An interactive website for informed contraception choice: randomised evaluation of Contraception Choices.

OBJECTIVE: Improving use of effective contraception to prevent unintended pregnancy is a global priority, but misperceptions and concerns about contraception are common. Our objective was to evaluate an interactive website to aid informed choice of contraception. METHODS: The Contraception Choices website is an interactive digital intervention which offers tailored advice to aid contraception decision-making (www.contraceptionchoices.org). In a parallel single-blind trial, we randomised 927 women aged 15-30 years from six clinic settings to access the intervention website (n = 464) or to a waiting-list control group (n = 463). The study was initially a feasibility trial, evolving into an evaluation of efficacy, with two primary outcomes at six months: long-acting reversible contraception (LARC) use, and satisfaction with contraceptive method. Secondary outcomes included self-reported pregnancy and sexually transmitted infection diagnoses. Free-text comments on the 3 and 6 month outcome surveys were analysed thematically. FINDINGS: There was no significant difference between intervention and control groups in the proportion of women using LARC [30.4% intervention versus 31.0% control; adjusted odds ratio 0.87 (95% confidence interval 0.60 to 1.28)]; satisfaction with contraceptive method [82.6% versus 82.1%; adjusted ordinal odds ratio 0.93 (95% CI 0.69 to 1.25)]; self-reported pregnancy [3.3% versus 4.1%; adjusted odds ratio 0.90 (95% CI 0.45 to 1.79)] nor sexually transmitted infection [5.3% versus 4.7%; adjusted odds ratio 0.72 (95% CI 0.55 to 2.36)]. Highly positive free-text comments from intervention participants indicated that the website facilitates contraception choice and can help women feel better prepared before consultation with healthcare providers. INTERPRETATION: The Contraception Choices website was popular for its design, trustworthy information and decision aids but it was not associated with significant differences in use of LARC or satisfaction with contraceptive method. An interactive website can aid contraception choice, but interventions that address factors beyond women's control, such as access to services, and partner, family or community influences are needed to complement this approach. RESEARCH IN CONTEXT: Preventing unintended pregnancy through effective use of contraception is essential for women's health, but choosing between different contraceptive methods can be challenging, and the opportunity for adequate discussion during routine consultations is often constrained. EVIDENCE BEFORE THIS STUDY: We conducted two systematic literature reviews: 1) Factors influencing contraception choice, uptake and use: a meta-synthesis of systematic reviews; and 2) Effectiveness of interactive digital interventions (IDI) for contraception choice, uptake and use. For the first review we searched PubMed, CDSR, Epistemonikos, DoPHER, DARE, NHS Economic Evaluation Database, Campbell Library, NIHR Health Technology Assessment, and Health Evidence Canada databases for systematic reviews which addressed contraceptive choice, uptake or use, from 2000 to 2017. PROSPERO registration number: CRD42017081521 https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=81521. We synthesised the findings of 18 systematic reviews of mostly moderate or high quality. They highlighted the importance of women's knowledge, beliefs, perceptions of side effects and health risks, as well as relationship status, social network, economic and healthcare factors on contraception choice and use. For the second review, we searched 23 electronic databases, trials registers and reference lists for randomised controlled trials of IDI for contraception, including CENTRAL, MEDLINE, EMBASE, CINAHL, ERIC, ASSIA and PsycINFO, from start date to June 2017. PROSPERO registration number: CRD42017081636. We found only five randomised trials of IDI, all from the USA. Risk of bias prevented synthesis of results. www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=81636. ADDED VALUE OF THIS STUDY: Women's common concerns about contraception - fear of hormones, weight gain, cancer, infertility, mood changes, breaks from contraception and changes in bleeding patterns - underpinned development of a new interactive website (www.contraceptionchoices.org). Contraception Choices addresses women's concerns through succinct text; Q and A format (Frequently Asked Questions, Did you Know?; videos of women and health professionals); an effectiveness infographic, and an interactive decision aid (What's right for me?).In an online randomised trial with 927 women attending clinics, we found no association of the Contraception Choices intervention with the primary outcomes - satisfaction with contraceptive method and uptake of long-acting reversible methods at 6 months. Nor did we find an association with secondary adverse outcomes - sexually transmitted infections or pregnancy. Comments from women indicated that the website can meet young women's need for information on the benefits and drawbacks of contraception, help them to make informed decisions, and feel better prepared before healthcare consultations. Contraception Choices is now available on the NHS website: www.nhs.uk/conditions/contraception/which-method-suits-me. IMPLICATIONS OF ALL THE AVAILABLE EVIDENCE: Interactive digital interventions (websites) can aid contraception choice, but other intervention research is needed to address wider influences on unintended pregnancy, including partner views, friends, family, the media, wider society and experiences with healthcare professionals. Future research could examine the impact of the website in different settings, e.g. schools or different countries. We hypothesise that use of the website during contraceptive consultations might improve the efficiency or quality of consultation, for both patients and healthcare providers. Appropriate methodology and time-scale for evaluating digital health interventions remains a key question

Masses, radii, and orbits of small Kepler planets : The transition from gaseous to rocky planets

We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R ⊕. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O).Peer reviewedFinal Accepted Versio

Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen.

