Extraction of bioactive compounds from pecan nutshell: An added-value and low-cost alternative for an industrial waste.

The pecan nutshell [Carya illinoinensis (Wangenh) C. Koch] (PNS) is a source of bioactives with important beneficial properties for the human health. PNS represents between 40-50 % of total mass of the nut, resulting as waste without any added value for the food industry. Even though a variety of methods were already developed for bioactive extraction from this waste, unconventional methodologies, or those which apart from green chemistry principles, were discarded considering the cost of production, the sustainable development goals of United Nations and the feasibility of real inclusion of the technology in the food chain. Then, to add-value to this waste, a low-cost, green and easy-scalable extraction methodology was developed based on the determination of seven relevant factors by means of a factorial design and a Response Surface Methodology, allowing the extraction of bioactives with antioxidant capacity. The pecan nutshell extract had a high concentration of phenolic compounds (166 mg gallic acid equivalents-GAE/g dry weight-dw), flavonoids (90 mg catechin equivalent-CE/g dw) and condensed tannins (189 mg CE/g dw) -related also to the polymeric color (74.6 %)-, with high antioxidant capacities of ABTS+. radical inhibition (3665 µmol Trolox Equivalent-TE/g dw) and of iron reduction (1305 µmol TE/g dw). Several compounds associated with these determinations were identified by HPLC-ESI-MS/MS, such as [Epi]catechin-[Epi]catechin-[Epi]gallocatechin, myricetin, dihydroquercetins, dimers A and B of protoanthocyanidins, ellagitannins and ellagic acid derivatives. Hence, through the methodology developed here, we obtained a phenolic rich extract with possible benefits for human health, and of high industrial scalability for this co-product transformation.

Quality of life in chordoma survivors: results from the Chordoma Foundation Survivorship Survey.

OBJECTIVE: Chordomas are rare malignant bone tumors whose location in the skull base or spine, invasive surgical treatment, and accompanying adjuvant radiotherapy may all lead patients to experience poor quality of life (QOL). Limited research has been conducted on specific demographic and clinical factors associated with decreased QOL in chordoma survivors. Thus, the aim of the present study was to investigate several potential variables and their impact on specific QOL domains in these patients as well the frequencies of specific QOL challenges within these domains. METHODS: The Chordoma Foundation (CF) Survivorship Survey was electronically distributed to chordoma survivors subscribed to the CF Chordoma Connections forum. Survey questions assessed QOL in three domains: physical, emotional/cognitive, and social. The degree of impairment was assessed by grouping the participants into high- and low-challenge groups designated by having ≥ 5 or < 5 symptoms or challenges within a given QOL domain. Bivariate analysis of demographic and clinical characteristics between these groups was conducted using Fisher's exact test and the Mann-Whitney U-test. RESULTS: A total of 665 chordoma survivors at least partially completed the survey. On bivariate analysis, female sex was significantly associated with increased odds of significant emotional (p = 0.001) and social (p = 0.019) QOL burden. Younger survivors (age < 65 years) were significantly more likely to experience significant physical (p < 0.0001), emotional (p < 0.0001), and social (p < 0.0001) QOL burden. Skull base chordoma survivors had significantly higher emotional/cognitive QOL burden than spinal chordoma survivors (p = 0.022), while the converse was true for social QOL challenges (p = 0.0048). Survivors currently in treatment were significantly more likely to experience significant physical QOL challenges compared with survivors who completed their treatment > 10 years ago (p = 0.0074). Fear of cancer recurrence (FCR) was the most commonly reported emotional/cognitive QOL challenge (49.6%). Only 41% of the participants reported having their needs met for their physical QOL challenges as well as 25% for emotional/cognitive and 18% for social. CONCLUSIONS: The authors' findings suggest that younger survivors, female survivors, and survivors currently undergoing treatment for chordoma are at high risk for adverse QOL outcomes. Additionally, although nearly half of the participants reported a FCR, very few reported having adequate emotional/cognitive care. These findings may be useful in identifying specific groups of chordoma survivors vulnerable to QOL challenges and bring to light the need to expand care to meet the QOL needs for these patients.

Incidence of Diabetes Mellitus and Associated Factors in the Era of Antiretroviral Drugs With a Low Metabolic Toxicity Profile.

