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We hypothesized that the incubation for urethral gonorrhoea would be longer for men with oropharyngeal gonorrhoea than those without oropharyngeal gonorrhoea. We conducted a chart review of men who have sex with men with urethral gonorrhoea symptoms at a sexual health clinic between 2019 and 2021. The incubation period was defined as the number of days between men’s last sexual contact and onset of symptoms. We used a Mann–Whitney U test to compare differences in the median incubation for urethral gonorrhoea between men with and men without oropharyngeal gonorrhoea. There were 338 men with urethral symptoms (median age = 32 years; IQR: 28–39), and of these, 307 (90.1%) were tested for oropharyngeal gonorrhoea, of whom 124 (40.4%, 95% CI: 34.9–46.1) men had oropharyngeal and urethral gonorrhoea. We analyzed incubation data available for 190 (61.9%) of the 307 men, with 38.9% (74/190) testing positive for oropharyngeal gonorrhoea. The incubation for urethral gonorrhoea did not differ between 74 men (39%) with oropharyngeal gonorrhoea (median = 4 days; IQR: 2–6) and 116 men (61%) without oropharyngeal gonorrhoea (median = 2.5 days; IQR: 1–5) (p = 0.092). Research is needed to investigate gonorrhoea transmission from the oropharynx to the urethra.
A look back review of South Kerry Child and Adolescent Mental Health Services (CAMHS) in Ireland, known as the ‘Maskey report’ (MR), highlighted substandard prescribing practices. The aim of this ‘Maskey Impact Study’ (MIS) was to explore changes to child and adolescent psychiatrists’ prescribing practices following the MR.
Method:
The study was cross-sectional and mixed method. A study specific questionnaire was distributed electronically to psychiatrists working in CAMHS (n = 160).
Results:
102 psychiatrists participated in the study (response rate 63.8%). Perceived improvement in prescribing practices included improved medical record keeping (63.7%), consent documentation (53.9%), medication information provision (41.2%) and physical health monitoring (60.8%). However, 43.1% of psychiatrists reported a reluctance to prescribe medication even when clinically indicated and 50% were more likely to avoid off-label use. Most respondents reported increased stress levels (80.4%) with higher stress being significantly associated with reticence in prescribing (χ2 = 11.746, p < .001) and avoiding off-label use (χ2 = 15.392, p < 0.001). Thematic analysis highlighted increased medication hesitancy, enforced ‘meaningless’ bureaucracy and medication mistrust among families.
Discussion:
Although improvements reported are welcomed, the increased hesitancy of medication use, avoidance of prescribing more than one medication, and avoidance of off-label use, is of concern with potential unintended adverse consequences. Reluctance in prescribing may deprive youth of access to evidence-based treatments and limit exposure of NCHDs to the safe practice of consultant-initiated psychopharmacology. Further research will be important to determine if this impacts clinical care. Continued education in psychopharmacology is essential along with increased public awareness of the evidence for medication, to help restore public confidence and trust in psychopharmacology.
Inductively coupled plasma atomic emission spectrometry (ICP-AES) was used to study element ions in whole bodies of uninfected Biomphalaria glabrata snails and those experimentally infected with larval Schistosoma mansoni trematodes. Infected snails were analysed 8 weeks post-infection. Cohort snails that were left uninfected were analysed at the same time as the infected snails. Sixteen elements (aluminum, boron, barium, calcium, cadmium, copper, iron, potassium, magnesium, manganese, sodium, nickel, lead, selenium, tin and zinc) were found to be present in infected and uninfected whole bodies at concentrations above the detection limit of the ICP-AES analysis. Of these, calcium, cadmium, manganese and sodium were present in significantly higher amounts (Student's t-test, P<0.05) in whole infected versus whole uninfected snails. Variations in the present results compared with other studies reflect intrinsic differences in the larval trematode–snail systems used.
Screen time in infancy is linked to changes in social-emotional development but the pathway underlying this association remains unknown. We aim to provide mechanistic insights into this association using brain network topology and to examine the potential role of parent–child reading in mitigating the effects of screen time.
Methods
We examined the association of screen time on brain network topology using linear regression analysis and tested if the network topology mediated the association between screen time and later socio-emotional competence. Lastly, we tested if parent–child reading time was a moderator of the link between screen time and brain network topology.
