106 research outputs found
Policy and planning of prevention in Italy: Results from an appraisal of prevention plans developed by Regions for the period 2010-2012
Abstract
Health policies on disease prevention differ widely between countries. Studies suggest that different countries have much to learn from each other and that significant health gains could be achieved if all countries followed best practice. This paper describes the policy development and planning process relating to prevention activities in Italy, through a critical appraisal of Regional Prevention Plans (RPPs) drafted for the period 2010-2012. The analysis was performed using a specific evaluation tool developed by a Scientific Committee appointed by the Italian Ministry of Health. We appraised nineteen RPPs, comprising a total of 702 projects, most of them in the areas of universal prevention (62.9%) and prevention in high risk groups (27.0%). Italian Regions established prevention activities using an innovative combination of population and high-risk individuals approaches. However, some issues, such as the need to reduce health inequalities, were poorly addressed. The technical drafting of RPPs required some improvement; e.g. the evidence of the effectiveness and cost-effectiveness of the health interventions proposed was seldom reported. There were significant geographical differences across the Regions in the appraisal of RPPs. Our research suggests that continuous assessment of the planning process of prevention may become a very useful tool for monitoring, and ultimately strengthening, public health capacity in the field of prevention. Further research is needed to analyze determinants of regional variation
Failure or relapse predictors for the STREAM Stage 1 short regimen for RR-TB
BACKGROUND: STREAM (Standardised Treatment Regimens of Anti-tuberculosis drugs for Multidrug-Resistant Tuberculosis) Stage 1 demonstrated non-inferior efficacy of a short regimen for rifampicin-resistant TB (RR-TB) compared to a long regimen as recommended by the WHO. The present paper analyses factors associated with a definite or probable failure or relapse (FoR) event in participants receiving the Short regimen.METHODS: This analysis is restricted to 253 participants allocated to the Short regimen and is based on the protocol-defined modified intention to treat (mITT) population. Multivariable Cox regression models were built using backwards elimination with an exit probability of P = 0.157, equivalent to the Akaike Information Criterion, to identify factors independently associated with a definite or probable FoR event.RESULTS: Four baseline factors were identified as being significantly associated with the risk of definite or probable FoR (male sex, a heavily positive baseline smear grade, HIV co-infection and the presence of costophrenic obliteration). There was evidence of association of culture positivity at Week 8 and FoR in a second model and Week 16 smear positivity, presence of diabetes and of smoking in a third model.CONCLUSION: The factors associated with FoR outcomes identified in this analysis should be considered when determining the optimal shortened treatment regimen
The Evaluation of a Standardised Treatment Regimen of anti-Tuberculosis Drugs for Patients with MDR-TB (STREAM): study protocol for a randomised controlled trial
Background:
In contrast to drug-sensitive tuberculosis, the guidelines for the treatment of multi-drug-resistant
tuberculosis (MDR-TB) have a very poor evidence base; current recommendations, based on expert opinion, are
that patients should be treated for a minimum of 20 months. A series of cohort studies conducted in Bangladesh
identified a nine-month regimen with very promising results. There is a need to evaluate this regimen in comparison
with the currently recommended regimen in a randomized controlled trial in a variety of settings, including patients
with HIV-coinfection.
Methods/Design:
STREAM is a multi-centre randomized trial of n
on-inferiority design comparing a nine-month
regimen to the treatment currently recommended by th
e World Health Organization in patients with MDR
pulmonary TB with no evidence on line probe assay of fluoroquinolone or kanamycin resistance. The nine-month
regimen includes clofazimine and high-dose moxifloxacin and can be extended to 11 months in the event of delay
in smear conversion. The primary outcome is based on the bacteriological status of the patients at 27 months
post-randomization. Based on the assumption that the nine-month regimen will be slightly more effective than
the control regimen and, given a 10% margin of non-inferiority, a total of 400 patients are required to be enrolled. Health
economics data are being collected on all patients in selected sites.
Discussion:
The results from the study in Bangladesh and cohorts in progress elsewhere are encouraging, but
for this regimen to be recommended more widely than in a research setting, robust evidence is needed from
a randomized clinical trial. Results from the STREAM t
rial together with data fr
om ongoing cohorts should
provide the evidence necessary to revise current recommendations for the treatment for MDR-TB.
