Dutch Consensus Paper: A Consensus View on the Place of Neurostimulation Within the Treatment Arsenal of Five Reimbursed Indications for Neurostimulation in The Netherlands.

INTRODUCTION: After an interpretation trajectory, the Dutch Quality of Healthcare Institute recommended that for five indications, spinal cord stimulation, dorsal root ganglion stimulation, or occipital nerve stimulation, together referred to as neurostimulation, can be considered effective and be reimbursed in the Netherlands. These five indications are the well and largely studied, accepted neurostimulation indications in scientific literature. As an extension of this, all the scientific societies involved in the Netherlands were required to reach a consensus about the diagnosis and treatment of these five formulated indications to describe the place of neurostimulation within the treatment algorithm. This article describes the development process and content of the consensus paper. MATERIALS AND METHODS: A scientific committee, consisting of three anesthesiologists/pain physicians (one of whom acted as the working group's chair), a neurosurgeon, a neurologist, a rehabilitation physician, and three nurse practitioners, participated. A quality advisor of the Knowledge Institute of the Dutch Federation of Medical Specialists supported the committee. The committee participated on behalf of their various scientific and professional societies. Three sessions were organized during which the place of neurostimulation in the treatment algorithm of the five relevant indications was discussed extensively. A narrative literature review and experts' opinions formed the basis of decision-making in the process. RESULTS: For all five diagnoses, general and diagnosis-specific treatment requirements, conservative treatments, and minimally invasive treatments are listed. These treatments should be considered in the chronic pain management algorithm before eventually proceeding to neurostimulation. DISCUSSION/CONCLUSION: The content of this consensus view was discussed and compared with other literature on cost-effectiveness and the place in the algorithm of treating chronic pain. This Dutch consensus paper could ultimately contribute to the maintenance or expansion of neurostimulation and the reimbursement.

Eimeria ninakohlyakimovae casts NOX-independent NETosis and induces enhanced IL-12, TNF-α, IL-6, CCL2 and iNOS gene transcription in caprine PMN.

Eimeria ninakohlyakimovae represents a highly pathogenic coccidian parasite causing severe haemorrhagic typhlocolitis in goat kids worldwide. NETosis was recently described as an efficient defense mechanism of polymorphonuclear neutrophils (PMN) acting against different parasites in vitro and in vivo. In vitro interactions of caprine PMN with parasitic stages of E. ninakohlyakimovae (i. e. oocysts and sporozoites) as well as soluble oocyst antigens (SOA) were analyzed at different ratios, concentrations and time spans. Extracellular DNA staining was used to illustrate classical molecules induced during caprine NETosis [i. e. histones (H3) and neutrophil elastase (NE)] via antibody-based immunofluorescence analyses. Functional inhibitor treatments with DPI and DNase I were applied to unveil role of NADPH oxidase (NOX) and characterize DNA-backbone composition of E. ninakohlyakimovae-triggered caprine NETosis. Scanning electron microscopy (SEM)- and immunofluorescence-analyses demonstrated that caprine PMN underwent NETosis upon contact with sporozoites and oocysts of E. ninakohlyakimovae, ensnaring filaments which firmly entrapped parasites. Detailed co-localization studies of E. ninakohlyakimovae-induced caprine NETosis revealed presence of PMN-derived DNA being adorned with nuclear H3 and NE corroborating molecular characteristics of NETosis. E. ninakohlyakoimovae-induced caprine NETosis was found to be NOX-independent since DPI inhibition led to a slight decrease of NETosis. Exposure of caprine PMN to vital E. ninakohlyakimovae sporozoites as well as SOA resulted in up-regulation of IL-12, TNF-α, IL-6, CCL2 and iNOS gene transcription in stimulated PMN. Since vital E. ninakohlyakimovae-sporozoites induced caprine NETosis, this effective entrapment mechanism might reduce initial sporozoite epithelial host cell invasion during goat coccidiosis ultimately resulting in less macromeront formation and reduced merozoites I production.

