Condicionantes del éxito terapéutico de las infiltraciones de corticoides en el síndrome del dedo en resorte / Determinants of Therapeutic Success of Corticoids Injections in Trigger Finger Syndrome

Antecedentes y objetivo: El dedo en resorte es un motivo de consulta frecuente en el que las infiltraciones de corticoides juegan un papel terapéutico relevante en los grados de severidad intermedios cuando el tratamiento conservador no ha funcionado. Sin embargo, no existen criterios que permitan seleccionar qué pacientes se beneficiarán más de este procedimiento. El objetivo de nuestro estudio es identificar los condicionantes de éxito terapéutico de las infiltraciones de corticoides en estos pacientes. Materiales y métodos: Diseñamos un estudio prospectivo longitudinal basado en práctica clínica habitual con pacientes adultos, con diagnóstico clínico de dedo en resorte grado II o III, a quienes se les realizó una infiltración de 20mg de acetato de triamcinolona. Las variables desenlace fueron el alcanzar un grado Quinnell I o reducir en al menos una categoría la severidad del cuadro clínico, 2 meses después del procedimiento. Para determinar los condicionantes del alcance de los objetivos se realizó una modelización predictiva de regresión logística binaria utilizando aquellas variables que tuvieron una satisfactoria correlación univariante. Resultados: Se incluyeron 74 pacientes a lo largo de 3 años, 42 de los cuales (61,8%) tenían un grado Quinnell III. Tras la infiltración, 22 (32,4%) alcanzaron la resolución completa y 50 (73,5%), la resolución parcial. Las variables engrosamiento tendinoso (HR: 10,72; IC 95%: 2,88-39,93; p<0,001) y tiempo de evolución (HR: 1,23; IC 95%: 1,02-1,49; p=0,027) demostraron ser condicionantes predictoras del éxito terapéutico en la resolución completa. Para la modelización para resolución parcial las mismas variables demostraron ser condicionantes predictoras (HR: 5,57; IC 95%: 1,38-22,41; p=0,016 y HR: 1,18; IC 95% 0,99-1,41; p=0,051, respectivamente). El engrosamiento de la polea no demostró capacidad predictiva en ninguno de los 2 modelos.(AU)

Background and objective: Trigger finger is a frequent complaint in which corticosteroid infiltrations play a relevant therapeutic role in intermediate degrees of severity when conservative treatment has not worked. However, there are no criteria to select which patients will benefit most from this procedure. The present study aimed to identify the factors leading to the therapeutic success of corticosteroid infiltration in these patients. Materials and methods: We designed a prospective longitudinal study based on routine clinical practice with adult patients with a clinical diagnosis of trigger finger grade II or III on the Quinnell scale, who underwent an infiltration of 20mg of triamcinolone acetate. The outcome variables were to achieve a Quinnell grade I or reduce the severity of the symptoms by at least one category two months after the procedure. To identify the determinants of complete or partial therapeutic success, binary logistic regression predictive modelling was performed using those variables that had a satisfactory univariate correlation. Results: 74 patients were included over three years, 42 of whom (61.8%) were classified as Quinnell grade III. After infiltration, 22 (32.4%) achieved complete resolution and 50 (73.5%) partial resolution. The variables tendon thickening (HR 10.72; 95%CI 2.88-39.93; P<.001) and progression time (HR 1.23; 95%CI 1.02-1.49; P=.027) proved to be predictors of therapeutic success in complete resolution. For the modelling for partial resolution, the same variables proved to be determining predictors (HR 5.57; 95%CI 1.38-22.41; P=.016 and HR 1.18; 95%CI .99-1.41; P=.051, respectively). Pulley thickening did not demonstrate predictive ability in either model.(AU)

Valued attributes of professional support for people who repeatedly self-harm: A systematic review and meta-synthesis of first-hand accounts.

