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Introduction Joint Advisory Group (JAG) certification in endoscopy is awarded when trainees attain minimum competency standards for independent practice. A national evidence-based review was undertaken to update standards for training and certification in flexible sigmoidoscopy (FS).Methods A modified Delphi process was conducted between 2019 and 2020 with multisociety representation from experts and trainees. Following literature review and Grading of Recommendations, Assessment, Development and Evaluations appraisal, recommendation statements on FS training and certification were formulated and subjected to anonymous voting to obtain consensus. Accepted statements were peer-reviewed by national stakeholders for incorporation into the JAG FS certification pathway.Results In total, 41 recommendation statements were generated under the domains of: definition of competence (13), acquisition of competence (17), assessment of competence (7) and postcertification support (4). The consensus process led to revised criteria for colonoscopy certification, comprising: (A) achieving key performance indicators defined within British Society of Gastroenterology standards (ie, rectal retroversion >90%, polyp retrieval rate >90%, patient comfort Conclusion The UK standards for training and certification in FS have been updated to support training, uphold standards in FS and polypectomy, and provide support to the newly independent practitioner.

Introduction In the UK, endoscopy certification is awarded when trainees attain minimum competency standards for independent practice. A national evidence-based review was undertaken to update and develop standards and recommendations for colonoscopy training and certification.Methods Under the oversight of the Joint Advisory Group (JAG), a modified Delphi process was conducted between 2019 and 2020 with multisociety expert representation. Following literature review and Grading of Recommendations, Assessment, Development and Evaluations appraisal, recommendation statements on colonoscopy training and certification were formulated and subjected to anonymous voting to obtain consensus. Accepted statements were peer reviewed by JAG and relevant stakeholders for incorporation into the updated colonoscopy certification pathway.Results In total, 45 recommendation statements were generated under the domains of: definition of competence (13), acquisition of competence (20), assessment of competence (8) and postcertification support (4). The consensus process led to revised criteria for colonoscopy certification, comprising: (1) achieving key performance indicators defined within British Society of Gastroenterology standards (ie, unassisted caecal intubation rate >90%, rectal retroversion >90%, polyp detection rate >15%+, polyp retrieval rate >90%, patient comfort Conclusion The UK standards for training and certification in colonoscopy have been updated, culminating in a single-stage certification process with emphasis on polypectomy competency (SMSA Level 2+). These standards are intended to support training, improve standards of colonoscopy and polypectomy, and provide support to the newly independent practitioner.

The UK is currently playing a key role in the development of Mars Exploration, with scientists and engineers working on many current and upcoming missions such as the European Space Agency’s Mars Express satellite (2003 – present) and the upcoming Rosalind Franklin Rover (launch TBD). The camera onboard the Rosalind Franklin Rover was designed, built and tested at the Mullard Space Science Laboratory, part of University College London, in Surrey, England. The rover was also assembled at Airbus in Stevenage. These facts are not well known to the public in the UK, and our public engagement project, Eyes on Mars, aims to increase awareness of UK’s involvement in progressing Mars science and with this, promote STEM education in UK. We received funding from the Science and Technology Facilities Council’s Public Engagement Sparks Award and the Royal Astronomical Society education and outreach grant. To accomplish this, Eyes on Mars has two main foci – a social media campaign and providing resources to be used in classrooms, youth groups and at home. The social media campaign will showcase short and informal snippets of information that highlights Mars facts and various space careers. It will also include interviews of diverse individuals from across Europe that are in the space sector, specifically, highlighting their paths into STEM careers. Furthermore, Eyes on Mars has put together a selection of free resources that are available to download or given to participating schools to carry out science curriculum activities in class. We have provided various education videos, worksheets and activity plans, including making your own filter wheel similar to the filter wheel onboard the Rosalind Franklin Rover. All materials for this craft activity are provided by the Eyes on Mars team, and are sent out to schools or groups across the UK. Having both come from state-schools in the UK, and not being in the ‘top-set’ for science at school, Catherine Regan and Priya Patel are now PhD students in planetary physics, researching Mars. Both have been told at some point during their education that they weren’t “clever enough” for a career in science, and are now both working on space missions with NASA and the European Space Agency. We want to use Eyes on Mars to be role models for those that may not think they can succeed in science, and to highlight the different possibilities there are for a career in space, especially in the UK.

Global dust storms at Mars engulf the entire planet in a dusty haze, causing increases in temperature and ion escape as dust is lifted up to 80 km in altitude. The two most recent storms occurred in 2007 (Mars Year (MY) 28) and 2018 (MY34), and have been observed by spacecrafts such as Mars Express (MEx). MEx has been operating at Mars since 2004, and has produced a long time-base of plasma measurements from as low as 250 km. Using MEx, we investigate whether the 2007 dust storm has influenced the magnetosphere of Mars by looking at the position of the bow shock and induced magnetospheric boundary, compared to the expected position provided by 3D magnetohydrodynamical models. To identify boundary positions, we use data from the ASPERA-3 instrument (Analyser of Space Plasma and EneRgetic Atoms) onboard MEx, which contains an electron spectrometer (ELS), ion mass analyser (IMA), neutral particle imager (NPI) and neutral particle detector (NPD). For this study, we use data from ELS and IMA. We consider a number of influences on the boundary position, including the solar wind conditions and the crustal fields. Our study period includes time before, during, and after the MY28 global storm, and we expected the bow shock and induced magnetospheric boundary to increase in altitude due to the storm. Out results show that the system is more complex, and multiple influences need to be distinguished to leave any change due to the dust storm itself.

