Cs diffusion mechanisms in UO2 investigated by SIMS, TEM, and atomistic simulations.

Experimental investigations and atomistic simulations are combined to study the cesium diffusion processes at high temperature in UO2. After 133Cs implantation in UO2 samples, diffusion coefficients are determined using the depth profile evolution after annealing as measured by secondary ion mass spectrometry. An activation energy of 1.8 ± 0.2 eV is subsequently deduced in the 1300-1600 °C temperature range. Experimental results are compared to nudged elastic band simulations performed for different atomic paths including several types of uranium vacancy defects. Activation energies ranging from 0.49 up to 2.34 eV are derived, showing the influence of the defect (both in terms of type and concentration) on the Cs diffusion process. Finally, molecular dynamics simulations are performed, allowing the identification of preferential Cs trajectories that corroborate experimental observations.

Resource implications of the latent tuberculosis cascade of care: a time and motion study in five countries.

BACKGROUND: The End TB Strategy calls for global scale-up of preventive treatment for latent tuberculosis infection (LTBI), but little information is available about the associated human resource requirements. Our study aimed to quantify the healthcare worker (HCW) time needed to perform the tasks associated with each step along the LTBI cascade of care for household contacts of TB patients. METHODS: We conducted a time and motion (TAM) study between January 2018 and March 2019, in which consenting HCWs were observed throughout a typical workday. The precise time spent was recorded in pre-specified categories of work activities for each step along the cascade. A linear mixed model was fit to estimate the time at each step. RESULTS: A total of 173 HCWs in Benin, Canada, Ghana, Indonesia, and Vietnam participated. The greatest amount of time was spent for the medical evaluation (median: 11 min; IQR: 6-16), while the least time was spent on reading a tuberculin skin test (TST) (median: 4 min; IQR: 2-9). The greatest variability was seen in the time spent for each medical evaluation, while TST placement and reading showed the least variability. The total time required to complete all steps along the LTBI cascade, from identification of household contacts (HHC) through to treatment initiation ranged from 1.8 h per index TB patient in Vietnam to 5.2 h in Ghana. CONCLUSIONS: Our findings suggest that the time requirements are very modest to perform each step in the latent TB cascade of care, but to achieve full identification and management of all household contacts will require additional human resources in many settings.

Association between Bacillus Calmette-Guérin vaccination and lymphoma: a population-based birth cohort study.

BACKGROUND: Most risk factors for lymphoma identified so far relate to immunosuppression, but its aetiology remains unclear. OBJECTIVES: We investigated whether Bacillus Calmette-Guérin (BCG) vaccination is associated with lymphoma, overall and separately for Hodgkin's lymphoma (HL) and non-Hodgkin's lymphoma (NHL). METHODS: A cohort of 400 611 subjects born in the province of Québec, Canada, between 1970 and 1974 was used. Information on BCG vaccination was extracted from the Quebec BCG Vaccination Registry. Lymphomas cases were individuals who had ≥2 health encounters, medical visits or hospitalizations, for lymphoma within 2 months or who were identified through the Quebec Tumor Registry. Cox proportional hazard regression was used to estimate hazard ratios (HRs) and 95% confidence interval (CI), adjusting for potential confounders. RESULTS: A total of 178 335 (46.0%) subjects were BCG-vaccinated, and 1478 (0.38%) cases of lymphomas were ascertained. Amongst them, 922 were identified as NHL and 421 as HL. After adjustment, no association was observed between BCG vaccination and either lymphoma (any type) (HR = 1.03, 95% CI: 0.96-1.11) or NHL (HR = 0.99, 95% CI: 0.86-1.13). For HL, nonproportional hazards were observed. Before the age of 18, the risk of HL was elevated amongst vaccinated individuals (HR = 2.26, 95% CI: 1.39-3.69). However after 18 years of age, no association was found (HR = 0.93, 95% CI: 0.75-1.15). CONCLUSION: Bacillus Calmette-Guérin vaccination may increase the risk of HL before 18 years of age, but residual confounding cannot entirely be excluded. Given the benefits of BCG vaccination, these results need to be reproduced in other populations before firm conclusions can be drawn.

Exploring the interior of cuticles and compressions of fossil plants by FIB-SEM milling and image microscopy.

