Antibiotic use is a major driver of antibiotic resistance. Although delayed antibiotic prescription is a recommended strategy to reduce antibiotic use, practices vary; it appears less commonly used in southern European countries where antibiotic consumption is highest. Despite these variations, few qualitative studies have explored general practitioners’ perceptions of delayed antibiotic prescription. We therefore aimed to explore and describe the perceptions of delayed antibiotic prescription for respiratory tract infections among general practitioners in Malta.This qualitative phenomenographic study was conducted in Malta. A semi-structured interview guide was developed in English, pilot tested and revised accordingly. Interview topics included views on antibiotic resistance, antibiotic use and delayed antibiotic prescription for respiratory tract infections, and barriers and facilitators to antibiotic prescription. Individual, face-to-face interviews were held in 2014 with a quota sample of 20 general practitioners and transcribed verbatim. Data were subsequently analysed using a phenomenographic approach.General practitioners perceived delayed antibiotic prescription in five qualitatively different ways: (A) “The Service Provider”–maintaining a good general practitioner-patient relationship to retain patients and avoid doctor-shopping, (B) “The Uncertainty Avoider”–reaching a compromise and providing treatment just in case, (C) “The Comforter”–providing the patient comfort and reassurance, (D) “The Conscientious Practitioner”–empowering and educating patients, and limiting antibiotic use, and (E) “The Holder of Professional Power”–retaining general practitioner responsibility by employing a wait-and-see approach. Although general practitioners were largely positive towards delayed antibiotic prescription, not all supported the strategy; some preferred a wait-and-see approach with follow-up. Many delayed antibiotic prescription users selectively practiced delayed prescription with patients they trusted or who they believed had a certain level of knowledge and understanding. They also preferred a patient-led approach with a one to three day delay; post-dating delayed antibiotic prescriptions was uncommon.In this study we have shown that general practitioners hold varying perceptions about delayed antibiotic prescription and that there is variation in the way delayed antibiotic prescription is employed in Malta. Whilst delayed antibiotic prescription is utilised in Malta, not all general practitioners support the strategy, and motivations and practices differ. In high consumption settings, formal and standardised implementation of delayed antibiotic prescription could help curb antibiotic overuse. Diagnosis-specific delayed antibiotic prescription recommendations should also be incorporated into guidelines. Finally, further investigation into patients’ and pharmacists’ views on delayed antibiotic prescription is required.NCT03218930 Antibiotic resistance (ABR) is an imminent threat and a complex challenge that continues to plague modern medicine. It places immense burden on patient outcomes, healthcare expenditure and society as a whole . In EuroAntibiotic prescription in primary care is a major driver of ABR  and respA number of studies have suggested several strategies to limit unnecessary antibiotic use, including the distribution of national antibiotic guidelines, communication skills training and introduction of point-of-care rapid diagnostic testing, among others . DelayedIt is not uncommon for practitioners to initiate DAP strategies of their own accord without well-established guidelines. This results in varying approaches to DAP, including: (i) providing an antibiotic prescription and instructing patients to use it after a given timeframe if symptoms persist or worsen (patient-led strategy), (ii) post-dating (or forward-dating) the prescription so that patients cannot purchase it before a specified date, (iii) instructing patients to return to collect the prescription at a later date if needed, or (iv) requesting that the patient call the clinic/practitioner to issue a prescription should certain criteria be met . An obseMalta is a southern European country with the second highest antibiotic consumption rates in Europe . Indeed,This study provided baseline data for the Maltese Antibiotic Stewardship Programme in the Community (MASPIC) project, a quasiexperimental social marketing intervention aiming to improve GPs’ antibiotic prescribing behaviour for acute respiratory tract complaints in Malta. A study protocol with a detailed description of the design has been published elsewhere . In briefocus of attention, or awareness, whilst the referential aspect illustrates the meaning of the phenomenon to the person, or how the meaning is created , I would ask them to phone me, to tell me what’s happening. At least I would have feedback and then I can make sure that they really need it.”(GP J)GPs in this category perceived DAP as a way of being considerate and understanding towards patients who fear that their clinical condition may deteriorate and require antibiotic treatment. Although similar to the “Uncertainty Avoiders” in wanting to play it safe, the rationale of GPs in this category was different. Rather than providing treatment to avoid uncertainty, GPs mainly focussed on being receptive of patients’ needs. They empathised with the patient and provided a DAP to provide patient comfort and reassurance knowing that they would have a prescription in hand should they get worse. GPs in this category seemed driven by their emotions and when they perceived that patients were overanxious about their condition, they felt that providing a DAP helps put the patient’s mind to rest.“If you tell them [patients] I’m not going to prescribe you antibiotics… they freak out literally. So, I found that giving them a delayed prescription puts their mind at rest… they don’t need to come back again if these things happen.”(GP S)GPs in this category did not provide DAPs to patients unless they had a certain level of understanding and were trustworthy or regular clients. Otherwise they advised the patient to re-consult in person.“It depends on whether I see that the patient will follow my orders or not… There are some people… who you cannot even be certain whether they understood you or not even though you explain things to them over and over again. Then there are others who are eager to understand and to follow it out… So to those I have a higher tendency to do that [give a delayed antibiotic prescription]… then there are those who are literally too scared and will probably not wait… then you’re risking.”(GP G)GPs in this category questioned whether DAP is indeed best practice. To them, a pitfall of DAP is that GPs cannot know whether patients actually follow their advice following receipt of a DAP, which is why trust was a dominating decisive factor for utilising this strategy.“I’m not sure about what happens actually at the pharmacy … I don’t know what they [the patients] are doing at the end of the day. So I’m not 100% sure whether it’s the right thing to do.”(GP S)As with the “Uncertainty Avoiders”, some GPs tried to overcome this challenge by requesting patients to call back for advice prior to purchasing the antibiotic. They also provided thorough verbal explanation to the patient and a written note on the prescription to make it clear to the pharmacist that the antibiotic should not be dispensed on the day of the prescription.“Sometimes I might write the antibiotic, I tell them wait two days, I tell them if things get worse phone me and I’ll guide you by phone whether to buy it or not, and I find that system works well, but I have to do that with I mean, first of all the patient is intelligent, and the patient which I know regularly.”(GP D)Recognising the threat of ABR, GPs within this category were very concerned about the rampant use of antibiotics in Malta and the rise in ABR. GPs in this category showed deeper understanding of the concept of DAP and were avid users of this method. They perceived DAP as a useful tool for educating and empowering patients, providing an opportunity to teach and convince them that antibiotics are not always necessary.“I think it’s [delayed antibiotic prescription] a useful tool, it’s a tool especially for educating people as I said, you know they realise that the child got better without the antibiotic… it also gives the… patient power that he can be in charge… I think it’s very educational… it’s a good tool.”(GP B)DAP was also perceived as a strategy intended to limit antibiotic use when they are not required thereby in their view, practising safer medicine.“It’s a good practice [delayed antibiotic prescription]… I think you’re increasing safety in practice and decreasing use when it’s not required especially in children.”(GP P)To these GPs, mutual trust was important. In fact, they selectively provided DAPs to patients with full understanding of the concept and who had a certain level of knowledge and awareness. They also reflected upon the impact of DAP on their own practice, on how patients respond positively to this approach and the long-term societal gains derived from it.“I do a lot of delayed prescribing when I realise the mother is capable of understanding. When the mother walks in and demands antibiotics I wouldn’t do it because I know that she’s going to give it.”(GP B)One private sector GP mentioned working closely with pharmacists so as to ensure that the DAP strategy works as intended. He also stressed the importance of patient communication in DAP and kept in touch with patients to help guide them should they need to dispense the DAP.“…a lot of them come to the pharmacy so there’s already this relationship… when I prescribe normally I come out of the clinic, go to the pharmacist, explain what he’s going to do.”(GP P)“I’ll keep in touch with them, and I’ve got notes so in that case if they don’t phone me up I’ll phone them up, at least pass on a message.”(GP P)In this perception the GP focuses on him/herself and how, as a doctor, s/he should act according to his/her training and expertise, to determine if and when patients need antibiotics. GPs within this category were very sure of themselves regarding when antibiotics should and should not be given. As the medical professional, they believed that ensuring good patient outcomes is their sole responsibility. Therefore antibiotic prescription decisions should not be transferred onto the patient. As a result, GPs with this perception considered DAP unsafe practice. They did not practice DAP and were not interested in utilising a DAP strategy in the future. They would rather use a wait-and-see approach in cases where they do not believe that antibiotics are warranted at the time of the first consultation. To them, it was important and justified to re-evaluate the patient in person during a follow-up visit if symptoms persist or worsen rather than give a prescription.“I usually don’t do it [delay a prescription]. I usually caution the patient and tell him, look here, if you get a temperature, if the conditions gets worse, just call again. Just to make sure that it’s really needed … I don’t do it on purpose; I think it’s justified… to revise the situation.”