Cost-effectiveness of somatrogon in the Spanish pediatric population with growth hormone deficiency.

OBJECTIVE: To analyze the cost-effectiveness of weekly somatrogon compared to daily growth hormones (GH-d) in the pediatric population of Spain with growth hormone deficiency (GHD). METHODS: Markov model with two states (patients with or without GH-d or somatrogon treatment) in prepubertal children (3 to 11 years and 3 to 12 years in girls and boys, respectively) with GHD in isolation or as part of multiple pituitary hormone deficiency and without previous treatment, from the perspective of the National Health System. The simulation of the economic model ends at the age of 18. The costs of hormones and monitoring were obtained from Spanish sources. The utilities were obtained from the literature. Spanish clinical experts validated the assumptions of the model. RESULTS: In the deterministic analysis, somatrogon would be cost-effective, compared to GH-d, with a cost per QALY (quality-adjusted life year) gained of €19,259 and a clinically relevant QALY gain (0.336). This result was confirmed in deterministic sensitivity analyses. According to the probabilistic analysis, somatrogon would be the dominant treatment, with a 61% probability of a willingness to pay of €25,000 per QALY gained. CONCLUSION: Compared to GH-d, somatrogon is cost-effective in the Spanish pediatric population with GHD.

Volatile fatty acid platform - a cornerstone for the circular bioeconomy.

Annually, the EU produces more than 100 million tonnes of urban biowaste, which is largely under-valorized and in some cases even still landfilled without any energy or material recovery. If Europe wants to be ready for the future, it will need to make better use of this large biomass potential within a circular economy approach. The research project funded by the European Commission under the Horizon 2020 programme entitled 'VOLATILE-Biowaste derived volatile fatty acid platform for biopolymers, bioactive compounds and chemical building blocks' aimed to produce volatile fatty acids (VFAs) from biowaste for reprocessing into products, materials or substances to close the material loop. During the project, the partners were able to obtain average volatile fatty acid yields of 627 g COD/kg organic matter (OM) for food waste, 448 g COD/kg OM for separately collected vegetable, garden and fruit waste (VGF) and 384 g COD/kg OM for the organic fraction of municipal solid waste (OF-MSW) at concentrations ranging from 12 to 48 g/L, 6 to 40 g/L and 13 to 26 g/L, respectively. A membrane filtration cascade consisting of micro-, ultra- and nano-filtration followed by reverse osmosis was identified as a feasible way to purify and concentrate the VFA effluent, making them a suitable carbon source for further fermentation processes. Besides technical optimization, socio-economic and legal aspects associated with this platform technology were also studied and show that although this technology is still in development, it is providing an answer to changing societal and market expectations both regarding organic waste treatment and bio-based production strategies. Based on the current technological, economic and market evolutions, it is expected that the VFAP will play an important role in organic waste treatment in the coming years.

Cost-effectiveness analysis of treatment sequences containing tofacitinib for the treatment of rheumatoid arthritis in Spain.

OBJECTIVE: To assess the cost-effectiveness of tofacitinib-containing treatment sequences versus sequences containing only standard biological therapies in patients with moderate-to-severe rheumatoid arthritis (RA) after the failure of conventional synthetic disease-modifying antirheumatic drugs (csDMARD-IR population) and in patients previously treated with methotrexate (MTX) who show an inadequate response to second-line therapy with any tumour necrosis factor inhibitor (TNFi-IR population). METHODS: A patient-level microsimulation model estimated, from the perspective of the Spanish Public NHS, lifetime costs and quality-adjusted life years (QALY) for treatment sequences starting with tofacitinib (5 mg twice daily) followed by biological therapies versus sequences of biological treatments only. Concomitant treatment with MTX was considered. Model's parameters comprised demographic and clinical inputs (initial Health Assessment Questionnaire [HAQ] score and clinical response to short- and long-term treatment). Efficacy was measured by means of HAQ score changes using mixed treatment comparisons and data from long-term extension (LTE) trials. Serious adverse events (SAEs) data were derived from the literature. Total cost estimation (€, 2018) included drug acquisition, parenteral administration, disease progression and SAE management. RESULTS: In the csDMARD-IR population, sequences starting with tofacitinib proved dominant options (more QALYs and lower costs) versus the corresponding sequences without tofacitinib. In the TNFi-IR population, first-line treatment with tofacitinib+MTX followed by scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX proved dominant versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX; and tofacitinib+MTX➔scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX versus scTocilizumab+MTX➔scAbatacept+MTX➔rituximab+MTX➔certolizumab+MTX was less effective but remained a cost-saving option. CONCLUSIONS: Inclusion of tofacitinib seems a dominant strategy in moderate-to-severe RA patients after csDMARDs failure. Tofacitinib, as initial third-line therapy, proved a cost-saving strategy (€- 337,489/QALY foregone) in moderate-to-severe TNFi-IR RA patients. Key points • Therapeutical approach in rheumatoid arthritis (RA) consisted in sequences of several therapies during patient lifetime. • Treatment sequences initiating with tofacitinib followed by biological drugs provided higher health effects in csDMARDs-IR population, compared with sequences containing only biological drugs. • In both csDMARD-IR and TNFi-IR RA populations, initiating treatment with tofacitinib was associated to lower treatment costs for the Spanish National Health System.