Therapeutic interventions are an important adjunct to self-help strategies for people who self-harm. There is little guidance for those offering therapy on the effective components of interventions for people who self-harm. This was a systematic review aiming to identify the factors that contribute to positive experiences of therapy as described by people who have reduced or stopped self-harm. The review followed PRISMA guidelines to locate and synthesize peer-reviewed qualitative studies describing experiences of therapy among people who had reduced or stopped self-harm. Study selection, data extraction, and quality assessment were peer reviewed and conducted for at least two researchers independently. Relevant first-hand quotations were extracted from eligible studies and synthesized using a thematic analysis in collaboration with experts with personal and professional experience of self-harm. Twenty-three studies met eligibility criteria. Themes identified in the reported accounts were arranged under two meta-themes. 'Positive aspects of seeing a professional' identified aspects of professional care that were common to all encounters: the value of sharing, space to talk and reflect, and the boundaries inherent in contact with a professional. 'Positive attributes of individual professionals' depended upon individual characteristics: the ability to build reciprocal trust by being non-judgemental, showing genuine empathic concern, and being confident to talk about and respond directly to self-harm. Our review indicates that therapeutic alliance is perceived as key to effective professional help for self-harm, irrespective of underlying principles of therapy. All forms of therapy should be timely and reliable and centred around the needs of the individual and their experience of self-harm.

Determinants of therapeutic success of corticoids injections in trigger finger syndrome.

BACKGROUND AND OBJECTIVE: Trigger finger is a frequent complaint in which corticosteroid infiltrations play a relevant therapeutic role in intermediate degrees of severity when conservative treatment has not worked. However, there are no criteria to select which patients will benefit most from this procedure. The present study aimed to identify the factors leading to the therapeutic success of corticosteroid infiltration in these patients. MATERIALS AND METHODS: We designed a prospective longitudinal study based on routine clinical practice with adult patients with a clinical diagnosis of trigger finger grade II or III on the Quinnell scale, who underwent an infiltration of 20 mg of triamcinolone acetate. The outcome variables were to achieve a Quinnell grade I or reduce the severity of the symptoms by at least one category two months after the procedure. To identify the determinants of complete or partial therapeutic success, binary logistic regression predictive modelling was performed using those variables that had a satisfactory univariate correlation. RESULTS: 74 patients were included over three years, 42 of whom (61.8%) were classified as Quinnell grade III. After infiltration, 22 (32.4%) achieved complete resolution and 50 (73.5%) partial resolution. The variables tendon thickening (HR 10.72; 95%CI 2.88-39.93; P < .001) and progression time (HR 1.23; 95%CI 1.02-1.49; P = .027) proved to be predictors of therapeutic success in complete resolution. For the modelling for partial resolution, the same variables proved to be determining predictors (HR 5.57; 95%CI 1.38-22.41; P = .016 and HR 1.18; 95%CI .99-1.41; P = .051, respectively). Pulley thickening did not demonstrate predictive ability in either model. DISCUSSION AND CONCLUSIONS: Our results indicate that the demonstration of finger flexor apparatus thickening is the main determining factor for the success of corticosteroid infiltrations in this pathology. This is in agreement with the histological findings of specimens obtained from both tenosynovial and pulley tissue. In the former, in addition to an infiltrate of inflammatory characteristics, the presence of chondrocytoid cells producing hyaluronic acid is demonstrated. Although the therapeutic success of infiltrations in previous studies reaches 70%, the recurrence rate is similar after 12 months. The selection of patients with tendon thickening ensures therapeutic success in the short term, could reduce recurrence in the long term, and avoid delay in release surgery.

Delivering brief physical activity interventions in primary care: a systematic review.

BACKGROUND: Physical activity (PA) brief interventions (BIs) involving screening and/or advice are recommended in primary care but frequency of delivery is unknown. AIM: To examine the extent to which PA BIs are delivered in primary care, and explore factors associated with delivery, receipt, and patient receptivity. DESIGN AND SETTING: A mixed-methods systematic review of studies conducted worldwide, with a narrative synthesis of results. METHOD: CINAHL, EMBASE, MEDLINE, and APA PsycINFO index databases were searched for qualitative and quantitative studies, dating from January 2012 to June 2020, that reported the level of delivery and/or receipt of PA BIs in primary care, and/or factors affecting delivery, receipt, and patient receptivity. Quality was assessed using the Mixed Methods Appraisal Tool. Attitudes towards and barriers to delivery were coded into the Theoretical Domains Framework and the Capability, Opportunity, and Motivation Behaviour model. RESULTS: After screening a total of 13 066 records, 66 articles were included in the review. The extent of PA screening and advice in primary care varied widely (2.4%-100% and 0.6%-100%, respectively). PA advice was delivered more often to patients with a higher body mass index, lower PA levels, and/or more comorbidities. Barriers - including a lack of time and training/guidelines - remain, despite recommendations from the World Health Organization and National Institute for Health and Care Excellence that PA advice should be provided in primary care. Few studies explored patients' receptivity to advice. CONCLUSION: PA BIs are not delivered frequently or consistently in primary care. Addressing barriers to delivery through system-level changes and training programmes could improve and increase the advice given. Understanding when patients are receptive to PA interventions could enhance health professionals' confidence in their delivery.