We present the first study of cuticles and compressions of fossil leaves by Focused Ion Beam Scanning Electron Microscopy (FIB-SEM). Cavities preserved inside fossil leaf compressions corresponding to substomatal chambers have been observed for the first time and several new features were identified in the cross-section cuts. These results open a new way in the investigation of the three-dimensional structures of both micro- and nanostructural features of fossil plants. Moreover, the application of the FIB-SEM technique to both fossils and extant plant remains represent a new source of taxonomical, palaeoenvironmental and palaeoclimatic information.

Exacerbation risk in severe asthma is stratified by inflammatory phenotype using longitudinal measures of sputum eosinophils.

BACKGROUND: Airway inflammatory phenotyping is increasingly applied to subjects with asthma. However, its relationship to clinical outcomes in difficult asthma is incompletely elucidated. OBJECTIVE: The goal of our study was to determine the relationship between exacerbation rates and phenotypes of difficult asthma based on the longitudinal measures of sputum eosinophils and neutrophils. METHODS: Subjects in the longitudinal observational study from two tertiary care centres that completed 1 year of observation and provided at least three sputum samples were classified by inflammatory phenotypes using previously established thresholds. Kaplan-Meier curves and univariable and multivariable Cox proportional hazard models were used to determine the association between inflammatory phenotypes and exacerbation rate. RESULTS: During the study, 115 exacerbations occurred in 73 severe asthmatic subjects. Subjects with the persistently eosinophilic phenotype had a significantly shorter time to first exacerbation and greater risk of exacerbation over a 1-year period than those with the non-eosinophilic phenotype based on the univariable and multivariable Cox proportional hazard model (hazard ratio [HR], 3.24; 95% confidence interval [CI], 1.35-7.72; adjusted HR, 3.90; 95% CI, 1.34-11.36). No significant differences in time to first exacerbation or exacerbation risk over a 1-year period were observed among the neutrophilic phenotypes. CONCLUSIONS: The persistent eosinophilic phenotype is associated with increased exacerbation risk compared with the non-eosinophilic phenotype in severe asthma. No differences in time to first exacerbation or exacerbation risk over a 1-year period were detected among neutrophilic phenotypes.

Phenotyping of difficult asthma using longitudinal physiological and biomarker measurements reveals significant differences in stability between clusters.

BACKGROUND: Although the heterogeneous nature of asthma has prompted asthma phenotyping with physiological or biomarker data, these studies have been mostly cross-sectional. Longitudinal studies that assess the stability of phenotypes based on a combination of physiological, clinical and biomarker data are currently lacking. Our objective was to assess the longitudinal stability of clusters derived from repeated measures of airway and physiological data over a 1-year period in moderate and severe asthmatics. METHODS: A total of 125 subjects, 48 with moderate asthma (MA) and 77 with severe asthma (SA) were evaluated every 3 months and monthly, respectively, over a 1-year period. At each 3-month time point, subjects were grouped into 4 asthma clusters (A, B, C, D) based on a combination of clinical (duration of asthma), physiological (FEV1 and BMI) and biomarker (sputum eosinophil count) variables, using k-means clustering. RESULTS: Majority of subjects in clusters A and C had severe asthma (93 % of subjects in cluster A and 79.5 % of subjects in cluster C at baseline). Overall, a total of 59 subjects (47 %) had stable cluster membership, remaining in clusters with the same subjects at each evaluation time. Cluster A was the least stable (21 % stability) and cluster B was the most stable cluster (71 % stability). Cluster stability was not influenced by changes in the dosage of inhaled corticosteroids. CONCLUSION: Asthma phenotyping based on clinical, physiologic and biomarker data identified clusters with significant differences in longitudinal stability over a 1-year period. This finding indicates that the majority of patients within stable clusters can be phenotyped with reasonable accuracy after a single measurement of lung function and sputum eosinophilia, while patients in unstable clusters will require more frequent evaluation of these variables to be properly characterized.

Evaluation of recombinant antigens of Trypanosoma cruzi to diagnose infection in naturally infected dogs from Chaco region, Argentina.

