Occurrence of SARS-CoV-2 viremia is associated with genetic variants of genes related to COVID-19 pathogenesis.

Introduction: SARS-CoV-2 viral load has been related to COVID-19 severity. The main aim of this study was to evaluate the relationship between SARS-CoV-2 viremia and SNPs in genes previously studied by our group as predictors of COVID-19 severity. Materials and methods: Retrospective observational study including 340 patients hospitalized for COVID-19 in the University Hospital La Princesa between March 2020 and December 2021, with at least one viremia determination. Positive viremia was considered when viral load was above the quantifiable threshold (20 copies/ml). A total of 38 SNPs were genotyped. To study their association with viremia a multivariate logistic regression was performed. Results: The mean age of the studied population was 64.5 years (SD 16.6), 60.9% patients were male and 79.4% white non-Hispanic. Only 126 patients (37.1%) had at least one positive viremia. After adjustment by confounders, the presence of the minor alleles of rs2071746 (HMOX1; T/T genotype OR 9.9 p < 0.0001), rs78958998 (probably associated with SERPING1 expression; A/T genotype OR 2.3, p = 0.04 and T/T genotype OR 12.9, p < 0.0001), and rs713400 (eQTL for TMPRSS2; C/T + T/T genotype OR 1.86, p = 0.10) were associated with higher risk of viremia, whereas the minor alleles of rs11052877 (CD69; A/G genotype OR 0.5, p = 0.04 and G/G genotype OR 0.3, p = 0.01), rs2660 (OAS1; A/G genotype OR 0.6, p = 0.08), rs896 (VIPR1; T/T genotype OR 0.4, p = 0.02) and rs33980500 (TRAF3IP2; C/T + T/T genotype OR 0.3, p = 0.01) were associated with lower risk of viremia. Conclusion: Genetic variants in HMOX1 (rs2071746), SERPING1 (rs78958998), TMPRSS2 (rs713400), CD69 (rs11052877), TRAF3IP2 (rs33980500), OAS1 (rs2660) and VIPR1 (rs896) could explain heterogeneity in SARS-CoV-2 viremia in our population.

Clinico-pathologic factors associated with the occurrence of early and late metastatic spread in a cohort of breast cancer patients.

BACKGROUND AND OBJECTIVE: Distant metastatic spread in breast cancer patients is a complex phenomenon involving several prognostic factors. We focused our analysis on early metastatic breast cancer (EMBC) (occurring during the first 36 months) versus late metastatic breast cancer (LMBC) (occurring beyond 3 years) in order to ascertain their possible differential predictive factors. METHODS: diagnostic, surgical, and follow-up data were assessed for consecutive patients with breast cancer undergoing surgery between 1997 and 2019. We analysed the predictive factors for distant metastasis using both univariate and multivariate analysis. RESULTS: The median follow-up for this cohort of 2708 patients was 89 months. The median metastasis-free interval (FMI) for metastasis patients was 38 months (17 months for EMBC group and 76 months for LMBC group). Distant metastases developed in 12.9% (350/2708); 48% (168/350) of them as EMBC and 52% (182/350) as LMBC. Loco-regional recurrence and nodal extracapsular extension were the only common predictors for both. CONCLUSIONS: EMBC and LMBC appeared as two separate conditions, with a different outcome. In the EMBC group, tumour proliferation related factors were significant (histological grade, tumour size, body mass index), whereas for LMBC, other slow-acting factors seemed to be involved (screening program, tumour burden, bilateral tumour).

Clinical characteristics, time course, and outcomes of major bleeding according to bleeding site in patients with venous thromboembolism.

