scholarly journals Non-pharmaceutical interventions, vaccination and the Delta variant: epidemiological insights from modelling England’s COVID-19 roadmap out of lockdown

Author(s):  
Raphael Sonabend ◽  
Lilith K. Whittles ◽  
Natsuko Imai ◽  
Pablo N Perez-Guzman ◽  
Edward S Knock ◽  
...  

AbstractBackgroundEngland’s COVID-19 “roadmap out of lockdown” set out the timeline and conditions for the stepwise lifting of non-pharmaceutical interventions (NPIs) as vaccination roll-out continued. Here we assess the roadmap, the impact of the Delta variant, and potential future epidemic trajectories.MethodsWe extended a model of SARS-CoV-2 transmission to incorporate vaccination and multi-strain dynamics to explicitly capture the emergence of the Delta variant. We calibrated the model to English surveillance data using a Bayesian evidence synthesis framework, then modelled the potential trajectory of the epidemic for a range of different schedules for relaxing NPIs.FindingsThe roadmap was successful in offsetting the increased transmission resulting from lifting NPIs with increasing population immunity through vaccination. However due to the emergence of Delta, with an estimated transmission advantage of 73% (95%CrI: 68-79) over Alpha, fully lifting NPIs on 21 June 2021 as originally planned may have led to 3,400 (95%CrI: 1,300-4,400) peak daily hospital admissions under our central parameter scenario. Delaying until 19 July reduced peak hospitalisations by three-fold to 1,400 (95%CrI: 700-1,500) per day. There was substantial uncertainty in the epidemic trajectory, with particular sensitivity to estimates of vaccine effectiveness and the intrinsic transmissibility of Delta.InterpretationOur findings show that the risk of a large wave of COVID hospitalisations resulting from lifting NPIs can be substantially mitigated if the timing of NPI relaxation is carefully balanced against vaccination coverage. However, with Delta, it may not be possible to fully lift NPIs without a third wave of hospitalisations and deaths, even if vaccination coverage is high. Variants of concern, their transmissibility, vaccine uptake, and vaccine effectiveness must be carefully monitored as countries relax pandemic control measures.FundingNational Institute for Health Research, UK Medical Research Council, Wellcome Trust, UK Foreign, Commonwealth & Development Office.Research in contextEvidence before this studyWe searched PubMed up to 23 July 2021 with no language restrictions using the search terms: (COVID-19 or SARS-CoV-2 or 2019-nCoV or “novel coronavirus”) AND (vaccine or vaccination) AND (“non pharmaceutical interventions” OR “non-pharmaceutical interventions) AND (model*). We found nine studies that analysed the relaxation of controls with vaccination roll-out. However, none explicitly analysed real-world evidence balancing lifting of interventions, vaccination, and emergence of the Delta variant.Added value of this studyOur data synthesis approach combines real-world evidence from multiple data sources to retrospectively evaluate how relaxation of COVID-19 measures have been balanced with vaccination roll-out. We explicitly capture the emergence of the Delta variant, its transmissibility over Alpha, and quantify its impact on the roadmap. We show the benefits of maintaining NPIs whilst vaccine coverage continues to increase and capture key uncertainties in the epidemic trajectory after NPIs are lifted.Implications of all the available evidenceOur study shows that lifting interventions must be balanced carefully and cautiously with vaccine roll-out. In the presence of a new, highly transmissible variant, vaccination alone may not be enough to control COVID-19. Careful monitoring of vaccine uptake, effectiveness, variants, and changes in contact patterns as restrictions are lifted will be critical in any exit strategy.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
David A. Jenkins ◽  
Humaira Hussein ◽  
Reynaldo Martina ◽  
Pascale Dequen-O’Byrne ◽  
Keith R. Abrams ◽  
...  

