Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

A Rapid Response Mobile Application Improves First-Year Resident Clinical Performance During Simulated Care Events: A Randomized Controlled Trial.

BACKGROUND: Rapid response teams (RRTs) are critical to the timely and appropriate management of acutely decompensating patients. In the academic setting, the vital role of RRT leader is often filled by a junior resident physician who may lack the necessary medical knowledge and experience. Cognitive aids help improve guideline adherence and may support resident performance as they transition into leadership roles. OBJECTIVE: This study evaluated the impact of a rapid response mobile application on intern performance during simulated rapid response events. DESIGN: This randomized controlled trial compared the performance of interns in two simulated rapid response scenarios with and without access to the rapid response mobile application. The scenarios included anaphylaxis and supraventricular tachycardia (SVT). Simulations were video recorded and coded by trained raters. PARTICIPANTS: Interns in all specialties at our institution. MAIN MEASURES: Outcomes included (1) time to ordering critical medications (epinephrine and adenosine), (2) overall clinical performance using a checklist-based performance measure, and (3) usability of the mobile application. Enrollment and data collection occurred between November 2022 and February 2023. KEY RESULTS: Forty-four interns from 12 specialties were randomized to the intervention group (N = 22) and the control group (N = 22). Time to order critical medications was significantly reduced in the intervention group compared to control for anaphylaxis (P < 0.005) and SVT (P < 0.005). The intervention group had significantly higher performance scores compared to the control group for the anaphylaxis portion (P < 0.006). Usability scores for the rapid response toolkit were good. CONCLUSIONS: Access to a rapid response mobile application improved the quality of care administered by interns during two simulated rapid response scenarios as determined by a decrease in time to ordering critical medications and improved performance scores. The intervention group found the mobile application to be usable. This work adds to existing literature supporting the use of technology-based cognitive aids to improve patient care.

Adult-born neurons maintain hippocampal cholinergic inputs and support working memory during aging.

Adult neurogenesis is reduced during aging and impaired in disorders of stress, memory, and cognition though its normal function remains unclear. Moreover, a systems level understanding of how a small number of young hippocampal neurons could dramatically influence brain function is lacking. We examined whether adult neurogenesis sustains hippocampal connections cumulatively across the life span. Long-term suppression of neurogenesis as occurs during stress and aging resulted in an accelerated decline in hippocampal acetylcholine signaling and a slow and progressing emergence of profound working memory deficits. These deficits were accompanied by compensatory reorganization of cholinergic dentate gyrus inputs with increased cholinergic innervation to the ventral hippocampus and recruitment of ventrally projecting neurons by the dorsal projection. While increased cholinergic innervation was dysfunctional and corresponded to overall decreases in cholinergic levels and signaling, it could be recruited to correct the resulting memory dysfunction even in old animals. Our study demonstrates that hippocampal neurogenesis supports memory by maintaining the septohippocampal cholinergic circuit across the lifespan.  It also provides a systems level explanation for the progressive nature of memory deterioration during normal and pathological aging and indicates that the brain connectome is malleable by experience.

Blood pressure control in pregnant patients with chronic hypertension and diabetes: should <130/80 be the target?

