Clinical Integration of Artificial Intelligence for Breast Imaging.

This article describes an approach to planning and implementing artificial intelligence products in a breast screening service. It highlights the importance of an in-depth understanding of the end-to-end workflow and effective project planning by a multidisciplinary team. It discusses the need for monitoring to ensure that performance is stable and meets expectations, as well as focusing on the potential for inadvertantly generating inequality. New cross-discipline roles and expertise will be needed to enhance service delivery.

Risk of hospitalisation or death in households with a case of COVID-19 in England: an analysis using the HOSTED data set.

OBJECTIVE: To determine whether household contacts of confirmed cases of COVID-19 have an increased risk of hospitalisation or death. METHODS: We used the HOSTED data set of index cases of COVID-19 in England between June and November 2020, linked to Secondary Uses Service data on hospital episodes and Office for National Statistics' mortality data. Multivariable logistic regression models of the odds of household contacts being hospitalised or dying within six weeks of an index case, adjusted for case type, age, sex and calendar month were calculated. Excess risk was determined by comparing the first six weeks after the index case with 6-12 weeks after the index case in a survival analysis framework. RESULTS: Index cases were more likely to be hospitalised or die than either secondary cases or non-cases, having adjusted for age and sex. There was an increased risk of hospitalisation for non-cases (adjusted hazard ratio (aHR) 1.10; 95% confidence interval (CI) 1.04, 1.16) and of death (aHR 1.57; 95% CI 1.14, 2.16) in the first six weeks after an index case, compared to 6-12 weeks after. CONCLUSION: Risks of hospitalisation and mortality are predictably higher in cases compared to non-cases. The short-term increase in risks for non-case contacts following diagnosis of the index case may suggest incomplete case ascertainment among contacts, although this was relatively small.

HOSTED-England's Household Transmission Evaluation Dataset: preliminary findings from a novel passive surveillance system of COVID-19.

BACKGROUND: Household transmission of SARS-CoV-2 is an important component of the community spread of the pandemic. Little is known about the factors associated with household transmission, at the level of the case, contact or household, or how these have varied over the course of the pandemic. METHODS: The Household Transmission Evaluation Dataset (HOSTED) is a passive surveillance system linking laboratory-confirmed COVID-19 cases to individuals living in the same household in England. We explored the risk of household transmission according to: age of case and contact, sex, region, deprivation, month and household composition between April and September 2020, building a multivariate model. RESULTS: In the period studied, on average, 5.5% of household contacts in England were diagnosed as cases. Household transmission was most common between adult cases and contacts of a similar age. There was some evidence of lower transmission rates to under-16s [adjusted odds ratios (aOR) 0.70, 95% confidence interval (CI) 0.66-0.74). There were clear regional differences, with higher rates of household transmission in the north of England and the Midlands. Less deprived areas had a lower risk of household transmission. After controlling for region, there was no effect of deprivation, but houses of multiple occupancy had lower rates of household transmission [aOR 0.74 (0.66-0.83)]. CONCLUSIONS: Children are less likely to acquire SARS-CoV-2 via household transmission, and consequently there was no difference in the risk of transmission in households with children. Households in which cases could isolate effectively, such as houses of multiple occupancy, had lower rates of household transmission. Policies to support the effective isolation of cases from their household contacts could lower the level of household transmission.

Who is coming back for more chlamydia testing within non-specialist health services and where do they go? England, 2013-2016.

OBJECTIVES: To investigate patient demographics and venue type preferences within community settings associated with re-attendance for chlamydia testing. STUDY DESIGN: Data used for this analysis were obtained from the English National Chlamydia Screening Programme (NCSP) which focuses on prevention, control and treatment of chlamydia in sexually active under-25 year olds. A greater understanding of how young adults attend services helps to inform commissioners regarding where to focus resources within community settings. METHODS: Data from the Chlamydia surveillance system (CTAD) were used to count patient attendances at non-specialist sexual health services (SHSs) among 15-24-year-olds and monitor re-attendance for chlamydia testing within and between community services between 6 and 18 months of their first visit. RESULTS: From January 2013 to December 2016, 866,847 young people underwent 1,041,245 tests for chlamydia. Re-attendance for chlamydia testing was 20.1% (174,398/866,847). Re-attendance rate was 28.5% after a positive test and 19.5% after a negative test. For re-attenders, 64.2% used the same venue type for both visits. General practice (GP) and sexual and reproductive health services (SRH) were the most commonly re-attended services (31.0% and 30.6% respectively). CONCLUSIONS: Only one in five re-attended for chlamydia testing. Re-attendance was associated with having a positive result, accessibility and convenience. Patients are likely to return for testing to services they know. This should be considered by commissioners implementing new re-attendance guidance based on the NCSP.

