Liver iron concentration in dysmetabolic hyperferritinemia: Results from a prospective cohort of 276 patients.

INTRODUCTION AND OBJECTIVES: We aimed to study the liver iron concentration in patients referred for hyperferritinemia to six hospitals in the Basque Country and to determine if there were differences between patients with or without metabolic syndrome. PATIENTS AND METHODS: Metabolic syndrome was defined by accepted criteria. Liver iron concentration was determined by magnetic resonance imaging. RESULTS: We obtained the data needed to diagnose metabolic syndrome in 276 patients; a total of 135 patients (49%), 115/240 men (48%), and 20/36 women (55.6%) presented metabolic syndrome. In all 276 patients, an MRI for the determination of liver iron concentration (mean±SD) was performed. The mean liver iron concentration was 30.83±19.38 for women with metabolic syndrome, 38.84±25.50 for men with metabolic syndrome, and 37.66±24.79 (CI 95%; 33.44-41.88) for the whole metabolic syndrome group. In 141 patients (51%), metabolic syndrome was not diagnosed: 125/240 were men (52%) and 16/36 were women (44.4%). The mean liver iron concentration was 34.88±16.18 for women without metabolic syndrome, 44.48±38.16 for men without metabolic syndrome, and 43.39±36.43 (CI 95%, 37.32-49.46) for the whole non-metabolic syndrome group. Comparison of the mean liver iron concentration from both groups (metabolic syndrome vs non-metabolic syndrome) revealed no significant differences (p=0.12). CONCLUSIONS: Patients with hyperferritinemia and metabolic syndrome presented a mildly increased mean liver iron concentration that was not significantly different to that of patients with hyperferritinemia and non-metabolic syndrome.

[Frameless stereotactic biopsy: diagnostic yield and complications]. / Biopsia cerebral estereotáctica sin marco: capacidad diagnóstica y complicaciones.

OBJECTIVE: The aim of this study was to evaluate the variables that could modify the diagnostic yield of frameless stereotactic biopsy, as well as its complications. MATERIALS AND METHOD: This was a retrospective study of frameless stereotactic biopsies carried out between July 2008 and December 2011 at Donostia University Hospital. The variables studied were size, distance to the cortex, contrast uptake and location. RESULTS: A total of 70 patients were included (75 biopsies); 39 males and 31 females with an age range between 39 and 83 years. The total diagnostic yield in our series was 97.1%. For lesions >19mm, the technique offered a sensitivity of 95.2% (95% CI: 86.9-98.4) and specificity of 57.1% (95% CI: 25.0-84.2). The yield was lower for lesions within 17mm of the cortex: sensitivity of 74.6% (95% CI: 62.1-84.7) and specificity of 71.4% (95% CI: 29.0-96.3). Seven (10%) patients developed complications after the first biopsy and none after the second. CONCLUSIONS: The diagnostic yield was lower for lesions less than 2cm in size and located superficially. In this series we did not observe an increased rate of complications after a second biopsy.

Presurgical invasive mediastinal staging in lung cancer, unexpected N2 and long-term survival: a registry-based study with data from the Spanish group for video-assisted thoracic surgery.

Background: Mediastinal lymph node staging is a key element in the diagnosis of lung cancer. The combination of computed tomography (CT) and positron emission tomography (PET) has improved staging but some circumstances are known to influence their negative predictive value. The objective of this study was to assess the impact on survival of avoiding invasive mediastinal staging in surgical lung cancer patients with negative mediastinum in CT and PET and intermediate risk of unexpected pN2. Methods: Data were collected from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS), from December 2016 to March 2018. For this study, patients were selected if they had negative mediastinum in CT and PET findings but tumours >3 cm or located centrally, or with cN1 disease. Patients who did and did not undergo invasive staging [invasive group (IG) and non-invasive group (NIG)] were compared, analysing unexpected pN2 and survival with Kaplan-Meier curves and Cox regression. Results: A total of 2,826 patients underwent surgery for primary lung cancer. We selected 1,247 patients who had tumours >3 cm, central tumours or cN1. Invasive staging was performed in 275 (22.1%) cases. The unexpected pN2 rate was 9.6% in the NIG and 13.8% in the IG, but half of them were discovered prior to surgery in the IG. Five-year overall survival (OS) was poorer in the IG (52.4% vs. 64%; P<0.001). In the Cox regression model, male sex, older age, diabetes, synchronous tumour, lower diffusing capacity for carbon monoxide, larger tumour size, higher pathological N-stage, and IG status were significant independent risk factors. Conclusions: Invasive staging recommended by guidelines could be reduced with an appropriate selection in mediastinal CT- and PET-negative patients with risk factors for unexpected pN2, because rates of pN2 and survival did not worsen without invasive staging.

