The association between sleep quality, low back pain and disability: A prospective study in routine practice.

BACKGROUND: The objective of this study was to estimate the association between sleep quality (SQ) and improvements in low back pain (LBP) and disability, among patients treated for LBP in routine practice. METHODS: This prospective cohort study included 461 subacute and chronic LBP patients treated in 11 specialized centres, 14 primary care centres and eight physical therapy practices across 12 Spanish regions. LBP, leg pain, disability, catastrophizing, depression and SQ were assessed through validated questionnaires upon recruitment and 3 months later. Logistic regression models were developed to assess: (1) the association between the baseline score for SQ and improvements in LBP and disability at 3 months, and (2) the association between improvement in SQ and improvements in LBP and disability during the follow-up period. RESULTS: Seventy-three per cent of patients were subacute. Median scores at baseline were four points for both pain and disability, as assessed with a visual analog scale and the Roland-Morris Questionnaire, respectively. Regression models showed (OR [95% CI]) that baseline SQ was not associated with improvements in LBP (0.99 [0.94; 1.06]) or in disability (0.99 [0.93; 1.05]), although associations existed between 'improvement in SQ' and 'improvement in LBP' (4.34 [2.21; 8.51]), and 'improvement in SQ' and 'improvement in disability' (4.60 [2.29; 9.27]). CONCLUSIONS: Improvement in SQ is associated with improvements in LBP and in disability at 3-month follow-up, suggesting that they may reflect or be influenced by common factors. However, baseline SQ does not predict improvements in pain or disability. SIGNIFICANCE: In clinical practice, sleep quality, low back pain and disability are associated. However, sleep quality at baseline does not predict improvement in pain and disability.

Lectura crítica de revisiones sistemáticas y metanálisis en el diagnóstico por imagen / Critical reading of systematic reviews and meta-analyses about diagnostic imaging

Las revisiones sistemáticas de validez diagnóstica se han propuesto como la mejor herramienta metodológica para integrar toda la evidencia disponible y servir de apoyo en la decisión de utilizar, o no, una determinada prueba diagnóstica. Tienen por objeto sintetizar en una pareja de índices, generalmente sensibilidad y especificidad, o en forma de curva SROC, los resultados de los distintos estudios primarios obtenidos. Si bien existe un cierto paralelismo con las revisiones de eficacia de intervenciones terapéuticas, estas presentan peculiaridades que añaden complejidad al análisis e interpretación de los resultados. En este artículo se enfatizan aquellos aspectos metodológicos que permiten evaluar de forma crítica cuán válidos son los resultados de una revisión de validez de pruebas diagnósticas y se aportan unas nociones estadísticas básicas para comprender los resultados (AU)

Systematic reviews of diagnostic validity have been proposed as the best methodological tool to integrate all the available evidence and to help physicians decide whether to use a given diagnostic test. These studies aim to synthesize the results obtained in different primary studies into a couple of indices, generally sensitivity and specificity, or into a summary receiver operating characteristic (ROC) curve. Although there is a certain parallelism with reviews about the efficacy of therapeutic interventions, reviews of diagnostic validity have certain peculiarities that add complexity to the analysis and interpretation of the results. This article emphasizes the methodological aspects that make it possible to critically assess the extent to which the results of a review of the validity of diagnostic tests are valid and provides rudimentary knowledge of the statistics necessary to understand the results (AU)

[Critical reading of systematic reviews and meta-analyses about diagnostic imaging]. / Lectura crítica de revisiones sistemáticas y metanálisis en el diagnóstico por imagen.

Systematic reviews of diagnostic validity have been proposed as the best methodological tool to integrate all the available evidence and to help physicians decide whether to use a given diagnostic test. These studies aim to synthesize the results obtained in different primary studies into a couple of indices, generally sensitivity and specificity, or into a summary receiver operating characteristic (ROC) curve. Although there is a certain parallelism with reviews about the efficacy of therapeutic interventions, reviews of diagnostic validity have certain peculiarities that add complexity to the analysis and interpretation of the results. This article emphasizes the methodological aspects that make it possible to critically assess the extent to which the results of a review of the validity of diagnostic tests are valid and provides rudimentary knowledge of the statistics necessary to understand the results.

