Depression, perceived stress, and distress during pregnancy and EV-associated miRNA profiles in MADRES.

BACKGROUND: MicroRNA (miRNA) circulating in plasma has been proposed as biomarkers for a variety of diseases and stress measures, including depression, stress, and trauma. However, few studies have examined the relationship between stress and miRNA during pregnancy. METHODS: In this study, we examined associations between measures of stress and depression during pregnancy with miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, California. Extracellular-vesicle- (EV-) associated miRNA were isolated from maternal plasma and quantified using the Nanostring nCounter platform. Correlations for stress-associated miRNA were also calculated for 89 matching cord blood samples. RESULTS: Fifty miRNA were nominally associated with depression, perceived stress, and prenatal distress (raw p < 0.05) with 17 miRNA shared between two or more stress measures. Two miRNA (miR-150-5p and miR-148b-3p) remained marginally significant after FDR adjustment (p < 0.10). Fifteen PANTHER pathways were enriched for predicted gene targets of the 50 miRNA associated with stress. Clusters of maternal and neonate miRNA expression suggest a link between maternal and child profiles. LIMITATIONS: The study evaluated 142 miRNA and was not an exhaustive analysis of all discovered miRNA. Evaluations for stress, depression and trauma were based on self-reported instruments, rather than diagnostic tools. CONCLUSIONS: Depression and stress during pregnancy are associated with some circulating EV miRNA. Given that EV miRNA play important roles in maternal-fetal communication, this may have downstream consequences for maternal and child health, and underscore the importance of addressing mental health during pregnancy, especially in health disparities populations.

Extracellular vesicle-enriched miRNA profiles across pregnancy in the MADRES cohort.

MicroRNA (miRNA) circulating in plasma have been proposed as biomarkers for a variety of conditions and diseases, including complications during pregnancy. During pregnancy, about 15-25% of maternal plasma exosomes, a small size-class of EVs, are hypothesized to originate in the placenta, and may play a role in communication between the fetus and mother. However, few studies have addressed changes in miRNA over the course of pregnancy with repeated measures, nor focused on diverse populations. We describe changes in miRNA in early and late pregnancy from the MADRES cohort of primarily low-income Hispanic women based in Los Angeles, CA. miRNA derived from extracellular-vesicles (EVs) were isolated from maternal blood plasma samples collected in early and late pregnancy. In this study, we identified 64 of 130 detectable miRNA which significantly increased with gestational age at the time of collection (GA), and 26 which decreased with GA. Possible fetal sex-specific associations were observed for 30 of these 90 significant miRNA. Predicted gene targets for miRNA significantly associated with GA were identified using MirDIP and were found to be enriched for Gene Ontology categories that included energetic and metabolic processes but were underrepresented in immune-related categories. Circulating EV-associated miRNA during pregnancy are likely important for maternal-fetal communication, and may play roles in supporting and maintaining a healthy pregnancy, given the changing needs of the fetus.

Cost effectiveness of contraceptives in the United States.

BACKGROUND: The study was conducted to estimate the relative cost effectiveness of contraceptives in the United States from a payer's perspective. METHODS: A Markov model was constructed to simulate costs for 16 contraceptive methods and no method over a 5-year period. Failure rates, adverse event rates and resource utilization were derived from the literature. Sensitivity analyses were performed on costs and failure rates. RESULTS: Any contraceptive method is superior to "no method". The three least expensive methods were the copper-T intrauterine device (IUD) (US$647), vasectomy (US$713) and levonorgestrel (LNG)-20 intrauterine system (IUS) (US$930). Results were sensitive to the cost of contraceptive methods, the cost of an unintended pregnancy and plan disenrollment rates. CONCLUSION: The copper-T IUD, vasectomy and the LNG-20 IUS are the most cost-effective contraceptive methods available in the United States. Differences in method costs, the cost of an unintended pregnancy and time horizon are influential factors that determine the overall value of a contraceptive method.

Disease-specific cost savings of treating nighttime versus daytime gastroesophageal reflux disease in an employed population.