Correction: Sera selected from national STI surveillance system shows Chlamydia trachomatis PgP3 antibody correlates with time since infection and number of previous infections.

[This corrects the article DOI: 10.1371/journal.pone.0208652.].

Has Chlamydia trachomatis prevalence in young women in England, Scotland and Wales changed? Evidence from national probability surveys.

We evaluate the utility of the National Surveys of Attitudes and Sexual Lifestyles (Natsal) undertaken in 2000 and 2010, before and after the introduction of the National Chlamydia Screening Programme, as an evidence source for estimating the change in prevalence of Chlamydia trachomatis (CT) in England, Scotland and Wales. Both the 2000 and 2010 surveys tested urine samples for CT by Nucleic Acid Amplification Tests (NAATs). We examined the sources of uncertainty in estimates of CT prevalence change, including sample size and adjustments for test sensitivity and specificity, survey non-response and informative non-response. In 2000, the unadjusted CT prevalence was 4.22% in women aged 18-24 years; in 2010, CT prevalence was 3.92%, a non-significant absolute difference of 0.30 percentage points (95% credible interval -2.8 to 2.0). In addition to uncertainty due to small sample size, estimates were sensitive to specificity, survey non-response or informative non-response, such that plausible changes in any one of these would be enough to either reverse or double any likely change in prevalence. Alternative ways of monitoring changes in CT incidence and prevalence over time are discussed.

Diagnostic accuracy of a prototype rapid chlamydia and gonorrhoea recombinase polymerase amplification assay: a multicentre cross-sectional preclinical evaluation.

OBJECTIVES: Rapid and accurate sexually transmitted infection diagnosis can reduce onward transmission and improve treatment efficacy. We evaluated the accuracy of a 15-minute run-time recombinase polymerase amplification-based prototype point-of-care test (TwistDx) for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). METHODS: Prospective, multicentre study of symptomatic and asymptomatic patients attending three English sexual health clinics. Research samples provided were additional self-collected vulvovaginal swab (SCVS) (female participants) and first-catch urine (FCU) aliquot (female and male participants). Samples were processed blind to the comparator (routine clinic CT/NG nucleic acid amplification test (NAAT)) results. Discrepancies were resolved using Cepheid CT/NG GeneXpert. RESULTS: Both recombinase polymerase amplification and routine clinic NAAT results were available for 392 male and 395 female participants. CT positivity was 8.9% (35/392) (male FCU), 7.3% (29/395) (female FCU) and 7.1% (28/395) (SCVS). Corresponding NG positivity was 3.1% (12/392), 0.8% (3/395) and 0.8% (3/395). Specificity and positive predictive values were 100% for all sample types and both organisms, except male CT FCU (99.7% specificity (95% confidence interval (CI) 98.4-100.0; 356/357), 97.1% positive predictive value (95% CI 84.7-99.9; 33/34)). For CT, sensitivity was ≥94.3% for FCU and SCVS. CT sensitivity for female FCU was higher (100%; 95% CI, 88.1-100; 29/29) than for SCVS (96.4%; 95% CI, 81.7-99.9; 27/28). NG sensitivity and negative predictive values were 100% in FCU (male and female). CONCLUSIONS: This prototype test has excellent performance characteristics, comparable to currently used NAATs, and fulfils several World Health Organization ASSURED criteria. Its rapidity without loss of performance suggests that once further developed and commercialized, this test could positively affect clinical practice and public health.

GooD4Mum: A general practice-based quality improvement collaborative for diabetes prevention in women with previous gestational diabetes.