Cost effectiveness analysis of fesoterodine compared to mirabegron in first-line therapy setting for overactive bladder with urge urinary incontinence, from the Spanish National Health System perspective. / Análisis de coste efectividad de fesoterodina comparado con mirabegron en el marco de tratamiento de primera línea para vejiga hiperactiva con incontinencia urinaria de urgencia, desde la perspectiva del Sistema Nacional de Salud español.

OBJECTIVES: To evaluate the cost-effectiveness of first-line treatment of Overactive Bladder (OAB) with fesoterodine relative to mirabegron, from the Spanish National Health System (NHS) perspective. METHODS: A decision tree model was developed to represent a typical clinical process of 52-week of treatment for an OAB patient with urge urinary incontinence (UUI) initiating first-line therapy with fesoterodine 4mg, including optional titration to 8mg, vs.mirabegron 50mg. Efficacy data were obtained from a Bayesian indirect treatment meta-analysis. Patients with UUI of less than one episode/day were defined as treatment responder and persistence was assessed at weeks 4, 12 and 24. At week 12, non-responders discontinued treatment permanently. Quality-adjusted life years (QALYs) were calculated based on time spent in responder and non-responder states. OAB-related drug and medical care costs including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections and depression) were modeled and expressed in €2015. RESULTS: At week 52, the percentage of responders was 20.8% for patients starting on fesoterodine 4mg who optionally titrated to 8mg and 19.4% for patients treated with mirabegron. QALYs were slightly higher with fesoterodine than mirabegron (0.7703vs. 0.7668, difference=0.0035). Fesoterodine treatment also had slightly higher total costs than mirabegron (3,296€vs. 3,217, difference=79€), resulting in a cost of 22,523/QALY€ gained for fesoterodine versus mirabegron. Probabilistic sensitivity analysis confirmed the slight advantage of fesoterodine with a 61.1% probability of being cost-effective at the 30,000€ willingness-to-pay for 1QALY threshold. CONCLUSIONS: Given the relatively small 1-year cost difference between the two treatments, fesoterodine can be considered a cost-effective option relative to mirabegron for the first-line management of OAB with UUI in Spain.

Cost-effectiveness of three echinocandins and fluconazole in the treatment of candidemia and/or invasive candidiasis in nonneutropenic adult patients.

OBJECTIVE: To estimate the cost-effectiveness of three echinocandins (anidulafungin, caspofungin, and micafungin) and generic fluconazole in the treatment of nonneutropenic adult patients with candidemia and/or invasive candidiasis in intensive care units in Spain. MATERIALS AND METHODS: A decision-tree model was applied. The success and safety (hepatic and renal adverse effects) of first-line treatments were obtained from meta-analyses and systematic reviews of clinical trials. In the case of failure, a second-line treatment (liposomal amphotericin B after the echinocandins, or one of the echinocandins after fluconazole) was administered. The duration of the treatments (14 days total) was established by a panel of clinical experts using the Delphi method and according to Infectious Diseases Society of America guidelines. The cost of the medications and renal toxicity were considered. Deterministic and probabilistic sensitivity analysis using Monte Carlo simulations were carried out. RESULTS: The total cost of the treatment of candidemia and/or invasive candidiasis with anidulafungin, caspofungin, micafungin, and fluconazole was €5,483, €5,968, €6,231, and €2,088, respectively. Anidulafungin was the dominant treatment (more effective, less expensive) compared to micafungin and caspofungin. The cost of achieving one more patient successfully treated with anidulafungin, caspofungin, and micafungin compared to fluconazole was €17,199, €23,962, and €27,339, respectively. The result remained stable, despite modification of the duration of the first-line and second-line treatments, as well as most of the dosing regimens. The probabilistic analysis also remained stable. CONCLUSION: In accordance with this economic study, anidulafungin would produce savings and would be the dominant treatment compared with micafungin and caspofungin in nonneutropenic adult patients with candidemia and/or invasive candidiasis in intensive care units in Spain.

[Spontaneous hepatic rupture during pregnancy. Report of a case. Review of the literature]. / Ruptura hepática espontánea en el embarazo. Presentación de un caso. Revisión de la literatura.

