You can reach her a lcarr@mjhlifesciences.com.

At ACR Convergence 2022, Hyun Son, PharmD, discussed the role of the FDA’s Drug Shortage Staff in preventing and mitigating drug shortages.

Five minutes of a doctor’s time could cost patients $50

Cleveland Clinic begins charging for doctors’ time spent responding to some electronic messages

At ACR Convergence 2022, Amit Golding, MD, PhD, outlined drugs recently approved by the FDA, and discussed the requirements for biosimilars to meet approval.

Allopurinol use linked to lower risk of first-ever coronary event

Exposure to more than 100 mg was linked to significantly lower odds ratios for first-ever ACS event for women.

Volume of fat mass negatively impacts severity of fibromyalgia

The association between type of body composition and fibromyalgia was evaluated using 43 women with clinically diagnosed fibromyalgia.

Articles

A look ahead at this week in women's health from Contemporary OB/GYN: 

This week on Contemporary OB/GYN: November 21 to November 25

The US Food and Drug Administration (FDA) has been tackling the drug shortage through its Drug Shortage Staff (DSS), which was outlined by Hyun Son, PharmD, at the American College of Rheumatology (ACR) Convergence 2022.

The DSS is an office within the FDA made to manage and resolve drug shortage situations, bringing safe and effective drugs to patients. Tasks of the DSS include creating short- and long-term strategies to combat drug shortages, making decisions that fully account for risks and benefits, and distributing information.

Key communication occurs between the DSS and other groups to manage drug shortages. The DSS receives information on disruptions to drug distribution from manufacturers, and provides shortage information to pharmacists, patients, providers, researchers, and other US agencies. Important information is also exchanged between the DSS and international authorities.

According to Son, early notification is key to preventing and mitigating drug shortages. Products should be prioritized if they are medically necessary, with the risks and benefits of the drugs considered. The DSS works to maintain availability while minimizing risks to patients and works with firms to address problems.

Son discussed the “FDA toolbox,” a set of guidelines the DSS follows when managing drug shortages. These include making other suppliers aware of potential shortage concerns, encouraging firms to look at demand and supply, and maintaining regulatory discretion.

The FDA toolbox also outlines expedited review of company proposals, listing proposals such as new manufacturing site, increased expiry date, new raw material source, and changes in specifications. Changes in importation from other countries was also discussed, using triamcinolone hexacetonide injection as an example.

According to Section 506C of the Federal Food, Drug, and Cosmetic Act and FDA regulations, manufacturers must notify the FDA of permanent discontinuation of a drug or interruption of manufacturing that will cause a supply disruption. This notification should come at least 6 months in advance regardless of market share and is not limited to medically necessary products.

Notifications that must be sent to the DSS include plans for upgrades, manufacturing issues, raw material batch failures, and product quality issues. Individuals in the public marketplace can also send the DSS notifications on shortages through their public email, drugshortages@fda.hhs.gov.

The DSS also receives information on current inventory, production plans, and distribution data from manufacturers. This data is used to estimate the supply gap, and has led to many prevented drug shortages, including over 150 in 2020.

The drug supply chain as outlined by Son went from suppliers, to manufacturers, to wholesalers, to pharmacies and hospitals, and to patients and health care providers. Interruptions generally occur at the wholesale level.

In 2011, shortages peaked at 251, then decreased through 2016. In 2020, there were 43 new shortages. Son noted that these shortages could occur for months or years depending on precipitating events.

While the FDA works closely with manufacturers to address problems, it cannot require a company to make a drug, a company to make more of a drug, or how much a drug is distributed. Instead, the FDA can require notifications by manufacturers on supply disruptions, delays, discontinuations, and certain manufacturing changes.

Son stated that shortages in 2020 were mainly because of COVID-19. To combat the pandemic, the DSS has continued early outreach to manufacturers. The FDA has also posted guidance on COVID-19 and has granted Emergency Use Authorizations to certain drugs.

Efforts have also been made to assist manufacturers during a shortage, such as expedited approvals to increase production and temporary extended use of distributed lots near expiration. According to Son, these efforts prevented 199 shortages in 2020.