BACKGROUND: Bleeding is the most dreaded complication of anticoagulant therapy for acute venous thromboembolism (VTE). Limited data exist about patient characteristics, time course and outcomes of major bleeding, according to the bleeding site. METHODS: We used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry (03/2001-07/2018) and identified patients who suffered from major bleeding during anticoagulation. We assessed patient characteristics, time course, and 30-day outcomes including mortality, re-bleeding, and VTE recurrences, according to bleeding site. RESULTS: Among 78,136 patients with VTE receiving anticoagulation, 2244 (2.9%) suffered from major bleeding (gastrointestinal in 800, intracranial in 417, hematoma in 410, genitourinary in 222, retroperitoneal in 145; other sites in 250). There were variations in baseline characteristics, including older age (P < 0.001) and predominance of women (70.2% [95% confidence interval [CI]]: 65.6-74.6% versus 50.5%, 95% CI: 48.2-52.9, P < 0.001) in patients with hematoma, compared with other patients. Overall, 82.7% of hematomas and 81.4% of retroperitoneal bleeds occurred in the first 90 days after the diagnosis of the VTE event, compared with only 50.6% of intracranial bleeds. Across the bleeding subgroups, 30-day all-cause mortality rates were highest in patients who suffered from intracranial bleeding (41.0%; 99% confidence interval [CI]: 34.8-47.4%), and lowest in patients who suffered from hematoma (17.8%; 99% CI: 13.2-23.2%). Patients who suffered from a major bleeding event in the first 30 days after VTE had significantly higher odds at 90-day follow-up to develop mortality (including from bleeding), recurrent VTE, and recurrent major bleeding (all Ps < 0.001). Variations were observed in the results according to the bleeding site. CONCLUSIONS: Major bleeding is a serious complication in VTE patients. Patient characteristics, time course and outcomes varied substantially according to the bleeding site. Additional studies are needed to tease out the impact of patient risk factors, treatment regimens, and a potential distinct effect from the site of bleeding. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02832245 (RIETE registry).

Prediction of Major Bleeding in Anticoagulated Patients for Venous Thromboembolism: Comparison of the RIETE and the VTE-BLEED Scores.

The performance of validated bleeding risk scores in patients with venous thromboembolism (VTE) could be different depending on the time after index event or the site of bleeding. In this study we compared the "classic" Registro Informatizado de Enfermedad TromboEmbólica (RIETE) score and the more recently developed VTE-BLEED score for the prediction of major bleeding in patients under anticoagulant therapy in different time intervals after VTE diagnosis. Out of 82,239 patients with acute VTE, the proportion of high-risk patients according to the RIETE and VTE-BLEED scores was 7.1 and 62.3%, respectively. The performance of both scores across the different study periods (first 30 days after VTE diagnosis, days 31-90, days 91-180, and days 181-360) was similar, with areas under the receiving operating characteristics (ROC) curve (AUC) ranging between 0.69 and 0.72. However, the positive predictive values were low, ranging between 0.6 and 3.9 (better for early major bleeding than for later periods). A sensitivity analysis limited to patients with unprovoked VTE showed comparable results. Both scores showed a trend toward a better prediction of extracranial than intracranial major bleeding, the RIETE score resulting more useful for early extracranial bleeding and the VTE-BLEED for late intracranial hemorrhages. Our study reveals that the usefulness of available bleeding scores may vary depending on the characteristics of the patient population and the time frame evaluated. Dynamic scores could be more useful for this purpose.

Clinical remission and subsequent relapse in patients with juvenile idiopathic arthritis: predictive factors according to therapeutic approach.

BACKGROUND: Juvenile idiopathic arthritis constitutes a significant cause of disability and quality of life impairment in pediatric and adult patients. The aim of this study was to ascertain clinical remission (CR) and subsequent relapse in juvenile idiopathic arthritis (JIA) patients, according to therapeutic approach and JIA subtype. Evidence in literature regarding its predictors is scarce. METHODS: We conducted an observational, ambispective study. Patients diagnosed of JIA, treated with synthetic and/or biologic disease modifying antirheumatic drugs (DMARD) were included and followed-up to December 31st, 2015. Primary outcome was clinical remission defined by Wallace criteria, both on and off medication. In order to ascertain CR according to therapeutic approach, DMARD treatments were divided in four groups: 1) synthetic DMARD (sDMARD) alone, 2) sDMARD combined with another sDMARD, 3) sDMARD combined with biologic DMARD (bDMARD), and 4) bDMARD alone. RESULTS: A total of 206 patients who received DMARD treatment were included. At the time the follow-up was completed, 70% of the patients in the cohort had attained CR at least once (144 out of 206), and 29% were in clinical remission off medication (59 out of 206). According to treatment group, CR was more frequently observed in patients treated with synthetic DMARD alone (53%). Within this group, CR was associated with female sex, oligoarticular persistent subtypes, ANA positivity, Methotrexate treatment and absence of HLA B27, comorbidities and DMARD toxicity. 124 DMARD treatments (62%) were withdrawn, 64% of which relapsed. Lower relapse rates were observed in those patients with persistent oligoarticular JIA (93%) when DMARD dose was tapered before withdrawal (77%). CONCLUSIONS: More than two thirds of JIA patients attained CR along the 9 years of follow-up, and nearly one third achieved CR off medication. Females with early JIA onset, lower active joint count and ANA positivity were the ones achieving and sustaining remission more frequently, especially when receiving synthetic DMARD alone and in the absence of HLA B27, comorbidities or previous DMARD toxicity.

