Applicability of an unsupervised cluster model developed on first wave COVID-19 patients in second/third wave critically ill patients.

OBJECTIVE: To validate the unsupervised cluster model (USCM) developed during the first pandemic wave in a cohort of critically ill patients from the second and third pandemic waves. DESIGN: Observational, retrospective, multicentre study. SETTING: Intensive Care Unit (ICU). PATIENTS: Adult patients admitted with COVID-19 and respiratory failure during the second and third pandemic waves. INTERVENTIONS: None. MAIN VARIABLES OF INTEREST: Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. To validate our original USCM, we assigned a phenotype to each patient of the validation cohort. The performance of the classification was determined by Silhouette coefficient (SC) and general linear modelling. In a post-hoc analysis we developed and validated a USCM specific to the validation set. The model's performance was measured using accuracy test and area under curve (AUC) ROC. RESULTS: A total of 2330 patients (mean age 63 [53-82] years, 1643 (70.5%) male, median APACHE II score (12 [9-16]) and SOFA score (4 [3-6]) were included. The ICU mortality was 27.2%. The USCM classified patients into 3 clinical phenotypes: A (n = 1206 patients, 51.8%); B (n = 618 patients, 26.5%), and C (n = 506 patients, 21.7%). The characteristics of patients within each phenotype were significantly different from the original population. The SC was -0.007 and the inclusion of phenotype classification in a regression model did not improve the model performance (0.79 and 0.78 ROC for original and validation model). The post-hoc model performed better than the validation model (SC -0.08). CONCLUSION: Models developed using machine learning techniques during the first pandemic wave cannot be applied with adequate performance to patients admitted in subsequent waves without prior validation.

Association of obesity on the outcome of critically ill patients affected by COVID-19.

OBJECTIVE: To evaluate the impact of obesity on ICU mortality. DESIGN: Observational, retrospective, multicentre study. SETTING: Intensive Care Unit (ICU). PATIENTS: Adults patients admitted with COVID-19 and respiratory failure. INTERVENTIONS: None. PRIMARY VARIABLES OF INTEREST: Collected data included demographic and clinical characteristics, comorbidities, laboratory tests and ICU outcomes. Body mass index (BMI) impact on ICU mortality was studied as (1) a continuous variable, (2) a categorical variable obesity/non-obesity, and (3) as categories defined a priori: underweight, normal, overweight, obesity and Class III obesity. The impact of obesity on mortality was assessed by multiple logistic regression and Smooth Restricted cubic (SRC) splines for Cox hazard regression. RESULTS: 5,206 patients were included, 20 patients (0.4%) as underweight, 887(17.0%) as normal, 2390(46%) as overweight, 1672(32.1) as obese and 237(4.5%) as class III obesity. The obesity group patients (n = 1909) were younger (61 vs. 65 years, p < 0.001) and with lower severity scores APACHE II (13 [9-17] vs. 13[10-17, p < 0.01) than non-obese. Overall ICU mortality was 28.5% and not different for obese (28.9%) or non-obese (28.3%, p = 0.65). Only Class III obesity (OR = 2.19, 95%CI 1.44-3.34) was associated with ICU mortality in the multivariate and SRC analysis. CONCLUSIONS: COVID-19 patients with a BMI > 40 are at high risk of poor outcomes in the ICU. An effective vaccination schedule and prolonged social distancing should be recommended.

The Role of the Kynurenine Pathway in the Pathophysiology of Frailty, Sarcopenia, and Osteoporosis.

Tryptophan is an essential nutrient required to generate vitamin B3 (niacin), which is mainly involved in energy metabolism and DNA production. Alterations in tryptophan metabolism could have significant effects on aging and musculoskeletal health. The kynurenine pathway, essential in tryptophan catabolism, is modulated by inflammatory factors that are increased in older persons, a process known as inflammaging. Osteoporosis, sarcopenia, osteosarcopenia, and frailty have also been linked with chronically increased levels of inflammatory factors. Due to the disruption of the kynurenine pathway by chronic inflammation and/or changes in the gut microbiota, serum levels of toxic metabolites are increased and are associated with the pathophysiology of those conditions. In contrast, anabolic products of this pathway, such as picolinic acid, have demonstrated a positive effect on skeletal muscle and bone. In addition, physical activity can modulate this pathway by promoting the secretion of anabolic kynurenines. According to the evidence collected, kynurenines could have a promising role as biomarkers for osteoporosis sarcopenia, osteosarcopenia, and frailty in older persons. In addition, some of these metabolites could become important targets for developing new pharmacological treatments for these conditions.