Objective: The incidence of type 2 diabetes mellitus (T2DM) has risen dramatically. Among people living with HIV (PLHIV), chronic disease (now >15 cases/1000 in the general population worldwide) and long-term exposure to antiretroviral therapy (ART) can alter metabolic processes early, favoring insulin resistance and T2DM. We retrospectively studied the incidence of T2DM and associated factors in the Cohort of the Spanish AIDS Research Network, a prospective cohort of PLHIV enrolled at diagnosis and before initiation of ART. Methods: PLHIV were aged >18 years and ART naive at inclusion. The incidence of new diagnoses of T2DM after initiation of ART (per 1000 person-years) was calculated. Predictors of a diagnosis of T2DM were identified by a Cox proportional hazards model adjusted for statistically significant and clinically relevant variables. Results: Cumulative incidence was 5.9 (95% CI, 5.1-6.7) per 1000 person-years, increasing significantly in persons aged >50 years to 14.4 (95% CI, 10.4-19.3). Median time to diagnosis of T2DM was 27 months. Only age and higher education were significant. Interestingly, higher education was associated with a 33% reduction in the incidence of T2DM. Having received tenofovir disoproxil fumarate + (lamivudine or emtricitabine) + rilpivirine was almost significant as a protective factor (hazard ratio, 0.49; 95% CI, .24-1.01; P = .05). Conclusions: The incidence of T2DM in PLHIV in Spain was high, especially in persons aged >50 years. Age was the factor most closely associated with onset, and educational level was the factor most associated with reduced risk. We highlight the lack of association between HIV-related factors and T2DM and show that, within nonnucleoside reverse transcriptase inhibitors, rilpivirine could prove more benign for metabolic comorbidities.

Chronological pattern of venous thromboembolism (VTE) occurrence impacts in survival of pancreatic ductal adenocarcinoma (PDAC).

BACKGROUND: Limited data exist on the prognostic significance of the chronology of VTE in patients with PDAC. METHODS: Medical data and survival characteristics of patients treated for PDAC from 2019 to 2021 were retrospectively reviewed. Early VTE was defined as occurring within the three months of PDAC diagnosis. RESULTS: 197 patients were included, 54 (27.4%) developed a VTE. Early appearance of VTE was associated with worse prognosis: median overall survival (mOS) VTE < 3 months 8.5 months (HR 1.65, 95% CI 1.11-2.46; p = 0.014), mOS VTE > 3 months 12.8 months (HR 0.78, 95% CI 0.39-1.54; p = 0.5) and mOS patients without VTE 11.4 months (95% CI 10.1-15.4). There was no significant association between the patient's VTE risk according to the Khorana risk score (KRS) (chi2 test p-value = 0.9). CONCLUSION: Early VTE is a prognostic factor in PDAC, which may identify a more aggressive subtype.

Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics.

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

Breast cancer risk for the joint exposure to metals and metalloids in women: Results from the EPIC-Spain cohort.

Environmental factors play a role in breast cancer development. While metals and metalloids (MMs) include some carcinogens, their association with breast cancer depends on the element studied. Most studies focus on individual MMs, but the combined effects of metal mixtures remain unclear. The aim of this study was to analyze the relationship between the joint exposure to MMs and the risk of developing female breast cancer. We conducted a case-control study within the multicenter prospective EPIC-Spain cohort. Study population comprised 292 incident cases and 286 controls. Plasma concentrations of 16 MMs were quantified at recruitment. Potential confounders were collected using a questionnaire and anthropometric measurements. Mixed-effects logistic regression models were built to explore the effect of individual MMs. Quantile-based g computation models were applied to identify the main mixture components and to estimate the joint effect of the metal mixture. The geometric means were highest for Cu (845.6 ng/ml) and Zn (604.8 ng/ml). Cases had significantly higher Cu concentrations (p = 0.010) and significantly lower Zn concentrations (p < 0.001). Cu (+0.42) and Mn (+0.13) showed the highest positive weights, whereas Zn (-0.61) and W (-0.16) showed the highest negative weights. The joint effect of the metal mixture was estimated at an OR = 4.51 (95%CI = 2.32-8.79), suggesting a dose-response relationship. No evidence of non-linearity or non-additivity was found. An unfavorable exposure profile, primarily characterized by high Cu and low Zn levels, could lead to a significant increase in the risk of developing female breast cancer. Further studies are warranted to confirm these findings.

Energy-Efficient Ingestible Drug Delivery System in the Dynamic Gastrointestinal Environment.

