Safety and immunogenicity of heterologous COVID-19 vaccine regimens to deal with product shortage: A randomised clinical trial in an elderly population.

Objectives: In a context of COVID-19 vaccine shortages, this study sought to evaluate the safety and efficacy of receiving one dose of Gam-COVID-Vac rAd26 followed by a second COVID-19 vaccine dose of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV in a cohort of older adults. Study design: Single-centre, randomised, open label, non-inferiority trial. Methods: Adults aged ≥65 years who had received one dose of Gam-COVID-Vac rAd26 were randomised in a 1:1:1 ratio to receive a second-dose COVID-19 vaccination of either Gam-COVID-Vac rAd5, ChAdOx1 nCoV-19 or BBIBP-CorV. The primary outcome was the assessment of the humoral immune response to vaccination (i.e. antibody titres of SARS-CoV-2 spike protein at 28 days after second-dose vaccination). In addition, neutralising antibody titres at day 28 for the three schedules were measured. Results: Of 85 participants who were enrolled in the study between 26 and July 30, 2021, 31 individuals were randomised to receive Gam-COVID-Vac rAd5, 27 to ChAdOx1 nCoV-19 and 27 to BBIBP-CorV. The mean age of participants was 68.2 years (SD 2.9) and 49 (57.6%) were female. Participants who received Gam-COVID-Vac rAd5 and ChAdOx1 nCoV1-19 showed significantly increased anti-S titres at 28 days after second-dose vaccination, but this magnitude of difference was not observed for those who received BBIBP-CorV. The ratio between the geometric mean at day 28 and baseline within each group was 11.8 (6.98-19.89) among patients assigned to Gam-COVID-Vac rAd26/rAd5, 4.81 (2.14-10.81) for the rAd26/ChAdOx1 nCoV-19 group and 1.53 (0.74-3.20) for the rAd26/BBIBP-CorV group. All of the schedules were shown to be safe. Conclusions: The findings in this study contribute to the scarce information published on the safety and immunogenicity of Gam-COVID-Vac heterologous regimens and will help the development of guidelines and vaccine programme management.

Environmental asbestos exposure and clustering of malignant mesothelioma in community: a spatial analysis in a population-based case-control study.

BACKGROUND: Neighborhood exposure to asbestos increases the risk of developing malignant mesothelioma (MM) in residents who live near asbestos mines and asbestos product plants. The area of Casale Monferrato (Northwest Italy) was impacted by several sources of asbestos environmental pollution, due to the presence of the largest Italian asbestos cement (AC) plant. In the present study, we examined the spatial variation of MM risk in an area with high levels of asbestos pollution and secondly, and we explored the pattern of clustering. METHODS: A population-based case-control study conducted between 2001 and 2006 included 200 cases and 348 controls. Demographic and occupational data along with residential information were recorded. Bivariate Kernel density estimation was used to map spatial variation in disease risk while an adjusted logistic model was applied to estimate the impact of residential distance from the AC plant. Kulldorf test and Cuzick Edward test were then performed. RESULTS: One hundred ninety-six cases and 322 controls were included in the analyses. The contour plot of the cases to controls ratio showed a well-defined peak of MM incidence near the AC factory, and the risk decreased monotonically in all directions when large bandwidths were used. However, considering narrower smoothing parameters, several peaks of increased risk were reported. A constant trend of decreasing OR with increasing distance was observed, with estimates of 10.9 (95% CI 5.32-22.38) and 10.48 (95%CI 4.54-24.2) for 0-5 km and 5-10 km, respectively (reference > 15 km). Finally, a significant (p < 0.0001) excess of cases near the pollution source was identified and cases are spatially clustered relative to the controls until 13 nearest neighbors. CONCLUSIONS: In this study, we found an increasing pattern of mesothelioma risk in the area around a big AC factory and we detected secondary clusters of cases due to local exposure points, possibly associated to the use of asbestos materials.

Developing an Electronic Record Tool Representative of Primary Health Care in the Public Health Care System of Buenos Aires City.

