Author's response to reviews Title: Prevalence and epidemiological correlates and treatment outcome of HCV infection in an Italian prison setting Authors: Micaela Brandolini (m.brandolini@smatteo.pv.it) Stefano Novati (s.novati@smatteo.pv.it) Annalisa De Silvestri (a.desilvestri@smatteo.pv.it) Carmine Tinelli (Ctinelli@smatteo.pv.it) Savino Patruno (sfa.patruno@smatteo.pv.it) Roberto Ranieri (roberto.ranieri@ao-sanpaolo.it) Elena Seminari (e.seminari@smatteo.pv.it) Version: 3 Date: 8 October 2013 Author's response to reviews: see over
Answer to reviewers Reviewer's report Title: Prevalence and epidemiological correlates and treatment outcome of HCV infection in an Italian prison setting Version: 2 Date: 21 August 2013 Reviewer: Dora Dumont Reviewer's report: The authors have made significant improvements. Some revisions are still necessary for publication and the article still requires editing by a native English speaker, but I encourage the editors to continue working with the authors to bring this article to publication. Essential revisions: Abstract 1. The authors have provided an abstract as requested, but it is unwieldy and should be reduced to standard length (usually 250 words). In particular, only the most important results should be reported in the Abstract. As suggested, abstract was shortened Introduction 2. Para. 2: Please clarify in the Ministry of Health made it necessary not only to test and treat all intra-venous drug abuse associated with infection and this is followed by: as a result, HCV screening should be offered to all inmates. So does the Ministry s policy dictate universal screening, only all IV drug users must be tested, or only those identified as abusers? It seems important context whether prisons are indeed supposed to be testing universally or only in cases they identify as drug abuse The sentence has been modified as follows: the Italian Ministry of Health made it necessary not only to test and treat all intra-venous drug abuse associated infections but also to promote educational programs to improve prison inmate awareness on preventive measures and therapeutic needs, as a result HCV screening should be offered to all inmates at admission. 3. Introduction para. 3 and Methods para. 2: Please align #2 in the aims Methods 4. Para. 3: The Ministry of Justice study approved this study should this be The Ministry of Justice approved this study or some more specific entity within the Ministry? The sentence is correct 5. Para. 4: statistical analysis please identify the different groups of inmates compared (presumably sex and origin). It is highly preferable that you provide an operational definition of foreigners for the international audience, if you define them by nation of birth and not citizenship The sentence has been modified as follows: Baseline patients characteristics (age, gender, nation of birth and HIV/HBV coinfection) were described for the overall sample and according to HCV
infection. The Student s t test was used to compare continuous variables and the Chi-square test was used to study the association between categorical variables. Discussion 6. Para. 1: dedicated personnel to this specific duty this is the first mention: does this mean there are medical staff solely for HCV testing? The answer is yes, MB was a fellow at that time and was dedicated to the screening procedures within the study. 7. Para. 1: Since your results fall at the low end of the range of prevalence estimates for Italy, it would be helpful if you discussed this finding: what is different about the studies finding prevalence of 40%? Are they facility-specific? Is there a wide range of testing practices across the country, despite the Ministry of Justice s policy? The explanation requested are reported in the below in the discussion, among limitations. We tend to think that the discussion structure can be left as done before, the sentence has been modified according to suggestions. The principal limitation of this study is represented by its being a single center study, so that the extent of generalizability of our findings to the prisoner s population thus remains unclear, despite the fact the Opera represents one of the larger Italian prisons. Data on HCV prevalence reported by other Italian authors are slightly higher than the ones reported in the present study [3-4]. The reason for this difference may be explained by the fact that the population detained in Milano Opera is different from those of smaller prisons, as in Milano Opera are detained those prisoner sentenced for a period longer than three years coming from all the Country for different major crimes and in smaller prisons are detained prisoners for minor offences (usually intravenous drug abusers). Despite roughly 30% of patients restricted at the time of survey were not test for HCV infection, demographic differences between those tested and not tested were not observed, not altering the reproducibility of the data. Other studies [3-4] report data on a subset of the examined population (less than 50%) and this might have biased the reproducibility of the results. 8. Para. 3: This one-sentence paragraph appears incomplete. It might be combined with a discussion of gender differences for a fuller discussion of demographic variation. The following sentence has been added: Compared to Italian, foreign prisoners showed a lower prevalence of HCV infection, with African born patients, among foreigners, demonstrating the highest one, as published elsewhere [2]. Not surprisingly, women had a higher prevalence of HCV infection than men, as hhigher rates of Hepatitis B and C, HIV, and sexually transmitted infection, estimated at 2 10 times that of the general population was observed among imprisoned women, moreover, women had a significantly higher prevalence of all medical and psychiatric conditions and drug dependence when compared with imprisoned men 9. Para. 4: did not complete diagnostic procedures due to the need to plan prison officer escort this type of specific reason for failure of testing procedure requires documentation. Is this reason derived from clinical chart notations, or is it anecdotal evidence from conversations with prison staff? The sentence has been changed as follows: Twenty per cent were untreated as they did not had specialist consultation and/or did not complete diagnostic procedures mainly due to organizing deficit and logistic problems.
