 Mae'r grwp y gallwn cynyddiad arall o'r perthynau bwysig iawn cymdiann désig neu'i ddechrau eistedd yn ysafelwyr. Fe dweud o hyd arni, mae'r fryd neu'r bywau sydd yn ddiforol a'r ardal yn rharm�odd ddweud, ac yna'r bwysig iawn am y ff Ganhwysig, ac yna'r bwysig, ac mae'r bwysig iawn angen i gwybod â'r bywau hwnnaeth和fyn nhw yn eu cymunod. a'r cyd-fagwadau newydd yw'r cyd-fagwadau. Mae'r cyd-fagwadau newydd o'r cyd-fagwadau yn ymgyrch yn ymgyrch i'ch gweithio'r ysgol ac mae'r cyd-fagwadau yn ymgyrch ymddynt yn bobl a gwybod ei hwn yn ymgyrch o'r rhanwg. Mae'n mynd i'w ddweud ymgyrch yn y poddwyll yn y cyd-fagwadau yn y gweld â'r cyd-fagwadau. Ymgyrch yn ymgyrch ymgyrch yn cyd-fagwadau is the development of the SARS-CoV-2 vaccines, and as we can see from this figure, the development of these SARS-CoV-2 vaccines happened at record time, not one, but several candidates were developed, trialled and approved within 12 months, but this was just the beginning of their journey. The next stage is to deliver these to the target population, which is the whole world at the moment, and Tanahashi, in a classic paper, outlined five dimensions or five challenges in terms of achieving high coverage of interventions. The first is availability, so that it's about achieving delivery supply chains and training the healthcare workforce to deliver the interventions. The next challenge is making the intervention accessible. So even though we provide it in our health services, not all of the population may be able to reach the service and there may be barriers to do with cost, transport or physical barriers. And even for the population that can access the intervention, there may be a smaller proportion who are willing to use the intervention and that's reflected in the acceptability ring. And then the next level is of those who accept the intervention, a smaller proportion will actually use it for various reasons. And of those who use the intervention, not all of them will receive effective care due to lack of adherence or not using the intervention as it was intended. So going back to the COVID vaccine example, we can see here huge global disparities in. Coverage and availability of vaccines with North American, Western Europe having very good availability and being on track to achieve high coverage by the end of this year, but Sub-Saharan Africa and much of Asia having very limited supply and being on a much slower trajectory towards achieving full coverage. But even with plentiful supply of vaccines and even a surplus of vaccines, there may be a limit to the coverage that can be achieved. And what we can see here with the UK, Germany and the United States is that they're reaching a plateau in terms of the level of coverage. And a lot of this is to do with the acceptability. There's a section of the population who aren't willing to be vaccinated. So now moving on from one global pandemic to another, which has been with us for longer, which is anti antibiotic resistance. And specifically, I want to focus for the rest of this talk on interventions aimed to reduce antibiotic prescribing in primary health care. In this paper by Katie Bell and colleagues, they looked at several interventions to minimise antibiotic prescribing for acute respiratory infections in primary care and tried to estimate which of them would have the highest impact at population level. So they multiplied the reported trial effectiveness by the population uptake. They compared four interventions, delayed prescribing, pro-calcitonian tests, C reactive protein tests and shared decision making. And they extracted from Cochran systematic reviews, the summary relative risks. And these were all very highly effective interventions. Then they looked at the uptake and they saw what you can see here in green is a very small proportion of doctors use these interventions and use them as intended. And so thereby they didn't prescribe antibiotics. Another small proportion in yellow use the intervention, but they didn't follow the recommendations and they still prescribed antibiotics. But the biggest proportion here is doctors who didn't use the intervention at all. And that poses the biggest constraint for these interventions in achieving population impact. So then looking at the numbers, we can see here that none of the interventions had very high uptake. They were all below 30 percent and this translates into population impacts that are much smaller than the effectiveness reported in the trials. So now I want to illustrate this with an example from our work in Vietnam. We've just completed the ICAP trial, which is looking at the implementation of C reactive protein point of care testing to improve antibiotic prescribing in primary health care settings. The background to this comes from the same systematic review that was reported by Katie Bell and showed a significant effect of C reactive protein tests in reducing antibiotic prescribing. But these trials were all done in high income countries. So following on from this, our colleagues at our crew did a trial in Vietnam, which also demonstrated that CRP was highly effective at reducing antibiotic prescribing in primary health care. And this was followed by another trial in Thailand and Myanmar, which showed a small but significant reduction in antibiotic prescribing in this setting as