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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.

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: 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

The effectiveness of inactivated vaccines (VE) against symptomatic and severe COVID-19 caused by omicron is unknown. We conducted a nationwide, test-negative, case-control study to estimate VE for homologous and heterologous (BNT162b2) booster doses in adults who received two doses of CoronaVac in Brazil in the Omicron context. Analyzing 1,386,544 matched-pairs, VE against symptomatic disease was 8.6% (95% CI, 5.6–11.5) and 56.8% (95% CI, 56.3–57.3) in the period 8–59 days after receiving a homologous and heterologous booster, respectively. During the same interval, VE against severe Covid-19 was 73.6% (95% CI, 63.9–80.7) and 86.0% (95% CI, 84.5–87.4) after receiving a homologous and heterologous booster, respectively. Waning against severe Covid-19 after 120 days was only observed after a homologous booster. Heterologous booster might be preferable to individuals with completed primary series inactivated vaccine.

Rationale: Recommended initial empiric antimicrobial treatment covers the most common bacterial pathogens; however, community-acquired pneumonia (CAP) may be caused by microorganisms not targeted b...

BackgroundThe benefit of vaccination in people who experienced a prior SARS-CoV-2 infection remains unclear.ObjectiveTo estimate the effectiveness of primary (two-dose) and booster (third dose) vaccination against Omicron infection among people with a prior documented infection.DesignTest-negative case-control study.SettingYale New Haven Health System facilities.ParticipantsVaccine eligible people who received SARS-CoV-2 RT-PCR testing between November 1, 2021, and January 31, 2022.MeasurementsWe conducted two analyses, each with an outcome of Omicron BA.1 infection (S-gene target failure defined) and each stratified by prior SARS-CoV-2 infection status. We estimated the effectiveness of primary and booster vaccination. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds among boosted and booster eligible people.ResultsOverall, 10,676 cases and 119,397 controls were included (6.1% and 7.8% occurred following a prior infection, respectively). The effectiveness of primary vaccination 14-149 days after 2nd dose was 36.1% (CI, 7.1% to 56.1%) for people with and 28.5% (CI, 20.0% to 36.2%) without prior infection. The odds ratio comparing boosted and booster eligible people with prior infection was 0.83 (CI, 0.56 to 1.23), whereas the odds ratio comparing boosted and booster eligible people without prior infection was 0.51 (CI, 0.46 to 0.56).LimitationsMisclassification, residual confounding, reliance on TaqPath assay analyzed samples.ConclusionWhile primary vaccination provided protection against BA.1 infection among people with and without prior infection, booster vaccination was only associated with additional protection in people without prior infection. These findings support primary vaccination in people regardless of prior infection status but suggest that infection history should be considered when evaluating the need for booster vaccination.Primary Funding SourceBeatrice Kleinberg Neuwirth and Sendas Family Funds, Merck and Co through their Merck Investigator Studies Program, and the Yale Schools of Public Health and Medicine.

Postauthorization observational studies play a key role in understanding COVID-19 vaccine effectiveness following the demonstration of efficacy in clinical trials. Although bias due to confounding, selection bias, and misclassification can be mitigated through careful study design, unmeasured confounding is likely to remain in these observational studies. Phase III trials of COVID-19 vaccines have shown that protection from vaccination does not occur immediately, meaning that COVID-19 risk should be similar in recently vaccinated and unvaccinated individuals, in the absence of confounding or other bias. Several studies have used the estimated effectiveness among recently vaccinated individuals as a negative control exposure to detect bias in vaccine effectiveness estimates. In this paper, we introduce a theoretical framework to describe the interpretation of such a bias indicator in test-negative studies, and outline strong assumptions that would allow vaccine effectiveness among recently vaccinated individuals to serve as a negative control exposure.

