Individual quality assessment of autografting by probability estimation for clinical endpoints: a prospective validation study from the European group for blood and marrow transplantation.

The aim of supportive autografting is to reduce the side effects from stem cell transplantation and avoid procedure-related health disadvantages for patients at the lowest possible cost and resource expenditure. Economic evaluation of health care is becoming increasingly important. We report clinical and laboratory data collected from 397 consecutive adult patients (173 non-Hodgkin lymphoma, 30 Hodgkin lymphoma, 160 multiple myeloma, 7 autoimmune diseases, and 28 acute leukemia) who underwent their first autologous peripheral blood stem cell transplantation (PBSCT). We considered primary endpoints evaluating health economic efficacy (eg, antibiotic administration, transfusion of blood components, and time in hospital), secondary endpoints evaluating toxicity (in accordance with Common Toxicity Criteria), and tertiary endpoints evaluating safety (ie, the risk of regimen-related death or disease progression within the first year after PBSCT). A time-dependent grading of efficacy is proposed with day 21 for multiple myeloma and day 25 for the other disease categories (depending on the length of the conditioning regimen) as the acceptable maximum time in hospital, which together with antibiotics, antifungal, or transfusion therapy delineates four groups: favorable (≤7 days on antibiotics and no transfusions; ≤21 [25] days in hospital), intermediate (from 7 to 10 days on antibiotics and 7 days on antibiotics, >3 but 30/34 days in hospital after transplantation), and very unfavorable (>10 days on antibiotics, >6 transfusions; >30 to 34 days in hospital). The multivariate analysis showed that (1) PBSC harvests of ≥4 × 106/kg CD34 + cells in 1 apheresis procedure were associated with a favorable outcome in all patient categories except acute myelogenous leukemia and acute lymphoblastic leukemia (P = .001), (2) ≥5 × 106/kg CD34 + cells infused predicted better transplantation outcome in all patient categories (P 500 mL) (P = .002), and (5) patients with a central venous catheter during both collection and infusion of PBSC had a more favorable outcome post-PBSCT than peripheral access (P = .007). The type of mobilization regimen did not affect the outcome of auto-PBSCT. The present study identified predictive variables, which may be useful in future individual pretransplantation probability evaluations with the goal to improve supportive care

An overview of the cutaneous porphyrias

This is an overview of the cutaneous porphyrias. It is a narrative review based on the published literature and my personal experience; it is not based on a formal systematic search of the literature. The cutaneous porphyrias are a diverse group of conditions due to inherited or acquired enzyme defects in the porphyrin–haem biosynthetic pathway. All the cutaneous porphyrias can have (either as a consequence of the porphyria or as part of the cause of the porphyria) involvement of other organs as well as the skin. The single commonest cutaneous porphyria in most parts of the world is acquired porphyria cutanea tarda, which is usually due to chronic liver disease and liver iron overload. The next most common cutaneous porphyria, erythropoietic protoporphyria, is an inherited disorder in which the accumulation of bile-excreted protoporphyrin can cause gallstones and, rarely, liver disease. Some of the porphyrias that cause blistering (usually bullae) and fragility (clinically and histologically identical to porphyria cutanea tarda) can also be associated with acute neurovisceral porphyria attacks, particularly variegate porphyria and hereditary coproporphyria. Management of porphyria cutanea tarda mainly consists of visible-light photoprotection measures while awaiting the effects of treating the underlying liver disease (if possible) and treatments to reduce serum iron and porphyrin levels. In erythropoietic protoporphyria, the underlying cause can be resolved only with a bone marrow transplant (which is rarely justifiable in this condition), so management consists particularly of visible-light photoprotection and, in some countries, narrowband ultraviolet B phototherapy. Afamelanotide is a promising and newly available treatment for erythropoietic protoporphyria and has been approved in Europe since 2014

Comparing the effect of STan (cardiotocographic electronic fetal monitoring (CTG) plus analysis of the ST segment of the fetal electrocardiogram) with CTG alone on emergency caesarean section rates: study protocol for the STan Australian Randomised controlled Trial (START).