Results
Infant screen time was significantly associated with the emotion processing-cognitive control network integration (p = 0.005). This network integration also significantly mediated the association between screen time and both measures of socio-emotional competence (BRIEF-2 Emotion Regulation Index, p = 0.04; SEARS total score, p = 0.04). Parent–child reading time significantly moderated the association between screen time and emotion processing-cognitive control network integration (β = −0.640, p = 0.005).
Conclusion
Our study identified emotion processing-cognitive control network integration as a plausible biological pathway linking screen time in infancy and later socio-emotional competence. We also provided novel evidence for the role of parent–child reading in moderating the association between screen time and topological brain restructuring in early childhood.
RadioTalk is a communication platform that enabled members of the Radio Galaxy Zoo (RGZ) citizen science project to engage in discussion threads and provide further descriptions of the radio subjects they were observing in the form of tags and comments. It contains a wealth of auxiliary information which is useful for the morphology identification of complex and extended radio sources. In this paper, we present this new dataset, and for the first time in radio astronomy, we combine text and images to automatically classify radio galaxies using a multi-modal learning approach. We found incorporating text features improved classification performance which demonstrates that text annotations are rare but valuable sources of information for classifying astronomical sources, and suggests the importance of exploiting multi-modal information in future citizen science projects. We also discovered over 10000 new radio sources beyond the RGZ-DR1 catalogue in this dataset.
Clinical trials provide the “gold standard” evidence for advancing the practice of medicine, even as they evolve to integrate real-world data sources. Modern clinical trials are increasingly incorporating real-world data sources – data not intended for research and often collected in free-living contexts. We refer to trials that incorporate real-world data sources as real-world trials. Such trials may have the potential to enhance the generalizability of findings, facilitate pragmatic study designs, and evaluate real-world effectiveness. However, key differences in the design, conduct, and implementation of real-world vs traditional trials have ramifications in data management that can threaten their desired rigor.
Methods:
Three examples of real-world trials that leverage different types of data sources – wearables, medical devices, and electronic health records are described. Key insights applicable to all three trials in their relationship to Data and Safety Monitoring Boards (DSMBs) are derived.
Results:
Insight and recommendations are given on four topic areas: A. Charge of the DSMB; B. Composition of the DSMB; C. Pre-launch Activities; and D. Post-launch Activities. We recommend stronger and additional focus on data integrity.
Conclusions:
Clinical trials can benefit from incorporating real-world data sources, potentially increasing the generalizability of findings and overall trial scale and efficiency. The data, however, present a level of informatic complexity that relies heavily on a robust data science infrastructure. The nature of monitoring the data and safety must evolve to adapt to new trial scenarios to protect the rigor of clinical trials.
Growth patterns of breastfed infants show substantial inter-individual differences, partly influenced by breast milk (BM) nutritional composition. However, BM nutritional composition does not accurately indicate BM nutrient intakes. This study aimed to examine the associations between both BM intake volumes and macronutrient intakes with infant growth. Mother–infant dyads (n 94) were recruited into the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) from a single maternity hospital at birth; all infants received exclusive breast-feeding (EBF) for at least 6 weeks. Infant weight, length and skinfolds thicknesses (adiposity) were repeatedly measured from birth to 12 months. Post-feed BM samples were collected at 6 weeks to measure TAG (fat), lactose (carbohydrate) (both by 1H-NMR) and protein concentrations (Dumas method). BM intake volume was estimated from seventy infants between 4 and 6 weeks using dose-to-the-mother deuterium oxide (2H2O) turnover. In the full cohort and among sixty infants who received EBF for 3+ months, higher BM intake at 6 weeks was associated with initial faster growth between 0 and 6 weeks (β + se 3·58 + 0·47 for weight and 4·53 + 0·6 for adiposity gains, both P < 0·0001) but subsequent slower growth between 3 and 12 months (β + se − 2·27 + 0·7 for weight and −2·65 + 0·69 for adiposity gains, both P < 0·005). BM carbohydrate and protein intakes at 4–6 weeks were positively associated with early (0–6 weeks) but tended to be negatively related with later (3–12 months) adiposity gains, while BM fat intake showed no association, suggesting that carbohydrate and protein intakes may have more functional relevance to later infant growth and adiposity.