BACKGROUND: COVID-19 vaccines have proven highly effective among individuals without a previous SARS-CoV-2 infection, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with previous infection is less clear. We aimed to estimate the effectiveness of four COVID-19 vaccines against symptomatic infection, hospitalisation, and death for individuals with laboratory-confirmed previous SARS-CoV-2 infection. METHODS: Using national COVID-19 notification, hospitalisation, and vaccination datasets from Brazil, we did a test-negative, case-control study to assess the effectiveness of four vaccines (CoronaVac [Sinovac], ChAdOx1 nCoV-19 [AstraZeneca], Ad26.COV2.S [Janssen], and BNT162b2 [Pfizer-BioNtech]) for individuals with laboratory-confirmed previous SARS-CoV-2 infection. We matched cases with RT-PCR positive, symptomatic COVID-19 with up to ten controls with negative RT-PCR tests who presented with symptomatic illnesses, restricting both groups to tests done at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity and the odds of hospitalisation or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines. FINDINGS: Between Feb 24, 2020, and Nov 11, 2021, we identified 213 457 individuals who had a subsequent, symptomatic illness with RT-PCR testing done at least 90 days after their initial SARS-CoV-2 infection and after the vaccination programme started. Among these, 30 910 (14·5%) had a positive RT-PCR test consistent with reinfection, and we matched 22 566 of these cases with 145 055 negative RT-PCR tests from 68 426 individuals as controls. Among individuals with previous SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection 14 or more days from vaccine series completion was 39·4% (95% CI 36·1-42·6) for CoronaVac, 56·0% (51·4-60·2) for ChAdOx1 nCoV-19, 44·0% (31·5-54·2) for Ad26.COV2.S, and 64·8% (54·9-72·4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1 nCoV-19, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose than after the first dose. Effectiveness against hospitalisation or death 14 or more days from vaccine series completion was 81·3% (75·3-85·8) for CoronaVac, 89·9% (83·5-93·8) for ChAdOx1 nCoV-19, 57·7% (-2·6 to 82·5) for Ad26.COV2.S, and 89·7% (54·3-97·7) for BNT162b2. INTERPRETATION: All four vaccines conferred additional protection against symptomatic infections and severe outcomes among individuals with previous SARS-CoV-2 infection. The provision of a full vaccine series to individuals after recovery from COVID-19 might reduce morbidity and mortality. FUNDING: Brazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS, Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, and Generalitat de Catalunya.

Background Strong spontaneous inspiratory efforts can be difficult to control and prohibit protective mechanical ventilation. Instead of using deep sedation and neuromuscular blockade, the authors hypothesized that perineural administration of lidocaine around the phrenic nerve would reduce tidal volume (VT) and peak transpulmonary pressure in spontaneously breathing patients with acute respiratory distress syndrome. Methods An established animal model of acute respiratory distress syndrome with six female pigs was used in a proof-of-concept study. The authors then evaluated this technique in nine mechanically ventilated patients under pressure support exhibiting driving pressure greater than 15 cm H2O or VT greater than 10 ml/kg of predicted body weight. Esophageal and transpulmonary pressures, electrical activity of the diaphragm, and electrical impedance tomography were measured in pigs and patients. Ultrasound imaging and a nerve stimulator were used to identify the phrenic nerve, and perineural lidocaine was administered sequentially around the left and right phrenic nerves. Results Results are presented as median [interquartile range, 25th to 75th percentiles]. In pigs, VT decreased from 7.4 ml/kg [7.2 to 8.4] to 5.9 ml/kg [5.5 to 6.6] (P < 0.001), as did peak transpulmonary pressure (25.8 cm H2O [20.2 to 27.2] to 17.7 cm H2O [13.8 to 18.8]; P < 0.001) and driving pressure (28.7 cm H2O [20.4 to 30.8] to 19.4 cm H2O [15.2 to 22.9]; P < 0.001). Ventilation in the most dependent part decreased from 29.3% [26.4 to 29.5] to 20.1% [15.3 to 20.8] (P < 0.001). In patients, VT decreased (8.2 ml/ kg [7.9 to 11.1] to 6.0 ml/ kg [5.7 to 6.7]; P < 0.001), as did driving pressure (24.7 cm H2O [20.4 to 34.5] to 18.4 cm H2O [16.8 to 20.7]; P < 0.001). Esophageal pressure, peak transpulmonary pressure, and electrical activity of the diaphragm also decreased. Dependent ventilation only slightly decreased from 11.5% [8.5 to 12.6] to 7.9% [5.3 to 8.6] (P = 0.005). Respiratory rate did not vary. Variables recovered 1 to 12.7 h [6.7 to 13.7] after phrenic nerve block. Conclusions Phrenic nerve block is feasible, lasts around 12 h, and reduces VT and driving pressure without changing respiratory rate in patients under assisted ventilation. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Purpose We explore the hypothesis that critically ill patients developing ICU-acquired pneumonia (ICU-AP) have worse outcomes and an altered inflammatory response if their ICU admission was sepsis-related. Methods Prospective cohort study in two centers. Patients with ICU-AP were evaluated according to their previous exposure to sepsis at ICU-admission. Demographic variables, comorbidities, severity scores at admission and at the time of acquisition of ICU-AP, and serum biomarkers of the inflammatory response were evaluated. Primary outcome: 90-day mortality. Secondary outcomes: ICU and hospital length of stay, mortality at days 28 and 180, in-hospital mortality, ventilator-free days (day-28), and inflammatory response. Propensity scoring weighted the risk of previously-acquired sepsis. Multivariate analysis evaluated the risk of mortality by day-90. Sensitivity analyses evaluated the primary outcome in different subgroups. Results Of 341 patients enrolled, 147 had sepsis on ICU-admission. Adjusted risk of mortality at 90 days did not differ overall [hazard ratio (HR) = 0.94(CI:0.65–1.37)], nor in subpopulations with a confirmed etiology of pneumonia [HR = 0.93(CI:0.57–1.53)] or sepsis [HR = 0.91(0.54–1.55)], ventilator-associated pneumonia (VAP) [HR = 1.01(CI:0.61–1.68)], nor non-VAP ICU-AP [HR = 0.83(CI:0.40–1.71)]. No differences were found in clinical secondary outcomes, the inflammatory response was similar. Conclusions Previous sepsis does not appear to predispose to higher mortality nor worse outcomes in patients who develop ICU-acquired pneumonia.