(GP C)These GPs also shared the view that patients are generally non-compliant to treatment and still believe that they will not get better without antibiotics. In fact GPs expressed that they would not trust that patients would follow instruction should they provide a DAP.“…usually if you do that [give a delayed prescription] they go and buy them [antibiotics] just to avoid having to wait…”(GP C)The outcome space created does not truly reflect a hierarchical structure among the different categories of description . It rathTo our knowledge, this is the first time GPs’ perceptions of DAP have been explored in the Mediterranean region. The main contribution of our study is that DAP can be perceived in five qualitatively different ways–(A) to maintain a good GP-patient relationship to retain patients and avoid doctor-shopping, (B) to address clinical uncertainty and reduce the risk of complications, (C) to comfort and reassure the patient, (D) to empower and educate patients, and limit antibiotic use, and (E) not to be practised as prescription is the GPs’ responsibility. This corroborates previous results that suggest that antibiotic prescribing is influenced by a range of social and cultural factors –42. WhilIt has previously been reported that GPs prescribe antibiotics to safeguard their relationship with patients  and the It has been shown that patients who expect antibiotics and receive a DAP are more likely to consume them ,43. On tCultural drivers have arguably provided the best understanding of the heterogeneity of antibiotic use in Europe . These sMalta has the second highest uncertainty avoidance score in Europe . It is tHowever, DAP does not provide the practitioner with an estimate of the severity of illness. As a result, effective, low-cost, rapid diagnostic testing could play a role in helping reduce antibiotic use. Their introduction could add more diagnostic certainty and therefore eliminate the need for any type of prescription, including DAP. Indeed in an RCT conducted in the Netherlands it was shown that DAPs provided following CRP testing resulted in 50% lower antibiotic use than in the control group . Even soSeveral studies have found that prescribers are unwilling to include patients in making a treatment decision and would rather have the patient follow-up in person, deeming it safer practice ,44,46,53GPs in the Maltese private sector who actively practiced DAP seemed to try to overcome this conundrum by maintaining close contact with patients following a DAP. By doing so they could give advice and instruct patients whether to start antibiotic treatment, thereby retaining some sense of control. Interestingly, studies in the UK found that prescribers felt uncomfortable with the lack of follow-up and not knowing the outcome of the DAP was demotivating ,46. SimiIn contrast to the above, GPs have also expressed that by shifting responsibility, patients are empowered to make their own decisions, giving them an educational opportunity ,43,45,53In stark contrast, UK prescribers did not share these views. They were rather concerned that DAP can provide patients with potentially contradictory messages about when antibiotics should be used ,46. BritA recent study showed that most patients with respiratory tract complaints consult GPs within the first three symptomatic days in Malta . Given tIt is evident from our study that patient trust, having a well-established GP-patient relationship and the patient’s level of understanding and awareness, weighed heavily on a GP’s decision whether to provide a DAP or not. Whilst the “Uncertainty Avoiders”, “Comforters” and “Conscientious Practitioners” selectively used DAP with patients they believed would follow advice, “Holders of Professional Power” seemed to lack trust that patients will follow advice and in fact preferred to follow-up the patient. Similar selectivity of use has been reported by GPs in Norway, the UK and New Zealand ,43,45,46Some of our informants attempted to overcome these barriers by providing instruction , or post-dating the prescription although this was not commonly practiced. Others chose to stay in contact with their patients. In a UK study, GPs were reluctant to post-date prescriptions as they felt they were too restrictive and demonstrated lack of patient trust . These vAs is customary in qualitative studies, we used a small, non-probability sample. However, in order to ascertain variation in background factors and gather rich experiences, participants were selected using quota sampling. This strategy considers sizes and proportions of subsamples, with subgroups ultimately reflecting corresponding proportions in the population , thus alSince participation was voluntary, it is possible that study participants differ from other GPs given that may have been more interested in the topic. Nonetheless, we identified rich variation in GPs’ perceptions on DAP. We believe that although our findings are context-specific, they are relevant and could be transferable to other contexts with similar characteristics, especially Mediterranean countries which, like Malta, tend to score high in uncertainty avoidance and power distance.To ensure trustworthiness of our results we provided a thick description of the research methods used and the findings emerging from the primary data, illustrated by interview excerpts. We also used investigator triangulation by incorporating the perspective of researchers with different professional and cultural backgrounds during the analysis. The research team made an active effort to bracket any preconceptions that might influence the interpretation of the results. A dialogical reliability strategy was applied by reaching a negotiated consensus on the final abstractions summarising our findings. Therefore, the reliability of our study builds upon the interpretative awareness of the research team.In this study we have shown that GPs hold varying perceptions about DAP and that there is variation in the way DAP is employed in Malta. Since DAP is already being practised, better implementation of DAP will not require drastic behaviour changes although several key issues must be addressed. It is evident that requesting that patients return to collect a DAP results in lower antibiotic use than patient-led DAP strategies ,11,47,58Patient-collection strategies may not be optimal given the Maltese primary care set-up. Instead, post-dating DAPs coupled with structured patient advice and reassurance is probably the safest approach but requires widespread dissemination of information about the purpose of a DAP strategy, formalisation of guidelines and educational opportunities for doctors, pharmacists and the general public alike. Since the effective implementation of DAP entails that pharmacists dispense DAPs appropriately and as intended, further research is needed to better understand pharmacists’ views on DAP and their dispensing practices, particularly since some GPs seem to exhibit distrust in pharmacists dispensing DAPs as intended. Awareness and education among the general public must also be improved in order for them to understand the natural course of viral illnesses and that they should engage in self-care before visiting a GP; early consultation should be discouraged. Delayed antibiotic recommendations for each diagnosis that take the natural progression of illness into account should be incorporated into guidelines. For certain conditions like sinusitis and bronchitis it may be worth considering a longer delay.Since GPs in this study exhibited several and contrasting perceptions of DAP, further investigation into patient views on DAP is required, particularly since GP views on DAP do not always concur with that of patients . Being oDAP has been shown to reduce antibiotic use for RTIs, even in high antibiotic consumption settings like Spain –16. We t 10 Oct 2019PONE-D-19-22885General practitioners’ perceptions of delayed antibiotic prescription: a phenomenographic studyPLOS ONEDear Mrs Saliba-Gustafsson,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. 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Please remove your figures from within your manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately.  These will be automatically included in the reviewers’ PDF.[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: PartlyReviewer #2: Yes**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/AReviewer #2: N/A**********3. 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Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: This manuscript reports findings of a qualitative phenomenological study that explored the views of GPs in Malta on delayed antibiotic prescription (DAP). The researchers claim that 'this is the first time GPs' perceptions of DAP have been explored in the Mediterranean region'. Funding seems to indicate that this study is part of a doctoral research program.In general, the reporting in this manuscript seems to have followed the COREQ checklist. I was slightly surprised that the University of Malta HREC has exempted this research from even a minimal risk approval because there are clearly inherent risks of such research with health care professionals - privacy/confidentiality breaches, GPs may feel defensive, GPs may feel they are being scrutinised, GPs may feel obliged to participate, etc. The researchers nevertheless seem to have complied with research ethics protocols. However, whether this is adequate for Plos One, I will leave it with the Editorial Board.Below are my feedback for the researchers' consideration :1. There is inadequate definition and description of DAP in INTRODUCTION. It is a distinct prescribing practice that needs to be defined properly for non-medical readers.2. Similarly, there is inadequate description of the MASPIC project that the study is supposed to be providing baseline data for. I assume this is the 1st author's doctoral project??3. The interviews were conducted in 2014 - 5 years ago?? Why has it taken so long to submit for publication?4. Description of the 30 GPs contacted and the demographics of the final 20 GPs including Table 1 should be in RESULTS, not METHODS.5. There is inadequate description of HOW the interview guide was developed. No mention of the questions being translated to Maltese and yet the interviews were conducted in both languages. Presumably then the Maltese interview transcripts would have had to be translated to English as well. Was the translation done by a qualified translator? If not, why not? Was it back-translated to ensure accuracy?6. Researchers said the three interview questions were open-ended and yet the very first question was a close question. Please explain.7. The researchers used 'n=' at the end of each of the five themes and these numbers add up to 20, indicating the 20 interviews. I find this totally inappropriate. In fact, throughout DISCUSSION as well as in the last section (outcome space) of RESULTS, the researchers described many areas of overlap of the GPs views across the five categories. So, how can any one interview be so neatly categorised?? I would like the researchers to re-think the way they present their results so that the inherent complexities are not artificially minimised.8. Discussion was generally well-written although a couple of interesting common features in the five themes were not discussed adequately - eg. GPs seemingly distrust of pharmacists, GPs' views that patients are generally non-compliant.9. I thought the use of Hofstede's national