BACKGROUND: Cardiotocography is almost ubiquitous in its use in intrapartum care. Although it has been demonstrated that there is some benefit from continuous intrapartum fetal monitoring using cardiotocography, there is also an increased risk of caesarean section which is accompanied by short-term and long-term risks to the mother and child. There is considerable potential to reduce unnecessary operative delivery with up to a 60% false positive diagnosis of fetal distress using cardiotocography alone. ST analysis of the fetal electrocardiogram is a promising adjunct to cardiotocography alone, and permits detection of metabolic acidosis of the fetus, potentially reducing false positive diagnosis of fetal distress. METHODS: This study will be a single-centre, parallel-group, randomised controlled trial, conducted over 3 years. The primary hypothesis will be that the proportion of women with an emergency caesarean section on ST analysis will not equal that for women on cardiotocography monitoring alone. Participants will be recruited at the Women's and Children's Hospital, a high-risk specialty facility with approximately 5000 deliveries per annum. A total of 1818 women will be randomised to the treatment or conventional arm with an allocation ratio of 1:1, stratified by parity. The primary outcome is emergency caesarean section (yes/no). Statistical analysis will follow standard methods for randomised trials and will be performed on an intention-to-treat basis. Secondary maternal and neonatal outcomes will also be analysed. Additional study outcomes include psychosocial outcomes, patient preferences and cost-effectiveness. DISCUSSION: Approximately 20% of Australian babies are delivered by emergency caesarean section. This will be the first Australian trial to examine ST analysis of the fetal electrocardiogram as an adjunct to cardiotocography as a potential method for reducing this proportion. The trial will be among the first to comprehensively examine ST analysis, taking into account the impact on psychosocial well-being as well as cost-effectiveness. This research will provide Australian evidence for clinical practice and guideline development as well as for policy-makers and consumers to make informed, evidence-based choices about care in labour. TRIAL REGISTRATION: ANZCTR, ACTRN1261800006268 . Registered on 19 January 2018

Oceanographic processes and products around the Iberian margin: a new multidisciplinary approach

Our understanding of the role of bottom currents and associated oceanographic processes (e.g, overflows, barotropic tidal currents) including intermittent processes (e.g, vertical eddies, deep sea storms, horizontal vortices, internal waves and tsunamis) is rapidly evolving. Many deep-water processes remain poorly understood due to limited direct observations, but may generate significant depositional and erosional features on both short-and long-term time scales. This paper describes these oceanographic processes and examines their potential role in the sedimentary features around the Iberian margin. The paper explores the implications of the processes studied, given their secondary role relative to other factors such as mass-transport and turbiditic processes. An integrated interpretation of these oceanographic processes requires an understanding of contourites, sea-floor features, their spatial and temporal evolution, and the near-bottom flows that form them. Given their complex, three-dimensional and temporally-variable nature, integration of these processes into sedimentary, oceanographic and climatological frameworks will require a multidisciplinary approach that includes Geology, Physical Oceanography, Paleoceanography and Benthic Biology. This approach will synthesize oceanographic data, seafloor morphology, sediments and seismic images to improve our knowledge of permanent and intermittent processes around Iberia, and evaluate their conceptual and regional role in the sedimentary evolution of the margin. © 2015, Instituto Geologico y Minero de Espana. All rights reservedEl conocimiento del papel de las corrientes de fondo y los procesos oceanográficos asociados (overflows, corrientes de marea barotrópicas, etc), incluyendo procesos intermitentes (eddies, tormentas profundas, ondas internas, tsunamis, etc), está evolucionando rápidamente. Muchos de estos procesos son poco conocidos, en parte debido a que las observaciones directas son limitadas, si bien pueden generar importantes rasgos deposicionales y/o erosivos a escalas temporales de corto o largo periodo. Este artículo describe dichos procesos oceanográficos y examina su influencia en la presencia de rasgos sedimentarios alrededor del margen Ibérico. El trabajo discute las implicaciones de dichos procesos y el papel secundario que juegan en relación a otros factores tales como los procesos de transporte gravitacionales en masa y los turbidíticos. Para un mejor conocimiento de la sedimentación marina profunda, y en concreto de los sistemas contorníticos, se requiere de una interpretación de estos procesos oceanográficos, cuál es su evolución espacial y temporal, cómo afectan a las corrientes de fondo y cómo se ven afectados por la topografía submarina. Sin embargo, dada su complejidad y su variable naturaleza tridimensional y temporal, es necesario que estos procesos se integren en un marco sedimentológico, oceanográfico y climatológico con un enfoque multidisciplinar que incluyan la Geología, la Oceanografía Física, la Paleoceanografía y la Biología bentónica. Esta integración requiere de una mayor compilación de datos oceanográficos, de un mejor conocimiento de la morfología del fondo marino, y de una mejor caracterización de los sedimentos en ambientes profundos. Todo ello permitirá mejorar nuestro conocimiento de los procesos permanentes e intermitentes alrededor de Iberia y evaluar su verdadero efecto en la evolución sedimentaria delos márgenes continentales que le rodeanPostprint0,000