Aspirin use for cancer prevention: A systematic review of public, patient and healthcare provider attitudes and adherence behaviours.

We undertook a systematic review to synthesise the data on attitudes and behaviour towards the use of aspirin for cancer prevention, and healthcare providers' attitudes towards implementing aspirin in practice. Searches were carried out across 12 databases (e.g. MEDLINE, EMBASE). We used the Mixed Methods Appraisal Tool to evaluate study quality, and conducted a narrative synthesis of the data. The review was pre-registered (PROSPERO: CRD42018093453). Thirty-eight studies were identified. Uptake and adherence data were all from trials. Trials recruited healthy participants, those at higher risk of cancer, and those with cancer. Four studies reported moderate to high (40.9-77.7%) uptake to an aspirin trial among people who were eligible. Most trials (18/22) reported high day-to-day adherence (≥80%). Three trials observed no association between gender and adherence. One trial found no association between adherence and colorectal cancer risk. Three studies reported moderate to high (43.6-76.0%) hypothetical willingness to use aspirin. Two studies found that a high proportion of healthcare providers (72.0-76.0%) perceived aspirin to be a suitable cancer prevention option. No qualitative studies were identified. The likelihood that eligible users of aspirin would participate in a trial evaluating the use of aspirin for preventive therapy was moderate to high. Among participants in a trial, day-to-day adherence was high. Further research is needed to identify uptake and adherence rates in routine care, the factors affecting aspirin use, and the barriers to implementing aspirin into clinical care.

El Sistema Personalizado de Dosificación (SPD) como herramienta para mejorar la adherencia en la farmacia comunitaria. A propósito de un caso / The unit dose drug distribution system as a tool to improve adherence in community pharmacy. About a case

ANTECEDENTES: Paciente varón de 60 años, fumador y de bajo estrato social y cultural. Dependiente para todas sus actividades de la vida diaria, es atendido por su madre, una anciana de 86 años. El paciente presenta un cuadro pluripatológico antes de la intervención farmacéutica, destacando: infección crónica por VIH, combinación de medicamentos de uso hospitalario con medicamentos dispensados en la farmacia comunitaria y continuas incidencias en la dispensación en receta electrónica por no ajustarse a las pautas posológicas establecidas por su médico. La evaluación del paciente por el equipo multidisciplinar lo considera un paciente de riesgo y que precisa ayuda en la toma de la medicación; el paciente es no adherente según el test Morisky Green Levine reducido. La intervención farmacéutica consiste en la elaboración de SPD para el paciente. RESULTADOS: Tras 12 meses utilizando los SPD, dejaron de producirse desajustes en la dispensación en receta electrónica y los SPD que devuelve a la farmacia comunitaria muestran que ha tomado toda la medicación. El cálculo de la tasa Proportion of Days Covered (PDC) indica que es cumplidor para la mayoría de los tratamientos. CONCLUSIÓN: La elaboración de SPD a un paciente con patologías crónicas complejas resultó ser una intervención farmacéutica eficaz para mejorar su adherencia farmacológica

BACKGROUND: 60 years old male patient, smoker and of low social and cultural stratum. He is dependent for all his activities of daily life, he is cared for by his mother, an 86 year old women. The patient presents a multiple pathological picture before the pharmaceutical intervention, highlighting: chronic HIV infection, a mixture of hospital use drugs and community pharmacy dispensed drugs apart from continuous incidents in the dispensing by electronic prescription due to lack of adherence to his doctor dosage guidelines. The evaluation of the patient by the multidisciplinary team reveals a risk patient who needs help in taking medication; the patient is not adherent to his treatments according to Morisky Green Levine reduced test. The pharmaceutical intervention consists on the elaboration of unit dose drug distribution system to the patient. RESULTS: After 12 months using the dose drug distribution system, misalignments in electronic prescription dispensing stopped and the dose drug distribution systems that the patient brought back to the community pharmacy showed that the patient has taken the medication. The Proportion of Days Covered (PDC) ratio showed that the patient was compliant with most of the treatments. CONCLUSION: The elaboration of dose drug distribution system to a patient with complex chronic pathologies was an effective pharmaceutical intervention to improve his treatment adherence

Long-term issues and supportive care needs of adolescent and young adult childhood brain tumour survivors and their caregivers: A systematic review.

