Landscape review of global real-world data sources for studying medication use in pregnancy and lactation that support regulatory decision making.

PURPOSE: Most pregnant people take at least one medication during gestation or while breastfeeding, however data are lacking on the safety of medication use in these populations. We conducted a landscape review of real-world data sources specific to medication use in pregnancy and breastfeeding populations that have met, or have potential to meet, health authorities' requirements for post-authorization safety studies. METHODS: A 2-phase approach identified data sources from literature, publicly available registers of non-interventional post-authorization studies of pregnant women, existing database inventories, and emerging data sources known to the authors. RESULTS: Required key attributes were assessed according to current regulatory guidance, resulting in selection of 49 suitable data sources. All global regions were represented, with North America (37%) and Europe (33%) most common; 12% of the data sources included pregnancy information from low-to middle-income countries. Administrative healthcare claims (25%) and electronic healthcare records (21%) comprised the largest types of data sources. Across data sources, 53% were managed by national or regional governments, 27% by industry, and 20% by academic institutions. Maternal age, diagnoses, prenatal care, and reproductive history were available in most, whereas fewer included demographic data (e.g., race/ethnicity). Breastfeeding data were collected in 37% of the final data sources. CONCLUSION: We conducted a systematic approach to data source evaluation of pregnancy and breastfeeding to be used as a resource for investigators to consider when designing pregnancy-related research studies to satisfy regulatory requirements.

Maternal health equity in Georgia: a Delphi consensus approach to definition and research priorities.

BACKGROUND: Pregnancy-related mortality in the United States is the greatest among all high-income countries, and Georgia has one of the highest maternal mortality rates-almost twice the national rate. Furthermore, inequities exist in rates of pregnancy-related deaths. In Georgia, non-Hispanic Black women are nearly 3 times more likely to die from pregnancy-related complications than non-Hispanic White women. Unlike health equity, a clear definition of maternal health equity is lacking, overall and in Georgia specifically, but is needed to reach consensus and align stakeholders for action. Therefore, we used a modified Delphi method to define maternal health equity in Georgia and to determine research priorities based on gaps in understanding of maternal health in Georgia. METHODS: Thirteen expert members of the Georgia Maternal Health Research for Action Steering Committee (GMHRA-SC) participated in an iterative, consensus-driven, modified Delphi study comprised of 3 rounds of anonymous surveys. In round 1 (web-based survey), experts generated open-ended concepts of maternal health equity and listed research priorities. In rounds 2 (web-based meeting) and 3 (web-based survey), the definition and research priorities suggested during round 1 were categorized into concepts for ranking based on relevance, importance, and feasibility. Final concepts were subjected to a conventional content analysis to identify general themes. RESULTS: The consensus definition of maternal health equity created after undergoing the Delphi method is: maternal health equity is the ultimate goal and ongoing process of ensuring optimal perinatal experiences and outcomes for everyone as the result of practices and policies free of interpersonal or structural bias that tackle current and historical injustices, including social, structural, and political determinants of health impacting the perinatal period and life course. This definition highlights addressing the current and historical injustices manifested in the social determinants of health, and the structural and political structures that impact the perinatal experience. CONCLUSION: The maternal health equity definition and identified research priorities will guide the GMHRA-SC and the broader maternal health community for research, practice, and advocacy in Georgia.

Global Cross-Sectional Study Evaluating the Attitudes towards a COVID-19 Vaccine in Pregnant and Postpartum Women.

Pregnant and postpartum women have an increased risk of severe complications from COVID-19. Many clinical guidelines recommend vaccination of these populations, and it is therefore critical to understand their attitudes toward COVID-19 vaccines. We conducted a cross-sectional online survey in November 2020 of currently pregnant and ≤1-year postpartum women in Brazil, India, the United Kingdom (UK), and the United States (US) that assessed their openness to COVID-19 vaccines and reasons for vaccine hesitancy. Logistic regression analyses were conducted to evaluate openness to receiving a vaccine. Out of 2010 respondents, 67% were open to receiving a COVID-19 vaccine themselves. Among pregnant and postpartum participants, 72% and 57% were willing to receive a vaccine, respectively. Vaccine openness varied significantly by country: India (87%), Brazil (71%), UK (59%), and US (52%). Across all participants, among the 33% who were unsure/not open to receiving a COVID-19 vaccine, the most common reason cited was safety/side effect concerns (51%). Participants were similarly open to their children/other family members receiving a COVID-19 vaccine. Presence of a comorbidity, a positive COVID-19 test result, and pregnancy were all significantly associated with positive vaccine acceptance. Targeted outreach to address pregnant and postpartum women's concerns about the COVID-19 vaccine is needed.