Summary Background WHO is developing a global strategy towards eliminating cervical cancer as a public health problem, which proposes an elimination threshold of four cases per 100 000 women and includes 2030 triple-intervention coverage targets for scale-up of human papillomavirus (HPV) vaccination to 90%, twice-lifetime cervical screening to 70%, and treatment of pre-invasive lesions and invasive cancer to 90%. We assessed the impact of achieving the 90–70–90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century. We also assessed the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals (SDGs)—a one-third reduction in premature mortality from non-communicable diseases by 2030. Methods The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC) involves three independent, dynamic models of HPV infection, cervical carcinogenesis, screening, and precancer and invasive cancer treatment. Reductions in age-standardised rates of cervical cancer mortality in 78 low-income and lower-middle-income countries (LMICs) were estimated for three core scenarios: girls-only vaccination at age 9 years with catch-up for girls aged 10–14 years; girls-only vaccination plus once-lifetime screening and cancer treatment scale-up; and girls-only vaccination plus twice-lifetime screening and cancer treatment scale-up. Vaccination was assumed to provide 100% lifetime protection against infections with HPV types 16, 18, 31, 33, 45, 52, and 58, and to scale up to 90% coverage in 2020. Cervical screening involved HPV testing at age 35 years, or at ages 35 years and 45 years, with scale-up to 45% coverage by 2023, 70% by 2030, and 90% by 2045, and we assumed that 50% of women with invasive cervical cancer would receive appropriate surgery, radiotherapy, and chemotherapy by 2023, which would increase to 90% by 2030. We summarised results using the median (range) of model predictions. Findings In 2020, the estimated cervical cancer mortality rate across all 78 LMICs was 13·2 (range 12·9–14·1) per 100 000 women. Compared to the status quo, by 2030, vaccination alone would have minimal impact on cervical cancer mortality, leading to a 0·1% (0·1–0·5) reduction, but additionally scaling up twice-lifetime screening and cancer treatment would reduce mortality by 34·2% (23·3–37·8), averting 300 000 (300 000–400 000) deaths by 2030 (with similar results for once-lifetime screening). By 2070, scaling up vaccination alone would reduce mortality by 61·7% (61·4–66·1), averting 4·8 million (4·1–4·8) deaths. By 2070, additionally scaling up screening and cancer treatment would reduce mortality by 88·9% (84·0–89·3), averting 13·3 million (13·1–13·6) deaths (with once-lifetime screening), or by 92·3% (88·4–93·0), averting 14·6 million (14·1–14·6) deaths (with twice-lifetime screening). By 2120, vaccination alone would reduce mortality by 89·5% (86·6–89·9), averting 45·8 million (44·7–46·4) deaths. By 2120, additionally scaling up screening and cancer treatment would reduce mortality by 97·9% (95·0–98·0), averting 60·8 million (60·2–61·2) deaths (with once-lifetime screening), or by 98·6% (96·5–98·6), averting 62·6 million (62·1–62·8) deaths (with twice-lifetime screening). With the WHO triple-intervention strategy, over the next 10 years, about half (48% [45–55]) of deaths averted would be in sub-Saharan Africa and almost a third (32% [29–34]) would be in South Asia; over the next 100 years, almost 90% of deaths averted would be in these regions. For premature deaths (age 30–69 years), the WHO triple-intervention strategy would result in rate reductions of 33·9% (24·4–37·9) by 2030, 96·2% (94·3–96·8) by 2070, and 98·6% (96·9–98·8) by 2120. Interpretation These findings emphasise the importance of acting immediately on three fronts to scale up vaccination, screening, and treatment for pre-invasive and invasive cervical cancer. In the next 10 years, a one-third reduction in the rate of premature mortality from cervical cancer in LMICs is possible, contributing to the realisation of the 2030 UN SDGs. Over the next century, successful implementation of the WHO elimination strategy would reduce cervical cancer mortality by almost 99% and save more than 62 million women's lives. Funding WHO, UNDP, UN Population Fund, UNICEF–WHO–World Bank Special Program of Research, Development and Research Training in Human Reproduction, Germany Federal Ministry of Health, National Health and Medical Research Council Australia, Centre for Research Excellence in Cervical Cancer Control, Canadian Institute of Health Research, Compute Canada, and Fonds de recherche du Quebec–Sante.