OBJECTIVE: Long-term issues following diagnosis and treatment of a childhood brain tumour often become apparent as the survivor enters adolescence and young adulthood. Their caregivers may additionally face long-term impacts on their emotional and psychological functioning. This review synthesised evidence on the issues and supportive care needs of adolescent and young adult (AYA) survivors of a brain tumour diagnosed in childhood and their caregivers. METHODS: Electronic databases were searched up until September 2017. All studies reporting on issues or needs of childhood brain tumour survivors (aged 14-39) and their caregivers were included. Narrative synthesis methods were used to summarise, integrate, and interpret findings. RESULTS: Fifty-six articles (49 studies) met the inclusion criteria. Social issues (ie, isolation and impaired daily functioning) were most commonly reported by survivors, followed by cognitive (ie, impaired memory and attention) and physical issues (ie, endocrine dysfunctions and fatigue). Survivors experienced poorer social functioning and sexual functioning and were less likely to be employed or have children, when compared with other AYA cancer survivors. Caregivers experienced reduced support as the survivor moved into young adulthood. Caregivers reported uncertainty, increased responsibilities, and problems maintaining their own self-well-being and family relationships. Few studies reported on supportive care needs. Survivors expressed a need for better educational support and age-specific psychosocial services. CONCLUSIONS: Surviving a childhood brain tumour can be particularly challenging for AYA survivors and their caregivers. Robust structured research is needed to identify specific support needs of both survivors and their caregivers and how these can be optimally addressed.

The relationship between obesity and tertiary education outcomes: a systematic review.

Previous reviews have documented an overall weak or uncertain association between obesity and school-based educational attainment in children and young people. However, up to half of young adults will go on to further college or university education by age 30. The study aim was to systematically review evidence on the association between obesity and tertiary education outcomes in young men and women. A search of multiple databases, including Embase, Global Health, ERIC, Medline, PsycInfo, and Science Citation Index was conducted in March 2018. Cross-sectional and longitudinal studies were included that reported on young people aged 16+, an association between obesity and academic achievement, and a comparison to healthy weight students. Risk of bias was assessed using criteria from the STROBE checklist. From 1297 records, 16 studies met all inclusion criteria. All six cross-sectional studies and 8/10 longitudinal studies reported lower educational achievement by students with obesity. All longitudinal studies were at low risk of bias but four cross-sectional studies were at medium risk and two at high risk of bias. Three of four studies showed reduced enrolment, in 6/8 graduation was less likely, and all 6 studies reporting on performance showed this was lower in those with obesity. Five of nine studies reported that obesity had a greater impact on educational achievement for women. Overall, there is compelling evidence of weight bias in that students with obesity do less well in tertiary education than their healthy weight peers. It is likely that university/college attainment is less impacted by socio-economic factors than school-based achievement. A better understanding of the processes that underpin this weight bias is needed, including stakeholder (student, staff) experiences of weight stigma, perceived or enacted. Responsive actions could mirror those to address disability or gender bias, or in health promotion in tertiary education settings.

Phenotype-loci associations in networks of patients with rare disorders: application to assist in the diagnosis of novel clinical cases.

Copy number variations (CNVs) are genomic structural variations (deletions, duplications, or translocations) that represent the 4.8-9.5% of human genome variation in healthy individuals. In some cases, CNVs can also lead to disease, being the etiology of many known rare genetic/genomic disorders. Despite the last advances in genomic sequencing and diagnosis, the pathological effects of many rare genetic variations remain unresolved, largely due to the low number of patients available for these cases, making it difficult to identify consistent patterns of genotype-phenotype relationships. We aimed to improve the identification of statistically consistent genotype-phenotype relationships by integrating all the genetic and clinical data of thousands of patients with rare genomic disorders (obtained from the DECIPHER database) into a phenotype-patient-genotype tripartite network. Then we assessed how our network approach could help in the characterization and diagnosis of novel cases in clinical genetics. The systematic approach implemented in this work is able to better define the relationships between phenotypes and specific loci, by exploiting large-scale association networks of phenotypes and genotypes in thousands of rare disease patients. The application of the described methodology facilitated the diagnosis of novel clinical cases, ranking phenotypes by locus specificity and reporting putative new clinical features that may suggest additional clinical follow-ups. In this work, the proof of concept developed over a set of novel clinical cases demonstrates that this network-based methodology might help improve the precision of patient clinical records and the characterization of rare syndromes.