OBJECTIVE: The extent to which proton pump inhibitors (PPIs) can offset direct medical costs by reducing symptoms related to gastroesophageal reflux disease (GERD) in order to improve work productivity is not well understood. This study aimed to evaluate the economic impact of treating GERD with PPIs versus no treatment, from an employer's perspective. STUDY DESIGN: An economic model was developed to simulate symptom reduction and breakthrough symptoms as well as associated costs over 1 year among a population of 100,000 with a 20% GERD prevalence rate. Medical costs, including GERD-related office visits, hospitalisations and procedures, were delineated by symptom severity. Indirect costs represented the monetised work productivity loss. PPI treatment costs $2/day (standard dose). RESULTS: The GERD burden was substantial ($62,500,000). Treatment yielded $32,600,000 in savings ($1,630 saved/patient/year), mostly from reducing indirect costs. Treatment produced greater savings among nighttime GERD patients throughout the PPI cost range ($1-$5/day). Savings dropped if the price of standard doses of PPI exceeded $3.92/day for the treatment of daytime GERD patients.

Economic burden of patients with anemia in selected diseases.

OBJECTIVE: To examine the economic impact of patients with anemia in selected diseases. METHODS: A retrospective cohort design was used to estimate the differences in costs between anemic and nonanemic patients. The analysis used administrative claims data (1999-2001) from a US population to assess direct costs and disability and productivity data (1997-2001) to estimate indirect costs. Adult patients with a diagnosis of rheumatoid arthritis (RA), inflammatory bowel disease (IBD), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), cancer, or congestive heart failure (CHF) were identified. Costs were estimated using a generalized linear model, adjusting for age, sex, comorbidities, and disease severity. The adjustment variables for disease severity were based on ICD-9, HCPCS, or pharmacy codes. These costs were projected to a 1-million-member, similar population. RESULTS: The percentage of anemia patients varied among conditions (6.9-26.1%); the CKD population had the highest prevalence. CKD anemic patients incurred the greatest average annual direct costs ($78,209), followed by CHF ($72,078) and cancer ($60,447). After adjusting for baseline characteristics including severity, the difference in direct costs between anemic and nonanemic patients decreased for all diseases; CHF patients incurred the greatest adjusted cost difference between anemic and nonanemic ($29,511), followed by CKD ($20,529) and cancer ($18,418). Unmeasured severity and coding bias may account for a portion of the differences in the adjusted cost. CONCLUSION: Anemia may substantially increase health-care costs at a level that is economically very relevant, despite the fact that these patients may comprise only one tenth of the overall anemic population.

A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn's disease treated with azathioprine or 6-mercaptopurine.

BACKGROUND: Azathioprine (AZA) is effective for the maintenance of a steroid free remission in Crohn's disease (CD). Thiopurine methyltransferase (TPMT) is important for the metabolism of AZA and influences the production of active AZA metabolites. AZA dose selection based on pharmacogenetic testing of TPMT and metabolite monitoring (MM) may offer a safety and efficacy advantage over traditional dosing strategies. We performed a decision analysis to estimate the potential costs and effectiveness of TPMT screening and MM as disease management strategies for CD. METHODS: Strategies applying TPMT and/or MM to influence treatment decisions were compared to community care (CC). The impact on toxicity minimization and improved time to initial and sustained response was evaluated. A 1-yr model was developed from the third-party payer perspective for mild to moderately chronically active, steroid-treated CD patients. Effectiveness and toxicity defined by time to response CD activity index (CDAI <150, +/- steroids) or time to sustained response (CDAI <150, off steroids x 8 wk) and reduction in leukopenic events, respectively. One- and two-way sensitivity analyses were conducted to determine the effect of varying individual estimates from those used in the base-case analysis. RESULTS: MM, TPMT, and TPMT + MM strategies as compared to CC achieved an earlier time to initial response (18.66, 18.96, and 19.10 vs. 22.41 wk, respectively) and sustained response (39.83, 42.91, and 39.8 vs. 45.36 wk, respectively). The least costly strategy at 1 yr was TPMT ($3,861) and the most costly strategy was CC ($7,142). Each alternative strategy was shown to dominate CC (i.e., less costs and faster time to response or sustained response). The cost-effectiveness rankings were robust to sensitivity analyses on key variables. CONCLUSION: The addition of alternative strategies to CC may improve AZA outcomes and reduce the total cost of care for steroid treated chronically active CD patients, with TPMT being more beneficial for initial response to treatment and MM being more beneficial for sustained response to treatment.