AIMS: Gestational diabetes (GDM) and Type 2 diabetes pose tremendous health and economic burdens as worldwide incidence increases. Primary care-based systematic diabetes screening and prevention programs could be effective in women with previous GDM. GooD4Mum aimed to determine whether a Quality Improvement Collaborative (QIC) would improve postpartum diabetes screening and prevention planning in women with previous GDM in general practice. METHODS: Fifteen general practices within Victoria (Australia) participated in a 12-month QIC, consisting of baseline and four quarterly audits, guideline-led workshops and Plan-Do-Study-Act feedback cycles after each audit. The primary outcome measures were the proportion of women on local GDM registers completing a diabetes screening test and a diabetes prevention planning consultation within the previous 15 months. RESULTS: Diabetes screening increased with rates more than doubled from 26% to 61% and postpartum screening increased from 43%-60%. Diabetes prevention planning consultations did not show the same level of increase (0%-10%). The recording of body mass index improved overall (51%-69%) but the number of women with normal body mass index did not. CONCLUSIONS: GooD4Mum supported increased diabetes screening and the monitoring of high risk women with previous GDM in general practice.

Qualitative impact assessment of an educational workshop on primary care practitioner attitudes to NICE HIV testing guidelines.

BACKGROUND: In 2013, Public Health England piloted the '3Cs (chlamydia, contraception, condoms) and HIV (human immunodeficiency virus)' educational intervention in 460 GP surgeries. The educational HIV workshop aimed to improve the ability and confidence of staff to offer HIV testing in line with national guidelines. AIM: To qualitatively assess the impact of an educational workshop on GP staff's attitudes to NICE HIV testing guidelines. DESIGN & SETTING: Qualitative interviews with GP staff across England before and after an educational HIV workshop. METHOD: Thirty-two GP staff (15 before and 17 after educational HIV workshop) participated in interviews exploring their views and current practice of HIV testing. Interview transcripts were thematically analysed and examined, using the components of the theory of planned behaviour (TPB) and normalisation process theory (NPT) as a framework. RESULTS: GPs reported that the educational HIV workshop resulted in increased knowledge of, and confidence to offer, HIV tests based on indicator conditions. However, overall participants felt they needed additional HIV training around clinical care pathways for offering tests, giving positive HIV results, and current treatments and outcomes. Participants did not see a place for point-of-care testing in general practice. CONCLUSION: Implementation of national HIV guidelines will require multiple educational sessions, especially to implement testing guidelines for indicator conditions in areas of low HIV prevalence. Additional role-play or discussions around scripts suggesting how to offer an HIV test may improve participants' confidence and facilitate increased testing. Healthcare assistants (HCAs) may need specific training to ensure that they are skilled in offering HIV testing within new patient checks.

Sera selected from national STI surveillance system shows Chlamydia trachomatis PgP3 antibody correlates with time since infection and number of previous infections.

BACKGROUND: Seroprevalence surveys of Chlamydia trachomatis (CT) antibodies are promising for estimating age-specific CT cumulative incidence, however accurate estimates require improved understanding of antibody response to CT infection. METHODS: We used GUMCAD, England's national sexually transmitted infection (STI) surveillance system, to select sera taken from female STI clinic attendees on the day of or after a chlamydia diagnosis. Serum specimens were collected from laboratories and tested anonymously on an indirect and a double-antigen ELISA, both of which are based on the CT-specific Pgp3 antigen. We used cross-sectional and longitudinal descriptive analyses to explore the relationship between seropositivity and a) cumulative number of chlamydia diagnoses and b) time since most recent chlamydia diagnosis. RESULTS: 919 samples were obtained from visits when chlamydia was diagnosed and 812 during subsequent follow-up visits. Pgp3 seropositivity using the indirect ELISA increased from 57.1% (95% confidence interval: 53.2-60.7) on the day of a first-recorded chlamydia diagnosis to 89.6% (95%CI: 79.3-95.0) on the day of a third or higher documented diagnosis. With the double-antigen ELISA, the increase was from 61.1% (95%CI: 53.2-60.7) to 97.0% (95%CI: 88.5-99.3). Seropositivity decreased with time since CT diagnosis on only the indirect assay, to 49.3% (95%CI: 40.9-57.7) two or more years after a first diagnosis and 51.9% (95%CI: 33.2-70.0) after a repeat diagnosis. CONCLUSION: Seropositivity increased with cumulative number of infections, and decreased over time after diagnosis on the indirect ELISA, but not on the double-antigen ELISA. This is the first study to demonstrate the combined impact of number of chlamydia diagnoses, time since diagnosis, and specific ELISA on Pgp3 seropositivity. Our findings are being used to inform models estimating age-specific chlamydia incidence over time using serial population-representative serum sample collections, to enable accurate public health monitoring of chlamydia.

