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Abstract Patients with cancer were excluded from pivotal randomized clinical trials of COVID-19 vaccine products, and available observational evidence on vaccine effectiveness (VE) focused mostly on mild, and not severe COVID-19, which is the ultimate goal of vaccination for high-risk groups. Here, using primary care electronic health records from Catalonia, Spain (SIDIAP), we built two large cohorts of vaccinated and matched control cancer patients with a primary vaccination scheme (n = 184,744) and a booster (n = 108,534). Most patients received a mRNA-based product in primary (76.2%) and booster vaccination (99.9%). Patients had 51.8% (95% CI 40.3%−61.1%) and 58.4% (95% CI 29.3%−75.5%) protection against COVID-19 hospitalization and COVID-19 death respectively after full vaccination (two-doses) and 77.9% (95% CI 69.2%−84.2%) and 80.2% (95% CI 63.0%−89.4%) after booster. Compared to primary vaccination, the booster dose provided higher peak protection during follow-up. Calibration of VE estimates with negative outcomes, and sensitivity analyses with slight different population and COVID-19 outcomes definitions provided similar results. Our results confirm the role of primary and booster COVID-19 vaccination in preventing COVID-19 severe events in patients with cancer and highlight the need for the additional dose in this population.

Summary: Background: The emergence of COVID-19 variants with immune scape and the waning of primary vaccine schemes effectiveness have prompted many countries to indicate first and second booster COVID-19 vaccine doses to prevent severe COVID-19. However, current available evidence on second booster dose effectiveness are mostly limited to high-income countries, older adults, and mRNA-based vaccination schemes scenarios. We aimed to investigate the relative vaccine effectiveness (rVE) of the fourth dose compared to three doses for severe COVID-19 outcomes in Brazil; and compare the rVE of a fourth dose with an mRNA vaccine compared to adenovirus-based product in the same settings. Methods: We performed a target emulated trial using a population-based cohort of individuals aged 40 years or older who have received a homologous primary scheme of CoronaVac, ChAdOx1, or BNT162b2, and any third dose product and were eligible for the fourth dose in Brazil. The primary outcome was COVID-19 associated hospitalization or death. We built Cohort A matching individuals vaccinated with a fourth dose to individuals who received three doses to estimate the rVE of the fourth dose. We built Cohort B, a subset of Cohort A, matching mRNA-based (mRNA) to adenovirus-based fourth dose vaccinated individuals to compare their relative hazards for severe COVID-19. Findings: 46,693,484 individuals were included in Cohort A and 6,763,016 in Cohort B. 45% of them were aged between 40 and 60 years old, and 48% between 60 and 79 years old. In Cohort A, the most common previous series was a ChAdOx1 two-dose followed by BNT162b2 (44%), and a CoronaVac two-dose followed by a BNT162b2 (36%). Among those fourth dose vaccinated, 36.9% received ChAdOx1, 32.7% Ad26.COV2.S, 25.8% BNT162b2, and 4.7% CoronaVac. In Cohort B, among those who received an adenovirus fourth dose, 53.7% received ChAdOx1 and 46.3% received Ad26.COV2.S. The estimated rVE for the primary outcome of four doses compared to three doses was 44.1% (95% CI 42.3–46.0), with some waning during follow-up (rVE 7–60 days 46.8% [95% CI 44.4–49.1], rVE after 120 days 33.8% [95% CI 18.0–46.6]). Among fourth dose vaccinated individuals, mRNA-based vaccinated individuals had lower hazards for hospitalization or death compared to adenovirus-vaccinated individuals (HR 0.81, 95% CI 0.75–0.87). After 120 days, no difference in hazards between groups was observed (HR 1.35, 95% CI 0.93–1.97). Similar findings were observed for hospitalization and death separately, except no evidence for differences between fourth dose brands for death in Cohort B. Interpretation: In a heterogeneous scenario of primary and first booster vaccination combinations, a fourth dose provided meaningful and durable protection against severe COVID-19 outcomes. Compared to adenovirus-based booster, a fourth dose wild-type mRNA vaccine was associated with immediate lower hazards of hospitalization or death unsustained after 120 days. Funding: None.