culture model to help explain the differences in prescribing habits in different countries is appropriate. However, there is inadequate explanation of the dimensions in the model particularly 'uncertainty avoidance' and 'power distance'.10. Researchers recommend further research to explore patients' views on DAP. Given pharmacists' important role in DAP and yet GPs in this study seemed to have mixed feelings about pharmacists' effectiveness, it will also be necessary to explore pharmacists' views or include pharmacists in future research to ensure the integrity of the implementation of DAP. I think some discussion of this aspect (pharmacists' role) of DAP is also necessary in DISCUSSION.Reviewer #2: SummaryIn their manuscript, “General practitioners perceptions of delayed antibiotic prescription: a phenomenographic study,” Saliba-Gustafsson and colleagues describe a qualitative study of the attitudes of Maltese General Practitioners (GPs) towards delayed antibiotic prescriptions (DAP). The investigators developed an English-language interview guide that covered many topics having to do with antibiotic resistance, antibiotic use, and antibiotic prescribing, including DAP; conducted 20 interviews with GPs; recorded and transcribed the conversations; and had 2 investigators concurrently code the transcripts using a phenomenographic approach.The investigators divided the 20 respondents into 5 groups based on attitudes towards DAP: 1) Service Providers, 2) Uncertainty Avoiders, 3) Comforters, 4) Conscientious Practitioners, and 5) Power Holders.Major CommentsThe topic is interesting and important. Delayed antibiotic prescribing is used widely, studied often, mentioned in many antibiotic prescribing guidelines, and is controversial. The quotes provided by the authors are illustrative.To reveal my own bias, I think delayed antibiotic prescribing is a bad idea for a host of reasons. Guidelines are clear about when to use antibiotics for most respiratory tract infections. DAP ignore the natural history of respiratory infections ; does not make microbiological sense; sends a confusing, mixed-message to patients; and does not improve patient outcomes. In using DAP, physicians are abdicating their professional responsibility to patients. Thus, I would categorize myself as a “Power Holder.” Despite being a “Power Holder,” I recognize the potential of “perfection being the worst enemy of the good,” and am open to the possibility that DAP has the potential to reduce overall antibiotic use in the right circumstances.I have a few General Comments about the conduct of the study and reporting of the manuscript.First, the interview was much broader than simply asking the GPs about delayed antibiotic prescribing. As such, it is unclear how the coding, analysis, and development of the “graphical space” in the present manuscript relates to other topics covered in the interview guide. How did the investigators decide to focus a manuscript on delayed antibiotic prescribing? Are there other manuscripts that the investigators have or anticipate will emerge from these data?Second, it is overly simplistic that GPs be categorized into mutually exclusive groups. Individual GPs probably have multiple attitudes and rationales for DAP. Individual GPs could have expressed multiple reasons for DAP. For me personally, as a physician who would probably be categorized here as a “Power Holder,” I like to think that I also practice conscientiously, comfort my patients, and provide good service. Occasionally, I might even strive to avoid uncertainty. Similarly, the GPs in this study did not simply announce themselves in one of these 5 categories. There must have been varying degrees of overlap.Third, in the Abstract and generally, the authors are never explicit about what clinical situations the GPs are considering when discussing DAP. The three general questions about DAP on page 7, likewise, do not specify a particular clinical situation. Could the GPs have had very different things in mind when discussing DAP? Were they considering only treatment of respiratory infections? Urinary symptoms? GI problems? Other situations?Minor CommentsPage 3, Line 48: The authors state “This study shows numerous behavioral drivers impact how delayed antibiotic prescription is perceived,” but the term “behavioral drivers” is not defined and is unclear. “Behavioral drivers” sounds like much more specific factors  that lead to simpler behaviors , rather than the complex socio-cognitive-emotional factors that are leading to the complex behavior of DAP.Page 4, Line 75: The authors make an excellent argument against DAP. They should make sure that DAP be implemented carefully and conscientiously in the right circumstances if it is principally being used to decrease inappropriate antibiotic use.Page 5, Line 86: For context, the authors should provide actual metrics of antibiotic use in Malta and comparison countries (high and low utilizing). Other contextual information that would be helpful to the reader would be monthly average Maltese income, the cost of a GP visit, and the out-of-pocket cost of antibiotics.Page 8, Line 162: Here and elsewhere in the manuscript, the authors need to clarify what they mean by “bracketing their own preconceptions.” It sounds like they are literally using brackets to indicate their own preconceived notions when coding and analyzing the qualitative data. Is that what they mean or is this a more general, figurative term for keeping their own preconceived notions in mind?Page 10, Line 202: Here and in other places in the manuscript, the authors imply that having the patient call the GP is not an option. In the US, a major reason given for delayed antibiotic prescribing (and antibiotic overprescribing) is efficiency: clinicians do not have time to field phone calls from patients following-up. I was surprised to not see this come up as a reason or a GP archetype (“Efficiency Seekers” maybe).Page 15, Line 328: The term “Power Holder” has a negative connotation. The 5 GPs who are in this category are doing what they feel, in their best professional opinion, is in their patients’ best interest. A less negative term, like “Professionally Focused” or “Responsibility,” would be better.Page 18, Line 390: It is not right that “other modes of delivery…were not mentioned by the informants.” There is discussion about returning and calling the clinic.Page 20, Line 432: Suddenly only referring to the GP categories by letter designations makes the text very hard to follow. The authors should continue using the descriptive categories.Page 20, Line 433: The authors state that Categories B and C “consistently [applied]” DAP, but it seems that only Category A, “Service Providers,” were consistent in giving out DAPs. The authors need to clarify.Page 20, Line 449 : I am skeptical that “low-cost, rapid diagnostic testing” is going to solve antibiotic overprescribing. There is ample evidence of testing being unused or the results being “ignored,” as the authors themselves point out. Most inappropriate antibiotic prescribing is not a result of a lack of diagnostic knowledge – you don’t need more information when someone clinically has a cold – but a result of emotional, social, and cultural factors.Page 21, Line 454: In describing antibiotic prescribing in the face of a negative rapid antigen test, presumably this was for pharyngitis.Page 21, Line 461: The authors write “These GPs exhibited a more paternalistic consultation style…” But there were no actual observations of practice in this study. This needs to be reworded such that – if this is true – the GPs “described” a more paternalistic style. **********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  31 Oct 2019Response to editorial requests:1. “Please include additional information regarding the interview guide used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, you mention that a pilot guide was tested and altered. On whom was this pilot tested and how many were included?”- More information regarding the development of the interview guide has now been provided in the methods section (lines 163-165).2. “Please remove your figures from within your manuscript file, leaving only the individual TIFF/EPS image files, uploaded separately. These will be automatically included in the reviewers’ PDF.”- Figure has now been removed from the manuscript file as requested and uploaded separately.Responses to reviewer 1’s comments:1. “This manuscript reports findings of a qualitative phenomenological study that explored the views of GPs in Malta on delayed antibiotic prescription (DAP).”- Firstly we would like to thank the reviewer for the thorough comments we received. We have included our comments point-by-point below.- We would like to clarify that we used a phenomenographic approach rather than a phenomenological approach as they are two different qualitative research methods. Whilst in phenomenology one seeks to explore a phenomenon through people's lived experiences, in phenomenography one investigates the different ways that people understand or perceive a phenomenon, in our case how GPs understand/perceive DAP.2. “I was slightly surprised that the University of Malta HREC has exempted this research from even a minimal risk approval because there are clearly inherent risks of such research with health care professionals - privacy/confidentiality breaches, GPs may feel defensive, GPs may feel they are being scrutinised, GPs may feel obliged to participate, etc. The researchers nevertheless seem to have complied with research ethics protocols.”- Despite the fact that following assessment of our study, the research ethics committee in Malta deemed this study exempt of approval (application and letter from the ethics review board can be provided if necessary), we ensured to adhere to ethical guidelines nonetheless. Participants participated voluntarily without coercion or payment. A thorough explanation about the purpose of the study was provided over the phone at the recruitment stage but also in person before the initiation of the interview. Participants were also asked to provide signed written consent. We ensured confidentiality throughout through appropriate data management protocols and by using non-identifiable data when presenting the results.3. “There is inadequate definition and description of DAP in INTRODUCTION. It is a distinct prescribing practice that needs to be defined properly for non-medical readers.”- A description of the different ways DAP is employed in practice has now been provided in the introduction as requested (lines 84-90).4. “Similarly, there is inadequate description of the MASPIC project that the study is supposed to be providing baseline data for. I assume this is the 1st author's doctoral project?”- A study protocol for the MASPIC project has already been published and is referred to in the text. However, we have now included a very brief outline of the project in order to make it clear that this study pertains to the pre-intervention phase (lines 116-120). You are correct in assuming that this is the first author’s doctoral project. We however we do not think that it is relevant or necessary to note this in the article.5. “The interviews were conducted in 2014 - 5 years ago?? Why has it taken so long to submit for publication?”