10. Final para.: You suggest the prevalence you found is lower than in other studies because prisoners at Opera are coming from all over for different crimes and different from those detained in smaller prisons. Since HCV is overwhelmingly associated with injection drug use, is the issue a) drug use differs among these different prison populations or b) testing differs substantially among different facilities? This and several of the questions above are raised because you may be suggesting important explanations for wide variation in testing and/or point estimates, but it is not clear which and whether this is definitely the case. The sentence has been changes as follows: Data on HCV prevalence reported by other Italian authors are slightly higher than the ones reported in the present study [3-4]. The reason for this difference may be explained by the fact that the population detained in Milano Opera is different from those of smaller prisons, as in Milano Opera are detained those prisoner sentenced for a period longer than three years collected from all the Country for different major crimes (that are not strictly associated with illicit drug abuse) and in smaller prisons are detained prisoners for minor offences (usually intravenous drug abusers). Moreover, despite roughly 30% of patients restricted at the time of survey were not test for HCV infection, demographic differences between those tested and not tested were not observed, not altering the reproducibility of the data. Other studies [3-4] report data on a subset of the examined population (less than 50%) and this might have biased the reproducibility of the results. Stylistic: Tables: please move N(%) from row to column headers to reduce redundancy Done Level of interest: An article of importance in its field Quality of written English: Needs some language corrections before being published Statistical review: No, the manuscript does not need to be seen by a statistician. Declaration of competing interests: I declare that I have no competing interests. Reviewer's report Title: Prevalence and epidemiological correlates of HCV infection in an Italian prison setting Version: 2 Date: 18 August 2013 Reviewer: Sarah Larney Reviewer's report: Although this revision of the manuscript is much improved, there are still issues to be addressed. Title: Should more appropriate reflect the aims and data presented it needs to mention that there is data on treatment entry and completion. The title has been changed, as follows: Prevalence and epidemiological correlates and treatment outcome of HCV infection in an Italian prison setting.
Abstract: The second sentence says that the aim of the study is to test feasibility of a screening program, and then evaluate treatment completion. The aims at the end of the introduction are to evaluate HCV prevalence and correlates, estimate the number needing treatment and were actually treated, and then calculate SVR. There needs to be consistency what are the actual aims of the paper? The sentence in the abstract has been modified as follows: The aim of the present study is to test in the feasibility of a screening programme for HCV infection an Italian prison and to evaluate the treatment outcomes. Methods: Under statistical analysis, I think the word quantitative should be continuous The text has been changed according with suggestions: continuous ones Results: This section remains difficult to read and understand. The first paragraph is fine. The second paragraph could be split into two or three paragraphs, according to subject matter. The second paragraph has been splitted There is no call-out to Table 2 in the text this needs to be added. The text has been changed according with suggestions: Among the 695 inmates tested (tab 2), The results from the table don t all need to be noted in the text; just the important ones should be described. Description of demographic data has been deleted, as suggested. Demographic characteristics of the 695 inmates tested are summarized by tab 2. The method section notes that a logistic regression was undertaken. I d like to see the results of this included in table 2. The results have been included in table 2 Discussion: The sentence beginning According to different studies needs some revision to be more circumspect. Do the numbers (20% to 40%) refer to number of HCV antibody positive inmates? If so, it is unlikely that all of these people need treatment, therefore the statement roughly 13000 to 25000 patients in prison need treatment is unlikely to be accurate. The sentence has been changed as follows: roughly 10000 to 20000 patients in prison potentially need treatment (considering that roughly 20% of patients testing antibody positive don t need treatment). The second paragraph of the discussion is disjointed. The information regarding mortality and end-stage liver disease is not related to the point that it is difficult to undertake HCV screening in prison. These are both legitimate points, but the mortality/esld points belong elsewhere in the discussion. The third paragraph of the discussion restates a finding and notes that a similar finding has been noted elsewhere. But what are the implications of this finding? What does it mean for screening, treatment etc.?
The information regarding mortality and end-stage liver disease has been repositioned in the discussion, as follows: confirming that in prison HCV treatment is an important option to be offered to inmates. HCV prognosis is worse if not appropriately treated, as evidenced by reduced mortality in patients successfully treated [16]. In a recent study conducted in Texas, end stage liver disease mortality in prison The language at the top of what is currently page 10 needs some careful thought there is no cure for HIV perhaps the word should be treatment? As suggested Treatment has been used instead of cure I m unsure what is meant by discrete rate of virologic success. The authors may wish to consider that another reason for the lower HCV prevalence observed here compared to other studies is that HCV prevalence appears to be decreasing over time. Level of interest: An article whose findings are important to those with closely related research interests Quality of written English: Needs some language corrections before being published Statistical review: No, the manuscript does not need to be seen by a statistician. Declaration of competing interests: I declare that I have no competing interests