The Primary Health Care strategy is based on organization of interdisciplinary teams and comprehensive approach to health, disease and health care processes. To strengthen information systems so that they represent primary health care complexities, participatory meetings were held with primary care practitioners from the public health care system of Buenos Aires City. Terms for the record tool and its components were chosen using consensus methodologies. This process involved 300 practitioners from 49 centers, and submission of 21 proposals. It was decided to change the term "Electronic Medical Record" with "Comprehensive Health Record." It was also agreed that, apart from "Reason for Consultation," the field "Problem Situation" would be added, that "Care Service" would be replaced with "Care Act," and that a new module "Health Team Management and Education Activities" would be included to document practitioners team activities.

Mejora en el diagnóstico y tratamiento oportuno del accidente cerebrovascular en Argentina / Improvement in the diagnosis and timely treatment of stroke in Argentina

INTRODUCCIÓN No existe evidencia de que la conformación de redes de atención y procesos de mejora de la calidad en Argentina se relacionen con mejores resultados en el tratamiento del infarto agudo de miocardio. OBJETIVOS Evaluar las principales causas de demora y/o no reperfusión en pacientes con accidente cerebrovascular agudo isquémico, determinando si la conformación de redes de atención, derivación precoz y mejora de la calidad produce mejores resultados. MÉTODOS Se realizó un análisis de línea de base, con registro inicial de pacientes en seis centros de referencia. En aquellos pacientes que no recibieron tratamiento apropiado (demora o falta de reperfusión), se analizaron las causas raíz. En cada centro se desarrollaron posibles intervenciones ajustadas a estas causas. RESULTADOS En el período comprendido entre junio de 2015 y marzo de 2016 se evaluó por servicio de emergencias de 6 hospitales de Argentina a un total de 224 pacientes con diagnóstico presuntivo de ACV/AIT dentro de las 72 horas de evolución, con una media de edad de 66±14 años y un 59,8% de hombres. De ellos, 165 pacientes (73%) fueron ACV isquémicos. De los 165 ACV isquémicos, fueron tratados con trombolíticos n=28 (16,9%) de los pacientes. El tiempo desde el inicio de los síntomas y el tratamiento con TL promedio fue de 187 minutos. Un 83,1% de los pacientes no recibió tratamiento oportuno. Las principales causas fueron el desconocimiento de los pacientes y las demoras en el traslado y diagnóstico. DISCUSIÓN Fue factible identificar las principales causas de demora en el tratamiento del ACV y diseñar redes de atención y ciclos de mejora. Esto puede mejorar los resultados de la reperfusión, que tiene un gran impacto en la mortalidad.

CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma.

BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma.

The sociodemographic patterning of opposition to raising taxes on tobacco and restricting tobacco advertisements in Argentina.

BACKGROUND: Argentina has enacted important tobacco control initiatives in recent years. Yet little is known about the social patterning of attitudes toward tobacco control. Research is needed to explore what predicts opposition to tobacco control initiatives such as higher taxes on tobacco and the prohibition of tobacco advertising. STUDY DESIGN: Secondary analysis of Argentina's Global Adult Tobacco Survey (N = 6645). METHODS: Binary logistic regression analysis examining opposition to raising tobacco taxes and banning tobacco publicity. Models were stratified by smoking status. RESULTS: Respondents generally indicated very little opposition to either tobacco control measure, with only 15.6% of respondents opposed to increasing taxes on tobacco products and 9.6% opposed to banning tobacco advertisements. Smoking status is the most important predictor of opposition to increasing taxes (OR = 7.85, 95% CI = 6.60-9.34) and banning advertisements (OR = 1.72, 95% CI = 1.39-2.11). Opposition to these measures is most likely among young respondents (aged 15-24) and least likely among older age groups (55-64 and 65 or over), compared to the 25-34 age group. Stratified models suggest that the effect of age may be different for smokers and non-smokers. Low income is a significant predictor of opposition, but only in stratified models for smokers. CONCLUSION: There is general support for stronger tobacco control measures in Argentina. Opposition to raising taxes on tobacco products and banning tobacco advertisement appears to be concentrated among young smokers with low and medium levels of household income.