Ingestible electronics are promising platforms for on-demand health monitoring and drug delivery. However, these devices and their actuators must operate in the gastrointestinal (GI) environment, which has a pH range of 1 to 8. Drug delivery systems using electrochemical dissolution of metal films are particularly susceptible to pH changes. Optimal operation in this dynamic environment stands to transform our capacity to help patients across a range of conditions. Here we present an energy-efficient ingestible electronic electrochemical drug delivery system to support subjects through operation in this dynamic environment. The proposed system consists of a drug reservoir sealed with an electrochemically dissolvable gold membrane and an electronic subsystem. An electronic subsystem controls the rate of gold dissolution by sensing and adapting to the pH of the GI environment and provides an option for energy-efficient drug delivery, reducing energy consumption by up to 42.8 %. Integrating the electronics with electrochemical drug delivery enables the proposed system to adapt to the dynamic physiological environments which makes it suitable for drug and/or therapeutic delivery at different locations in the GI tract.

Can OpenEHR, ISO 13606, and HL7 FHIR Work Together? An Agnostic Approach for the Selection and Application of Electronic Health Record Standards to the Next-Generation Health Data Spaces.

In order to maximize the value of electronic health records (EHRs) for both health care and secondary use, it is necessary for the data to be interoperable and reusable without loss of the original meaning and context, in accordance with the findable, accessible, interoperable, and reusable (FAIR) principles. To achieve this, it is essential for health data platforms to incorporate standards that facilitate addressing needs such as formal modeling of clinical knowledge (health domain concepts) as well as the harmonized persistence, query, and exchange of data across different information systems and organizations. However, the selection of these specifications has not been consistent across the different health data initiatives, often applying standards to address needs for which they were not originally designed. This issue is essential in the current scenario of implementing the European Health Data Space, which advocates harmonization, interoperability, and reuse of data without regulating the specific standards to be applied for this purpose. Therefore, this viewpoint aims to establish a coherent, agnostic, and homogeneous framework for the use of the most impactful EHR standards in the new-generation health data spaces: OpenEHR, International Organization for Standardization (ISO) 13606, and Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR). Thus, a panel of EHR standards experts has discussed several critical points to reach a consensus that will serve decision-making teams in health data platform projects who may not be experts in these EHR standards. It was concluded that these specifications possess different capabilities related to modeling, flexibility, and implementation resources. Because of this, in the design of future data platforms, these standards must be applied based on the specific needs they were designed for, being likewise fully compatible with their combined functional and technical implementation.

A Retrospective Analysis of High Resolution Ultrasound Evaluation of the "Split Fat Sign" in Peripheral Nerve Sheath Tumors.

Peripheral nerve sheath tumors (PNST) comprise schwannomas and neurofibromas. The finding of increased adipose tissue around benign PNSTs has been described as the "split fat sign" on magnetic resonance imaging exams, which is suggestive of an intramuscular or intermuscular location of the tumor. However, few studies have described this sign as a salient ultrasound feature of PNSTs. The main purpose of this study was to retrospectively evaluate the presence of increased fatty tissue deposition around benign PNSTs diagnosed by high-resolution ultrasound. In addition, we aimed to corroborate the presence of vascularization around the affected area. A retrospective analysis of ten cases of PNSTs and two cases of post-traumatic neuromas diagnosed by high-resolution ultrasound was performed with a Logiq® P8 ultrasound with a 2-11 MHz multifrequency linear probe L3-12-D (central frequency: 10 MHz). Localized types of neurofibromas and schwannomas in any location were seen as predominantly hypoechoic tumors with an oval or fusiform shape. Exiting and entering nerves (tail sign) were observed in six cases, showing localized lesions both in intermuscular and subcutaneous locations. The presence of increased hyperechoic tissue (the split fat sign) was noted in cases of solitary intermuscular and intramuscular peripheral nerve sheath tumors, mainly the schwannomas. Though small tumors did not demonstrate the tail sign, the increase in adipose tissue and vascularity on US was well demonstrated. In conclusion, the nerve in continuity forms the basis of the ultrasonographic diagnosis of PNSTs. However, high-resolution US can convincingly demonstrate the increased presence of fat in the upper and lower poles as well as circumferentially in intermuscular or intramuscular benign PNSTs.

Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortium.

Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES -1.18 years [95% CI -2.05, -0.32]), had fewer respiratory symptoms (RD -0.15 [95% CI -0.33, -0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD -0.35 [95% CI -0.64, -0.07]), lower lymphocyte count (ES -0.16 × 109/uL [95% CI -0.30, -0.01]), lower C-reactive protein (ES -28.5 mg/L [95% CI -46.3, -10.7]), and lower troponin (ES -0.14 ng/mL [95% CI -0.26, -0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES -1.6 years [95% CI -2.5, -0.8]), had less frequent SIRS (RD -0.18 [95% CI -0.30, -0.05]), lower lymphocyte count (ES -0.39 × 109/uL [95% CI -0.52, -0.25]), lower troponin (ES -0.16 ng/mL [95% CI -0.30, -0.01]) and less frequently received anticoagulation therapy (RD -0.19 [95% CI -0.37, -0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (-1.3 days [95% CI -2.3, -0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None.

Development and validation of COEWS (COVID-19 Early Warning Score) for hospitalized COVID-19 with laboratory features: A multicontinental retrospective study.

Background: The emergence of new SARS-CoV-2 variants with significant immune-evasiveness, the relaxation of measures for reducing the number of infections, the waning of immune protection (particularly in high-risk population groups), and the low uptake of new vaccine boosters, forecast new waves of hospitalizations and admission to intensive care units. There is an urgent need for easily implementable and clinically effective Early Warning Scores (EWSs) that can predict the risk of complications within the next 24-48 hr. Although EWSs have been used in the evaluation of COVID-19 patients, there are several clinical limitations to their use. Moreover, no models have been tested on geographically distinct populations or population groups with varying levels of immune protection. Methods: We developed and validated COVID-19 Early Warning Score (COEWS), an EWS that is automatically calculated solely from laboratory parameters that are widely available and affordable. We benchmarked COEWS against the widely used NEWS2. We also evaluated the predictive performance of vaccinated and unvaccinated patients. Results: The variables of the COEWS predictive model were selected based on their predictive coefficients and on the wide availability of these laboratory variables. The final model included complete blood count, blood glucose, and oxygen saturation features. To make COEWS more actionable in real clinical situations, we transformed the predictive coefficients of the COEWS model into individual scores for each selected feature. The global score serves as an easy-to-calculate measure indicating the risk of a patient developing the combined outcome of mechanical ventilation or death within the next 48 hr.The discrimination in the external validation cohort was 0.743 (95% confidence interval [CI]: 0.703-0.784) for the COEWS score performed with coefficients and 0.700 (95% CI: 0.654-0.745) for the COEWS performed with scores. The area under the receiver operating characteristic curve (AUROC) was similar in vaccinated and unvaccinated patients. Additionally, we observed that the AUROC of the NEWS2 was 0.677 (95% CI: 0.601-0.752) in vaccinated patients and 0.648 (95% CI: 0.608-0.689) in unvaccinated patients. Conclusions: The COEWS score predicts death or MV within the next 48 hr based on routine and widely available laboratory measurements. The extensive external validation, its high performance, its ease of use, and its positive benchmark in comparison with the widely used NEWS2 position COEWS as a new reference tool for assisting clinical decisions and improving patient care in the upcoming pandemic waves. Funding: University of Vienna.

Effectiveness of adding pain neuroscience education to telerehabilitation in patients with carpal tunnel syndrome: A randomized controlled trial.

BACKGROUND: Previous studies have shown positive results of pain neuroscience education (PNE) combined with exercise in patients with chronic musculoskeletal disorders. However, the effects of this intervention in patients with carpal tunnel syndrome (CTS) admitted to a telerehabilitation program remain unexplored. OBJECTIVE: To compare the effectiveness of a 6-week telerehabilitation program based on PNE + exercise versus exercise alone on patient-reported outcomes after treatment and at 6-weeks post-treatment follow-up in patients with CTS awaiting surgery. DESIGN: Randomized controlled trial. METHODS: Thirty participants were randomly assigned to the PNE + exercise or exercise-only group. Outcome measures included pain intensity, pain catastrophizing, kinesiophobia, symptom severity, function, symptoms of anxiety and depression, quality of life, self-perception of improvement. Inferential analyses of the data were performed using a two-factor mixed analysis of variance. RESULTS: Twenty-five participants completed the study. A significant time × group interaction with a large effect size was observed for kinesiophobia (F = 6.67, p = 0.005, ηp2 = 0.225) and symptom severity (F = 4.82, p = 0.013, ηp2 = 0.173). No significant interaction was observed for the other variables (p > 0.05). A significant difference in self-perceived improvement was observed in favor of the PNE + exercise group after treatment (p < 0.05). Although there were significant and clinically relevant improvements within the PNE + exercise group in pain intensity and catastrophizing, there were no significant differences between the groups. CONCLUSIONS: The addition of PNE to a telerehabilitation exercise program showed short-term improvements in kinesiophobia and symptom severity and greater self-perceived improvement in patients with CTS awaiting surgery. This study highlighted the benefits of including PNE in telerehabilitation interventions for patients with CTS.

