Cost minimisation analysis of fingolimod vs natalizumab as a second line of treatment for relapsing-remitting multiple sclerosis.

INTRODUCTION: At present, there is a lack of economic assessments of second-line treatments for relapsing-recurring multiple sclerosis. The aim of this study was to compare the efficiency between fingolimod and natalizumab in Spain. METHODS: A cost minimisation analysis model was developed for a 2-year horizon. The same relapse rate was applied to both treatment arms and the cost of resources was calculated using Spain's stipulated rates for 2012 in euros. The analysis was conducted from the perspective of Spain's national health system and an annual discount rate of 3% was applied to future costs. A sensitivity analysis was performed to validate the robustness of the model. RESULTS: Indirect comparison of fingolimod with natalizumab revealed no significant differences (hazard ratio between 0.82 and 1.07). The total direct cost, considering a 2-year analytical horizon, a 7.5% discount stipulated by Royal Decree, and a mean annual relapse rate of 0.22, was € 40914.72 for fingolimod and € 45890.53 for natalizumab. Of the total direct costs that were analysed, the maximum cost savings derived from prescribing fingolimod prescription was € 4363.63, corresponding to lower administration and treatment maintenance costs. Based on the sensitivity analysis performed, fingolimod use was associated with average savings of 11% (range 3.1%-18.7%). CONCLUSIONS: Fingolimod is more efficient than natalizumab as a second-line treatment option for relapsing-remitting multiple sclerosis and it generates savings for the Spanish national health system.

Fast protocol for the diagnosis of lysosomal diseases in nonimmune hydrops fetalis.

OBJECTIVE: Nonimmune hydrops fetalis (NIHF) is defined by the excessive fluid accumulation in more than one foetal compartments and body cavities because of nonimmune reasons. It has been described that 14 lysosomal diseases may be causative of NIHF. The aim of this study was to design a fast protocol to investigate the most frequent lysosomal diseases that are reported that may cause NIHF. METHOD: We analysed the glycosaminoglycans excretion in the amniotic fluid supernatant and four different lysosomal enzymatic activities in the amniotic cultured cells of the different NIHF amniotic fluids we received. RESULTS: We investigated 30 NIHF cases, using this fast protocol. We detected two cases of NIHF because of lysosomal diseases, which represent 6.6%. We diagnosed one case of mucopolysaccharidosis type VII and one case of Gaucher disease. CONCLUSION: The fast protocol we designed analyses seven of the most frequent lysosomal pathologies that have been described that may cause NIHF, with only five different determinations, which make the analysis of NIHF fast, cost-effective and without need of too much amniotic fluid. We believe this protocol may be useful for the analysis of lysosomal diseases in NIHF.

Fertility prediction in dairy goats from Murciano-Granadina breed: The role of sperm evaluation and female traits.

Fertility is one of the most economically important traits in farm animals, due to the direct and indirect costs associated to low pregnancy rates. Thus, one of the priority goals in animal reproduction is to predict the performance that the semen doses will have in vivo based on the quality values obtained in laboratory assays. Attempts have been made for getting a predictive model of fertility of frozen-thawed sperm in dairy goats, but similar studies have not been conducted for chilled goat buck sperm doses that are mostly used for artificial insemination in many countries including Spain. We study how parameters of in vitro sperm quality and characteristics of Murciano-Granadina dairy goats may affect the in vivo fertility obtained after artificial insemination with semen doses chilled at 4 °C. Moreover, this information was used for obtaining predictive models of the fertility. Sixty-three ejaculates from 13 males were used to prepare chilled doses for the insemination of 495 goats over 13 sessions. Fresh and chilled sperm were evaluated for motility and plasma membrane integrity with a computer-assisted sperm analysis system and flow cytometry, respectively. Fertility was determined at parturition, according to the kidding goats. Overall fertility was 59.6%. Pearson's correlation coefficients between in vivo fertility and quality variables of fresh sperm were not significant and were low (below 0.34 in absolute value) for chilled sperm. Females' characteristics had a low negative impact on fertility (correlation coefficients of -0.19 with age, -0.20 with parturitions and -0.11 with total milk yield obtained in the best lactation). Fixed and mixed logistic regression procedures were used trying to explain the fertility results. None of the models accurately predicted fertility, but the best models included the percentage of total motile sperm or average path velocity from fresh semen, age of the females and the session effect (uncontrolled environmental effects). These analyses showed that primiparous goats were 2.42 times more likely to get pregnant than goats that had kidded four or more times. Our field assay data on fertility in Murciano-Granadina dairy goats highlighted the importance of making quality controls of sperm, of choosing the doses presenting high percentages of motile sperm exhibiting regular trajectories and of selecting the youngest goats for AI, after their first kidding. Efforts should continue to obtain better predictive models for improving fertility in goat dairy herds.

Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program.

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyzes, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.

Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program. / Recomendaciones de la Sociedad Española de Cirugía Torácica y de la Sección de Cardiotorácica y Cirugía Vascular de la Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor, para los pacientes sometidos a cirugía pulmonar incluidos en un programa de recuperación intensificada.

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyses, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.

Incorporating posttransplant cyclophosphamide-based prophylaxis as standard-of-care outside the haploidentical setting: challenges and review of the literature.

Posttransplant high-dose cyclophosphamide (PTCy) effectively prevents GvHD after haploidentical SCT. However, its use in HLA-matched SCT has been less explored. Fifty-six consecutive patients who underwent allo-SCT for hematological malignancies have been included in this prospective single-center protocol. Donors have been HLA-identical siblings, fully-matched unrelated or 1-allele-mismatched unrelated donors in 30%, 32%, and 37% of cases, respectively. Nine patients have received a TBI-containing MAC regimen, while the remaining (84%) received RIC platforms based on Fludarabine plus Busulfan/Melphalan. Due to the high graft failure (GF) rate (21%) in a preliminary analysis in the allo-RIC cohort (n = 29), protocol amendments have been implemented, with no further cases of GF after the introduction of mini-thiotepa (0/18). The overall incidence of grade II-IV acute GvHD is 24% (95% CI: 17-31%) with four steroid-refractory cases. Severe chronic GvHD has occurred in only 1 of 43 evaluable cases. The 1-year NRM and relapse are 18% (95% CI: 12-26%) and 30% (18-42%) and the OS and DFS are 78% and 64%, respectively. These outcomes support the feasibility of using PTCy as a SOC outside the haplo-setting, albeit mini-thiotepa (3 mg/kg) was incorporated in the standard allo-RIC platforms to prevent GF. Despite the limitations of a single-center experience and the short follow-up, these protocols show promising results with particular benefit in reducing the occurrence of moderate-to-severe GvHD.

Recently acquired HIV infection in Spain (2003-2005): introduction of the serological testing algorithm for recent HIV seroconversion.

BACKGROUND: Identification of recent HIV infections provides a description of the current pattern of HIV transmission and, consequently, can help to design better preventive interventions. Our study shows the first implementation in Spain of the Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS) strategy. We assess the viability of introducing STARHS in our setting and describe the frequency and epidemiological characteristics of recent infections (RIs). METHODS: Between 2003 and 2005, HIV-positive blood samples drawn for diagnostic purposes were collected from 28 Spanish laboratories to be tested using STARHS. Samples from patients with a previous HIV diagnosis, age <18 years, <200 CD4 cells/microL or clinical AIDS criteria were excluded from the analysis. RESULTS: A total of 660 (19.2%) samples were classified as RI. Most people identified with RI were male (79.8%) with a median age of 33.1 years, and 62.5% occurred among men who have sex with men (MSM). Immigrants made up 26.5% of individuals identified with RIs, with 48.7% coming from South America. Among the individuals with RI, at least 16.5% had reported another sexually transmitted infection (STI) during the year before the HIV diagnosis. CONCLUSION: The study shows that the implementation of STARHS in our setting is feasible and has highlighted important features of the local HIV epidemic, such as the ongoing spread of HIV among MSM, the potential role of STIs in RIs and the vulnerability of immigrants as a new target population.

Protective ventilation with high versus low positive end-expiratory pressure during one-lung ventilation for thoracic surgery (PROTHOR): study protocol for a randomized controlled trial.

