scholarly journals Developing a model to predict individualised treatment for gonorrhoea: a modelling study

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e042893
Author(s):  
Lucy Findlater ◽  
Hamish Mohammed ◽  
Maya Gobin ◽  
Helen Fifer ◽  
Jonathan Ross ◽  
...  

ObjectiveTo develop a tool predicting individualised treatment for gonorrhoea, enabling treatment with previously recommended antibiotics, to reduce use of last-line treatment ceftriaxone.DesignA modelling study.SettingEngland and Wales.ParticipantsIndividuals accessing sentinel health services.InterventionDeveloping an Excel model which uses participants’ demographic, behavioural and clinical characteristics to predict susceptibility to legacy antibiotics. Model parameters were calculated using data for 2015–2017 from the Gonococcal Resistance to Antimicrobials Surveillance Programme.Main outcome measuresEstimated number of doses of ceftriaxone saved, and number of people delayed effective treatment, by model use in clinical practice. Model outputs are the predicted risk of resistance to ciprofloxacin, azithromycin, penicillin and cefixime, in groups of individuals with different combinations of characteristics (gender, sexual orientation, number of recent sexual partners, age, ethnicity), and a treatment recommendation.ResultsBetween 2015 and 2017, 8013 isolates were collected: 64% from men who have sex with men, 18% from heterosexual men and 18% from women. Across participant subgroups, stratified by all predictors, resistance prevalence was high for ciprofloxacin (range: 11%–51%) and penicillin (range: 6%–33%). Resistance prevalence for azithromycin and cefixime ranged from 0% to 13% and for ceftriaxone it was 0%. Simulating model use, 88% of individuals could be given cefixime and 10% azithromycin, saving 97% of ceftriaxone doses, with 1% of individuals delayed effective treatment.ConclusionsUsing demographic and behavioural characteristics, we could not reliably identify a participant subset in which ciprofloxacin or penicillin would be effective. Cefixime resistance was almost universally low; however, substituting ceftriaxone for near-uniform treatment with cefixime risks re-emergence of resistance to cefixime and ceftriaxone. Several subgroups had low azithromycin resistance, but widespread azithromycin monotherapy risks resistance at population level. However, this dataset had limitations; further exploration of individual characteristics to predict resistance to a wider range of legacy antibiotics may still be appropriate.

Author(s):  
Shaun Bowler

This chapter analyzes to what extent variation in political institutions affects political support. The chapter observes that the existing research is not always clear on which institutions should produce what kind of effect, although a general expectation is that institutional arrangements improve political support when they give citizens an increased sense of connection to the political process. In general then, we should expect institutions that strengthen the quality of representation to strengthen political support. This general expectation is specified in six hypotheses that are tested using data from the ESS 2012. The chapter demonstrates that electoral systems that provide voters with more choice about candidates, multiparty governments, and “responsive” legislatures, correlate positively with political support. However, compared to other macro-level factors and individual characteristics, the effects of political institutions on political support are modest. The chapter concludes that the prospects for institutional reform to strengthen political support are limited.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1516
Author(s):  
Daniel Gratz ◽  
Alexander J Winkle ◽  
Seth H Weinberg ◽  
Thomas J Hund

The voltage-gated Na+ channel Nav1.5 is critical for normal cardiac myocyte excitability. Mathematical models have been widely used to study Nav1.5 function and link to a range of cardiac arrhythmias. There is growing appreciation for the importance of incorporating physiological heterogeneity observed even in a healthy population into mathematical models of the cardiac action potential. Here, we apply methods from Bayesian statistics to capture the variability in experimental measurements on human atrial Nav1.5 across experimental protocols and labs. This variability was used to define a physiological distribution for model parameters in a novel model formulation of Nav1.5, which was then incorporated into an existing human atrial action potential model. Model validation was performed by comparing the simulated distribution of action potential upstroke velocity measurements to experimental measurements from several different sources. Going forward, we hope to apply this approach to other major atrial ion channels to create a comprehensive model of the human atrial AP. We anticipate that such a model will be useful for understanding excitability at the population level, including variable drug response and penetrance of variants linked to inherited cardiac arrhythmia syndromes.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Mendez-Lopez ◽  
D Stuckler ◽  
T Noori ◽  
J C Semenza

Abstract Background Syphilis transmission has increased markedly over the past two decades in Europe, concentrated in men who have sex with men. We test alternative potential social and behavioral individual- and population-level determinants of this resurgence. Methods Two rounds of the cross-sectional European Men who have sex with men Internet Survey (EMIS 2010 and 2017, n = 272,902) were used to fit multi-level linear probability models to evaluate determinants of the incidence of self-reported syphilis, capturing risky sexual behaviours and pre-exposure prophylaxis use, among others, adjusting for potential sociodemographic confounders. Results Self-reported syphilis incidence rates rose by about 1.8 percentage points (within the last 12 months) and 3.9 (within the last 5 years) between the 2010 and 2017 waves, after adjusting for sociodemographic factors. HIV status was a major risk factor for syphilis infection (27.6 ppt higher incident rate, 95%CI: 24.7 to 30.5). A dose-response relationship was observed between greater numbers of condomless non-steady partners and syphilis infection, with more than 10 partners estimating increases in the probability of diagnosis of over 25 ppt (11-20 partners vs none: 24.5 ppt, 95%CI: 20.5 to 28.5); further, we observed evidence of mediation for number of condomless non-steady partners, which attenuated the estimated rise in 2017 vs 2010 by about 35%. STI testing uptake also accounted for a substantial increase in syphilis incidence signaling higher detection rates over time. While country-level PrEP use was linked to greater number of condomless partners, there was no substantial impact of population-wide factors, including GDP and PrEP use, on overall syphilis trends. Conclusions Risky sexual behavior changes, particularly condomless sex with non-steady partners, appears to be a major contributing factor to rising syphilis incidence. Further research is needed to understand what accounts for this substantial behavior change. Key messages Increased number of condomless non-steady partners accounts for a substantial rise in syphilis trends. Population-level PrEP use was linked to increasing numbers of condomless non-steady partners but had no substantial impact on overall syphilis trends.


