Women's experiences of over-the-counter and prescription medication during pregnancy in the UK: findings from survey free-text responses and narrative interviews

Objectives To explore women’s experiences of over-the-counter and prescription medication advice and use during pregnancy. Design A study design consisting of an online survey and nested in-depth interviews with a subsample of participants. We analysed data from survey free-text responses and in-depth interviews using thematic analysis. Quantitative survey data is published elsewhere. Setting The UK. Participants Women were eligible if living in the UK, aged 16–45 years, were pregnant or had been pregnant in the last 5 years regardless of pregnancy outcome. A total of 7090 women completed the survey, and 34 women who collectively had experienced 68 pregnancies were subsequently interviewed. Results Medication prescribing and use during pregnancy was common. The prescribing, dispensing and taking of some advised medications were restricted through women’s or prescribers’ fear of fetal harm. Lack of adherence to national prescribing guidance, conflicting professional opinion and poor communication resulted in maternal anxiety, avoidable morbidity and women negotiating complex and distressing pathways to obtain recommended medications. In contrast, some women felt overmedicated and that pharmacological treatments were used without exploring other options first. Conclusion Increased translation of national guidance into practice and greater personalisation of antenatal care are needed to improve the safety, efficacy and personalisation of prescribing in pregnancy

Disparities in the Use of assisted Reproductive Technologies after Breast Cancer: a Population-Based Study

PURPOSE: Equitable access to oncofertility services is a key component of cancer survivorship care, but factors affecting access and use remain understudied. METHODS: to describe disparities in assisted reproductive technology (ART) use among women with breast cancer in California, we conducted a population-based cohort study using linked oncology, ART, and demographic data. We identified women age 18-45 years diagnosed with invasive breast cancer between 2000 and 2015. The primary outcome was ART use-including oocyte/embryo cryopreservation or embryo transfer-after cancer diagnosis. We used log-binomial regression to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) to identify factors associated with ART use. RESULTS: Among 36,468 women with invasive breast cancer, 206 (0.56%) used ART. Women significantly less likely to use ART were age 36-45 years at diagnosis (vs. 18-35 years: PR = 0.17, 95% CI 0.13-0.22); non-Hispanic Black or Hispanic (vs. non-Hispanic White: PR = 0.31, 95% CI 0.21-0.46); had at least one child (vs. no children: adjusted PR [aPR] = 0.39, 95% CI 0.25-0.60); or lived in non-urban areas (vs. urban: aPR = 0.28, 95% CI 0.10-0.75), whereas women more likely to use ART lived in high-SES areas (vs. low-/middle-SES areas: aPR = 2.93, 95% CI 2.04-4.20) or had private insurance (vs. public/other insurance: aPR = 2.95, 95% CI 1.59-5.49). CONCLUSION: Women with breast cancer who are socially or economically disadvantaged, or who already had a child, are substantially less likely to use ART after diagnosis. The implementation of policies or programs targeting more equitable access to fertility services for women with cancer is warranted

Disparities in Fertility-Sparing Treatment and Use of assisted Reproductive Technology after a Diagnosis of Cervical, Ovarian, or Endometrial Cancer

OBJECTIVE: to assess the presence of sociodemographic and clinical disparities in fertility-sparing treatment and assisted reproductive technology (ART) use among patients with a history of cervical, endometrial, or ovarian cancer. METHODS: We conducted a population-based cohort study of patients aged 18-45 years who were diagnosed with cervical cancer (stage IA, IB), endometrial cancer (grade 1, stage IA, IB), or ovarian cancer (stage IA, IC) between January 1, 2000, and December 31, 2015, using linked data from the CCR (California Cancer Registry), the California Office of Statewide Health Planning and Development, and the Society for Assisted Reproductive Technology. The primary outcome was receipt of fertility-sparing treatment , defined as surgical or medical treatment to preserve the uterus and at least one ovary. The secondary outcome was fertility preservation , defined as ART use after cancer diagnosis. Multivariable logistic regression analysis was used to estimate odds ratios and 95% CIs for the association between fertility-sparing treatment and exposures of interest: age at diagnosis, race and ethnicity, health insurance, socioeconomic status, rurality, and parity. RESULTS: We identified 7,736 patients who were diagnosed with cervical, endometrial, or ovarian cancer with eligible histology. There were 850 (18.8%) fertility-sparing procedures among 4,521 cases of cervical cancer, 108 (7.2%) among 1,504 cases of endometrial cancer, and 741 (43.3%) among 1,711 cases of ovarian cancer. Analyses demonstrated nonuniform patterns of sociodemographic disparities by cancer type for fertility-sparing treatment, and ART. Fertility-sparing treatment was more likely among young patients, overall, and of those in racial and ethnic minority groups among survivors of cervical and ovarian cancer. Use of ART was low (n=52) and was associated with a non-Hispanic White race and ethnicity designation, being of younger age (18-35 years), and having private insurance. CONCLUSION: This study demonstrates that clinical and sociodemographic disparities exist in the receipt of fertility-sparing treatment and ART use among patients with a history of cervical, endometrial, or ovarian cancer

