Among women initiating new prescription contraception, we investigated the relationship between recent depression and a range of contraceptive behaviors.
We used medical and pharmacy records of ...52,325 women ages 19 to 29 who initiated prescription contraception (pills, patches or rings, injectables, and long-acting reversible contraceptives) in 2014−2016 at a large integrated healthcare system in Northern California. Women had continuous enrollment for a year before and after initiating, and no records of prescription contraceptive use in the year before initiating. Depression in the year prior to initiation was dichotomized into (1) no depression indicator (reference group) or (2) depression diagnosis or redeemed antidepressant. Multinomial logistic regression models examined the associations between depression and method type initiated, and contraceptive patterns, timing of discontinuation, inconsistent use, and switching methods over a year after initiating, adjusting for sociodemographics and testing for interactions between depression and having a recent birth or abortion.
Women with recent depression were more likely to initiate methods other than the pill, and the association was stronger for patches or rings vs pills among those with a recent birth compared to those without. Among women initiating all methods and the pill, those with depression were more likely to discontinue their method, use it inconsistently, and switch from it than use it continuously for a year.
Women with recent depression were less likely to initiate the pill; and when the pill was initiated, those with depression were more likely to discontinue use, use it inconsistently, and switch from it.
Women with recent depression indicators should be followed closely to ensure they have the support they need to meet their reproductive goals. Those who wish to avoid pregnancy may benefit from methods that do not require daily use.
Abstract Background A humanitarian crisis associated with the mass movement of refugees across Europe has been occurring since 2014. The county of Kent, located in the south east of England and ...containing the port Dover, has seen large increases in arrivals of unaccompanied children. We aimed to carry out a structured assessment of their health needs. Methods In accordance with the Children's Act 1989 and 2004, looked-after children, including unaccompanied children, should be offered an initial health assessment to identify their needs. We analysed the results of 154 initial health assessments of unaccompanied children arriving in Kent in 2015. Although selection of the assessments was opportunistic, the sample was broadly representative of the wider cohort of unaccompanied children in Kent. The need for interventions such as immunisation and screening was reviewed. Findings 989 unaccompanied young people entered Kent in 2015. Median age of the 154 children given an initial health assessment was 16 years (IQR 15·9–17·2); 145 (94%) were boys. The most common country of origin was Eritrea (62 children, 41%), followed by Afghanistan (24, 16%) and Syria (20, 13%). Psychological symptoms were reported in 63 children (41%), including symptoms of post-traumatic stress disorder (24, 16%). Dental disease (eg, decay and caries) was reported in 60 (46%) of 130 children examined. Dermatology signs, including fungal infection, scabies, and scars, were seen in 26 children (17%). Most symptoms reported were easily treatable, although symptoms of acute infection were recorded in a small number of children. Almost all the 989 unaccompanied young people needed catch-up immunisation. All of them came from countries with a moderate to high prevalence of chronic hepatitis B infection, and 700 children (71%) met WHO criteria for tuberculosis screening. Interpretation The key health needs identified were psychological symptoms (particularly of post-traumatic stress disorder), dental health, and dermatology complaints. Although physical complaints were common, most were non-acute and could be managed in the community. Infectious disease is an important issue in this cohort, which can be managed through simple, preventive measures such as immunisation and screening. Funding None.
Rare genetic variants cause pulmonary arterial hypertension, but the contribution of common genetic variation to disease risk and natural history is poorly characterised. We tested for genome-wide ...association for pulmonary arterial hypertension in large international cohorts and assessed the contribution of associated regions to outcomes.
We did two separate genome-wide association studies (GWAS) and a meta-analysis of pulmonary arterial hypertension. These GWAS used data from four international case-control studies across 11 744 individuals with European ancestry (including 2085 patients). One GWAS used genotypes from 5895 whole-genome sequences and the other GWAS used genotyping array data from an additional 5849 individuals. Cross-validation of loci reaching genome-wide significance was sought by meta-analysis. Conditional analysis corrected for the most significant variants at each locus was used to resolve signals for multiple associations. We functionally annotated associated variants and tested associations with duration of survival. All-cause mortality was the primary endpoint in survival analyses.
A locus near SOX17 (rs10103692, odds ratio 1·80 95% CI 1·55–2·08, p=5·13 × 10–15) and a second locus in HLA-DPA1 and HLA-DPB1 (collectively referred to as HLA-DPA1/DPB1 here; rs2856830, 1·56 1·42–1·71, p=7·65 × 10–20) within the class II MHC region were associated with pulmonary arterial hypertension. The SOX17 locus had two independent signals associated with pulmonary arterial hypertension (rs13266183, 1·36 1·25–1·48, p=1·69 × 10–12; and rs10103692). Functional and epigenomic data indicate that the risk variants near SOX17 alter gene regulation via an enhancer active in endothelial cells. Pulmonary arterial hypertension risk variants determined haplotype-specific enhancer activity, and CRISPR-mediated inhibition of the enhancer reduced SOX17 expression. The HLA-DPA1/DPB1 rs2856830 genotype was strongly associated with survival. Median survival from diagnosis in patients with pulmonary arterial hypertension with the C/C homozygous genotype was double (13·50 years 95% CI 12·07 to >13·50) that of those with the T/T genotype (6·97 years 6·02–8·05), despite similar baseline disease severity.