Determinants of between-hospital variations in outcomes for patients admitted with COPD exacerbations: findings from a nationwide clinical audit (AUDIPOC) in Spain.

BACKGROUND: Previous studies have demonstrated significant variability in the processes of care and outcomes of chronic obstructive pulmonary disease (COPD) exacerbations. The AUDIPOC is a Spanish nationwide clinical audit that identified large between-hospital variations in care and clinical outcomes. Here, we test the hypothesis that these variations can be attributed to either patient characteristics, hospital characteristics and/or the so-called hospital-clustering effect, which indicates that patients with similar characteristics may experience different processes of care and outcomes depending on the hospital to which they are admitted. METHODS: A clinical audit of 5178 COPD patients consecutively admitted to 129 Spanish public hospitals was performed, with a 90-day follow-up. Multilevel regression analysis was conducted to model the probability of patients experiencing adverse outcomes. For each outcome, an empty model (with no independent variables) was fitted to assess the clustering effect, followed by a model adjusted for the patient- and hospital-level covariables. The hospital-clustering effect was estimated using the intracluster correlation coefficient (ICC); the cluster heterogeneity was estimated with the median odds ratio (MOR), and the coefficients of predictors were estimated with the odds ratio (OR). RESULTS: In the empty models, the ICC (MOR) for inpatient mortality and the follow-up mortality and readmission were 0.10 (1.80), 0.08 (1.65) and 0.01 (1.24), respectively. In the adjusted models, the variables that most represented the patients' clinical conditions and interventions were identified as outcome predictors and further reduced the hospital variations. By contrast, the resource factors were primarily unrelated with outcomes. CONCLUSIONS: This study demonstrates a noteworthy reduction in the observed crude between-hospital variation in outcomes after accounting for the hospital-cluster effect and the variables representing patient's clinical conditions. This emphasises the predictor importance of the patients' clinical conditions and interventions, and understates the impacts of hospital resources and organisational factors.

Assessment of the reproducibility of oligoclonal IgM band detection for its application in daily clinical practice.

BACKGROUND: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice. METHODS: The presence of OCMB was analysed by IEF and western blot with prior reduction of pentameric IgM. We assayed the reproducibility of this test in a blinded multicentre study performed in 13 university hospitals. Paired-CSF and serum samples from 52 neurological patients were assayed at every centre. RESULTS: Global analysis rendered a concordance of 89.8% with a kappa value of 0.71. CONCLUSION: These data indicate that OCMB detection by means of IEF and western blot with IgM reduction shows a good interlaboratory reproducibility and thus can be used in daily clinical setting.

A preliminary model to avoid the overestimation of sample size in bioequivalence studies.

Often the only available data in literature for sample size estimations in bioequivalence studies is intersubject variability, which tends to result in overestimation of sample size. In this paper, we proposed a preliminary model of intrasubject variability based on intersubject variability for Cmax and AUC data from randomized, crossovers, bioequivalence (BE) studies. From 93 Cmax and 121 AUC data from test-reference comparisons that fulfilled BE criteria, we calculated intersubject variability for the reference formulation and intrasubject variability from ANOVA. Lineal and exponential models (y=a(1-e-bx)) were fitted weighted by the inverse of the variance, to predict the intrasubject variability based on intersubject variability. To validate the model we calculated the coefficient of cross-validation of data from 30 new BE studies. The models fit very well (R2=0.997 and 0.990 for Cmax and AUC respectively) and the cross-validation correlation were 0.847 for Cmax and 0.572 for AUC. A preliminary model analyses allow us to estimate the intrasubject variability based on intersubject variability for sample size calculation purposes in BE studies. This approximation provides an opportunity for sample size reduction avoiding unnecessary exposure of healthy volunteers. Further modelling studies are desirable to confirm these results especially suggestions of the higher intersubject variability range.

Visual analogue scales for grading faecal incontinence and quality of life: their relationship with the Jorge-Wexner score and Rockwood scale.