HIPECT4: multicentre, randomized clinical trial to evaluate safety and efficacy of Hyperthermic intra-peritoneal chemotherapy (HIPEC) with Mitomycin C used during surgery for treatment of locally advanced colorectal carcinoma.

BACKGROUND: Local relapse and peritoneal carcinomatosis (PC) for pT4 colon cancer is estimated in 15,6% and 36,7% for 12 months and 36 months from surgical resection respectively, achieving a 5 years overall survival of 6%. There are promising results using prophylactic HIPEC in this group of patients, and it is estimated that up to 26% of all T4 colon cancer could benefit from this treatment with a minimal morbidity. Adjuvant HIPEC is effective to avoid the possibility of peritoneal seeding after surgical resection. Taking into account these results and the cumulative experience in HIPEC use, we will lead a randomized controlled trial to determine the effectiveness and safety of adjuvant treatment with HIPEC vs. standard treatment in patients with colon cancer at high risk of peritoneal recurrence (pT4). METHODS/DESIGN: The aim of this study is to determine the effectiveness and safety of adjuvant HIPEC in preventing the development of PC in patients with colon cancer with a high risk of peritoneal recurrence (cT4). This study will be carried out in 15 Spanish HIPEC centres. Eligible for inclusion are patients who underwent curative resection for cT4NxM0 stage colon cancer. After resection of the primary tumour, 200 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously after the primary resection. Mitomycin C will be used as chemotherapeutic agent, for 60 min at 42-43 °C. Primary endpoint is loco-regional control (LC) in months and the rate of loco-regional control (%LC) at 12 months and 36 months after resection. DISCUSSION: We assumed that adjuvant HIPEC will reduce the expected absolute risk of peritoneal recurrence from 36% to 18% at 36 months for T4 colon-rectal carcinoma. TRIAL REGISTRATION: NCT02614534 ( clinicaltrial.gov ) Nov-2015.

Dismenorrea por syndrome de Herlyn-Werner-Wunderich syndrome / Dismenorrea por syndrome de Herlyn-Werner-Wunderich Syndrome

El síndrome de Herlyn-Werner-Wünderlich (HWW) constituye una rara anomalía congénita mülleriana caracterizada por la aso-ciación de útero didelfo, septum vaginal y agenesia renal homolateral. Presentamos el caso de una paciente de 48 años de edadremitida por dismenorrea y que finalmente es diagnosticada de éste síndrome. Durante el examen físico se visualiza fondo de sacoen cara lateral izquierda de la vagina, lo que sería compatible con una vagina rudimentaria. La resonancia magnética confirmaeste hallazgo y muestra un útero didelfo bicollix así como agenesia renal izquierda. Debido a la edad de la paciente y a la ausenciade deseo genésico se realiza histerectomía total con doble anexectomía

Herlyn-Werner-Wünderlich syndrome (HWW) is a rare Mullerian congenital abnormality. This syndrome is characterized by the association between didelphis uterus, obstructive vaginal septum, and homolateral renal agenesis. We report the case of a 48-year old female who was diagnosed with this syndrome in the context of dysmenorrhea and pelvic pain. During physical examination, an orifice on the left lateral aspect of the vagina was visualized and it was compatible with a rudimentary vagina. Magnetic resonance confirmed this finding and showed a didelphis uterus and left renal agenesis. Due to the age of the patient and the absence of gestational desire, a total hysterectomy with double-annexectomy was performed

Eimeria ninakohlyakimovae induces NADPH oxidase-dependent monocyte extracellular trap formation and upregulates IL-12 and TNF-α, IL-6 and CCL2 gene transcription.