Optimization of clean extraction methods to isolate carotenoids from the microalga Neochloris oleoabundans and subsequent chemical characterization using liquid chromatography tandem mass spectrometry.

A novel experimental design was used to optimize the extraction of carotenoids from Neochloris oleoabundans using pressurized liquid extraction with food-grade solvents such as ethanol and limonene. Experimental factors, including the extraction temperature and the solvent composition, were optimized using a three-level factorial design. The response variables extraction yield and total amount of carotenoids were assessed. The statistical analysis of the results provided mathematical models to predict the behavior of the responses as a function of the factors involved in the process. The optimum conditions predicted by the model developed in this study were 112 °C as the extraction temperature and 100% ethanol as the extraction solvent. Chemical characterization of the extracts obtained was performed by means of high-performance liquid chromatography-tandem mass spectrometry. The results obtained demonstrated that, under certain growth conditions (photoautotrophically cultured in a medium supplemented with 0.3 g L(-1) KNO3), N. oleoabundans accumulated significant total amounts of the carotenoids (from 57.4 to 120.2 mg carotenoids per gram of extract depending on the extraction conditions), mainly lutein, cantaxanthin, zeaxanthin, and astaxanthin monoesters and diesters.

Non-invasive measurement of liver iron concentration by magnetic resonance imaging and its clinical usefulness.

Determination of liver iron concentration by magnetic resonance imaging (MRI) is becoming the new technique of choice for the diagnosis of iron overload in hereditary haemochromatosis and other liver iron surcharge diseases. Determination of hepatic iron concentration obtained by liver biopsy has been the gold standard for years. The development of MRI techniques, via signal intensity ratio methods or relaxometry, has provided a non-invasive and more accurate approach to the diagnosis of liver iron overload. This article reviews the available MRI methods for the determination of liver iron concentration and also evaluates the technique for the diagnosis and quantification of iron overload in different clinical practice scenarios.

Effect of viral eradication with direct-acting antiviral agents on iron parameters in patients with chronic hepatitis c and hyperferritinemia.

Background: Patients with chronic hepatitis C are at increased risk for hyperferritinemia (HF). Abnormalities of serum iron parameters are frequently observed in patients with chronic hepatitis C (CHC). About a third of patients have increased iron parameters. Recently, studies on the effect of direct-acting antiviral agents (DAAs) in HCV eradication in patients with increased serum iron has been published, demonstrating the restoration of normal iron status. The aim of this study was to evaluate the effect of viral eradication with DDAs in patients with CHC and HF. Methods: Retrospective study conducted from January 2018 to December 2020 including patients treated with DAAs for HCV. Pre-treatment (PreT) and post-treatment (PostT) serum ferritin values were evaluated in all patients. Inclusion criteria: Pret HF (>400 µg/L); CHC patients treated with DAA achieving sustained viral response (SVR). Exclusion criteria: No PreT or PostT HF available; no SVR; lost patients. Results: From 621 patients treated with DAAs for CHC, 77 presented HF (12.40%), and 74 were included in the study. Fifty nine were men (79.73%) with a mean age 58.33, SD 8.68; PreT mean ferritin: 893.20 (SD 1037.09); PostT: 264.17 (SD 161.33); PreT mean transferrin saturation: 40.96 (SD 15.71); PostT: 29.82 (SD 11.17); PreT mean serum iron 152.32 (SD 62.07), PostT: 109.32 (SD 39.49). When we compared PreT and PostT iron parameters, significant statistical differences were present considering ferritin (p = 0.0000), transferrin saturation (p = 0.0000), and iron (p = 0.0002) determinations. Conclusions: SVR after DAAs for CHC induces a statistically significant reduction on iron parameters.