Abstract Background Indigenous people have historically suffered devastating impacts from epidemics and continue to have lower access to healthcare and be especially vulnerable to respiratory infections. We estimated the coverage and effectiveness of Covid-19 vaccines against laboratory-confirmed Covid-19 cases among indigenous people in Brazil. Methods We linked nationwide Covid-19 vaccination data with flu-like surveillance records and studied a cohort of vaccinated indigenous people aged ≥ 5 years between 18th January 2021 and 1st March 2022. We considered individuals unexposed from the date they received the first dose of vaccine until the 13th day of vaccination, partially vaccinated from the 14th day after the first dose until the 13th day after receiving the second dose, and fully vaccinated onwards. We estimated the Covid-19 vaccination coverage and used Poisson regression to calculate the relative risks (RR) and vaccine effectiveness (VE) of CoronaVac, ChAdOx1, and BNT162b2 against Covid-19 laboratory-confirmed cases incidence, mortality, hospitalisation, and hospital-progression to Intensive Care Unit (ICU) or death. VE was estimated as (1-RR)*100, comparing unexposed to partially or fully vaccinated. Results By 1st March 2022, 48.7% (35.0-62.3) of eligible indigenous people vs. 74.8% (57.9–91.8) overall Brazilians had been fully vaccinated for Covid-19. Among fully vaccinated indigenous people, we found a lower risk of symptomatic cases (RR: 0.47, 95%CI: 0.40–0.56) and mortality (RR: 0.47, 95%CI: 0.14–1.56) after the 14th day of the second dose. VE for the three Covid-19 vaccines combined was 53% (95%CI:44–60%) for symptomatic cases, 53% (95%CI:-56-86%) for mortality and 41% (95%CI:-35-75%) for hospitalisation. In our sample, we found that vaccination did not reduce Covid-19 related hospitalisation. However, among hospitalised patients, we found a lower risk of progression to ICU (RR: 0.14, 95%CI: 0.02–0.81; VE: 87%, 95%CI:27–98%) and Covid-19 death (RR: 0.04, 95%CI:0.01–0.10; VE: 96%, 95%CI: 90–99%) after the 14th day of the second dose. Conclusions Lower coverage but similar Covid-19 VE among indigenous people than overall Brazilians suggest the need to expand access, timely vaccination, and urgently offer booster doses to achieve a great level of protection among this group.

This study investigates the effectiveness of COVID-19 vaccine boosters following a primary series of CoronaVac vaccination. Using data from Brazil during the Omicron wave, the authors show that boosters provided protection against severe disease, with higher effectiveness from a BNT162b2 than CoronaVac booster.

BackgroundThe lack of precise definitions and terminological consensus about the impact studies of COVID-19 vaccination leads to confusing statements from the scientific community about what a vaccination impact study is.ObjectiveThe present work presents a narrative review, describing and discussing COVID-19 vaccination impact studies, mapping their relevant characteristics, such as study design, approaches and outcome variables, while analyzing their similarities, distinctions, and main insights.MethodsThe articles screening, regarding title, abstract, and full-text reading, included papers addressing perspectives about the impact of vaccines on population outcomes. The screening process included articles published before June 10, 2022, based on the initial papers’ relevance to this study’s research topics. The main inclusion criteria were data analyses and study designs based on statistical modelling or comparison of pre- and post-vaccination population.ResultsThe review included 18 studies evaluating the vaccine impact in a total of 48 countries, including 32 high-income countries (United States, Israel, and 30 Western European countries) and 16 low- and middle-income countries (Brazil, Colombia, and 14 Eastern European countries). We summarize the main characteristics of the vaccination impact studies analyzed in this narrative review.ConclusionAlthough all studies claim to address the impact of a vaccination program, they differ significantly in their objectives since they adopt different definitions of impact, methodologies, and outcome variables. These and other differences are related to distinct data sources, designs, analysis methods, models, and approaches.