Sex-stratified and age-adjusted social gradients in tobacco in Argentina and Uruguay: evidence from the Global Adult Tobacco Survey (GATS).

OBJECTIVE: To examine social gradients in tobacco use in Argentina and Uruguay, using newly available directly comparable data sets. METHODS: Secondary analysis of Global Adult Tobacco Survey data from Argentina (N=6645) and Uruguay (N=5581). Social gradients in current tobacco use, exposure to secondhand smoke, and cessation attempt were examined with sex-stratified and age-adjusted logistic regression. RESULTS: Among men, there is evidence of higher odds of being a current smoker among respondents with lower levels of education, but the association is only statistically significant for respondents with less than primary education in Uruguay (OR=2.15, 95% CI 1.22 to 3.77). Similarly, women with lower levels of education have higher odds of being a current smoker in Uruguay. The association between education and exposure to secondhand smoke is broadly similar for both sexes in both countries, with generally higher odds among groups with low education, though the relationship is only statistically significant among men in Uruguay (OR=1.77, 95% CI 1.08 to 2.92). In both countries, respondents with lower levels of education in general have higher odds of having attempted to quit smoking in the past year, although these associations did not attain statistical significance. CONCLUSIONS: Social gradients in tobacco use, exposure to secondhand smoke and cessation attempts are broadly similar in both countries. Efforts to evaluate the long-term effects of tobacco control efforts in these countries should monitor how policies affect national averages, and the social gradients that are embedded in aggregate data.

Study of socio-economic characteristics, diagnosis and outcome of women participating or not participating in mammogram screening.

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer death in women. Early detection is essential to reduce cancer mortality. Studying participation in an organised breast cancer screening program is important in order to evaluate the program effectiveness. Breast screening both enables minimally invasive breast surgery and reduces cause-specific mortality. METHODS: The main objective of this study was to evaluate, through the use of a questionnaire, the influence of socio-economic characteristics (age, education, occupational status, participation in other screening programs etc.) on participation in a mammography screening program organized by the local health units (LHU) of Novara and Verbano-Cusio-Ossola, located in the Italian region of Piedmont. A sample of 500 women was identified. Eligible participants included women aged 50-69 years, resident in the area of the LHUs of Novara and Verbano-Cusio-Ossola who had been invited to participate in the screening program 2006-2007. Twenty six women were excluded, leaving 474 women in the final analysis: 23 women were unable to be contacted due to incorrect contact details and 3 women were unable to complete the questionnaire due to neurodegenerative diseases. A postal questionnaire was sent by post during 2008-2009. Two postal reminders were sent to non-responders, followed by a phone call. One group of women received an additional copy of the questionnaire with the first postal reminder and another group received only the reminder letter. The socio-personal profiles and their influence in women's participation in the screening program were evaluated. RESULTS: Among the responders, 93% of the women (348/374) received a mammogram at least once following LHU invitation for check-up. 74.1% of women got a mammogram at least once using the organized screening program, an additional 17.8% got a mammogram in a private clinic, and the type of prevention was unknown for 8.1% of the women. 25.3% began having mammogram for prevention before the age of 45. CONCLUSIONS: A screening program is a sanitary intervention of secondary prevention and the identification of the attitude towards this kind of prevention is quite complex. Some causes of non-participation in this screening program were the belief that mammogram is not necessary, fear of pain, and presence of family problems. This study obtained a higher response than expected and the data also allowed an assessment of the degree of participation of women in the prevention services, identifying that most of them carried out a mammogram using an organized screening program.

Mesothelioma risk after 40†years since first exposure to asbestos: a pooled analysis.