Social determinants of health associated with COVID-19 severity during pregnancy: a multinational cohort study (in the International Registry of Coronavirus Exposure in Pregnancy).

BACKGROUND: The COVID-19 pandemic has caused morbidity and mortality, particularly among vulnerable populations. We aimed to assess social and demographic characteristics associated with COVID-19 severity among symptomatic participants during pregnancy. METHODS: The International Registry of Coronavirus Exposure in Pregnancy is a multinational, longitudinal observational cohort study of adult participants tested for SARS-CoV-2 or who received clinical diagnosis of COVID-19 during pregnancy (NCT04366986). Disease severity status of mild, moderate, or severe was determined based on symptoms and healthcare utilization. Stratified by current versus recent pregnancy at enrollment, univariate mixed-effects logistic regression modeling was used to characterize association between social and demographic characteristics with COVID-19 severity, using a cumulative mixed effect model with country as a random effect. RESULTS: The odds of developing more severe COVID-19 (odds ratio [95% confidence interval]) were higher among participants with lower socioeconomic status (poor: 2.72 [2.01,3.69]; lower-middle class: 2.07 [1.62,2.65] vs wealthy), among participants with lower educational attainment (high school: 1.68 [1.39,2.03]; < high school (1.77 [1.25,2.51] vs graduate education). Participants over 25 years of age had lower odds of severe COVID-19 versus participants < 25 years (25-34: 0.69 [0.56,0.85]; 35-50: 0.62 [0.48,0.80]). Employment in food services was also associated with increased odds of more severe COVID-19, whereas employment in healthcare and within home, and primiparity were associated with lower severity. CONCLUSIONS: Findings suggest that employment setting and economic status have strong associations with COVID-19 severity, which warrants considering social determinants of health in the context of assessing risk factors of more severe COVID-19 during pregnancy. TRIAL REGISTRATION: IRCEP was registered with the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) [EUPAS37360] and clinicaltrials.gov [NCT04366986].

Sex differences in sequelae from COVID-19 infection and in long COVID syndrome: a review.

OBJECTIVE: We conducted literature reviews to uncover differential effects of sex on sequelae from coronavirus disease 2019 (COVID-19) and on long COVID syndrome. METHODS: Two authors independently searched OvidSP in Embase, Medline, Biosis, and Derwent Drug File. Publications reporting original, sex-disaggregated data for sequelae of COVID-19 (published before August 2020) and long COVID syndrome (published before June 2021) were included in the reviews. The association between COVID-19 sequelae (i.e. lasting <4 weeks after symptom onset) and sex, and between long COVID syndrome (i.e. lasting >4 weeks after symptom onset) and sex, was determined by odds ratio (OR) and 95% confidence interval (CI) (statistical significance defined by 95% CI not including 1). RESULTS: Of 4346 publications identified, 23 and 12 met eligibility criteria for COVID-19 sequelae and long COVID syndrome, respectively. COVID-19 sequelae in the categories of psychiatric/mood (OR = 1.80; 95% CI: 1.35-2.41), ENT (OR = 1.42; 95% CI: 1.39-1.46), musculoskeletal (OR = 1.15; 95% CI: 1.14-1.16), and respiratory (OR = 1.09; 95% CI: 1.08-1.11) were significantly more likely among females (vs. males), whereas renal sequelae (OR = 0.83; 95% CI: 0.75-0.93) were significantly more likely among males. The likelihood of having long COVID syndrome was significantly greater among females (OR = 1.22; 95% CI: 1.13-1.32), with the odds of ENT (OR = 2.28; 95% CI: 1.94-2.67), GI (OR = 1.60; 95% CI: 1.04-2.44), psychiatric/mood (OR = 1.58; 95% CI: 1.37-1.82), neurological (OR = 1.30; 95% CI: 1.03-1.63), dermatological (OR = 1.29; 95% CI: 1.05-1.58), and other (OR = 1.36; 95% CI: 1.25-1.49) disorders significantly higher among females and the odds of endocrine (OR = 0.75; 95% CI: 0.69-0.81) and renal disorders (OR = 0.74; 95% CI: 0.64-0.86) significantly higher among males. CONCLUSIONS: Sex-disaggregated differences for COVID-19 sequelae and long COVID syndrome were observed. Few COVID-19 studies report sex-disaggregated data, underscoring the need for further sex-based research/reporting of COVID-19 disease.

Maternal health expert feedback on the attributes of a predictive analytics tool to improve pregnancy-related cardiovascular and mental health outcomes in the United States.