BACKGROUND: The purpose of this study was to determine the probability of substituting two validated methods frequently used for scoring severity and quality of life of faecal incontinence (FI) by a single score represented in a visual analogue scale (VAS). METHODS: One hundred and three consecutive unselected patients affected by FI of different aetiologies were prospectively included in the study. Evaluation of the continence status and quality of life referred to the last month was scored by (1) Jorge-Wexner score, (2) Rockwood FIQL scale, (3) Visual Analogue Scale for Faecal Incontinence (VASFI), and (4) Visual Analogue Scale for Quality of Life (VASQL). Patients unable to respond accurately to one or more of the questionnaires were excluded. The Bland and Altman method was applied to evaluate the agreement between Jorge-Wexner and VASFI. Correlation between both the analogue scales (VASFI and VASQL) and each one with each of the four FIQL scale scores was first determined by an analysis of simple correlation with each subscale and thereafter by multiple regression analysis following the backward strategy. RESULTS: Comparison of VASFI with the Jorge-Wexner score shows that the two methods are neither concordant nor interchangeable, and in a given patient, the differences between both may fluctuate between 5.4 and -10.6 (95 % confidence interval). Correlation of VASFI and VASQL shows that the correlation between both the analogue scales is middling (r (2) = 0.543, ß coefficient -0.538). Correlation of VASFI and FIQL subscales shows that in simple regression analysis, VASFI correlates with lifestyle, coping/behaviour, and embarrassment, but after multiple regression analysis, VASFI correlates significantly only with embarrassment. Correlation of VASQL and FIQL subscales shows that in simple regression analysis, VASQL correlates with lifestyle, coping/behaviour, and embarrassment, but after multiple regression analysis, VASQL only correlates significantly with coping/behaviour. CONCLUSIONS: This study shows that a VAS for FI cannot replace the Jorge-Wexner score and a VAS for quality of life cannot substitute all the four subscales of FIQL. Severity of FI and its impact on quality of life expressed in a VAS only have a fair correlation, showing that they do not assess the same issues, which is also supported by the finding that VASFI correlates significantly only with the embarrassment subscale of FIQL.

Vertebral endplate changes are not associated with chronic low back pain among Southern European subjects: a case control study.

BACKGROUND AND PURPOSE: Data on the association between vertebral endplate changes and low back pain are contradictory. This study was designed to assess whether this association exists among Southern European subjects. MATERIALS AND METHODS: Patients in this study serving as cases were 35-50 years of age with low back pain lasting >90 days, for whom a lumbar MR imaging had been prescribed. Controls were subjects 35-50 years of age, having a cranial MR imaging for headache with normal findings, and no history of clinically relevant LBP. Two hundred forty cases and 64 controls were recruited consecutively in the radiology services across 6 cities in Spain. Imaging findings and subject characteristics were gathered through previously validated instruments. Radiologists who interpreted MRI were blinded to the subject characteristics. A multivariate logistic regression model was developed to assess the association of vertebral endplate changes with LBP, adjusting for sex, age, body mass index, lifetime exposure to smoking, physical activity, disk degeneration, and the interaction between disk degeneration and vertebral endplate changes. RESULTS: Vertebral endplate changes were found in 80.4% of the cases and in 87.5% of the controls. In the regression model, disk degeneration was the only variable showing a confounding effect. Results showed that after adjusting for disk degeneration, the presence of vertebral endplate changes is associated with the absence of chronic LBP (OR for LBP: 0.31; 95% CI, 0.10-0.95). CONCLUSIONS: In Southern European subjects, vertebral endplate changes are not associated with chronic LBP.

Utility of oligoclonal IgG band detection for MS diagnosis in daily clinical practice.

An early and accurate diagnosis of multiple sclerosis (MS) is very important, since it allows early treatment initiation, which reduces the activity of the disease. Oligoclonal IgG band (OCGB) detection is a good ancillary tool for MS diagnosis. However, it was argued that its usefulness was limited by the high interlaboratory variability. In the last years, different techniques for OCGB detection have appeared. We performed a blinded aleatorized multicenter study in 19 Spanish hospitals to assess the accuracy and reproducibility of OCGB detection in this new scenario. We studied cerebrospinal fluid (CSF) and serum samples from 114 neurological patients. Every hospital contributed to the study with triplicated pairs of CSF and serum samples of six patients and analyzed 18 different samples. Global analysis rendered a sensitivity of 92.1%, a specificity of 95.1% and a Kappa value of 0.81. This shows that current techniques for OCGB detection have good accuracy and a high interlaboratory reproducibility and thus, represent a good tool for MS diagnosis. When we analyzed separately the different techniques used for OCGB detection, the highest concordance was observed in western blot with alkaline phosphatase detection (kappa=0.91). This indicates that high sensitivity techniques improve the reproducibility of this assay.