This is the first study to report that common genetic variation at loci in an enhancer near SOX17 and in HLA-DPA1/DPB1 is associated with pulmonary arterial hypertension. Impairment of SOX17 function might be more common in pulmonary arterial hypertension than suggested by rare mutations in SOX17. Further studies are needed to confirm the association between HLA typing or rs2856830 genotyping and survival, and to determine whether HLA typing or rs2856830 genotyping improves risk stratification in clinical practice or trials.
UK NIHR, BHF, UK MRC, Dinosaur Trust, NIH/NHLBI, ERS, EMBO, Wellcome Trust, EU, AHA, ACClinPharm, Netherlands CVRI, Dutch Heart Foundation, Dutch Federation of UMC, Netherlands OHRD and RNAS, German DFG, German BMBF, APH Paris, INSERM, Université Paris-Sud, and French ANR.
•IRIS contains one of the largest biorepositories from a cervical cancer screening program.•Embedded in the clinical laboratory, the research team selected and processed specimens for long-term ...storage.•Over 415,000 specimens were collected from 77,920 women in an integrated healthcare system.•During 5 years of follow-up, 74% of women had at least one follow-up screening test.•IRIS was facilitated by opt-out consent and access to clinical outcomes in the electronic health record.
: Biomarkers of Human Papillomavirus (HPV) cervical carcinogenesis are critical to address questions of how to triage and manage women who screen positive for high-risk HPV (HrHPV) and identify those at highest cancer risk.
: We describe the development of a large biorepository of cervical specimens for the Improving Risk Informed HPV Screening Study (IRIS) using residual specimens collected in the regional laboratory from women aged 25 and older who had cervical cancer screening or follow-up testing with high-risk human papillomavirus (HrHPV) testing and liquid-based cytology (co-testing) at Kaiser Permanente Northern California (KPNC) from January 2016 to August 2018. Specimen selection, processing for long-term storage, follow-up tracking, consent and demographic and clinical characteristics of the women in the IRIS cohort are described.
: Selecting from 897,680 women who had at least one co-test during the study period, we collected 199,403 baseline and 216,390 follow-up HrHPV and cytology specimens from a stratified random sample of 81,348 women, of which 3,428 (4.2%) opted out of the study and were excluded. The majority (79.9%) of the baseline specimens were from HrHPV-positive women. The mean age was 36 years, and the cohort is racially/ethnically diverse with 56% of women being Hispanic or non-white. Over two-thirds of the cohort were members of KPNC for two or more years prior to inclusion. Of the 77,920 women included in the cohort, 57,414 (73.7%) had at least one follow-up co-test.
: Use of specimens from the biorepository will elucidate molecular mechanisms underlying HPV carcinogenesis and inform more effective screening and follow-up strategies.
Background
The timing of hospital admission for women with spontaneous labor onset and the criteria used to assess active labor progress and diagnose labor dystocia may significantly influence ...women's risk for primary cesarean birth. Our aims were to assess associations of labor status at admission (i.e., preactive or active) and active labor progress (i.e., dystocic or physiologic) with oxytocin augmentation, cesarean birth, and adverse neonatal outcome rates.
Methods
A sample of low‐risk, nulliparous women admitted to hospitals for spontaneous labor onset was extracted from the Consortium on Safe Labor (n = 27 077). Binomial logistic regression was used to assess associations between labor classifications and outcomes.
Results
At admission, 68.0% of women were in preactive labor and 32.0% were in active labor. Cesarean rates for these groups were 18.0% and 7.2%, respectively (adjusted odds ratio AOR 2.69; 95% CI 2.45‐2.96). Oxytocin augmentation and adverse neonatal outcomes were more likely for women admitted in preactive labor. Among women admitted in active labor, 9.3% experienced labor dystocia and 90.7% progressed physiologically. Cesarean rates for these groups were 20.4% and 5.9%, respectively (AOR 3.02; 95% CI 2.45‐3.73). Nearly half of the cesareans performed for dystocia among women admitted in active labor occurred when cervical dilation was physiologic. Oxytocin augmentation and adverse neonatal outcomes were more likely when active labor was dystocic.
Conclusions
Adoption of evidence‐based, standardized approaches for diagnosing active labor onset, assessing labor progress, and diagnosing dystocia may safely decrease oxytocin augmentation and cesarean birth rates in the United States.
A superconducting transition-edge sensor (TES) microcalorimeter is an ideal X-ray detector for experiments at accelerator facilities because of good energy resolution and high efficiency. To study ...the performance of the TES detector with a high-intensity pulsed charged-particle beam, we measured X-ray spectra with a pulsed muon beam at the Japan Proton Accelerator Research Complex (J-PARC) in Japan. We found substantial temporal shifts of the X-ray energy correlated with the arrival time of the pulsed muon beam, which was reasonably explained by pulse pileup due to the incidence of energetic particles from the initial pulsed beam.