BACKGROUND: The Chronic Hypertension and Pregnancy Study demonstrated that a target blood pressure of <140/90 mm Hg during pregnancy is associated with improved perinatal outcomes. Outside of pregnancy, pharmacologic therapy for patients with diabetes and hypertension is adjusted to a target blood pressure of <130/80 mm Hg. During pregnancy, patients with both diabetes and chronic hypertension may also benefit from tighter control with a target blood pressure <130/80 mm Hg. OBJECTIVE: We compared perinatal outcomes in patients with hypertension and diabetes who achieved blood pressure <130/80 vs 130 to 139/80 to 89 mm Hg. STUDY DESIGN: This was a secondary analysis of a multcenter randomized controlled trial. Participants were included in this secondary analysis if they had diabetes diagnosed prior to pregnancy or at <20 weeks of gestation and at least 2 recorded blood pressure measurements prior to delivery. Average systolic and diastolic blood pressure were calculated using ambulatory antenatal blood pressures. The primary composite outcome was preeclampsia with severe features, indicated preterm birth <35 weeks, or placental abruption. Secondary outcomes were components of the primary outcome, cesarean delivery, fetal or neonatal death, neonatal intensive care unit admission, and small for gestational age. Comparisons were made between those with an average systolic blood pressure <130 mm Hg and average diastolic blood pressure <80 mm Hg and those with an average systolic blood pressure 130 to 139 mm Hg or diastolic blood pressure 80 to 89 mm Hg using Student's t test and chi-squared tests. Multivariable log-binomial regression models were used to evaluate risk ratios between blood pressure groups for dichotomous outcomes while accounting for baseline covariates. RESULTS: Of 434 participants included, 150 (34.6%) had an average blood pressure less than 130/80 mm Hg. Participants with an average blood pressure less than 130/80 were more likely to be on antihypertensive medications at the start of pregnancy and more likely to have newly diagnosed diabetes mellitus prior to 20 weeks. Participants with an average blood pressure less than 130/80 mm Hg were less likely to have the primary adverse perinatal outcome (19.3% vs 46.5%, adjusted relative risk 0.43, 95% confidence interval 0.30-0.61, P<.01), with decreased risks specifically of preeclampsia with severe features (adjusted relative risk 0.35, 95% confidence interval 0.23-0.54) and indicated preterm birth prior to 35 weeks (adjusted relative risk 0.44, 95% confidence interval 0.24-0.79). The risk of neonatal intensive care unit admission was lower in the lower blood pressure group (adjusted relative risk 0.74, 95% confidence interval 0.59-0.94). No differences were noted in cesarean delivery (adjusted relative risk 1.04, 95% confidence interval 0.90-1.20), fetal or neonatal death (adjusted relative risk 0.59, 95% confidence interval 0.12-2.92). Small for gestational age less than the 10th percentile was lower in the lower blood pressure group (adjusted relative risk 0.37, 95% confidence interval 0.14-0.96). CONCLUSION: In those with chronic hypertension and diabetes prior to 20 weeks, achieving an average goal blood pressure of <130/80 mm Hg may be associated with improved perinatal outcomes.

Mate selection: A useful approach to maximize genetic gain and control inbreeding in genomic and conventional oil palm (Elaeis guineensis Jacq.) hybrid breeding.

Genomic selection (GS) is an effective method for the genetic improvement of complex traits in plants and animals. Optimization approaches could be used in conjunction with GS to further increase its efficiency and to limit inbreeding, which can increase faster with GS. Mate selection (MS) typically uses a metaheuristic optimization algorithm, simulated annealing, to optimize the selection of individuals and their matings. However, in species with long breeding cycles, this cannot be studied empirically. Here, we investigated this aspect with forward genetic simulations on a high-performance computing cluster and massively parallel computing, considering the oil palm hybrid breeding example. We compared MS and simple methods of inbreeding management (limitation of the number of individuals selected per family, prohibition of self-fertilization and combination of these two methods), in terms of parental inbreeding and genetic progress over four generations of genomic selection and phenotypic selection. The results showed that, compared to the conventional method without optimization, MS could lead to significant decreases in inbreeding and increases in annual genetic progress, with the magnitude of the effect depending on MS parameters and breeding scenarios. The optimal solution retained by MS differed by five breeding characteristics from the conventional solution: selected individuals covering a broader range of genetic values, fewer individuals selected per full-sib family, decreased percentage of selfings, selfings preferentially made on the best individuals and unbalanced number of crosses among selected individuals, with the better an individual, the higher the number of times he is mated. Stronger slowing-down in inbreeding could be achieved with other methods but they were associated with a decreased genetic progress. We recommend that breeders use MS, with preliminary analyses to identify the proper parameters to reach the goals of the breeding program in terms of inbreeding and genetic gain.

Screening of Triploid Banana Population Under Natural and Controlled Black Sigatoka Disease for Genomic Selection.

Black sigatoka disease (BSD) is the most important foliar threat in banana production, and breeding efforts against it should take advantage of genomic selection (GS), which has become one of the most explored tools to increase genetic gain, save time, and reduce selection costs. To evaluate the potential of GS in banana for BSD, 210 triploid accessions were obtained from the African Banana and Plantain Research Center to constitute a training population. The variability in the population was assessed at the phenotypic level using BSD- and agronomic-related traits and at the molecular level using single-nucleotide polymorphisms (SNPs). The analysis of variance showed a significant difference between accessions for almost all traits measured, although at the genomic group level, there was no significant difference for BSD-related traits. The index of non-spotted leaves among accessions ranged from 0.11 to 0.8. The accessions screening in controlled conditions confirmed the susceptibility of all genomic groups to BSD. The principal components analysis with phenotypic data revealed no clear diversity partition of the population. However, the structure analysis and the hierarchical clustering analysis with SNPs grouped the population into four clusters and two subpopulations, respectively. The field and laboratory screening of the banana GS training population confirmed that all genomic groups are susceptible to BSD but did not reveal any genetic structure, whereas SNP markers exhibited clear genetic structure and provided useful information in the perspective of applying GS.