Author(s):  
Josefine Atzendorf ◽  
Stefan Gruber

AbstractEpidemic control measures that aim to introduce social distancing help to decelerate the spread of the COVID-19 pandemic. However, their consequences in terms of mental well-being might be negative, especially for older adults. While existing studies mainly focus on the time during the first lockdown, we look at the weeks afterward in order to measure the medium-term consequences of the first wave of the pandemic. Using data from the SHARE Corona Survey, we include retired respondents aged 60 and above from 25 European countries plus Israel. Combining SHARE data with macro-data from the Oxford COVID-19 Government Response Tracker allows us to include macro-indicators at the country level, namely the number of deaths per 100,000 and the number of days with stringent epidemic control measures, in addition to individual characteristics. The findings show that both macro-indicators are influential for increased feelings of sadness/depression, but that individual factors are crucial for explaining increased feelings of loneliness in the time after the first lockdown. Models with interaction terms reveal that the included macro-indicators have negative well-being consequences, particularly for the oldest survey participants. Additionally, the results reveal that especially those living alone had a higher risk for increased loneliness in the time after the first COVID-19 wave.


Holzforschung ◽  
2010 ◽  
Vol 64 (4) ◽  
Author(s):  
J. Paul McLean ◽  
Robert Evans ◽  
John R. Moore

Abstract Sitka spruce (Picea sitchensis) is the most widely planted commercial tree species in the United Kingdom and Ireland. Because of the increasing use of this species for construction, the ability to predict wood stiffness is becoming more important. In this paper, a number of models are developed using data on cellulose abundance and orientation obtained from the SilviScan-3 system to predict the longitudinal modulus of elasticity (MOE) of small defect-free specimens. Longitudinal MOE was obtained from both bending tests and a sonic resonance technique. Overall, stronger relationships were found between the various measures of cellulose abundance and orientation and the dynamic MOE obtained from the sonic resonance measurements, rather than with the static MOE obtained from bending tests. There was only a moderate relationship between wood bulk density and dynamic MOE (R2=0.423), but this relationship was improved when density was divided by microfibril angle (R2=0.760). The best model for predicting both static and dynamic MOE involved the product of bulk density and the coefficient of variation in the azimuthal intensity profile (R2=0.725 and 0.862, respectively). The model parameters obtained for Sitka spruce differed from those obtained in earlier studies on Pinus radiata and Eucalyptus delegatensis, indicating that the model might require recalibration before it can be applied to different species.


2018 ◽  
Vol 5 (6) ◽  
Author(s):  
Jonathan Colasanti ◽  
Jeri Sumitani ◽  
C Christina Mehta ◽  
Yiran Zhang ◽  
Minh Ly Nguyen ◽  
...  

Abstract Background Rapid entry programs (REPs) improve time to antiretroviral therapy (ART) initiation (TAI) and time to viral suppression (TVS). We assessed the feasibility and effectiveness of a REP in a large HIV clinic in Atlanta, Georgia, serving a predominately un- or underinsured population. Methods The Rapid Entry and ART in Clinic for HIV (REACH) program was implemented on May 16, 2016. We performed a retrospective cohort study with the main independent variable being period of enrollment: January 1, 2016, through May 15, 2016 (pre-REACH); May 16, 2016, through July 31, 2016 (post-REACH). Included individuals were HIV-infected and new to the clinic with detectable HIV-1 RNA. Six-month follow-up data were collected for each participant. Survival analyses were conducted for TVS. Logistic and linear regression analyses were used to evaluate secondary outcomes: attendance at first clinic visit, viral suppression, TAI, and time to first attended provider visit. Results There were 117 pre-REACH and 90 post-REACH individuals. Median age (interquartile range [IQR]) was 35 (25–45) years, 80% were male, 91% black, 60% men who have sex with men, 57% uninsured, and 44% active substance users. TVS decreased from 77 (62–96) to 57 (41–70) days (P < .0022). Time to first attended provider visit decreased from 17 to 5 days, and TAI from 21 to 7 days (P < .0001), each remaining significant in adjusted models. Conclusions This is the largest rapid entry cohort described in the United States and suggests that rapid entry is feasible and could have a positive impact on HIV transmission at the population level.


2017 ◽  
Vol 4 (7) ◽  
pp. e311-e320 ◽  
Author(s):  
Steven M Goodreau ◽  
Eli S Rosenberg ◽  
Samuel M Jenness ◽  
Nicole Luisi ◽  
Sarah E Stansfield ◽  
...  

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