Systematic review of the evidence on orthotic devices for the management of knee instability related to neuromuscular and central nervous system disorders.

OBJECTIVES: To assess the effectiveness of orthotic devices for the management of instability of the knee in adults with a neuromuscular disorder or central nervous system disorder. DESIGN: A systematic review of primary studies. SETTING: Community. PARTICIPANTS: Adults with a neuromuscular disorder or central nervous system disorder and impaired walking ability due to instability of the knee. INTERVENTIONS: Orthoses with the clinical aim of controlling knee instability, for example, knee-ankle-foot orthoses, ankle-foot orthoses and knee orthoses or mixed design with no restrictions in design or material. PRIMARY AND SECONDARY OUTCOME MEASURES: Condition-specific or generic patient-reported outcome measures assessing function, disability, independence, activities of daily living, quality of life or psychosocial outcomes; pain; walking ability; functional assessments; biomechanical analysis; adverse effects; usage; patient satisfaction and the acceptability of a device; and resource utilisation data. RESULTS: Twenty-one studies including 478 patients were included. Orthotic devices were evaluated in patients with postpolio syndrome, poststroke syndrome, inclusion body myositis and spinal cord injury. The review included 2 randomised controlled trials (RCTs), 3 non-randomised controlled studies and 16 case series. Most were small, single-centre studies with only 6 of 21 following patients for 1 year or longer. They met between one and five of nine quality criteria and reported methods and results poorly. They mainly assessed outcomes related to gait analysis and energy consumption with limited use of standardised, validated, patient-reported outcome measures. There was an absence of evidence on outcomes of direct importance to patients such as reduction in pain and falls. CONCLUSIONS: There is a need for high-quality research, particularly RCTs, of orthotic devices for knee instability related to neuromuscular and central nervous system conditions. This research should address outcomes important to patients. There may also be value in developing a national registry. REGISTRATION NUMBER SYSTEMATIC REVIEW: PROSPERO (CRD42014010180).

Structural and functional analogies and differences between histidine decarboxylase and aromatic l-amino acid decarboxylase molecular networks: Biomedical implications.

Human histidine decarboxylase (HDC) and dopa decarboxilase (DDC) are highly homologous enzymes responsible for the synthesis of biogenic amines (BA) like histamine, and serotonin and dopamine, respectively. The enzymes share many structural and functional analogies, while their product metabolisms also follow similar patterns that are confluent in some metabolic steps. They are involved in common physiological functions, such as neurotransmission, gastrointestinal track function, immunity, cell growth and cell differentiation. As a consequence, metabolic elements of both BA subfamilies are also co-participants in a long list of human diseases. This review summarizes the analogies and differences in their origin (HDC and DDC) as well as their common pathophysiological scenarios. The major gaps of information are also underlined, as they delay the possibility of holistic approaches that would help personalized medicine and pharmacological initiatives for prevalent and rare diseases.

Systematic identification of phenotypically enriched loci using a patient network of genomic disorders.

BACKGROUND: Network medicine is a promising new discipline that combines systems biology approaches and network science to understand the complexity of pathological phenotypes. Given the growing availability of personalized genomic and phenotypic profiles, network models offer a robust integrative framework for the analysis of "omics" data, allowing the characterization of the molecular aetiology of pathological processes underpinning genetic diseases. METHODS: Here we make use of patient genomic data to exploit different network-based analyses to study genetic and phenotypic relationships between individuals. For this method, we analyzed a dataset of structural variants and phenotypes for 6,564 patients from the DECIPHER database, which encompasses one of the most comprehensive collections of pathogenic Copy Number Variations (CNVs) and their associated ontology-controlled phenotypes. We developed a computational strategy that identifies clusters of patients in a synthetic patient network according to their genetic overlap and phenotype enrichments. RESULTS: Many of these clusters of patients represent new genotype-phenotype associations, suggesting the identification of newly discovered phenotypically enriched loci (indicative of potential novel syndromes) that are currently absent from reference genomic disorder databases such as ClinVar, OMIM or DECIPHER itself. CONCLUSIONS: We provide a high-resolution map of pathogenic phenotypes associated with their respective significant genomic regions and a new powerful tool for diagnosis of currently uncharacterized mutations leading to deleterious phenotypes and syndromes.

[Quality of life after brachytherapy or robot-assisted radical prostatectomy for localized prostate cancer]. / Evaluación de la calidad de vida de la braquiterapia vs prostatectomia robotizada en pacientes con carcinoma prostático localizado. Revisión sistemática.