Industry can also support the prevention and mitigation of drug shortages. This involves placing safeguards to combat vulnerabilities of their supply chain and early communication about possible shortages. When a shortage is unavoidable, shortage information can be posted on the FDA website.

The FDA has also introduced the CARES Act, which requires prioritized risk management plans (RMPs) from manufacturers of drug products that are life-supporting, life-sustaining, or made to prevent debilitating conditions. RMPs allow strategies to be implemented which can prevent supply disruptions.

This article originally appeared on Contemporary Pediatrics®.

Son, H. FDA: Pediatric Update. Presented at: ACR Convergence 2022, Philadelphia, Pennsylvania. November 11 to November 14, 2022.

How the FDA prevents drug shortages

Chemical hair straightening may increase uterine cancer risk

A new NIH study found women who used chemical hair straightening products to be at a higher risk for uterine cancer than women who didn’t use these products.

FDA approves IUD to prevent pregnancy for up to 8 years

The Food and Drug Administration (FDA) has approved Medicine360’s supplemental new drug application to extend the use of its levongestrel-releasing intrauterine system 52mg (LILETTA) to prevent pregnancy for up to 8 years.

Alyssa Dweck, MD, discusses some recent positive data presented at the 2022 NAMS meeting regarding Clairvee (Bonafide Health) as a potential treatment for vaginal odor.

Iranian hackers emerge as cyberthreat to health care computer networks

‘Charming Kitten’ believed to be a front for Islamic Revolutionary Guard Corps, according to HHS’ cybersecurity agency.

Daré Bioscience announces grant to develop vaginal thermosetting gel for delivery of live biotherapeutics

Daré Bioscience announced yesterday that it has received a grant from the Bill & Melinda Gates Foundation of $584,986 to support its efforts related to the development of a vaginal thermosetting gel formulation for the delivery of live biotherapeutics that can be reconstituted at the point of care.

FDA grants accelerated approval to mirvetuximab soravtansine-gynx for ovarian cancer

This is the first FDA-approved ADC for platinum-resistant disease, according to ImmunoGen.

Take a look back at this week's top news stories. 

In case you missed it: November 14 to November 18

Maternal consumption of caffeine during pregnancy could lead to shorter stature for infants during childhood, according to a recent study.

Although caffeine consumption during pregnancy has been associated with lower birth weight, about 8 in 10 pregnant people consume caffeine. Studies have also associated high amounts of caffeine consumption during pregnancy with increased infant weight, body mass index (BMI), and obesity risk.

To determine the effects of different rates of maternal caffeine consumption on child weight, BMI, and fat mass, investigators conducted Environmental Influences on Child Health OutcomesFetal Growth Studies (ECHO-FGS). Participants included 1116 mothers and singleton birth children.

Children aged 4 to 8 years were measured for BMI, weight, height, fat mass index and percentage, and obesity risk. Data was also collected on caffeine and paraxanthine concentrations in maternal plasma during pregnancy.

A Collaborative Perinatal Project (CPP) was referenced for data comparison. The study measured child height and weight at birth, 4 months, 8 months, 12 months, 3 years, 4 years, 7 years, and 8 years. Both studies converted scores to standardized height and weight from the Centers for Disease Control and Prevention.

Caffeine and paraxanthine were measured in plasma samples collected during the first trimester. During this time, caffeine is metabolized to paraxanthine in about 3 hours. This metabolism increases to up to 10 hours in the third trimester.

Covariates included maternal age, smoking status, socioeconomic status, self-report race and ethnicity, parity, marriage status, and study site. In the CPP study, only nonsmokers were included, and in the ECHO-FGS, adjustments were made for maternal education.

There were 788 children in the ECHO-FGS. Among women participants, 31.4% were non-Hispanic Black women, 30% non-Hispanic White women, 25.5% Hispanic women, and 13.2% Asian or Pacific Islander women. Lesser caffeine consumption was often observed in younger women and non-Hispanic Black women.

Children had a mean age of 6.8 years, and 23.7% of children were overweight or had obesity. About 52% of children were boys.

Median maternal caffeine concentration was 168.5ng/mL, and the median maternal paraxanthine concentration was 73.8ng/mL. These data indicate a daily median consumption of under 50 mg. Children in this cohort had a height difference of 1.5 cm less and a weight difference of 1.1 kg less at age 7.