A randomised clinical trial on cardiotocography plus fetal blood sampling versus cardiotocography plus ST-analysis of the fetal electrocardiogram (STAN®) for intrapartum monitoring

<p>Abstract</p> <p>Background</p> <p>Cardiotocography (CTG) is worldwide the method for fetal surveillance during labour. However, CTG alone shows many false positive test results and without fetal blood sampling (FBS), it results in an increase in operative deliveries without improvement of fetal outcome. FBS requires additional expertise, is invasive and has often to be repeated during labour. Two clinical trials have shown that a combination of CTG and ST-analysis of the fetal electrocardiogram (ECG) reduces the rates of metabolic acidosis and instrumental delivery. However, in both trials FBS was still performed in the ST-analysis arm, and it is therefore still unknown if the observed results were indeed due to the ST-analysis or to the use of FBS in combination with ST-analysis.</p> <p>Methods/Design</p> <p>We aim to evaluate the effectiveness of non-invasive monitoring (CTG + ST-analysis) as compared to normal care (CTG + FBS), in a multicentre randomised clinical trial setting. Secondary aims are: 1) to judge whether ST-analysis of fetal electrocardiogram can significantly decrease frequency of performance of FBS or even replace it; 2) perform a cost analysis to establish the economic impact of the two treatment options.</p> <p>Women in labour with a gestational age ≥ 36 weeks and an indication for CTG-monitoring can be included in the trial.</p> <p>Eligible women will be randomised for fetal surveillance with CTG and, if necessary, FBS or CTG combined with ST-analysis of the fetal ECG.</p> <p>The primary outcome of the study is the incidence of serious metabolic acidosis (defined as pH < 7.05 and Bd_ecf> 12 mmol/L in the umbilical cord artery). Secondary outcome measures are: instrumental delivery, neonatal outcome (Apgar score, admission to a neonatal ward), incidence of performance of FBS in both arms and cost-effectiveness of both monitoring strategies across hospitals.</p> <p>The analysis will follow the intention to treat principle. The incidence of metabolic acidosis will be compared across both groups. Assuming a reduction of metabolic acidosis from 3.5% to 2.1 %, using a two-sided test with an alpha of 0.05 and a power of 0.80, in favour of CTG plus ST-analysis, about 5100 women have to be randomised. Furthermore, the cost-effectiveness of CTG and ST-analysis as compared to CTG and FBS will be studied.</p> <p>Discussion</p> <p>This study will provide data about the use of intrapartum ST-analysis with a strict protocol for performance of FBS to limit its incidence. We aim to clarify to what extent intrapartum ST-analysis can be used without the performance of FBS and in which cases FBS is still needed.</p> <p>Trial Registration Number</p> <p>ISRCTN95732366</p

Delivering 21st century Antarctic and Southern Ocean science

The Antarctic Roadmap Challenges (ARC) project identified critical requirements to deliver high priority Antarctic research in the 21st century. The ARC project addressed the challenges of enabling technologies, facilitating access, providing logistics and infrastructure, and capitalizing on international co-operation. Technological requirements include: i) innovative automated in situ observing systems, sensors and interoperable platforms (including power demands), ii) realistic and holistic numerical models, iii) enhanced remote sensing and sensors, iv) expanded sample collection and retrieval technologies, and v) greater cyber-infrastructure to process ‘big data’ collection, transmission and analyses while promoting data accessibility. These technologies must be widely available, performance and reliability must be improved and technologies used elsewhere must be applied to the Antarctic. Considerable Antarctic research is field-based, making access to vital geographical targets essential. Future research will require continent- and ocean-wide environmentally responsible access to coastal and interior Antarctica and the Southern Ocean. Year-round access is indispensable. The cost of future Antarctic science is great but there are opportunities for all to participate commensurate with national resources, expertise and interests. The scope of future Antarctic research will necessitate enhanced and inventive interdisciplinary and international collaborations. The full promise of Antarctic science will only be realized if nations act together

Vitamin B12 status in patients of Turkish and Dutch descent with depression: A comparative cross-sectional study