OBJECTIVES: To perform a systematic bibliographic review of the literature assessing the quality of life and complications of robotic prostatectomy (RP) versus low-dose rate brachytherapy (LDR-BT) in patients with localized prostate cancer (PCa). PubMed, EMBASE and Cochrane, Centre for Reviews and Dissemination, Emergency Care Research Institute, Web of Knowledge, Technology Evaluation Center, Clinical Evidence, Uptodate, Hayes and Drug Effectiveness Review Project. Systematic reviews and prospective studies comparing RP to LDR-BT in men with localized PCa were included. The primary outcome was quality of life and the secondary endpoint complications rate. RESULTS: Three systematic reviews and four prospective studies were included. RP showed better results than LDR-BT for SF-12-physical domain (p<0.01) and faster recovery to pre-operative scores. LDR-BT improved scores for UCLAPCI questionnaire-urinary and sexual domains compared to RP during the first three years of follow-up (p<0.001). First postoperative year urinary incontinence rate was favorable for LDR-BT (88.0% vs 84.5%, p<0.001). No differences for intestinal function scores for the first three post-intervention years (p = 0.02) were found. Major complications of LDR-BT were gastrointestinal and genitourinary toxicity, although pooled weighted events rate of the studies was not analyzed. CONCLUSIONS: LDR-BT improves quality of life in terms of urinary and sexual function in patients with localized PCa vs RP during the first three years post-intervention.

The Clinical and Cost Effectiveness of Aflibercept in Combination with Irinotecan and Fluorouracil-Based Therapy (FOLFIRI) for the Treatment of Metastatic Colorectal Cancer Which has Progressed Following Prior Oxaliplatin-Based Chemotherapy: a Critique of the Evidence.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of aflibercept (Sanofi) to submit clinical and cost-effectiveness evidence for aflibercept in combination with irinotecan and fluorouracil-based therapy [irinotecan/5-fluorouracil/folinic acid (FOLFIRI)] for the treatment of metastatic colorectal cancer which has progressed following prior oxaliplatin-based chemotherapy, as part of the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA307 issued in March 2014. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. The clinical effectiveness data were derived from one good-quality double-blind randomised controlled trial (RCT), the VELOUR trial, which compared aflibercept plus FOLFIRI with placebo plus FOLFIRI. This RCT found a small but statistically significant increase in overall survival (OS); the difference in median OS was 1.44 months (13.5 months in the aflibercept group and 12.06 months in the placebo group). There was also a statistically significant increase in progression-free survival (PFS) with aflibercept; the difference in median PFS was 2.23 months (6.9 months in the aflibercept group and 4.67 months in the placebo group). However, grade 3-4 adverse events were more frequent in the aflibercept group than the placebo group: 83.5% compared with 62.5%. Treatment-emergent adverse events led to permanent discontinuation of treatment in 26.8% of patients in the aflibercept group and 12.1% of patients in the placebo group. The manufacturer's submission included an estimation of mean OS benefit based on extrapolation of the data, which was considerably longer than the median OS benefit reported (4.7 vs. 1.44 months). The ERG considered this to be an over estimate. The base-case incremental cost-effectiveness ratio (ICER) for the overall population was reported by the manufacturer to be £36,294 per quality-adjusted life-year (QALY). After correcting the model programming and updating the model to include the ERG's preferred parameter estimates, the ICER from the ERG's alternative base case was £54,368 per QALY. The extrapolation of the OS curves was the key cost-effectiveness driver and a major source of uncertainty in the model. Additional scenarios related to the extrapolation of OS undertaken by the ERG resulted in ICERs between £62,894 and £92,089 per QALY. After consideration of the manufacturer's submission and the ERG's critique, and submissions from other stakeholders, the NICE Appraisal Committee concluded that aflibercept in combination with irinotecan and fluorouracil-based therapy could not be considered a cost effective use of National Health Service resources for treating metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen. Aflibercept in combination with irinotecan and fluorouracil-based therapy is not recommended for the treatment of metastatic colorectal cancer that is resistant to or has progressed after an oxaliplatin-containing regimen in NICE guidance TA307.

PhenUMA: a tool for integrating the biomedical relationships among genes and diseases.