Prevalence and predictive value of ICD-11 post-traumatic stress disorder and Complex PTSD diagnoses in children and adolescents exposed to a single-event trauma.

BACKGROUND: The 11th edition of the International Classification of Diseases (ICD-11) made a number of significant changes to the diagnostic criteria for post-traumatic stress disorder (PTSD). We sought to determine the prevalence and 3-month predictive values of the new ICD-11 PTSD criteria relative to ICD-10 PTSD, in children and adolescents following a single traumatic event. ICD-11 also introduced a diagnosis of Complex PTSD (CPTSD), proposed to typically result from prolonged, chronic exposure to traumatic experiences, although the CPTSD diagnostic criteria do not require a repeated experience of trauma. We therefore explored whether children and adolescents demonstrate ICD-11 CPTSD features following exposure to a single-incident trauma. METHOD: Data were analysed from a prospective cohort study of youth aged 8-17 years who had attended an emergency department following a single trauma. Assessments of PTSD, CPTSD, depressive and anxiety symptoms were performed at two to four weeks (n = 226) and nine weeks (n = 208) post-trauma, allowing us to calculate and compare the prevalence and predictive value of ICD-10 and ICD-11 PTSD criteria, along with CPTSD. Predictive abilities of different diagnostic thresholds were undertaken using positive/negative predictive values, sensitivity/specificity statistics and logistic regressions. RESULTS: At Week 9, 15 participants (7%) were identified as experiencing ICD-11 PTSD, compared to 23 (11%) experiencing ICD-10 PTSD. There was no significant difference in comorbidity rates between ICD-10 and ICD-11 PTSD diagnoses. Ninety per cent of participants with ICD-11 PTSD also met criteria for at least one CPTSD feature. Five participants met full CPTSD criteria. CONCLUSIONS: Reduced prevalence of PTSD associated with the use of ICD-11 criteria is likely to reduce identification of PTSD relative to using ICD-10 criteria but not relative to DSM-4 and DSM-5 criteria. Diagnosis of CPTSD is likely to be infrequent following single-incident trauma

Trauma memory characteristics and neurocognitive performance in youth exposed to single-event trauma

Cognitive models of posttraumatic stress disorder (PTSD) highlight characteristics of trauma memories, such as disorganisation, as key mechanisms in the aetiology of the disorder. However, studies investigating trauma memory in youth have provided inconsistent findings. Research has highlighted that PTSD in youth may be accompanied by difficulties in neurocognitive functioning, potentially impacting ability to recall the trauma memory. The present study sought to investigate both trauma memory characteristics and neurocognitive functioning in youth aged 8–17 years. Youths exposed to single-event trauma, with (N = 29, Mage = 13.6, 21 female) and without (N = 40, Mage = 13.3, 21 female) a diagnosis of PTSD, completed self-report measures of trauma memory, a narrative memory task and a set of neurocognitive tests two to six months post-trauma. A group of non trauma-exposed youths (N = 36, Mage = 13.9, 27 female) were compared on narrative and neurocognitive tasks. Results indicated that trauma memories in youth with, versus without, PTSD were more sensory-laden, temporally disrupted, difficult to verbally access, and formed a more ‘central’ part of their identity. Greater differences were observed for self-reported memory characteristics compared to narrative characteristics. No between group differences in neurocognitive function were observed. Self-reported trauma memory characteristics highlight an important factor in the aetiology of PTSD. The observed lack of significant differences in neurocognitive ability potentially suggests that cognitive factors represent a more relevant treatment target than neurocognitive factors in single-event PTSD. Further research to understand the cognitive factors represented by self-reported trauma memory characteristics is recommended

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

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

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer’s disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer’s disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer’s disease and other tau-mediated neurodegenerative diseases