Background: Phase 3 PREEMPT established safety and efficacy of 155-195U onabotulinumtoxinA in adults with chronic migraine (CM). This analysis of the PREDICT study (NCT02502123) evaluates real-world effectiveness and safety of 155U, 156-195U and 195U-onabotulinumtoxinA in CM. Methods: Patients received onabotulinumtoxinA approximately every 12-weeks (≤7 treatment cycles [Tx]) per Canadian product monograph). Primary endpoint was mean change from baseline in Migraine-Specific Quality of Life (MSQ) at Tx4. Headache days, physician and patient satisfaction were evaluated. Analysis stratified safety population (≥1 onabotulinumtoxin A dose) into 3 groups (155U,156-195U,195U) by dose received on ≥3 of the first 4 Tx. Results: 184 patients received ≥1 onabotulinumtoxin A dose (155U, n=68; 156-195U, n=156; 195U, n=13 on ≥3 Tx). Headache days decreased over time compared to baseline (Tx4: -7.1[6.7] 155U; -6.5[6.7] 156-195U; -11.2[6.4] 195U). Physicians rated most patients as improved, and majority of patients were satisfied at final visit (80.8% 155U; 83.6% 156-195U; 90% 195U). Treatment-emergent adverse events (TEAEs) were reported in 18/68(26.5%) patients in 155U-group, 41/65(63.1%) in 156-195U-group and 10/13(76.9%) in 195U-group; treatment-related TEAEs were 9(13.2%), 10(15.4%) and 3(23.1%) respectively; serious TEAEs were 0, 3(4.6%) and 1(7.7%), none treatment-related. Conclusions: Long-term treatment with 155U, 156-195U, and 195U-onabotulinumtoxinA in PREDICT was safe and effective CM treatment. No new safety signals were identified.
PREDICT was a Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA treatment for chronic migraine (CM). We descriptively assess health resource utilization, work productivity, and acute medication use.
Methods:
OnabotulinumtoxinA (155–195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Participants completed a 4-item health resource utilization questionnaire and 6-item Work Productivity and Activity Impairment Questionnaire: Specific Health Problem V2.0. Acute medication use was recorded in daily headache diaries. Treatment-emergent adverse events were recorded throughout the study.
Results:
A total of 197 participants were enrolled, and 184 received ≥1 treatment with onabotulinumtoxinA and were included in the analysis. Between baseline and the final visit, there were decreases in the percentage of participants who reported headache-related healthcare professional visit(s) (96.2% to 76.8%) and those who received headache-related diagnostic testing (37.5% to 9.9%). Reductions from baseline were also observed in the mean number of headache-related visits to an emergency room/urgent care clinic (2.5 to 1.4) and median headache-related hospital admissions (4.0 to 1.0). OnabotulinumtoxinA improved work productivity and reduced the mean (standard deviation) number of hours missed from work over a 7-day period (6.1 [9.7] to 3.0 [6.8]). Mean (standard deviation) acute medication use decreased from baseline (15.2 [7.6] to 9.1 [6.5] days). No new safety signals were identified.
Conclusions:
Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA treatment for CM in the Canadian population reduces health resource utilization and acute medication use and improves workplace productivity, supporting the long-term benefits of using onabotulinumtoxinA for CM.
Background: Patients with DNM1-encephalopathy almost exclusively have missense variants, mostly in the GTPase domain of DNM1. Delayed myelination has been reported in at least three patients with DNM1-encephalopathy, all with missense mutations in the DNM1 central domain. Only one DNM1 splice-site variant has previously been reported, and the authors questioned whether the variant accounted for all aspects of the patient’s phenotype. Methods: Case-Report. Results: Our patient had hypotonia and brief multifocal tonic seizures from age-1-month. He still has profound global developmental delay, daily seizures and microcephaly. MRI-Brain at age-21-months showed T2 hyperintensity in the bilateral periventricular and subcortical white matter; spectroscopy showed a questionable lactate peak and an elevated choline peak relative to N-acetylaspartate. Clinical gene-panel identified a heterozygous de novo pathogenic variant in intron 9 of DNM1 (c.1197-8G > A; IVS9- 8G>A). In-silico tools categorized this variant as deleterious secondary to a splicing defect. RT-PCR analysis on peripheral blood was unsuccessful as DNM1 expression is extremely low outside of the brain. Conclusions: Our patient carried the same DNM1 variant previously reported, indicating this is a recurrent pathogenic splice-site variant. The spectroscopic abnormalities suggest a possible element of demyelination in DNM1 variants of the central domain, though the mechanism remains unclear.
