Estudios de polimorfismos genéticos TNF-alfa (238 y 308), IL-10 (1082), MTHFR (677) y del DAS-28, como predictores de la respuesta al tratamiento con Infliximab, en la Artritis Reumática.

RESUMEN La importancia de la artritis reumatoide como enfermedad crónica y progresiva, prevalente e incapacitante, plantea el problema de establecer un tratamiento efectivo y precoz para ralentizar en lo posible el curso de la enfermedad y evitar la utilización de medicamentos innecesarios teniendo en cuenta que los medicamentos biológicos de última generación no están exentos de reacciones adversas importantes. En este trabajo se aborda la capacidad de los polimorfismos en los genes del TNF-alfa en las posiciones 238 y 308, de la Interleukina-10 en la posición 1082, de gen de la metilen-tetra-hidro-folato-reductasa (MTHFR) en la posición 677, así como del indicador DAS28 como predictores de la respuesta al tratamiento con infliximab en los pacientes con Artritis Reumatoide. Se trata de un estudio observacional prospectivo-retrospectivo sobre 74 pacientes, a los que se le ha realizado un seguimiento clínico durante unas 30 administraciones del fármaco, aproximadamente unos 4 años, según protocolo habitual de utilización (0, 2 semanas, 4 semanas, y luego cada 8 semanas).Se han agrupado los pacientes en función de su grado de respuesta al tratamiento con infliximab, clasificándose a los pacientes en tres grupos; pacientes respondedores, no respondedores y respondedores temporales que son aquellos que inicialmente han respondido al tratamiento, pero que durante el seguimiento, atendiendo al juicio clínico de los reumatólogos, siendo este la variable independiente del estudio. Se recogen, entre otros, los parámetros clínicos habituales necesarios para el cálculo del DAS28, y que son la Velocidad de sedimentación sanguínea (VSG), el número de articulaciones dolorosas, el número de articulaciones tumefactas, el estado general valorado por el enfermo, y finalmente las reacciones adversas acontecidas durante el seguimiento. La determinación de los polimorfismos genéticos se ha realizado mediante la técnica de la reacción en cadena de la polimerasa (PCR). Para el tratamiento estadístico de los polimorfismos se han realizado análisis de frecuencia, y para la comparación de los datos clínicos entre los grupos de pacientes, tanto basales como tras cada administración, se ha realizado un análisis de la varianza, determinandose con posterioridad los grupos diferenciados mediante pruebas de diferencia mínima significativa (DMS) y Bonferroni y para determinar la evolución a lo largo del tiempo del DAS28 se realiza un análisis lineal multivariante, con posterior comparación entre las distintas administraciones mediante DMS y Bonferroni. Los resultados obtenidos a partir de los análisis de frecuencias parecen indicar que la influencia de los polimorfismos estudiados, el sexo, el factor reumatoide y las causas de finalización del tratamiento, no tienen relación significativa con la mejor o peor respuesta al tratamiento. Así mismo, la correlación entre la valoración clínica del reumatólogo y la valoración según el indicador DAS-28 no parece ser alta, por lo que se plantean posibles limitaciones para la utilización de este indicador, como serían la forma en que se establece el valor basal de partida, ya que las variaciones antes de iniciar el tratamiento pueden ser muy significativas y de una magnitud similar a las que este indicador registra cuando se produce respuesta al tratamiento. Así mismo, el tiempo de evolución necesario y conveniente para observar la totalidad de de la eficacia del tratamiento puede no ser suficiente tal y como se lleva a cabo actualmente. Finalmente el hecho de que este indicador no tenga en cuenta la intensidad de partida de la enfermedad, son elementos de controversia en la utilización de este indicador. Así mismo se propone la conveniencia de utilizar el %DAS28 como elemento de valoración de la respuesta al tratamiento con Infliximab, pues parece que esta simple transformación es capaz de predecir de forma más precoz que el DAS-28, la respuesta de los pacientes. __________________________________________________________________________________________________Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease that mainly affects the synovial joints and that has a worldwide prevalence of 1%, affecting women and men disproportionately (2:1, respectively). Early, aggressive disease management is critical for halting disease progression and joint destruction in these patients. Biologic therapies represent more affective and tolerable treatment options than clasical antirheumatic drugs. Currently, two classes of biologic agents are approved for RA: tumor necrosis factor (TNF) inhibitors and interleukin-1 receptor antagonists. In the present study we have investigated whether two polymorphisms in the promoter region of the TNF-alpha gene (-308 G/A and -238 G/A), one of the interleukin-10 gene (IL-10)( -1082 G/A), and one of 5,10-methylenetetrahydrofolate reductase (MTHFR)(-677C/T), as well as the DAS28 index can be used as predictive on the response of RA patients to infliximab (a TNF-alpha inhibitor) treatment. This is an observational prospective/retrospective non-randomized clinical follow-up study on 74 RA patients submitted to infliximab treatment following the standard protocol (0, 2, 4 and 8 weeks and then 1 dose every 8 weeks) for a total of 30 doses. Depending on the clinical response to the drug (the independent variable of the study) patients were considered responders, non-responders and temporarily responders. Data on standard clinical parameters needed for DAS28 calculation were collected, including Globular Sedimentation Speed, number of painful and tumefied joints, general wellness state self-evaluated by the patient and, finally, adverse reactions to the drug observed along treatment period. Genetic polymorphisms were studied by polymerase chain reactionrestriction fragment length polymorphisms analysis, and the significance of difference in allele frequency calculated. To compare the evolution of DAS28 index a lineal multivariate analysis was performed. A statistical relationship between the evolution of RA in response to the infliximab treatment and allele frequency of the different polymorphisms or between infliximab treatment and clinical and laboratory parameters studied could not be found. Moreover, there are controversial elements as to the convenience to use DAS28 as an index to evaluate the response to infliximab treatmen