Dogs are considered the main mammal reservoir of Trypanosoma cruzi in domiciliary environments. Consequently, accurate detection of T. cruzi infection in canine populations is epidemiologically relevant. Here, we analysed the utility of the T. cruzi recombinant antigens FRA, SAPA, CP1, Ag1 and a SAPA/TSSA VI mixture, in an ELISA format. We used a positive control group of sera obtained from 38 dogs from the Chaco region in Argentina with positive homogenate-ELISA reaction, all of them also positive by xenodiagnosis and/or PCR. The negative group included 19 dogs from a nonendemic area. Sensitivity, specificity, area under the curve (AUC) of the receiver operating charactheristic (ROC) curve and Kappa index were obtained to compare the diagnostic efficiency of the tests. The SAPA/TSSA VI had the highest performance, with a sensitivity of 94.7% and an AUC ROC of 0.99 that indicates high accuracy. Among individual antigens, SAPA-ELISA yielded the highest sensitivity (86.8%) and AUC ROC (0.96), whereas FRA-ELISA was the least efficient test (sensitivity = 36.8%; AUC ROC = 0.53). Our results showed that the use of SAPA/TSSA VI in ELISAs could be a useful tool to study dogs naturally infected with T. cruzi in endemic areas.

Determinants of Bacillus Calmette-Guérin (BCG) vaccination among Québec children.

OBJECTIVES: To identify determinants of Bacillus Calmette-Guérin (BCG) vaccination among children born in Québec, Canada, in 1974, the last year of the systematic vaccination campaign. METHOD: A retrospective birth cohort was assembled in 2011 through probabilistic linkage of administrative databases (n=81,496). Potential determinants were documented from administrative databases and by interviewing a subset of subjects (n=1643) in 2012. Analyses were conducted among subjects with complete data, 71,658 (88%) birth cohort subjects and 1154 (70%) interviewed subjects, then redone using multiple imputation. Determinants of BCG vaccination during the organized vaccination program (in 1974), and after the program (1975 onwards) were assessed separately. Logistic regression with backward elimination was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Overall, 46% of subjects were BCG vaccinated, 43% during the program and 4% after it ended. BCG vaccination during the program was associated with parents' birthplace and urban or rural residence. BCG vaccination after the organized program was only related to ethnocultural origin of the child's grandparents. CONCLUSION: Different factors were related to vaccination within and after the organized program. Determinants of BCG vaccination in Québec, Canada, have never been studied and will be useful for future research and vaccination campaigns.

Oxygen hole states in zirconia lattices: quantitative aspects of their cathodoluminescence emission.

Systematic assessments of cathodoluminescence (CL) spectroscopy, Raman spectroscopy (RS), and X-ray diffraction (XRD) are presented for pure zirconia and for a series of Y-doped zirconia powders (henceforth, simply referred to as undoped ZrO2 and YSZ powders, respectively) synthesized according to a coprecipitation method of Zr and Y chlorides. Emphasis is placed here on spectral emissions related to oxygen-vacancy sites (i.e., oxygen hole states) equally detected from undoped and Y-doped ZrO2 samples, either as intrinsic defects or, extrinsically induced, by means of cathodoluminescence. Most counterintuitively, the undoped ZrO2 sample (i.e., the one with presumably the lowest amount of oxygen vacancies) experienced the strongest CL emission. A progressive "quenching" effect on CL emission with increasing the fraction of Y(3+) dopant could also be observed because the intrinsic vacancies present in the undoped lattice are the most efficient since they can trap two electrons to gain electrical neutrality. However, as soon as Y(3+) ions are introduced in the system, those intrinsic vacancies migrate to Y-sites in next-nearest-neighbor locations, namely in a less efficient lattice location. This phenomenon is tentatively referred to as "delocalization" of vacancy sites. Moreover, the fact that Y-doped zirconia series presents quite similar CL spectra compared to the undoped zirconia could be an evidence that the radiative centers of undoped and Y-doped ZrO2 are basically the same. A fitting procedure has been made aiming to give a rational description of the variation of the spectra morphology, and a parameter able to describe the monoclinic to tetragonal phase transformation has been found. This parameter and the overall set of CL data enabled us to quantitatively assess polymorphic phase fractions by CL spectroscopy in the scanning electron microscope.