Advancing the public health applications of Chlamydia trachomatis serology.

Genital Chlamydia trachomatis infection is the most commonly diagnosed sexually transmitted infection. Trachoma is caused by ocular infection with C trachomatis and is the leading infectious cause of blindness worldwide. New serological assays for C trachomatis could facilitate improved understanding of C trachomatis epidemiology and prevention. C trachomatis serology offers a means of investigating the incidence of chlamydia infection and might be developed as a biomarker of scarring sequelae, such as pelvic inflammatory disease. Therefore, serological assays have potential as epidemiological tools to quantify unmet need, inform service planning, evaluate interventions including screening and treatment, and to assess new vaccine candidates. However, questions about the performance characteristics and interpretation of C trachomatis serological assays remain, which must be addressed to advance development within this field. In this Personal View, we explore the available information about C trachomatis serology and propose several priority actions. These actions involve development of target product profiles to guide assay selection and assessment across multiple applications and populations, establishment of a serum bank to facilitate assay development and evaluation, and development of technical and statistical methods for assay evaluation and analysis of serological findings. The field of C trachomatis serology will benefit from collaboration across the public health community to align technological developments with their potential applications.

100 years of STIs in the UK: a review of national surveillance data.

OBJECTIVES: The 1916 Royal Commission on Venereal Diseases was established in response to epidemics of syphilis and gonorrhoea in the UK. In the 100 years since the Venereal Diseases Act (1917), the UK has experienced substantial scientific, economic and demographic changes. We describe historical and recent trends in STIs in the UK. METHODS: We analysed surveillance data derived from STI clinics' statistical returns from 1917 to 2016. RESULTS: Since 1918, gonorrhoea and syphilis diagnoses have fluctuated, reflecting social, economic and technological trends. Following spikes after World Wars I and II, rates declined before re-emerging during the 1960s. At that time, syphilis was more common in men, suggestive of transmission within the men who have sex with men (MSM) population. Behaviour change following the emergence of HIV/AIDS in the 1980s is thought to have facilitated a precipitous decline in diagnoses of both STIs in the mid-1980s. Since the early 2000s, gonorrhoea and syphilis have re-emerged as major public health concerns due to increased transmission among MSM and the spread of antimicrobial-resistant gonorrhoea. Chlamydia and genital warts are now the most commonly diagnosed STIs in the UK and have been the focus of public health interventions, including the national human papillomavirus vaccination programme, which has led to substantial declines in genital warts in young people, and the National Chlamydia Screening Programme in England. Since the 1980s, MSM, black ethnic minorities and young people have experienced the highest STI rates. CONCLUSION: Although diagnoses have fluctuated over the last century, STIs continue to be an important public health concern, often affecting more marginalised groups in society. Prevention must remain a public health priority and, as we enter a new era of sexual healthcare provision including online services, priority must be placed on maintaining prompt access for those at greatest risk of STIs.

Is previous azithromycin treatment associated with azithromycin resistance in Neisseria gonorrhoeae? A cross-sectional study using national surveillance data in England.

OBJECTIVES: It has been suggested that treatment of STIs with azithromycin may facilitate development of azithromycin resistance in Neisseria gonorrhoeae (NG) by exposing the organism to suboptimal doses. We investigated whether treatment history for non-rectal Chlamydia trachomatis (CT), non-gonococcal urethritis (NGU) or NG (proxies for azithromycin exposure) in sexual health (GUM) services was associated with susceptibility of NG to azithromycin. METHODS: Azithromycin susceptibility data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP 2013-2015, n=4606) and additional high-level azithromycin-resistant isolates (HL-AziR) identified by the Public Health England reference laboratory (2013-2016, n=54) were matched to electronic patient records in the national GUMCAD STI surveillance dataset (2012-2016). Descriptive and regression analyses were conducted to examine associations between history of previous CT/NGU/NG and subsequent susceptibility of NG to azithromycin. RESULTS: Modal azithromycin minimum inhibitory concentration (MIC) was 0.25 mg/L (one dilution below the resistance breakpoint) in those with and without history of previous CT/NGU/NG (previous 1 month/6 months). There were no differences in MIC distribution by history of CT/NGU (P=0.98) or NG (P=0.85) in the previous 1 month/6 months or in the odds of having an elevated azithromycin MIC (>0.25 mg/L) (Adjusted OR for CT/NGU 0.97 (95% CI 0.76 to 1.25); adjusted OR for NG 0.82 (95% CI: 0.65 to 1.04)) compared with those with no CT/NGU/NG in the previous 6 months. Among patients with HL-AziR NG, 3 (4%) were treated for CT/NGU and 2 (3%) for NG in the previous 6 months, compared with 6% and 8%, respectively for all GRASP patients. CONCLUSIONS: We found no evidence of an association between previous treatment for CT/NGU or NG in GUM services and subsequent presentation with an azithromycin-resistant strain. As many CT diagnoses occur in non-GUM settings, further research is needed to determine whether azithromycin-resistant NG is associated with azithromycin exposure in other settings and for other conditions.