Summary Background The WHO Director-General has issued a call for action to eliminate cervical cancer as a public health problem. To help inform global efforts, we modelled potential human papillomavirus (HPV) vaccination and cervical screening scenarios in low-income and lower-middle-income countries (LMICs) to examine the feasibility and timing of elimination at different thresholds, and to estimate the number of cervical cancer cases averted on the path to elimination. Methods The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC), which consists of three independent transmission-dynamic models identified by WHO according to predefined criteria, projected reductions in cervical cancer incidence over time in 78 LMICs for three standardised base-case scenarios: girls-only vaccination; girls-only vaccination and once-lifetime screening; and girls-only vaccination and twice-lifetime screening. Girls were vaccinated at age 9 years (with a catch-up to age 14 years), assuming 90% coverage and 100% lifetime protection against HPV types 16, 18, 31, 33, 45, 52, and 58. Cervical screening involved HPV testing once or twice per lifetime at ages 35 years and 45 years, with uptake increasing from 45% (2023) to 90% (2045 onwards). The elimination thresholds examined were an average age-standardised cervical cancer incidence of four or fewer cases per 100 000 women-years and ten or fewer cases per 100 000 women-years, and an 85% or greater reduction in incidence. Sensitivity analyses were done, varying vaccination and screening strategies and assumptions. We summarised results using the median (range) of model predictions. Findings Girls-only HPV vaccination was predicted to reduce the median age-standardised cervical cancer incidence in LMICs from 19·8 (range 19·4–19·8) to 2·1 (2·0–2·6) cases per 100 000 women-years over the next century (89·4% [86·2–90·1] reduction), and to avert 61·0 million (60·5–63·0) cases during this period. Adding twice-lifetime screening reduced the incidence to 0·7 (0·6–1·6) cases per 100 000 women-years (96·7% [91·3–96·7] reduction) and averted an extra 12·1 million (9·5–13·7) cases. Girls-only vaccination was predicted to result in elimination in 60% (58–65) of LMICs based on the threshold of four or fewer cases per 100 000 women-years, in 99% (89–100) of LMICs based on the threshold of ten or fewer cases per 100 000 women-years, and in 87% (37–99) of LMICs based on the 85% or greater reduction threshold. When adding twice-lifetime screening, 100% (71–100) of LMICs reached elimination for all three thresholds. In regions in which all countries can achieve cervical cancer elimination with girls-only vaccination, elimination could occur between 2059 and 2102, depending on the threshold and region. Introducing twice-lifetime screening accelerated elimination by 11–31 years. Long-term vaccine protection was required for elimination. Interpretation Predictions were consistent across our three models and suggest that high HPV vaccination coverage of girls can lead to cervical cancer elimination in most LMICs by the end of the century. Screening with high uptake will expedite reductions and will be necessary to eliminate cervical cancer in countries with the highest burden. Funding WHO, UNDP, UN Population Fund, UNICEF–WHO–World Bank Special Program of Research, Development and Research Training in Human Reproduction, Canadian Institute of Health Research, Fonds de recherche du Quebec–Sante, Compute Canada, National Health and Medical Research Council Australia Centre for Research Excellence in Cervical Cancer Control.

Background SEER-reported cervical cancer incidence rates reflect the total female population including women no longer at risk due to hysterectomy. Hysterectomy rates have been declining in the United States as alternative treatments have become available, which could result in an apparent increase in SEER-reported cervical cancer rates. We aimed to obtain nationally representative historical data on hysterectomy rates in USA, use trends analysis to project rates back to 1935 and forward to 2035, and then predict the impact of changing hysterectomy rates on SEER-reported cervical cancer rates. Methods We performed a systematic search of Medline, Embase, Premedline, Cochrane Central databases and extracted nationally-representative hysterectomy incidence data from 1965 to 2009, including data on the number of cervix-preserving (subtotal) procedures. We then projected rates back to 1935, and forward to 2035 based on trends from joinpoint regression. These rates were then used to estimate hysterectomy prevalence out to 2035, and then to predict the impact of changing hysterectomy rates on SEER-reported cervical cancer rates to 2035. We examined alternative assumptions regarding projected hysterectomy incidence rates out to 2035, including a scenario in which rates decline no further from 2009 rates, and a scenario where rates decline at twice the baseline rate. Results Estimated age-standardized hysterectomy incidence increased from 2.4 to 10.6 per 1000 women between 1935 and 1975. Thereafter, rates are predicted to fall to 3.9 per 1000 by 2035. Subtotal hysterectomy procedures declined from being the predominant method in 1935 to less than 12% of procedures from 1970 onwards. Consequently, holding all else constant, an increase in SEER-reported age-standardized cervical cancer incidence rates (ages 0–85+) of 9% is expected from 2009 to 2035. The predictions were minimally impacted by alternative scenarios for future hysterectomy rates. Conclusions Declining hysterectomy rates have implications for the interpretation of SEER-reported cervical cancer rates. A background increase in cervical cancer rates due to decreasing population hysterectomy exposure may partially offset expected decreases from recent cervical screening changes recommended by the US Preventive Services Task Force. Evaluations of new cervical cancer prevention opportunities should consider the background impact of historical and projected hysterectomy rates.

Background The natural history of human papillomavirus (HPV)-induced cervical cancer (CC) is not directly observable, yet the age of HPV acquisition and duration of preclinical disease (dwell time) influences the effectiveness of alternative preventive policies. We performed a Cancer Intervention and Surveillance Modeling Network (CISNET) comparative modeling analysis to characterize the age of acquisition of cancer-causing HPV infections and implied dwell times for distinct phases of cervical carcinogenesis. Methods Using four CISNET-cervical models with varying underlying structures but fit to common US epidemiological data, we estimated the age of acquisition of causal HPV infections and dwell times associated with three phases of cancer development: HPV, high-grade precancer, and cancer sojourn time. We stratified these estimates by HPV genotype under both natural history and CC screening scenarios, because screening prevents cancer development that affects the mix of detected cancers. Results The median time from HPV acquisition to cancer detection ranged from 17.5 to 26.0 years across the four models. Three models projected that 50% of unscreened women acquired their causal HPV infection between ages 19 and 23 years, whereas one model projected these infections occurred later (age 34 years). In the context of imperfect compliance with US screening guidelines, the median age of causal infection was 4.4–15.9 years later compared with model projections in the absence of screening. Conclusions These validated CISNET-CC models, which reflect some uncertainty in the development of CC, elucidate important drivers of HPV vaccination and CC screening policies and emphasize the value of comparative modeling when evaluating public health policies.