Abstract Background Network Meta-Analysis (NMA) is a key component of submissions to reimbursement agencies world-wide, especially when there is limited direct head-to-head evidence for multiple technologies from randomised controlled trials (RCTs). Many NMAs include only data from RCTs. However, real-world evidence (RWE) is also becoming widely recognised as a valuable source of clinical data. This study aims to investigate methods for the inclusion of RWE in NMA and its impact on the level of uncertainty around the effectiveness estimates, with particular interest in effectiveness of fingolimod. Methods A range of methods for inclusion of RWE in evidence synthesis were investigated by applying them to an illustrative example in relapsing remitting multiple sclerosis (RRMS). A literature search to identify RCTs and RWE evaluating treatments in RRMS was conducted. To assess the impact of inclusion of RWE on the effectiveness estimates, Bayesian hierarchical and adapted power prior models were applied. The effect of the inclusion of RWE was investigated by varying the degree of down weighting of this part of evidence by the use of a power prior. Results Whilst the inclusion of the RWE led to an increase in the level of uncertainty surrounding effect estimates in this example, this depended on the method of inclusion adopted for the RWE. ‘Power prior’ NMA model resulted in stable effect estimates for fingolimod yet increasing the width of the credible intervals with increasing weight given to RWE data. The hierarchical NMA models were effective in allowing for heterogeneity between study designs, however, this also increased the level of uncertainty. Conclusion The ‘power prior’ method for the inclusion of RWE in NMAs indicates that the degree to which RWE is taken into account can have a significant impact on the overall level of uncertainty. The hierarchical modelling approach further allowed for accommodating differences between study types. Consequently, further work investigating both empirical evidence for biases associated with individual RWE studies and methods of elicitation from experts on the extent of such biases is warranted.


Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1607-P
Author(s):  
MAYU HAYASHI ◽  
KATSUTARO MORINO ◽  
KAYO HARADA ◽  
MIKI ISHIKAWA ◽  
ITSUKO MIYAZAWA ◽  
...  

Author(s):  
Marta Torres-Ferrús ◽  
Victor J. Gallardo ◽  
Alicia Alpuente ◽  
Edoardo Caronna ◽  
Eulalia Gine-Cipres ◽  
...  

2020 ◽  
Vol 8 (1) ◽  
pp. e000985 ◽  
Author(s):  
Jeff Yufeng Yang ◽  
Tiansheng Wang ◽  
Virginia Pate ◽  
John B Buse ◽  
Til Stürmer

BackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with increased occurrence of Fournier’s gangrene (FG), a rare but serious form of necrotizing fasciitis, leading to a warning from the Food and Drug Administration. Real-world evidence on FG is needed to validate this warning.MethodsWe used data from IBM MarketScan (2013–2017) to compare the incidence of FG among adult patients who initiated either SGLT2i, a dipeptidyl peptidase-4 inhibitor (DPP4i), or any non-SGLT2i antihyperglycemic medication. FG was defined using inpatient International Classification of Diseases, Ninth Edition and Tenth Edition diagnosis codes 608.83 and N49.3, respectively, combined with procedure codes for debridement, surgery, or systemic antibiotics. We estimated crude incidence rates (IRs) using Poisson regression, and crude and adjusted HRs (aHR) and 95% CIs using standardized mortality ratio-weighted Cox proportional hazards models. Sensitivity analyses examined the impact of alternative outcome definitions.ResultsWe identified 211 671 initiators of SGLT2i (n=93 197) and DPP4i (n=118 474), and 305 329 initiators of SGLT2i (n=32 868) and non-SGLT2i (n=272 461). Crude FG IR ranged from 3.2 to 3.8 cases per 100 000 person-years during a median follow-up of 0.51–0.58 years. Compared with DPP4i, SGLT2i initiation was not associated with increased risk of FG for any outcome definition, with aHR estimates ranging from 0.25 (0.04–1.74) to 1.14 (0.86–1.51). In the non-SGLT2i comparison, we observed an increased risk of FG for SGLT2i initiators when using FG diagnosis codes alone, using all diagnosis settings (aHR 1.80; 0.53–6.11) and inpatient diagnoses only (aHR 4.58; 0.99–21.21).ConclusionsNo evidence of increased risk of FG associated with SGLT2i was observed compared with DPP4i, arguably the most relevant clinical comparison. However, uncertainty remains based on potentially higher risk in the broader comparison with all non-SGLT2i antihyperglycemic agents and the rarity of FG.Trial registration numberEUPAS Register Number 30018.


2019 ◽  
Vol 14 (10) ◽  
pp. S588
Author(s):  
C. Pettengell ◽  
J. Law ◽  
L. Le ◽  
M. Sung ◽  
S. Lau ◽  
...  