Acenocoumarol Pharmacogenetic Dosing Algorithm versus Usual Care in Patients with Venous Thromboembolism: A Randomised Clinical Trial.

Patients with venous thromboembolism (VTE) require immediate treatment with anticoagulants such as acenocoumarol. This multicentre randomised clinical trial evaluated the effectiveness of a dosing pharmacogenetic algorithm versus a standard-of-care dose adjustment at the beginning of acenocoumarol treatment. We included 144 patients with VTE. On the day of recruitment, a blood sample was obtained for genotyping (CYP2C9*2, CYP2C9*3, VKORC1, CYP4F2, APOE). Dose adjustment was performed on day 3 or 4 after the start of treatment according to the assigned group and the follow-up was at 12 weeks. The principal variable was the percentage of patients with an international normalised ratio (INR) within the therapeutic range on day 7. Thirty-four (47.2%) patients had an INR within the therapeutic range at day 7 after the start of treatment in the genotype-guided group compared with 14 (21.9%) in the control group (p = 0.0023). There were no significant differences in the time to achieve a stable INR, the number of INRs within the range in the first 6 weeks and at the end of study. Our results suggest the use of a pharmacogenetic algorithm for patients with VTE could be useful in achieving target INR control in the first days of treatment.

Refinement of a modified simplified Pulmonary Embolism Severity Index for elderly patients with acute pulmonary embolism.

OBJECTIVE: To evaluate the utility of a modified (i.e., without the variable "Age >80 years") simplified Pulmonary Embolism Severity Index (sPESI) in elderly patients with acute symptomatic pulmonary embolism (PE), and to derive and validate a refined version of the sPESI for identification of elderly patients at low risk of adverse events. METHODS: The study included normotensive patients aged >80 years with acute PE enrolled in the RIETE registry. We used multivariable logistic regression analysis to create a new risk score to predict 30-day all-cause mortality. We externally validated the new risk score in elderly patients from the COMMAND VTE registry. RESULTS: Multivariable logistic regression identified four predictors for mortality: high-risk sPESI, immobilization, coexisting deep vein thrombosis (DVT), and plasma creatinine >2 mg/dL. In the RIETE derivation cohort, the new model classified fewer patients as low risk (4.0% [401/10,106]) compared to the modified sPESI (35% [3522/10,106]). Low-risk patients based on the new model had a lower 30-day mortality than those based on the modified sPESI (1.2% [95% CI, 0.4-2.9%] versus 4.7% [95% CI, 4.0-5.4%]). In the COMMAND VTE validation cohort, 1.5% (3/206) of patients were classified as having low risk of death according to the new model, and the overall 30-day mortality of this group was 0% (95% CI, 0-71%), compared to 5.9% (95% CI, 3.1-10.1%) in the high-risk group. CONCLUSIONS: For predicting short-term mortality among elderly patients with acute PE, this study suggests that the new model has a substantially higher sensitivity than the modified sPESI. A minority of these patients might benefit from safe outpatient therapy of their disease.

Influence of Visitors on the Time Budget, Ranging and Strata Use of Lowe's Monkey (Cercopithecus lowei) at Boabeng-Fiema Monkey Sanctuary, Ghana.