Extracellular trap (ET) formation has been demonstrated as novel effector mechanism against diverse pathogens in polymorphonuclear neutrophils (PMN), eosinophils, mast cells, macrophages and recently also in monocytes. In the current study, we show that E. ninakohlyakimovae triggers the deliverance of monocyte-derived ETs in vitro. Fluorescence illustrations as well as scanning electron microscopy (SEM) analyses showed that monocyte-derived ET formation was rapidly induced upon exposure to viable sporozoites, sporocysts and oocysts of E. ninakohlyakimovae. Classical features of monocyte-released ETs were confirmed by the co-localization of extracellular DNA adorned with myeloperoxidase (MPO) and histones (H3) in parasite-entrapping structures. The treatment of caprine monocyte ET structures with NADPH oxidase inhibitor diphenylene iodondium (DPI) significantly reduced ETosis confirming the essential role of reactive oxygen species (ROS) in monocyte mediated ETs formation. Additionally, co-culture of monocytes with viable sporozoites and soluble oocyst antigen (SOA) induced distinct levels of cytokine and chemokine gene transcription. Thus, the transcription of genes encoding for IL-12 and TNF-α was significantly upregulated after sporozoite encounter. In contrast IL-6 and CCL2 gene transcripts were rather weakly induced by parasites. Conversely, SOA only induced the up-regulation of IL-6 and CCL2 gene transcription, and failed to enhance transcripts of IL-12 and TNF-α in vitro. We here report on monocyte-triggered ETs as novel effector mechanism against E. ninakohlyakimovae. Our results strongly suggest that monocyte-mediated innate immune reactions might play an important role in early host immune reactions against E. ninakohlyakimovae in goats.

The impact of a computerized physician order entry system on medical errors with antineoplastic drugs 5 years after its implementation.

WHAT IS KNOWN AND OBJECTIVE: Computerized physician order entry (CPOE) systems reduce medical errors (MEs). Nevertheless, a CPOE system may also lead to new types of errors, especially when it is first implemented. The objectives of this study were to determine the impact of a CPOE on the number of MEs and to identify the types of MEs in prescriptions issued by the Haematology Department 5 years after the implementation of the CPOE system. METHODS: We conducted a prospective analytical study on the implementation of a CPOE system at the Pharmacy Department of the Hospital Ramon y Cajal (Madrid, Spain). The study comprised three phases: a pre-implementation phase, an implementation phase conducted in the Haematology Department and a post-implementation phase, which was conducted 5 years after the implementation of the CPOE system. One hundred and fifty prescriptions per pre- and post-implementation phase were consecutively included in the study. A previously described classification scheme was used to detect and classify MEs. RESULTS AND DISCUSSION: The implementation of a CPOE system was associated with a large reduction in MEs. One hundred and fourteen patients (pre-implementation phase) were compared to 82 patients (post-implementation phase). The total number of MEs per 100 patients decreased from 236·8 (95% CI: 212·1-261·3) to 10·9 (95% CI: 5·8-19·6), with an absolute risk reduction of 36·2 (95% CI: 32·6-39·9). The percentage of prescriptions with an ME decreased from 37·5% to 1·2% (P < 0.001). In the pre-implementation phase, the drugs most frequently associated with MEs were rituximab (35·9%), cyclophosphamide (13%) and methotrexate (7%). In the post-implementation phase, 44·4% of prescription errors involved methotrexate. Five years after the implementation of the CPOE system, the majority of MEs were eliminated, the number of remaining errors (quantity, concentration and ambiguous prescription errors) decreased, and no new types of ME were detected. WHAT IS NEW AND CONCLUSION: The CPOE system almost completely eliminated MEs with antineoplastic drugs in the Haematology Department. No new types of MEs were observed once physicians had become accustomed to using the system. However, some MEs were not eliminated. Constant diligence is needed to analyse and evaluate MEs associated with the CPOE system and their causes, such that the limitations of CPOE can be identified and overcome and the medication-use process associated with antineoplastic agents improved.

Conserving large carnivores: dollars and fence.