A 30-Min Nucleic Acid Amplification Point-of-Care Test for Genital Chlamydia trachomatis Infection in Women: A Prospective, Multi-center Study of Diagnostic Accuracy.

BACKGROUND: Rapid Point-Of-Care Tests for Chlamydia trachomatis (CT) may reduce onward transmission and reproductive sexual health (RSH) sequelae by reducing turnaround times between diagnosis and treatment. The io® single module system (Atlas Genetics Ltd.) runs clinical samples through a nucleic acid amplification test (NAAT)-based CT cartridge, delivering results in 30min. METHODS: Prospective diagnostic accuracy study of the io® CT-assay in four UK Genito-Urinary Medicine (GUM)/RSH clinics on additional-to-routine self-collected vulvovaginal swabs. Samples were tested "fresh" within 10days of collection, or "frozen" at -80°C for later testing. Participant characteristics were collected to assess risk factors associated with CT infection. RESULTS: CT prevalence was 7.2% (51/709) overall. Sensitivity, specificity, positive and negative predictive values of the io® CT assay were, respectively, 96.1% (95% Confidence Interval (CI): 86.5-99.5), 97.7% (95%CI: 96.3-98.7), 76.6% (95%CI: 64.3-86.2) and 99.7% (95%CI: 98.9-100). The only risk factor associated with CT infection was being a sexual contact of an individual with CT. CONCLUSIONS: The io® CT-assay is a 30-min, fully automated, high-performing NAAT currently CE-marked for CT diagnosis in women, making it a highly promising diagnostic to enable specific treatment, initiation of partner notification and appropriately intensive health promotion at the point of care.

Detection of Chlamydia trachomatis in rectal specimens in women and its association with anal intercourse: a systematic review and meta-analysis.

OBJECTIVES: Chlamydia trachomatis is the most commonly diagnosed bacterial STI. Lack of prevalence and risk factor data for rectal chlamydia in women has testing and treatment implications, as azithromycin (a first-line urogenital chlamydia treatment) may be less effective for rectal chlamydia. We conducted a systematic review of studies on women in high-income countries to estimate rectal chlamydia prevalence, concurrency with urogenital chlamydia and associations with reported anal intercourse (AI). DESIGN: Systematic review and four meta-analyses conducted using random-effects modelling. DATA SOURCES: Medline, Embase, Cumulative Index to Nursing and Allied Health Literature, PsycINFO and the Cochrane Database were searched for articles published between January 1997 and October 2017. ELIGIBILITY CRITERIA: Studies reporting rectal chlamydia positivity in heterosexual women aged ≥15 years old in high-income countries were included. Studies must have used nucleic acid amplification tests and reported both the total number of women tested for rectal chlamydia and the number of rectal chlamydia infections detected. Conference abstracts, case reports and studies with self-reported diagnoses were excluded. Data extracted included setting, rectal and urogenital chlamydia testing results, AI history, and demographics. RESULTS: Fourteen eligible studies were identified, all among diverse populations attending sexual health services. Among routine clinic-attending women, summary rectal chlamydia positivity was 6.0% (95% CI 3.2% to 8.9%); summary concurrent rectal chlamydia infection was 68.1% in those who tested positive for urogenital chlamydia (95% CI 56.6% to 79.6%); and of those who tested negative for urogenital chlamydia, 2.2% (95% CI 0% to 5.2%) were positive for rectal chlamydia. Reported AI was not associated with rectal chlamydia (summary risk ratio 0.90; 95% CI 0.75 to 1.10). CONCLUSIONS: High levels of rectal chlamydia infection have been shown in women with urogenital chlamydia infection. The absence of association between reported AI and rectal chlamydia suggests AI is not an adequate indicator for rectal testing. Further work is needed to determine policy and practice for routine rectal testing in women.