2007 and 2018 saw global scale dust storms engulfing the entirety of Mars, lasting several months. These events have a profound impact across Mars, with dust reaching altitudes up to 80 km and global temperatures rising by up to 40 K. This significant change in the Martian atmosphere may lead to changes in the ionosphere and above. During the 2007 storm, it was seen in Mars Express (MEx) radar data that ionisation created in the lower atmosphere is observed at higher altitudes, with an altitude dependent enhancement in plasma density over crustal magnetic fields (Venkateswara et al., 2019). It may be likely that during these dust events, atmosphere loss is enhanced. MEx launched in 2003, became operational in 2004 and is still collecting data today. Onboard are seven scientific instruments which are answering questions about the atmosphere, surface and geology at Mars, whilst looking for signs of water and life. With a period of seven hours, MEx provides extensive coverage of data collection. One of the seven instruments, the Analyzer of Space Plasmas and Energetic Atoms (ASPERA-3) has produced a long time-base of plasma measurements from as low as 250 km. ASPERA-3 aims to investigate the interaction of the solar wind with the Martian atmosphere, looking at the mechanisms that may enhance the loss of gases from Mars. ASPERA-3 will be used to investigate the effects the 2007 and 2018 global dust storms had on the plasma environment by comparing data before, during, and after the event. Of particular interest are plasma measurements over radial magnetic fields from crustal anomalies, where transport of charged particles is guided out of the atmosphere. The before, during, and after effects will shed light on to the influence dust storms have on the escaping plasma measured by ASPERA-3 and how dust changes the local plasma escape directly from the atmosphere. Our initial study focuses on data from the electron spectrometer (ELS) where we investigate how the energy distribution and peak energy value varies in altitude above the Martian surface. We will also relate our observations back down to the Martian surface, where we will investigate how surface features may influence the atmosphere and ionosphere above them. This will focus on the southern hemispheric crustal fields and geological features, such as impact basins and volcanoes.

Summary Background To eliminate cervical cancer as a public health problem, WHO currently recommends routine vaccination of adolescent girls with two doses of the human papillomavirus (HPV) vaccine before sexual debut. However, many countries have yet to implement this because of financial or logistical barriers to delivering two doses outside the infant immunisation programme. Methods Using three independent HPV transmission models, we estimated the long-term health benefits and cost-effectiveness of one-dose versus two-dose HPV vaccination, in 192 countries, assuming that one dose of the vaccine gives either a shorter duration of full protection (20 or 30 years) or lifelong protection but lower vaccine efficacy (e.g., 80%) compared to two doses. We simulated routine vaccination with the 9-valent HPV vaccine in 10-year-old girls at 80% coverage for the years 2021–2120, with a one-year catch-up of 80% 11–14-year-old girls on the first year of the programme. Findings Over the next century, one-dose vaccination at 80% coverage could avert 64 million (80%UI 62·2–64·8) and 66·6 million (80%UI 63·4–69·1) cervical cancer cases should one dose of the vaccine confer 20 and 30 years of protection, respectively. Should one dose of the vaccine provide lifelong protection at 80% vaccine efficacy, 68·4 million (80%UI 63·8–69·4) cervical cancer cases could be prevented. Across all country income groups, two-dose schedules conferring lifelong protection would avert only slightly more cases (2·1–8·7 million) than the one-dose scenarios explored. Around 330 to 5230 additional girls need to be vaccinated with the second dose to prevent one cervical cancer case, depending on the epidemiological profiles of the country. Interpretation Results were consistent across the three independent models and suggest that one-dose vaccination has similar health benefits to a two-dose programme while simplifying vaccine delivery, reducing costs and alleviating vaccine supply constraints. Funding Bill & Melinda Gates Foundation Research in context Evidence before this study Primary prevention of cervical cancer is now available with human papillomavirus (HPV) vaccination. Initially administered as a three-dose regimen, the HPV vaccine schedule recommended by WHO has now switched to two doses for individuals below the age of 15 years. Although WHO recommends all countries to routinely immunise adolescent girls with two doses, many low- and middle-income countries, with high disease burden, have yet to implement national HPV vaccination programmes because of the challenges of delivering two vaccine doses to adolescent females. Recently, HPV vaccine implementation in many countries has been further delayed due to constraints in vaccine supply and difficulties in access during COVID-19 epidemics. These financial, logistical, and supply constraints have motivated research into one-dose vaccination schedules. Evidence emerging from trials and observational studies suggests that one dose may also provide a high level of protection against incident and persistent HPV infections. If proven effective, the one-dose HPV vaccination schedule would simplify vaccine delivery and lower costs of national vaccination programmes, potentially enabling more countries to implement one and as a result, facilitating global cervical cancer prevention. We searched PubMed for trials, cohort and modelling studies published in 2018 and 2020, with the terms “(health impact OR impact OR modelling OR cost-effectiveness OR CEA OR durability OR effectiveness) AND (HPV OR human papillomavirus OR cervical cancer)” and identified 151 results. Ten published articles—four trials, three cohort studies, two modelling analyses, one systematic review of trials—evaluated the population impact of one dose of the vaccine on cervical cancer disease outcome among females and all studies showed one dose of the vaccine might be as effective as two doses in preventing HPV infection. However as the trials and cohorts were single-country studies in select populations, the global impact remains unknown. Both published modelling analyses only used one model to estimate the impact of one-dose vaccination, and only examined a few countries. To our knowledge, no published article has modelled the global impact of routine one-dose vaccination on cervical cancer prevention by synthesising the results from more than one model. Added value of this study This study presents the first evidence on the potential global impact of a routine one-dose regimen, from a comparative modelling analysis that synthesises results from three published dynamic models calibrated to countries with varying epidemiological and demographic profiles. We found consistent results across all models suggesting that routine one-dose vaccination provides the majority of health benefits to the two-dose programme should a single dose of the vaccine confer more than 20 years of protection at full potential efficacy or 80% efficacy with lifelong protection. Implications of all the available evidence Findings suggest that routine one-dose vaccinations could avert almost as many cervical cancer cases as a two-dose programme. The one-dose regimen would be cheaper and easier to implement for most countries while alleviating vaccine supply constraints. To cope with the COVID-19 pandemic, many governments have had to implement stringent physical distancing measures, which has led to the suspension of routine immunisation programmes. Public health authorities grapple with the logistic challenges of delivering immunisation services while minimising the risk of SARS-CoV-2 transmission. Compared to the two-dose vaccination schedule, a one-dose vaccination schedule would reduce interactions between vaccinees and health workers, simplifying vaccine delivery while also decreasing SARS-CoV-2 exposure.