BACKGROUND: The risk of malignant mesothelioma (MM) increases proportionally to the cumulative exposure, and to the 3rd or 4th power of time since first exposed, to asbestos. However, little is known about the risk of MM after more than 40 years since first exposure because most epidemiological studies do not have follow-up for sufficient periods of time. METHODS: The data from six cohort studies of exposed workers and two cohorts with residential exposure have been pooled. A nested case control design matched cases and controls on calendar period and age. Conditional logistic regression modelled the relationship between time since first exposure and risk of MM. RESULTS: The combined data consisted of 22,048 people with asbestos exposure (5769 women), 707 cases of pleural MM (165 in women) and 155 cases of peritoneal MM (32 in women). Median time since first exposure for pleural MM cases was 38.4 years (IQR 31.3-45.3). Median duration of exposure for pleural MM cases was 3.75 years (IQR 0.7-18.2). The rate and risk of pleural MM increased until 45 years following first exposure and then appeared to increase at a slower power of time since first exposure. The rate of increase in peritoneal MM over the 10-50 years since first exposure continued to increase. CONCLUSIONS: Exposure to asbestos confers a long-term risk of developing pleural and peritoneal mesothelioma which increases following cessation of exposure. While the rate of increase appears to start to level out after 40-50 years no one survives long enough for the excess risk to disappear.

The HSE Management Standards Indicator Tool: concurrent and construct validity.

BACKGROUND: The Health & Safety Executive Management Standards Indicator Tool (HSE-MS IT) is a questionnaire commonly used to assess work-related stress risks at an organizational level. A critical factor in determining whether this instrument is actually useful is that higher levels of stress risk in the work-design domains should predict higher levels of stress and stress-related outcomes in workers. Only a few studies, however, have addressed this issue. AIMS: To test both the concurrent and construct validity of the HSE-MS IT, by relating it with another widely used instrument, the Job Content Questionnaire (JCQ), and by examining its relationships with a set of work-related stress outcomes. METHODS: An anonymous cross-sectional questionnaire was administered to a sample of employees in an Italian municipality. The questionnaire included the HSE-MS IT, self-reported measures of job satisfaction, job motivation and stress at work, the Satisfaction with Life Scale and the reduced form of the JCQ. RESULTS: A total of 760 out of 779 employees completed the questionnaire. Results showed moderate to strong correlation among the corresponding HSE-MS IT and JCQ scales. Hierarchical regression highlighted the specific contribution of each of the HSE-MS IT scales in predicting three relevant work-related stress outcomes (self-reported stress, job satisfaction and job motivation), after controlling for gender, age and life satisfaction. CONCLUSIONS: Our findings consolidated the HSE-MS IT validity and showed the specific sensitivity of its scales to assess different aspects of work-related distress, including self-perception of stress at work. These results can have practical implications for the occupational well-being of employees.

Impacto del marketing de alimentos y bebidas dirigido a niños en Argentina / Impact of marketing of food and beverages intended for children in Argentina

INTRODUCCIÓN El sobrepeso y la obesidad en niños están creciendo en Argentina, lo que impactará en la ocurrencia de enfermedades en el mediano plazo. Uno de los determinantes del consumo de alimentos y bebidas altos en calorías, grasas saturadas, sodio y azúcares refinados es el marketing de alimentos orientado a la población infantil. OBJETIVOS Describir la situación actual de la promoción de alimentos orientados a niños en Argentina. MÉTODOS Se desarrolló una investigación descriptiva, cuantitativa y cualitativa, que abordó tres aspectos: relevamiento del marco regulatorio y legislación a nivel nacional; monitoreo de 402 horas de canales de cable y aire con programación infantil; y categorización de las publicidades de alimentos emitidas según tipo, perfil nutricional y técnicas de persuasión empleadas. Para evaluar la percepción materna, se realizaron entrevistas en profundidad. RESULTADOS Se observó la ausencia de normativas claras y precisas, con criterios nutricionales, para regular la publicidad de alimentos dirigida al público infantil. El 20,9% de las publicidades emitidas en el horario infantil correspondió a alimentos (en promedio: 0,68±0,36 minutos/hora). Los lácteos, golosinas y comidas rápidas fueron los alimentos con mayor presencia. Los elementos de persuasión más utilizados fueron diversión, felicidad, fantasía, imaginación, palatabilidad, novedad, jingles y personajes. En general, las madres mostraron preocupación por la publicidad de alimentos no saludables y coincidieron en que el envoltorio, las promociones y la utilización de personajes conocidos es un incentivo para la adquisición de ciertos alimentos. DISCUSIÓN Dada la mayor prevalencia de sobrepeso evidenciada durante los últimos años en la población infantil en Argentina, el campo de la publicidad dirigida a niños presenta una oportunidad para mejorar la oferta de alimentos saludable.

