Absence of evidence or evidence of absence - a review of the evidence for hydroxychloroquine as a potential candidate for prophylaxis against COVID-19

Clinical trials are investigating several agents as potential options for pre-exposure prophylaxis and post-exposure prophylaxis to prevent infection with COVID-19. A particular focus has been high risk groups including healthcare workers. Chloroquine (CQ) and hydroxychloroquine (HCQ) are the predominant agents in terms of numbers of clinical trials listed on Clinicaltrials.gov. However, CQ/HCQ have not been proven as an effective treatment option for COVID-19, and it is currently unclear what benefit, if any, is available to support their use in a prophylactic role. Four randomised control trials have been published so far which have examined the effect of HCQ as pre-exposure (PrEP) and post-exposure prophylaxis (PEP). This study summarises the evidence to date for HCQ as a potential prophylactic option for PEP and PrEP, presents both the aggregated and disaggregated data and details the gaps in the evidence base. The absolute risk differences for the pre-exposure prophylaxis studies were -0.3% to -2% and for the post prophylaxis studies were -0.6% and -2.4%. There were more adverse events noted in the hydroxychloroquine arms across all four studie

Cost-effectiveness of population-based screening for colorectal cancer: a comparison of guaiac-based faecal occult blood testing, faecal immunochemical testing and flexible sigmoidoscopy.

Several colorectal cancer-screening tests are available, but it is uncertain which provides the best balance of risks and benefits within a screening programme. We evaluated cost-effectiveness of a population-based screening programme in Ireland based on (i) biennial guaiac-based faecal occult blood testing (gFOBT) at ages 55-74, with reflex faecal immunochemical testing (FIT); (ii) biennial FIT at ages 55-74; and (iii) once-only flexible sigmoidoscopy (FSIG) at age 60

Using resource modelling to inform decision making and service planning: the case of colorectal cancer screening in Ireland

Background: Organised colorectal cancer screening is likely to be cost-effective, but cost-effectiveness results alone may not help policy makers to make decisions about programme feasibility or service providers to plan programme delivery. For these purposes, estimates of the impact on the health services of actually introducing screening in the target population would be helpful. However, these types of analyses are rarely reported. As an illustration of such an approach, we estimated annual health service resource requirements and health outcomes over the first decade of a population-based colorectal cancer screening programme in Ireland. Methods: A Markov state-transition model of colorectal neoplasia natural history was used. Three core screening scenarios were considered: (a) flexible sigmoidoscopy (FSIG) once at age 60, (b) biennial guaiac-based faecal occult blood tests (gFOBT) at 55–74 years, and (c) biennial faecal immunochemical tests (FIT) at 55–74 years. Three alternative FIT roll-out scenarios were also investigated relating to age-restricted screening (55–64 years) and staggered age-based roll-out across the 55–74 age group. Parameter estimates were derived from literature review, existing screening programmes, and expert opinion. Results were expressed in relation to the 2008 population (4.4 million people, of whom 700,800 were aged 55–74). Results: FIT-based screening would deliver the greatest health benefits, averting 164 colorectal cancer cases and 272 deaths in year 10 of the programme. Capacity would be required for 11,095-14,820 diagnostic and surveillance colonoscopies annually, compared to 381–1,053 with FSIG-based, and 967–1,300 with gFOBT-based, screening. With FIT, in year 10, these colonoscopies would result in 62 hospital admissions for abdominal bleeding, 27 bowel perforations and one death. Resource requirements for pathology, diagnostic radiology, radiotherapy and colorectal resection were highest for FIT. Estimates depended on screening uptake. Alternative FIT roll-out scenarios had lower resource requirements. Conclusions: While FIT-based screening would quite quickly generate attractive health outcomes, it has heavy resource requirements. These could impact on the feasibility of a programme based on this screening modality. Staggered age-based roll-out would allow time to increase endoscopy capacity to meet programme requirements. Resource modelling of this type complements conventional cost-effectiveness analyses and can help inform policy making and service planning

Additional file 5: Table S5. of Evaluating the neonatal BCG vaccination programme in Ireland

Cost of long term complications of meningitis (PDF 109 kb

Additional file 2: Table S2. of Evaluating the neonatal BCG vaccination programme in Ireland

Resource utilisation and unit cost data for the direct cost estimate for an episode of pulmonary TB. (PDF 113 kb

Additional file 1: Table S1. of Evaluating the neonatal BCG vaccination programme in Ireland

Resource utilisation and unit cost data for the direct cost estimate for an episode of latent TB (LTBI). (PDF 93 kb

Additional file 4: Table S4. of Evaluating the neonatal BCG vaccination programme in Ireland

Resource utilisation and unit cost data for the direct cost estimate for an episode of TB Meningitis (PDF 123 kb

Population-level impact, herd immunity, and elimination after human papillomavirus vaccination: a systematic review and meta-analysis of predictions from transmission-dynamic models

Background Modelling studies have been widely used to inform human papillomavirus (HPV) vaccination policy decisions; however, many models exist and it is not known whether they produce consistent predictions of population-level effectiveness and herd effects. We did a systematic review and meta-analysis of model predictions of the long-term population-level effectiveness of vaccination against HPV 16, 18, 6, and 11 infection in women and men, to examine the variability in predicted herd effects, incremental benefit of vaccinating boys, and potential for HPV-vaccine-type elimination.Methods We searched MEDLINE and Embase for transmission-dynamic modelling studies published between Jan 1, 2009, and April 28, 2015, that predicted the population-level impact of vaccination on HPV 6, 11, 16, and 18 infections in high-income countries. We contacted authors to determine whether they were willing to produce new predictions for standardised scenarios. Strategies investigated were girls-only vaccination and girls and boys vaccination at age 12 years. Base-case vaccine characteristics were 100% efficacy and lifetime protection. We did sensitivity analyses by varying vaccination coverage, vaccine efficacy, and duration of protection. For all scenarios we pooled model predictions of relative reductions in HPV prevalence (RRprev) over time after vaccination and summarised results using the median and 10th and 90th percentiles (80% uncertainty intervals [UI]).Findings 16 of 19 eligible models from ten high-income countries provided predictions. Under base-case assumptions, 40% vaccination coverage and girls-only vaccination, the RRprev of HPV 16 among women and men was 0 . 53 (80% UI 0.46-0.68) and 0.36 (0.28-0.61), respectively, after 70 years. With 80% girls-only vaccination coverage, the RRprev of HPV 16 among women and men was 0.93 (0.90-1.00) and 0.83 (0.75-1.00), respectively. Vaccinating boys in addition to girls increased the RRprev of HPV 16 among women and men by 0.18 (0.13-0.32) and 0.35 (0.27-0.39) for 40% coverage, and 0.07 (0.00-0.10) and 0.16 (0.01-0.25) for 80% coverage, respectively. The RRprev were greater for HPV 6, 11, and 18 than for HPV 16 for all scenarios investigated. Finally at 80% coverage, most models predicted that girls and boys vaccination would eliminate HPV 6, 11, 16, and 18, with a median RRprev of 1.00 for women and men for all four HPV types. Variability in pooled findings was low, but increased with lower vaccination coverage and shorter vaccine protection (from lifetime to 20 years).Interpretation Although HPV models differ in structure, data used for calibration, and settings, our population-level predictions were generally concordant and suggest that strong herd effects are expected from vaccinating girls only, even with coverage as low as 20%. Elimination of HPV 16, 18, 6, and 11 is possible if 80% coverage in girls and boys is reached and if high vaccine efficacy is maintained over time. Copyright (C) The Author(s). Published by Elsevier Ltd