Summary: Background: Omega-3 fatty acids are critical for neuropsychological functioning. Adolescence is increasingly believed to entail brain vulnerability to dietary intake. The potential benefit on adolescent neurodevelopment of consuming walnuts, a source of omega-3 alpha-linolenic acid (ALA), remains unclear. Methods: We conducted a 6-month multi-school-based randomised controlled nutrition intervention trial to assess whether walnut consumption has beneficial effects on the neuropsychological and behavioural development of adolescents. The study took place between 04/01/2016 and 06/30/2017 in twelve different high schools in Barcelona, Spain (ClinicalTrials.gov Identifier: NCT02590848). A total of 771 healthy teenagers aged 11–16 years were randomised into two equal groups (intervention or control). The intervention group received 30 g/day of raw walnut kernels to be incorporated into their diet for 6 months. Multiple primary endpoints concerning neuropsychological (working memory, attention, fluid intelligence, and executive function) and behavioural (socio-emotional and attention deficit hyperactivity disorder [ADHD] symptoms) development were assessed at baseline and after intervention. Red blood cell (RBC) ALA status was determined at baseline and 6 months as a measure of compliance. Main analyses were based on intention-to-treat using a linear mixed-effects model. A per-protocol effect of the intervention was analysed using inverse-probability weighting to account for post-randomisation prognostic factors (including adherence) using generalised estimating equations. Findings: In intention-to-treat analyses, at 6 months there were no statistically significant changes between the intervention and control groups for all primary endpoints. RBC ALA (%) significantly increased only in the intervention group, coefficient = 0.04 (95% Confidence Interval (CI) = 0.03, 0.06; p

Here, the authors investigate the effectiveness of the Oxford-AstraZeneca (ChAdOx1) vaccine during extensive Gamma variant SARS-CoV-2 circulation in São Paulo state, Brazil, and find that a two-dose regime is more effective than one dose against mild to severe Covid-19 outcomes in older adults.

Background The benefit of primary and booster vaccination in people who experienced a prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains unclear. The objective of this study was to estimate the effectiveness of primary (two-dose series) and booster (third dose) mRNA vaccination against Omicron (lineage BA.1) infection among people with a prior documented infection. Methods and findings We conducted a test-negative case–control study of reverse transcription PCRs (RT-PCRs) analyzed with the TaqPath (Thermo Fisher Scientific) assay and recorded in the Yale New Haven Health system from November 1, 2021, to April 30, 2022. Overall, 11,307 cases (positive TaqPath analyzed RT-PCRs with S-gene target failure [SGTF]) and 130,041 controls (negative TaqPath analyzed RT-PCRs) were included (median age: cases: 35 years, controls: 39 years). Among cases and controls, 5.9% and 8.1% had a documented prior infection (positive SARS-CoV-2 test record ≥90 days prior to the included test), respectively. We estimated the effectiveness of primary and booster vaccination relative to SGTF-defined Omicron (lineage BA.1) variant infection using a logistic regression adjusted for date of test, age, sex, race/ethnicity, insurance, comorbidities, social venerability index, municipality, and healthcare utilization. The effectiveness of primary vaccination 14 to 149 days after the second dose was 41.0% (95% confidence interval (CI): 14.1% to 59.4%, p 0.006) and 27.1% (95% CI: 18.7% to 34.6%, p < 0.001) for people with and without a documented prior infection, respectively. The effectiveness of booster vaccination (≥14 days after booster dose) was 47.1% (95% CI: 22.4% to 63.9%, p 0.001) and 54.1% (95% CI: 49.2% to 58.4%, p < 0.001) in people with and without a documented prior infection, respectively. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds of infection among boosted (≥14 days after booster dose) and booster-eligible people (≥150 days after second dose). The odds ratio (OR) comparing boosted and booster-eligible people with a documented prior infection was 0.79 (95% CI: 0.54 to 1.16, p 0.222), whereas the OR comparing boosted and booster-eligible people without a documented prior infection was 0.54 (95% CI: 0.49 to 0.59, p < 0.001). This study’s limitations include the risk of residual confounding, the use of data from a single system, and the reliance on TaqPath analyzed RT-PCR results. Conclusions In this study, we observed that primary vaccination provided significant but limited protection against Omicron (lineage BA.1) infection among people with and without a documented prior infection. While booster vaccination was associated with additional protection against Omicron BA.1 infection in people without a documented prior infection, it was not found to be associated with additional protection among people with a documented prior infection. These findings support primary vaccination in people regardless of documented prior infection status but suggest that infection history may impact the relative benefit of booster doses. Using a Test-Negative Case-Control Analysis, Dr Margaret L. Lind and colleagues, investigate the association between primary or booster COVID-19 mRNA vaccination and omicron lineage BA.1 SARS-CoV-2 infection in people with a prior SARS-CoV-2 infection. Author summary Why was this study done? mRNA COVID-19 vaccines provide lower levels of protection against Omicron (BA.1 lineage) infections than previously circulating variants. Prior to the emergence of the Omicron variant, primary vaccination (first two mRNA vaccine doses) afforded protection against reinfection among people with prior infections. The benefit of primary and booster vaccination against Omicron (BA.1 lineage) infections remains unclear among people with prior infections. What did the researchers do and find? We evaluated the benefit of primary series and booster mRNA vaccine doses against Omicron (BA.1 lineage, defined by S-gene target failure) infection among people with and without documented prior infections. We found that primary vaccination was associated with statistically significant but low levels of protection against Omicron (BA.1 lineage) infection among people with and without a documented prior infection. Booster vaccination was found to be associated with protection beyond that afforded by the primary series among people without a documented prior infection, but we did not observe a significant increase in protection among people with a documented prior infection. What do these findings mean? Primary vaccination provides limited but significant protection against Omicron (BA.1 lineage) infection regardless of prior infection history. The relative benefits of a booster dose may be affected by a person’s history of prior SARS-CoV-2 infection.

