Pharmacogenetics and individualizing drug treatment during pregnancy

Pharmacogenetics as a tool to aid clinicians implement individualized pharmacotherapy is utilized in some areas of medicine. Pharmacogenetics in pregnancy is still a developing field. However, there are several areas of obstetric therapeutics where data are emerging that give glimpses into future therapeutic possibilities. These include opioid pain management, antihypertensive therapy, antidepressant medications, preterm labor tocolytics, antenatal corticosteroids and drugs for nausea and vomiting of pregnancy, to name a few. More data are needed to populate the therapeutic models and to truly determine if pharmacogenetics will aid in individualizing pharmacotherapy in pregnancy. The objective of this review is to summarize current data and highlight research needs

Incentives for increasing prenatal care use by women in order to improve maternal and neonatal outcomes

BACKGROUND: Prenatal care is recommended during pregnancy as a method to improve neonatal and maternal outcomes. Improving the use of prenatal care is important, particularly for women at moderate to high risk of adverse outcomes. Incentives are sometimes utilized to encourage women to attend prenatal care visits. OBJECTIVES: To determine whether incentives are an effective tool to increase utilization of timely prenatal care among women. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2015) and the reference lists of all retrieved studies. SELECTION CRITERIA: Randomized controlled trials (RCTs), quasi-RCTs, and cluster-RCTs that utilized direct incentives to pregnant women explicitly linked to initiation and frequency of prenatal care were included. Incentives could include cash, vouchers, coupons or products not generally offered to women as a standard of prenatal care. Comparisons were to no incentives and to incentives not linked directly to utilization of care. We also planned to compare different types of interventions, i.e. monetary versus products or services. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and methodological quality. Two review authors independently extracted data. Data were checked for accuracy. MAIN RESULTS: We identified 11 studies (19 reports), six of which we excluded. Five studies, involving 11,935 pregnancies were included, but only 1893 pregnancies contributed data regarding our specified outcomes. Incentives in the studies included cash, gift card, baby carrier, baby blanket or taxicab voucher and were compared with no incentives. Meta-analysis was performed for only one outcome 'Return for postpartum care' and this outcome was not pre-specified in our protocol. Other analyses were restricted to data from single studies.Trials were at a moderate risk of bias overall. Randomization and allocation were adequate and risk of selection bias was low in three studies and unclear in two studies. None of the studies were blinded to the participants. Blinding of outcome assessors was adequate in one study, but was limited or not described in the remaining four studies. Risk of attrition was deemed to be low in all studies that contributed data to the review. Two of the studies reported or analyzed data in a manner that was not consistent with the predetermined protocol and thus were deemed to be at high risk. The other three studies were low risk for reporting bias. The largest two of the five studies comprising the majority of participants took place in rural, low-income, homogenously Hispanic communities in Central America. This setting introduces a number of confounding factors that may affect generalizability of these findings to ethnically and economically diverse urban communities in developed countries.The five included studies of incentive programs did not report any of this review's primary outcomes: preterm birth, small-for-gestational age, or perinatal death.In terms of this review's secondary outcomes, pregnant women receiving incentives were no more likely to initiate prenatal care (risk ratio (RR) 1.04, 95% confidence interval (CI) 0.78 to 1.38, one study, 104 pregnancies). Pregnant women receiving incentives were more likely to attend prenatal visits on a frequent basis (RR 1.18, 95% CI 1.01 to 1.38, one study, 606 pregnancies) and obtain adequate prenatal care defined by number of "procedures" such as testing blood sugar or blood pressure, vaccinations and counseling about breastfeeding and birth control (mean difference (MD) 5.84, 95% CI 1.88 to 9.80, one study, 892 pregnancies). In contrast, women who received incentives were more likely to deliver by cesarean section (RR 1.97, 95% CI 1.18 to 3.30, one study, 979 pregnancies) compared to those women who did not receive incentives.Women who received incentives were no more likely to return for postpartum care based on results of meta-analysis (average RR 0.75, 95% CI 0.21 to 2.64, two studies, 833 pregnancies, Tau² = 0.81, I² = 98%). However, there was substantial heterogeneity in this analysis so a subgroup analysis was performed and this identified a clear difference between subgroups based on the type of incentive being offered. In one study, women receiving non-cash incentives were more likely to return for postpartum care (RR 1.26, 95% CI 1.09 to 1.47, 240 pregnancies) than women who did not receive non-cash incentives. In another study, women receiving cash incentives were less likely to return for postpartum care (RR 0.43, 95% CI 0.30 to 0.62, 593 pregnancies) than women who did not receive cash incentives.No data were identified for the following secondary outcomes: frequency of prenatal care; pre-eclampsia; satisfaction with birth experience; maternal mortality; low birthweight (less than 2500 g); infant macrosomia (birthweight greater than 4000 g); or five-minute Apgar less than seven. AUTHORS' CONCLUSIONS: The included studies did not report on this review's main outcomes: preterm birth, small-for-gestational age, or perinatal death. There is limited evidence that incentives may increase utilization and quality of prenatal care, but may also increase cesarean rate. Overall, there is insufficient evidence to fully evaluate the impact of incentives on prenatal care initiation. There are conflicting data as to the impact of incentives on return for postpartum care. Two of the five studies which accounted for the majority of women in this review were conducted in rural, low-income, overwhelmingly Hispanic communities in Central America, thus limiting the external validity of these results.There is a need for high-quality RCTs to determine whether incentive program increase prenatal care use and improve maternal and neonatal outcomes. Incentive programs, in particular cash-based programs, as suggested in this review and in several observational studies may improve the frequency and ensure adequate quality of prenatal care. No peer-reviewed data have been made publicly available for one of the largest incentive-based prenatal programs - the statewide Medicaid-based programs within the United States. These observational data represent an important starting point for future research with significant implications for policy development and allocation of healthcare resources. The disparate findings related to attending postpartum care should also be further explored as the findings were limited by the number of studies. Future large RCTs are needed to focus on the outcomes of preterm birth, small-for-gestational age and perinatal outcomes

