Clinical complications after a traumatic brain injury and its relation with brain biomarkers.

We aimed to find out which are the most frequent complications for patients who suffer a traumatic brain injury (TBI) and its relation with brain biomarker levels. We conducted a hospital cohort study with patients who attended the Hospital Emergency Department between 1 June 2018 and 31 December 2020. Different variables were collected such as biomarkers levels after 6 h and 12 h of TBI (S100, NSE, UCHL1 and GFAP), clinical and sociodemographic variables, complementary tests, and complications 48 h and 7 days after TBI. Qualitative variables were analysed with Pearson's chi-square test, and quantitative variables with the Mann-Whitney U test. A multivariate logistic regression model for the existence of complications one week after discharge was performed to assess the discriminatory capacity of the clinical variables. A total of 51 controls and 540 patients were included in this study. In the TBI group, the mean age was 83 years, and 53.9% of the patients were male. Complications at seven days were associated with the severity of TBI (p < 0.05) and the number of platelets (p = 0.016). All biomarkers except GFAP showed significant differences in their distribution of values according to gender, with significantly higher values of the three biomarkers for women with respect to men. Patients with complications presented significantly higher S100 values (p < 0.05). The patient's baseline status, the severity of the TBI and the S100 levels can be very important elements in determining whether a patient may develop complications in the few hours after TBI.

Platelet levels and age are determinants of survival after mild-moderate TBI: A prospective study in Spain.

Introduction: Traumatic brain injury (TBI) is a very important reason for consultation in emergency departments. Methods: A hospital cohort study with patients who attended a hospital emergency department between June 1, 2018 and December 31, 2020 due to TBI was studied. Clinical and sociodemographic variables were recorded. The levels of biomarkers and management variables were used. Qualitative variables were analyzed using Pearson's chi-square test, and quantitative variables using the Mann-Whitney U-test. Survival analyses were performed by fitting a multivariable Cox regression model for patient survival during the follow-up of the study in relation to the patient's characteristics upon admission to the emergency department. Results: A total of 540 patients were included. The mean age was 83 years, and 53.9% of the patients were men. Overall, 112 patients (20.7%) died during the study follow-up. The mortality rate per 100 person-years was 14.33 (11.8-17.24), the most frequent mechanism being falls in the home, with none caused on public roads. The multivariable Cox proportional hazards model showed that survival after TBI was significantly associated with age, S100 levels, Charlson index, patient's institutionalized status, the place where the TBI occurred, and hemoglobin and platelet levels. Discussion: The most common profile for a patient with a TBI was male and aged between 80 and 90 years. The combination of the variables age, Charlson index, place of TBI occurrence, and hemoglobin and platelet levels could offer early prediction of survival in our population independently of TBI severity. With the data obtained, a therapeutic algorithm could be established for patients suffering from mild TBI, allowing the patient to be supervised at home, avoiding futile referrals to emergency services.

Risk of New-Diagnosed Atrial Fibrillation After Transient Ischemic Attack.

Background: Transient ischemic attack (TIA) provides a unique opportunity to optimize secondary preventive treatments to avoid subsequent ischemic stroke (SIS). Although atrial fibrillation (AF) is the leading cause of cardioembolism in IS and anticoagulation prevents stroke recurrence (SR), limited data exists about the risk of new-diagnosed AF (NDAF) after TIA and the consequences of the diagnostic delay. The aim of our study was to determine this risk in a cohort of TIA patients with long-term follow-up. Methods: We carried out a prospective cohort study of 723 consecutive TIA patients from January 2006 to June 2010. Median follow-up was 6.5 (5.0-9.6) years. In a subgroup of 204 (28.2%) consecutive patients, a panel of biomarkers was assessed during the first 24 h of the onset of symptoms. Multivariate analyses were performed to find out the associated factors of NDAF. Kaplan-Meier analysis was also performed to analyzed risk of SIS. Results: NDAF was indentified in 116 (16.0%) patients: 42 (36.2%) during admission, 18 (15.5%) within first year, 29 (25%) between one and five years and 27 (23.3%) beyond 5 years. NDAF was associated with sex (female) [hazard ratio (HR) 1.61 (95% CI, 1.07- 2.41)], age [[HR 1.05 (95% CI, 1.03-1.07)], previous ischemic heart disease (IHD) [HR 1.84, (95% CI 1.15-2.97)] and cortical DWI pattern [HR 2.81 (95% CI, 1.87-4.21)]. In the Kaplan-Meier analysis, NT-proBNP ≥ 218.2 pg/ml (log-rank test P < 0.001) was associated with significant risk of NDAF during the first 5 years of follow-up. Patients with NDAF after admission and before 5 years of follow-up had the highest risk of SIS (P = 0.002). Conclusion: The risk of NDAF after TIA is clinically relevant. We identified clinical and neuroimaging factors of NDAF. In addition, NT-proBNP was related to NDAF. Our results can be used to evaluate the benefit of long-term cardiac monitoring in selected patients.