Golimumab improves health-related quality of life of patients with moderate-to-severe ulcerative colitis: Results of the go-care study.

BACKGROUND: In recent years, improvement of Health-Related Quality of Life (HRQoL) in Ulcerative colitis (UC) has become a relevant measure for treatment efficacy. METHODS: We report results from a multicenter prospective study in Italy investigating HRQoL in adult patients with UC treated with golimumab (GLM). Patients who had shown clinical response after a 6-week induction phase (w0), were followed for an additional 48 weeks (w48) (total 54-week treatment). RESULTS: Of the 159 patients enrolled 90 completed the study. Compared to values at the beginning of treatment (n = 137), significant improvements were observed for mean total Inflammatory Bowel Disease Questionnaire (IBDQ) scores at w0 (168.5) and w48 (181.7). Patients with baseline PMS above the median tended to have greater improvements in IBDQ at w0 (OR 2.037, p = 0.033) and w48 (OR 3.292, p = 0.027). Compared to beginning of GLM treatment, the mean Full Mayo Score (FMS) decreased by 5.9 points at w48, while mean Partial Mayo Score (PMS) decreased by 3.9 points at w0 and by 4.9 points at w48. CONCLUSIONS: GLM improved HRQoL, disease activity and inflammatory biomarkers in UC patients with moderate-to-severely active disease. The greater the burden of disease activity at baseline, the greater the improvement of HRQoL after 24 and 48 weeks of treatment.

Effect of topical corticosteroids on allergic airway inflammation and disease severity in obstructive sleep apnoea.

BACKGROUND: The incidence of sleep-related breathing disorders is correlated with lower and upper airway inflammatory diseases, such as asthma and allergic rhinitis. We hypothesized that corticosteroids treatment would lead to a greater reduction in disease severity in obstructive sleep apnoea syndrome (OSAS) patients with concomitant allergic rhinitis vs. non-allergic OSAS patients by reducing the level of inflammation in upper airway tissues. OBJECTIVE: This study was performed to determine whether treatment with intranasal corticosteroids could reduce upper airway inflammation and improve sleep parameters in obstructive sleep apnoea syndrome patients with or without concomitant allergic rhinitis. METHODS: Obstructive sleep apnoea syndrome patients with (n = 34) or without (n = 21) documented allergic rhinitis voluntarily enrolled in the study and were assessed at baseline and after corticosteroids treatment for 10-12 weeks. Sleep studies were performed and biopsies were obtained from the inferior turbinate, nasopharynx, and uvula. The apnoea-hypopnoea index, sleep quality, and level of daytime alertness were determined, and immunocytochemistry was used to phenotype tissue inflammation. RESULTS: Standard sleep indices improved following treatment in the entire cohort of obstructive sleep apnoea syndrome patients, with greater improvement seen in the allergic rhinitis group. Allergic rhinitis patients demonstrated significantly improved O2 saturation and a lower supine apnoea-hypopnoea index score after corticosteroid treatment; similar improvements were not seen in the non-allergic rhinitis group. Eosinophilia was detected at all three sites in the allergic rhinitis group, but not in the non-allergic rhinitis group. Following treatment, fewer eosinophils and CD4 lymphocytes were documented at all three biopsy sites in the allergic group; the reduction in inflammation was less apparent in the non-allergic rhinitis group. CONCLUSION: This study has provided important molecular and clinical evidence regarding the ability of corticosteroids to reduce upper airway inflammation and improve obstructive sleep apnoea syndrome morbidity patients with concomitant allergic rhinitis.

Impact of sleep disorder treatment on fatigue in multiple sclerosis.

