How will transitioning from cytology to HPV testing change the balance between the benefits and harms of cervical cancer screening? Estimates of the impact on cervical cancer, treatment rates and adverse obstetric outcomes in Australia, a high vaccination coverage country

Primary HPV screening enables earlier diagnosis of cervical lesions compared to cytology, however, its effect on the risk of treatment and adverse obstetric outcomes has not been extensively investigated. We estimated the cumulative lifetime risk (CLR) of cervical cancer and excisional treatment, and change in adverse obstetric outcomes in HPV unvaccinated women and cohorts offered vaccination (>70% coverage in 12-13 years) for the Australian cervical screening program. Two-yearly cytology screening (ages 18-69 years) was compared to 5-yearly primary HPV screening with partial genotyping for HPV16/18 (ages 25-74 years). A dynamic model of HPV transmission, vaccination, cervical screening and treatment for precancerous lesions was coupled with an individual-based simulation of obstetric complications. For cytology screening, the CLR of cervical cancer diagnosis, death and treatment was estimated to be 0.649%, 0.198% and 13.4% without vaccination and 0.182%, 0.056% and 6.8%, in vaccinated women, respectively. For HPV screening, relative reductions of 33% and 22% in cancer risk for unvaccinated and vaccinated women are predicted, respectively, compared to cytology. Without the implementation of vaccination, a 4% increase in treatment risk for HPV versus cytology screening would have been expected, implying a possible increase in pre-term delivery (PTD) and low birth weight (LBW) events of 19 to 35 and 14 to 37, respectively, per 100,000 unvaccinated women. However, in vaccinated women, treatment risk will decrease by 13%, potentially leading to 4 to 41 fewer PTD events and from 2 more to 52 fewer LBW events per 100,000 vaccinated women. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. In unvaccinated women in cohorts offered vaccination as 12-13 year olds, no change to lifetime treatment risk is expected with HPV screening. HPV screening starting at age 25 in populations with high vaccination coverage, is therefore expected to both improve the benefits (further decrease risk of cervical cancer) and reduce the harms (reduce treatments and possible obstetric complications) associated with cervical cancer screening

Psychiatric diagnoses, trauma, and suicidiality

BACKGROUND: This study aimed to examine the associations between psychiatric diagnoses, trauma and suicidiality in psychiatric patients at intake. METHODS: During two months, all consecutive patients (n = 139) in a psychiatric hospital in Western Norway were interviewed (response rate 72%). RESULTS: Ninety-one percent had been exposed to at least one trauma; 69 percent had been repeatedly exposed to trauma for longer periods of time. Only 7% acquired a PTSD diagnosis. The comorbidity of PTSD and other psychiatric diagnoses were 78%. A number of diagnoses were associated with specific traumas. Sixty-seven percent of the patients reported suicidal thoughts in the month prior to intake; thirty-one percent had attempted suicide in the preceding week. Suicidal ideation, self-harming behaviour, and suicide attempts were associated with specific traumas. CONCLUSION: Traumatised patients appear to be under- or misdiagnosed which could have an impact on the efficiency of treatment

A rapid high-performance semi-automated tool to measure total kidney volume from MRI in autosomal dominant polycystic kidney disease.

OBJECTIVES: To develop a high-performance, rapid semi-automated method (Sheffield TKV Tool) for measuring total kidney volume (TKV) from magnetic resonance images (MRI) in patients with autosomal dominant polycystic kidney disease (ADPKD). METHODS: TKV was initially measured in 61 patients with ADPKD using the Sheffield TKV Tool and its performance compared to manual segmentation and other published methods (ellipsoidal, mid-slice, MIROS). It was then validated using an external dataset of MRI scans from 65 patients with ADPKD. RESULTS: Sixty-one patients (mean age 45 ± 14 years, baseline eGFR 76 ± 32 ml/min/1.73 m2) with ADPKD had a wide range of TKV (258-3680 ml) measured manually. The Sheffield TKV Tool was highly accurate (mean volume error 0.5 ± 5.3% for right kidney, - 0.7 ± 5.5% for left kidney), reproducible (intra-operator variability - 0.2 ± 1.3%; inter-operator variability 1.1 ± 2.9%) and outperformed published methods. It took less than 6 min to execute and performed consistently with high accuracy in an external MRI dataset of T2-weighted sequences with TKV acquired using three different scanners and measured using a different segmentation methodology (mean volume error was 3.45 ± 3.96%, n = 65). CONCLUSIONS: The Sheffield TKV Tool is operator friendly, requiring minimal user interaction to rapidly, accurately and reproducibly measure TKV in this, the largest reported unselected European patient cohort with ADPKD. It is more accurate than estimating equations and its accuracy is maintained at larger kidney volumes than previously reported with other semi-automated methods. It is free to use, can run as an independent executable and will accelerate the application of TKV as a prognostic biomarker for ADPKD into clinical practice. KEY POINTS: • This new semi-automated method (Sheffield TKV Tool) to measure total kidney volume (TKV) will facilitate the routine clinical assessment of patients with ADPKD. • Measuring TKV manually is time consuming and laborious. • TKV is a prognostic indicator in ADPKD and the only imaging biomarker approved by the FDA and EMA