Liver steatosis in patients with rheumatoid arthritis treated with methotrexate is associated with body mass index.

BACKGROUND: Methotrexate (MTX) is the usual first-line treatment for rheumatoid arthritis (RA). Long-term use of MTX has been associated with liver steatosis (LS) and liver fibrosis (LF). AIM: To determine if LS in patients treated with MTX for RA is associated with MTX cumulative dose (MTX-CD), metabolic syndrome (MtS), body mass index (BMI), the male sex, or LF. METHODS: A single-center, prospective study of patients receiving MTX for RA was performed from February 2019 to February 2020. The inclusion criteria were patients aged 18 years or older diagnosed with RA by a rheumatologist and being treated with MTX (without limitation on the duration of treatment). The exclusion criteria were previous diagnosis of liver disease (hepatitis B or C virus infection, known nonalcoholic fatty liver disease), alcohol consumption greater than 60 g/d in males or 40 g/d in females, human immunodeficiency virus infection on antiretroviral therapy, diabetes mellitus, chronic renal failure, congestive heart failure, or BMI greater than 30 kg/m². Patients receiving leflunomide in the 3 years prior to the study were also excluded. Transient elastography (FibroScan, Echosens®, Paris, France) was used for fibrosis determination (LF > 7 KpA) and computer attenuation parameter (CAP) for LS (CAP > 248 dB/m). Demographic variables, laboratory data, MTX-CD (> 4000 mg), MtS criteria, BMI (> 25), transient elastography, and CAP scores were collected from all patients. RESULTS: Fifty-nine patients were included. Forty-three were female (72.88%), and the mean age was 61.52 years (standard deviation: 11.73). When we compared MTX-CD ≤ 4000 mg (26 patients; 14 with LS and 12 without) with > 4000 mg (33 patients; 12 with LS and 21 without), no statistical differences were found (P = 0.179). We compared CAP scores stratified by MtS, BMI, sex, and LF. There were no significant differences in CAP scores based on the presence of MtS [CAP/MtS: 50 no MtS (84.75%); 9 MtS (15.25%); P = 0.138], the male sex (CAP/sex: 8 male/18 female LS; 8 male/25 female no LS; P = 0.576), or LF [CAP/fibrosis: 53 no LF (89.83%); 6 LF (10.17%); P = 0.239]. LS determined by CAP was significantly associated with BMI > 25 (CAP/BMI: 22 BMI ≤ 25 (37.29%); 37 BMI > 25 (62.71%); P = 0.002]. CONCLUSION: LS in patients with RA treated with MTX was not associated with MTX-CD, LF, the male sex, or MtS. However, BMI was significantly related to LS in these patients.

Results in mediastinal lymph node staging of surgical lung cancer: Data from the prospective cohort of the Spanish Video-Assisted Thoracic Surgery Group.