BACKGROUND: Postoperative pulmonary complications (PPC) may result in longer duration of in-hospital stay and even mortality. Both thoracic surgery and intraoperative mechanical ventilation settings add considerably to the risk of PPC. It is unclear if one-lung ventilation (OLV) for thoracic surgery with a strategy of intraoperative high positive end-expiratory pressure (PEEP) and recruitment maneuvers (RM) reduces PPC, compared to low PEEP without RM. METHODS: PROTHOR is an international, multicenter, randomized, controlled, assessor-blinded, two-arm trial initiated by investigators of the PROtective VEntilation NETwork. In total, 2378 patients will be randomly assigned to one of two different intraoperative mechanical ventilation strategies. Investigators screen patients aged 18 years or older, scheduled for open thoracic or video-assisted thoracoscopic surgery under general anesthesia requiring OLV, with a maximal body mass index of 35 kg/m2, and a planned duration of surgery of more than 60 min. Further, the expected duration of OLV shall be longer than two-lung ventilation, and lung separation is planned with a double lumen tube. Patients will be randomly assigned to PEEP of 10 cmH2O with lung RM, or PEEP of 5 cmH2O without RM. During two-lung ventilation tidal volume is set at 7 mL/kg predicted body weight and, during OLV, it will be decreased to 5 mL/kg. The occurrence of PPC will be recorded as a collapsed composite of single adverse pulmonary events and represents the primary endpoint. DISCUSSION: PROTHOR is the first randomized controlled trial in patients undergoing thoracic surgery with OLV that is adequately powered to compare the effects of intraoperative high PEEP with RM versus low PEEP without RM on PPC. The results of the PROTHOR trial will support anesthesiologists in their decision to set intraoperative PEEP during protective ventilation for OLV in thoracic surgery. TRIAL REGISTRATION: The trial was registered in clinicaltrials.gov ( NCT02963025 ) on 15 November 2016.

Correction to: Protective ventilation with high versus low positive end-expiratory pressure during one-lung ventilation for thoracic surgery (PROTHOR): study protocol for a randomized controlled trial.

After publication of the original article [1], the authors have notified us that two of the collaborator first and last names have been inverted in the "PROTHOR Investigators" table.

Review of difficult airway management in thoracic surgery. / Revisión del manejo de la vía aérea díficil en cirugía torácica.

The management of difficult airway (DA) in thoracic surgery is more difficult due to the need for lung separation or isolation and frequent presence of associated upper and lower airway problems. We performed an article review analysing 818 papers published with clinical evidence indexed in Pubmed that allowed us to develop an algorithm. The best airway management in predicted DA is tracheal intubation and independent bronchial blockers guided by fibroscopy maintaining spontaneous ventilation. For unpredicted DA, the use of videolaryngoscopes is recommended initially, and adequate neuromuscular relaxation (rocuronium/sugammadex), among other maneuvers. In both cases, double lumen tubes should be reserved for when lung separation is absolutely indicated. Finally, extubation should be a time of maximum care and be performed according to the safety measures of the Difficult Arway Society.

Frequency and risk factors for thrombosis in idiopathic myelofibrosis: analysis in a series of 155 patients from a single institution.

Thrombosis is a frequent complication of polycythemia vera and essential thrombocythemia, but its incidence and predisposing factors in idiopathic myelofibrosis (IM) are unknown. In 18 (11.6%) of 155 patients diagnosed with IM in a single institution, 31 thrombotic events (19 arterial, 12 venous) were registered after a mean follow-up of 4.2 (s.d.: 4.5) years. In six patients, the thrombosis was simultaneous to or appeared a few months before IM diagnosis and 14 had one or more thrombotic episodes. When compared with the general population, a significant increase was observed in the incidence of venous thrombosis (odds ratio 17.5, 95% confidence interval: 10.3-31.4). At multivariate analysis, the initial variables associated with an increased risk of thrombosis were thrombocytosis (platelets >450 x 10(9)/l, P=0.001), presence of one cardiovascular risk factor (arterial hypertension, smoking, hypercholesterolemia, or diabetes, P=0.003), cellular phase of myelofibrosis (P=0.005), and Hb >11 g/dl (P=0.02). Considering post-diagnosis events, the 5-year thrombosis-free survival probability was 90.4% in the series, 80.6% for patients with platelets >450 x 10(9)/l, 82.6% for patients with one cardiovascular risk factor, and 85.1% for those in cellular phase. These results indicate an increased thrombotic risk for IM patients with hyperproliferative features and/or coexistent cardiovascular risk factors.