Basal IL-6 and S100b levels are associated with infarct volume.

OBJECTIVES: The study of biomarkers related to the infarct volume of acute ischaemic stroke (AIS) is a valuable clinical strategy. We conducted a prospective study to evaluate the relationship between a wide panel of biomarkers involved in different biochemical pathways and lesion volume. MATERIALS & METHODS: We studied 332 patients with AIS. Infarct volume was calculated from diffusion weighted imaging (DWI). Blood samples were drawn within 24 h of symptom onset to test a panel of biomarkers that included high-sensitivity C-reactive protein (hs-CRP), IL-6, neuron-specific enolase (NSE), N-terminal pro-B-type natriuretic peptide (NT-ProBNP), S100b, troponin and IL-10. RESULTS: The median lesion volume was 2.5 cc (IQR: 0.6-15.3). Patients with previous atrial fibrillation, cardioembolic aetiology and total anterior circulation infarct TACI classification had higher lesion volumes than those without them. Patients with previous recent TIA had smaller ischaemic lesions than those without it. Age and NIHSS were significantly correlated with lesion volume. In a linear regression analysis adjusted by aetiology, S100b and IL-6 emerged as the only biomarkers independently associated with infarct volume. In contrast, previous recent TIA and small-vessel disease were inversely related to infarct volume. CONCLUSIONS: The correlation between the two blood marker levels and ischaemic lesion volume would support the use of these biomarkers as a surrogate endpoint in AIS, especially in centres without DWI 24/7 but these could not substitute basic neuroimaging. Our findings should be further explored in larger, preferably multicentre studies.

Inflammatory Response of Ischemic Tolerance in Circulating Plasma: Preconditioning-Induced by Transient Ischemic Attack (TIA) Phenomena in Acute Ischemia Patients (AIS).

Introduction: Ischemic tolerance (IT) refers to a state where cells are resistant to the damaging effects caused by periods of ischemia. In a clinical scenario, the IT phenomenon would be activated by a recent transient ischemic attack (TIA) before an ischemic stroke (IS). The characterization of inflammatory protein expression patterns will contribute to improved understanding of IT. Methods: A total of 477 IS patients from nine hospitals, recruited between January 2011 and January 2016, were included in the current study and divided in three groups: 438 (91.9%) patients without previous TIA (group 1), 22 (4.6%) patients who suffered TIA 24 h before IS (group 2), and 17 (3.5%) patients who suffered TIA between 24 h and 7 days prior to IS (group 3). An inflammatory biomarker panel (IL-6, NT-proBNP, hsCRP, hs-Troponin, NSE, and S-100b) on plasma and a cytokine antibody array was performed to achieve the preconditioning signature potentially induced by TIA phenomena. Primary outcome was modified rankin scale (mRs) score at 90 days. Results: Recent previous TIA was associated with better clinical outcome at 90 days (median mRS of group 1: 2.0 [1.0-4.0]; group 2: 2.0 [0.0-3.0]; group 3: 1.0 [0-2.5]; p = 0.086) and smaller brain lesion (group 1: 3.7 [0.7-18.3]; group 2: 0.8 [0.3-8.9]; group 3: 0.6 [0.1-5.5] mL; p = 0.006). All inflammation biomarkers were down regulated in the groups of recent TIA prior to IS compared to those who did not suffer a TIA events. Moreover, a cytokine antibody array revealed 30 differentially expressed proteins between the three groups. Among them, HRG1-alpha (Fold change 74.4 between group 1 and 2; 74.2 between group 1 and 3) and MAC-1 (Fold change 0.05 between group 1 and 2; 0.06 between group 1 and 3) expression levels would better stratify patients with TIA 7 days before IS. These two proteins showed an earlier inflammation profile that was not detectable by the biomarker panel. Conclusion: Inflammatory pathways were activated by transient ischemic attack, however the period of time between this event and a further ischemic stroke could be determined by a protein signature that would contribute to define the role of ischemic tolerance induced by TIA.