- Due to lack of human resources and the fact that two of the co-authors were out on maternity leave on separate occasions, seeing the project to its completion was prioritised. As a result, work towards a publication was put on hold. Nonetheless, this study shows the pre-intervention results of our project and sets the stage for future publications related to the MASPIC project. Of note, apart from the MASPIC intervention project , no other initiatives in the primary healthcare setting targeting our study population’s antibiotic prescribing behaviour have been carried out, and so we believe that this manuscript it still very relevant. Our future publications will continue to present results of the impact that the intervention had on GPs’ antibiotic prescribing behaviour post-intervention.6. “Description of the 30 GPs contacted and the demographics of the final 20 GPs including Table 1 should be in RESULTS, not METHODS.”- It is customary in qualitative phenomenographic studies to present GPs’ characteristics in the methods section. We do not analyse GPs’ demographic data, rather we simply provide it to give the reader a better picture of who our study respondents were. Therefore we strongly believe that describing our study population belongs in the methods section together with a thick description of the study setting.7. “There is inadequate description of HOW the interview guide was developed. No mention of the questions being translated to Maltese and yet the interviews were conducted in both languages. Presumably then the Maltese interview transcripts would have had to be translated to English as well. Was the translation done by a qualified translator? If not, why not? Was it back-translated to ensure accuracy?”- More information regarding the development of the interview guide has now been provided in the methods section (lines 163-165).- Since Malta is a bilingual nation, the interview guides were developed and conducted in English, therefore our description was misleading and this has now been rectified in the test. However, although all GPs understood English, some felt more comfortable responding to the questions in Maltese or often a mixture of both languages, and they were allowed to do so. Since the interviewer was fluent in both languages it did not impact or hinder the interview flow. A better description of this has been provided in the text (lines 173-178).- The interviews were transcribed verbatim and the responses translated by the first author, who was also the sole interviewer and fluent in both languages. Seldom were a few phrases which were a little harder to interpret discussed with a licensed Maltese proof-reader (lines 185-188).8. “Researchers said the three interview questions were open-ended and yet the very first question was a close question. Please explain.” - Thank you for correctly pointing out that only two of the three questions were in fact open-ended. We have now rectified this in the text (line 167).9. “The researchers used 'n=' at the end of each of the five themes and these numbers add up to 20, indicating the 20 interviews. I find this totally inappropriate. In fact, throughout DISCUSSION as well as in the last section (outcome space) of RESULTS, the researchers described many areas of overlap of the GPs views across the five categories. So, how can anyone interview be so neatly categorised?? I would like the researchers to re-think the way they present their results so that the inherent complexities are not artificially minimised.”- Thank you for this important point and observation. This comment is largely reflected in another comment provided later by reviewer 2 (comment #4) and so in line with both comments we realise that providing a frequency to each category of description is indeed very misleading. As is correctly noted, GPs’ perceptions may vary across the various categories of description and GPs can therefore not be categorised in this way. In order to avoid further misinterpretation of our findings, we have removed the number of GPs within each category. Our results should reflect the collectively different ways DAP can be understood.10. “Discussion was generally well-written although a couple of interesting common features in the five themes were not discussed adequately - eg. GPs seemingly distrust of pharmacists, GPs' views that patients are generally non-compliant.”- We recommend further research on pharmacists’ involvement in DAP and this has briefly been included in the conclusion (lines 599-602). GPs’ views that patients are generally non-compliant had to do a lot with patient trust; trusting that they will use the DAP as intended. We discuss this briefly in lines 547-553.We also recommend further investigation into patients views on DAP (lines 609-614).11. “I thought the use of Hofstede's national culture model to help explain the differences in prescribing habits in different countries is appropriate. However, there is inadequate explanation of the dimensions in the model particularly 'uncertainty avoidance' and 'power distance'.”- We have expanded a little bit more on the different cultural dimensions and the definitions for uncertainty avoidance and power distance in particular , and how it impacts GPs antibiotic prescribing as well as patients.12. “Researchers recommend further research to explore patients' views on DAP. Given pharmacists' important role in DAP and yet GPs in this study seemed to have mixed feelings about pharmacists' effectiveness, it will also be necessary to explore pharmacists' views or include pharmacists in future research to ensure the integrity of the implementation of DAP. I think some discussion of this aspect (pharmacists' role) of DAP is also necessary in DISCUSSION.”- We appreciate your comment and drawing this very valid point to our attention. Pharmacists’ role in DAP was not something that we focussed on or asked GPs directly about. In fact GPs brought this up spontaneously themselves and so we did not have enough data to delve into this aspect too much. That being said, pharmacists certainly play a very important role in the DAP dynamic and given that some GPs were sceptical towards pharmacists’ practices and that they may be dispensing DAPs prematurely, further investigation is certainly warranted. Since we only briefly discussed this we have expanded a little bit more about it in the text (lines 599-602). In lines 596-599 we briefly mention the need for GPs, pharmacists as well as patients to be included in future development of DAP strategies.Responses to reviewer 2’s comments:1. “In their manuscript, “General practitioners perceptions of delayed antibiotic prescription: a phenomenographic study,” Saliba-Gustafsson and colleagues describe a qualitative study of the attitudes of Maltese General Practitioners (GPs) towards delayed antibiotic prescriptions (DAP).”- Firstly we would like to thank the reviewer for the thorough comments we received. We have included our comments point-by-point below.- We would just like to clarify that it is not GPs’ attitudes towards DAP that we investigated but rather their perceptions. Describing how one perceives a phenomenon essentially means describing how one views, understands or interprets something and is often ingrained in how one experiences the phenomenon. Investigating a person’s attitudes on the other hand takes it a step further. An attitude is more closely related to the behaviour and explores the person’s stance on the matter, i.e. whether they tend to be in favour of it or not. Perceptions are often considered precursors attitudes.- Exploring perceptions (rather than attitudes) therefore justifies our use of a phenomenographic study design. In phenomenography, the goal is to describe the different ways that people understand or perceive a phenomenon, in our case how GPs understand/perceive DAP. Rather than exploring attitudes, one explores what a phenomenon (DAP in our case) means to a person and what their focus is. A phenomenon is typically understood by people in a limited number of ways  and with distinct variations in focus and meaning.- The study design sub-heading in the methods section has been restructured and we have expanded on phenomenography a little further to better explain the design (lines 123-133).2. “To reveal my own bias, I think delayed antibiotic prescribing is a bad idea for a host of reasons. Guidelines are clear about when to use antibiotics for most respiratory tract infections. DAP ignore the natural history of respiratory infections ; does not make microbiological sense; sends a confusing, mixed-message to patients; and does not improve patient outcomes. In using DAP, physicians are abdicating their professional responsibility to patients. Thus, I would categorize myself as a “Power Holder.” Despite being a “Power Holder,” I recognize the potential of “perfection being the worst enemy of the good,” and am open to the possibility that DAP has the potential to reduce overall antibiotic use in the right circumstances.”- We can understand your argument against the use of a DAP strategy to reduce antibiotic use since guidelines are clear that antibiotics can be avoided in many RTI. However cultural perceptions of medical care vary greatly by setting. In settings like ours, guidelines are not necessarily relied on, adhered to, trusted or used, and so we must devise alternative strategies to mediate the problem. Whilst improving guideline adherence is of course a priority, there is plenty of evidence, especially in Europe, that DAP can play an important role in reducing unnecessary antibiotic use, particularly in settings with high uncertainty avoidance cultures where ambiguity and uncertainty are not tolerated well. Numerous studies have shown that DAP can provide the needed reassurance (to both GPs and patients) and can indeed effectively reduce antibiotic use. In addition, although controversial, DAP can have an indirect impact on patients belief that antibiotics are necessary for RTIs and be less likely to re-consult for a similar illness in the future. We hope that this came across clearly in our introduction and we believe that we provided a balanced argument in both our discussion and conclusion.- That being said, we believe that a more structured, formal and standardised DAP strategy must be implemented to ensure that DAPs are, first and foremost not provided prematurely , and provided with clear rationale, explanation and structured advice to the patient in order to avoid mixed messages.3. “The interview was much broader than simply asking the GPs about delayed antibiotic prescribing. As such, it is unclear how the coding, analysis, and development of the “graphical space” in the present manuscript relates to other topics covered in the interview guide. How did the investigators decide to focus a manuscript on delayed antibiotic prescribing? Are there other manuscripts that the investigators have or anticipate will emerge from these data?”- As is described in Table 2, although the entire interview transcript was considered in the analysis, particularly since GPs sometimes spontaneously brought up DAP before the interviewer even got to ask any specific questions, most of the data extracted from the interviews were taken from the three questions specified in the methods section. However reading the entire transcript was important; it not only allowed the co-analysts to gain familiarity with the material, but also understand what DAP means to the GP and what their main focus is. As is stated in Table 2, the co-analysts really honed in on significant statements where GPs described their thoughts about and experiences with DAP, whilst keeping the following questions in mind: “What does this tell me about the way the GP perceives DAP?” “What does DAP mean to the GP and what is his/her main focus?”