Validação de indicadores de qualidade do cuidado cirúrgico no Sistema Único de Saúde

OBJETIVO: Validar um conjunto de indicadores para monitoramento da qualidade dos procedimentos cirúrgicos no Sistema Único de Saúde (SUS). MÉTODOS: Estudo de validação desenvolvido em 5 etapas: 1) revisão de literatura; 2) priorização de indicadores; 3) validação de conteúdo dos indicadores por método de consenso RAND/UCLA; 4) estudo piloto para análise da confiabilidade; e 5) desenvolvimento de instrutivo para tabulação dos indicadores de resultado para monitoramento via sistemas de informações oficiais. RESULTADOS: A partir da revisão de literatura, foram identificados 217 indicadores de qualidade cirúrgica. Os indicadores excluídos foram: indicadores baseados em evidências científicas inferiores a 1A, similares, específicos, que correspondiam a eventos sentinelas; e aqueles que não se aplicavam ao contexto do SUS. Foram submetidos ao consenso de especialistas 26 indicadores com alto nível de evidência científica. Foram validados 22 indicadores, dos quais 14 indicadores de processo e 8 indicadores de resultado com índice de validação de conteúdo ≥80%. Dos indicadores de processo validados, 6 foram considerados confiáveis substancialmente (Coeficiente de Kappa entre 0,6 e 0,8; p < 0,05) e 2 tiveram confiabilidade quase perfeita (coeficiente de Kappa > 0,8, p < 0,05), quando analisada a concordância interavaliador. Foi possível mensurar e estabelecer mecanismo de tabulação para TabWin para 7 indicadores de resultado. CONCLUSÃO: O estudo contribui com o desenvolvimento de um conjunto de indicadores cirúrgicos potencialmente eficazes para o monitoramento da qualidade do cuidado e segurança do paciente nos serviços hospitalares do SUS.OBJECTIVE: To validate a set of indicators for monitoring the quality of surgical procedures in the Unified Health System (SUS). METHODS: Validation study developed in 5 stages: 1) literature review; 2) prioritization of indicators; 3) content validation of indicators by RAND/UCLA consensus method; 4) pilot study for reliability analysis; and 5) development of instruction for tabulation of outcome indicators for monitoring via official information systems. RESULTS: From the literature review, 217 indicators of surgical quality were identified. The excluded indicators were: those based on scientific evidence lower than 1A, similar, specific, which corresponded to sentinel events; and those that did not apply to the SUS context. Twenty-six indicators with a high level of scientific evidence were submitted to expert consensus. Twenty-two indicators were validated, of which 14 process indicators and 8 outcome indicators with content validation index ≥80%. Of the validated process indicators, 6 were considered substantially reliable (Kappa coefficient between 0.6 and 0.8; p < 0.05) and 2 had almost perfect reliability (Kappa coefficient > 0.8, p < 0.05), when the inter-rater agreement was analyzed. One could measure and establish tabulation mechanism for TabWin for 7 outcome indicators. CONCLUSION: The study contributes to the development of a set of potentially effective surgical indicators for monitoring the quality of care and patient safety in SUS hospital services