Aims: To evaluate total costs and health consequences of a colorectal cancer (CRC) screening program with colonoscopy, fecal immunochemical tests (FIT), and expanded use of multitarget stool DNA (mt-sDNA) from the perspectives of Integrated Delivery Networks (IDNs) and payers in the United States. Materials and methods: We developed a budget impact and cost-consequence model that simulates CRC screening for eligible 50- to 75-year-old adults. A status quo scenario and an increased mt-sDNA scenario were modeled. The status quo includes the current screening mix of colonoscopy (83%), FIT (11%), and mt-sDNA (6%) modalities. The increased mt-sDNA scenario increases mt-sDNA utilization to 28% over 10 years. Costs for both the IDN and the payer perspectives incorporated diagnostic and surveillance colonoscopies, adverse events (AEs), and CRC treatment. The IDN perspective included screening program costs, composed of direct nonmedical (e.g. patient navigation) and indirect (e.g. administration) costs. It was assumed that IDNs do not incur the costs for stool-based screening tests or bowel preparation for colonoscopies. Results: In a population of one million covered lives, the 10-year incremental cost savings incurred by increasing mt-sDNA utilization was $16.2 M for the IDN and $3.3 M for the payer. The incremental savings per-person-per-month were $0.14 and $0.03 for the IDN and payer, respectively. For both perspectives, increased diagnostic colonoscopy costs were offset by reductions in screening colonoscopies, surveillance colonoscopies, and AEs. Extending screening eligibility to 45- to 75-year-olds slightly decreased the overall cost savings. Limitations: The natural history of CRC was not simulated; however, many of the utilized parameters were extracted from highly vetted natural history models or published literature. Direct nonmedical and indirect costs for CRC screening programs are applied on a per-person-per modality basis, whereas in reality some of these costs may be fixed. Conclusions: Increased mt-sDNA utilization leads to fewer colonoscopies, less AEs, and lower overall costs for both IDNs and payers, reducing overall screening program costs and increasing the number of cancers detected while maintaining screening adherence rates over 10 years.

The human papillomavirus (HPV) vaccines may provide some level of cross‐protection against high‐risk HPV genotypes not directly targeted by the vaccines. We evaluated the long‐term health and economic impacts of routine HPV vaccination using either the nonavalent HPV vaccine or the bivalent HPV vaccine in the context of 48 Gavi‐eligible countries. We used a multi‐modeling approach to compare the bivalent with or without cross‐protection and the nonavalent HPV vaccine. The optimal, that is, most cost‐effective, vaccine was the vaccine with an incremental cost‐effectiveness ratio below the per‐capita gross domestic product (GDP) for each country. By 2100 and assuming 70% HPV vaccination coverage, a bivalent vaccine without cross‐protection, a bivalent vaccine with favorable cross‐protection and the nonavalent vaccine were projected to avert 14.9, 17.2 and 18.5 million cumulative cases of cervical cancer across all 48 Gavi‐eligible countries, respectively. The relative value of the bivalent vaccine compared to the nonavalent vaccine increased assuming a bivalent vaccine conferred high cross‐protection. For example, assuming a cost‐effectiveness threshold of per‐capita GDP, the nonavalent vaccine was optimal in 83% (n = 40) of countries if the bivalent vaccine did not confer cross‐protection; however, the proportion of countries decreased to 63% (n = 30) if the bivalent vaccine conferred high cross‐protection. For lower cost‐effectiveness thresholds, the bivalent vaccine was optimal in a greater proportion of countries, under both cross‐protection assumptions. Although the nonavalent vaccine is projected to avert more cases of cervical cancer, the bivalent vaccine with favorable cross‐protection can prevent a considerable number of cases and would be considered a high‐value vaccine for many Gavi‐eligible countries.