- As you rightly point out, we are currently working on another article which utilises the rest of the material collected from these interviews. The reason we focused on DAP specifically in this article is that we had very rich data on DAP which allowed us to analyse this particular prescription strategy in more detail. Furthermore, since DAP was later included as an intervention component when the intervention was implemented between 2016 and 2017, exploring GPs’ perceptions on DAP in further depth was important in order to deliver the most effective DAP strategy possible.4. “It is overly simplistic that GPs be categorized into mutually exclusive groups. Individual GPs probably have multiple attitudes and rationales for DAP. Individual GPs could have expressed multiple reasons for DAP. For me personally, as a physician who would probably be categorized here as a “Power Holder,” I like to think that I also practice conscientiously, comfort my patients, and provide good service. Occasionally, I might even strive to avoid uncertainty. Similarly, the GPs in this study did not simply announce themselves in one of these 5 categories. There must have been varying degrees of overlap.”- Thank you for pointing this out to us. We would just like to refer you to our methods section where we explained that in phenomenography, “The outcome space is often presented in a hierarchical order since some perceptions may be more complex or include more than one aspect of the phenomenon.” (lines 193-195) In phenomenography it is normal for categories of description to build upon one another. Although our outcome space does not reflect a true hierarchy because we did not identify one, we do understand that GPs do not exclusively fall within distinct categories of description and that by providing numbers we may have misled readers into believing that GPs are categorised into mutually exclusive groups. Whilst the categories of description themselves are mutually exclusive (that is what one strives to identify in phenomenographic studies), as you correctly pointed out, GPs cannot be “placed in boxes” and simply assigned to a category as perceptions may vary across the different categories of description. This is reflected in our description of the outcome space (lines 387-401). Therefore in order to avoid further misinterpretation of our findings, we have now removed the number of GPs within each category. Our results should rather reflect the collectively different ways DAP can be perceived.5. “In the Abstract and generally, the authors are never explicit about what clinical situations the GPs are considering when discussing DAP. The three general questions about DAP on page 7, likewise, do not specify a particular clinical situation. Could the GPs have had very different things in mind when discussing DAP? Were they considering only treatment of respiratory infections? Urinary symptoms? GI problems? Other situations?”- GPs were indeed asked to share their views on DAP in the context of RTIs. In order to make this more clear we have now added this to the manuscript title, aim (lines 27-29 and 110-111), as well as the methods section (lines 32-33 and 167).6. “Page 3, Line 48: The authors state “This study shows that numerous behavioural drivers impact how delayed antibiotic prescription is perceived.” but the term “behavioural drivers” is not defined and is unclear. “Behavioural drivers” sounds like much more specific factors  that lead to simpler behaviours , rather than the complex socio-cognitive-emotional factors that are leading to the complex behaviour of DAP.”- This has now been reformulated entirely (lines 50-52).7. “Page 5, Line 86: For context, the authors should provide actual metrics of antibiotic use in Malta and comparison countries (high and low utilizing). Other contextual information that would be helpful to the reader would be monthly average Maltese income, the cost of a GP visit, and the out-of-pocket cost of antibiotics.”- We have now restricted the last paragraph in our introduction and included more information on the antibiotic consumption rates in Malta compared to the European average as well as the top two reasons for antibiotic consumption, namely sore throat and the flu (lines 97-103).- Regarding including the monthly average Maltese income and cost of antibiotics, since we do not discuss this in the paper, we do not believe it to be relevant.- Since there are currently no official documents stating GPs’ consultation fees it would be hard to provide a number and so we do not feel that we can provide one. As mentioned in the study setting description in the methods section however, public healthcare centres are free-of-charge.8. “Page 8, Line 162: Here and elsewhere in the manuscript, the authors need to clarify what they mean by “bracketing their own preconceptions.” It sounds like they are literally using brackets to indicate their own preconceived notions when coding and analyzing the qualitative data. Is that what they mean or is this a more general, figurative term for keeping their own preconceived notions in mind?”- The concept of bracketing is a widely used term in qualitative research. As you have later correctly suggested, what it essentially means is that in order for the researchers’ preconceptions not to influence the findings, one makes an active effort to set aside any prior assumptions, knowledge or views on the phenomenon being investigated. We have added a short explanation in the text (lines 195-197).- Both the co-analysts possessed different professional backgrounds and preunderstandings of the topic and context. It was therefore very important for us to be aware of our own views and understanding (bracketing) and to discuss our own interpretation of the findings until we finally came to a consensus.9. “Page 10, Line 202: Here and in other places in the manuscript, the authors imply that having the patient call the GP is not an option. In the US, a major reason given for delayed antibiotic prescribing (and antibiotic overprescribing) is efficiency: clinicians do not have time to field phone calls from patients following-up. I was surprised to not see this come up as a reason or a GP archetype (“Efficiency Seekers” maybe).”- Using DAP in order to save time was a point never raised by GPs in this context actually. Perhaps it is because of the very close relationship GPs have to their patients as well as the ease of access patients have should they feel that they need to return for a follow up.- In this manuscript, what we put forward is the fact that we do not believe that patient-collection strategies will be perceived as optimal in this context, primarily due to the fact that some GPs stated that they do not want to be perceived as avaricious by requesting that patients return for follow-up and because GPs often work in single-handed practices on a first-come first-served basis and so from a practical point of view, requesting patients to return simply to collect an antibiotic prescription may be considered burdensome not only by the GP but also the patient.10. “Page 15, Line 328: The term “Power Holder” has a negative connotation. The 5 GPs who are in this category are doing what they feel, in their best professional opinion, is in their patients’ best interest. A less negative term, like “Professionally Focused” or “Responsibility” would be better.”- The terms ‘Uncertainty Avoidance’ and ‘Power Distance’ are specific Hofstede socio-anthropological nomenclatures and his dimensions have provided the main explanations for the variation in antibiotic use and quality indicators within EU countries. In this setting, we believe that our term is appropriate and best describes those doctors who are typically reluctant to involve patients in the prescribing decision as they believe that it is their sole responsibly as the healthcare professional. Describing this group as “Power Holders” has no bearing on their quality or conscientiousness of medical practice.- However, we want to avoid being perceived by readers as judgmental as we do not intend to negatively characterize informants. In fact we believe that we describe “Power Holders” in our results objectively and with slight changes to the discussion based on the reviewers’ suggestions, we have made sure to continue to remain impartial. Nonetheless, we have modified “The Power Holder: retaining GP responsibility by employing a wait-and-see approach” slightly to “Holder of professional power: retaining GP responsibility by employing a wait-and-see approach”.11. Page 18, Line 390: It is not right that “other modes of delivery…were not mentioned by the informants.” There is discussion about returning and calling the clinic.- GPs typically request that patients call back to follow-up with the patient, either to (a) provide over-the-phone guidance so that the patient can then go purchase the antibiotic using a prescription that was provided to them during an earlier face-to-face consultation, or to (b) request the patient to return to the clinic for another in-person visit. We have now made this clearer in the text (lines 436-437). As we described later in the text, GPs do not mention requesting patients to come back simply to pick up a prescription as in done in some other settings. As we also mentioned that some GPs may choose not to provide delayed antibiotic prescriptions at all, but rather use a wait-and-see approach, requesting patients to return for a follow-up should they feel worse.12. “Page 20, Line 432: Suddenly only referring to the GP categories by letter designations makes the text very hard to follow. The authors should continue using the descriptive categories.”- This has now been modified to include the descriptive category names as recommended throughout the text.13. Page 20, Line 433: The authors state that Categories B and C “consistently [applied]” DAP, but it seems that only Category A, “Service Providers,” were consistent in giving out DAPs. The authors need to clarify.- In order to avoid misinterpretation we have removed “consistent” from the text (line 470-472). 14. “Page 20, Line 449 : I am sceptical that “low-cost, rapid diagnostic testing” is going to solve antibiotic overprescribing. There is ample evidence of testing being unused or the results being “ignored,” as the authors themselves point out. Most inappropriate antibiotic prescribing is not a result of a lack of diagnostic knowledge – you don’t need more information when someone clinically has a cold – but a result of emotional, social, and cultural factors.”- Certainly low-cost rapid diagnostic tests cannot be introduced on their own but as part of a multi-faceted intervention which addresses other factors and needs. If marketed as a package then diagnostic testing may, rather than be used for clinical presentations which are more straightforward (like a cold as you mention), be used for cases/particular diagnoses where GPs are truly doubtful of the aetiology and the test will provide more diagnostic certainty. It may also help reassure patients when they do indeed have a viral infection and antibiotics are unnecessary, particularly in cases where patients might demand them. So we still do believe that, in this setting, rapid diagnostics could prove beneficial. However as we noted above, in combination with other initiatives also aimed at reducing antibiotic use. The impact will of course need to be evaluated.15. Page 21, Line 454: In describing antibiotic prescribing in the face of a negative rapid antigen test, presumably this was for pharyngitis.