Doctors' opinions on clinical coordination between primary and secondary care in the Catalan healthcare system.

OBJECTIVE: To analyse doctors' opinions on clinical coordination between primary and secondary care in different healthcare networks and on the factors influencing it. METHODS: A qualitative descriptive-interpretative study was conducted, based on semi-structured interviews. A two-stage theoretical sample was designed: 1) healthcare networks with different management models; 2) primary care and secondary care doctors in each network. Final sample size (n = 50) was reached by saturation. A thematic content analysis was conducted. RESULTS: In all networks doctors perceived that primary and secondary care given to patients was coordinated in terms of information transfer, consistency and accessibility to SC following a referral. However, some problems emerged, related to difficulties in acceding non-urgent secondary care changes in prescriptions and the inadequacy of some referrals across care levels. Doctors identified the following factors: 1) organizational influencing factors: coordination is facilitated by mechanisms that facilitate information transfer, communication, rapid access and physical proximity that fosters positive attitudes towards collaboration; coordination is hindered by the insufficient time to use mechanisms, unshared incentives in prescription and, in two networks, the change in the organizational model; 2) professional factors: clinical skills and attitudes towards coordination. CONCLUSIONS: Although doctors perceive that primary and secondary care is coordinated, they also highlighted problems. Identified factors offer valuable insights on where to direct organizational efforts to improve coordination.

Metabolomics Predicts Neuroimaging Characteristics of Transient Ischemic Attack Patients.

BACKGROUND: Neuroimaging is essential for the diagnosis and prognosis of transient ischemic attack (TIA). The discovery of a plasmatic biomarker related to neuroimaging findings is of enormous interest because, despite its relevance, magnetic resonance diffusion weighted imaging (DWI) is not always available in all hospitals that attend to TIA patients. METHODS: Metabolomic analyses were performed by liquid chromatography coupled to mass spectrometry in order to establish the metabolomic patterns of positive DWI, DWI patterns and acute ischemic lesion volumes. We used these methods with an initial TIA cohort of 129 patients and validated them with a 2nd independent cohort of 152 patients. FINDINGS: Positive DWI was observed in 115 (40.9%) subjects and scattered pearls in one arterial territory was the most frequent lesion pattern (35.7%). The median acute ischemic lesion volume was 0.33 (0.15-1.90)cm3. We detected a specific metabolomic profile common to both cohorts for positive DWI (11 molecules including creatinine, threoninyl-threonine, N-acetyl-glucosamine, lyso phosphatidic acid and cholesterol-related molecules) and ischemic lesion volume (10 molecules including lysophosphatidylcholine, hypoxanthine/threonate, and leucines). Moreover lysophospholipids and creatinine clearly differed the subcortical DWI pattern from other patterns. INTERPRETATION: There are specific metabolomic profiles associated with representative neuroimaging features in TIA patients. Our findings could allow the development of serum biomarkers related to acute ischemic lesions and specific acute ischemic patterns.

Continuity of clinical management and information across care levels: perceptions of users of different healthcare areas in the Catalan national health system.