well. But both of these trials were traditional randomised control trials. They were individually randomized and they weren't delivered in routine care settings. There had been no pragmatic trial in a lower middle income country. So we wondered what would happen if we translated these interventions into routine care. And we looked back at the systematic review article where they had done a subgroup analysis on individually randomized trials and cluster randomized trials. So trials randomized by health facility, which are more like routine care. And the routine care trials showed a much stronger effect. And they hypothesized that this was because of contamination in the individually randomized trials with the same doctors seeing patients in both the intervention and the control groups and transferring some of their changed prescribing practice into the control group as well. But on the other hand, when we translate our intervention into a real world setting, as we've seen in the example of covid vaccines, we may lose some impact because of lower uptake. So in the the original trial in Vietnam, it showed a 30% relative reduction in prescribing, but there was 100% uptake because it was a controlled trial setting and all patients were given the CRP test. In a real world setting, the uptake may be much lower than that. And if it's 50% uptake will have the population impact. And as the uptake decreases, the impact will decrease. So now let's go on to the study design. The primary research question was what impact does CRP points of care testing have on the proportion of patients aged 1 to 65 with respiratory infections who are prescribed an antibiotic and this is in routine primary care. So it's a pragmatic randomized control trial. In a traditional randomized control trial, the risk population is screened to see if they meet the eligibility criteria and patients who meet the criteria and consent to being part of the trial are randomized. In a pragmatic trial, we train the doctors to identify which patients the test is recommended for. So the doctors decide who to use the test for and consent is done at facility level, so it's not done at patient level and it doesn't interrupt the routine clinical consultation. This is one of the commune health centres included in our study. And the study was done in Nandling province, which is 100 kilometres southeast of Hanoi. It was in three districts and 48 commune health centres. These were randomized to two arms, half with the CRP testing intervention, half with routine care. And a subsample of patients was followed up after two weeks to ask about subsequent antibiotic use, duration of symptoms and any adverse events. And we also linked to hospital data to look at hospitalization rates. The intervention was the ACTIM CRP rapid diagnostic test kit, which comes with a lateral flow test and a tube of buffer. The doctor takes a prick of blood from the finger and puts it onto the test strip. Results are available in five minutes and provide a semi-quantitative measure of C reactive protein, which is a biomarker of inflammation and can be used to differentiate between bacterial and viral infections. So doctors were trained to follow the following guidelines. If the level of CRP was below 10 milligrams per litre, no antibiotics are recommended. It's very unlikely to be a bacterial infection. If the CRP is between 10 and 40, antibiotics are also unlikely to be needed, but doctors can prescribe on their discretion based on their clinical decision. And above 40 milligrams per litre, we combined the top two groups. Antibiotics are recommended and referral if necessary. And now I'll hand over to Ngha, who will give us an overview of the preliminary results. Thanks, Sonia. So I applied to present firstly about the trial profile. In total, 73 common health centres were accessed for the eligibility and among 25 centres were excluded because did not fulfill the inclusion criteria. For example, 14 centres did not have a physics and and 11 centres recruited less than 40 AI patients per month. That is not a sufficient number of the case load. So the remaining 40 centres were then enrol and randomized to either the routine care arm or the CRP point of care test intervention arm. Next, please. So the trial started in June last year and the data were collected monthly from the common health centre electronic system. And now over the first month of the intervention, the average take rate of the CRP intervention was 11 percent. This were calculated based on the total eligible AI patient recorded in the CAC electronic system, where we aware that there's number of the patients did not visit the CAC in person, but they were restricted. So the CRP intervention could not could not target those patients leading to the underestimate of the rap take rate calculations. Next, please. So to try to to be able to calculate the rap take rate of the interventions more accurately, since October last year, we introduced a screening log book beside the CAC existing electronic system to require the healthcare provider recasted only the patient that visited the CAC in person and to exclude the non-presenting patients. And also additionally in early this year, the community sensitisation package will also added to increase the exposure to the intervention in the intervention arm