Improving the accuracy of genomic predictions in an outcrossing species with hybrid cultivars between heterozygote parents: a case study of oil palm (Elaeis guineensis Jacq.).

Genomic selection (GS) is a method of marker-assisted selection revolutionizing crop improvement, but it can still be optimized. For hybrid breeding between heterozygote parents of different populations or species, specific aspects can be considered to increase GS accuracy: (1) training population genotyping, i.e., only genotyping the hybrid parents or also a sample of hybrid individuals, and (2) marker effects modeling, i.e., using population-specific effects of single nucleotide polymorphism alleles model (PSAM) or across-population SNP genotype model (ASGM). Here, this was investigated empirically for the prediction of the performances of oil palm hybrids for yield traits. The GS model was trained on 352 hybrid crosses and validated on 213 independent hybrid crosses. The training and validation hybrid parents and 399 training hybrid individuals were genotyping by sequencing. Despite the small proportion of hybrid individuals genotyped and low parental heterozygosity, GS prediction accuracy increased on average by 5% (range 1.4-31.3%, depending on trait and model) when training was done using genomic data on hybrids and parents compared with only parental genomic data. With ASGM, GS prediction accuracy increased on average by 3% (- 10.2 to 40%, depending on trait and genotyping strategy) compared with PSAM. We conclude that the best GS strategy for oil palm is to aggregate genomic data of parents and hybrid individuals and to ignore the parental origin of marker alleles (ASGM). To gain a better insight into these results, future studies should examine the respective effect of capturing genetic variability within crosses and taking segregation distortion into account when genotyping hybrid individuals, and investigate the factors controlling the relative performances of ASGM and PSAM in hybrid crops.

Towards an artificial human lung: modelling organ-like complexity to aid mechanistic understanding.

Respiratory diseases account for over 5 million deaths yearly and are a huge burden to healthcare systems worldwide. Murine models have been of paramount importance to decode human lung biology in vivo, but their genetic, anatomical, physiological and immunological differences with humans significantly hamper successful translation of research into clinical practice. Thus, to clearly understand human lung physiology, development, homeostasis and mechanistic dysregulation that may lead to disease, it is essential to develop models that accurately recreate the extraordinary complexity of the human pulmonary architecture and biology. Recent advances in micro-engineering technology and tissue engineering have allowed the development of more sophisticated models intending to bridge the gap between the native lung and its replicates in vitro Alongside advanced culture techniques, remarkable technological growth in downstream analyses has significantly increased the predictive power of human biology-based in vitro models by allowing capture and quantification of complex signals. Refined integrated multi-omics readouts could lead to an acceleration of the translational pipeline from in vitro experimental settings to drug development and clinical testing in the future. This review highlights the range and complexity of state-of-the-art lung models for different areas of the respiratory system, from nasal to large airways, small airways and alveoli, with consideration of various aspects of disease states and their potential applications, including pre-clinical drug testing. We explore how development of optimised physiologically relevant in vitro human lung models could accelerate the identification of novel therapeutics with increased potential to translate successfully from the bench to the patient's bedside.

Genomic selection in tropical perennial crops and plantation trees: a review.

To overcome the multiple challenges currently faced by agriculture, such as climate change and soil deterioration, more efficient plant breeding strategies are required. Genomic selection (GS) is crucial for the genetic improvement of quantitative traits, as it can increase selection intensity, shorten the generation interval, and improve selection accuracy for traits that are difficult to phenotype. Tropical perennial crops and plantation trees are of major economic importance and have consequently been the subject of many GS articles. In this review, we discuss the factors that affect GS accuracy (statistical models, linkage disequilibrium, information concerning markers, relatedness between training and target populations, the size of the training population, and trait heritability) and the genetic gain expected in these species. The impact of GS will be particularly strong in tropical perennial crops and plantation trees as they have long breeding cycles and constrained selection intensity. Future GS prospects are also discussed. High-throughput phenotyping will allow constructing of large training populations and implementing of phenomic selection. Optimized modeling is needed for longitudinal traits and multi-environment trials. The use of multi-omics, haploblocks, and structural variants will enable going beyond single-locus genotype data. Innovative statistical approaches, like artificial neural networks, are expected to efficiently handle the increasing amounts of heterogeneous multi-scale data. Targeted recombinations on sites identified from profiles of marker effects have the potential to further increase genetic gain. GS can also aid re-domestication and introgression breeding. Finally, GS consortia will play an important role in making the best of these opportunities. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01326-4.