Ultrastructural analysis of different-made staplers' staples.

AIM: Recently, Chinese-made mechanical staplers with lower price respect to American-made ones have been introduced in clinical practice. In literature, small case series compare the clinical outcomes of different staplers concluding that the new stapler devices perform as well as the American ones. The aim of this study is to compare with an ultrastructural analysis the staples of different staplers in order to verify the existence of differences that might explain significant price disparity and condition clinical outcomes. METHODS: Each stapler was subjected to morphological analysis, energy dispersive X-Ray spectroscopy, metal release assessment followed by inductively coupled plasma mass spectroscopy. P-values were considered statistically significant when <0.05. RESULTS: Autosuture staples have square section whereas the other American one and Chinese made staples have round sections. Roughness index and chips presence before and after ageing tests were comparable for all samples except for Ethicon Endo-Surgery stapler. Energy dispersive X-Ray spectroscopy showed that all staplers are made of pure Titanium but Ethicon Endo-Surgery staples are made with an alloy. Metal release analysis release statistically significant differences between samples in simulated body fluid 20 days solution (P=0.002) and in Aquaregia at 14 days solution. Discussion. Stapling devices have became routinely used in gastrointestinal surgery mainly because of operative time reduction. Recently, new Chinese-made mechanical staplers, with significantly lower prices, have been introduced in clinical practice. In literature, there are some studies that compare clinical outcomes of American-made and Chinese-made staplers on small groups of patients but doesn't exist any work which consider structural differences between traditional and new devices. In our study, for the first time, we propose a comparison between two American-made staplers and three Chinese-made staplers which evaluate morphology, metal composition and chemical staples release. CONCLUSION: Our study suggest that there are some ultrastructural differences between commercially available staplers with no correlation to price disparity. More studies are needed to confirm our results and to verify if our findings could condition clinical outcomes.

Changes in the social gradients for Pap smears and mammograms in Argentina: evidence from the 2005 and 2009 National Risk Factor Surveys.

OBJECTIVES: To identify changes in the social gradients for Pap smears and mammograms in Argentina. STUDY DESIGN: Secondary analysis of the 2005 and 2009 Argentine National Risk Factor Surveys. METHODS: Logistic regression analysis was used to examine social gradients by income and education, adjusting for age and health insurance. RESULTS: The proportion of women who received a Pap smear in the previous 2 years increased from 51.6% in 2005 to 60.5% in 2009 (χ(2) = 344.8, P < 0.001). A significant increase was also seen in the receipt of a mammogram in the previous 2 years by women aged ≥50 years, with an increase from 39.6% in 2005 to 52.6% in 2009 (χ(2) = 279.6, P < 0.001). In 2005, low-income women were most likely not to have received a Pap test [odds ratio (OR) = 3.27, 95% confidence interval (CI) = 2.70-3.98], followed by medium-income women (OR = 1.73, 95% CI = 1.41-2.12), compared with high-income women. The gradient by education was of a similar magnitude, and both income and education gradients remained stable from 2005 to 2009. Restricting the analysis to eight provinces that have been deemed to be high priority due to their high levels of mortality from cervical cancer reveals an increasing income-based gradient in Pap smears. In contrast, inequalities in mammography diminished across the country, with a significant reduction in the social gradient measured either by income or education. In contrast to high-income women, low-income women experienced higher odds of not having a mammogram, but the gap diminished over time [OR = 4.14 (95% CI = 2.96-5.78) in 2005 vs OR = 2.37 (95% CI = 1.81-3.11) in 2009]. CONCLUSION: Social gradients in cancer screening are changing in Argentina. There are signs of a reduction in inequalities in mammograms, although this is attenuated by indications that inequalities in Pap smear utilization in priority provinces are growing. Surveillance of population indicators is needed to verify whether these short-term changes persist over time.