Rationale: Compliance with sepsis bundles is associated with better outcomes, but information to support structural actions that might improve compliance is scarce. Few studies have evaluated bundle compliance in different time periods, with conflicting results. Objectives: To evaluate the association of sepsis identification during the daytime versus during the nighttime and on weekdays versus weekends with 3-hour sepsis treatment bundle compliance. Methods: This was an observational, multicenter study including patients with sepsis admitted between 2010 and 2017 to 10 hospitals in Brazil. Our exposures of interest were daytime (7:00 a.m.-6:59 p.m.) versus nighttime (7:00 p.m.-6:59 a.m.) and weekdays (Monday 7:00 a.m.-Friday 6:59 p.m.) versus weekends (Friday 7:00 p.m.-Monday 6:59 a.m.). Our primary outcome was full compliance with the 3-hour sepsis treatment bundles. We adjusted by potential confounding factors with multivariable logistic regression models. Results: Of 11,737 patients (8,733 sepsis and 3,004 septic shock), 3-hour bundle compliance was 79.1% and hospital mortality was 24.7%. The adjusted odds ratio (adjOR) for 3-hour full bundle compliance for patients diagnosed during the daytime versus during the nighttime was 1.35 (95% confidence interval [CI], 1.23-1.49; P < 0.001) and was more pronounced in the emergency department (adjOR, 1.55; 95% CI, 1.35-1.77; P < 0.001) than in nonemergency areas (adjOR, 1.19; 95% CI, 1.04-1.37; P = 0.014). Overall, there was no association between diagnosis on the weekends versus on weekdays and 3-hour full bundle compliance (adjOR, 1.08; 95% CI, 0.98-1.19; P = 0.115), although there was an association among those diagnosed in nonemergency areas (adjOR, 1.15; 95% CI, 1.00-1.32; P = 0.047). The lower compliance observed for sepsis diagnosed during the nighttime was more evident 2 years after implementation of the quality improvement initiative. Conclusions: Compliance with sepsis bundles was associated with the moment of sepsis diagnosis. The place of diagnosis and the time from campaign implementation were factors modifying this association. Our results support areas for better design of quality improvement initiatives to mitigate the influence of the period of sepsis diagnosis on treatment compliance. Dr. Azevedo is supported by a grant from the National Council for Scientific and Technological Development (CNPq)

The accuracy of the signs and tests that clinicians use to diagnose ventilator-associated pneumonia (VAP) and initiate antibiotic treatment has not been well characterized. We sought to characterize and compare the accuracy of physical examination, chest radiography, endotracheal aspirate (ETA), bronchoscopic sampling cultures (protected specimen brush [PSB] and bronchoalveolar lavage [BAL]), and CPIS > 6 to diagnose VAP. We searched six databases from inception through September 2019 and selected English-language studies investigating accuracy of any of the above tests for VAP diagnosis. Reference standard was histopathological analysis. Two reviewers independently extracted data and assessed study quality. We included 25 studies (1639 patients). The pooled sensitivity and specificity of physical examination findings for VAP were poor: fever (66.4% [95% confidence interval [CI]: 40.7–85.0], 53.9% [95% CI 34.5–72.2]) and purulent secretions (77.0% [95% CI 64.7–85.9], 39.0% [95% CI 25.8–54.0]). Any infiltrate on chest radiography had a sensitivity of 88.9% (95% CI 73.9–95.8) and specificity of 26.1% (95% CI 15.1–41.4). ETA had a sensitivity of 75.7% (95% CI 51.5–90.1) and specificity of 67.9% (95% CI 40.5–86.8). Among bronchoscopic sampling methods, PSB had a sensitivity of 61.4% [95% CI 43.7–76.5] and specificity of 76.5% [95% CI 64.2–85.6]; while BAL had a sensitivity of 71.1% [95% CI 49.9–85.9] and specificity of 79.6% [95% CI 66.2–85.9]. CPIS > 6 had a sensitivity of 73.8% (95% CI 50.6–88.5) and specificity of 66.4% (95% CI 43.9–83.3). Classic clinical indicators had poor accuracy for diagnosis of VAP. Reliance upon these indicators in isolation may result in misdiagnosis and potentially unnecessary antimicrobial use. Electronic supplementary material The online version of this article (10.1007/s00134-020-06036-z) contains supplementary material, which is available to authorized users.

