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.

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.

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.

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.

The behaviour-conservation interface.

In the past four years, there have been several attempts to apply studies of animal behaviour to conservation. Knowledge of individuals' behaviour has the potential to alter understanding of how populations fare in fragmented habitats, the responses of populations to exploitation and disturbance, disease susceptibility, effective population size, captive breeding and reintroduction efforts, and population monitoring and modelling. It can even be useful in understanding human conservation actions.

Interspecific Killing among Mammalian Carnivores.

Interspecific killing among mammalian carnivores is common in nature and accounts for up to 68% of known mortalities in some species. Interactions may be symmetrical (both species kill each other) or asymmetrical (one species kills the other), and in some interactions adults of one species kill young but not adults of the other. There is a positive significant relationship between the body masses of solitary killer species and body masses of their victim species, and grouping species kill larger victims than solitary species. Interactions and consumption of the victim appear more common when food is scarce or disputed. In response to killers, victim species may alter their use of space, activity patterns, and form groups. Consequences of interspecific killing include population reduction or even extinction, and reduction and enhancement of prey populations, and may therefore have important implications for conservation and management of carnivores and their prey.

Maduración cervical con misoprostol / Misoprostol cervix maturation

Los comprimidos para empleo oral de Misoprostol se están usando tanto en el extranjero como en nuestro país para la inducción del trabajo de parto, verificándose con ellos una alta eficacia en el obtención de dinámica uterina, con muy buena seguridad materna y fetal. No hay información respecto al uso de Misoprostol como inductor de maduración del cuello uterino en dosis bajas. Se realiza un estudio en pacientes embarazadas de alto riesgo obstétrico, cuyo objetivo es la evaluación del uso de prostaglandinas en bajas dosis como inductor de la maduración del cuello uterino. Se obtiene un 64,60 por ciento de puntuación máxima según Bishop (13 puntos) con un promedio de 4 aplicaciones, en un 5,30 por ciento se obtiene 10 a 12 puntos, 10,61 por ciento sólo 7 a 9 puntos, 20,35 por ciento 6 o menos puntos. Al considerar sólo la modificación del puntaje de Bishop, (es decir Bishop final- Bishop inicial) logramos en un 63,71 por ciento de las pacientes una elevación de 8 o más puntos lo cual es estadísticamente significativo. Se obtiene como conclusión que: la administración de misoprostol a dosis de 25 microgramos por la vía transvaginal, es una excelente alternativa como inductor de maduración del cuello uterino constituyéndose en una acción segura y fácil de usar en embarazadas de alto riesgo obstétrico

Embarazo en el ligamento ancho / Broad ligament pregnancy

Presentamos un caso clínico de embarazo ectópico, diagnosticado al momento del parto, ubicado en el ligamento ancho derecho. Corresponde a un embarazo de 39 semanas, en una paciente de 22 años, multípara de un parto cesárea. Se comenta frecuencia, diagnóstico y tratamiento

Working together in Peru--language needn't be a problem!

International, co-operative links between dental schools are an increasingly common occurrence, especially in relation to elective visits for under-graduates. However, in this feature for FDI World Norman Whitehouse and Gillian Jones from the Cardiff Dental School in Wales, UK, describe how they came to meet and assist Teresa Rios Caro in Peru, in rather different circumstances, and how language need not be a barrier when goodwill prevails.

Pursuit-deterrence revisited.

Pursuit-deterrent signals - signals used by prey that apparently convince predators not to pursue them - were discovered 15 years ago, but their existence continues to rest on shaky empirical evidence. First, pursuit-deterrent signals are usually inferred by eliminating competing hypotheses rather than testing predictions derived from the pursuit-deterrent hypothesis directly. Second, the strength of selection pressures maintaining such signals in prey populations are unknown because behavioral ecologists infrequently observe natural predation attempts. Third, the nature of information passing between prey and predators is open to misinterpretation because measures are rarely taken to separate signals that advertise perception of the predator from those that advertise perception and the prey's condition.