[Applications for bronchial blockers in thoracic surgery]. / Aplicaciones de los bloqueadores bronquiales en cirugía torácica.

One-lung ventilation is commonly used to facilitate visualization of the field during thoracic surgery. New devices for performing this technique that have become available over the past 2 decades include the Univent bronchial blocker incorporated in a single-lumen tube, the Arndt endobronchial blocker, and the Cohen endobronchial blocker. Although insertion of a double-lumen tube is still the method used most often to isolate the lung, bronchial blockade is an increasingly common technique and, in certain clinical settings, provides advantages over the double-lumen tube. This review provides an update on new concepts in the use of bronchial blockers as a technique for lung isolation and one-lung ventilation. The literature search was performed on MEDLINE through PubMed using the keywords bronchial blockers and thoracic surgery. The search span started with 1982-the year the first modern bronchial blocker was described - and ended with February 2006.

Recomendaciones de la Sociedad Española de Cirugía Torácica y de la Sección de Cardiotorácica y Cirugía Vascular de la Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor, para los pacientes sometidos a cirugía pulmonar incluidos en un programa de recuperación intensificada / Recommendations of the Society of Thoracic Surgery and the Section of Cardiothoracic and Vascular Surgery of the Spanish Society of Anesthesia, Resuscitation and Pain Therapy, for patients undergoing lung surgery included in an intensified recovery program

En los últimos años se están implementando programas multidisciplinares que incluyen diferentes actuaciones durante el periodo pre, intra y postoperatorio, encaminadas a disminuir el estrés perioperatorio y, por tanto, a mejorar los resultados de los pacientes sometidos a intervenciones quirúrgicas. Inicialmente, estos programas se desarrollaron para cirugía colorrectal y de ahí se han ido extendiendo a otras cirugías. La cirugía torácica, considerada de elevada complejidad, al igual que otras cirugías con una alta tasa de morbimortalidad postoperatoria, puede ser una de las especialidades que más se beneficien de la implantación de estos programas. En esta revisión se presentan las recomendaciones elaboradas por diferentes especialidades implicadas en los cuidados perioperatorios de los pacientes que requieren la resección de un tumor pulmonar. Para la elaboración de las recomendaciones presentadas en esta guía se han tenido en cuenta los metaanálisis, las revisiones sistemáticas, los estudios controlados aleatorizados y no aleatorizados y los estudios retrospectivos realizados en pacientes sometidos a este tipo de intervenciones. Para la clasificación de las recomendaciones se ha empleado la escala GRADE, valorando, por un lado, el nivel de evidencia publicado sobre cada aspecto concreto, y por otro, la fuerza de la recomendación con la que los autores proponen su aplicación. Las recomendaciones consideradas más importantes para este tipo de cirugía son las que se refieren a la prehabilitación, a la minimización de la agresión quirúrgica, a la excelencia en el manejo del dolor perioperatorio y a los cuidados postoperatorios encaminados a proporcionar una rápida rehabilitación postoperatoria.(AU)

In recent years, multidisciplinary programs have been implemented that include different actions during the pre, intra and postoperative period, aimed at reducing perioperative stress and therefore improving the results of patients undergoing surgical interventions. Initially, these programs were developed for colorectal surgery and from there they have been extended to other surgeries. Thoracic surgery, considered highly complex, like other surgeries with a high postoperative morbidity and mortality rate, may be one of the specialties that most benefit from the implementation of these programs. This review presents the recommendations made by different specialties involved in the perioperative care of patients who require resection of a lung tumor. Meta-analyses, systematic reviews, randomized and non-randomized controlled studies, and retrospective studies conducted in patients undergoing this type of intervention have been taken into account in preparing the recommendations presented in this guide. The GRADE scale has been used to classify the recommendations, assessing on the one hand the level of evidence published on each specific aspect and, on the other hand, the strength of the recommendation with which the authors propose its application. The recommendations considered most important for this type of surgery are those that refer to pre-habilitation, minimization of surgical aggression, excellence in the management of perioperative pain and postoperative care aimed at providing rapid postoperative rehabilitation.(AU)

Benefit of continuous treatment for responders with newly diagnosed multiple myeloma in the randomized FIRST trial.