A scoping review of the use of exercise-based upper extremity injury prevention programs for industrial workers.

STUDY DESIGN: This study is a scoping review. INTRODUCTION: Exercise-based upper extremity injury prevention programs are used by employers to reduce the cost of work-related injuries in the industrial work setting. PURPOSE OF THE STUDY: The purpose of the study was to identify, report, and evaluate all published literature that describes exercise-based upper extremity injury prevention programs used with an industrial workforce. METHODS: A systematic search of Medline, ProQuest, Pubmed, and Worldcat databases was performed. Data extracted included the type of outcome tool used, the outcome that was measured, the components of the exercise program, and the effectiveness toward reducing injury. RESULTS: 14 studies were included in the final analysis and summary. 12 articles included strengthening (85%) 10 included stretching (71%), 2 included health coaching (14%), and 2 included work simulation (14%). The most prevalent treatment approach was combined stretching and strengthening which accounted for 5 of the 14 studies, or 36%. The intervention period ranged from 4 weeks to 1 year and the program frequency ranged from before every work shift to weekly performance. There were 22 different outcome measures with health condition reported in 12 of 14 studies (86%) and function reported in 7 of 14 studies (50%). DISCUSSION AND CONCLUSIONS: Although many of the studies showed positive benefits to the exercise program, there is a wide variance in the current literature regarding the implementation, supervision, and exercise components of an upper extremity injury prevention program in an industrial work setting. Because there is no commonly-accepted exercise program, a conclusion regarding effectiveness cannot be generalized outside of the environment, supervision requirements, frequency, and duration in which the research was performed. There is a need for improved reporting techniques and a preferred program to be replicated across multiple work settings in order to allow generalizability of findings.

The Care of American Indian Children in North Carolina: Protecting Our Future and Our Heritage.

Native American children face many different challenges when it comes to their health. They are predisposed to an increased rate of diseases such as diabetes and asthma. Traditional medicine is still practiced in many Native communities. As health care professionals, we must be culturally sensitive to their needs. One way to improve Native health care is to increase the number of Native physicians practicing in their communities.

Proteomic Analysis of Azacitidine-Induced Degradation Profiles Identifies Multiple Chromatin and Epigenetic Regulators Including Uhrf1 and Dnmt1 as Sensitive to Azacitidine.

DNA methylation is a critical epigenetic modification that is established and maintained across the genome by DNA methyltransferase enzymes (Dnmts). Altered patterns of DNA methylation are a frequent occurrence in many tumor genomes, and inhibitors of Dnmts have become important epigenetic drugs. Azacitidine is a cytidine analog that is incorporated into DNA and induces the specific inhibition and proteasomal-mediated degradation of Dnmts. The downstream effects of azacitidine on CpG methylation and on gene transcription have been widely studied in many systems, but how azacitidine impacts the proteome is not well-understood. In addition, with its specific ability to induce the rapid degradation of Dnmts (in particular, the primary maintenance DNA methyltransferase, Dnmt1), it may be employed as a specific chemical knockdown for investigating the Dnmt1-associated functional or physical interactome. In this study, we use quantitative proteomics to analyze the degradation profile of proteins in the nuclear proteome of cells treated with azacitidine. We identify specific proteins as well as multiple pathways and processes that are impacted by azacitidine. The Dnmt1 interaction partner, Uhrf1, exhibits significant azacitidine-induced degradation, and this azacitidine-induced degradation is independent of the levels of Dnmt1 protein. We identify multiple other chromatin- and epigenetic-associated factors, including the bromodomain-containing transcriptional regulator, Brd2. We show that azacitidine induces highly specific perturbations of the Dnmt1-associated proteome, and while interaction partners such as Uhrf1 are sensitive to azacitidine, others such as the Dnmt1 interaction partner and stability regulator, Usp7, are not. In summary, we have conducted the first comprehensive proteomic analysis of the azacitidine-sensitive nuclear proteome, and we show how 5-azacitidine can be used as a specific probe to explore Dnmt- and chromatin-related protein networks.