BMI scores, child fat mass index, and fat percentage did not vary between groups. There was also no greater risk of being overweight or having obesity due to caffeine or paraxanthine concentration.

In the study, children born to mothers who had consumed caffeine often had a shorter stature in the first 8 years of life. These results are consisted with those of prior studies, indicating that maternal caffeine consumption is linked to long-term reductions in growth.

Gleason JL, Sundaram R, Mitro SD, Hinkle SN, Gilman SE, Zhang C, et al. Association of maternal caffeine consumption during pregnancy with child growth. 

 2022;5(10):e2239609. doi:10.1001/jamanetworkopen.2022.39609

A recent study found that children born to mothers who had consumed caffeine during pregnancy often had a reduced height during childhood compared with those born to mothers who had not consumed caffeine.

Caffeine consumption during pregnancy could stunt childhood growth

Women who experience poor sleep quality may have less success with IVF than women who experience higher quality sleep, according to a study conducted by Marco Reschini, MSc, of the infertility unit at Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Via M. Fanti, in Milan, Italy.

Between September and December 2019, researchers recruited 263 women who were receiving services from the infertility unit at Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico. At the time of oocytes collection, study participants answered questions about sleep and psychological health on 3 surveys—the Pittsburgh Sleep Quality Index (PSQI), the Fertility Problem Inventory (FPI), and the Hospital Anxiety and Depression Scale (HADS). Researchers examined age, job status, and education, in addition to a number of health factors such as body mass index and smoking. They also looked at how long the women had been infertile, previous deliveries, serum FSH (IU/mL), serum Anti-Müllerian Hormone (AMH) (ng/mL), antral follicle count (AFC), and indication for IVF.1 This data was examined with the results of the surveys, which were given in Italian and required the women to be native speakers.

Study participants were excluded if they did not speak fluent Italian, and if they had a neurologic or severe psychiatric disorder such as bipolar disorder, schizophrenia, or major depressive disorder. Women with obstructive sleep apnea syndrome and conditions that may reduce embryo implantation such as endometrial polyps, submucosal fibroids, hydrosalpinx, and uterine formations were also excluded.

Thirty-one percent of women (81) had a successful pregnancy. Researchers noted that, in these successful pregnancies, ovarian reserve was preserved better and the women were younger. There was no difference in FPI and HADS scores.

“Conversely, a statistically significant difference emerged for the PSQI score, the median [interquartile range] in pregnant and non-pregnant women being 4 [3–5] and 5 [3–7], respectively (p = 0.004). The crude and adjusted OR of pregnancy in women with a PSQI > 5 (indicating impaired sleep quality) was 0.46 (95% CI 0.25–0.86, p = 0.02) and 0.50 (95% CI: 0.26–0.94, p = 0.03), respectively,” researchers reported. They also said that poor sleep quality was common in women seeking IVF and could affect the procedure.

“Taken together, our findings highlighted that assessing sleep quality in women undergoing IVF is clinically relevant, due to its association not only with outcome of the procedure, but also with women’s overall psychological health,” researchers concluded. Reschini and colleagues noted that poor sleep quality was also linked to poor psychological health, indicating that treating poor sleep quality could improve these outcomes as well.

Lubna Mohammed, MBBS, lecturer of research at the California Institute of Behavioral Neurosciences and Psychology in Fairfield, California, spoke with 

® as a subject-matter expert. For Mohammed, the most important information for providers to take away from this study is the recommendation to inquire about the quality of sleep of women undergoing the IVF process. Mohammed added that future research should concentrate on studying the impact of sleep improvement on the outcomes of the procedure. “It can also be targeted at studying if poor sleep is related to women having unhealthy lifestyles and how lifestyle changes precisely impact sleep,” she said. She noted an important limitation of this study—the absence of a control group, and the fact that sleep quality was measured using self-reported sleep measures. “Other options like sleep tracking devices can also be considered for future research, Mohammed said.

Reschini M, Buoli M, Facchin F, et al. Women's quality of sleep and in vitro fertilization success. 

 2022;12(1):17477. Published 2022 Oct 19. doi:10.1038/s41598-022-22534-0

A study published in the journal Scientific Reports may shed light on a potential connection between sleep quality and IVF success.