Wildlife tourism could be a conservation tool; however, it may disrupt the natural behaviors of wild animals. We examined how wildlife tourism affects Lowe's monkeys (Cercopithecus lowei) at the Boabeng-Fiema Monkey Sanctuary, central Ghana. We examined and compared the time budget, aggression patterns, home range size and strata use of two C. lowei groups-one with a high level of provisioning by visitors/tour guides (HP group) versus one with a low level of provisioning by visitors/tour guides (LP group). We found evidence that the HP group fed less and rested more than the LP group. The HP group significantly increased the time spent feeding and decreased their time resting, but no significant differences were recorded for moving or socializing either in the presence of small or big groups of visitors (i.e., 1-10 visitors or > 10 visitors). In the presence of one to ten visitors, the HP group monkeys increased the use of ground by 22.10% and decreased the use of medium and high tree strata by 15.43% and 11.6%, respectively. Agonistic behaviors (i.e., threat, chase, and attack) were three times higher in the HP group (e.g., open-jawed gaze gesture or head-bobbing). In the presence of visitors, aggression in the HP group increased from 12.81% to 30.18%. The home range size of the C. lowei HP group was smaller (4.68 ha) compared to the LP group (14.25 ha) (i.e., 50.56% difference). The LP group spent significantly less time socializing and more time moving. They fed more on fruits and insects. On average, the daily travel of LP group was 0.58 km more than the HP group (i.e., 22.80% difference), and the former group also spent significantly more time in the mid strata of the canopy. Our results showed that continued provisioning of the monkeys with human foods is detrimental to their natural behavior of the monkeys and could have negative long-term effects on the conservation efforts for the species.

Predicting the risk for major bleeding in elderly patients with venous thromboembolism using the Charlson index. Findings from the RIETE.

Old patients receiving anticoagulant therapy for venous thromboembolism (VTE) are at an increased risk for bleeding. We used data from the RIETE registry to assess the prognostic ability of the Comorbidity Charlson Index (CCI) to predict the risk for major bleeding in patients aged > 75 years receiving anticoagulation for VTE beyond the third month. We calculated the area under the receiver-operating characteristic curve (AUC), the category-based net reclassification index (NRI) and the net benefit (NB). We included 4303 patients with a median follow-up of 706 days (interquartile range [IQR] 462-1101). Of these, 147 (3%) developed major bleeding (27 died of bleeding). The AUC was 0.569 (95% CI 0.524-0.614). Patients with CCI ≤ 4 points were at a lower risk for adverse outcomes than those with CCI > 10 (major bleeding 0.81 (95% CI 0.53-1.19) vs. 2.21 (95% CI 1.18-3.79) per 100 patient-years; p < 0.05; all-cause death 1.9 (95% CI 1.45-2.44) vs. 15.67 (95% CI 12.63-19.22) per 100 patient-years; p < 0.05). A cut-off point of 4 points (CCI4) had a sensitivity of 82% (95% CI 75-89) and a specificity of 30% (95% CI 29-31) to predict major bleeding beyond the third month. CCI4 reclassification improved the NB of the RIETE bleeding score to predict bleeding beyond the third month (CCI4 NB 1.78% vs. RIETE NB 0.44%). Although the AUC of the CCI to predict major bleeding was modest, it could become an additional help to select patients aged > 75 years that obtain more benefit of extended anticoagulation, due to a lower risk for bleeding and better survival.

Procrastination at the Core of Physical Activity (PA) and Perceived Quality of Life: A New Approach for Counteracting Lower Levels of PA Practice.

Faced with the demonstrated need to engage in physical activity (PA), lack of time is the argument commonly used to justify low or non-existent levels of PA. Underlying this argument, the accomplishment of procrastination behaviour seems to be related to the less time dedicated to practicing PA and the low perception of the quality of life. With this in mind, the purpose of this study is to show that dedicating different amounts of time to PA affects the perceived quality of life and the widespread problem of procrastination. We hypothesise that greater time investment in PA is related to greater perceived quality of life and less procrastination. In all, 621 practitioners of PA (347 men, 274 women) between 18 and 83 years old (M = 35.43, SD = 14.45) filled out validated versions of the World Health Organization quality of life assessment (WHOQOL-BREF) and the Pure Procrastination Scale. Results showed that people who do enough PA have a more positive perception of the quality of life in the domains of physical and psychological health; this perception, in turn, is related to lower levels of procrastination. Likewise, socio-demographic characteristics such as gender and the main activity presented significant associations with various quality of life domains and procrastination. In sum, the benefits of improvements in quality of life and reductions in procrastination identified in this study are sensitive to the time spent on PA, which suggests that a strategy to promote the practice of PA would improve time management and, thus, counteract procrastination.

Malignant Solitary Fibrous Tumour of the Breast Mimicking a Benign Tumor.