- Thank you for pointing this out. We have now specified in the text that it was indeed acute pharyngitis cases that were prescribed antibiotics despite having a negative rapid antigen test (line 493).16. Page 21, Line 461: The authors write “These GPs exhibited a more paternalistic consultation style…” But there were no actual observations of practice in this study. This needs to be reworded such that – if this is true – the GPs “described” a more paternalistic style. - The entire sentence has been reworded (line 500-501). In order to further explain high power distance societies as objectively as possible without coming across as judgemental, a thicker description of how a high power distance society impacts both doctors and patients has now been provided (lines 516-520).AttachmentResponse to reviewers_191028.docxSubmitted filename: Click here for additional data file. 7 Nov 2019General practitioners’ perceptions of delayed antibiotic prescription for respiratory tract infections: a phenomenographic studyPONE-D-19-22885R1Dear Dr. Saliba-Gustafsson,We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact With kind regards,Vijayaprasad GopichandranAcademic EditorPLOS ONEAdditional Editor Comments :Reviewers' comments: 15 Nov 2019PONE-D-19-22885R1 General practitioners’ perceptions of delayed antibiotic prescription for respiratory tract infections: a phenomenographic study Dear Dr. Saliba-Gustafsson:I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. For any other questions or concerns, please email Thank you for submitting your work to PLOS ONE.With kind regards,PLOS ONE Editorial Office Staffon behalf ofDr. Vijayaprasad Gopichandran Academic EditorPLOS ONE


Plasticized–Poly(vinyl chloride) (P-PVC) for cables and insulation requires performances related to outdoor, indoor and submarine contexts and reduction of noxious release of HCl-containing fumes in case of thermal degradation or fire. Introducing suitable nanomaterials in polymer-based nanocomposites can be an answer to this clue. In this work, an industry-compliant cable-grade P-PVC formulation was added with nanostructured materials belonging to the family of Polyhedral Oligomeric Silsesquioxane (POSS). The effects of the nanomaterials, alone and in synergy with HCl scavenging agents as zeolites and hydrotalcites, on the thermal stability and HCl evolution of P-PVC were deeply investigated by thermogravimetric analysis and reference ASTM methods. Moreover, hardness and mechanical properties were studied in order to highlight the effects of these additives in the perspective of final industrial uses. The data demonstrated relevant improvements in the thermal stability of the samples added with nanomaterials, already with concentrations of POSS down to 0.31 phr and interesting additive effects of POSS with zeolites and hydrotalcites for HCl release reduction without losing mechanical performances. Polyvinylchloride (PVC) is a polymeric material, employed in a huge number of applications, ranging from medical devices, automotive, flooring, luxury goods, clothing and construction . The benTo match the expected performances, P-PVC products are currently formulated using a large number of additives as stabilisers and lubricants operating during the production process, plasticisers, processing aids, impact modifiers and pigments. The fundamentals on standard P-PVC additives and formulations are widely detailed in the literature . Low-cosThe principal drawback for P-PVC formulations for electric and electronic application is the production of aggressive HCl-containing fumes in case of thermal degradation and combustion, and the main challenge is further improving the heat resistance, the thermal stability upon time and the reduction of noxious and toxic emission in case of heating and fire. Heating promotes the elimination of HCl from the PVC backbone that in turns self-accelerates the degradation with the so-called unzipping mechanism. The onset of dehydrochlorination unlocks an avalanche effect, with release of HCl fumes and the formation of distributed unsaturations within the polymer, causing the loss of the chemical and physical features and the change of colour to brown/black . ThermalP-PVC formulations for cables, however, need to side the amount and rate of HCl evolution upon heating and the resistance to ageing to the preservation or improvement of rheology, mechanical resistance and flexibility during processing and use. Furthermore, additives should also be preferably colourless, odourless, compatible to the polymeric matrix, non-migrating and cost effective . In thisProcessing of the polymers, made by dry blending, compounding and extrusion were performed on the scale of about tenth kilograms using pilot scale machinery, fully compliant with the industrial specifications for production, to better meet the interests of compounders. Finally, the produced materials were characterized by fundamental lab methods as Thermogravimetrical Analysis and compared with industrial reference tests (ISO/ASTM/CEI EN standards) for cable-grade formulations characterization, to understand how the molecular features of the nanoadditives, their amount and their nanometric dispersion can modify the P-PVC properties to better exploit the effects due to nanosized additives and reaching relevant final performances.The reference P-PVC (REF) for cable applications is a formulation containing a standard series of co-additives in order to tailor the properties for specific process conditions and final features. A typical industrial formulation for cable-grade P-PVC was selected, whose composition (according to the common formulation procedure based on p.h.r.–parts for hundred resin) is reported in POSS were purchased from Hybrid Plastics Inc.  and used as received. POSS were selected on the basis of the technical data sheets provided by the producer. POSS basically can be featured by a closed cage A with a 11.In this work, close cage POSS were used with Vinyl functionality  and glycidyl propyl ether groups . Open cage POSS were employed with isobutyl  and phenyl  organic moieties+ exchanged, in powder form with 100 mesh granulometry, purchased from Tosoh Inc. and used as received12. X-zeolite was a Zeolum F9 X-type Zeolite Na2O3:MgO 39:61 wt.) and carbonate ions (10 wt.%) as interlayer anions13. Hydrotalcite was purchased by Sasol as commercial sample PURAL® MG 61 HT, with a layer composition based on MgAl hydroxides  were treated with conventional industrial dry blending apparatus for 2 minutes using a mixing profile varying the mixing speed from 1000 to 2900 rpm  and thenThe P-PVC ribbons were studied according to standard methods listed in Thermogravimetrical analysis (TGA) was performed on a SetSys Evolution instrument by Setaram . As reported, samples were measured in ramp heating conditions (RT–800 °C) with a heating rate of 10°C/min and under an Ar flow of 20 mL/min. Isothemal measurements were performed with the same apparatus, setting the temperature using a fast heating to target temperature (>30 °C/min), using Ar flow at 20 mL/min.The effects of nanoadditives in The most effective additives were then used in combination, coupling hybrid  with inorganic fillers (HTLC or X-ZEO) to explore the effects of their co-presence. P-PVC nanocomposite samples under the form of ribbons are shown in POSS nanoadditives show remarkable effects already during the extrusion process. POSS, during the melt processing in the twin screw extruder, change relevantly the viscosity of P-PVC due to their homogeneous distribution at nanoscale level. The process torque value recorded during extrusion of the formulations is reported in the ESI section . In a prOn the basis of the process parameters, only the set of samples with one and two additives providing flow features similar to the REF sample were further characterized from the thermal stability viewpoint, while the high flow formulations were discarded because they are scarcely relevant in real applications, being less or not workable in an industrial plant.For the complete understanding of the results of TGA analyses, a premise on PVC degradation steps is mandatory. In the degradation of PVC, the release of HCl causes an autocatalytic effect promoting a first step of generation of conjugated double bonds along the polymer chain, and a second step of condensation, where Diels Alder cyclisation and cross-linking of polyene segments cause the formation of aromatic fractions , and theSamples were tested using TGA under inert (Ar flow) condition both in temperature ramp and in isothermal conditions. In ramp heating measurements, the calculation and graphical representation of the DTG derivative  highlights the presence of the two degradation steps described above. Using both TGA and DTG profiles, the effects of the nanofillers on the degradation mechanism were evaluated in terms of different parameters. From TGA plots, the increase of the thermal stability was related to the shift in temperature of the onset of degradation. The onset point was conventionally defined as the temperature where the degradation rate reaches the 0.5 wt.%/°C and this temperature was established on the basis of the behaviour of REF sample. The temperature shift  for the maximum rate of HCl evolution after the onset (highlighted by the DTG plot) was related to the stabilization of the primary dehydrochlorination, operated on the nucleation process by removing or avoiding the degradation of labile sites. Afterwards, at higher temperature, changes in the DTG profiles were related to the impact of nanofiller(s) on secondary processes (secondary dehydrochlorination and conjugation) due to stabilization or hindering its evolution or absorbing it without release in the gas phase.The ramp TGA profiles of samples obtained with a single additive are reported in These evidences underline an active role for POSS with potentially reactive R groups ; despite the low concentration, their homogeneous distribution in the polymer favour the interactions with the P-PVC matrix that can take place either during the extrusion process or upon the thermal treatment. In particular, POSS presence seems to reduce the amount and/or the reactivity of the already claimed labile sites that are responsible of the preliminary formation of degradation “nucleation centers” . The glicidyl POSS/inorganic nanomaterials synergy was preliminarily investigated in combination with X-ZEO to assess the best range of nanoaddition. Ramp TGA analyses on P-PVC formulated with amounts of X-Zeolite from 0.31 to 0.62 phr  highlighAccording to the definition of onset temperature for REF P-PVC, isothermal TGA analyses were performed at 265 °C under Ar atmosphere. The study on GlyPOSS/X-ZEO formulations see  show thaThis indication suggested an extensive investigation of inorganic nanomaterials in combination with GlyPOSS in concentrations around 1 phr. The combination of POSS with layered