BACKGROUND: The integration of health care has become a priority in most health systems, as patients increasingly receive care from several professionals in various different settings and institutions, particularly those with chronic conditions and multi-morbidities. Continuity of care is defined as one patient experiencing care over time as connected and coherent with his or her health needs and personal circumstances. The objective is to analyse perceptions of continuity of clinical management and information across care levels and the factors influencing it, from the viewpoint of users of the Catalan national health system. METHODS: A descriptive-interpretative qualitative study was conducted using a phenomenological approach. A two-stage theoretical sample was selected: (i) the study contexts: healthcare areas in Catalonia with different services management models; (ii) users ≥ 18 years of age who were attended to at both care levels for the same health problem. Data were collected by means of individual semi-structured interviews with patients (n = 49). All interviews were recorded and transcribed. A thematic content analysis was conducted segmented by study area, with a mixed generation of categories and triangulation of analysts. RESULTS: Patients in all three areas generally perceived that continuity of clinical management across levels existed, on referring to consistent care (same diagnosis and treatment by doctors of both care levels, no incompatibilities of prescribed medications, referrals across levels when needed) and accessibility across levels (timeliness of appointments). In terms of continuity of information, patients in most areas mentioned the existence of information sharing via computer and its adequate usage. Only a few discontinuity elements were reported such as long waiting times for specific tests performed in secondary care or insufficient use of electronic medical records by locum doctors. Different factors influencing continuity were identified by patients, relating to the health system itself (clear distribution of roles between primary and secondary care), health services organizations (care coordination mechanisms, co-location, insufficient resources) and physicians (willingness to collaborate, commitment to patient care, the primary care physician's technical competence). CONCLUSIONS: Care continuity across care levels is experienced by patients in the areas studied, with certain exceptions that highlight where there is room for improvement. Influencing factors offer valuable insights on where to direct coordination efforts.

Development and testing of indicators to measure coordination of clinical information and management across levels of care.

BACKGROUND: Coordination across levels of care is becoming increasingly important due to rapid advances in technology, high specialisation and changes in the organization of healthcare services; to date, however, the development of indicators to evaluate coordination has been limited. The aim of this study is to develop and test a set of indicators to comprehensively evaluate clinical coordination across levels of care. METHODS: A systematic review of literature was conducted to identify indicators of clinical coordination across levels of care. These indicators were analysed to identify attributes of coordination and classified accordingly. They were then discussed within an expert team and adapted or newly developed, and their relevance, scientific soundness and feasibility were examined. The indicators were tested in three healthcare areas of the Catalan health system. RESULTS: 52 indicators were identified addressing 11 attributes of clinical coordination across levels of care. The final set consisted of 21 output indicators. Clinical information transfer is evaluated based on information flow (4) and the adequacy of shared information (3). Clinical management coordination indicators evaluate care coherence through diagnostic testing (2) and medication (1), provision of care at the most appropriate level (2), completion of diagnostic process (1), follow-up after hospital discharge (4) and accessibility across levels of care (4). The application of indicators showed differences in the degree of clinical coordination depending on the attribute and area. CONCLUSION: A set of rigorous and scientifically sound measures of clinical coordination across levels of care were developed based on a literature review and discussion with experts. This set of indicators comprehensively address the different attributes of clinical coordination in main transitions across levels of care. It could be employed to identify areas in which health services can be improved, as well as to measure the effect of efforts to improve clinical coordination in healthcare organizations.

Metabolomics predicts stroke recurrence after transient ischemic attack.

OBJECTIVE: To discover, by using metabolomics, novel candidate biomarkers for stroke recurrence (SR) with a higher prediction power than present ones. METHODS: Metabolomic analysis was performed by liquid chromatography coupled to mass spectrometry in plasma samples from an initial cohort of 131 TIA patients recruited <24 hours after the onset of symptoms. Pattern analysis and metabolomic profiling, performed by multivariate statistics, disclosed specific SR and large-artery atherosclerosis (LAA) biomarkers. The use of these methods in an independent cohort (162 subjects) confirmed the results obtained in the first cohort. RESULTS: Metabolomics analyses could predict SR using pattern recognition methods. Low concentrations of a specific lysophosphatidylcholine (LysoPC[16:0]) were significantly associated with SR. Moreover, LysoPC(20:4) also arose as a potential SR biomarker, increasing the prediction power of age, blood pressure, clinical features, duration of symptoms, and diabetes scale (ABCD2) and LAA. Individuals who present early (<3 months) recurrence have a specific metabolomic pattern, differing from non-SR and late SR subjects. Finally, a potential LAA biomarker, LysoPC(22:6), was also described. CONCLUSIONS: The use of metabolomics in SR biomarker research improves the predictive power of conventional predictors such as ABCD2 and LAA. Moreover, pattern recognition methods allow us to discriminate not only SR patients but also early and late SR cases.

[Comparative analysis of serological tests performed in immigrants in the Lleida health area]. / Análisis comparativo de las serologías realizadas a los inmigrantes en la región sanitaria de Lleida.

OBJECTIVE: Evaluate the process of screening and detection of HIV, HBV, HCV and syphilis in the province of Lleida by determining the proportions of positive results in the different groups during one year. DESIGN: Descriptive, multicentre study of all the serological tests performed in immigrants and natives attended in 2007. SETTING: Province of Lleida (Spain). PARTICIPANTS: 255,410 users. MAIN MEASUREMENTS: Age, sex, country of origin and period of residence in Spain, and the results for HIV, hepatitis B, hepatitis C and syphilis. We calculated the proportions in which a serological test had been requested, and examined the association between the rates of positive tests and the geographical area of origin, and calculated age-adjusted rates taking the age distribution of the native population as the reference. RESULTS: Risk of HBV was 4.6 times higher in immigrants than in natives (11.7 times in sub-Saharan Africans). The rate of positive syphilis tests was three times higher in the immigrant group. For HIV the PR was 2.3 (sub-Saharan Africans 7.4). For hepatitis C the risk was lower in immigrants than in natives (PR=0.4). CONCLUSIONS: Immigrants have a higher probability of testing positive in screening in hepatitis B, syphilis and HIV. The rates differ significantly according to the origin of the immigrant.

Identification of recent HIV-1 infection among newly diagnosed cases in Catalonia, Spain (2006-08).

BACKGROUND: Quantification and description of patients recently infected by HIV can provide an accurate estimate of the dynamics of HIV transmission. Between 2006 and 2008 in Catalonia, we estimated the prevalence of recent HIV infection among newly diagnosed cases, described the epidemiological characteristics of the infection according to whether it was recent, long-standing or advanced, and identified factors associated with recent infection. METHODS: A Test for Recent Infection (TRI) was performed in serum samples from patients newly diagnosed with HIV. Two different TRI were used: the Vironostika-LS assay (January 2006-May 2007) and the BED-CEIA CEIA (June 2007 onwards). Samples were obtained within the first 6 months of diagnosis. Patients whose samples tested positive in the TRI were considered recently infected. RESULTS: Of 1125 newly diagnosed patients, 79.9% were men (median age, 35.4 years), 38.7% were born outside Spain, 48.9% were men who have sex with men (MSM) and 10.6% presented other sexually transmitted infections. The overall percentage of recent infection was 23.0%, which increased significantly, from 18.1% in 2006 to 26.2% in 2008. This percentage was higher for patients from South America (27.6%). Factors associated with recent infection were acquiring infection through sexual contact between MSM [odds ratio (OR) 2.0; 95% confidence interval (95% CI) 1.1-3.9], compared with acquiring infection through heterosexual relations and being under 30 years of age (OR 5.9; 95% CI 1.9-17.4), compared with being over 50 years of age. CONCLUSION: The highest percentage of recent infection was identified in MSM, suggesting either a higher incidence or a greater frequency of HIV testing. Information regarding testing patterns is necessary to correctly interpret data from recently infected individuals. Systems to monitor the HIV epidemic should include both parameters.

Prevalence of transmitted antiretroviral resistance and distribution of HIV-1 subtypes among patients with recent infection in Catalonia (Spain) between 2003 and 2005.