Can sleep quality affect the results of in vitro fertilization?

Dextromethorphan was not a successful adjunctive pain management option for medication abortion, according to research results published in 

Through a randomized, double-blinded, placebo-controlled trial, investigators used data from 156 women who were eligible for medication abortion at Planned Parenthood of Western Pennsylvania to evaluate dextromethorphan (DXM) as a non-narcotic option for post-abortion pain management.

Investigators randomized 156 women to adjunctively take DXM—loading dose 60 mg and 2 subsequent 30 mg doses at 2 and 5 hours after misoprostol administration—or placebo combined with nonsteroidal anti-inflammatory medications (NSAIDS) and/or opioids for pain. Patients reported pain scores and satisfaction 2, 5, 8, and 24 hours after misoprostol administration via a secure texting application. The study’s primary outcomes were worst pain score and total analgesic use.

Patients were able to opt for a printed oxycodone prescription—10 tabs of 5 mg—to fill at their pharmacy. All patients received routine counseling to take ibuprofen—600 mg orally every 6 hours as needed and/or acetaminophen for pain control during the medication abortion process and to secondarily use the prescribed opioid as needed.

Results showed no difference in worst pain scores for patients receiving DXM versus placebo (8.0 vs 7.0 

0.06), or in total milligram usage of ibuprofen (800 mg vs 610 mg, 

 = .62), acetaminophen (10000 mg vs 1300 mg, 

 = 0.51). Patients randomized to placebo were significantly more likely to be satisfied with their pain control (91% vs 75%, p = 0.02).

Patients receiving placebo were significantly more likely to rate their pain control as good or very good, compared to the DXM group (91% vs 75%, 

= 0.02). While patient age was a differing factor between groups (25.8 vs 27.4, 

< 0.05), dissatisfaction scores did not differ by patient age after adjustments (95% vs 71%, 

Of total patients, 124 (79%) opted to receive oxycodone prescriptions. Of those, 78 (63%) filled their prescriptions, and 6 of/156 (40%) reported taking any oxycodone during their medication abortion.

Patients who opted for an opioid prescription but did not get it filled reported lower rates of satisfaction in the DXM arm compared to placebo (70% vs 95% 

Investigators found worse pain scores and significantly less satisfaction in the DXM group overall, contrary to previous research that found DXM beneficial as an adjunctive option for gynecologic surgery.

“Given that patients do experience severe pain during this process, we should seek to improve patient use of ibuprofen, which is effective, and counsel patients on safe disposal of unused opioids,” the investigators concluded.

Ferguson GP, Achilles SL, Meyn LA, et al. Dextromethorphan as a novel nonopioid adjunctive agent for pain control with medication abortion: A randomized controlled trial. 

. Published online November 2022. doi:10.1016/j.contraception.2022.10.010

Results from a randomized controlled trial study suggest dextromethorphan may even worsen patient pain experience. 

Dextromethorphan ineffective adjuvant option for medication abortion pain management

At the American College of Rheumatology (ACR) Convergence 2022, Amit Golding, MD, PhD, medical officer for the US Food and Drug Administration (FDA), provided updates on recent FDA approvals for drugs and discussed how biosimilars are approved.

Golding outlined the 4 categories of similarity between adult and pediatric conditions. Different conditions show no overlap, dissimilar conditions contain slight overlap with significant differences, similar conditions show significant overlap with slight differences, and same conditions show significant overlap with no clear significant differences.

The first approval discussed by Golding was the use of belimumab IV (BENLYSTA; GlaxoSmithKline plc) for pediatric lupus nephritis in patients aged 5 to 17 years. Approval was based on established efficacy in adults and a successful study in pediatric patients. The pediatric dosage is 10 mg/kg in 2-week intervals for the first 3 doses, followed by 4-week intervals, matching the adult dosage.

Another approval was the use of ustekinumab SC (Stelara; Janssen Pharmaceuticals) for psoriatic arthritis in pediatric patients aged 6 to 17 years. The approval followed efficacy in adults and completed studies in pediatric patients with plaque psoriasis. A dosage based on weight is given 4 weeks after the initial dose, then every following 12 weeks.

Golding also discussed a study for secukinumab (COSENTYX; Novartis) for pediatric psoriatic arthritis and enthesitis-related arthritis. The study evaluated the treatment in pediatric patients aged 2 to under 18 years. In part 2 of the study, participants were randomized to secukinumab or placebo, with a primary endpoint of time to flare.

Following the study, approval was given to the product. Adverse events were mild and matched the safety profile for secukinumab, and efficacy for reducing flare rate was proven.

In discussing biosimilars, Golding described them as treatments that are highly similar and with, “no clinically meaningful differences from the FDA approved reference product.” They use the same mechanisms for conditions of use, which have been previously approved for the reference product. Biosimilars should meet the standards of safety, purity, and potency.

To evaluate differences in products, Golding recommended analytical study. Golding also stated that a biosimilar should have similar efficacy and safety as the reference product, and that an assessment of immunogenicity should be conducted.

Golding, A. Pediatric rheumatology FDA update 2022 ACR Convergence November 14, 2022. Presented at: ACR Convergence 2022, Philadelphia, Pennsylvania. November 11 to November 14, 2022.

Updates on FDA drug approvals

What are some of the challenges about diagnosing recurrent VVC [vulvovaginal candidiasis]? Do you think people are very aware in the community at large?

The first issue really, as far as diagnosis is concerned, is so-called self-diagnosis. This is the ability of any individual woman to be able to diagnose with great certainty that her symptoms are attributable to a yeast. Self-diagnoses are remarkably inaccurate. I know there’s always going to be some argument from the people listening in on this, participants hearing this, watching this video, but really there are numerous good objective studies that show just how unreliable self-diagnosis is. That doesn’t mean patients, women, don’t have symptoms, it simply means that the symptoms are entirely nonspecific. There’s nothing unique to the symptoms that says, “Oh, I obviously do have a yeast infection.” Repeatedly, women are referred to me because of recurrent candida vaginitis, and when I start interrogating and talking to them, and getting a history, and we do the appropriate tests, we find that there’s a lot of overdiagnosis of recurrent infections and there are some elements of underdiagnosis, especially for chronic disease. But you’ve already outlined the various symptoms involved, so the next issue, as far as diagnosis is concerned, it’s not difficult to diagnose once the patient finds herself visiting a practitioner, and this is not a telehealth visit. Telehealth is a wonderful advance in medicine and science, but in the diagnosis of vaginitis it’s about 10 steps backwards. You cannot diagnose reliably any form of vulvovaginal disease without seeing a practitioner who takes a history and does a good physical examination as well as the appropriate immediate local tests that are available within the doctor’s office.

I agree with you. The physical exam is invaluable and we’ll touch upon the concept of overdiagnosis, underdiagnosis in a little bit and how the impact of telehealth and teleprescribing, and you had mentioned that people are misdiagnosing or over the counter, we don’t have confirmation of diagnoses, so overdiagnosis. Every vaginitis is not yeast. Sometimes there’s BV [bacterial vaginosis]. Sometimes there’s a mixed infection. Sometimes it’s vulvovaginal atrophy. I think part of the issue that we are seeing is we have created this issue where there is a lot of telephone diagnosis and treatment because we didn’t have a choice with COVID-19, and then we’re overtreating. We’re seeing the emergence of resistance. We’re seeing more nonalbicans candidiasis. We’re seeing a variety of things that are changing in the landscape.

Videos

Michael L. Krychman, MD, and Jack D. Sobel, MD, review diagnostic criteria of diagnosis of RVVC and the impact of misdiagnosis.

The Challenges of Diagnosing Recurrent Vulvovaginal Candidiasis

Welcome to this Peers & Perspectives® presentation titled, “Expert Perspectives on Recurrent Vulvovaginal Candidiasis Management.” I’m Dr Michael Krychman, a clinical health professor from the University of California, Irvine, located in Orange County, California. It’s a pleasure today to be joined with Dr Jack Sobel from Wayne State University in Detroit, Michigan, to discuss considerations and strategies for the practical management of vulvovaginal candidiasis. Dr Sobel, welcome to our program today and let’s jump right in. I know that you and I both have renewed interest in vulvovaginal candidiasis. The landscape is changing. Before we go into that, let’s talk a little bit about the pathophysiology, the differences between sporadic and RVVC [recurrent vulvovaginal candidiasis]. How do you specifically define that? We want to talk about signs and symptoms, risk factors, and what have you; why don’t you get us started on that?