inorganic nanofillers, in particular a commercial carbonate-substituted hydrotalcite, is still more relevant . The case of GlyPOSS_0.62 is interesting as there is a residual evident effect also after thermal ageing, where the induction time  can be still observed. When POSS are coupled with zeolite or HTLC, formulations containing X-type zeolite and POSS gain between 20–25% of induction time increase, and formulations with POSS and HTLC reach the best performances both in direct test and after thermal ageing, though the role and effect of POSS is not evident.Limiting Oxygen Index (LOI) measured according to ASTM D 2863 see  on the sThe best performing sample (HTLC_5/GlyPOSS_0.62) according to previous analyses was also tested, together with samples with the two nanomaterials alone, with reference method for HCl evolution as CEI EN 50267-2-1/IEC 60754-1 to better highlight the role of POSS with HCl scavengers as HTLC . The metPhysical properties like hardness are in general modified by the presence of nanoadditives; in several cases the materials are softened by the presence of the POSS, whether alone or in co-presence of dispersed X-type zeolite. When layered materials are present, an increase of hardness was found. The obtained good performances in thermal stability must be sided by mechanical properties not different from REF sample and the nanomaterials-containing formulations must be compliant to the requirements for potential industrial end-user applications. Mechanical tensile test ASTM D638 on standard dogbone samples (obtained by cutting the ribbons), and Sh.A (15’’) hardness test according to ISO 868 were thus carried out and the results are collected in At first, POSS with different chemical features were molecularly distributed as unique nanoadditive within P-PVC proving their ability to promote a relevantly different thermal behavior for the unzipping reactions of P-PVC towards conjugated polyaromatic systems, and their efficacy was demonstrated with amounts between 0.3 to 1 phr.The evidence of effects down to 0.3 phr concentration is probably related to the molecular nature of this nanomaterial, with organic moieties directly bound to silica cage. Its compositional and structural homogeneity can allow an improved distribution, reaching molecular level, with respect to other nanofillers. Once R groups are able to interact with the polymer, the distribution promote a widespread interconnection with the polymer. As a general consideration, it appears clear that POSS role in this study is significantly influenced by the nature of the cage structure  and the potential role of R modifiers . In all these cases, peculiar effects were seen on the thermal degradation under nitrogen. Among all the POSS, the most interesting results, balancing overall results about the thermal behaviour under the different test methodologies and the mechanical features, came from GlyPOSS. This material introduces a ceramic cage surrounded by epoxy terminated organic arms. The explanation of its relevant efficacy can be related to the role, known in literature, of epoxidized oils as secondary stabilizers used to enhance the effectiveness of conventional additives as metal soaps, as acceptors for the free hydrogen chloride ,37 and rThen, the use of POSS together with active inorganic materials able to interact with evolved HCl (X type zeolite and carbonate-substituted HTLC) proved that in the presence of amounts of inorganics between 1.25 and 5 phr, the decomposition profile is dramatically modified, and additives have a role in the different steps of thermal degradation of PVC that can be highlighted.In particular, POSS and their combination with HTLC and X-ZEO highlight that the influence on the degradation steps of PVC provide a longer time stability in isothermal conditions. This effect is further enhanced with the evolution of the degradation for some formulations, as X-ZEO1.25/GlyPOSS0.62, HTLC5/GlyPOSS0.62 and HTLC5/VyPOSS0.62, which show up to 100% increase of delay time vs. reference in isothermal conditions , bottom.Cable grade formulations based on P-PVC can be improved for their performances, in particular concerning thermal stability and HCl release reduction, by the use of nanomaterials in amounts relevantly smaller (down to 0.31 phr) than usually employed fillers for polymer compounding. HTLC_5/GlyPOSS_0.62 resulted the best performing sample when considering thermal stability and HCl release while maintaining mechanical properties similar to REF sample. It must be noted that POSS, POSS/Zeolite and POSS/HTLC systems have several beneficial aspects being colourless, odourless, tasteless and non-migrating [


Changes in the salt attack resistance of concrete using ground granulated blast furnace slag (GGBFS) were examined based on different curing conditions. These conditions were divided into air and underwater curing. Three concrete mixes with GGBFS replacement ratios of 0% (control group), 30% and 60% were fabricated. Then, evaluation of concrete compressive strength, evaluation of chloride ion diffusion coefficient and electrochemical impedance spectroscopy (EIS) were performed. As the GGBFS replacement ratio increased, the concrete compressive strength of the air cured specimens decreased compared to the underwater cured specimens. With respect to the chloride ion diffusion coefficient measurements, the coefficient decreased as the GGBFS replacement ratio increased. However, the diffusion coefficient of the air cured specimen relative to the underwater cured ones increased up to two times. The EIS results showed that as the GGBFS replacement ratio increased, |Z| increased in every frequency range. However, the |Z| of the air cured specimen was lower than the underwater cured one. This showed the same tendency as the evaluation results of the chloride ion diffusion coefficient. The performance of concrete is determined by its strength and durability. As the durability of concrete has recently emerged as a critical social issue, the development of high-quality concrete with high durability is urgently needed. The most important problem affecting the durability of reinforced concrete is the deterioration of embedded rebars due to corrosion ,2. The rReinforced concrete structures in areas affected by the marine environment require considerable maintenance costs owing to rebar corrosion caused by chloride ion penetration. The construction of reinforced concrete structures with excellent resistance to the marine environment is critical, not only from the point of view of stability of the structure, but also from the economic aspect ,7,8. One2 emissions into the atmosphere [It has been reported in literature that using these additives in concrete is environmentally friendly because it helps reduce COmosphere . Furthermosphere ,28,29,30However, one problem that has been continuously noted is that the replacement of cement with ground granulated blast furnace slag (GGBFS) is associated with high variations in quality and high dependency on the curing environment. In particular, with regard to the curing environment, it is reported that when cement is replaced with GGBFS, the pore structure of concrete changes greatly among underwater curing, air dry curing and carbonation ,35,36,37Thus, when GGBFS is used in concrete, the curing conditions have a high correlation with resistance performance against the deteriorating factors of concrete. Therefore, systematic research is required on the variation of resistance of concrete with GGBFS to salt damage according to the curing conditions. To evaluate the effects of curing conditions on concrete containing GGBFS, in this study, the chloride ion penetration resistance of concrete was measured and compared for different curing environments for concrete specimens that were further divided as air-dry cured and underwater cured. Furthermore, the impedances of rebars embedded in concrete were measured and compared. The results of this study are expected to provide basic data on the effects of curing conditions on resistance to chloride ingress of concrete with GGBFS.3  was used in this study. In addition, Grade-80 GGBFS of ASTM C 989 [2/gcm  was used. Type 1 ordinary Portland cement (OPC) of ASTM C 150  with a dTM C 989  with a BTo reduce the effect of aggregates between the rebar and concrete cover, the maximum size of coarse aggregates was limited to 13 mm and the fine aggregates were prepared by mixing crushed sand and washed sea sand. In South Korea, it is common to use a combination of crushed aggregates and washed (decontaminated chloride) sea sand owing to the depletion of river sand ,45. The For this experiment, nine types of concrete specimens were prepared according to the GGBFS replacement ratio and W/B ratio: three GGBFS replacement ratios of OPC 100%, OPC 70% + GGBFS 30% and OPC 40% + GGBFS 60% and three W/B ratios of 40%, 50% and 60%. Immediately after the concrete was mixed for specimen fabrication, it was poured into a Ø100 × 200 mm cylindrical mold and sealed. The specimen was demolded 24 h later and cured for 28 days. After the curing was complete, the specimen was cut into samples of height 50 mm and the two samples from the middle of the specimen were used. The reinforced concrete specimens were prepared by fixing a ∅13 mm rebar at the center of the Ø100 × 200 mm cylindrical mold and then pouring the concrete into the mold. For the rebar embedded in the concrete, SD-400 deformed rebars were used. After the rebar surface was cleaned by grit blast, an epoxy coating was applied to the surface and only a length of 100 mm at the center of the concrete specimen was exposed. To compare the salt damage resistances of concrete specimens according to the curing conditions, the concrete specimen poured in the mold was demolded after 24 h. Then, the concrete specimens were cured separately for by air and underwater curing for 28 days. The air curing conditions were a temperature of 20 ± 2 °C and relative humidity of 60 ± 5%. For underwater curing, the specimen was completely immersed in water at a temperature of 20 ± 2 °C.The concrete compressive strength was evaluated in accordance with ASTM C39  at 3, 7 To evaluate resistance to chloride ingress of concrete, it is most accurate to conduct exposure test. However, exposure test need a very long time. Therefore, it is common to evaluate the resistance and diffusion coefficient of harmful ions of concrete using electrochemical acceleration. In general, ASTM C 1202 and NT-BUILD 492 are used for evaluating chloride ingress in concrete. In this study, among the chloride ion penetration resistance evaluation methods, the chloride migration coefficient from non-steady-state migration experiments were conducted by NT BUILD 492 , which i2 solution was filled in a desiccator using a vacuum pump and the specimen was immersed in the solution. The inside of the desiccator was maintained in a vacuum state using a vacuum pump and the pores in the concrete were filled with saturated Ca(OH)2 solution. When the pretreatment was complete, chloride ion diffusion cells were prepared as shown in 30V) was measured. Next, the actual applied voltage was adjusted by finding the range of current according to the initial value in This experiment is a non-steady-state electric migration experiment to determine the chloride migration coefficient of the repair material composed of concrete, mortar and cement. Concrete specimens of size Ø100 × 50 mm were prepared, saturated Ca(OH)3 solution was sprayed on the split section, discolored parts appeared on the specimen depending on the penetration depth of the chloride ions. The diffusion coefficient was determined using the average of seven measurements in 10 mm intervals of the chloride penetration depth.After the test, the specimen was split in the axial direction into two pieces. When 0.1N AgNOnssmD is a non-steady-state migration coefficient (×10−12 m2/s)U is the absolute value of the applied voltage (V)T is the average of the initial and final temperatures in the anolyte solution (°C)L is the thickness of the specimen (mm)t is the test duration (hour)Equation (1) is used to estimate the diffusion coefficient from the chloride ion penetration depth .