Background: Data to inform evidence-based policy of human papillomavirus (HPV) vaccine delivery strategies in low- and middle-income countries are limited. We examined the cost-effectiveness of campaign compared with routine delivery strategies of adolescent female HPV vaccination in Uganda. Methods: We used a multiple modeling approach that captured HPV transmission, cervical carcinogenesis, and population demographics to project health and economic outcomes associated with HPV vaccination. Costs included vaccination and operational costs and cervical cancer costs over the lifetimes of the current female population in Uganda. Health outcomes included number of cervical cancer cases and disability-adjusted life years (DALY). Incremental cost-effectiveness ratios (i.e., cost per DALY averted) were calculated and compared against gross domestic product (GDP) per capita. Results: Compared with routine HPV vaccination of 9-year-old girls at 70% coverage, campaign vaccination yielded greater health benefits if campaigns occurred frequently and targeted a wide age range. Campaign delivery strategies were both less costly and more effective than routine HPV vaccination. Campaign vaccination of 9- to 30-year-old girls/women at a 3-year frequency (40% coverage) was considered cost-effective compared with the GDP per capita threshold for Uganda ($674 in U.S. 2015 dollars). Conclusions: We projected that campaign HPV vaccination would provide substantial population health benefits compared with routine vaccination. Expanding the target age range of campaign vaccination up to age 30 years may be an efficient strategy, depending on the achievable coverage level and campaign frequency. Impact: In settings where routine health systems infrastructure may be limited, reaching adolescent populations with a campaign delivery strategy may be an efficient use of resources.

Women with HIV face an increased risk of human papillomavirus (HPV) acquisition and persistence, cervical intraepithelial neoplasia, and invasive cervical cancer. Our objective was to determine the cost-effectiveness of different cervical cancer screening strategies among women with HIV in South Africa.We modified a mathematical model of HPV infection and cervical disease to reflect coinfection with HIV. The model was calibrated to epidemiologic data from HIV-infected women in South Africa. Clinical and economic data were drawn from in-country data sources. The model was used to project reductions in the lifetime risk of cervical cancer and incremental cost-effectiveness ratios (ICERs) of Pap and HPV DNA screening and management algorithms beginning at HIV diagnosis, at 1-, 2-, or 3-year intervals. Strategies with an ICER below South Africa's 2016 per capita gross domestic product (US$5270) were considered "cost-effective."HPV testing followed by treatment (test-and-treat) at 2-year intervals was the most effective strategy that was also cost-effective, reducing lifetime cancer risk by 56.6% with an ICER of US$3010 per year of life saved. Other cost-effective strategies included Pap (referral threshold: HSIL+) at 1-, 2-, and 3-year intervals, and HPV test-and-treat at 3-year intervals. Pap (ASCUS+), HPV testing with 16/18 genotyping, and HPV testing with Pap or visual triage of HPV-positive women were less effective and more costly than alternatives.Considering per capita gross domestic product as the benchmark for cost-effectiveness, HPV test-and-treat is optimal in South Africa. At lower cost-effectiveness benchmarks, Pap (HSIL+) would be optimal.

Background Cervical cancer is the leading cause of cancer death for women in Uganda, despite the potential for prevention through organised screening. Community-based self-collected human papillomavirus (HPV) testing has been proposed to reduce barriers to screening. Objective Our objective was to evaluate the cost-effectiveness of the Advances in Screening and Prevention of Reproductive Cancers (ASPIRE) trial, conducted in Kisenyi, Uganda in April 2014 (n=500). The trial compared screening uptake and compliance with follow-up in two arms: (1) community-based (ie, home or workplace) self-collected HPV testing (facilitated by community health workers) with clinic-based visual inspection with acetic acid (VIA) triage of HPV-positive women (‘HPV-VIA’) and (2) clinic-based VIA (‘VIA’). In both arms, VIA was performed at the local health unit by midwives with VIA-positive women receiving immediate treatment with cryotherapy. Design We informed a Monte Carlo simulation model of HPV infection and cervical cancer with screening uptake, compliance and retrospective cost data from the ASPIRE trial; additional cost, test performance and treatment effectiveness data were drawn from observational studies. The model was used to assess the cost-effectiveness of each arm of ASPIRE, as well as an HPV screen-and-treat strategy (‘HPV-ST’) involving community-based self-collected HPV testing followed by treatment for all HPV-positive women at the clinic. Outcome measures The primary outcomes were reductions in cervical cancer risk and incremental cost-effectiveness ratios (ICERs), expressed in dollars per year of life saved (YLS). Results HPV-ST was the most effective and cost-effective screening strategy, reducing the lifetime absolute risk of cervical cancer from 4.2% (range: 3.8%–4.7%) to 3.5% (range: 3.2%–4%), 2.8% (range: 2.4%–3.1%) and 2.4% (range: 2.1%–2.7%) with ICERs of US$130 (US$110–US$150) per YLS, US$240 (US$210–US$280) per YLS, and US$470 (US$410–US$550) per YLS when performed one, three and five times per lifetime, respectively. Findings were robust across sensitivity analyses, unless HPV costs were more than quadrupled. Conclusions Community-based self-collected HPV testing followed by treatment for HPV-positive women has the potential to be an effective and cost-effective screening strategy.