BACKGROUND: We recently reported that sleep disorders are significantly associated with fatigue in multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to assess the effects of sleep disorder treatment on fatigue and related clinical outcomes in MS. METHODS: This was a controlled, non-randomized clinical treatment study. Sixty-two MS patients completed standardized questionnaires including the Fatigue Severity Scale (FSS), Multidimensional Fatigue Inventory (MFI), Epworth Sleepiness scale (ESS) and Pittsburgh Sleep Quality Index (PSQI), and underwent polysomnography (PSG). Patients with sleep disorders were offered standard treatment. Fifty-six subjects repeated the questionnaires after ≥ three months, and were assigned to one of three groups: sleep disorders that were treated (SD-Tx, n=21), sleep disorders remaining untreated (SD-NonTx, n=18) and no sleep disorder (NoSD, n=17). RESULTS: FSS and MFI general and mental fatigue scores improved significantly from baseline to follow-up in SD-Tx (p <0.03), but not SD-NonTx or NoSD subjects. ESS and PSQI scores also improved significantly in SD-Tx subjects (p <0.001). Adjusted multivariate analyses confirmed significant effects of sleep disorder treatment on FSS (-0.87, p = 0.005), MFI general fatigue score (p = 0.034), ESS (p = 0.042) and PSQI (p = 0.023). CONCLUSION: Treatment of sleep disorders can improve fatigue and other clinical outcomes in MS.

Performance of different Trypanosoma cruzi antigens in the diagnosis of Chagas disease in patients with American cutaneous leishmaniasis from a co-endemic region in Argentina.

OBJECTIVE: To determine the ability of recombinant antigens to detect cases of infection with Trypanosoma cruzi among cases of infection with Leishmania spp. by serological methods. METHODS: Sera from 41 patients infected with Leishmania spp. were evaluated with ELISA using single (FRA, CP1 and TSSAVI) or pooled (commercial Rec-ELISA) recombinant proteins or homogenate antigens (commercial H-ELISA). As there is no gold standard antigen to discriminate Chagas disease from leishmaniasis, the correlation of results between defined antigens and the homogenate was made with Kappa Index (KI), the level of correlation considered being used as a criterion of specificity. RESULTS: Single recombinant antigens and Rec-ELISA showed good correlation (KI > 0.8). A low correlation (KI < 0.66) was observed between the results from single recombinant antigens or the commercial recombinant kit and H-ELISA. CONCLUSIONS: The highly correlated results between T. cruzi single or pooled recombinant proteins are indicative of the usefulness of recombinant antigens for Chagas diagnosis. Our results also indicate that in the city of Oran in Argentina, between 12% and 17% of patients with leishmaniasis are also infected with Chagas disease. The high KI values between TSSAVI and the other recombinant proteins suggest that in these patients, the infection may be caused by T. cruzi II and/or V and/or VI lineages.

Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone.

We report a woman with primary amenorrhoea and infertility associated with an isolated deficiency of pituitary follicle-stimulating hormone (FSH), but normal luteinizing hormone (LH) secretion. Ovulation was induced by administration of exogenous FSH and resulted in a successful pregnancy. Sequence analysis of the FSH beta-subunit gene indicated that she is homozygous for a two nucleotide frameshift deletion in the coding sequence. Her mother and son are heterozygous for this mutation. This deletion results in an alteration of amino acid codons 61-86 followed by a premature termination codon. The predicted truncated beta-subunit peptide lacks regions which are important for association with the alpha subunit and for binding to and activation of the FSH receptor. Abnormalities of FSH structure or function might be an under recognised but treatable cause of infertility.

Influence of natural seawater variables on the corrosion behaviour of aluminium-magnesium alloy.

Corrosion is an important issue for alloys in natural seawater, where microorganisms can accelerate or mitigate corrosion. Al-Mg alloys are used for marine activities and various associated technologies. Here, the behaviour of AA5083 alloy was investigated in natural seawater with marine exposure lasting up to 50 days and detailing the first 8 days in two experimental series. Experimental work was carried out, including semi-field tests in natural seawater (biotic conditions) compared with abiotic conditions. The open circuit potential (OCP) measurements, during the immersion time, exhibited significantly different behaviours: an OCP downward displacement occurred under abiotic conditions, while, in biotic conditions OCP remained generally stable since the beginning of the immersion, revealing an inhibiting effect of the biological activity on the Al-Mg corrosion. This was accompanied by different surface modifications under biotic conditions: surface and cross-section characterization, performed by scanning electron microscopy with energy dispersive X-ray spectroscopy, showed less corrosion developed on the surface after 8-day immersion and formation of a protective layer during 50-day immersion. The present study shows that marine biological activity positively influences the Al alloy corrosion process, with surface modifications resulting in a protective effect counteracting the aggressiveness of chloride ions.