Masturbation is a common sexual practice in men, and saliva is often used as a lubricant during masturbation by men who have sex with men. However, the role of saliva use during masturbation in the transmission of chlamydia is still unclear. We developed population-level, susceptible-infected-susceptible compartmental models to explore the role of saliva use during masturbation on the transmission of chlamydia at multiple anatomical sites. In this study, we simulated both solo masturbation and mutual masturbation. Our baseline model did not include masturbation but included transmission routes (anal sex, oral-penile sex, rimming, kissing and sequential sexual practices) we have previously validated (model 1). We added masturbation to model 1 to develop the second model (model 2). We calibrated the model to five clinical datasets separately to assess the effects of masturbation on the prevalence of site-specific infection. The inclusion of masturbation (model 2) significantly worsened the ability of the models to replicate the prevalence of C. trachomatis. Using model 2 and the five data sets, we estimated that saliva use during masturbation was responsible for between 3.9% [95% confidence interval (CI) 2.0–6.8] and 6.2% (95% CI 3.8–10.5) of incident chlamydia cases at all sites. Our models suggest that saliva use during masturbation is unlikely to play a major role in chlamydia transmission between men, and even if it does have a role, about one in seven cases of urethral chlamydia might arise from masturbation.
The PREDICT study assessed real-world, long-term health-related quality of life in adults with chronic migraine (CM) receiving onabotulinumtoxinA.
Methods:
Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA for CM. OnabotulinumtoxinA (155–195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Primary endpoint: mean change in Migraine-Specific Quality of Life Questionnaire (MSQ) at treatment 4 (Tx4) versus baseline. Secondary endpoints: mean change in MSQ at final visit versus baseline, and headache days.
Results:
184 participants (average age 45 years; 84.8% female; 94.6% Caucasian) received ≥1 onabotulinumtoxinA treatment; 150 participants completed 4 treatments (1 year) and 123 completed all 7 treatment cycles (2 years). Mean (SD) onabotulinumtoxinA dose per treatment cycle was 171 (18) U and treatment interval was 13.2 (1.8) weeks. Baseline mean (SD) 20.9 (6.7) headache days/month decreased (Tx1: −3.5 [6.3]; Tx4: −6.5 [6.6]; p < 0.0001 versus baseline). Mean (SD) increased from baseline in MSQ at Tx4 (restrictive: 21.5 [24.3], preventive: 19.5 [24.7], emotional: 22.9 [32.9]) and the final visit (restrictive: 21.3 [23.0], preventive: 19.2 [23.7], emotional: 27.4 [30.7]), exceeding minimal important differences (all p < 0.0001). Seventy-seven (41.8%) participants reported 168 treatment-emergent adverse events (TEAEs); 38 TEAEs (12.0%) were considered treatment-related. Four (2.2%) participants reported six serious TEAEs; none were considered treatment-related. No new safety signals were identified.
Conclusions:
Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA for CM in Canada improved MSQ scores and reduced headache frequency and severity, adding to the body of evidence on the long-term safety and effectiveness of onabotulinumtoxinA for CM.
The purpose of this study was to examine the patterns of complementary and integrative health (CIH) use among adults with a racial/ethnic minority background and a mental illness. A secondary data analysis of 2017 National Health Interview Survey (N = 793) was conducted using chi-square, multivariate logistic regression, and multinomial logistic regression. Overall, Black/African Americans and Hispanic/Latinx groups remained the least proportional of CIH therapies utilization. Being a male, Black/African American or Latinx/Hispanic and had work experience were predictors of the least use of the CIH therapies. Research is needed to bridge the gaps on the CIH use among a racial/ethnic minority with mental illness and to enhance the equitable and collaborative mental health care in the community.
Faraday complexity describes whether a spectropolarimetric observation has simple or complex magnetic structure. Quickly determining the Faraday complexity of a spectropolarimetric observation is important for processing large, polarised radio surveys. Finding simple sources lets us build rotation measure grids, and finding complex sources lets us follow these sources up with slower analysis techniques or further observations. We introduce five features that can be used to train simple, interpretable machine learning classifiers for estimating Faraday complexity. We train logistic regression and extreme gradient boosted tree classifiers on simulated polarised spectra using our features, analyse their behaviour, and demonstrate our features are effective for both simulated and real data. This is the first application of machine learning methods to real spectropolarimetry data. With 95% accuracy on simulated ASKAP data and 90% accuracy on simulated ATCA data, our method performs comparably to state-of-the-art convolutional neural networks while being simpler and easier to interpret. Logistic regression trained with our features behaves sensibly on real data and its outputs are useful for sorting polarised sources by apparent Faraday complexity.