Influence of nomenclature in the interpretation of lumbar disk contour on MR imaging: a comparison of the agreement using the combined task force and the nordic nomenclatures.

BACKGROUND AND PURPOSE: The CTF nomenclature had not been tested in clinical practice. The purpose of this study was to compare the reliability and diagnostic confidence in the interpretation of disk contours on lumbar 1.5T MR imaging when using the CTF and the Nordic nomenclatures. MATERIALS AND METHODS: Five general radiologists from 3 hospitals blindly and independently assessed intravertebral herniations (Schmorl node) and disk contours on the lumbar MR imaging of 53 patients with low back pain, on 4 occasions. Measures were taken to minimize the risk of recall bias. The Nordic nomenclature was used for the first 2 assessments, and the CTF nomenclature, in the remaining 2. Radiologists had not previously used either of the 2 nomenclatures. κ statistics were calculated separately for reports deriving from each nomenclature and were categorized as almost perfect (0.81-1.00), substantial (0.61-0.80), moderate (0.41-0.60), fair (0.21-0.40), slight (0.00-0.20), and poor (<0.00). RESULTS: Categorization of intra- and interobserver agreement was the same across nomenclatures. Intraobserver reliability was substantial for intravertebral herniations and disk contour abnormalities. Interobserver reliability was moderate for intravertebral herniations and fair to moderate for disk contour. CONCLUSIONS: In conditions close to clinical practice, regardless of the specific nomenclature used, a standardized nomenclature supports only moderate interobserver agreement. The Nordic nomenclature increases self-confidence in an individual observer's report but is less clear regarding the classification of disks as normal versus bulged.

Utility of diagnostic tests in the follow-up of egg-allergic children.

BACKGROUND: Better knowledge of the accuracy of a skin prick test (SPT) and specific IgE (sIgE) levels to egg allergens would help to identify persistent egg-allergic children, avoiding unnecessary risky challenges. This study was designed to assess the accuracy of a SPT and sIgE levels to egg allergens in order to determine persistent egg allergy in IgE-mediated allergic children after an egg-free diet. METHODS: Children below 16 years were prospectively and consecutively recruited. Inclusion criteria were: allergy to egg proteins (children with a positive clinical case of IgE-mediated egg allergy and a positive SPT to egg allergens and/or positive sIgE levels), and strict egg avoidance diet followed for at least 6 months. Clinical histories were recorded and all patients underwent SPTs, sIgE levels to egg allergens and the gold standard -a double-blind placebo-controlled egg challenge (DBPCFG). DBPCFG was interpreted without knowledge of the results of the other tests and vice-versa. A SPT and sIgE levels' ROC curves analysis was performed to compare the diagnostic performance of the different tests. RESULTS: Finally, 157 children were included in the study. One hundred out of these 157 children (63.7%) had a positive oral challenge. Ninety-six were male (61%), and the median age was 2.5 years. One hundred and three (66.9%) had atopic dermatitis. A 7 mm egg white prick test had a positive likelihood ratio (+LR) of 6.7, and a level of 1.3 KU/L egg white-sIgE had a +LR of 5.1. A 7 mm egg white SPT had a positive predictive value of 92.3% (95% CI 85.1-99.5), and for a 9 mm egg white SPT this value was 95.6% (95% CI 87.3-100.0). For egg white-sIgE, 1.5 KU/L had a positive predictive value of 90.4% (95% CI 82.4-98.4) and for 25 KU/L it was 100.0% (95% CI 100.0-100.0). SPTs with ovotransferrin and lysozyme showed the lowest accuracy, followed by yolk and ovalbumin SPTs. CONCLUSION: This study is the first to evaluate both tests (SPT and sIgE levels) and all egg allergens to determine the persistence of egg allergy in IgE-mediated allergic children. Measuring the SPT and sIgE levels is useful to predict persistent allergy in these children, especially with the egg white complete extract. An oral challenge should not be performed in egg allergic paediatric patients with either an egg white prick test above 7 mm or a white egg-sIgE determination above 1.3 KU/L, because there is a 90% probability of remaining allergic.