ObjectiveTo estimate the change in odds of covid-19 over time following primary series completion of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech) in São Paulo state, Brazil.DesignTest negative case-control study.SettingCommunity testing for covid-19 in São Paulo state, Brazil.ParticipantsAdults aged 18-120 years who were residents of São Paulo state, without a previous laboratory-confirmed covid-19 infection, who received only two doses of CoronaVac, and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 30 September 2021.Main outcome measuresRT-PCR-confirmed symptomatic covid-19 and associated hospital admissions and deaths. Cases were pair-matched to test-negative controls by age (in 5-year bands), municipality of residence, healthcare worker (HCW) status, and date of RT-PCR test (±3 days). Conditional logistic regression was adjusted for sex, number of covid-19-associated comorbidities, race, and previous acute respiratory infection.ResultsFrom 137,820 eligible individuals, 37,929 cases with symptomatic covid-19 and 25,756 test-negative controls with covid-19 symptoms were formed into 37,929 matched pairs. Adjusted odds ratios of symptomatic covid-19 increased with time since series completion, and this increase was greater in younger individuals, and among HCWs compared to non-HCWs. Adjusted odds ratios of covid-19 hospitalisation or death were significantly increased from 98 days since series completion, compared to individuals vaccinated 14-41 days previously: 1.40 (95% confidence interval 1.09 to 1.79) from 98-125 days, 1.55 (1.16 to 2.07) from 126-153 days, 1.56 (1.12 to 2.18) from 154-181 days, and 2.12 (1.39-3.22) from 182 days.ConclusionsIn the general population of São Paulo state, Brazil, an increase in odds of moderate and severe covid-19 outcomes was observed over time following primary series completion with CoronaVac.What is already known on this topic-The effectiveness of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech) against moderate and severe covid-19 has been demonstrated in clinical trials and observational studies.-Observational studies have suggested that effectiveness of other covid-19 vaccines appears to decrease over time, prompting many countries to deploy additional doses for individuals who have completed their primary series.-There is currently no evidence for change in the rate of breakthrough infection in individuals who have received a primary series of CoronaVac.What this study adds-In individuals receiving two doses of CoronaVac, the odds of symptomatic covid-19 increased over time since series completion.-Larger increases in covid-19 odds were observed in individuals aged 18-40, and in healthcare workers compared to non-healthcare workers.-Odds of covid-19 hospitalisation or death increased over time since series completion, but to a lesser extent.

Background The influence of urbanicity on hypertension prevalence remains poorly understood. We conducted a systematic review and meta-analysis to assess the difference in hypertension prevalence between urban and rural areas in low-income and middle-income countries (LMICs), where the most pronounced urbanisation is underway. Methods and findings We searched PubMed, Web of Science, Scopus, and Embase, from 01/01/1990 to 10/03/2022. We included population-based studies with ≥400 participants 15 years and older, selected by using a valid sampling technique, from LMICs that reported the urban-rural difference in hypertension prevalence using similar blood pressure measurements. We excluded abstracts, reviews, non-English studies, and those with exclusively self-reported hypertension prevalence. Study selection, quality assessment, and data extraction were performed by 2 independent reviewers following a standardised protocol. Our primary outcome was the urban minus rural prevalence of hypertension. Hypertension was defined as systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure as ≥90 mm Hg and could include use of antihypertensive medication, self-reported diagnosis, or both. We investigated heterogeneity using study-level and socioeconomic country-level indicators. We conducted meta-analysis and meta-regression using random-effects models. This systematic review and meta-analysis has been registered with PROSPERO (CRD42018091671). We included 299 surveys from 66 LMICs, including 19,770,946 participants (mean age 45.4 ± SD = 9 years, 53.0% females and 63.1% from rural areas). The pooled prevalence of hypertension was 30.5% (95% CI, 28.9, 32.0) in urban areas and 27.9% (95% CI, 26.3, 29.6) in rural areas, resulting in a pooled urban-rural difference of 2.45% (95% CI, 1.57, 3.33, I-square: 99.71%, tau-square: 0.00524, Pheterogeneity < 0.001). Hypertension prevalence increased over time and the rate of change was greater in rural compared to urban areas, resulting in a pooled urban-rural difference of 5.75% (95% CI, 4.02, 7.48) in the period 1990 to 2004 and 1.38% (95% CI, 0.40, 2.37) in the period 2005 to 2020, p < 0.001 for time period. We observed substantial heterogeneity in the urban-rural difference of hypertension, which was partially explained by urban-rural definition, probably high risk of bias in sampling, country income status, region, and socioeconomic indicators. The urban-rural difference was 5.67% (95% CI, 4.22, 7.13) in low, 2.74% (95% CI, 1.41, 4.07) in lower-middle and −1.22% (95% CI, −2.73, 0.28) in upper-middle-income countries in the period 1990 to 2020, p < 0.001 for country income. The urban-rural difference was highest for South Asia (7.50%, 95% CI, 5.73, 9.26), followed by sub-Saharan Africa (4.24%, 95% CI, 2.62, 5.86) and reversed for Europe and Central Asia (−6.04%, 95% CI, −9.06, −3.01), in the period 1990 to 2020, p < 0.001 for region. Finally, the urban-rural difference in hypertension prevalence decreased nonlinearly with improvements in Human Development Index and infant mortality rate. Limitations included lack of data available from all LMICs and variability in urban and rural definitions in the literature. Conclusions The prevalence of hypertension in LMICs increased between 1990 and 2020 in both urban and rural areas, but with a stronger trend in rural areas. The urban minus rural hypertension difference decreased with time, and with country-level socioeconomic development. Focused action, particularly in rural areas, is needed to tackle the burden of hypertension in LMICs.