High-Resolution Nanoscale Solid-State Nuclear Magnetic Resonance Spectroscopy

We present a new method for high-resolution nanoscale magnetic resonance imaging (nano-MRI) that combines the high spin sensitivity of nanowire-based magnetic resonance detection with high spectral resolution nuclear magnetic resonance (NMR) spectroscopy. By applying NMR pulses designed using optimal control theory, we demonstrate a factor of $500$ reduction of the proton spin resonance linewidth in a $(50\text{-nm})^{\text{3}}$ volume of polystyrene and image proton spins in one dimension with a spatial resolution below $2~\text{nm}$.Comment: Main text: 8 pages, 6 figures; supplementary information: 10 pages, 10 figure

A magnetar engine for short GRBs and kilonovae

We investigate the influence of magnetic fields on the evolution of binary neutron-star (BNS) merger remnants via three-dimensional (3D) dynamical-spacetime general-relativistic (GR) magnetohydrodynamic (MHD) simulations. We evolve a postmerger remnant with an initial poloidal magnetic field, resolve the magnetoturbulence driven by shear flows, and include a microphysical finite-temperature equation of state (EOS). A neutrino leakage scheme that captures the overall energetics and lepton number exchange is also included. We find that turbulence induced by the magnetorotational instability (MRI) in the hypermassive neutron star (HMNS) amplifies magnetic field to beyond magnetar-strength ($10^{15}\, \mathrm{G}$). The ultra-strong toroidal field is able to launch a relativistic jet from the HMNS. We also find a magnetized wind that ejects neutron-rich material with a rate of $\dot{M}_{\mathrm{ej}} \simeq 1 \times10^{-1}\, \mathrm{M_{\odot}\, s^{-1}}$. The total ejecta mass in our simulation is $5\times 10^{-3}\, \mathrm{M_{\odot}}$. This makes the ejecta from the HMNS an important component in BNS mergers and a promising source of $r$-process elements that can power a kilonova. The jet from the HMNS reaches a terminal Lorentz factor of $\sim 5$ in our highest-resolution simulation. The formation of this jet is aided by neutrino-cooling preventing the accretion disk from protruding into the polar region. As neutrino pair-annihilation and radiative processes in the jet (which were not included in the simulations) will boost the Lorentz factor in the jet further, our simulations demonstrate that magnetars formed in BNS mergers are a viable engine for short gamma-ray bursts (sGRBs).Comment: Resubmitted versio