OBJECTIVES: The objective of this study was to assess the diagnostic performance of combined computerised tomography (CT) and positron emission tomography (PET) in mediastinal staging of surgical lung cancer based on data obtained from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS). METHODS: A total of 2782 patients underwent surgery for primary lung carcinoma. We analysed diagnostic success in mediastinal lymph node staging (cN2) using CT and PET. Bivariate and multivariate analyses were performed of the factors involved in this success. The risk of unexpected pN2 disease was analysed for cases in which an invasive testing is recommended: cN1, the tumour centrally located or the tumour diameter >3 cm. RESULTS: The overall success of CT together with PET was 82.9% with a positive predictive value of 0.21 and negative predictive value of 0.93. If the tumour was larger than 3 cm and for each unit increase in mediastinal SUVmax, the probability of success was lower with OR 0.59 (0.44-0.79) and 0.71 (0.66-0.75), respectively. In the video-assisted thoracic surgery (VATS) approach, the probability of success was higher with OR 2.04 (1.52-2.73). The risk of unexpected pN2 increased with the risk factors cN1, the tumour centrally located or the tumour diameter >3 cm: from 4.5% (0 factors) to 18.8% (3 factors) but did not differ significantly as a function of whether invasive testing was performed. CONCLUSIONS: CT and PET together have a high negative predictive value. The overall success of the staging is lower in the case of tumours >3 cm and high mediastinal SUVmax, and it is higher when VATS is performed. The risk of unexpected pN2 is higher if the disease is cN1, the tumour centrally located or the tumour diameter >3 cm but does not vary significantly as a function of whether patients have undergone invasive testing.

Autologous Tragal Perichondrium Graft for Vocal Fold Scar and Sulcus Vocalis.

Between 2006 and 2016 in a Tertiary Academic Center, 11 patients underwent phonomicrosurgery with tragal perichondrium graft placement in Reinke's space for the treatment of sulcus (Ford type 2) and vocal fold scar. A total of six patients out of 11 had an additional autologous fat implantation in order to improve the glottic closure. We evaluated the functional outcome using the Spanish validated version of the VHI- 30 before and 6 months after the surgery. We also measured the subjective appreciation of the obtained outcome, a perceptual voice evaluation using GRBAS scale, and changes in videostroboscopy examinations concerning mucosal wave and glottic closure. In the VHI-30 questionnaire, we observed an improvement in all patients (six of which showed an improvement of 50% or more) with statistically significant results (P = 0.003), and no significant differences between sulcus (Ford type 2) and vocal cord scar patients (P = 0.7579). The results obtained from the single question assessing changes in voice quality showed a high improvement in seven patients. According to the GRBAS scale, all cases improved. Concerning the results of the videostroboscopy, two patients obtained very favorable results, eight of them presented a moderate recovery and only one improved slightly. The following complications were identified: two granulomas, a graft extrusion and a tragal infection. The tragal perichondrium used as an autograft in Reinke's space appears to be a safe and satisfactory choice, comparable to other grafts such as temporalis fascia or autologous fat.

Large granular lymphocyte leukaemia study at the University Hospital of Donostia.

INTRODUCTION: Large granular lymphocyte (LGL) leukaemia is considered a mature T-cell or natural killer (NK) cell neoplasm, characterised by a clonal proliferation of LGL. AIMS: To analyse the characteristics and to establish (if possible) the prognostic parameters of these patients diagnosed in a single centre: University Hospital of Donostia. METHODS: We retrospectively studied data about 308 patients with LGL leukaemia diagnosed in our centre. RESULTS: The frequency of T-LGL leukaemia and chronic lymphoproliferative disorder of NK cells was 89% and 6.8% respectively, and no aggressive NK-LGL leukaemia was seen in our population. The median age at diagnosis was 65.7 years and male-to-female ratio was 1.08. 59% of our patients were asymptomatic at the time of diagnosis. Most patients presented lymphocytosis and 63.6% more than 20% LGLs in the peripheral blood count, but it has to be taken into account that these results may be influenced by the selection bias of our study, as we recognised these patients as 'alarms of the laboratory analysers'. Neutropenia was the most common cytopenia, and autoimmune disorders were described in 16.5% of the patients. Only 12 patients (3.9%) required treatment, a much lower percentage that the one reported in the literature, and this is consistent with the fact that patients were less symptomatic than in other series, as we expected. The 5-year and 15-year overall survival was 92% and 87%, respectively. CONCLUSIONS: Our patients may represent the even more benign end of the spectrum of clonal T LGL and NK proliferations.

Tobacco as biofactory for biologically active hPL production: a human hormone with potential applications in type-1 diabetes.