Background Indigenous people have historically suffered devastating impacts from epidemics and continue to have lower access to healthcare and be especially vulnerable to respiratory infectious. 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 Jan 2021 and 1st Mar 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 Mar 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. 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. Among hospitalised patients, VE was 87% (95%CI:27–98%) for progression to ICU and 96% (95%CI: 90–99%) for death. 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.

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 PM2.5outdoors 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. The research leading to these results received funding from the European Research Council under ERC Grant Agreement number 336167 for the CHAI Project. The third wave of data collection and village socio-demographic surveys for the APCAPS study were funded by the Wellcome Trust (Grant: 084674/Z). OTR is funded by a Sara Borrell fellowship (CD19/00110) from the Instituto de Salud Carlos III. CT was funded through a Ramón y Cajal fellowship (RYC-2015-17402) awarded by the Spanish Ministry of Economy and Competitiveness. We acknowledge support from the Spanish Ministry of Science and Innovation and State Research Agency through the “Centro de Excelencia Severo Ochoa 2019–2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program.

Purpose: The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM‑RPG) was to formulate evidence‑based guidance for the use of dexmedetomidine for sedation in invasively mechanically ventilated adults in the intensive care unit (ICU).Methods: We adhered to the methodology for trustworthy clinical practice guidelines, including use of the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence, and the Evidence-to-Decision framework to generate recommendations. The guideline panel comprised 28 international panelists, including content experts, ICU clinicians, methodologists, and patient representatives. Through teleconferences and web‑based discussions, the panel provided input on the balance and magnitude of the desirable and undesirable effects, the certainty of evidence, patients' values and preferences, costs and resources, feasibility, acceptability, and research priorities.Results: The ICM‑RPG panel issued one weak recommendation (suggestion) based on overall moderate certainty of evidence: "In invasively mechanically ventilated adult ICU patients, we suggest using dexmedetomidine over other sedative agents, if the desirable effects including a reduction in delirium are valued over the undesirable effects including an increase in hypotension and bradycardia".Conclusion: This ICM-RPG provides updated evidence-based guidance on the use of dexmedetomidine for sedation in mechanically ventilated adults, and outlines uncertainties and research priorities.Keywords: Clinical practice guideline; Dexmedetomidine; ICM-RPG; Sedation.© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.