Exploring why a complex intervention piloted in general practices did not result in an increase in chlamydia screening and diagnosis: a qualitative evaluation using the fidelity of implementation model.

BACKGROUND: Chlamydia trachomatis (chlamydia) is the most commonly diagnosed sexually transmitted infection (STI) in England; approximately 70% of diagnoses are in sexually active young adults aged under 25. To facilitate opportunistic chlamydia screening in general practice, a complex intervention, based on a previously successful Chlamydia Intervention Randomised Trial (CIRT), was piloted in England. The modified intervention (3Cs and HIV) aimed to encourage general practice staff to routinely offer chlamydia testing to all 15-24 year olds regardless of the type of consultation. However, when the 3Cs (chlamydia screening, signposting to contraceptive services, free condoms) and HIV was offered to a large number of general practitioner (GP) surgeries across England, chlamydia screening was not significantly increased. This qualitative evaluation addresses the following aims: a) Explore why the modified intervention did not increase screening across all general practices. b) Suggest recommendations for future intervention implementation. METHODS: Phone interviews were carried out with 26 practice staff, at least 5 months after their initial educational workshop, exploring their opinions on the workshop and intervention implementation in the real world setting. Interview transcripts were thematically analysed and further examined using the fidelity of implementation model. RESULTS: Participants who attended had a positive attitude towards the workshops, but attendee numbers were low. Often, the intervention content, as detailed in the educational workshops, was not adhered to: practice staff were unaware of any on-going trainer support; computer prompts were only added to the female contraception template; patients were not encouraged to complete the test immediately; complete chlamydia kits were not always readily available to the clinicians; and videos and posters were not utilised. Staff reported that financial incentives, themselves, were not a motivator; competing priorities and time were identified as major barriers. CONCLUSION: Not adhering to the exact intervention model may explain the lack of significant increases in chlamydia screening. To increase fidelity of implementation outside of Randomised Controlled Trial (RCT) conditions, and consequently, improve likelihood of increased screening, future public health interventions in general practices need to have: more specific action planning within the educational workshop; computer prompts added to systems and used; all staff attending the workshop; and on-going practice staff support with feedback of progress on screening and diagnosis rates fed back to all staff.

Chlamydia sequelae cost estimates used in current economic evaluations: does one-size-fit-all?

BACKGROUND: Current evidence suggests that chlamydia screening programmes can be cost-effective, conditional on assumptions within mathematical models. We explored differences in cost estimates used in published economic evaluations of chlamydia screening from seven countries (four papers each from UK and the Netherlands, two each from Sweden and Australia, and one each from Ireland, Canada and Denmark). METHODS: From these studies, we extracted management cost estimates for seven major chlamydia sequelae. In order to compare the influence of different sequelae considered in each paper and their corresponding management costs on the total cost per case of untreated chlamydia, we applied reported unit sequelae management costs considered in each paper to a set of untreated infection to sequela progression probabilities. All costs were adjusted to 2013/2014 Great British Pound (GBP) values. RESULTS: Sequelae management costs ranged from £171 to £3635 (pelvic inflammatory disease); £953 to £3615 (ectopic pregnancy); £546 to £6752 (tubal factor infertility); £159 to £3341 (chronic pelvic pain); £22 to £1008 (epididymitis); £11 to £1459 (neonatal conjunctivitis) and £433 to £3992 (neonatal pneumonia). Total cost of sequelae per case of untreated chlamydia ranged from £37 to £412. CONCLUSIONS: There was substantial variation in cost per case of chlamydia sequelae used in published chlamydia screening economic evaluations, which likely arose from different assumptions about disease management pathways and the country perspectives taken. In light of this, when interpreting these studies, the reader should be satisfied that the cost estimates used sufficiently reflect the perspective taken and current disease management for their respective context.