Objective: Although there is evidence for the association between air pollution and decreased lung function in children, evidence for adolescents and young adults is scarce. For a peri-urban area in India, we evaluated the association of ambient PM2.5 and household air pollution with lung function for young adults who had recently attained their expected maximum lung function. Methods: We measured, using a standardized protocol, forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) in participants aged 20–26 years from the third follow-up of the population-based APCAPCS cohort (2010–2012) in 28 Indian villages. We estimated annual average PM2.5 outdoors at residence using land-use regression. Biomass cooking fuel (a proxy for levels of household air pollution) was self-reported. We fitted a within-between linear-mixed model with random intercepts by village, adjusting for potential confounders. Results: We evaluated 1,044 participants with mean age of 22.8 (SD = 1) years (range 20–26 years); 327 participants (31%) were female. Only males reported use of tobacco smoking (9% of all participants, 13% of males). The mean ambient PM2.5 exposure was 32.9 (SD = 2.8) µg/m3; 76% reported use of biomass as cooking fuel. The adjusted association between 1 µg/m3 increase in PM2.5 was −27 ml (95% CI, −89 to 34) for FEV1 and −5 ml (95% CI, −93 to 76) for FVC. The adjusted association between use of biomass was −112 ml (95% CI, −211 to −13) for FEV1 and −142 ml (95% CI, −285 to 0) for FVC. The adjusted association was of greater magnitude for those with unvented stove (−158 ml, 95% CI, −279 to −36 for FEV1 and −211 ml, 95% CI, −386 to −36 for FVC). Conclusions: We observed negative associations between ambient PM2.5 and household air pollution and lung function in young adults who had recently attained their maximum lung function.