Wide-ranging outcomes have been reported for surgical and non-surgical management of T3 laryngeal carcinomas. This study compared the outcomes of T3 tumours treated with laryngectomy or (chemo)radiotherapy in the northeast of England.
Methods
The outcomes of T3 laryngeal carcinoma treatment at three centres (2007–2016) were retrospectively analysed using descriptive statistics and survival curves.
Results
Of 179 T3 laryngeal carcinomas, 68 were treated with laryngectomies, 57 with chemoradiotherapy and 32 with radiotherapy. There was no significant five-year survival difference between treatment with laryngectomy (34.1 per cent) and chemoradiotherapy (48.6 per cent) (p = 0.184). The five-year overall survival rate for radiotherapy (12.5 per cent) was significantly inferior compared to laryngectomy and chemoradiotherapy (p = 0.003 and p < 0.001, respectively). The recurrence rates were 22.1 per cent for laryngectomy, 17.5 per cent for chemoradiotherapy and 50 per cent for radiotherapy. There were significant differences in recurrence rates when laryngectomy (p = 0.005) and chemoradiotherapy (p = 0.001) were compared to radiotherapy.
Conclusion
Laryngectomy and chemoradiotherapy had significantly higher five-year overall survival and lower recurrence rates compared with radiotherapy alone. Laryngectomy should be considered in patients unsuitable for chemotherapy, as it may convey a significant survival advantage over radiotherapy alone.
Gonorrhoea cases in women have been rising in Australia in the 2010s but the cause of the increase is not well understood. This cross-sectional study aimed to describe the characteristics of genital gonorrhoea infection in women attending the Melbourne Sexual Health Centre, Australia. Gonorrhoea cases were diagnosed by nucleic acid amplification test (NAAT) and/or culture. Genitourinary specimens were obtained in 12 869 clinic visits in women aged 16 years or above between August 2017 and August 2018. Genital gonorrhoea was detected in 142 (1.1%) of the visits. Almost half of the cases were asymptomatic, 47.9% [95% confidence interval (CI) 39.8–56.1%]; yellow, green or pus-like vaginal discharge was present in 11.3% (95% CI 7.0–17.6%) and other genital symptoms in 40.8% (95% CI 33.1–49.1%) of the cases. The mean time between last sexual contact and onset of symptoms was 7.3 days and between the onset of symptoms to presentation to the clinic was 12.1 days. Half of the cases of genital gonorrhoea among women are asymptomatic and these cases would have been missed by testing of only symptomatic women. Further epidemiological and behavioural research is required to understand the temporal changes in sexual practices among women in Australia.
The turbulent amplification of cosmic magnetic fields depends upon the material properties of the host plasma. In many hot, dilute astrophysical systems, such as the intracluster medium (ICM) of galaxy clusters, the rarity of particle–particle collisions allows departures from local thermodynamic equilibrium. These departures – pressure anisotropies – exert anisotropic viscous stresses on the plasma motions that inhibit their ability to stretch magnetic-field lines. We present an extensive numerical study of the fluctuation dynamo in a weakly collisional plasma using magnetohydrodynamic (MHD) equations endowed with a field-parallel viscous (Braginskii) stress. When the stress is limited to values consistent with a pressure anisotropy regulated by firehose and mirror instabilities, the Braginskii-MHD dynamo largely resembles its MHD counterpart, particularly when the magnetic field is dynamically weak. If instead the parallel viscous stress is left unabated – a situation relevant to recent kinetic simulations of the fluctuation dynamo and, we argue, to the early stages of the dynamo in a magnetized ICM – the dynamo changes its character, amplifying the magnetic field while exhibiting many characteristics reminiscent of the saturated state of the large-Prandtl-number (${Pm}\gtrsim {1}$) MHD dynamo. We construct an analytic model for the Braginskii-MHD dynamo in this regime, which successfully matches simulated dynamo growth rates and magnetic-energy spectra. A prediction of this model, confirmed by our numerical simulations, is that a Braginskii-MHD plasma without pressure-anisotropy limiters will not support a dynamo if the ratio of perpendicular and parallel viscosities is too small. This ratio reflects the relative allowed rates of field-line stretching and mixing, the latter of which promotes resistive dissipation of the magnetic field. In all cases that do exhibit a viable dynamo, the generated magnetic field is organized into folds that persist into the saturated state and bias the chaotic flow to acquire a scale-dependent spectral anisotropy.