Conservationists often advocate for landscape approaches to wildlife management while others argue for physical separation between protected species and human communities, but direct empirical comparisons of these alternatives are scarce. We relate African lion population densities and population trends to contrasting management practices across 42 sites in 11 countries. Lion populations in fenced reserves are significantly closer to their estimated carrying capacities than unfenced populations. Whereas fenced reserves can maintain lions at 80% of their potential densities on annual management budgets of $500 km(-2) , unfenced populations require budgets in excess of $2000 km(-2) to attain half their potential densities. Lions in fenced reserves are primarily limited by density dependence, but lions in unfenced reserves are highly sensitive to human population densities in surrounding communities, and unfenced populations are frequently subjected to density-independent factors. Nearly half the unfenced lion populations may decline to near extinction over the next 20-40 years.

Validación de una clasificación de errores de medicación para su utilización en quimioterapia / Validating a Classification Scheme for Medication Errors to be Used in Chemotherapy

Objetivo Validar una hoja de clasificación de errores de medicación asociados a medicamentos antineoplásicos. Métodos Estudio prospectivo. Se diseñó una hoja de recogida de datos sobre la base de la clasificación de la American Society of Health-System Pharmacists. Dos observadores revisaron las líneas de tratamiento de las prescripciones de quimioterapia del Servicio de Hematología durante un mes y clasificaron los errores detectados. Se analizó la concordancia interobservador mediante el test del índice kappa. Se revisaron las categorías de error en las que se obtuvo una concordancia moderada o inferior y se valoró si era necesaria su modificación. Resultados Se analizaron un total de 23 categorías de error y se revisaron 162 líneas de tratamiento. Únicamente una de las categorías fue valorable en función de su prevalencia de error, la de prescripción incompleta o ambigua (índice kappa=0,458=concordancia moderada). Se analizaron las causas y se desglosaron subapartados dentro de esta categoría. Conclusión Nuestros resultados evidenciaron la necesidad de la revisión de la clasificación de errores. Es necesario disponer de herramientas validadas para avanzar en la caracterización de este tipo de errores de medicación (AU)

Objective To validate a classification sheet for medication errors associated with antineoplastic medication. Method Prospective study. A data sheet was designed based on ASHP's classification. Two observers reviewed the treatment prescribed for chemotherapy from the Haematology Department during a month and they classified the errors detected. The interobserver concordance was analysed using the kappa index test. The error categories with a moderate or lower concordance were reviewed, and the need to modify them was evaluated. Results A total of 23 error categories were analysed and 162 lines of treatment were reviewed. Only one of the categories was assessable in accordance with its error prevalence, which was the category for incomplete or ambiguous prescriptions (kappa index=0.458=moderate concordance). The causes were analysed and subsections within this category itemised. Conclusion Our results proved the need to review error classification. Validated tools need to be made available so as to make progress in characterising this type of medication error (AU)

Effects of trophy hunting on lion and leopard populations in Tanzania.

Tanzania holds most of the remaining large populations of African lions (Panthera leo) and has extensive areas of leopard habitat (Panthera pardus), and both species are subjected to sizable harvests by sport hunters. As a first step toward establishing sustainable management strategies, we analyzed harvest trends for lions and leopards across Tanzania's 300,000 km(2) of hunting blocks. We summarize lion population trends in protected areas where lion abundance has been directly measured and data on the frequency of lion attacks on humans in high-conflict agricultural areas. We place these findings in context of the rapidly growing human population in rural Tanzania and the concomitant effects of habitat loss, human-wildlife conflict, and cultural practices. Lion harvests declined by 50% across Tanzania between 1996 and 2008, and hunting areas with the highest initial harvests suffered the steepest declines. Although each part of the country is subject to some form of anthropogenic impact from local people, the intensity of trophy hunting was the only significant factor in a statistical analysis of lion harvest trends. Although leopard harvests were more stable, regions outside the Selous Game Reserve with the highest initial leopard harvests again showed the steepest declines. Our quantitative analyses suggest that annual hunting quotas be limited to 0.5 lions and 1.0 leopard/1000 km(2) of hunting area, except hunting blocks in the Selous Game Reserve, where harvests should be limited to 1.0 lion and 3.0 leopards/1000 km(2) .