BackgroundCOVID-19 vaccines have proven highly effective among SARS-CoV-2 naive individuals, but their effectiveness in preventing symptomatic infection and severe outcomes among individuals with prior infection is less clear.MethodsUtilizing national COVID-19 notification, hospitalization, and vaccination datasets from Brazil, we performed a case-control study using a test-negative design to assess the effectiveness of four vaccines (CoronaVac, ChAdOx1, Ad26.COV2.S and BNT162b2) among individuals with laboratory-confirmed prior SARS-CoV-2 infection. We matched RT-PCR positive, symptomatic COVID-19 cases with RT-PCR-negative controls presenting with symptomatic illnesses, restricting both groups to tests performed at least 90 days after an initial infection. We used multivariable conditional logistic regression to compare the odds of test positivity, and the odds of hospitalization or death due to COVID-19, according to vaccination status and time since first or second dose of vaccines.FindingsAmong individuals with prior SARS-CoV-2 infection, vaccine effectiveness against symptomatic infection ≥ 14 days from vaccine series completion was 39.4% (95% CI 36.1-42.6) for CoronaVac, 56.0% (95% CI 51.4-60.2) for ChAdOx1, 44.0% (95% CI 31.5-54.2) for Ad26.COV2.S, and 64.8% (95% CI 54.9-72.4) for BNT162b2. For the two-dose vaccine series (CoronaVac, ChAdOx1, and BNT162b2), effectiveness against symptomatic infection was significantly greater after the second dose compared with the first dose. Effectiveness against hospitalization or death ≥ 14 days from vaccine series completion was 81.3% (95% CI 75.3-85.8) for CoronaVac, 89.9% (95% CI 83.5-93.8) for ChAdOx1, 57.7% (95% CI −2.6-82.5) for Ad26.COV2.S, and 89.7% (95% CI 54.3-97.7) for BNT162b2.InterpretationAll four vaccines conferred additional protection against symptomatic infections and severe outcomes among individuals with previous SARS-CoV-2 infection. Provision of a full vaccine series to individuals following recovery from COVID-19 may reduce morbidity and mortality.FundingBrazilian National Research Council, Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro, Oswaldo Cruz Foundation, JBS S.A., Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation, Generalitat de Catalunya.RESEARCH IN CONTEXTEvidence before this studyWe searched PubMed, medRxiv, and SSRN for articles published from January 1, 2020 until December 15, 2021, with no language restrictions, using the search terms “vaccine effectiveness” AND “previous*” AND (“SARS-CoV-2” OR “COVID-19”). We found several studies evaluating ChAdOx1 and BNT162b2, and one additionally reporting on mRNA-1273 and Ad26.COV2.S, which found that previously infected individuals who were vaccinated had lower risk of symptomatic SARS-CoV-2 infection. One study found that risk of hospitalization was lower for previously infected individuals after a full series of BNT162b2 or mRNA-1273. Limited evidence is available comparing effectiveness of one versus two doses among individuals with prior infection. No studies reported effectiveness of inactivated vaccines among previously infected individuals.Added value of this studyWe used national databases of COVID-19 case surveillance, laboratory testing, and vaccination from Brazil to investigate effectiveness of CoronaVac, ChAdOx1, Ad26.COV2.S and BNT162b2 among individuals with a prior, laboratory-confirmed SARS-CoV-2 infection. We matched >22,000 RT-PCR-confirmed re-infections with >145,000 RT-PCR-negative controls using a test-negative design. All four vaccines were effective against symptomatic SARS-CoV-2 infections, with effectiveness from 14 days after series completion ranging from 39-65%. For vaccines with two-dose regimens, the second dose provided significantly increased effectiveness compared with one dose. Effectiveness against COVID-19-associated hospitalization or death from 14 days after series completion was >80% for CoronaVac, ChAdOx1and BNT162b2.Implications of all the available evidenceWe find evidence that four vaccines, using three different platforms, all provide protection to previously infected individuals against symptomatic SARS-CoV-2 infection and severe outcomes, with a second dose conferring significant additional benefits. These results support the provision of a full vaccine series among individuals with prior SARS-CoV-2 infection.

Background Little is known about zoonotic tuberculosis (zTB) due to Mycobacterium bovis burden across the globe. The aim of this study was to describe zTB surveillance programs in selected WHO signatory countries and to assess the relationship of the disease with the country’s income level and the risk of M. bovis transmission. Methods We searched the main articles databases and grey literature for guide documents published between 1980 and 2019. For inclusion, the articles and guide documents had to be in English, French, Portuguese, Spanish, or Italian. Only original articles and narrative and systematic reviews were accepted and the guide documents were required to be available on official websites. We excluded articles that did not focus on epidemiology, control and surveillance. We used bovine TB cases in livestock and wildlife populations as a proxy for the country’s risk of zTB using data from the World Organization for Animal Health (OIE) published from 2015 to 2018. Countries were classified according to income level (World Bank’s classification) and strength of zTB surveillance. The study was registered in PROSPERO under number CRD42018090603. Findings We included 13 articles and 208 guide documents including data from 119/194 countries (61.3%). We found a lack of surveillance data about zTB in over half (89.9%) of the 119 WHO signatory countries. Most surveillance systems perform passive surveillance and are not integrated into the One Health perspective, which was operating in 4/119 (3.4%) countries, all high-income. Many of these countries (71/119, 59.7%) have M. bovis circulating in their cattle herds, but only ~10% of them have implemented zTB surveillance activities. Interpretation Our findings highlight weaknesses in zTB surveillance worldwide, with a consequent lack of information that could support an adequate understanding of disease burden, especially in countries at major risk for M. bovis transmission. To meet this challenge, efforts will be needed to promote intersectoral policies, implementing the One Health strategy.