Obstructive sleep apnea is associated with fatigue in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) patients often suffer from fatigue. OBJECTIVE: We evaluated the relationship of obstructive sleep apnea (OSA) to fatigue and sleepiness in MS patients. METHODS: Ambulatory MS patients without known sleep disorders and healthy controls underwent diagnostic polysomnography and a multiple sleep latency test (objective sleepiness measure). Fatigue was measured with the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI), and subjective sleepiness by Epworth Sleepiness Scale. Covariates included age, sex, body mass index, Expanded Disability Status Scale (EDSS), depression, pain, nocturia, restless legs syndrome, and medication. RESULTS: OSA (apnea-hypopnea index ≥ 15) was found in 36 of 62 MS subjects and 15 of 32 controls. After adjusting for confounders, severe fatigue (FSS ≥ 5) and MFI-mental fatigue (>group median) were associated with OSA and respiratory-related arousals in MS, but not control subjects. Subjective and objective sleepiness were not related to OSA in either group. In a multivariate model, variables independently associated with severe fatigue in MS were severe OSA [OR 17.33, 95% CI 2.53-199.84], EDSS [OR 1.88, 95% CI 1.21-3.25], and immunomodulating treatment [OR 0.14, 95% CI 0.023-0.65]. CONCLUSIONS: OSA was frequent in MS and was associated with fatigue but not sleepiness, independent of MS-related disability and other covariates.

Inflammatory markers and BDNF in obstructive sleep apnea (OSA) in Parkinson's disease (PD).

OBJECTIVE: Obstructive sleep apnea (OSA) exacerbates Parkinson's disease (PD) manifestations including cognitive dysfunction. Both OSA and PD have been associated with inflammation. Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive function. We aimed to investigate inflammatory cytokines and BDNF in relation to OSA and PD symptoms. METHODS: In a prospective observational study, patients with PD underwent overnight polysomnography. Morning serum levels of interleukin (IL)-1ß, IL-6, IL-8, TNFα, and BDNF were quantified at baseline (n = 64) and 6 months (n = 38). Outcomes included non-motor and motor standard scores; Montreal Cognitive Assessment (MoCA); and Epworth Sleepiness scale (ESS). Associations were assessed using linear regression, adjusting for age, sex and body mass index. RESULTS: At baseline, IL-6 was associated with the Apnea-Hypopnea Index (ß = 0.013, p = 0.03), and the Oxygen Desaturation Index (ß = 0.028, p = 0.002). No other associations between cytokines and sleep parameters were found. Motor dysfunction was associated with IL-6 (ß = 0.03, p = 0.001). ESS was associated non-significantly with IL-6 (ß = 0.04, p = 0.07) and BDNF (ß = 555, p = 0.06). At follow-up, change in IL-6 was associated with change in non-motor (ß = 0.08, p = 0.007), and motor (ß = 0.03, p = 0.001) symptoms. Change in BDNF was associated with change in ESS (ß = 1450, p = 0.02). INTERPRETATION: We found an association between IL-6 levels and both OSA severity and PD motor dysfunction. At follow-up, increasing IL-6 correlated with deterioration of motor and non-motor PD symptoms. Increasing BDNF correlated with increasing sleepiness. Further work with a larger sample size is needed, but our results support the hypothesis that OSA-related inflammation plays a role in PD manifestations and progression.

Patterns and characteristics of TB among key risk groups in Canada, 1993-2018.

BACKGROUND: Canada has a low incidence of TB, although certain groups are disproportionately affected.OBJECTIVE: To describe and compare the epidemiology, trends and characteristics of TB in Quebec, Canada, among all patients reported during 1993-2018.METHODS: Demographics and risk factors were compared for the three groups accounting for most TB diagnoses reported in Quebec (foreign-born, Canadian-born non-Indigenous and Inuit). Average annual incidence and incidence rate ratios (IRRs) were estimated and compared using Poisson regression.RESULTS: Of 6,941 persons with a first episode of TB, 4,077 (59%) were foreign-born, 2,314 (33%) were Canadian-born non-Indigenous and 389 (6%) were Inuit. The average annual incidence for foreign-born, Canadian-born non-Indigenous and Inuit was respectively 17.0, 1.4 and 137.1 per 100,000 population. Compared to Canadian-born non-Indigenous, the IRR for foreign-born and Inuit was respectively 12.3 (95% CI 11.6-12.9) and 98.7 (95% CI 88.6-109.9). There was evidence of community transmission among the Inuit, with more than 80% of patients having a TB contact (2012-2018 data) and 65% (251/389) of diagnoses in those aged <25 years.CONCLUSION: Although TB rates among the Canadian-born non-Indigenous are extremely low, there are persistent and distinct TB epidemics among the foreign-born and Inuit. Tailored approaches to TB prevention and care are needed to address TB among high-risk populations in low TB incidence settings.