Klebsiella pneumoniae is a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study of K. pneumoniae clinical isolates in hospital patients. Whole-genome sequence (WGS) data reveals a diverse pathogen population, including other species within the K. pneumoniae species complex (18%). Several infections were caused by K. variicola/K. pneumoniae hybrids, one of which shows evidence of nosocomial transmission. A wide range of antimicrobial resistance (AMR) phenotypes are observed, and diverse genetic mechanisms identified (mainly plasmid-borne genes). ESBLs are correlated with presence of other acquired AMR genes (median n = 10). Bacterial genomic features associated with nosocomial onset are ESBLs (OR 2.34, p = 0.015) and rhamnose-positive capsules (OR 3.12, p < 0.001). Virulence plasmid-encoded features (aerobactin, hypermucoidy) are observed at low-prevalence (<3%), mostly in community-onset cases. WGS-confirmed nosocomial transmission is implicated in just 10% of cases, but strongly associated with ESBLs (OR 21, p < 1 × 10-11). We estimate 28% risk of onward nosocomial transmission for ESBL-positive strains vs 1.7% for ESBL-negative strains. These data indicate that K. pneumoniae infections in hospitalised patients are due largely to opportunistic infections with diverse strains, with an additional burden from nosocomially-transmitted AMR strains and community-acquired hypervirulent strains

Defining the Effect of the 16p11.2 Duplication on Cognition, Behavior, and Medical Comorbidities

IMPORTANCE The 16p11.2 BP4-BP5 duplication is the copy number variant most frequently associated with autism spectrum disorder (ASD), schizophrenia, and comorbidities such as decreased body mass index (BMI). OBJECTIVES To characterize the effects of the 16p11.2 duplication on cognitive, behavioral, medical, and anthropometric traits and to understand the specificity of these effects by systematically comparing results in duplication carriers and reciprocal deletion carriers, who are also at risk for ASD. DESIGN, SETTING, AND PARTICIPANTS This international cohort study of 1006 study participants compared 270 duplication carriers with their 102 intrafamilial control individuals, 390 reciprocal deletion carriers, and 244 deletion controls from European and North American cohorts. Data were collected from August 1, 2010, to May 31, 2015 and analyzed from January 1 to August 14, 2015. Linear mixed models were used to estimate the effect of the duplication and deletion on clinical traits by comparison with noncarrier relatives. MAIN OUTCOMES AND MEASURES Findings on the Full-Scale IQ (FSIQ), Nonverbal IQ, and Verbal IQ; the presence of ASD or other DSM-IV diagnoses; BMI; head circumference; and medical data. RESULTS Among the 1006 study participants, the duplication was associated with a mean FSIQ score that was lower by 26.3 points between proband carriers and noncarrier relatives and a lower mean FSIQ score (16.2-11.4 points) in nonproband carriers. The mean overall effect of the deletion was similar (-22.1 points; P 100) compared with the deletion group (P < .001). Parental FSIQ predicted part of this variation (approximately 36.0% in hereditary probands). Although the frequency of ASD was similar in deletion and duplication proband carriers (16.0% and 20.0%, respectively), the FSIQ was significantly lower (by 26.3 points) in the duplication probands with ASD. There also were lower head circumference and BMI measurements among duplication carriers, which is consistent with the findings of previous studies. CONCLUSIONS AND RELEVANCE The mean effect of the duplication on cognition is similar to that of the reciprocal deletion, but the variance in the duplication is significantly higher, with severe and mild subgroups not observed with the deletion. These results suggest that additional genetic and familial factors contribute to this variability. Additional studies will be necessary to characterize the predictors of cognitive deficits

Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9

Abstract: Background: We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. Methods: Published and individual participant level data (300,000+ participants) were combined to construct a weighted PCSK9 gene-centric score (GS). Seventeen randomized placebo controlled PCSK9 inhibitor trials were included, providing data on 79,578 participants. Results were scaled to a one mmol/L lower LDL-C concentration. Results: The PCSK9 GS (comprising 4 SNPs) associations with plasma lipid and apolipoprotein levels were consistent in direction with treatment effects. The GS odds ratio (OR) for myocardial infarction (MI) was 0.53 (95% CI 0.42; 0.68), compared to a PCSK9 inhibitor effect of 0.90 (95% CI 0.86; 0.93). For ischemic stroke ORs were 0.84 (95% CI 0.57; 1.22) for the GS, compared to 0.85 (95% CI 0.78; 0.93) in the drug trials. ORs with type 2 diabetes mellitus (T2DM) were 1.29 (95% CI 1.11; 1.50) for the GS, as compared to 1.00 (95% CI 0.96; 1.04) for incident T2DM in PCSK9 inhibitor trials. No genetic associations were observed for cancer, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, or Alzheimer’s disease – outcomes for which large-scale trial data were unavailable. Conclusions: Genetic variation at the PCSK9 locus recapitulates the effects of therapeutic inhibition of PCSK9 on major blood lipid fractions and MI. While indicating an increased risk of T2DM, no other possible safety concerns were shown; although precision was moderate

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Masses, radii, and orbits of small Kepler planets: the transition from gaseous to rocky planets

We report on the masses, sizes, and orbits of the planets orbiting 22 Kepler stars. There are 49 planet candidates around these stars, including 42 detected through transits and 7 revealed by precise Doppler measurements of the host stars. Based on an analysis of the Kepler brightness measurements, along with high-resolution imaging and spectroscopy, Doppler spectroscopy, and (for 11 stars) asteroseismology, we establish low false-positive probabilities (FPPs) for all of the transiting planets (41 of 42 have an FPP under 1%), and we constrain their sizes and masses. Most of the transiting planets are smaller than three times the size of Earth. For 16 planets, the Doppler signal was securely detected, providing a direct measurement of the planet's mass. For the other 26 planets we provide either marginal mass measurements or upper limits to their masses and densities; in many cases we can rule out a rocky composition. We identify six planets with densities above 5 g cm-3, suggesting a mostly rocky interior for them. Indeed, the only planets that are compatible with a purely rocky composition are smaller than 2 R ⊕. Larger planets evidently contain a larger fraction of low-density material (H, He, and H2O)