Using artificial intelligence and predictive modelling to enable learning healthcare systems (LHS) for pandemic preparedness.

In anticipation of potential future pandemics, we examined the challenges and opportunities presented by the COVID-19 outbreak. This analysis highlights how artificial intelligence (AI) and predictive models can support both patients and clinicians in managing subsequent infectious diseases, and how legislators and policymakers could support these efforts, to bring learning healthcare system (LHS) from guidelines to real-world implementation. This report chronicles the trajectory of the COVID-19 pandemic, emphasizing the diverse data sets generated throughout its course. We propose strategies for harnessing this data via AI and predictive modelling to enhance the functioning of LHS. The challenges faced by patients and healthcare systems around the world during this unprecedented crisis could have been mitigated with an informed and timely adoption of the three pillars of the LHS: Knowledge, Data and Practice. By harnessing AI and predictive analytics, we can develop tools that not only detect potential pandemic-prone diseases early on but also assist in patient management, provide decision support, offer treatment recommendations, deliver patient outcome triage, predict post-recovery long-term disease impacts, monitor viral mutations and variant emergence, and assess vaccine and treatment efficacy in real-time. A patient-centric approach remains paramount, ensuring patients are both informed and actively involved in disease mitigation strategies.

Improving shared decision making for lung cancer treatment by developing and validating an open-source web based patient decision aid for stage I-II non-small cell lung cancer.

The aim of this study was to develop and evaluate a proof-of-concept open-source individualized Patient Decision Aid (iPDA) with a group of patients, physicians, and computer scientists. The iPDA was developed based on the International Patient Decision Aid Standards (IPDAS). A previously published questionnaire was adapted and used to test the user-friendliness and content of the iPDA. The questionnaire contained 40 multiple-choice questions, and answers were given on a 5-point Likert Scale (1-5) ranging from "strongly disagree" to "strongly agree." In addition to the questionnaire, semi-structured interviews were conducted with patients. We performed a descriptive analysis of the responses. The iPDA was evaluated by 28 computer scientists, 21 physicians, and 13 patients. The results demonstrate that the iPDA was found valuable by 92% (patients), 96% (computer scientists), and 86% (physicians), while the treatment information was judged useful by 92%, 96%, and 95%, respectively. Additionally, the tool was thought to be motivating for patients to actively engage in their treatment by 92%, 93%, and 91% of the above respondents groups. More multimedia components and less text were suggested by the respondents as ways to improve the tool and user interface. In conclusion, we successfully developed and tested an iPDA for patients with stage I-II Non-Small Cell Lung Cancer (NSCLC).

Treatment Effectiveness of Azithromycin and Doxycycline in Uncomplicated Rectal and Vaginal Chlamydia trachomatis Infections in Women: A Multicenter Observational Study (FemCure).

BACKGROUND: Rectal infections with Chlamydia trachomatis (CT) are prevalent in women visiting a sexually transmitted infection outpatient clinic, but it remains unclear what the most effective treatment is. We assessed the effectiveness of doxycycline and azithromycin for the treatment of rectal and vaginal chlamydia in women. METHODS: This study is part of a prospective multicenter cohort study (FemCure). Treatment consisted of doxycycline (100 mg twice daily for 7 days) in rectal CT-positive women, and of azithromycin (1 g single dose) in vaginally positive women who were rectally untested or rectally negative. Participants self-collected rectal and vaginal samples at enrollment (treatment time-point) and during 4 weeks of follow-up. The endpoint was microbiological cure by a negative nucleic acid amplification test at 4 weeks. Differences between cure proportions and 95% confidence intervals (CIs) were calculated. RESULTS: We analyzed 416 patients, of whom 319 had both rectal and vaginal chlamydia at enrollment, 22 had rectal chlamydia only, and 75 had vaginal chlamydia only. In 341 rectal infections, microbiological cure in azithromycin-treated women was 78.5% (95% CI, 72.6%-83.7%; n = 164/209) and 95.5% (95% CI, 91.0%-98.2%; n = 126/132) in doxycycline-treated women (difference, 17.0% [95% CI, 9.6%-24.7%]; P < .001). In 394 vaginal infections, cure was 93.5% (95% CI, 90.1%-96.1%; n = 246/263) in azithromycin-treated women and 95.4% (95% CI, 90.9%-98.2%; n = 125/131) in doxycycline-treated women (difference, 1.9% [95% CI, -3.6% to 6.7%]; P = .504). CONCLUSIONS: The effectiveness of doxycycline is high and exceeds that of azithromycin for the treatment of rectal CT infections in women. CLINICAL TRIALS REGISTRATION: NCT02694497.