The SARS-CoV-2 Gamma variant spread rapidly across Brazil, causing substantial infection and death waves. We use individual-level patient records following hospitalisation with suspected or confirmed COVID-19 to document the extensive shocks in hospital fatality rates that followed Gamma’s spread across 14 state capitals, and in which more than half of hospitalised patients died over sustained time periods. We show that extensive fluctuations in COVID-19 in-hospital fatality rates also existed prior to Gamma’s detection, and were largely transient after Gamma’s detection, subsiding with hospital demand. Using a Bayesian fatality rate model, we find that the geographic and temporal fluctuations in Brazil’s COVID-19 in-hospital fatality rates are primarily associated with geographic inequities and shortages in healthcare capacity. We project that approximately half of Brazil’s COVID-19 deaths in hospitals could have been avoided without pre-pandemic geographic inequities and without pandemic healthcare pressure. Our results suggest that investments in healthcare resources, healthcare optimization, and pandemic preparedness are critical to minimize population wide mortality and morbidity caused by highly transmissible and deadly pathogens such as SARS-CoV-2, especially in low- and middle-income countries., One sentence summary COVID-19 in-hospital fatality rates fluctuate dramatically in Brazil, and these fluctuations are primarily associated with geographic inequities and shortages in healthcare capacity.

Objectives: To estimate vaccine effectiveness after the first and second dose of ChAdOx1 nCoV-19 against symptomatic COVID-19 and infection in a socially vulnerable community in Brazil when Gamma and Delta were the predominant variants circulating. Methods: We conducted a test-negative study in the community Complexo da Maré, the largest group of slums (n = 16) in Rio de Janeiro, Brazil, from January 17, 2021 to November 27, 2021. We selected RT-qPCR positive and negative tests from a broad community testing program. The primary outcome was symptomatic COVID-19 (positive RT-qPCR test with at least one symptom) and the secondary outcome was infection (any positive RT-qPCR test). Vaccine effectiveness was estimated as 1 - OR, which was obtained from adjusted logistic regression models. Results: We included 10 077 RT-qPCR tests (6,394, 64% from symptomatic and 3,683, 36% from asymptomatic individuals). The mean age was 40 (SD: 14) years, and the median time between vaccination and RT-qPCR testing among vaccinated was 41 (25-75 percentile: 21-62) days for the first dose and 36 (25-75 percentile: 17-59) days for the second dose. Adjusted vaccine effectiveness against symptomatic COVID-19 was 31.6% (95% CI, 12.0-46.8) 21 days after the first dose and 65.1% (95% CI, 40.9-79.4) 14 days after the second dose. Adjusted vaccine effectiveness against COVID-19 infection was 31.0% (95% CI, 12.7-45.5) 21 days after the first dose and 59.0% (95% CI, 33.1-74.8) 14 days after the second dose. Discussion: ChAdOx1 nCoV-19 was effective in reducing symptomatic COVID-19 in a socially vulnerable community in Brazil when Gamma and Delta were the predominant variants circulating.

We conducted a test-negative study design at the community “Complexo da Maré”, the largest group of favelas in Rio de Janeiro, Brazil, when Gamma and Delta were the predominant variants circulating. We estimated 42.4% (95% CI, 24.6, 56.0) protection against symptomatic COVID-19 after 21 days of one dose of ChAdOx1.

We used a test-negative design to estimate the vaccine effectiveness of Ad26.COV2.S (Janssen) against symptomatic COVID-19 and clinical outcomes in Mato-Grosso do Sul, Brazil. We analyzed 11,817 RT-PCR tests. The mean age was 37 (SD=17) years, 2,308 (20%) of individuals more or equal than 50 years and almost two-thirds of the population was Brown/Pardo. Adjusted effectiveness against symptomatic COVID-19 after 28 days of the single dose was 50.9% (95% CI, 35.5-63.0). Adjusted effectiveness against clinical outcomes was 72.9% (95% CI, 35.1-91.1) for hospitalization, 92.5% (95% CI, 54.9-99.6) for ICU admission, 88.7% (95% CI, 17.9-99.5) for mechanical ventilation and 90.5% (95% CI, 31.5-99.6) for death. Despite lacking precision on some estimates, a single dose of Ad26.COV2.S vaccine continues to protect specially for severe forms of COVID-19 in the context of new variants.