Primary membranous nephropathy (MN) is caused by antibodies against podocyte antigens, especially the type M receptor of phospholipase A2 (PLA2R) and thrombospondin type-1 domain containing 7 A (THSD7A). This study’s aim was the determination of anti-PLA2R, anti-THSD7A serum antibodies, and anti-PLA2R renal tissue staining prevalence in a Latin population with MN, as well as evaluating their role as biomarkers for disease activity. The performance of the two anti-PLA2R serum diagnostic methods—ELISA and indirect immunofluorescence (IFI)—was evaluated for the diagnosis of MN. Fifty-nine patients, including 29 with MN, 18 with lupus membranous nephropathy (LMN) and 12 with focal and segmental glomerulosclerosis (FSGS), were evaluated for serum antibodies. Renal biopsies were also evaluated for the presence of anti-PLA2R staining. Twenty-one patients with MN were followed for 1 year. Patients with LMN and FSGS were negative for both antibodies. All 29 MN patients were negative for anti-THSD7A; 16 MN patients were positive for anti-PLA2R by ELISA and/or IFI, and 3 MN patients were positive for anti-PLA2R only by IFI. Thus, the anti-PLA2R ELISA test demonstrated 45% sensitivity and 97% specificity, while the IFI test showed, respectively, 55% and 100% in our MN patients. Among the 28 MN renal biopsies, 20 presented anti-PLA2R positive staining, corresponding to a 72% sensitivity. Positive correlations were observed between the anti-PLA2R ELISA titer and proteinuria. In conclusion, determination of anti-PLA2R antibodies in the MN Latin population showed similar rates to those reported for other populations. The anti-PLA2R serum levels correlated with MN disease activity.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, Gamma, emerged in the city of Manaus in late 2020 during a large resurgence of coronavirus disease (COVID-19), and has spread throughout Brazil. The effectiveness of vaccines in settings with widespread Gamma variant transmission has not been reported. Methods: We performed a matched test-negative case-control study to estimate the effectiveness of an inactivated vaccine, CoronaVac, in healthcare workers (HCWs) in Manaus, where the Gamma variant accounted for 86% of genotyped SARS-CoV-2 samples at the peak of its epidemic. We performed an early analysis of effectiveness following administration of at least one vaccine dose and an analysis of effectiveness of the two-dose schedule. The primary outcome was symptomatic SARS-CoV-2 infection. Findings: For the early at-least-one-dose and two-dose analyses the study population was, respectively, 53,176 and 53,153 HCWs residing in Manaus and aged 18 years or older, with complete information on age, residence, and vaccination status. Among 53,153 HCWs eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from 19 January, 2021 to 13 April, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive. 393 and 418 case-control pairs were selected for the early and two-dose analyses, respectively, matched on calendar time, age, and neighbourhood. Among those who had received both vaccine doses before the RT-PCR sample collection date, the average time from second dose to sample collection date was 14 days (IQR 7-24). In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness (VE), 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose. However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI -54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose. A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first dose (aOR 2.11, 95% CI 1.36-3.27) suggests that unmeasured confounding led to downward bias in the vaccine effectiveness estimate. Interpretation: Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic Gamma variant transmission. However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented. Funding: Fundação Oswaldo Cruz (Fiocruz); Municipal Health Secretary of Manaus; Fundação de Vigilância em Saúde do Amazonas

Abstract Background Data on the methods used for microbiological diagnosis of hospital-acquired pneumonia (HAP) are mainly extrapolated from ventilator-associated pneumonia. HAP poses additional challenges for respiratory sampling, and the utility of sputum or distal sampling in HAP has not been comprehensively evaluated, particularly in HAP admitted to the ICU. Methods We analyzed 200 patients with HAP from six ICUs in a teaching hospital in Barcelona, Spain. The respiratory sampling methods used were divided into non-invasive [sputum and endotracheal aspirate (EAT)] and invasive [fiberoptic-bronchoscopy aspirate (FBAS), and bronchoalveolar lavage (BAL)]. Results A median of three diagnostic methods were applied [range 2–4]. At least one respiratory sampling method was applied in 93% of patients, and two or more were applied in 40%. Microbiological diagnosis was achieved in 99 (50%) patients, 69 (70%) by only one method (42% FBAS, 23% EAT, 15% sputum, 9% BAL, 7% blood culture, and 4% urinary antigen). Seventy-eight (39%) patients underwent a fiberoptic-bronchoscopy when not receiving mechanical ventilation. Higher rates of microbiological diagnosis were observed in the invasive group (56 vs. 39%, p = 0.018). Patients with microbiological diagnosis more frequently presented changes in their empirical antibiotic scheme, mainly de-escalation. Conclusions A comprehensive approach might be undertaken for microbiological diagnosis in critically ill nonventilated HAP. Sputum sampling determined one third of microbiological diagnosis in HAP patients who were not subsequently intubated. Invasive methods were associated with higher rates of microbiological diagnosis.