BACKGROUND: Several types of genetic interactions in humans can be directly or indirectly associated with the causal effects of mutations. These interactions are usually based on their co-associations to biological processes, coexistence in cellular locations, coexpression in cell lines, physical interactions and so on. In addition, pathological processes can present similar phenotypes that have mutations either in the same genomic location or in different genomic regions. Therefore, integrative resources for all of these complex interactions can help us prioritize the relationships between genes and diseases that are most deserving to be studied by researchers and physicians. RESULTS: PhenUMA is a web application that displays biological networks using information from biomedical and biomolecular data repositories. One of its most innovative features is to combine the benefits of semantic similarity methods with the information taken from databases of genetic diseases and biological interactions. More specifically, this tool is useful in studying novel pathological relationships between functionally related genes, merging diseases into clusters that share specific phenotypes or finding diseases related to reported phenotypes. CONCLUSIONS: This framework builds, analyzes and visualizes networks based on both functional and phenotypic relationships. The integration of this information helps in the discovery of alternative pathological roles of genes, biological functions and diseases. PhenUMA represents an advancement toward the use of new technologies for genomics and personalized medicine.

Citation searching: a systematic review case study of multiple risk behaviour interventions.

BACKGROUND: The value of citation searches as part of the systematic review process is currently unknown. While the major guides to conducting systematic reviews state that citation searching should be carried out in addition to searching bibliographic databases there are still few studies in the literature that support this view. Rather than using a predefined search strategy to retrieve studies, citation searching uses known relevant papers to identify further papers. METHODS: We describe a case study about the effectiveness of using the citation sources Google Scholar, Scopus, Web of Science and OVIDSP MEDLINE to identify records for inclusion in a systematic review.We used the 40 included studies identified by traditional database searches from one systematic review of interventions for multiple risk behaviours. We searched for each of the included studies in the four citation sources to retrieve the details of all papers that have cited these studies.We carried out two analyses; the first was to examine the overlap between the four citation sources to identify which citation tool was the most useful; the second was to investigate whether the citation searches identified any relevant records in addition to those retrieved by the original database searches. RESULTS: The highest number of citations was retrieved from Google Scholar (1680), followed by Scopus (1173), then Web of Science (1095) and lastly OVIDSP (213). To retrieve all the records identified by the citation tracking searching all four resources was required. Google Scholar identified the highest number of unique citations.The citation tracking identified 9 studies that met the review's inclusion criteria. Eight of these had already been identified by the traditional databases searches and identified in the screening process while the ninth was not available in any of the databases when the original searches were carried out. It would, however, have been identified by two of the database search strategies if searches had been carried out later. CONCLUSIONS: Based on the results from this investigation, citation searching as a supplementary search method for systematic reviews may not be the best use of valuable time and resources. It would be useful to verify these findings in other reviews.

Ruxolitinib for the treatment of myelofibrosis: a NICE single technology appraisal.

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ruxolitinib (Novartis) to submit clinical and cost-effectiveness evidence for ruxolitinib within its licensed indication (the treatment of disease-related splenomegaly or symptoms in adult patients with myelofibrosis), according to the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company submission, the ERG review and the resulting NICE guidance TA289 issued in June 2013. The ERG critically reviewed the evidence presented in the manufacturer's submission and identified areas requiring clarification, for which the manufacturer provided additional evidence. The main clinical effectiveness data were derived from two phase III, multicentre, randomised controlled trials (RCTs): Controlled myelofibrosis study with oral JAK inhibitor treatment (COMFORT)-II compared ruxolitinib with best available therapy (BAT), and COMFORT-I compared ruxolitinib with placebo. These RCTs demonstrated that ruxolitinib confers significant benefits in terms of spleen size reduction and improvement in symptom burden. In the COMFORT-II trial, a reduction in spleen volume of ≥35 % was achieved in 28 % of ruxolitinib-treated patients compared with 0 % of patients in the BAT group (p < 0.001) at 48 weeks, and there was a mean change in spleen volume of -30.1 versus +7.3 % (p < 0.001). Ruxolitinib also provided significant improvements in myelofibrosis-associated symptoms and health-related quality-of-life compared with BAT and placebo. The ERG concluded that ruxolitinib appears to reduce splenomegaly and its associated symptoms, but that there was considerable uncertainty surrounding the manufacturer's cost-effectiveness estimates due to limitations in the manufacturer's model. The manufacturer's model did not allow for disease progression, did not accurately capture symptomatic relief, had several implausible or unjustified assumptions, and there were several parameter choices that the ERG found sub-optimal. ERG sensitivity analyses found that nearly all plausible adjustments to the model reduced the cost effectiveness of ruxolitinib. It is very likely that the base-case incremental cost-effectiveness ratio of £73,980/quality-adjusted life-year presented by the manufacturer represents a best-case scenario. The NICE Appraisal Committee concluded that ruxolitinib was clinically effective, but could not be considered a cost effective use of National Health Service (NHS) resources for treating disease-related splenomegaly or symptoms in adults with myelofibrosis. Ruxolitinib is not recommended for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythaemia vera myelofibrosis and post-essential thrombocythaemia myelofibrosis in NICE TA289.