India has the highest burden of cervical cancer in the world. To estimate the consequences of delaying implementation of organized cervical cancer screening, we projected the avertable burden of disease under different implementation scenarios of a screening program. We used an individual‐based microsimulation model of human papillomavirus (HPV) infection and cervical cancer calibrated to epidemiologic data from India to project age‐specific cancer incidence and mortality reductions associated with screening (once‐in‐a‐lifetime among women aged 30–34 years) with one‐visit visual inspection with acetic acid (VIA) and one‐ and two‐visit HPV DNA testing. We then applied these reductions to a population model to project the lifetime cervical cancer cases and deaths averted under different implementation scenarios taking place from 2017 to 2026: (1) immediate implementation of screening with currently available screening tests (one‐visit VIA, two‐visit HPV testing); (2) immediate implementation of screening with currently available screening tests, with a switch to point‐of‐care one‐visit HPV testing in 5 years; and (3) 5‐year delayed implementation of screening with current screening tests or point‐of‐care HPV testing. Immediate implementation of two‐visit HPV testing with a switch to one‐visit HPV testing averted 574,100 cases and 382,500 deaths over the lifetimes of 81.4 million 30‐ to 34‐year‐old women screened once between 2017 and 2026. Delayed implementation with a one‐visit HPV test averted 209,300 cases and 139,100 deaths. Delaying implementation of screening programs in high‐burden settings will result in substantial morbidity and mortality among women beyond the age for adolescent HPV vaccination., What's new? Nearly one‐quarter of cervical cancer cases worldwide occur in India. Nonetheless, while the disease can be prevented through screening for precancerous lesions, very few Indian women receive Pap tests. Here, the authors estimated cervical cancer burden in India assuming different screening program implementation scenarios, including immediate implementation with both one‐visit VIA and two‐visit human papillomavirus (HPV) testing and delayed implementation with a one‐visit HPV test. Models showed that immediate implementation of two‐visit HPV testing averted more than double the number of cases and deaths from cervical cancer among 30‐ to 34‐year‐old women compared with delayed implementation with one‐visit HPV testing.

To estimate the health impact, financial costs, and cost-effectiveness of scaling-up coverage of human papillomavirus (HPV) vaccination (young girls) and cervical cancer screening (women of screening age) for women in countries that will likely need donor assistance.We used a model-based approach to synthesize population, demographic, and epidemiological data from 50 low- and lower-middle-income countries. Models were used to project the costs (US $), lifetime health impact (cervical cancer cases, deaths averted), and cost-effectiveness (US $ per disability adjusted life year [DALY] averted) of: (1) two-dose HPV-16/18 vaccination of girls aged 10 years; (2) once-in-a-lifetime screening, with treatment when needed, of women aged 35 years with either HPV DNA testing or visual inspection with acetic acid (VIA); and (3) cervical cancer treatment over a 10-year roll-out.We estimated that both HPV vaccination and screening would be very cost-effective, and a comprehensive program could avert 5.2 million cases, 3.7 million deaths, and 22.0 million DALYs over the lifetimes of the intervention cohorts for a total 10-year program cost of US $3.2 billion.Investment in HPV vaccination of young girls and cervical cancer screen-and-treat programs in low- and lower-middle-income countries could avert a substantial burden of disease while providing good value for public health dollars.

Importance Evidence on the relative benefits and harms of primary high-risk human papillomavirus (hrHPV) testing is needed to inform guidelines. Objective To inform the US Preventive Services Task Force by modeling the benefits and harms of various cervical cancer screening strategies. Design, Setting, and Participants Microsimulation model of a hypothetical cohort of women initiating screening at age 21 years. Exposures Screening with cytology, hrHPV testing, and cytology and hrHPV cotesting, varying age to switch from cytology to hrHPV testing or cotesting (25, 27, 30 years), rescreening interval (3, 5 years), and triage options for hrHPV-positive results (16/18 genotype, cytology testing). Current guidelines-based screening strategies comprised cytology alone every 3 years starting at age 21 years, with or without a switch to cytology and hrHPV cotesting every 5 years from ages 30 to 65 years. Complete adherence for all 19 strategies was assumed. Main Outcomes and Measures Lifetime number of tests, colposcopies, disease detection, false-positive results, cancer cases and deaths, life-years, and efficiency ratios expressing the trade-off of harms (ie, colposcopies, tests) vs benefits (life-years gained, cancer cases averted). Efficient strategies were those that yielded more benefit and less harm than another strategy or a lower harm to benefit ratio than a strategy with less harms. Results Compared with no screening, all modeled cervical cancer screening strategies were estimated to result in substantial reductions in cancer cases and deaths and gains in life-years. The effectiveness of screening across the different strategies was estimated to be similar, with primary hrHPV-based and alternative cotesting strategies having slightly higher effectiveness and greater harms than current guidelines-based cytology testing. For example, cervical cancer deaths associated with the guidelines-based strategies ranged from 0.30 to 0.76 deaths per 1000 women, whereas new strategies involving primary hrHPV testing or cotesting were associated with fewer cervical cancer deaths, ranging from 0.23 to 0.29 deaths per 1000 women. In all analyses, primary hrHPV testing strategies occurring at 5-year intervals were efficient. For example, 5-year primary hrHPV testing (cytology triage) based on switching from cytology to hrHPV screening at ages 30 years, 27 years, and 25 years had ratios per life-year gained of 73, 143, and 195 colposcopies, respectively. In contrast, strategies involving 3-year hrHPV testing had much higher ratios, ranging from 2188 to 3822 colposcopies per life-year gained. In most analyses, strategies involving cotesting were not efficient. Conclusions and Relevance In this microsimulation modeling study, it was estimated that primary hrHPV screening may represent a reasonable balance of harms and benefits when performed every 5 years. Switching from cytology to hrHPV testing at age 30 years yielded the most efficient harm to benefit ratio when using colposcopy as a proxy for harms.