OBJECTIVES: The objectives of this study were to assess the prevalence of transmitted HIV-1 drug resistances (TDR) and HIV-1 subtypes in recently infected patients in Catalonia between 2003 and 2005 and to describe the characteristics of these patients according to the presence or absence of TDR and HIV-1 subtype. METHODS: After application of the Serological Testing Algorithm for Recent HIV Seroconversion (STARHS), residual aliquots of serum samples from recently infected antiretroviral-naïve individuals were genotyped. FASTA sequences were analyzed using the HIVDB Program. The World Health Organization 2009 List of Mutations for Surveillance of Transmitted HIV-1 Drug Resistant HIV Strains was used to estimate the prevalence of TDR. RESULTS: Of 182 recently infected patients, 14 (7.7%) presented TDR. Seven (3.8%) had genotypic evidence of TDR against non-nucleoside reverse transcriptase inhibitors, 6 (3.3%) against nucleoside reverse transcriptase inhibitors, 3 (1.6%) against protease inhibitors (PIs), and only 2 individuals (1.1%) presented TDR against more than one class of drugs. Thirty-five (19.2%) patients were infected with a non-B HIV-1 subtype. CONCLUSION: This is the first study to estimate the prevalence of TDR in recently infected patients in Catalonia. The results are similar to those of studies performed in other Spanish regions. Correct monitoring of these parameters requires systematic epidemiologic surveillance of transmitted resistance.

Kinetics and spatial distribution of OTA in Aspergillus carbonarius cultures.

The aim of this study was to characterize Ochratoxin A (OTA) production by Aspergillus carbonarius under different environmental conditions, and to elucidate the diffusion capacity of OTA throughout synthetic medium. One strain belonging to the species A. carbonarius isolated from vine dried fruit was single-point inoculated onto triplicate synthetic nutrient medium plates at two water activities (0.92 and 0.97) and two temperatures (20 and 30 degrees C). Daily radii were measured and OTA production was tested after 4, 7, 10, 14 and 18 days of incubation at four distances from the centre of colony (1-4 cm). OTA production was detected mainly at 0.97 a(w). Earlier production was detected at 30 degrees C (optimum for growth), whereas maximum OTA concentrations were found at 20 degrees C. OTA production was detected from mycelium that was only a few days old and attained its optimum when mycelium was 4-7 days old at 0.97 a(w). OTA diffusion was observed at 0.92 a(w) and 20 degrees C. Thus OTA production is discernable in young A. carbonarius mycelium and diffusion of the toxin has been shown to occur in a solid substrate.

Effects of fungal interaction on ochratoxin A production by A. carbonarius at different temperatures and a(w).

Ochratoxin A is a well-known mycotoxin produced by species of the genera Penicillium and Aspergillus. OTA-producing species from A. section Nigri are considered the source of OTA detected in grapes, dried vine fruits and wines. Other fungi present in grapes during their maturation can grow and interact with OTA-producing Aspergillus species and affect OTA production. In this study seven fungi (Alternaria alternata, Cladosporium herbarum, Eurotium amstelodami, Trichoderma harzianum, Penicillium decumbens, P. janthinellum and Candida sp.) disolated from grapes and dried vine fruits were grown in SNM medium paired with OTA-positive A. carbonarius at two temperatures (20 and 30 degrees C) and at two water activities (0.92 and 0.97). OTA production was tested after 5, 7, 10, 14 and 18 days of incubation, at four distances (1, 2, 3 and 4 cm) from A. carbonarius inoculation point in the inter-colony axis. At 0.92 a(w) OTA production was almost negligible. At 0.97 a(w) and 30 degrees C OTA accumulation was reduced when A. carbonarius was grown in paired cultures, particularly with A. alternata, C. herbarum, P. decumbens and P. janthinellum. At 0.97 a(w) and 20 degrees C, there was no clear effect of the interacting species on OTA accumulation; in general E. amstelodami and Candida sp. seemed to stimulate OTA production, whereas T. harzianum and P. decumbens reduced it. Competing mycoflora acted as an additional control factor against OTA accumulation at 30 degrees C; but at 20 degrees C, where OTA production is optimal, this did not happen. Thus maintaining the temperature of grapes at or above 30 degrees C during dehydration may provide some control against OTA accumulation in grapes.