Background: Adolescence, when the most complex behaviors are refined to adult sophistication, represents a major window of opportunity and vulnerability for neuropsychological development. To support and protect this complex and active brain growth, different nutritional components considered essential need to be acquired from the diet. For instance, omega-3 fatty acids are mainly obtained from seafood, seeds, and walnuts. Known for their rich lipid profile, walnuts contain sizable amounts of an essential fatty acid, alpha-linolenic acid (ALA), the vegetable omega-3 fatty acid that is the precursor of two longer-chain omega-3 polyunsaturated fatty acids (omega-3 PUFA): docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. While there is growing evidence of neuropsychological improvements in the young developing brain associated with omega-3 PUFA intake, few studies have examined whether consuming walnuts during adolescence entails similar beneficial effects. There is a need to further explore the ways in which walnuts influence youthful brain function, particularly for the long-term. Thus, we designed the WALNUTs study (WSS), a population-based randomized controlled trial conducted in adolescents in Barcelona, Spain. We hypothesize that walnut intake will increase omega-3 PUFA tissue availability (particularly ALA) to a level that enhances the neuropsychological development during adolescence.Methodology/Design: We conducted a 6-month population-based randomized controlled trial in teenagers (n = 800) and we aimed to determine the effectiveness of the intervention (four walnuts per day, or 30 kernel g, ~1.5g of ALA) in enhancing brain neuropsychological and socio-emotional development compared to a control group with no walnut intervention. Before randomization, different neuropsychological tests were recorded for all participants, and blood samples (in a subsample of participants) were collected to measure omega-3 PUFA levels at baseline, and all again, after randomization and the intervention. The data is now collected and we will conduct linear regression models to assess the effect of the intervention.Discussion: The WALNUTs (WSS) study results will allow us to better understand the role of plant-based omega-3 PUFA intake from regular walnut consumption on neuropsychological development during adolescence. Results could be translated into nutritional public health recommendations targeting teenagers.Trial Registration:ClinicalTrials.gov, U.S. National Library of Medicine, National Institutes of Health # NCT02590848. Retrospectively registered 29/10/2015.

Objective: Air pollution is a leading preventable risk factor for cardiovascular diseases. Previous studies mostly relied on concentrations at residence, which might not represent personal exposure. Personal air pollution exposure has a greater variability compared with levels of ambient air pollution, facilitating evaluation of exposure-response functions and vascular pathophysiology. We aimed to evaluate the association between predicted annual personal exposure to PM2.5 and black carbon (BC) and three vascular damage markers in peri-urban South India. Methods: We analyzed the third wave of the APCAPS cohort (2010–2012), which recruited participants from 28 villages. We used predicted personal exposure to PM2.5 and BC derived from 610 participant-days of 24 h average gravimetric PM2.5 and BC measurements and predictors related to usual time-activity. Outcomes included carotid intima-media thickness (CIMT), carotid-femoral pulse wave velocity (cf-PWV) and augmentation index (AIx). We fit linear mixed models, adjusting for potential confounders and accounting for the clustered data structure. We evaluated nonlinear associations using generalized additive mixed models. Results: Of the 3017 participants (mean age 38 years), 1453 (48%) were women. The average PM2.5 exposure was 51 µg/m3 (range 13–85) for men, and 61 µg/m3 (range 40–120) for women, while the average BC was 4 µg/m3 (range 3–7) for men and 8 µg/m3 (range 3–22) for women. A 10 μg/m3 increase of PM2.5 was positively associated with CIMT (0.026 mm, 95% CI 0.014, 0.037), cf-PWV (0.069 m/s, 95% CI 0.008, 0.131) and AIx (0.8%, 95% CI 0.3, 1.3) among men. The exposure-response function for PM2.5 and AIx among men showed non-linearity, particularly within the exposure range dominated by tobacco smoking and occupational exposures. Both PM2.5 and BC were positively associated with AIx among women (0.6%, 95% CI 0.2, 1.0, per 10 μg/m3 PM2.5; 0.5%, 95% CI 0.1, 0.8, per 2 μg/m3 BC). Conclusions: Personal exposure to particulate matter was associated with vascular damage in a peri-urban population in South India. Personal exposure to particulate matter appears to have gender-specific effects on the type of vascular damage, potentially reflecting differences in sources of personal exposure by gender.