Newborn Screening for SCID: Experience in Spain (Catalonia)

Linfocitos T; Cribado de recién nacidos; Inmunodeficiencia combinada severaLimfòcits T; Cribratge de nounats; Immunodeficiència combinada severaT-lymphocytes; Newborn screening; Severe combined immunodeficiencyNewborn screening (NBS) for severe combined immunodeficiency (SCID) started in Catalonia in January-2017, being the first Spanish and European region to universally include this testing. In Spain, a pilot study with 5000 samples was carried out in Seville in 2014; also, a research project with about 35,000 newborns will be carried out in 2021–2022 in the NBS laboratory of Eastern Andalusia. At present, the inclusion of SCID is being evaluated in Spain. The results obtained in the first three and a half years of experience in Catalonia are presented here. All babies born between January-2017 and June-2020 were screened through TREC-quantification in DBS with the Enlite Neonatal TREC-kit from PerkinElmer. A total of 222,857 newborns were screened, of which 48 tested positive. During the study period, three patients were diagnosed with SCID: an incidence of 1 in 74,187 newborns; 17 patients had clinically significant T-cell lymphopenia (non-SCID) with an incidence of 1 in 13,109 newborns who also benefited from the NBS program. The results obtained provide further evidence of the benefits of early diagnosis and curative treatment to justify the inclusion of this disease in NBS programs. A national NBS program is needed, also to define the exact SCID incidence in Spain

Surgical Infection Reduction Program of the Observatory of Surgical Infection (PRIQ-O): Delphi prioritization and consensus document on recommendations for the prevention of surgical site infection

La infección de localización quirúrgica es la complicación más frecuente y más evitable de la cirugía, pero las guías clínicas para su prevención tienen un seguimiento insuficiente. Presentamos los resultados de un consenso Delphi realizado por un panel de expertos de 17 sociedades científicas con revisión crítica de la evidencia científica y guías internacionales, para seleccionar las medidas con mayor grado de evidencia y facilitar su implementación. Se revisaron 40 medidas y se emitieron 53 recomendaciones. Se priorizan 10 medidas principales para su inclusión en bundles de prevención: ducha preoperatoria; correcta higiene quirúrgica de manos; no eliminación del vello del campo quirúrgico o eliminación con maquinilla eléctrica; profilaxis antibiótica sistémica adecuada; uso de abordajes mínimamente invasivos; descontaminación de la piel con soluciones alcohólicas; mantenimiento de la normotermia; protectores-retractores plásticos de herida; cambio de guantes intraoperatorio, y cambio de material quirúrgico y auxiliar antes del cierre de las heridasSurgical site infection is the most frequent and avoidable complication of surgery, but clinical guidelines for its prevention are insufficiently followed. We present the results of a Delphi consensus carried out by a panel of experts from 17 Scientific Societies with a critical review of the scientific evidence and international guidelines, to select the measures with the highest degree of evidence and facilitate their implementation. Forty measures were reviewed and 53 recommendations were issued. Ten main measures were prioritized for inclusion in prevention bundles: preoperative shower; correct surgical hand hygiene; no hair removal from the surgical field or removal with electric razors; adequate systemic antibiotic prophylaxis; use of minimally invasive approaches; skin decontamination with alcoholic solutions; maintenance of normothermia; plastic wound protectors-retractors; intraoperative glove change; and change of surgical and auxiliary material before wound closur

First universal newborn screening program for severe combined immunodeficiency in Europe: two-years' experience in Catalonia (Spain)