Intracranial Gliosarcoma: A National Cancer Database Survey of Clinical Predictors for Overall Survival.

OBJECTIVE: Gliosarcoma (GSM) is a variant of glioblastoma, 1 of the most common and aggressive primary brain tumors in adults. Our study seeks to analyze a large cohort of patients with GSM in the National Cancer Database (NCDB) to elucidate clinical predictors of overall survival (OS). METHODS: Data was collected on patients diagnosed with histologically-confirmed GSM using the NCDB (2004-2016). OS was determined via univariate Kaplan-Meier analysis. Bivariate and multivariate Cox proportional-hazards analyses were also utilized. RESULTS: Our cohort of 1015 patients had a median age at diagnosis of 61 years. Six hundred thirty-one (62.2%) were male, 896 (89.0%) were Caucasian, and 698 (68.8%) lacked any comorbidities. Median OS was 11.5 months. Regarding treatment, 264 (26.5%) patients underwent surgery (S) only (OS = 5.19 months), 61 (6.1%) underwent surgery and radiotherapy (S + RT) (OS = 6.87 months), 20 (2.0%) underwent surgery and chemotherapy (S + CT); (OS = 15.51 months), and 653 (65.4%) underwent S + CT + RT (triple) combination therapy (OS = 13.8 months). Notably, on bivariate analysis, S + CT (Hazard ratio [HR] = 0.59, P-value = 0.04) and triple therapy (HR = 0.57, P < 0.01) were associated with increased OS. S + RT was not significantly associated with OS. Similarly, on multivariate Cox proportional-hazards analyses, gross total resection (HR = 0.76, P = 0.02), S + CT (HR = 0.46, P < 0.01), and triple therapy (HR = 0.52, P < 0.01) predicted significantly increased OS. Furthermore, age >60 years old (HR = 1.03, P < 0.01) and the presence of comorbidities (HR = 1.43, P < 0.01) predicted significantly decreased OS. CONCLUSIONS: Despite maximal multimodal treatment, GSMs have poor median OS. NCDB data suggest age, comorbidities, extent of resection, and adjuvant treatment each minimally delays poor outcomes.

An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean.

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region's continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the "need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics". Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%-99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.

COVID-19 vaccines reduce mortality in hospitalized patients with oxygen requirements: Differences between vaccine subtypes. A multicontinental cohort study.

The aim of this study was to analyze whether the coronavirus disease 2019 (COVID-19) vaccine reduces mortality in patients with moderate or severe COVID-19 disease requiring oxygen therapy. A retrospective cohort study, with data from 148 hospitals in both Spain (111 hospitals) and Argentina (37 hospitals), was conducted. We evaluated hospitalized patients for COVID-19 older than 18 years with oxygen requirements. Vaccine protection against death was assessed through a multivariable logistic regression and propensity score matching. We also performed a subgroup analysis according to vaccine type. The adjusted model was used to determine the population attributable risk. Between January 2020 and May 2022, we evaluated 21,479 COVID-19 hospitalized patients with oxygen requirements. Of these, 338 (1.5%) patients received a single dose of the COVID-19 vaccine and 379 (1.8%) were fully vaccinated. In vaccinated patients, mortality was 20.9% (95% confidence interval [CI]: 17.9-24), compared to 19.5% (95% CI: 19-20) in unvaccinated patients, resulting in a crude odds ratio (OR) of 1.07 (95% CI: 0.89-1.29; p = 0.41). However, after considering the multiple comorbidities in the vaccinated group, the adjusted OR was 0.73 (95% CI: 0.56-0.95; p = 0.02) with a population attributable risk reduction of 4.3% (95% CI: 1-5). The higher risk reduction for mortality was with messenger RNA (mRNA) BNT162b2 (Pfizer) (OR 0.37; 95% CI: 0.23-0.59; p < 0.01), ChAdOx1 nCoV-19 (AstraZeneca) (OR 0.42; 95% CI: 0.20-0.86; p = 0.02), and mRNA-1273 (Moderna) (OR 0.68; 95% CI: 0.41-1.12; p = 0.13), and lower with Gam-COVID-Vac (Sputnik) (OR 0.93; 95% CI: 0.6-1.45; p = 0.76). COVID-19 vaccines significantly reduce the probability of death in patients suffering from a moderate or severe disease (oxygen therapy).