Agreement in the interpretation of magnetic resonance images of the lumbar spine.

BACKGROUND: Correlation between clinical features and magnetic resonance imaging (MRI) findings is essential in low-back-pain patients. Most previous studies have analyzed concordance in the interpretation of lumbar MRI among a few radiologists who worked together. This may have overestimated concordance. PURPOSE: To evaluate intra- and interobserver agreement in the interpretation of lumbar MRI performed in an open 0.2 T system. MATERIAL AND METHODS: Seven radiologists from two different geographic settings in Spain interpreted the lumbar MRIs of 50 subjects representative of the general Danish population aged 40 years. The radiologists interpreted the images in routine clinical practice, having no knowledge of the clinical and demographic characteristics of the subjects and blinded to their colleagues' assessments. Six of the radiologists evaluated the same MRIs 14 days later, having no knowledge of the previous results. Data on the existence of disc degeneration, high-intensity zones, disc contour, Schmorl nodes, Modic changes, osteophytes, spondylolisthesis, and spinal stenosis were collected in the Nordic Modic Consensus Group Classification form. Intra- and interobserver agreement was analyzed for variables with a prevalence >or=10% and

Análisis de la calidad de los estudios de evaluación de pruebas diagnósticas / No disponible

A pesar de la importancia del diagnóstico en el desarrollo de una buena práctica clínica, la investigación que evalúa el valor de las pruebas diagnósticas es de baja calidad metodológica. Por otro lado, los artículos que describen esta investigación presentan importantes defectos y carencias que hacen difícil la tarea de evaluar críticamente las evidencias disponibles sobre el valor de una prueba. En este artículo se recuerdan los elementos del diseño más importantes de estos estudios de investigación y se describe una herramienta validada para la evaluación de la calidad metodológica de la investigación sobre diagnóstico (AU)

La Red Española de Investigadores en Dolencias de la Espalda (REIDE). Definición y actividad / No disponible

No disponible

Long-term outcome of acute tubular necrosis: a contribution to its natural history.

As long-term outcome studies of acute renal failure (ARF) are scarce and non-homogeneous, we studied 187 consecutive acute tubular necrosis (ATN) patients without previous nephropathies, discharged alive from our hospital between October 77 and December 92 and followed-up until December 99 (range 7-22 years; median 7.2). Variables were analyzed at the time of the acute episode and during follow-up. In 2000-2001 a clinical evaluation was made in 58 of the 82 patients still alive. Ten patients were lost to follow-up and 95 died. In 59% death was related with the disease present when the ATN developed. Kaplan-Meir survival curve showed 89, 67, 50, and 40% at 1, 5, 10, and 15 years, respectively, after discharge. Survival curves were significantly better (log-rank P<0.001) among the youngest, those surviving a polytrauma, those without comorbidity and surprisingly those treated in intensive care units. The proportional Cox model showed that age (hazard ratio (HR) 1.04 per year of age; P=0.000), presence of comorbid factors (HR 4.29; P=0.006), surgical admission (HR 0.45; P=0.000), and male sex (HR 1.72; P=0.020) were the variables associated with long-term follow-up. In the evaluated patients renal function was normal in 81%. Long-term outcome after ARF depends on absence of co-morbid factors, cause of initial admission and age. Although the late mortality rate is high and related with the original disease, renal function is adequate in most patients.

Idoneidad de las derivaciones de Atención Primaria a especialidades médicas hospitalarias / Adequacy of primary care referrals to medical specialities

INTRODUCCIÓN. El objetivo de este estudio es conocer la idoneidad de las interconsultas dirigidas desde Atención Primaria a especialidades médicas hospitalarias analizando sus características desde el punto de vista de las dos partes implicadas. MÉTODOS. Cuatro médicos (2 de Atención Primaria y 2 Internistas hospitalarios) analizaron retrospectivamente las peticiones de interconsulta y las notas de la primera consulta de 225 pacientes seleccionados aleatoriamente entre las consultas realizadas entre enero y julio de 2003 en un hospital de carácter provincial. RESULTADOS. El 26% de las interconsultas se consideraron innecesarias si se exige el acuerdo de los cuatro observadores (el 26,6% adecuadas y sin acuerdo en el 47,2% restante), y 37% cuando sólo se requiere que coincidan tres de los cuatro investigadores. La categoría en la que se alcanza un mayor grado de acuerdo es la de las consultas inadecuadas. Estas interconsultas corresponden a pacientes más jóvenes, procedentes del medio urbano, se acompañan de hojas de solicitud de consulta de peor calidad y generan un menor número de revisiones. CONCLUSIONES. Las consultas externas médicas hospitalarias están lastradas por un número muy elevado de IC no adecuadas o innecesarias, a las que se remiten pacientes con características diferentes de aquellos remitidos para consultas consideradas adecuadas