Newborn screening; Severe combined immunodeficiency; T-cell receptor excision circlesCribratge de nadons; Immunodeficiència combinada greu; Cercles d'excisió de receptors de cèl·lules TCribado de recién nacidos; Inmunodeficiencia combinada grave; Círculos de escisión de receptores de células TSevere combined immunodeficiency (SCID), the most severe form of T-cell immunodeficiency, can be screened at birth by quantifying T-cell receptor excision circles (TRECs) in dried blood spot (DBS) samples. Early detection of this condition speeds up the establishment of appropriate treatment and increases the patient's life expectancy. Newborn screening for SCID started in January 2017 in Catalonia, the first Spanish and European region to universally include this testing. The results obtained in the first 2 years of experience are evaluated here. All babies born between January 2017 and December 2018 were screened. TREC quantification in DBS (1.5 mm diameter) was performed with the Enlite Neonatal TREC kit from PerkinElmer (Turku, Finland). In 2018, the retest cutoff in the detection algorithm was updated based on the experience gained in the first year, and changed from 34 to 24 copies/μL. This decreased the retest rate from 3.34 to 1.4% (global retest rate, 2.4%), with a requested second sample rate of 0.23% and a positive detection rate of 0.02%. Lymphocyte phenotype (T, B, NK populations), expression of CD45RA/RO isoforms, percentage and intensity of TCR αβ and TCR γδ, presence of HLA-DR+ T lymphocytes, and in vitro lymphocyte proliferation were studied in all patients by flow cytometry. Of 130,903 newborns screened, 30 tested positive, 15 of which were male. During the study period, one patient was diagnosed with SCID: incidence, 1 in 130,903 births in Catalonia. Thirteen patients had clinically significant T-cell lymphopenia (non-SCID) with an incidence of 1 in 10,069 newborns (43% of positive detections). Nine patients were considered false-positive cases because of an initially normal lymphocyte count with normalization of TRECs between 3 and 6 months of life, four infants had transient lymphopenia due to an initially low lymphocyte count with recovery in the following months, and three patients are still under study. The results obtained provide further evidence of the benefits of including this disease in newborn screening programs. Longer follow-up is needed to define the exact incidence of SCID in Catalonia

Surgical Infection Reduction Program of the Observatory of Surgical Infection (PRIQ-O): Delphi prioritization and consensus document on recommendations for the prevention of surgical site infection

[ES] La infección de localización quirúrgica es la complicación más frecuente y más evitable de la cirugía, pero las guías clínicas para su prevención tienen un seguimiento insuficiente. Presentamos los resultados de un consenso Delphi realizado por un panel de expertos de 17 sociedades científicas con revisión crítica de la evidencia científica y guías internacionales, para seleccionar las medidas con mayor grado de evidencia y facilitar su implementación. Se revisaron 40 medidas y se emitieron 53 recomendaciones. Se priorizan 10 medidas principales para su inclusión en bundles de prevención: ducha preoperatoria; correcta higiene quirúrgica de manos; no eliminación del vello del campo quirúrgico o eliminación con maquinilla eléctrica; profilaxis antibiótica sistémica adecuada; uso de abordajes mínimamente invasivos; descontaminación de la piel con soluciones alcohólicas; mantenimiento de la normotermia; protectores-retractores plásticos de herida; cambio de guantes intraoperatorio, y cambio de material quirúrgico y auxiliar antes del cierre de las heridas.[EN] Surgical site infection is the most frequent and avoidable complication of surgery, but clinical guidelines for its prevention are insufficiently followed. We present the results of a Delphi consensus carried out by a panel of experts from 17 Scientific Societies with a critical review of the scientific evidence and international guidelines, to select the measures with the highest degree of evidence and facilitate their implementation. Forty measures were reviewed and 53 recommendations were issued. Ten main measures were prioritized for inclusion in prevention bundles: preoperative shower; correct surgical hand hygiene; no hair removal from the surgical field or removal with electric razors; adequate systemic antibiotic prophylaxis; use of minimally invasive approaches; skin decontamination with alcoholic solutions; maintenance of normothermia; plastic wound protectors-retractors; intraoperative glove change; and change of surgical and auxiliary material before wound closure.Peer reviewe

Predictive Power of the "Trigger Tool" for the detection of adverse events in general surgery: a multicenter observational validation study

Background In spite of the global implementation of standardized surgical safety checklists and evidence-based practices, general surgery remains associated with a high residual risk of preventable perioperative complications and adverse events. This study was designed to validate the hypothesis that a new “Trigger Tool” represents a sensitive predictor of adverse events in general surgery. Methods An observational multicenter validation study was performed among 31 hospitals in Spain. The previously described “Trigger Tool” based on 40 specific triggers was applied to validate the predictive power of predicting adverse events in the perioperative care of surgical patients. A prediction model was used by means of a binary logistic regression analysis. Results The prevalence of adverse events among a total of 1,132 surgical cases included in this study was 31.53%. The “Trigger Tool” had a sensitivity and specificity of 86.27% and 79.55% respectively for predicting these adverse events. A total of 12 selected triggers of overall 40 triggers were identified for optimizing the predictive power of the “Trigger Tool”. Conclusions The “Trigger Tool” has a high predictive capacity for predicting adverse events in surgical procedures. We recommend a revision of the original 40 triggers to 12 selected triggers to optimize the predictive power of this tool, which will have to be validated in future studies

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified