Building Blocks for the Long-acting and Permanent Contraceptives Coordinated Registry Network.

Objectives: A multistakeholder expert group under the Women's Health Technology Coordinated Registry Network (WHT-CRN) was organized to develop the foundation for national infrastructure capturing the performance of long-acting and permanent contraceptives. The group, consisting of representatives from professional societies, the US Food and Drug Administration, academia, industry and the patient community, was assembled to discuss the role and feasibility of the CRN and to identify the core data elements needed to assess contraceptive medical product technologies. Design: We applied a Delphi survey method approach to achieve consensus on a core minimum data set for the future CRN. A series of surveys were sent to the panel and answered by each expert anonymously and individually. Results from the surveys were collected, collated and analyzed by a study design team from Weill Cornell Medicine. After the first survey, questions for subsequent surveys were based on the analysis process and conference call discussions with group members. This process was repeated two times over a 6-month time period until consensus was achieved. Results: Twenty-three experts participated in the Delphi process. Participation rates in the first and second round of the Delphi survey were 83% and 100%, respectively. The working group reached final consensus on 121 core data elements capturing reproductive/gynecological history, surgical history, general medical history, encounter information, long-acting/permanent contraceptive index procedures and follow-up, procedures performed in conjunction with the index procedure, product removal, medications, complications related to the long-acting and/or permanent contraceptive procedure, pregnancy and evaluation of safety and effectiveness outcomes. Conclusions: The WHT-CRN expert group produced a consensus-based core set of data elements that allow the study of current and future contraceptives. These data elements influence patient and provider decisions about treatments and include important outcomes related to safety and effectiveness of these medical devices, which may benefit other women's health stakeholders.

Scientific, ethical, and legal considerations for the inclusion of pregnant people in clinical trials.

Clinical trials to address the COVID-19 public health emergency have broadly excluded pregnant people from participation, illustrating a long-standing trend of clinical trial exclusion that has led to a clear knowledge gap and unmet need in the treatment and prevention of medical conditions experienced during pregnancy and of pregnancy-related conditions. Drugs (includes products such as drugs, biologics, biosimilars and vaccines) approved for a certain medical condition in adults are also approved for use in pregnant adults with the same medical condition, unless contraindicated for use in pregnancy. However, there are limited pregnancy-specific data on risks and benefits of drugs in pregnant people, despite their approval for all adults. The United States Food and Drug Administration-approved medical products are used widely by pregnant people, 90% of whom take at least 1 medication during the course of their pregnancy despite there being sparse data from clinical trials on these products in pregnancy. This overall lack of clinical data precludes informed decision-making, causing clinicians and pregnant patients to have to decide whether to pursue treatment without an adequate understanding of potential effects. Although some United States Food and Drug Administration initiatives and other federal efforts have helped to promote the inclusion of pregnant people in clinical research, broader collaboration and reforms are needed to address challenges related to the design and conduct of trials that enroll pregnant people, and to forge a culture of widespread inclusion of pregnant people in clinical research. This article summarizes the scientific, ethical, and legal considerations governing research conducted during pregnancy, as discussed during a recent subject matter expert convening held by the Duke-Margolis Center for Health Policy and the United States Food and Drug Administration on this topic. This article also recommends strategies for overcoming impediments to inclusion and trial conduct.

Accidental Flibanserin Ingestion in Children Causing Acute Respiratory and Central Nervous System Depression: What Health Care Professionals Need to Know.

This commentary serves to raise awareness for health care professionals about the potential risks of accidental ingestion of flibanserin tablets by children. Flibanserin was approved by the U.S. Food and Drug Administration (FDA) for the treatment of acquired generalized hypoactive sexual desire disorder in premenopausal women. Since its approval in 2015, the FDA has identified five reports of serious accidental ingestion by toddlers. All five children, boys with ages ranging from 18 months to 2 years, presented with central nervous system and respiratory depression, and two of them required intubation. A combination of hypertension, hyperthermia, and seizure-like activity was also seen in four of the five children. The clinical manifestation resembles serotonin syndrome (eg, tachycardia, hypertension, and muscle stiffness). As flibanserin use increases, greater awareness by health care professionals regarding the risk of accidental pediatric ingestion is needed to facilitate preventative counseling for patients with young children.

EXOGENOUS Sex Hormones and Sex Hormone Receptor Modulators in COVID-19: Rationale and Clinical Pharmacology Considerations.

Male patients with coronavirus disease 2019 (COVID-19) fare much worse than female patients in COVID-19 severity and mortality according to data from several studies. Because of this sex disparity, researchers hypothesize that the use of exogenous sex hormone therapy and sex hormone receptor modulators might provide therapeutic potential for patients with COVID-19. Repurposing approved drugs or drug candidates at late-stage clinical development could expedite COVID-19 therapy development because their clinical formulation, routes of administration, dosing regimen, clinical pharmacology, and potential adverse events have already been established or characterized in humans. A number of exogenous sex hormones and sex hormone receptor modulators are currently or will be under clinical investigation for COVID-19 therapy. In this review, we discuss the rationale for exogenous sex hormones and sex hormone receptor modulators in COVID-19 treatment, summarize ongoing and planned clinical trials, and discuss some of the clinical pharmacology considerations on clinical study design. To inform clinical study design and facilitate the clinical development of exogenous sex hormones and sex hormone receptor modulators for COVID-19 therapy, clinical investigators should pay attention to clinical pharmacology factors, such as dosing regimen, special populations (i.e., geriatrics, pregnancy, lactation, and renal/hepatic impairment), and drug interactions.

Pentosan associated retinal pigmentary changes: FDA's perspective on an emerging postmarketing safety finding.

INTRODUCTION AND HYPOTHESIS: Recent publications describe pigmentary changes in the retina associated with the use of pentosan polysulfate sodium, the only FDA-approved oral agent for relief of bladder pain or discomfort associated with interstitial cystitis. METHODS: To evaluate this association, we reviewed data from the FDA Adverse Event Reporting System and published case reports and observational studies. RESULTS: The totality of clinical and epidemiology evidence does not resolve the question of causation between pentosan use and retinal pigmentary changes; however, several elements support a potential association. CONCLUSION: Here, we provide our perspective on the available evidence the agency weighed when retinal pigmentary changes were added to pentosan labeling. It is important for urogynecologists prescribing pentosan to be aware of this potential association and be vigilant about assessing eye health in pentosan users.

Prescription medications for use in pregnancy-perspective from the US Food and Drug Administration.

Obstetrical healthcare providers frequently field questions about the safety of medications recommended or prescribed to their pregnant patients. Most women use as least 1 medication during pregnancy; however, there is little information about the safety or appropriate dosing of many medications during this phase of life. In addition, the development of drugs for use in pregnant women trails behind the development of drugs intended for other sectors of the population. Our goal is to inform the obstetrics community about the US Food and Drug Administration authority and their role in approving drugs for marketing. We begin with the statutes that led to the creation of the Food and Drug Administration and its current organization. We then cover drug development and the Food and Drug Administration review process, including the role of the advisory committee. The different types of drug approvals are discussed, with some specific examples. Finally, we enumerate the drugs specifically approved for use in obstetrics and contrast them with drugs commonly used by pregnant women and drugs used "off-label" during pregnancy. The Food and Drug Administration is committed to protecting and advancing the public health of pregnant women by guiding the development and ensuring the availability of effective and safe therapeutics for obstetrical indications and for medical conditions during pregnancy. We hope this review will inspire more research addressing drug use during pregnancy.

Launching the Reduction of Peripartum Racial/Ethnic Disparities Bundle: A Quality Improvement Project.

INTRODUCTION: Health care organizations have a responsibility to reduce racial and ethnic perinatal health disparities. In the United States, Black women experience the worst perinatal outcomes. The process for successfully addressing this problem in clinical practice remains unclear. PROCESS: A community hospital implemented components of the Alliance for Innovation on Maternal Health Reduction of Peripartum Racial/Ethnic Disparities Patient Safety Bundle. The purpose was to collect and share perinatal disparities data, increase staff awareness of perinatal racial and ethnic disparities, and engage staff to address these disparities at the project site. Perinatal care data were reviewed by race and ethnicity and results were shared with staff. Staff were engaged through a series of activities including a Health Equity Party, implicit bias workshop, Snack and Learn sessions, online modules, 2 grand rounds, and the establishment of a Health Equity Committee. OUTCOMES: Racial and/or ethnic disparities were identified for perinatal outcomes and experience of care indicators including rates of cesarean birth, newborn mortality, and 30-day readmission. Of the staff 137 (65.9%) participated in project activities. The majority of participants were registered nurses (n = 82). Certified nurse-midwives (n = 10) were the profession with the highest rate of attendance (83.3%). Staff developed 26 new recommendations to address racial and ethnic disparities in care. After project implementation, mean scores of High Provider Attribution, an indicator of readiness to address health disparities, increased from preimplementation scores (P = .01). There was also a significant increase in the number of staff who reported engaging in activities to address the health care needs of racial and ethnic minority patients (P < .001). DISCUSSION: This quality improvement project demonstrated that interventions at the health care organization level can be effective in influencing health care providers and staff to address racial and ethnic perinatal disparities.

Evidence-based pregnancy testing in clinical trials: Recommendations from a multi-stakeholder development process.

Most clinical trials exclude pregnant women in order to avoid the possibility of adverse embryonic and/or fetal effects. Currently, there are no evidence-based guidelines regarding appropriate methods for identifying early pregnancy among research subjects. This lack of guidance results in wide variation in pregnancy testing plans, leading to the potential for inadequate protection against embryonic or fetal exposure in some cases and unnecessary burdens on research participants in others, as well as inefficiencies caused by disagreements among sponsors, investigators, and regulators. To address this issue, the Clinical Trials Transformation Initiative convened content experts and stakeholders to develop recommendations for pregnancy testing in clinical research based on currently available evidence. Recommendations included: 1) the study protocol should clearly state the rationale for pregnancy testing and the plan for handling positive and indeterminate tests; 2) protocols should include an assessment of the pregnancy testing plan advantages (reduced risk of embryo/fetal exposure) versus the burdens (participant burden, study team workload, costs); 3) protocols should assess the participant burdens regarding the likelihood of false negative and false positive results; 4) participant administered home pregnancy testing should be avoided in clinical trials; and 5) the consent process should describe the extent of knowledge about the study intervention's potential risk to the embryo/fetus and the limitations and consequences of pregnancy testing. CTTI has also developed an online tool to help implement these recommendations.

Domperidone for Lactation: What Health Care Providers Need to Know.

This commentary serves to raise health care provider awareness about the regulatory status and available evidence regarding domperidone for insufficient lactation. Breastfeeding provides significant health benefits for mothers and infants, and insufficient milk production remains the most common reason for early weaning. Domperidone, a dopamine receptor antagonist that may increase milk production, is not approved for any human use in the United States. It is approved in some countries for certain gastrointestinal disorders, but is not approved in any country for lactation enhancement. Domperidone is associated with serious cardiac arrhythmias. The U.S. Food and Drug Administration (FDA) issued an import alert in 2004, updated in 2012, explaining that the importation of domperidone is illegal with limited exceptions, including when imported pursuant to an investigational new drug application. The FDA also issued a public safety warning regarding the use of domperidone for lactation. Nonetheless, domperidone is sometimes being obtained illegally and used in attempts to increase milk production in lactating mothers. There is limited quality evidence for the effectiveness of domperidone for lactation enhancement. In contrast, considerable information exists on domperidone's cardiac risks including QT prolongation, torsades de pointes, and sudden cardiac death, including among lactating women. In light of limited efficacy data that do not offset safety concerns from a public health perspective, we continue to caution against using domperidone for lactation enhancement. Research and drug development are needed to address the significant unmet medical need for lactation disorders.

Preconception counseling and care in the setting of HIV: clinical characteristics and comorbidities.

OBJECTIVE: To describe the demographic and clinical characteristics of HIV-infected individuals and HIV-affected couples who were referred for preconception counseling (PCC) at a large urban US-based HIV clinic. METHODS: Electronic medical records were reviewed for HIV-infected individuals and HIV-affected couples. Medical, reproductive, surgical, psychosocial, and family history data were abstracted. Univariate analyses were done. RESULTS: There were 8 single HIV-infected women and 100 HIV-affected couples who underwent PCC. HIV-infected women were older (mean age 35 years versus 32 years, P = 0.06), were more likely to smoke (23% versus 0%, P < 0.01), and had more medical comorbidities (57% versus 33%, P = 0.04) than HIV-uninfected women. The majority of couples were serodiscordant (77%), and of these couples, 32% had a detectable plasma viral load and 33% report inconsistent condom use. CONCLUSIONS: HIV-infected women have a number of medical and psychosocial issues, including those related to HIV that may increase the risk of adverse pregnancy outcomes and HIV perinatal and sexual transmission. PCC is an important intervention to optimize maternal management to improve perinatal outcomes and minimize transmission risks.

A randomized trial of chewing gum to prevent postoperative ileus after laparotomy for benign gynecologic surgery.

OBJECTIVE: To assess whether chewing gum prevents postoperative ileus after laparotomy for benign gynecologic surgery. METHODS: A randomized study was conducted from December 1, 2010, to February 29, 2012. Patients scheduled to undergo laparotomy were randomly assigned to receive chewing gum or routine care after surgery. A chart review was performed to establish incidence of nausea and vomiting, use of antiemetics, cases of postoperative ileus (≥2 episodes of emesis of 100 mL or more, with abdominal distention and absence of bowel sounds), and time to discharge. Inpatient surveys recorded the time to specific events. RESULTS: A total of 109 patients were randomly assigned to receive chewing gum (n=51) or routine postoperative care (n=58). Fewer participants assigned to receive chewing gum than routine care experienced postoperative nausea (16 [31.4%] versus 29 [50.0%]; P=0.049) and postoperative ileus (0 vs. 5 [8.6%]; P=0.032). There were no differences in the need for postoperative antiemetics, episodes of postoperative vomiting, readmissions, repeat surgeries, time to first hunger, time to toleration of clear liquids, time to regular diet, time to first flatus, or time to discharge. CONCLUSION: Chewing gum after laparotomy for gynecologic surgery is safe and lowers the incidence of postoperative ileus and nausea. ClinicalTrials.gov:NCT01579175.

Surgical site infections after hysterectomy among HIV-infected women in the HAART era: a single institution's experience from 1999-2012.

OBJECTIVE: We sought to determine risk factors associated with surgical site infection (SSI) among a cohort of human immunodeficiency virus (HIV)-infected women undergoing hysterectomy during the era of highly active antiretroviral therapy. STUDY DESIGN: This is a retrospective study of HIV-infected women who underwent a hysterectomy for benign indications at a tertiary care center. Electronic medical records were reviewed from January 1999 through December 2012. SSI was defined using Centers for Disease Control and Prevention criteria. RESULTS: There were 77 HIV-infected women who underwent a hysterectomy: 47 (61%) were abdominal; 16 (21%) were laparoscopic or robot-assisted; and 14 (18%) were vaginal. Acquired immune deficiency syndrome was diagnosed in 58% of patients, and 75% of patients self-reported use of highly active antiretroviral therapy at the time of surgery. There were 17 (22%) SSIs; 5 (29%) superficial incisional wound infections, 3 (18%) vaginal cuff cellulitis, and 9 (53%) pelvic abscesses were diagnosed. After multivariable logistic regression, preoperative albumin level (adjusted odds ratio [aOR], 0.14; 95% confidence interval [CI], 0.02-0.86) and minimally invasive hysterectomy (aOR, 0.16; 95% CI, 0.03-0.84) were associated with decreased SSI. Preoperative absolute CD4 count was not associated with SSI (aOR, 0.99; 95% CI, 0.99-1). CONCLUSION: Low preoperative serum albumin levels and abdominal hysterectomy are associated with increased risk of SSIs in HIV-infected women.

Retroperitoneal leiomyoma: a case report.

BACKGROUND: Retroperitoneal leiomyomata are rare neoplasms. These masses can be asymptomatic or can cause pelvic discomfort, urinary frequency, abdominal fullness or back pain. CASE: A 28-year-old, nulliparous female presented with worsening dysmenorrhea and bulk symptoms from fibroids. MRI revealed an exophytic anterior lower uterine segment fibroid with internal degeneration. During surgery the fibroid was discovered to be retroperitoneal in location, contrary to preoperative imaging findings. Pathology confirmed a benign leiomyoma. CONCLUSION: The treatment for these masses is complete excision. The retroperitoneal location of this fibroid was not evident on preoperative ultrasound and MRI. Imaging can be used only as a guide for operative planning and does not always represent the anatomy accurately. Surgical excision is required, and only at surgery will the exact anatomical location of the fibroid be ascertained.

Update on trends for inpatient surgical management of tubal ectopic pregnancy in Maryland.

OBJECTIVES: In Maryland, an analysis from 1994-1999 found that most hospitalized patients with tubal pregnancy underwent extirpative operations. The objective of this study was to determine whether practice patterns had changed over time. METHODS: Using the Maryland Health Service Cost Review Commission (HSCRC) database from January 1, 2000-December 31, 2004, subjects were identified by ICD-9 code 633.1, tubal pregnancy. The incidence of hospitalization was estimated based on state census data. Cases were analyzed by demographics, presentation, surgeon volume for ectopics, surgical treatment, length of stay, and charges. RESULTS: There were 2292 cases of tubal pregnancy identified, yielding an incidence for hospitalization of 4.81 per 10,000 women. The mean age of subjects was 29.6. Most were admitted through the emergency department (76.8%). Extirpative procedures were used in 88.01%. ER admission and increasing age were associated with extirpative surgery. Mean length of stay was 1.86 days; mean total charges were $5480.11. CONCLUSIONS: A greater percentage of hospitalized ectopics were treated radically than prior. This may be due to acuity of presentation or regional surgical practices and preferences. Continued surveillance and a move toward improvement of Maryland's outcomes for ectopic pregnancy is needed. We propose an algorithm for emergency triage and management of pregnancy in an unknown location toward this end.

A national analysis of the relationship between hospital volume, academic center status, and surgical outcomes for abdominal hysterectomy done for leiomyoma.

BACKGROUND: Volume-to-outcomes relationships have been established for high-risk surgical procedures. To determine whether hospital volume and academic center status affect surgical outcomes in a lower-risk procedure, morbidity and mortality in patients undergoing abdominal hysterectomy for leiomyoma were evaluated. STUDY DESIGN: Administrative data from the National Inpatient Sample were used to conduct a retrospective analysis of 172,344 individuals who had primary diagnoses of leiomyomata (ICD-9 diagnosis codes of 218.x in the first 2 positions) and who underwent abdominal hysterectomy (ICD-9 procedure codes 68.4 in the first 2 positions) from 1999 to 2003. Comparison was made between teaching hospitals versus nonteaching hospitals and annual case volume in quintiles. Morbidity was considered to be any postoperative condition that is not an expected outcome of hysterectomy and defined as instances in which a patient suffered hemorrhage, ureteral injury, bladder injury, intestinal injury, wound dehiscence, wound infection, deep vein thrombosis, pulmonary embolism, or required blood transfusion. RESULTS: A total of 37 deaths were observed. Mortality was not significantly related to hospital volume or academic medical center status. In contrast, morbidity was found to have a positive association with academic medical center status (odds ratio = 1.34; 95% CI, 1.23 to 1.45), although an inverse relationship between volume and morbidity was observed for extended length of stay (> 3 days) and blood transfusion outcomes in the first 3 (lowest) volume quintiles and for pulmonary embolism in the highest-volume quintile. No important association with volume was found for hemorrhage, ureteral injury, bladder injury, or intestinal injury. CONCLUSIONS: Unlike high-risk procedures, such as esophagectomy, pediatric cardiac surgery, and pancreaticoduodenectomy, mortality for abdominal hysterectomy done for benign indication does not improve with hospital volume or academic center status. The statistically significant positive association between academic medical center status and morbidity merits additional characterization to target areas for improvement.