Prevalence and outcomes of anemia in inflammatory bowel disease: a systematic review of the literature.

The prevalence of anemia in patients with inflammatory bowel disease ranges from 8.8% to 73.7% depending on the patient subpopulation. Anemia, one of many extraintestinal complications of ulcerative colitis and Crohn disease, is generally defined as a hemoglobin value <120 g/L or hematocrit <0.4; severe anemia is defined as a hemoglobin level <100 g/L. Many patients have been shown to be intolerant of oral iron replacement therapy or their anemia was refractory to such supplementation. Correction of anemia through the administration of intravenous iron saccharate and/or supplemental erythropoietin has been shown to improve patient hematologic indices and quality of life. Future studies are needed to determine the type of patients at highest risk of developing severe anemia as well as the treatment interventions with the most beneficial effect.

Economic analysis of contraceptives for women.

OBJECTIVE: To examine from the health care services payer perspective the economic consequences of contraceptives available to women in the United States. METHODS: A Markov model was constructed to compare effectiveness and costs among nine contraceptive methods (including 3-month injectable, oral contraceptives, intrauterine device (IUD), intrauterine system (IUS), barrier methods and surgical methods). Primary health states included initial/continued use, method failure and method discontinuation with transitions every year for 5 years. Plan disenrollment was also incorporated in the model. Estimates for probabilities of events, resource used, and costs for the base-case were derived from a comprehensive literature review, average wholesale drug prices, the 2000 Medicare Reimbursement Fee Schedule and MEDSTAT's 2000 DRG Guide, in conjunction with expert opinion. Sensitivity analyses were performed on all variables. RESULTS: Aside from vasectomy, which was outside the scope of this study, the most effective methods were tubal ligation, levonorgestrel (LNG)-20 IUS and copper T 380A IUD. The least expensive methods (accounting for all costs) were LNG-20 IUS, copper T 380A IUD and 3-month injectable; the 5-year cost/person were $1646, $1678 and $2195, respectively. CONCLUSION: From a third-party payer perspective, LNG-20 IUS and copper T 380A IUD dominated all reviewed methods, except for tubal ligation. However, the small increase in contraceptive efficacy with tubal ligation has a high cost. IUD and IUS device costs have a significant impact on the relative cost-effectiveness of these two methods.

Identifying patients with gastroesophageal reflux disease: validation of a practical screening tool.

A reliable, accurate noninvasive method for identifying patients with gastroesophageal reflux disease (GERD) in the primary care setting is needed. A population-based case-finding instrument may assist managed care organizations in identifying candidates for disease management or quality improvement programs. Our aim was to develop and validate a GERD case-finding instrument. A 12-item "GERD Screener" was developed based on literature review and expert opinion with questions about heartburn and regurgitation frequency and severity and medication use, as well demographics and exclusion criteria. Categorical and continuous scoring methods with and without medication use were developed a priori. Using a telephone interview in a medical group, we identified and enrolled 100 subjects with a history of GERD-like symptoms and 103 controls. Each subject completed the GERD Screener, a validated gastrointestinal symptom questionnaire, the Digestive Health Symptom Index (DHSI), and was evaluated independently by two gastroenterologists using a structured format. Agreement by the two physicians that symptoms were consistent with GERD and required an intervention was considered the gold standard. In all, 70 subjects were classified as having GERD and 106 as controls using the gold standard (K = 0.73; 95% CI, 0.63-0.82). The scoring method for the screening instrument using a continuous measure of GERD symptoms (frequency and severity) and weighted medication use resulted in an area under ROC of 0.89 (95% CI, 0.84-0.94). Using a cutoff of >9 points, this measure was 83% sensitive and 83% specific. Compared to the gold standard, the DHSI GERD subscale has an area under ROC of 0.89 (95% CI, 0.84-0.94). The GERD Screener was highly correlated with the DHSI GERD subscale, r = 0.78 (95% CI 0.72-0.83; P < 0.0001). In conclusion, the GERD Screener has demonstrated construct, convergent, and predictive validity. It is shorter than existing validated instruments, practical, and easily administered, which may reduce the response and administrative burden. This may serve as a valuable case-finding instrument in primary-care and managed-care organizations wishing to implement programs to improve the quality and efficiency of care.