Timing of intubation and ICU mortality in COVID-19 patients: a retrospective analysis of 4198 critically ill patients during the first and second waves.

BACKGROUND: The optimal time to intubate patients with SARS-CoV-2 pneumonia has not been adequately determined. While the use of non-invasive respiratory support before invasive mechanical ventilation might cause patient-self-induced lung injury and worsen the prognosis, non-invasive ventilation (NIV) is frequently used to avoid intubation of patients with acute respiratory failure (ARF). We hypothesized that delayed intubation is associated with a high risk of mortality in COVID-19 patients. METHODS: This is a secondary analysis of prospectively collected data from adult patients with ARF due to COVID-19 admitted to 73 intensive care units (ICUs) between February 2020 and March 2021. Intubation was classified according to the timing of intubation. To assess the relationship between early versus late intubation and mortality, we excluded patients with ICU length of stay (LOS) < 7 days to avoid the immortal time bias and we did a propensity score and a cox regression analysis. RESULTS: We included 4,198 patients [median age, 63 (54‒71) years; 71% male; median SOFA (Sequential Organ Failure Assessment) score, 4 (3‒7); median APACHE (Acute Physiology and Chronic Health Evaluation) score, 13 (10‒18)], and median PaO2/FiO2 (arterial oxygen pressure/ inspired oxygen fraction), 131 (100‒190)]; intubation was considered very early in 2024 (48%) patients, early in 928 (22%), and late in 441 (10%). ICU mortality was 30% and median ICU stay was 14 (7‒28) days. Mortality was higher in the "late group" than in the "early group" (37 vs. 32%, p < 0.05). The implementation of an early intubation approach was found to be an independent protective risk factor for mortality (HR 0.6; 95%CI 0.5‒0.7). CONCLUSIONS: Early intubation within the first 24 h of ICU admission in patients with COVID-19 pneumonia was found to be an independent protective risk factor of mortality. TRIAL REGISTRATION: The study was registered at Clinical-Trials.gov (NCT04948242) (01/07/2021).

Conventional and digital complete-arch implant impression techniques: An in vitro study comparing accuracy.

STATEMENT OF PROBLEM: Varying complete-arch digital-implant-scanning techniques have been described, but their accuracy remains uncertain. PURPOSE: The purpose of this in vitro investigation was to assess the effect of the implant angulation and impression method (conventional, intraoral digital scan, intraoral scan with a splinting framework, and combining cone beam computed tomography [CBCT] and intraoral scan) on the accuracy of complete arch implant recording. MATERIAL AND METHODS: The following 2 casts were obtained: one with 4 parallel (P group) and the other with 4 angled (up to 30 degrees) implant abutment analogs (NP group). Both the casts were digitized (7Series Scanner) (control file). The following 4 subgroups were created: conventional polyether impression with a splinted framework (CNV subgroup), intraoral scan (IOS subgroup), intraoral scan with a splinting framework (S-IOS subgroup), and intraoral scan combined with CBCT scan (CBCT-IOS subgroup) (n=10). For each file, an implant-supported bar was designed and imported into a program (Netfabb) to perform linear and angular interimplant abutment measurements. Two-way ANOVA (Analysis of Variance) and Tukey tests were selected to examine the data (α=.05). RESULTS: Implant angulation (P=.010) and impression method (P=.003) significantly influenced the linear trueness. The P group (112 µm) obtained better linear trueness than the NP group (144 µm). The CNV subgroup obtained the best linear trueness, while the IOS and CBCT-IOS showed the worst trueness. Group (P<.001) significantly influenced angular trueness. Group (P=.009) and subgroup (P<.001) influenced the linear precision. The P group (72 µm) obtained better linear precision than the NP group (91 µm). The IOS subgroup obtained the best linear precision. Group (P=.034) significantly influenced the angular precision. The P group (0.46 degrees) had higher angular precision compared with the NP group (0.60 degrees). CONCLUSIONS: Implant angulation and the impression methods tested, impacted the accuracy of the complete-arch implant recording. Parallel implants had better trueness and precision values than nonparallel implants. The conventional impression method showed the best trueness and precision. Among the digital implant scan methods assessed, the S-IOS and CBCT-IOS subgroups acquired significantly better trueness and precision than the IOS subgroup.