Integrating the Hierarchical Taxonomy of Psychopathology (HiTOP) Into Clinical Practice

Objective: Diagnosis is a cornerstone of clinical practice for mental health care providers, yet traditional diagnostic systems have well-known shortcomings, including inadequate reliability, high comorbidity, and marked within-diagnosis heterogeneity. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a data-driven, hierarchically based alternative to traditional classifications that conceptualizes psychopathology as a set of dimensions organized into increasingly broad, transdiagnostic spectra. Prior work has shown that using a dimensional approach improves reliability and validity, but translating a model like HiTOP into a workable system that is useful for health care providers remains a major challenge. / Method: The present work outlines the HiTOP model and describes the core principles to guide its integration into clinical practice. Results: Potential advantages and limitations of the HiTOP model for clinical utility are reviewed, including with respect to case conceptualization and treatment planning. A HiTOP approach to practice is illustrated and contrasted with an approach based on traditional nosology. Common barriers to using HiTOP in real-world health care settings and solutions to these barriers are discussed. / Conclusions: HiTOP represents a viable alternative to classifying mental illness that can be integrated into practice today, although research is needed to further establish its utility

The neuropathology of autism: defects of neurogenesis and neuronal migration, and dysplastic changes

Autism is characterized by a broad spectrum of clinical manifestations including qualitative impairments in social interactions and communication, and repetitive and stereotyped patterns of behavior. Abnormal acceleration of brain growth in early childhood, signs of slower growth of neurons, and minicolumn developmental abnormalities suggest multiregional alterations. The aim of this study was to detect the patterns of focal qualitative developmental defects and to identify brain regions that are prone to developmental alterations in autism. Formalin-fixed brain hemispheres of 13 autistic (4–60 years of age) and 14 age-matched control subjects were embedded in celloidin and cut into 200-μm-thick coronal sections, which were stained with cresyl violet and used for neuropathological evaluation. Thickening of the subependymal cell layer in two brains and subependymal nodular dysplasia in one brain is indicative of active neurogenesis in two autistic children. Subcortical, periventricular, hippocampal and cerebellar heterotopias detected in the brains of four autistic subjects (31%) reflect abnormal neuronal migration. Multifocal cerebral dysplasia resulted in local distortion of the cytoarchitecture of the neocortex in four brains (31%), of the entorhinal cortex in two brains (15%), of the cornu Ammonis in four brains and of the dentate gyrus in two brains. Cerebellar flocculonodular dysplasia detected in six subjects (46%), focal dysplasia in the vermis in one case, and hypoplasia in one subject indicate local failure of cerebellar development in 62% of autistic subjects. Detection of flocculonodular dysplasia in only one control subject and of a broad spectrum of focal qualitative neuropathological developmental changes in 12 of 13 examined brains of autistic subjects (92%) reflects multiregional dysregulation of neurogenesis, neuronal migration and maturation in autism, which may contribute to the heterogeneity of the clinical phenotype

Progress in achieving quantitative classification of psychopathology

Résumé: Les lacunes des classifications de la psychopathologie fondées sur des consensus d’experts ont conduit à de nombreuses tentatives actuelles pour classer la psychopathologie de manière quantitative. Dans cet article, nous passons en revue les progrès accomplis dans la réalisation d’une classification quantitative et empirique de la psychopathologie. Une littérature empirique substantielle montre que la psychopathologie est généralement plus dimensionnelle que catégorielle. Et lorsque la distinction entre une psychopathologie discrète et une psychopathologie continue est traitée comme une question de recherche, par opposition à une distinction basée sur un argument d’autorité, alors les preuves scientifiques soutiennent clairement l’hypothèse d’une psychopathologie continue. En outre, un corpus de littérature connexe montre comment les dimensions de la psychopathologie peuvent être organisées selon une hiérarchie qui va de dimensions très larges d’un niveau de type « spectre » à des groupes spécifiques et étroits de symptômes. De cette manière, une approche quantitative résout le « problème de la comorbidité » en modélisant explicitement la cooccurrence entre les signes et les symptômes au sein d’une hiérarchie détaillée et variée, maniant des concepts dimensionnels qui ont une utilité clinique directe. De nombreuses preuves concernant la structure dimensionnelle et hiérarchique de la psychopathologie ont conduit à la formation du consortium Hierarchical Taxonomy of Psychopathology (HiTOP, taxonomie hiérarchique de la psychopathologie). Il s’agit d’un groupe de 70 chercheurs travaillant ensemble pour étudier la classification empirique de la psychopathologie. Dans cet article, nous décrivons les objectifs et les axes de recherches actuels du consortium HiTOP. Ces objectifs concernent la poursuite des recherches sur l’organisation empirique de la psychopathologie ; le lien entre la personnalité et la psychopathologie ; l’utilité des construits empiriques de la psychopathologie, à la fois pour la recherche et pour la clinique ; et enfin, le développement de nouveaux modèles exhaustifs et d’instruments d’évaluation correspondant aux construits psychopathologiques dérivés d’une approche empirique. / Abstract: Shortcomings of approaches to classifying psychopathology based on expert consensus have given rise to contemporary efforts to classify psychopathology quantitatively. In this paper, we review progress in achieving a quantitative and empirical classification of psychopathology. A substantial empirical literature indicates that psychopathology is generally more dimensional than categorical. When the discreteness versus continuity of psychopathology is treated as a research question, as opposed to being decided as a matter of tradition, the evidence clearly supports the hypothesis of continuity. In addition, a related body of literature shows how psychopathology dimensions can be arranged in a hierarchy, ranging from very broad “spectrum level” dimensions, to specific and narrow clusters of symptoms. In this way, a quantitative approach solves the “problem of comorbidity” by explicitly modeling patterns of co-occurrence among signs and symptoms within a detailed and variegated hierarchy of dimensional concepts with direct clinical utility. Indeed, extensive evidence pertaining to the dimensional and hierarchical structure of psychopathology has led to the formation of the Hierarchical Taxonomy of Psychopathology (HiTOP) Consortium. This is a group of 70 investigators working together to study empirical classification of psychopathology. In this paper, we describe the aims and current foci of the HiTOP Consortium. These aims pertain to continued research on the empirical organization of psychopathology; the connection between personality and psychopathology; the utility of empirically based psychopathology constructs in both research and the clinic; and the development of novel and comprehensive models and corresponding assessment instruments for psychopathology constructs derived from an empirical approach