Viability-PCR Shows That NAAT Detects a High Proportion of DNA from Non-Viable Chlamydia trachomatis.

OBJECTIVES: According to the current guidelines for laboratory diagnosis of sexually transmitted infections (STIs), nucleic acid amplification tests (NAATs) are the preferred diagnostic method for Chlamydia trachomatis (CT) infections. However, NAATs amplify the available target DNA without discriminating between DNA originating from viable or non-viable CT. Assessing CT viability will provide more insights in the clinical and public health relevance of a CT positive test result. The aim of this study was to technically validate and implement viability-PCR (V-PCR) to asses CT viability. METHODS: Technical validation of V-PCR was performed by the assessment of predefined viability ratios of CT. Samples were subjected to V-PCR which consisted of propidium monoazide (PMA) treatment prior to DNA extraction followed by quantitative PCR (qPCR) targeting the ompA gene for the detection of CT DNA. Finally, V-PCR was applied to vaginal swabs of 50 CT positive patients, as indicated by routine NAAT, collected at our outpatient STD clinics before antimicrobial treatment. RESULTS: Technical validation of V-PCR showed that PMA treatment of heat-inactivated CT culture resulted in an almost complete loss of qPCR signal. PMA treated samples of the fresh viable CT culture showed no marked reduction of PCR signal, indicating that all DNA from viable CT could be detected. Applying V-PCR to clinical samples showed that in 36% of samples (18/50) less than 1% of CT DNA originated from viable bacteria. CONCLUSIONS: V-PCR showed to be a fast and easy method to assess CT viability in clinical samples, without the need of traditional challenging cell culture methods. Furthermore, V-PCR results of clinical samples have indicated that a substantial amount of the amplified CT DNA originated from non-viable cells. Although results might be influenced by cell death during transport, this study suggests that there is a potential overestimation of quantitative CT positivity by currently used NAATs.

Design of the FemCure study: prospective multicentre study on the transmission of genital and extra-genital Chlamydia trachomatis infections in women receiving routine care.

BACKGROUND: In women, anorectal infections with Chlamydia trachomatis (CT) are about as common as genital CT, yet the anorectal site remains largely untested in routine care. Anorectal CT frequently co-occurs with genital CT and may thus often be treated co-incidentally. Nevertheless, post-treatment detection of CT at both anatomic sites has been demonstrated. It is unknown whether anorectal CT may play a role in post-treatment transmission. This study, called FemCure, in women who receive routine treatment (either azithromycin or doxycycline) aims to understand the post-treatment transmission of anorectal CT infections, i.e., from their male sexual partner(s) and from and to the genital region of the same woman. The secondary objective is to evaluate other reasons for CT detection by nucleic acid amplification techniques (NAAT) such as treatment failure, in order to inform guidelines to optimize CT control. METHODS: A multicentre prospective cohort study (FemCure) is set up in which genital and/or anorectal CT positive women (n = 400) will be recruited at three large Dutch STI clinics located in South Limburg, Amsterdam and Rotterdam. The women self-collect anorectal and vaginal swabs before treatment, and at the end of weeks 1, 2, 4, 6, 8, 10, and 12. Samples are tested for presence of CT-DNA (by NAAT), load (by quantitative polymerase chain reaction -PCR), viability (by culture and viability PCR) and CT type (by multilocus sequence typing). Sexual exposure is assessed by online self-administered questionnaires and by testing samples for Y chromosomal DNA. Using logistic regression models, the impact of two key factors (i.e., sexual exposure and alternate anatomic site of infection) on detection of anorectal and genital CT will be assessed. DISCUSSION: The FemCure study will provide insight in the role of anorectal chlamydia infection in maintaining the CT burden in the context of treatment, and it will provide practical recommendations to reduce avoidable transmission. Implications will improve care strategies that take account of anorectal CT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02694497 .