Correction: Global Analysis of the Human Pathophenotypic Similarity Gene Network Merges Disease Module Components.

[This corrects the article on p. e56653 in vol. 8.].

Global analysis of the human pathophenotypic similarity gene network merges disease module components.

The molecular complexity of genetic diseases requires novel approaches to break it down into coherent biological modules. For this purpose, many disease network models have been created and analyzed. We highlight two of them, "the human diseases networks" (HDN) and "the orphan disease networks" (ODN). However, in these models, each single node represents one disease or an ambiguous group of diseases. In these cases, the notion of diseases as unique entities reduces the usefulness of network-based methods. We hypothesize that using the clinical features (pathophenotypes) to define pathophenotypic connections between disease-causing genes improve our understanding of the molecular events originated by genetic disturbances. For this, we have built a pathophenotypic similarity gene network (PSGN) and compared it with the unipartite projections (based on gene-to-gene edges) similar to those used in previous network models (HDN and ODN). Unlike these disease network models, the PSGN uses semantic similarities. This pathophenotypic similarity has been calculated by comparing pathophenotypic annotations of genes (human abnormalities of HPO terms) in the "Human Phenotype Ontology". The resulting network contains 1075 genes (nodes) and 26197 significant pathophenotypic similarities (edges). A global analysis of this network reveals: unnoticed pairs of genes showing significant pathophenotypic similarity, a biological meaningful re-arrangement of the pathological relationships between genes, correlations of biochemical interactions with higher similarity scores and functional biases in metabolic and essential genes toward the pathophenotypic specificity and the pleiotropy, respectively. Additionally, pathophenotypic similarities and metabolic interactions of genes associated with maple syrup urine disease (MSUD) have been used to merge into a coherent pathological module.Our results indicate that pathophenotypes contribute to identify underlying co-dependencies among disease-causing genes that are useful to describe disease modularity.

Evaluación del sistema de navegación magnética intracardiaca Niobe, revisión sistemática de la literatura científica / Assessment of intracardiac magnetic navigation system Niobe, systematic review

Introducción y objetivos. Los métodos actuales de ablación conllevan sistemas de navegación manual y ablación cardiaca, y presentan ciertas limitaciones. El objetivo de este trabajo ha sido evaluar la eficacia y seguridad de los nuevos sistemas de navegación magnética intracardiaca. Métodos. Se hizo una revisión sistemática en las bases MedLine, Embase, Cochrane Library, CRD, ECRI, Hayes y bases de datos de HTA. Como términos Mesh se usaron: "electrophisiologic techniques", "magnetics", "stereotaxic techniques", "heart catheterization" y "catheter ablation". Los criterios de inclusión fueron estudios con adultos y lesiones cardíacas. La intervención fue el sistema de navegación magnética intracardiaca Niobe®. Los resultados medidos fueron: tiempos totales de procedimiento, tiempo de fluoroscopia, tiempo de colocación del catéter, tiempo de mapeo y tiempo de ablación. La calidad se evaluó con los cuestionarios CASPe y STROBE...

Introduction and objective: Current methods of ablation involving manual navigation systems and cardiac ablation have some limitations. The aim of this study was to evaluate the efficacy and safety of intracardiac magnetic navigation systems. Methods: Systematic review in MedLine, Embase, Cochrane Library, Center for Review and Dissemination, ECRI, Hayes and HTA databases was performed. The used Mesh terms were: electrophisiologic techniques, magnetic, stereotaxic techniques, heart catheterization, and catheter ablation. Inclusion criteria werestudies whose populations were adults with cardiac lesions. The intervention was intracardiac magnetic navigation system Niobe ® versus manual cardiacnavigation techniques and manual ablation. The outcomes were total procedure time, fluoroscopy time, time of catheter positioning, mapping and ablation time. Quality of studies was assessed by CASPe and STROBE...