Evaluation of resistance to cassava mosaic disease in selected African cassava cultivars using combined molecular and greenhouse grafting tools.

Cassava mosaic disease (CMD) threatens cassava (Manihot esculenta) production in Africa. A total of 24 selected cultivars were screened against CMD using combined molecular and greenhouse grafting tools. Disease severity was recorded for 10 weeks after inoculation and the molecular markers associated with CMD2 were detected by PCR. CMD severity significantly differed (P < 0.0001) among cultivars. Twelve cultivars were morphologically resistant and eight of these possessed CMD2 and four did not. These results suggest that there are several CMD-resistant cassava cultivars that could be recommended for on-farm production and for conservation and breeding programs.

Cultural Connection and Well-being for American Indian Adolescents.

American Indian and Alaska Native (AI/AN) adolescents face health disparities resulting from historical traumas. There is a paucity of research focusing on mental health in AI/AN adolescents or the relationship between cultural connection and health. This project assesses the relationship between cultural identity and markers of mental health and well-being for AI/AN adolescents. Adolescents 12 to 18 years old from the Lumbee Tribe of North Carolina participated in this mixed-methods study. Phase 1, discussed in this manuscript, involved surveys using validated instruments to assess cultural connection and markers of mental health and well-being. Characteristics of the 122 AI/AN youth who completed the survey included: mean age 14.9 years (SD = 2.0); 61% (n = 75) assigned female at birth; 56% (n = 70) identified as female; and 4.1% (n = 5) identified as non-binary. Mean tribal affiliation (TA) and ethnic identity (EI) scores suggest strong cultural connection (TA: M = 3.1/5, SD = 0.6; EI: M = 3.4/5, SD = 0.9). Sleep quality (M = 2.63/5) and positive stress management (M = 2.06/5) were low. Bivariate and logistic regression demonstrated moderate positive correlations between EI and friendship, EI and emotional support, TA and friendship, and TA and emotional support. AI/AN adolescents in this sample have a moderate-strong connection with Native culture, marked by ethnic identity and tribal affiliation, and positive markers of mental health and well-being. Data from this study may be used for policy formulation to promote increased funding and programming addressing mental health for AI/AN youth.

Concurrent progestogen and cerclage to reduce preterm birth: a multicenter international retrospective cohort.

BACKGROUND: Both progestogens and cerclage are individually effective in preterm birth prevention in high risk pregnancies. However, national and international guidelines cite a lack of data available to comment on the potential benefit of concurrent progestogen therapy after cerclage has been placed. Studies to date have been small with mixed results regarding benefit of concurrent progestogen with cerclage leaving uncertainty regarding best clinical practice. OBJECTIVE: This study aimed to evaluate whether cerclage with progestogen therapy was superior to cerclage alone in the prevention of spontaneous preterm birth in singleton pregnancies. METHODS: This is an international retrospective cohort study of singleton pregnancies, without major anomaly or aneuploidy, and with cerclage placed at 10 different institutions in the United States and Colombia from June 2016 to June 2020. Exclusion criteria were lack of documentation regarding whether progestogen was prescribed, unavailable delivery outcome, and pregnancy termination (spontaneous or induced) before 16 weeks' gestation. The exposure of interest was progestogen use with cerclage placement, which included those who continued to use progestogen or who started progestogen after cerclage. The comparison group consisted of those without progestogen use after cerclage placement, which included those who had no progestogen use during the entire pregnancy or who initiated progestogen and then stopped it after cerclage placement. Progestogen type, cerclage indication, maternal baseline characteristics, and maternal/neonatal outcomes were collected. The primary outcome was spontaneous preterm birth at <37 weeks. The secondary outcomes were spontaneous preterm birth at <34 weeks, gestational age at delivery, and a composite neonatal outcome including ≥1 of the following: perinatal mortality, confirmed sepsis, grade III or IV intraventricular hemorrhage, retinopathy of prematurity, respiratory distress syndrome, and bronchopulmonary dysplasia. There were planned subgroup analyses by cerclage indication, progestogen type (vaginal progesterone vs 17-hydroxyprogesterone caproate), preterm birth history, and site. Continuous variables were compared in adjusted analyses with analysis of covariance, and categorical variables were compared with multivariable logistic regression, adjusting for potential confounders with adjusted odds ratio. A Cox regression survival curve was generated to compare latency to spontaneous delivery, censored after 37 weeks. RESULTS: During the study period, a total of 699 singletons met the inclusion criteria: 561 in the progestogen with cerclage group and 138 with cerclage alone. Baseline characteristics were similar, except the higher likelihood of previous spontaneous preterm birth in the progestogen group (61% vs 41%; P<.001). Within the progestogen group, 52% were on 17-hydroxyprogesterone caproate weekly, 44% on vaginal progesterone daily, and 3% on oral progesterone daily. Progestogen with cerclage was associated with a significantly lower frequency of spontaneous preterm birth <37 weeks (31% vs 39%; adjusted odds ratio, 0.59 [0.39-0.89]; P=.01) and <34 weeks (19% vs 27%; adjusted odds ratio, 0.55 [0.35-0.87]; P=.01), increased latency to spontaneous delivery (hazard ratio for spontaneous preterm birth <37 weeks, 0.66 [0.49-0.90]; P=.009), and lower frequency of perinatal death (7% vs 16%; adjusted odds ratio, 0.37 [0.20-0.67]; P=.001). In planned subgroup analyses, association with reduced odds of preterm birth <37 weeks persisted in those on vaginal progesterone, those without a previous preterm birth, those with ultrasound- or examination-indicated cerclage, those who started progestogen therapy before cerclage, and in sites restricted to the United States. CONCLUSION: Use of progestogen with cerclage was associated with reduced rates of spontaneous preterm birth and early spontaneous preterm birth compared with cerclage alone. Although this study was not sufficiently powered for subgroup analysis, the strength of evidence for benefit appeared greatest for those with ultrasound- or examination-indicated cerclage, and with vaginal progesterone. El resumen está disponible en Español al final del artículo.