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021

Impact of HPV sample self-collection for underscreened women in the renewed Cervical Screening Program.

Summary Objectives: In 2017, the National Cervical Screening Program in Australia will transition to 5-yearly primary HPV screening for all women, irrespective of human papillomavirus (HPV) vaccination status. As an adjunct to the mainstream program, HPV testing on self-collected samples will be offered under practitioner supervision to all unscreened and underscreened women aged 30–74 years. We quantified how different screening decisions affect the future risk of cervical cancer. Design: Simulation of outcomes for 100 000 previously unscreened women, aged 30 years and eligible for self-collection, using a well-established model of HPV natural history and cervical screening. Main outcome measures: Cumulative cancer diagnoses and deaths averted (compared with remaining unscreened) to age 84, number needed to treat for pre-cancer (NNT) to avert each cancer diagnosis. Results: One round of self-collected HPV screening at age 30 years would avert 908 cancer diagnoses and 364 cancer deaths in the cohort by age 84 (NNT, 5.8). Benefits would still be achieved were self-collected screening delayed to age 40 (922 fewer diagnoses; 426 fewer deaths; NNT, 3.7) or 50 (684 fewer diagnoses; 385 fewer deaths; NNT, 3.2). However, the benefits associated with joining the mainstream screening program would be substantially larger (2002, 1623 or 1091 fewer diagnoses and NNT of 4.9, 3.7 or 3.4 by joining at age 30, 40 or 50 years respectively). The relative benefits of joining the mainstream program were similar for cohorts who had been offered vaccination. Conclusions: Offering HPV self-collection has the potential to considerably improve outcomes for unscreened and underscreened women. Nevertheless, these findings underscore the need for concerted strategies to encourage these women to join the mainstream HPV screening program.The Policy1 model platform was developed earlier with grants from the National Health and Medical Research Council and with funding from the Medical Services Advisory Committee and Cancer Council NSW. Karen Canfell receives salary support (Career Development Fellowship) from the National Health and Medical Research Council. Megan Smith was awarded funding by the University of Sydney Postgraduate Research Support Scheme to partially reimburse travel expenses incurred to present this (and other) research at HPV2015 (Lisbon, 2015)

A Hepatitis B vaccine booster shot at age 10 could be cost-saving in China: But is it too soon to tell?

Worldwide, over 240 million people are living with chronic hepatitis B virus (HBV) infection (Ott et al., 2012), and 786,000 individuals die from HBV related deaths, including cirrhosis and liver cancer, each year (MacLachlan et al., 2015, Lozano et al., 2012). The HBV vaccine has been shown to be highly effective, and over one billion doses have been delivered worldwide (World Health Organisation, 2018). The burden of hepatitis B in China is one of the highest in the world, with almost one-third of the world’s hepatitis B cases diagnosed in China. The initial HBV vaccines were licensed in China in 1985 and from 1992 the government actively recommended vaccination of infants, including the first dose being administered within the first 24 hours of birth (Centers for Disease Control and Prevention, 2007, Wang et al., 2016). Since 2002, infant HBV vaccination has been government funded (Cui et al., 2017a). The program has achieved high coverage in infants, with 93.4% receiving three-doses for the 2005 birth cohort; 82.6% received the first dose within the first 24 h of birth (Centers for Disease Control and Prevention, 2007). Survey results have shown declines in hepatitis B virus surface antigen (HBsAg) prevalence in children aged 0–14 years from 10% in 1992 to <1% in 2014 (Cui et al., 2017a), and modelled analyses of HBV vaccination have consistently found that infant HBV vaccination, as well as catch-up vaccination for adolescents, is cost-saving for China (Hutton et al., 2010, Yin et al., 2015)