2-(Fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl (UCM-1306), an Orally Bioavailable Positive Allosteric Modulator of the Human Dopamine D1 Receptor for Parkinson's Disease.

Tolerance development caused by dopamine replacement with l-DOPA and therapeutic drawbacks upon activation of dopaminergic receptors with orthosteric agonists reveal a significant unmet need for safe and effective treatment of Parkinson's disease. In search for selective modulators of the D1 receptor, the screening of a chemical library and subsequent medicinal chemistry program around an identified hit resulted in new synthetic compound 26 [UCM-1306, 2-(fluoromethoxy)-4'-(S-methanesulfonimidoyl)-1,1'-biphenyl] that increases the dopamine maximal effect in a dose-dependent manner in human and mouse D1 receptors, is inactive in the absence of dopamine, modulates dopamine affinity for the receptor, exhibits subtype selectivity, and displays low binding competition with orthosteric ligands. The new allosteric modulator potentiates cocaine-induced locomotion and enhances l-DOPA recovery of decreased locomotor activity in reserpinized mice after oral administration. The behavior of compound 26 supports the interest of a positive allosteric modulator of the D1 receptor as a promising therapeutic approach for Parkinson's disease.

Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients.

BACKGROUND: Procalcitonin (PCT) and C-Reactive Protein (CRP) are useful biomarkers to differentiate bacterial from viral or fungal infections, although the association between them and co-infection or mortality in COVID-19 remains unclear. METHODS: The study represents a retrospective cohort study of patients admitted for COVID-19 pneumonia to 84 ICUs from ten countries between (March 2020-January 2021). Primary outcome was to determine whether PCT or CRP at admission could predict community-acquired bacterial respiratory co-infection (BC) and its added clinical value by determining the best discriminating cut-off values. Secondary outcome was to investigate its association with mortality. To evaluate the main outcome, a binary logistic regression was performed. The area under the curve evaluated diagnostic performance for BC prediction. RESULTS: 4635 patients were included, 7.6% fulfilled BC diagnosis. PCT (0.25[IQR 0.1-0.7] versus 0.20[IQR 0.1-0.5]ng/mL, p<0.001) and CRP (14.8[IQR 8.2-23.8] versus 13.3 [7-21.7]mg/dL, p=0.01) were higher in BC group. Neither PCT nor CRP were independently associated with BC and both had a poor ability to predict BC (AUC for PCT 0.56, for CRP 0.54). Baseline values of PCT<0.3ng/mL, could be helpful to rule out BC (negative predictive value 91.1%) and PCT≥0.50ng/mL was associated with ICU mortality (OR 1.5,p<0.001). CONCLUSIONS: These biomarkers at ICU admission led to a poor ability to predict BC among patients with COVID-19 pneumonia. Baseline values of PCT<0.3ng/mL may be useful to rule out BC, providing clinicians a valuable tool to guide antibiotic stewardship and allowing the unjustified overuse of antibiotics observed during the pandemic, additionally PCT≥0.50ng/mL might predict worsening outcomes.

Discovery of V-0219: A Small-Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 Receptor toward Oral Treatment for "Diabesity".

Peptidic agonists of the glucagon-like peptide-1 receptor (GLP-1R) have gained a prominent role in the therapy of type-2 diabetes and are being considered for reducing food intake in obesity. Potential advantages of small molecules acting as positive allosteric modulators (PAMs) of GLP-1R, including oral administration and reduced unwanted effects, could improve the utility of this class of drugs. Here, we describe the discovery of compound 9 (4-{[1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)piperidin-3-yl]methyl}morpholine, V-0219) that exhibits enhanced efficacy of GLP-1R stimulation, subnanomolar potency in the potentiation of insulin secretion, and no significant off-target activities. The identified GLP-1R PAM shows a remarkable in vivo activity, reducing food intake and improving glucose handling in normal and diabetic rodents. Enantioselective synthesis revealed oral efficacy for (S)-9 in animal models. Compound 9 behavior bolsters the interest of a small-molecule PAM of GLP-1R as a promising therapeutic approach for the increasingly prevalent obesity-associated diabetes.

Biomarker­driven phase Ib clinical trial of OPB­111077 in acute myeloid leukemia.