Trial registration:
This trial was registered with clincaltrials.gov (registration number: ISRCTN78372190) on 14 October 2010
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Reduction of diagnostic and treatment delays reduces rifampicin-resistant tuberculosis mortality in Rwanda
YesSETTING: In 2005, in response to the increasing prevalence of rifampicin-resistant tuberculosis (RR-TB) and poor treatment outcomes, Rwanda initiated the programmatic management of RR-TB, including expanded access to systematic rifampicin drug susceptibility testing (DST) and standardised treatment.OBJECTIVE: To describe trends in diagnostic and treatment delays and estimate their effect on RR-TB mortality.DESIGN: Retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality.RESULTS: Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016. Total delay in starting multidrug-resistant TB (MDR-TB) treatment of more than 100 days was associated with more than two-fold higher odds for dying. When delays were long, empirical RR-TB treatment initiation was associated with a lower mortality.CONCLUSION: The reduction of diagnostic and treatment delays reduced RR-TB mortality. We anticipate that universal testing for RR-TB, short diagnostic and therapeutic delays and effective standardised MDR-TB treatment will further decrease RR-TB mortality in Rwanda
Effectiveness of GenoType MTBDRsl in excluding TB drug resistance in a clinical trial
OBJECTIVES: To assess the performance of the GenoType MTBDRsl v1, a line-probe assay (LPA), to exclude baseline resistance to fluoroquinolones (FQs) and second-line injectables (SLIs) in the Standard Treatment Regimen of Anti-tuberculosis Drugs for Patients With MDR-TB 1 (STREAM 1) trial. METHODS: Direct sputum MTBDRsl results in the site laboratories were compared to indirect phenotypic drug susceptibility testing (pDST) results in the central laboratory, with DNA sequencing as a reference standard. RESULTS: Of 413 multidrug-resistant TB (MDR-TB) patients tested using MTBDRsl and pDST, 389 (94.2%) were FQ-susceptible and 7 (1.7%) FQ-resistant, while 17 (4.1%) had an inconclusive MTBDRsl result. For SLI, 372 (90.1%) were susceptible, 5 (1.2%) resistant and 36 (8.7%) inconclusive. There were 9 (2.3%) FQ discordant pDST/MTBDRsl results, of which 3 revealed a mutation and 5 (1.3%) SLI discordant pDST/MTBDRsl results, none of which were mutants on sequencing. Among the 17 FQ- and SLI MTBDRsl-inconclusive samples, sequencing showed 1 FQ- and zero SLI-resistant results, similar to frequencies among the conclusive MTBDRsl. The majority of inconclusive MTBDRsl results were associated with low bacillary load samples (acid-fast bacilli smear-negative or scantily positive) compared to conclusive results (P < 0.001). CONCLUSION: MTBDRsl can facilitate the rapid exclusion of FQ and SLI resistances for enrolment in clinical trials
Implications of Storing Urinary DNA from Different Populations for Molecular Analyses
Molecular diagnosis using urine is established for many sexually transmitted diseases and is increasingly used to diagnose tumours and other infectious diseases. Storage of urine prior to analysis, whether due to home collection or bio-banking, is increasingly advocated yet no best practice has emerged. Here, we examined the stability of DNA in stored urine in two populations over 28 days.Urine from 40 (20 male) healthy volunteers from two populations, Italy and Zambia, was stored at four different temperatures (RT, 4 degrees C, -20 degrees C & -80 degrees C) with and without EDTA preservative solution. Urines were extracted at days 0, 1, 3, 7 and 28 after storage. Human DNA content was measured using multi-copy (ALU J) and single copy (TLR2) targets by quantitative real-time PCR. Zambian and Italian samples contained comparable DNA quantity at time zero. Generally, two trends were observed during storage; no degradation, or rapid degradation from days 0 to 7 followed by little further degradation to 28 days. The biphasic degradation was always observed in Zambia regardless of storage conditions, but only twice in Italy.Site-specific differences in urine composition significantly affect the stability of DNA during storage. Assessing the quality of stored urine for molecular analysis, by using the type of strategy described here, is paramount before these samples are used for molecular prognostic monitoring, genetic analyses and disease diagnosis
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Prevalence and drivers of false-positive rifampicin-resistant Xpert MTB/RIF results: a prospective observational study in Rwanda
YesBackground: The Xpert MTB/RIF (Xpert) assay is used globally to rapidly diagnose tuberculosis and resistance to rifampicin. We investigated the frequency and predictors of false-positive findings of rifampicin resistance with Xpert. Methods: We did a prospective, observational study of individuals who were enrolled in a Rwandan nationwide diagnostic cohort study (DIAMA trial; NCT03303963). We included patients identified to have rifampicin resistance on initial Xpert testing. We did a repeat Xpert assay and used rpoB Sanger and deep sequencing alongside phenotypic drug susceptibility testing (pDST) to ascertain final rifampicin susceptibility status, with any (hetero)resistant result overriding. We used multivariable logistic regression to assess predictors of false rifampicin resistance on initial Xpert testing, adjusted for HIV status, tuberculosis treatment history, initial Xpert semi-quantitative bacillary load, and initial Xpert probe. Findings: Between May 4, 2017, and April 30, 2019, 175 people were identified with rifampicin resistance at initial Xpert testing, of whom 154 (88%) underwent repeat Xpert assay. 54 (35%) patients were confirmed as rifampicin resistant on repeat testing and 100 (65%) were not confirmed with resistance. After further testing and sequencing, 121 (79%) of 154 patients had a final confirmed status for rifampicin susceptibility. 57 (47%) of 121 patients were confirmed to have a false rifampicin resistance result and 64 (53%) had true rifampicin resistance. A high pretest probability of rifampicin resistance did not decrease the odds of false rifampicin resistance (adjusted odds ratio [aOR] 6·0, 95% CI 1·0–35·0, for new tuberculosis patients vs patients who needed retreatment). Ten (16%) of the 64 patients with true rifampicin resistance did not have confirmed rifampicin resistance on repeat Xpert testing, of whom four had heteroresistance. Of 63 patients with a very low bacillary load on Xpert testing, 54 (86%) were falsely diagnosed with rifampicin-resistant tuberculosis. Having a very low bacillary load on Xpert testing was strongly associated with false rifampicin resistance at the initial Xpert assay (aOR 63·6, 95% CI 9·9–410·4). Interpretation: The Xpert testing algorithm should include an assessment of bacillary load and retesting in case rifampicin resistance is detected on a paucibacillary sputum sample. Only when rifampicin resistance has been confirmed on repeat testing should multidrug-resistant tuberculosis treatment be started. When rifampicin resistance has not been confirmed on repeat testing, we propose that patients should be given first-line anti-tuberculosis drugs and monitored closely during treatment, including by baseline culture, pDST, and further Xpert testing.The European & Developing Countries Clinical Trials Partnership 2 programme, and Belgian Directorate General for Development Cooperation
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