Abstract
Objective
In response to COVID-19, the informatics community united to aggregate as much clinical data as possible to characterize this new disease and reduce its impact through ...collaborative analytics. The National COVID Cohort Collaborative (N3C) is now the largest publicly available HIPAA limited dataset in US history with over 6.4 million patients and is a testament to a partnership of over 100 organizations.
Materials and Methods
We developed a pipeline for ingesting, harmonizing, and centralizing data from 56 contributing data partners using 4 federated Common Data Models. N3C data quality (DQ) review involves both automated and manual procedures. In the process, several DQ heuristics were discovered in our centralized context, both within the pipeline and during downstream project-based analysis. Feedback to the sites led to many local and centralized DQ improvements.
Results
Beyond well-recognized DQ findings, we discovered 15 heuristics relating to source Common Data Model conformance, demographics, COVID tests, conditions, encounters, measurements, observations, coding completeness, and fitness for use. Of 56 sites, 37 sites (66%) demonstrated issues through these heuristics. These 37 sites demonstrated improvement after receiving feedback.
Discussion
We encountered site-to-site differences in DQ which would have been challenging to discover using federated checks alone. We have demonstrated that centralized DQ benchmarking reveals unique opportunities for DQ improvement that will support improved research analytics locally and in aggregate.
Conclusion
By combining rapid, continual assessment of DQ with a large volume of multisite data, it is possible to support more nuanced scientific questions with the scale and rigor that they require.
Kwon DH, Bennett W, Herberg S, Bastone P, Pippig S, Rodriguez NA, Susin C, Wikesjö UME. Evaluation of an injectable rhGDF‐5/PLGA construct for minimally invasive periodontal regenerative procedures: ...a histological study in the dog. J Clin Periodontol 2010; 37: 390–397. doi: 10.1111/j.1600‐051X.2010.01546.x.
Aim: To evaluate the injectability, biocompatibility, safety, and periodontal wound healing/regeneration following application of a novel bioresorbable recombinant human growth/differentiation factor‐5 (rhGDF‐5)/poly(lactic‐co‐glycolic acid) (PLGA) construct.
Material and Methods: Periodontal pockets (3 × 6 mm, width × depth) were surgically created over the buccal roots of the second and fourth mandibular pre‐molars in eight adult Hound Labrador mongrel dogs. Surgeries including injection of the rhGDF‐5/PLGA construct into the pockets were sequenced that four animals provided 2‐/4‐week and four animals 6‐/8‐week observations of sites receiving rhGDF‐5/PLGA or serving as sham‐surgery control.
Results: The rhGDF‐5/PLGA construct was easy to prepare and apply. Approximately 0.2 ml (93 μg rhGDF‐5)/tooth was used. Clinical and radiographic healing was exemplary without adverse events. Healing was characterized by a non‐specific connective tissue attachment, acellular/cellular cementum, periodontal ligament (PDL), bone regeneration, and a junctional epithelium. PLGA fragments were observed in 4/7, 2/8, and 1/8 sites at 2, 4, and 6 weeks, respectively. Associated inflammatory reactions exhibited no limiting effect on periodontal wound healing/regeneration. Root resorption/ankylosis was not observed. Bone formation showed apparent increased maturity (lamellar bone) at 6 weeks in sites receiving rhGDF‐5/PLGA compared with the control. Both protocols exhibited significant increases in PDL, cementum, and bone regeneration over time, without significant differences between treatments. In time, PDL and cementum regeneration was twofold greater for the control at 4 weeks (p=0.04) while increased bone formation was observed at sites receiving rhGDF‐5/PLGA (p<0.01).
Conclusions: In conclusion, the rhGDF‐5/PLGA construct appears to be a safe technology for injectable, ease‐of‐use application of rhGDF‐5‐stimulated periodontal wound healing/regeneration. Additional work to optimize the polymer carrier and rhGDF‐5 release kinetics/dose might be required before evaluating the efficacy of this technology in clinical settings using minimally invasive approaches.
Arrays of superconducting transition-edge sensor (TES) microcalorimeters are attractive for some X-ray experiments where the combination of higher collection efficiency than crystal spectrometers and ...much better energy resolution than semiconductor detectors is enabling. For hard X-ray (>2 keV) applications, a TES is often integrated with an extra absorber to extend its dynamic range, quantum efficiency and collecting area. For >100 keV applications, millimeter size absorbers have been manually attached to TES pixels after fabrication. At lower energies, the absorber size needs to be much smaller, because a large heat capacity degrades energy resolution. In that case, the absorber is directly electroplated or evaporated on the TES during the fabrication process. In this work, we present TES microcalorimeters optimized for the intermediate hard X-ray energy region (20 keV ~ 100 keV) that have thick absorbers directly deposited during the TES fabrication process. This microcalorimeter is designed to measure high-resolution muonic atom transition X-ray spectra as a method to study quantum electrodynamics (QED) effects. The absorber is comprised of evaporated gold and electroplated bismuth layers and is designed to optimize dynamic range, collecting efficiency, and energy resolution in the 20 keV to 45 keV energy range. A prototype with pure gold absorbers has been fabricated and characterized, in order to obtain a first experimental reference in the detector development process.
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