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S664-S665
Author(s):  
J Kearns ◽  
L Scullion ◽  
C Masterson ◽  
N Kennedy ◽  
C Butcher

Abstract Background Budesonide MMX is indicated for the induction of remission in mild to moderate Ulcerative Colitis (UC) patients when 5-ASA treatment is not sufficient. Unlike traditional first-generation glucocorticoid steroids such as prednisolone, budesonide MMX has demonstrated a robust safety profile, comparable to placebo in several randomised controlled trials1,2,3. There is however limited real-world evidence to substantiate this safety claim in clinical practice. The aim of this observational analysis is to evaluate the tolerability and ease of administration of budesonide MMX in the real-world setting using prednisolone as a benchmark. Methods Patients receiving treatment for mild to moderate UC were identified in 3 treatment centres between April and October 2019. After providing privacy and data consent, patients completed a detailed nurse-led questionnaire regarding their experiences with prednisolone treatment. Following 6 weeks of therapy with budesonide MMX, patients were sent a follow-up questionnaire. Data from both the initial and subsequent questionnaires were entered by the nurse into a database for assimilation and analysis. Results Twenty-eight patients completed initial and follow-up questionnaires. Of these, 78.6% (n = 22) had experienced ≥1 prednisolone-related side effects. In comparison, following treatment with budesonide MMX, 21.4% (n = 6) reported ≥1 side effects. Instances of these side effects are shown in Figure 1. 46.4% of patients (n = 13) reported the impact of prednisolone-related side effects on daily life as moderate or severe vs. 7.1% (n = 2) following treatment with budesonide MMX. By week 2 of treatment with budesonide MMX, rectal bleeding was resolved in 32.1% of patients (n = 9) and stool frequency in 35.7% (n = 10). 93.1% (n = 27) found the instructions to take budesonide MMX given by the health care professional very easy to understand and of those expressing a preference, 71.1% of patients (n = 19) would take budesonide MMX again if prescribed. Additional data will be presented. Conclusion Data from this ‘real-world’ observational study appear to support the safely profile of budesonide MMX reported in clinical trials. The incidence of patients who experienced > 1 side-effect was nearly 4 times lower for budesonide vs. prednisolone. In addition, budesonide MMX therapy was acceptable to the majority of patients and accompanying instructions easy to understand. Additional data will be presented. References


Vaccine ◽  
2020 ◽  
Vol 38 (6) ◽  
pp. 1345-1351 ◽  
Author(s):  
Madleen Orumaa ◽  
Susanne K. Kjaer ◽  
Christian Dehlendorff ◽  
Christian Munk ◽  
Anne Olaug Olsen ◽  
...  

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
A Lahchaichi ◽  
M Ben Hadj ◽  
H Bouguerra ◽  
K Talmoudi ◽  
A Bahrini ◽  
...  

Abstract Introduction Vaccination against hepatitis B represents the most effective preventive measure to reduce the global impact of this infection. In Tunisia hepatitis B vaccination was introduced for health professionals in 1992 and for the general population in 1995. The objectives of this study were to evaluate the impact of vaccination twenty years after its introduction. Methods It was a descriptive study of data provided by the national survey of prevalence of Hepatitis B in Tunisia, which was a household-based study conducted in 2015. Blood samples sent to the reference laboratory to test markers of hepatitis B virus infection. The Vaccine effectiveness rate was calculated using the following formula: VE = 1 - Odds-ratio (OR), where OR = ratio of odds of being vaccinated among subjects with positive HBsAg test results to the odds of being vaccinated among subjects with negative HBsAg test results. Results Approximately a quarter of our population reported having been vaccinated against HBV, a coverage rate of 26.9%. Among subjects above 20 years of age, this rate was 85.3%. Besides, 83.7% of vaccinated subjects had received the three required doses of the HBV vaccine. Analysis of vaccination status by great regions of the country showed that the vaccination coverage rate was higher in the southern region. Regarding HBsAg prevalence, the rate was significantly higher among unvaccinated subjects 0.3% vs 2.2% in those vaccinated (OR = 0.11 [0.07-0.18]). We found that among vaccinated subjects, the serologic response rate at vaccination was only 63.2% which represented 16.2% of the total population. The vaccine effectiveness indicated that vaccination reduced by 88.6% the risk of HBV infection. Conclusions These results demonstrate that vaccination against hepatitis B introduced in the national immunization schedule since 1995 has reduced the infection although the vaccination coverage rate remains below 90%. Key messages Importance of vaccination that reduced by 88.6% the risk of HBV infection. More effort required to raise awareness about vaccination against HBV.


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