OPB-111077 is a novel, highly specific oral signal transducer and activator of transcription 3 inhibitor that has exhibited good efficacy against solid and blood cancers, including acute myeloid leukemia (AML), in preclinical models. In the present study, a phase 1b, two-stage, 3+3 dose-escalation clinical trial [dose level (DL)1 of 200 mg/day and DL2 of 250 mg/day on a once daily dose schedule in 28-day cycles] was conducted to assess the maximum tolerated dose (MTD), safety profile and the preliminary antitumor activity of OPB-111077 in patients with high-risk AML. A preliminary preclinical analysis evaluated the anti-proliferative activity of OPB-111077 in 19 patients with AML with a Vivia Biotech ex vivo PharmaFlow precision medicine test. A total of 12 patients were ultimately enrolled in the trial: 5 patients (42%) were treated with DL1, and 7 (58%) were escalated to DL2 of OPB-111077. Dose-limiting toxicities were not observed and the MTD was not reached. In addition, the most frequently reported treatment-emergent adverse events were nausea, vomiting and fatigue. Finally, clinical activity (overall response) was observed in 3 patients (25%). On the whole, the present study demonstrates that OPB-111077 exhibits a good safety and tolerability profile and an acceptable clinical response in patients with high-risk AML. A biomarker-driven design is useful for selecting the study population upfront.

Corticosteroid treatment and mortality in mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients: a multicentre cohort study.

BACKGROUND: Some unanswered questions persist regarding the effectiveness of corticosteroids for severe coronavirus disease 2019 (COVID-19) patients. We aimed to assess the clinical effect of corticosteroids on intensive care unit (ICU) mortality among mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients. METHODS: This was a retrospective study of prospectively collected data conducted in 70 ICUs (68 Spanish, one Andorran, one Irish), including mechanically ventilated COVID-19-associated ARDS patients admitted between February 6 and September 20, 2020. Individuals who received corticosteroids for refractory shock were excluded. Patients exposed to corticosteroids at admission were matched with patients without corticosteroids through propensity score matching. Primary outcome was all-cause ICU mortality. Secondary outcomes were to compare in-hospital mortality, ventilator-free days at 28 days, respiratory superinfection and length of stay between patients with corticosteroids and those without corticosteroids. We performed survival analysis accounting for competing risks and subgroup sensitivity analysis. RESULTS: We included 1835 mechanically ventilated COVID-19-associated ARDS, of whom 1117 (60.9%) received corticosteroids. After propensity score matching, ICU mortality did not differ between patients treated with corticosteroids and untreated patients (33.8% vs. 30.9%; p = 0.28). In survival analysis, corticosteroid treatment at ICU admission was associated with short-term survival benefit (HR 0.53; 95% CI 0.39-0.72), although beyond the 17th day of admission, this effect switched and there was an increased ICU mortality (long-term HR 1.68; 95% CI 1.16-2.45). The sensitivity analysis reinforced the results. Subgroups of age < 60 years, severe ARDS and corticosteroids plus tocilizumab could have greatest benefit from corticosteroids as short-term decreased ICU mortality without long-term negative effects were observed. Larger length of stay was observed with corticosteroids among non-survivors both in the ICU and in hospital. There were no significant differences for the remaining secondary outcomes. CONCLUSIONS: Our results suggest that corticosteroid treatment for mechanically ventilated COVID-19-associated ARDS had a biphasic time-dependent effect on ICU mortality. Specific subgroups showed clear effect on improving survival with corticosteroid use. Therefore, further research is required to identify treatment-responsive subgroups among the mechanically ventilated COVID-19-associated ARDS patients.

Mortality comparison between the first and second/third waves among 3,795 critical COVID-19 patients with pneumonia admitted to the ICU: A multicentre retrospective cohort study.