S(+)-ketamine for control of perioperative pain and prevention of post thoracotomy pain syndrome: a randomized, double-blind study.

BACKGROUND: Post-thoracotomy pain syndrome (PTPS) often complicates the long term outcome of patients; its appearance has been related to perioperative acute pain. The main goal of this study was to evaluate a possible role of S(+)-ketamine in the prevention of PTPS up to 6 months and secondarily its efficacy in the control of perioperative pain when added to thoracic epidural analgesia (TEA) and adjuvants. METHODS: Sixty-six patients underwent thoracotomy under general anesthesia. A thoracic epidural catheter was placed for levobupivacaine and sufentanil administration. Thirty-three patients received an i.v. infusion of S(+)-ketamine (Group S(+)K) for 60 hours and 33 patients received i.v. placebo (Group PLAC). Pain was evaluated by Numeric Rating Scale (NRS) during the whole study. All patients had supplementary doses of analgesics, as needed, to have NRS targeted to a value of ≤3 in the 1st and <3 in the following days. Neuropathic Pain Symptom Inventory (NPSI) was evaluated at 1, 3 and 6 months. RESULTS: All patients had NRS ≤3 in the early postoperative period and NPSI was less or equal to 1 in the follow-up control for each group with no significant difference at three (P=0.67, OR 0.8 [IC95% 0.3-2.2]) and at six months (P=0.23, OR 1.9 [0.7-5.4]). Incidence of moderate PTPS was 24.6% at 3 and 21.1% at six months while severe PTPS was 6.6% at 3 and 1.8% at six months. No difference was detected in NRS and NPSI at 3 and 6 months between groups. CONCLUSION: S(+)-ketamine had no effects in respect to placebo in the prevention of PTPS at 3 and 6 months but had a significant role in maintaining a NRS≤3 in the early postoperative period. A tight control of perioperative pain seems to be associated with a low incidence of moderate and severe PTPS.

Reduction in hospital admissions for acute coronary syndrome after the successful implementation of 100% smoke-free legislation in Argentina: a comparison with partial smoking restrictions.

BACKGROUND: Several studies have shown a decrease in acute coronary syndrome (ACS) admissions after the implementation of 100% smoke-free legislation. However, no studies have been conducted in developing countries. METHODS: We conducted a time series analysis of ACS hospital admissions in Santa Fe province and Buenos Aires city, Argentina. In 2006, Santa Fe implemented a 100% smoke-free law and Buenos Aires implemented a partial law with designated smoking areas and exceptions. Age-standardised ACS admissions rates were compared before and after the implementation of the laws in each district. Smoking prevalence, compliance with legislation and exposure to secondhand smoke (SHS) was also assessed in both districts. RESULTS: In Santa Fe an immediate decrease in ACS admissions was observed after implementation (-2.5 admissions per 100,000, p=0.03; 13% reduction), compared with no change in Buenos Aires city (rate ratio Santa Fe vs Buenos Aires: 0.74, 95% CI 0.63 to 0.86, p≤0.001). In Santa Fe, the immediate effect was followed by a persistent decrease in admissions due to ACS (-0.26 admissions per 100,000 per month). Smoking prevalence did not change significantly in either district during the same period. In both districts, there was a reduction in self-reported SHS exposure, with a trend towards lower exposure in Santa Fe province. No other comprehensive tobacco control interventions were implemented during the study period. CONCLUSIONS: A 100% smoke-free law was more effective than a partial restriction law in reducing ACS admissions. An immediate effect was followed by a sustained decrease in ACS admissions. Smoke-free initiatives can be also effective in decreasing acute coronary events in developing countries.

The interactions of age, sex, body mass index, genetics, and steroid weight-based doses on tacrolimus dosing requirement after adult kidney transplantation.