by the loudest speaker by advertising the CRP test in 24 village of the CRP. Next, please. So after the introducing the screening log book in both arm to improve the documentation of the total eligible AI patients, we can see the uptake rate increase with the average of the 41 percent in the eight months. This increase not because of the increasing in the number of the CRP tested, but because of the decline in the eligible AI patients recorded in the screening log book. Next, please. However, the data from the log book, we also also be biased in the recommendations because several common health common health centres, they just recorded the patients with the CRP tested only so the data in the log book was not reliable enough for us to do the analysis. That's why we decided to base the intention to treat analysis in the whole population of AI patients from the CSC electronic system with nearly 40,000 patients because were extracted from this system and the absolute reduction in antibiotic prescription was 5 percent from 98 percent in the control arm to the 93 percent in the CRP. Next. And the larger reduction was observed in the purple phone analysis for the group of the 2,606 patients received the CRP test. That antibiotic prescription in this group was 71 percent. In about half of the patients with the CRP tested, they have low CRP value, less than 10 in the ground per litre, which is antibiotic prescription was not recommended. And only 51 percent of those patients received initial antibiotic prescriptions. The reduction remains significant for the patient with the immediate CRP value from 10 to 40 milligram per litre. And for the patient with the high CRP value of about 40, we didn't see any increase of antibiotic significant increase in the antibiotic prescription next week. So it's mean that when the CRP were performed, the healthcare worker did comply with the guidance of the CRP based therapy and one of the secondary end points assessing about the duration of symptoms, we observed the similarity between arms indicating that the CRP intervention could help to reduce antibiotic prescription without compromising patient recovery as similar to the fighting from previous published trials in what time come and low and middle income settings as Soniarity presented in the previous slides next week. However, we also observed the considerable low CRP uptake rate. So we conducted a number of the interviews with healthcare workers and the patients to understanding better about the reason associated with this low uptake rate. And from the healthcare worker perspective, several reasons were reported instructing the patient expectation for antibiotics when they visit the health facilities. Doctors want to maintain the relationship with their patients who are living in the same and small village. Lack of the consultation time, limited consultation skill and some healthcare workers so expressed their doubts in the CRP credibility. And as I mentioned in the earlier slide that there was the number of the non-presenting patient that our intervention could not target. And obviously some impact from the COVID-19 situation that restricted the number of visits for the patient with the COVID-like symptoms next week. From the patient perspective, the interview patient reported some reasons regarding then limited knowledge about the AI, the acute respiratory illness, antibiotics and antibiotic resistance in general. And most of them show the mis-perception about the antibiotic functions that can have to recover disease quickly. And also they received the limited explanation about the CRP test. So they do not really understand about the purpose and also why they did to take the CRP test. Last but not least, some patients also expect the fee of the pain. So they refuse to take the test next week. So with the pragmatic trial to minimise the disruption to the practice, I will intervene and face to the big challenge of the low uptake rate. So among the 98% of the patient, nearly 100% of the AI patient receiving antibiotics in the common health centres, only 40% of them be sending the CFC in person and only 41% of the patient be sending accepted the CRP test, resulting in only 16% of the patient with the AI expo to the intervention and the remaining bigger parts of the 48% send it the other activities or more appropriate intervention to reduce the appropriate antibiotic use. So even you see the positive outcomes were achieved. The finding from considerable low uptake rates emphasised that in different settings with the country's face health facility and culture feature, likely have different barriers that need to be identified and addressed with appropriate interventions, for example, combining CRP intervention with other ASP activities to achieve optimal effectiveness in uptake of any new diagnostic technology. Next week. So to end our talk, I would like to thank to all the investigators in the study team from Bokhrul, Vietnam, Moru, Thailand, and Fai in Switzerland, also with the local partners from National Hospital for Tropical Diseases, the province of this Department of Health and especially thanks to all the doctors, nurses and the patients from participating 14 common health centres for their great collaboration in doing the study implementations. Thank you very much for your listening.