[Validating a classification scheme for medication errors to be used in chemotherapy]. / Validación de una clasificación de errores de medicación para su utilización en quimioterapia.

OBJECTIVE: To validate a classification sheet for medication errors associated with antineoplastic medication. METHOD: Prospective study. A data sheet was designed based on ASHP's classification. Two observers reviewed the treatment prescribed for chemotherapy from the Haematology Department during a month and they classified the errors detected. The interobserver concordance was analysed using the kappa index test. The error categories with a moderate or lower concordance were reviewed, and the need to modify them was evaluated. RESULTS: A total of 23 error categories were analysed and 162 lines of treatment were reviewed. Only one of the categories was assessable in accordance with its error prevalence, which was the category for incomplete or ambiguous prescriptions (kappa index=0.458=moderate concordance). The causes were analysed and subsections within this category itemised. CONCLUSION: Our results proved the need to review error classification. Validated tools need to be made available so as to make progress in characterising this type of medication error.

[Laparoscopic treatment of ovarian vein syndrome]. / Tratamiento laparoscópico del síndrome de la vena ovárica.

OBJECTIVE: We report a case of Ovarian Vein Syndrome, describe its clinical symptoms and discuss its diagnosis and management including laparoscopic surgery treatment. MATERIALS AND METHODS: A 36-year-old female with right kidney recurring pain was studied by means of abdominal RX, urography, CT, MRI and ultrasonography and finally diagnosed from Ovarian Vein Syndrome. The case was resolved with laparoscopic surgery. CONCLUSIONS: Ovarian Vein Syndrome is an uncommon disorder. Differential diagnosis must be done with external processes that cause ureteral obstruction. Surgery is the first line treatment when clinical symptoms are present and, in our opinion,laparoscopic surgery is the best approach to treat this pathology.

Tratamiento laparoscópico del síndrome de la vena ovárica / Laparoscopic treatment of ovarian vein syndrome

Objetivo: Presentamos un caso de síndrome de la vena ovárica, describimos su presentación clínica y discutimos su diagnóstico y tratamiento incluyendo la cirugía laparoscópica. Material y Métodos: Mujer de 36 años de edad con clínica de cólico renal derecho recurrente que tras ser estudiada mediante radiología de abdomen, urografías, TAC, RM y ecografía es diagnosticada finalmente de síndrome de la vena ovárica. El caso se resuelve con cirugía laparoscópica. Conclusiones: El síndrome de la vena ovárica es una entidad poco frecuente. El diagnóstico diferencial se debe hacer con procesos extrínsecos que producen obstrucción ureteral. El tratamiento es quirúrgico cuando produce síntomas y pensamos que actualmente debe hacerse por vía laparoscópica

Objective: We report a case of Ovarian Vein Syndrome, describe its clinical symptoms and discuss its diagnosis and management including laparoscopic surgery treatment. Materials and Methods: A 36-year-old female with right kidney recurring pain was studied by means of abdominal RX, urography, CT, MRI and ultrasonography and finally diagnosed from Ovarian Vein Syndrome. The case was resolved with laparoscopic surgery. Conclusions: Ovarian Vein Syndrome is an uncommon disorder. Differential diagnosis must be done with external processes that cause ureteral obstruction. Surgery is the first line treatment when clinical symptoms are present and, in our opinion, laparoscopic surgery is the best approach to treat this pathology

Pseudoaneurisma postinfarto del ventrículo izquierdo: hallazgos en resonancia magnética / Left vewntricule pseudoaneurysm following myocardial infarction: MRI findings

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Tumores fetales: I parte / Fetal tumors: Part I

Se presenta una revisión sistemática y resumida de los diferentes tumores fetales, haciendo énfasis en su diagnóstico prenatal y posibles tratamientos intrauterinos. En esta primera parte se introduce el tema y se analizan tumores del sistema nervioso central, cara y cuello.