PURPOSE: The aim of this study was to evaluate the effect of different clinical covariates on tacrolimus dose requirements in adult kidney transplant patients with a specific focus on drug interactions. PATIENTS: Tacrolimus dosing requirement, normalized by drug levels and expressed as the concentration/dose (C/D) ratio as a surrogate index of tacrolimus bioavailability, was employed to identify four categories of tacrolimus dosing requirement, namely, very high, high, small, and very-small, in very fast, fast, slow, and very slow metabolizers, respectively. Steroid weight-based doses were analyzed instead of fixed doses, and genetic analysis of cytochrome P450 (CYP) 3A5*1/*3 and multi-drug resistance 1 (MDR1) C3435T and C1236T polymorphisms were performed RESULTS: Multivariate analysis on 450 adult transplant patients identified six risk factors for being slow metabolizers and therefore requiring small tacrolimus doses: male sex (OR 1.615, p = 0.020); age >60 years (OR 2.456, p = 0.0005); body mass index ≥ 25 (OR 1.546, p = 0.046), hepatitis C virus positivity (OR 2.800, p = 0.0004); low steroid dose <0.06 mg/kg (OR 3.101, p < 0.0001). Patients with a small tacrolimus requirement were at increased risk for multiple infections (OR 1.533, p = 0.0008) and higher systolic blood pressure (OR 1.385, p = 0.022) and showed a significant association with the CYP3A5*3/*3 genotype adjusted by MDR1 polymorphisms C3435T and C1236T (OR 8.104, p = 0.0001). CONCLUSIONS: Our results demonstrate the importance of the interaction among genetic and clinical factors in conditioning tacrolimus disposition, with corticosteroid weight-based dose being the only modifiable risk factor for tacrolimus requirement. As the tacrolimus dosing requirement increases with increasing tacrolimus clearance through concomitant steroid use, undesirable changes in tacrolimus levels may occur when steroid doses are tapered, predominantly in slow metabolizers. This often neglected drug interaction has to be monitored to optimize tacrolimus exposure in kidney transplant patients.

XRCC1 and ERCC1 variants modify malignant mesothelioma risk: a case-control study.

Malignant pleural mesothelioma (MPM) is a rare aggressive tumor associated with asbestos exposure. The possible role of genetic factors has also been suggested and MPM has been associated with single nucleotide polymorphisms (SNPs) of xenobiotic and oxidative metabolism enzymes. We have identified an association of the DNA repair gene XRCC1 with MPM in the population of Casale Monferrato, a town exposed to high asbestos pollution. To extend this observation we examined 35 SNPs in 15 genes that could be involved in MPM carcinogenicity in 220 MPM patients and 296 controls from two case-control studies conducted in Casale (151 patients, 252 controls) and Turin (69 patients, 44 controls), respectively. Unconditional multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Two DNA repair genes were associated with MPM, i.e. XRCC1 and ERCC1. Considering asbestos-exposed only, the risk increased with the increasing number of XRCC1-399Q alleles (Casale: OR=1.44, 95%CI 1.02-2.03; Casale+Turin: OR=1.34, 95%CI 0.98-1.84) or XRCC1 -77T alleles (Casale+Turin: OR=1.33, 95%CI 0.97-1.81). The XRCC1-TGGGGGAACAGA haplotype was significantly associated with MPM (Casale: OR=1.76, 95%CI 1.04-2.96). Patients heterozygotes for ERCC1 N118N showed an increased OR in all subjects (OR=1.66, 95%CI 1.06-2.60) and in asbestos-exposed only (OR=1.59, 95%CI 1.01-2.50). When the dominant model was considered (i.e. ERCC1 heterozygotes CT plus homozygotes CC versus homozygotes TT) the risk was statistically significant both in all subjects (OR=1.61, 95%CI 1.06-2.47) and in asbestos-exposed only (OR=1.56, 95%CI 1.02-2.40). The combination of ERCC1 N118N and XRCC1 R399Q was statistically significant (Casale: OR=2.02, 95%CI 1.01-4.05; Casale+Turin: OR=2.39, 95%CI 1.29-4.43). The association of MPM with DNA repair genes support the hypothesis that an increased susceptibility to DNA damage may favour asbestos carcinogenicity.

HLA-class I markers and multiple sclerosis susceptibility in the Italian population.