Objective To estimate the effectiveness of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech), against symptomatic covid-19 in the elderly population of São Paulo state, Brazil during widespread circulation of the gamma variant. Design Test negative case-control study. Setting Community testing for covid-19 in São Paulo state, Brazil. Participants 43 774 adults aged ≥70 years who were residents of São Paulo state and underwent reverse transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 from 17 January to 29 April 2021. 26 433 cases with symptomatic covid-19 and 17 622 test negative controls with covid-19 symptoms were formed into 13 283 matched sets, one case with to up to five controls, according to age, sex, self-reported race, municipality of residence, previous covid-19 status, and date of RT-PCR test (±3 days). Intervention Vaccination with a two dose regimen of CoronaVac. Main outcome measures RT-PCR confirmed symptomatic covid-19 and associated hospital admissions and deaths. Results Adjusted vaccine effectiveness against symptomatic covid-19 was 24.7% (95% confidence interval 14.7% to 33.4%) at 0-13 days and 46.8% (38.7% to 53.8%) at ≥14 days after the second dose. Adjusted vaccine effectiveness against hospital admissions was 55.5% (46.5% to 62.9%) and against deaths was 61.2% (48.9% to 70.5%) at ≥14 days after the second dose. Vaccine effectiveness ≥14 days after the second dose was highest for the youngest age group (70-74 years)—59.0% (43.7% to 70.2%) against symptomatic disease, 77.6% (62.5% to 86.7%) against hospital admissions, and 83.9% (59.2% to 93.7%) against deaths—and declined with increasing age. Conclusions Vaccination with CoronaVac was associated with a reduction in symptomatic covid-19, hospital admissions, and deaths in adults aged ≥70 years in a setting with extensive transmission of the gamma variant. Vaccine protection was, however, low until completion of the two dose regimen, and vaccine effectiveness was observe to decline with increasing age among this elderly population.

Background: There is limited information on the inequity of access to vaccination in low-and-middle-income countries during the COVID-19 pandemic. Here, we described the progression of the Brazilian immunisation program for COVID-19, and the association of socioeconomic development with vaccination rates, considering the potential protective effect of primary health care coverage. Methods: We performed an ecological analysis of COVID-19 immunisation data from the Brazilian National Immunization Program from January 17 to August 31, 2021. We analysed the dynamics of vaccine coverage in the adult population of 5,570 Brazilian municipalities. We estimated the association of human development index (HDI) levels (low, medium, and high) with age-sex standardised first dose coverage using a multivariable negative binomial regression model. We evaluated the interaction between the HDI and primary health care coverage. Finally, we compared the adjusted monthly progression of vaccination rates, hospital admission and in-hospital death rates among HDI levels. Findings: From January 17 to August 31, 2021, 202,427,355 COVID-19 vaccine doses were administered in Brazil. By the end of the period, 64·2% of adults had first and 31·4% second doses, with more than 90% of those aged ≥60 years with primary scheme completed. Four distinct vaccine platforms were used in the country, ChAdOx1-S/nCoV-19, Sinovac-CoronaVac, BNT162b2, Ad26.COV2.S, composing 44·8%, 33·2%, 19·6%, and 2·4% of total doses, respectively. First dose coverage differed between municipalities with high, medium, and low HDI (Median [interquartile range] 72 [66, 79], 68 [61, 75] and 63 [55, 70] doses per 100 people, respectively). Municipalities with low (Rate Ratio [RR, 95% confidence interval]: 0·87 [0·85-0·88]) and medium (RR [95% CI]: 0·94 [0·93-0·95]) development were independently associated with lower vaccination rates compared to those with high HDI. Primary health care coverage modified the association of HDI and vaccination rate, improving vaccination rates in those municipalities of low HDI and high primary health care coverage. Low HDI municipalities presented a delayed decrease in adjusted in-hospital death rates by first dose coverage compared to high HDI locations. Interpretation: In Brazil, socioeconomic disparities negatively impacted the first dose vaccination rate. However, the primary health care mitigated these disparities, suggesting that the primary health care coverage guarantees more equitable access to vaccines in vulnerable locations. Funding: This work is part of the Grand Challenges ICODA pilot initiative, delivered by Health Data Research UK and funded by the Bill & Melinda Gates Foundation and the Minderoo Foundation. This study was supported by the National Council for Scientific and Technological Development (CNPq), the Coordination for the Improvement of Higher Education Personnel (CAPES) - Finance Code 001, Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (FAPERJ) and the Pontifical Catholic University of Rio de Janeiro.

Studies of critically ill hematopoietic stem cell transplantation (HSCT) recipients have mainly been single-center and focused on allogenic HSCT recipients. We aimed to describe a cohort of autologous HSCT with an unplanned intensive care unit (ICU) admission.This study is a retrospective cohort study of autologous HSCT performed as a treatment for a hematological malignancy, during their first unplanned ICU admission in 50 hospitals in Brazil. We assessed the hospital mortality and the association between mechanical ventilation, vasopressors, and renal replacement therapy and hospital mortality in autologous HSCT recipients, adjusted for potential confounders.We included 301 patients. Multiple myeloma was the most common malignancy driving to HSCT. ICU and hospital mortality were 22.9% and 37.5%, respectively. After adjustment for potential confounders, mechanical ventilation (OR = 9.10; CI 95%, 4.82-17.15) was associated with hospital mortality, but vasopressors (OR = 1.43; CI 95%, 0.77-2.64) and renal replacement therapy (OR = 1.30; CI 95%, 0.63-2.66) were not.In this large cohort of critically ill autologous HSCT recipients, mechanical ventilation was the only organ support-therapy associated with increased mortality in autologous HSCT recipients.