BACKGROUND: It is unclear whether the changes in critical care throughout the pandemic have improved the outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care units (ICUs). METHODS: We conducted a retrospective cohort study in adults with COVID-19 pneumonia admitted to 73 ICUs from Spain, Andorra and Ireland between February 2020 and March 2021. The first wave corresponded with the period from February 2020 to June 2020, whereas the second/third waves occurred from July 2020 to March 2021. The primary outcome was ICU mortality between study periods. Mortality predictors and differences in mortality between COVID-19 waves were identified using logistic regression. FINDINGS: As of March 2021, the participating ICUs had included 3795 COVID-19 pneumonia patients, 2479 (65·3%) and 1316 (34·7%) belonging to the first and second/third waves, respectively. Illness severity scores predicting mortality were lower in the second/third waves compared with the first wave according with the Acute Physiology and Chronic Health Evaluation system (median APACHE II score 12 [IQR 9-16] vs 14 [IQR 10-19]) and the organ failure assessment score (median SOFA 4 [3-6] vs 5 [3-7], p<0·001). The need of invasive mechanical ventilation was high (76·1%) during the whole study period. However, a significant increase in the use of high flow nasal cannula (48·7% vs 18·2%, p<0·001) was found in the second/third waves compared with the first surge. Significant changes on treatments prescribed were also observed, highlighting the remarkable increase on the use of corticosteroids to up to 95.9% in the second/third waves. A significant reduction on the use of tocilizumab was found during the study (first wave 28·9% vs second/third waves 6·2%, p<0·001), and a negligible administration of lopinavir/ritonavir, hydroxychloroquine, and interferon during the second/third waves compared with the first wave. Overall ICU mortality was 30·7% (n = 1166), without significant differences between study periods (first wave 31·7% vs second/third waves 28·8%, p = 0·06). No significant differences were found in ICU mortality between waves according to age subsets except for the subgroup of 61-75 years of age, in whom a reduced unadjusted ICU mortality was observed in the second/third waves (first 38·7% vs second/third 34·0%, p = 0·048). Non-survivors were older, with higher severity of the disease, had more comorbidities, and developed more complications. After adjusting for confounding factors through a multivariable analysis, no significant association was found between the COVID-19 waves and mortality (OR 0·81, 95% CI 0·64-1·03; p = 0·09). Ventilator-associated pneumonia rate increased significantly during the second/third waves and it was independently associated with ICU mortality (OR 1·48, 95% CI 1·19-1·85, p<0·001). Nevertheless, a significant reduction both in the ICU and hospital length of stay in survivors was observed during the second/third waves. INTERPRETATION: Despite substantial changes on supportive care and management, we did not find significant improvement on case-fatality rates among critical COVID-19 pneumonia patients. FUNDING: Ricardo Barri Casanovas Foundation (RBCF2020) and SEMICYUC.

Merging intraoral scans and CBCT: a novel technique for improving the accuracy of 3D digital models for implant-supported complete-arch fixed dental prostheses.

AIM: A technique for merging digital intraoral and CBCT scans for implant-supported complete-arch fixed dental prostheses (FDPs) is described. The aim is to improve the dimensional accuracy of intraoral scans in edentulous arches. MATERIALS AND METHOD: Two files are recorded: an intraoral scan and a CBCT scan, both obtained with scan bodies connected to the implants in the same position. The intraoral scan is then divided into several fragments and realigned, taking as reference the position of the implants recorded in the CBCT file. RESULTS: An improved intraoral digital model with corrected implant positions appropriate for complete-arch implant FDPs is generated. CONCLUSION: The methodology proposed can minimize possible intraoral scanning error and deliver more reliable digital impressions for implant-supported complete-arch FDPs.

L2-CalSat: A Calibration Satellite for Ultra-Sensitive CMB Polarization Space Missions.

In this work, the use of a calibration satellite (L2-CalSat) flying in formation with a Cosmic Microwave Background (CMB) polarization mission in an orbit located at the second Lagrange point, is proposed. The new generation of CMB telescopes are expected to reach unprecedented levels of sensitivity to allow a very precise measurement of the B-mode of polarization, the curl-like polarization component expected from gravitational waves coming from Starobinski inflationary models. Due to the CMB polarized signal weakness, the instruments must be subjected to very precise calibration processes before and after launching. Celestial sources are often used as external references for calibration after launch, but these sources are not perfectly characterized. As a baseline option, L2-CalSat is based on the CubeSat standard and serves as a perfectly known source of a reference signal to reduce polarization measurements uncertainty. A preliminary design of L2-CalSat is described and, according to the scanning strategy followed by the telescope, the influence of the relative position between the spacecrafts in the calibration process is studied. This new calibration element will have a huge impact on the performance of CMB space missions, providing a significant improvement in the measurements accuracy without requiring new and costly technological developments.

Deploying unsupervised clustering analysis to derive clinical phenotypes and risk factors associated with mortality risk in 2022 critically ill patients with COVID-19 in Spain.