Human placental lactogen (hPL) is a peptidic hormone that belongs to the short list of growth factors that could treat type-1 diabetes through pancreatic islet transplantation. Placental lactogen has the capacity to improve islet survival and function before or after transplantation. In this study, transgenic tobacco plants were used as a novel expression system for the production of recombinant hPL protein (rhPL). The expression vector pNEKhPL2 containing hPL cDNA was introduced into tobacco plants; the transcriptional activity was confirmed by real-time PCR, and the rhPL levels reached 1% of the total soluble protein (TSP) content in plants cultivated in the greenhouse. In vitro bioassays using the rat insulinoma (INS-1) cell line showed that recombinant protein was able to induce cell proliferation and activate the JAK-2/STAT-5 signal transduction pathway, demonstrating that plant cells can produce the biologically active hPL protein. To further characterize the plant expression system for hPL production, we analyzed the stability of the protein during the life cycle of tobacco plants as well as the transmission of the transgenic trait to the progeny. The recombinant protein was stably accumulated in young leaves, reaching the maximum level in the first month (6.51 µg/g of fresh weight), but showing a decreasing trend of 26% from the initial sampling time until the end of plant's life cycle. The progeny of the selected pNEKhPL2 plant showed in vitro expression levels of up to 1.1% of TSP. Our results therefore indicate that transgenic plants are a suitable expression system for hPL production.

Phone Speech Recognition Improvement in Noisy Environment: Use of a Bluetooth Accessory.

OBJECTIVE: To evaluate speech understanding in noise and patient satisfaction using the new Cochlear Wireless Phone Clip device. MATERIAL AND METHODS: Twenty-nine experienced cochlear implant (CI) users (>6 months usage) were situated in a soundproof room where a 65 dB SPL Spanish cocktail noise was generated continuously from 4 loudspeakers. Lists of disyllabic words were presented through the clinic landline telephone to the patients. Patients were tested first holding the phone and then with the Cochlear Phone Clip© paired to the CP910 using various mixing ratios (2:1, 4:1, and Phone Clip© only). RESULTS: Statistically significant (P < .001) improvement of speech recognition performance was found in cell phone usage by wireless transmission and also when using this new device. Kepler questionnaire results showed that before using Phone Clip in everyday life, 55.2% of patients described themselves highly or greatly affected by their deafness for telephone use and 80% moderately to greatly affected. Kim questionnaire results showed statistically significant differences (P < .001) in the subjective satisfaction of the Bluetooth-implemented CI compared to the conventional mode for sound quality, noise interference, and sound accuracy. CONCLUSIONS: The wireless Phone Clip© device helps implanted people to improve subjective and objective speech recognition performance through the phone in noisy environments.

Prevalence study of intermittent hormonal therapy of Prostate Cancer patients in Spain.

Background: Although intermittent androgen deprivation therapy was introduced many years ago to improve patients' quality of life with the same carcinologic efficiency as continuous hormonal therapy, recent data suggest that those patients could be overtreated. This study aims to estimate the prevalence of prostate cancer patients receiving intermittent androgen deprivation therapy in Spain. Methods: A retrospective, longitudinal study was conducted using electronic drug dispensation data from four Spanish autonomous communities, which encompass 17.23 million inhabitants (36.22% of the total population in Spain). We estimated intermittent androgen therapy use (%IAD) and the prevalence of patients under intermittent androgen therapy (P IAD) overall and stratified by region. Other outcome variables included the pharmaceutical forms dispensed and the total direct annual expenditure on androgen deprivation therapy-associated medications. Results: A total of 863,005 dispensations corresponding to a total of 65,752 men were identified, treated with either luteinizing hormone-releasing hormone (LHRH) analogues (353,162) administered alone or in combination with anti-androgens (509,843). Overall, the mean (±SD) age of the patients was 76.9 (±10.4) years. Results revealed that the mean annual P IAD along the study was 6.6% in the total population studied, and the overall %IAD during the five-year study period was 5.6%. The mean cost of hormonal therapy per year was 25 million euros for LHRH analogues and 6.3 million euros for anti-androgens. Conclusions:  An important proportion of prostate cancer patients in Spain could benefit from intermittent androgen therapy during the study period while avoiding overtreatment harms associated with continuous hormonal therapy.