The phase 3, randomized Frontline Investigation of Revlimid and Dexamethasone Versus Standard Thalidomide (FIRST) trial investigating lenalidomide plus low-dose dexamethasone until disease progression (Rd continuous) vs melphalan, prednisone and thalidomide for 12 cycles (MPT) and Rd for 18 cycles (Rd18) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) showed that Rd continuous prolonged progression-free survival and overall survival compared with MPT. A subanalysis of the FIRST trial was conducted to determine the benefits of Rd continuous in patients with NDMM based on depth of response. Patients randomized 1:1:1 to Rd continuous, Rd18 or MPT were divided into subgroups based on best response: complete response (CR; n=290), ⩾very good partial response (VGPR; n=679), ⩾partial response (PR; n=1 225) or ⩽stable disease (n=299). Over 13% of patients receiving Rd continuous who achieved ⩾VGPR as best response did so beyond 18 months of treatment. Rd continuous reduced the risk of progression or death by 67%, 51% and 35% vs MPT in patients with CR, ⩾VGPR and ⩾PR, respectively. Similarly, Rd continuous reduced the risk of progression or death by 61%, 54% and 38% vs Rd18 in patients with CR, ⩾VGPR and ⩾PR, respectively. In patients with CR, ⩾VGPR or ⩾PR, 4-year survival rates in the Rd continuous arm (81.1%, 73.1% or 64.6%, respectively) were higher vs MPT (70.8%, 59.8% or 57.2%, respectively) and similar vs Rd18 (76.5%, 67.7% and 62.5%, respectively). Rd continuous improved efficacy outcomes in all responding patients, including those with CR, compared with fixed duration treatment.

Bortezomib and thalidomide maintenance after stem cell transplantation for multiple myeloma: a PETHEMA/GEM trial.

The phase III trial GEM05MENOS65 randomized 390 patients 65 years old or younger with newly diagnosed symptomatic multiple myeloma (MM) to receive induction with thalidomide/dexamethasone, bortezomib/thalidomide/dexamethasone and Vincristine, BCNU, melphalan, cyclophosphamide, prednisone/vincristine, BCNU, doxorubicin, dexamethasone bortezomib (VBMCP/VBAD/B) followed by autologous stem cell transplantation (ASCT) with MEL-200. After ASCT, a second randomization was performed to compare thalidomide/bortezomib (TV), thalidomide (T) and alfa-2b interferon (alfa2-IFN). Maintenance treatment consisted of TV (thalidomide 100 mg daily plus one cycle of intravenous bortezomib at 1.3 mg/m2 on days 1, 4, 8 and 11 every 3 months) versus T (100 mg daily) versus alfa2-IFN (3 MU three times per week) for up to 3 years. A total of 271 patients were randomized (TV: 91; T: 88; alfa2-IFN: 92). The complete response (CR) rate with maintenance was improved by 21% with TV, 11% with T and 17% with alfa2-IFN (P, not significant). After a median follow-up of 58.6 months, the progression-free survival (PFS) was significantly longer with TV compared with T and alfa2-IFN (50.6 vs 40.3 vs 32.5 months, P=0.03). Overall survival was not significantly different among the three arms. Grade 2-3 peripheral neuropathy was observed in 48.8%, 34.4% and 1% of patients treated with TV, T and alfa2-IFN, respectively. In conclusion, bortezomib and thalidomide maintenance resulted in a significantly longer PFS when compared with thalidomide or alfa2-IFN. (no. EUDRA 2005-001110-41).