INTRODUCTION. This study aims to know the adequacy of specialized care referrals from Primary Care to hospital medical specialities, analyzing their characteristics from the point of view of the two parties involved. METHODS. Four doctors (2 from primary care and 2 hospital internists) retrospectively analyzed the specialized care requests and notes of the first consultation of 225 patients randomly selected among the consultations made between January and July 2003 in a provincial Hospital. RESULTS. A total of 26% of the specialized care referrals were considered unnecessary if agreement of four observers is required (26.6% adequate and no agreement in the remaining 47.2%) and 37% were considered unnecessary when three of the four investigators had to agree. The category that reaches the highest degree of agreement is that of inadequate consultations. These referrals correspond to younger patients, from urban setting. They are accompanied by consultation request sheets having worse quality and generate fewer reviews. CONCLUSIONS. The hospital out-patient visits are hindered by a very high number of inadequate or unnecessary specialized care consultations, to which patients are sent with characteristics different from those sent with consultations that are considered to be adequate

Phacoemulsification in previously vitrectomized patients: an analysis of the surgical results in 100 eyes as well as the factors contributing to the cataract formation.

PURPOSE: To evaluate the safety and effectiveness of phacoemulsification with clear corneal incision in previously vitrectomized patients as well as factors affecting the development time and type of cataract occurring after pars plana vitrectomy (PPV). METHODS: The authors conducted a prospective study of 100 consecutive eyes of patients who developed a cataract after PPV. Three groups were established based on the underlying vitreoretinal pathology. The main outcome measurements were intraoperative and postoperative complications and changes in best-corrected visual acuity (BCVA). RESULTS: The median interval between PPV and phacoemulsification was 11.5 months. Patients with proliferative diabetic retinopathy required phacoemulsification earlier (p=0.018). Posterior subcapsular cataracts developed more frequently in patients <50 years (73.7%, p=0.000) and affected those who underwent vitrectomy primarily for complicated retinal detachment (48.8%, p=0.046). Intraoperative complications included posterior capsular tears (4%), luxated nucleus into vitreous (2%), and zonular dialysis (5%). Postoperative complications were vitreous hemorrhage (6%), retinal redetachment (4%), pupillary synechiae (6%), ocular hypertension (4%), and Seidel phenomenon (3%). Posterior Nd:YAG laser capsulotomy was required in 44% of eyes. BCVA was improved in 85% of cases at the end of follow-up (median, 15.5 months). Twenty-one patients with one functioning eye (61.9%) demonstrated visual improvement compared with 79 patients with bilateral vision (91.1%; p=0.003). CONCLUSIONS: The technique allows stable improvement in BCVA through long follow-ups. It is more risky than in nonvitrectomized eyes. The visual results after phacoemulsification in vitrectomized eyes seem to be limited by retinal comorbidity and surgical complications.

Sesgos en los estudios sobre pruebas diagnósticas / Biases in studies on diagnostic tests

Aunque el diagnóstico desempeña un papel central en la actividad clínica, los médicos reciben escaso entrenamiento formal en la utilización de pruebas diagnósticas durante su formación académica. Además la calidad de la investigación publicada sobre evaluación de pruebas diagnósticas es pobre. En esta nota se repasan los aspectos de diseño de esos estudios y la cuantificación empírica del impacto de los sesgos relacionados con ellos

Although the diagnosis plays a central role in the clinical practice, physicians receive scarce formal training in the use of diagnostic tests during their academic education. Furthermore, the quality of the investigation published on diagnostic test evaluation is poor. In this note, the aspects of these studies' design and the empiric quantification of the impact of the biases related with them are reviewed