Teaching and learning how to make informed health choices: Protocol for a context analysis in Spanish primary schools.

Introduction The Informed Health Choices (IHC) project developed learning resources to teach primary school children (10 to 12-year-olds) to assess treatment claims and make informed health choices. The aim of our study is to explore the educational context for teaching and learning critical thinking about health in Spanish primary schools. Methods During the 2020-2021 school year, we will conduct 1) a systematic assessment of educational documents and resources, and 2) semi-structured interviews with key education and health stakeholders. In the systematic assessment of educational documents and resources, we will include state and autonomous communities' curriculums, school educational projects, and commonly used textbooks and other health teaching materials. In the semi-structured interviews, we will involve education and health policy makers, developers of learning resources, developers of health promotion and educational interventions, head teachers, teachers, families, and paediatric primary care providers. We will design and pilot a data extraction form and a semi-structured interview guide to collect the data. We will perform a quantitative and a qualitative analysis of the data to explore how critical thinking about health is being taught and learned in Spanish primary schools. Conclusion We will identify opportunities for and barriers to teaching and learning critical thinking about health in Spanish primary schools. We will formulate recommendations-for both practice and research purposes-on how to use, adapt (if needed), and implement the IHC resources in this context.

Evaluation of the predictive value of the hematopoietic progenitor cell count using an automated hematology analyzer for CD34+ stem cell mobilization and apheresis product yield.

INTRODUCTION: We evaluated the value of hematopoietic progenitor cells (HPCs) counted in Sysmex XN analyzers to predict the mobilization and collection of CD34+ cells in apheresis for stem cell transplantation. METHODS: Eighty patients who underwent stem cell transplantation were enrolled (50 autologous and 30 allogeneic). In the autologous group, patients were considered poor mobilizers when the CD34+ count was <10 × 106 /L or <20 × 106 /L in patients with multiple myeloma who were going to undergo two transplants. ROC curves were generated, and HPC cutoffs were calculated. RESULTS: The correlation between the HPC and CD34+ cell counts was good. Two algorithms were proposed. In the first algorithm, samples collected the day before apheresis, negative and positive HPC cutoffs were selected to detect poor and good mobilization and, therefore, the need or not to administer plerixafor. In the second algorithm, samples collected pre-apheresis, the negative HPC cutoff was an indication to delay apheresis; an HPC higher than the optimal cutoff was an indication to start apheresis. When the HPC values were between these cutoffs, there was an indication to count CD34+ cells for a better decision-making. Finally, in samples collected pre-apheresis, HPC counts could be used to predict patients who would have poor CD34+ cell collections. In the allogeneic group, all the donors mobilized well, and very few needed two apheresis procedures. CONCLUSIONS: The HPC count is useful for decision-making in the management of patients subjected to apheresis procedures to collect peripheral blood stem cells.

Learning to make informed health choices: Protocol for a pilot study in schools in Barcelona.

Introduction: The Informed Health Choices (IHC) project has developed learning resources to teach primary school children (10 to 12-year-olds) to assess treatment claims and make informed health choices. The aim of our study is to explore both the students' and teachers' experience when using these resources in the context of Barcelona (Spain). Methods: During the 2019-2020 school year, we will conduct a pilot study with 4 th and 5 th-year primary school students (9 to 11-year-olds) from three schools in Barcelona. The intervention in the schools will include: 1) a workshop with the teachers, and 2) lessons to the students. The data collection will include: 1) assessment of the IHC resources by the teachers before the lessons, 2) non-participatory observations during the lessons, 3) semi-structured interviews with the students after a lesson, 4) assessment of the lessons by the teachers after a lesson, 5) treatment claim assessment by the students at the end of the lessons, and 6) assessment of the IHC resources by the teachers at the end of the lessons. We will use ad hoc questionnaires and guides to register the data. We will perform a quantitative and qualitative analysis of the data to explore understandability, desirability, suitability, usefulness, facilitators and barriers of the resources. The most relevant results will be discussed and some recommendations on how to use, how to adapt (if needed), and how to implement the IHC resources to this context will be agreed. The findings of the contextualization activities could inform the design of a cluster-randomised trial, to determine the effectiveness of the IHC resources in this context prior to scaling-up its use. Ethical considerations: The study protocol has obtained an approval exemption from the Ethics Committee of the Hospital de la Santa Creu i Sant Pau (Barcelona, Spain).