Quality of endoscopic screening for colorectal cancer in Italy: A national survey.

BACKGROUND: Colorectal cancer (CRC) is a major healthcare problem all over the world and screening is effective in reducing mortality and increasing survival. Since colonoscopy has a central role in faecal immunochemical test (FIT)-based CRC screening and surveillance, consistent quality measures are essential to ensure quality and outcomes. Nevertheless, screening modalities in clinical practice may differ according to the centers experience and the local availability of instrumentation and devices. AIMS: to assess the quality of endoscopic screening for CRC and adherence to international guidelines across Gastroenterology Departments in Italy. METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. RESULTS: Data from 64 hospitals from 17 Italian regions were analyzed. 32/64 (50.0%) were from northern, 12/64 (18.75%) from central and 20/64 (31.25%) from southern Italy. Each center is equipped with a median of 5.0 (3.5-7.0) endoscopists involved in CRC screening, 71.4% of which are gastroenterologists. After a positive FIT, most centers (93.8%) schedule a colonoscopy within 3 months. High-definition video endoscopy is routinely performed in 68.8% and chromoendoscopy in 53.1% of centers. Withdrawal time is ≥6 min in 79.9% and cecal intubation rate is ≥90% in 94.4% of departments. Finally, in 92.7% of centers adenoma detection rate (ADR) overcome the minimum standard of 25%. Analyzing the data by regional areas, a significant higher number of median endoscopic examinations/year (6500 vs 4000 and 3000, respectively, p = 0.024) and of endoscopists per center (6.5 vs 5.0 and 3.5, respectively, p < 0.001) has been registered in the northern compared to central-southern centers. CONCLUSIONS: Data from this survey show adequacy and good quality of endoscopic screening for CRC in Italy, highlighting, at the same time, relevant deficiencies and a discrepancy in procedural attitudes between the different centers. These findings call for a urgent action to overcome the shortcomings, refine and homogenize the behaviour of all screening centers in the national territory and improve the outcomes.

Implementing the 4R and 9H regimens for TB preventive treatment in Indonesia.

BACKGROUND: The implementation of tuberculosis preventive treatment (TPT) is challenging especially in resource-limited settings. As part of a Phase 3 trial on TPT, we described our experience with the use of rifampicin for 4 months (4R) and isoniazid for 9 months (9H) in Indonesia.METHODS: In 2011-2017, children and adults with latent TB infection were randomised to either 4R or 9H and followed until 16 months after randomisation for children and 28 months for adults. The primary outcome was the treatment completion rate. Secondary outcomes were Grade 3-5 adverse events (AEs), active TB occurrence, and health costs.RESULTS: A total of 157 children and 860 adults were enrolled. The 4R treatment completion rate was significantly higher than that of 9H (78.7% vs. 65.5%), for a rate difference of 13.2% (95% CI 7.1-19.2). No Grade 3-5 AEs were reported in children; in adults, it was lower in 4R (0.4%) compared to 9H (2.8%). The incidence of active TB was lower with 4R than with 9H (0.09/100 person-year vs. 0.36/100 person-year) (rate difference: -0.36/100 person-year). The total cost per patient was lower for the 4R regimen than for the 9H regimen (USD151.9 vs. USD179.4 in adults and USD152.9 vs. USD206.5 in children)CONCLUSIONS: Completion and efficacy rates for 4R were better than for 9H. Compared to 9H, 4R was cheaper in all age groups, safer in adults and equally safe in children. The Indonesian TB program could benefit from these benefits of the 4R regimen.