Abstract Background We previously evaluated the efficacy of a ventilatory strategy to achieve expiratory flow bias and positive end-expiratory pressure (EFB + PEEP) or the Trendelenburg position (TP) for the prevention of ventilator-associated pneumonia (VAP). These preventive measures were aimed at improving mucus clearance and reducing pulmonary aspiration of bacteria-laden oropharyngeal secretions. This secondary analysis is aimed at evaluating the effects of aforementioned interventions on systemic inflammation and to substantiate the value of clinical parameters and cytokines in the diagnosis of VAP. Methods Twenty female pigs were randomized to be positioned in the semirecumbent/prone position, and ventilated with duty cycle 0.33 and without PEEP (control); positioned as in the control group, PEEP 5 cmH2O, and duty cycle to achieve expiratory flow bias (EFB+PEEP); ventilated as in the control group, but in the Trendelenburg position (Trendelenburg). Following randomization, P. aeruginosa was instilled into the oropharynx. Systemic cytokines and tracheal secretions P. aeruginosa concentration were quantified every 24h. Lung biopsies were collected for microbiological confirmation of VAP. Results In the control, EFB + PEEP, and Trendelenburg groups, lung tissue Pseudomonas aeruginosa concentration was 2.4 ± 1.5, 1.9 ± 2.1, and 0.3 ± 0.6 log cfu/mL, respectively (p = 0.020). Whereas, it was 2.4 ± 1.9 and 0.6 ± 0.9 log cfu/mL in animals with or without VAP (p

RESUMO Objetivo: Avaliar o custo-efetividade da inserção de cateter venoso central guiada por ultrassonografia em tempo real, em comparação com a técnica tradicional, que é baseada na técnica de reparos anatômicos externos, sob a perspectiva da fonte pagadora. Métodos: Uma simulação teórica, baseada em dados de literatura internacional foi aplicada ao contexto brasileiro, ou seja, ao Sistema Único de Saúde (SUS). Foi estruturada uma árvore de decisão, que apresentava as duas técnicas para inserção de cateter venoso central: ultrassonografia em tempo real versus reparos anatômicos externos. As probabilidades de falha e complicações foram extraídas de uma busca nas bases PubMed e Embase, e os valores associados ao procedimento e às complicações foram extraídos de pesquisa de mercado e do Departamento de Informática do Sistema Único de Saúde (DATASUS). Cada alternativa de passagem do cateter venoso central teve um custo calculado por meio do seguimento de cada um dos possíveis caminhos da árvore de decisão. A razão de custo-efetividade incremental foi calculada considerando-se a divisão do custo incremental médio da técnica de ultrassonografia em tempo real comparada à técnica de reparos anatômicos externos pelo benefício incremental médio, em termos de complicações evitadas. Resultados: O custo final médio avaliado pela árvore de decisão, considerando a incorporação da ultrassonografia em tempo real e a redução de custo por diminuição de complicações, para a técnica de reparos anatômicos externos foi de R$262,27 e, para ultrassonografia em tempo real, de R$187,94. O custo incremental final foi de -R$74,33 por cateter venoso central. A razão de custo-efetividade incremental foi -R$2.494,34 por pneumotórax evitado. Conclusão: A inserção de cateter venoso central com auxílio de ultrassonografia em tempo real esteve associada à diminuição da taxa de falhas e complicações, além de hipoteticamente reduzir custos na perspectiva da fonte pagadora, no caso o SUS.

The clinical course of intensive care unit (ICU) patients may be complicated by a large spectrum of lower respiratory tract infections (LRTI), defined by specific epidemiological, clinical and microbiological aspects. A European network for ICU-related respiratory infections (ENIRRIs), supported by the European Respiratory Society, has been recently established, with the aim at studying all respiratory tract infective episodes except community-acquired ones. A multicentre, observational study is in progress, enrolling more than 1000 patients fulfilling the clinical, biochemical and radiological findings consistent with a LRTI. This article describes the methodology of this study. A specific interest is the clinical impact of non-ICU-acquired nosocomial pneumonia requiring ICU admission, non-ventilator-associated LRTIs occurring in the ICU, and ventilator-associated tracheobronchitis. The clinical meaning of microbiologically negative infectious episodes and specific details on antibiotic administration modalities, dosages and duration are also highlighted. Recently released guidelines address many unresolved questions which might be answered by such large-scale observational investigations. In light of the paucity of data regarding such topics, new interesting information is expected to be obtained from our network research activities, contributing to optimisation of care for critically ill patients in the ICU.