The spontaneous hepatic rupture during pregnancy or puerperium has been reported as a rare complication, with an extraordinary severity. Usually it's a pregnancy hypertensive disease complication. Since 1990 it had been reported 120 cases from this pathology in the world literature. We reported a case from a patient who presented spontaneous hepatic rupture during the immediately puerperium and a world literature revision.

[Ectopic pregnancy in abdominal cavity. Report of a case and review of the literature]. / Embarazo ectópico en cavidad abdominal. Presentación de un caso y revisión de la literatura.

A case of ectopic pregnancy in peritoneal cavity is presented, the clinic evolution and the resolution are mentioned a world literature revision was done giving special attention to the historic aspects, the incidence, classification, diagnosis and treatment. Finally, a comment about the surgery technique and the placenta management.

[Twin pregnancy complicated by one intrauterine fetal death. Report of a case and review of the literature]. / Embarazo gemelar complicado con pérdida de un producto in utero. Presentación de un caso y revisión de la literatura.

The intrauterine fetal death in a gemelar pregnancy is a rare complication with an incidence from 0.5 to 6.8% of all gemelar pregnancies with a conservative management for the mother and the surviving fetus. The complications are due to the passage of tromboplastic substance from the death fetus to the surviving fetus, through intravascular communications specially in monocorionic placenta producing nervous central system, kidney and skin alterations, mainly in the surviving fetus and coagulation system alterations in the mother. We present a case of a gemelar pregnancy with a fetal loss in utero with repercussions in the surviving fetus in the nervous central system. At the same time we made a literature review.

[Human papillomavirus infection in male genitalia]. / Infección por virus del papiloma humano en genitales masculinos.

A prospective and transversal study in 100 patients since January to December of 1994, was done, to know the human papiloma virus infection prevalence in male genitals. The patients were studied by a clinical history, genital area colposcopic revision after acetic acid 5% application, biopsy of the lesion and histopathology study. The patients age was among 16 to 71 years old, with a media of 38.8 years old. The sexual activity beginning was from 12 to 27 years old, with an average of 18 years old. Forty one percent of the patients have had sexual relations with prostitutes, 26% have had sexually transmitted diseases, 9% of the patients referred only 1 sexual mate and 82% had human papiloma virus infection.

[Current concepts on human papillomavirus infection]. / Conceptos actuales sobre la infección por virus del papiloma humano.

The human papilloma virus presents a multidimensional problem for gynecologist and urologist. The human papilloma virus infection (HPVI) incidence has been increased, so that at present it's the viral infection most common of the genital tract. The HPV is transmitted for sexual contact but it has not been explained the infection mechanism of the virus-cell interaction of the host. The long term consequences of the sexual transmission diseases are more serious in female than in male. The majority have a little of symptoms, so that frequently they do not receive treatment, and therefore have pregnancy, sterility and infertility, transplacental infection of the fetus, preterm and newborn infection along the contaminated genital tract. In addition, the genital HPV is associated with cervical dysplasia and it can be important in the cervical cancer development. The treatment is multiple and includes cytotoxic agents, surgery, immunotherapy and laser abrasion.

[Heterologous adenosarcoma of the Müllerian ducts in adolescence. Presentation of clinical case and review of the literature]. / Adenosarcoma mulleriano heterólogo en la adolescencia. Presentación de un caso clínico y revisión de la literatura.

This is the case of a 16 years old female with an histopathologic diagnosis of mullerian heterologous adenosarcoma, a non-frequent entity in the adolescence. We carried out a bibliographic review about uterine sarcomas, clinic aspect, classification, epidemiology, prognosis and treatment.

[Obstetrical hysterectomy. Retrospective study over the past 3 years. General Hospital of Mexico]. / Histerectomía obstétrica. Estudio retrospectivo en los últimos tres años. Hospital General de México.

A retrospective, observational and analytical study about Obstetric-Hysterectomy on Hospital General of Mexico patients during a period of 3 years of study. The mean objective was to analyze the Hysterectomy in the pregnant puerperal stage (Obstetric-Hysterectomy), during the resolution of the problems that the pregnancy, delivery and puerperium determinate, as soon as the association of the complications during the pregnant puerperal stage that condition on the realization of this procedure, so that we can diminish the morbimortality of this procedure. We analyzed the following variables: age, ginecobstetric history, surgery indication, diagnostic omission, surgeons, surgery time, the turn when it was made, reintervention, surgery complications, the use of blood and antibiotics, days at hospital and mortality. We concluded the necessity of a national incidence, to know the most frequent indications and the morbimortality set the example to determine the diminution of the complications, the mortality and know the guides to follow in this procedure.

[Skin endometriosis in abdominal scar after cesarean section. Case report and review of the literature]. / Endometriosis cutánea en cicatriz abdominal, posterior a operación cesárea. Informe de un caso y revisión de la literatura.