Identify pregnancy-related challenges and opportunities to improve maternal health care in the United States and understand the potential role of predictive analytics tool(s) in bridging the existing gaps, specifically, in CVD (cardiovascular disease) and depression. Experts in maternal health care, research, patient advocacy, CVD, psychiatry, and technology were interviewed during February and March of 2020. Additionally, published literature was reviewed to assess existing data, insights, and best practices that might help develop effective predictive analytics tool(s). The majority (78%) of the 18 experts interviewed were women. The feedback revealed several insights, including multiple barriers to diagnosis and treatment of pregnancy-related CVD and depression. In experts' collective opinion, predictive analytics could play an important role in maternal health care and in limiting pregnancy-related CVD and depression, but it must be grounded in quality data and integrate with existing health management systems. A holistic approach to maternal health that factors in racial-ethnic, regional, and socioeconomic disparities is needed that starts with preconception counseling and continues through 1 year postpartum. Predictive analytics tool(s) that are based on diverse and high-quality data could bridge some of the existing gaps in maternal health care and potentially help limit pregnancy-related CVD and depression.

Preferences of Patients with Chronic Hepatitis B - A Discrete Choice Experiment on the Acceptability of Functional Cure.

BACKGROUND: Current antiviral therapies for chronic hepatitis B (CHB) rarely achieve functional cure, thus often requiring lifelong therapy. A therapy achieving functional cure in a significant percentage of patients could change the treatment landscape substantially. However, the acceptability of functional cure by patients is unknown, especially if associated with additional treatment burden. METHODS: A Discrete Choice Experiment (DCE) including patients with CHB was performed between 2018 and 2019 in Germany. Patient inclusion criteria were confirmed CHB; age of at least 18 years; no history of hepatocellular carcinoma; no HIV or HCV/HDV co-infection. The final DCE included the following attributes: route of administration (oral administration by tablets; subcutaneous injection + tablets; intramuscular electroporation + tablets), side effect frequency (0/1/3 days per month), functional cure (1%/30%/50% of patients), frequency of physician visits (monthly, half-yearly) and travel time to treating physician (15/45 min). RESULTS: The main analysis sample consisted of 108 patients with CHB (mean age: 49.1 years, female: 37.0%, average time since CHB diagnosis: 14.0 years, 52.8% with Hepatitis B surface antigen (HBsAg) chronic HBV infection). High efficacy was found to be the main driver of decisions for/against the presented treatment options (impacted 57% of patients' decisions), followed by therapy regimen (17%), safety profile (12%) and number of physician visits (11%). Latent class analysis revealed first insights into different decision patterns, with age, gender and previous side-effect experience affecting patients' decisions. CONCLUSION: In comparison to all other treatment-related attributes such as therapy regimen or safety profile, patients with CHB showed a strong preference towards a scenario where a substantial number of patients benefit from sustained disease remission, which mimics functional cure.

Evaluating the Effect of Standard of Care Treatment on Burden of Chronic Hepatitis B: A Retrospective Analysis of the United States Veterans Population.

INTRODUCTION: This study aimed to characterize chronic hepatitis B (CHB)-infected patients and estimate the association between nucleos(t)ide analogue (NA) persistence and economic outcomes using data from the Veterans Health Administration (VHA) database. METHODS: Patients (at least 18 years of age) with two or more claims for CHB and at least one pharmacy claim for NA were identified using VHA data from 1 April 2013 to 31 March 2018. The index date was the first NA prescription fill date during 1 October 2014 to 31 March 2017. Persistence and non-persistence to NA treatment were assessed during the first 2 years post index date. Non-persistence was defined as at least one failure to refill medication within 30 days from the run-out date. Generalized linear models were used to compare health care utilization and costs between persistent and non-persistent patients. RESULTS: Among patients treated with NAs (N = 2368), 1428 (60%) were CHB mono-infected and 748 (32%) were HIV co-infected. Total costs per patient per year (PPPY) were $39,240, $29,957, and $55,220 PPPY for NA-treated, mono-infected, and HIV co-infected patients, respectively. An inception cohort of 564 patients (24%), without a NA prescription in the 6 months pre-index period and at least 2 years of follow-up, was created. Persistence among the inception cohort was 29% for first year and 14% for first 2 years. After adjustment for baseline differences, persistent patients had lower cumulative overall health care costs compared to non-persistent patients, with a net cost saving of $851 (p > 0.05) in the first 2 years. CONCLUSION: CHB is associated with considerable economic burden. We observed suboptimal persistence to NAs which decreased over time. Short-term savings could be generated for CHB-infected patients when they remain persistent to NAs.