Solitary fibrous tumour (SFT) of the breast is exceedingly uncommon. Radiological assessment usually shows benign features. We report on a case of malignant SFT of the breast, while emphasizing the need for additional immunostains to reach a definitive diagnosis. Standard treatment consists of lesion removal with adequate margins.

Prostate cancer screening: guidelines review and laboratory issues.

Background Prostate-specific antigen (PSA) remains as the most used biomarker in the detection of early prostate cancer (PCa). Clinical practice guidelines (CPGs) are produced to facilitate incorporation of evidence into clinical practice. This is particularly useful when PCa screening remains controversial and guidelines diverge among different medical institutions, although opportunistic screening is not recommended. Methods We performed a systematic review of guidelines about PCa screening using PSA. Guidelines published since 2008 were included in this study. The most updated version of these CPGs was used for the evaluation. Results Twenty-two guidelines were selected for review. In 59% of these guidelines, recommendations were graded according to level of evidence (n = 13), but only 18% of the guidelines provided clear algorithms (n = 4). Each CPG was assessed using a checklist of laboratory issues, including pre-analytical, analytical, and post-analytical factors. We found that laboratory medicine specialists participate in 9% of the guidelines reviewed (n = 2) and laboratory issues were frequently omitted. We remarked that information concerning the consequences of World Health Organization (WHO) standard in PSA testing was considered by only two of 22 CPGs evaluated in this study. Conclusions We concluded that the quality of PCa early detection guidelines could be improved properly considering the laboratory issues in their development.

Profesionalismo y mindfulness: beneficios de la terapia cognitiva / Professionalism and mindfulness: Benefits of cognitive therapy

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The Prescription of Mobile Apps by Primary Care Teams: A Pilot Project in Catalonia.

BACKGROUND: In Catalonia, the Fundació TIC Salut Social's mHealth Office created the AppSalut Site to showcase to mobile apps in the field of health and social services. Its primary objective was to encourage the public to look after their health. The catalogue allows primary health care doctors to prescribe certified, connected apps, which guarantees a safe and reliable environment for their use. The generated data can be consulted by health care professionals and included in the patient's clinical history. This document presents the intervention and the major findings following a five-month pilot project conducted in the Barcelona area. OBJECTIVE: The objective of the pilot study was to test, in a real, controlled environment, the implementation of AppSalut. Specifically, we tested whether (1) the procedures corresponding to the prescription, transmission, and evaluation of the data functions correctly, (2) users interact successfully and accept the tool, and (3) the data travels through existing pathways in accordance with international standards. The evaluation is not based on clinical criteria, but rather on the usability and technological reliability of the intervention and its implementation in the context of primary care. METHODS: The project was presented to the Primary Care Team participants to encourage the involvement of doctors. The study involved at least 5 doctors and 5 patients per professional, chosen at their discretion and in accordance with their own clinical criteria. An initial consultation took place, during which the doctor discussed the pilot project with the patient and recommended the app. The patient was sent a text message (SMS, short message service) containing an access code. When the patient arrived home, they accessed their personal health record (PHR) to view the recommendation, download the app, and enter the access code. The patient was then able to start using the app. The data was collected in a standardized manner and automatically sent to the system. In a second visit, the patient looked at the data with their doctor on their clinical station screen. The latter was able to consult the information generated by the patient and select what to include in their electronic health record. In order to assess the performance of the system, three focus groups were performed and two ad-hoc case-specific questionnaires, one for doctors and one for patients, were sent by email. Response was voluntary. RESULTS: A total of 32 doctors made 79 recommendations of apps to patients. On average, the patients uploaded data 13 times per prescribed app, accounting for a total of 16 different variables. Results show that data traveled through the established channels in an adequate manner and in accordance with international standards. This includes the prescription of an app by a doctor, the patient accessing the recommendation via the PHR, app download by the patient from the official app stores, linking of the patient to the public platform through the app, the generation and visualization of the data on the primary care workstation, and its subsequent validation by the clinician. CONCLUSIONS: First, the choice of apps to be used is fundamental; the user's perception of the utility of the proposed tool being paramount. Second, thorough face-to-face support is vital for a smooth transition towards a more intense model of telemedicine. Last, a powerful limiting factor is the lack of control over people's ability to use the apps.

Estandarización ortográfica. Respuesta / Ortographic standarization. Answer

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