Scan endometriosis is a rare entity, commonly related after operation on the uterus or uterine tubes or a laparotomy procedure or other no pelvic surgical procedure, when transplantations of endometrial fragments were shed into the peritoneal cavity. We present a case of a 31 year woman, who had the clinical and histopathological diagnosis of scar endometriosis following cesarean section, treated with local surgical excision of the abnormal tissue, with a satisfactory response. And a review of world literature, was done.

[Meningioma in pregnancy. Report of a case and review of the literature]. / Meningioma y embarazo. Presentación de un caso y revisión de la literatura.

We present a case of a young woman who presented with meningioma and pregnancy association. This neoplasm is not frequent during pregnancy but when this association occurs, the neoplasma has a quickly growth because of the presence of estrogenic receptors. We observed the evolution of the product and the mother during pregnancy and puerperium. We made literature review.

Allergy to asticot maggots. Identification of allergens.

UNLABELLED: There are some written reports of allergic reactions after contact with Asticot larvae in anglers and occupationally exposed workers. Clinical and immunological studies were performed to confirm the allergens involved in the case of a 12-year-old male who developed respiratory symptoms shortly after contact with Asticot maggots used as fish bait. METHODS AND RESULTS: Aqueous extracts of Asticot maggots were taken for in vivo and in vitro tests. The protein concentration as determined by turbidimetric assay was 1.4 mg/ml. Skin prick test with Asticot extract was positive with an immediate response. Ten atopic and ten nonatopic control subjects did not react to the extract. Specific serum IgE antibodies against Asticot were found in the patient's serum (ELISA). Coomasie staining after SDS-PAGE separation of Asticot extract showed three protein bands of 30, 40 and 60 kDa. IgE immunoblot showed one antigenic band of 60 kDa specifically recognized by the patient's IgE. Specific nasal challenge test with Asticot extract using a Rhinospir 164 rhinomanometer showed immediate response (1/10 w/v), with a 200% increase in nasal resistances from baseline. CONCLUSIONS: One main allergen of MW 60 kDa was specifically recognized by our patient's IgE. There are no previous reports in the literature that characterize the allergens involved in Asticot hypersensitivity. Asticot maggots should be taken into account as a possible causative agent of respiratory symptoms due to a type I hypersensitivity mechanism in anglers who are exposed to emanations of these live fish baits.

Angioedema as a single manifestation of carcinoid syndrome in a bronchial carcinoid tumor.

BACKGROUND: The association of bronchial carcinoid tumours with carcinoid syndrome is extremely rare especially in the absence of metastasic disease, and the angioedema is not a typical sign of this syndrome. METHODS AND RESULTS: We report the case of a 39 year-old woman referred to our allergy department with recurrent episodes of angioedema. The aetiological study of angioedema did not show evidence of hypersensitivity to common inhalants, food allergens and latex. C1-inhibitor, C3, C4, C1q, proteinogram and immunoglobulins (IgA, IgG, IgM) all were normal. TSH determination gave normal results, too. Faecal analyses for parasites were negative. The haemogram showed moderate leucocytosis and hypocromic mycrocitic anaemia. The thoracic radiography showed a mediastinal node image in the right paratracheal region. Histology analyses of the samples were diagnostic of a typical carcinoid tumor. Levels of 5-hydroxyindolacetic acid (5-HIIA) were slightly increased. A superior lobectomy was performed and no new episodes of angioedema appeared after surgical intervention. CONCLUSIONS: We report the first case of typical bronchial carcionid tumour, without metastasic disease, with angioedema as a single manifestation of carcinoid syndrome. In our knowledge, only one case of Quincke's edema as part of typical carcinoid syndrome has been reported, in a case of primary midgut carcinoid tumor with metastasic disease to liver. It is very important to include complementary tests, as thoracic radiography, in the routine study of angioedema to reject malignant diseases.

Neurofibromatosis tipo 1. La necesidad de un reconocimiento clínico precoz / Type 1 neurofibromatosis. The need of an early diagnosis

La neurofibromatosis tipo 1 (NF-1) es una entidad claramente relacionada con la aparición de neoplasias en los niños. La NF-1 ha sido demostrada como factor pronóstico adverso ante neoplasias de nervios periféricos y del sistema nervioso central. El retraso diagnóstico y con ello la disminución en los porcentajes de resecabilidad, son factores que atentan contra la curación de estos pacientes. Por ello nos pareció oportuno revisar los criterios de diagnóstico, menejo y derivación para detectar en tiempo útil al portador de NF 1 e ingresarlo en seguimiento prospectivo, intentando de esa manera disminuir la morbimortalidad por tumores que ellos presentan.