Contextualising adverse events of special interest to characterise the baseline incidence rates in 24 million patients with COVID-19 across 26 databases: a multinational retrospective cohort study.

Background: Adverse events of special interest (AESIs) were pre-specified to be monitored for the COVID-19 vaccines. Some AESIs are not only associated with the vaccines, but with COVID-19. Our aim was to characterise the incidence rates of AESIs following SARS-CoV-2 infection in patients and compare these to historical rates in the general population. Methods: A multi-national cohort study with data from primary care, electronic health records, and insurance claims mapped to a common data model. This study's evidence was collected between Jan 1, 2017 and the conclusion of each database (which ranged from Jul 2020 to May 2022). The 16 pre-specified prevalent AESIs were: acute myocardial infarction, anaphylaxis, appendicitis, Bell's palsy, deep vein thrombosis, disseminated intravascular coagulation, encephalomyelitis, Guillain- Barré syndrome, haemorrhagic stroke, non-haemorrhagic stroke, immune thrombocytopenia, myocarditis/pericarditis, narcolepsy, pulmonary embolism, transverse myelitis, and thrombosis with thrombocytopenia. Age-sex standardised incidence rate ratios (SIR) were estimated to compare post-COVID-19 to pre-pandemic rates in each of the databases. Findings: Substantial heterogeneity by age was seen for AESI rates, with some clearly increasing with age but others following the opposite trend. Similarly, differences were also observed across databases for same health outcome and age-sex strata. All studied AESIs appeared consistently more common in the post-COVID-19 compared to the historical cohorts, with related meta-analytic SIRs ranging from 1.32 (1.05 to 1.66) for narcolepsy to 11.70 (10.10 to 13.70) for pulmonary embolism. Interpretation: Our findings suggest all AESIs are more common after COVID-19 than in the general population. Thromboembolic events were particularly common, and over 10-fold more so. More research is needed to contextualise post-COVID-19 complications in the longer term. Funding: None.

Healthcare outcomes in patients with HIV infection at a tertiary hospital during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has affected the care of patients with other diseases. Difficulty in access to healthcare during these months has been especially relevant for persons with HIV infection (PWH). This study therefore sought to ascertain the clinical outcomes and effectiveness of the measures implemented among PWH in a region with one of the highest incidence rates in Europe. METHODS: Retrospective, observational, pre-post intervention study to compare the outcomes of PWH attended at a high-complexity healthcare hospital from March to October 2020 and during the same months across the period 2016-2019. The intervention consisted of home drug deliveries and preferential use of non face-to-face consultations. The effectiveness of the measures implemented was determined by reference to the number of emergency visits, hospitalisations, mortality rate, and percentage of PWH with viral load >50copies, before and after the two pandemic waves. RESULTS: A total of 2760 PWH were attended from January 2016 to October 2020. During the pandemic, there was a monthly mean of 106.87 telephone consultations and 2075 home deliveries of medical drugs dispensed to ambulatory patients. No statistically significant differences were found between the rate of admission of patients with COVID-HIV co-infection and that of the remaining patients (1172.76 admissions/100,000 population vs. 1424.29, p=0.401) or in mortality (11.54% vs. 12.96%, p=0.939). The percentage of PWH with viral load >50copies was similar before and after the pandemic (1.20% pre-pandemic vs. 0.51% in 2020, p=0.078). CONCLUSION: Our results show that the strategies implemented during the first 8 months of the pandemic prevented any deterioration in the control and follow-up parameters routinely used on PWH. Furthermore, they contribute to the debate about how telemedicine and telepharmacy can fit into future healthcare models.

An Ontology-Based Approach for Consolidating Patient Data Standardized With European Norm/International Organization for Standardization 13606 (EN/ISO 13606) Into Joint Observational Medical Outcomes Partnership (OMOP) Repositories: Description of a Methodology.