Previous studies reported an association with multiple sclerosis (MS) of distinct HLA-class I markers, namely HLA-A*02, HLA-Cw*05 and MOG-142L. In this work, we tested the association with MS of A*02 and Cw*05 in 1273 Italian MS patients and 1075 matched controls, which were previously analyzed for MOG-142, and explored the relationship among these three markers in modulating MS risk. HLA-A*02 conferred a statistically robust MS protection (odds ratio, OR=0.61; 95% confidence intervals, CI=0.51-0.72, P<10(-9)), which was independent of DRB1*15 and of any other DRB1* allele and remained similar after accounting for the other two analyzed class I markers. Conversely, the protective effect we previously observed for MOG-142L was secondary to its linkage disequilibrium with A*02. Cw*05 was not associated considering the whole sample, but its presence significantly enhanced the protection in the HLA-A*02-positive group, independently of DRB1: the OR conferred by A*02 in Cw*05-positive individuals (0.22, 95% CI=0.13-0.38) was significantly lower than in Cw*05-negative individuals (0.69, 95% CI=0.58-0.83) with a significant (P=4.94 x 10(-5)) multiplicative interaction between the two markers. In the absence of A*02, Cw*05 behaved as a risk factor, particularly in combination with DRB1*03 (OR=3.89, P=0.0006), indicating that Cw*05 might be a marker of protective or risk haplotypes, respectively.

The Latin American Consortium of Studies in Obesity (LASO).

Current, high-quality data are needed to evaluate the health impact of the epidemic of obesity in Latin America. The Latin American Consortium of Studies of Obesity (LASO) has been established, with the objectives of (i) Accurately estimating the prevalence of obesity and its distribution by sociodemographic characteristics; (ii) Identifying ethnic, socioeconomic and behavioural determinants of obesity; (iii) Estimating the association between various anthropometric indicators or obesity and major cardiovascular risk factors and (iv) Quantifying the validity of standard definitions of the various indexes of obesity in Latin American population. To achieve these objectives, LASO makes use of individual data from existing studies. To date, the LASO consortium includes data from 11 studies from eight countries (Argentina, Chile, Colombia, Costa Rica, Dominican Republic, Peru, Puerto Rico and Venezuela), including a total of 32,462 subjects. This article describes the overall organization of LASO, the individual studies involved and the overall strategy for data analysis. LASO will foster the development of collaborative obesity research among Latin American investigators. More important, results from LASO will be instrumental to inform health policies aiming to curtail the epidemic of obesity in the region.

Interethnic differences in the accuracy of anthropometric indicators of obesity in screening for high risk of coronary heart disease.

BACKGROUND: Cut points for defining obesity have been derived from mortality data among Whites from Europe and the United States and their accuracy to screen for high risk of coronary heart disease (CHD) in other ethnic groups has been questioned. OBJECTIVE: To compare the accuracy and to define ethnic and gender-specific optimal cut points for body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) when they are used in screening for high risk of CHD in the Latin-American and the US populations. METHODS: We estimated the accuracy and optimal cut points for BMI, WC and WHR to screen for CHD risk in Latin Americans (n=18 976), non-Hispanic Whites (Whites; n=8956), non-Hispanic Blacks (Blacks; n=5205) and Hispanics (n=5803). High risk of CHD was defined as a 10-year risk > or =20% (Framingham equation). The area under the receiver operator characteristic curve (AUC) and the misclassification-cost term were used to assess accuracy and to identify optimal cut points. RESULTS: WHR had the highest AUC in all ethnic groups (from 0.75 to 0.82) and BMI had the lowest (from 0.50 to 0.59). Optimal cut point for BMI was similar across ethnic/gender groups (27 kg/m(2)). In women, cut points for WC (94 cm) and WHR (0.91) were consistent by ethnicity. In men, cut points for WC and WHR varied significantly with ethnicity: from 91 cm in Latin Americans to 102 cm in Whites, and from 0.94 in Latin Americans to 0.99 in Hispanics, respectively. CONCLUSION: WHR is the most accurate anthropometric indicator to screen for high risk of CHD, whereas BMI is almost uninformative. The same BMI cut point should be used in all men and women. Unique cut points for WC and WHR should be used in all women, but ethnic-specific cut points seem warranted among men.