Background: Studies have shown a clear relationship between depressive disorders and vitamin B12 deficiency. Gastroenteritis and Helicobacter pylori infections can cause vitamin B12 deficiency. Helicobacter pylori infections are not uncommon among people of Turkish descent in The Netherlands. Aim: To examine the frequency of vitamin B12 deficiency in depressive patients of Turkish descent and compare it to the frequency of vitamin B12 deficiency in depressive patients of Dutch descent. Methods: The present study is a comparative cross-sectional study of 47 patients of Turkish descent and 28 of Dutch descent. The depressive disorder diagnosis and differential diagnosis were made using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revision (SCID). The severity of the depressive symptoms was determined using the Beck Depression Inventory (BDI) and the 21-item Hamilton Depression Rating Scale (HAM-D-21). Serum baseline vitamin B6 and B12, folic acid and total serum homocysteine (tHcy) levels were measured. Results: The average ages of the patients of Turkish and Dutch descent were 40.57 and 44.75 years, respectively. There were no demonstrable differences between the serum vitamin B6, folic acid and tHcy levels in the two groups. The serum vitamin B12 levels were however clearly lower in the patients of Turkish descent than in those of Dutch descent. Vitamin B12 deficiency was however observed in 14 patients of Turkish descent and 1 of Dutch descent. This difference was significant. On the BDI, the patients of Turkish descent scored significantly higher than those of Dutch descent. Patients with vitamin B12 deficiency and those with hyperhomocysteinaemia had a significantly higher BDI score than patients with normal vitamin B12 and homocysteine levels. No relationship was observed with vitamin B12 and tHcy. Conclusion: Vitamin B12 deficiency occurs more frequently in depressive patients of Turkish than of Dutch descent. This is why it is advisable to test the vitamin B12 serum level in depressive patients of Turkish descent

The encounter with the unknown: Nurses lived experiences of their responsibility for the care of the patient in the Swedish ambulance service

Registered nurses (RNs) have, according to the Swedish National Board of Health and Welfare, the overall responsibility for the medical care in the ambulance care setting. Bringing RNs into the ambulance service are judged, according to earlier studies, to lead to a degree of professionalism with a higher quality of medical care. Implicitly in earlier studies, the work in the ambulance service involves interpersonal skills. The aim of this study was to describe RNs' experiences of being responsible for the care of the patient in the Swedish ambulance service. A reflective lifeworld approach within the perspective of caring science was used. Five RNs with at least five years experience from care in the ambulance care setting were interviewed. The findings show that the essence of the phenomenon is to prepare and create conditions for care and to accomplish care close to the patient. Three meaning constituents emerged in the descriptions: prepare and create conditions for the nursing care, to be there for the patient and significant others and create comfort for the patient and significant others. The responsibility is a complex phenomenon, with a caring perspective, emerging from the encounter with the unique human being

Prognostic impact of progression to induction chemotherapy and prior paclitaxel therapy in patients with germ cell tumors receiving salvage high-dose chemotherapy in the last 10 years: A study of the European Society for Blood and Marrow Transplantation Solid Tumors Working Party

Little is known about the prognostic impact of prior paclitaxel therapy and response to induction chemotherapy defined as the regimen preceding high-dose chemotherapy (HDCT) for the salvage therapy of advanced germ cell tumors. Twenty European Society for Blood and Marrow Transplantation centers contributed data on patients treated between 2002 and 2012. Paclitaxel used in either prior lines of therapy or in induction-mobilization regimens was considered. Multivariable Cox analyses of prespecified factors were undertaken on PFS and overall survival (OS). As of October 2013, data for 324 patients had been contributed to this study. One hundred and ninety-two patients (59.3%) had received paclitaxel. Sixty-one patients (19%) had a progression to induction chemotherapy, 234 (72%) a response (29 (9%) missing or granulocyte colony-stimulating factor without chemotherapy). Both progression to induction chemotherapy and prior paclitaxel were significantly associated with shorter OS univariably (P&lt;0.001 and P=0.032). On multivariable analysis from the model with fully available data (N=216) progression to induction was significantly prognostic for PFS and OS (P=0.003), but prior paclitaxel was not (P=0.674 and P=0.739). These results were confirmed after multiple imputation of missing data. Progression to induction chemotherapy could be demonstrated as an independent prognostic factor, in contrast to prior paclitaxel