with basic tasks because of the isolation.

“That the coping skills, that the isolation is a coping skill and all these things, and that I had to do that to survive.”

Lack of family and provider support and the VHA’s perceived focus on male veterans perpetuated this sense of isolation. Additionally, feeding the isolation were other maladaptive behaviors, such as alcoholism, weight gain, and anger.

“I was always an athlete until my MST, and I still find myself drinking whisky and wanting to smoke pot. It’s not that I want to, I guess it gives me a sense of relief, because my MST made me an alcoholic.”

Participants reported that successful treatment of MST must include treatment of other maladaptive behaviors and specific provider-behavior changes.

At times, providers contribute to female MST survivors’ feeling undervalued:

“I had an hour session and she kept looking at her watch and blowing me off, and I finally said, okay, I’m done, good-bye, after 45 minutes.”

Validation

Participants’ suggestions to improve MST treatment, including goal sharing, validation, knowledge, and support:

“They should have staff awareness groups, or focus groups to teach them the same thing that the patients are receiving as far as how to handle yourself, how to interact with others. Don’t bring your sh** from home into your job. You’re an employee, don’t take it personal.” (

Therapies for MST

A variety of modalities was recommended as helpful in coping with symptoms associated with MST. One female noted her therapy dog allowed her to get her first Papanicolaou (Pap) smear in years:

“Pelvic exams are like the seventh circle of hell. Like, God, you’d think I was being abducted by aliens or something. Last time, up here, they let me bring my little dog, which was extraordinarily helpful for me.”

For others, more traditional therapy such as prolonged exposure therapy or cognitive behavioral therapy, was helpful.

“After my prolonged exposure therapy; it saved my life. I’m not suicidal, and the only thing that’s really, really affected is sometimes I still have to sleep with a night light. Over 80% of the symptoms that I had and the problems that I had were alleviated with the therapy.”

Other veterans noted alternative therapies as beneficial for overcoming trauma:

“Yoga has really helped me with dealing with chronic pain and letting go of things that no longer serve me, and remembering about the inhale, the exhale, there’s a pause between the exhale and an inhale, where that’s where I make my choices, my thoughts, catch it, check it, change it, challenge my thoughts, that’s really, really helped me.”

From these concepts, and the specific suggestions female veterans provided for improvement in care, we developed a pictorial conceptual framework of the results. 

Discussion

This qualitative study of the quality of MST treatment with specific suggestions for improvement shows that the underlying force impacting health care in female survivors of MST is isolation. In turn, that isolation is perpetuated by personal beliefs, mental health, lack of support, and the VHA culture. While there was improvement in VHA care noted, female veterans offered many specific suggestions—simple ones that could be rapidly implemented—to enhance care. Many of these suggestions were targeted at provider-level behaviors such as validation, goal setting, knowledge (both about the military and about MST), and support.

Previous work showed that tangible (ie, words, being present) support rather than broad social support only generally helps reduces posttraumatic stress symptoms.¹⁵ These researchers found that tangible support moderated the relationship between number of lifetime traumas and PTSD. Schumm and colleagues also found that high social support predicted lower PTSD severity for inner-city women who experienced both child abuse and adult rape.¹⁶ A prior meta-analysis found social support was the strongest correlate of PTSD (effect size = 0.4).¹⁷

Our finding that female MST survivors desire verbal support from physicians may point to the inherent sense that validation helps healing, demonstrated by this meta-analysis. Importantly, the focus group participants did not specify the type of physician (psychiatrist, primary care provider, gynecologist, surgeon, etc) who needed to provide this support. Thus, we believe this suggestion is applicable to all physician interactions when the history of MST comes up. Physicians may be unaware of their profound impact in helping women recover from MST. This validation may also apply to survivors of other types of sexual trauma.

A second simple suggestion that arose from the focus groups was the need for broader options for MST therapy. Current data on the locations female veterans are treated for MST include specialty MST clinics, specialty PTSD clinics, psychosocial rehabilitation, and substance use disorder clinics, showing a wide range of settings.¹⁸ But female veterans are also asking for more services, including animal therapy, art therapy, yoga, and tai chi. While it may not be possible to offer every resource at every VHA facility, partnering with community services may help fulfill this veteran need. The advent of telehealth may also help address female veterans’ concerns about being surrounded by male patients and should be further explored.

The focus groups’ third suggestion for improvement in MST was better treatment for the health problems associated with sexual trauma, such as chronic pelvic pain, sexual dysfunction, and weight gain. It is important to note that the female veterans provided this list of associated health conditions from the broader facilitator question “What health problems do you think you have because of MST?” Females correctly identified common sequelae of sexual abuse, including pelvic pain and sexual dysfunction.^14,19 Weight gain and obesity have been associated with childhood sexual trauma and abuse, but they are not well studied in MST and may be worth further exploration.^20,21

Limitations

There are several inherent weaknesses in this study. The female veterans who agreed to participate in the focus group may not be representative of the entire population, particularly as survivors may be reluctant to talk about their MST experience. The participants in our focus groups were most commonly 2 decades past the MST and their experience with therapy may differ from that of women more recently traumatized and engaged in therapy. However, the fact that many of these females were still receiving some form of therapy 20 years after the traumatic event deserves attention.

Recall bias may have affected how female veterans described their experiences with MST treatment. We did not inquire about the timing of therapy and whether they sought VA care first, followed by community care, or vice versa. Finally, although the data were analyzed separately by 3 investigators, biases in data analysis may arise with qualitative methods.

Strengths of the study included the inherent patient-centered approach and ability to analyze data not readily extracted from patient records or validated questionnaires. Additionally, this qualitative approach allows for the discovery of patient-driven ideas and concerns. Our focus groups also contained a majority of minority females (including Hispanic and American Indian) populations that are frequently underrepresented in research.

Conclusion

Our data show there is still substantial room for improvement in the therapies and in the physician-level care for MST. While each treatment experience was unique, the collective agreement was that multimodal therapy was beneficial. However, the isolation that often comes from MST makes accessing care and treatment challenging. A crucial component to combating this isolation is provider validation and support for the female’s experience with MST. The simple act of hearing “I believe you” from the provider can make a huge impact on continuing to seek care and overcoming the consequences of MST.

Consider thinking outside the lower body for pelvic pain. Also today, treating obstructive sleep apnea with positive airway pressure decreased amyloid levels, spending on medical marketing increased by more than $12 billion over that past two decades, and one expert has advice on how you can get your work published.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Consider thinking outside the lower body for pelvic pain. Also today, treating obstructive sleep apnea with positive airway pressure decreased amyloid levels, spending on medical marketing increased by more than $12 billion over that past two decades, and one expert has advice on how you can get your work published.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify
 

Consider thinking outside the lower body for pelvic pain. Also today, treating obstructive sleep apnea with positive airway pressure decreased amyloid levels, spending on medical marketing increased by more than $12 billion over that past two decades, and one expert has advice on how you can get your work published.

Amazon Alexa

Apple Podcasts

Google Podcasts

Spotify