Spatial transcriptomic validation of a biomimetic model of fibrosis enables re-evaluation of a therapeutic antibody targeting LOXL2.

Matrix stiffening by lysyl oxidase-like 2 (LOXL2)-mediated collagen cross-linking is proposed as a core feedforward mechanism that promotes fibrogenesis. Failure in clinical trials of simtuzumab (the humanized version of AB0023, a monoclonal antibody against human LOXL2) suggested that targeting LOXL2 may not have disease relevance; however, target engagement was not directly evaluated. We compare the spatial transcriptome of active human lung fibrogenesis sites with different human cell culture models to identify a disease-relevant model. Within the selected model, we then evaluate AB0023, identifying that it does not inhibit collagen cross-linking or reduce tissue stiffness, nor does it inhibit LOXL2 catalytic activity. In contrast, it does potently inhibit angiogenesis consistent with an alternative, non-enzymatic mechanism of action. Thus, AB0023 is anti-angiogenic but does not inhibit LOXL2 catalytic activity, collagen cross-linking, or tissue stiffening. These findings have implications for the interpretation of the lack of efficacy of simtuzumab in clinical trials of fibrotic diseases.

Antihypertensive therapy and unplanned maternal postpartum health care utilization in patients with mild chronic hypertension.

OBJECTIVE: To test whether treatment of mild chronic hypertension (CHTN) in pregnancy is associated with lower rates of unplanned maternal healthcare utilization postpartum. METHODS: This was a secondary analysis of the CHTN and pregnancy (CHAP) study, a prospective, open-label, pragmatic, multicenter, randomized treatment trial of pregnant people with mild chronic hypertension. All patients with a postpartum follow-up assessment were included. The primary outcome was unplanned healthcare utilization, defined as unplanned postpartum clinic visits, Emergency Department or triage visits, or unplanned hospital admissions within six weeks postpartum. Differences in outcomes were compared between study groups (Active Group: blood pressure goal of<140/90 mm Hg, and Control Group: blood pressure goal of <160/105 mm Hg) and factors associated with outcomes were examined using logistic regression. RESULTS: A total of 2,293 patients were included with 1,157 (50.5%) in the active group and 1,136 (49.5%) in the control group. Rates of unplanned maternal postpartum health care utilization did not differ between treatment and control groups, (20.2% vs 23.3%, p=0.07, aOR 0.84, 95% CI 0.69-1.03. However, Emergency Department or triage/maternity evaluation unit visits were significantly lower in the Active group (10.2% vs 13.2%, p=0.03, aOR 0.76, 95% 0.58-0.99). Higher BMI at enrollment and cesarean delivery were associated with higher odds of unplanned postpartum healthcare utilization. CONCLUSION: While treatment of mild CHTN during pregnancy and postpartum was not significantly associated with overall unplanned healthcare resource utilization, it was associated with lower rates of postpartum Emergency Department and triage visits.

Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

Effects of Antihypertensive Therapy During Pregnancy on Postpartum Blood Pressure Control.

OBJECTIVE: To compare differences in postpartum blood pressure (BP) control (BP below 140/90 mm Hg) for participants with hypertension randomized to receive antihypertensive treatment compared with no treatment during pregnancy. METHODS: This study was a planned secondary analysis of a multicenter, open-label, randomized controlled trial (The CHAP [Chronic Hypertension and Pregnancy] trial). Pregnant participants with mild chronic hypertension (BP below 160/105 mm Hg) were randomized into two groups: active (antihypertensive treatment) or control (no treatment unless severe hypertension, BP 160/105 mm Hg or higher). Study outcomes were BP control below 140/90 mm Hg (primary) and medication nonadherence based on a composite score threshold (secondary) at the 6-week postpartum follow-up visit. Participants without follow-up BP measurements were excluded from analysis of the BP control outcome. Participants without health care professional-prescribed antihypertensives at delivery were excluded from the analysis of the adherence outcome. Multivariable logistic regression was used to adjust for potential confounders. RESULTS: Of 2,408 participants, 1,684 (864 active, 820 control) were included in the analysis. A greater percentage of participants in the active group achieved BP control (56.7% vs 51.5%; adjusted odds ratio [aOR] 1.22, 95% CI, 1.00-1.48) than in the control group. Postpartum antihypertensive prescription was higher in the active group (81.7% vs 58.4%, P <.001), and nonadherence did not differ significantly between groups (aOR 0.81, 95% CI, 0.64-1.03). CONCLUSION: Antihypertensive treatment of mild chronic hypertension during pregnancy was associated with better BP control below 140/90 mm Hg in the immediate postpartum period.

Optimal Timing of Delivery for Pregnant Individuals With Mild Chronic Hypertension.

OBJECTIVE: To investigate the optimal gestational age to deliver pregnant people with chronic hypertension to improve perinatal outcomes. METHODS: We conducted a planned secondary analysis of a randomized controlled trial of chronic hypertension treatment to different blood pressure goals. Participants with term, singleton gestations were included. Those with fetal anomalies and those with a diagnosis of preeclampsia before 37 weeks of gestation were excluded. The primary maternal composite outcome included death, serious morbidity (heart failure, stroke, encephalopathy, myocardial infarction, pulmonary edema, intensive care unit admission, intubation, renal failure), preeclampsia with severe features, hemorrhage requiring blood transfusion, or abruption. The primary neonatal outcome included fetal or neonatal death, respiratory support beyond oxygen mask, Apgar score less than 3 at 5 minutes, neonatal seizures, or suspected sepsis. Secondary outcomes included intrapartum cesarean birth, length of stay, neonatal intensive care unit admission, respiratory distress syndrome (RDS), transient tachypnea of the newborn, and hypoglycemia. Those with a planned delivery were compared with those expectantly managed at each gestational week. Adjusted odds ratios (aORs) with 95% CIs are reported. RESULTS: We included 1,417 participants with mild chronic hypertension; 305 (21.5%) with a new diagnosis in pregnancy and 1,112 (78.5%) with known preexisting hypertension. Groups differed by body mass index (BMI) and preexisting diabetes. In adjusted models, there was no association between planned delivery and the primary maternal or neonatal composite outcome in any gestational age week compared with expectant management. Planned delivery at 37 weeks of gestation was associated with RDS (7.9% vs 3.0%, aOR 2.70, 95% CI, 1.40-5.22), and planned delivery at 37 and 38 weeks was associated with neonatal hypoglycemia (19.4% vs 10.7%, aOR 1.97, 95% CI, 1.27-3.08 in week 37; 14.4% vs 7.7%, aOR 1.82, 95% CI, 1.06-3.10 in week 38). CONCLUSION: Planned delivery in the early-term period compared with expectant management was not associated with a reduction in adverse maternal outcomes. However, it was associated with increased odds of some neonatal complications. Delivery timing for individuals with mild chronic hypertension should weigh maternal and neonatal outcomes in each gestational week but may be optimized by delivery at 39 weeks.