Increased CAIDE dementia risk, cognition, CSF biomarkers, and vascular burden in healthy adults.

OBJECTIVE: To investigate the cognitive profile of healthy individuals with increased Cardiovascular Risk Factors, Aging and Dementia (CAIDE) dementia risk score and to explore whether this association is related to vascular burden and CSF biomarkers of amyloidosis and neurodegeneration. METHOD: Cognitively normal participants (mean age 57.6 years) from the Gipuzkoa Alzheimer Project study were classified as having high risk (HR; n = 82) or low risk (LR; n = 293) for dementia according to a CAIDE score cutoff of 9. Cognitive composites were compared between groups. We explored using generalized linear models the role of APOE genotype, MRI white matter hyperintensities (WMH), and CSF (n = 218) levels of ß-amyloid1-42 (Aß1-42), total tau (t-tau), and phosphorylated tau (p-tau) in the association between CAIDE score and cognition. RESULTS: HR participants obtained lower scores on executive function (EF) (p = 0.001) and visual perception and construction (VPC) (p < 0.001) composites. EF composite was associated with CAIDE score × p-tau (p = 0.001), CAIDE score × t-tau (p = 0.001), and WMH (p = 0.003). VPC composite was associated with APOE (p = 0.001), Aß1-42 (p = 0.004), the interaction APOE × Aß1-42 (p = 0.003), and WMH (p = 0.004). Performance on global memory was associated with Aß1-42 (p = 0.006), APOE (p = 0.008), and their interaction (p = 0.006). Analyses were adjusted for age, education, sex, premorbid intelligence, and stress. CONCLUSION: Healthy participants at increased dementia risk based on CAIDE scores show lower performance in EF and VPC. This difference is related to APOE, WMH, and Alzheimer biomarkers.

Design Characteristics Influence Performance of Clinical Prediction Rules in Validation: A Meta-Epidemiological Study.

BACKGROUND: Many new clinical prediction rules are derived and validated. But the design and reporting quality of clinical prediction research has been less than optimal. We aimed to assess whether design characteristics of validation studies were associated with the overestimation of clinical prediction rules' performance. We also aimed to evaluate whether validation studies clearly reported important methodological characteristics. METHODS: Electronic databases were searched for systematic reviews of clinical prediction rule studies published between 2006 and 2010. Data were extracted from the eligible validation studies included in the systematic reviews. A meta-analytic meta-epidemiological approach was used to assess the influence of design characteristics on predictive performance. From each validation study, it was assessed whether 7 design and 7 reporting characteristics were properly described. RESULTS: A total of 287 validation studies of clinical prediction rule were collected from 15 systematic reviews (31 meta-analyses). Validation studies using case-control design produced a summary diagnostic odds ratio (DOR) 2.2 times (95% CI: 1.2-4.3) larger than validation studies using cohort design and unclear design. When differential verification was used, the summary DOR was overestimated by twofold (95% CI: 1.2 -3.1) compared to complete, partial and unclear verification. The summary RDOR of validation studies with inadequate sample size was 1.9 (95% CI: 1.2 -3.1) compared to studies with adequate sample size. Study site, reliability, and clinical prediction rule was adequately described in 10.1%, 9.4%, and 7.0% of validation studies respectively. CONCLUSION: Validation studies with design shortcomings may overestimate the performance of clinical prediction rules. The quality of reporting among studies validating clinical prediction rules needs to be improved.