OBJECTIVES: To evaluate the effect of the intraoperative use of hydroxyethyl starch on the need for blood products in the perioperative period of oncologic surgery. The secondary end-points included the need for other blood products, the clotting profile, the intensive care unit mortality and length of stay. METHODS: Retrospective observational analysis in a tertiary oncologic ICU in Brazil including 894 patients submitted to oncologic surgery for a two-year period from September 2007. Patients were grouped according to whether hydroxyethyl starch was used during surgery (hydroxyethyl starch and No-hydroxyethyl starch groups) and compared using a propensity score analysis. A total of 385 propensity-matched patients remained in the analysis (97 in the No-hydroxyethyl starch group and 288 in the hydroxyethyl starch group). RESULTS: A higher percentage of patients in the hydroxyethyl starch group required red blood cell transfusion during surgery (26% vs. 14%; p = 0.016) and in the first 24 hours after surgery (5% vs. 0%; p = 0.015) but not in the 24- to 48-hour period after the procedure. There was no difference regarding the transfusion of other blood products, intensive care unit mortality or length of stay. CONCLUSION: Hydroxyethyl starch use in the intraoperative period of major oncologic surgery is associated with an increase in red blood cell transfusions. There are no differences in the need for other blood products, intensive care unit length of stay or mortality.

Microorganisms are able to form biofilms within respiratory secretions. Methods to disaggregate such biofilms before utilizing standard, rapid, or high throughput diagnostic technologies may aid in pathogen detection during ventilator associated pneumonia (VAP) diagnosis. Our aim was to determine if sonication of endotracheal aspirates (ETA) would increase the sensitivity of qualitative, semi-quantitative, and quantitative bacterial cultures in an animal model of pneumonia caused by Pseudomonas aeruginosa or by methicillin resistant Staphylococcus aureus (MRSA). Material and methods: P. aeruginosa or MRSA was instilled into the lungs or the oropharynx of pigs in order to induce severe VAP. Time point assessments for qualitative and quantitative bacterial cultures of ETA and bronchoalveolar lavage (BAL) samples were performed at 24, 48, and 72 h after bacterial instillation. In addition, at 72 h (autopsy), lung tissue was harvested to perform quantitative bacterial cultures. Each ETA sample was microbiologically processed with and without applying sonication for 5 min at 40 KHz before bacterial cultures. Sensitivity and specificity were determined using BAL as a gold-standard. Correlation with BAL and lung bacterial burden was also determined before and after sonication. Assessment of biofilm clusters and planktonic bacteria was performed through both optical microscopy utilizing Gram staining and Confocal Laser Scanning Microscopy utilizing the LIVE/DEAD®BacLight kit. Results: 33 pigs were included, 27 and 6 from P. aeruginosa and MRSA pneumonia models, respectively. Overall, we obtained 85 ETA, 69 (81.2%) from P. aeruginosa and 16 (18.8%) from MRSA challenged pigs. Qualitative cultures did not significantly change after sonication, whereas quantitative ETA cultures did significantly increase bacterial counting. Indeed, sonication consistently increased bacterial burden in ETAs at 24, 48, and 72 h after bacterial challenge. Sonication also improved sensitivity of ETA quantitative cultures and maintained specificity at levels previously reported and accepted for VAP diagnosis. Conclusion: The use of sonication in ETA respiratory samples needs to be clinically validated since sonication could potentially improve pathogen detection before standard, rapid, or high throughput diagnostic methods used in routine microbial diagnostics.

OBJECTIVES: To evaluate the effect of the intraoperative use of hydroxyethyl starch on the need for blood products in the perioperative period of oncologic surgery. The secondary end-points included the need for other blood products, the clotting profile, the intensive care unit mortality and length of stay. METHODS: Retrospective observational analysis in a tertiary oncologic ICU in Brazil including 894 patients submitted to oncologic surgery for a two-year period from September 2007. Patients were grouped according to whether hydroxyethyl starch was used during surgery (hydroxyethyl starch and No-hydroxyethyl starch groups) and compared using a propensity score analysis. A total of 385 propensity-matched patients remained in the analysis (97 in the No-hydroxyethyl starch group and 288 in the hydroxyethyl starch group). RESULTS: A higher percentage of patients in the hydroxyethyl starch group required red blood cell transfusion during surgery (26% vs. 14%; p = 0.016) and in the first 24 hours after surgery (5% vs. 0%; p = 0.015) but not in the 24- to 48-hour period after the procedure. There was no difference regarding the transfusion of other blood products, intensive care unit mortality or length of stay. CONCLUSION: Hydroxyethyl starch use in the intraoperative period of major oncologic surgery is associated with an increase in red blood cell transfusions. There are no differences in the need for other blood products, intensive care unit length of stay or mortality.