BACKGROUND: The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. METHODS: Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 ICUs in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient's factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. RESULTS: The database included a total of 2022 patients (mean age 64 [IQR 5-71] years, 1423 (70.4%) male, median APACHE II score (13 [IQR 10-17]) and SOFA score (5 [IQR 3-7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A (mild) phenotype (537; 26.7%) included older age (< 65 years), fewer abnormal laboratory values and less development of complications, B (moderate) phenotype (623, 30.8%) had similar characteristics of A phenotype but were more likely to present shock. The C (severe) phenotype was the most common (857; 42.5%) and was characterized by the interplay of older age (> 65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications. CONCLUSION: The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a "one-size-fits-all" model in practice.

Preventive Efficacy of Tenofovir/Emtricitabine Against Severe Acute Respiratory Syndrome Coronavirus 2 Among Pre-Exposure Prophylaxis Users.

BACKGROUND: The preventive effect that tenofovir/emtricitabine (FTC) could have against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human immunodeficiency virus-negative people is unknown. The objective of this study was to analyze the seroprevalence and clinical manifestations of COVID-19 among users of pre-exposure prophylaxis (PrEP), disoproxil fumarate/FTC (TDF/FTC), or tenofovir alafenamide (TAF)/FTC and to compare it to that of a control group. METHODS: An observational descriptive study of the seroprevalence of antibodies for SARS-CoV-2 among men who have sex with men and transgender women without use of PrEP (Group 1; n = 250) and PrEP users with TDF/FTC (n = 409) or TAF/FTC (n = 91) (Group 2; n = 500) was conducted from May11, 2020 to June 27, 2020. All participants were provided with a structured questionnaire that collected information on the variables to be analyzed, and testing for immunoglobulin G antibodies to SARS-CoV-2 (chemiluminescent microparticle immunoassay) was then carried out. RESULTS: The seroprevalence of SARS-CoV-2 was 9.2% (95% confidence interval [CI], 5.9-13.5) in the group without PrEP and 15.0% (95% CI, 12.0-18.4) in the group with PrEP (P = .026). Among users of TDF/FTC it was 14.7% (95% CI, 11.4-18.5), and in users of TAF/FTC it was 16.5% (95% CI, 9.5-25.7) (P = .661). In those who tested positive for SARS-CoV-2 and receiving PrEP, 57.4% manifested symptoms, compared with 78.3% in the control group (P = .070). In users of TDF/FTC the figure was 53.3% and in users of TAF/FTC the figure was 73.3% (P = .100). The duration of symptoms was 11.5 days in the control group, 9.0 days in PrEP users (P = .116), 7.0 days in users of TDF/FTC, and 13.0 days in users of TAF/FTC (P = .100). CONCLUSIONS: Users of PrEP, TDF/FTC, or TAF/FTC presented a higher seroprevalence to SARS-CoV-2 than the control group. No statistically significant differences were found in relation to clinical manifestations. The PrEP users should use the same prevention measures as those indicated for the general population.

Are legume-based recipes an appropriate source of nutrients for healthy ageing? A prospective cohort study.

Although legumes are rich in protein and fibre, and low in saturated fat and Na, traditional legume-based recipes include substantial amounts of processed meat, salt and potatoes, which could counteract the potential benefits of legumes. This prospective study aimed to assess the longitudinal association of consumption of different types of legumes, and traditional legume-based recipes, with unhealthy ageing in older adults. Data were taken from 2505 individuals aged ≥60 years from the Seniors-ENRICA cohort. Habitual legume consumption was assessed in 2008-2010 with a validated diet history. Unhealthy ageing was measured in the 2013, 2015 and 2017 follow-up waves, with a fifty-two-item multidimensional health deficit accumulation index (DAI) which ranges from 0 (best) to 100 (worst health). The mean age was 68·7 years, with 53·1 % of women. Among study participants, 78·4 % reported consumption of legumes, with a mean intake of 57·9 g/d. Multivariable-adjusted linear regression models did not show an association between total legume consumption and the DAI over a 7-year follow-up (non-standardised coefficient for the second and highest v. the lowest tertile of consumption: 0·94 (95 % CI -0·30, 2·17) and 0·18 (95 % CI -1·07, 1·43), respectively; Ptrend = 0·35). Similar results were observed for the 3-year and 5-year follow-ups and, separately, for lentils, beans, chickpeas and traditional legume-based recipes. According to the results obtained, consumption of legumes and traditional legume-based recipes is not associated with unhealthy ageing and can be part of a healthy diet in old age.