Thanks for introducing the subject, Michael. I think to obtain some sort of perspective of what recurrent disease is, we need to recognize that about 70% of women are going to have a vaginal yeast infection sooner or later during their reproductive years. We know that candida vaginitis is just so much less common in postmenopausal women, and it is very rare prior to puberty and onset of menses. Having said that, most women will have an occasional or sporadic attack, and that’s going to be about 80% to 90% of women will have an occasional, or what we call now, a sporadic attack. It may occur with a certain trigger, or it may occur spontaneously without any recognizable triggers. An example of a trigger for that sporadic attack may be recent exposure to an antibiotic given for influenza or for sinusitis, and often for a reason that you really didn’t need to get antibiotics in the first place. Probably half the episodes of sporadic attacks occur without a recognized triggering mechanism. That’s very important because sometimes patients just don’t identify, or physicians are unable to attribute a trigger in sporadic attacks. When we’re talking about recurrent infections, we’ve arbitrarily set this at 3 or more attacks per year, and this is a completely different ballgame. This is a world of repeated attacks, which can be 12 attacks a year. It really creates havoc in the life of a patient because they’re going from one attack to the other. They see practitioners on a regular basis. It has a very profound effect on their normal lives. They’re having symptoms repeatedly or chronically and it has a major impact on their normal, healthy sex lives and seemingly they are taking antifungal agents almost all the time.

You’re making a good point. Quality of life is certainly a big issue and there’s sexuality issues, relationship issues. You also talked about the medical economic implications of visiting the health care professional quite often. Their symptoms are quite distressing: the burning, itching, pain. Even vulvar and vaginal awareness, where they can’t even sit. For me, in my clinical practice, the impact of VVC and RVVC is astronomical and we have to move away from the concept of “just another yeast infection” as well, right? I appreciate what you’re saying in terms of the impact and, sometimes, lack of risk factors.

Michael L. Krychman, MD and Jack D. Sobel, MD, talk about the signs and symptoms of vulvovaginal candidiasis as well as its effect on patient quality of life.

Pathophysiology and Impact of Vulvovaginal Candidiasis

Bacterial vaginosis during pregnancy may lead to adverse outcomes, such as preterm birth, preterm delivery, and spontaneous abortion, according to results from a meta-analysis.

Researchers conducted a meta-analysis to delve deeper into the connection between bacterial vaginosis in early pregnancy and preterm birth. From November 2018 to March 2020, they searched PubMed, Cochrane, Google Scholar, and LILAC for data relating to bacterial vaginosis and preterm birth. They only included studies that were published from 2008 to 2018 and those that offered statistical data. They excluded studies that only consisted of conceptual and qualitative data. The search ultimately led to data from 20,894 women across 11 studies.

Researchers then evaluated the findings of each study, extracting various outcomes and conclusions. They combined the results—risk ratios (RR) and odds ratios (OR)—for deeper analysis. For women with bacterial vaginosis during pregnancy, the combined odds of preterm birth or preterm delivery was 2.79 (2.29-3.41).

Through their evaluation, they found that preterm birth was more than 2 times as likely in pregnant women with bacterial vaginosis than those without the infection (OR= 2.79; 95% CI, 2.29 to 3.41). Bacterial vaginosis was also found to be a greater risk factor for preterm delivery in late pregnancy, increasing the odds 4-fold.

Researchers also examined the conclusions of each study, ultimately identifying bacterial vaginosis in early pregnancy as a significant risk factor for preterm delivery and spontaneous abortion. They also found that the administration of clindamycin at <22 weeks’ gestation significantly reduced the risk for preterm birth.


Mohanty T, Doke PP, Khuroo SR. Effect of bacterial vaginosis on preterm birth: a meta-analysis [published online ahead of print, 2022 Oct 17]. 

. 2022;10.1007/s00404-022-06817-5. doi:10.1007/s00404-022-06817-5

Bacterial vaginosis during pregnancy may lead to increased risks for preterm birth, preterm delivery, and spontaneous abortion, according to new research in the Archives of Gynecology and Obstetrics.