(1)DnssThe impedance of the embedded rebar based on the concrete mix and curing conditions was measured using electrochemical impedance spectroscopy (EIS). The experimental apparatus used in this experiment included a Potentiostat . The three-electrode system for the experiment was setup using the rebar as the working electrode (WE), STS304 as the counter electrode (CE) and Ag/AgCl as the reference electrode (RE). According to electrochemical theory, a simple electrochemical electrode system can be described by an equivalent circuit ,49,50, as denotes the solution resistance, Cdl denotes the capacitance of an electrical double layer and Rp denotes the polarization resistance by charge transfer reaction. Here, Rs corresponds to the impedance of the highest frequency and Rs + Rp corresponds to the impedance of the lowest frequency. Regarding the rebars embedded in concrete, the Rp of the rebar is composed of the resistance of the film Rf and the charge transfer resistance Rct [p. In the EIS experiment, it can be assumed that the value of the Bode plot at 100 kHz is equal to Rs and the value of the plot at 0.1 Hz is equal to Rs + Rp. Therefore, Rp can be calculated.Rance Rct ,51,52,53UW is the result of underwater curing conditionIA is the result of air-dry curing conditionEquation (2) is used for estimating the rate of change for compressive strength by curing condition.The descending order of the measured initial compressive strengths of the concretes is OPC > S3 > S6. However, the 28-day compressive strength of the S3-40-W specimen was 53.6 MPa, which is higher than the 51.7 MPa of the OPC-40-W specimen. The difference was less than 2 MPa, which is not large. This seems to be due to the expression of compressive strength caused by the latent hydraulic activity of the GGBFS. In every specimen, the tendency of decreasing compressive strength with increasing W/B ratio was observed ,31,39.In particular, the concrete mixed with GGBFS showed higher dependence on underwater curing for the strength expression than on the OPC. The strength reduction rate of the air-dry cured specimen relative to the underwater cured specimen was less than 8% for the OPC. However, the concrete mixed with additives showed 10–20% strength reduction rates at most levels. The OPC showed a lower strength reduction rate as the W/B increased. This seems to be because many hydration products were generated by the hydration reaction of cement as there was sufficient curing water. The specimen mixed with GGBFS showed a higher strength reduction rate as the W/B increased. This is attributed to the fact that the curing water was insufficient for latent hydraulic activity of the GGBFS and the generation of hydration products decreased owing to the lower absolute quantity of cement. Furthermore, the low age (28 d) was assumed to have had an effect as well. The S3-40 specimen showed a low strength reduction rate. This seems to be because the amount of mix water was sufficient for hydration of the cement and the GGBFS also partially showed latent hydraulic activity ,39.Furthermore, the concrete mixed with GGBFS that was air cured showed limited strength expression because the inside of the concrete was not dense owing to slow hydration reaction speed. This is also expected to affect the penetration resistance of chloride ions, which is affected by the porosity. Consequently, as the W/B is lower in the air curing condition, proper mixing of the GGBFS will be more effective in delaying rebar corrosion due to salt damage ,39.As a result of NT BUILD 492 test, Chloride ion diffusion coefficient increase according to W/B ratio increase. All 28-days air-dry cured specimens show higher chloride ion diffusion coefficient than all 28-days under-water cured specimens. Also, Increase rate of chloride ion diffusion coefficient of air-cured specimens by W/B are higher than one of water-cured specimens. Only the S3-40 specimen showed no change in the concrete chloride diffusion coefficient according to curing condition under the condition of W/B 40%. This seems to be because under the air curing condition at GGBFS and W/B replacements of 30% and 40%, dense pore structures were formed by the hydration of concrete and the latent hydraulic activity of GGBFS. In addition, at the W/B of 50% and 60% conditions, the chloride ion diffusion coefficient of the air cured specimen was higher than that of the underwater cured specimen. It was found that as the W/B increased, the chloride diffusion coefficient of the concrete according to the curing conditions increased .In the case of the OPC specimens, the increase rate of the concrete chloride diffusion coefficient decreased by the curing condition as the W/B increased. However, in the case of the OPC with GGBFS specimens, the increase rate of the concrete chloride diffusion by curing condition increased as the W/B increased. The increase rate of OPC was lowest at 17.94% but the increase by absolute value was the highest. The specimen that showed the highest increase rate was S3. The increase rate of the chloride diffusion coefficient of S3 was the lowest at 40% W/B but it was 111% at 60% W/B. All specimens using GGBFS showed high increase rates of chloride diffusion coefficient by the curing conditions as the W/B increased. This is consistent with the tendency of decreasing compressive strength of the air cured concrete relative to the underwater cured concrete mentioned in 2, which is approximately 3.28 times that of the OPC-40-W specimen, 418.46 Ωcm2 and 2.06 times that of the |Z| of the S3-40-W specimen, 668.19 Ωcm2.The descending order of measured impedance |Z| of the rebars embedded in concrete according to the applied frequency range was S6 > S3 > OPC. As the GGBFS replacement ratio of cement increased, the impedances of the rebars embedded in concrete increased ,52. For s and Rp for EIS measurement results of rebars embedded in concrete according to the curing conditions and GGBFS replacement ratios.s) in the high-frequency range decreased due to low chloride ion penetration resistance of the concrete of the OPC specimen. This also affects the |Z|(Rs + Rp) in the low-frequency range and shows the same tendency as the measurement results of the concrete chloride diffusion coefficient in the previous experiment [The OPC specimens showed differences in |Z| depending on W/B and curing conditions but the differences were not large over the entire frequency range. In the case of the OPC specimen, the |Z| values of the rebars embedded in the air cured concrete and underwater cured concrete did not show differences. This suggests that the corrosion resistance performance of the air curing condition is not much different from that of the underwater curing condition. However, the lowest |Z| was observed at every experimental level and the |Z| was low at the low- and high-frequency ranges. This suggests that the |Z| in the high-frequency range, which also affects the |Z| in the low-frequency range. Furthermore, the increase of |Z| of the underwater cured specimen relative to the air cured specimen seems to be due to the dense pore structure of concrete resulting from insufficient pore water for latent hydraulic activity of the GGBFS. As the W/B increases, the amount of pore water increases and the difference of |Z| according to the curing condition decreases. Therefore, this shows the same tendency as that of the chloride diffusion coefficient measurement results of concrete.However, as the GGBFS replacement ratio increased and W/B decreased, the impedance of the rebars embedded in the air cured specimen decreased compared to the underwater cured specimen. In the case of the S6-40 specimen, the impedance |Z| of the low-frequency range was 1374.26 Ωcms and Rp confirmed that the change of Rs in |Z| is larger than the change of Rp. This is due to the decrease in the chloride ion diffusion coefficient that causes an increase of the solution resistance (Rs) of the concrete. By measuring the impedances of the rebars embedded in concrete, the chloride ion diffusion coefficient of concrete can be determined [As the chloride ion diffusion coefficient increases, it was confirmed that the impedance decreased. Results of comparing and evaluating Rtermined ,56. Thistermined ,54,55.In this study, the effect of curing conditions on resistance to chloride ingress in concrete using GGBFS was investigated experimentally. Curing conditions were classified into air and underwater curing and cement type of concrete was classified as 0%, 30% and 60% according to the GGBFS replacement ratio. Resistance to chloride ingress was evaluated by measuring the chloride ion diffusion coefficient and impedance. The results are as follows.The evaluation results of the concrete compressive strength showed that the compressive strength of the air cured specimen decreased compared to the underwater cured specimen. As the GGBFS replacement ratio increased, the compressive strength reduction rate increased. The reason for this seems to be that when air curing is performed, pore water is not enough for sufficient exhibition of latent hydraulic activity of the GGBFS and thus, it decreases the generation of hydration products.The evaluation result of the concrete chloride ion diffusion coefficient showed that the chloride ion diffusion coefficient of the air cured specimen was higher than that of the underwater cured specimen. Furthermore, the higher the GGBFS replacement ratio, the lower is the chloride ion diffusion coefficient. The high fineness and latent hydraulic activity reaction of GGBFS decreased the concrete chloride ion diffusion coefficient compared to the OPC but when air curing was performed, the chloride ion diffusion coefficient increased relative to underwater curing.The impedance measurement results of rebars embedded in concrete showed that the |Z| of the air cured specimen decreased in every frequency range relative to the underwater cured one at all levels. As the GGBFS replacement ratio increased, |Z| increased in every frequency range. This showed the same tendency as the evaluation result of the concrete chloride ion diffusion coefficient. It is considered that the higher the chloride penetration resistance is, the higher is the |Z| value of the rebars embedded in concrete.As the GGBFS replacement rate increased, the performance of the underwater cured specimen was higher relative to the air cured specimen in every experiment. This suggests a high dependence on underwater curing. Therefore, when concrete is manufactured using GGBFS, special care should be devoted to the curing conditions.