BACKGROUND: To discover new knowledge from data, they must be correct and in a consistent format. OntoCR, a clinical repository developed at Hospital Clínic de Barcelona, uses ontologies to represent clinical knowledge and map locally defined variables to health information standards and common data models. OBJECTIVE: The aim of the study is to design and implement a scalable methodology based on the dual-model paradigm and the use of ontologies to consolidate clinical data from different organizations in a standardized repository for research purposes without loss of meaning. METHODS: First, the relevant clinical variables are defined, and the corresponding European Norm/International Organization for Standardization (EN/ISO) 13606 archetypes are created. Data sources are then identified, and an extract, transform, and load process is carried out. Once the final data set is obtained, the data are transformed to create EN/ISO 13606-normalized electronic health record (EHR) extracts. Afterward, ontologies that represent archetyped concepts and map them to EN/ISO 13606 and Observational Medical Outcomes Partnership Common Data Model (OMOP CDM) standards are created and uploaded to OntoCR. Data stored in the extracts are inserted into its corresponding place in the ontology, thus obtaining instantiated patient data in the ontology-based repository. Finally, data can be extracted via SPARQL queries as OMOP CDM-compliant tables. RESULTS: Using this methodology, EN/ISO 13606-standardized archetypes that allow for the reuse of clinical information were created, and the knowledge representation of our clinical repository by modeling and mapping ontologies was extended. Furthermore, EN/ISO 13606-compliant EHR extracts of patients (6803), episodes (13,938), diagnosis (190,878), administered medication (222,225), cumulative drug dose (222,225), prescribed medication (351,247), movements between units (47,817), clinical observations (6,736,745), laboratory observations (3,392,873), limitation of life-sustaining treatment (1,298), and procedures (19,861) were created. Since the creation of the application that inserts data from extracts into the ontologies is not yet finished, the queries were tested and the methodology was validated by importing data from a random subset of patients into the ontologies using a locally developed Protégé plugin ("OntoLoad"). In total, 10 OMOP CDM-compliant tables ("Condition_occurrence," 864 records; "Death," 110; "Device_exposure," 56; "Drug_exposure," 5609; "Measurement," 2091; "Observation," 195; "Observation_period," 897; "Person," 922; "Visit_detail," 772; and "Visit_occurrence," 971) were successfully created and populated. CONCLUSIONS: This study proposes a methodology for standardizing clinical data, thus allowing its reuse without any changes in the meaning of the modeled concepts. Although this paper focuses on health research, our methodology suggests that the data be initially standardized per EN/ISO 13606 to obtain EHR extracts with a high level of granularity that can be used for any purpose. Ontologies constitute a valuable approach for knowledge representation and standardization of health information in a standard-agnostic manner. With the proposed methodology, institutions can go from local raw data to standardized, semantically interoperable EN/ISO 13606 and OMOP repositories.

Quality of Life in Chordoma Co-Survivors: Results from the Chordoma Foundation Survivorship Survey.

BACKGROUND: Chordomas are a rare form of aggressive bone cancer and are associated with poor quality of life (QOL). The present study sought to characterize demographic and clinical characteristics associated with QOL in chordoma co-survivors (caregivers of patients with chordoma) and assess whether co-survivors access care for QOL challenges. METHODS: The Chordoma Foundation Survivorship Survey was electronically distributed to chordoma co-survivors. Survey questions assessed emotional/cognitive and social QOL, with significant QOL challenges being defined as experiencing ≥5 challenges within either of these domains. The Fisher exact test and Mann-Whitney U test were used to analyze bivariate associations between patient/caretaker characteristics and QOL challenges. RESULTS: Among the 229 respondents to our survey, nearly half (48.5%) reported a high number (≥5) of emotional/cognitive QOL challenges. Co-survivors younger than 65 years were significantly more likely to experience a high number of emotional/cognitive QOL challenges (P < 0.0001), whereas co-survivors >10 years past the end of treatment were significantly less likely to experience a high number of emotional/cognitive QOL challenges (P = 0.012). When asked about access to resources, a lack of knowledge of resources to address their emotional/cognitive and social QOL issues (34% and 35%, respectively) was the most common response. CONCLUSIONS: Our findings suggest that younger co-survivors are at high risk for adverse emotional QOL outcomes. In addition, more than one third of co-survivors did not know about resources to address their QOL issues. Our study may help guide organizational efforts to provide care and support to patients with chordoma and their loved ones.

Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19.

BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.