Background Patient encounters are the core learning activity of Australian general practice (family practice) training. Exposure to patient demographics and presentations may vary from one general practice registrar (vocational trainee) to another. This can affect comprehensiveness of training. Currently, there is no mechanism to systematically capture the content of GP registrar consultations. The aim of the Registrar Clinical Encounters in Training (ReCEnT) study is to document longitudinally the nature and associations of consultation-based clinical and educational experiences of general practice registrars. Methods/design This is an ongoing prospective multi-site cohort study of general practice registrars’ consultations, entailing paper-based recording of consultation data. The study setting is general practices affiliated with three geographically-based Australian general practice regional training providers. Registrars record details of 60 consecutive consultations. Data collected includes registrar demographics, details of the consultation, patient demographics, reasons for encounter and problems managed. Problems managed are coded with the International Classification of Primary Care (second edition) classification system. Additionally, registrars record educational factors related to the encounter. The study will follow the clinical exposure of each registrar six-monthly over the 18 months to two years (full-time equivalent) of their general practice training program. Conclusions The study will provide data on a range of factors (patient, registrar and consultation factors). This data will be used to inform a range of educational decisions as well as being used to answer educational research questions. We plan to use ReCEnT as a formative assessment tool for registrars and help identify and address educational needs. The study will facilitate program evaluation by the participating training providers and thus improve articulation of educational programs with practice experience. From the research point of view it will address an evidence gap – the in-practice clinical and educational experience of general practice trainees, determinants of these experiences, and the determinants of registrars’ patterns of practice (for example, prescribing practice) over the course of their training.

Background. Increasing the recruitment of doctors, including general practitioners (GPs), to rural areas is recognised as a health priority internationally. Australian GP trainees (registrars) complete a mandatory minimum of 6 months training in a rural area. The rationale for this includes the expectation of increased likelihood of a future choice of rural practice location. Method. A qualitative study employing semistructured in-depth interviews and a modified grounded methodology. Participants were 15 registrars from an Australian GP postgraduate training program. Results. Though generally a rewarding clinical learning experience, negative aspects of the rural placement included the disruption to personal lives of rural relocation and the stresses involved in higher levels of clinical responsibility. These stressors could undermine rather than enhance clinical confidence. Anxiety and depression were accompaniments for some registrars. Intention to practice rurally was little influenced by this compulsory placement. Conclusions. Findings of positive effects on rural practice destination in studies of medical undergraduates should not be generalised to GP registrars. The positive clinical learning experience of most registrars in rural terms must be balanced with the social dislocation involved in rural relocation and the adverse effects of the rural experience, for some registrars, on professional confidence and psychological well being. What is known about the topic? The rationale for compulsory rural placements during general practitioner vocational training includes an assumption that this will increase rural GP workforce. Undergraduate training in rural environments is known to enhance recruitment to rural practice. What does this paper add? Despite considerable positive educational and training outcomes for many registrars, compulsory rural training placements cause significant social dislocation for many registrars and were in this study associated with psychological morbidity in some registrars. Placements are unlikely to significantly increase rural GP workforce. What are the implications for practitioners? Compulsory rural placements can be a negative experience for GP registrars. Findings of positive effects of rural training experience on career intentions and rural workplace destination in studies of medical undergraduates should not be generalised to compulsory rural placements for general practice registrars.

The possibility of the transmission of anthrax to the fetus of pregnant animals following the inoculation of these animals with anthrax cultures was denied for many years. Pollender, Brauell, Davaine, Bollinger, Wolff and others contended, as a result of experimental work, that the placenta of the experimental animals used afforded an impermeable barrier against this micro-organism. To Strauss and Chamberland1must be given the credit for proving that intra-uterine infection may be induced experimentally in animals. These investigators, by the use of modern methods (cultures and animal inoculation of these cultures), were able to prove that the placental barrier was not as impermeable as previous workers believed, and that while not constantly, yet in a good proportion of experiments, infection of the fetus could be produced. Subsequently, other writers confirmed these conclusions, using various animals (guinea-pigs, dogs, pigs) for inoculation. There are extremely few reports in the literature of

The characteristics of the spinal fluid in postdiphtheric paralysis has received scant attention in our own literature. There were no observations published in this country, as far as we could ascertain, until the report made previously by one of us (J. C. R.). Foreign workers, especially French clinicians, have published their investigations in a small number of cases. There has not been accumulated as yet, however, a sufficient amount of information on the subject to establish conclusively the cytologic and chemical alteration, if any, which may be encountered. An exact knowledge of the condition of the spinal fluid in postdiphtheric paralysis is of some importance for two reasons: first, to determine the presence or absence of a reaction on the part of the meninges to the toxins of the diphtheria bacillus, and second, to assist in the differential diagnosis of this condition from certain other diseases which may be accompanied